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

Stomach Adenocarcinoma (Primary solid tumor)

21 August 2015 | analyses__2015_08_21

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 STAD-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1V69HW5

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 STAD-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: 195
Number of samples: 274
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 5 :[ clus1 ] 63
pheno.type: 2 - 5 :[ clus2 ] 63
pheno.type: 3 - 5 :[ clus3 ] 44
pheno.type: 4 - 5 :[ clus4 ] 40
pheno.type: 5 - 5 :[ clus5 ] 64

For the expression subtypes of 23365 genes in 275 samples, GSEA found enriched gene sets in each cluster using 274 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA G1 PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA IL2RB PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA TNFR1 PATHWAY, KEGG PYRIMIDINE METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RIBOSOME, KEGG RNA DEGRADATION

And common core enriched genes are PCNA, CCNH, CDK7, LIG1, POLD1, POLD2, POLE, POLE2, POLE3, RBX1

clus2

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA ALK PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA BCR PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA FCER1 PATHWAY

And common core enriched genes are CACNA1C, PRKACB, ADCY2, ADCY4, ADCY9, RYR2, SLC8A1, ADCY5, ADRA1A, ADRA1D

clus3

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG GALACTOSE METABOLISM, KEGG FATTY ACID METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS, KEGG OXIDATIVE PHOSPHORYLATION, KEGG GLUTATHIONE METABOLISM, KEGG O GLYCAN BIOSYNTHESIS, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

And common core enriched genes are ADH1A, ADH1C, ADH7, CYP2C19, CYP2C8, CYP2C9, CYP3A7, UGT1A1, UGT2A3, UGT2B11

clus4

Top enriched gene sets are BIOCARTA HIVNEF PATHWAY, BIOCARTA DEATH PATHWAY, BIOCARTA TNFR1 PATHWAY, KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG CITRATE CYCLE TCA CYCLE, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG FATTY ACID METABOLISM, KEGG OXIDATIVE PHOSPHORYLATION, KEGG PYRIMIDINE METABOLISM

And common core enriched genes are DLD, IDH1, IDH2, HMGCL, ALDOB, ALDOC, FBP1, PFKL, PFKP, ACO1

clus5

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA CARM ER PATHWAY, BIOCARTA G1 PATHWAY, BIOCARTA MPR PATHWAY, BIOCARTA CHREBP2 PATHWAY, KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG CYSTEINE AND METHIONINE METABOLISM, KEGG LYSINE DEGRADATION, KEGG HISTIDINE METABOLISM

And common core enriched genes are ACACA, FASN, GCK, MLXIPL, PKLR, PPP2R1B, PPP2R2C, PPP2R3B, PRKAA2, PRKAB2

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 G1 PATHWAY	27	genes.ES.table	0.49	1.5	0.062	0.2	0.89	0.41	0.12	0.36	0.14	0.007
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.56	1.7	0.031	0.093	0.52	0.48	0.21	0.38	0.039	0.005
BIOCARTA HIVNEF PATHWAY	56	genes.ES.table	0.46	1.6	0.058	0.13	0.71	0.55	0.26	0.41	0.067	0.006
BIOCARTA IL2RB PATHWAY	37	genes.ES.table	0.51	1.5	0.11	0.18	0.85	0.43	0.17	0.36	0.12	0.008
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.5	1.8	0.018	0.095	0.44	0.56	0.25	0.42	0	0.009
BIOCARTA TNFR1 PATHWAY	28	genes.ES.table	0.57	1.8	0.023	0.1	0.4	0.46	0.21	0.36	0	0.01
KEGG PYRIMIDINE METABOLISM	94	genes.ES.table	0.5	1.8	0.0077	0.11	0.39	0.47	0.19	0.38	0	0.012
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.59	1.7	0.038	0.096	0.54	0.55	0.2	0.44	0.04	0.006
KEGG RIBOSOME	81	genes.ES.table	0.64	1.8	0.028	0.088	0.45	0.91	0.34	0.61	0	0.008
KEGG RNA DEGRADATION	56	genes.ES.table	0.54	1.8	0.0094	0.09	0.3	0.54	0.22	0.42	0	0.01

genes ES table in pathway: BIOCARTA G1 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	POLE2	POLE2	POLE2	338	0.32	0.041	YES
2	RFC4	RFC4	RFC4	378	0.32	0.094	YES
3	DDB2	DDB2	DDB2	410	0.31	0.15	YES
4	LIG1	LIG1	LIG1	438	0.3	0.2	YES
5	POLD1	POLD1	POLD1	480	0.3	0.25	YES
6	RFC5	RFC5	RFC5	502	0.29	0.3	YES
7	CDK7	CDK7	CDK7	612	0.28	0.34	YES
8	GTF2H3	GTF2H3	GTF2H3	637	0.27	0.38	YES
9	RFC2	RFC2	RFC2	661	0.27	0.43	YES
10	PCNA	PCNA	PCNA	739	0.26	0.47	YES
11	POLE	POLE	POLE	856	0.24	0.51	YES
12	RFC3	RFC3	RFC3	1138	0.22	0.53	YES
13	MNAT1	MNAT1	MNAT1	1894	0.17	0.53	YES
14	RPA3	RPA3	RPA3	1935	0.17	0.56	YES
15	POLD2	POLD2	POLD2	1974	0.17	0.58	YES
16	POLE3	POLE3	POLE3	2146	0.16	0.6	YES
17	GTF2H4	GTF2H4	GTF2H4	2829	0.13	0.6	YES
18	RFC1	RFC1	RFC1	2891	0.13	0.62	YES
19	CCNH	CCNH	CCNH	2920	0.13	0.64	YES
20	RPA2	RPA2	RPA2	3047	0.13	0.66	YES
21	GTF2H2	GTF2H2	GTF2H2	3600	0.11	0.65	YES
22	RBX1	RBX1	RBX1	3929	0.1	0.65	YES
23	RPA1	RPA1	RPA1	4029	0.1	0.67	YES
24	ERCC3	ERCC3	ERCC3	5315	0.071	0.62	NO
25	GTF2H1	GTF2H1	GTF2H1	5510	0.067	0.62	NO
26	POLE4	POLE4	POLE4	5559	0.066	0.63	NO
27	CUL4A	CUL4A	CUL4A	5685	0.064	0.64	NO
28	ERCC2	ERCC2	ERCC2	5702	0.063	0.65	NO
29	RAD23A	RAD23A	RAD23A	5978	0.058	0.65	NO
30	ERCC8	ERCC8	ERCC8	7395	0.03	0.59	NO
31	XPC	XPC	XPC	7813	0.022	0.57	NO
32	CETN2	CETN2	CETN2	7910	0.02	0.57	NO
33	POLD3	POLD3	POLD3	7975	0.019	0.57	NO
34	ERCC1	ERCC1	ERCC1	8082	0.017	0.57	NO
35	DDB1	DDB1	DDB1	9194	-0.0053	0.52	NO
36	POLD4	POLD4	POLD4	9414	-0.01	0.52	NO
37	XPA	XPA	XPA	9686	-0.015	0.51	NO
38	GTF2H5	GTF2H5	GTF2H5	10395	-0.03	0.48	NO
39	CUL4B	CUL4B	CUL4B	10962	-0.041	0.46	NO
40	ERCC6	ERCC6	ERCC6	11142	-0.045	0.46	NO
41	RPA4	RPA4	RPA4	14699	-0.13	0.33	NO
42	ERCC4	ERCC4	ERCC4	15107	-0.14	0.33	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 G1 PATHWAY.

Figure S2. 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 FAS 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	IFNG	IFNG	IFNG	8	0.54	0.098	YES
2	PSMB9	PSMB9	PSMB9	210	0.36	0.16	YES
3	PSMC1	PSMC1	PSMC1	782	0.25	0.18	YES
4	PSME2	PSME2	PSME2	792	0.25	0.22	YES
5	PSMB8	PSMB8	PSMB8	1163	0.22	0.24	YES
6	PSMA5	PSMA5	PSMA5	1255	0.21	0.28	YES
7	PSMD12	PSMD12	PSMD12	1407	0.2	0.31	YES
8	PSMA4	PSMA4	PSMA4	1432	0.2	0.34	YES
9	PSMC6	PSMC6	PSMC6	1547	0.19	0.37	YES
10	PSMB2	PSMB2	PSMB2	1655	0.18	0.4	YES
11	PSMA6	PSMA6	PSMA6	1755	0.18	0.43	YES
12	PSME1	PSME1	PSME1	1893	0.17	0.46	YES
13	PSMD14	PSMD14	PSMD14	2129	0.16	0.48	YES
14	PSMD6	PSMD6	PSMD6	2194	0.16	0.5	YES
15	POMP	POMP	POMP	2455	0.15	0.52	YES
16	PSMA2	PSMA2	PSMA2	2629	0.14	0.54	YES
17	PSMA1	PSMA1	PSMA1	2697	0.14	0.56	YES
18	PSMD2	PSMD2	PSMD2	2914	0.13	0.57	YES
19	PSMB6	PSMB6	PSMB6	3150	0.12	0.58	YES
20	PSMA3	PSMA3	PSMA3	3160	0.12	0.6	YES
21	PSMD11	PSMD11	PSMD11	3310	0.12	0.62	YES
22	PSMB1	PSMB1	PSMB1	3495	0.12	0.63	YES
23	PSMD13	PSMD13	PSMD13	3748	0.11	0.64	YES
24	PSMB7	PSMB7	PSMB7	4333	0.094	0.63	YES
25	PSMB5	PSMB5	PSMB5	4361	0.093	0.65	YES
26	SHFM1	SHFM1	SHFM1	4599	0.088	0.66	YES
27	PSMD1	PSMD1	PSMD1	4688	0.086	0.67	YES
28	PSMC4	PSMC4	PSMC4	4922	0.08	0.67	YES
29	PSMD8	PSMD8	PSMD8	5188	0.075	0.67	YES
30	PSME3	PSME3	PSME3	5364	0.07	0.68	YES
31	PSMD3	PSMD3	PSMD3	5424	0.069	0.69	YES
32	PSMC2	PSMC2	PSMC2	5600	0.065	0.69	YES
33	PSMB3	PSMB3	PSMB3	6053	0.057	0.68	NO
34	PSMD7	PSMD7	PSMD7	6106	0.056	0.69	NO
35	PSMC5	PSMC5	PSMC5	6480	0.048	0.68	NO
36	PSME4	PSME4	PSME4	6821	0.041	0.68	NO
37	PSMC3	PSMC3	PSMC3	7162	0.034	0.67	NO
38	PSMA7	PSMA7	PSMA7	8865	0.0017	0.59	NO
39	PSMB4	PSMB4	PSMB4	8907	0.00089	0.59	NO
40	PSMF1	PSMF1	PSMF1	9563	-0.013	0.56	NO
41	PSMD4	PSMD4	PSMD4	9687	-0.015	0.56	NO
42	PSMA8	PSMA8	PSMA8	12430	-0.072	0.45	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 FAS PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FAS 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 HIVNEF 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	KLRD1	KLRD1	KLRD1	40	0.46	0.042	YES
2	TAP1	TAP1	TAP1	78	0.42	0.08	YES
3	TAP2	TAP2	TAP2	138	0.39	0.12	YES
4	KIR3DL2	KIR3DL2	KIR3DL2	217	0.36	0.14	YES
5	CIITA	CIITA	CIITA	401	0.31	0.17	YES
6	KIR2DL1	KIR2DL1	KIR2DL1	423	0.31	0.19	YES
7	HSPA1B	HSPA1B	HSPA1B	464	0.3	0.22	YES
8	HLA-DQB1	HLA-DQB1	HLA-DQB1	514	0.29	0.25	YES
9	KLRC1	KLRC1	KLRC1	554	0.28	0.27	YES
10	KIR2DL2	KIR2DL2	KIR2DL2	586	0.28	0.3	YES
11	KLRC2	KLRC2	KLRC2	601	0.28	0.32	YES
12	HLA-DMA	HLA-DMA	HLA-DMA	610	0.28	0.35	YES
13	HLA-DQA1	HLA-DQA1	HLA-DQA1	636	0.27	0.37	YES
14	KLRC4	KLRC4	KLRC4	663	0.27	0.4	YES
15	HLA-DMB	HLA-DMB	HLA-DMB	737	0.26	0.42	YES
16	HLA-DRB5	HLA-DRB5	HLA-DRB5	788	0.25	0.44	YES
17	PSME2	PSME2	PSME2	792	0.25	0.46	YES
18	HLA-DOA	HLA-DOA	HLA-DOA	908	0.24	0.48	YES
19	HLA-F	HLA-F	HLA-F	954	0.24	0.5	YES
20	CD8A	CD8A	CD8A	1009	0.23	0.52	YES
21	HLA-DPA1	HLA-DPA1	HLA-DPA1	1047	0.23	0.54	YES
22	HLA-DRA	HLA-DRA	HLA-DRA	1325	0.21	0.55	YES
23	HLA-DPB1	HLA-DPB1	HLA-DPB1	1490	0.2	0.56	YES
24	PSME1	PSME1	PSME1	1893	0.17	0.56	YES
25	CD74	CD74	CD74	1951	0.17	0.57	YES
26	IFI30	IFI30	IFI30	2154	0.16	0.57	YES
27	HSPA4	HSPA4	HSPA4	2167	0.16	0.59	YES
28	TAPBP	TAPBP	TAPBP	2266	0.16	0.6	YES
29	CTSS	CTSS	CTSS	2276	0.16	0.61	YES
30	RFXANK	RFXANK	RFXANK	2617	0.14	0.61	YES
31	HLA-G	HLA-G	HLA-G	2685	0.14	0.62	YES
32	IFNA1	IFNA1	IFNA1	2765	0.14	0.63	YES
33	HLA-DQA2	HLA-DQA2	HLA-DQA2	3061	0.13	0.63	YES
34	HSPA6	HSPA6	HSPA6	3130	0.12	0.64	YES
35	RFX5	RFX5	RFX5	3169	0.12	0.65	YES
36	CD4	CD4	CD4	3369	0.12	0.65	YES
37	CTSL1	CTSL1	CTSL1	3386	0.12	0.66	YES
38	LTA	LTA	LTA	3486	0.12	0.67	YES
39	B2M	B2M	B2M	3490	0.12	0.68	YES
40	LGMN	LGMN	LGMN	3511	0.11	0.69	YES
41	HLA-E	HLA-E	HLA-E	3750	0.11	0.69	YES
42	CTSB	CTSB	CTSB	3885	0.1	0.69	YES
43	HSP90AA1	HSP90AA1	HSP90AA1	4012	0.1	0.7	YES
44	HSPA5	HSPA5	HSPA5	4026	0.1	0.7	YES
45	HLA-C	HLA-C	HLA-C	5237	0.073	0.66	NO
46	PSME3	PSME3	PSME3	5364	0.07	0.66	NO
47	HSPA8	HSPA8	HSPA8	5455	0.068	0.66	NO
48	HLA-A	HLA-A	HLA-A	5620	0.065	0.66	NO
49	PDIA3	PDIA3	PDIA3	5857	0.06	0.66	NO
50	CALR	CALR	CALR	6460	0.048	0.63	NO
51	CD8B	CD8B	CD8B	7586	0.027	0.59	NO
52	CANX	CANX	CANX	8018	0.018	0.57	NO
53	NFYA	NFYA	NFYA	8099	0.016	0.57	NO
54	NFYC	NFYC	NFYC	8404	0.011	0.55	NO
55	NFYB	NFYB	NFYB	9697	-0.016	0.5	NO
56	CREB1	CREB1	CREB1	11255	-0.048	0.43	NO
57	RFXAP	RFXAP	RFXAP	12148	-0.066	0.4	NO
58	HSPA1A	HSPA1A	HSPA1A	14816	-0.13	0.3	NO
59	HSPA1L	HSPA1L	HSPA1L	14892	-0.13	0.3	NO
60	HSPA2	HSPA2	HSPA2	21539	-0.41	0.049	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 HIVNEF PATHWAY.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA HIVNEF 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 IL2RB 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	MCM2	MCM2	MCM2	159	0.38	0.046	YES
2	MCM5	MCM5	MCM5	229	0.35	0.092	YES
3	MCM4	MCM4	MCM4	290	0.33	0.14	YES
4	POLE2	POLE2	POLE2	338	0.32	0.18	YES
5	RFC4	RFC4	RFC4	378	0.32	0.22	YES
6	LIG1	LIG1	LIG1	438	0.3	0.26	YES
7	FEN1	FEN1	FEN1	472	0.3	0.3	YES
8	POLD1	POLD1	POLD1	480	0.3	0.34	YES
9	PRIM2	PRIM2	PRIM2	497	0.29	0.38	YES
10	RFC5	RFC5	RFC5	502	0.29	0.42	YES
11	RFC2	RFC2	RFC2	661	0.27	0.45	YES
12	POLA2	POLA2	POLA2	711	0.26	0.49	YES
13	PRIM1	PRIM1	PRIM1	722	0.26	0.52	YES
14	PCNA	PCNA	PCNA	739	0.26	0.56	YES
15	POLE	POLE	POLE	856	0.24	0.59	YES
16	MCM6	MCM6	MCM6	909	0.24	0.62	YES
17	RFC3	RFC3	RFC3	1138	0.22	0.64	YES
18	RNASEH2A	RNASEH2A	RNASEH2A	1149	0.22	0.67	YES
19	DNA2	DNA2	DNA2	1214	0.21	0.7	YES
20	MCM3	MCM3	MCM3	1387	0.2	0.72	YES
21	MCM7	MCM7	MCM7	1473	0.2	0.74	YES
22	RPA3	RPA3	RPA3	1935	0.17	0.74	YES
23	POLD2	POLD2	POLD2	1974	0.17	0.77	YES
24	POLE3	POLE3	POLE3	2146	0.16	0.78	YES
25	SSBP1	SSBP1	SSBP1	2147	0.16	0.8	YES
26	RFC1	RFC1	RFC1	2891	0.13	0.79	NO
27	RPA2	RPA2	RPA2	3047	0.13	0.8	NO
28	RPA1	RPA1	RPA1	4029	0.1	0.77	NO
29	POLE4	POLE4	POLE4	5559	0.066	0.71	NO
30	RNASEH2B	RNASEH2B	RNASEH2B	5972	0.058	0.7	NO
31	RNASEH1	RNASEH1	RNASEH1	7294	0.032	0.65	NO
32	POLD3	POLD3	POLD3	7975	0.019	0.62	NO
33	POLD4	POLD4	POLD4	9414	-0.01	0.56	NO
34	RNASEH2C	RNASEH2C	RNASEH2C	12133	-0.066	0.45	NO
35	RPA4	RPA4	RPA4	14699	-0.13	0.35	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 IL2RB PATHWAY.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL2RB 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 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	SFN	SFN	SFN	36	0.47	0.023	YES
2	CDC45	CDC45	CDC45	72	0.43	0.043	YES
3	CHEK1	CHEK1	CHEK1	116	0.4	0.062	YES
4	CCNA2	CCNA2	CCNA2	139	0.39	0.081	YES
5	MAD2L1	MAD2L1	MAD2L1	141	0.39	0.1	YES
6	CDC25A	CDC25A	CDC25A	145	0.39	0.12	YES
7	MCM2	MCM2	MCM2	159	0.38	0.14	YES
8	CCNB1	CCNB1	CCNB1	173	0.38	0.16	YES
9	BUB1B	BUB1B	BUB1B	205	0.36	0.18	YES
10	MCM5	MCM5	MCM5	229	0.35	0.19	YES
11	CDC7	CDC7	CDC7	256	0.34	0.21	YES
12	PTTG1	PTTG1	PTTG1	284	0.33	0.23	YES
13	MCM4	MCM4	MCM4	290	0.33	0.24	YES
14	BUB1	BUB1	BUB1	301	0.33	0.26	YES
15	CDK1	CDK1	CDK1	309	0.33	0.28	YES
16	PKMYT1	PKMYT1	PKMYT1	322	0.33	0.29	YES
17	ESPL1	ESPL1	ESPL1	323	0.33	0.31	YES
18	CDC20	CDC20	CDC20	436	0.3	0.32	YES
19	E2F2	E2F2	E2F2	476	0.3	0.33	YES
20	TTK	TTK	TTK	579	0.28	0.34	YES
21	MDM2	MDM2	MDM2	584	0.28	0.36	YES
22	CDK7	CDK7	CDK7	612	0.28	0.37	YES
23	PLK1	PLK1	PLK1	635	0.27	0.38	YES
24	CCNB2	CCNB2	CCNB2	643	0.27	0.4	YES
25	E2F5	E2F5	E2F5	646	0.27	0.41	YES
26	SKP2	SKP2	SKP2	688	0.26	0.42	YES
27	TP53	TP53	TP53	715	0.26	0.43	YES
28	PCNA	PCNA	PCNA	739	0.26	0.45	YES
29	CCND1	CCND1	CCND1	753	0.26	0.46	YES
30	CDC25C	CDC25C	CDC25C	802	0.25	0.47	YES
31	MYC	MYC	MYC	823	0.25	0.48	YES
32	MCM6	MCM6	MCM6	909	0.24	0.49	YES
33	CDC6	CDC6	CDC6	929	0.24	0.5	YES
34	CCNE2	CCNE2	CCNE2	1075	0.22	0.51	YES
35	TFDP1	TFDP1	TFDP1	1323	0.21	0.51	YES
36	MCM3	MCM3	MCM3	1387	0.2	0.51	YES
37	RB1	RB1	RB1	1453	0.2	0.52	YES
38	MCM7	MCM7	MCM7	1473	0.2	0.53	YES
39	CHEK2	CHEK2	CHEK2	1672	0.18	0.53	YES
40	BUB3	BUB3	BUB3	1809	0.18	0.53	YES
41	CDK2	CDK2	CDK2	1860	0.17	0.54	YES
42	E2F1	E2F1	E2F1	2095	0.16	0.54	YES
43	HDAC1	HDAC1	HDAC1	2133	0.16	0.55	YES
44	CDC27	CDC27	CDC27	2488	0.15	0.54	YES
45	CDC23	CDC23	CDC23	2803	0.14	0.53	YES
46	CDKN1A	CDKN1A	CDKN1A	2809	0.14	0.54	YES
47	SMC1A	SMC1A	SMC1A	2814	0.13	0.54	YES
48	CCNH	CCNH	CCNH	2920	0.13	0.55	YES
49	E2F3	E2F3	E2F3	2938	0.13	0.55	YES
50	FZR1	FZR1	FZR1	3036	0.13	0.55	YES
51	MAD2L2	MAD2L2	MAD2L2	3040	0.13	0.56	YES
52	SMC3	SMC3	SMC3	3389	0.12	0.55	YES
53	CDC14B	CDC14B	CDC14B	3531	0.11	0.55	YES
54	YWHAH	YWHAH	YWHAH	3570	0.11	0.55	YES
55	CDC25B	CDC25B	CDC25B	3728	0.11	0.55	YES
56	CUL1	CUL1	CUL1	3815	0.11	0.56	YES
57	ATR	ATR	ATR	3824	0.11	0.56	YES
58	RBL1	RBL1	RBL1	3911	0.1	0.56	YES
59	RBX1	RBX1	RBX1	3929	0.1	0.57	YES
60	YWHAE	YWHAE	YWHAE	3930	0.1	0.57	YES
61	E2F4	E2F4	E2F4	4208	0.097	0.56	NO
62	HDAC2	HDAC2	HDAC2	4338	0.094	0.56	NO
63	STAG1	STAG1	STAG1	4474	0.091	0.56	NO
64	ANAPC4	ANAPC4	ANAPC4	4672	0.086	0.56	NO
65	YWHAG	YWHAG	YWHAG	4717	0.085	0.56	NO
66	YWHAZ	YWHAZ	YWHAZ	4952	0.08	0.55	NO
67	CDK4	CDK4	CDK4	5006	0.078	0.56	NO
68	ANAPC10	ANAPC10	ANAPC10	5032	0.078	0.56	NO
69	ANAPC1	ANAPC1	ANAPC1	5362	0.07	0.55	NO
70	YWHAQ	YWHAQ	YWHAQ	5413	0.069	0.55	NO
71	CDKN2C	CDKN2C	CDKN2C	5515	0.067	0.55	NO
72	GADD45A	GADD45A	GADD45A	5986	0.058	0.53	NO
73	SMC1B	SMC1B	SMC1B	6000	0.058	0.53	NO
74	RAD21	RAD21	RAD21	6095	0.056	0.53	NO
75	WEE1	WEE1	WEE1	6135	0.055	0.53	NO
76	TGFB1	TGFB1	TGFB1	6157	0.055	0.53	NO
77	ANAPC11	ANAPC11	ANAPC11	6245	0.053	0.53	NO
78	GSK3B	GSK3B	GSK3B	6372	0.05	0.53	NO
79	ANAPC5	ANAPC5	ANAPC5	6399	0.049	0.53	NO
80	CDKN1B	CDKN1B	CDKN1B	6554	0.046	0.53	NO
81	CDKN2D	CDKN2D	CDKN2D	6593	0.046	0.53	NO
82	PRKDC	PRKDC	PRKDC	7337	0.031	0.5	NO
83	CDC26	CDC26	CDC26	7924	0.02	0.47	NO
84	ANAPC13	ANAPC13	ANAPC13	8117	0.016	0.46	NO
85	SKP1	SKP1	SKP1	8148	0.016	0.46	NO
86	STAG2	STAG2	STAG2	8395	0.011	0.45	NO
87	ANAPC2	ANAPC2	ANAPC2	8696	0.005	0.44	NO
88	ANAPC7	ANAPC7	ANAPC7	8732	0.0045	0.44	NO
89	ZBTB17	ZBTB17	ZBTB17	9006	-0.0012	0.43	NO
90	CDC16	CDC16	CDC16	9233	-0.0062	0.42	NO
91	CCNB3	CCNB3	CCNB3	9362	-0.0087	0.41	NO
92	SMAD3	SMAD3	SMAD3	9475	-0.011	0.41	NO
93	SMAD2	SMAD2	SMAD2	10159	-0.025	0.38	NO
94	EP300	EP300	EP300	10230	-0.026	0.38	NO
95	CCNE1	CCNE1	CCNE1	11038	-0.043	0.34	NO
96	YWHAB	YWHAB	YWHAB	11282	-0.048	0.33	NO
97	MAD1L1	MAD1L1	MAD1L1	11505	-0.052	0.33	NO
98	CCND3	CCND3	CCND3	12393	-0.071	0.29	NO
99	RBL2	RBL2	RBL2	12495	-0.074	0.29	NO
100	SMAD4	SMAD4	SMAD4	12820	-0.081	0.28	NO
101	CDC14A	CDC14A	CDC14A	13140	-0.089	0.27	NO
102	CCND2	CCND2	CCND2	13374	-0.094	0.26	NO
103	CDK6	CDK6	CDK6	13965	-0.11	0.24	NO
104	GADD45B	GADD45B	GADD45B	14031	-0.11	0.25	NO
105	PTTG2	PTTG2	PTTG2	14438	-0.12	0.24	NO
106	ABL1	ABL1	ABL1	14586	-0.12	0.24	NO
107	TGFB3	TGFB3	TGFB3	14893	-0.13	0.23	NO
108	CDKN2B	CDKN2B	CDKN2B	14903	-0.13	0.23	NO
109	CREBBP	CREBBP	CREBBP	14963	-0.13	0.24	NO
110	CDKN2A	CDKN2A	CDKN2A	14966	-0.13	0.24	NO
111	CCNA1	CCNA1	CCNA1	15965	-0.16	0.21	NO
112	ATM	ATM	ATM	17640	-0.21	0.14	NO
113	TGFB2	TGFB2	TGFB2	18151	-0.22	0.13	NO
114	WEE2	WEE2	WEE2	18255	-0.23	0.14	NO
115	TFDP2	TFDP2	TFDP2	19029	-0.26	0.12	NO
116	GADD45G	GADD45G	GADD45G	19684	-0.29	0.11	NO
117	CDKN1C	CDKN1C	CDKN1C	22173	-0.49	0.021	NO

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

Figure S10. 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 TNFR1 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	XRN1	XRN1	XRN1	556	0.28	0.022	YES
2	EXOSC9	EXOSC9	EXOSC9	595	0.28	0.067	YES
3	EXOSC7	EXOSC7	EXOSC7	760	0.25	0.1	YES
4	MPHOSPH6	MPHOSPH6	MPHOSPH6	1028	0.23	0.13	YES
5	LSM6	LSM6	LSM6	1331	0.2	0.15	YES
6	EXOSC2	EXOSC2	EXOSC2	1338	0.2	0.18	YES
7	RQCD1	RQCD1	RQCD1	1382	0.2	0.22	YES
8	ENO1	ENO1	ENO1	1586	0.19	0.24	YES
9	HSPD1	HSPD1	HSPD1	1706	0.18	0.26	YES
10	CNOT6	CNOT6	CNOT6	1761	0.18	0.29	YES
11	LSM5	LSM5	LSM5	1776	0.18	0.32	YES
12	EXOSC3	EXOSC3	EXOSC3	2114	0.16	0.33	YES
13	CNOT7	CNOT7	CNOT7	2187	0.16	0.35	YES
14	PATL1	PATL1	PATL1	2200	0.16	0.38	YES
15	ENO2	ENO2	ENO2	2382	0.15	0.4	YES
16	DCP2	DCP2	DCP2	2979	0.13	0.39	YES
17	EXOSC8	EXOSC8	EXOSC8	3005	0.13	0.41	YES
18	LSM7	LSM7	LSM7	3243	0.12	0.42	YES
19	LSM1	LSM1	LSM1	3420	0.12	0.43	YES
20	HSPA9	HSPA9	HSPA9	3530	0.11	0.45	YES
21	CNOT10	CNOT10	CNOT10	3567	0.11	0.46	YES
22	LSM4	LSM4	LSM4	3676	0.11	0.48	YES
23	PNPT1	PNPT1	PNPT1	3687	0.11	0.5	YES
24	DIS3	DIS3	DIS3	3721	0.11	0.51	YES
25	DCPS	DCPS	DCPS	4518	0.09	0.49	YES
26	EXOSC5	EXOSC5	EXOSC5	4547	0.089	0.51	YES
27	EXOSC4	EXOSC4	EXOSC4	4577	0.088	0.52	YES
28	LSM2	LSM2	LSM2	4791	0.083	0.52	YES
29	PAPD7	PAPD7	PAPD7	4829	0.082	0.54	YES
30	EXOSC10	EXOSC10	EXOSC10	5068	0.077	0.54	YES
31	NAA38	NAA38	NAA38	5501	0.068	0.53	NO
32	LSM3	LSM3	LSM3	5611	0.065	0.54	NO
33	WDR61	WDR61	WDR61	6176	0.054	0.52	NO
34	EXOSC6	EXOSC6	EXOSC6	6312	0.052	0.52	NO
35	C1D	C1D	C1D	6330	0.051	0.53	NO
36	CNOT1	CNOT1	CNOT1	6542	0.046	0.53	NO
37	EDC4	EDC4	EDC4	6594	0.045	0.53	NO
38	PAPOLG	PAPOLG	PAPOLG	6680	0.044	0.54	NO
39	DDX6	DDX6	DDX6	7058	0.037	0.53	NO
40	ZCCHC7	ZCCHC7	ZCCHC7	7557	0.027	0.51	NO
41	PARN	PARN	PARN	7927	0.02	0.5	NO
42	CNOT4	CNOT4	CNOT4	7931	0.02	0.5	NO
43	CNOT6L	CNOT6L	CNOT6L	8122	0.016	0.49	NO
44	EXOSC1	EXOSC1	EXOSC1	8690	0.0051	0.47	NO
45	PAPOLA	PAPOLA	PAPOLA	9301	-0.0077	0.44	NO
46	PAPOLB	PAPOLB	PAPOLB	9613	-0.014	0.43	NO
47	CNOT2	CNOT2	CNOT2	10117	-0.024	0.41	NO
48	XRN2	XRN2	XRN2	10367	-0.029	0.41	NO
49	EDC3	EDC3	EDC3	10875	-0.04	0.39	NO
50	CNOT3	CNOT3	CNOT3	10902	-0.04	0.4	NO
51	DCP1A	DCP1A	DCP1A	11620	-0.054	0.38	NO
52	SKIV2L2	SKIV2L2	SKIV2L2	11677	-0.056	0.38	NO
53	SKIV2L	SKIV2L	SKIV2L	12022	-0.064	0.38	NO
54	TTC37	TTC37	TTC37	16231	-0.17	0.22	NO
55	ENO3	ENO3	ENO3	16454	-0.17	0.24	NO
56	DCP1B	DCP1B	DCP1B	18034	-0.22	0.2	NO

Figure S11. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA TNFR1 PATHWAY.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PYRIMIDINE METABOLISM

Table 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	POLR3G	POLR3G	POLR3G	9	0.54	0.038	YES
2	RRM2	RRM2	RRM2	67	0.44	0.067	YES
3	TYMS	TYMS	TYMS	121	0.4	0.094	YES
4	TYMP	TYMP	TYMP	129	0.4	0.12	YES
5	TK1	TK1	TK1	213	0.36	0.14	YES
6	POLE2	POLE2	POLE2	338	0.32	0.16	YES
7	DPYD	DPYD	DPYD	359	0.32	0.18	YES
8	RRM2B	RRM2B	RRM2B	400	0.31	0.2	YES
9	DUT	DUT	DUT	403	0.31	0.23	YES
10	POLD1	POLD1	POLD1	480	0.3	0.24	YES
11	PRIM2	PRIM2	PRIM2	497	0.29	0.26	YES
12	UPP1	UPP1	UPP1	657	0.27	0.28	YES
13	DTYMK	DTYMK	DTYMK	676	0.27	0.3	YES
14	POLA2	POLA2	POLA2	711	0.26	0.31	YES
15	PRIM1	PRIM1	PRIM1	722	0.26	0.33	YES
16	POLE	POLE	POLE	856	0.24	0.34	YES
17	PNP	PNP	PNP	920	0.24	0.36	YES
18	TK2	TK2	TK2	963	0.23	0.37	YES
19	RRM1	RRM1	RRM1	1261	0.21	0.37	YES
20	NT5C3	NT5C3	NT5C3	1281	0.21	0.39	YES
21	CMPK2	CMPK2	CMPK2	1467	0.2	0.39	YES
22	POLR1B	POLR1B	POLR1B	1540	0.19	0.4	YES
23	DCK	DCK	DCK	1632	0.19	0.41	YES
24	UMPS	UMPS	UMPS	1791	0.18	0.42	YES
25	POLD2	POLD2	POLD2	1974	0.17	0.42	YES
26	NME1-NME2	NME1-NME2	NME1-NME2	2027	0.17	0.43	YES
27	POLR3K	POLR3K	POLR3K	2039	0.16	0.44	YES
28	POLR2D	POLR2D	POLR2D	2139	0.16	0.45	YES
29	POLE3	POLE3	POLE3	2146	0.16	0.46	YES
30	POLR2H	POLR2H	POLR2H	2229	0.16	0.47	YES
31	POLR3B	POLR3B	POLR3B	2358	0.15	0.48	YES
32	POLR2F	POLR2F	POLR2F	2380	0.15	0.48	YES
33	DCTD	DCTD	DCTD	2587	0.14	0.49	YES
34	NUDT2	NUDT2	NUDT2	2660	0.14	0.49	YES
35	CAD	CAD	CAD	3071	0.13	0.48	YES
36	ZNRD1	ZNRD1	ZNRD1	3321	0.12	0.48	YES
37	POLA1	POLA1	POLA1	3350	0.12	0.49	YES
38	POLR2A	POLR2A	POLR2A	3382	0.12	0.5	YES
39	POLR3D	POLR3D	POLR3D	3668	0.11	0.49	YES
40	PNPT1	PNPT1	PNPT1	3687	0.11	0.5	YES
41	NME6	NME6	NME6	4015	0.1	0.49	YES
42	POLR1C	POLR1C	POLR1C	4122	0.099	0.49	YES
43	POLR1A	POLR1A	POLR1A	4219	0.097	0.5	YES
44	POLR1E	POLR1E	POLR1E	4295	0.095	0.5	YES
45	POLR2L	POLR2L	POLR2L	4470	0.091	0.5	NO
46	POLR2E	POLR2E	POLR2E	4844	0.082	0.49	NO
47	NT5C2	NT5C2	NT5C2	5215	0.074	0.48	NO
48	POLE4	POLE4	POLE4	5559	0.066	0.47	NO
49	NT5C	NT5C	NT5C	5823	0.061	0.46	NO
50	DHODH	DHODH	DHODH	5862	0.06	0.46	NO
51	POLR1D	POLR1D	POLR1D	5883	0.06	0.46	NO
52	TXNRD1	TXNRD1	TXNRD1	6151	0.055	0.46	NO
53	POLR2G	POLR2G	POLR2G	6296	0.052	0.45	NO
54	ITPA	ITPA	ITPA	6815	0.041	0.43	NO
55	CANT1	CANT1	CANT1	6857	0.04	0.44	NO
56	ENTPD4	ENTPD4	ENTPD4	6960	0.038	0.43	NO
57	POLR2I	POLR2I	POLR2I	7003	0.038	0.43	NO
58	POLR3A	POLR3A	POLR3A	7285	0.032	0.42	NO
59	CMPK1	CMPK1	CMPK1	7498	0.029	0.42	NO
60	POLR2J	POLR2J	POLR2J	7547	0.028	0.42	NO
61	POLR3H	POLR3H	POLR3H	7662	0.025	0.41	NO
62	UCK2	UCK2	UCK2	7839	0.022	0.41	NO
63	POLR2C	POLR2C	POLR2C	7950	0.02	0.4	NO
64	POLD3	POLD3	POLD3	7975	0.019	0.4	NO
65	POLR2J2	POLR2J2	POLR2J2	8005	0.018	0.4	NO
66	POLD4	POLD4	POLD4	9414	-0.01	0.34	NO
67	CDA	CDA	CDA	9445	-0.011	0.34	NO
68	POLR2J3	POLR2J3	POLR2J3	9562	-0.013	0.34	NO
69	TXNRD2	TXNRD2	TXNRD2	9762	-0.017	0.33	NO
70	ENTPD6	ENTPD6	ENTPD6	9811	-0.018	0.33	NO
71	POLR2K	POLR2K	POLR2K	10429	-0.03	0.3	NO
72	NME3	NME3	NME3	10498	-0.032	0.3	NO
73	UPP2	UPP2	UPP2	11033	-0.043	0.28	NO
74	UCKL1	UCKL1	UCKL1	11404	-0.05	0.27	NO
75	NT5E	NT5E	NT5E	11418	-0.051	0.27	NO
76	POLR3GL	POLR3GL	POLR3GL	11598	-0.054	0.27	NO
77	POLR2B	POLR2B	POLR2B	11809	-0.059	0.26	NO
78	AK3	AK3	AK3	12105	-0.065	0.26	NO
79	NME7	NME7	NME7	12138	-0.066	0.26	NO
80	POLR3C	POLR3C	POLR3C	13352	-0.094	0.21	NO
81	CTPS2	CTPS2	CTPS2	13526	-0.098	0.21	NO
82	NT5M	NT5M	NT5M	13557	-0.098	0.22	NO
83	UCK1	UCK1	UCK1	14101	-0.11	0.2	NO
84	POLR3F	POLR3F	POLR3F	14304	-0.12	0.2	NO
85	UPB1	UPB1	UPB1	14700	-0.13	0.19	NO
86	UPRT	UPRT	UPRT	15019	-0.13	0.19	NO
87	DPYS	DPYS	DPYS	15982	-0.16	0.16	NO
88	ENTPD1	ENTPD1	ENTPD1	17269	-0.2	0.11	NO
89	NME5	NME5	NME5	18045	-0.22	0.094	NO
90	NME4	NME4	NME4	18538	-0.24	0.089	NO
91	NT5C1A	NT5C1A	NT5C1A	19313	-0.27	0.074	NO
92	ENTPD5	ENTPD5	ENTPD5	19617	-0.28	0.081	NO
93	ENTPD3	ENTPD3	ENTPD3	20561	-0.34	0.064	NO
94	ENTPD8	ENTPD8	ENTPD8	21392	-0.4	0.056	NO

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

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

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	LMNB1	LMNB1	LMNB1	77	0.43	0.13	YES
2	BAG4	BAG4	BAG4	171	0.38	0.24	YES
3	CASP2	CASP2	CASP2	477	0.3	0.32	YES
4	LMNB2	LMNB2	LMNB2	490	0.29	0.41	YES
5	RB1	RB1	RB1	1453	0.2	0.43	YES
6	CASP8	CASP8	CASP8	1734	0.18	0.48	YES
7	MAP2K4	MAP2K4	MAP2K4	2434	0.15	0.49	YES
8	DFFB	DFFB	DFFB	2996	0.13	0.51	YES
9	CASP3	CASP3	CASP3	3839	0.11	0.5	YES
10	TNF	TNF	TNF	4137	0.099	0.52	YES
11	MAP3K1	MAP3K1	MAP3K1	4669	0.086	0.52	YES
12	FADD	FADD	FADD	4697	0.085	0.55	YES
13	DFFA	DFFA	DFFA	4850	0.082	0.57	YES
14	ARHGDIB	ARHGDIB	ARHGDIB	5885	0.06	0.54	NO
15	SPTAN1	SPTAN1	SPTAN1	6232	0.053	0.54	NO
16	LMNA	LMNA	LMNA	6681	0.044	0.54	NO
17	TRADD	TRADD	TRADD	6818	0.041	0.54	NO
18	PARP1	PARP1	PARP1	7035	0.037	0.55	NO
19	PRKDC	PRKDC	PRKDC	7337	0.031	0.54	NO
20	PAK2	PAK2	PAK2	7566	0.027	0.54	NO
21	RIPK1	RIPK1	RIPK1	7645	0.026	0.55	NO
22	PAK1	PAK1	PAK1	8187	0.015	0.53	NO
23	MAP3K7	MAP3K7	MAP3K7	8197	0.014	0.53	NO
24	TNFRSF1A	TNFRSF1A	TNFRSF1A	8641	0.0059	0.51	NO
25	MAPK8	MAPK8	MAPK8	11155	-0.045	0.42	NO
26	CRADD	CRADD	CRADD	11615	-0.054	0.41	NO
27	MADD	MADD	MADD	13423	-0.096	0.36	NO
28	JUN	JUN	JUN	15541	-0.15	0.31	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 AMINOACYL TRNA BIOSYNTHESIS.

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

genes ES table in pathway: KEGG RIBOSOME

Table 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	THOC3	THOC3	THOC3	151	0.39	0.029	YES
2	HSPA1B	HSPA1B	HSPA1B	464	0.3	0.043	YES
3	SNRPG	SNRPG	SNRPG	1238	0.21	0.029	YES
4	LSM6	LSM6	LSM6	1331	0.2	0.044	YES
5	SNRPA1	SNRPA1	SNRPA1	1392	0.2	0.06	YES
6	SNRPD1	SNRPD1	SNRPD1	1417	0.2	0.078	YES
7	SNRPF	SNRPF	SNRPF	1686	0.18	0.083	YES
8	SMNDC1	SMNDC1	SMNDC1	1764	0.18	0.096	YES
9	SNRNP40	SNRNP40	SNRNP40	1769	0.18	0.11	YES
10	LSM5	LSM5	LSM5	1776	0.18	0.13	YES
11	DHX15	DHX15	DHX15	1939	0.17	0.14	YES
12	PPIH	PPIH	PPIH	2213	0.16	0.14	YES
13	PRPF4	PRPF4	PRPF4	2232	0.16	0.15	YES
14	EIF4A3	EIF4A3	EIF4A3	2243	0.16	0.17	YES
15	TRA2B	TRA2B	TRA2B	2277	0.16	0.18	YES
16	SNRPA	SNRPA	SNRPA	2292	0.15	0.2	YES
17	SNRPE	SNRPE	SNRPE	2397	0.15	0.2	YES
18	PHF5A	PHF5A	PHF5A	2409	0.15	0.22	YES
19	U2AF1	U2AF1	U2AF1	2421	0.15	0.23	YES
20	PPIL1	PPIL1	PPIL1	2466	0.15	0.24	YES
21	AQR	AQR	AQR	2538	0.14	0.25	YES
22	PRPF40A	PRPF40A	PRPF40A	2558	0.14	0.26	YES
23	HNRNPA1	HNRNPA1	HNRNPA1	2628	0.14	0.28	YES
24	SNRPC	SNRPC	SNRPC	3111	0.12	0.27	YES
25	HSPA6	HSPA6	HSPA6	3130	0.12	0.28	YES
26	SNRPB	SNRPB	SNRPB	3210	0.12	0.28	YES
27	LSM7	LSM7	LSM7	3243	0.12	0.29	YES
28	MAGOH	MAGOH	MAGOH	3326	0.12	0.3	YES
29	SF3B3	SF3B3	SF3B3	3449	0.12	0.31	YES
30	LSM4	LSM4	LSM4	3676	0.11	0.31	YES
31	HNRNPC	HNRNPC	HNRNPC	3678	0.11	0.32	YES
32	SF3B14	SF3B14	SF3B14	3769	0.11	0.32	YES
33	EFTUD2	EFTUD2	EFTUD2	4098	0.1	0.32	YES
34	PLRG1	PLRG1	PLRG1	4140	0.099	0.33	YES
35	WBP11	WBP11	WBP11	4148	0.099	0.34	YES
36	U2AF2	U2AF2	U2AF2	4157	0.098	0.34	YES
37	DDX23	DDX23	DDX23	4211	0.097	0.35	YES
38	HNRNPA3	HNRNPA3	HNRNPA3	4271	0.096	0.36	YES
39	TRA2A	TRA2A	TRA2A	4296	0.095	0.36	YES
40	BCAS2	BCAS2	BCAS2	4321	0.094	0.37	YES
41	HNRNPK	HNRNPK	HNRNPK	4387	0.093	0.38	YES
42	PRPF19	PRPF19	PRPF19	4399	0.092	0.39	YES
43	CHERP	CHERP	CHERP	4497	0.09	0.39	YES
44	MAGOHB	MAGOHB	MAGOHB	4540	0.089	0.4	YES
45	NCBP1	NCBP1	NCBP1	4543	0.089	0.4	YES
46	HNRNPU	HNRNPU	HNRNPU	4636	0.087	0.41	YES
47	RBM17	RBM17	RBM17	4752	0.084	0.41	YES
48	LSM2	LSM2	LSM2	4791	0.083	0.42	YES
49	PRPF31	PRPF31	PRPF31	4793	0.083	0.42	YES
50	TXNL4A	TXNL4A	TXNL4A	4837	0.082	0.43	YES
51	SNRPD3	SNRPD3	SNRPD3	4842	0.082	0.44	YES
52	SF3B5	SF3B5	SF3B5	4863	0.082	0.44	YES
53	TCERG1	TCERG1	TCERG1	4938	0.08	0.45	YES
54	HNRNPM	HNRNPM	HNRNPM	5051	0.078	0.45	YES
55	SNRPD2	SNRPD2	SNRPD2	5115	0.076	0.46	YES
56	NHP2L1	NHP2L1	NHP2L1	5318	0.071	0.45	YES
57	SNRNP70	SNRNP70	SNRNP70	5333	0.071	0.46	YES
58	USP39	USP39	USP39	5418	0.069	0.46	YES
59	THOC2	THOC2	THOC2	5442	0.069	0.47	YES
60	HSPA8	HSPA8	HSPA8	5455	0.068	0.47	YES
61	NAA38	NAA38	NAA38	5501	0.068	0.48	YES
62	LSM3	LSM3	LSM3	5611	0.065	0.48	YES
63	SF3A2	SF3A2	SF3A2	5625	0.065	0.48	YES
64	SF3A3	SF3A3	SF3A3	6279	0.052	0.46	YES
65	CCDC12	CCDC12	CCDC12	6497	0.047	0.46	YES
66	SNRPB2	SNRPB2	SNRPB2	6567	0.046	0.46	YES
67	DHX16	DHX16	DHX16	6580	0.046	0.46	YES
68	PUF60	PUF60	PUF60	6582	0.046	0.46	YES
69	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	6596	0.045	0.47	YES
70	BUD31	BUD31	BUD31	6603	0.045	0.47	YES
71	PCBP1	PCBP1	PCBP1	6621	0.045	0.48	YES
72	SF3B2	SF3B2	SF3B2	6631	0.045	0.48	YES
73	CDC40	CDC40	CDC40	6643	0.044	0.48	YES
74	RBM25	RBM25	RBM25	6669	0.044	0.49	YES
75	RBMX	RBMX	RBMX	6675	0.044	0.49	YES
76	RBM22	RBM22	RBM22	6759	0.042	0.49	YES
77	SNW1	SNW1	SNW1	6766	0.042	0.49	YES
78	SNRNP27	SNRNP27	SNRNP27	6884	0.04	0.49	NO
79	SART1	SART1	SART1	7014	0.037	0.49	NO
80	PRPF38B	PRPF38B	PRPF38B	7256	0.033	0.48	NO
81	XAB2	XAB2	XAB2	7387	0.03	0.48	NO
82	CWC15	CWC15	CWC15	7545	0.028	0.48	NO
83	PRPF38A	PRPF38A	PRPF38A	7580	0.027	0.48	NO
84	THOC1	THOC1	THOC1	7625	0.026	0.48	NO
85	DHX38	DHX38	DHX38	7673	0.025	0.48	NO
86	PRPF18	PRPF18	PRPF18	7772	0.023	0.48	NO
87	CDC5L	CDC5L	CDC5L	7875	0.021	0.47	NO
88	ACIN1	ACIN1	ACIN1	7969	0.019	0.47	NO
89	PRPF8	PRPF8	PRPF8	8040	0.018	0.47	NO
90	SF3B1	SF3B1	SF3B1	8231	0.014	0.46	NO
91	DHX8	DHX8	DHX8	8263	0.013	0.46	NO
92	DDX46	DDX46	DDX46	8481	0.0093	0.45	NO
93	SF3A1	SF3A1	SF3A1	8589	0.007	0.45	NO
94	SNRNP200	SNRNP200	SNRNP200	9086	-0.0029	0.43	NO
95	ZMAT2	ZMAT2	ZMAT2	9087	-0.003	0.43	NO
96	RBM8A	RBM8A	RBM8A	9114	-0.0034	0.43	NO
97	SYF2	SYF2	SYF2	9184	-0.005	0.42	NO
98	DDX5	DDX5	DDX5	9791	-0.017	0.4	NO
99	SF3B4	SF3B4	SF3B4	9849	-0.018	0.4	NO
100	SLU7	SLU7	SLU7	10455	-0.031	0.37	NO
101	DDX42	DDX42	DDX42	10888	-0.04	0.36	NO
102	CRNKL1	CRNKL1	CRNKL1	11649	-0.055	0.33	NO
103	PQBP1	PQBP1	PQBP1	11848	-0.06	0.33	NO
104	PRPF3	PRPF3	PRPF3	12163	-0.067	0.32	NO
105	PRPF6	PRPF6	PRPF6	13078	-0.088	0.29	NO
106	CTNNBL1	CTNNBL1	CTNNBL1	13575	-0.099	0.27	NO
107	HSPA1A	HSPA1A	HSPA1A	14816	-0.13	0.23	NO
108	HSPA1L	HSPA1L	HSPA1L	14892	-0.13	0.24	NO
109	PPIE	PPIE	PPIE	19718	-0.29	0.052	NO
110	HSPA2	HSPA2	HSPA2	21539	-0.41	0.0095	NO
111	PRPF40B	PRPF40B	PRPF40B	21649	-0.42	0.044	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 RIBOSOME.

Figure S18. 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 DEGRADATION

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	CCND1	CCND1	CCND1	753	0.26	0.068	YES
2	TFDP1	TFDP1	TFDP1	1323	0.21	0.12	YES
3	RB1	RB1	RB1	1453	0.2	0.2	YES
4	NFKB1	NFKB1	NFKB1	1814	0.18	0.25	YES
5	CDK2	CDK2	CDK2	1860	0.17	0.32	YES
6	CHUK	CHUK	CHUK	2183	0.16	0.37	YES
7	HRAS	HRAS	HRAS	2227	0.16	0.43	YES
8	CDKN1A	CDKN1A	CDKN1A	2809	0.14	0.45	YES
9	IKBKB	IKBKB	IKBKB	4605	0.088	0.41	YES
10	RHOA	RHOA	RHOA	5005	0.078	0.42	YES
11	CDK4	CDK4	CDK4	5006	0.078	0.45	YES
12	RELA	RELA	RELA	5330	0.071	0.47	YES
13	RAC1	RAC1	RAC1	5467	0.068	0.49	YES
14	IKBKG	IKBKG	IKBKG	5667	0.064	0.5	YES
15	CDKN1B	CDKN1B	CDKN1B	6554	0.046	0.48	NO
16	NFKBIA	NFKBIA	NFKBIA	6942	0.039	0.48	NO
17	MAPK1	MAPK1	MAPK1	7457	0.029	0.47	NO
18	AKT1	AKT1	AKT1	7485	0.029	0.48	NO
19	PAK1	PAK1	PAK1	8187	0.015	0.46	NO
20	PIK3CA	PIK3CA	PIK3CA	9652	-0.015	0.4	NO
21	RAF1	RAF1	RAF1	9852	-0.018	0.4	NO
22	CCNE1	CCNE1	CCNE1	11038	-0.043	0.36	NO
23	CDK6	CDK6	CDK6	13965	-0.11	0.27	NO
24	MAPK3	MAPK3	MAPK3	14744	-0.13	0.29	NO
25	PIK3R1	PIK3R1	PIK3R1	15725	-0.15	0.31	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 RNA DEGRADATION.

Figure S20. 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

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 NO1 PATHWAY	29	genes.ES.table	0.54	1.7	0.016	0.061	0.61	0.31	0.13	0.27	0.03	0
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.5	1.8	0.0063	0.048	0.38	0.29	0.12	0.25	0	0
BIOCARTA ALK PATHWAY	35	genes.ES.table	0.53	1.7	0.0081	0.06	0.57	0.4	0.19	0.32	0.027	0
BIOCARTA AT1R PATHWAY	31	genes.ES.table	0.43	1.7	0.016	0.055	0.5	0.32	0.26	0.24	0.022	0
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.54	1.8	0.029	0.049	0.46	0.42	0.26	0.31	0	0
BIOCARTA BIOPEPTIDES PATHWAY	41	genes.ES.table	0.54	2	0	0.047	0.11	0.32	0.18	0.26	0	0.012
BIOCARTA HDAC PATHWAY	25	genes.ES.table	0.65	1.9	0.002	0.032	0.19	0.64	0.26	0.47	0	0
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.51	1.7	0.029	0.062	0.59	0.5	0.28	0.36	0.029	0
BIOCARTA ERK PATHWAY	26	genes.ES.table	0.43	1.6	0.057	0.094	0.8	0.31	0.24	0.23	0.057	0
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.55	1.8	0.019	0.048	0.37	0.4	0.26	0.3	0	0

genes ES table in pathway: BIOCARTA NO1 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	KCNMA1	KCNMA1	KCNMA1	12	1.4	0.031	YES
2	PPP1R12B	PPP1R12B	PPP1R12B	17	1.3	0.062	YES
3	MYLK	MYLK	MYLK	18	1.3	0.094	YES
4	MYH11	MYH11	MYH11	23	1.3	0.12	YES
5	MRVI1	MRVI1	MRVI1	79	1.2	0.15	YES
6	ACTG2	ACTG2	ACTG2	84	1.2	0.18	YES
7	KCNMB1	KCNMB1	KCNMB1	112	1.2	0.2	YES
8	ADCY5	ADCY5	ADCY5	120	1.1	0.23	YES
9	GUCY1A3	GUCY1A3	GUCY1A3	161	1.1	0.25	YES
10	PRKG1	PRKG1	PRKG1	178	1.1	0.28	YES
11	CACNA1C	CACNA1C	CACNA1C	223	1	0.3	YES
12	AGTR1	AGTR1	AGTR1	245	1	0.32	YES
13	GUCY1B3	GUCY1B3	GUCY1B3	254	0.99	0.34	YES
14	ITPR1	ITPR1	ITPR1	302	0.96	0.37	YES
15	NPR2	NPR2	NPR2	350	0.93	0.38	YES
16	EDNRA	EDNRA	EDNRA	352	0.93	0.41	YES
17	NPR1	NPR1	NPR1	358	0.92	0.43	YES
18	CALD1	CALD1	CALD1	400	0.9	0.45	YES
19	MYL9	MYL9	MYL9	454	0.87	0.47	YES
20	ACTA2	ACTA2	ACTA2	493	0.84	0.48	YES
21	PRKCB	PRKCB	PRKCB	496	0.84	0.5	YES
22	PPP1R14A	PPP1R14A	PPP1R14A	557	0.82	0.52	YES
23	ADCY4	ADCY4	ADCY4	582	0.81	0.54	YES
24	PTGIR	PTGIR	PTGIR	641	0.78	0.56	YES
25	ADCY2	ADCY2	ADCY2	880	0.7	0.56	YES
26	RAMP3	RAMP3	RAMP3	912	0.69	0.58	YES
27	AVPR1A	AVPR1A	AVPR1A	1024	0.66	0.59	YES
28	CALCRL	CALCRL	CALCRL	1069	0.65	0.6	YES
29	ADCY9	ADCY9	ADCY9	1132	0.63	0.61	YES
30	PRKACB	PRKACB	PRKACB	1371	0.58	0.62	YES
31	PPP1R12A	PPP1R12A	PPP1R12A	1648	0.52	0.62	YES
32	RAMP2	RAMP2	RAMP2	1717	0.51	0.62	YES
33	PLA2G2C	PLA2G2C	PLA2G2C	1728	0.51	0.64	YES
34	PLA2G5	PLA2G5	PLA2G5	1739	0.51	0.65	YES
35	ADRA1A	ADRA1A	ADRA1A	1897	0.48	0.65	YES
36	RAMP1	RAMP1	RAMP1	1933	0.48	0.66	YES
37	ADRA1D	ADRA1D	ADRA1D	1934	0.48	0.67	YES
38	PRKCH	PRKCH	PRKCH	2156	0.44	0.67	YES
39	GUCY1A2	GUCY1A2	GUCY1A2	2476	0.4	0.67	NO
40	PLCB1	PLCB1	PLCB1	2737	0.37	0.66	NO
41	PRKCE	PRKCE	PRKCE	3437	0.31	0.64	NO
42	PRKCA	PRKCA	PRKCA	3486	0.3	0.65	NO
43	PLCB4	PLCB4	PLCB4	4251	0.25	0.62	NO
44	ROCK1	ROCK1	ROCK1	4436	0.23	0.62	NO
45	KCNMB4	KCNMB4	KCNMB4	4552	0.23	0.62	NO
46	PLCB2	PLCB2	PLCB2	4673	0.22	0.62	NO
47	ITPR2	ITPR2	ITPR2	4725	0.22	0.62	NO
48	PRKCQ	PRKCQ	PRKCQ	5224	0.19	0.6	NO
49	GNA12	GNA12	GNA12	5241	0.18	0.6	NO
50	GNAQ	GNAQ	GNAQ	5400	0.18	0.6	NO
51	PLA2G2D	PLA2G2D	PLA2G2D	5456	0.17	0.6	NO
52	MYL6	MYL6	MYL6	5570	0.17	0.6	NO
53	PRKCG	PRKCG	PRKCG	5786	0.16	0.6	NO
54	KCNMB2	KCNMB2	KCNMB2	5893	0.15	0.6	NO
55	ADCY7	ADCY7	ADCY7	5945	0.15	0.6	NO
56	ADORA2A	ADORA2A	ADORA2A	5998	0.15	0.6	NO
57	MYLK3	MYLK3	MYLK3	6076	0.14	0.6	NO
58	PRKACA	PRKACA	PRKACA	6190	0.14	0.6	NO
59	CALM1	CALM1	CALM1	6926	0.11	0.57	NO
60	PPP1CB	PPP1CB	PPP1CB	7036	0.1	0.56	NO
61	ARHGEF12	ARHGEF12	ARHGEF12	7114	0.1	0.56	NO
62	ROCK2	ROCK2	ROCK2	7153	0.099	0.56	NO
63	AVPR1B	AVPR1B	AVPR1B	7267	0.095	0.56	NO
64	GNA13	GNA13	GNA13	7442	0.088	0.56	NO
65	CACNA1S	CACNA1S	CACNA1S	7940	0.071	0.53	NO
66	ADCY8	ADCY8	ADCY8	8035	0.068	0.53	NO
67	BRAF	BRAF	BRAF	8264	0.06	0.52	NO
68	PLA2G2A	PLA2G2A	PLA2G2A	8668	0.046	0.51	NO
69	PLA2G12A	PLA2G12A	PLA2G12A	8874	0.039	0.5	NO
70	PLA2G4A	PLA2G4A	PLA2G4A	9211	0.028	0.48	NO
71	MAPK1	MAPK1	MAPK1	9217	0.028	0.48	NO
72	CACNA1D	CACNA1D	CACNA1D	9284	0.026	0.48	NO
73	PRKACG	PRKACG	PRKACG	9313	0.026	0.48	NO
74	ADRA1B	ADRA1B	ADRA1B	9349	0.024	0.48	NO
75	ARHGEF1	ARHGEF1	ARHGEF1	9761	0.012	0.46	NO
76	MYL6B	MYL6B	MYL6B	10352	-0.0043	0.44	NO
77	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	10443	-0.0068	0.43	NO
78	GNA11	GNA11	GNA11	10467	-0.0074	0.43	NO
79	ADCY1	ADCY1	ADCY1	10483	-0.0079	0.43	NO
80	PLA2G10	PLA2G10	PLA2G10	10551	-0.0096	0.43	NO
81	CALM2	CALM2	CALM2	10732	-0.014	0.42	NO
82	RAF1	RAF1	RAF1	10780	-0.015	0.42	NO
83	KCNMB3	KCNMB3	KCNMB3	11355	-0.029	0.39	NO
84	RHOA	RHOA	RHOA	11442	-0.032	0.39	NO
85	ARAF	ARAF	ARAF	12105	-0.048	0.36	NO
86	CACNA1F	CACNA1F	CACNA1F	12147	-0.049	0.36	NO
87	ADCY6	ADCY6	ADCY6	12164	-0.05	0.36	NO
88	GNAS	GNAS	GNAS	12344	-0.054	0.36	NO
89	CALM3	CALM3	CALM3	12450	-0.057	0.35	NO
90	CYP4A22	CYP4A22	CYP4A22	12587	-0.06	0.35	NO
91	ARHGEF11	ARHGEF11	ARHGEF11	12834	-0.066	0.34	NO
92	MAP2K2	MAP2K2	MAP2K2	12984	-0.07	0.33	NO
93	PLA2G1B	PLA2G1B	PLA2G1B	13200	-0.075	0.33	NO
94	MAPK3	MAPK3	MAPK3	13505	-0.081	0.31	NO
95	PRKX	PRKX	PRKX	13690	-0.086	0.31	NO
96	PPP1CC	PPP1CC	PPP1CC	14598	-0.11	0.27	NO
97	CYP4A11	CYP4A11	CYP4A11	14943	-0.11	0.26	NO
98	CALML6	CALML6	CALML6	15248	-0.12	0.25	NO
99	PLA2G12B	PLA2G12B	PLA2G12B	15734	-0.13	0.23	NO
100	MAP2K1	MAP2K1	MAP2K1	16023	-0.14	0.22	NO
101	PLA2G2E	PLA2G2E	PLA2G2E	16984	-0.16	0.18	NO
102	CALML3	CALML3	CALML3	17041	-0.16	0.18	NO
103	PLA2G2F	PLA2G2F	PLA2G2F	17082	-0.16	0.18	NO
104	CALML5	CALML5	CALML5	17639	-0.18	0.16	NO
105	PLA2G6	PLA2G6	PLA2G6	18074	-0.19	0.15	NO
106	PLA2G4E	PLA2G4E	PLA2G4E	18381	-0.2	0.14	NO
107	MYLK2	MYLK2	MYLK2	18841	-0.21	0.12	NO
108	PPP1CA	PPP1CA	PPP1CA	19784	-0.25	0.088	NO
109	ADORA2B	ADORA2B	ADORA2B	19793	-0.25	0.094	NO
110	ITPR3	ITPR3	ITPR3	21138	-0.32	0.042	NO
111	PRKCD	PRKCD	PRKCD	21234	-0.33	0.045	NO
112	PLCB3	PLCB3	PLCB3	21561	-0.36	0.039	NO
113	PLA2G3	PLA2G3	PLA2G3	21720	-0.37	0.041	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 NO1 PATHWAY.

Figure S22. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NO1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA AGR PATHWAY

Table 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	PLN	PLN	PLN	3	1.4	0.043	YES
2	ITGA7	ITGA7	ITGA7	44	1.2	0.08	YES
3	DES	DES	DES	116	1.2	0.11	YES
4	ADCY5	ADCY5	ADCY5	120	1.1	0.15	YES
5	SGCD	SGCD	SGCD	154	1.1	0.18	YES
6	ITGA9	ITGA9	ITGA9	188	1	0.21	YES
7	DMD	DMD	DMD	197	1	0.24	YES
8	CACNA1C	CACNA1C	CACNA1C	223	1	0.27	YES
9	SGCA	SGCA	SGCA	227	1	0.3	YES
10	CACNB2	CACNB2	CACNB2	231	1	0.33	YES
11	IGF1	IGF1	IGF1	288	0.97	0.36	YES
12	TPM2	TPM2	TPM2	303	0.95	0.38	YES
13	LAMA2	LAMA2	LAMA2	345	0.93	0.41	YES
14	SLC8A1	SLC8A1	SLC8A1	421	0.89	0.44	YES
15	TGFB3	TGFB3	TGFB3	560	0.81	0.45	YES
16	ADCY4	ADCY4	ADCY4	582	0.81	0.48	YES
17	ITGA1	ITGA1	ITGA1	627	0.79	0.5	YES
18	CACNA2D1	CACNA2D1	CACNA2D1	676	0.77	0.52	YES
19	ITGB3	ITGB3	ITGB3	732	0.75	0.54	YES
20	ADCY2	ADCY2	ADCY2	880	0.7	0.56	YES
21	TPM1	TPM1	TPM1	1115	0.63	0.56	YES
22	ADCY9	ADCY9	ADCY9	1132	0.63	0.58	YES
23	ITGA5	ITGA5	ITGA5	1274	0.6	0.6	YES
24	CACNA2D3	CACNA2D3	CACNA2D3	1275	0.6	0.61	YES
25	PRKACB	PRKACB	PRKACB	1371	0.58	0.63	YES
26	ACTC1	ACTC1	ACTC1	1372	0.58	0.64	YES
27	RYR2	RYR2	RYR2	1525	0.55	0.65	YES
28	ITGA10	ITGA10	ITGA10	1544	0.54	0.67	YES
29	ITGA8	ITGA8	ITGA8	1660	0.52	0.68	YES
30	SGCB	SGCB	SGCB	2501	0.4	0.66	NO
31	SGCG	SGCG	SGCG	2513	0.4	0.67	NO
32	TGFB2	TGFB2	TGFB2	2775	0.36	0.67	NO
33	TGFB1	TGFB1	TGFB1	3569	0.3	0.64	NO
34	CACNB4	CACNB4	CACNB4	3610	0.3	0.65	NO
35	ITGAV	ITGAV	ITGAV	4014	0.26	0.64	NO
36	ITGA4	ITGA4	ITGA4	4105	0.26	0.64	NO
37	ITGB1	ITGB1	ITGB1	4388	0.24	0.64	NO
38	CACNB3	CACNB3	CACNB3	4605	0.22	0.63	NO
39	MYL3	MYL3	MYL3	4609	0.22	0.64	NO
40	ITGB5	ITGB5	ITGB5	4716	0.22	0.64	NO
41	TTN	TTN	TTN	4783	0.21	0.64	NO
42	CACNG7	CACNG7	CACNG7	4814	0.21	0.65	NO
43	ITGA11	ITGA11	ITGA11	5098	0.19	0.64	NO
44	CACNG4	CACNG4	CACNG4	5289	0.18	0.64	NO
45	ADCY7	ADCY7	ADCY7	5945	0.15	0.62	NO
46	CACNA2D2	CACNA2D2	CACNA2D2	6171	0.14	0.61	NO
47	ITGB8	ITGB8	ITGB8	6179	0.14	0.61	NO
48	PRKACA	PRKACA	PRKACA	6190	0.14	0.62	NO
49	CACNG1	CACNG1	CACNG1	6466	0.13	0.61	NO
50	ITGB7	ITGB7	ITGB7	7668	0.08	0.56	NO
51	ACTB	ACTB	ACTB	7790	0.076	0.56	NO
52	CACNA1S	CACNA1S	CACNA1S	7940	0.071	0.55	NO
53	ADCY8	ADCY8	ADCY8	8035	0.068	0.55	NO
54	MYL2	MYL2	MYL2	8922	0.038	0.51	NO
55	CACNB1	CACNB1	CACNB1	8931	0.037	0.51	NO
56	TPM4	TPM4	TPM4	9095	0.032	0.51	NO
57	LMNA	LMNA	LMNA	9201	0.029	0.5	NO
58	CACNG8	CACNG8	CACNG8	9273	0.026	0.5	NO
59	CACNA1D	CACNA1D	CACNA1D	9284	0.026	0.5	NO
60	PRKACG	PRKACG	PRKACG	9313	0.026	0.5	NO
61	CACNA2D4	CACNA2D4	CACNA2D4	9936	0.0067	0.47	NO
62	ADCY1	ADCY1	ADCY1	10483	-0.0079	0.45	NO
63	TNNC1	TNNC1	TNNC1	10729	-0.014	0.44	NO
64	CACNG6	CACNG6	CACNG6	11366	-0.03	0.41	NO
65	EMD	EMD	EMD	12003	-0.046	0.38	NO
66	CACNA1F	CACNA1F	CACNA1F	12147	-0.049	0.38	NO
67	ADCY6	ADCY6	ADCY6	12164	-0.05	0.38	NO
68	GNAS	GNAS	GNAS	12344	-0.054	0.37	NO
69	DAG1	DAG1	DAG1	12420	-0.056	0.37	NO
70	CACNG3	CACNG3	CACNG3	13045	-0.071	0.35	NO
71	ADRB1	ADRB1	ADRB1	13100	-0.073	0.35	NO
72	ACTG1	ACTG1	ACTG1	13404	-0.079	0.34	NO
73	PRKX	PRKX	PRKX	13690	-0.086	0.32	NO
74	CACNG2	CACNG2	CACNG2	14038	-0.093	0.31	NO
75	TNNT2	TNNT2	TNNT2	14164	-0.097	0.31	NO
76	TNF	TNF	TNF	14329	-0.1	0.31	NO
77	ITGA3	ITGA3	ITGA3	14478	-0.1	0.3	NO
78	ITGA2B	ITGA2B	ITGA2B	14836	-0.11	0.29	NO
79	ITGB6	ITGB6	ITGB6	15068	-0.12	0.28	NO
80	CACNG5	CACNG5	CACNG5	15090	-0.12	0.29	NO
81	ATP2A2	ATP2A2	ATP2A2	15341	-0.12	0.28	NO
82	MYBPC3	MYBPC3	MYBPC3	15997	-0.14	0.25	NO
83	ITGA2	ITGA2	ITGA2	16190	-0.14	0.25	NO
84	ITGB4	ITGB4	ITGB4	16586	-0.15	0.24	NO
85	MYH6	MYH6	MYH6	17224	-0.17	0.21	NO
86	ITGA6	ITGA6	ITGA6	17560	-0.18	0.2	NO
87	MYH7	MYH7	MYH7	18504	-0.2	0.17	NO
88	TNNI3	TNNI3	TNNI3	19295	-0.23	0.14	NO
89	TPM3	TPM3	TPM3	20365	-0.27	0.1	NO

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

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

genes ES table in pathway: BIOCARTA ALK PATHWAY

Table 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	PLN	PLN	PLN	3	1.4	0.024	YES
2	MYLK	MYLK	MYLK	18	1.3	0.047	YES
3	CHRM2	CHRM2	CHRM2	56	1.2	0.066	YES
4	TACR2	TACR2	TACR2	113	1.2	0.084	YES
5	PDE1A	PDE1A	PDE1A	204	1	0.098	YES
6	CACNA1C	CACNA1C	CACNA1C	223	1	0.11	YES
7	CACNA1H	CACNA1H	CACNA1H	234	1	0.13	YES
8	AGTR1	AGTR1	AGTR1	245	1	0.15	YES
9	TRPC1	TRPC1	TRPC1	263	0.98	0.16	YES
10	ITPKB	ITPKB	ITPKB	293	0.96	0.18	YES
11	ITPR1	ITPR1	ITPR1	302	0.96	0.2	YES
12	ATP2B4	ATP2B4	ATP2B4	315	0.95	0.21	YES
13	PTGER3	PTGER3	PTGER3	328	0.94	0.23	YES
14	EDNRA	EDNRA	EDNRA	352	0.93	0.24	YES
15	PHKG1	PHKG1	PHKG1	374	0.91	0.26	YES
16	SLC8A1	SLC8A1	SLC8A1	421	0.89	0.27	YES
17	PTGFR	PTGFR	PTGFR	453	0.87	0.28	YES
18	HTR2A	HTR2A	HTR2A	491	0.84	0.3	YES
19	PRKCB	PRKCB	PRKCB	496	0.84	0.31	YES
20	CYSLTR1	CYSLTR1	CYSLTR1	579	0.81	0.32	YES
21	ADCY4	ADCY4	ADCY4	582	0.81	0.34	YES
22	GNAL	GNAL	GNAL	663	0.78	0.34	YES
23	RYR3	RYR3	RYR3	697	0.76	0.36	YES
24	PDE1B	PDE1B	PDE1B	743	0.75	0.37	YES
25	PDE1C	PDE1C	PDE1C	769	0.74	0.38	YES
26	ADCY2	ADCY2	ADCY2	880	0.7	0.39	YES
27	SLC8A2	SLC8A2	SLC8A2	886	0.7	0.4	YES
28	PLCD4	PLCD4	PLCD4	919	0.69	0.41	YES
29	ADRB2	ADRB2	ADRB2	993	0.67	0.42	YES
30	LHCGR	LHCGR	LHCGR	1001	0.67	0.43	YES
31	AVPR1A	AVPR1A	AVPR1A	1024	0.66	0.44	YES
32	GRPR	GRPR	GRPR	1047	0.65	0.45	YES
33	GRIN2A	GRIN2A	GRIN2A	1075	0.64	0.46	YES
34	GNA14	GNA14	GNA14	1117	0.63	0.47	YES
35	ADCY9	ADCY9	ADCY9	1132	0.63	0.48	YES
36	CAMK2A	CAMK2A	CAMK2A	1171	0.62	0.49	YES
37	ADRB3	ADRB3	ADRB3	1255	0.6	0.49	YES
38	HTR2B	HTR2B	HTR2B	1291	0.59	0.5	YES
39	TBXA2R	TBXA2R	TBXA2R	1304	0.59	0.51	YES
40	PRKACB	PRKACB	PRKACB	1371	0.58	0.52	YES
41	P2RX7	P2RX7	P2RX7	1438	0.56	0.53	YES
42	RYR2	RYR2	RYR2	1525	0.55	0.53	YES
43	TACR1	TACR1	TACR1	1636	0.53	0.54	YES
44	PTGER1	PTGER1	PTGER1	1684	0.52	0.54	YES
45	NOS1	NOS1	NOS1	1786	0.5	0.55	YES
46	ADRA1A	ADRA1A	ADRA1A	1897	0.48	0.55	YES
47	PDGFRB	PDGFRB	PDGFRB	1916	0.48	0.56	YES
48	HTR7	HTR7	HTR7	1930	0.48	0.57	YES
49	ADRA1D	ADRA1D	ADRA1D	1934	0.48	0.57	YES
50	EDNRB	EDNRB	EDNRB	2214	0.43	0.57	YES
51	BDKRB1	BDKRB1	BDKRB1	2226	0.43	0.58	YES
52	CAMK2G	CAMK2G	CAMK2G	2260	0.43	0.58	YES
53	PDGFRA	PDGFRA	PDGFRA	2324	0.42	0.59	YES
54	SLC25A4	SLC25A4	SLC25A4	2395	0.41	0.59	YES
55	CAMK4	CAMK4	CAMK4	2641	0.38	0.59	YES
56	BST1	BST1	BST1	2676	0.38	0.59	YES
57	PLCB1	PLCB1	PLCB1	2737	0.37	0.59	YES
58	PLCG2	PLCG2	PLCG2	2785	0.36	0.6	YES
59	F2R	F2R	F2R	2890	0.36	0.6	YES
60	NOS3	NOS3	NOS3	3001	0.34	0.6	YES
61	CCKAR	CCKAR	CCKAR	3478	0.3	0.58	YES
62	PRKCA	PRKCA	PRKCA	3486	0.3	0.59	YES
63	PPP3CB	PPP3CB	PPP3CB	3614	0.3	0.59	YES
64	PPP3CC	PPP3CC	PPP3CC	3653	0.29	0.59	YES
65	CACNA1G	CACNA1G	CACNA1G	3799	0.28	0.59	YES
66	DRD5	DRD5	DRD5	3852	0.28	0.59	YES
67	PLCD1	PLCD1	PLCD1	3865	0.28	0.6	YES
68	P2RX2	P2RX2	P2RX2	3878	0.28	0.6	YES
69	CYSLTR2	CYSLTR2	CYSLTR2	4071	0.26	0.6	NO
70	OXTR	OXTR	OXTR	4181	0.25	0.6	NO
71	PLCB4	PLCB4	PLCB4	4251	0.25	0.6	NO
72	HRH1	HRH1	HRH1	4547	0.23	0.59	NO
73	PLCB2	PLCB2	PLCB2	4673	0.22	0.59	NO
74	P2RX1	P2RX1	P2RX1	4696	0.22	0.59	NO
75	ITPR2	ITPR2	ITPR2	4725	0.22	0.59	NO
76	EGFR	EGFR	EGFR	4995	0.2	0.58	NO
77	PLCE1	PLCE1	PLCE1	5295	0.18	0.57	NO
78	GNAQ	GNAQ	GNAQ	5400	0.18	0.57	NO
79	HRH2	HRH2	HRH2	5430	0.18	0.57	NO
80	ATP2B3	ATP2B3	ATP2B3	5599	0.17	0.57	NO
81	PRKCG	PRKCG	PRKCG	5786	0.16	0.56	NO
82	LTB4R2	LTB4R2	LTB4R2	5792	0.16	0.57	NO
83	HTR6	HTR6	HTR6	5878	0.15	0.56	NO
84	PLCG1	PLCG1	PLCG1	5898	0.15	0.57	NO
85	ADCY7	ADCY7	ADCY7	5945	0.15	0.57	NO
86	ATP2B2	ATP2B2	ATP2B2	5973	0.15	0.57	NO
87	ADORA2A	ADORA2A	ADORA2A	5998	0.15	0.57	NO
88	MYLK3	MYLK3	MYLK3	6076	0.14	0.57	NO
89	PRKACA	PRKACA	PRKACA	6190	0.14	0.57	NO
90	CD38	CD38	CD38	6239	0.14	0.57	NO
91	CHRM3	CHRM3	CHRM3	6334	0.13	0.56	NO
92	DRD1	DRD1	DRD1	6630	0.12	0.55	NO
93	PTAFR	PTAFR	PTAFR	6756	0.12	0.55	NO
94	CALM1	CALM1	CALM1	6926	0.11	0.55	NO
95	BDKRB2	BDKRB2	BDKRB2	7021	0.1	0.54	NO
96	NTSR1	NTSR1	NTSR1	7132	0.1	0.54	NO
97	AVPR1B	AVPR1B	AVPR1B	7267	0.095	0.54	NO
98	ATP2A3	ATP2A3	ATP2A3	7308	0.093	0.54	NO
99	CACNA1B	CACNA1B	CACNA1B	7334	0.092	0.54	NO
100	ERBB4	ERBB4	ERBB4	7644	0.081	0.52	NO
101	CACNA1S	CACNA1S	CACNA1S	7940	0.071	0.51	NO
102	ADCY8	ADCY8	ADCY8	8035	0.068	0.51	NO
103	PPP3CA	PPP3CA	PPP3CA	8054	0.067	0.51	NO
104	ADCY3	ADCY3	ADCY3	8259	0.06	0.5	NO
105	SLC25A31	SLC25A31	SLC25A31	8442	0.054	0.49	NO
106	TRHR	TRHR	TRHR	8737	0.044	0.48	NO
107	CACNA1A	CACNA1A	CACNA1A	8903	0.038	0.47	NO
108	PPP3R2	PPP3R2	PPP3R2	8981	0.036	0.47	NO
109	PHKB	PHKB	PHKB	9155	0.03	0.46	NO
110	GRM1	GRM1	GRM1	9264	0.027	0.46	NO
111	CACNA1D	CACNA1D	CACNA1D	9284	0.026	0.46	NO
112	PRKACG	PRKACG	PRKACG	9313	0.026	0.46	NO
113	ADRA1B	ADRA1B	ADRA1B	9349	0.024	0.46	NO
114	P2RX6	P2RX6	P2RX6	9665	0.014	0.44	NO
115	PLCZ1	PLCZ1	PLCZ1	9681	0.014	0.44	NO
116	SLC25A6	SLC25A6	SLC25A6	9838	0.0099	0.44	NO
117	PHKA1	PHKA1	PHKA1	9866	0.0092	0.44	NO
118	TNNC2	TNNC2	TNNC2	10198	-0.00034	0.42	NO
119	PTK2B	PTK2B	PTK2B	10248	-0.0018	0.42	NO
120	CAMK2D	CAMK2D	CAMK2D	10326	-0.0038	0.42	NO
121	GNA11	GNA11	GNA11	10467	-0.0074	0.41	NO
122	ADCY1	ADCY1	ADCY1	10483	-0.0079	0.41	NO
123	CACNA1E	CACNA1E	CACNA1E	10574	-0.01	0.4	NO
124	TNNC1	TNNC1	TNNC1	10729	-0.014	0.4	NO
125	CALM2	CALM2	CALM2	10732	-0.014	0.4	NO
126	SPHK1	SPHK1	SPHK1	11064	-0.022	0.38	NO
127	P2RX5	P2RX5	P2RX5	11218	-0.026	0.38	NO
128	PLCD3	PLCD3	PLCD3	11371	-0.03	0.37	NO
129	HTR4	HTR4	HTR4	11373	-0.03	0.37	NO
130	CHRM5	CHRM5	CHRM5	11525	-0.034	0.37	NO
131	GRM5	GRM5	GRM5	11551	-0.034	0.36	NO
132	CACNA1F	CACNA1F	CACNA1F	12147	-0.049	0.34	NO
133	RYR1	RYR1	RYR1	12252	-0.052	0.34	NO
134	GNAS	GNAS	GNAS	12344	-0.054	0.33	NO
135	CALM3	CALM3	CALM3	12450	-0.057	0.33	NO
136	CHRNA7	CHRNA7	CHRNA7	12522	-0.058	0.33	NO
137	CAMK2B	CAMK2B	CAMK2B	12584	-0.06	0.32	NO
138	GRIN2C	GRIN2C	GRIN2C	12879	-0.067	0.31	NO
139	ADRB1	ADRB1	ADRB1	13100	-0.073	0.3	NO
140	PPP3R1	PPP3R1	PPP3R1	13349	-0.078	0.3	NO
141	CHP2	CHP2	CHP2	13435	-0.08	0.29	NO
142	CCKBR	CCKBR	CCKBR	13465	-0.081	0.29	NO
143	PRKX	PRKX	PRKX	13690	-0.086	0.28	NO
144	CACNA1I	CACNA1I	CACNA1I	13868	-0.089	0.28	NO
145	ATP2B1	ATP2B1	ATP2B1	14985	-0.11	0.23	NO
146	CALML6	CALML6	CALML6	15248	-0.12	0.22	NO
147	CHRM1	CHRM1	CHRM1	15295	-0.12	0.22	NO
148	ATP2A2	ATP2A2	ATP2A2	15341	-0.12	0.22	NO
149	PHKA2	PHKA2	PHKA2	15610	-0.13	0.21	NO
150	VDAC2	VDAC2	VDAC2	15727	-0.13	0.21	NO
151	NOS2	NOS2	NOS2	16215	-0.14	0.19	NO
152	TACR3	TACR3	TACR3	16464	-0.15	0.18	NO
153	ATP2A1	ATP2A1	ATP2A1	16922	-0.16	0.16	NO
154	GRIN2D	GRIN2D	GRIN2D	16979	-0.16	0.16	NO
155	GNA15	GNA15	GNA15	17003	-0.16	0.16	NO
156	CALML3	CALML3	CALML3	17041	-0.16	0.17	NO
157	GRIN1	GRIN1	GRIN1	17463	-0.17	0.15	NO
158	CALML5	CALML5	CALML5	17639	-0.18	0.15	NO
159	VDAC3	VDAC3	VDAC3	17815	-0.18	0.14	NO
160	P2RX4	P2RX4	P2RX4	17852	-0.18	0.14	NO
161	VDAC1	VDAC1	VDAC1	18149	-0.19	0.13	NO
162	PPID	PPID	PPID	18611	-0.21	0.12	NO
163	SLC25A5	SLC25A5	SLC25A5	18809	-0.21	0.11	NO
164	MYLK2	MYLK2	MYLK2	18841	-0.21	0.11	NO
165	SPHK2	SPHK2	SPHK2	19095	-0.22	0.11	NO
166	P2RX3	P2RX3	P2RX3	19646	-0.24	0.085	NO
167	ADORA2B	ADORA2B	ADORA2B	19793	-0.25	0.083	NO
168	HTR2C	HTR2C	HTR2C	20464	-0.28	0.058	NO
169	ITPR3	ITPR3	ITPR3	21138	-0.32	0.034	NO
170	ERBB2	ERBB2	ERBB2	21142	-0.32	0.039	NO
171	PHKG2	PHKG2	PHKG2	21328	-0.34	0.037	NO
172	PLCB3	PLCB3	PLCB3	21561	-0.36	0.033	NO
173	ERBB3	ERBB3	ERBB3	21575	-0.36	0.038	NO
174	ITPKA	ITPKA	ITPKA	22422	-0.54	0.0098	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 ALK PATHWAY.

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

genes ES table in pathway: BIOCARTA AT1R PATHWAY

Table 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	HAND2	HAND2	HAND2	6	1.4	0.098	YES
2	FGF2	FGF2	FGF2	192	1	0.16	YES
3	IGF1	IGF1	IGF1	288	0.97	0.23	YES
4	NFATC4	NFATC4	NFATC4	289	0.96	0.3	YES
5	PRKAR2B	PRKAR2B	PRKAR2B	589	0.8	0.34	YES
6	CTF1	CTF1	CTF1	1004	0.67	0.37	YES
7	PRKACB	PRKACB	PRKACB	1371	0.58	0.4	YES
8	NFATC1	NFATC1	NFATC1	1473	0.56	0.43	YES
9	PIK3R1	PIK3R1	PIK3R1	1743	0.51	0.45	YES
10	CAMK1	CAMK1	CAMK1	2519	0.39	0.45	YES
11	CAMK4	CAMK4	CAMK4	2641	0.38	0.47	YES
12	ACTA1	ACTA1	ACTA1	2824	0.36	0.49	YES
13	MYH2	MYH2	MYH2	3151	0.33	0.5	YES
14	PIK3CG	PIK3CG	PIK3CG	3339	0.32	0.51	YES
15	PPP3CB	PPP3CB	PPP3CB	3614	0.3	0.52	YES
16	PPP3CC	PPP3CC	PPP3CC	3653	0.29	0.54	YES
17	AGT	AGT	AGT	3821	0.28	0.55	YES
18	PIK3CA	PIK3CA	PIK3CA	3858	0.28	0.57	YES
19	NKX2-5	NKX2-5	NKX2-5	3961	0.27	0.58	YES
20	CREBBP	CREBBP	CREBBP	4817	0.21	0.56	NO
21	CAMK1G	CAMK1G	CAMK1G	4895	0.2	0.57	NO
22	EDN1	EDN1	EDN1	5237	0.18	0.57	NO
23	NFATC2	NFATC2	NFATC2	5950	0.15	0.55	NO
24	HAND1	HAND1	HAND1	5977	0.15	0.56	NO
25	PRKAR1A	PRKAR1A	PRKAR1A	6817	0.11	0.53	NO
26	CALM1	CALM1	CALM1	6926	0.11	0.53	NO
27	PPP3CA	PPP3CA	PPP3CA	8054	0.067	0.49	NO
28	PRKAR2A	PRKAR2A	PRKAR2A	8189	0.062	0.48	NO
29	MAPK14	MAPK14	MAPK14	8362	0.056	0.48	NO
30	CSNK1A1	CSNK1A1	CSNK1A1	8788	0.042	0.46	NO
31	MAPK1	MAPK1	MAPK1	9217	0.028	0.45	NO
32	PRKACG	PRKACG	PRKACG	9313	0.026	0.44	NO
33	NFATC3	NFATC3	NFATC3	9373	0.024	0.44	NO
34	AKT1	AKT1	AKT1	10617	-0.011	0.39	NO
35	CALM2	CALM2	CALM2	10732	-0.014	0.39	NO
36	RAF1	RAF1	RAF1	10780	-0.015	0.38	NO
37	RPS6KB1	RPS6KB1	RPS6KB1	10992	-0.02	0.38	NO
38	CALM3	CALM3	CALM3	12450	-0.057	0.32	NO
39	NPPA	NPPA	NPPA	12506	-0.058	0.32	NO
40	HBEGF	HBEGF	HBEGF	12791	-0.065	0.31	NO
41	GSK3B	GSK3B	GSK3B	13180	-0.074	0.3	NO
42	MAPK3	MAPK3	MAPK3	13505	-0.081	0.29	NO
43	LIF	LIF	LIF	13593	-0.083	0.29	NO
44	FKBP1A	FKBP1A	FKBP1A	13743	-0.087	0.29	NO
45	ELSPBP1	ELSPBP1	ELSPBP1	15656	-0.13	0.22	NO
46	MAP2K1	MAP2K1	MAP2K1	16023	-0.14	0.21	NO
47	MAPK8	MAPK8	MAPK8	17069	-0.16	0.18	NO
48	GATA4	GATA4	GATA4	17107	-0.16	0.18	NO
49	CALR	CALR	CALR	17840	-0.18	0.17	NO
50	PRKAR1B	PRKAR1B	PRKAR1B	18121	-0.19	0.17	NO
51	HRAS	HRAS	HRAS	18575	-0.2	0.16	NO
52	F2	F2	F2	20157	-0.26	0.11	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 AT1R PATHWAY.

Figure S28. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AT1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA BCR 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	ITGA7	ITGA7	ITGA7	44	1.2	0.046	YES
2	DES	DES	DES	116	1.2	0.086	YES
3	SGCD	SGCD	SGCD	154	1.1	0.13	YES
4	ITGA9	ITGA9	ITGA9	188	1	0.16	YES
5	DMD	DMD	DMD	197	1	0.2	YES
6	CACNA1C	CACNA1C	CACNA1C	223	1	0.24	YES
7	SGCA	SGCA	SGCA	227	1	0.28	YES
8	CACNB2	CACNB2	CACNB2	231	1	0.32	YES
9	LAMA2	LAMA2	LAMA2	345	0.93	0.35	YES
10	SLC8A1	SLC8A1	SLC8A1	421	0.89	0.38	YES
11	CTNNA3	CTNNA3	CTNNA3	522	0.83	0.4	YES
12	ITGA1	ITGA1	ITGA1	627	0.79	0.43	YES
13	CACNA2D1	CACNA2D1	CACNA2D1	676	0.77	0.46	YES
14	ITGB3	ITGB3	ITGB3	732	0.75	0.48	YES
15	TCF7L1	TCF7L1	TCF7L1	783	0.74	0.51	YES
16	ACTN2	ACTN2	ACTN2	1034	0.66	0.52	YES
17	ITGA5	ITGA5	ITGA5	1274	0.6	0.54	YES
18	CACNA2D3	CACNA2D3	CACNA2D3	1275	0.6	0.56	YES
19	RYR2	RYR2	RYR2	1525	0.55	0.57	YES
20	ITGA10	ITGA10	ITGA10	1544	0.54	0.59	YES
21	GJA1	GJA1	GJA1	1604	0.53	0.6	YES
22	ITGA8	ITGA8	ITGA8	1660	0.52	0.62	YES
23	ACTN1	ACTN1	ACTN1	1804	0.5	0.63	YES
24	SGCB	SGCB	SGCB	2501	0.4	0.62	NO
25	SGCG	SGCG	SGCG	2513	0.4	0.63	NO
26	LEF1	LEF1	LEF1	3271	0.32	0.61	NO
27	CACNB4	CACNB4	CACNB4	3610	0.3	0.61	NO
28	ITGAV	ITGAV	ITGAV	4014	0.26	0.6	NO
29	ITGA4	ITGA4	ITGA4	4105	0.26	0.61	NO
30	ITGB1	ITGB1	ITGB1	4388	0.24	0.6	NO
31	CACNB3	CACNB3	CACNB3	4605	0.22	0.6	NO
32	ITGB5	ITGB5	ITGB5	4716	0.22	0.6	NO
33	CACNG7	CACNG7	CACNG7	4814	0.21	0.61	NO
34	ITGA11	ITGA11	ITGA11	5098	0.19	0.6	NO
35	CDH2	CDH2	CDH2	5114	0.19	0.61	NO
36	CACNG4	CACNG4	CACNG4	5289	0.18	0.61	NO
37	CACNA2D2	CACNA2D2	CACNA2D2	6171	0.14	0.57	NO
38	ITGB8	ITGB8	ITGB8	6179	0.14	0.58	NO
39	TCF7	TCF7	TCF7	6291	0.14	0.58	NO
40	CACNG1	CACNG1	CACNG1	6466	0.13	0.58	NO
41	ITGB7	ITGB7	ITGB7	7668	0.08	0.53	NO
42	ACTB	ACTB	ACTB	7790	0.076	0.52	NO
43	CACNA1S	CACNA1S	CACNA1S	7940	0.071	0.52	NO
44	CACNB1	CACNB1	CACNB1	8931	0.037	0.48	NO
45	LMNA	LMNA	LMNA	9201	0.029	0.47	NO
46	CACNG8	CACNG8	CACNG8	9273	0.026	0.47	NO
47	CACNA1D	CACNA1D	CACNA1D	9284	0.026	0.47	NO
48	ACTN3	ACTN3	ACTN3	9301	0.026	0.47	NO
49	CACNA2D4	CACNA2D4	CACNA2D4	9936	0.0067	0.44	NO
50	ACTN4	ACTN4	ACTN4	10416	-0.0062	0.42	NO
51	CTNNA1	CTNNA1	CTNNA1	11229	-0.026	0.38	NO
52	CTNNA2	CTNNA2	CTNNA2	11267	-0.027	0.38	NO
53	CACNG6	CACNG6	CACNG6	11366	-0.03	0.38	NO
54	EMD	EMD	EMD	12003	-0.046	0.35	NO
55	CACNA1F	CACNA1F	CACNA1F	12147	-0.049	0.35	NO
56	CTNNB1	CTNNB1	CTNNB1	12333	-0.054	0.34	NO
57	DAG1	DAG1	DAG1	12420	-0.056	0.34	NO
58	CACNG3	CACNG3	CACNG3	13045	-0.071	0.32	NO
59	ACTG1	ACTG1	ACTG1	13404	-0.079	0.3	NO
60	TCF7L2	TCF7L2	TCF7L2	14030	-0.093	0.28	NO
61	CACNG2	CACNG2	CACNG2	14038	-0.093	0.28	NO
62	ITGA3	ITGA3	ITGA3	14478	-0.1	0.27	NO
63	ITGA2B	ITGA2B	ITGA2B	14836	-0.11	0.25	NO
64	ITGB6	ITGB6	ITGB6	15068	-0.12	0.25	NO
65	CACNG5	CACNG5	CACNG5	15090	-0.12	0.25	NO
66	ATP2A2	ATP2A2	ATP2A2	15341	-0.12	0.25	NO
67	ITGA2	ITGA2	ITGA2	16190	-0.14	0.21	NO
68	ITGB4	ITGB4	ITGB4	16586	-0.15	0.2	NO
69	ITGA6	ITGA6	ITGA6	17560	-0.18	0.16	NO
70	DSC2	DSC2	DSC2	20470	-0.28	0.047	NO
71	DSP	DSP	DSP	20961	-0.31	0.037	NO
72	PKP2	PKP2	PKP2	21004	-0.31	0.047	NO
73	JUP	JUP	JUP	21341	-0.34	0.045	NO
74	DSG2	DSG2	DSG2	21349	-0.34	0.057	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 BCR PATHWAY.

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

genes ES table in pathway: BIOCARTA BIOPEPTIDES PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MYLK	MYLK	MYLK	18	1.3	0.14	YES
2	PRKCB	PRKCB	PRKCB	496	0.84	0.21	YES
3	MAPT	MAPT	MAPT	1094	0.64	0.26	YES
4	CAMK2A	CAMK2A	CAMK2A	1171	0.62	0.32	YES
5	GNAI1	GNAI1	GNAI1	1819	0.49	0.34	YES
6	STAT5B	STAT5B	STAT5B	2081	0.45	0.38	YES
7	CAMK2G	CAMK2G	CAMK2G	2260	0.43	0.42	YES
8	FYN	FYN	FYN	2415	0.41	0.46	YES
9	STAT5A	STAT5A	STAT5A	3475	0.3	0.44	YES
10	PRKCA	PRKCA	PRKCA	3486	0.3	0.48	YES
11	AGT	AGT	AGT	3821	0.28	0.49	YES
12	AGTR2	AGTR2	AGTR2	3856	0.28	0.52	YES
13	STAT4	STAT4	STAT4	4113	0.26	0.54	YES
14	SOS1	SOS1	SOS1	5501	0.17	0.49	NO
15	PLCG1	PLCG1	PLCG1	5898	0.15	0.49	NO
16	STAT2	STAT2	STAT2	6399	0.13	0.48	NO
17	CALM1	CALM1	CALM1	6926	0.11	0.47	NO
18	JAK2	JAK2	JAK2	7110	0.1	0.48	NO
19	STAT3	STAT3	STAT3	7339	0.092	0.48	NO
20	STAT6	STAT6	STAT6	8000	0.069	0.45	NO
21	MAPK14	MAPK14	MAPK14	8362	0.056	0.44	NO
22	MAPK1	MAPK1	MAPK1	9217	0.028	0.41	NO
23	PTK2B	PTK2B	PTK2B	10248	-0.0018	0.36	NO
24	SHC1	SHC1	SHC1	10307	-0.0033	0.36	NO
25	CAMK2D	CAMK2D	CAMK2D	10326	-0.0038	0.36	NO
26	GNA11	GNA11	GNA11	10467	-0.0074	0.36	NO
27	CALM2	CALM2	CALM2	10732	-0.014	0.34	NO
28	RAF1	RAF1	RAF1	10780	-0.015	0.34	NO
29	GNB1	GNB1	GNB1	11697	-0.038	0.31	NO
30	CALM3	CALM3	CALM3	12450	-0.057	0.28	NO
31	CAMK2B	CAMK2B	CAMK2B	12584	-0.06	0.28	NO
32	MAP2K2	MAP2K2	MAP2K2	12984	-0.07	0.27	NO
33	GRB2	GRB2	GRB2	13477	-0.081	0.26	NO
34	MAPK3	MAPK3	MAPK3	13505	-0.081	0.27	NO
35	STAT1	STAT1	STAT1	14130	-0.096	0.25	NO
36	GNGT1	GNGT1	GNGT1	15245	-0.12	0.21	NO
37	MAP2K1	MAP2K1	MAP2K1	16023	-0.14	0.19	NO
38	MAPK8	MAPK8	MAPK8	17069	-0.16	0.16	NO
39	KNG1	KNG1	KNG1	18736	-0.21	0.11	NO
40	F2	F2	F2	20157	-0.26	0.079	NO
41	CDK5	CDK5	CDK5	20535	-0.28	0.093	NO

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

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

genes ES table in pathway: BIOCARTA HDAC PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MYLK	MYLK	MYLK	18	1.3	0.023	YES
2	ITGA7	ITGA7	ITGA7	44	1.2	0.045	YES
3	CHRM2	CHRM2	CHRM2	56	1.2	0.067	YES
4	FGF10	FGF10	FGF10	72	1.2	0.088	YES
5	CFL2	CFL2	CFL2	73	1.2	0.11	YES
6	ITGA9	ITGA9	ITGA9	188	1	0.12	YES
7	FGF2	FGF2	FGF2	192	1	0.14	YES
8	FGF7	FGF7	FGF7	243	1	0.16	YES
9	MRAS	MRAS	MRAS	304	0.95	0.17	YES
10	MYL9	MYL9	MYL9	454	0.87	0.18	YES
11	FGFR1	FGFR1	FGFR1	471	0.86	0.2	YES
12	ITGA1	ITGA1	ITGA1	627	0.79	0.2	YES
13	ITGB3	ITGB3	ITGB3	732	0.75	0.21	YES
14	ARHGEF6	ARHGEF6	ARHGEF6	1020	0.66	0.21	YES
15	ACTN2	ACTN2	ACTN2	1034	0.66	0.22	YES
16	MYH10	MYH10	MYH10	1251	0.6	0.23	YES
17	ITGA5	ITGA5	ITGA5	1274	0.6	0.24	YES
18	FGF14	FGF14	FGF14	1429	0.56	0.24	YES
19	FGF5	FGF5	FGF5	1430	0.56	0.25	YES
20	RDX	RDX	RDX	1463	0.56	0.26	YES
21	ITGA10	ITGA10	ITGA10	1544	0.54	0.26	YES
22	FGF1	FGF1	FGF1	1560	0.54	0.27	YES
23	PPP1R12A	PPP1R12A	PPP1R12A	1648	0.52	0.28	YES
24	ITGA8	ITGA8	ITGA8	1660	0.52	0.29	YES
25	GSN	GSN	GSN	1731	0.51	0.29	YES
26	PIK3R1	PIK3R1	PIK3R1	1743	0.51	0.3	YES
27	ACTN1	ACTN1	ACTN1	1804	0.5	0.31	YES
28	PIP5K1C	PIP5K1C	PIP5K1C	1860	0.49	0.32	YES
29	ENAH	ENAH	ENAH	1863	0.49	0.32	YES
30	FGD1	FGD1	FGD1	1906	0.48	0.33	YES
31	PDGFRB	PDGFRB	PDGFRB	1916	0.48	0.34	YES
32	FGF13	FGF13	FGF13	1960	0.47	0.35	YES
33	PDGFC	PDGFC	PDGFC	1974	0.47	0.36	YES
34	VCL	VCL	VCL	1996	0.46	0.36	YES
35	PDGFD	PDGFD	PDGFD	2023	0.46	0.37	YES
36	WASF1	WASF1	WASF1	2107	0.45	0.37	YES
37	CYFIP2	CYFIP2	CYFIP2	2218	0.43	0.38	YES
38	BDKRB1	BDKRB1	BDKRB1	2226	0.43	0.38	YES
39	PIK3CD	PIK3CD	PIK3CD	2303	0.42	0.39	YES
40	PDGFRA	PDGFRA	PDGFRA	2324	0.42	0.4	YES
41	PIP4K2A	PIP4K2A	PIP4K2A	2514	0.4	0.39	YES
42	PAK3	PAK3	PAK3	2693	0.37	0.39	YES
43	FN1	FN1	FN1	2697	0.37	0.4	YES
44	SSH1	SSH1	SSH1	2853	0.36	0.4	YES
45	F2R	F2R	F2R	2890	0.36	0.4	YES
46	ABI2	ABI2	ABI2	2973	0.35	0.41	YES
47	NCKAP1L	NCKAP1L	NCKAP1L	2985	0.35	0.41	YES
48	MSN	MSN	MSN	3018	0.34	0.42	YES
49	RRAS	RRAS	RRAS	3022	0.34	0.42	YES
50	APC	APC	APC	3129	0.33	0.42	YES
51	PIK3CG	PIK3CG	PIK3CG	3339	0.32	0.42	YES
52	PIK3R5	PIK3R5	PIK3R5	3412	0.31	0.42	YES
53	TIAM1	TIAM1	TIAM1	3467	0.31	0.43	YES
54	ITGAL	ITGAL	ITGAL	3514	0.3	0.43	YES
55	FGF16	FGF16	FGF16	3576	0.3	0.43	YES
56	ARHGEF4	ARHGEF4	ARHGEF4	3609	0.3	0.44	YES
57	FGFR2	FGFR2	FGFR2	3739	0.28	0.44	YES
58	WAS	WAS	WAS	3768	0.28	0.44	YES
59	DOCK1	DOCK1	DOCK1	3800	0.28	0.44	YES
60	PIK3CA	PIK3CA	PIK3CA	3858	0.28	0.45	YES
61	ITGAV	ITGAV	ITGAV	4014	0.26	0.44	YES
62	ITGA4	ITGA4	ITGA4	4105	0.26	0.44	YES
63	PIK3R3	PIK3R3	PIK3R3	4225	0.25	0.44	YES
64	ITGB1	ITGB1	ITGB1	4388	0.24	0.44	YES
65	ITGAD	ITGAD	ITGAD	4426	0.23	0.44	YES
66	ROCK1	ROCK1	ROCK1	4436	0.23	0.45	YES
67	PIP4K2B	PIP4K2B	PIP4K2B	4585	0.22	0.44	YES
68	ITGAM	ITGAM	ITGAM	4586	0.22	0.45	YES
69	PFN2	PFN2	PFN2	4623	0.22	0.45	YES
70	FGF18	FGF18	FGF18	4638	0.22	0.46	YES
71	CHRM4	CHRM4	CHRM4	4653	0.22	0.46	YES
72	DIAPH2	DIAPH2	DIAPH2	4665	0.22	0.46	YES
73	VAV1	VAV1	VAV1	4674	0.22	0.47	YES
74	ITGB5	ITGB5	ITGB5	4716	0.22	0.47	YES
75	WASF2	WASF2	WASF2	4755	0.21	0.47	YES
76	SOS2	SOS2	SOS2	4860	0.21	0.47	YES
77	EGFR	EGFR	EGFR	4995	0.2	0.47	YES
78	GNG12	GNG12	GNG12	5020	0.2	0.47	YES
79	CD14	CD14	CD14	5083	0.19	0.47	YES
80	FGD3	FGD3	FGD3	5084	0.19	0.47	YES
81	ITGA11	ITGA11	ITGA11	5098	0.19	0.48	YES
82	ITGB2	ITGB2	ITGB2	5201	0.19	0.48	YES
83	GNA12	GNA12	GNA12	5241	0.18	0.48	YES
84	TMSB4Y	TMSB4Y	TMSB4Y	5242	0.18	0.48	YES
85	SOS1	SOS1	SOS1	5501	0.17	0.47	NO
86	APC2	APC2	APC2	5566	0.17	0.47	NO
87	FGF22	FGF22	FGF22	5976	0.15	0.46	NO
88	MYLK3	MYLK3	MYLK3	6076	0.14	0.46	NO
89	ITGB8	ITGB8	ITGB8	6179	0.14	0.45	NO
90	CHRM3	CHRM3	CHRM3	6334	0.13	0.45	NO
91	PDGFB	PDGFB	PDGFB	6370	0.13	0.45	NO
92	ITGAX	ITGAX	ITGAX	6549	0.12	0.44	NO
93	FGF9	FGF9	FGF9	6557	0.12	0.45	NO
94	BDKRB2	BDKRB2	BDKRB2	7021	0.1	0.43	NO
95	PPP1CB	PPP1CB	PPP1CB	7036	0.1	0.43	NO
96	PIKFYVE	PIKFYVE	PIKFYVE	7102	0.1	0.43	NO
97	ARHGEF12	ARHGEF12	ARHGEF12	7114	0.1	0.43	NO
98	ROCK2	ROCK2	ROCK2	7153	0.099	0.43	NO
99	RAC2	RAC2	RAC2	7272	0.095	0.42	NO
100	GNA13	GNA13	GNA13	7442	0.088	0.42	NO
101	MYH9	MYH9	MYH9	7533	0.085	0.42	NO
102	SSH2	SSH2	SSH2	7646	0.081	0.41	NO
103	ITGB7	ITGB7	ITGB7	7668	0.08	0.41	NO
104	ACTB	ACTB	ACTB	7790	0.076	0.41	NO
105	TMSB4X	TMSB4X	TMSB4X	7916	0.072	0.4	NO
106	BRAF	BRAF	BRAF	8264	0.06	0.39	NO
107	ARHGEF7	ARHGEF7	ARHGEF7	8464	0.053	0.38	NO
108	MYL2	MYL2	MYL2	8922	0.038	0.36	NO
109	RRAS2	RRAS2	RRAS2	9153	0.03	0.35	NO
110	MAPK1	MAPK1	MAPK1	9217	0.028	0.35	NO
111	ACTN3	ACTN3	ACTN3	9301	0.026	0.35	NO
112	SCIN	SCIN	SCIN	9543	0.018	0.34	NO
113	BAIAP2	BAIAP2	BAIAP2	9589	0.016	0.34	NO
114	IQGAP1	IQGAP1	IQGAP1	9631	0.015	0.34	NO
115	ARHGEF1	ARHGEF1	ARHGEF1	9761	0.012	0.33	NO
116	FGF12	FGF12	FGF12	9974	0.0058	0.32	NO
117	NCKAP1	NCKAP1	NCKAP1	10177	0.00014	0.31	NO
118	ACTN4	ACTN4	ACTN4	10416	-0.0062	0.3	NO
119	PXN	PXN	PXN	10631	-0.012	0.29	NO
120	INSRR	INSRR	INSRR	10757	-0.015	0.29	NO
121	PAK7	PAK7	PAK7	10763	-0.015	0.29	NO
122	CRKL	CRKL	CRKL	10769	-0.015	0.29	NO
123	RAF1	RAF1	RAF1	10780	-0.015	0.28	NO
124	CRK	CRK	CRK	10878	-0.018	0.28	NO
125	CYFIP1	CYFIP1	CYFIP1	10900	-0.018	0.28	NO
126	PFN4	PFN4	PFN4	10966	-0.02	0.28	NO
127	PDGFA	PDGFA	PDGFA	10978	-0.02	0.28	NO
128	CDC42	CDC42	CDC42	10991	-0.02	0.28	NO
129	WASL	WASL	WASL	11127	-0.024	0.27	NO
130	PFN1	PFN1	PFN1	11158	-0.024	0.27	NO
131	RHOA	RHOA	RHOA	11442	-0.032	0.26	NO
132	CHRM5	CHRM5	CHRM5	11525	-0.034	0.26	NO
133	ARPC1B	ARPC1B	ARPC1B	11786	-0.04	0.25	NO
134	MYLPF	MYLPF	MYLPF	11832	-0.042	0.24	NO
135	ARAF	ARAF	ARAF	12105	-0.048	0.23	NO
136	MYL12A	MYL12A	MYL12A	12531	-0.058	0.22	NO
137	VAV3	VAV3	VAV3	12595	-0.06	0.21	NO
138	PAK2	PAK2	PAK2	12670	-0.062	0.21	NO
139	MYL10	MYL10	MYL10	12839	-0.066	0.2	NO
140	FGF19	FGF19	FGF19	12949	-0.069	0.2	NO
141	MAP2K2	MAP2K2	MAP2K2	12984	-0.07	0.2	NO
142	ARPC2	ARPC2	ARPC2	13008	-0.07	0.2	NO
143	FGF20	FGF20	FGF20	13358	-0.078	0.19	NO
144	ACTG1	ACTG1	ACTG1	13404	-0.079	0.19	NO
145	MAPK3	MAPK3	MAPK3	13505	-0.081	0.18	NO
146	RAC1	RAC1	RAC1	13925	-0.091	0.17	NO
147	FGF3	FGF3	FGF3	13949	-0.091	0.17	NO
148	ARPC1A	ARPC1A	ARPC1A	14146	-0.096	0.16	NO
149	KRAS	KRAS	KRAS	14305	-0.1	0.16	NO
150	ARPC3	ARPC3	ARPC3	14459	-0.1	0.15	NO
151	ITGA3	ITGA3	ITGA3	14478	-0.1	0.15	NO
152	FGF11	FGF11	FGF11	14535	-0.1	0.15	NO
153	TIAM2	TIAM2	TIAM2	14544	-0.1	0.15	NO
154	PTK2	PTK2	PTK2	14591	-0.11	0.15	NO
155	PPP1CC	PPP1CC	PPP1CC	14598	-0.11	0.15	NO
156	EGF	EGF	EGF	14641	-0.11	0.15	NO
157	CFL1	CFL1	CFL1	14781	-0.11	0.15	NO
158	ITGA2B	ITGA2B	ITGA2B	14836	-0.11	0.15	NO
159	MYL12B	MYL12B	MYL12B	14899	-0.11	0.15	NO
160	ITGAE	ITGAE	ITGAE	15065	-0.12	0.14	NO
161	ITGB6	ITGB6	ITGB6	15068	-0.12	0.14	NO
162	CHRM1	CHRM1	CHRM1	15295	-0.12	0.14	NO
163	ARPC5	ARPC5	ARPC5	15699	-0.13	0.12	NO
164	MAP2K1	MAP2K1	MAP2K1	16023	-0.14	0.11	NO
165	ITGA2	ITGA2	ITGA2	16190	-0.14	0.1	NO
166	FGF17	FGF17	FGF17	16203	-0.14	0.11	NO
167	IQGAP2	IQGAP2	IQGAP2	16342	-0.15	0.1	NO
168	ITGB4	ITGB4	ITGB4	16586	-0.15	0.096	NO
169	SSH3	SSH3	SSH3	17049	-0.16	0.078	NO
170	CSK	CSK	CSK	17089	-0.16	0.08	NO
171	DIAPH1	DIAPH1	DIAPH1	17285	-0.17	0.074	NO
172	PIK3CB	PIK3CB	PIK3CB	17359	-0.17	0.074	NO
173	ITGA6	ITGA6	ITGA6	17560	-0.18	0.068	NO
174	FGF4	FGF4	FGF4	17869	-0.18	0.058	NO
175	GIT1	GIT1	GIT1	18218	-0.19	0.046	NO
176	EZR	EZR	EZR	18264	-0.2	0.047	NO
177	PIP5K1A	PIP5K1A	PIP5K1A	18432	-0.2	0.043	NO
178	PIK3R2	PIK3R2	PIK3R2	18680	-0.21	0.036	NO
179	LIMK1	LIMK1	LIMK1	18702	-0.21	0.039	NO
180	MYLK2	MYLK2	MYLK2	18841	-0.21	0.037	NO
181	PAK1	PAK1	PAK1	18907	-0.22	0.038	NO
182	LIMK2	LIMK2	LIMK2	18977	-0.22	0.039	NO
183	FGF23	FGF23	FGF23	18998	-0.22	0.042	NO
184	SLC9A1	SLC9A1	SLC9A1	19143	-0.22	0.039	NO
185	MYH14	MYH14	MYH14	19267	-0.23	0.038	NO
186	FGF8	FGF8	FGF8	19476	-0.24	0.033	NO
187	BCAR1	BCAR1	BCAR1	19511	-0.24	0.036	NO
188	FGF21	FGF21	FGF21	19633	-0.24	0.035	NO
189	PPP1CA	PPP1CA	PPP1CA	19784	-0.25	0.033	NO
190	PIP4K2C	PIP4K2C	PIP4K2C	19917	-0.25	0.032	NO
191	MYL5	MYL5	MYL5	20116	-0.26	0.027	NO
192	F2	F2	F2	20157	-0.26	0.03	NO
193	FGFR4	FGFR4	FGFR4	20202	-0.27	0.033	NO
194	NRAS	NRAS	NRAS	20271	-0.27	0.035	NO
195	ARPC5L	ARPC5L	ARPC5L	21100	-0.32	0.0042	NO
196	PIP5K1B	PIP5K1B	PIP5K1B	21267	-0.33	0.0028	NO
197	PAK4	PAK4	PAK4	21462	-0.35	0.00054	NO
198	VAV2	VAV2	VAV2	21478	-0.35	0.0063	NO
199	RAC3	RAC3	RAC3	21917	-0.4	-0.006	NO
200	FGFR3	FGFR3	FGFR3	22186	-0.45	-0.0098	NO
201	DIAPH3	DIAPH3	DIAPH3	22374	-0.51	-0.0087	NO
202	IQGAP3	IQGAP3	IQGAP3	22436	-0.54	-0.0016	NO
203	PAK6	PAK6	PAK6	22508	-0.59	0.006	NO

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

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

genes ES table in pathway: BIOCARTA EGF PATHWAY

Table 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	ITGA7	ITGA7	ITGA7	44	1.2	0.042	YES
2	DES	DES	DES	116	1.2	0.079	YES
3	SGCD	SGCD	SGCD	154	1.1	0.12	YES
4	ITGA9	ITGA9	ITGA9	188	1	0.15	YES
5	DMD	DMD	DMD	197	1	0.19	YES
6	CACNA1C	CACNA1C	CACNA1C	223	1	0.22	YES
7	SGCA	SGCA	SGCA	227	1	0.26	YES
8	CACNB2	CACNB2	CACNB2	231	1	0.29	YES
9	IGF1	IGF1	IGF1	288	0.97	0.32	YES
10	TPM2	TPM2	TPM2	303	0.95	0.36	YES
11	LAMA2	LAMA2	LAMA2	345	0.93	0.39	YES
12	SLC8A1	SLC8A1	SLC8A1	421	0.89	0.41	YES
13	TGFB3	TGFB3	TGFB3	560	0.81	0.44	YES
14	ITGA1	ITGA1	ITGA1	627	0.79	0.46	YES
15	CACNA2D1	CACNA2D1	CACNA2D1	676	0.77	0.49	YES
16	ITGB3	ITGB3	ITGB3	732	0.75	0.51	YES
17	TPM1	TPM1	TPM1	1115	0.63	0.52	YES
18	ITGA5	ITGA5	ITGA5	1274	0.6	0.53	YES
19	CACNA2D3	CACNA2D3	CACNA2D3	1275	0.6	0.55	YES
20	ACTC1	ACTC1	ACTC1	1372	0.58	0.57	YES
21	PRKAA2	PRKAA2	PRKAA2	1496	0.55	0.58	YES
22	RYR2	RYR2	RYR2	1525	0.55	0.6	YES
23	ITGA10	ITGA10	ITGA10	1544	0.54	0.62	YES
24	ITGA8	ITGA8	ITGA8	1660	0.52	0.63	YES
25	SGCB	SGCB	SGCB	2501	0.4	0.61	YES
26	SGCG	SGCG	SGCG	2513	0.4	0.62	YES
27	PRKAG2	PRKAG2	PRKAG2	2529	0.39	0.63	YES
28	TGFB2	TGFB2	TGFB2	2775	0.36	0.63	YES
29	TGFB1	TGFB1	TGFB1	3569	0.3	0.61	YES
30	CACNB4	CACNB4	CACNB4	3610	0.3	0.62	YES
31	PRKAB2	PRKAB2	PRKAB2	3995	0.26	0.61	YES
32	ITGAV	ITGAV	ITGAV	4014	0.26	0.62	YES
33	ITGA4	ITGA4	ITGA4	4105	0.26	0.62	YES
34	ITGB1	ITGB1	ITGB1	4388	0.24	0.62	YES
35	CACNB3	CACNB3	CACNB3	4605	0.22	0.62	YES
36	MYL3	MYL3	MYL3	4609	0.22	0.62	YES
37	ITGB5	ITGB5	ITGB5	4716	0.22	0.63	YES
38	TTN	TTN	TTN	4783	0.21	0.63	YES
39	CACNG7	CACNG7	CACNG7	4814	0.21	0.64	YES
40	ITGA11	ITGA11	ITGA11	5098	0.19	0.63	NO
41	CACNG4	CACNG4	CACNG4	5289	0.18	0.63	NO
42	CACNA2D2	CACNA2D2	CACNA2D2	6171	0.14	0.6	NO
43	ITGB8	ITGB8	ITGB8	6179	0.14	0.6	NO
44	CACNG1	CACNG1	CACNG1	6466	0.13	0.59	NO
45	ITGB7	ITGB7	ITGB7	7668	0.08	0.54	NO
46	ACTB	ACTB	ACTB	7790	0.076	0.54	NO
47	CACNA1S	CACNA1S	CACNA1S	7940	0.071	0.54	NO
48	IL6	IL6	IL6	8040	0.068	0.53	NO
49	PRKAB1	PRKAB1	PRKAB1	8606	0.048	0.51	NO
50	MYL2	MYL2	MYL2	8922	0.038	0.5	NO
51	CACNB1	CACNB1	CACNB1	8931	0.037	0.5	NO
52	TPM4	TPM4	TPM4	9095	0.032	0.49	NO
53	LMNA	LMNA	LMNA	9201	0.029	0.49	NO
54	CACNG8	CACNG8	CACNG8	9273	0.026	0.49	NO
55	CACNA1D	CACNA1D	CACNA1D	9284	0.026	0.49	NO
56	CACNA2D4	CACNA2D4	CACNA2D4	9936	0.0067	0.46	NO
57	TNNC1	TNNC1	TNNC1	10729	-0.014	0.42	NO
58	CACNG6	CACNG6	CACNG6	11366	-0.03	0.4	NO
59	EMD	EMD	EMD	12003	-0.046	0.37	NO
60	ACE	ACE	ACE	12077	-0.048	0.37	NO
61	CACNA1F	CACNA1F	CACNA1F	12147	-0.049	0.37	NO
62	DAG1	DAG1	DAG1	12420	-0.056	0.36	NO
63	CACNG3	CACNG3	CACNG3	13045	-0.071	0.33	NO
64	ACTG1	ACTG1	ACTG1	13404	-0.079	0.32	NO
65	CACNG2	CACNG2	CACNG2	14038	-0.093	0.29	NO
66	TNNT2	TNNT2	TNNT2	14164	-0.097	0.29	NO
67	TNF	TNF	TNF	14329	-0.1	0.29	NO
68	PRKAG1	PRKAG1	PRKAG1	14436	-0.1	0.29	NO
69	ITGA3	ITGA3	ITGA3	14478	-0.1	0.29	NO
70	ITGA2B	ITGA2B	ITGA2B	14836	-0.11	0.28	NO
71	PRKAA1	PRKAA1	PRKAA1	14982	-0.11	0.28	NO
72	ITGB6	ITGB6	ITGB6	15068	-0.12	0.28	NO
73	CACNG5	CACNG5	CACNG5	15090	-0.12	0.28	NO
74	ATP2A2	ATP2A2	ATP2A2	15341	-0.12	0.27	NO
75	MYBPC3	MYBPC3	MYBPC3	15997	-0.14	0.25	NO
76	ITGA2	ITGA2	ITGA2	16190	-0.14	0.24	NO
77	ITGB4	ITGB4	ITGB4	16586	-0.15	0.23	NO
78	MYH6	MYH6	MYH6	17224	-0.17	0.21	NO
79	ITGA6	ITGA6	ITGA6	17560	-0.18	0.2	NO
80	MYH7	MYH7	MYH7	18504	-0.2	0.17	NO
81	TNNI3	TNNI3	TNNI3	19295	-0.23	0.14	NO
82	TPM3	TPM3	TPM3	20365	-0.27	0.1	NO

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

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

genes ES table in pathway: BIOCARTA ERK PATHWAY

Table 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	GNAO1	GNAO1	GNAO1	100	1.2	0.041	YES
2	ADCY5	ADCY5	ADCY5	120	1.1	0.084	YES
3	WNT9A	WNT9A	WNT9A	306	0.95	0.11	YES
4	PRKCB	PRKCB	PRKCB	496	0.84	0.14	YES
5	FZD4	FZD4	FZD4	547	0.82	0.17	YES
6	MITF	MITF	MITF	574	0.81	0.2	YES
7	ADCY4	ADCY4	ADCY4	582	0.81	0.23	YES
8	TCF7L1	TCF7L1	TCF7L1	783	0.74	0.25	YES
9	WNT9B	WNT9B	WNT9B	836	0.72	0.27	YES
10	ADCY2	ADCY2	ADCY2	880	0.7	0.3	YES
11	ADCY9	ADCY9	ADCY9	1132	0.63	0.31	YES
12	CAMK2A	CAMK2A	CAMK2A	1171	0.62	0.34	YES
13	WNT2B	WNT2B	WNT2B	1177	0.62	0.36	YES
14	KIT	KIT	KIT	1193	0.62	0.38	YES
15	TYRP1	TYRP1	TYRP1	1361	0.58	0.4	YES
16	PRKACB	PRKACB	PRKACB	1371	0.58	0.42	YES
17	FZD1	FZD1	FZD1	1502	0.55	0.44	YES
18	FZD7	FZD7	FZD7	1617	0.53	0.45	YES
19	GNAI1	GNAI1	GNAI1	1819	0.49	0.46	YES
20	FZD8	FZD8	FZD8	1884	0.49	0.48	YES
21	EDNRB	EDNRB	EDNRB	2214	0.43	0.48	YES
22	CAMK2G	CAMK2G	CAMK2G	2260	0.43	0.49	YES
23	DCT	DCT	DCT	2281	0.42	0.51	YES
24	POMC	POMC	POMC	2602	0.38	0.51	YES
25	PLCB1	PLCB1	PLCB1	2737	0.37	0.52	YES
26	LEF1	LEF1	LEF1	3271	0.32	0.51	YES
27	PRKCA	PRKCA	PRKCA	3486	0.3	0.51	YES
28	CREB3L2	CREB3L2	CREB3L2	3500	0.3	0.52	YES
29	KITLG	KITLG	KITLG	3787	0.28	0.52	NO
30	PLCB4	PLCB4	PLCB4	4251	0.25	0.51	NO
31	PLCB2	PLCB2	PLCB2	4673	0.22	0.5	NO
32	WNT6	WNT6	WNT6	4757	0.21	0.5	NO
33	CREBBP	CREBBP	CREBBP	4817	0.21	0.51	NO
34	EDN1	EDN1	EDN1	5237	0.18	0.5	NO
35	GNAQ	GNAQ	GNAQ	5400	0.18	0.5	NO
36	GNAI2	GNAI2	GNAI2	5478	0.17	0.5	NO
37	PRKCG	PRKCG	PRKCG	5786	0.16	0.49	NO
38	ADCY7	ADCY7	ADCY7	5945	0.15	0.49	NO
39	PRKACA	PRKACA	PRKACA	6190	0.14	0.48	NO
40	TCF7	TCF7	TCF7	6291	0.14	0.49	NO
41	FZD2	FZD2	FZD2	6569	0.12	0.48	NO
42	CREB1	CREB1	CREB1	6785	0.11	0.47	NO
43	CALM1	CALM1	CALM1	6926	0.11	0.47	NO
44	WNT1	WNT1	WNT1	7465	0.087	0.45	NO
45	WNT10B	WNT10B	WNT10B	7854	0.074	0.44	NO
46	ADCY8	ADCY8	ADCY8	8035	0.068	0.43	NO
47	WNT16	WNT16	WNT16	8301	0.059	0.42	NO
48	FZD3	FZD3	FZD3	8340	0.057	0.42	NO
49	DVL2	DVL2	DVL2	8624	0.047	0.41	NO
50	TYR	TYR	TYR	8802	0.041	0.4	NO
51	DVL3	DVL3	DVL3	8824	0.041	0.41	NO
52	MAPK1	MAPK1	MAPK1	9217	0.028	0.39	NO
53	PRKACG	PRKACG	PRKACG	9313	0.026	0.39	NO
54	FZD10	FZD10	FZD10	9350	0.024	0.39	NO
55	EP300	EP300	EP300	9763	0.012	0.37	NO
56	CAMK2D	CAMK2D	CAMK2D	10326	-0.0038	0.34	NO
57	WNT10A	WNT10A	WNT10A	10349	-0.0043	0.34	NO
58	ADCY1	ADCY1	ADCY1	10483	-0.0079	0.34	NO
59	ASIP	ASIP	ASIP	10620	-0.011	0.33	NO
60	CALM2	CALM2	CALM2	10732	-0.014	0.33	NO
61	RAF1	RAF1	RAF1	10780	-0.015	0.33	NO
62	CREB3	CREB3	CREB3	11166	-0.024	0.31	NO
63	ADCY6	ADCY6	ADCY6	12164	-0.05	0.27	NO
64	CTNNB1	CTNNB1	CTNNB1	12333	-0.054	0.26	NO
65	GNAS	GNAS	GNAS	12344	-0.054	0.26	NO
66	CALM3	CALM3	CALM3	12450	-0.057	0.26	NO
67	CAMK2B	CAMK2B	CAMK2B	12584	-0.06	0.26	NO
68	MAP2K2	MAP2K2	MAP2K2	12984	-0.07	0.24	NO
69	WNT4	WNT4	WNT4	13021	-0.071	0.24	NO
70	WNT2	WNT2	WNT2	13159	-0.074	0.24	NO
71	GSK3B	GSK3B	GSK3B	13180	-0.074	0.24	NO
72	WNT5B	WNT5B	WNT5B	13236	-0.076	0.24	NO
73	WNT7A	WNT7A	WNT7A	13258	-0.076	0.24	NO
74	WNT11	WNT11	WNT11	13328	-0.078	0.24	NO
75	MAPK3	MAPK3	MAPK3	13505	-0.081	0.24	NO
76	PRKX	PRKX	PRKX	13690	-0.086	0.24	NO
77	TCF7L2	TCF7L2	TCF7L2	14030	-0.093	0.22	NO
78	KRAS	KRAS	KRAS	14305	-0.1	0.22	NO
79	CALML6	CALML6	CALML6	15248	-0.12	0.18	NO
80	GNAI3	GNAI3	GNAI3	15329	-0.12	0.18	NO
81	FZD6	FZD6	FZD6	15592	-0.13	0.17	NO
82	MAP2K1	MAP2K1	MAP2K1	16023	-0.14	0.16	NO
83	FZD9	FZD9	FZD9	16290	-0.14	0.15	NO
84	WNT3	WNT3	WNT3	16655	-0.15	0.14	NO
85	WNT7B	WNT7B	WNT7B	16696	-0.15	0.15	NO
86	CREB3L1	CREB3L1	CREB3L1	16858	-0.16	0.15	NO
87	CALML3	CALML3	CALML3	17041	-0.16	0.14	NO
88	WNT3A	WNT3A	WNT3A	17545	-0.18	0.13	NO
89	CALML5	CALML5	CALML5	17639	-0.18	0.13	NO
90	CREB3L3	CREB3L3	CREB3L3	17719	-0.18	0.14	NO
91	WNT5A	WNT5A	WNT5A	18042	-0.19	0.13	NO
92	WNT8B	WNT8B	WNT8B	18417	-0.2	0.12	NO
93	HRAS	HRAS	HRAS	18575	-0.2	0.12	NO
94	FZD5	FZD5	FZD5	20128	-0.26	0.062	NO
95	DVL1	DVL1	DVL1	20140	-0.26	0.072	NO
96	NRAS	NRAS	NRAS	20271	-0.27	0.076	NO
97	PLCB3	PLCB3	PLCB3	21561	-0.36	0.033	NO
98	CREB3L4	CREB3L4	CREB3L4	21784	-0.38	0.038	NO

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

Figure S38. 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 FCER1 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	RAB23	RAB23	RAB23	139	1.1	0.068	YES
2	GLI3	GLI3	GLI3	203	1	0.14	YES
3	WNT9A	WNT9A	WNT9A	306	0.95	0.19	YES
4	PTCH2	PTCH2	PTCH2	392	0.91	0.25	YES
5	GLI2	GLI2	GLI2	550	0.82	0.3	YES
6	GLI1	GLI1	GLI1	648	0.78	0.35	YES
7	GAS1	GAS1	GAS1	682	0.77	0.4	YES
8	WNT9B	WNT9B	WNT9B	836	0.72	0.44	YES
9	DHH	DHH	DHH	922	0.69	0.48	YES
10	WNT2B	WNT2B	WNT2B	1177	0.62	0.51	YES
11	PRKACB	PRKACB	PRKACB	1371	0.58	0.54	YES
12	SMO	SMO	SMO	1671	0.52	0.56	YES
13	PTCH1	PTCH1	PTCH1	1989	0.46	0.58	YES
14	SUFU	SUFU	SUFU	2950	0.35	0.56	NO
15	HHIP	HHIP	HHIP	3051	0.34	0.58	NO
16	WNT6	WNT6	WNT6	4757	0.21	0.52	NO
17	PRKACA	PRKACA	PRKACA	6190	0.14	0.47	NO
18	BTRC	BTRC	BTRC	6620	0.12	0.46	NO
19	WNT1	WNT1	WNT1	7465	0.087	0.42	NO
20	BMP4	BMP4	BMP4	7569	0.084	0.42	NO
21	WNT10B	WNT10B	WNT10B	7854	0.074	0.42	NO
22	FBXW11	FBXW11	FBXW11	8067	0.066	0.41	NO
23	BMP8A	BMP8A	BMP8A	8239	0.061	0.41	NO
24	WNT16	WNT16	WNT16	8301	0.059	0.41	NO
25	CSNK1A1	CSNK1A1	CSNK1A1	8788	0.042	0.39	NO
26	CSNK1A1L	CSNK1A1L	CSNK1A1L	9169	0.03	0.38	NO
27	CSNK1G3	CSNK1G3	CSNK1G3	9234	0.028	0.38	NO
28	PRKACG	PRKACG	PRKACG	9313	0.026	0.37	NO
29	CSNK1E	CSNK1E	CSNK1E	10169	0.00031	0.34	NO
30	WNT10A	WNT10A	WNT10A	10349	-0.0043	0.33	NO
31	BMP6	BMP6	BMP6	11491	-0.033	0.28	NO
32	CSNK1D	CSNK1D	CSNK1D	13012	-0.07	0.22	NO
33	WNT4	WNT4	WNT4	13021	-0.071	0.22	NO
34	WNT2	WNT2	WNT2	13159	-0.074	0.22	NO
35	GSK3B	GSK3B	GSK3B	13180	-0.074	0.22	NO
36	WNT5B	WNT5B	WNT5B	13236	-0.076	0.23	NO
37	WNT7A	WNT7A	WNT7A	13258	-0.076	0.23	NO
38	WNT11	WNT11	WNT11	13328	-0.078	0.23	NO
39	PRKX	PRKX	PRKX	13690	-0.086	0.22	NO
40	CSNK1G2	CSNK1G2	CSNK1G2	13719	-0.086	0.23	NO
41	ZIC2	ZIC2	ZIC2	14549	-0.1	0.2	NO
42	LRP2	LRP2	LRP2	15421	-0.12	0.17	NO
43	BMP7	BMP7	BMP7	16139	-0.14	0.15	NO
44	BMP5	BMP5	BMP5	16417	-0.15	0.14	NO
45	WNT3	WNT3	WNT3	16655	-0.15	0.14	NO
46	WNT7B	WNT7B	WNT7B	16696	-0.15	0.15	NO
47	IHH	IHH	IHH	16948	-0.16	0.15	NO
48	WNT5A	WNT5A	WNT5A	18042	-0.19	0.12	NO
49	WNT8B	WNT8B	WNT8B	18417	-0.2	0.11	NO
50	STK36	STK36	STK36	18542	-0.2	0.12	NO
51	BMP2	BMP2	BMP2	18633	-0.21	0.13	NO
52	SHH	SHH	SHH	18727	-0.21	0.14	NO
53	CSNK1G1	CSNK1G1	CSNK1G1	18893	-0.22	0.15	NO
54	BMP8B	BMP8B	BMP8B	20308	-0.27	0.1	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: BIOCARTA FCER1 PATHWAY.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 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
KEGG GLYCOLYSIS GLUCONEOGENESIS	59	genes.ES.table	0.46	1.7	0.023	0.23	0.56	0.36	0.15	0.3	0.1	0.043
KEGG PENTOSE PHOSPHATE PATHWAY	25	genes.ES.table	0.48	1.5	0.064	0.27	0.86	0.2	0.062	0.19	0.19	0.032
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.57	1.7	0.022	0.29	0.53	0.34	0.064	0.32	0.13	0.08
KEGG GALACTOSE METABOLISM	25	genes.ES.table	0.5	1.6	0.051	0.24	0.8	0.4	0.13	0.35	0.16	0.028
KEGG FATTY ACID METABOLISM	39	genes.ES.table	0.5	1.6	0.055	0.24	0.77	0.56	0.18	0.46	0.15	0.026
KEGG STEROID HORMONE BIOSYNTHESIS	43	genes.ES.table	0.47	1.5	0.041	0.28	0.88	0.35	0.11	0.31	0.2	0.026
KEGG OXIDATIVE PHOSPHORYLATION	112	genes.ES.table	0.56	2.1	0.0021	0.04	0.038	0.69	0.26	0.51	0	0.014
KEGG GLUTATHIONE METABOLISM	45	genes.ES.table	0.46	1.5	0.064	0.27	0.86	0.49	0.21	0.38	0.18	0.027
KEGG O GLYCAN BIOSYNTHESIS	29	genes.ES.table	0.55	1.6	0.027	0.27	0.76	0.34	0.042	0.33	0.17	0.043
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	42	genes.ES.table	0.5	1.7	0.027	0.26	0.55	0.43	0.14	0.37	0.11	0.058

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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	ATP4B	ATP4B	ATP4B	143	0.44	0.046	YES
2	ATP4A	ATP4A	ATP4A	169	0.42	0.096	YES
3	ATP6V0D2	ATP6V0D2	ATP6V0D2	1112	0.2	0.077	YES
4	COX17	COX17	COX17	1429	0.17	0.084	YES
5	UQCRHL	UQCRHL	UQCRHL	1474	0.16	0.1	YES
6	NDUFS7	NDUFS7	NDUFS7	1614	0.15	0.11	YES
7	UQCR10	UQCR10	UQCR10	1820	0.14	0.12	YES
8	LHPP	LHPP	LHPP	1841	0.14	0.14	YES
9	ATP6V0B	ATP6V0B	ATP6V0B	1853	0.14	0.15	YES
10	NDUFA2	NDUFA2	NDUFA2	1987	0.13	0.16	YES
11	UQCRQ	UQCRQ	UQCRQ	2086	0.13	0.18	YES
12	COX11	COX11	COX11	2191	0.12	0.18	YES
13	ATP5G3	ATP5G3	ATP5G3	2242	0.12	0.2	YES
14	NDUFA7	NDUFA7	NDUFA7	2381	0.11	0.2	YES
15	ATP6V0D1	ATP6V0D1	ATP6V0D1	2478	0.11	0.21	YES
16	NDUFA1	NDUFA1	NDUFA1	2503	0.11	0.23	YES
17	NDUFB10	NDUFB10	NDUFB10	2665	0.1	0.23	YES
18	UQCRC2	UQCRC2	UQCRC2	2729	0.1	0.24	YES
19	ATP6V0A2	ATP6V0A2	ATP6V0A2	2771	0.1	0.25	YES
20	UQCRH	UQCRH	UQCRH	2915	0.095	0.26	YES
21	UQCRB	UQCRB	UQCRB	2939	0.095	0.27	YES
22	ATP5D	ATP5D	ATP5D	2969	0.094	0.28	YES
23	PPA2	PPA2	PPA2	2974	0.093	0.29	YES
24	NDUFV2	NDUFV2	NDUFV2	3033	0.092	0.3	YES
25	NDUFB3	NDUFB3	NDUFB3	3085	0.09	0.31	YES
26	NDUFC1	NDUFC1	NDUFC1	3143	0.089	0.31	YES
27	ATP6V0C	ATP6V0C	ATP6V0C	3153	0.089	0.32	YES
28	NDUFA4	NDUFA4	NDUFA4	3193	0.088	0.33	YES
29	COX7B	COX7B	COX7B	3235	0.086	0.34	YES
30	COX4I1	COX4I1	COX4I1	3266	0.085	0.35	YES
31	NDUFS2	NDUFS2	NDUFS2	3273	0.085	0.36	YES
32	ATP5I	ATP5I	ATP5I	3407	0.081	0.36	YES
33	COX8A	COX8A	COX8A	3433	0.08	0.37	YES
34	UQCR11	UQCR11	UQCR11	3529	0.078	0.38	YES
35	ATP5G2	ATP5G2	ATP5G2	3567	0.077	0.39	YES
36	ATP5F1	ATP5F1	ATP5F1	3568	0.077	0.4	YES
37	COX5A	COX5A	COX5A	3584	0.077	0.4	YES
38	NDUFA3	NDUFA3	NDUFA3	3592	0.077	0.41	YES
39	COX6B2	COX6B2	COX6B2	3608	0.076	0.42	YES
40	COX6A1	COX6A1	COX6A1	3643	0.075	0.43	YES
41	NDUFB1	NDUFB1	NDUFB1	3646	0.075	0.44	YES
42	NDUFB6	NDUFB6	NDUFB6	3676	0.074	0.44	YES
43	COX7C	COX7C	COX7C	3697	0.074	0.45	YES
44	NDUFB7	NDUFB7	NDUFB7	3734	0.073	0.46	YES
45	NDUFS8	NDUFS8	NDUFS8	3760	0.072	0.47	YES
46	NDUFV1	NDUFV1	NDUFV1	3966	0.068	0.47	YES
47	NDUFS4	NDUFS4	NDUFS4	3996	0.067	0.47	YES
48	NDUFB5	NDUFB5	NDUFB5	4057	0.065	0.48	YES
49	NDUFB9	NDUFB9	NDUFB9	4073	0.065	0.49	YES
50	NDUFS3	NDUFS3	NDUFS3	4141	0.064	0.49	YES
51	COX5B	COX5B	COX5B	4219	0.062	0.5	YES
52	COX4I2	COX4I2	COX4I2	4311	0.06	0.5	YES
53	ATP6V0E2	ATP6V0E2	ATP6V0E2	4413	0.058	0.5	YES
54	NDUFAB1	NDUFAB1	NDUFAB1	4527	0.055	0.5	YES
55	NDUFA6	NDUFA6	NDUFA6	4566	0.054	0.51	YES
56	COX15	COX15	COX15	4577	0.054	0.51	YES
57	COX7A2L	COX7A2L	COX7A2L	4681	0.052	0.52	YES
58	NDUFB4	NDUFB4	NDUFB4	4690	0.052	0.52	YES
59	NDUFS6	NDUFS6	NDUFS6	4693	0.052	0.53	YES
60	ATP5H	ATP5H	ATP5H	4813	0.049	0.53	YES
61	COX6B1	COX6B1	COX6B1	4900	0.047	0.53	YES
62	UQCRC1	UQCRC1	UQCRC1	5181	0.042	0.52	YES
63	ATP6V0E1	ATP6V0E1	ATP6V0E1	5228	0.041	0.52	YES
64	NDUFA10	NDUFA10	NDUFA10	5303	0.04	0.53	YES
65	SDHA	SDHA	SDHA	5319	0.039	0.53	YES
66	ATP5G1	ATP5G1	ATP5G1	5364	0.039	0.53	YES
67	NDUFB8	NDUFB8	NDUFB8	5424	0.038	0.54	YES
68	COX6C	COX6C	COX6C	5441	0.037	0.54	YES
69	NDUFB2	NDUFB2	NDUFB2	5459	0.037	0.54	YES
70	ATP6V1G1	ATP6V1G1	ATP6V1G1	5518	0.036	0.55	YES
71	ATP6V1D	ATP6V1D	ATP6V1D	5528	0.036	0.55	YES
72	ATP5J	ATP5J	ATP5J	5566	0.035	0.55	YES
73	SDHC	SDHC	SDHC	5567	0.035	0.56	YES
74	ATP5A1	ATP5A1	ATP5A1	5723	0.032	0.55	YES
75	NDUFA11	NDUFA11	NDUFA11	5728	0.032	0.56	YES
76	NDUFS5	NDUFS5	NDUFS5	5746	0.032	0.56	YES
77	CYC1	CYC1	CYC1	5783	0.032	0.56	YES
78	ATP5B	ATP5B	ATP5B	5973	0.028	0.56	NO
79	SDHB	SDHB	SDHB	6033	0.027	0.56	NO
80	ATP12A	ATP12A	ATP12A	6121	0.026	0.56	NO
81	TCIRG1	TCIRG1	TCIRG1	6218	0.024	0.56	NO
82	ATP5E	ATP5E	ATP5E	6352	0.022	0.55	NO
83	COX7A2	COX7A2	COX7A2	6454	0.02	0.55	NO
84	ATP6V1E1	ATP6V1E1	ATP6V1E1	6662	0.016	0.54	NO
85	ATP6V1A	ATP6V1A	ATP6V1A	6980	0.011	0.53	NO
86	PPA1	PPA1	PPA1	7375	0.0049	0.51	NO
87	ATP6V1E2	ATP6V1E2	ATP6V1E2	7576	0.002	0.5	NO
88	ATP5C1	ATP5C1	ATP5C1	7691	0.00038	0.5	NO
89	SDHD	SDHD	SDHD	7793	-0.0011	0.5	NO
90	NDUFS1	NDUFS1	NDUFS1	7975	-0.0037	0.49	NO
91	ATP5L	ATP5L	ATP5L	7984	-0.0038	0.49	NO
92	COX7B2	COX7B2	COX7B2	7998	-0.004	0.49	NO
93	UQCRFS1	UQCRFS1	UQCRFS1	8179	-0.0068	0.48	NO
94	NDUFA5	NDUFA5	NDUFA5	8625	-0.013	0.46	NO
95	NDUFA8	NDUFA8	NDUFA8	8769	-0.015	0.46	NO
96	ATP6V1C2	ATP6V1C2	ATP6V1C2	8838	-0.016	0.46	NO
97	ATP6V0A1	ATP6V0A1	ATP6V0A1	9100	-0.019	0.45	NO
98	NDUFA9	NDUFA9	NDUFA9	9157	-0.02	0.45	NO
99	ATP6AP1	ATP6AP1	ATP6AP1	9212	-0.021	0.45	NO
100	NDUFV3	NDUFV3	NDUFV3	9513	-0.025	0.44	NO
101	ATP6V1B2	ATP6V1B2	ATP6V1B2	10174	-0.033	0.41	NO
102	ATP6V1F	ATP6V1F	ATP6V1F	10282	-0.035	0.41	NO
103	ATP6V1C1	ATP6V1C1	ATP6V1C1	10459	-0.038	0.41	NO
104	ATP6V1H	ATP6V1H	ATP6V1H	12325	-0.063	0.33	NO
105	COX10	COX10	COX10	12981	-0.072	0.31	NO
106	ATP6V0A4	ATP6V0A4	ATP6V0A4	14327	-0.091	0.26	NO
107	ATP6V1B1	ATP6V1B1	ATP6V1B1	14825	-0.098	0.25	NO
108	COX8C	COX8C	COX8C	14888	-0.099	0.26	NO
109	NDUFA4L2	NDUFA4L2	NDUFA4L2	15502	-0.11	0.25	NO
110	COX7A1	COX7A1	COX7A1	18818	-0.17	0.12	NO
111	COX6A2	COX6A2	COX6A2	19321	-0.19	0.12	NO
112	ATP6V1G2	ATP6V1G2	ATP6V1G2	20129	-0.21	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: KEGG GLYCOLYSIS GLUCONEOGENESIS.

Figure S42. 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 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	CYP2C19	CYP2C19	CYP2C19	15	0.77	0.069	YES
2	ALDH3A1	ALDH3A1	ALDH3A1	19	0.75	0.14	YES
3	ADH1C	ADH1C	ADH1C	24	0.72	0.2	YES
4	GSTA1	GSTA1	GSTA1	79	0.52	0.25	YES
5	UGT2B15	UGT2B15	UGT2B15	99	0.49	0.29	YES
6	CYP3A7	CYP3A7	CYP3A7	216	0.39	0.32	YES
7	AKR1C3	AKR1C3	AKR1C3	235	0.38	0.35	YES
8	UGT1A1	UGT1A1	UGT1A1	241	0.37	0.39	YES
9	CYP2C9	CYP2C9	CYP2C9	280	0.35	0.42	YES
10	CYP2C8	CYP2C8	CYP2C8	285	0.35	0.45	YES
11	AKR1C2	AKR1C2	AKR1C2	339	0.33	0.48	YES
12	ALDH3B1	ALDH3B1	ALDH3B1	426	0.31	0.5	YES
13	GSTA2	GSTA2	GSTA2	432	0.31	0.53	YES
14	CYP2S1	CYP2S1	CYP2S1	517	0.28	0.55	YES
15	ADH7	ADH7	ADH7	560	0.27	0.57	YES
16	DHDH	DHDH	DHDH	620	0.26	0.59	YES
17	UGT2A3	UGT2A3	UGT2A3	750	0.24	0.61	YES
18	GSTT1	GSTT1	GSTT1	917	0.22	0.62	YES
19	UGT2B11	UGT2B11	UGT2B11	1468	0.16	0.61	YES
20	MGST3	MGST3	MGST3	1548	0.16	0.62	YES
21	GSTZ1	GSTZ1	GSTZ1	1744	0.14	0.62	YES
22	GSTA3	GSTA3	GSTA3	1800	0.14	0.64	YES
23	ADH1A	ADH1A	ADH1A	1966	0.13	0.64	YES
24	UGT2B28	UGT2B28	UGT2B28	2005	0.13	0.65	YES
25	GSTO2	GSTO2	GSTO2	2028	0.13	0.66	YES
26	ADH1B	ADH1B	ADH1B	2373	0.11	0.66	NO
27	ADH4	ADH4	ADH4	3100	0.09	0.63	NO
28	GSTM4	GSTM4	GSTM4	3415	0.081	0.62	NO
29	ADH6	ADH6	ADH6	3432	0.08	0.63	NO
30	CYP2E1	CYP2E1	CYP2E1	3461	0.08	0.64	NO
31	MGST2	MGST2	MGST2	3664	0.075	0.64	NO
32	GSTP1	GSTP1	GSTP1	4078	0.065	0.62	NO
33	EPHX1	EPHX1	EPHX1	4139	0.064	0.63	NO
34	MGST1	MGST1	MGST1	4268	0.061	0.63	NO
35	GSTM3	GSTM3	GSTM3	4472	0.056	0.62	NO
36	GSTK1	GSTK1	GSTK1	4833	0.049	0.61	NO
37	UGT2B7	UGT2B7	UGT2B7	4932	0.047	0.61	NO
38	AKR1C4	AKR1C4	AKR1C4	7680	0.00052	0.49	NO
39	GSTO1	GSTO1	GSTO1	8225	-0.0073	0.46	NO
40	GSTM1	GSTM1	GSTM1	11074	-0.046	0.34	NO
41	GSTA4	GSTA4	GSTA4	11100	-0.046	0.35	NO
42	ALDH3B2	ALDH3B2	ALDH3B2	12641	-0.067	0.28	NO
43	UGT2B10	UGT2B10	UGT2B10	13486	-0.079	0.25	NO
44	ALDH1A3	ALDH1A3	ALDH1A3	13579	-0.08	0.26	NO
45	ADH5	ADH5	ADH5	14163	-0.088	0.24	NO
46	CYP3A43	CYP3A43	CYP3A43	14864	-0.099	0.22	NO
47	CYP1A2	CYP1A2	CYP1A2	14994	-0.1	0.22	NO
48	UGT2A1	UGT2A1	UGT2A1	15653	-0.11	0.2	NO
49	CYP1A1	CYP1A1	CYP1A1	15949	-0.12	0.2	NO
50	CYP2F1	CYP2F1	CYP2F1	16398	-0.12	0.19	NO
51	GSTM5	GSTM5	GSTM5	16414	-0.12	0.2	NO
52	CYP2B6	CYP2B6	CYP2B6	16535	-0.13	0.21	NO
53	UGT2B17	UGT2B17	UGT2B17	17539	-0.14	0.18	NO
54	UGT2B4	UGT2B4	UGT2B4	17874	-0.15	0.17	NO
55	GSTT2	GSTT2	GSTT2	18448	-0.16	0.16	NO
56	CYP1B1	CYP1B1	CYP1B1	20911	-0.24	0.077	NO

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

Figure S44. 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 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	CYP2C19	CYP2C19	CYP2C19	15	0.77	0.081	YES
2	ADH1C	ADH1C	ADH1C	24	0.72	0.16	YES
3	UGT2B15	UGT2B15	UGT2B15	99	0.49	0.21	YES
4	RDH12	RDH12	RDH12	176	0.41	0.25	YES
5	CYP3A7	CYP3A7	CYP3A7	216	0.39	0.29	YES
6	ALDH1A1	ALDH1A1	ALDH1A1	232	0.38	0.33	YES
7	UGT1A1	UGT1A1	UGT1A1	241	0.37	0.36	YES
8	CYP2C9	CYP2C9	CYP2C9	280	0.35	0.4	YES
9	CYP2C8	CYP2C8	CYP2C8	285	0.35	0.44	YES
10	DHRS3	DHRS3	DHRS3	414	0.31	0.46	YES
11	CYP4A11	CYP4A11	CYP4A11	518	0.28	0.49	YES
12	ADH7	ADH7	ADH7	560	0.27	0.52	YES
13	UGT2A3	UGT2A3	UGT2A3	750	0.24	0.53	YES
14	RETSAT	RETSAT	RETSAT	1020	0.2	0.54	YES
15	DHRS9	DHRS9	DHRS9	1109	0.2	0.56	YES
16	RDH5	RDH5	RDH5	1250	0.18	0.57	YES
17	PNPLA4	PNPLA4	PNPLA4	1425	0.17	0.58	YES
18	UGT2B11	UGT2B11	UGT2B11	1468	0.16	0.6	YES
19	DHRS4	DHRS4	DHRS4	1814	0.14	0.6	YES
20	ADH1A	ADH1A	ADH1A	1966	0.13	0.61	YES
21	UGT2B28	UGT2B28	UGT2B28	2005	0.13	0.62	YES
22	RDH16	RDH16	RDH16	2059	0.13	0.63	YES
23	ADH1B	ADH1B	ADH1B	2373	0.11	0.63	YES
24	BCMO1	BCMO1	BCMO1	2375	0.11	0.64	YES
25	DGAT2	DGAT2	DGAT2	2523	0.11	0.65	YES
26	CYP2A7	CYP2A7	CYP2A7	2603	0.11	0.65	YES
27	RDH10	RDH10	RDH10	2743	0.1	0.66	YES
28	ADH4	ADH4	ADH4	3100	0.09	0.65	NO
29	ADH6	ADH6	ADH6	3432	0.08	0.65	NO
30	UGT2B7	UGT2B7	UGT2B7	4932	0.047	0.58	NO
31	CYP4A22	CYP4A22	CYP4A22	5413	0.038	0.57	NO
32	CYP2A6	CYP2A6	CYP2A6	6252	0.023	0.53	NO
33	AWAT2	AWAT2	AWAT2	6332	0.022	0.53	NO
34	CYP26B1	CYP26B1	CYP26B1	6890	0.013	0.51	NO
35	CYP2A13	CYP2A13	CYP2A13	7350	0.0053	0.49	NO
36	DGAT1	DGAT1	DGAT1	7723	-0.000045	0.47	NO
37	RDH8	RDH8	RDH8	8326	-0.0087	0.45	NO
38	RDH11	RDH11	RDH11	8624	-0.013	0.44	NO
39	RPE65	RPE65	RPE65	11271	-0.048	0.32	NO
40	LRAT	LRAT	LRAT	12977	-0.072	0.26	NO
41	DHRS4L2	DHRS4L2	DHRS4L2	13429	-0.078	0.24	NO
42	UGT2B10	UGT2B10	UGT2B10	13486	-0.079	0.25	NO
43	ADH5	ADH5	ADH5	14163	-0.088	0.23	NO
44	CYP3A43	CYP3A43	CYP3A43	14864	-0.099	0.21	NO
45	CYP1A2	CYP1A2	CYP1A2	14994	-0.1	0.21	NO
46	UGT2A1	UGT2A1	UGT2A1	15653	-0.11	0.2	NO
47	CYP26C1	CYP26C1	CYP26C1	15798	-0.11	0.2	NO
48	CYP1A1	CYP1A1	CYP1A1	15949	-0.12	0.21	NO
49	CYP2B6	CYP2B6	CYP2B6	16535	-0.13	0.2	NO
50	ALDH1A2	ALDH1A2	ALDH1A2	16974	-0.13	0.19	NO
51	UGT2B17	UGT2B17	UGT2B17	17539	-0.14	0.18	NO
52	UGT2B4	UGT2B4	UGT2B4	17874	-0.15	0.18	NO
53	CYP26A1	CYP26A1	CYP26A1	21566	-0.28	0.048	NO

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

Figure S46. 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 GALACTOSE METABOLISM

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	CYP2C19	CYP2C19	CYP2C19	15	0.77	0.066	YES
2	ALDH3A1	ALDH3A1	ALDH3A1	19	0.75	0.13	YES
3	ADH1C	ADH1C	ADH1C	24	0.72	0.19	YES
4	GSTA1	GSTA1	GSTA1	79	0.52	0.24	YES
5	UGT2B15	UGT2B15	UGT2B15	99	0.49	0.28	YES
6	FMO3	FMO3	FMO3	162	0.42	0.31	YES
7	CYP3A7	CYP3A7	CYP3A7	216	0.39	0.34	YES
8	UGT1A1	UGT1A1	UGT1A1	241	0.37	0.38	YES
9	FMO4	FMO4	FMO4	271	0.35	0.4	YES
10	CYP2C9	CYP2C9	CYP2C9	280	0.35	0.44	YES
11	CYP2C8	CYP2C8	CYP2C8	285	0.35	0.47	YES
12	FMO5	FMO5	FMO5	315	0.34	0.49	YES
13	ALDH3B1	ALDH3B1	ALDH3B1	426	0.31	0.52	YES
14	GSTA2	GSTA2	GSTA2	432	0.31	0.54	YES
15	ADH7	ADH7	ADH7	560	0.27	0.56	YES
16	UGT2A3	UGT2A3	UGT2A3	750	0.24	0.57	YES
17	GSTT1	GSTT1	GSTT1	917	0.22	0.58	YES
18	UGT2B11	UGT2B11	UGT2B11	1468	0.16	0.57	YES
19	MGST3	MGST3	MGST3	1548	0.16	0.58	YES
20	GSTZ1	GSTZ1	GSTZ1	1744	0.14	0.59	YES
21	GSTA3	GSTA3	GSTA3	1800	0.14	0.6	YES
22	MAOA	MAOA	MAOA	1851	0.14	0.61	YES
23	ADH1A	ADH1A	ADH1A	1966	0.13	0.62	YES
24	UGT2B28	UGT2B28	UGT2B28	2005	0.13	0.62	YES
25	GSTO2	GSTO2	GSTO2	2028	0.13	0.64	YES
26	ADH1B	ADH1B	ADH1B	2373	0.11	0.63	NO
27	CYP2A7	CYP2A7	CYP2A7	2603	0.11	0.63	NO
28	ADH4	ADH4	ADH4	3100	0.09	0.62	NO
29	GSTM4	GSTM4	GSTM4	3415	0.081	0.61	NO
30	ADH6	ADH6	ADH6	3432	0.08	0.61	NO
31	CYP2E1	CYP2E1	CYP2E1	3461	0.08	0.62	NO
32	MGST2	MGST2	MGST2	3664	0.075	0.62	NO
33	GSTP1	GSTP1	GSTP1	4078	0.065	0.6	NO
34	MGST1	MGST1	MGST1	4268	0.061	0.6	NO
35	GSTM3	GSTM3	GSTM3	4472	0.056	0.6	NO
36	GSTK1	GSTK1	GSTK1	4833	0.049	0.59	NO
37	UGT2B7	UGT2B7	UGT2B7	4932	0.047	0.59	NO
38	MAOB	MAOB	MAOB	5493	0.037	0.56	NO
39	CYP2D6	CYP2D6	CYP2D6	5814	0.031	0.55	NO
40	CYP2A6	CYP2A6	CYP2A6	6252	0.023	0.54	NO
41	CYP2A13	CYP2A13	CYP2A13	7350	0.0053	0.49	NO
42	GSTO1	GSTO1	GSTO1	8225	-0.0073	0.45	NO
43	GSTM1	GSTM1	GSTM1	11074	-0.046	0.33	NO
44	GSTA4	GSTA4	GSTA4	11100	-0.046	0.33	NO
45	ALDH3B2	ALDH3B2	ALDH3B2	12641	-0.067	0.27	NO
46	UGT2B10	UGT2B10	UGT2B10	13486	-0.079	0.24	NO
47	ALDH1A3	ALDH1A3	ALDH1A3	13579	-0.08	0.24	NO
48	ADH5	ADH5	ADH5	14163	-0.088	0.22	NO
49	CYP3A43	CYP3A43	CYP3A43	14864	-0.099	0.2	NO
50	CYP1A2	CYP1A2	CYP1A2	14994	-0.1	0.2	NO
51	UGT2A1	UGT2A1	UGT2A1	15653	-0.11	0.18	NO
52	GSTM5	GSTM5	GSTM5	16414	-0.12	0.16	NO
53	CYP2B6	CYP2B6	CYP2B6	16535	-0.13	0.17	NO
54	UGT2B17	UGT2B17	UGT2B17	17539	-0.14	0.13	NO
55	UGT2B4	UGT2B4	UGT2B4	17874	-0.15	0.13	NO
56	GSTT2	GSTT2	GSTT2	18448	-0.16	0.12	NO
57	FMO2	FMO2	FMO2	20229	-0.21	0.061	NO
58	AOX1	AOX1	AOX1	21342	-0.26	0.035	NO
59	FMO1	FMO1	FMO1	21344	-0.26	0.058	NO

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

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GALACTOSE 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 FATTY ACID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AKR1B10	AKR1B10	AKR1B10	20	0.74	0.14	YES
2	FBP1	FBP1	FBP1	131	0.45	0.22	YES
3	FBP2	FBP2	FBP2	159	0.42	0.3	YES
4	GMDS	GMDS	GMDS	398	0.32	0.34	YES
5	ALDOB	ALDOB	ALDOB	499	0.29	0.39	YES
6	GMPPB	GMPPB	GMPPB	600	0.26	0.44	YES
7	PMM2	PMM2	PMM2	928	0.21	0.46	YES
8	AKR1B1	AKR1B1	AKR1B1	1348	0.17	0.48	YES
9	PFKFB2	PFKFB2	PFKFB2	1355	0.17	0.51	YES
10	GMPPA	GMPPA	GMPPA	1361	0.17	0.54	YES
11	TSTA3	TSTA3	TSTA3	1446	0.17	0.57	YES
12	HK1	HK1	HK1	2785	0.1	0.53	NO
13	HK2	HK2	HK2	2786	0.1	0.55	NO
14	PFKFB3	PFKFB3	PFKFB3	4889	0.048	0.46	NO
15	PFKL	PFKL	PFKL	4913	0.047	0.47	NO
16	MPI	MPI	MPI	6852	0.014	0.39	NO
17	TPI1	TPI1	TPI1	7244	0.007	0.37	NO
18	PFKP	PFKP	PFKP	8273	-0.0079	0.33	NO
19	PMM1	PMM1	PMM1	9187	-0.02	0.29	NO
20	FUK	FUK	FUK	11337	-0.049	0.2	NO
21	PFKFB1	PFKFB1	PFKFB1	12069	-0.059	0.18	NO
22	ALDOC	ALDOC	ALDOC	13369	-0.077	0.14	NO
23	MTMR1	MTMR1	MTMR1	13788	-0.083	0.14	NO
24	MTMR2	MTMR2	MTMR2	13927	-0.085	0.15	NO
25	PHPT1	PHPT1	PHPT1	14529	-0.094	0.14	NO
26	MTMR7	MTMR7	MTMR7	15081	-0.1	0.13	NO
27	SORD	SORD	SORD	15329	-0.11	0.14	NO
28	MTMR6	MTMR6	MTMR6	16971	-0.13	0.093	NO
29	KHK	KHK	KHK	18104	-0.16	0.072	NO
30	HK3	HK3	HK3	18715	-0.17	0.077	NO
31	PFKFB4	PFKFB4	PFKFB4	21092	-0.25	0.018	NO
32	PFKM	PFKM	PFKM	21471	-0.27	0.052	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 FATTY ACID METABOLISM.

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

genes ES table in pathway: KEGG STEROID HORMONE BIOSYNTHESIS

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	GALE	GALE	GALE	386	0.32	0.047	YES
2	GMDS	GMDS	GMDS	398	0.32	0.11	YES
3	GMPPB	GMPPB	GMPPB	600	0.26	0.15	YES
4	NANS	NANS	NANS	767	0.23	0.19	YES
5	PMM2	PMM2	PMM2	928	0.21	0.23	YES
6	CHIA	CHIA	CHIA	941	0.21	0.27	YES
7	GFPT1	GFPT1	GFPT1	1067	0.2	0.31	YES
8	UAP1	UAP1	UAP1	1188	0.19	0.34	YES
9	GMPPA	GMPPA	GMPPA	1361	0.17	0.36	YES
10	PGM1	PGM1	PGM1	1409	0.17	0.4	YES
11	TSTA3	TSTA3	TSTA3	1446	0.17	0.43	YES
12	CHIT1	CHIT1	CHIT1	1867	0.14	0.44	YES
13	CYB5R1	CYB5R1	CYB5R1	2484	0.11	0.43	YES
14	GALK2	GALK2	GALK2	2778	0.1	0.44	YES
15	HK1	HK1	HK1	2785	0.1	0.46	YES
16	HK2	HK2	HK2	2786	0.1	0.48	YES
17	GNPNAT1	GNPNAT1	GNPNAT1	2905	0.096	0.49	YES
18	CMAS	CMAS	CMAS	3095	0.09	0.5	YES
19	AMDHD2	AMDHD2	AMDHD2	3969	0.067	0.48	NO
20	UGDH	UGDH	UGDH	4060	0.065	0.49	NO
21	GALT	GALT	GALT	5174	0.042	0.45	NO
22	UGP2	UGP2	UGP2	6750	0.015	0.38	NO
23	MPI	MPI	MPI	6852	0.014	0.38	NO
24	PGM3	PGM3	PGM3	6866	0.013	0.38	NO
25	HEXB	HEXB	HEXB	7412	0.0044	0.36	NO
26	GALK1	GALK1	GALK1	7686	0.00046	0.35	NO
27	GCK	GCK	GCK	9021	-0.018	0.29	NO
28	PMM1	PMM1	PMM1	9187	-0.02	0.29	NO
29	NAGK	NAGK	NAGK	9380	-0.023	0.28	NO
30	GPI	GPI	GPI	9434	-0.023	0.29	NO
31	UXS1	UXS1	UXS1	9842	-0.029	0.27	NO
32	HEXA	HEXA	HEXA	10287	-0.035	0.26	NO
33	PGM2	PGM2	PGM2	10548	-0.039	0.26	NO
34	FUK	FUK	FUK	11337	-0.049	0.23	NO
35	GNPDA1	GNPDA1	GNPDA1	14170	-0.089	0.12	NO
36	NPL	NPL	NPL	14304	-0.091	0.14	NO
37	GNE	GNE	GNE	15354	-0.11	0.11	NO
38	RENBP	RENBP	RENBP	16470	-0.12	0.088	NO
39	HK3	HK3	HK3	18715	-0.17	0.023	NO
40	GNPDA2	GNPDA2	GNPDA2	19355	-0.19	0.032	NO
41	NANP	NANP	NANP	20043	-0.21	0.044	NO
42	GFPT2	GFPT2	GFPT2	22332	-0.35	0.014	NO

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

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

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

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	ALDH3A1	ALDH3A1	ALDH3A1	19	0.75	0.088	YES
2	ADH1C	ADH1C	ADH1C	24	0.72	0.17	YES
3	FBP1	FBP1	FBP1	131	0.45	0.22	YES
4	FBP2	FBP2	FBP2	159	0.42	0.27	YES
5	ALDH3B1	ALDH3B1	ALDH3B1	426	0.31	0.3	YES
6	ALDOB	ALDOB	ALDOB	499	0.29	0.33	YES
7	ALDH2	ALDH2	ALDH2	516	0.28	0.36	YES
8	ADH7	ADH7	ADH7	560	0.27	0.39	YES
9	ACSS2	ACSS2	ACSS2	1182	0.19	0.38	YES
10	ACSS1	ACSS1	ACSS1	1235	0.18	0.4	YES
11	PGM1	PGM1	PGM1	1409	0.17	0.42	YES
12	AKR1A1	AKR1A1	AKR1A1	1523	0.16	0.43	YES
13	ADH1A	ADH1A	ADH1A	1966	0.13	0.43	YES
14	G6PC2	G6PC2	G6PC2	2186	0.12	0.43	YES
15	ADH1B	ADH1B	ADH1B	2373	0.11	0.44	YES
16	GALM	GALM	GALM	2380	0.11	0.45	YES
17	HK1	HK1	HK1	2785	0.1	0.44	YES
18	HK2	HK2	HK2	2786	0.1	0.46	YES
19	ADH4	ADH4	ADH4	3100	0.09	0.45	YES
20	ALDH9A1	ALDH9A1	ALDH9A1	3274	0.085	0.46	YES
21	ADH6	ADH6	ADH6	3432	0.08	0.46	YES
22	PCK1	PCK1	PCK1	3985	0.067	0.44	NO
23	BPGM	BPGM	BPGM	4222	0.062	0.44	NO
24	ALDH3A2	ALDH3A2	ALDH3A2	4660	0.052	0.42	NO
25	ALDOA	ALDOA	ALDOA	4662	0.052	0.43	NO
26	PCK2	PCK2	PCK2	4683	0.052	0.44	NO
27	PFKL	PFKL	PFKL	4913	0.047	0.43	NO
28	ALDH7A1	ALDH7A1	ALDH7A1	5467	0.037	0.41	NO
29	LDHB	LDHB	LDHB	5631	0.034	0.41	NO
30	PGK1	PGK1	PGK1	6220	0.024	0.39	NO
31	PDHA1	PDHA1	PDHA1	6651	0.017	0.37	NO
32	TPI1	TPI1	TPI1	7244	0.007	0.34	NO
33	G6PC	G6PC	G6PC	8104	-0.0056	0.31	NO
34	PFKP	PFKP	PFKP	8273	-0.0079	0.3	NO
35	DLD	DLD	DLD	8298	-0.0084	0.3	NO
36	PKLR	PKLR	PKLR	8627	-0.013	0.29	NO
37	GCK	GCK	GCK	9021	-0.018	0.27	NO
38	PDHB	PDHB	PDHB	9225	-0.021	0.26	NO
39	GPI	GPI	GPI	9434	-0.023	0.26	NO
40	GAPDH	GAPDH	GAPDH	9534	-0.025	0.26	NO
41	ENO1	ENO1	ENO1	10031	-0.032	0.24	NO
42	LDHA	LDHA	LDHA	10509	-0.039	0.22	NO
43	PGM2	PGM2	PGM2	10548	-0.039	0.22	NO
44	LDHAL6B	LDHAL6B	LDHAL6B	11516	-0.051	0.19	NO
45	PKM2	PKM2	PKM2	12573	-0.066	0.15	NO
46	ALDH3B2	ALDH3B2	ALDH3B2	12641	-0.067	0.15	NO
47	ALDOC	ALDOC	ALDOC	13369	-0.077	0.13	NO
48	ALDH1A3	ALDH1A3	ALDH1A3	13579	-0.08	0.13	NO
49	ADH5	ADH5	ADH5	14163	-0.088	0.12	NO
50	PGAM2	PGAM2	PGAM2	14353	-0.091	0.12	NO
51	PGAM4	PGAM4	PGAM4	15712	-0.11	0.072	NO
52	LDHAL6A	LDHAL6A	LDHAL6A	16502	-0.12	0.052	NO
53	PGAM1	PGAM1	PGAM1	16873	-0.13	0.051	NO
54	HK3	HK3	HK3	18715	-0.17	-0.01	NO
55	DLAT	DLAT	DLAT	19147	-0.18	-0.0077	NO
56	ENO3	ENO3	ENO3	20603	-0.23	-0.045	NO
57	PFKM	PFKM	PFKM	21471	-0.27	-0.051	NO
58	ENO2	ENO2	ENO2	22417	-0.37	-0.049	NO
59	ALDH1B1	ALDH1B1	ALDH1B1	22634	-0.5	0.0004	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 OXIDATIVE PHOSPHORYLATION.

Figure S54. 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 GLUTATHIONE 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	B4GALT4	B4GALT4	B4GALT4	266	0.36	0.088	YES
2	B3GALT5	B3GALT5	B3GALT5	413	0.31	0.17	YES
3	FUT2	FUT2	FUT2	416	0.31	0.26	YES
4	B3GNT3	B3GNT3	B3GNT3	458	0.3	0.34	YES
5	FUT4	FUT4	FUT4	855	0.22	0.38	YES
6	FUT3	FUT3	FUT3	1320	0.18	0.41	YES
7	GCNT2	GCNT2	GCNT2	1379	0.17	0.45	YES
8	FUT6	FUT6	FUT6	1512	0.16	0.49	YES
9	B4GALT1	B4GALT1	B4GALT1	2579	0.11	0.48	YES
10	B3GNT5	B3GNT5	B3GNT5	2624	0.1	0.5	YES
11	ABO	ABO	ABO	2640	0.1	0.53	YES
12	B4GALT3	B4GALT3	B4GALT3	3562	0.077	0.51	NO
13	B3GNT1	B3GNT1	B3GNT1	3878	0.07	0.52	NO
14	ST3GAL6	ST3GAL6	ST3GAL6	4022	0.066	0.53	NO
15	B3GNT2	B3GNT2	B3GNT2	4638	0.053	0.52	NO
16	FUT5	FUT5	FUT5	5061	0.044	0.51	NO
17	B3GALT1	B3GALT1	B3GALT1	5326	0.039	0.51	NO
18	FUT1	FUT1	FUT1	6463	0.02	0.47	NO
19	B4GALT2	B4GALT2	B4GALT2	11120	-0.046	0.27	NO
20	FUT7	FUT7	FUT7	12957	-0.072	0.21	NO
21	ST8SIA1	ST8SIA1	ST8SIA1	14051	-0.087	0.19	NO
22	B3GALT2	B3GALT2	B3GALT2	14484	-0.094	0.2	NO
23	ST3GAL4	ST3GAL4	ST3GAL4	19137	-0.18	0.04	NO
24	ST3GAL3	ST3GAL3	ST3GAL3	19285	-0.18	0.085	NO
25	B3GNT4	B3GNT4	B3GNT4	20581	-0.23	0.091	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 GLUTATHIONE METABOLISM.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLUTATHIONE 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 O GLYCAN BIOSYNTHESIS

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	PLA2G10	PLA2G10	PLA2G10	10	0.81	0.13	YES
2	CYP2C19	CYP2C19	CYP2C19	15	0.77	0.26	YES
3	AKR1B10	AKR1B10	AKR1B10	20	0.74	0.38	YES
4	CYP3A7	CYP3A7	CYP3A7	216	0.39	0.44	YES
5	CYP2C9	CYP2C9	CYP2C9	280	0.35	0.5	YES
6	CYP2C8	CYP2C8	CYP2C8	285	0.35	0.55	YES
7	PLA2G3	PLA2G3	PLA2G3	1464	0.16	0.53	NO
8	CYP2J2	CYP2J2	CYP2J2	3058	0.091	0.47	NO
9	CYP2E1	CYP2E1	CYP2E1	3461	0.08	0.47	NO
10	PLA2G2D	PLA2G2D	PLA2G2D	3891	0.069	0.46	NO
11	PLA2G1B	PLA2G1B	PLA2G1B	4013	0.066	0.46	NO
12	PLA2G6	PLA2G6	PLA2G6	12837	-0.07	0.087	NO
13	PLA2G12A	PLA2G12A	PLA2G12A	12862	-0.07	0.097	NO
14	CYP3A43	CYP3A43	CYP3A43	14864	-0.099	0.025	NO
15	CYP1A2	CYP1A2	CYP1A2	14994	-0.1	0.036	NO
16	PLA2G2E	PLA2G2E	PLA2G2E	15716	-0.11	0.023	NO
17	PLA2G4A	PLA2G4A	PLA2G4A	16284	-0.12	0.018	NO
18	PLA2G2F	PLA2G2F	PLA2G2F	16293	-0.12	0.038	NO
19	PLA2G12B	PLA2G12B	PLA2G12B	17511	-0.14	0.0079	NO
20	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	18730	-0.17	-0.018	NO
21	PLA2G4E	PLA2G4E	PLA2G4E	19275	-0.18	-0.011	NO
22	PLA2G5	PLA2G5	PLA2G5	20830	-0.24	-0.041	NO
23	PLA2G2C	PLA2G2C	PLA2G2C	20856	-0.24	-0.0024	NO
24	ALOX15	ALOX15	ALOX15	20879	-0.24	0.036	NO
25	PLA2G2A	PLA2G2A	PLA2G2A	21130	-0.25	0.067	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 O GLYCAN BIOSYNTHESIS.

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

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

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	ATP2A3	ATP2A3	ATP2A3	257	0.36	0.016	YES
2	EIF2AK3	EIF2AK3	EIF2AK3	348	0.33	0.036	YES
3	BACE2	BACE2	BACE2	450	0.3	0.054	YES
4	CASP7	CASP7	CASP7	585	0.26	0.067	YES
5	IL1B	IL1B	IL1B	728	0.24	0.078	YES
6	BAD	BAD	BAD	1217	0.18	0.07	YES
7	CACNA1F	CACNA1F	CACNA1F	1241	0.18	0.083	YES
8	UQCRHL	UQCRHL	UQCRHL	1474	0.16	0.085	YES
9	ERN1	ERN1	ERN1	1527	0.16	0.094	YES
10	MAPK3	MAPK3	MAPK3	1579	0.16	0.1	YES
11	NDUFS7	NDUFS7	NDUFS7	1614	0.15	0.11	YES
12	UQCR10	UQCR10	UQCR10	1820	0.14	0.12	YES
13	NDUFA2	NDUFA2	NDUFA2	1987	0.13	0.12	YES
14	UQCRQ	UQCRQ	UQCRQ	2086	0.13	0.12	YES
15	CAPN2	CAPN2	CAPN2	2234	0.12	0.12	YES
16	ATP5G3	ATP5G3	ATP5G3	2242	0.12	0.13	YES
17	NDUFA7	NDUFA7	NDUFA7	2381	0.11	0.14	YES
18	ITPR3	ITPR3	ITPR3	2442	0.11	0.14	YES
19	NDUFA1	NDUFA1	NDUFA1	2503	0.11	0.15	YES
20	NDUFB10	NDUFB10	NDUFB10	2665	0.1	0.15	YES
21	CHP2	CHP2	CHP2	2716	0.1	0.15	YES
22	UQCRC2	UQCRC2	UQCRC2	2729	0.1	0.16	YES
23	GNAQ	GNAQ	GNAQ	2857	0.097	0.16	YES
24	UQCRH	UQCRH	UQCRH	2915	0.095	0.16	YES
25	UQCRB	UQCRB	UQCRB	2939	0.095	0.17	YES
26	ATP5D	ATP5D	ATP5D	2969	0.094	0.18	YES
27	NDUFV2	NDUFV2	NDUFV2	3033	0.092	0.18	YES
28	NDUFB3	NDUFB3	NDUFB3	3085	0.09	0.18	YES
29	NDUFC1	NDUFC1	NDUFC1	3143	0.089	0.19	YES
30	NDUFA4	NDUFA4	NDUFA4	3193	0.088	0.19	YES
31	COX7B	COX7B	COX7B	3235	0.086	0.2	YES
32	COX4I1	COX4I1	COX4I1	3266	0.085	0.2	YES
33	NDUFS2	NDUFS2	NDUFS2	3273	0.085	0.21	YES
34	COX8A	COX8A	COX8A	3433	0.08	0.21	YES
35	UQCR11	UQCR11	UQCR11	3529	0.078	0.21	YES
36	MME	MME	MME	3551	0.077	0.21	YES
37	ATP5G2	ATP5G2	ATP5G2	3567	0.077	0.22	YES
38	ATP5F1	ATP5F1	ATP5F1	3568	0.077	0.22	YES
39	COX5A	COX5A	COX5A	3584	0.077	0.23	YES
40	FADD	FADD	FADD	3587	0.077	0.24	YES
41	NDUFA3	NDUFA3	NDUFA3	3592	0.077	0.24	YES
42	COX6B2	COX6B2	COX6B2	3608	0.076	0.25	YES
43	COX6A1	COX6A1	COX6A1	3643	0.075	0.25	YES
44	NDUFB1	NDUFB1	NDUFB1	3646	0.075	0.26	YES
45	NDUFB6	NDUFB6	NDUFB6	3676	0.074	0.26	YES
46	COX7C	COX7C	COX7C	3697	0.074	0.26	YES
47	APH1A	APH1A	APH1A	3713	0.073	0.27	YES
48	NDUFB7	NDUFB7	NDUFB7	3734	0.073	0.27	YES
49	NDUFS8	NDUFS8	NDUFS8	3760	0.072	0.28	YES
50	NDUFV1	NDUFV1	NDUFV1	3966	0.068	0.27	YES
51	NDUFS4	NDUFS4	NDUFS4	3996	0.067	0.28	YES
52	NDUFB5	NDUFB5	NDUFB5	4057	0.065	0.28	YES
53	NDUFB9	NDUFB9	NDUFB9	4073	0.065	0.28	YES
54	NDUFS3	NDUFS3	NDUFS3	4141	0.064	0.28	YES
55	COX5B	COX5B	COX5B	4219	0.062	0.29	YES
56	COX4I2	COX4I2	COX4I2	4311	0.06	0.29	YES
57	CASP9	CASP9	CASP9	4314	0.06	0.29	YES
58	CASP3	CASP3	CASP3	4389	0.058	0.29	YES
59	NDUFAB1	NDUFAB1	NDUFAB1	4527	0.055	0.29	YES
60	NDUFA6	NDUFA6	NDUFA6	4566	0.054	0.29	YES
61	COX7A2L	COX7A2L	COX7A2L	4681	0.052	0.29	YES
62	NDUFB4	NDUFB4	NDUFB4	4690	0.052	0.3	YES
63	NDUFS6	NDUFS6	NDUFS6	4693	0.052	0.3	YES
64	ATP5H	ATP5H	ATP5H	4813	0.049	0.3	YES
65	APAF1	APAF1	APAF1	4830	0.049	0.3	YES
66	COX6B1	COX6B1	COX6B1	4900	0.047	0.3	YES
67	TNFRSF1A	TNFRSF1A	TNFRSF1A	4915	0.047	0.3	YES
68	CALML6	CALML6	CALML6	4937	0.047	0.31	YES
69	PSEN1	PSEN1	PSEN1	5049	0.044	0.3	YES
70	CACNA1S	CACNA1S	CACNA1S	5063	0.044	0.31	YES
71	UQCRC1	UQCRC1	UQCRC1	5181	0.042	0.3	YES
72	NDUFA10	NDUFA10	NDUFA10	5303	0.04	0.3	YES
73	SDHA	SDHA	SDHA	5319	0.039	0.3	YES
74	ATP5G1	ATP5G1	ATP5G1	5364	0.039	0.3	YES
75	NDUFB8	NDUFB8	NDUFB8	5424	0.038	0.3	YES
76	COX6C	COX6C	COX6C	5441	0.037	0.31	YES
77	NDUFB2	NDUFB2	NDUFB2	5459	0.037	0.31	YES
78	CYCS	CYCS	CYCS	5477	0.037	0.31	YES
79	ATP5J	ATP5J	ATP5J	5566	0.035	0.31	YES
80	SDHC	SDHC	SDHC	5567	0.035	0.31	YES
81	TNF	TNF	TNF	5615	0.034	0.31	YES
82	FAS	FAS	FAS	5616	0.034	0.32	YES
83	NCSTN	NCSTN	NCSTN	5664	0.033	0.32	YES
84	ATP5A1	ATP5A1	ATP5A1	5723	0.032	0.32	YES
85	NDUFS5	NDUFS5	NDUFS5	5746	0.032	0.32	YES
86	CYC1	CYC1	CYC1	5783	0.032	0.32	YES
87	PSENEN	PSENEN	PSENEN	5935	0.029	0.31	NO
88	ATP5B	ATP5B	ATP5B	5973	0.028	0.31	NO
89	SDHB	SDHB	SDHB	6033	0.027	0.31	NO
90	ATP5E	ATP5E	ATP5E	6352	0.022	0.3	NO
91	COX7A2	COX7A2	COX7A2	6454	0.02	0.3	NO
92	PLCB2	PLCB2	PLCB2	6716	0.016	0.29	NO
93	CALML5	CALML5	CALML5	6797	0.014	0.28	NO
94	PLCB3	PLCB3	PLCB3	6869	0.013	0.28	NO
95	BID	BID	BID	7033	0.01	0.28	NO
96	PPP3R2	PPP3R2	PPP3R2	7080	0.0094	0.28	NO
97	CASP8	CASP8	CASP8	7236	0.0071	0.27	NO
98	CAPN1	CAPN1	CAPN1	7274	0.0064	0.27	NO
99	CALM3	CALM3	CALM3	7402	0.0046	0.26	NO
100	ATP5C1	ATP5C1	ATP5C1	7691	0.00038	0.25	NO
101	SDHD	SDHD	SDHD	7793	-0.0011	0.24	NO
102	GRIN2A	GRIN2A	GRIN2A	7839	-0.0018	0.24	NO
103	ITPR1	ITPR1	ITPR1	7955	-0.0033	0.24	NO
104	HSD17B10	HSD17B10	HSD17B10	7960	-0.0034	0.24	NO
105	NDUFS1	NDUFS1	NDUFS1	7975	-0.0037	0.24	NO
106	COX7B2	COX7B2	COX7B2	7998	-0.004	0.24	NO
107	UQCRFS1	UQCRFS1	UQCRFS1	8179	-0.0068	0.23	NO
108	ATF6	ATF6	ATF6	8430	-0.01	0.22	NO
109	NDUFA5	NDUFA5	NDUFA5	8625	-0.013	0.21	NO
110	LPL	LPL	LPL	8648	-0.013	0.21	NO
111	IDE	IDE	IDE	8726	-0.014	0.21	NO
112	NDUFA8	NDUFA8	NDUFA8	8769	-0.015	0.21	NO
113	CALM1	CALM1	CALM1	8836	-0.016	0.21	NO
114	CALM2	CALM2	CALM2	8956	-0.017	0.2	NO
115	ADAM10	ADAM10	ADAM10	9145	-0.02	0.2	NO
116	NDUFA9	NDUFA9	NDUFA9	9157	-0.02	0.2	NO
117	ATP2A1	ATP2A1	ATP2A1	9238	-0.021	0.19	NO
118	ATP2A2	ATP2A2	ATP2A2	9307	-0.022	0.19	NO
119	NDUFV3	NDUFV3	NDUFV3	9513	-0.025	0.19	NO
120	GAPDH	GAPDH	GAPDH	9534	-0.025	0.19	NO
121	APOE	APOE	APOE	10077	-0.032	0.16	NO
122	PPP3CA	PPP3CA	PPP3CA	10193	-0.034	0.16	NO
123	PPP3R1	PPP3R1	PPP3R1	10203	-0.034	0.16	NO
124	APP	APP	APP	10587	-0.04	0.15	NO
125	PLCB4	PLCB4	PLCB4	10975	-0.044	0.14	NO
126	CDK5	CDK5	CDK5	11043	-0.045	0.14	NO
127	PPP3CC	PPP3CC	PPP3CC	12595	-0.066	0.073	NO
128	MAPK1	MAPK1	MAPK1	13031	-0.073	0.059	NO
129	GSK3B	GSK3B	GSK3B	14068	-0.087	0.019	NO
130	COX8C	COX8C	COX8C	14888	-0.099	-0.01	NO
131	PSEN2	PSEN2	PSEN2	14909	-0.1	-0.0036	NO
132	NDUFA4L2	NDUFA4L2	NDUFA4L2	15502	-0.11	-0.022	NO
133	GRIN2C	GRIN2C	GRIN2C	15693	-0.11	-0.022	NO
134	GRIN2D	GRIN2D	GRIN2D	15805	-0.11	-0.018	NO
135	PPP3CB	PPP3CB	PPP3CB	16592	-0.13	-0.044	NO
136	SNCA	SNCA	SNCA	16676	-0.13	-0.038	NO
137	GRIN1	GRIN1	GRIN1	17255	-0.14	-0.054	NO
138	ADAM17	ADAM17	ADAM17	17343	-0.14	-0.047	NO
139	NAE1	NAE1	NAE1	17464	-0.14	-0.042	NO
140	ITPR2	ITPR2	ITPR2	18302	-0.16	-0.067	NO
141	COX7A1	COX7A1	COX7A1	18818	-0.17	-0.077	NO
142	LRP1	LRP1	LRP1	18949	-0.18	-0.07	NO
143	PLCB1	PLCB1	PLCB1	19091	-0.18	-0.063	NO
144	COX6A2	COX6A2	COX6A2	19321	-0.19	-0.06	NO
145	CACNA1D	CACNA1D	CACNA1D	19460	-0.19	-0.052	NO
146	CDK5R1	CDK5R1	CDK5R1	19761	-0.2	-0.05	NO
147	APBB1	APBB1	APBB1	20548	-0.23	-0.069	NO
148	CALML3	CALML3	CALML3	21522	-0.27	-0.092	NO
149	CACNA1C	CACNA1C	CACNA1C	21739	-0.29	-0.08	NO
150	GRIN2B	GRIN2B	GRIN2B	21837	-0.29	-0.063	NO
151	BACE1	BACE1	BACE1	21955	-0.3	-0.045	NO
152	NOS1	NOS1	NOS1	22054	-0.32	-0.026	NO
153	MAPT	MAPT	MAPT	22110	-0.32	-0.0052	NO
154	RYR3	RYR3	RYR3	22488	-0.39	0.0069	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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

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

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 clus4 enriched pathways

Table 6. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus4. 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 HIVNEF PATHWAY	56	genes.ES.table	0.43	1.5	0.1	0.19	0.89	0.45	0.27	0.33	0.12	0.004
BIOCARTA DEATH PATHWAY	31	genes.ES.table	0.58	1.8	0.015	0.097	0.4	0.32	0.14	0.28	0	0.009
BIOCARTA TNFR1 PATHWAY	28	genes.ES.table	0.54	1.7	0.03	0.11	0.54	0.39	0.21	0.31	0.046	0.004
KEGG GLYCOLYSIS GLUCONEOGENESIS	59	genes.ES.table	0.47	1.8	0.0066	0.088	0.44	0.44	0.19	0.36	0	0.004
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.76	2.2	0	0.0097	0.01	0.79	0.18	0.65	0	0.003
KEGG PENTOSE PHOSPHATE PATHWAY	25	genes.ES.table	0.6	1.9	0	0.054	0.14	0.44	0.14	0.38	0	0.01
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.66	2	0	0.038	0.086	0.59	0.17	0.49	0	0.006
KEGG FATTY ACID METABOLISM	39	genes.ES.table	0.51	1.6	0.039	0.14	0.67	0.51	0.18	0.42	0.069	0.006
KEGG OXIDATIVE PHOSPHORYLATION	112	genes.ES.table	0.45	1.6	0.12	0.15	0.71	0.48	0.24	0.37	0.078	0.004
KEGG PYRIMIDINE METABOLISM	94	genes.ES.table	0.46	1.6	0.031	0.14	0.7	0.44	0.18	0.36	0.071	0.004

genes ES table in pathway: BIOCARTA HIVNEF PATHWAY

Table S31. 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	PCK2	PCK2	PCK2	107	0.55	0.099	YES
2	PCK1	PCK1	PCK1	289	0.42	0.17	YES
3	IDH3A	IDH3A	IDH3A	585	0.33	0.22	YES
4	IDH2	IDH2	IDH2	701	0.3	0.27	YES
5	SUCLG1	SUCLG1	SUCLG1	842	0.28	0.32	YES
6	PDHA1	PDHA1	PDHA1	984	0.26	0.36	YES
7	SUCLG2	SUCLG2	SUCLG2	1097	0.25	0.4	YES
8	DLD	DLD	DLD	1125	0.25	0.45	YES
9	IDH3B	IDH3B	IDH3B	1634	0.21	0.47	YES
10	FH	FH	FH	1757	0.2	0.5	YES
11	DLST	DLST	DLST	1901	0.19	0.53	YES
12	SDHB	SDHB	SDHB	1912	0.19	0.56	YES
13	CS	CS	CS	2039	0.19	0.6	YES
14	DLAT	DLAT	DLAT	2580	0.16	0.6	YES
15	SUCLA2	SUCLA2	SUCLA2	2594	0.16	0.63	YES
16	IDH3G	IDH3G	IDH3G	2765	0.16	0.65	YES
17	ACO2	ACO2	ACO2	3065	0.14	0.67	YES
18	SDHD	SDHD	SDHD	3390	0.13	0.68	YES
19	MDH2	MDH2	MDH2	3453	0.13	0.7	YES
20	SDHA	SDHA	SDHA	3537	0.13	0.72	YES
21	IDH1	IDH1	IDH1	3858	0.12	0.73	YES
22	ACO1	ACO1	ACO1	3869	0.12	0.75	YES
23	OGDH	OGDH	OGDH	4156	0.11	0.76	YES
24	MDH1	MDH1	MDH1	4630	0.1	0.76	NO
25	PDHB	PDHB	PDHB	7603	0.042	0.64	NO
26	SDHC	SDHC	SDHC	9116	0.016	0.57	NO
27	PC	PC	PC	9307	0.013	0.57	NO
28	ACLY	ACLY	ACLY	10127	-0.00041	0.53	NO
29	OGDHL	OGDHL	OGDHL	16536	-0.13	0.27	NO

Figure S61. 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 HIVNEF PATHWAY.

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA HIVNEF 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 S32. 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	NOS2	NOS2	NOS2	15	0.79	0.065	YES
2	XDH	XDH	XDH	78	0.58	0.11	YES
3	FAR2	FAR2	FAR2	80	0.58	0.16	YES
4	EPHX2	EPHX2	EPHX2	131	0.52	0.2	YES
5	SLC27A2	SLC27A2	SLC27A2	403	0.37	0.22	YES
6	ACSL5	ACSL5	ACSL5	435	0.36	0.25	YES
7	AMACR	AMACR	AMACR	489	0.35	0.28	YES
8	PEX7	PEX7	PEX7	539	0.34	0.3	YES
9	DHRS4	DHRS4	DHRS4	663	0.31	0.32	YES
10	IDH2	IDH2	IDH2	701	0.3	0.34	YES
11	PXMP2	PXMP2	PXMP2	903	0.27	0.36	YES
12	PEX11A	PEX11A	PEX11A	908	0.27	0.38	YES
13	MLYCD	MLYCD	MLYCD	915	0.27	0.4	YES
14	DECR2	DECR2	DECR2	1040	0.26	0.42	YES
15	HMGCL	HMGCL	HMGCL	1126	0.25	0.44	YES
16	ACSL6	ACSL6	ACSL6	1253	0.24	0.45	YES
17	PEX1	PEX1	PEX1	1349	0.23	0.46	YES
18	HSD17B4	HSD17B4	HSD17B4	1393	0.22	0.48	YES
19	NUDT12	NUDT12	NUDT12	1597	0.21	0.49	YES
20	PEX6	PEX6	PEX6	1601	0.21	0.51	YES
21	ABCD4	ABCD4	ABCD4	1737	0.2	0.52	YES
22	ABCD3	ABCD3	ABCD3	1823	0.2	0.53	YES
23	PEX2	PEX2	PEX2	2557	0.16	0.51	YES
24	PEX11B	PEX11B	PEX11B	2613	0.16	0.52	YES
25	PEX11G	PEX11G	PEX11G	2702	0.16	0.53	YES
26	MVK	MVK	MVK	2782	0.15	0.54	YES
27	GSTK1	GSTK1	GSTK1	2791	0.15	0.55	YES
28	SCP2	SCP2	SCP2	3153	0.14	0.55	YES
29	ABCD1	ABCD1	ABCD1	3498	0.13	0.55	YES
30	IDH1	IDH1	IDH1	3858	0.12	0.54	YES
31	PEX14	PEX14	PEX14	3894	0.12	0.55	YES
32	CRAT	CRAT	CRAT	3975	0.12	0.55	YES
33	SOD1	SOD1	SOD1	3999	0.12	0.56	YES
34	PAOX	PAOX	PAOX	4098	0.11	0.57	YES
35	HACL1	HACL1	HACL1	4215	0.11	0.57	YES
36	ACAA1	ACAA1	ACAA1	4737	0.098	0.56	YES
37	PEX10	PEX10	PEX10	4896	0.094	0.56	YES
38	PEX16	PEX16	PEX16	5160	0.087	0.55	YES
39	AGXT	AGXT	AGXT	5256	0.085	0.56	YES
40	GNPAT	GNPAT	GNPAT	5272	0.084	0.56	YES
41	PEX26	PEX26	PEX26	5394	0.081	0.56	YES
42	PRDX5	PRDX5	PRDX5	5448	0.08	0.57	YES
43	AGPS	AGPS	AGPS	5469	0.08	0.57	YES
44	PECR	PECR	PECR	5475	0.08	0.58	YES
45	PXMP4	PXMP4	PXMP4	5754	0.074	0.57	NO
46	CAT	CAT	CAT	5794	0.074	0.58	NO
47	PEX5	PEX5	PEX5	6029	0.069	0.57	NO
48	NUDT19	NUDT19	NUDT19	6216	0.065	0.57	NO
49	EHHADH	EHHADH	EHHADH	6260	0.065	0.58	NO
50	PEX13	PEX13	PEX13	7053	0.05	0.55	NO
51	ACOX3	ACOX3	ACOX3	7245	0.048	0.54	NO
52	PHYH	PHYH	PHYH	8114	0.033	0.5	NO
53	HAO2	HAO2	HAO2	8126	0.033	0.51	NO
54	PIPOX	PIPOX	PIPOX	8493	0.027	0.49	NO
55	ACOT8	ACOT8	ACOT8	9681	0.0068	0.44	NO
56	PRDX1	PRDX1	PRDX1	9838	0.004	0.43	NO
57	SOD2	SOD2	SOD2	9883	0.0034	0.43	NO
58	FAR1	FAR1	FAR1	10792	-0.012	0.39	NO
59	MPV17	MPV17	MPV17	10874	-0.014	0.39	NO
60	SLC25A17	SLC25A17	SLC25A17	11026	-0.016	0.38	NO
61	ACOX1	ACOX1	ACOX1	11733	-0.029	0.36	NO
62	CROT	CROT	CROT	12363	-0.041	0.33	NO
63	PEX3	PEX3	PEX3	12479	-0.043	0.33	NO
64	BAAT	BAAT	BAAT	12877	-0.05	0.32	NO
65	ACSL3	ACSL3	ACSL3	12946	-0.052	0.32	NO
66	PMVK	PMVK	PMVK	13379	-0.06	0.3	NO
67	MPV17L	MPV17L	MPV17L	14710	-0.087	0.25	NO
68	ACSL4	ACSL4	ACSL4	14784	-0.089	0.26	NO
69	HAO1	HAO1	HAO1	15983	-0.11	0.21	NO
70	ACSL1	ACSL1	ACSL1	16033	-0.12	0.22	NO
71	DAO	DAO	DAO	16988	-0.14	0.19	NO
72	PEX12	PEX12	PEX12	17101	-0.14	0.2	NO
73	DDO	DDO	DDO	19406	-0.21	0.11	NO
74	ABCD2	ABCD2	ABCD2	22229	-0.38	0.018	NO

Figure S63. 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 S64. 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 TNFR1 PATHWAY

Table S33. 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	KHK	KHK	KHK	114	0.54	0.084	YES
2	ALDOB	ALDOB	ALDOB	121	0.53	0.17	YES
3	PFKFB2	PFKFB2	PFKFB2	152	0.5	0.25	YES
4	PFKFB4	PFKFB4	PFKFB4	177	0.48	0.33	YES
5	SORD	SORD	SORD	293	0.42	0.4	YES
6	FUK	FUK	FUK	442	0.36	0.45	YES
7	PFKL	PFKL	PFKL	1425	0.22	0.44	YES
8	PMM2	PMM2	PMM2	1503	0.22	0.48	YES
9	FBP1	FBP1	FBP1	1543	0.21	0.51	YES
10	GMDS	GMDS	GMDS	1745	0.2	0.53	YES
11	PFKP	PFKP	PFKP	2254	0.18	0.54	YES
12	PMM1	PMM1	PMM1	2429	0.17	0.56	YES
13	ALDOC	ALDOC	ALDOC	2600	0.16	0.58	YES
14	TPI1	TPI1	TPI1	2922	0.15	0.59	YES
15	GMPPB	GMPPB	GMPPB	3006	0.15	0.61	YES
16	TSTA3	TSTA3	TSTA3	3123	0.14	0.63	YES
17	AKR1B10	AKR1B10	AKR1B10	3317	0.14	0.64	YES
18	GMPPA	GMPPA	GMPPA	3647	0.13	0.65	YES
19	MPI	MPI	MPI	3944	0.12	0.66	YES
20	MTMR6	MTMR6	MTMR6	4978	0.092	0.63	NO
21	MTMR1	MTMR1	MTMR1	5546	0.079	0.61	NO
22	PFKFB3	PFKFB3	PFKFB3	6669	0.057	0.57	NO
23	HK2	HK2	HK2	7261	0.047	0.56	NO
24	MTMR7	MTMR7	MTMR7	7739	0.039	0.54	NO
25	HK3	HK3	HK3	7984	0.035	0.54	NO
26	FBP2	FBP2	FBP2	8396	0.028	0.52	NO
27	PHPT1	PHPT1	PHPT1	9234	0.014	0.49	NO
28	PFKM	PFKM	PFKM	9252	0.014	0.49	NO
29	PFKFB1	PFKFB1	PFKFB1	10284	-0.0034	0.44	NO
30	MTMR2	MTMR2	MTMR2	15124	-0.096	0.25	NO
31	HK1	HK1	HK1	20630	-0.26	0.045	NO
32	AKR1B1	AKR1B1	AKR1B1	20840	-0.27	0.08	NO

Figure S65. 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 TNFR1 PATHWAY.

Figure S66. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 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 S34. 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	ALDOB	ALDOB	ALDOB	121	0.53	0.14	YES
2	RBKS	RBKS	RBKS	694	0.3	0.2	YES
3	DERA	DERA	DERA	799	0.28	0.28	YES
4	RPIA	RPIA	RPIA	940	0.27	0.35	YES
5	PFKL	PFKL	PFKL	1425	0.22	0.39	YES
6	FBP1	FBP1	FBP1	1543	0.21	0.44	YES
7	GPI	GPI	GPI	2143	0.18	0.47	YES
8	PFKP	PFKP	PFKP	2254	0.18	0.51	YES
9	ALDOC	ALDOC	ALDOC	2600	0.16	0.54	YES
10	PGD	PGD	PGD	2968	0.15	0.57	YES
11	PGM2	PGM2	PGM2	3087	0.14	0.6	YES
12	PGM1	PGM1	PGM1	4089	0.11	0.59	NO
13	TKT	TKT	TKT	7538	0.043	0.45	NO
14	TALDO1	TALDO1	TALDO1	7648	0.041	0.46	NO
15	FBP2	FBP2	FBP2	8396	0.028	0.43	NO
16	H6PD	H6PD	H6PD	9105	0.016	0.4	NO
17	RPE	RPE	RPE	9249	0.014	0.4	NO
18	PFKM	PFKM	PFKM	9252	0.014	0.4	NO
19	PGLS	PGLS	PGLS	9303	0.013	0.41	NO
20	PRPS2	PRPS2	PRPS2	11088	-0.018	0.33	NO
21	LOC729020	LOC729020	LOC729020	13427	-0.061	0.25	NO
22	TKTL2	TKTL2	TKTL2	13829	-0.069	0.25	NO
23	G6PD	G6PD	G6PD	15981	-0.11	0.18	NO
24	PRPS1	PRPS1	PRPS1	17896	-0.16	0.14	NO
25	TKTL1	TKTL1	TKTL1	20136	-0.23	0.11	NO

Figure S67. 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 S68. 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 CITRATE CYCLE TCA CYCLE

Table S35. 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	ACADS	ACADS	ACADS	238	0.44	0.062	YES
2	ACAA2	ACAA2	ACAA2	533	0.34	0.1	YES
3	BCKDHB	BCKDHB	BCKDHB	632	0.32	0.15	YES
4	HADH	HADH	HADH	746	0.29	0.19	YES
5	AUH	AUH	AUH	928	0.27	0.23	YES
6	HIBCH	HIBCH	HIBCH	969	0.26	0.27	YES
7	HMGCS2	HMGCS2	HMGCS2	999	0.26	0.31	YES
8	DLD	DLD	DLD	1125	0.25	0.35	YES
9	HMGCL	HMGCL	HMGCL	1126	0.25	0.39	YES
10	MCCC1	MCCC1	MCCC1	1351	0.23	0.41	YES
11	PCCA	PCCA	PCCA	1590	0.21	0.44	YES
12	HADHA	HADHA	HADHA	1893	0.19	0.46	YES
13	PCCB	PCCB	PCCB	1899	0.19	0.49	YES
14	MCCC2	MCCC2	MCCC2	2087	0.18	0.51	YES
15	HADHB	HADHB	HADHB	2266	0.18	0.53	YES
16	MCEE	MCEE	MCEE	2339	0.17	0.56	YES
17	ECHS1	ECHS1	ECHS1	2671	0.16	0.57	YES
18	MUT	MUT	MUT	2986	0.15	0.58	YES
19	ACAT2	ACAT2	ACAT2	3244	0.14	0.59	YES
20	ALDH1B1	ALDH1B1	ALDH1B1	3608	0.13	0.59	YES
21	ALDH9A1	ALDH9A1	ALDH9A1	3638	0.13	0.61	YES
22	HIBADH	HIBADH	HIBADH	3824	0.12	0.62	YES
23	ACADSB	ACADSB	ACADSB	3958	0.12	0.64	YES
24	ALDH2	ALDH2	ALDH2	4143	0.11	0.65	YES
25	ACAA1	ACAA1	ACAA1	4737	0.098	0.64	NO
26	HMGCS1	HMGCS1	HMGCS1	6066	0.068	0.59	NO
27	EHHADH	EHHADH	EHHADH	6260	0.065	0.59	NO
28	IVD	IVD	IVD	6492	0.06	0.59	NO
29	HSD17B10	HSD17B10	HSD17B10	6907	0.053	0.58	NO
30	ACADM	ACADM	ACADM	7577	0.042	0.56	NO
31	ACAD8	ACAD8	ACAD8	8023	0.034	0.54	NO
32	ALDH6A1	ALDH6A1	ALDH6A1	8033	0.034	0.55	NO
33	ABAT	ABAT	ABAT	8361	0.029	0.54	NO
34	ALDH3A2	ALDH3A2	ALDH3A2	8610	0.025	0.53	NO
35	BCAT2	BCAT2	BCAT2	9610	0.008	0.49	NO
36	ALDH7A1	ALDH7A1	ALDH7A1	10844	-0.013	0.44	NO
37	OXCT1	OXCT1	OXCT1	10898	-0.014	0.44	NO
38	OXCT2	OXCT2	OXCT2	10909	-0.014	0.44	NO
39	ACAT1	ACAT1	ACAT1	12423	-0.042	0.38	NO
40	IL4I1	IL4I1	IL4I1	13501	-0.062	0.34	NO
41	BCKDHA	BCKDHA	BCKDHA	13806	-0.068	0.34	NO
42	DBT	DBT	DBT	14361	-0.08	0.33	NO
43	AOX1	AOX1	AOX1	20374	-0.24	0.1	NO

Figure S69. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG CITRATE CYCLE TCA CYCLE.

Figure S70. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CITRATE CYCLE TCA CYCLE, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PENTOSE PHOSPHATE PATHWAY

Table S36. 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	PLCB3	PLCB3	PLCB3	128	0.52	0.025	YES
2	NDUFA9	NDUFA9	NDUFA9	726	0.3	0.016	YES
3	CREB3L1	CREB3L1	CREB3L1	1242	0.24	0.0067	YES
4	UQCRC2	UQCRC2	UQCRC2	1277	0.23	0.019	YES
5	NDUFA10	NDUFA10	NDUFA10	1285	0.23	0.032	YES
6	CYC1	CYC1	CYC1	1452	0.22	0.038	YES
7	ATP5G3	ATP5G3	ATP5G3	1542	0.21	0.046	YES
8	APAF1	APAF1	APAF1	1544	0.21	0.059	YES
9	NDUFS7	NDUFS7	NDUFS7	1624	0.21	0.068	YES
10	COX6C	COX6C	COX6C	1911	0.19	0.066	YES
11	SDHB	SDHB	SDHB	1912	0.19	0.078	YES
12	PPARG	PPARG	PPARG	1949	0.19	0.087	YES
13	CASP3	CASP3	CASP3	1969	0.19	0.098	YES
14	CYCS	CYCS	CYCS	2038	0.19	0.1	YES
15	VDAC3	VDAC3	VDAC3	2092	0.18	0.11	YES
16	NDUFS2	NDUFS2	NDUFS2	2110	0.18	0.12	YES
17	UQCRC1	UQCRC1	UQCRC1	2166	0.18	0.13	YES
18	COX5A	COX5A	COX5A	2213	0.18	0.14	YES
19	SLC25A5	SLC25A5	SLC25A5	2291	0.18	0.15	YES
20	NDUFA5	NDUFA5	NDUFA5	2382	0.17	0.15	YES
21	RCOR1	RCOR1	RCOR1	2417	0.17	0.16	YES
22	TBPL1	TBPL1	TBPL1	2468	0.17	0.17	YES
23	VDAC1	VDAC1	VDAC1	2501	0.16	0.18	YES
24	GRIN2B	GRIN2B	GRIN2B	2514	0.16	0.19	YES
25	ATP5F1	ATP5F1	ATP5F1	2527	0.16	0.2	YES
26	ATP5A1	ATP5A1	ATP5A1	2597	0.16	0.2	YES
27	ATP5G1	ATP5G1	ATP5G1	2620	0.16	0.21	YES
28	ATP5B	ATP5B	ATP5B	2797	0.15	0.21	YES
29	NDUFB2	NDUFB2	NDUFB2	2806	0.15	0.22	YES
30	NDUFS1	NDUFS1	NDUFS1	2865	0.15	0.23	YES
31	NDUFA1	NDUFA1	NDUFA1	2866	0.15	0.24	YES
32	PPID	PPID	PPID	2917	0.15	0.24	YES
33	ATP5D	ATP5D	ATP5D	2933	0.15	0.25	YES
34	CASP8	CASP8	CASP8	2985	0.15	0.26	YES
35	DNAH3	DNAH3	DNAH3	3086	0.14	0.26	YES
36	UQCRFS1	UQCRFS1	UQCRFS1	3092	0.14	0.27	YES
37	CASP9	CASP9	CASP9	3145	0.14	0.27	YES
38	NDUFV1	NDUFV1	NDUFV1	3285	0.14	0.28	YES
39	NDUFA4L2	NDUFA4L2	NDUFA4L2	3344	0.14	0.28	YES
40	SDHD	SDHD	SDHD	3390	0.13	0.29	YES
41	SDHA	SDHA	SDHA	3537	0.13	0.29	YES
42	UQCRH	UQCRH	UQCRH	3547	0.13	0.3	YES
43	UQCRHL	UQCRHL	UQCRHL	3729	0.12	0.29	YES
44	HTT	HTT	HTT	3818	0.12	0.3	YES
45	COX5B	COX5B	COX5B	3827	0.12	0.3	YES
46	COX4I1	COX4I1	COX4I1	3846	0.12	0.31	YES
47	NDUFS3	NDUFS3	NDUFS3	3847	0.12	0.32	YES
48	ATP5C1	ATP5C1	ATP5C1	3865	0.12	0.32	YES
49	COX6A1	COX6A1	COX6A1	3925	0.12	0.33	YES
50	NDUFAB1	NDUFAB1	NDUFAB1	3990	0.12	0.33	YES
51	SOD1	SOD1	SOD1	3999	0.12	0.34	YES
52	TP53	TP53	TP53	4056	0.12	0.34	YES
53	TAF4	TAF4	TAF4	4136	0.11	0.35	YES
54	UQCRB	UQCRB	UQCRB	4148	0.11	0.35	YES
55	UQCR10	UQCR10	UQCR10	4337	0.11	0.35	YES
56	NDUFB9	NDUFB9	NDUFB9	4371	0.11	0.36	YES
57	NDUFA8	NDUFA8	NDUFA8	4446	0.1	0.36	YES
58	HDAC1	HDAC1	HDAC1	4488	0.1	0.36	YES
59	DNAH1	DNAH1	DNAH1	4602	0.1	0.36	YES
60	COX7B	COX7B	COX7B	4635	0.1	0.37	YES
61	UQCRQ	UQCRQ	UQCRQ	4666	0.1	0.37	YES
62	TAF4B	TAF4B	TAF4B	4714	0.098	0.38	YES
63	NDUFA6	NDUFA6	NDUFA6	4762	0.097	0.38	YES
64	NDUFB3	NDUFB3	NDUFB3	5042	0.09	0.37	YES
65	PPARGC1A	PPARGC1A	PPARGC1A	5045	0.09	0.38	YES
66	VDAC2	VDAC2	VDAC2	5056	0.09	0.38	YES
67	TFAM	TFAM	TFAM	5165	0.087	0.38	YES
68	COX7A2	COX7A2	COX7A2	5176	0.086	0.39	YES
69	DCTN4	DCTN4	DCTN4	5347	0.083	0.38	YES
70	TBP	TBP	TBP	5354	0.082	0.39	YES
71	COX6B1	COX6B1	COX6B1	5370	0.082	0.39	YES
72	ATP5J	ATP5J	ATP5J	5405	0.081	0.4	YES
73	NDUFB6	NDUFB6	NDUFB6	5655	0.076	0.39	NO
74	NDUFC1	NDUFC1	NDUFC1	5742	0.075	0.39	NO
75	CREB3L3	CREB3L3	CREB3L3	5930	0.071	0.39	NO
76	NDUFS4	NDUFS4	NDUFS4	6060	0.068	0.38	NO
77	COX7A2L	COX7A2L	COX7A2L	6140	0.067	0.38	NO
78	HDAC2	HDAC2	HDAC2	6280	0.064	0.38	NO
79	PLCB4	PLCB4	PLCB4	6371	0.063	0.38	NO
80	CLTB	CLTB	CLTB	6507	0.06	0.38	NO
81	NDUFA7	NDUFA7	NDUFA7	6658	0.058	0.38	NO
82	COX8A	COX8A	COX8A	6692	0.057	0.38	NO
83	DCTN2	DCTN2	DCTN2	6886	0.054	0.37	NO
84	NDUFA2	NDUFA2	NDUFA2	6927	0.053	0.37	NO
85	COX7C	COX7C	COX7C	6992	0.052	0.37	NO
86	NDUFB10	NDUFB10	NDUFB10	7044	0.051	0.38	NO
87	NDUFV3	NDUFV3	NDUFV3	7239	0.048	0.37	NO
88	POLR2H	POLR2H	POLR2H	7363	0.046	0.37	NO
89	NDUFB1	NDUFB1	NDUFB1	7373	0.046	0.37	NO
90	ATP5H	ATP5H	ATP5H	7395	0.045	0.37	NO
91	SLC25A6	SLC25A6	SLC25A6	7640	0.041	0.36	NO
92	UQCR11	UQCR11	UQCR11	7702	0.04	0.36	NO
93	CLTC	CLTC	CLTC	7756	0.039	0.36	NO
94	POLR2E	POLR2E	POLR2E	7819	0.038	0.36	NO
95	NDUFB8	NDUFB8	NDUFB8	7953	0.036	0.36	NO
96	EP300	EP300	EP300	8165	0.032	0.35	NO
97	CLTA	CLTA	CLTA	8300	0.03	0.34	NO
98	NDUFA4	NDUFA4	NDUFA4	8310	0.029	0.35	NO
99	IFT57	IFT57	IFT57	8350	0.029	0.35	NO
100	AP2B1	AP2B1	AP2B1	8354	0.029	0.35	NO
101	TBPL2	TBPL2	TBPL2	8560	0.026	0.34	NO
102	NDUFS5	NDUFS5	NDUFS5	8575	0.026	0.34	NO
103	NRF1	NRF1	NRF1	8599	0.025	0.34	NO
104	AP2S1	AP2S1	AP2S1	8777	0.022	0.34	NO
105	BBC3	BBC3	BBC3	8911	0.02	0.33	NO
106	POLR2A	POLR2A	POLR2A	8951	0.019	0.33	NO
107	ATP5G2	ATP5G2	ATP5G2	9023	0.018	0.33	NO
108	SDHC	SDHC	SDHC	9116	0.016	0.32	NO
109	POLR2K	POLR2K	POLR2K	9120	0.016	0.32	NO
110	NDUFB7	NDUFB7	NDUFB7	9501	0.0099	0.31	NO
111	POLR2L	POLR2L	POLR2L	9567	0.0088	0.31	NO
112	CREBBP	CREBBP	CREBBP	9629	0.0076	0.3	NO
113	SP1	SP1	SP1	9718	0.0061	0.3	NO
114	NDUFB4	NDUFB4	NDUFB4	9763	0.0054	0.3	NO
115	POLR2D	POLR2D	POLR2D	9818	0.0044	0.3	NO
116	SOD2	SOD2	SOD2	9883	0.0034	0.29	NO
117	NDUFB5	NDUFB5	NDUFB5	9896	0.0032	0.29	NO
118	BAX	BAX	BAX	9966	0.0022	0.29	NO
119	DNAL4	DNAL4	DNAL4	10038	0.0011	0.29	NO
120	POLR2F	POLR2F	POLR2F	10117	-0.00026	0.28	NO
121	POLR2G	POLR2G	POLR2G	10120	-0.00037	0.28	NO
122	POLR2B	POLR2B	POLR2B	10317	-0.004	0.28	NO
123	NDUFS6	NDUFS6	NDUFS6	10564	-0.0082	0.26	NO
124	POLR2C	POLR2C	POLR2C	10673	-0.01	0.26	NO
125	GPX1	GPX1	GPX1	10788	-0.012	0.26	NO
126	NDUFA3	NDUFA3	NDUFA3	10875	-0.014	0.25	NO
127	REST	REST	REST	10891	-0.014	0.25	NO
128	NDUFV2	NDUFV2	NDUFV2	11062	-0.017	0.25	NO
129	COX6B2	COX6B2	COX6B2	11214	-0.02	0.24	NO
130	ATP5E	ATP5E	ATP5E	11295	-0.021	0.24	NO
131	GNAQ	GNAQ	GNAQ	11538	-0.025	0.23	NO
132	SIN3A	SIN3A	SIN3A	11568	-0.026	0.23	NO
133	AP2A1	AP2A1	AP2A1	11637	-0.027	0.23	NO
134	NDUFS8	NDUFS8	NDUFS8	11647	-0.028	0.23	NO
135	UCP1	UCP1	UCP1	11821	-0.031	0.22	NO
136	AP2M1	AP2M1	AP2M1	11838	-0.031	0.22	NO
137	CREB3L2	CREB3L2	CREB3L2	12054	-0.035	0.22	NO
138	DNAI2	DNAI2	DNAI2	12149	-0.037	0.22	NO
139	CREB1	CREB1	CREB1	12319	-0.04	0.21	NO
140	DCTN1	DCTN1	DCTN1	12353	-0.041	0.21	NO
141	POLR2J	POLR2J	POLR2J	12581	-0.045	0.2	NO
142	POLR2I	POLR2I	POLR2I	12707	-0.047	0.2	NO
143	CLTCL1	CLTCL1	CLTCL1	12718	-0.047	0.2	NO
144	AP2A2	AP2A2	AP2A2	12863	-0.05	0.2	NO
145	POLR2J2	POLR2J2	POLR2J2	12923	-0.051	0.2	NO
146	CREB3	CREB3	CREB3	13343	-0.059	0.18	NO
147	COX4I2	COX4I2	COX4I2	13563	-0.064	0.18	NO
148	GRIN1	GRIN1	GRIN1	13741	-0.067	0.18	NO
149	SLC25A4	SLC25A4	SLC25A4	14134	-0.075	0.16	NO
150	GRM5	GRM5	GRM5	14522	-0.083	0.15	NO
151	DNAI1	DNAI1	DNAI1	14610	-0.085	0.15	NO
152	BDNF	BDNF	BDNF	14728	-0.087	0.15	NO
153	SLC25A31	SLC25A31	SLC25A31	14876	-0.09	0.15	NO
154	DNAH2	DNAH2	DNAH2	15304	-0.1	0.14	NO
155	PLCB1	PLCB1	PLCB1	15428	-0.1	0.14	NO
156	HAP1	HAP1	HAP1	15936	-0.11	0.12	NO
157	CREB3L4	CREB3L4	CREB3L4	16116	-0.12	0.12	NO
158	PLCB2	PLCB2	PLCB2	16348	-0.12	0.12	NO
159	COX8C	COX8C	COX8C	16605	-0.13	0.11	NO
160	POLR2J3	POLR2J3	POLR2J3	17756	-0.16	0.072	NO
161	COX7B2	COX7B2	COX7B2	18102	-0.17	0.066	NO
162	DLG4	DLG4	DLG4	18146	-0.17	0.074	NO
163	CREB5	CREB5	CREB5	18354	-0.17	0.075	NO
164	COX7A1	COX7A1	COX7A1	19803	-0.22	0.023	NO
165	DNAL1	DNAL1	DNAL1	20008	-0.23	0.028	NO
166	ITPR1	ITPR1	ITPR1	20436	-0.25	0.023	NO
167	TGM2	TGM2	TGM2	20611	-0.26	0.03	NO
168	HIP1	HIP1	HIP1	21303	-0.29	0.017	NO
169	COX6A2	COX6A2	COX6A2	21421	-0.3	0.029	NO
170	DNALI1	DNALI1	DNALI1	22479	-0.43	0.0073	NO

Figure S71. 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 S72. 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 S37. 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	SEPSECS	SEPSECS	SEPSECS	544	0.34	0.029	YES
2	AARS2	AARS2	AARS2	546	0.33	0.082	YES
3	PARS2	PARS2	PARS2	590	0.32	0.13	YES
4	MARS2	MARS2	MARS2	659	0.31	0.18	YES
5	FARSB	FARSB	FARSB	738	0.3	0.22	YES
6	LARS2	LARS2	LARS2	812	0.28	0.26	YES
7	DARS2	DARS2	DARS2	920	0.27	0.3	YES
8	WARS2	WARS2	WARS2	939	0.27	0.34	YES
9	EPRS	EPRS	EPRS	1608	0.21	0.35	YES
10	YARS2	YARS2	YARS2	1850	0.2	0.37	YES
11	HARS2	HARS2	HARS2	1875	0.19	0.4	YES
12	IARS	IARS	IARS	1926	0.19	0.43	YES
13	NARS	NARS	NARS	1991	0.19	0.45	YES
14	NARS2	NARS2	NARS2	2104	0.18	0.48	YES
15	IARS2	IARS2	IARS2	2246	0.18	0.5	YES
16	LARS	LARS	LARS	2341	0.17	0.52	YES
17	QARS	QARS	QARS	2453	0.17	0.54	YES
18	SARS	SARS	SARS	2482	0.17	0.57	YES
19	MTFMT	MTFMT	MTFMT	2703	0.16	0.58	YES
20	CARS2	CARS2	CARS2	2816	0.15	0.6	YES
21	FARSA	FARSA	FARSA	3600	0.13	0.59	YES
22	PSTK	PSTK	PSTK	3792	0.12	0.6	YES
23	EARS2	EARS2	EARS2	4034	0.12	0.61	YES
24	YARS	YARS	YARS	4257	0.11	0.62	YES
25	RARS	RARS	RARS	4287	0.11	0.63	YES
26	GARS	GARS	GARS	4365	0.11	0.64	YES
27	VARS	VARS	VARS	4742	0.097	0.64	YES
28	VARS2	VARS2	VARS2	4848	0.095	0.66	YES
29	KARS	KARS	KARS	5093	0.089	0.66	YES
30	CARS	CARS	CARS	5112	0.088	0.67	YES
31	RARS2	RARS2	RARS2	5617	0.077	0.66	NO
32	TARS	TARS	TARS	6122	0.067	0.65	NO
33	HARS	HARS	HARS	6809	0.055	0.63	NO
34	AARS	AARS	AARS	7303	0.047	0.61	NO
35	FARS2	FARS2	FARS2	7874	0.037	0.59	NO
36	MARS	MARS	MARS	8360	0.029	0.58	NO
37	DARS	DARS	DARS	9268	0.014	0.54	NO
38	SARS2	SARS2	SARS2	14577	-0.084	0.32	NO
39	TARSL2	TARSL2	TARSL2	14745	-0.088	0.32	NO
40	WARS	WARS	WARS	17714	-0.16	0.22	NO

Figure S73. 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 S74. 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 FATTY ACID METABOLISM

Table S38. 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	ACSS2	ACSS2	ACSS2	81	0.58	0.1	YES
2	PCK2	PCK2	PCK2	107	0.55	0.2	YES
3	PCK1	PCK1	PCK1	289	0.42	0.26	YES
4	PDHA1	PDHA1	PDHA1	984	0.26	0.28	YES
5	ME2	ME2	ME2	990	0.26	0.33	YES
6	ACSS1	ACSS1	ACSS1	1032	0.26	0.37	YES
7	DLD	DLD	DLD	1125	0.25	0.41	YES
8	PKLR	PKLR	PKLR	1881	0.19	0.41	YES
9	ACYP1	ACYP1	ACYP1	2157	0.18	0.43	YES
10	DLAT	DLAT	DLAT	2580	0.16	0.44	YES
11	ACAT2	ACAT2	ACAT2	3244	0.14	0.44	YES
12	MDH2	MDH2	MDH2	3453	0.13	0.45	YES
13	ALDH1B1	ALDH1B1	ALDH1B1	3608	0.13	0.47	YES
14	ME1	ME1	ME1	3631	0.13	0.49	YES
15	ALDH9A1	ALDH9A1	ALDH9A1	3638	0.13	0.51	YES
16	ACACA	ACACA	ACACA	4088	0.11	0.51	YES
17	ALDH2	ALDH2	ALDH2	4143	0.11	0.53	YES
18	LDHD	LDHD	LDHD	4403	0.11	0.54	YES
19	MDH1	MDH1	MDH1	4630	0.1	0.55	YES
20	HAGHL	HAGHL	HAGHL	4882	0.094	0.55	YES
21	ACOT12	ACOT12	ACOT12	5869	0.072	0.52	NO
22	LDHA	LDHA	LDHA	5935	0.071	0.53	NO
23	GRHPR	GRHPR	GRHPR	7056	0.05	0.49	NO
24	PDHB	PDHB	PDHB	7603	0.042	0.47	NO
25	PKM2	PKM2	PKM2	7901	0.036	0.47	NO
26	GLO1	GLO1	GLO1	8488	0.027	0.45	NO
27	ALDH3A2	ALDH3A2	ALDH3A2	8610	0.025	0.44	NO
28	LDHAL6B	LDHAL6B	LDHAL6B	9043	0.017	0.43	NO
29	PC	PC	PC	9307	0.013	0.42	NO
30	ACACB	ACACB	ACACB	10755	-0.012	0.36	NO
31	ALDH7A1	ALDH7A1	ALDH7A1	10844	-0.013	0.36	NO
32	HAGH	HAGH	HAGH	11860	-0.032	0.32	NO
33	ACAT1	ACAT1	ACAT1	12423	-0.042	0.3	NO
34	ME3	ME3	ME3	14059	-0.073	0.24	NO
35	ACYP2	ACYP2	ACYP2	15545	-0.1	0.19	NO
36	LDHAL6A	LDHAL6A	LDHAL6A	15580	-0.1	0.21	NO
37	AKR1B1	AKR1B1	AKR1B1	20840	-0.27	0.026	NO
38	LDHB	LDHB	LDHB	21458	-0.3	0.052	NO

Figure S75. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG FATTY ACID METABOLISM.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG FATTY ACID METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

Table S39. 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	OTC	OTC	OTC	14	0.79	0.068	YES
2	NOS2	NOS2	NOS2	15	0.79	0.14	YES
3	CKMT1A	CKMT1A	CKMT1A	23	0.74	0.2	YES
4	CKMT1B	CKMT1B	CKMT1B	30	0.7	0.26	YES
5	AGMAT	AGMAT	AGMAT	108	0.54	0.31	YES
6	MAOA	MAOA	MAOA	133	0.51	0.35	YES
7	ABP1	ABP1	ABP1	195	0.47	0.39	YES
8	NAGS	NAGS	NAGS	477	0.35	0.41	YES
9	ASS1	ASS1	ASS1	486	0.35	0.44	YES
10	CPS1	CPS1	CPS1	569	0.33	0.46	YES
11	ACY1	ACY1	ACY1	853	0.28	0.47	YES
12	GOT1	GOT1	GOT1	875	0.28	0.5	YES
13	ASL	ASL	ASL	1103	0.25	0.51	YES
14	GLS	GLS	GLS	1647	0.21	0.5	YES
15	SAT2	SAT2	SAT2	1710	0.2	0.52	YES
16	OAT	OAT	OAT	1942	0.19	0.52	YES
17	P4HA2	P4HA2	P4HA2	2486	0.17	0.51	NO
18	ALDH18A1	ALDH18A1	ALDH18A1	3345	0.14	0.49	NO
19	ALDH1B1	ALDH1B1	ALDH1B1	3608	0.13	0.49	NO
20	ALDH9A1	ALDH9A1	ALDH9A1	3638	0.13	0.5	NO
21	ODC1	ODC1	ODC1	3735	0.12	0.5	NO
22	AMD1	AMD1	AMD1	3926	0.12	0.5	NO
23	ALDH2	ALDH2	ALDH2	4143	0.11	0.5	NO
24	ARG2	ARG2	ARG2	4607	0.1	0.49	NO
25	GOT2	GOT2	GOT2	4835	0.095	0.49	NO
26	PYCRL	PYCRL	PYCRL	4915	0.093	0.5	NO
27	PYCR1	PYCR1	PYCR1	5157	0.087	0.49	NO
28	SMS	SMS	SMS	6424	0.062	0.44	NO
29	PRODH2	PRODH2	PRODH2	7661	0.04	0.39	NO
30	PYCR2	PYCR2	PYCR2	7754	0.039	0.39	NO
31	LAP3	LAP3	LAP3	7821	0.038	0.39	NO
32	NOS3	NOS3	NOS3	8235	0.031	0.38	NO
33	GLS2	GLS2	GLS2	8336	0.029	0.37	NO
34	ALDH3A2	ALDH3A2	ALDH3A2	8610	0.025	0.36	NO
35	P4HA1	P4HA1	P4HA1	9038	0.017	0.34	NO
36	CKMT2	CKMT2	CKMT2	10281	-0.0033	0.29	NO
37	ARG1	ARG1	ARG1	10469	-0.0065	0.28	NO
38	SRM	SRM	SRM	10485	-0.0068	0.28	NO
39	ALDH7A1	ALDH7A1	ALDH7A1	10844	-0.013	0.27	NO
40	PRODH	PRODH	PRODH	11176	-0.019	0.26	NO
41	GATM	GATM	GATM	11194	-0.019	0.26	NO
42	ALDH4A1	ALDH4A1	ALDH4A1	12017	-0.035	0.22	NO
43	GLUD1	GLUD1	GLUD1	12480	-0.043	0.21	NO
44	P4HA3	P4HA3	P4HA3	15581	-0.1	0.078	NO
45	DAO	DAO	DAO	16988	-0.14	0.028	NO
46	GLUL	GLUL	GLUL	19075	-0.2	-0.048	NO
47	ADC	ADC	ADC	20601	-0.25	-0.093	NO
48	CKM	CKM	CKM	20877	-0.27	-0.082	NO
49	NOS1	NOS1	NOS1	21589	-0.31	-0.086	NO
50	MAOB	MAOB	MAOB	21678	-0.32	-0.062	NO
51	CKB	CKB	CKB	21695	-0.32	-0.035	NO
52	GLUD2	GLUD2	GLUD2	22460	-0.42	-0.032	NO
53	GAMT	GAMT	GAMT	22556	-0.46	0.0038	NO

Figure S77. 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 S78. 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 PYRIMIDINE METABOLISM

Table S40. 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	CHP2	CHP2	CHP2	9	0.82	0.043	YES
2	PLCB3	PLCB3	PLCB3	128	0.52	0.066	YES
3	GRIN2D	GRIN2D	GRIN2D	350	0.39	0.077	YES
4	NDUFA9	NDUFA9	NDUFA9	726	0.3	0.076	YES
5	CASP7	CASP7	CASP7	868	0.28	0.084	YES
6	IL1B	IL1B	IL1B	968	0.26	0.094	YES
7	UQCRC2	UQCRC2	UQCRC2	1277	0.23	0.093	YES
8	NDUFA10	NDUFA10	NDUFA10	1285	0.23	0.1	YES
9	CYC1	CYC1	CYC1	1452	0.22	0.11	YES
10	ATP5G3	ATP5G3	ATP5G3	1542	0.21	0.12	YES
11	APAF1	APAF1	APAF1	1544	0.21	0.13	YES
12	NDUFS7	NDUFS7	NDUFS7	1624	0.21	0.14	YES
13	NAE1	NAE1	NAE1	1854	0.2	0.14	YES
14	COX6C	COX6C	COX6C	1911	0.19	0.14	YES
15	SDHB	SDHB	SDHB	1912	0.19	0.15	YES
16	CASP3	CASP3	CASP3	1969	0.19	0.16	YES
17	CYCS	CYCS	CYCS	2038	0.19	0.17	YES
18	MME	MME	MME	2099	0.18	0.18	YES
19	NDUFS2	NDUFS2	NDUFS2	2110	0.18	0.18	YES
20	UQCRC1	UQCRC1	UQCRC1	2166	0.18	0.19	YES
21	COX5A	COX5A	COX5A	2213	0.18	0.2	YES
22	PSEN1	PSEN1	PSEN1	2337	0.17	0.2	YES
23	NDUFA5	NDUFA5	NDUFA5	2382	0.17	0.21	YES
24	GRIN2B	GRIN2B	GRIN2B	2514	0.16	0.21	YES
25	ATP5F1	ATP5F1	ATP5F1	2527	0.16	0.22	YES
26	ATP5A1	ATP5A1	ATP5A1	2597	0.16	0.23	YES
27	ATP5G1	ATP5G1	ATP5G1	2620	0.16	0.24	YES
28	MAPK3	MAPK3	MAPK3	2623	0.16	0.24	YES
29	ATP5B	ATP5B	ATP5B	2797	0.15	0.24	YES
30	NDUFB2	NDUFB2	NDUFB2	2806	0.15	0.25	YES
31	ITPR3	ITPR3	ITPR3	2813	0.15	0.26	YES
32	NDUFS1	NDUFS1	NDUFS1	2865	0.15	0.26	YES
33	NDUFA1	NDUFA1	NDUFA1	2866	0.15	0.27	YES
34	CDK5	CDK5	CDK5	2876	0.15	0.28	YES
35	ATP5D	ATP5D	ATP5D	2933	0.15	0.29	YES
36	CASP8	CASP8	CASP8	2985	0.15	0.29	YES
37	UQCRFS1	UQCRFS1	UQCRFS1	3092	0.14	0.3	YES
38	CASP9	CASP9	CASP9	3145	0.14	0.3	YES
39	NDUFV1	NDUFV1	NDUFV1	3285	0.14	0.3	YES
40	NDUFA4L2	NDUFA4L2	NDUFA4L2	3344	0.14	0.3	YES
41	SDHD	SDHD	SDHD	3390	0.13	0.31	YES
42	BID	BID	BID	3457	0.13	0.32	YES
43	SDHA	SDHA	SDHA	3537	0.13	0.32	YES
44	UQCRH	UQCRH	UQCRH	3547	0.13	0.32	YES
45	UQCRHL	UQCRHL	UQCRHL	3729	0.12	0.32	YES
46	COX5B	COX5B	COX5B	3827	0.12	0.32	YES
47	COX4I1	COX4I1	COX4I1	3846	0.12	0.33	YES
48	NDUFS3	NDUFS3	NDUFS3	3847	0.12	0.34	YES
49	ATP5C1	ATP5C1	ATP5C1	3865	0.12	0.34	YES
50	COX6A1	COX6A1	COX6A1	3925	0.12	0.35	YES
51	NDUFAB1	NDUFAB1	NDUFAB1	3990	0.12	0.35	YES
52	UQCRB	UQCRB	UQCRB	4148	0.11	0.35	YES
53	UQCR10	UQCR10	UQCR10	4337	0.11	0.35	YES
54	NDUFB9	NDUFB9	NDUFB9	4371	0.11	0.35	YES
55	NDUFA8	NDUFA8	NDUFA8	4446	0.1	0.35	YES
56	COX7B	COX7B	COX7B	4635	0.1	0.35	YES
57	UQCRQ	UQCRQ	UQCRQ	4666	0.1	0.35	YES
58	NDUFA6	NDUFA6	NDUFA6	4762	0.097	0.36	YES
59	ADAM10	ADAM10	ADAM10	4927	0.093	0.35	YES
60	GAPDH	GAPDH	GAPDH	5007	0.091	0.35	YES
61	NDUFB3	NDUFB3	NDUFB3	5042	0.09	0.36	YES
62	COX7A2	COX7A2	COX7A2	5176	0.086	0.36	YES
63	CAPN1	CAPN1	CAPN1	5319	0.083	0.35	YES
64	COX6B1	COX6B1	COX6B1	5370	0.082	0.36	YES
65	ATP5J	ATP5J	ATP5J	5405	0.081	0.36	YES
66	NDUFB6	NDUFB6	NDUFB6	5655	0.076	0.35	NO
67	CALML6	CALML6	CALML6	5706	0.075	0.35	NO
68	NDUFC1	NDUFC1	NDUFC1	5742	0.075	0.36	NO
69	TNF	TNF	TNF	6011	0.07	0.35	NO
70	NDUFS4	NDUFS4	NDUFS4	6060	0.068	0.35	NO
71	COX7A2L	COX7A2L	COX7A2L	6140	0.067	0.35	NO
72	PLCB4	PLCB4	PLCB4	6371	0.063	0.34	NO
73	CALM1	CALM1	CALM1	6598	0.058	0.34	NO
74	NDUFA7	NDUFA7	NDUFA7	6658	0.058	0.34	NO
75	COX8A	COX8A	COX8A	6692	0.057	0.34	NO
76	APH1A	APH1A	APH1A	6724	0.056	0.34	NO
77	HSD17B10	HSD17B10	HSD17B10	6907	0.053	0.33	NO
78	NDUFA2	NDUFA2	NDUFA2	6927	0.053	0.34	NO
79	ATP2A1	ATP2A1	ATP2A1	6930	0.053	0.34	NO
80	COX7C	COX7C	COX7C	6992	0.052	0.34	NO
81	ATP2A3	ATP2A3	ATP2A3	7036	0.051	0.34	NO
82	NDUFB10	NDUFB10	NDUFB10	7044	0.051	0.34	NO
83	NDUFV3	NDUFV3	NDUFV3	7239	0.048	0.34	NO
84	NDUFB1	NDUFB1	NDUFB1	7373	0.046	0.33	NO
85	FADD	FADD	FADD	7379	0.045	0.33	NO
86	ATP5H	ATP5H	ATP5H	7395	0.045	0.34	NO
87	CALM3	CALM3	CALM3	7485	0.044	0.34	NO
88	APP	APP	APP	7559	0.042	0.33	NO
89	MAPK1	MAPK1	MAPK1	7701	0.04	0.33	NO
90	UQCR11	UQCR11	UQCR11	7702	0.04	0.33	NO
91	BACE2	BACE2	BACE2	7759	0.039	0.33	NO
92	CALM2	CALM2	CALM2	7944	0.036	0.32	NO
93	NDUFB8	NDUFB8	NDUFB8	7953	0.036	0.33	NO
94	GSK3B	GSK3B	GSK3B	7959	0.035	0.33	NO
95	EIF2AK3	EIF2AK3	EIF2AK3	7965	0.035	0.33	NO
96	NDUFA4	NDUFA4	NDUFA4	8310	0.029	0.32	NO
97	ATP2A2	ATP2A2	ATP2A2	8412	0.028	0.31	NO
98	NDUFS5	NDUFS5	NDUFS5	8575	0.026	0.31	NO
99	IDE	IDE	IDE	8817	0.022	0.3	NO
100	CAPN2	CAPN2	CAPN2	8874	0.02	0.3	NO
101	ATP5G2	ATP5G2	ATP5G2	9023	0.018	0.29	NO
102	SDHC	SDHC	SDHC	9116	0.016	0.29	NO
103	CACNA1D	CACNA1D	CACNA1D	9455	0.011	0.27	NO
104	NDUFB7	NDUFB7	NDUFB7	9501	0.0099	0.27	NO
105	NDUFB4	NDUFB4	NDUFB4	9763	0.0054	0.26	NO
106	ERN1	ERN1	ERN1	9785	0.0049	0.26	NO
107	NCSTN	NCSTN	NCSTN	9829	0.0041	0.26	NO
108	CALML3	CALML3	CALML3	9874	0.0035	0.26	NO
109	NDUFB5	NDUFB5	NDUFB5	9896	0.0032	0.26	NO
110	PSENEN	PSENEN	PSENEN	10314	-0.0039	0.24	NO
111	NDUFS6	NDUFS6	NDUFS6	10564	-0.0082	0.23	NO
112	ATF6	ATF6	ATF6	10636	-0.0094	0.22	NO
113	PPP3R1	PPP3R1	PPP3R1	10684	-0.01	0.22	NO
114	NDUFA3	NDUFA3	NDUFA3	10875	-0.014	0.21	NO
115	NDUFV2	NDUFV2	NDUFV2	11062	-0.017	0.21	NO
116	CALML5	CALML5	CALML5	11145	-0.018	0.2	NO
117	TNFRSF1A	TNFRSF1A	TNFRSF1A	11211	-0.019	0.2	NO
118	COX6B2	COX6B2	COX6B2	11214	-0.02	0.2	NO
119	ATP5E	ATP5E	ATP5E	11295	-0.021	0.2	NO
120	GNAQ	GNAQ	GNAQ	11538	-0.025	0.19	NO
121	NDUFS8	NDUFS8	NDUFS8	11647	-0.028	0.19	NO
122	PPP3CB	PPP3CB	PPP3CB	11685	-0.028	0.19	NO
123	LRP1	LRP1	LRP1	11952	-0.034	0.18	NO
124	LPL	LPL	LPL	12104	-0.036	0.17	NO
125	ITPR2	ITPR2	ITPR2	12630	-0.046	0.15	NO
126	GRIN2C	GRIN2C	GRIN2C	12731	-0.048	0.15	NO
127	COX4I2	COX4I2	COX4I2	13563	-0.064	0.12	NO
128	PPP3CA	PPP3CA	PPP3CA	13705	-0.066	0.11	NO
129	GRIN1	GRIN1	GRIN1	13741	-0.067	0.12	NO
130	PPP3R2	PPP3R2	PPP3R2	13753	-0.068	0.12	NO
131	ADAM17	ADAM17	ADAM17	14711	-0.087	0.081	NO
132	APOE	APOE	APOE	15264	-0.099	0.062	NO
133	PLCB1	PLCB1	PLCB1	15428	-0.1	0.06	NO
134	PSEN2	PSEN2	PSEN2	16278	-0.12	0.029	NO
135	PLCB2	PLCB2	PLCB2	16348	-0.12	0.032	NO
136	COX8C	COX8C	COX8C	16605	-0.13	0.028	NO
137	BAD	BAD	BAD	16860	-0.13	0.024	NO
138	FAS	FAS	FAS	17224	-0.14	0.015	NO
139	CDK5R1	CDK5R1	CDK5R1	18043	-0.16	-0.012	NO
140	COX7B2	COX7B2	COX7B2	18102	-0.17	-0.0062	NO
141	BACE1	BACE1	BACE1	18434	-0.18	-0.012	NO
142	CACNA1F	CACNA1F	CACNA1F	18986	-0.19	-0.026	NO
143	CACNA1C	CACNA1C	CACNA1C	19731	-0.22	-0.047	NO
144	COX7A1	COX7A1	COX7A1	19803	-0.22	-0.039	NO
145	CACNA1S	CACNA1S	CACNA1S	19953	-0.23	-0.033	NO
146	SNCA	SNCA	SNCA	20325	-0.24	-0.037	NO
147	ITPR1	ITPR1	ITPR1	20436	-0.25	-0.029	NO
148	RYR3	RYR3	RYR3	20572	-0.25	-0.021	NO
149	MAPT	MAPT	MAPT	21245	-0.29	-0.036	NO
150	COX6A2	COX6A2	COX6A2	21421	-0.3	-0.027	NO
151	NOS1	NOS1	NOS1	21589	-0.31	-0.018	NO
152	GRIN2A	GRIN2A	GRIN2A	22350	-0.4	-0.031	NO
153	APBB1	APBB1	APBB1	22385	-0.4	-0.011	NO
154	PPP3CC	PPP3CC	PPP3CC	22431	-0.42	0.0094	NO

Figure S79. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG PYRIMIDINE METABOLISM.

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PYRIMIDINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

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 clus5 enriched pathways

Table 7. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus5. 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	0.33	1	0.45	1	1	0.21	0.18	0.17	1	0.75
BIOCARTA CARM ER PATHWAY	33	genes.ES.table	0.38	1.4	0.076	1	0.94	0.39	0.28	0.28	1	0.66
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.34	1	0.45	1	1	0.37	0.29	0.26	1	0.76
BIOCARTA MPR PATHWAY	32	genes.ES.table	0.32	1.3	0.13	1	0.98	0.22	0.17	0.18	1	0.74
BIOCARTA CHREBP2 PATHWAY	39	genes.ES.table	0.43	1.8	0.015	0.95	0.47	0.26	0.15	0.22	0	0.28
KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM	31	genes.ES.table	0.34	1.1	0.3	1	1	0.45	0.31	0.31	1	0.79
KEGG GLYCINE SERINE AND THREONINE METABOLISM	30	genes.ES.table	0.49	1.5	0.049	1	0.85	0.4	0.21	0.32	1	0.6
KEGG CYSTEINE AND METHIONINE METABOLISM	33	genes.ES.table	0.36	1.3	0.15	1	0.99	0.091	0.0091	0.09	1	0.64
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.35	1.2	0.24	1	1	0.26	0.21	0.2	1	0.66
KEGG HISTIDINE METABOLISM	28	genes.ES.table	0.32	1	0.39	1	1	0.18	0.071	0.17	1	0.8

genes ES table in pathway: BIOCARTA NO1 PATHWAY

Table S41. 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	PPP2R2C	PPP2R2C	PPP2R2C	854	0.39	0.04	YES
2	MLXIPL	MLXIPL	MLXIPL	1462	0.34	0.08	YES
3	PRKAA2	PRKAA2	PRKAA2	1495	0.33	0.15	YES
4	ACACA	ACACA	ACACA	1659	0.32	0.2	YES
5	PPP2R3B	PPP2R3B	PPP2R3B	1685	0.32	0.26	YES
6	PPP2R1B	PPP2R1B	PPP2R1B	2570	0.27	0.28	YES
7	PKLR	PKLR	PKLR	2815	0.26	0.32	YES
8	PRKAB2	PRKAB2	PRKAB2	3066	0.24	0.36	YES
9	FASN	FASN	FASN	3457	0.23	0.39	YES
10	GCK	GCK	GCK	3486	0.23	0.43	YES
11	YWHAB	YWHAB	YWHAB	7751	0.12	0.27	NO
12	PRKAA1	PRKAA1	PRKAA1	8194	0.11	0.27	NO
13	PRKAB1	PRKAB1	PRKAB1	8665	0.1	0.27	NO
14	PPP2R2D	PPP2R2D	PPP2R2D	10054	0.073	0.22	NO
15	YWHAG	YWHAG	YWHAG	10585	0.064	0.21	NO
16	YWHAE	YWHAE	YWHAE	10896	0.058	0.21	NO
17	PRKAR1A	PRKAR1A	PRKAR1A	11061	0.055	0.21	NO
18	PPP2R1A	PPP2R1A	PPP2R1A	11344	0.05	0.21	NO
19	PPP2R5D	PPP2R5D	PPP2R5D	11503	0.047	0.21	NO
20	PPP2R5A	PPP2R5A	PPP2R5A	11551	0.047	0.22	NO
21	PRKAG1	PRKAG1	PRKAG1	11643	0.045	0.22	NO
22	PPP2R4	PPP2R4	PPP2R4	12091	0.037	0.21	NO
23	PPP2R5B	PPP2R5B	PPP2R5B	12654	0.026	0.19	NO
24	YWHAQ	YWHAQ	YWHAQ	12715	0.025	0.19	NO
25	YWHAZ	YWHAZ	YWHAZ	12913	0.022	0.19	NO
26	PPP2R3A	PPP2R3A	PPP2R3A	13546	0.01	0.16	NO
27	PRKAR1B	PRKAR1B	PRKAR1B	13585	0.0095	0.16	NO
28	PRKACA	PRKACA	PRKACA	15006	-0.019	0.1	NO
29	MLX	MLX	MLX	15019	-0.019	0.11	NO
30	PRKAR2A	PRKAR2A	PRKAR2A	15362	-0.025	0.098	NO
31	PRKACG	PRKACG	PRKACG	15864	-0.035	0.083	NO
32	PRKAG2	PRKAG2	PRKAG2	17074	-0.063	0.042	NO
33	PRKACB	PRKACB	PRKACB	17900	-0.085	0.022	NO
34	PPP2R5C	PPP2R5C	PPP2R5C	18255	-0.094	0.026	NO
35	PPP2R5E	PPP2R5E	PPP2R5E	18469	-0.1	0.036	NO
36	YWHAH	YWHAH	YWHAH	19300	-0.13	0.025	NO
37	PPP2CB	PPP2CB	PPP2CB	19587	-0.14	0.041	NO
38	PPP2R2B	PPP2R2B	PPP2R2B	20996	-0.21	0.021	NO
39	PRKAR2B	PRKAR2B	PRKAR2B	21601	-0.26	0.046	NO

Figure S81. 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 S82. 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 CARM ER PATHWAY

Table S42. 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	GLDC	GLDC	GLDC	85	0.59	0.099	YES
2	CBS	CBS	CBS	206	0.52	0.18	YES
3	PHGDH	PHGDH	PHGDH	633	0.42	0.24	YES
4	PSPH	PSPH	PSPH	786	0.4	0.3	YES
5	AGXT	AGXT	AGXT	968	0.38	0.36	YES
6	GAMT	GAMT	GAMT	2029	0.3	0.36	YES
7	PIPOX	PIPOX	PIPOX	2189	0.29	0.4	YES
8	AGXT2	AGXT2	AGXT2	2690	0.26	0.43	YES
9	GLYCTK	GLYCTK	GLYCTK	2901	0.25	0.46	YES
10	DAO	DAO	DAO	3791	0.22	0.46	YES
11	GNMT	GNMT	GNMT	4520	0.2	0.46	YES
12	BHMT	BHMT	BHMT	4671	0.19	0.49	YES
13	SARDH	SARDH	SARDH	5623	0.17	0.47	NO
14	CHDH	CHDH	CHDH	6972	0.13	0.44	NO
15	ALAS2	ALAS2	ALAS2	8482	0.1	0.39	NO
16	SHMT1	SHMT1	SHMT1	9162	0.09	0.37	NO
17	PSAT1	PSAT1	PSAT1	11385	0.05	0.28	NO
18	MAOB	MAOB	MAOB	11694	0.044	0.28	NO
19	SRR	SRR	SRR	11947	0.039	0.27	NO
20	GCAT	GCAT	GCAT	12697	0.026	0.24	NO
21	SHMT2	SHMT2	SHMT2	15449	-0.027	0.13	NO
22	AOC2	AOC2	AOC2	15525	-0.028	0.13	NO
23	CTH	CTH	CTH	15804	-0.034	0.12	NO
24	ALAS1	ALAS1	ALAS1	15899	-0.036	0.12	NO
25	GATM	GATM	GATM	16320	-0.045	0.11	NO
26	DLD	DLD	DLD	16522	-0.05	0.11	NO
27	MAOA	MAOA	MAOA	20676	-0.2	-0.037	NO
28	SDS	SDS	SDS	20843	-0.2	-0.009	NO
29	AOC3	AOC3	AOC3	21429	-0.24	0.0073	NO
30	DMGDH	DMGDH	DMGDH	21697	-0.27	0.042	NO

Figure S83. 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 S84. 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 G1 PATHWAY

Table S43. 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	HDAC6	HDAC6	HDAC6	1140	0.36	0.029	YES
2	PPARGC1A	PPARGC1A	PPARGC1A	1603	0.33	0.08	YES
3	GRIP1	GRIP1	GRIP1	2030	0.3	0.13	YES
4	HDAC11	HDAC11	HDAC11	2548	0.27	0.16	YES
5	HDAC5	HDAC5	HDAC5	2587	0.27	0.22	YES
6	HDAC2	HDAC2	HDAC2	3673	0.22	0.22	YES
7	BRCA1	BRCA1	BRCA1	4202	0.2	0.24	YES
8	MED1	MED1	MED1	4211	0.2	0.29	YES
9	ERCC3	ERCC3	ERCC3	5028	0.18	0.29	YES
10	PELP1	PELP1	PELP1	5225	0.18	0.32	YES
11	HDAC8	HDAC8	HDAC8	5475	0.17	0.35	YES
12	HDAC10	HDAC10	HDAC10	6232	0.15	0.35	YES
13	TBP	TBP	TBP	6305	0.15	0.38	YES
14	NR0B1	NR0B1	NR0B1	9388	0.086	0.26	NO
15	GTF2E1	GTF2E1	GTF2E1	10273	0.069	0.24	NO
16	HDAC4	HDAC4	HDAC4	11649	0.045	0.19	NO
17	SPEN	SPEN	SPEN	11782	0.042	0.19	NO
18	EP300	EP300	EP300	12391	0.031	0.17	NO
19	CCND1	CCND1	CCND1	13496	0.011	0.12	NO
20	HDAC1	HDAC1	HDAC1	13783	0.0058	0.11	NO
21	NCOR2	NCOR2	NCOR2	14179	-0.0024	0.094	NO
22	POLR2A	POLR2A	POLR2A	14689	-0.013	0.075	NO
23	HDAC7	HDAC7	HDAC7	15461	-0.027	0.047	NO
24	CARM1	CARM1	CARM1	15932	-0.037	0.034	NO
25	GTF2A1	GTF2A1	GTF2A1	16375	-0.047	0.025	NO
26	CREBBP	CREBBP	CREBBP	16789	-0.056	0.019	NO
27	NRIP1	NRIP1	NRIP1	16975	-0.06	0.024	NO
28	GTF2F1	GTF2F1	GTF2F1	17742	-0.08	0.0076	NO
29	PHB2	PHB2	PHB2	18104	-0.09	0.012	NO
30	HDAC3	HDAC3	HDAC3	19518	-0.14	-0.021	NO
31	HDAC9	HDAC9	HDAC9	19875	-0.15	-0.0025	NO
32	SRA1	SRA1	SRA1	20379	-0.18	0.015	NO
33	ESR1	ESR1	ESR1	22461	-0.39	0.008	NO

Figure S85. 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 S86. 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 MPR PATHWAY

Table S44. 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	PRPF40B	PRPF40B	PRPF40B	200	0.52	0.047	YES
2	PPIE	PPIE	PPIE	1407	0.34	0.03	YES
3	PRPF3	PRPF3	PRPF3	1718	0.32	0.051	YES
4	CRNKL1	CRNKL1	CRNKL1	2726	0.26	0.035	YES
5	PRPF6	PRPF6	PRPF6	3401	0.23	0.03	YES
6	THOC1	THOC1	THOC1	3512	0.23	0.05	YES
7	CTNNBL1	CTNNBL1	CTNNBL1	3521	0.23	0.074	YES
8	HSPA1L	HSPA1L	HSPA1L	3969	0.21	0.078	YES
9	SF3B4	SF3B4	SF3B4	4374	0.2	0.081	YES
10	HSPA1A	HSPA1A	HSPA1A	4534	0.2	0.096	YES
11	HSPA6	HSPA6	HSPA6	5393	0.17	0.076	YES
12	SNRNP200	SNRNP200	SNRNP200	5446	0.17	0.092	YES
13	RBM8A	RBM8A	RBM8A	5499	0.17	0.11	YES
14	PPIL1	PPIL1	PPIL1	5607	0.17	0.12	YES
15	USP39	USP39	USP39	5795	0.16	0.13	YES
16	PRPF4	PRPF4	PRPF4	6013	0.16	0.14	YES
17	DHX16	DHX16	DHX16	6026	0.16	0.15	YES
18	SNRPB	SNRPB	SNRPB	6047	0.16	0.17	YES
19	SNRPB2	SNRPB2	SNRPB2	6129	0.15	0.18	YES
20	SNRPA1	SNRPA1	SNRPA1	6190	0.15	0.2	YES
21	PQBP1	PQBP1	PQBP1	6424	0.15	0.2	YES
22	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	6437	0.15	0.22	YES
23	CDC5L	CDC5L	CDC5L	7007	0.13	0.21	YES
24	LSM5	LSM5	LSM5	7121	0.13	0.22	YES
25	SF3B3	SF3B3	SF3B3	7145	0.13	0.23	YES
26	PUF60	PUF60	PUF60	7491	0.12	0.23	YES
27	PRPF31	PRPF31	PRPF31	7944	0.11	0.22	YES
28	RBM17	RBM17	RBM17	8008	0.11	0.23	YES
29	SNRPC	SNRPC	SNRPC	8036	0.11	0.24	YES
30	SNRPE	SNRPE	SNRPE	8049	0.11	0.25	YES
31	EFTUD2	EFTUD2	EFTUD2	8529	0.1	0.24	YES
32	DHX8	DHX8	DHX8	8839	0.096	0.24	YES
33	SART1	SART1	SART1	8895	0.095	0.25	YES
34	CCDC12	CCDC12	CCDC12	9063	0.092	0.25	YES
35	THOC2	THOC2	THOC2	9178	0.09	0.25	YES
36	PRPF38A	PRPF38A	PRPF38A	9233	0.089	0.26	YES
37	PPIH	PPIH	PPIH	9284	0.088	0.27	YES
38	PRPF19	PRPF19	PRPF19	9380	0.086	0.27	YES
39	CWC15	CWC15	CWC15	9622	0.082	0.27	YES
40	MAGOH	MAGOH	MAGOH	9647	0.081	0.28	YES
41	HSPA1B	HSPA1B	HSPA1B	10055	0.073	0.27	YES
42	HNRNPU	HNRNPU	HNRNPU	10079	0.073	0.28	YES
43	TRA2A	TRA2A	TRA2A	10176	0.071	0.28	YES
44	SNRPD1	SNRPD1	SNRPD1	10184	0.071	0.29	YES
45	PRPF40A	PRPF40A	PRPF40A	10192	0.071	0.29	YES
46	EIF4A3	EIF4A3	EIF4A3	10251	0.07	0.3	YES
47	SNRPG	SNRPG	SNRPG	10375	0.067	0.3	YES
48	SF3B2	SF3B2	SF3B2	10400	0.067	0.31	YES
49	SNRNP70	SNRNP70	SNRNP70	10524	0.065	0.31	YES
50	SF3B1	SF3B1	SF3B1	10741	0.061	0.3	YES
51	SNRNP27	SNRNP27	SNRNP27	10782	0.06	0.31	YES
52	U2AF2	U2AF2	U2AF2	10797	0.06	0.32	YES
53	DDX42	DDX42	DDX42	10876	0.058	0.32	YES
54	SMNDC1	SMNDC1	SMNDC1	10976	0.057	0.32	YES
55	LSM2	LSM2	LSM2	11028	0.056	0.32	YES
56	DDX23	DDX23	DDX23	11030	0.056	0.33	YES
57	MAGOHB	MAGOHB	MAGOHB	11131	0.054	0.33	YES
58	CHERP	CHERP	CHERP	11175	0.053	0.34	YES
59	RBMX	RBMX	RBMX	11217	0.053	0.34	YES
60	PRPF18	PRPF18	PRPF18	11254	0.052	0.34	YES
61	SNRPD3	SNRPD3	SNRPD3	11377	0.05	0.34	YES
62	ACIN1	ACIN1	ACIN1	11416	0.049	0.35	YES
63	LSM4	LSM4	LSM4	11485	0.048	0.35	YES
64	SNW1	SNW1	SNW1	11591	0.046	0.35	YES
65	SNRNP40	SNRNP40	SNRNP40	11629	0.045	0.35	YES
66	DDX46	DDX46	DDX46	11632	0.045	0.36	YES
67	PHF5A	PHF5A	PHF5A	11638	0.045	0.36	YES
68	NCBP1	NCBP1	NCBP1	11950	0.039	0.35	NO
69	NHP2L1	NHP2L1	NHP2L1	12008	0.038	0.35	NO
70	DHX38	DHX38	DHX38	12083	0.037	0.36	NO
71	SF3A3	SF3A3	SF3A3	12208	0.034	0.35	NO
72	HSPA2	HSPA2	HSPA2	12265	0.033	0.36	NO
73	PRPF8	PRPF8	PRPF8	12362	0.032	0.35	NO
74	TRA2B	TRA2B	TRA2B	12427	0.03	0.35	NO
75	DDX5	DDX5	DDX5	12575	0.028	0.35	NO
76	BUD31	BUD31	BUD31	12611	0.027	0.35	NO
77	PCBP1	PCBP1	PCBP1	12633	0.027	0.35	NO
78	SF3B14	SF3B14	SF3B14	12734	0.025	0.35	NO
79	SNRPA	SNRPA	SNRPA	12855	0.023	0.35	NO
80	RBM25	RBM25	RBM25	12868	0.022	0.35	NO
81	SNRPD2	SNRPD2	SNRPD2	12928	0.021	0.35	NO
82	HNRNPM	HNRNPM	HNRNPM	13022	0.02	0.35	NO
83	TCERG1	TCERG1	TCERG1	13105	0.018	0.35	NO
84	DHX15	DHX15	DHX15	13203	0.016	0.34	NO
85	HNRNPC	HNRNPC	HNRNPC	13242	0.016	0.34	NO
86	U2AF1	U2AF1	U2AF1	13422	0.013	0.34	NO
87	PRPF38B	PRPF38B	PRPF38B	13739	0.0066	0.32	NO
88	TXNL4A	TXNL4A	TXNL4A	13784	0.0058	0.32	NO
89	WBP11	WBP11	WBP11	13858	0.0044	0.32	NO
90	LSM3	LSM3	LSM3	13927	0.0029	0.32	NO
91	SF3A1	SF3A1	SF3A1	14103	-0.00081	0.31	NO
92	HNRNPK	HNRNPK	HNRNPK	14135	-0.0015	0.31	NO
93	THOC3	THOC3	THOC3	14327	-0.0054	0.3	NO
94	XAB2	XAB2	XAB2	14403	-0.0071	0.3	NO
95	CDC40	CDC40	CDC40	14487	-0.0088	0.3	NO
96	HNRNPA3	HNRNPA3	HNRNPA3	14538	-0.0098	0.3	NO
97	SNRPF	SNRPF	SNRPF	14728	-0.013	0.29	NO
98	AQR	AQR	AQR	14927	-0.017	0.28	NO
99	PLRG1	PLRG1	PLRG1	15220	-0.022	0.27	NO
100	HSPA8	HSPA8	HSPA8	15278	-0.023	0.27	NO
101	SF3A2	SF3A2	SF3A2	15477	-0.027	0.26	NO
102	LSM6	LSM6	LSM6	15708	-0.032	0.26	NO
103	SF3B5	SF3B5	SF3B5	15845	-0.035	0.26	NO
104	SLU7	SLU7	SLU7	15863	-0.035	0.26	NO
105	RBM22	RBM22	RBM22	16310	-0.045	0.24	NO
106	ZMAT2	ZMAT2	ZMAT2	16529	-0.05	0.24	NO
107	HNRNPA1	HNRNPA1	HNRNPA1	16559	-0.051	0.24	NO
108	LSM7	LSM7	LSM7	16685	-0.054	0.24	NO
109	BCAS2	BCAS2	BCAS2	16875	-0.058	0.24	NO
110	SYF2	SYF2	SYF2	16882	-0.058	0.25	NO
111	NAA38	NAA38	NAA38	17352	-0.07	0.24	NO

Figure S87. 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 MPR PATHWAY.

Figure S88. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA MPR 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 CHREBP2 PATHWAY

Table S45. 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	115	0.56	0.13	YES
2	MYT1	MYT1	MYT1	1671	0.32	0.14	YES
3	CDK1	CDK1	CDK1	2958	0.25	0.14	YES
4	GNAS	GNAS	GNAS	3119	0.24	0.2	YES
5	PAQR7	PAQR7	PAQR7	3255	0.24	0.25	YES
6	GNAI1	GNAI1	GNAI1	3775	0.22	0.28	YES
7	CDC25C	CDC25C	CDC25C	3951	0.21	0.32	YES
8	SRC	SRC	SRC	5774	0.16	0.28	NO
9	PAQR5	PAQR5	PAQR5	6283	0.15	0.3	NO
10	CCNB1	CCNB1	CCNB1	8115	0.11	0.24	NO
11	HRAS	HRAS	HRAS	8313	0.11	0.26	NO
12	ACTA1	ACTA1	ACTA1	9976	0.075	0.21	NO
13	PRKAR1A	PRKAR1A	PRKAR1A	11061	0.055	0.17	NO
14	GNB1	GNB1	GNB1	11627	0.045	0.16	NO
15	PRKAR1B	PRKAR1B	PRKAR1B	13585	0.0095	0.073	NO
16	ARPC5	ARPC5	ARPC5	13863	0.0043	0.062	NO
17	ACTR3	ACTR3	ACTR3	14472	-0.0085	0.037	NO
18	ACTR2	ACTR2	ACTR2	14708	-0.013	0.03	NO
19	PRKAR2A	PRKAR2A	PRKAR2A	15362	-0.025	0.0068	NO
20	MAPK3	MAPK3	MAPK3	15618	-0.03	0.0029	NO
21	MAPK1	MAPK1	MAPK1	15647	-0.031	0.0091	NO
22	PRKACG	PRKACG	PRKACG	15864	-0.035	0.0082	NO
23	ARPC2	ARPC2	ARPC2	16281	-0.044	0.00066	NO
24	ARPC1A	ARPC1A	ARPC1A	16338	-0.046	0.0094	NO
25	ARPC1B	ARPC1B	ARPC1B	16406	-0.047	0.018	NO
26	ARPC3	ARPC3	ARPC3	16433	-0.048	0.029	NO
27	CAP1	CAP1	CAP1	16468	-0.049	0.039	NO
28	PIN1	PIN1	PIN1	17691	-0.078	0.0042	NO
29	PRKACB	PRKACB	PRKACB	17900	-0.085	0.016	NO
30	RPS6KA1	RPS6KA1	RPS6KA1	21209	-0.23	-0.076	NO
31	PRKAR2B	PRKAR2B	PRKAR2B	21601	-0.26	-0.03	NO
32	PGR	PGR	PGR	22045	-0.31	0.026	NO

Figure S89. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA CHREBP2 PATHWAY.

Figure S90. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CHREBP2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

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

Table S46. 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	TUBB2B	TUBB2B	TUBB2B	191	0.52	0.072	YES
2	TUBB1	TUBB1	TUBB1	310	0.48	0.14	YES
3	TUBB3	TUBB3	TUBB3	332	0.47	0.21	YES
4	TUBB2A	TUBB2A	TUBB2A	366	0.47	0.28	YES
5	TUBA3E	TUBA3E	TUBA3E	2955	0.25	0.21	NO
6	TUBA3C	TUBA3C	TUBA3C	4060	0.21	0.19	NO
7	FYN	FYN	FYN	4062	0.21	0.22	NO
8	TUBA8	TUBA8	TUBA8	5135	0.18	0.2	NO
9	NCK2	NCK2	NCK2	6458	0.15	0.17	NO
10	CTNNB1	CTNNB1	CTNNB1	9203	0.089	0.059	NO
11	ROCK1	ROCK1	ROCK1	9357	0.086	0.065	NO
12	TUBB8	TUBB8	TUBB8	9371	0.086	0.078	NO
13	NCL	NCL	NCL	9884	0.077	0.067	NO
14	TUBA1C	TUBA1C	TUBA1C	10127	0.072	0.068	NO
15	ARPC5L	ARPC5L	ARPC5L	10634	0.063	0.055	NO
16	ROCK2	ROCK2	ROCK2	11347	0.05	0.031	NO
17	TUBB	TUBB	TUBB	11419	0.049	0.036	NO
18	ARHGEF2	ARHGEF2	ARHGEF2	11701	0.044	0.03	NO
19	CDH1	CDH1	CDH1	12216	0.034	0.012	NO
20	YWHAQ	YWHAQ	YWHAQ	12715	0.025	-0.0058	NO
21	YWHAZ	YWHAZ	YWHAZ	12913	0.022	-0.011	NO
22	PRKCA	PRKCA	PRKCA	13674	0.0078	-0.044	NO
23	ARPC5	ARPC5	ARPC5	13863	0.0043	-0.051	NO
24	CTTN	CTTN	CTTN	14399	-0.0069	-0.074	NO
25	TUBA1A	TUBA1A	TUBA1A	14862	-0.016	-0.092	NO
26	ITGB1	ITGB1	ITGB1	15004	-0.018	-0.095	NO
27	TUBA3D	TUBA3D	TUBA3D	15242	-0.023	-0.1	NO
28	TLR5	TLR5	TLR5	15518	-0.028	-0.11	NO
29	ABL1	ABL1	ABL1	15539	-0.029	-0.11	NO
30	TUBA4A	TUBA4A	TUBA4A	15646	-0.031	-0.11	NO
31	TUBA1B	TUBA1B	TUBA1B	15663	-0.031	-0.1	NO
32	OCLN	OCLN	OCLN	16017	-0.039	-0.11	NO
33	ARPC2	ARPC2	ARPC2	16281	-0.044	-0.12	NO
34	ACTG1	ACTG1	ACTG1	16314	-0.045	-0.11	NO
35	ARPC1A	ARPC1A	ARPC1A	16338	-0.046	-0.1	NO
36	ARPC1B	ARPC1B	ARPC1B	16406	-0.047	-0.1	NO
37	ARPC3	ARPC3	ARPC3	16433	-0.048	-0.095	NO
38	WASL	WASL	WASL	16679	-0.054	-0.097	NO
39	TUBB6	TUBB6	TUBB6	17093	-0.063	-0.11	NO
40	CDC42	CDC42	CDC42	17336	-0.069	-0.11	NO
41	RHOA	RHOA	RHOA	17540	-0.074	-0.1	NO
42	ACTB	ACTB	ACTB	17780	-0.081	-0.1	NO
43	KRT18	KRT18	KRT18	18063	-0.089	-0.1	NO
44	NCK1	NCK1	NCK1	19162	-0.12	-0.13	NO
45	LY96	LY96	LY96	19408	-0.13	-0.12	NO
46	CLDN1	CLDN1	CLDN1	20198	-0.17	-0.13	NO
47	TUBAL3	TUBAL3	TUBAL3	20223	-0.17	-0.1	NO
48	EZR	EZR	EZR	20353	-0.18	-0.082	NO
49	TLR4	TLR4	TLR4	20860	-0.2	-0.073	NO
50	CD14	CD14	CD14	21499	-0.25	-0.062	NO
51	HCLS1	HCLS1	HCLS1	22368	-0.36	-0.044	NO
52	WAS	WAS	WAS	22374	-0.37	0.012	NO

Figure S91. 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 S92. 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 GLYCINE SERINE AND THREONINE METABOLISM

Table S47. 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	DNMT3B	DNMT3B	DNMT3B	6	0.76	0.15	YES
2	DNMT3A	DNMT3A	DNMT3A	72	0.6	0.27	YES
3	CBS	CBS	CBS	206	0.52	0.36	YES
4	DNMT3L	DNMT3L	DNMT3L	2552	0.27	0.31	NO
5	BHMT	BHMT	BHMT	4671	0.19	0.26	NO
6	ENOPH1	ENOPH1	ENOPH1	5731	0.16	0.24	NO
7	APIP	APIP	APIP	6738	0.14	0.22	NO
8	AHCY	AHCY	AHCY	6883	0.14	0.24	NO
9	TAT	TAT	TAT	7153	0.13	0.26	NO
10	MAT1A	MAT1A	MAT1A	7206	0.13	0.28	NO
11	LDHAL6A	LDHAL6A	LDHAL6A	8048	0.11	0.26	NO
12	SRM	SRM	SRM	9974	0.075	0.2	NO
13	TRDMT1	TRDMT1	TRDMT1	10448	0.066	0.19	NO
14	LDHB	LDHB	LDHB	10724	0.061	0.19	NO
15	LDHAL6B	LDHAL6B	LDHAL6B	10811	0.06	0.2	NO
16	MAT2A	MAT2A	MAT2A	10929	0.057	0.2	NO
17	AMD1	AMD1	AMD1	12317	0.032	0.15	NO
18	DNMT1	DNMT1	DNMT1	12556	0.028	0.14	NO
19	MPST	MPST	MPST	12615	0.027	0.14	NO
20	MTR	MTR	MTR	13253	0.015	0.12	NO
21	SMS	SMS	SMS	13408	0.013	0.11	NO
22	AHCYL1	AHCYL1	AHCYL1	13727	0.0069	0.1	NO
23	ADI1	ADI1	ADI1	14257	-0.004	0.079	NO
24	IL4I1	IL4I1	IL4I1	14471	-0.0085	0.071	NO
25	CTH	CTH	CTH	15804	-0.034	0.019	NO
26	GOT1	GOT1	GOT1	17043	-0.062	-0.023	NO
27	LDHA	LDHA	LDHA	17059	-0.062	-0.012	NO
28	GOT2	GOT2	GOT2	17180	-0.066	-0.0042	NO
29	MTAP	MTAP	MTAP	17520	-0.074	-0.0046	NO
30	CDO1	CDO1	CDO1	19859	-0.15	-0.078	NO
31	SDS	SDS	SDS	20843	-0.2	-0.081	NO
32	MAT2B	MAT2B	MAT2B	21894	-0.29	-0.07	NO
33	AHCYL2	AHCYL2	AHCYL2	22625	-0.52	0.0008	NO

Figure S93. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM.

Figure S94. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG CYSTEINE AND METHIONINE METABOLISM

Table S48. 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	MGAT5B	MGAT5B	MGAT5B	1398	0.34	-0.0038	YES
2	B4GALT3	B4GALT3	B4GALT3	2393	0.28	-0.00044	YES
3	DOLPP1	DOLPP1	DOLPP1	2554	0.27	0.038	YES
4	ALG10B	ALG10B	ALG10B	2941	0.25	0.064	YES
5	DPM1	DPM1	DPM1	2973	0.25	0.1	YES
6	RPN2	RPN2	RPN2	3548	0.23	0.12	YES
7	MOGS	MOGS	MOGS	3691	0.22	0.15	YES
8	ST6GAL1	ST6GAL1	ST6GAL1	3758	0.22	0.18	YES
9	TUSC3	TUSC3	TUSC3	3773	0.22	0.22	YES
10	MAN2A2	MAN2A2	MAN2A2	3817	0.22	0.26	YES
11	MAN1B1	MAN1B1	MAN1B1	4240	0.2	0.27	YES
12	ALG8	ALG8	ALG8	4262	0.2	0.31	YES
13	ALG12	ALG12	ALG12	5251	0.18	0.29	YES
14	ALG6	ALG6	ALG6	6172	0.15	0.28	YES
15	ALG3	ALG3	ALG3	6354	0.15	0.3	YES
16	DPM3	DPM3	DPM3	6587	0.14	0.31	YES
17	DPM2	DPM2	DPM2	6921	0.14	0.32	YES
18	MAN1A1	MAN1A1	MAN1A1	7187	0.13	0.33	YES
19	ALG10	ALG10	ALG10	8139	0.11	0.3	YES
20	DPAGT1	DPAGT1	DPAGT1	8209	0.11	0.32	YES
21	MGAT4A	MGAT4A	MGAT4A	8224	0.11	0.34	YES
22	DDOST	DDOST	DDOST	8766	0.098	0.33	YES
23	GANAB	GANAB	GANAB	8961	0.094	0.34	YES
24	B4GALT2	B4GALT2	B4GALT2	9559	0.083	0.33	NO
25	ALG14	ALG14	ALG14	9602	0.082	0.34	NO
26	STT3A	STT3A	STT3A	10026	0.074	0.33	NO
27	ALG5	ALG5	ALG5	10706	0.062	0.31	NO
28	STT3B	STT3B	STT3B	11186	0.053	0.3	NO
29	RPN1	RPN1	RPN1	11281	0.052	0.3	NO
30	MAN1C1	MAN1C1	MAN1C1	11496	0.048	0.3	NO
31	B4GALT1	B4GALT1	B4GALT1	12028	0.038	0.29	NO
32	MAN1A2	MAN1A2	MAN1A2	12335	0.032	0.28	NO
33	ALG2	ALG2	ALG2	13228	0.016	0.24	NO
34	ALG9	ALG9	ALG9	14011	0.0013	0.21	NO
35	DAD1	DAD1	DAD1	14181	-0.0025	0.2	NO
36	MGAT5	MGAT5	MGAT5	15100	-0.02	0.16	NO
37	MGAT2	MGAT2	MGAT2	15586	-0.03	0.15	NO
38	ALG1	ALG1	ALG1	16449	-0.048	0.12	NO
39	MGAT4B	MGAT4B	MGAT4B	17057	-0.062	0.1	NO
40	MGAT3	MGAT3	MGAT3	17568	-0.075	0.091	NO
41	MGAT1	MGAT1	MGAT1	17707	-0.079	0.098	NO
42	ALG13	ALG13	ALG13	19880	-0.15	0.028	NO
43	FUT8	FUT8	FUT8	21713	-0.27	-0.0068	NO
44	MAN2A1	MAN2A1	MAN2A1	21799	-0.28	0.037	NO

Figure S95. 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 CYSTEINE AND METHIONINE METABOLISM.

Figure S96. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CYSTEINE AND METHIONINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG LYSINE DEGRADATION

Table S49. 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	OGDHL	OGDHL	OGDHL	28	0.67	0.11	YES
2	SUV420H2	SUV420H2	SUV420H2	391	0.46	0.17	YES
3	SETDB1	SETDB1	SETDB1	1179	0.36	0.19	YES
4	SUV39H2	SUV39H2	SUV39H2	1800	0.31	0.21	YES
5	AADAT	AADAT	AADAT	1916	0.3	0.26	YES
6	PIPOX	PIPOX	PIPOX	2189	0.29	0.29	YES
7	EHMT2	EHMT2	EHMT2	3231	0.24	0.29	YES
8	ASH1L	ASH1L	ASH1L	3850	0.22	0.3	YES
9	ACAT2	ACAT2	ACAT2	4479	0.2	0.3	YES
10	SUV420H1	SUV420H1	SUV420H1	4621	0.19	0.32	YES
11	PLOD2	PLOD2	PLOD2	4733	0.19	0.35	YES
12	SUV39H1	SUV39H1	SUV39H1	6108	0.15	0.32	NO
13	WHSC1	WHSC1	WHSC1	6857	0.14	0.3	NO
14	PLOD3	PLOD3	PLOD3	6909	0.14	0.32	NO
15	AASDHPPT	AASDHPPT	AASDHPPT	7075	0.13	0.34	NO
16	SETMAR	SETMAR	SETMAR	7463	0.12	0.34	NO
17	EHMT1	EHMT1	EHMT1	7947	0.11	0.34	NO
18	BBOX1	BBOX1	BBOX1	8917	0.094	0.31	NO
19	SETD1A	SETD1A	SETD1A	8922	0.094	0.33	NO
20	ALDH7A1	ALDH7A1	ALDH7A1	10453	0.066	0.27	NO
21	PLOD1	PLOD1	PLOD1	10532	0.065	0.28	NO
22	OGDH	OGDH	OGDH	11249	0.052	0.25	NO
23	SETDB2	SETDB2	SETDB2	11256	0.052	0.26	NO
24	SETD8	SETD8	SETD8	11532	0.047	0.26	NO
25	SETD2	SETD2	SETD2	12348	0.032	0.23	NO
26	ALDH9A1	ALDH9A1	ALDH9A1	12857	0.023	0.21	NO
27	DOT1L	DOT1L	DOT1L	12883	0.022	0.21	NO
28	NSD1	NSD1	NSD1	13501	0.011	0.18	NO
29	AASS	AASS	AASS	13511	0.011	0.19	NO
30	SETD1B	SETD1B	SETD1B	13726	0.0069	0.18	NO
31	GCDH	GCDH	GCDH	14104	-0.00082	0.16	NO
32	TMLHE	TMLHE	TMLHE	14760	-0.014	0.13	NO
33	ACAT1	ACAT1	ACAT1	14928	-0.017	0.13	NO
34	AASDH	AASDH	AASDH	15659	-0.031	0.1	NO
35	WHSC1L1	WHSC1L1	WHSC1L1	16549	-0.051	0.071	NO
36	HADHA	HADHA	HADHA	16698	-0.054	0.074	NO
37	ECHS1	ECHS1	ECHS1	16886	-0.058	0.075	NO
38	ALDH3A2	ALDH3A2	ALDH3A2	17858	-0.083	0.046	NO
39	DLST	DLST	DLST	18847	-0.11	0.02	NO
40	ALDH1B1	ALDH1B1	ALDH1B1	20242	-0.17	-0.013	NO
41	ALDH2	ALDH2	ALDH2	21225	-0.23	-0.02	NO
42	HADH	HADH	HADH	21387	-0.24	0.012	NO
43	SETD7	SETD7	SETD7	21642	-0.26	0.044	NO

Figure S97. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG LYSINE DEGRADATION.

Figure S98. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LYSINE DEGRADATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG HISTIDINE METABOLISM

Table S50. 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	TAF4	TAF4	TAF4	482	0.44	0.079	YES
2	GTF2IRD1	GTF2IRD1	GTF2IRD1	2606	0.27	0.046	YES
3	GTF2H4	GTF2H4	GTF2H4	3136	0.24	0.078	YES
4	TAF6L	TAF6L	TAF6L	3293	0.24	0.12	YES
5	TAF7L	TAF7L	TAF7L	3374	0.23	0.17	YES
6	TAF2	TAF2	TAF2	3681	0.22	0.21	YES
7	TAF11	TAF11	TAF11	4001	0.21	0.24	YES
8	TAF6	TAF6	TAF6	5100	0.18	0.24	YES
9	TAF5	TAF5	TAF5	6139	0.15	0.23	YES
10	TBP	TBP	TBP	6305	0.15	0.25	YES
11	TAF1L	TAF1L	TAF1L	6617	0.14	0.27	YES
12	TAF9B	TAF9B	TAF9B	6726	0.14	0.3	YES
13	GTF2F2	GTF2F2	GTF2F2	7017	0.13	0.32	YES
14	TAF1	TAF1	TAF1	7397	0.12	0.33	YES
15	TAF5L	TAF5L	TAF5L	7500	0.12	0.35	YES
16	TBPL1	TBPL1	TBPL1	7884	0.12	0.36	YES
17	GTF2E1	GTF2E1	GTF2E1	10273	0.069	0.27	NO
18	TAF10	TAF10	TAF10	10593	0.064	0.27	NO
19	GTF2I	GTF2I	GTF2I	11053	0.055	0.26	NO
20	GTF2H1	GTF2H1	GTF2H1	11946	0.039	0.23	NO
21	TAF7	TAF7	TAF7	13280	0.015	0.18	NO
22	TAF12	TAF12	TAF12	15205	-0.022	0.096	NO
23	GTF2H3	GTF2H3	GTF2H3	15234	-0.022	0.1	NO
24	GTF2A1	GTF2A1	GTF2A1	16375	-0.047	0.06	NO
25	GTF2E2	GTF2E2	GTF2E2	17544	-0.075	0.025	NO
26	TAF9	TAF9	TAF9	17659	-0.078	0.038	NO
27	GTF2F1	GTF2F1	GTF2F1	17742	-0.08	0.052	NO
28	GTF2A2	GTF2A2	GTF2A2	18198	-0.093	0.054	NO
29	TAF13	TAF13	TAF13	18462	-0.1	0.065	NO
30	GTF2B	GTF2B	GTF2B	18865	-0.11	0.073	NO
31	TBPL2	TBPL2	TBPL2	19163	-0.12	0.088	NO
32	TAF4B	TAF4B	TAF4B	19634	-0.14	0.099	NO
33	GTF2H2	GTF2H2	GTF2H2	19746	-0.15	0.13	NO

Figure S99. 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 S100. 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

Methods & Data

Input

Gene set database = c2.cp.v3.0-2.symbols.gmt
Expression data file = STAD-TP.mRNAseq_RPKM_log2.txt
Phenotype data file = STAD-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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