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

Testicular Germ Cell Tumors (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2016): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in TGCT-TP. Broad Institute of MIT and Harvard. doi:10.7908/C14B30TN

Overview

Introduction

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

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

Summary

Table 1. Get Full Table basic data info

basic data info
Number of Gene Sets: 731
Number of samples: 150
Original number of Gene Sets: 1320
Maximum gene set size: 933

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 7 :[ clus1 ] 34
pheno.type: 2 - 7 :[ clus2 ] 30
pheno.type: 3 - 7 :[ clus3 ] 33
pheno.type: 4 - 7 :[ clus4 ] 22
pheno.type: 5 - 7 :[ clus5 ] 8
pheno.type: 6 - 7 :[ clus6 ] 22
pheno.type: 7 - 7 :[ clus7 ] 1

For the expression subtypes of 19071 genes in 151 samples, GSEA found enriched gene sets in each cluster using 150 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG CYTOSOLIC DNA SENSING PATHWAY, KEGG T CELL RECEPTOR SIGNALING PATHWAY, KEGG AUTOIMMUNE THYROID DISEASE, KEGG ALLOGRAFT REJECTION, ST T CELL SIGNAL TRANSDUCTION, PID ATM PATHWAY, PID PI3KCIPATHWAY, PID IFNGPATHWAY, PID IL23PATHWAY, PID IL8CXCR2 PATHWAY

And common core enriched genes are PIK3R3, CSF2, CSF2RA, CSF2RB, GAB2, IL2, IL2RA, IL2RB, IL2RG, IL3RA

clus2

Top enriched gene sets are KEGG HOMOLOGOUS RECOMBINATION, PID BARD1PATHWAY, REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX, REACTOME MEIOSIS, REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S, REACTOME GENERIC TRANSCRIPTION PATHWAY, REACTOME RNA POL I TRANSCRIPTION, REACTOME RNA POL III TRANSCRIPTION, REACTOME OLFACTORY SIGNALING PATHWAY, REACTOME 3 UTR MEDIATED TRANSLATIONAL REGULATION

And common core enriched genes are HIST1H2AB, HIST1H2AC, HIST1H2AD, HIST1H2AE, HIST1H2AJ, HIST1H2BA, HIST1H2BB, HIST1H2BC, HIST1H2BD, HIST1H2BE

clus3

Top enriched gene sets are KEGG CITRATE CYCLE TCA CYCLE, KEGG SELENOAMINO ACID METABOLISM, KEGG RNA DEGRADATION, KEGG RNA POLYMERASE, KEGG SPLICEOSOME, KEGG HUNTINGTONS DISEASE, BIOCARTA MPR PATHWAY, PID HIF2PATHWAY, PID MYC ACTIVPATHWAY, REACTOME TRANSLATION

And common core enriched genes are EXOSC1, EXOSC2, EXOSC3, EXOSC4, EXOSC7, EXOSC8, EXOSC9, KHSRP, PARN, ASNS

clus4

Top enriched gene sets are KEGG LONG TERM POTENTIATION, KEGG NEUROTROPHIN SIGNALING PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA AT1R PATHWAY, SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES, PID ENDOTHELINPATHWAY, PID NOTCH PATHWAY, PID EPHBFWDPATHWAY, PID PS1PATHWAY, PID P75NTRPATHWAY

And common core enriched genes are JUN, EGFR, CCND1, EIF2C4, MAML2, MAML3, MAMLD1, NOTCH2, NOTCH3, NOTCH4

clus5

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG OXIDATIVE PHOSPHORYLATION, KEGG GLUTATHIONE METABOLISM, KEGG ETHER LIPID METABOLISM, KEGG PYRUVATE METABOLISM, KEGG PROPANOATE METABOLISM, KEGG VASOPRESSIN REGULATED WATER REABSORPTION, KEGG PARKINSONS DISEASE, KEGG PRION DISEASES, KEGG PATHOGENIC ESCHERICHIA COLI INFECTION

And common core enriched genes are ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5G3, ATP5H, ATP5O, COX4I1, COX4I2, COX5A

clus6

Top enriched gene sets are KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS, KEGG PPAR SIGNALING PATHWAY, KEGG PEROXISOME, ST WNT BETA CATENIN PATHWAY, PID HNF3BPATHWAY, PID P75NTRPATHWAY, PID SYNDECAN 4 PATHWAY, REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION

And common core enriched genes are F2, ABAT, ACAA1, ACAA2, ACAD8, ACADSB, ACAT1, ALDH1B1, ALDH2, ALDH3A2

Results

Subtype clus1 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG CYTOSOLIC DNA SENSING PATHWAY	43	genes.ES.table	0.64	1.5	0.089	1	0.96	0.46	0.21	0.37	1	0.78
KEGG T CELL RECEPTOR SIGNALING PATHWAY	108	genes.ES.table	0.51	1.4	0.17	1	0.99	0.32	0.11	0.28	1	0.57
KEGG AUTOIMMUNE THYROID DISEASE	37	genes.ES.table	0.71	1.4	0.14	1	0.99	0.81	0.2	0.65	1	0.56
KEGG ALLOGRAFT REJECTION	35	genes.ES.table	0.73	1.3	0.18	1	1	0.77	0.19	0.63	1	0.6
ST T CELL SIGNAL TRANSDUCTION	44	genes.ES.table	0.56	1.4	0.13	1	0.98	0.36	0.1	0.33	1	0.72
PID ATM PATHWAY	34	genes.ES.table	0.4	1.4	0.18	1	1	0.65	0.38	0.4	1	0.6
PID PI3KCIPATHWAY	49	genes.ES.table	0.52	1.4	0.2	1	0.99	0.39	0.22	0.3	1	0.53
PID IFNGPATHWAY	40	genes.ES.table	0.43	1.5	0.13	1	0.98	0.3	0.19	0.24	1	0.74
PID IL23PATHWAY	36	genes.ES.table	0.67	1.4	0.095	1	0.98	0.5	0.14	0.43	1	0.68
PID IL8CXCR2 PATHWAY	34	genes.ES.table	0.53	1.4	0.14	1	0.99	0.32	0.12	0.28	1	0.6

genes ES table in pathway: KEGG CYTOSOLIC DNA SENSING 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	CSF2	CSF2	CSF2	328	0.63	0.083	YES
2	IL2RA	IL2RA	IL2RA	666	0.51	0.15	YES
3	CSF2RB	CSF2RB	CSF2RB	744	0.49	0.22	YES
4	IL2	IL2	IL2	923	0.45	0.28	YES
5	PIK3CD	PIK3CD	PIK3CD	989	0.43	0.34	YES
6	IL2RG	IL2RG	IL2RG	1067	0.41	0.41	YES
7	GAB2	GAB2	GAB2	1252	0.38	0.46	YES
8	PIK3R3	PIK3R3	PIK3R3	1335	0.37	0.51	YES
9	IL2RB	IL2RB	IL2RB	1937	0.29	0.53	YES
10	JAK3	JAK3	JAK3	2100	0.27	0.56	YES
11	CSF2RA	CSF2RA	CSF2RA	2179	0.26	0.6	YES
12	JAK2	JAK2	JAK2	2468	0.24	0.62	YES
13	IL3RA	IL3RA	IL3RA	2627	0.22	0.65	YES
14	IL5	IL5	IL5	2684	0.22	0.68	YES
15	JAK1	JAK1	JAK1	4654	0.12	0.59	NO
16	IL3	IL3	IL3	4717	0.11	0.61	NO
17	SOS1	SOS1	SOS1	5109	0.098	0.6	NO
18	PTPN6	PTPN6	PTPN6	5159	0.097	0.62	NO
19	PIK3R2	PIK3R2	PIK3R2	5400	0.089	0.62	NO
20	INPPL1	INPPL1	INPPL1	7174	0.04	0.53	NO
21	PIK3R1	PIK3R1	PIK3R1	8082	0.018	0.48	NO
22	PIK3CB	PIK3CB	PIK3CB	9588	-0.018	0.41	NO
23	GRB2	GRB2	GRB2	9946	-0.027	0.39	NO
24	PIK3CA	PIK3CA	PIK3CA	10184	-0.032	0.39	NO
25	IL5RA	IL5RA	IL5RA	13315	-0.13	0.24	NO
26	HRAS	HRAS	HRAS	14393	-0.18	0.21	NO
27	SHC1	SHC1	SHC1	14614	-0.19	0.23	NO

Figure S1. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG CYTOSOLIC DNA SENSING PATHWAY.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CYTOSOLIC DNA SENSING 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 T CELL RECEPTOR SIGNALING 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	CSF2	CSF2	CSF2	328	0.63	0.054	YES
2	IL2RA	IL2RA	IL2RA	666	0.51	0.093	YES
3	CSF2RB	CSF2RB	CSF2RB	744	0.49	0.14	YES
4	IL2	IL2	IL2	923	0.45	0.18	YES
5	PIK3CD	PIK3CD	PIK3CD	989	0.43	0.23	YES
6	IL2RG	IL2RG	IL2RG	1067	0.41	0.27	YES
7	GAB2	GAB2	GAB2	1252	0.38	0.3	YES
8	TEC	TEC	TEC	1295	0.38	0.34	YES
9	HCK	HCK	HCK	1310	0.38	0.39	YES
10	PIK3R3	PIK3R3	PIK3R3	1335	0.37	0.43	YES
11	CBL	CBL	CBL	1731	0.31	0.44	YES
12	VAV1	VAV1	VAV1	1750	0.31	0.48	YES
13	IL2RB	IL2RB	IL2RB	1937	0.29	0.5	YES
14	JAK3	JAK3	JAK3	2100	0.27	0.52	YES
15	CSF2RA	CSF2RA	CSF2RA	2179	0.26	0.55	YES
16	BLNK	BLNK	BLNK	2446	0.24	0.56	YES
17	JAK2	JAK2	JAK2	2468	0.24	0.58	YES
18	IL3RA	IL3RA	IL3RA	2627	0.22	0.6	YES
19	IL5	IL5	IL5	2684	0.22	0.62	YES
20	STAT5A	STAT5A	STAT5A	3932	0.15	0.57	NO
21	SYK	SYK	SYK	4158	0.14	0.58	NO
22	CRK	CRK	CRK	4509	0.12	0.57	NO
23	JAK1	JAK1	JAK1	4654	0.12	0.58	NO
24	IL3	IL3	IL3	4717	0.11	0.58	NO
25	STAT5B	STAT5B	STAT5B	4776	0.11	0.6	NO
26	SOS1	SOS1	SOS1	5109	0.098	0.59	NO
27	PTPN6	PTPN6	PTPN6	5159	0.097	0.6	NO
28	PIK3R2	PIK3R2	PIK3R2	5400	0.089	0.59	NO
29	INPPL1	INPPL1	INPPL1	7174	0.04	0.5	NO
30	LYN	LYN	LYN	7362	0.034	0.5	NO
31	RAPGEF1	RAPGEF1	RAPGEF1	7499	0.031	0.5	NO
32	FYN	FYN	FYN	7696	0.027	0.49	NO
33	PIK3R1	PIK3R1	PIK3R1	8082	0.018	0.47	NO
34	PIK3CB	PIK3CB	PIK3CB	9588	-0.018	0.39	NO
35	GRB2	GRB2	GRB2	9946	-0.027	0.38	NO
36	PIK3CA	PIK3CA	PIK3CA	10184	-0.032	0.37	NO
37	PRKACB	PRKACB	PRKACB	10671	-0.043	0.35	NO
38	YWHAZ	YWHAZ	YWHAZ	11816	-0.074	0.3	NO
39	CRKL	CRKL	CRKL	12707	-0.1	0.26	NO
40	IL5RA	IL5RA	IL5RA	13315	-0.13	0.24	NO
41	YES1	YES1	YES1	13789	-0.15	0.24	NO
42	HRAS	HRAS	HRAS	14393	-0.18	0.22	NO
43	SHC1	SHC1	SHC1	14614	-0.19	0.23	NO

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

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

genes ES table in pathway: KEGG AUTOIMMUNE THYROID DISEASE

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	AIM2	AIM2	AIM2	319	0.64	0.076	YES
2	IL18	IL18	IL18	485	0.56	0.15	YES
3	ZBP1	ZBP1	ZBP1	886	0.45	0.19	YES
4	IL1B	IL1B	IL1B	1107	0.41	0.24	YES
5	IFNA21	IFNA21	IFNA21	1449	0.35	0.27	YES
6	CCL4L2	CCL4L2	CCL4L2	1454	0.35	0.32	YES
7	RIPK3	RIPK3	RIPK3	1511	0.34	0.37	YES
8	CCL5	CCL5	CCL5	1686	0.32	0.41	YES
9	CCL4	CCL4	CCL4	1699	0.32	0.45	YES
10	IKBKE	IKBKE	IKBKE	2144	0.27	0.47	YES
11	CXCL10	CXCL10	CXCL10	2250	0.26	0.5	YES
12	CASP1	CASP1	CASP1	2541	0.23	0.52	YES
13	POLR1C	POLR1C	POLR1C	2774	0.21	0.54	YES
14	PYCARD	PYCARD	PYCARD	2949	0.2	0.56	YES
15	TREX1	TREX1	TREX1	3293	0.18	0.56	YES
16	NFKBIB	NFKBIB	NFKBIB	3341	0.18	0.59	YES
17	MAVS	MAVS	MAVS	3836	0.15	0.58	YES
18	POLR3G	POLR3G	POLR3G	3848	0.15	0.6	YES
19	IRF7	IRF7	IRF7	3884	0.15	0.62	YES
20	IL6	IL6	IL6	4027	0.14	0.64	YES
21	IL33	IL33	IL33	4416	0.12	0.63	NO
22	POLR3A	POLR3A	POLR3A	5225	0.094	0.6	NO
23	POLR3F	POLR3F	POLR3F	5712	0.08	0.59	NO
24	CHUK	CHUK	CHUK	5954	0.073	0.59	NO
25	POLR3C	POLR3C	POLR3C	6212	0.065	0.58	NO
26	ADAR	ADAR	ADAR	6930	0.046	0.55	NO
27	IKBKB	IKBKB	IKBKB	7000	0.045	0.56	NO
28	POLR3GL	POLR3GL	POLR3GL	7050	0.043	0.56	NO
29	TBK1	TBK1	TBK1	7710	0.026	0.53	NO
30	RELA	RELA	RELA	7802	0.024	0.53	NO
31	NFKBIA	NFKBIA	NFKBIA	8597	0.0051	0.49	NO
32	POLR3D	POLR3D	POLR3D	8785	0.00086	0.48	NO
33	DDX58	DDX58	DDX58	8838	-0.00043	0.48	NO
34	POLR1D	POLR1D	POLR1D	8919	-0.0023	0.47	NO
35	RIPK1	RIPK1	RIPK1	8953	-0.0029	0.47	NO
36	POLR3B	POLR3B	POLR3B	8959	-0.003	0.47	NO
37	IRF3	IRF3	IRF3	9344	-0.012	0.45	NO
38	IFNB1	IFNB1	IFNB1	11071	-0.054	0.37	NO
39	POLR3H	POLR3H	POLR3H	11076	-0.054	0.38	NO
40	IKBKG	IKBKG	IKBKG	11121	-0.056	0.38	NO
41	POLR3K	POLR3K	POLR3K	11461	-0.064	0.37	NO
42	NFKB1	NFKB1	NFKB1	11593	-0.068	0.38	NO
43	TMEM173	TMEM173	TMEM173	12930	-0.11	0.32	NO

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

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG AUTOIMMUNE THYROID DISEASE, 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 ALLOGRAFT REJECTION

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	CD80	CD80	CD80	568	0.54	0.09	YES
2	CD28	CD28	CD28	755	0.48	0.19	YES
3	GRAP2	GRAP2	GRAP2	1174	0.4	0.26	YES
4	PIK3R3	PIK3R3	PIK3R3	1335	0.37	0.33	YES
5	MAP3K8	MAP3K8	MAP3K8	1580	0.34	0.39	YES
6	CD86	CD86	CD86	1603	0.33	0.46	YES
7	VAV1	VAV1	VAV1	1750	0.31	0.53	YES
8	LCK	LCK	LCK	3268	0.18	0.49	NO
9	RICTOR	RICTOR	RICTOR	3905	0.15	0.49	NO
10	MAP3K14	MAP3K14	MAP3K14	4727	0.11	0.47	NO
11	TRIB3	TRIB3	TRIB3	4799	0.11	0.49	NO
12	PIK3R2	PIK3R2	PIK3R2	5400	0.089	0.48	NO
13	MTOR	MTOR	MTOR	5870	0.075	0.47	NO
14	LYN	LYN	LYN	7362	0.034	0.4	NO
15	FYN	FYN	FYN	7696	0.027	0.39	NO
16	PIK3R1	PIK3R1	PIK3R1	8082	0.018	0.37	NO
17	AKT2	AKT2	AKT2	9255	-0.0099	0.31	NO
18	RAC1	RAC1	RAC1	9270	-0.01	0.31	NO
19	GRB2	GRB2	GRB2	9946	-0.027	0.28	NO
20	AKT3	AKT3	AKT3	10036	-0.029	0.28	NO
21	PIK3CA	PIK3CA	PIK3CA	10184	-0.032	0.28	NO
22	SRC	SRC	SRC	10831	-0.048	0.26	NO
23	AKT1	AKT1	AKT1	10865	-0.049	0.27	NO
24	MLST8	MLST8	MLST8	11033	-0.053	0.27	NO
25	CDC42	CDC42	CDC42	11253	-0.059	0.27	NO
26	MAPKAP1	MAPKAP1	MAPKAP1	11670	-0.07	0.27	NO
27	PAK2	PAK2	PAK2	11806	-0.074	0.28	NO
28	THEM4	THEM4	THEM4	12435	-0.095	0.26	NO
29	PAK1	PAK1	PAK1	12688	-0.1	0.28	NO
30	PDPK1	PDPK1	PDPK1	13023	-0.12	0.28	NO
31	YES1	YES1	YES1	13789	-0.15	0.28	NO

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

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

genes ES table in pathway: ST T CELL SIGNAL TRANSDUCTION

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	TUBA3D	TUBA3D	TUBA3D	62	0.94	0.25	YES
2	TUBA3C	TUBA3C	TUBA3C	73	0.92	0.49	YES
3	TUBB3	TUBB3	TUBB3	4108	0.14	0.32	NO
4	TCP1	TCP1	TCP1	4733	0.11	0.32	NO
5	CCT2	CCT2	CCT2	4971	0.1	0.33	NO
6	CCT6A	CCT6A	CCT6A	5247	0.094	0.34	NO
7	CCT8	CCT8	CCT8	5508	0.086	0.35	NO
8	PFDN2	PFDN2	PFDN2	5746	0.079	0.36	NO
9	PFDN1	PFDN1	PFDN1	7088	0.042	0.3	NO
10	CCT5	CCT5	CCT5	7406	0.033	0.29	NO
11	CCT3	CCT3	CCT3	7459	0.032	0.3	NO
12	CCT4	CCT4	CCT4	7709	0.026	0.29	NO
13	TUBA4A	TUBA4A	TUBA4A	8642	0.0044	0.25	NO
14	PFDN6	PFDN6	PFDN6	8646	0.0043	0.25	NO
15	CCT7	CCT7	CCT7	8900	-0.0019	0.23	NO
16	PFDN5	PFDN5	PFDN5	8981	-0.0034	0.23	NO
17	TUBB1	TUBB1	TUBB1	10081	-0.03	0.18	NO
18	TUBA1C	TUBA1C	TUBA1C	10160	-0.031	0.18	NO
19	ACTB	ACTB	ACTB	10340	-0.036	0.18	NO
20	TUBA1A	TUBA1A	TUBA1A	12272	-0.089	0.11	NO
21	PFDN4	PFDN4	PFDN4	12910	-0.11	0.1	NO
22	VBP1	VBP1	VBP1	13838	-0.15	0.096	NO
23	TUBB6	TUBB6	TUBB6	13946	-0.16	0.13	NO
24	TUBB2B	TUBB2B	TUBB2B	14808	-0.21	0.14	NO
25	TUBB2A	TUBB2A	TUBB2A	15956	-0.3	0.16	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: ST T CELL SIGNAL TRANSDUCTION.

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

genes ES table in pathway: PID ATM 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	IFNG	IFNG	IFNG	644	0.52	0.07	YES
2	IL1B	IL1B	IL1B	1107	0.41	0.13	YES
3	CBL	CBL	CBL	1731	0.31	0.16	YES
4	PIAS1	PIAS1	PIAS1	2300	0.25	0.18	YES
5	JAK2	JAK2	JAK2	2468	0.24	0.22	YES
6	CASP1	CASP1	CASP1	2541	0.23	0.26	YES
7	IRF1	IRF1	IRF1	2669	0.22	0.3	YES
8	DAPK1	DAPK1	DAPK1	3089	0.19	0.32	YES
9	STAT1	STAT1	STAT1	3093	0.19	0.35	YES
10	IRF9	IRF9	IRF9	3235	0.18	0.38	YES
11	CAMK2G	CAMK2G	CAMK2G	3342	0.18	0.41	YES
12	IFNGR1	IFNGR1	IFNGR1	3666	0.16	0.43	YES
13	JAK1	JAK1	JAK1	4654	0.12	0.4	NO
14	PIAS4	PIAS4	PIAS4	4999	0.1	0.4	NO
15	MAPK1	MAPK1	MAPK1	5497	0.086	0.39	NO
16	RAP1B	RAP1B	RAP1B	5547	0.085	0.41	NO
17	MTOR	MTOR	MTOR	5870	0.075	0.41	NO
18	MAP3K1	MAP3K1	MAP3K1	5945	0.073	0.42	NO
19	PTPN2	PTPN2	PTPN2	6898	0.047	0.38	NO
20	EP300	EP300	EP300	7177	0.04	0.37	NO
21	RAPGEF1	RAPGEF1	RAPGEF1	7499	0.031	0.36	NO
22	PRKCD	PRKCD	PRKCD	7675	0.027	0.36	NO
23	PIK3R1	PIK3R1	PIK3R1	8082	0.018	0.34	NO
24	CREBBP	CREBBP	CREBBP	8270	0.013	0.33	NO
25	MAP3K11	MAP3K11	MAP3K11	8359	0.01	0.33	NO
26	PTGES2	PTGES2	PTGES2	9087	-0.0058	0.29	NO
27	MAP2K1	MAP2K1	MAP2K1	9247	-0.0097	0.28	NO
28	STAT3	STAT3	STAT3	9399	-0.014	0.28	NO
29	SOCS1	SOCS1	SOCS1	9959	-0.027	0.26	NO
30	PIK3CA	PIK3CA	PIK3CA	10184	-0.032	0.25	NO
31	CEBPB	CEBPB	CEBPB	10298	-0.034	0.25	NO
32	AKT1	AKT1	AKT1	10865	-0.049	0.23	NO
33	PTPN11	PTPN11	PTPN11	11337	-0.061	0.22	NO
34	RAP1A	RAP1A	RAP1A	11551	-0.067	0.22	NO
35	CAMK2D	CAMK2D	CAMK2D	12072	-0.083	0.21	NO
36	CAMK2A	CAMK2A	CAMK2A	12250	-0.089	0.22	NO
37	CRKL	CRKL	CRKL	12707	-0.1	0.22	NO
38	MAPK3	MAPK3	MAPK3	12851	-0.11	0.23	NO
39	CAMK2B	CAMK2B	CAMK2B	15047	-0.22	0.16	NO
40	SMAD7	SMAD7	SMAD7	15375	-0.25	0.19	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: PID ATM PATHWAY.

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

genes ES table in pathway: PID PI3KCIPATHWAY

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	CD28	CD28	CD28	755	0.48	0.011	YES
2	CTLA4	CTLA4	CTLA4	810	0.47	0.058	YES
3	ITK	ITK	ITK	826	0.47	0.1	YES
4	RASGRP4	RASGRP4	RASGRP4	844	0.46	0.15	YES
5	RASGRP2	RASGRP2	RASGRP2	912	0.45	0.2	YES
6	CD3D	CD3D	CD3D	940	0.44	0.24	YES
7	ITPKA	ITPKA	ITPKA	975	0.44	0.28	YES
8	GRAP2	GRAP2	GRAP2	1174	0.4	0.32	YES
9	PTPRC	PTPRC	PTPRC	1261	0.38	0.35	YES
10	LCP2	LCP2	LCP2	1316	0.37	0.39	YES
11	PAK7	PAK7	PAK7	1373	0.36	0.42	YES
12	RASGRP1	RASGRP1	RASGRP1	1470	0.35	0.46	YES
13	CBL	CBL	CBL	1731	0.31	0.47	YES
14	VAV1	VAV1	VAV1	1750	0.31	0.51	YES
15	ZAP70	ZAP70	ZAP70	1830	0.3	0.53	YES
16	LAT	LAT	LAT	1935	0.29	0.56	YES
17	LCK	LCK	LCK	3268	0.18	0.51	NO
18	NFKBIB	NFKBIB	NFKBIB	3341	0.18	0.52	NO
19	NFKBIE	NFKBIE	NFKBIE	3532	0.17	0.53	NO
20	PAK3	PAK3	PAK3	3739	0.16	0.53	NO
21	FBXW7	FBXW7	FBXW7	4021	0.14	0.53	NO
22	NCK1	NCK1	NCK1	4335	0.13	0.53	NO
23	SOS1	SOS1	SOS1	5109	0.098	0.5	NO
24	CSK	CSK	CSK	5114	0.098	0.51	NO
25	MAPK1	MAPK1	MAPK1	5497	0.086	0.5	NO
26	NFKB2	NFKB2	NFKB2	5955	0.073	0.48	NO
27	ITPKB	ITPKB	ITPKB	6104	0.069	0.48	NO
28	RASGRP3	RASGRP3	RASGRP3	6515	0.057	0.47	NO
29	PLCG1	PLCG1	PLCG1	6988	0.045	0.45	NO
30	RAF1	RAF1	RAF1	8160	0.016	0.39	NO
31	NFKBIA	NFKBIA	NFKBIA	8597	0.0051	0.36	NO
32	DTYMK	DTYMK	DTYMK	8827	-0.00013	0.35	NO
33	PRDX1	PRDX1	PRDX1	9296	-0.011	0.33	NO
34	GRB2	GRB2	GRB2	9946	-0.027	0.3	NO
35	PAK4	PAK4	PAK4	10642	-0.042	0.26	NO
36	NFKB1	NFKB1	NFKB1	11593	-0.068	0.22	NO
37	NFAT5	NFAT5	NFAT5	11754	-0.072	0.22	NO
38	PAK2	PAK2	PAK2	11806	-0.074	0.23	NO
39	PAK1	PAK1	PAK1	12688	-0.1	0.19	NO
40	DAG1	DAG1	DAG1	13310	-0.13	0.17	NO
41	NFKBIL1	NFKBIL1	NFKBIL1	14439	-0.18	0.13	NO
42	SOS2	SOS2	SOS2	15880	-0.29	0.086	NO
43	PAK6	PAK6	PAK6	16481	-0.35	0.091	NO
44	EPHB2	EPHB2	EPHB2	17051	-0.42	0.1	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: PID PI3KCIPATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: PID PI3KCIPATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID IFNGPATHWAY

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	IL12B	IL12B	IL12B	4	1.3	0.12	YES
2	MPO	MPO	MPO	130	0.81	0.18	YES
3	IL18RAP	IL18RAP	IL18RAP	288	0.66	0.23	YES
4	IL23R	IL23R	IL23R	357	0.62	0.28	YES
5	TNF	TNF	TNF	403	0.6	0.34	YES
6	IL18	IL18	IL18	485	0.56	0.38	YES
7	CXCL9	CXCL9	CXCL9	575	0.54	0.42	YES
8	IFNG	IFNG	IFNG	644	0.52	0.47	YES
9	IL12RB1	IL12RB1	IL12RB1	811	0.47	0.5	YES
10	CD3E	CD3E	CD3E	879	0.46	0.54	YES
11	IL2	IL2	IL2	923	0.45	0.57	YES
12	IL1B	IL1B	IL1B	1107	0.41	0.6	YES
13	STAT4	STAT4	STAT4	1111	0.41	0.64	YES
14	IL19	IL19	IL19	1219	0.39	0.67	YES
15	CD4	CD4	CD4	2120	0.27	0.64	YES
16	JAK2	JAK2	JAK2	2468	0.24	0.65	YES
17	IL24	IL24	IL24	2662	0.22	0.66	YES
18	IL18R1	IL18R1	IL18R1	2768	0.21	0.67	YES
19	STAT1	STAT1	STAT1	3093	0.19	0.67	NO
20	STAT5A	STAT5A	STAT5A	3932	0.15	0.64	NO
21	IL6	IL6	IL6	4027	0.14	0.64	NO
22	TYK2	TYK2	TYK2	6053	0.07	0.54	NO
23	NOS2	NOS2	NOS2	6874	0.048	0.51	NO
24	RELA	RELA	RELA	7802	0.024	0.46	NO
25	IL17F	IL17F	IL17F	7890	0.022	0.46	NO
26	PIK3R1	PIK3R1	PIK3R1	8082	0.018	0.45	NO
27	NFKBIA	NFKBIA	NFKBIA	8597	0.0051	0.42	NO
28	STAT3	STAT3	STAT3	9399	-0.014	0.38	NO
29	PIK3CA	PIK3CA	PIK3CA	10184	-0.032	0.34	NO
30	CCL2	CCL2	CCL2	11311	-0.061	0.29	NO
31	NFKB1	NFKB1	NFKB1	11593	-0.068	0.28	NO
32	SOCS3	SOCS3	SOCS3	13921	-0.16	0.17	NO
33	ALOX12B	ALOX12B	ALOX12B	14926	-0.21	0.14	NO
34	CXCL1	CXCL1	CXCL1	15031	-0.22	0.15	NO
35	ITGA3	ITGA3	ITGA3	15910	-0.29	0.13	NO
36	IL23A	IL23A	IL23A	16751	-0.38	0.12	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: PID IFNGPATHWAY.

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

genes ES table in pathway: PID IL23PATHWAY

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	BLK	BLK	BLK	735	0.49	0.06	YES
2	CD19	CD19	CD19	929	0.44	0.14	YES
3	PIK3CD	PIK3CD	PIK3CD	989	0.43	0.22	YES
4	CD79A	CD79A	CD79A	1247	0.38	0.29	YES
5	BTK	BTK	BTK	1391	0.36	0.35	YES
6	CBL	CBL	CBL	1731	0.31	0.4	YES
7	VAV1	VAV1	VAV1	1750	0.31	0.46	YES
8	CD79B	CD79B	CD79B	2336	0.25	0.48	YES
9	BLNK	BLNK	BLNK	2446	0.24	0.52	YES
10	PLCG2	PLCG2	PLCG2	2854	0.21	0.54	YES
11	PIK3AP1	PIK3AP1	PIK3AP1	3318	0.18	0.55	YES
12	STIM1	STIM1	STIM1	3728	0.16	0.56	YES
13	CBLB	CBLB	CBLB	3772	0.15	0.59	YES
14	SYK	SYK	SYK	4158	0.14	0.6	YES
15	NCK1	NCK1	NCK1	4335	0.13	0.61	YES
16	CALM2	CALM2	CALM2	5097	0.099	0.59	NO
17	SOS1	SOS1	SOS1	5109	0.098	0.61	NO
18	ITPR3	ITPR3	ITPR3	6415	0.06	0.56	NO
19	PLCG1	PLCG1	PLCG1	6988	0.045	0.53	NO
20	LYN	LYN	LYN	7362	0.034	0.52	NO
21	FYN	FYN	FYN	7696	0.027	0.51	NO
22	PIK3R1	PIK3R1	PIK3R1	8082	0.018	0.49	NO
23	GRB2	GRB2	GRB2	9946	-0.027	0.4	NO
24	ORAI1	ORAI1	ORAI1	9964	-0.027	0.4	NO
25	SH3KBP1	SH3KBP1	SH3KBP1	10028	-0.028	0.41	NO
26	CALM1	CALM1	CALM1	10278	-0.034	0.4	NO
27	ITPR2	ITPR2	ITPR2	10773	-0.046	0.38	NO
28	CALM3	CALM3	CALM3	11375	-0.062	0.36	NO
29	SHC1	SHC1	SHC1	14614	-0.19	0.23	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: PID IL23PATHWAY.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: PID IL23PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID IL8CXCR2 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ELOVL3	ELOVL3	ELOVL3	65	0.93	0.12	YES
2	GPAT2	GPAT2	GPAT2	268	0.68	0.2	YES
3	DGAT2	DGAT2	DGAT2	508	0.56	0.26	YES
4	ELOVL6	ELOVL6	ELOVL6	818	0.47	0.31	YES
5	LPIN2	LPIN2	LPIN2	2109	0.27	0.27	YES
6	GK	GK	GK	2259	0.25	0.3	YES
7	ACSL4	ACSL4	ACSL4	2635	0.22	0.31	YES
8	LPCAT4	LPCAT4	LPCAT4	2941	0.2	0.32	YES
9	AGPAT6	AGPAT6	AGPAT6	2959	0.2	0.34	YES
10	LPIN1	LPIN1	LPIN1	3138	0.19	0.36	YES
11	ACSL5	ACSL5	ACSL5	3648	0.16	0.36	YES
12	ELOVL4	ELOVL4	ELOVL4	3718	0.16	0.37	YES
13	ACSL1	ACSL1	ACSL1	3730	0.16	0.39	YES
14	LCLAT1	LCLAT1	LCLAT1	5361	0.09	0.32	NO
15	AGPAT4	AGPAT4	AGPAT4	5447	0.087	0.32	NO
16	ACSL6	ACSL6	ACSL6	5637	0.082	0.33	NO
17	TECR	TECR	TECR	6444	0.059	0.29	NO
18	AGPAT5	AGPAT5	AGPAT5	6734	0.052	0.28	NO
19	ACLY	ACLY	ACLY	7411	0.033	0.25	NO
20	LPCAT1	LPCAT1	LPCAT1	7558	0.03	0.25	NO
21	AGPAT2	AGPAT2	AGPAT2	8371	0.01	0.21	NO
22	ACACA	ACACA	ACACA	9966	-0.027	0.13	NO
23	DGAT1	DGAT1	DGAT1	10377	-0.036	0.11	NO
24	ELOVL7	ELOVL7	ELOVL7	10576	-0.041	0.1	NO
25	AGPAT1	AGPAT1	AGPAT1	11512	-0.066	0.064	NO
26	ELOVL5	ELOVL5	ELOVL5	11583	-0.068	0.07	NO
27	HSD17B12	HSD17B12	HSD17B12	12111	-0.084	0.053	NO
28	ACSL3	ACSL3	ACSL3	12302	-0.09	0.055	NO
29	LPIN3	LPIN3	LPIN3	13477	-0.14	0.011	NO
30	GPD1	GPD1	GPD1	13828	-0.15	0.013	NO
31	ELOVL2	ELOVL2	ELOVL2	13987	-0.16	0.026	NO
32	FASN	FASN	FASN	14207	-0.17	0.037	NO
33	SLC25A1	SLC25A1	SLC25A1	14276	-0.18	0.056	NO
34	GPAM	GPAM	GPAM	14754	-0.2	0.058	NO
35	GPD1L	GPD1L	GPD1L	14957	-0.22	0.076	NO
36	ELOVL1	ELOVL1	ELOVL1	14992	-0.22	0.1	NO
37	AGPAT3	AGPAT3	AGPAT3	15161	-0.23	0.12	NO
38	AGPAT9	AGPAT9	AGPAT9	18161	-0.6	0.047	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: PID IL8CXCR2 PATHWAY.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: PID IL8CXCR2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG HOMOLOGOUS RECOMBINATION	26	genes.ES.table	0.52	1.4	0.17	1	0.99	0.62	0.34	0.4	0.81	0.43
PID BARD1PATHWAY	29	genes.ES.table	0.53	1.5	0.082	1	0.93	0.69	0.38	0.43	0.56	0.33
REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX	49	genes.ES.table	0.53	1.4	0.16	1	0.99	0.76	0.41	0.45	0.76	0.41
REACTOME MEIOSIS	105	genes.ES.table	0.67	1.6	0.06	1	0.91	0.45	0.12	0.4	1	0.6
REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S	57	genes.ES.table	0.51	1.4	0.18	1	0.99	0.7	0.41	0.42	0.84	0.44
REACTOME GENERIC TRANSCRIPTION PATHWAY	342	genes.ES.table	0.39	1.5	0.1	1	0.98	0.49	0.24	0.38	0.67	0.37
REACTOME RNA POL I TRANSCRIPTION	81	genes.ES.table	0.71	1.5	0.069	1	0.92	0.47	0.12	0.42	0.68	0.38
REACTOME RNA POL III TRANSCRIPTION	33	genes.ES.table	0.47	1.5	0.1	1	0.92	0.46	0.24	0.35	0.79	0.42
REACTOME OLFACTORY SIGNALING PATHWAY	53	genes.ES.table	0.59	1.4	0.059	1	1	0.47	0.13	0.41	0.86	0.44
REACTOME 3 UTR MEDIATED TRANSLATIONAL REGULATION	106	genes.ES.table	0.47	1.4	0.21	1	1	0.74	0.41	0.44	0.89	0.46

genes ES table in pathway: KEGG HOMOLOGOUS RECOMBINATION

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	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	3	1.1	0.063	YES
2	HIST1H2BL	HIST1H2BL	HIST1H2BL	11	0.96	0.12	YES
3	HIST1H2AB	HIST1H2AB	HIST1H2AB	22	0.9	0.16	YES
4	HIST1H4C	HIST1H4C	HIST1H4C	170	0.65	0.19	YES
5	HIST1H4D	HIST1H4D	HIST1H4D	174	0.64	0.23	YES
6	HIST1H4J	HIST1H4J	HIST1H4J	190	0.63	0.26	YES
7	HIST1H2BM	HIST1H2BM	HIST1H2BM	217	0.61	0.29	YES
8	HIST1H2BA	HIST1H2BA	HIST1H2BA	268	0.57	0.32	YES
9	HIST1H2AE	HIST1H2AE	HIST1H2AE	273	0.57	0.36	YES
10	HIST1H2BE	HIST1H2BE	HIST1H2BE	353	0.53	0.38	YES
11	HIST1H2BO	HIST1H2BO	HIST1H2BO	374	0.53	0.41	YES
12	HIST1H2BB	HIST1H2BB	HIST1H2BB	454	0.49	0.43	YES
13	HIST1H2AC	HIST1H2AC	HIST1H2AC	485	0.48	0.46	YES
14	HIST1H4H	HIST1H4H	HIST1H4H	487	0.48	0.48	YES
15	HIST1H2BG	HIST1H2BG	HIST1H2BG	558	0.46	0.5	YES
16	HIST1H2BD	HIST1H2BD	HIST1H2BD	569	0.46	0.53	YES
17	HIST1H4E	HIST1H4E	HIST1H4E	574	0.45	0.56	YES
18	HIST1H4K	HIST1H4K	HIST1H4K	597	0.45	0.58	YES
19	HIST1H4I	HIST1H4I	HIST1H4I	733	0.41	0.59	YES
20	HIST1H2BK	HIST1H2BK	HIST1H2BK	845	0.38	0.61	YES
21	HIST3H2BB	HIST3H2BB	HIST3H2BB	883	0.38	0.63	YES
22	HIST1H2BC	HIST1H2BC	HIST1H2BC	885	0.38	0.65	YES
23	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1103	0.34	0.66	YES
24	HIST1H2BF	HIST1H2BF	HIST1H2BF	1571	0.28	0.65	YES
25	HIST1H4F	HIST1H4F	HIST1H4F	1831	0.25	0.65	YES
26	HIST1H4B	HIST1H4B	HIST1H4B	1838	0.25	0.66	YES
27	POLE2	POLE2	POLE2	1988	0.23	0.66	YES
28	HIST1H2AD	HIST1H2AD	HIST1H2AD	1989	0.23	0.68	YES
29	HIST4H4	HIST4H4	HIST4H4	2055	0.23	0.69	YES
30	HIST1H2BI	HIST1H2BI	HIST1H2BI	2106	0.22	0.7	YES
31	DNA2	DNA2	DNA2	2397	0.2	0.69	NO
32	HIST1H2BH	HIST1H2BH	HIST1H2BH	2727	0.18	0.68	NO
33	HIST1H4A	HIST1H4A	HIST1H4A	3146	0.16	0.67	NO
34	LIG1	LIG1	LIG1	3404	0.15	0.67	NO
35	POLE	POLE	POLE	3724	0.13	0.66	NO
36	PRIM2	PRIM2	PRIM2	4083	0.12	0.64	NO
37	HIST2H2BE	HIST2H2BE	HIST2H2BE	4377	0.11	0.64	NO
38	PRIM1	PRIM1	PRIM1	4601	0.1	0.63	NO
39	HIST1H2BN	HIST1H2BN	HIST1H2BN	4694	0.1	0.63	NO
40	POLD1	POLD1	POLD1	5593	0.077	0.59	NO
41	RPA1	RPA1	RPA1	5703	0.074	0.58	NO
42	RUVBL2	RUVBL2	RUVBL2	6088	0.064	0.57	NO
43	RUVBL1	RUVBL1	RUVBL1	6173	0.061	0.57	NO
44	POT1	POT1	POT1	6678	0.049	0.54	NO
45	FEN1	FEN1	FEN1	6977	0.042	0.53	NO
46	RPA3	RPA3	RPA3	7048	0.04	0.53	NO
47	NHP2	NHP2	NHP2	7138	0.038	0.53	NO
48	PCNA	PCNA	PCNA	7766	0.024	0.5	NO
49	RFC4	RFC4	RFC4	8066	0.018	0.48	NO
50	TERT	TERT	TERT	8558	0.0058	0.45	NO
51	RFC2	RFC2	RFC2	8660	0.0035	0.45	NO
52	RFC3	RFC3	RFC3	9044	-0.0052	0.43	NO
53	POLD2	POLD2	POLD2	9052	-0.0054	0.43	NO
54	POLA1	POLA1	POLA1	9355	-0.013	0.41	NO
55	TERF2IP	TERF2IP	TERF2IP	9522	-0.017	0.41	NO
56	RPA2	RPA2	RPA2	9883	-0.025	0.39	NO
57	ACD	ACD	ACD	9974	-0.028	0.38	NO
58	POLD3	POLD3	POLD3	10139	-0.032	0.38	NO
59	DKC1	DKC1	DKC1	10217	-0.035	0.38	NO
60	HIST1H4L	HIST1H4L	HIST1H4L	10796	-0.05	0.35	NO
61	H2AFZ	H2AFZ	H2AFZ	10901	-0.053	0.35	NO
62	TERF2	TERF2	TERF2	11071	-0.058	0.34	NO
63	HIST2H2AC	HIST2H2AC	HIST2H2AC	11111	-0.059	0.34	NO
64	POLA2	POLA2	POLA2	11932	-0.082	0.3	NO
65	RFC5	RFC5	RFC5	13112	-0.13	0.25	NO
66	TINF2	TINF2	TINF2	13335	-0.14	0.24	NO
67	WRAP53	WRAP53	WRAP53	13393	-0.14	0.25	NO
68	POLD4	POLD4	POLD4	13499	-0.14	0.25	NO
69	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	13602	-0.15	0.25	NO
70	H2AFX	H2AFX	H2AFX	14283	-0.19	0.23	NO
71	TERF1	TERF1	TERF1	14294	-0.19	0.24	NO
72	HIST2H4A	HIST2H4A	HIST2H4A	14707	-0.22	0.23	NO

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

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

genes ES table in pathway: PID BARD1PATHWAY

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	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	3	1.1	0.036	YES
2	HIST1H3C	HIST1H3C	HIST1H3C	5	1.1	0.07	YES
3	HIST1H2BL	HIST1H2BL	HIST1H2BL	11	0.96	0.1	YES
4	HIST1H2AB	HIST1H2AB	HIST1H2AB	22	0.9	0.13	YES
5	HIST1H3A	HIST1H3A	HIST1H3A	67	0.76	0.15	YES
6	HIST1H3H	HIST1H3H	HIST1H3H	139	0.67	0.17	YES
7	HIST1H4C	HIST1H4C	HIST1H4C	170	0.65	0.18	YES
8	HIST1H4D	HIST1H4D	HIST1H4D	174	0.64	0.2	YES
9	HIST1H4J	HIST1H4J	HIST1H4J	190	0.63	0.22	YES
10	HIST1H2BM	HIST1H2BM	HIST1H2BM	217	0.61	0.24	YES
11	HIST1H2BA	HIST1H2BA	HIST1H2BA	268	0.57	0.26	YES
12	HIST1H2AE	HIST1H2AE	HIST1H2AE	273	0.57	0.28	YES
13	HIST1H2BE	HIST1H2BE	HIST1H2BE	353	0.53	0.29	YES
14	HIST1H2BO	HIST1H2BO	HIST1H2BO	374	0.53	0.3	YES
15	HIST1H2BB	HIST1H2BB	HIST1H2BB	454	0.49	0.31	YES
16	HIST1H2AC	HIST1H2AC	HIST1H2AC	485	0.48	0.33	YES
17	HIST1H4H	HIST1H4H	HIST1H4H	487	0.48	0.34	YES
18	HIST1H2BG	HIST1H2BG	HIST1H2BG	558	0.46	0.35	YES
19	HIST1H2BD	HIST1H2BD	HIST1H2BD	569	0.46	0.37	YES
20	HIST1H4E	HIST1H4E	HIST1H4E	574	0.45	0.38	YES
21	HIST1H4K	HIST1H4K	HIST1H4K	597	0.45	0.39	YES
22	HIST1H4I	HIST1H4I	HIST1H4I	733	0.41	0.4	YES
23	HIST1H2BK	HIST1H2BK	HIST1H2BK	845	0.38	0.41	YES
24	HIST3H2BB	HIST3H2BB	HIST3H2BB	883	0.38	0.42	YES
25	HIST1H2BC	HIST1H2BC	HIST1H2BC	885	0.38	0.43	YES
26	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1103	0.34	0.43	YES
27	HIST1H3I	HIST1H3I	HIST1H3I	1114	0.33	0.44	YES
28	HIST1H3B	HIST1H3B	HIST1H3B	1144	0.33	0.44	YES
29	LZTS1	LZTS1	LZTS1	1283	0.31	0.45	YES
30	HIST1H3G	HIST1H3G	HIST1H3G	1307	0.31	0.46	YES
31	HIST1H3D	HIST1H3D	HIST1H3D	1392	0.3	0.46	YES
32	TAF4B	TAF4B	TAF4B	1451	0.29	0.47	YES
33	ERCC6	ERCC6	ERCC6	1555	0.28	0.47	YES
34	HIST1H2BF	HIST1H2BF	HIST1H2BF	1571	0.28	0.48	YES
35	TAF5	TAF5	TAF5	1699	0.26	0.48	YES
36	HIST1H4F	HIST1H4F	HIST1H4F	1831	0.25	0.48	YES
37	HIST1H4B	HIST1H4B	HIST1H4B	1838	0.25	0.49	YES
38	GTF2A1	GTF2A1	GTF2A1	1897	0.24	0.49	YES
39	HIST1H2AD	HIST1H2AD	HIST1H2AD	1989	0.23	0.5	YES
40	HIST4H4	HIST4H4	HIST4H4	2055	0.23	0.5	YES
41	HIST1H2BI	HIST1H2BI	HIST1H2BI	2106	0.22	0.5	YES
42	CCNT1	CCNT1	CCNT1	2115	0.22	0.51	YES
43	TAF13	TAF13	TAF13	2130	0.22	0.52	YES
44	HIST1H3E	HIST1H3E	HIST1H3E	2206	0.21	0.52	YES
45	SNAPC4	SNAPC4	SNAPC4	2264	0.21	0.52	YES
46	MTERF	MTERF	MTERF	2321	0.21	0.53	YES
47	POLR3C	POLR3C	POLR3C	2509	0.19	0.52	YES
48	SNAPC1	SNAPC1	SNAPC1	2563	0.19	0.52	YES
49	ELL	ELL	ELL	2576	0.19	0.53	YES
50	POLR2K	POLR2K	POLR2K	2726	0.18	0.53	YES
51	HIST1H2BH	HIST1H2BH	HIST1H2BH	2727	0.18	0.53	YES
52	HIST1H4A	HIST1H4A	HIST1H4A	3146	0.16	0.52	YES
53	GTF2A2	GTF2A2	GTF2A2	3154	0.16	0.52	YES
54	POU2F1	POU2F1	POU2F1	3280	0.15	0.52	YES
55	CBX3	CBX3	CBX3	3296	0.15	0.52	YES
56	BRF2	BRF2	BRF2	3378	0.15	0.52	YES
57	GTF2E1	GTF2E1	GTF2E1	3399	0.15	0.53	YES
58	POLRMT	POLRMT	POLRMT	3469	0.14	0.53	YES
59	POLR2F	POLR2F	POLR2F	3501	0.14	0.53	YES
60	TCEA1	TCEA1	TCEA1	3643	0.14	0.53	YES
61	SNRPE	SNRPE	SNRPE	3645	0.14	0.53	YES
62	POLR3D	POLR3D	POLR3D	3939	0.12	0.52	YES
63	TAF1B	TAF1B	TAF1B	4045	0.12	0.52	YES
64	GTF3C2	GTF3C2	GTF3C2	4090	0.12	0.52	YES
65	POLR1C	POLR1C	POLR1C	4150	0.12	0.52	YES
66	KAT2B	KAT2B	KAT2B	4156	0.12	0.52	YES
67	POLR2I	POLR2I	POLR2I	4235	0.12	0.52	YES
68	SNRPD3	SNRPD3	SNRPD3	4277	0.11	0.52	YES
69	POLR2D	POLR2D	POLR2D	4305	0.11	0.53	YES
70	TCEB1	TCEB1	TCEB1	4365	0.11	0.53	YES
71	HIST2H2BE	HIST2H2BE	HIST2H2BE	4377	0.11	0.53	YES
72	POLR3A	POLR3A	POLR3A	4401	0.11	0.53	YES
73	POLR3B	POLR3B	POLR3B	4412	0.11	0.54	YES
74	GTF3C3	GTF3C3	GTF3C3	4430	0.11	0.54	YES
75	TAF6	TAF6	TAF6	4445	0.11	0.54	YES
76	GTF3C4	GTF3C4	GTF3C4	4595	0.1	0.54	YES
77	LSM11	LSM11	LSM11	4626	0.1	0.54	YES
78	CSTF2	CSTF2	CSTF2	4689	0.1	0.54	YES
79	HIST1H2BN	HIST1H2BN	HIST1H2BN	4694	0.1	0.54	YES
80	SUPT5H	SUPT5H	SUPT5H	4734	0.1	0.54	YES
81	HIST1H3J	HIST1H3J	HIST1H3J	4843	0.097	0.54	NO
82	SNRPG	SNRPG	SNRPG	5064	0.091	0.53	NO
83	TFB2M	TFB2M	TFB2M	5158	0.088	0.53	NO
84	POLR2B	POLR2B	POLR2B	5188	0.087	0.53	NO
85	GTF2E2	GTF2E2	GTF2E2	5270	0.085	0.53	NO
86	SNAPC2	SNAPC2	SNAPC2	5399	0.082	0.52	NO
87	CCNT2	CCNT2	CCNT2	5561	0.077	0.52	NO
88	SNRPB	SNRPB	SNRPB	5664	0.074	0.51	NO
89	CLP1	CLP1	CLP1	5739	0.073	0.51	NO
90	SUPT16H	SUPT16H	SUPT16H	5826	0.07	0.51	NO
91	PAPOLA	PAPOLA	PAPOLA	5909	0.068	0.51	NO
92	POLR1B	POLR1B	POLR1B	5978	0.066	0.51	NO
93	NFX1	NFX1	NFX1	6009	0.066	0.51	NO
94	GTF2H2B	GTF2H2B	GTF2H2B	6034	0.065	0.51	NO
95	NCBP2	NCBP2	NCBP2	6067	0.064	0.51	NO
96	POLR1A	POLR1A	POLR1A	6094	0.064	0.51	NO
97	H3F3A	H3F3A	H3F3A	6142	0.062	0.51	NO
98	SNAPC3	SNAPC3	SNAPC3	6147	0.062	0.51	NO
99	RNPS1	RNPS1	RNPS1	6205	0.061	0.51	NO
100	CDK7	CDK7	CDK7	6222	0.06	0.51	NO
101	HIST1H3F	HIST1H3F	HIST1H3F	6360	0.057	0.5	NO
102	TAF1	TAF1	TAF1	6369	0.057	0.51	NO
103	TAF1C	TAF1C	TAF1C	6597	0.051	0.5	NO
104	ZNF143	ZNF143	ZNF143	6618	0.05	0.5	NO
105	RBM8A	RBM8A	RBM8A	6741	0.048	0.49	NO
106	CTDP1	CTDP1	CTDP1	6845	0.045	0.49	NO
107	CPSF1	CPSF1	CPSF1	6907	0.044	0.48	NO
108	ZNF473	ZNF473	ZNF473	6987	0.042	0.48	NO
109	TCEB3	TCEB3	TCEB3	7109	0.039	0.48	NO
110	TBP	TBP	TBP	7140	0.038	0.48	NO
111	SUPT4H1	SUPT4H1	SUPT4H1	7150	0.038	0.48	NO
112	U2AF1	U2AF1	U2AF1	7204	0.036	0.48	NO
113	POLR2J	POLR2J	POLR2J	7247	0.036	0.48	NO
114	TAF11	TAF11	TAF11	7257	0.035	0.48	NO
115	POLR3F	POLR3F	POLR3F	7371	0.033	0.47	NO
116	SNRPF	SNRPF	SNRPF	7627	0.027	0.46	NO
117	RRN3	RRN3	RRN3	7704	0.026	0.45	NO
118	ERCC3	ERCC3	ERCC3	7748	0.025	0.45	NO
119	GTF2B	GTF2B	GTF2B	7821	0.024	0.45	NO
120	TAF4	TAF4	TAF4	7963	0.02	0.44	NO
121	U2AF2	U2AF2	U2AF2	8029	0.019	0.44	NO
122	CPSF7	CPSF7	CPSF7	8037	0.019	0.44	NO
123	HIST2H3D	HIST2H3D	HIST2H3D	8215	0.014	0.43	NO
124	NUDT21	NUDT21	NUDT21	8219	0.014	0.43	NO
125	PCF11	PCF11	PCF11	8234	0.014	0.43	NO
126	SNAPC5	SNAPC5	SNAPC5	8236	0.014	0.43	NO
127	CPSF2	CPSF2	CPSF2	8246	0.014	0.43	NO
128	MNAT1	MNAT1	MNAT1	8285	0.012	0.43	NO
129	CDK9	CDK9	CDK9	8420	0.0092	0.42	NO
130	WHSC2	WHSC2	WHSC2	8433	0.0088	0.42	NO
131	POLR3E	POLR3E	POLR3E	8484	0.0074	0.42	NO
132	CPSF3	CPSF3	CPSF3	8556	0.0058	0.42	NO
133	ERCC2	ERCC2	ERCC2	8570	0.0054	0.42	NO
134	TCEB2	TCEB2	TCEB2	8734	0.0018	0.41	NO
135	GTF3C5	GTF3C5	GTF3C5	8768	0.001	0.41	NO
136	GTF2H4	GTF2H4	GTF2H4	8981	-0.0036	0.4	NO
137	DHX38	DHX38	DHX38	9020	-0.0047	0.39	NO
138	POLR1D	POLR1D	POLR1D	9021	-0.0047	0.39	NO
139	NCBP1	NCBP1	NCBP1	9022	-0.0048	0.39	NO
140	CSTF1	CSTF1	CSTF1	9024	-0.0048	0.39	NO
141	GTF2H2	GTF2H2	GTF2H2	9093	-0.0066	0.39	NO
142	GTF2F1	GTF2F1	GTF2F1	9183	-0.0086	0.39	NO
143	TFAM	TFAM	TFAM	9285	-0.011	0.38	NO
144	CDC40	CDC40	CDC40	9294	-0.011	0.38	NO
145	RNMT	RNMT	RNMT	9315	-0.012	0.38	NO
146	THOC4	THOC4	THOC4	9577	-0.018	0.37	NO
147	TAF1A	TAF1A	TAF1A	9663	-0.02	0.36	NO
148	POLR2H	POLR2H	POLR2H	9671	-0.02	0.36	NO
149	BRF1	BRF1	BRF1	9706	-0.021	0.36	NO
150	CSTF3	CSTF3	CSTF3	9743	-0.022	0.36	NO
151	UBTF	UBTF	UBTF	9767	-0.022	0.36	NO
152	TAF9	TAF9	TAF9	9791	-0.023	0.36	NO
153	SRRM1	SRRM1	SRRM1	9794	-0.023	0.36	NO
154	TAF10	TAF10	TAF10	9803	-0.024	0.36	NO
155	MBD2	MBD2	MBD2	9966	-0.028	0.35	NO
156	POLR2E	POLR2E	POLR2E	10049	-0.03	0.35	NO
157	GTF2F2	GTF2F2	GTF2F2	10127	-0.032	0.35	NO
158	GTF2H1	GTF2H1	GTF2H1	10225	-0.035	0.34	NO
159	SLBP	SLBP	SLBP	10280	-0.036	0.34	NO
160	COBRA1	COBRA1	COBRA1	10285	-0.036	0.34	NO
161	RDBP	RDBP	RDBP	10478	-0.041	0.33	NO
162	TH1L	TH1L	TH1L	10512	-0.042	0.33	NO
163	SSRP1	SSRP1	SSRP1	10568	-0.043	0.33	NO
164	POLR2L	POLR2L	POLR2L	10762	-0.049	0.32	NO
165	HIST1H4L	HIST1H4L	HIST1H4L	10796	-0.05	0.32	NO
166	SSB	SSB	SSB	10798	-0.05	0.32	NO
167	PABPN1	PABPN1	PABPN1	10885	-0.053	0.32	NO
168	H2AFZ	H2AFZ	H2AFZ	10901	-0.053	0.32	NO
169	HIST2H2AC	HIST2H2AC	HIST2H2AC	11111	-0.059	0.31	NO
170	LSM10	LSM10	LSM10	11115	-0.059	0.31	NO
171	GTF2H3	GTF2H3	GTF2H3	11435	-0.068	0.3	NO
172	POLR2C	POLR2C	POLR2C	11490	-0.069	0.3	NO
173	POLR3H	POLR3H	POLR3H	11550	-0.071	0.3	NO
174	CCNH	CCNH	CCNH	11717	-0.076	0.29	NO
175	TAF12	TAF12	TAF12	11759	-0.077	0.29	NO
176	POLR3K	POLR3K	POLR3K	12275	-0.094	0.27	NO
177	RNGTT	RNGTT	RNGTT	12298	-0.095	0.27	NO
178	H3F3B	H3F3B	H3F3B	12581	-0.1	0.26	NO
179	MAPK3	MAPK3	MAPK3	12625	-0.11	0.26	NO
180	POLR2A	POLR2A	POLR2A	12890	-0.12	0.25	NO
181	MAGOH	MAGOH	MAGOH	12904	-0.12	0.25	NO
182	PTRF	PTRF	PTRF	13591	-0.15	0.22	NO
183	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	13602	-0.15	0.22	NO
184	NFIB	NFIB	NFIB	13667	-0.15	0.22	NO
185	POLR3GL	POLR3GL	POLR3GL	14067	-0.18	0.21	NO
186	H2AFX	H2AFX	H2AFX	14283	-0.19	0.2	NO
187	HIST2H4A	HIST2H4A	HIST2H4A	14707	-0.22	0.19	NO
188	UPF3B	UPF3B	UPF3B	14923	-0.23	0.18	NO
189	POLR2G	POLR2G	POLR2G	15731	-0.3	0.15	NO
190	EHMT2	EHMT2	EHMT2	15977	-0.33	0.15	NO
191	HIST2H3C	HIST2H3C	HIST2H3C	17361	-0.48	0.09	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: PID BARD1PATHWAY.

Figure S24. Get High-res Image For the top 5 core enriched genes in the pathway: PID BARD1PATHWAY, 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: REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX

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	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	3	1.1	0.041	YES
2	HIST1H3C	HIST1H3C	HIST1H3C	5	1.1	0.081	YES
3	HIST1H2BL	HIST1H2BL	HIST1H2BL	11	0.96	0.12	YES
4	HIST1H2AB	HIST1H2AB	HIST1H2AB	22	0.9	0.15	YES
5	HIST1H3A	HIST1H3A	HIST1H3A	67	0.76	0.17	YES
6	HIST1H3H	HIST1H3H	HIST1H3H	139	0.67	0.19	YES
7	HIST1H4C	HIST1H4C	HIST1H4C	170	0.65	0.22	YES
8	HIST1H4D	HIST1H4D	HIST1H4D	174	0.64	0.24	YES
9	HIST1H4J	HIST1H4J	HIST1H4J	190	0.63	0.26	YES
10	HIST1H2BM	HIST1H2BM	HIST1H2BM	217	0.61	0.28	YES
11	HIST1H2BA	HIST1H2BA	HIST1H2BA	268	0.57	0.3	YES
12	HIST1H2AE	HIST1H2AE	HIST1H2AE	273	0.57	0.32	YES
13	HIST1H2BE	HIST1H2BE	HIST1H2BE	353	0.53	0.34	YES
14	HIST1H2BO	HIST1H2BO	HIST1H2BO	374	0.53	0.35	YES
15	DMC1	DMC1	DMC1	437	0.5	0.37	YES
16	HIST1H2BB	HIST1H2BB	HIST1H2BB	454	0.49	0.39	YES
17	HIST1H2AC	HIST1H2AC	HIST1H2AC	485	0.48	0.4	YES
18	HIST1H4H	HIST1H4H	HIST1H4H	487	0.48	0.42	YES
19	HIST1H2BG	HIST1H2BG	HIST1H2BG	558	0.46	0.43	YES
20	HIST1H2BD	HIST1H2BD	HIST1H2BD	569	0.46	0.45	YES
21	HIST1H4E	HIST1H4E	HIST1H4E	574	0.45	0.46	YES
22	HIST1H4K	HIST1H4K	HIST1H4K	597	0.45	0.48	YES
23	MSH4	MSH4	MSH4	606	0.44	0.5	YES
24	HIST1H4I	HIST1H4I	HIST1H4I	733	0.41	0.5	YES
25	HIST1H2BK	HIST1H2BK	HIST1H2BK	845	0.38	0.51	YES
26	SMC1B	SMC1B	SMC1B	874	0.38	0.52	YES
27	HIST3H2BB	HIST3H2BB	HIST3H2BB	883	0.38	0.54	YES
28	HIST1H2BC	HIST1H2BC	HIST1H2BC	885	0.38	0.55	YES
29	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1103	0.34	0.55	YES
30	HIST1H3I	HIST1H3I	HIST1H3I	1114	0.33	0.56	YES
31	HIST1H3B	HIST1H3B	HIST1H3B	1144	0.33	0.57	YES
32	FKBP6	FKBP6	FKBP6	1297	0.31	0.58	YES
33	HIST1H3G	HIST1H3G	HIST1H3G	1307	0.31	0.59	YES
34	HIST1H3D	HIST1H3D	HIST1H3D	1392	0.3	0.59	YES
35	RAD51	RAD51	RAD51	1474	0.29	0.6	YES
36	HIST1H2BF	HIST1H2BF	HIST1H2BF	1571	0.28	0.6	YES
37	BLM	BLM	BLM	1610	0.27	0.61	YES
38	SYCP2	SYCP2	SYCP2	1711	0.26	0.62	YES
39	SYCP3	SYCP3	SYCP3	1718	0.26	0.63	YES
40	HIST1H4F	HIST1H4F	HIST1H4F	1831	0.25	0.63	YES
41	HIST1H4B	HIST1H4B	HIST1H4B	1838	0.25	0.64	YES
42	TEX12	TEX12	TEX12	1960	0.23	0.64	YES
43	HIST1H2AD	HIST1H2AD	HIST1H2AD	1989	0.23	0.65	YES
44	HIST4H4	HIST4H4	HIST4H4	2055	0.23	0.65	YES
45	HIST1H2BI	HIST1H2BI	HIST1H2BI	2106	0.22	0.66	YES
46	SYCP1	SYCP1	SYCP1	2171	0.22	0.66	YES
47	HIST1H3E	HIST1H3E	HIST1H3E	2206	0.21	0.67	YES
48	MND1	MND1	MND1	2722	0.18	0.65	NO
49	HIST1H2BH	HIST1H2BH	HIST1H2BH	2727	0.18	0.65	NO
50	HIST1H4A	HIST1H4A	HIST1H4A	3146	0.16	0.64	NO
51	SYNE2	SYNE2	SYNE2	3148	0.16	0.64	NO
52	NBN	NBN	NBN	3607	0.14	0.62	NO
53	STAG3	STAG3	STAG3	4065	0.12	0.6	NO
54	BRCA2	BRCA2	BRCA2	4121	0.12	0.6	NO
55	HIST2H2BE	HIST2H2BE	HIST2H2BE	4377	0.11	0.6	NO
56	HIST1H2BN	HIST1H2BN	HIST1H2BN	4694	0.1	0.58	NO
57	HIST1H3J	HIST1H3J	HIST1H3J	4843	0.097	0.58	NO
58	REC8	REC8	REC8	5320	0.084	0.56	NO
59	SMC3	SMC3	SMC3	5412	0.081	0.56	NO
60	ATR	ATR	ATR	5525	0.078	0.55	NO
61	CDK2	CDK2	CDK2	5663	0.074	0.55	NO
62	RPA1	RPA1	RPA1	5703	0.074	0.55	NO
63	RAD51C	RAD51C	RAD51C	5923	0.068	0.54	NO
64	H3F3A	H3F3A	H3F3A	6142	0.062	0.53	NO
65	BRCA1	BRCA1	BRCA1	6310	0.058	0.52	NO
66	HIST1H3F	HIST1H3F	HIST1H3F	6360	0.057	0.52	NO
67	ATM	ATM	ATM	6421	0.056	0.52	NO
68	RBBP8	RBBP8	RBBP8	6444	0.055	0.52	NO
69	POT1	POT1	POT1	6678	0.049	0.51	NO
70	DIDO1	DIDO1	DIDO1	6879	0.045	0.5	NO
71	RPA3	RPA3	RPA3	7048	0.04	0.5	NO
72	CDK4	CDK4	CDK4	7101	0.039	0.49	NO
73	RAD21	RAD21	RAD21	7126	0.038	0.49	NO
74	STAG1	STAG1	STAG1	7804	0.024	0.46	NO
75	SMC1A	SMC1A	SMC1A	7841	0.023	0.46	NO
76	STAG2	STAG2	STAG2	7843	0.023	0.46	NO
77	UBE2I	UBE2I	UBE2I	7859	0.023	0.46	NO
78	PRDM9	PRDM9	PRDM9	8065	0.018	0.45	NO
79	HIST2H3D	HIST2H3D	HIST2H3D	8215	0.014	0.44	NO
80	TERF2IP	TERF2IP	TERF2IP	9522	-0.017	0.37	NO
81	RPA2	RPA2	RPA2	9883	-0.025	0.36	NO
82	ACD	ACD	ACD	9974	-0.028	0.35	NO
83	MRE11A	MRE11A	MRE11A	10118	-0.032	0.34	NO
84	MLH1	MLH1	MLH1	10345	-0.038	0.33	NO
85	RAD50	RAD50	RAD50	10600	-0.044	0.32	NO
86	HIST1H4L	HIST1H4L	HIST1H4L	10796	-0.05	0.31	NO
87	H2AFZ	H2AFZ	H2AFZ	10901	-0.053	0.31	NO
88	TOP3A	TOP3A	TOP3A	10961	-0.055	0.31	NO
89	TERF2	TERF2	TERF2	11071	-0.058	0.31	NO
90	HIST2H2AC	HIST2H2AC	HIST2H2AC	11111	-0.059	0.31	NO
91	SUN2	SUN2	SUN2	11727	-0.076	0.28	NO
92	H3F3B	H3F3B	H3F3B	12581	-0.1	0.24	NO
93	MLH3	MLH3	MLH3	12823	-0.12	0.23	NO
94	MSH5	MSH5	MSH5	13171	-0.13	0.21	NO
95	LMNB1	LMNB1	LMNB1	13204	-0.13	0.22	NO
96	TINF2	TINF2	TINF2	13335	-0.14	0.21	NO
97	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	13602	-0.15	0.2	NO
98	SYNE1	SYNE1	SYNE1	13610	-0.15	0.21	NO
99	H2AFX	H2AFX	H2AFX	14283	-0.19	0.18	NO
100	TERF1	TERF1	TERF1	14294	-0.19	0.19	NO
101	HSPA2	HSPA2	HSPA2	14636	-0.21	0.18	NO
102	HIST2H4A	HIST2H4A	HIST2H4A	14707	-0.22	0.18	NO
103	LMNA	LMNA	LMNA	16353	-0.36	0.11	NO
104	TEX15	TEX15	TEX15	17112	-0.45	0.085	NO
105	HIST2H3C	HIST2H3C	HIST2H3C	17361	-0.48	0.089	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: REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX.

Figure S26. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX, 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: REACTOME MEIOSIS

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	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	3	1.1	0.058	YES
2	HIST1H2BL	HIST1H2BL	HIST1H2BL	11	0.96	0.11	YES
3	HIST1H2AB	HIST1H2AB	HIST1H2AB	22	0.9	0.15	YES
4	HIST1H4C	HIST1H4C	HIST1H4C	170	0.65	0.18	YES
5	HIST1H4D	HIST1H4D	HIST1H4D	174	0.64	0.21	YES
6	HIST1H4J	HIST1H4J	HIST1H4J	190	0.63	0.24	YES
7	HIST1H2BM	HIST1H2BM	HIST1H2BM	217	0.61	0.27	YES
8	HIST1H2BA	HIST1H2BA	HIST1H2BA	268	0.57	0.3	YES
9	HIST1H2AE	HIST1H2AE	HIST1H2AE	273	0.57	0.33	YES
10	HIST1H2BE	HIST1H2BE	HIST1H2BE	353	0.53	0.35	YES
11	HIST1H2BO	HIST1H2BO	HIST1H2BO	374	0.53	0.38	YES
12	HIST1H2BB	HIST1H2BB	HIST1H2BB	454	0.49	0.4	YES
13	HIST1H2AC	HIST1H2AC	HIST1H2AC	485	0.48	0.42	YES
14	HIST1H4H	HIST1H4H	HIST1H4H	487	0.48	0.45	YES
15	HIST1H2BG	HIST1H2BG	HIST1H2BG	558	0.46	0.47	YES
16	HIST1H2BD	HIST1H2BD	HIST1H2BD	569	0.46	0.49	YES
17	HIST1H4E	HIST1H4E	HIST1H4E	574	0.45	0.51	YES
18	HIST1H4K	HIST1H4K	HIST1H4K	597	0.45	0.54	YES
19	HIST1H4I	HIST1H4I	HIST1H4I	733	0.41	0.55	YES
20	HIST1H2BK	HIST1H2BK	HIST1H2BK	845	0.38	0.56	YES
21	SMC1B	SMC1B	SMC1B	874	0.38	0.58	YES
22	HIST3H2BB	HIST3H2BB	HIST3H2BB	883	0.38	0.6	YES
23	HIST1H2BC	HIST1H2BC	HIST1H2BC	885	0.38	0.62	YES
24	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1103	0.34	0.62	YES
25	FKBP6	FKBP6	FKBP6	1297	0.31	0.63	YES
26	HIST1H2BF	HIST1H2BF	HIST1H2BF	1571	0.28	0.63	YES
27	SYCP2	SYCP2	SYCP2	1711	0.26	0.64	YES
28	SYCP3	SYCP3	SYCP3	1718	0.26	0.65	YES
29	HIST1H4F	HIST1H4F	HIST1H4F	1831	0.25	0.66	YES
30	HIST1H4B	HIST1H4B	HIST1H4B	1838	0.25	0.67	YES
31	TEX12	TEX12	TEX12	1960	0.23	0.68	YES
32	HIST1H2AD	HIST1H2AD	HIST1H2AD	1989	0.23	0.69	YES
33	HIST4H4	HIST4H4	HIST4H4	2055	0.23	0.69	YES
34	HIST1H2BI	HIST1H2BI	HIST1H2BI	2106	0.22	0.7	YES
35	SYCP1	SYCP1	SYCP1	2171	0.22	0.71	YES
36	HIST1H2BH	HIST1H2BH	HIST1H2BH	2727	0.18	0.69	NO
37	HIST1H4A	HIST1H4A	HIST1H4A	3146	0.16	0.68	NO
38	SYNE2	SYNE2	SYNE2	3148	0.16	0.68	NO
39	STAG3	STAG3	STAG3	4065	0.12	0.64	NO
40	HIST2H2BE	HIST2H2BE	HIST2H2BE	4377	0.11	0.63	NO
41	HIST1H2BN	HIST1H2BN	HIST1H2BN	4694	0.1	0.62	NO
42	REC8	REC8	REC8	5320	0.084	0.59	NO
43	SMC3	SMC3	SMC3	5412	0.081	0.59	NO
44	ATR	ATR	ATR	5525	0.078	0.59	NO
45	BRCA1	BRCA1	BRCA1	6310	0.058	0.55	NO
46	POT1	POT1	POT1	6678	0.049	0.53	NO
47	DIDO1	DIDO1	DIDO1	6879	0.045	0.53	NO
48	RAD21	RAD21	RAD21	7126	0.038	0.52	NO
49	STAG1	STAG1	STAG1	7804	0.024	0.48	NO
50	SMC1A	SMC1A	SMC1A	7841	0.023	0.48	NO
51	STAG2	STAG2	STAG2	7843	0.023	0.48	NO
52	UBE2I	UBE2I	UBE2I	7859	0.023	0.48	NO
53	TERF2IP	TERF2IP	TERF2IP	9522	-0.017	0.4	NO
54	ACD	ACD	ACD	9974	-0.028	0.37	NO
55	HIST1H4L	HIST1H4L	HIST1H4L	10796	-0.05	0.33	NO
56	H2AFZ	H2AFZ	H2AFZ	10901	-0.053	0.33	NO
57	TERF2	TERF2	TERF2	11071	-0.058	0.32	NO
58	HIST2H2AC	HIST2H2AC	HIST2H2AC	11111	-0.059	0.32	NO
59	SUN2	SUN2	SUN2	11727	-0.076	0.3	NO
60	LMNB1	LMNB1	LMNB1	13204	-0.13	0.22	NO
61	TINF2	TINF2	TINF2	13335	-0.14	0.22	NO
62	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	13602	-0.15	0.22	NO
63	SYNE1	SYNE1	SYNE1	13610	-0.15	0.23	NO
64	H2AFX	H2AFX	H2AFX	14283	-0.19	0.2	NO
65	TERF1	TERF1	TERF1	14294	-0.19	0.21	NO
66	HSPA2	HSPA2	HSPA2	14636	-0.21	0.2	NO
67	HIST2H4A	HIST2H4A	HIST2H4A	14707	-0.22	0.21	NO
68	LMNA	LMNA	LMNA	16353	-0.36	0.14	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: REACTOME MEIOSIS.

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

genes ES table in pathway: REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S

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	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	3	1.1	0.044	YES
2	HIST1H3C	HIST1H3C	HIST1H3C	5	1.1	0.086	YES
3	HIST1H2BL	HIST1H2BL	HIST1H2BL	11	0.96	0.12	YES
4	HIST1H2AB	HIST1H2AB	HIST1H2AB	22	0.9	0.16	YES
5	HIST1H3A	HIST1H3A	HIST1H3A	67	0.76	0.18	YES
6	HIST1H3H	HIST1H3H	HIST1H3H	139	0.67	0.2	YES
7	HIST1H4C	HIST1H4C	HIST1H4C	170	0.65	0.23	YES
8	HIST1H4D	HIST1H4D	HIST1H4D	174	0.64	0.25	YES
9	HIST1H4J	HIST1H4J	HIST1H4J	190	0.63	0.28	YES
10	HIST1H2BM	HIST1H2BM	HIST1H2BM	217	0.61	0.3	YES
11	HIST1H2BA	HIST1H2BA	HIST1H2BA	268	0.57	0.32	YES
12	HIST1H2AE	HIST1H2AE	HIST1H2AE	273	0.57	0.34	YES
13	HIST1H2BE	HIST1H2BE	HIST1H2BE	353	0.53	0.36	YES
14	HIST1H2BO	HIST1H2BO	HIST1H2BO	374	0.53	0.37	YES
15	HIST1H2BB	HIST1H2BB	HIST1H2BB	454	0.49	0.39	YES
16	HIST1H2AC	HIST1H2AC	HIST1H2AC	485	0.48	0.41	YES
17	HIST1H4H	HIST1H4H	HIST1H4H	487	0.48	0.42	YES
18	HIST1H2BG	HIST1H2BG	HIST1H2BG	558	0.46	0.44	YES
19	HIST1H2BD	HIST1H2BD	HIST1H2BD	569	0.46	0.46	YES
20	HIST1H4E	HIST1H4E	HIST1H4E	574	0.45	0.47	YES
21	HIST1H4K	HIST1H4K	HIST1H4K	597	0.45	0.49	YES
22	HIST1H4I	HIST1H4I	HIST1H4I	733	0.41	0.5	YES
23	HIST1H2BK	HIST1H2BK	HIST1H2BK	845	0.38	0.51	YES
24	HIST3H2BB	HIST3H2BB	HIST3H2BB	883	0.38	0.52	YES
25	HIST1H2BC	HIST1H2BC	HIST1H2BC	885	0.38	0.53	YES
26	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1103	0.34	0.53	YES
27	HIST1H3I	HIST1H3I	HIST1H3I	1114	0.33	0.55	YES
28	HIST1H3B	HIST1H3B	HIST1H3B	1144	0.33	0.56	YES
29	LZTS1	LZTS1	LZTS1	1283	0.31	0.56	YES
30	HIST1H3G	HIST1H3G	HIST1H3G	1307	0.31	0.57	YES
31	HIST1H3D	HIST1H3D	HIST1H3D	1392	0.3	0.58	YES
32	ERCC6	ERCC6	ERCC6	1555	0.28	0.58	YES
33	HIST1H2BF	HIST1H2BF	HIST1H2BF	1571	0.28	0.59	YES
34	HIST1H4F	HIST1H4F	HIST1H4F	1831	0.25	0.59	YES
35	HIST1H4B	HIST1H4B	HIST1H4B	1838	0.25	0.6	YES
36	HIST1H2AD	HIST1H2AD	HIST1H2AD	1989	0.23	0.6	YES
37	HIST4H4	HIST4H4	HIST4H4	2055	0.23	0.6	YES
38	HIST1H2BI	HIST1H2BI	HIST1H2BI	2106	0.22	0.61	YES
39	HIST1H3E	HIST1H3E	HIST1H3E	2206	0.21	0.61	YES
40	SNAPC4	SNAPC4	SNAPC4	2264	0.21	0.62	YES
41	MTERF	MTERF	MTERF	2321	0.21	0.62	YES
42	POLR3C	POLR3C	POLR3C	2509	0.19	0.62	YES
43	SNAPC1	SNAPC1	SNAPC1	2563	0.19	0.62	YES
44	POLR2K	POLR2K	POLR2K	2726	0.18	0.62	YES
45	HIST1H2BH	HIST1H2BH	HIST1H2BH	2727	0.18	0.63	YES
46	HIST1H4A	HIST1H4A	HIST1H4A	3146	0.16	0.61	NO
47	POU2F1	POU2F1	POU2F1	3280	0.15	0.61	NO
48	CBX3	CBX3	CBX3	3296	0.15	0.62	NO
49	BRF2	BRF2	BRF2	3378	0.15	0.62	NO
50	POLRMT	POLRMT	POLRMT	3469	0.14	0.62	NO
51	POLR2F	POLR2F	POLR2F	3501	0.14	0.62	NO
52	POLR3D	POLR3D	POLR3D	3939	0.12	0.6	NO
53	TAF1B	TAF1B	TAF1B	4045	0.12	0.6	NO
54	GTF3C2	GTF3C2	GTF3C2	4090	0.12	0.61	NO
55	POLR1C	POLR1C	POLR1C	4150	0.12	0.61	NO
56	KAT2B	KAT2B	KAT2B	4156	0.12	0.61	NO
57	HIST2H2BE	HIST2H2BE	HIST2H2BE	4377	0.11	0.6	NO
58	POLR3A	POLR3A	POLR3A	4401	0.11	0.61	NO
59	POLR3B	POLR3B	POLR3B	4412	0.11	0.61	NO
60	GTF3C3	GTF3C3	GTF3C3	4430	0.11	0.62	NO
61	GTF3C4	GTF3C4	GTF3C4	4595	0.1	0.61	NO
62	HIST1H2BN	HIST1H2BN	HIST1H2BN	4694	0.1	0.61	NO
63	HIST1H3J	HIST1H3J	HIST1H3J	4843	0.097	0.6	NO
64	TFB2M	TFB2M	TFB2M	5158	0.088	0.59	NO
65	SNAPC2	SNAPC2	SNAPC2	5399	0.082	0.58	NO
66	POLR1B	POLR1B	POLR1B	5978	0.066	0.55	NO
67	GTF2H2B	GTF2H2B	GTF2H2B	6034	0.065	0.55	NO
68	POLR1A	POLR1A	POLR1A	6094	0.064	0.55	NO
69	H3F3A	H3F3A	H3F3A	6142	0.062	0.55	NO
70	SNAPC3	SNAPC3	SNAPC3	6147	0.062	0.56	NO
71	CDK7	CDK7	CDK7	6222	0.06	0.55	NO
72	HIST1H3F	HIST1H3F	HIST1H3F	6360	0.057	0.55	NO
73	TAF1C	TAF1C	TAF1C	6597	0.051	0.54	NO
74	ZNF143	ZNF143	ZNF143	6618	0.05	0.54	NO
75	TBP	TBP	TBP	7140	0.038	0.51	NO
76	POLR3F	POLR3F	POLR3F	7371	0.033	0.5	NO
77	RRN3	RRN3	RRN3	7704	0.026	0.49	NO
78	ERCC3	ERCC3	ERCC3	7748	0.025	0.48	NO
79	HIST2H3D	HIST2H3D	HIST2H3D	8215	0.014	0.46	NO
80	SNAPC5	SNAPC5	SNAPC5	8236	0.014	0.46	NO
81	MNAT1	MNAT1	MNAT1	8285	0.012	0.46	NO
82	POLR3E	POLR3E	POLR3E	8484	0.0074	0.45	NO
83	ERCC2	ERCC2	ERCC2	8570	0.0054	0.44	NO
84	GTF3C5	GTF3C5	GTF3C5	8768	0.001	0.43	NO
85	GTF2H4	GTF2H4	GTF2H4	8981	-0.0036	0.42	NO
86	POLR1D	POLR1D	POLR1D	9021	-0.0047	0.42	NO
87	GTF2H2	GTF2H2	GTF2H2	9093	-0.0066	0.42	NO
88	TFAM	TFAM	TFAM	9285	-0.011	0.41	NO
89	TAF1A	TAF1A	TAF1A	9663	-0.02	0.39	NO
90	POLR2H	POLR2H	POLR2H	9671	-0.02	0.39	NO
91	BRF1	BRF1	BRF1	9706	-0.021	0.39	NO
92	UBTF	UBTF	UBTF	9767	-0.022	0.38	NO
93	MBD2	MBD2	MBD2	9966	-0.028	0.38	NO
94	POLR2E	POLR2E	POLR2E	10049	-0.03	0.37	NO
95	GTF2H1	GTF2H1	GTF2H1	10225	-0.035	0.36	NO
96	POLR2L	POLR2L	POLR2L	10762	-0.049	0.34	NO
97	HIST1H4L	HIST1H4L	HIST1H4L	10796	-0.05	0.34	NO
98	SSB	SSB	SSB	10798	-0.05	0.34	NO
99	H2AFZ	H2AFZ	H2AFZ	10901	-0.053	0.34	NO
100	HIST2H2AC	HIST2H2AC	HIST2H2AC	11111	-0.059	0.33	NO
101	GTF2H3	GTF2H3	GTF2H3	11435	-0.068	0.31	NO
102	POLR3H	POLR3H	POLR3H	11550	-0.071	0.31	NO
103	CCNH	CCNH	CCNH	11717	-0.076	0.3	NO
104	POLR3K	POLR3K	POLR3K	12275	-0.094	0.28	NO
105	H3F3B	H3F3B	H3F3B	12581	-0.1	0.27	NO
106	MAPK3	MAPK3	MAPK3	12625	-0.11	0.27	NO
107	PTRF	PTRF	PTRF	13591	-0.15	0.22	NO
108	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	13602	-0.15	0.23	NO
109	NFIB	NFIB	NFIB	13667	-0.15	0.23	NO
110	POLR3GL	POLR3GL	POLR3GL	14067	-0.18	0.22	NO
111	H2AFX	H2AFX	H2AFX	14283	-0.19	0.21	NO
112	HIST2H4A	HIST2H4A	HIST2H4A	14707	-0.22	0.2	NO
113	EHMT2	EHMT2	EHMT2	15977	-0.33	0.14	NO
114	HIST2H3C	HIST2H3C	HIST2H3C	17361	-0.48	0.089	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: REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S, 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: REACTOME GENERIC TRANSCRIPTION 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	LZTS1	LZTS1	LZTS1	1283	0.31	0.028	YES
2	SNAPC4	SNAPC4	SNAPC4	2264	0.21	0.04	YES
3	POLR3C	POLR3C	POLR3C	2509	0.19	0.086	YES
4	SNAPC1	SNAPC1	SNAPC1	2563	0.19	0.14	YES
5	POLR2K	POLR2K	POLR2K	2726	0.18	0.19	YES
6	POU2F1	POU2F1	POU2F1	3280	0.15	0.21	YES
7	BRF2	BRF2	BRF2	3378	0.15	0.25	YES
8	POLR2F	POLR2F	POLR2F	3501	0.14	0.28	YES
9	POLR3D	POLR3D	POLR3D	3939	0.12	0.3	YES
10	GTF3C2	GTF3C2	GTF3C2	4090	0.12	0.33	YES
11	POLR1C	POLR1C	POLR1C	4150	0.12	0.36	YES
12	POLR3A	POLR3A	POLR3A	4401	0.11	0.38	YES
13	POLR3B	POLR3B	POLR3B	4412	0.11	0.41	YES
14	GTF3C3	GTF3C3	GTF3C3	4430	0.11	0.44	YES
15	GTF3C4	GTF3C4	GTF3C4	4595	0.1	0.47	YES
16	SNAPC2	SNAPC2	SNAPC2	5399	0.082	0.45	NO
17	SNAPC3	SNAPC3	SNAPC3	6147	0.062	0.43	NO
18	ZNF143	ZNF143	ZNF143	6618	0.05	0.42	NO
19	TBP	TBP	TBP	7140	0.038	0.4	NO
20	POLR3F	POLR3F	POLR3F	7371	0.033	0.4	NO
21	SNAPC5	SNAPC5	SNAPC5	8236	0.014	0.36	NO
22	POLR3E	POLR3E	POLR3E	8484	0.0074	0.35	NO
23	GTF3C5	GTF3C5	GTF3C5	8768	0.001	0.34	NO
24	POLR1D	POLR1D	POLR1D	9021	-0.0047	0.32	NO
25	POLR2H	POLR2H	POLR2H	9671	-0.02	0.3	NO
26	BRF1	BRF1	BRF1	9706	-0.021	0.3	NO
27	POLR2E	POLR2E	POLR2E	10049	-0.03	0.29	NO
28	POLR2L	POLR2L	POLR2L	10762	-0.049	0.27	NO
29	SSB	SSB	SSB	10798	-0.05	0.28	NO
30	POLR3H	POLR3H	POLR3H	11550	-0.071	0.26	NO
31	POLR3K	POLR3K	POLR3K	12275	-0.094	0.26	NO
32	NFIB	NFIB	NFIB	13667	-0.15	0.23	NO
33	POLR3GL	POLR3GL	POLR3GL	14067	-0.18	0.26	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: REACTOME GENERIC TRANSCRIPTION PATHWAY.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME GENERIC TRANSCRIPTION 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: REACTOME RNA POL I TRANSCRIPTION

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	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	3	1.1	0.05	YES
2	HIST1H3C	HIST1H3C	HIST1H3C	5	1.1	0.098	YES
3	HIST1H2BL	HIST1H2BL	HIST1H2BL	11	0.96	0.14	YES
4	HIST1H2AB	HIST1H2AB	HIST1H2AB	22	0.9	0.18	YES
5	HIST1H3A	HIST1H3A	HIST1H3A	67	0.76	0.21	YES
6	HIST1H3H	HIST1H3H	HIST1H3H	139	0.67	0.24	YES
7	HIST1H4C	HIST1H4C	HIST1H4C	170	0.65	0.26	YES
8	HIST1H4D	HIST1H4D	HIST1H4D	174	0.64	0.29	YES
9	HIST1H4J	HIST1H4J	HIST1H4J	190	0.63	0.32	YES
10	HIST1H2BM	HIST1H2BM	HIST1H2BM	217	0.61	0.34	YES
11	HIST1H2BA	HIST1H2BA	HIST1H2BA	268	0.57	0.37	YES
12	HIST1H2AE	HIST1H2AE	HIST1H2AE	273	0.57	0.39	YES
13	HIST1H2BE	HIST1H2BE	HIST1H2BE	353	0.53	0.41	YES
14	HIST1H2BO	HIST1H2BO	HIST1H2BO	374	0.53	0.43	YES
15	HIST1H2BB	HIST1H2BB	HIST1H2BB	454	0.49	0.45	YES
16	HIST1H2AC	HIST1H2AC	HIST1H2AC	485	0.48	0.47	YES
17	HIST1H4H	HIST1H4H	HIST1H4H	487	0.48	0.49	YES
18	HIST1H2BG	HIST1H2BG	HIST1H2BG	558	0.46	0.51	YES
19	HIST1H2BD	HIST1H2BD	HIST1H2BD	569	0.46	0.53	YES
20	HIST1H4E	HIST1H4E	HIST1H4E	574	0.45	0.55	YES
21	HIST1H4K	HIST1H4K	HIST1H4K	597	0.45	0.57	YES
22	HIST1H4I	HIST1H4I	HIST1H4I	733	0.41	0.58	YES
23	HIST1H2BK	HIST1H2BK	HIST1H2BK	845	0.38	0.59	YES
24	HIST3H2BB	HIST3H2BB	HIST3H2BB	883	0.38	0.6	YES
25	HIST1H2BC	HIST1H2BC	HIST1H2BC	885	0.38	0.62	YES
26	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1103	0.34	0.62	YES
27	HIST1H3I	HIST1H3I	HIST1H3I	1114	0.33	0.64	YES
28	HIST1H3B	HIST1H3B	HIST1H3B	1144	0.33	0.65	YES
29	HIST1H3G	HIST1H3G	HIST1H3G	1307	0.31	0.66	YES
30	HIST1H3D	HIST1H3D	HIST1H3D	1392	0.3	0.66	YES
31	ERCC6	ERCC6	ERCC6	1555	0.28	0.67	YES
32	HIST1H2BF	HIST1H2BF	HIST1H2BF	1571	0.28	0.68	YES
33	HIST1H4F	HIST1H4F	HIST1H4F	1831	0.25	0.68	YES
34	HIST1H4B	HIST1H4B	HIST1H4B	1838	0.25	0.69	YES
35	HIST1H2AD	HIST1H2AD	HIST1H2AD	1989	0.23	0.69	YES
36	HIST4H4	HIST4H4	HIST4H4	2055	0.23	0.7	YES
37	HIST1H2BI	HIST1H2BI	HIST1H2BI	2106	0.22	0.7	YES
38	HIST1H3E	HIST1H3E	HIST1H3E	2206	0.21	0.71	YES
39	POLR2K	POLR2K	POLR2K	2726	0.18	0.69	NO
40	HIST1H2BH	HIST1H2BH	HIST1H2BH	2727	0.18	0.7	NO
41	HIST1H4A	HIST1H4A	HIST1H4A	3146	0.16	0.68	NO
42	CBX3	CBX3	CBX3	3296	0.15	0.68	NO
43	TAF1B	TAF1B	TAF1B	4045	0.12	0.65	NO
44	POLR1C	POLR1C	POLR1C	4150	0.12	0.65	NO
45	KAT2B	KAT2B	KAT2B	4156	0.12	0.65	NO
46	HIST2H2BE	HIST2H2BE	HIST2H2BE	4377	0.11	0.64	NO
47	HIST1H2BN	HIST1H2BN	HIST1H2BN	4694	0.1	0.63	NO
48	HIST1H3J	HIST1H3J	HIST1H3J	4843	0.097	0.63	NO
49	POLR1B	POLR1B	POLR1B	5978	0.066	0.57	NO
50	GTF2H2B	GTF2H2B	GTF2H2B	6034	0.065	0.57	NO
51	POLR1A	POLR1A	POLR1A	6094	0.064	0.57	NO
52	H3F3A	H3F3A	H3F3A	6142	0.062	0.57	NO
53	CDK7	CDK7	CDK7	6222	0.06	0.57	NO
54	HIST1H3F	HIST1H3F	HIST1H3F	6360	0.057	0.57	NO
55	TAF1C	TAF1C	TAF1C	6597	0.051	0.56	NO
56	RRN3	RRN3	RRN3	7704	0.026	0.5	NO
57	ERCC3	ERCC3	ERCC3	7748	0.025	0.5	NO
58	HIST2H3D	HIST2H3D	HIST2H3D	8215	0.014	0.47	NO
59	MNAT1	MNAT1	MNAT1	8285	0.012	0.47	NO
60	ERCC2	ERCC2	ERCC2	8570	0.0054	0.46	NO
61	GTF2H4	GTF2H4	GTF2H4	8981	-0.0036	0.43	NO
62	POLR1D	POLR1D	POLR1D	9021	-0.0047	0.43	NO
63	GTF2H2	GTF2H2	GTF2H2	9093	-0.0066	0.43	NO
64	TAF1A	TAF1A	TAF1A	9663	-0.02	0.4	NO
65	POLR2H	POLR2H	POLR2H	9671	-0.02	0.4	NO
66	UBTF	UBTF	UBTF	9767	-0.022	0.4	NO
67	MBD2	MBD2	MBD2	9966	-0.028	0.39	NO
68	GTF2H1	GTF2H1	GTF2H1	10225	-0.035	0.38	NO
69	HIST1H4L	HIST1H4L	HIST1H4L	10796	-0.05	0.35	NO
70	H2AFZ	H2AFZ	H2AFZ	10901	-0.053	0.34	NO
71	HIST2H2AC	HIST2H2AC	HIST2H2AC	11111	-0.059	0.34	NO
72	GTF2H3	GTF2H3	GTF2H3	11435	-0.068	0.32	NO
73	CCNH	CCNH	CCNH	11717	-0.076	0.31	NO
74	H3F3B	H3F3B	H3F3B	12581	-0.1	0.27	NO
75	MAPK3	MAPK3	MAPK3	12625	-0.11	0.27	NO
76	PTRF	PTRF	PTRF	13591	-0.15	0.23	NO
77	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	13602	-0.15	0.23	NO
78	H2AFX	H2AFX	H2AFX	14283	-0.19	0.21	NO
79	HIST2H4A	HIST2H4A	HIST2H4A	14707	-0.22	0.19	NO
80	EHMT2	EHMT2	EHMT2	15977	-0.33	0.14	NO
81	HIST2H3C	HIST2H3C	HIST2H3C	17361	-0.48	0.089	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: REACTOME RNA POL I TRANSCRIPTION.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME RNA POL I TRANSCRIPTION, 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: REACTOME RNA POL III TRANSCRIPTION

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	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	3	1.1	0.048	YES
2	HIST1H2BL	HIST1H2BL	HIST1H2BL	11	0.96	0.089	YES
3	HIST1H2AB	HIST1H2AB	HIST1H2AB	22	0.9	0.13	YES
4	HIST1H4C	HIST1H4C	HIST1H4C	170	0.65	0.15	YES
5	HIST1H4D	HIST1H4D	HIST1H4D	174	0.64	0.17	YES
6	HIST1H4J	HIST1H4J	HIST1H4J	190	0.63	0.2	YES
7	HIST1H2BM	HIST1H2BM	HIST1H2BM	217	0.61	0.22	YES
8	HIST1H2BA	HIST1H2BA	HIST1H2BA	268	0.57	0.24	YES
9	HIST1H2AE	HIST1H2AE	HIST1H2AE	273	0.57	0.27	YES
10	HIST1H2BE	HIST1H2BE	HIST1H2BE	353	0.53	0.29	YES
11	HIST1H2BO	HIST1H2BO	HIST1H2BO	374	0.53	0.31	YES
12	HIST1H2BB	HIST1H2BB	HIST1H2BB	454	0.49	0.33	YES
13	HIST1H2AC	HIST1H2AC	HIST1H2AC	485	0.48	0.34	YES
14	HIST1H4H	HIST1H4H	HIST1H4H	487	0.48	0.36	YES
15	HIST1H2BG	HIST1H2BG	HIST1H2BG	558	0.46	0.38	YES
16	HIST1H2BD	HIST1H2BD	HIST1H2BD	569	0.46	0.4	YES
17	HIST1H4E	HIST1H4E	HIST1H4E	574	0.45	0.42	YES
18	HIST1H4K	HIST1H4K	HIST1H4K	597	0.45	0.44	YES
19	HIST1H4I	HIST1H4I	HIST1H4I	733	0.41	0.45	YES
20	HIST1H2BK	HIST1H2BK	HIST1H2BK	845	0.38	0.46	YES
21	SMC1B	SMC1B	SMC1B	874	0.38	0.47	YES
22	HIST3H2BB	HIST3H2BB	HIST3H2BB	883	0.38	0.49	YES
23	HIST1H2BC	HIST1H2BC	HIST1H2BC	885	0.38	0.5	YES
24	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1103	0.34	0.51	YES
25	FKBP6	FKBP6	FKBP6	1297	0.31	0.51	YES
26	HIST1H2BF	HIST1H2BF	HIST1H2BF	1571	0.28	0.51	YES
27	SYCP2	SYCP2	SYCP2	1711	0.26	0.51	YES
28	SYCP3	SYCP3	SYCP3	1718	0.26	0.52	YES
29	HIST1H4F	HIST1H4F	HIST1H4F	1831	0.25	0.53	YES
30	HIST1H4B	HIST1H4B	HIST1H4B	1838	0.25	0.54	YES
31	CASC5	CASC5	CASC5	1908	0.24	0.54	YES
32	CENPA	CENPA	CENPA	1931	0.24	0.55	YES
33	TEX12	TEX12	TEX12	1960	0.23	0.56	YES
34	POLE2	POLE2	POLE2	1988	0.23	0.57	YES
35	HIST1H2AD	HIST1H2AD	HIST1H2AD	1989	0.23	0.58	YES
36	HIST4H4	HIST4H4	HIST4H4	2055	0.23	0.58	YES
37	HIST1H2BI	HIST1H2BI	HIST1H2BI	2106	0.22	0.59	YES
38	SYCP1	SYCP1	SYCP1	2171	0.22	0.6	YES
39	DNA2	DNA2	DNA2	2397	0.2	0.59	YES
40	OIP5	OIP5	OIP5	2598	0.19	0.59	YES
41	HIST1H2BH	HIST1H2BH	HIST1H2BH	2727	0.18	0.59	YES
42	HJURP	HJURP	HJURP	2997	0.17	0.58	YES
43	CENPP	CENPP	CENPP	3125	0.16	0.58	YES
44	HIST1H4A	HIST1H4A	HIST1H4A	3146	0.16	0.59	YES
45	SYNE2	SYNE2	SYNE2	3148	0.16	0.6	YES
46	LIG1	LIG1	LIG1	3404	0.15	0.59	NO
47	CENPK	CENPK	CENPK	3706	0.13	0.58	NO
48	POLE	POLE	POLE	3724	0.13	0.58	NO
49	STAG3	STAG3	STAG3	4065	0.12	0.57	NO
50	PRIM2	PRIM2	PRIM2	4083	0.12	0.58	NO
51	HIST2H2BE	HIST2H2BE	HIST2H2BE	4377	0.11	0.56	NO
52	SMARCA5	SMARCA5	SMARCA5	4562	0.1	0.56	NO
53	PRIM1	PRIM1	PRIM1	4601	0.1	0.56	NO
54	HIST1H2BN	HIST1H2BN	HIST1H2BN	4694	0.1	0.56	NO
55	CENPQ	CENPQ	CENPQ	5052	0.091	0.55	NO
56	REC8	REC8	REC8	5320	0.084	0.54	NO
57	SMC3	SMC3	SMC3	5412	0.081	0.54	NO
58	ATR	ATR	ATR	5525	0.078	0.53	NO
59	POLD1	POLD1	POLD1	5593	0.077	0.53	NO
60	RPA1	RPA1	RPA1	5703	0.074	0.53	NO
61	RUVBL2	RUVBL2	RUVBL2	6088	0.064	0.51	NO
62	RUVBL1	RUVBL1	RUVBL1	6173	0.061	0.51	NO
63	BRCA1	BRCA1	BRCA1	6310	0.058	0.5	NO
64	CENPO	CENPO	CENPO	6359	0.057	0.5	NO
65	CENPI	CENPI	CENPI	6661	0.05	0.49	NO
66	POT1	POT1	POT1	6678	0.049	0.49	NO
67	DIDO1	DIDO1	DIDO1	6879	0.045	0.48	NO
68	FEN1	FEN1	FEN1	6977	0.042	0.48	NO
69	RPA3	RPA3	RPA3	7048	0.04	0.48	NO
70	RAD21	RAD21	RAD21	7126	0.038	0.48	NO
71	NHP2	NHP2	NHP2	7138	0.038	0.48	NO
72	MLF1IP	MLF1IP	MLF1IP	7489	0.03	0.46	NO
73	PCNA	PCNA	PCNA	7766	0.024	0.45	NO
74	STAG1	STAG1	STAG1	7804	0.024	0.45	NO
75	SMC1A	SMC1A	SMC1A	7841	0.023	0.44	NO
76	STAG2	STAG2	STAG2	7843	0.023	0.45	NO
77	UBE2I	UBE2I	UBE2I	7859	0.023	0.45	NO
78	CENPN	CENPN	CENPN	7889	0.022	0.44	NO
79	CENPH	CENPH	CENPH	7893	0.022	0.45	NO
80	RFC4	RFC4	RFC4	8066	0.018	0.44	NO
81	NPM1	NPM1	NPM1	8540	0.006	0.41	NO
82	TERT	TERT	TERT	8558	0.0058	0.41	NO
83	RFC2	RFC2	RFC2	8660	0.0035	0.41	NO
84	RFC3	RFC3	RFC3	9044	-0.0052	0.39	NO
85	POLD2	POLD2	POLD2	9052	-0.0054	0.39	NO
86	POLA1	POLA1	POLA1	9355	-0.013	0.37	NO
87	TERF2IP	TERF2IP	TERF2IP	9522	-0.017	0.36	NO
88	RPA2	RPA2	RPA2	9883	-0.025	0.34	NO
89	ACD	ACD	ACD	9974	-0.028	0.34	NO
90	POLD3	POLD3	POLD3	10139	-0.032	0.34	NO
91	DKC1	DKC1	DKC1	10217	-0.035	0.33	NO
92	HIST1H4L	HIST1H4L	HIST1H4L	10796	-0.05	0.3	NO
93	H2AFZ	H2AFZ	H2AFZ	10901	-0.053	0.3	NO
94	TERF2	TERF2	TERF2	11071	-0.058	0.29	NO
95	HIST2H2AC	HIST2H2AC	HIST2H2AC	11111	-0.059	0.29	NO
96	ITGB3BP	ITGB3BP	ITGB3BP	11145	-0.06	0.3	NO
97	SUN2	SUN2	SUN2	11727	-0.076	0.27	NO
98	POLA2	POLA2	POLA2	11932	-0.082	0.26	NO
99	RSF1	RSF1	RSF1	12238	-0.093	0.25	NO
100	RFC5	RFC5	RFC5	13112	-0.13	0.21	NO
101	LMNB1	LMNB1	LMNB1	13204	-0.13	0.21	NO
102	TINF2	TINF2	TINF2	13335	-0.14	0.21	NO
103	WRAP53	WRAP53	WRAP53	13393	-0.14	0.21	NO
104	POLD4	POLD4	POLD4	13499	-0.14	0.21	NO
105	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	13602	-0.15	0.21	NO
106	SYNE1	SYNE1	SYNE1	13610	-0.15	0.22	NO
107	RBBP4	RBBP4	RBBP4	13773	-0.16	0.22	NO
108	H2AFX	H2AFX	H2AFX	14283	-0.19	0.2	NO
109	TERF1	TERF1	TERF1	14294	-0.19	0.2	NO
110	HSPA2	HSPA2	HSPA2	14636	-0.21	0.2	NO
111	HIST2H4A	HIST2H4A	HIST2H4A	14707	-0.22	0.2	NO
112	RBBP7	RBBP7	RBBP7	15627	-0.29	0.16	NO
113	LMNA	LMNA	LMNA	16353	-0.36	0.14	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: REACTOME RNA POL III TRANSCRIPTION.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME RNA POL III TRANSCRIPTION, 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: REACTOME OLFACTORY SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	BARD1	BARD1	BARD1	901	0.37	0.099	YES
2	RAD51	RAD51	RAD51	1474	0.29	0.18	YES
3	FANCD2	FANCD2	FANCD2	2436	0.2	0.21	YES
4	FANCA	FANCA	FANCA	3014	0.16	0.24	YES
5	NBN	NBN	NBN	3607	0.14	0.27	YES
6	TOPBP1	TOPBP1	TOPBP1	3733	0.13	0.31	YES
7	FANCE	FANCE	FANCE	4077	0.12	0.34	YES
8	UBE2L3	UBE2L3	UBE2L3	4230	0.12	0.38	YES
9	XRCC6	XRCC6	XRCC6	5081	0.09	0.37	YES
10	PRKDC	PRKDC	PRKDC	5440	0.08	0.38	YES
11	ATR	ATR	ATR	5525	0.078	0.41	YES
12	XRCC5	XRCC5	XRCC5	5607	0.076	0.44	YES
13	CDK2	CDK2	CDK2	5663	0.074	0.46	YES
14	EWSR1	EWSR1	EWSR1	5722	0.073	0.49	YES
15	BRCA1	BRCA1	BRCA1	6310	0.058	0.48	YES
16	ATM	ATM	ATM	6421	0.056	0.5	YES
17	RBBP8	RBBP8	RBBP8	6444	0.055	0.52	YES
18	FANCC	FANCC	FANCC	6848	0.045	0.51	YES
19	FANCG	FANCG	FANCG	6918	0.044	0.53	YES
20	CCNE1	CCNE1	CCNE1	7172	0.037	0.53	YES
21	PCNA	PCNA	PCNA	7766	0.024	0.51	NO
22	FANCF	FANCF	FANCF	8181	0.015	0.49	NO
23	NPM1	NPM1	NPM1	8540	0.006	0.47	NO
24	FANCL	FANCL	FANCL	8611	0.0048	0.47	NO
25	CSTF1	CSTF1	CSTF1	9024	-0.0048	0.45	NO
26	UBE2D3	UBE2D3	UBE2D3	9987	-0.028	0.41	NO
27	MRE11A	MRE11A	MRE11A	10118	-0.032	0.42	NO
28	RAD50	RAD50	RAD50	10600	-0.044	0.41	NO
29	TP53	TP53	TP53	12062	-0.087	0.37	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: REACTOME OLFACTORY SIGNALING PATHWAY.

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

genes ES table in pathway: REACTOME 3 UTR MEDIATED TRANSLATIONAL REGULATION

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	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	3	1.1	0.048	YES
2	HIST1H3C	HIST1H3C	HIST1H3C	5	1.1	0.094	YES
3	HIST1H2BL	HIST1H2BL	HIST1H2BL	11	0.96	0.13	YES
4	HIST1H2AB	HIST1H2AB	HIST1H2AB	22	0.9	0.17	YES
5	HIST1H3A	HIST1H3A	HIST1H3A	67	0.76	0.2	YES
6	HIST1H3H	HIST1H3H	HIST1H3H	139	0.67	0.22	YES
7	HIST1H4C	HIST1H4C	HIST1H4C	170	0.65	0.25	YES
8	HIST1H4D	HIST1H4D	HIST1H4D	174	0.64	0.28	YES
9	HIST1H4J	HIST1H4J	HIST1H4J	190	0.63	0.3	YES
10	HIST1H2BM	HIST1H2BM	HIST1H2BM	217	0.61	0.33	YES
11	HIST1H2BA	HIST1H2BA	HIST1H2BA	268	0.57	0.35	YES
12	HIST1H2AE	HIST1H2AE	HIST1H2AE	273	0.57	0.37	YES
13	HIST1H2BE	HIST1H2BE	HIST1H2BE	353	0.53	0.39	YES
14	HIST1H2BO	HIST1H2BO	HIST1H2BO	374	0.53	0.41	YES
15	DMC1	DMC1	DMC1	437	0.5	0.43	YES
16	HIST1H2BB	HIST1H2BB	HIST1H2BB	454	0.49	0.45	YES
17	HIST1H2AC	HIST1H2AC	HIST1H2AC	485	0.48	0.47	YES
18	HIST1H4H	HIST1H4H	HIST1H4H	487	0.48	0.49	YES
19	HIST1H2BG	HIST1H2BG	HIST1H2BG	558	0.46	0.5	YES
20	HIST1H2BD	HIST1H2BD	HIST1H2BD	569	0.46	0.52	YES
21	HIST1H4E	HIST1H4E	HIST1H4E	574	0.45	0.54	YES
22	HIST1H4K	HIST1H4K	HIST1H4K	597	0.45	0.56	YES
23	MSH4	MSH4	MSH4	606	0.44	0.58	YES
24	HIST1H4I	HIST1H4I	HIST1H4I	733	0.41	0.59	YES
25	HIST1H2BK	HIST1H2BK	HIST1H2BK	845	0.38	0.6	YES
26	HIST3H2BB	HIST3H2BB	HIST3H2BB	883	0.38	0.61	YES
27	HIST1H2BC	HIST1H2BC	HIST1H2BC	885	0.38	0.63	YES
28	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1103	0.34	0.63	YES
29	HIST1H3I	HIST1H3I	HIST1H3I	1114	0.33	0.65	YES
30	HIST1H3B	HIST1H3B	HIST1H3B	1144	0.33	0.66	YES
31	HIST1H3G	HIST1H3G	HIST1H3G	1307	0.31	0.66	YES
32	HIST1H3D	HIST1H3D	HIST1H3D	1392	0.3	0.67	YES
33	RAD51	RAD51	RAD51	1474	0.29	0.68	YES
34	HIST1H2BF	HIST1H2BF	HIST1H2BF	1571	0.28	0.68	YES
35	BLM	BLM	BLM	1610	0.27	0.69	YES
36	HIST1H4F	HIST1H4F	HIST1H4F	1831	0.25	0.69	YES
37	HIST1H4B	HIST1H4B	HIST1H4B	1838	0.25	0.7	YES
38	HIST1H2AD	HIST1H2AD	HIST1H2AD	1989	0.23	0.7	YES
39	HIST4H4	HIST4H4	HIST4H4	2055	0.23	0.71	YES
40	HIST1H2BI	HIST1H2BI	HIST1H2BI	2106	0.22	0.72	YES
41	HIST1H3E	HIST1H3E	HIST1H3E	2206	0.21	0.72	YES
42	MND1	MND1	MND1	2722	0.18	0.7	NO
43	HIST1H2BH	HIST1H2BH	HIST1H2BH	2727	0.18	0.71	NO
44	HIST1H4A	HIST1H4A	HIST1H4A	3146	0.16	0.69	NO
45	NBN	NBN	NBN	3607	0.14	0.68	NO
46	BRCA2	BRCA2	BRCA2	4121	0.12	0.65	NO
47	HIST2H2BE	HIST2H2BE	HIST2H2BE	4377	0.11	0.64	NO
48	HIST1H2BN	HIST1H2BN	HIST1H2BN	4694	0.1	0.63	NO
49	HIST1H3J	HIST1H3J	HIST1H3J	4843	0.097	0.63	NO
50	CDK2	CDK2	CDK2	5663	0.074	0.59	NO
51	RPA1	RPA1	RPA1	5703	0.074	0.59	NO
52	RAD51C	RAD51C	RAD51C	5923	0.068	0.58	NO
53	H3F3A	H3F3A	H3F3A	6142	0.062	0.57	NO
54	BRCA1	BRCA1	BRCA1	6310	0.058	0.57	NO
55	HIST1H3F	HIST1H3F	HIST1H3F	6360	0.057	0.57	NO
56	ATM	ATM	ATM	6421	0.056	0.56	NO
57	RBBP8	RBBP8	RBBP8	6444	0.055	0.57	NO
58	RPA3	RPA3	RPA3	7048	0.04	0.54	NO
59	CDK4	CDK4	CDK4	7101	0.039	0.54	NO
60	PRDM9	PRDM9	PRDM9	8065	0.018	0.48	NO
61	HIST2H3D	HIST2H3D	HIST2H3D	8215	0.014	0.48	NO
62	RPA2	RPA2	RPA2	9883	-0.025	0.39	NO
63	MRE11A	MRE11A	MRE11A	10118	-0.032	0.38	NO
64	MLH1	MLH1	MLH1	10345	-0.038	0.37	NO
65	RAD50	RAD50	RAD50	10600	-0.044	0.36	NO
66	HIST1H4L	HIST1H4L	HIST1H4L	10796	-0.05	0.35	NO
67	H2AFZ	H2AFZ	H2AFZ	10901	-0.053	0.35	NO
68	TOP3A	TOP3A	TOP3A	10961	-0.055	0.35	NO
69	HIST2H2AC	HIST2H2AC	HIST2H2AC	11111	-0.059	0.34	NO
70	H3F3B	H3F3B	H3F3B	12581	-0.1	0.27	NO
71	MLH3	MLH3	MLH3	12823	-0.12	0.26	NO
72	MSH5	MSH5	MSH5	13171	-0.13	0.25	NO
73	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	13602	-0.15	0.23	NO
74	H2AFX	H2AFX	H2AFX	14283	-0.19	0.2	NO
75	HIST2H4A	HIST2H4A	HIST2H4A	14707	-0.22	0.19	NO
76	TEX15	TEX15	TEX15	17112	-0.45	0.082	NO
77	HIST2H3C	HIST2H3C	HIST2H3C	17361	-0.48	0.089	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: REACTOME 3 UTR MEDIATED TRANSLATIONAL REGULATION.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME 3 UTR MEDIATED TRANSLATIONAL REGULATION, 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 CITRATE CYCLE TCA CYCLE	30	genes.ES.table	0.49	1.6	0.067	0.22	0.86	0.5	0.2	0.4	0.095	0.042
KEGG SELENOAMINO ACID METABOLISM	26	genes.ES.table	0.52	1.7	0.023	0.22	0.79	0.62	0.28	0.44	0.081	0.053
KEGG RNA DEGRADATION	57	genes.ES.table	0.48	1.7	0.071	0.22	0.76	0.68	0.37	0.43	0.077	0.056
KEGG RNA POLYMERASE	29	genes.ES.table	0.51	1.6	0.074	0.23	0.87	0.69	0.37	0.43	0.097	0.044
KEGG SPLICEOSOME	114	genes.ES.table	0.57	1.8	0.012	0.35	0.34	0.78	0.36	0.5	0	0.081
KEGG HUNTINGTONS DISEASE	172	genes.ES.table	0.39	1.7	0.033	0.24	0.64	0.58	0.33	0.4	0.069	0.063
BIOCARTA MPR PATHWAY	34	genes.ES.table	0.5	1.7	0.014	0.23	0.67	0.32	0.16	0.27	0.069	0.059
PID HIF2PATHWAY	34	genes.ES.table	0.55	1.6	0.033	0.23	0.88	0.29	0.12	0.26	0.11	0.044
PID MYC ACTIVPATHWAY	79	genes.ES.table	0.5	1.8	0.018	0.28	0.4	0.46	0.22	0.35	0	0.064
REACTOME TRANSLATION	147	genes.ES.table	0.49	1.6	0.097	0.23	0.89	0.73	0.4	0.44	0.1	0.041

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

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	ATF3	ATF3	ATF3	1141	0.38	0.048	YES
2	DDIT3	DDIT3	DDIT3	1177	0.38	0.15	YES
3	IL8	IL8	IL8	1625	0.3	0.21	YES
4	ASNS	ASNS	ASNS	1629	0.3	0.3	YES
5	EXOSC3	EXOSC3	EXOSC3	2522	0.21	0.31	YES
6	EXOSC2	EXOSC2	EXOSC2	3036	0.18	0.33	YES
7	CCL2	CCL2	CCL2	3094	0.18	0.38	YES
8	EXOSC4	EXOSC4	EXOSC4	3150	0.17	0.42	YES
9	EXOSC8	EXOSC8	EXOSC8	3434	0.16	0.45	YES
10	EXOSC7	EXOSC7	EXOSC7	3446	0.16	0.5	YES
11	EXOSC9	EXOSC9	EXOSC9	3533	0.16	0.54	YES
12	HSPA5	HSPA5	HSPA5	3684	0.15	0.57	YES
13	KHSRP	KHSRP	KHSRP	4269	0.12	0.58	YES
14	EXOSC1	EXOSC1	EXOSC1	4366	0.12	0.6	YES
15	PARN	PARN	PARN	4463	0.12	0.63	YES
16	ATF4	ATF4	ATF4	4464	0.12	0.67	YES
17	EIF2AK3	EIF2AK3	EIF2AK3	5510	0.081	0.63	NO
18	EIF2S1	EIF2S1	EIF2S1	6311	0.059	0.61	NO
19	IGFBP1	IGFBP1	IGFBP1	7070	0.038	0.58	NO
20	DIS3	DIS3	DIS3	7904	0.017	0.54	NO
21	EXOSC5	EXOSC5	EXOSC5	8174	0.01	0.53	NO
22	NFYB	NFYB	NFYB	8335	0.0066	0.52	NO
23	EXOSC6	EXOSC6	EXOSC6	8540	0.00097	0.51	NO
24	ATF6	ATF6	ATF6	8857	-0.007	0.5	NO
25	HERPUD1	HERPUD1	HERPUD1	9319	-0.019	0.48	NO
26	DCP2	DCP2	DCP2	9993	-0.037	0.45	NO
27	NFYA	NFYA	NFYA	11521	-0.083	0.4	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 CITRATE CYCLE TCA CYCLE.

Figure S42. 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 SELENOAMINO ACID METABOLISM

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	GTF2H2	GTF2H2	GTF2H2	1068	0.4	-0.027	YES
2	GTF2H2B	GTF2H2B	GTF2H2B	1178	0.37	-0.0056	YES
3	MAGOH	MAGOH	MAGOH	1272	0.35	0.015	YES
4	NUP54	NUP54	NUP54	1877	0.27	0.0029	YES
5	SNRPA1	SNRPA1	SNRPA1	2033	0.25	0.013	YES
6	NUP205	NUP205	NUP205	2411	0.22	0.0091	YES
7	SNRPF	SNRPF	SNRPF	2450	0.22	0.023	YES
8	CDK7	CDK7	CDK7	2480	0.21	0.037	YES
9	SEH1L	SEH1L	SEH1L	2546	0.21	0.049	YES
10	UPF3B	UPF3B	UPF3B	2631	0.2	0.059	YES
11	NUP37	NUP37	NUP37	2656	0.2	0.073	YES
12	POLR2H	POLR2H	POLR2H	2721	0.2	0.084	YES
13	MNAT1	MNAT1	MNAT1	2775	0.19	0.095	YES
14	POLR2G	POLR2G	POLR2G	2841	0.19	0.11	YES
15	SF3A3	SF3A3	SF3A3	2845	0.19	0.12	YES
16	TXNL4A	TXNL4A	TXNL4A	2879	0.19	0.13	YES
17	THOC4	THOC4	THOC4	2880	0.19	0.14	YES
18	NUP43	NUP43	NUP43	2967	0.18	0.15	YES
19	NUP88	NUP88	NUP88	3053	0.18	0.16	YES
20	SNRNP40	SNRNP40	SNRNP40	3120	0.17	0.17	YES
21	GTF2H3	GTF2H3	GTF2H3	3160	0.17	0.18	YES
22	NUP85	NUP85	NUP85	3210	0.17	0.19	YES
23	EIF4E	EIF4E	EIF4E	3279	0.17	0.2	YES
24	SNRPD1	SNRPD1	SNRPD1	3356	0.16	0.21	YES
25	YBX1	YBX1	YBX1	3540	0.16	0.21	YES
26	FUS	FUS	FUS	3560	0.15	0.22	YES
27	SNRPG	SNRPG	SNRPG	3699	0.15	0.22	YES
28	PCBP1	PCBP1	PCBP1	3754	0.14	0.23	YES
29	RBM8A	RBM8A	RBM8A	3851	0.14	0.24	YES
30	NUP155	NUP155	NUP155	3886	0.14	0.24	YES
31	PCBP2	PCBP2	PCBP2	3945	0.14	0.25	YES
32	POM121	POM121	POM121	3971	0.14	0.26	YES
33	CSTF3	CSTF3	CSTF3	4060	0.13	0.26	YES
34	HNRNPD	HNRNPD	HNRNPD	4070	0.13	0.28	YES
35	PRPF4	PRPF4	PRPF4	4130	0.13	0.28	YES
36	EFTUD2	EFTUD2	EFTUD2	4155	0.13	0.29	YES
37	PABPN1	PABPN1	PABPN1	4177	0.13	0.3	YES
38	RBMX	RBMX	RBMX	4323	0.12	0.3	YES
39	DNAJC8	DNAJC8	DNAJC8	4341	0.12	0.31	YES
40	HNRNPA0	HNRNPA0	HNRNPA0	4349	0.12	0.32	YES
41	CSTF2	CSTF2	CSTF2	4356	0.12	0.32	YES
42	SNRPD3	SNRPD3	SNRPD3	4387	0.12	0.33	YES
43	LSM10	LSM10	LSM10	4475	0.12	0.34	YES
44	SNRPA	SNRPA	SNRPA	4544	0.11	0.34	YES
45	NCBP2	NCBP2	NCBP2	4564	0.11	0.35	YES
46	HNRNPH1	HNRNPH1	HNRNPH1	4651	0.11	0.35	YES
47	SNRPB2	SNRPB2	SNRPB2	4770	0.11	0.35	YES
48	PRPF8	PRPF8	PRPF8	4805	0.1	0.36	YES
49	SRRM1	SRRM1	SRRM1	4816	0.1	0.36	YES
50	HNRNPA3	HNRNPA3	HNRNPA3	4870	0.1	0.37	YES
51	POLR2A	POLR2A	POLR2A	4945	0.099	0.37	YES
52	HNRNPM	HNRNPM	HNRNPM	4949	0.099	0.38	YES
53	NUP35	NUP35	NUP35	4968	0.098	0.39	YES
54	NUP153	NUP153	NUP153	5027	0.096	0.39	YES
55	SNRPB	SNRPB	SNRPB	5034	0.096	0.4	YES
56	POLR2E	POLR2E	POLR2E	5070	0.095	0.4	YES
57	HNRNPC	HNRNPC	HNRNPC	5257	0.088	0.4	YES
58	CPSF3	CPSF3	CPSF3	5297	0.087	0.4	YES
59	NHP2L1	NHP2L1	NHP2L1	5328	0.086	0.41	YES
60	POLR2F	POLR2F	POLR2F	5349	0.086	0.41	YES
61	SF3B14	SF3B14	SF3B14	5379	0.085	0.42	YES
62	CDC40	CDC40	CDC40	5480	0.082	0.42	YES
63	PTBP1	PTBP1	PTBP1	5553	0.08	0.42	YES
64	U2AF1	U2AF1	U2AF1	5558	0.08	0.43	YES
65	GTF2F2	GTF2F2	GTF2F2	5570	0.079	0.43	YES
66	HNRNPL	HNRNPL	HNRNPL	5661	0.076	0.43	YES
67	LSM2	LSM2	LSM2	5663	0.076	0.44	YES
68	HNRNPK	HNRNPK	HNRNPK	5719	0.075	0.44	YES
69	RNMT	RNMT	RNMT	5757	0.074	0.44	YES
70	CCNH	CCNH	CCNH	5816	0.072	0.45	YES
71	POLR2C	POLR2C	POLR2C	5834	0.072	0.45	YES
72	RNGTT	RNGTT	RNGTT	5837	0.072	0.46	YES
73	NUP50	NUP50	NUP50	5871	0.071	0.46	YES
74	NUP107	NUP107	NUP107	5927	0.07	0.46	YES
75	CSTF1	CSTF1	CSTF1	5956	0.068	0.46	YES
76	CPSF1	CPSF1	CPSF1	5969	0.068	0.47	YES
77	SF3B2	SF3B2	SF3B2	6057	0.066	0.47	YES
78	U2AF2	U2AF2	U2AF2	6116	0.064	0.47	YES
79	NCBP1	NCBP1	NCBP1	6118	0.064	0.48	YES
80	SLBP	SLBP	SLBP	6153	0.063	0.48	YES
81	NUP93	NUP93	NUP93	6160	0.063	0.48	YES
82	DHX9	DHX9	DHX9	6233	0.061	0.48	YES
83	NFX1	NFX1	NFX1	6262	0.06	0.49	YES
84	PHF5A	PHF5A	PHF5A	6292	0.059	0.49	YES
85	HNRNPA1	HNRNPA1	HNRNPA1	6315	0.059	0.49	YES
86	GTF2F1	GTF2F1	GTF2F1	6330	0.058	0.5	YES
87	HNRNPU	HNRNPU	HNRNPU	6452	0.055	0.49	YES
88	SNRPE	SNRPE	SNRPE	6487	0.054	0.5	YES
89	RAE1	RAE1	RAE1	6489	0.054	0.5	YES
90	RNPS1	RNPS1	RNPS1	6512	0.053	0.5	YES
91	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	6520	0.053	0.5	YES
92	SF3B3	SF3B3	SF3B3	6528	0.052	0.51	YES
93	SF3A2	SF3A2	SF3A2	6576	0.051	0.51	YES
94	SF3A1	SF3A1	SF3A1	6577	0.051	0.51	YES
95	SNRPD2	SNRPD2	SNRPD2	6695	0.048	0.51	YES
96	SMC1A	SMC1A	SMC1A	6769	0.046	0.51	YES
97	POLR2J	POLR2J	POLR2J	6803	0.045	0.51	YES
98	ADARB1	ADARB1	ADARB1	6806	0.045	0.52	YES
99	GTF2H1	GTF2H1	GTF2H1	6876	0.043	0.51	YES
100	SF3B4	SF3B4	SF3B4	6911	0.042	0.52	YES
101	POLR2L	POLR2L	POLR2L	6976	0.04	0.52	NO
102	POLR2I	POLR2I	POLR2I	7113	0.037	0.51	NO
103	AAAS	AAAS	AAAS	7179	0.036	0.51	NO
104	NUPL2	NUPL2	NUPL2	7219	0.034	0.51	NO
105	PRPF6	PRPF6	PRPF6	7315	0.032	0.51	NO
106	CCAR1	CCAR1	CCAR1	7364	0.031	0.51	NO
107	DDX23	DDX23	DDX23	7370	0.03	0.51	NO
108	CPSF2	CPSF2	CPSF2	7395	0.03	0.51	NO
109	GTF2H4	GTF2H4	GTF2H4	7399	0.03	0.51	NO
110	NUP210	NUP210	NUP210	7456	0.028	0.51	NO
111	NUP133	NUP133	NUP133	7555	0.025	0.51	NO
112	ERCC2	ERCC2	ERCC2	7607	0.024	0.51	NO
113	HNRNPR	HNRNPR	HNRNPR	7648	0.023	0.51	NO
114	CD2BP2	CD2BP2	CD2BP2	7653	0.023	0.51	NO
115	CLP1	CLP1	CLP1	7658	0.023	0.51	NO
116	NUDT21	NUDT21	NUDT21	7752	0.021	0.51	NO
117	SNRNP70	SNRNP70	SNRNP70	7842	0.019	0.5	NO
118	NUPL1	NUPL1	NUPL1	7990	0.015	0.5	NO
119	RANBP2	RANBP2	RANBP2	8139	0.011	0.49	NO
120	POLR2B	POLR2B	POLR2B	8266	0.008	0.48	NO
121	SF3B5	SF3B5	SF3B5	8286	0.0076	0.48	NO
122	POLR2K	POLR2K	POLR2K	8316	0.0069	0.48	NO
123	POLR2D	POLR2D	POLR2D	8363	0.0056	0.48	NO
124	DHX38	DHX38	DHX38	8373	0.0054	0.48	NO
125	ERCC3	ERCC3	ERCC3	8413	0.0044	0.48	NO
126	NUP188	NUP188	NUP188	8595	-0.00044	0.47	NO
127	PAPOLA	PAPOLA	PAPOLA	8662	-0.0021	0.46	NO
128	CPSF7	CPSF7	CPSF7	8717	-0.0035	0.46	NO
129	SNRNP200	SNRNP200	SNRNP200	8861	-0.0071	0.46	NO
130	PCF11	PCF11	PCF11	8866	-0.0072	0.46	NO
131	HNRNPF	HNRNPF	HNRNPF	9109	-0.013	0.44	NO
132	SF3B1	SF3B1	SF3B1	9329	-0.019	0.43	NO
133	NUP62	NUP62	NUP62	9419	-0.022	0.43	NO
134	NXF1	NXF1	NXF1	9981	-0.036	0.4	NO
135	METTL3	METTL3	METTL3	10133	-0.04	0.4	NO
136	NUP214	NUP214	NUP214	10148	-0.041	0.4	NO
137	ADAR	ADAR	ADAR	10266	-0.044	0.4	NO
138	HNRNPH2	HNRNPH2	HNRNPH2	10468	-0.05	0.39	NO
139	TPR	TPR	TPR	10900	-0.063	0.37	NO
140	APOBEC1	APOBEC1	APOBEC1	10947	-0.065	0.38	NO
141	SUPT5H	SUPT5H	SUPT5H	11003	-0.066	0.38	NO
142	ZNF473	ZNF473	ZNF473	11154	-0.071	0.37	NO
143	HNRNPUL1	HNRNPUL1	HNRNPUL1	11515	-0.082	0.36	NO
144	RBM5	RBM5	RBM5	13059	-0.13	0.29	NO
145	LSM11	LSM11	LSM11	13268	-0.14	0.29	NO
146	A1CF	A1CF	A1CF	15357	-0.24	0.2	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 SELENOAMINO ACID METABOLISM.

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

genes ES table in pathway: KEGG RNA DEGRADATION

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	ATF3	ATF3	ATF3	1141	0.38	-0.014	YES
2	DDIT3	DDIT3	DDIT3	1177	0.38	0.03	YES
3	IL8	IL8	IL8	1625	0.3	0.043	YES
4	ASNS	ASNS	ASNS	1629	0.3	0.079	YES
5	PDIA6	PDIA6	PDIA6	2206	0.24	0.078	YES
6	DNAJB11	DNAJB11	DNAJB11	2461	0.22	0.09	YES
7	EXOSC3	EXOSC3	EXOSC3	2522	0.21	0.11	YES
8	HYOU1	HYOU1	HYOU1	2612	0.2	0.13	YES
9	LMNA	LMNA	LMNA	2671	0.2	0.15	YES
10	EXOSC2	EXOSC2	EXOSC2	3036	0.18	0.16	YES
11	CCL2	CCL2	CCL2	3094	0.18	0.18	YES
12	EXOSC4	EXOSC4	EXOSC4	3150	0.17	0.19	YES
13	HSP90B1	HSP90B1	HSP90B1	3375	0.16	0.2	YES
14	EXOSC8	EXOSC8	EXOSC8	3434	0.16	0.22	YES
15	EXOSC7	EXOSC7	EXOSC7	3446	0.16	0.24	YES
16	EXOSC9	EXOSC9	EXOSC9	3533	0.16	0.25	YES
17	HSPA5	HSPA5	HSPA5	3684	0.15	0.26	YES
18	SHC1	SHC1	SHC1	3710	0.15	0.28	YES
19	SULT1A3	SULT1A3	SULT1A3	3874	0.14	0.28	YES
20	KHSRP	KHSRP	KHSRP	4269	0.12	0.28	YES
21	EXOSC1	EXOSC1	EXOSC1	4366	0.12	0.29	YES
22	PARN	PARN	PARN	4463	0.12	0.3	YES
23	ATF4	ATF4	ATF4	4464	0.12	0.31	YES
24	C19orf10	C19orf10	C19orf10	4746	0.11	0.31	YES
25	PDIA5	PDIA5	PDIA5	4757	0.11	0.32	YES
26	YIF1A	YIF1A	YIF1A	4777	0.11	0.34	YES
27	CALR	CALR	CALR	4848	0.1	0.34	YES
28	DDX11	DDX11	DDX11	5037	0.096	0.35	YES
29	TSPYL2	TSPYL2	TSPYL2	5225	0.09	0.35	YES
30	MBTPS2	MBTPS2	MBTPS2	5463	0.082	0.34	YES
31	EIF2AK3	EIF2AK3	EIF2AK3	5510	0.081	0.35	YES
32	EXTL3	EXTL3	EXTL3	5563	0.08	0.36	YES
33	DNAJC3	DNAJC3	DNAJC3	5618	0.078	0.36	YES
34	KDELR3	KDELR3	KDELR3	5693	0.076	0.37	YES
35	KLHDC3	KLHDC3	KLHDC3	5936	0.069	0.37	NO
36	EIF2S1	EIF2S1	EIF2S1	6311	0.059	0.35	NO
37	IGFBP1	IGFBP1	IGFBP1	7070	0.038	0.32	NO
38	XBP1	XBP1	XBP1	7072	0.038	0.32	NO
39	FKBP14	FKBP14	FKBP14	7118	0.037	0.32	NO
40	ACADVL	ACADVL	ACADVL	7147	0.036	0.33	NO
41	SRPRB	SRPRB	SRPRB	7522	0.026	0.31	NO
42	ATP6V0D1	ATP6V0D1	ATP6V0D1	7716	0.022	0.3	NO
43	DIS3	DIS3	DIS3	7904	0.017	0.3	NO
44	SERP1	SERP1	SERP1	8117	0.012	0.29	NO
45	GOSR2	GOSR2	GOSR2	8121	0.012	0.29	NO
46	EXOSC5	EXOSC5	EXOSC5	8174	0.01	0.29	NO
47	ARFGAP1	ARFGAP1	ARFGAP1	8236	0.0088	0.28	NO
48	NFYB	NFYB	NFYB	8335	0.0066	0.28	NO
49	EXOSC6	EXOSC6	EXOSC6	8540	0.00097	0.27	NO
50	PREB	PREB	PREB	8631	-0.0012	0.26	NO
51	ATF6	ATF6	ATF6	8857	-0.007	0.25	NO
52	SSR1	SSR1	SSR1	9274	-0.018	0.23	NO
53	HERPUD1	HERPUD1	HERPUD1	9319	-0.019	0.23	NO
54	SRPR	SRPR	SRPR	9653	-0.028	0.22	NO
55	WIPI1	WIPI1	WIPI1	9654	-0.028	0.22	NO
56	DCTN1	DCTN1	DCTN1	9824	-0.033	0.22	NO
57	ZBTB17	ZBTB17	ZBTB17	9873	-0.034	0.22	NO
58	DCP2	DCP2	DCP2	9993	-0.037	0.22	NO
59	ADD1	ADD1	ADD1	10084	-0.039	0.22	NO
60	HDGF	HDGF	HDGF	10505	-0.05	0.2	NO
61	SYVN1	SYVN1	SYVN1	10696	-0.057	0.2	NO
62	SEC31A	SEC31A	SEC31A	10717	-0.058	0.2	NO
63	DNAJB9	DNAJB9	DNAJB9	10802	-0.06	0.21	NO
64	CXXC1	CXXC1	CXXC1	10873	-0.063	0.21	NO
65	CTDSP2	CTDSP2	CTDSP2	11032	-0.067	0.21	NO
66	TATDN2	TATDN2	TATDN2	11041	-0.067	0.22	NO
67	GSK3A	GSK3A	GSK3A	11238	-0.073	0.22	NO
68	NFYA	NFYA	NFYA	11521	-0.083	0.21	NO
69	EDEM1	EDEM1	EDEM1	12142	-0.1	0.19	NO
70	TLN1	TLN1	TLN1	12234	-0.1	0.2	NO
71	TPP1	TPP1	TPP1	13033	-0.13	0.17	NO
72	WFS1	WFS1	WFS1	13153	-0.14	0.18	NO
73	MBTPS1	MBTPS1	MBTPS1	13682	-0.16	0.18	NO
74	CUL7	CUL7	CUL7	13788	-0.16	0.19	NO
75	PPP2R5B	PPP2R5B	PPP2R5B	16312	-0.3	0.093	NO
76	ERN1	ERN1	ERN1	17612	-0.42	0.076	NO

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

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

genes ES table in pathway: KEGG RNA POLYMERASE

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	PSMB2	PSMB2	PSMB2	1782	0.28	-0.065	YES
2	PSMD11	PSMD11	PSMD11	1865	0.27	-0.042	YES
3	PSMB6	PSMB6	PSMB6	1976	0.26	-0.021	YES
4	PSMD10	PSMD10	PSMD10	2184	0.24	-0.0069	YES
5	PSMA5	PSMA5	PSMA5	2209	0.24	0.016	YES
6	EXOSC3	EXOSC3	EXOSC3	2522	0.21	0.022	YES
7	PSMB3	PSMB3	PSMB3	2556	0.21	0.042	YES
8	PSMC4	PSMC4	PSMC4	2609	0.2	0.06	YES
9	PSMD12	PSMD12	PSMD12	2627	0.2	0.08	YES
10	HSPB1	HSPB1	HSPB1	2748	0.2	0.094	YES
11	PSMA7	PSMA7	PSMA7	2758	0.2	0.11	YES
12	PSMA2	PSMA2	PSMA2	3005	0.18	0.12	YES
13	EXOSC2	EXOSC2	EXOSC2	3036	0.18	0.14	YES
14	PSMD3	PSMD3	PSMD3	3098	0.18	0.15	YES
15	EXOSC4	EXOSC4	EXOSC4	3150	0.17	0.17	YES
16	PSMA1	PSMA1	PSMA1	3170	0.17	0.18	YES
17	PSMD7	PSMD7	PSMD7	3368	0.16	0.19	YES
18	EXOSC8	EXOSC8	EXOSC8	3434	0.16	0.2	YES
19	EXOSC7	EXOSC7	EXOSC7	3446	0.16	0.22	YES
20	EXOSC9	EXOSC9	EXOSC9	3533	0.16	0.23	YES
21	PSMB5	PSMB5	PSMB5	3705	0.15	0.24	YES
22	PSMC2	PSMC2	PSMC2	3716	0.15	0.25	YES
23	PSME4	PSME4	PSME4	3749	0.14	0.26	YES
24	PSMC1	PSMC1	PSMC1	4002	0.14	0.27	YES
25	MAPKAPK2	MAPKAPK2	MAPKAPK2	4018	0.13	0.28	YES
26	HNRNPD	HNRNPD	HNRNPD	4070	0.13	0.29	YES
27	PSMB7	PSMB7	PSMB7	4212	0.13	0.3	YES
28	PSMA6	PSMA6	PSMA6	4218	0.13	0.31	YES
29	KHSRP	KHSRP	KHSRP	4269	0.12	0.32	YES
30	EIF4G1	EIF4G1	EIF4G1	4295	0.12	0.33	YES
31	PSMD6	PSMD6	PSMD6	4328	0.12	0.34	YES
32	EXOSC1	EXOSC1	EXOSC1	4366	0.12	0.35	YES
33	HSPA8	HSPA8	HSPA8	4395	0.12	0.36	YES
34	PSMA3	PSMA3	PSMA3	4434	0.12	0.37	YES
35	PARN	PARN	PARN	4463	0.12	0.38	YES
36	HSPA1B	HSPA1B	HSPA1B	4531	0.12	0.39	YES
37	PSMC5	PSMC5	PSMC5	4546	0.11	0.4	YES
38	PSMC3	PSMC3	PSMC3	4554	0.11	0.42	YES
39	PSMD5	PSMD5	PSMD5	4600	0.11	0.42	YES
40	PSMB1	PSMB1	PSMB1	4612	0.11	0.44	YES
41	PSMB4	PSMB4	PSMB4	4675	0.11	0.44	YES
42	RPS27A	RPS27A	RPS27A	4686	0.11	0.45	YES
43	PSMD2	PSMD2	PSMD2	4743	0.11	0.46	YES
44	PSMD14	PSMD14	PSMD14	4935	0.1	0.46	YES
45	PSMA4	PSMA4	PSMA4	4995	0.098	0.47	YES
46	YWHAZ	YWHAZ	YWHAZ	5472	0.082	0.45	YES
47	DCP1A	DCP1A	DCP1A	5526	0.081	0.46	YES
48	PSMD13	PSMD13	PSMD13	5549	0.08	0.47	YES
49	TNPO1	TNPO1	TNPO1	5566	0.079	0.47	YES
50	ZFP36L1	ZFP36L1	ZFP36L1	5578	0.079	0.48	YES
51	PSMD4	PSMD4	PSMD4	5666	0.076	0.48	YES
52	PSMD1	PSMD1	PSMD1	5970	0.068	0.48	NO
53	PSMC6	PSMC6	PSMC6	6175	0.062	0.47	NO
54	XPO1	XPO1	XPO1	6692	0.048	0.45	NO
55	UBA52	UBA52	UBA52	6757	0.047	0.45	NO
56	PABPC1	PABPC1	PABPC1	6776	0.046	0.45	NO
57	PSMD8	PSMD8	PSMD8	7181	0.035	0.44	NO
58	PRKCA	PRKCA	PRKCA	7253	0.033	0.44	NO
59	DIS3	DIS3	DIS3	7904	0.017	0.4	NO
60	PSMD9	PSMD9	PSMD9	8104	0.012	0.4	NO
61	EXOSC5	EXOSC5	EXOSC5	8174	0.01	0.39	NO
62	EXOSC6	EXOSC6	EXOSC6	8540	0.00097	0.37	NO
63	ELAVL1	ELAVL1	ELAVL1	8610	-0.00083	0.37	NO
64	PRKCD	PRKCD	PRKCD	8793	-0.0054	0.36	NO
65	YWHAB	YWHAB	YWHAB	8973	-0.0096	0.35	NO
66	PSME2	PSME2	PSME2	9219	-0.016	0.34	NO
67	MAPK14	MAPK14	MAPK14	9605	-0.027	0.32	NO
68	DCP2	DCP2	DCP2	9993	-0.037	0.31	NO
69	NUP214	NUP214	NUP214	10148	-0.041	0.3	NO
70	AKT1	AKT1	AKT1	10949	-0.065	0.27	NO
71	PSME1	PSME1	PSME1	11030	-0.067	0.27	NO
72	ANP32A	ANP32A	ANP32A	11134	-0.07	0.27	NO
73	PSMF1	PSMF1	PSMF1	11150	-0.071	0.28	NO
74	PSMB10	PSMB10	PSMB10	12004	-0.098	0.24	NO
75	PSMB8	PSMB8	PSMB8	12633	-0.12	0.22	NO
76	ZFP36	ZFP36	ZFP36	12811	-0.12	0.23	NO
77	TNFSF13	TNFSF13	TNFSF13	12967	-0.13	0.23	NO
78	PSMB9	PSMB9	PSMB9	13665	-0.16	0.21	NO
79	PSMA8	PSMA8	PSMA8	15143	-0.22	0.16	NO
80	MAPK11	MAPK11	MAPK11	15258	-0.23	0.18	NO
81	XRN1	XRN1	XRN1	15464	-0.24	0.19	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 RNA POLYMERASE.

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

genes ES table in pathway: KEGG SPLICEOSOME

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	HSPA6	HSPA6	HSPA6	922	0.44	-0.012	YES
2	HSPA2	HSPA2	HSPA2	1122	0.39	0.011	YES
3	MAGOH	MAGOH	MAGOH	1272	0.35	0.033	YES
4	PPIH	PPIH	PPIH	1654	0.3	0.038	YES
5	MAGOHB	MAGOHB	MAGOHB	1882	0.27	0.048	YES
6	SNRPA1	SNRPA1	SNRPA1	2033	0.25	0.061	YES
7	THOC3	THOC3	THOC3	2218	0.24	0.072	YES
8	SNRPF	SNRPF	SNRPF	2450	0.22	0.078	YES
9	SNRPC	SNRPC	SNRPC	2716	0.2	0.08	YES
10	WBP11	WBP11	WBP11	2826	0.19	0.091	YES
11	SF3A3	SF3A3	SF3A3	2845	0.19	0.11	YES
12	BCAS2	BCAS2	BCAS2	2863	0.19	0.12	YES
13	PPIL1	PPIL1	PPIL1	2878	0.19	0.14	YES
14	TXNL4A	TXNL4A	TXNL4A	2879	0.19	0.15	YES
15	THOC4	THOC4	THOC4	2880	0.19	0.17	YES
16	PRPF38A	PRPF38A	PRPF38A	2929	0.18	0.18	YES
17	RBM22	RBM22	RBM22	3002	0.18	0.19	YES
18	SNRNP40	SNRNP40	SNRNP40	3120	0.17	0.2	YES
19	ZMAT2	ZMAT2	ZMAT2	3269	0.17	0.21	YES
20	LSM3	LSM3	LSM3	3324	0.16	0.22	YES
21	SNRPD1	SNRPD1	SNRPD1	3356	0.16	0.23	YES
22	SNRNP27	SNRNP27	SNRNP27	3449	0.16	0.24	YES
23	SNRPG	SNRPG	SNRPG	3699	0.15	0.24	YES
24	PCBP1	PCBP1	PCBP1	3754	0.14	0.25	YES
25	BUD31	BUD31	BUD31	3755	0.14	0.26	YES
26	DHX15	DHX15	DHX15	3809	0.14	0.27	YES
27	EIF4A3	EIF4A3	EIF4A3	3812	0.14	0.28	YES
28	RBM8A	RBM8A	RBM8A	3851	0.14	0.29	YES
29	LSM7	LSM7	LSM7	3946	0.14	0.3	YES
30	LSM6	LSM6	LSM6	4014	0.14	0.3	YES
31	HSPA1A	HSPA1A	HSPA1A	4022	0.13	0.32	YES
32	PRPF4	PRPF4	PRPF4	4130	0.13	0.32	YES
33	EFTUD2	EFTUD2	EFTUD2	4155	0.13	0.33	YES
34	DHX8	DHX8	DHX8	4157	0.13	0.34	YES
35	RBMX	RBMX	RBMX	4323	0.12	0.34	YES
36	SNRPD3	SNRPD3	SNRPD3	4387	0.12	0.35	YES
37	HSPA8	HSPA8	HSPA8	4395	0.12	0.36	YES
38	PRPF40A	PRPF40A	PRPF40A	4462	0.12	0.37	YES
39	SMNDC1	SMNDC1	SMNDC1	4468	0.12	0.38	YES
40	HSPA1B	HSPA1B	HSPA1B	4531	0.12	0.38	YES
41	SNRPA	SNRPA	SNRPA	4544	0.11	0.39	YES
42	NCBP2	NCBP2	NCBP2	4564	0.11	0.4	YES
43	DDX46	DDX46	DDX46	4575	0.11	0.41	YES
44	PPIE	PPIE	PPIE	4607	0.11	0.42	YES
45	THOC2	THOC2	THOC2	4690	0.11	0.42	YES
46	CWC15	CWC15	CWC15	4714	0.11	0.43	YES
47	SNRPB2	SNRPB2	SNRPB2	4770	0.11	0.44	YES
48	PRPF8	PRPF8	PRPF8	4805	0.1	0.44	YES
49	PUF60	PUF60	PUF60	4849	0.1	0.45	YES
50	HNRNPA3	HNRNPA3	HNRNPA3	4870	0.1	0.46	YES
51	HNRNPM	HNRNPM	HNRNPM	4949	0.099	0.46	YES
52	SNRPB	SNRPB	SNRPB	5034	0.096	0.46	YES
53	NAA38	NAA38	NAA38	5236	0.09	0.46	YES
54	PRPF3	PRPF3	PRPF3	5253	0.089	0.47	YES
55	HNRNPC	HNRNPC	HNRNPC	5257	0.088	0.48	YES
56	NHP2L1	NHP2L1	NHP2L1	5328	0.086	0.48	YES
57	SF3B14	SF3B14	SF3B14	5379	0.085	0.48	YES
58	PRPF18	PRPF18	PRPF18	5458	0.082	0.49	YES
59	CDC40	CDC40	CDC40	5480	0.082	0.49	YES
60	U2AF1	U2AF1	U2AF1	5558	0.08	0.5	YES
61	SYF2	SYF2	SYF2	5576	0.079	0.5	YES
62	TCERG1	TCERG1	TCERG1	5635	0.077	0.5	YES
63	LSM2	LSM2	LSM2	5663	0.076	0.51	YES
64	HNRNPK	HNRNPK	HNRNPK	5719	0.075	0.51	YES
65	USP39	USP39	USP39	5747	0.074	0.52	YES
66	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	5781	0.073	0.52	YES
67	PQBP1	PQBP1	PQBP1	5907	0.07	0.52	YES
68	SF3B2	SF3B2	SF3B2	6057	0.066	0.52	YES
69	U2AF2	U2AF2	U2AF2	6116	0.064	0.52	YES
70	NCBP1	NCBP1	NCBP1	6118	0.064	0.53	YES
71	SART1	SART1	SART1	6169	0.062	0.53	YES
72	TRA2B	TRA2B	TRA2B	6211	0.061	0.53	YES
73	LSM5	LSM5	LSM5	6267	0.06	0.53	YES
74	PHF5A	PHF5A	PHF5A	6292	0.059	0.54	YES
75	HNRNPA1	HNRNPA1	HNRNPA1	6315	0.059	0.54	YES
76	HNRNPU	HNRNPU	HNRNPU	6452	0.055	0.54	YES
77	CDC5L	CDC5L	CDC5L	6470	0.054	0.54	YES
78	SNRPE	SNRPE	SNRPE	6487	0.054	0.55	YES
79	SF3B3	SF3B3	SF3B3	6528	0.052	0.55	YES
80	PRPF19	PRPF19	PRPF19	6539	0.052	0.55	YES
81	SF3A2	SF3A2	SF3A2	6576	0.051	0.56	YES
82	SF3A1	SF3A1	SF3A1	6577	0.051	0.56	YES
83	LSM4	LSM4	LSM4	6597	0.051	0.56	YES
84	RBM17	RBM17	RBM17	6688	0.048	0.56	YES
85	SNRPD2	SNRPD2	SNRPD2	6695	0.048	0.57	YES
86	SLU7	SLU7	SLU7	6765	0.046	0.57	YES
87	CTNNBL1	CTNNBL1	CTNNBL1	6832	0.044	0.57	YES
88	DDX42	DDX42	DDX42	6906	0.042	0.57	YES
89	SF3B4	SF3B4	SF3B4	6911	0.042	0.57	YES
90	PRPF31	PRPF31	PRPF31	7217	0.034	0.56	NO
91	PRPF6	PRPF6	PRPF6	7315	0.032	0.55	NO
92	DDX23	DDX23	DDX23	7370	0.03	0.55	NO
93	SNW1	SNW1	SNW1	7408	0.029	0.55	NO
94	AQR	AQR	AQR	7423	0.029	0.56	NO
95	ISY1	ISY1	ISY1	7524	0.026	0.55	NO
96	SNRNP70	SNRNP70	SNRNP70	7842	0.019	0.54	NO
97	DHX16	DHX16	DHX16	8013	0.014	0.53	NO
98	SF3B5	SF3B5	SF3B5	8286	0.0076	0.52	NO
99	DHX38	DHX38	DHX38	8373	0.0054	0.51	NO
100	CRNKL1	CRNKL1	CRNKL1	8480	0.0027	0.51	NO
101	CCDC12	CCDC12	CCDC12	8647	-0.0015	0.5	NO
102	DDX5	DDX5	DDX5	8710	-0.0032	0.5	NO
103	SNRNP200	SNRNP200	SNRNP200	8861	-0.0071	0.49	NO
104	ACIN1	ACIN1	ACIN1	8895	-0.0079	0.49	NO
105	CHERP	CHERP	CHERP	8898	-0.008	0.49	NO
106	PLRG1	PLRG1	PLRG1	9116	-0.014	0.48	NO
107	SF3B1	SF3B1	SF3B1	9329	-0.019	0.47	NO
108	TRA2A	TRA2A	TRA2A	9389	-0.021	0.47	NO
109	PRPF38B	PRPF38B	PRPF38B	9453	-0.023	0.46	NO
110	RBM25	RBM25	RBM25	9474	-0.023	0.46	NO
111	THOC1	THOC1	THOC1	9518	-0.025	0.46	NO
112	XAB2	XAB2	XAB2	9895	-0.034	0.45	NO
113	PRPF40B	PRPF40B	PRPF40B	13182	-0.14	0.29	NO
114	HSPA1L	HSPA1L	HSPA1L	16001	-0.28	0.16	NO

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

Figure S50. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG SPLICEOSOME, 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 HUNTINGTONS DISEASE

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	RPL36A	RPL36A	RPL36A	1164	0.38	-0.046	YES
2	MAGOH	MAGOH	MAGOH	1272	0.35	-0.038	YES
3	RPL3L	RPL3L	RPL3L	1613	0.3	-0.044	YES
4	TGS1	TGS1	TGS1	1780	0.28	-0.041	YES
5	PSMB2	PSMB2	PSMB2	1782	0.28	-0.03	YES
6	PSMD11	PSMD11	PSMD11	1865	0.27	-0.023	YES
7	NUP54	NUP54	NUP54	1877	0.27	-0.013	YES
8	PSMB6	PSMB6	PSMB6	1976	0.26	-0.0075	YES
9	RPL21	RPL21	RPL21	2102	0.24	-0.0042	YES
10	PSMD10	PSMD10	PSMD10	2184	0.24	0.0012	YES
11	PSMA5	PSMA5	PSMA5	2209	0.24	0.0095	YES
12	RPL26L1	RPL26L1	RPL26L1	2249	0.23	0.017	YES
13	NUP205	NUP205	NUP205	2411	0.22	0.017	YES
14	SNRPF	SNRPF	SNRPF	2450	0.22	0.024	YES
15	RPL39	RPL39	RPL39	2483	0.21	0.031	YES
16	EXOSC3	EXOSC3	EXOSC3	2522	0.21	0.038	YES
17	SEH1L	SEH1L	SEH1L	2546	0.21	0.045	YES
18	PSMB3	PSMB3	PSMB3	2556	0.21	0.053	YES
19	GEMIN7	GEMIN7	GEMIN7	2608	0.2	0.059	YES
20	PSMC4	PSMC4	PSMC4	2609	0.2	0.067	YES
21	PSMD12	PSMD12	PSMD12	2627	0.2	0.074	YES
22	UPF3B	UPF3B	UPF3B	2631	0.2	0.083	YES
23	NUP37	NUP37	NUP37	2656	0.2	0.09	YES
24	PHAX	PHAX	PHAX	2679	0.2	0.096	YES
25	HSPB1	HSPB1	HSPB1	2748	0.2	0.1	YES
26	PSMA7	PSMA7	PSMA7	2758	0.2	0.11	YES
27	C2orf29	C2orf29	C2orf29	2849	0.19	0.11	YES
28	WDR77	WDR77	WDR77	2931	0.18	0.11	YES
29	SMN2	SMN2	SMN2	2959	0.18	0.12	YES
30	NUP43	NUP43	NUP43	2967	0.18	0.13	YES
31	PSMA2	PSMA2	PSMA2	3005	0.18	0.13	YES
32	EXOSC2	EXOSC2	EXOSC2	3036	0.18	0.14	YES
33	RPL24	RPL24	RPL24	3051	0.18	0.14	YES
34	NUP88	NUP88	NUP88	3053	0.18	0.15	YES
35	PSMD3	PSMD3	PSMD3	3098	0.18	0.16	YES
36	EXOSC4	EXOSC4	EXOSC4	3150	0.17	0.16	YES
37	PSMA1	PSMA1	PSMA1	3170	0.17	0.17	YES
38	GSPT2	GSPT2	GSPT2	3184	0.17	0.17	YES
39	NUP85	NUP85	NUP85	3210	0.17	0.18	YES
40	EIF4E	EIF4E	EIF4E	3279	0.17	0.18	YES
41	LSM3	LSM3	LSM3	3324	0.16	0.19	YES
42	SNRPD1	SNRPD1	SNRPD1	3356	0.16	0.19	YES
43	PSMD7	PSMD7	PSMD7	3368	0.16	0.2	YES
44	ETF1	ETF1	ETF1	3413	0.16	0.2	YES
45	EXOSC8	EXOSC8	EXOSC8	3434	0.16	0.21	YES
46	EXOSC7	EXOSC7	EXOSC7	3446	0.16	0.21	YES
47	GEMIN4	GEMIN4	GEMIN4	3463	0.16	0.22	YES
48	EXOSC9	EXOSC9	EXOSC9	3533	0.16	0.22	YES
49	CLNS1A	CLNS1A	CLNS1A	3543	0.16	0.23	YES
50	GEMIN6	GEMIN6	GEMIN6	3581	0.15	0.23	YES
51	SNRPG	SNRPG	SNRPG	3699	0.15	0.23	YES
52	PSMB5	PSMB5	PSMB5	3705	0.15	0.24	YES
53	PSMC2	PSMC2	PSMC2	3716	0.15	0.24	YES
54	PSME4	PSME4	PSME4	3749	0.14	0.25	YES
55	PATL1	PATL1	PATL1	3802	0.14	0.25	YES
56	EIF4A3	EIF4A3	EIF4A3	3812	0.14	0.26	YES
57	RBM8A	RBM8A	RBM8A	3851	0.14	0.26	YES
58	EIF4A1	EIF4A1	EIF4A1	3864	0.14	0.26	YES
59	NUP155	NUP155	NUP155	3886	0.14	0.27	YES
60	POM121	POM121	POM121	3971	0.14	0.27	YES
61	GEMIN5	GEMIN5	GEMIN5	3995	0.14	0.27	YES
62	PSMC1	PSMC1	PSMC1	4002	0.14	0.28	YES
63	LSM6	LSM6	LSM6	4014	0.14	0.28	YES
64	MAPKAPK2	MAPKAPK2	MAPKAPK2	4018	0.13	0.29	YES
65	RPS26	RPS26	RPS26	4024	0.13	0.3	YES
66	HNRNPD	HNRNPD	HNRNPD	4070	0.13	0.3	YES
67	RPL8	RPL8	RPL8	4151	0.13	0.3	YES
68	PSMB7	PSMB7	PSMB7	4212	0.13	0.3	YES
69	PSMA6	PSMA6	PSMA6	4218	0.13	0.31	YES
70	KHSRP	KHSRP	KHSRP	4269	0.12	0.31	YES
71	EIF4G1	EIF4G1	EIF4G1	4295	0.12	0.31	YES
72	RPL23A	RPL23A	RPL23A	4322	0.12	0.32	YES
73	PSMD6	PSMD6	PSMD6	4328	0.12	0.32	YES
74	EDC4	EDC4	EDC4	4360	0.12	0.32	YES
75	EXOSC1	EXOSC1	EXOSC1	4366	0.12	0.33	YES
76	SNRPD3	SNRPD3	SNRPD3	4387	0.12	0.33	YES
77	HSPA8	HSPA8	HSPA8	4395	0.12	0.34	YES
78	PSMA3	PSMA3	PSMA3	4434	0.12	0.34	YES
79	PARN	PARN	PARN	4463	0.12	0.34	YES
80	HSPA1B	HSPA1B	HSPA1B	4531	0.12	0.34	YES
81	PSMC5	PSMC5	PSMC5	4546	0.11	0.35	YES
82	PSMC3	PSMC3	PSMC3	4554	0.11	0.35	YES
83	NCBP2	NCBP2	NCBP2	4564	0.11	0.36	YES
84	PSMD5	PSMD5	PSMD5	4600	0.11	0.36	YES
85	PSMB1	PSMB1	PSMB1	4612	0.11	0.36	YES
86	PSMB4	PSMB4	PSMB4	4675	0.11	0.36	YES
87	RPS27A	RPS27A	RPS27A	4686	0.11	0.37	YES
88	PSMD2	PSMD2	PSMD2	4743	0.11	0.37	YES
89	RPL10	RPL10	RPL10	4758	0.11	0.37	YES
90	SMG5	SMG5	SMG5	4763	0.11	0.38	YES
91	RPL23	RPL23	RPL23	4867	0.1	0.38	YES
92	RPL12	RPL12	RPL12	4909	0.1	0.38	YES
93	CNOT8	CNOT8	CNOT8	4920	0.1	0.38	YES
94	PSMD14	PSMD14	PSMD14	4935	0.1	0.38	YES
95	DCPS	DCPS	DCPS	4940	0.099	0.39	YES
96	NUP35	NUP35	NUP35	4968	0.098	0.39	YES
97	PSMA4	PSMA4	PSMA4	4995	0.098	0.39	YES
98	NUP153	NUP153	NUP153	5027	0.096	0.4	YES
99	SNRPB	SNRPB	SNRPB	5034	0.096	0.4	YES
100	DDX20	DDX20	DDX20	5095	0.094	0.4	YES
101	RPL26	RPL26	RPL26	5114	0.094	0.4	YES
102	PPP2R2A	PPP2R2A	PPP2R2A	5145	0.092	0.4	YES
103	SMN1	SMN1	SMN1	5179	0.091	0.41	YES
104	PPP2CA	PPP2CA	PPP2CA	5184	0.091	0.41	YES
105	PRMT5	PRMT5	PRMT5	5196	0.091	0.41	YES
106	RPL27	RPL27	RPL27	5296	0.087	0.41	YES
107	RPL19	RPL19	RPL19	5466	0.082	0.41	YES
108	YWHAZ	YWHAZ	YWHAZ	5472	0.082	0.41	YES
109	DCP1A	DCP1A	DCP1A	5526	0.081	0.41	YES
110	FAU	FAU	FAU	5548	0.08	0.41	YES
111	PSMD13	PSMD13	PSMD13	5549	0.08	0.42	YES
112	CNOT6	CNOT6	CNOT6	5550	0.08	0.42	YES
113	TNPO1	TNPO1	TNPO1	5566	0.079	0.42	YES
114	RPL18A	RPL18A	RPL18A	5571	0.079	0.42	YES
115	ZFP36L1	ZFP36L1	ZFP36L1	5578	0.079	0.43	YES
116	RPS8	RPS8	RPS8	5595	0.078	0.43	YES
117	RPL17	RPL17	RPL17	5610	0.078	0.43	YES
118	LSM2	LSM2	LSM2	5663	0.076	0.43	YES
119	PSMD4	PSMD4	PSMD4	5666	0.076	0.44	YES
120	RPL14	RPL14	RPL14	5694	0.076	0.44	YES
121	RPS3	RPS3	RPS3	5695	0.075	0.44	YES
122	RPL11	RPL11	RPL11	5726	0.074	0.44	YES
123	RQCD1	RQCD1	RQCD1	5740	0.074	0.44	YES
124	RPLP2	RPLP2	RPLP2	5746	0.074	0.45	YES
125	RPS2	RPS2	RPS2	5831	0.072	0.44	YES
126	NUP50	NUP50	NUP50	5871	0.071	0.45	YES
127	RPS13	RPS13	RPS13	5919	0.07	0.45	YES
128	NUP107	NUP107	NUP107	5927	0.07	0.45	YES
129	PSMD1	PSMD1	PSMD1	5970	0.068	0.45	YES
130	RPL27A	RPL27A	RPL27A	5971	0.068	0.45	YES
131	RPL7	RPL7	RPL7	5973	0.068	0.45	YES
132	RPS4Y1	RPS4Y1	RPS4Y1	6081	0.065	0.45	YES
133	RPS25	RPS25	RPS25	6109	0.064	0.45	YES
134	NCBP1	NCBP1	NCBP1	6118	0.064	0.46	YES
135	RPS14	RPS14	RPS14	6145	0.063	0.46	YES
136	RPS21	RPS21	RPS21	6147	0.063	0.46	YES
137	NUP93	NUP93	NUP93	6160	0.063	0.46	YES
138	PSMC6	PSMC6	PSMC6	6175	0.062	0.46	YES
139	RPL38	RPL38	RPL38	6222	0.061	0.46	YES
140	RPS24	RPS24	RPS24	6265	0.06	0.46	YES
141	LSM5	LSM5	LSM5	6267	0.06	0.46	YES
142	RPL35A	RPL35A	RPL35A	6478	0.054	0.46	YES
143	SNRPE	SNRPE	SNRPE	6487	0.054	0.46	YES
144	RAE1	RAE1	RAE1	6489	0.054	0.46	YES
145	RNPS1	RNPS1	RNPS1	6512	0.053	0.46	YES
146	RPL10A	RPL10A	RPL10A	6534	0.052	0.46	YES
147	RPS9	RPS9	RPS9	6562	0.052	0.46	YES
148	RPS10	RPS10	RPS10	6564	0.052	0.46	YES
149	LSM4	LSM4	LSM4	6597	0.051	0.46	YES
150	XPO1	XPO1	XPO1	6692	0.048	0.46	YES
151	SNRPD2	SNRPD2	SNRPD2	6695	0.048	0.46	YES
152	RPL41	RPL41	RPL41	6730	0.047	0.46	YES
153	UBA52	UBA52	UBA52	6757	0.047	0.46	YES
154	RPS12	RPS12	RPS12	6761	0.046	0.47	YES
155	PABPC1	PABPC1	PABPC1	6776	0.046	0.47	YES
156	RPL30	RPL30	RPL30	6873	0.043	0.46	YES
157	RPS18	RPS18	RPS18	6917	0.042	0.46	YES
158	EIF4B	EIF4B	EIF4B	6921	0.042	0.46	YES
159	RPS27	RPS27	RPS27	6924	0.042	0.47	YES
160	RPL13	RPL13	RPL13	6937	0.041	0.47	YES
161	RPL37	RPL37	RPL37	6958	0.041	0.47	YES
162	RPL31	RPL31	RPL31	6960	0.041	0.47	YES
163	CNOT3	CNOT3	CNOT3	6969	0.041	0.47	YES
164	LSM1	LSM1	LSM1	6984	0.04	0.47	YES
165	RPLP0	RPLP0	RPLP0	7175	0.036	0.46	NO
166	AAAS	AAAS	AAAS	7179	0.036	0.46	NO
167	PSMD8	PSMD8	PSMD8	7181	0.035	0.47	NO
168	NUPL2	NUPL2	NUPL2	7219	0.034	0.46	NO
169	PRKCA	PRKCA	PRKCA	7253	0.033	0.46	NO
170	RPL22	RPL22	RPL22	7255	0.033	0.47	NO
171	RPSA	RPSA	RPSA	7270	0.033	0.47	NO
172	RPL3	RPL3	RPL3	7289	0.032	0.47	NO
173	PPP2R1A	PPP2R1A	PPP2R1A	7361	0.031	0.46	NO
174	RPS17	RPS17	RPS17	7371	0.03	0.46	NO
175	RPS23	RPS23	RPS23	7392	0.03	0.46	NO
176	RPS7	RPS7	RPS7	7454	0.028	0.46	NO
177	NUP210	NUP210	NUP210	7456	0.028	0.46	NO
178	RPL6	RPL6	RPL6	7458	0.028	0.46	NO
179	DCP1B	DCP1B	DCP1B	7508	0.027	0.46	NO
180	RPS15A	RPS15A	RPS15A	7519	0.026	0.46	NO
181	NUP133	NUP133	NUP133	7555	0.025	0.46	NO
182	RPSAP9	RPSAP9	RPSAP9	7587	0.025	0.46	NO
183	TNKS1BP1	TNKS1BP1	TNKS1BP1	7628	0.024	0.46	NO
184	RPL9	RPL9	RPL9	7674	0.023	0.46	NO
185	RPS15	RPS15	RPS15	7680	0.022	0.46	NO
186	CNOT10	CNOT10	CNOT10	7779	0.02	0.46	NO
187	RPL5	RPL5	RPL5	7814	0.019	0.46	NO
188	RPL35	RPL35	RPL35	7877	0.018	0.45	NO
189	DIS3	DIS3	DIS3	7904	0.017	0.45	NO
190	RPS20	RPS20	RPS20	7971	0.015	0.45	NO
191	NUPL1	NUPL1	NUPL1	7990	0.015	0.45	NO
192	RPS16	RPS16	RPS16	8091	0.012	0.44	NO
193	PSMD9	PSMD9	PSMD9	8104	0.012	0.44	NO
194	RANBP2	RANBP2	RANBP2	8139	0.011	0.44	NO
195	EXOSC5	EXOSC5	EXOSC5	8174	0.01	0.44	NO
196	RPS6	RPS6	RPS6	8189	0.0098	0.44	NO
197	RPL36	RPL36	RPL36	8289	0.0075	0.44	NO
198	RPS11	RPS11	RPS11	8302	0.0072	0.44	NO
199	RPL37A	RPL37A	RPL37A	8324	0.0067	0.44	NO
200	RPS29	RPS29	RPS29	8353	0.0059	0.43	NO
201	RPS3A	RPS3A	RPS3A	8355	0.0059	0.43	NO
202	RPL32	RPL32	RPL32	8474	0.0028	0.43	NO
203	SNUPN	SNUPN	SNUPN	8483	0.0026	0.43	NO
204	EXOSC6	EXOSC6	EXOSC6	8540	0.00097	0.42	NO
205	NUP188	NUP188	NUP188	8595	-0.00044	0.42	NO
206	ELAVL1	ELAVL1	ELAVL1	8610	-0.00083	0.42	NO
207	RPS5	RPS5	RPS5	8614	-0.00091	0.42	NO
208	PRKCD	PRKCD	PRKCD	8793	-0.0054	0.41	NO
209	RPS19	RPS19	RPS19	8799	-0.0055	0.41	NO
210	RPLP1	RPLP1	RPLP1	8913	-0.0084	0.41	NO
211	YWHAB	YWHAB	YWHAB	8973	-0.0096	0.4	NO
212	RPL13A	RPL13A	RPL13A	8974	-0.0097	0.4	NO
213	RPL4	RPL4	RPL4	8994	-0.01	0.4	NO
214	RPL7A	RPL7A	RPL7A	9015	-0.011	0.4	NO
215	PAIP1	PAIP1	PAIP1	9138	-0.014	0.4	NO
216	PSME2	PSME2	PSME2	9219	-0.016	0.39	NO
217	RPL15	RPL15	RPL15	9230	-0.017	0.39	NO
218	RPL29	RPL29	RPL29	9251	-0.017	0.39	NO
219	NUP62	NUP62	NUP62	9419	-0.022	0.38	NO
220	CASC3	CASC3	CASC3	9455	-0.023	0.38	NO
221	RPL18	RPL18	RPL18	9497	-0.024	0.38	NO
222	RPS4X	RPS4X	RPS4X	9501	-0.024	0.38	NO
223	MAPK14	MAPK14	MAPK14	9605	-0.027	0.38	NO
224	CNOT7	CNOT7	CNOT7	9751	-0.031	0.37	NO
225	EDC3	EDC3	EDC3	9881	-0.034	0.37	NO
226	RPL34	RPL34	RPL34	9986	-0.037	0.36	NO
227	DCP2	DCP2	DCP2	9993	-0.037	0.36	NO
228	SMG1	SMG1	SMG1	10109	-0.04	0.36	NO
229	NUP214	NUP214	NUP214	10148	-0.041	0.36	NO
230	CNOT2	CNOT2	CNOT2	10258	-0.044	0.36	NO
231	UPF2	UPF2	UPF2	10759	-0.058	0.33	NO
232	TPR	TPR	TPR	10900	-0.063	0.33	NO
233	AKT1	AKT1	AKT1	10949	-0.065	0.33	NO
234	PSME1	PSME1	PSME1	11030	-0.067	0.32	NO
235	RPL28	RPL28	RPL28	11113	-0.07	0.32	NO
236	ANP32A	ANP32A	ANP32A	11134	-0.07	0.32	NO
237	PSMF1	PSMF1	PSMF1	11150	-0.071	0.33	NO
238	SMG7	SMG7	SMG7	11188	-0.072	0.33	NO
239	SMG6	SMG6	SMG6	11245	-0.073	0.33	NO
240	CNOT4	CNOT4	CNOT4	11545	-0.083	0.32	NO
241	RPS28	RPS28	RPS28	11553	-0.084	0.32	NO
242	EIF4A2	EIF4A2	EIF4A2	11657	-0.087	0.32	NO
243	UPF3A	UPF3A	UPF3A	11915	-0.095	0.31	NO
244	PSMB10	PSMB10	PSMB10	12004	-0.098	0.31	NO
245	PSMB8	PSMB8	PSMB8	12633	-0.12	0.28	NO
246	ZFP36	ZFP36	ZFP36	12811	-0.12	0.27	NO
247	TNFSF13	TNFSF13	TNFSF13	12967	-0.13	0.27	NO
248	DDX6	DDX6	DDX6	13041	-0.13	0.27	NO
249	PSMB9	PSMB9	PSMB9	13665	-0.16	0.24	NO
250	PSMA8	PSMA8	PSMA8	15143	-0.22	0.18	NO
251	MAPK11	MAPK11	MAPK11	15258	-0.23	0.18	NO
252	XRN1	XRN1	XRN1	15464	-0.24	0.18	NO
253	FAM153A	FAM153A	FAM153A	16535	-0.31	0.13	NO

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

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG HUNTINGTONS DISEASE, 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 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	LDHD	LDHD	LDHD	387	0.65	0.071	YES
2	SLC25A4	SLC25A4	SLC25A4	1529	0.31	0.056	YES
3	TIMM8A	TIMM8A	TIMM8A	1725	0.29	0.086	YES
4	VDAC1	VDAC1	VDAC1	1917	0.26	0.11	YES
5	GRPEL1	GRPEL1	GRPEL1	1952	0.26	0.15	YES
6	TIMM10	TIMM10	TIMM10	1974	0.26	0.18	YES
7	DNAJC19	DNAJC19	DNAJC19	2125	0.24	0.21	YES
8	ATP5G1	ATP5G1	ATP5G1	2164	0.24	0.24	YES
9	FXN	FXN	FXN	2224	0.23	0.27	YES
10	TOMM40	TOMM40	TOMM40	2665	0.2	0.28	YES
11	TIMM22	TIMM22	TIMM22	2674	0.2	0.3	YES
12	HSPA9	HSPA9	HSPA9	2752	0.2	0.33	YES
13	TIMM50	TIMM50	TIMM50	2835	0.19	0.35	YES
14	TIMM8B	TIMM8B	TIMM8B	2884	0.19	0.38	YES
15	CHCHD4	CHCHD4	CHCHD4	2996	0.18	0.39	YES
16	IDH3G	IDH3G	IDH3G	3038	0.18	0.42	YES
17	TOMM7	TOMM7	TOMM7	3209	0.17	0.43	YES
18	TIMM44	TIMM44	TIMM44	3252	0.17	0.45	YES
19	CYC1	CYC1	CYC1	3266	0.17	0.48	YES
20	ATP5B	ATP5B	ATP5B	3337	0.16	0.5	YES
21	TOMM20	TOMM20	TOMM20	3571	0.15	0.51	YES
22	C18orf55	C18orf55	C18orf55	3841	0.14	0.51	YES
23	SAMM50	SAMM50	SAMM50	3850	0.14	0.53	YES
24	TIMM13	TIMM13	TIMM13	3972	0.14	0.54	YES
25	TIMM17A	TIMM17A	TIMM17A	4309	0.12	0.54	YES
26	HSPD1	HSPD1	HSPD1	4506	0.12	0.55	YES
27	TAZ	TAZ	TAZ	4594	0.11	0.56	YES
28	HSCB	HSCB	HSCB	4896	0.1	0.56	YES
29	SLC25A6	SLC25A6	SLC25A6	5099	0.094	0.56	YES
30	PMPCB	PMPCB	PMPCB	5124	0.093	0.57	YES
31	COQ2	COQ2	COQ2	5174	0.091	0.58	YES
32	TIMM9	TIMM9	TIMM9	5226	0.09	0.6	YES
33	COX17	COX17	COX17	5228	0.09	0.61	YES
34	MTX1	MTX1	MTX1	5299	0.087	0.62	YES
35	CS	CS	CS	5585	0.078	0.61	YES
36	GRPEL2	GRPEL2	GRPEL2	5682	0.076	0.62	YES
37	GFER	GFER	GFER	5778	0.073	0.62	YES
38	TOMM22	TOMM22	TOMM22	5999	0.067	0.62	NO
39	TIMM17B	TIMM17B	TIMM17B	7004	0.04	0.57	NO
40	SLC25A13	SLC25A13	SLC25A13	7333	0.031	0.56	NO
41	ATP5A1	ATP5A1	ATP5A1	7466	0.028	0.56	NO
42	PMPCA	PMPCA	PMPCA	7727	0.022	0.55	NO
43	TOMM5	TOMM5	TOMM5	8929	-0.0087	0.48	NO
44	ACO2	ACO2	ACO2	9266	-0.017	0.47	NO
45	TOMM70A	TOMM70A	TOMM70A	9340	-0.02	0.47	NO
46	BCS1L	BCS1L	BCS1L	9782	-0.031	0.45	NO
47	MTX2	MTX2	MTX2	9850	-0.033	0.45	NO
48	FXC1	FXC1	FXC1	10963	-0.065	0.4	NO
49	SLC25A12	SLC25A12	SLC25A12	13887	-0.17	0.27	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: BIOCARTA MPR PATHWAY.

Figure S54. 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: PID HIF2PATHWAY

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	FOSL1	FOSL1	FOSL1	71	1	0.066	YES
2	BCAT1	BCAT1	BCAT1	140	0.9	0.12	YES
3	TERT	TERT	TERT	143	0.89	0.18	YES
4	MYCT1	MYCT1	MYCT1	276	0.75	0.23	YES
5	LIN28B	LIN28B	LIN28B	520	0.58	0.25	YES
6	SLC2A1	SLC2A1	SLC2A1	648	0.52	0.28	YES
7	PMAIP1	PMAIP1	PMAIP1	1364	0.34	0.27	YES
8	RCC1	RCC1	RCC1	1417	0.33	0.29	YES
9	HMGA1	HMGA1	HMGA1	1432	0.33	0.31	YES
10	MYC	MYC	MYC	1727	0.29	0.31	YES
11	ENO1	ENO1	ENO1	1742	0.28	0.33	YES
12	LDHA	LDHA	LDHA	1839	0.27	0.34	YES
13	TK1	TK1	TK1	2107	0.24	0.35	YES
14	NDUFAF2	NDUFAF2	NDUFAF2	2158	0.24	0.36	YES
15	CCNB1	CCNB1	CCNB1	2324	0.22	0.37	YES
16	DDX18	DDX18	DDX18	2415	0.22	0.38	YES
17	CDC25A	CDC25A	CDC25A	2423	0.22	0.39	YES
18	NME1	NME1	NME1	2593	0.21	0.4	YES
19	SHMT1	SHMT1	SHMT1	2760	0.2	0.4	YES
20	ODC1	ODC1	ODC1	2838	0.19	0.41	YES
21	GAPDH	GAPDH	GAPDH	2904	0.19	0.42	YES
22	BAX	BAX	BAX	3020	0.18	0.42	YES
23	NPM1	NPM1	NPM1	3042	0.18	0.43	YES
24	HSPA4	HSPA4	HSPA4	3154	0.17	0.44	YES
25	BIRC5	BIRC5	BIRC5	3208	0.17	0.45	YES
26	EIF4E	EIF4E	EIF4E	3279	0.17	0.46	YES
27	PTMA	PTMA	PTMA	3361	0.16	0.46	YES
28	TAF12	TAF12	TAF12	3499	0.16	0.47	YES
29	NME2	NME2	NME2	3858	0.14	0.46	YES
30	EIF4A1	EIF4A1	EIF4A1	3864	0.14	0.47	YES
31	PIM1	PIM1	PIM1	3979	0.14	0.47	YES
32	TAF4B	TAF4B	TAF4B	4033	0.13	0.48	YES
33	PRDX3	PRDX3	PRDX3	4169	0.13	0.48	YES
34	E2F3	E2F3	E2F3	4211	0.13	0.48	YES
35	CAD	CAD	CAD	4281	0.12	0.49	YES
36	EIF4G1	EIF4G1	EIF4G1	4295	0.12	0.5	YES
37	HSPD1	HSPD1	HSPD1	4506	0.12	0.49	NO
38	RUVBL1	RUVBL1	RUVBL1	4939	0.099	0.48	NO
39	SMAD4	SMAD4	SMAD4	5053	0.095	0.48	NO
40	NCL	NCL	NCL	5064	0.095	0.48	NO
41	TP53	TP53	TP53	5517	0.081	0.46	NO
42	TAF10	TAF10	TAF10	5671	0.076	0.46	NO
43	RPL11	RPL11	RPL11	5726	0.074	0.46	NO
44	TAF9	TAF9	TAF9	5767	0.073	0.47	NO
45	KIR3DL1	KIR3DL1	KIR3DL1	5949	0.068	0.46	NO
46	EIF2S1	EIF2S1	EIF2S1	6311	0.059	0.45	NO
47	HSP90AA1	HSP90AA1	HSP90AA1	6353	0.058	0.45	NO
48	RUVBL2	RUVBL2	RUVBL2	6490	0.054	0.44	NO
49	SNAI1	SNAI1	SNAI1	6527	0.053	0.45	NO
50	IREB2	IREB2	IREB2	6736	0.047	0.44	NO
51	TFRC	TFRC	TFRC	6756	0.047	0.44	NO
52	UBTF	UBTF	UBTF	6922	0.042	0.44	NO
53	POLR3D	POLR3D	POLR3D	7002	0.04	0.43	NO
54	MTDH	MTDH	MTDH	7046	0.039	0.43	NO
55	CDK4	CDK4	CDK4	7149	0.036	0.43	NO
56	TRRAP	TRRAP	TRRAP	7635	0.024	0.41	NO
57	KAT5	KAT5	KAT5	7926	0.017	0.39	NO
58	SUPT7L	SUPT7L	SUPT7L	7929	0.016	0.39	NO
59	SUPT3H	SUPT3H	SUPT3H	8136	0.011	0.38	NO
60	PDCD10	PDCD10	PDCD10	8270	0.0078	0.38	NO
61	HUWE1	HUWE1	HUWE1	8276	0.0078	0.38	NO
62	ACTL6A	ACTL6A	ACTL6A	8442	0.0037	0.37	NO
63	EP300	EP300	EP300	8971	-0.0096	0.34	NO
64	KAT2A	KAT2A	KAT2A	9146	-0.014	0.33	NO
65	MAX	MAX	MAX	9408	-0.022	0.32	NO
66	MTA1	MTA1	MTA1	9785	-0.032	0.3	NO
67	MINA	MINA	MINA	10003	-0.037	0.3	NO
68	NBN	NBN	NBN	10086	-0.039	0.29	NO
69	CREBBP	CREBBP	CREBBP	11277	-0.074	0.24	NO
70	GPAM	GPAM	GPAM	12829	-0.12	0.16	NO
71	PEG10	PEG10	PEG10	13019	-0.13	0.16	NO
72	CDCA7	CDCA7	CDCA7	13643	-0.16	0.14	NO
73	CCND2	CCND2	CCND2	14152	-0.18	0.12	NO
74	MMP9	MMP9	MMP9	14615	-0.2	0.11	NO
75	PFKM	PFKM	PFKM	15185	-0.23	0.099	NO
76	SMAD3	SMAD3	SMAD3	15214	-0.23	0.11	NO
77	ID2	ID2	ID2	16278	-0.29	0.077	NO
78	BMI1	BMI1	BMI1	17764	-0.44	0.028	NO
79	SERPINI1	SERPINI1	SERPINI1	18417	-0.58	0.033	NO

Figure S55. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID HIF2PATHWAY.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: PID HIF2PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID MYC ACTIVPATHWAY

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	UCP1	UCP1	UCP1	1091	0.39	-0.034	YES
2	UQCRHL	UQCRHL	UQCRHL	1095	0.39	-0.01	YES
3	PDHA1	PDHA1	PDHA1	1260	0.36	0.0023	YES
4	SLC16A3	SLC16A3	SLC16A3	1373	0.34	0.017	YES
5	PDK3	PDK3	PDK3	1484	0.32	0.03	YES
6	DLAT	DLAT	DLAT	1486	0.32	0.049	YES
7	L2HGDH	L2HGDH	L2HGDH	1556	0.31	0.064	YES
8	UQCRH	UQCRH	UQCRH	1598	0.3	0.08	YES
9	NDUFS5	NDUFS5	NDUFS5	1670	0.29	0.094	YES
10	COX7B	COX7B	COX7B	1785	0.28	0.1	YES
11	LDHA	LDHA	LDHA	1839	0.27	0.12	YES
12	SLC16A1	SLC16A1	SLC16A1	1878	0.27	0.13	YES
13	ATP5H	ATP5H	ATP5H	2159	0.24	0.13	YES
14	ATP5G1	ATP5G1	ATP5G1	2164	0.24	0.15	YES
15	MDH2	MDH2	MDH2	2193	0.24	0.16	YES
16	NDUFS6	NDUFS6	NDUFS6	2349	0.22	0.16	YES
17	NDUFC2	NDUFC2	NDUFC2	2457	0.22	0.17	YES
18	PDHX	PDHX	PDHX	2479	0.21	0.18	YES
19	NDUFA9	NDUFA9	NDUFA9	2579	0.21	0.19	YES
20	IDH1	IDH1	IDH1	2675	0.2	0.2	YES
21	SUCLA2	SUCLA2	SUCLA2	2676	0.2	0.21	YES
22	COX5A	COX5A	COX5A	2787	0.19	0.22	YES
23	NDUFA4	NDUFA4	NDUFA4	2807	0.19	0.22	YES
24	NDUFA8	NDUFA8	NDUFA8	2855	0.19	0.23	YES
25	PDHB	PDHB	PDHB	2886	0.19	0.24	YES
26	NDUFAB1	NDUFAB1	NDUFAB1	2945	0.18	0.25	YES
27	IDH3G	IDH3G	IDH3G	3038	0.18	0.26	YES
28	NDUFA13	NDUFA13	NDUFA13	3041	0.18	0.27	YES
29	LDHB	LDHB	LDHB	3128	0.17	0.27	YES
30	CYC1	CYC1	CYC1	3266	0.17	0.28	YES
31	NDUFB10	NDUFB10	NDUFB10	3285	0.17	0.29	YES
32	ATP5B	ATP5B	ATP5B	3337	0.16	0.29	YES
33	IDH3B	IDH3B	IDH3B	3353	0.16	0.3	YES
34	ATP5J2	ATP5J2	ATP5J2	3374	0.16	0.31	YES
35	NDUFA6	NDUFA6	NDUFA6	3419	0.16	0.32	YES
36	IDH3A	IDH3A	IDH3A	3553	0.16	0.32	YES
37	ATP5I	ATP5I	ATP5I	3562	0.15	0.33	YES
38	SUCLG1	SUCLG1	SUCLG1	3583	0.15	0.34	YES
39	SDHD	SDHD	SDHD	3639	0.15	0.34	YES
40	COX5B	COX5B	COX5B	3666	0.15	0.35	YES
41	NDUFB9	NDUFB9	NDUFB9	3833	0.14	0.35	YES
42	DLD	DLD	DLD	3871	0.14	0.36	YES
43	ATP5C1	ATP5C1	ATP5C1	3881	0.14	0.36	YES
44	SDHB	SDHB	SDHB	3911	0.14	0.37	YES
45	ATP5F1	ATP5F1	ATP5F1	3939	0.14	0.38	YES
46	COX7C	COX7C	COX7C	3978	0.14	0.38	YES
47	COX8A	COX8A	COX8A	4046	0.13	0.39	YES
48	ATP5J	ATP5J	ATP5J	4083	0.13	0.4	YES
49	NDUFA3	NDUFA3	NDUFA3	4114	0.13	0.4	YES
50	NDUFA1	NDUFA1	NDUFA1	4121	0.13	0.41	YES
51	NDUFS8	NDUFS8	NDUFS8	4199	0.13	0.41	YES
52	COX6A1	COX6A1	COX6A1	4240	0.13	0.42	YES
53	CYCS	CYCS	CYCS	4247	0.13	0.42	YES
54	ATP5O	ATP5O	ATP5O	4257	0.13	0.43	YES
55	NDUFS7	NDUFS7	NDUFS7	4272	0.12	0.44	YES
56	COX4I1	COX4I1	COX4I1	4399	0.12	0.44	YES
57	PDP2	PDP2	PDP2	4403	0.12	0.45	YES
58	FH	FH	FH	4518	0.12	0.45	YES
59	UQCRFS1	UQCRFS1	UQCRFS1	4599	0.11	0.45	YES
60	NDUFB8	NDUFB8	NDUFB8	4729	0.11	0.45	YES
61	UQCRC2	UQCRC2	UQCRC2	4778	0.11	0.45	YES
62	ATP5L	ATP5L	ATP5L	4780	0.1	0.46	YES
63	NDUFA12	NDUFA12	NDUFA12	4859	0.1	0.46	YES
64	ATP5D	ATP5D	ATP5D	4903	0.1	0.46	YES
65	NDUFS4	NDUFS4	NDUFS4	5009	0.097	0.47	YES
66	NDUFV2	NDUFV2	NDUFV2	5074	0.095	0.47	YES
67	COX6C	COX6C	COX6C	5133	0.093	0.47	YES
68	NDUFS2	NDUFS2	NDUFS2	5213	0.09	0.47	YES
69	NDUFV1	NDUFV1	NDUFV1	5287	0.088	0.47	YES
70	NDUFB2	NDUFB2	NDUFB2	5359	0.086	0.47	YES
71	UQCR11	UQCR11	UQCR11	5406	0.084	0.48	YES
72	CS	CS	CS	5585	0.078	0.47	YES
73	COX6B1	COX6B1	COX6B1	5602	0.078	0.48	YES
74	NDUFB6	NDUFB6	NDUFB6	5611	0.078	0.48	YES
75	NDUFS1	NDUFS1	NDUFS1	5721	0.075	0.48	YES
76	UQCRQ	UQCRQ	UQCRQ	5779	0.073	0.48	YES
77	NDUFA11	NDUFA11	NDUFA11	5937	0.069	0.48	YES
78	UQCRB	UQCRB	UQCRB	6047	0.066	0.48	YES
79	DLST	DLST	DLST	6068	0.065	0.48	YES
80	NDUFB1	NDUFB1	NDUFB1	6156	0.063	0.48	YES
81	SDHC	SDHC	SDHC	6167	0.062	0.48	YES
82	NDUFA7	NDUFA7	NDUFA7	6206	0.061	0.48	YES
83	NDUFV3	NDUFV3	NDUFV3	6394	0.056	0.48	NO
84	NDUFA2	NDUFA2	NDUFA2	6404	0.056	0.48	NO
85	BSG	BSG	BSG	6517	0.053	0.48	NO
86	NDUFB7	NDUFB7	NDUFB7	6616	0.05	0.47	NO
87	NDUFB3	NDUFB3	NDUFB3	6704	0.048	0.47	NO
88	NDUFA5	NDUFA5	NDUFA5	6831	0.044	0.47	NO
89	UQCRC1	UQCRC1	UQCRC1	6905	0.042	0.47	NO
90	ETFA	ETFA	ETFA	6992	0.04	0.46	NO
91	PDK1	PDK1	PDK1	6995	0.04	0.47	NO
92	NDUFA10	NDUFA10	NDUFA10	7131	0.037	0.46	NO
93	ATP5A1	ATP5A1	ATP5A1	7466	0.028	0.44	NO
94	NDUFB5	NDUFB5	NDUFB5	7533	0.026	0.44	NO
95	ETFB	ETFB	ETFB	7630	0.024	0.44	NO
96	NDUFB4	NDUFB4	NDUFB4	7875	0.018	0.43	NO
97	NDUFS3	NDUFS3	NDUFS3	7911	0.017	0.43	NO
98	NDUFC1	NDUFC1	NDUFC1	8244	0.0086	0.41	NO
99	SDHA	SDHA	SDHA	9048	-0.012	0.37	NO
100	ACO2	ACO2	ACO2	9266	-0.017	0.36	NO
101	SLC16A8	SLC16A8	SLC16A8	9353	-0.02	0.35	NO
102	ATP5E	ATP5E	ATP5E	9500	-0.024	0.35	NO
103	NNT	NNT	NNT	10096	-0.04	0.32	NO
104	COX7A2L	COX7A2L	COX7A2L	10144	-0.041	0.32	NO
105	OGDH	OGDH	OGDH	11196	-0.072	0.27	NO
106	ETFDH	ETFDH	ETFDH	11464	-0.081	0.26	NO
107	IDH2	IDH2	IDH2	11525	-0.083	0.26	NO
108	PDPR	PDPR	PDPR	11790	-0.091	0.25	NO
109	UCP2	UCP2	UCP2	12437	-0.11	0.22	NO
110	PDP1	PDP1	PDP1	13160	-0.14	0.2	NO
111	D2HGDH	D2HGDH	D2HGDH	13769	-0.16	0.17	NO
112	PDK2	PDK2	PDK2	14936	-0.22	0.12	NO
113	SUCLG2	SUCLG2	SUCLG2	15607	-0.25	0.1	NO
114	PDK4	PDK4	PDK4	16857	-0.34	0.058	NO
115	UCP3	UCP3	UCP3	17705	-0.44	0.039	NO
116	ADHFE1	ADHFE1	ADHFE1	18236	-0.53	0.043	NO

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

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: PID MYC ACTIVPATHWAY, 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: REACTOME TRANSLATION

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	GTF2H2	GTF2H2	GTF2H2	1068	0.4	0.08	YES
2	GTF2H2B	GTF2H2B	GTF2H2B	1178	0.37	0.2	YES
3	CDK7	CDK7	CDK7	2480	0.21	0.21	YES
4	POLR2H	POLR2H	POLR2H	2721	0.2	0.26	YES
5	MNAT1	MNAT1	MNAT1	2775	0.19	0.32	YES
6	POLR2G	POLR2G	POLR2G	2841	0.19	0.39	YES
7	GTF2H3	GTF2H3	GTF2H3	3160	0.17	0.43	YES
8	NCBP2	NCBP2	NCBP2	4564	0.11	0.39	YES
9	POLR2A	POLR2A	POLR2A	4945	0.099	0.41	YES
10	POLR2E	POLR2E	POLR2E	5070	0.095	0.43	YES
11	POLR2F	POLR2F	POLR2F	5349	0.086	0.45	YES
12	GTF2F2	GTF2F2	GTF2F2	5570	0.079	0.46	YES
13	RNMT	RNMT	RNMT	5757	0.074	0.48	YES
14	CCNH	CCNH	CCNH	5816	0.072	0.5	YES
15	POLR2C	POLR2C	POLR2C	5834	0.072	0.52	YES
16	RNGTT	RNGTT	RNGTT	5837	0.072	0.55	YES
17	NCBP1	NCBP1	NCBP1	6118	0.064	0.55	YES
18	GTF2F1	GTF2F1	GTF2F1	6330	0.058	0.56	YES
19	POLR2J	POLR2J	POLR2J	6803	0.045	0.55	YES
20	GTF2H1	GTF2H1	GTF2H1	6876	0.043	0.56	YES
21	POLR2L	POLR2L	POLR2L	6976	0.04	0.57	YES
22	POLR2I	POLR2I	POLR2I	7113	0.037	0.58	YES
23	GTF2H4	GTF2H4	GTF2H4	7399	0.03	0.57	NO
24	ERCC2	ERCC2	ERCC2	7607	0.024	0.57	NO
25	POLR2B	POLR2B	POLR2B	8266	0.008	0.54	NO
26	POLR2K	POLR2K	POLR2K	8316	0.0069	0.54	NO
27	POLR2D	POLR2D	POLR2D	8363	0.0056	0.54	NO
28	ERCC3	ERCC3	ERCC3	8413	0.0044	0.54	NO
29	SUPT5H	SUPT5H	SUPT5H	11003	-0.066	0.42	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: REACTOME TRANSLATION.

Figure S60. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME TRANSLATION, 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
KEGG LONG TERM POTENTIATION	70	genes.ES.table	0.49	1.6	0.012	0.68	0.86	0.33	0.21	0.26	0.26	0.19
KEGG NEUROTROPHIN SIGNALING PATHWAY	126	genes.ES.table	0.41	1.7	0.0078	1	0.8	0.24	0.22	0.19	0.41	0.28
BIOCARTA AGR PATHWAY	36	genes.ES.table	0.57	1.6	0.014	0.94	0.82	0.33	0.19	0.27	0.35	0.24
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.53	1.7	0.0097	1	0.59	0.19	0.15	0.16	1	0.54
SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES	35	genes.ES.table	0.56	1.6	0.014	1	0.82	0.34	0.22	0.27	0.38	0.26
PID ENDOTHELINPATHWAY	63	genes.ES.table	0.58	1.6	0.002	0.75	0.86	0.35	0.18	0.29	0.29	0.2
PID NOTCH PATHWAY	59	genes.ES.table	0.51	1.7	0.004	1	0.76	0.34	0.2	0.27	0.36	0.26
PID EPHBFWDPATHWAY	40	genes.ES.table	0.54	1.6	0.006	0.81	0.82	0.28	0.17	0.23	0.3	0.21
PID PS1PATHWAY	46	genes.ES.table	0.55	1.7	0.004	1	0.72	0.26	0.18	0.22	0.41	0.27
PID P75NTRPATHWAY	69	genes.ES.table	0.46	1.6	0.0081	0.79	0.84	0.29	0.26	0.22	0.3	0.21

genes ES table in pathway: KEGG LONG TERM POTENTIATION

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	AGT	AGT	AGT	544	0.9	0.13	YES
2	EGFR	EGFR	EGFR	997	0.76	0.23	YES
3	AGTR1	AGTR1	AGTR1	1040	0.75	0.36	YES
4	JUN	JUN	JUN	1877	0.59	0.42	YES
5	MEF2C	MEF2C	MEF2C	2562	0.48	0.46	YES
6	PRKCA	PRKCA	PRKCA	2777	0.46	0.53	YES
7	SRC	SRC	SRC	5789	0.18	0.4	NO
8	MEF2A	MEF2A	MEF2A	6049	0.16	0.42	NO
9	SHC1	SHC1	SHC1	6206	0.16	0.44	NO
10	MAPK8	MAPK8	MAPK8	6435	0.14	0.45	NO
11	ATF2	ATF2	ATF2	6875	0.12	0.45	NO
12	SOS1	SOS1	SOS1	7134	0.11	0.45	NO
13	MAPK3	MAPK3	MAPK3	7678	0.087	0.44	NO
14	MAP2K4	MAP2K4	MAP2K4	8106	0.071	0.43	NO
15	MEF2D	MEF2D	MEF2D	8540	0.056	0.41	NO
16	CALM3	CALM3	CALM3	8952	0.041	0.4	NO
17	CALM1	CALM1	CALM1	9661	0.018	0.36	NO
18	GNAQ	GNAQ	GNAQ	9799	0.013	0.36	NO
19	ELK1	ELK1	ELK1	10046	0.0048	0.35	NO
20	PTK2	PTK2	PTK2	10121	0.0023	0.34	NO
21	RAC1	RAC1	RAC1	10632	-0.013	0.32	NO
22	PTK2B	PTK2B	PTK2B	10784	-0.017	0.32	NO
23	HRAS	HRAS	HRAS	11044	-0.025	0.31	NO
24	MAP3K1	MAP3K1	MAP3K1	11421	-0.036	0.29	NO
25	PAK1	PAK1	PAK1	11432	-0.036	0.3	NO
26	RAF1	RAF1	RAF1	11649	-0.043	0.29	NO
27	MAP2K1	MAP2K1	MAP2K1	11675	-0.044	0.3	NO
28	GRB2	GRB2	GRB2	11951	-0.051	0.29	NO
29	CALM2	CALM2	CALM2	12235	-0.059	0.29	NO
30	MAP2K2	MAP2K2	MAP2K2	12254	-0.06	0.3	NO
31	MAPK1	MAPK1	MAPK1	13847	-0.11	0.23	NO
32	PRKCB	PRKCB	PRKCB	16299	-0.23	0.14	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: KEGG LONG TERM POTENTIATION.

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LONG TERM POTENTIATION, 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 NEUROTROPHIN SIGNALING 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	MAMLD1	MAMLD1	MAMLD1	986	0.76	0.036	YES
2	MAML2	MAML2	MAML2	1170	0.72	0.11	YES
3	MAML3	MAML3	MAML3	1220	0.71	0.19	YES
4	CCND1	CCND1	CCND1	1321	0.69	0.26	YES
5	NOTCH4	NOTCH4	NOTCH4	1868	0.59	0.3	YES
6	JUN	JUN	JUN	1877	0.59	0.37	YES
7	NOTCH3	NOTCH3	NOTCH3	2753	0.46	0.38	YES
8	ST3GAL6	ST3GAL6	ST3GAL6	3125	0.41	0.41	YES
9	NOTCH2	NOTCH2	NOTCH2	3367	0.39	0.44	YES
10	EIF2C4	EIF2C4	EIF2C4	3406	0.38	0.48	YES
11	ST3GAL3	ST3GAL3	ST3GAL3	3472	0.38	0.52	YES
12	KAT2B	KAT2B	KAT2B	5989	0.17	0.41	NO
13	SEL1L	SEL1L	SEL1L	6429	0.14	0.4	NO
14	EIF2C3	EIF2C3	EIF2C3	6539	0.14	0.41	NO
15	CREBBP	CREBBP	CREBBP	7820	0.082	0.36	NO
16	POFUT1	POFUT1	POFUT1	7895	0.079	0.36	NO
17	RFNG	RFNG	RFNG	8072	0.073	0.36	NO
18	B4GALT1	B4GALT1	B4GALT1	8458	0.058	0.35	NO
19	TP53	TP53	TP53	8496	0.057	0.35	NO
20	TFDP1	TFDP1	TFDP1	8942	0.041	0.33	NO
21	MAML1	MAML1	MAML1	9007	0.039	0.33	NO
22	TMED2	TMED2	TMED2	9576	0.02	0.31	NO
23	TNRC6A	TNRC6A	TNRC6A	9630	0.018	0.31	NO
24	EIF2C1	EIF2C1	EIF2C1	9956	0.0082	0.29	NO
25	EIF2C2	EIF2C2	EIF2C2	10767	-0.016	0.25	NO
26	TNRC6B	TNRC6B	TNRC6B	11099	-0.026	0.23	NO
27	ATP2A2	ATP2A2	ATP2A2	11136	-0.027	0.24	NO
28	MFNG	MFNG	MFNG	11741	-0.045	0.21	NO
29	FURIN	FURIN	FURIN	11802	-0.047	0.21	NO
30	LFNG	LFNG	LFNG	12077	-0.055	0.2	NO
31	EP300	EP300	EP300	12302	-0.061	0.2	NO
32	RAB6A	RAB6A	RAB6A	12923	-0.079	0.18	NO
33	MOV10	MOV10	MOV10	13003	-0.082	0.18	NO
34	ATP2A1	ATP2A1	ATP2A1	13172	-0.088	0.18	NO
35	KAT2A	KAT2A	KAT2A	13749	-0.11	0.16	NO
36	TNRC6C	TNRC6C	TNRC6C	13929	-0.11	0.17	NO
37	SNW1	SNW1	SNW1	14104	-0.12	0.17	NO
38	E2F3	E2F3	E2F3	14253	-0.12	0.18	NO
39	E2F1	E2F1	E2F1	14934	-0.15	0.16	NO
40	RBPJ	RBPJ	RBPJ	15050	-0.16	0.17	NO
41	ATP2A3	ATP2A3	ATP2A3	17217	-0.32	0.096	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: KEGG NEUROTROPHIN SIGNALING PATHWAY.

Figure S64. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG NEUROTROPHIN SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA AGR 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	SLIT2	SLIT2	SLIT2	127	1.1	0.14	YES
2	SRGAP3	SRGAP3	SRGAP3	308	1	0.27	YES
3	CAP2	CAP2	CAP2	1297	0.69	0.31	YES
4	ROBO2	ROBO2	ROBO2	1379	0.68	0.39	YES
5	ROBO3	ROBO3	ROBO3	2140	0.54	0.42	YES
6	ROBO1	ROBO1	ROBO1	2231	0.53	0.49	YES
7	PAK7	PAK7	PAK7	3033	0.42	0.5	YES
8	SOS2	SOS2	SOS2	3715	0.35	0.52	YES
9	GPC1	GPC1	GPC1	3841	0.34	0.55	YES
10	PFN2	PFN2	PFN2	4218	0.3	0.57	YES
11	PAK6	PAK6	PAK6	6274	0.15	0.49	NO
12	ABL1	ABL1	ABL1	6622	0.13	0.48	NO
13	EVL	EVL	EVL	6693	0.13	0.5	NO
14	SOS1	SOS1	SOS1	7134	0.11	0.49	NO
15	ENAH	ENAH	ENAH	7530	0.094	0.48	NO
16	SRGAP2	SRGAP2	SRGAP2	7802	0.083	0.48	NO
17	CLASP1	CLASP1	CLASP1	7996	0.076	0.48	NO
18	NCK2	NCK2	NCK2	9921	0.0094	0.38	NO
19	NCK1	NCK1	NCK1	9970	0.0077	0.38	NO
20	PAK2	PAK2	PAK2	10040	0.005	0.37	NO
21	CDC42	CDC42	CDC42	10156	0.0015	0.37	NO
22	PAK4	PAK4	PAK4	10612	-0.013	0.35	NO
23	RAC1	RAC1	RAC1	10632	-0.013	0.35	NO
24	PAK1	PAK1	PAK1	11432	-0.036	0.31	NO
25	CAP1	CAP1	CAP1	13875	-0.11	0.2	NO
26	ABL2	ABL2	ABL2	14560	-0.14	0.18	NO
27	PFN1	PFN1	PFN1	14648	-0.14	0.19	NO
28	VASP	VASP	VASP	14746	-0.14	0.21	NO
29	SRGAP1	SRGAP1	SRGAP1	14922	-0.15	0.22	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 AGR PATHWAY.

Figure S66. 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 AT1R PATHWAY

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	CNTN1	CNTN1	CNTN1	158	1.1	0.045	YES
2	DNER	DNER	DNER	649	0.86	0.061	YES
3	HEY1	HEY1	HEY1	754	0.83	0.096	YES
4	HES1	HES1	HES1	874	0.79	0.13	YES
5	MAMLD1	MAMLD1	MAMLD1	986	0.76	0.16	YES
6	MAML2	MAML2	MAML2	1170	0.72	0.18	YES
7	MAML3	MAML3	MAML3	1220	0.71	0.22	YES
8	CCND1	CCND1	CCND1	1321	0.69	0.24	YES
9	HES5	HES5	HES5	1401	0.67	0.27	YES
10	NOTCH4	NOTCH4	NOTCH4	1868	0.59	0.28	YES
11	JUN	JUN	JUN	1877	0.59	0.3	YES
12	DLL1	DLL1	DLL1	1901	0.58	0.33	YES
13	DLL4	DLL4	DLL4	2024	0.56	0.35	YES
14	TLE2	TLE2	TLE2	2248	0.53	0.37	YES
15	NOTCH3	NOTCH3	NOTCH3	2753	0.46	0.36	YES
16	JAG1	JAG1	JAG1	3107	0.41	0.36	YES
17	ST3GAL6	ST3GAL6	ST3GAL6	3125	0.41	0.38	YES
18	HDAC11	HDAC11	HDAC11	3148	0.41	0.4	YES
19	NOTCH2	NOTCH2	NOTCH2	3367	0.39	0.41	YES
20	DLK1	DLK1	DLK1	3380	0.38	0.43	YES
21	EIF2C4	EIF2C4	EIF2C4	3406	0.38	0.44	YES
22	ST3GAL3	ST3GAL3	ST3GAL3	3472	0.38	0.46	YES
23	HDAC4	HDAC4	HDAC4	3925	0.33	0.45	NO
24	HEYL	HEYL	HEYL	5011	0.23	0.4	NO
25	NCOR2	NCOR2	NCOR2	5268	0.22	0.4	NO
26	MYC	MYC	MYC	5411	0.2	0.4	NO
27	TLE4	TLE4	TLE4	5604	0.19	0.4	NO
28	HDAC8	HDAC8	HDAC8	5795	0.18	0.4	NO
29	DTX4	DTX4	DTX4	5821	0.18	0.41	NO
30	MIB1	MIB1	MIB1	5932	0.17	0.41	NO
31	KAT2B	KAT2B	KAT2B	5989	0.17	0.42	NO
32	HEY2	HEY2	HEY2	6326	0.15	0.41	NO
33	SEL1L	SEL1L	SEL1L	6429	0.14	0.41	NO
34	EIF2C3	EIF2C3	EIF2C3	6539	0.14	0.41	NO
35	APH1A	APH1A	APH1A	7094	0.11	0.38	NO
36	TBL1X	TBL1X	TBL1X	7204	0.11	0.38	NO
37	CDK8	CDK8	CDK8	7501	0.095	0.37	NO
38	CREBBP	CREBBP	CREBBP	7820	0.082	0.36	NO
39	POFUT1	POFUT1	POFUT1	7895	0.079	0.36	NO
40	RFNG	RFNG	RFNG	8072	0.073	0.36	NO
41	TBL1XR1	TBL1XR1	TBL1XR1	8110	0.071	0.36	NO
42	DTX1	DTX1	DTX1	8164	0.069	0.36	NO
43	TLE1	TLE1	TLE1	8370	0.062	0.35	NO
44	B4GALT1	B4GALT1	B4GALT1	8458	0.058	0.35	NO
45	TP53	TP53	TP53	8496	0.057	0.35	NO
46	NCOR1	NCOR1	NCOR1	8553	0.055	0.35	NO
47	ADAM17	ADAM17	ADAM17	8662	0.051	0.34	NO
48	MIB2	MIB2	MIB2	8739	0.048	0.34	NO
49	NUMB	NUMB	NUMB	8753	0.048	0.34	NO
50	TFDP1	TFDP1	TFDP1	8942	0.041	0.34	NO
51	HIF1A	HIF1A	HIF1A	9005	0.039	0.34	NO
52	MAML1	MAML1	MAML1	9007	0.039	0.34	NO
53	HDAC10	HDAC10	HDAC10	9458	0.024	0.32	NO
54	TMED2	TMED2	TMED2	9576	0.02	0.31	NO
55	TNRC6A	TNRC6A	TNRC6A	9630	0.018	0.31	NO
56	HDAC6	HDAC6	HDAC6	9682	0.016	0.31	NO
57	EIF2C1	EIF2C1	EIF2C1	9956	0.0082	0.29	NO
58	APH1B	APH1B	APH1B	9992	0.0068	0.29	NO
59	ADAM10	ADAM10	ADAM10	10038	0.005	0.29	NO
60	NCSTN	NCSTN	NCSTN	10066	0.0043	0.29	NO
61	HDAC7	HDAC7	HDAC7	10139	0.0019	0.28	NO
62	HDAC2	HDAC2	HDAC2	10360	-0.0051	0.27	NO
63	HDAC3	HDAC3	HDAC3	10558	-0.011	0.26	NO
64	SKP1	SKP1	SKP1	10667	-0.014	0.26	NO
65	EIF2C2	EIF2C2	EIF2C2	10767	-0.016	0.25	NO
66	HDAC9	HDAC9	HDAC9	11046	-0.025	0.24	NO
67	TNRC6B	TNRC6B	TNRC6B	11099	-0.026	0.24	NO
68	ATP2A2	ATP2A2	ATP2A2	11136	-0.027	0.24	NO
69	HDAC5	HDAC5	HDAC5	11418	-0.036	0.22	NO
70	HDAC1	HDAC1	HDAC1	11553	-0.04	0.22	NO
71	FBXW7	FBXW7	FBXW7	11718	-0.045	0.21	NO
72	MFNG	MFNG	MFNG	11741	-0.045	0.21	NO
73	FURIN	FURIN	FURIN	11802	-0.047	0.21	NO
74	LFNG	LFNG	LFNG	12077	-0.055	0.2	NO
75	PSEN1	PSEN1	PSEN1	12155	-0.057	0.2	NO
76	EP300	EP300	EP300	12302	-0.061	0.2	NO
77	TLE3	TLE3	TLE3	12511	-0.068	0.19	NO
78	PSENEN	PSENEN	PSENEN	12560	-0.069	0.19	NO
79	CCNC	CCNC	CCNC	12642	-0.072	0.19	NO
80	RPS27A	RPS27A	RPS27A	12698	-0.073	0.19	NO
81	ARRB1	ARRB1	ARRB1	12860	-0.078	0.18	NO
82	RAB6A	RAB6A	RAB6A	12923	-0.079	0.18	NO
83	MOV10	MOV10	MOV10	13003	-0.082	0.18	NO
84	ATP2A1	ATP2A1	ATP2A1	13172	-0.088	0.18	NO
85	KAT2A	KAT2A	KAT2A	13749	-0.11	0.15	NO
86	TNRC6C	TNRC6C	TNRC6C	13929	-0.11	0.15	NO
87	SNW1	SNW1	SNW1	14104	-0.12	0.15	NO
88	E2F3	E2F3	E2F3	14253	-0.12	0.14	NO
89	CUL1	CUL1	CUL1	14474	-0.13	0.14	NO
90	RBX1	RBX1	RBX1	14608	-0.14	0.14	NO
91	JAG2	JAG2	JAG2	14639	-0.14	0.14	NO
92	ARRB2	ARRB2	ARRB2	14722	-0.14	0.15	NO
93	E2F1	E2F1	E2F1	14934	-0.15	0.14	NO
94	UBA52	UBA52	UBA52	14980	-0.15	0.15	NO
95	RBPJ	RBPJ	RBPJ	15050	-0.16	0.15	NO
96	DTX2	DTX2	DTX2	15749	-0.19	0.12	NO
97	PSEN2	PSEN2	PSEN2	15825	-0.2	0.13	NO
98	ATP2A3	ATP2A3	ATP2A3	17217	-0.32	0.072	NO
99	NEURL	NEURL	NEURL	18172	-0.5	0.046	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: BIOCARTA AT1R PATHWAY.

Figure S68. 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: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES

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	DCX	DCX	DCX	37	1.3	0.016	YES
2	SCN2B	SCN2B	SCN2B	76	1.2	0.03	YES
3	UNC5C	UNC5C	UNC5C	118	1.1	0.043	YES
4	SLIT2	SLIT2	SLIT2	127	1.1	0.057	YES
5	CNTN1	CNTN1	CNTN1	158	1.1	0.071	YES
6	COL9A1	COL9A1	COL9A1	166	1.1	0.085	YES
7	CNTN2	CNTN2	CNTN2	205	1.1	0.097	YES
8	TRPC4	TRPC4	TRPC4	264	1	0.11	YES
9	NCAM1	NCAM1	NCAM1	274	1	0.12	YES
10	SRGAP3	SRGAP3	SRGAP3	308	1	0.13	YES
11	CNTN6	CNTN6	CNTN6	428	0.95	0.14	YES
12	PLXNB3	PLXNB3	PLXNB3	495	0.92	0.15	YES
13	COL9A2	COL9A2	COL9A2	536	0.9	0.16	YES
14	TRPC3	TRPC3	TRPC3	539	0.9	0.17	YES
15	COL2A1	COL2A1	COL2A1	553	0.9	0.18	YES
16	SCN7A	SCN7A	SCN7A	613	0.87	0.19	YES
17	SEMA3E	SEMA3E	SEMA3E	658	0.86	0.2	YES
18	GDNF	GDNF	GDNF	663	0.86	0.21	YES
19	ST8SIA2	ST8SIA2	ST8SIA2	698	0.84	0.22	YES
20	GFRA1	GFRA1	GFRA1	706	0.84	0.23	YES
21	SEMA5A	SEMA5A	SEMA5A	779	0.82	0.24	YES
22	CACNB4	CACNB4	CACNB4	857	0.8	0.24	YES
23	SLIT3	SLIT3	SLIT3	886	0.79	0.25	YES
24	CACNA1G	CACNA1G	CACNA1G	908	0.78	0.26	YES
25	NTN1	NTN1	NTN1	970	0.76	0.27	YES
26	EGFR	EGFR	EGFR	997	0.76	0.28	YES
27	ALCAM	ALCAM	ALCAM	1025	0.75	0.29	YES
28	GFRA2	GFRA2	GFRA2	1215	0.71	0.29	YES
29	COL3A1	COL3A1	COL3A1	1242	0.7	0.3	YES
30	TRPC6	TRPC6	TRPC6	1276	0.7	0.3	YES
31	CAP2	CAP2	CAP2	1297	0.69	0.31	YES
32	COL5A2	COL5A2	COL5A2	1298	0.69	0.32	YES
33	COL1A1	COL1A1	COL1A1	1330	0.69	0.33	YES
34	SEMA6D	SEMA6D	SEMA6D	1344	0.69	0.34	YES
35	ROBO2	ROBO2	ROBO2	1379	0.68	0.34	YES
36	CNTNAP1	CNTNAP1	CNTNAP1	1422	0.67	0.35	YES
37	DPYSL4	DPYSL4	DPYSL4	1457	0.66	0.36	YES
38	CACNA1S	CACNA1S	CACNA1S	1469	0.66	0.37	YES
39	COL4A5	COL4A5	COL4A5	1603	0.63	0.37	YES
40	COL5A1	COL5A1	COL5A1	1739	0.61	0.37	YES
41	NRP2	NRP2	NRP2	1784	0.6	0.37	YES
42	ITGA2	ITGA2	ITGA2	1882	0.59	0.38	YES
43	UNC5A	UNC5A	UNC5A	1894	0.58	0.38	YES
44	DCC	DCC	DCC	2109	0.55	0.38	YES
45	ROBO3	ROBO3	ROBO3	2140	0.54	0.39	YES
46	COL1A2	COL1A2	COL1A2	2180	0.54	0.39	YES
47	ROBO1	ROBO1	ROBO1	2231	0.53	0.4	YES
48	COL6A3	COL6A3	COL6A3	2243	0.53	0.4	YES
49	RHOB	RHOB	RHOB	2245	0.53	0.41	YES
50	MYH11	MYH11	MYH11	2258	0.53	0.42	YES
51	CACNB2	CACNB2	CACNB2	2269	0.52	0.42	YES
52	DNM1	DNM1	DNM1	2296	0.52	0.43	YES
53	SLIT1	SLIT1	SLIT1	2337	0.52	0.43	YES
54	ITGA1	ITGA1	ITGA1	2417	0.5	0.44	YES
55	SCN2A	SCN2A	SCN2A	2567	0.48	0.43	YES
56	CD24	CD24	CD24	2637	0.47	0.44	YES
57	UNC5B	UNC5B	UNC5B	2771	0.46	0.44	YES
58	SPTA1	SPTA1	SPTA1	2852	0.45	0.44	YES
59	NRTN	NRTN	NRTN	2888	0.44	0.44	YES
60	AGRN	AGRN	AGRN	2911	0.44	0.45	YES
61	COL6A2	COL6A2	COL6A2	2952	0.43	0.45	YES
62	RPS6KA2	RPS6KA2	RPS6KA2	2967	0.43	0.45	YES
63	COL6A1	COL6A1	COL6A1	3002	0.43	0.46	YES
64	PAK7	PAK7	PAK7	3033	0.42	0.46	YES
65	PLXNA3	PLXNA3	PLXNA3	3173	0.41	0.46	YES
66	MET	MET	MET	3334	0.39	0.46	YES
67	UNC5D	UNC5D	UNC5D	3345	0.39	0.46	YES
68	PSPN	PSPN	PSPN	3385	0.38	0.46	YES
69	NRP1	NRP1	NRP1	3439	0.38	0.47	YES
70	MYL9	MYL9	MYL9	3528	0.37	0.47	YES
71	SPTBN5	SPTBN5	SPTBN5	3533	0.37	0.47	YES
72	ARTN	ARTN	ARTN	3535	0.37	0.48	YES
73	TRIO	TRIO	TRIO	3626	0.36	0.48	YES
74	NTN4	NTN4	NTN4	3630	0.36	0.48	YES
75	SEMA3A	SEMA3A	SEMA3A	3649	0.36	0.49	YES
76	ITGB3	ITGB3	ITGB3	3650	0.36	0.49	YES
77	RPS6KA6	RPS6KA6	RPS6KA6	3671	0.35	0.49	YES
78	ABLIM1	ABLIM1	ABLIM1	3673	0.35	0.5	YES
79	DPYSL3	DPYSL3	DPYSL3	3699	0.35	0.5	YES
80	SOS2	SOS2	SOS2	3715	0.35	0.51	YES
81	CACNB1	CACNB1	CACNB1	3774	0.34	0.51	YES
82	COL4A3	COL4A3	COL4A3	3814	0.34	0.51	YES
83	GPC1	GPC1	GPC1	3841	0.34	0.51	YES
84	ITGAV	ITGAV	ITGAV	3876	0.33	0.52	YES
85	LAMB1	LAMB1	LAMB1	3940	0.33	0.52	YES
86	CACNA1H	CACNA1H	CACNA1H	3993	0.32	0.52	YES
87	ERBB2	ERBB2	ERBB2	3999	0.32	0.52	YES
88	PLXNB1	PLXNB1	PLXNB1	4004	0.32	0.53	YES
89	MYH14	MYH14	MYH14	4099	0.31	0.53	YES
90	SCN3B	SCN3B	SCN3B	4194	0.3	0.52	YES
91	SCN5A	SCN5A	SCN5A	4199	0.3	0.53	YES
92	PFN2	PFN2	PFN2	4218	0.3	0.53	YES
93	NEO1	NEO1	NEO1	4282	0.3	0.53	YES
94	ITGA5	ITGA5	ITGA5	4328	0.29	0.53	YES
95	RRAS	RRAS	RRAS	4408	0.28	0.53	YES
96	SIAH2	SIAH2	SIAH2	4594	0.27	0.53	YES
97	DOCK1	DOCK1	DOCK1	4607	0.27	0.53	YES
98	FARP2	FARP2	FARP2	4669	0.26	0.53	YES
99	ANK3	ANK3	ANK3	4679	0.26	0.53	YES
100	COL4A2	COL4A2	COL4A2	4682	0.26	0.54	YES
101	KCNQ2	KCNQ2	KCNQ2	4693	0.26	0.54	YES
102	COL4A1	COL4A1	COL4A1	4705	0.26	0.54	YES
103	COL9A3	COL9A3	COL9A3	4833	0.25	0.54	YES
104	ABLIM3	ABLIM3	ABLIM3	4844	0.25	0.54	YES
105	ARHGEF12	ARHGEF12	ARHGEF12	4852	0.25	0.55	YES
106	RGMB	RGMB	RGMB	4866	0.25	0.55	YES
107	MYH10	MYH10	MYH10	4947	0.24	0.55	NO
108	SPTBN2	SPTBN2	SPTBN2	5233	0.22	0.53	NO
109	PLXNA2	PLXNA2	PLXNA2	5276	0.22	0.54	NO
110	ROCK2	ROCK2	ROCK2	5462	0.2	0.53	NO
111	PLXNC1	PLXNC1	PLXNC1	5528	0.2	0.53	NO
112	COL4A4	COL4A4	COL4A4	5670	0.19	0.52	NO
113	SRC	SRC	SRC	5789	0.18	0.52	NO
114	TRPC7	TRPC7	TRPC7	5955	0.17	0.51	NO
115	PLXNA1	PLXNA1	PLXNA1	6078	0.16	0.51	NO
116	FGFR1	FGFR1	FGFR1	6142	0.16	0.51	NO
117	KCNQ3	KCNQ3	KCNQ3	6216	0.16	0.5	NO
118	PAK6	PAK6	PAK6	6274	0.15	0.5	NO
119	ABL1	ABL1	ABL1	6622	0.13	0.49	NO
120	EVL	EVL	EVL	6693	0.13	0.48	NO
121	PIP5K1C	PIP5K1C	PIP5K1C	7061	0.11	0.47	NO
122	ITGA9	ITGA9	ITGA9	7073	0.11	0.47	NO
123	TLN1	TLN1	TLN1	7078	0.11	0.47	NO
124	MYL6	MYL6	MYL6	7127	0.11	0.47	NO
125	SOS1	SOS1	SOS1	7134	0.11	0.47	NO
126	RGMA	RGMA	RGMA	7217	0.11	0.47	NO
127	PLXND1	PLXND1	PLXND1	7279	0.1	0.46	NO
128	RPS6KA3	RPS6KA3	RPS6KA3	7294	0.1	0.46	NO
129	ST8SIA4	ST8SIA4	ST8SIA4	7328	0.1	0.46	NO
130	DLG1	DLG1	DLG1	7337	0.1	0.47	NO
131	DPYSL2	DPYSL2	DPYSL2	7395	0.099	0.46	NO
132	ENAH	ENAH	ENAH	7530	0.094	0.46	NO
133	PITPNA	PITPNA	PITPNA	7573	0.092	0.46	NO
134	MYH9	MYH9	MYH9	7619	0.09	0.46	NO
135	SCN1B	SCN1B	SCN1B	7671	0.088	0.45	NO
136	MAPK3	MAPK3	MAPK3	7678	0.087	0.46	NO
137	ITGB1	ITGB1	ITGB1	7717	0.086	0.45	NO
138	SRGAP2	SRGAP2	SRGAP2	7802	0.083	0.45	NO
139	PRNP	PRNP	PRNP	7860	0.08	0.45	NO
140	AP2A2	AP2A2	AP2A2	7935	0.078	0.45	NO
141	CLASP1	CLASP1	CLASP1	7996	0.076	0.44	NO
142	FYN	FYN	FYN	8057	0.074	0.44	NO
143	MYO10	MYO10	MYO10	8235	0.066	0.43	NO
144	RDX	RDX	RDX	8402	0.06	0.42	NO
145	SPTAN1	SPTAN1	SPTAN1	8423	0.06	0.42	NO
146	LAMC1	LAMC1	LAMC1	8550	0.055	0.42	NO
147	CREB1	CREB1	CREB1	8562	0.054	0.42	NO
148	MYL12B	MYL12B	MYL12B	8730	0.049	0.41	NO
149	NUMB	NUMB	NUMB	8753	0.048	0.41	NO
150	RPS6KA4	RPS6KA4	RPS6KA4	8788	0.047	0.41	NO
151	PLCG1	PLCG1	PLCG1	8857	0.045	0.41	NO
152	SEMA7A	SEMA7A	SEMA7A	8983	0.04	0.4	NO
153	KIAA1598	KIAA1598	KIAA1598	9070	0.037	0.4	NO
154	MSN	MSN	MSN	9144	0.034	0.39	NO
155	ROCK1	ROCK1	ROCK1	9170	0.034	0.39	NO
156	AP2A1	AP2A1	AP2A1	9199	0.033	0.39	NO
157	SPTBN1	SPTBN1	SPTBN1	9520	0.022	0.37	NO
158	CDK5R1	CDK5R1	CDK5R1	9547	0.021	0.37	NO
159	RHOC	RHOC	RHOC	9550	0.021	0.37	NO
160	RPS6KA5	RPS6KA5	RPS6KA5	9626	0.018	0.37	NO
161	NRAS	NRAS	NRAS	9770	0.014	0.36	NO
162	AP2B1	AP2B1	AP2B1	9890	0.01	0.36	NO
163	NCK2	NCK2	NCK2	9921	0.0094	0.35	NO
164	NCK1	NCK1	NCK1	9970	0.0077	0.35	NO
165	PAK2	PAK2	PAK2	10040	0.005	0.35	NO
166	PTK2	PTK2	PTK2	10121	0.0023	0.34	NO
167	CDC42	CDC42	CDC42	10156	0.0015	0.34	NO
168	KIF4A	KIF4A	KIF4A	10228	-0.00062	0.34	NO
169	EZR	EZR	EZR	10330	-0.0042	0.33	NO
170	CFL1	CFL1	CFL1	10338	-0.0044	0.33	NO
171	CDK1	CDK1	CDK1	10347	-0.0047	0.33	NO
172	RHOA	RHOA	RHOA	10396	-0.0062	0.33	NO
173	PAK4	PAK4	PAK4	10612	-0.013	0.32	NO
174	RAC1	RAC1	RAC1	10632	-0.013	0.32	NO
175	ARHGEF11	ARHGEF11	ARHGEF11	10939	-0.022	0.3	NO
176	L1CAM	L1CAM	L1CAM	11043	-0.025	0.3	NO
177	HRAS	HRAS	HRAS	11044	-0.025	0.3	NO
178	CRMP1	CRMP1	CRMP1	11061	-0.026	0.3	NO
179	CLTC	CLTC	CLTC	11202	-0.029	0.29	NO
180	PAK1	PAK1	PAK1	11432	-0.036	0.28	NO
181	LAMA1	LAMA1	LAMA1	11537	-0.04	0.27	NO
182	RAF1	RAF1	RAF1	11649	-0.043	0.27	NO
183	MAP2K1	MAP2K1	MAP2K1	11675	-0.044	0.27	NO
184	CSNK2A1	CSNK2A1	CSNK2A1	11893	-0.049	0.26	NO
185	KRAS	KRAS	KRAS	11950	-0.051	0.25	NO
186	GRB2	GRB2	GRB2	11951	-0.051	0.25	NO
187	AP2S1	AP2S1	AP2S1	12033	-0.053	0.25	NO
188	DNM2	DNM2	DNM2	12162	-0.057	0.24	NO
189	MAP2K2	MAP2K2	MAP2K2	12254	-0.06	0.24	NO
190	STIP1	STIP1	STIP1	12315	-0.062	0.24	NO
191	KIF4B	KIF4B	KIF4B	12316	-0.062	0.24	NO
192	CSNK2B	CSNK2B	CSNK2B	12442	-0.065	0.23	NO
193	AP2M1	AP2M1	AP2M1	12456	-0.066	0.23	NO
194	FES	FES	FES	12588	-0.07	0.23	NO
195	CLTA	CLTA	CLTA	12638	-0.071	0.23	NO
196	RANBP9	RANBP9	RANBP9	12701	-0.073	0.22	NO
197	TREM2	TREM2	TREM2	12730	-0.074	0.22	NO
198	CSNK2A2	CSNK2A2	CSNK2A2	12745	-0.074	0.22	NO
199	DPYSL5	DPYSL5	DPYSL5	12905	-0.079	0.22	NO
200	YWHAB	YWHAB	YWHAB	13020	-0.082	0.21	NO
201	LIMK1	LIMK1	LIMK1	13096	-0.085	0.21	NO
202	ANK1	ANK1	ANK1	13641	-0.1	0.18	NO
203	HFE2	HFE2	HFE2	13709	-0.1	0.18	NO
204	HSP90AB1	HSP90AB1	HSP90AB1	13792	-0.11	0.18	NO
205	MAPK1	MAPK1	MAPK1	13847	-0.11	0.17	NO
206	SEMA6A	SEMA6A	SEMA6A	13852	-0.11	0.18	NO
207	CAP1	CAP1	CAP1	13875	-0.11	0.18	NO
208	CACNB3	CACNB3	CACNB3	14050	-0.12	0.17	NO
209	SPTB	SPTB	SPTB	14066	-0.12	0.17	NO
210	RHOG	RHOG	RHOG	14178	-0.12	0.16	NO
211	NCAN	NCAN	NCAN	14216	-0.12	0.16	NO
212	SDCBP	SDCBP	SDCBP	14435	-0.13	0.15	NO
213	ABL2	ABL2	ABL2	14560	-0.14	0.15	NO
214	SH3GL2	SH3GL2	SH3GL2	14646	-0.14	0.15	NO
215	PFN1	PFN1	PFN1	14648	-0.14	0.15	NO
216	LIMK2	LIMK2	LIMK2	14721	-0.14	0.15	NO
217	VASP	VASP	VASP	14746	-0.14	0.15	NO
218	NRCAM	NRCAM	NRCAM	14899	-0.15	0.14	NO
219	RND1	RND1	RND1	14917	-0.15	0.14	NO
220	SRGAP1	SRGAP1	SRGAP1	14922	-0.15	0.14	NO
221	HSP90AA1	HSP90AA1	HSP90AA1	14993	-0.16	0.14	NO
222	WASL	WASL	WASL	15196	-0.16	0.13	NO
223	RPS6KA1	RPS6KA1	RPS6KA1	15383	-0.17	0.13	NO
224	SEMA4A	SEMA4A	SEMA4A	15689	-0.19	0.11	NO
225	TYROBP	TYROBP	TYROBP	16095	-0.22	0.094	NO
226	CDK5	CDK5	CDK5	16129	-0.22	0.095	NO
227	SIAH1	SIAH1	SIAH1	16294	-0.23	0.09	NO
228	SPTBN4	SPTBN4	SPTBN4	16573	-0.25	0.078	NO
229	SEMA4D	SEMA4D	SEMA4D	16719	-0.27	0.074	NO
230	DLG3	DLG3	DLG3	16790	-0.27	0.074	NO
231	PRKCQ	PRKCQ	PRKCQ	17023	-0.3	0.066	NO
232	CACNA1I	CACNA1I	CACNA1I	17156	-0.31	0.063	NO
233	ITGA2B	ITGA2B	ITGA2B	17267	-0.33	0.062	NO
234	PTPRC	PTPRC	PTPRC	17313	-0.33	0.064	NO
235	RAC2	RAC2	RAC2	17450	-0.35	0.061	NO
236	CD72	CD72	CD72	17599	-0.38	0.058	NO
237	SCN8A	SCN8A	SCN8A	17703	-0.4	0.058	NO
238	SCN4A	SCN4A	SCN4A	17826	-0.42	0.057	NO
239	TRPC5	TRPC5	TRPC5	18456	-0.57	0.032	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: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES.

Figure S70. Get High-res Image For the top 5 core enriched genes in the pathway: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID ENDOTHELINPATHWAY

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	WIF1	WIF1	WIF1	12	1.4	0.11	YES
2	DKK2	DKK2	DKK2	24	1.3	0.22	YES
3	SSPO	SSPO	SSPO	203	1.1	0.3	YES
4	DKK1	DKK1	DKK1	935	0.77	0.32	YES
5	FZD1	FZD1	FZD1	1081	0.74	0.37	YES
6	CCND1	CCND1	CCND1	1321	0.69	0.41	YES
7	JUN	JUN	JUN	1877	0.59	0.43	YES
8	DLL1	DLL1	DLL1	1901	0.58	0.48	YES
9	NKD1	NKD1	NKD1	2160	0.54	0.51	YES
10	HNF1A	HNF1A	HNF1A	2250	0.53	0.55	YES
11	FOS	FOS	FOS	2800	0.45	0.55	YES
12	NOTCH1	NOTCH1	NOTCH1	3359	0.39	0.55	YES
13	KREMEN2	KREMEN2	KREMEN2	4310	0.29	0.53	NO
14	CTNNB1	CTNNB1	CTNNB1	5299	0.21	0.49	NO
15	MYC	MYC	MYC	5411	0.2	0.5	NO
16	WNT1	WNT1	WNT1	5770	0.18	0.5	NO
17	AES	AES	AES	6069	0.16	0.5	NO
18	LRP6	LRP6	LRP6	6881	0.12	0.46	NO
19	CTBP1	CTBP1	CTBP1	6928	0.12	0.47	NO
20	APC	APC	APC	7074	0.11	0.47	NO
21	APH1A	APH1A	APH1A	7094	0.11	0.48	NO
22	TAB1	TAB1	TAB1	7581	0.091	0.46	NO
23	MAPK3	MAPK3	MAPK3	7678	0.087	0.46	NO
24	CREBBP	CREBBP	CREBBP	7820	0.082	0.46	NO
25	DTX1	DTX1	DTX1	8164	0.069	0.45	NO
26	TLE1	TLE1	TLE1	8370	0.062	0.44	NO
27	FBXW11	FBXW11	FBXW11	8379	0.061	0.45	NO
28	GSK3B	GSK3B	GSK3B	9279	0.03	0.4	NO
29	PPP2R5D	PPP2R5D	PPP2R5D	9347	0.028	0.4	NO
30	APH1B	APH1B	APH1B	9992	0.0068	0.37	NO
31	ADAM10	ADAM10	ADAM10	10038	0.005	0.37	NO
32	NCSTN	NCSTN	NCSTN	10066	0.0043	0.37	NO
33	CSNK1A1	CSNK1A1	CSNK1A1	10194	0.00041	0.36	NO
34	AXIN1	AXIN1	AXIN1	10995	-0.023	0.32	NO
35	NEDD4	NEDD4	NEDD4	11336	-0.033	0.3	NO
36	HDAC1	HDAC1	HDAC1	11553	-0.04	0.3	NO
37	PPARD	PPARD	PPARD	11597	-0.042	0.3	NO
38	NLK	NLK	NLK	11860	-0.048	0.29	NO
39	CSNK2A1	CSNK2A1	CSNK2A1	11893	-0.049	0.29	NO
40	PSEN1	PSEN1	PSEN1	12155	-0.057	0.28	NO
41	MAP3K7	MAP3K7	MAP3K7	12292	-0.061	0.28	NO
42	DVL1	DVL1	DVL1	12526	-0.068	0.27	NO
43	PSENEN	PSENEN	PSENEN	12560	-0.069	0.28	NO
44	MAPK1	MAPK1	MAPK1	13847	-0.11	0.22	NO
45	RBPJ	RBPJ	RBPJ	15050	-0.16	0.17	NO
46	FRAT1	FRAT1	FRAT1	18407	-0.56	0.034	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: PID ENDOTHELINPATHWAY.

Figure S72. Get High-res Image For the top 5 core enriched genes in the pathway: PID ENDOTHELINPATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID NOTCH PATHWAY

Table 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	COL9A1	COL9A1	COL9A1	166	1.1	0.039	YES
2	CNTN2	CNTN2	CNTN2	205	1.1	0.083	YES
3	NCAM1	NCAM1	NCAM1	274	1	0.12	YES
4	COL9A2	COL9A2	COL9A2	536	0.9	0.15	YES
5	COL2A1	COL2A1	COL2A1	553	0.9	0.19	YES
6	GDNF	GDNF	GDNF	663	0.86	0.22	YES
7	ST8SIA2	ST8SIA2	ST8SIA2	698	0.84	0.25	YES
8	GFRA1	GFRA1	GFRA1	706	0.84	0.29	YES
9	CACNB4	CACNB4	CACNB4	857	0.8	0.31	YES
10	CACNA1G	CACNA1G	CACNA1G	908	0.78	0.34	YES
11	GFRA2	GFRA2	GFRA2	1215	0.71	0.36	YES
12	COL3A1	COL3A1	COL3A1	1242	0.7	0.39	YES
13	COL5A2	COL5A2	COL5A2	1298	0.69	0.42	YES
14	COL1A1	COL1A1	COL1A1	1330	0.69	0.44	YES
15	CACNA1S	CACNA1S	CACNA1S	1469	0.66	0.46	YES
16	COL4A5	COL4A5	COL4A5	1603	0.63	0.48	YES
17	COL5A1	COL5A1	COL5A1	1739	0.61	0.5	YES
18	COL1A2	COL1A2	COL1A2	2180	0.54	0.5	YES
19	COL6A3	COL6A3	COL6A3	2243	0.53	0.52	YES
20	CACNB2	CACNB2	CACNB2	2269	0.52	0.54	YES
21	SPTA1	SPTA1	SPTA1	2852	0.45	0.53	YES
22	NRTN	NRTN	NRTN	2888	0.44	0.55	YES
23	AGRN	AGRN	AGRN	2911	0.44	0.57	YES
24	COL6A2	COL6A2	COL6A2	2952	0.43	0.58	YES
25	COL6A1	COL6A1	COL6A1	3002	0.43	0.6	YES
26	PSPN	PSPN	PSPN	3385	0.38	0.6	YES
27	SPTBN5	SPTBN5	SPTBN5	3533	0.37	0.6	YES
28	ARTN	ARTN	ARTN	3535	0.37	0.62	YES
29	CACNB1	CACNB1	CACNB1	3774	0.34	0.62	YES
30	COL4A3	COL4A3	COL4A3	3814	0.34	0.64	YES
31	CACNA1H	CACNA1H	CACNA1H	3993	0.32	0.64	YES
32	COL4A2	COL4A2	COL4A2	4682	0.26	0.62	NO
33	COL4A1	COL4A1	COL4A1	4705	0.26	0.62	NO
34	COL9A3	COL9A3	COL9A3	4833	0.25	0.63	NO
35	SPTBN2	SPTBN2	SPTBN2	5233	0.22	0.62	NO
36	COL4A4	COL4A4	COL4A4	5670	0.19	0.6	NO
37	SRC	SRC	SRC	5789	0.18	0.6	NO
38	FGFR1	FGFR1	FGFR1	6142	0.16	0.59	NO
39	SOS1	SOS1	SOS1	7134	0.11	0.54	NO
40	ST8SIA4	ST8SIA4	ST8SIA4	7328	0.1	0.54	NO
41	MAPK3	MAPK3	MAPK3	7678	0.087	0.52	NO
42	PRNP	PRNP	PRNP	7860	0.08	0.52	NO
43	FYN	FYN	FYN	8057	0.074	0.51	NO
44	SPTAN1	SPTAN1	SPTAN1	8423	0.06	0.49	NO
45	CREB1	CREB1	CREB1	8562	0.054	0.49	NO
46	SPTBN1	SPTBN1	SPTBN1	9520	0.022	0.44	NO
47	RPS6KA5	RPS6KA5	RPS6KA5	9626	0.018	0.44	NO
48	NRAS	NRAS	NRAS	9770	0.014	0.43	NO
49	PTK2	PTK2	PTK2	10121	0.0023	0.41	NO
50	CDK1	CDK1	CDK1	10347	-0.0047	0.4	NO
51	HRAS	HRAS	HRAS	11044	-0.025	0.36	NO
52	RAF1	RAF1	RAF1	11649	-0.043	0.33	NO
53	MAP2K1	MAP2K1	MAP2K1	11675	-0.044	0.33	NO
54	KRAS	KRAS	KRAS	11950	-0.051	0.32	NO
55	GRB2	GRB2	GRB2	11951	-0.051	0.32	NO
56	MAP2K2	MAP2K2	MAP2K2	12254	-0.06	0.31	NO
57	YWHAB	YWHAB	YWHAB	13020	-0.082	0.27	NO
58	MAPK1	MAPK1	MAPK1	13847	-0.11	0.23	NO
59	CACNB3	CACNB3	CACNB3	14050	-0.12	0.23	NO
60	SPTB	SPTB	SPTB	14066	-0.12	0.23	NO
61	NCAN	NCAN	NCAN	14216	-0.12	0.23	NO
62	SPTBN4	SPTBN4	SPTBN4	16573	-0.25	0.12	NO
63	CACNA1I	CACNA1I	CACNA1I	17156	-0.31	0.1	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: PID NOTCH PATHWAY.

Figure S74. Get High-res Image For the top 5 core enriched genes in the pathway: PID NOTCH PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID EPHBFWDPATHWAY

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	CNTN1	CNTN1	CNTN1	158	1.1	0.057	YES
2	SSPO	SSPO	SSPO	203	1.1	0.12	YES
3	CNTN6	CNTN6	CNTN6	428	0.95	0.16	YES
4	DNER	DNER	DNER	649	0.86	0.2	YES
5	MAML2	MAML2	MAML2	1170	0.72	0.22	YES
6	CCND1	CCND1	CCND1	1321	0.69	0.25	YES
7	MFAP2	MFAP2	MFAP2	1651	0.62	0.27	YES
8	NOTCH4	NOTCH4	NOTCH4	1868	0.59	0.29	YES
9	DLL1	DLL1	DLL1	1901	0.58	0.33	YES
10	DLL4	DLL4	DLL4	2024	0.56	0.35	YES
11	ADAM12	ADAM12	ADAM12	2103	0.55	0.38	YES
12	DNM1	DNM1	DNM1	2296	0.52	0.4	YES
13	MFAP5	MFAP5	MFAP5	2533	0.49	0.42	YES
14	NOTCH3	NOTCH3	NOTCH3	2753	0.46	0.44	YES
15	JAG1	JAG1	JAG1	3107	0.41	0.44	YES
16	NOTCH1	NOTCH1	NOTCH1	3359	0.39	0.45	YES
17	NOTCH2	NOTCH2	NOTCH2	3367	0.39	0.47	YES
18	DLK1	DLK1	DLK1	3380	0.38	0.5	YES
19	GATA3	GATA3	GATA3	3821	0.34	0.49	YES
20	CDKN1A	CDKN1A	CDKN1A	3885	0.33	0.51	YES
21	NCOR2	NCOR2	NCOR2	5268	0.22	0.45	NO
22	MYC	MYC	MYC	5411	0.2	0.45	NO
23	MIB1	MIB1	MIB1	5932	0.17	0.44	NO
24	CTBP1	CTBP1	CTBP1	6928	0.12	0.39	NO
25	APH1A	APH1A	APH1A	7094	0.11	0.39	NO
26	DTX1	DTX1	DTX1	8164	0.069	0.34	NO
27	NCOR1	NCOR1	NCOR1	8553	0.055	0.32	NO
28	NUMB	NUMB	NUMB	8753	0.048	0.31	NO
29	MAML1	MAML1	MAML1	9007	0.039	0.3	NO
30	RAB11A	RAB11A	RAB11A	9473	0.024	0.28	NO
31	APH1B	APH1B	APH1B	9992	0.0068	0.25	NO
32	ADAM10	ADAM10	ADAM10	10038	0.005	0.25	NO
33	NCSTN	NCSTN	NCSTN	10066	0.0043	0.25	NO
34	MARK2	MARK2	MARK2	10664	-0.014	0.22	NO
35	SKP1	SKP1	SKP1	10667	-0.014	0.22	NO
36	SKP2	SKP2	SKP2	10859	-0.019	0.21	NO
37	HDAC1	HDAC1	HDAC1	11553	-0.04	0.17	NO
38	FBXW7	FBXW7	FBXW7	11718	-0.045	0.17	NO
39	FURIN	FURIN	FURIN	11802	-0.047	0.17	NO
40	ITCH	ITCH	ITCH	11958	-0.051	0.16	NO
41	PSEN1	PSEN1	PSEN1	12155	-0.057	0.15	NO
42	EP300	EP300	EP300	12302	-0.061	0.15	NO
43	PSENEN	PSENEN	PSENEN	12560	-0.069	0.14	NO
44	EPS15	EPS15	EPS15	12774	-0.075	0.13	NO
45	RBBP8	RBBP8	RBBP8	12963	-0.08	0.13	NO
46	KDM1A	KDM1A	KDM1A	13073	-0.084	0.13	NO
47	YY1	YY1	YY1	13562	-0.1	0.11	NO
48	IL4	IL4	IL4	13569	-0.1	0.11	NO
49	SPEN	SPEN	SPEN	14130	-0.12	0.092	NO
50	LNX1	LNX1	LNX1	14329	-0.13	0.089	NO
51	ENO1	ENO1	ENO1	14426	-0.13	0.091	NO
52	CUL1	CUL1	CUL1	14474	-0.13	0.097	NO
53	JAG2	JAG2	JAG2	14639	-0.14	0.096	NO
54	CBL	CBL	CBL	14816	-0.15	0.096	NO
55	RBPJ	RBPJ	RBPJ	15050	-0.16	0.093	NO
56	MYCBP	MYCBP	MYCBP	16716	-0.27	0.021	NO
57	DLL3	DLL3	DLL3	18086	-0.48	-0.023	NO
58	NEURL	NEURL	NEURL	18172	-0.5	0.0026	NO
59	PTCRA	PTCRA	PTCRA	18819	-0.74	0.012	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: PID EPHBFWDPATHWAY.

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

genes ES table in pathway: PID PS1PATHWAY

Table 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	CAMK2B	CAMK2B	CAMK2B	232	1	0.028	YES
2	NTF3	NTF3	NTF3	344	0.98	0.059	YES
3	NTRK2	NTRK2	NTRK2	380	0.97	0.094	YES
4	NGF	NGF	NGF	468	0.93	0.12	YES
5	MAPK10	MAPK10	MAPK10	581	0.88	0.15	YES
6	CALML3	CALML3	CALML3	646	0.86	0.18	YES
7	NTF4	NTF4	NTF4	1350	0.68	0.17	YES
8	SHC4	SHC4	SHC4	1609	0.63	0.18	YES
9	CALML5	CALML5	CALML5	1740	0.61	0.2	YES
10	IRS1	IRS1	IRS1	1771	0.61	0.22	YES
11	JUN	JUN	JUN	1877	0.59	0.24	YES
12	BCL2	BCL2	BCL2	2185	0.54	0.24	YES
13	NTRK1	NTRK1	NTRK1	2205	0.54	0.26	YES
14	CAMK2A	CAMK2A	CAMK2A	2321	0.52	0.27	YES
15	TP73	TP73	TP73	2512	0.49	0.28	YES
16	RPS6KA2	RPS6KA2	RPS6KA2	2967	0.43	0.27	YES
17	NGFR	NGFR	NGFR	3062	0.42	0.28	YES
18	SHC2	SHC2	SHC2	3068	0.42	0.3	YES
19	PIK3R1	PIK3R1	PIK3R1	3070	0.42	0.32	YES
20	IRAK3	IRAK3	IRAK3	3201	0.4	0.32	YES
21	NGFRAP1	NGFRAP1	NGFRAP1	3486	0.38	0.32	YES
22	RPS6KA6	RPS6KA6	RPS6KA6	3671	0.35	0.33	YES
23	SOS2	SOS2	SOS2	3715	0.35	0.34	YES
24	CAMK4	CAMK4	CAMK4	3736	0.35	0.35	YES
25	IRS4	IRS4	IRS4	3741	0.34	0.36	YES
26	AKT3	AKT3	AKT3	3822	0.34	0.37	YES
27	MAGED1	MAGED1	MAGED1	3849	0.34	0.38	YES
28	KIDINS220	KIDINS220	KIDINS220	3958	0.32	0.39	YES
29	IRS2	IRS2	IRS2	3965	0.32	0.4	YES
30	BDNF	BDNF	BDNF	4090	0.31	0.41	YES
31	BAD	BAD	BAD	4447	0.28	0.4	NO
32	MAPK13	MAPK13	MAPK13	4903	0.24	0.38	NO
33	SHC3	SHC3	SHC3	5074	0.23	0.38	NO
34	CAMK2D	CAMK2D	CAMK2D	5160	0.22	0.39	NO
35	GAB1	GAB1	GAB1	5237	0.22	0.39	NO
36	FOXO3	FOXO3	FOXO3	5668	0.19	0.38	NO
37	NFKB1	NFKB1	NFKB1	5784	0.18	0.38	NO
38	SHC1	SHC1	SHC1	6206	0.16	0.36	NO
39	MAPK14	MAPK14	MAPK14	6350	0.15	0.36	NO
40	AKT1	AKT1	AKT1	6362	0.15	0.36	NO
41	MAPK8	MAPK8	MAPK8	6435	0.14	0.36	NO
42	MAPKAPK2	MAPKAPK2	MAPKAPK2	6596	0.13	0.36	NO
43	ABL1	ABL1	ABL1	6622	0.13	0.36	NO
44	RELA	RELA	RELA	6847	0.12	0.36	NO
45	MAP3K3	MAP3K3	MAP3K3	6970	0.12	0.36	NO
46	SOS1	SOS1	SOS1	7134	0.11	0.35	NO
47	PIK3CA	PIK3CA	PIK3CA	7220	0.11	0.35	NO
48	FRS2	FRS2	FRS2	7255	0.1	0.35	NO
49	RPS6KA3	RPS6KA3	RPS6KA3	7294	0.1	0.36	NO
50	MAPK7	MAPK7	MAPK7	7380	0.099	0.35	NO
51	MAPK3	MAPK3	MAPK3	7678	0.087	0.34	NO
52	SH2B1	SH2B1	SH2B1	7846	0.081	0.34	NO
53	IKBKB	IKBKB	IKBKB	7940	0.078	0.33	NO
54	AKT2	AKT2	AKT2	8051	0.074	0.33	NO
55	MAPK11	MAPK11	MAPK11	8090	0.072	0.33	NO
56	IRAK4	IRAK4	IRAK4	8153	0.07	0.33	NO
57	TP53	TP53	TP53	8496	0.057	0.32	NO
58	ARHGDIA	ARHGDIA	ARHGDIA	8617	0.052	0.31	NO
59	CAMK2G	CAMK2G	CAMK2G	8691	0.05	0.31	NO
60	IRAK2	IRAK2	IRAK2	8733	0.048	0.31	NO
61	RPS6KA4	RPS6KA4	RPS6KA4	8788	0.047	0.31	NO
62	MAPK9	MAPK9	MAPK9	8804	0.046	0.31	NO
63	PLCG1	PLCG1	PLCG1	8857	0.045	0.31	NO
64	CALM3	CALM3	CALM3	8952	0.041	0.3	NO
65	PRDM4	PRDM4	PRDM4	8965	0.041	0.3	NO
66	YWHAQ	YWHAQ	YWHAQ	9250	0.032	0.29	NO
67	GSK3B	GSK3B	GSK3B	9279	0.03	0.29	NO
68	PIK3R2	PIK3R2	PIK3R2	9302	0.03	0.29	NO
69	IRAK1	IRAK1	IRAK1	9385	0.027	0.29	NO
70	RPS6KA5	RPS6KA5	RPS6KA5	9626	0.018	0.28	NO
71	CALM1	CALM1	CALM1	9661	0.018	0.27	NO
72	SORT1	SORT1	SORT1	9756	0.014	0.27	NO
73	NRAS	NRAS	NRAS	9770	0.014	0.27	NO
74	PTPN11	PTPN11	PTPN11	9913	0.0095	0.26	NO
75	YWHAZ	YWHAZ	YWHAZ	10131	0.0021	0.25	NO
76	PIK3R3	PIK3R3	PIK3R3	10153	0.0015	0.25	NO
77	CDC42	CDC42	CDC42	10156	0.0015	0.25	NO
78	MAP2K5	MAP2K5	MAP2K5	10157	0.0014	0.25	NO
79	RAP1A	RAP1A	RAP1A	10179	0.00072	0.25	NO
80	MAP3K5	MAP3K5	MAP3K5	10316	-0.0036	0.24	NO
81	NTRK3	NTRK3	NTRK3	10319	-0.0037	0.24	NO
82	ATF4	ATF4	ATF4	10342	-0.0045	0.24	NO
83	ARHGDIB	ARHGDIB	ARHGDIB	10389	-0.0059	0.24	NO
84	RHOA	RHOA	RHOA	10396	-0.0062	0.24	NO
85	CRK	CRK	CRK	10521	-0.0099	0.23	NO
86	RAC1	RAC1	RAC1	10632	-0.013	0.23	NO
87	ZNF274	ZNF274	ZNF274	11004	-0.024	0.21	NO
88	HRAS	HRAS	HRAS	11044	-0.025	0.21	NO
89	CALML6	CALML6	CALML6	11071	-0.026	0.21	NO
90	PRKCD	PRKCD	PRKCD	11112	-0.027	0.21	NO
91	SH2B3	SH2B3	SH2B3	11210	-0.03	0.2	NO
92	MAP3K1	MAP3K1	MAP3K1	11421	-0.036	0.19	NO
93	TRAF6	TRAF6	TRAF6	11508	-0.038	0.19	NO
94	YWHAH	YWHAH	YWHAH	11617	-0.042	0.18	NO
95	RAF1	RAF1	RAF1	11649	-0.043	0.18	NO
96	MAP2K1	MAP2K1	MAP2K1	11675	-0.044	0.18	NO
97	NFKBIA	NFKBIA	NFKBIA	11732	-0.045	0.18	NO
98	CRKL	CRKL	CRKL	11881	-0.049	0.18	NO
99	KRAS	KRAS	KRAS	11950	-0.051	0.18	NO
100	GRB2	GRB2	GRB2	11951	-0.051	0.18	NO
101	MAP2K7	MAP2K7	MAP2K7	12132	-0.056	0.17	NO
102	PSEN1	PSEN1	PSEN1	12155	-0.057	0.17	NO
103	CALM2	CALM2	CALM2	12235	-0.059	0.17	NO
104	MAP2K2	MAP2K2	MAP2K2	12254	-0.06	0.17	NO
105	RIPK2	RIPK2	RIPK2	12376	-0.064	0.17	NO
106	YWHAE	YWHAE	YWHAE	12635	-0.071	0.16	NO
107	RAP1B	RAP1B	RAP1B	12797	-0.076	0.15	NO
108	YWHAB	YWHAB	YWHAB	13020	-0.082	0.14	NO
109	PDK1	PDK1	PDK1	13731	-0.11	0.11	NO
110	MAPK1	MAPK1	MAPK1	13847	-0.11	0.11	NO
111	PLCG2	PLCG2	PLCG2	14456	-0.13	0.079	NO
112	YWHAG	YWHAG	YWHAG	14597	-0.14	0.077	NO
113	CSK	CSK	CSK	14599	-0.14	0.082	NO
114	RAPGEF1	RAPGEF1	RAPGEF1	14953	-0.15	0.07	NO
115	NFKBIE	NFKBIE	NFKBIE	15051	-0.16	0.07	NO
116	RPS6KA1	RPS6KA1	RPS6KA1	15383	-0.17	0.06	NO
117	BAX	BAX	BAX	15903	-0.2	0.04	NO
118	PIK3CB	PIK3CB	PIK3CB	15904	-0.2	0.047	NO
119	BRAF	BRAF	BRAF	16029	-0.21	0.049	NO
120	MAPK12	MAPK12	MAPK12	16788	-0.27	0.019	NO
121	PIK3CG	PIK3CG	PIK3CG	16995	-0.29	0.019	NO
122	NFKBIB	NFKBIB	NFKBIB	17123	-0.31	0.024	NO
123	PIK3R5	PIK3R5	PIK3R5	17810	-0.42	0.0039	NO
124	PIK3CD	PIK3CD	PIK3CD	17828	-0.42	0.019	NO
125	FASLG	FASLG	FASLG	18328	-0.54	0.013	NO
126	SH2B2	SH2B2	SH2B2	18674	-0.66	0.02	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: PID PS1PATHWAY.

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: PID PS1PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID P75NTRPATHWAY

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	SSPO	SSPO	SSPO	203	1.1	0.12	YES
2	GLI3	GLI3	GLI3	328	0.99	0.24	YES
3	SHH	SHH	SHH	2214	0.53	0.21	YES
4	GNAI1	GNAI1	GNAI1	3066	0.42	0.22	YES
5	SPOP	SPOP	SPOP	3510	0.37	0.24	YES
6	RAB23	RAB23	RAB23	3744	0.34	0.27	YES
7	FOXA2	FOXA2	FOXA2	3854	0.34	0.31	YES
8	GLI2	GLI2	GLI2	4492	0.28	0.31	YES
9	SMO	SMO	SMO	4615	0.27	0.33	YES
10	GNAZ	GNAZ	GNAZ	4689	0.26	0.36	YES
11	GNG2	GNG2	GNG2	4829	0.25	0.39	YES
12	SUFU	SUFU	SUFU	4920	0.24	0.41	YES
13	IFT88	IFT88	IFT88	5534	0.2	0.4	YES
14	RBBP7	RBBP7	RBBP7	5825	0.18	0.41	YES
15	AKT1	AKT1	AKT1	6362	0.15	0.4	YES
16	PRKACA	PRKACA	PRKACA	6368	0.15	0.42	YES
17	GNAO1	GNAO1	GNAO1	6708	0.13	0.42	YES
18	SAP30	SAP30	SAP30	6725	0.13	0.43	YES
19	LGALS3	LGALS3	LGALS3	6862	0.12	0.44	YES
20	CREBBP	CREBBP	CREBBP	7820	0.082	0.4	NO
21	PTCH1	PTCH1	PTCH1	8076	0.073	0.4	NO
22	FBXW11	FBXW11	FBXW11	8379	0.061	0.39	NO
23	GNAI2	GNAI2	GNAI2	8616	0.052	0.38	NO
24	CSNK1G2	CSNK1G2	CSNK1G2	8624	0.052	0.39	NO
25	GLI1	GLI1	GLI1	8757	0.048	0.39	NO
26	CSNK1G1	CSNK1G1	CSNK1G1	8822	0.046	0.39	NO
27	MTSS1	MTSS1	MTSS1	9015	0.039	0.38	NO
28	GSK3B	GSK3B	GSK3B	9279	0.03	0.38	NO
29	SIN3B	SIN3B	SIN3B	9285	0.03	0.38	NO
30	CSNK1G3	CSNK1G3	CSNK1G3	9340	0.028	0.38	NO
31	GNB1	GNB1	GNB1	9357	0.028	0.38	NO
32	GNAI3	GNAI3	GNAI3	9709	0.016	0.36	NO
33	CSNK1A1	CSNK1A1	CSNK1A1	10194	0.00041	0.34	NO
34	HDAC2	HDAC2	HDAC2	10360	-0.0051	0.33	NO
35	RBBP4	RBBP4	RBBP4	10465	-0.0083	0.33	NO
36	CSNK1D	CSNK1D	CSNK1D	10477	-0.0084	0.33	NO
37	STK36	STK36	STK36	10487	-0.0087	0.33	NO
38	PRKCD	PRKCD	PRKCD	11112	-0.027	0.3	NO
39	HDAC1	HDAC1	HDAC1	11553	-0.04	0.28	NO
40	MAP2K1	MAP2K1	MAP2K1	11675	-0.044	0.28	NO
41	CSNK1E	CSNK1E	CSNK1E	12146	-0.056	0.26	NO
42	PIAS1	PIAS1	PIAS1	12385	-0.064	0.26	NO
43	SIN3A	SIN3A	SIN3A	12413	-0.064	0.26	NO
44	KIF3A	KIF3A	KIF3A	13433	-0.096	0.22	NO
45	XPO1	XPO1	XPO1	14211	-0.12	0.2	NO
46	SAP18	SAP18	SAP18	14707	-0.14	0.19	NO
47	ARRB2	ARRB2	ARRB2	14722	-0.14	0.21	NO
48	IFT172	IFT172	IFT172	15476	-0.18	0.19	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: PID P75NTRPATHWAY.

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: PID P75NTRPATHWAY, 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
KEGG GLYCOLYSIS GLUCONEOGENESIS	61	genes.ES.table	0.49	1.5	0.04	1	0.96	0.18	0.089	0.16	0.83	0.44
KEGG OXIDATIVE PHOSPHORYLATION	115	genes.ES.table	0.49	1.7	0.072	1	0.78	0.82	0.44	0.46	0.67	0.39
KEGG GLUTATHIONE METABOLISM	49	genes.ES.table	0.53	1.6	0.015	1	0.86	0.47	0.31	0.33	0.59	0.37
KEGG ETHER LIPID METABOLISM	30	genes.ES.table	0.59	1.6	0.021	1	0.85	0.23	0.11	0.21	0.66	0.4
KEGG PYRUVATE METABOLISM	40	genes.ES.table	0.51	1.6	0.023	1	0.88	0.32	0.23	0.25	0.63	0.38
KEGG PROPANOATE METABOLISM	32	genes.ES.table	0.46	1.6	0.03	1	0.85	0.12	0.051	0.12	0.76	0.42
KEGG VASOPRESSIN REGULATED WATER REABSORPTION	44	genes.ES.table	0.47	1.7	0.01	1	0.72	0.11	0.081	0.1	0.64	0.38
KEGG PARKINSONS DISEASE	113	genes.ES.table	0.47	1.7	0.04	1	0.59	0.66	0.38	0.41	1	0.53
KEGG PRION DISEASES	35	genes.ES.table	0.51	1.5	0.046	1	0.95	0.2	0.1	0.18	0.97	0.49
KEGG PATHOGENIC ESCHERICHIA COLI INFECTION	53	genes.ES.table	0.47	1.7	0.0043	1	0.6	0.23	0.17	0.19	0.61	0.36

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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	COX7A1	COX7A1	COX7A1	601	0.46	0.0084	YES
2	PARK2	PARK2	PARK2	661	0.44	0.044	YES
3	COX7B2	COX7B2	COX7B2	892	0.4	0.066	YES
4	TH	TH	TH	1029	0.37	0.092	YES
5	COX6B2	COX6B2	COX6B2	1138	0.36	0.12	YES
6	SLC25A31	SLC25A31	SLC25A31	1196	0.35	0.14	YES
7	COX8C	COX8C	COX8C	1200	0.35	0.18	YES
8	COX4I2	COX4I2	COX4I2	1728	0.29	0.17	YES
9	COX6A2	COX6A2	COX6A2	3192	0.18	0.11	YES
10	SLC25A4	SLC25A4	SLC25A4	3224	0.18	0.12	YES
11	NDUFS4	NDUFS4	NDUFS4	3586	0.16	0.12	YES
12	UBE2L6	UBE2L6	UBE2L6	3598	0.16	0.13	YES
13	NDUFA3	NDUFA3	NDUFA3	3882	0.14	0.13	YES
14	NDUFB2	NDUFB2	NDUFB2	3938	0.14	0.14	YES
15	NDUFC1	NDUFC1	NDUFC1	3990	0.14	0.15	YES
16	NDUFB1	NDUFB1	NDUFB1	3998	0.14	0.16	YES
17	NDUFA2	NDUFA2	NDUFA2	4158	0.13	0.16	YES
18	NDUFV2	NDUFV2	NDUFV2	4309	0.13	0.17	YES
19	NDUFB9	NDUFB9	NDUFB9	4343	0.13	0.18	YES
20	NDUFS7	NDUFS7	NDUFS7	4365	0.12	0.18	YES
21	ATP5H	ATP5H	ATP5H	4372	0.12	0.2	YES
22	NDUFAB1	NDUFAB1	NDUFAB1	4390	0.12	0.2	YES
23	UQCRQ	UQCRQ	UQCRQ	4485	0.12	0.21	YES
24	NDUFS6	NDUFS6	NDUFS6	4493	0.12	0.22	YES
25	COX6C	COX6C	COX6C	4516	0.12	0.23	YES
26	PINK1	PINK1	PINK1	4519	0.12	0.24	YES
27	UQCR11	UQCR11	UQCR11	4541	0.12	0.25	YES
28	ATP5D	ATP5D	ATP5D	4625	0.12	0.26	YES
29	NDUFA8	NDUFA8	NDUFA8	4711	0.12	0.26	YES
30	COX7A2	COX7A2	COX7A2	4736	0.11	0.27	YES
31	NDUFC2	NDUFC2	NDUFC2	4744	0.11	0.28	YES
32	NDUFB7	NDUFB7	NDUFB7	4789	0.11	0.29	YES
33	NDUFB6	NDUFB6	NDUFB6	4827	0.11	0.3	YES
34	COX5B	COX5B	COX5B	4842	0.11	0.3	YES
35	NDUFS8	NDUFS8	NDUFS8	4860	0.11	0.31	YES
36	GPR37	GPR37	GPR37	4868	0.11	0.32	YES
37	COX7C	COX7C	COX7C	4872	0.11	0.33	YES
38	UQCRHL	UQCRHL	UQCRHL	4878	0.11	0.34	YES
39	CYCS	CYCS	CYCS	4916	0.11	0.35	YES
40	COX5A	COX5A	COX5A	4955	0.11	0.36	YES
41	NDUFS3	NDUFS3	NDUFS3	5105	0.1	0.36	YES
42	SDHB	SDHB	SDHB	5167	0.1	0.36	YES
43	NDUFA5	NDUFA5	NDUFA5	5339	0.098	0.36	YES
44	UCHL1	UCHL1	UCHL1	5399	0.097	0.37	YES
45	NDUFB10	NDUFB10	NDUFB10	5437	0.096	0.37	YES
46	UQCRH	UQCRH	UQCRH	5513	0.094	0.38	YES
47	SDHA	SDHA	SDHA	5728	0.089	0.37	YES
48	NDUFB3	NDUFB3	NDUFB3	5851	0.086	0.38	YES
49	ATP5E	ATP5E	ATP5E	5870	0.086	0.38	YES
50	NDUFA1	NDUFA1	NDUFA1	5957	0.084	0.38	YES
51	COX8A	COX8A	COX8A	6022	0.083	0.39	YES
52	COX6A1	COX6A1	COX6A1	6067	0.082	0.39	YES
53	PARK7	PARK7	PARK7	6087	0.082	0.4	YES
54	NDUFA4	NDUFA4	NDUFA4	6093	0.082	0.41	YES
55	COX4I1	COX4I1	COX4I1	6163	0.08	0.41	YES
56	NDUFA7	NDUFA7	NDUFA7	6185	0.08	0.42	YES
57	NDUFS5	NDUFS5	NDUFS5	6192	0.079	0.42	YES
58	UQCRFS1	UQCRFS1	UQCRFS1	6273	0.078	0.42	YES
59	HTRA2	HTRA2	HTRA2	6324	0.077	0.43	YES
60	UBB	UBB	UBB	6348	0.076	0.43	YES
61	NDUFB8	NDUFB8	NDUFB8	6353	0.076	0.44	YES
62	UBA7	UBA7	UBA7	6371	0.076	0.45	YES
63	SLC25A6	SLC25A6	SLC25A6	6480	0.074	0.45	YES
64	ATP5O	ATP5O	ATP5O	6512	0.073	0.45	YES
65	COX6B1	COX6B1	COX6B1	6544	0.072	0.46	YES
66	SDHD	SDHD	SDHD	6643	0.07	0.46	YES
67	UQCRB	UQCRB	UQCRB	6848	0.067	0.45	YES
68	NDUFV1	NDUFV1	NDUFV1	6880	0.066	0.46	YES
69	ATP5G3	ATP5G3	ATP5G3	6952	0.065	0.46	YES
70	SLC25A5	SLC25A5	SLC25A5	6966	0.064	0.46	YES
71	UBE2J2	UBE2J2	UBE2J2	7113	0.062	0.46	YES
72	ATP5F1	ATP5F1	ATP5F1	7148	0.061	0.46	YES
73	NDUFB5	NDUFB5	NDUFB5	7200	0.06	0.47	YES
74	NDUFB4	NDUFB4	NDUFB4	7229	0.06	0.47	YES
75	ATP5C1	ATP5C1	ATP5C1	7263	0.059	0.47	YES
76	COX7B	COX7B	COX7B	7454	0.056	0.47	NO
77	NDUFA9	NDUFA9	NDUFA9	7627	0.053	0.46	NO
78	UBE2J1	UBE2J1	UBE2J1	7631	0.053	0.47	NO
79	UQCR10	UQCR10	UQCR10	7866	0.049	0.46	NO
80	ATP5G1	ATP5G1	ATP5G1	7930	0.048	0.46	NO
81	NDUFA10	NDUFA10	NDUFA10	7945	0.047	0.46	NO
82	COX7A2L	COX7A2L	COX7A2L	8032	0.046	0.46	NO
83	ATP5A1	ATP5A1	ATP5A1	8177	0.043	0.46	NO
84	ATP5J	ATP5J	ATP5J	8212	0.043	0.46	NO
85	NDUFA6	NDUFA6	NDUFA6	8281	0.041	0.46	NO
86	VDAC3	VDAC3	VDAC3	8395	0.04	0.46	NO
87	VDAC2	VDAC2	VDAC2	8479	0.038	0.46	NO
88	CYC1	CYC1	CYC1	8510	0.038	0.46	NO
89	NDUFV3	NDUFV3	NDUFV3	8615	0.036	0.46	NO
90	ATP5B	ATP5B	ATP5B	9326	0.025	0.42	NO
91	UQCRC1	UQCRC1	UQCRC1	9606	0.021	0.41	NO
92	NDUFS2	NDUFS2	NDUFS2	9617	0.021	0.41	NO
93	ATP5G2	ATP5G2	ATP5G2	9669	0.02	0.41	NO
94	UBE2L3	UBE2L3	UBE2L3	9968	0.015	0.4	NO
95	PPID	PPID	PPID	10008	0.015	0.4	NO
96	UQCRC2	UQCRC2	UQCRC2	10011	0.015	0.4	NO
97	SDHC	SDHC	SDHC	10038	0.014	0.4	NO
98	UBE2G1	UBE2G1	UBE2G1	10178	0.012	0.39	NO
99	SLC6A3	SLC6A3	SLC6A3	10699	0.0034	0.36	NO
100	VDAC1	VDAC1	VDAC1	11012	-0.0014	0.35	NO
101	CASP9	CASP9	CASP9	11443	-0.008	0.32	NO
102	LRRK2	LRRK2	LRRK2	11521	-0.0091	0.32	NO
103	CASP3	CASP3	CASP3	11790	-0.014	0.31	NO
104	NDUFS1	NDUFS1	NDUFS1	12252	-0.021	0.28	NO
105	UBA1	UBA1	UBA1	12872	-0.033	0.26	NO
106	UBE2G2	UBE2G2	UBE2G2	13515	-0.044	0.22	NO
107	NDUFA4L2	NDUFA4L2	NDUFA4L2	14313	-0.06	0.19	NO
108	SNCAIP	SNCAIP	SNCAIP	14759	-0.071	0.17	NO
109	SEPT5	SEPT5	SEPT5	14889	-0.075	0.17	NO
110	SLC18A2	SLC18A2	SLC18A2	15265	-0.085	0.16	NO
111	SLC18A1	SLC18A1	SLC18A1	15387	-0.089	0.16	NO
112	APAF1	APAF1	APAF1	16007	-0.11	0.14	NO
113	SNCA	SNCA	SNCA	18052	-0.27	0.053	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: KEGG GLYCOLYSIS GLUCONEOGENESIS.

Figure S82. 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 OXIDATIVE PHOSPHORYLATION

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	TUBA3E	TUBA3E	TUBA3E	231	0.62	0.085	YES
2	TUBA3C	TUBA3C	TUBA3C	349	0.55	0.16	YES
3	TUBAL3	TUBAL3	TUBAL3	354	0.55	0.25	YES
4	TUBA3D	TUBA3D	TUBA3D	500	0.49	0.32	YES
5	LY96	LY96	LY96	1333	0.33	0.33	YES
6	TUBA8	TUBA8	TUBA8	1803	0.28	0.35	YES
7	WAS	WAS	WAS	1995	0.26	0.38	YES
8	TLR5	TLR5	TLR5	2505	0.22	0.38	YES
9	TUBB8	TUBB8	TUBB8	2570	0.22	0.42	YES
10	TUBA4A	TUBA4A	TUBA4A	2717	0.2	0.44	YES
11	HCLS1	HCLS1	HCLS1	2793	0.2	0.47	YES
12	CD14	CD14	CD14	3246	0.17	0.47	YES
13	ARPC1B	ARPC1B	ARPC1B	4697	0.12	0.41	NO
14	PRKCA	PRKCA	PRKCA	5555	0.093	0.38	NO
15	TUBA1C	TUBA1C	TUBA1C	5725	0.089	0.39	NO
16	CLDN1	CLDN1	CLDN1	6014	0.083	0.39	NO
17	ARPC5L	ARPC5L	ARPC5L	6016	0.083	0.4	NO
18	TLR4	TLR4	TLR4	6102	0.081	0.41	NO
19	TUBB3	TUBB3	TUBB3	6146	0.08	0.42	NO
20	ARPC3	ARPC3	ARPC3	6154	0.08	0.43	NO
21	FYN	FYN	FYN	6276	0.078	0.44	NO
22	CTTN	CTTN	CTTN	6985	0.064	0.41	NO
23	ARPC2	ARPC2	ARPC2	7724	0.051	0.38	NO
24	ARPC5	ARPC5	ARPC5	8060	0.045	0.37	NO
25	TUBA1A	TUBA1A	TUBA1A	8771	0.034	0.33	NO
26	ARPC1A	ARPC1A	ARPC1A	8800	0.033	0.34	NO
27	ARPC4	ARPC4	ARPC4	9407	0.024	0.31	NO
28	EZR	EZR	EZR	9551	0.022	0.31	NO
29	TUBA1B	TUBA1B	TUBA1B	9603	0.021	0.31	NO
30	ACTG1	ACTG1	ACTG1	9725	0.019	0.3	NO
31	ACTB	ACTB	ACTB	10174	0.012	0.28	NO
32	CDC42	CDC42	CDC42	10278	0.01	0.28	NO
33	WASL	WASL	WASL	10283	0.01	0.28	NO
34	NCK1	NCK1	NCK1	10671	0.0039	0.26	NO
35	NCL	NCL	NCL	10753	0.0026	0.26	NO
36	NCK2	NCK2	NCK2	10761	0.0025	0.26	NO
37	TUBB6	TUBB6	TUBB6	10839	0.0014	0.25	NO
38	YWHAQ	YWHAQ	YWHAQ	11073	-0.0023	0.24	NO
39	TUBB	TUBB	TUBB	11286	-0.0054	0.23	NO
40	RHOA	RHOA	RHOA	11294	-0.0056	0.23	NO
41	TUBB2B	TUBB2B	TUBB2B	11477	-0.0086	0.22	NO
42	KRT18	KRT18	KRT18	11734	-0.013	0.21	NO
43	TUBB2A	TUBB2A	TUBB2A	11943	-0.016	0.2	NO
44	ARHGEF2	ARHGEF2	ARHGEF2	12624	-0.028	0.17	NO
45	ITGB1	ITGB1	ITGB1	12709	-0.03	0.17	NO
46	TUBB1	TUBB1	TUBB1	13485	-0.044	0.14	NO
47	YWHAZ	YWHAZ	YWHAZ	14141	-0.057	0.11	NO
48	ABL1	ABL1	ABL1	14851	-0.074	0.085	NO
49	ROCK1	ROCK1	ROCK1	15294	-0.086	0.076	NO
50	CTNNB1	CTNNB1	CTNNB1	15831	-0.1	0.064	NO
51	OCLN	OCLN	OCLN	17181	-0.18	0.02	NO
52	ROCK2	ROCK2	ROCK2	17650	-0.22	0.03	NO
53	CDH1	CDH1	CDH1	18067	-0.28	0.052	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: KEGG OXIDATIVE PHOSPHORYLATION.

Figure S84. 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 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	PLA2G2A	PLA2G2A	PLA2G2A	36	1.1	0.23	YES
2	PLA2G5	PLA2G5	PLA2G5	103	0.82	0.39	YES
3	PLA2G1B	PLA2G1B	PLA2G1B	684	0.44	0.45	YES
4	GPAT2	GPAT2	GPAT2	1114	0.36	0.5	YES
5	PLA2G2D	PLA2G2D	PLA2G2D	1179	0.35	0.56	YES
6	PLA2G4A	PLA2G4A	PLA2G4A	1492	0.31	0.61	YES
7	AGPAT9	AGPAT9	AGPAT9	2710	0.21	0.59	NO
8	PLA2G2F	PLA2G2F	PLA2G2F	4201	0.13	0.54	NO
9	AGPAT2	AGPAT2	AGPAT2	7265	0.059	0.39	NO
10	PLA2G12A	PLA2G12A	PLA2G12A	8001	0.046	0.36	NO
11	LPCAT4	LPCAT4	LPCAT4	8447	0.039	0.34	NO
12	AGPAT6	AGPAT6	AGPAT6	9168	0.028	0.31	NO
13	GPD1L	GPD1L	GPD1L	10057	0.014	0.26	NO
14	PLD1	PLD1	PLD1	11020	-0.0015	0.22	NO
15	LPCAT1	LPCAT1	LPCAT1	11413	-0.0075	0.2	NO
16	AGPAT1	AGPAT1	AGPAT1	12154	-0.02	0.16	NO
17	GNPAT	GNPAT	GNPAT	12253	-0.021	0.16	NO
18	LCLAT1	LCLAT1	LCLAT1	12403	-0.024	0.16	NO
19	AGPAT3	AGPAT3	AGPAT3	13258	-0.04	0.12	NO
20	AGPAT5	AGPAT5	AGPAT5	13486	-0.044	0.12	NO
21	PLD2	PLD2	PLD2	13620	-0.046	0.12	NO
22	PLA2G10	PLA2G10	PLA2G10	14542	-0.066	0.084	NO
23	GPAM	GPAM	GPAM	16169	-0.12	0.022	NO
24	PLA2G4D	PLA2G4D	PLA2G4D	16789	-0.15	0.019	NO
25	AGPAT4	AGPAT4	AGPAT4	17445	-0.2	0.026	NO
26	GPD1	GPD1	GPD1	18171	-0.29	0.046	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: KEGG GLUTATHIONE METABOLISM.

Figure S86. 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 ETHER LIPID METABOLISM

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	AQP2	AQP2	AQP2	25	1.2	0.22	YES
2	AQP4	AQP4	AQP4	203	0.65	0.32	YES
3	AVPR2	AVPR2	AVPR2	362	0.54	0.41	YES
4	AVP	AVP	AVP	974	0.38	0.45	YES
5	PRKACG	PRKACG	PRKACG	1549	0.31	0.47	YES
6	CREB3L1	CREB3L1	CREB3L1	2337	0.23	0.47	NO
7	VAMP2	VAMP2	VAMP2	3322	0.17	0.45	NO
8	AQP3	AQP3	AQP3	4079	0.14	0.43	NO
9	ARHGDIB	ARHGDIB	ARHGDIB	4839	0.11	0.41	NO
10	STX4	STX4	STX4	5776	0.088	0.38	NO
11	PRKACA	PRKACA	PRKACA	6532	0.073	0.35	NO
12	CREB3	CREB3	CREB3	6542	0.072	0.37	NO
13	ADCY3	ADCY3	ADCY3	6761	0.068	0.37	NO
14	DYNC2LI1	DYNC2LI1	DYNC2LI1	6805	0.067	0.38	NO
15	CREB3L4	CREB3L4	CREB3L4	7514	0.055	0.35	NO
16	DYNC1LI1	DYNC1LI1	DYNC1LI1	7637	0.053	0.35	NO
17	ARHGDIA	ARHGDIA	ARHGDIA	7860	0.049	0.35	NO
18	DCTN5	DCTN5	DCTN5	8289	0.041	0.33	NO
19	DCTN2	DCTN2	DCTN2	8524	0.038	0.33	NO
20	DYNLL1	DYNLL1	DYNLL1	9048	0.029	0.31	NO
21	DCTN6	DCTN6	DCTN6	9434	0.024	0.29	NO
22	DYNC1I1	DYNC1I1	DYNC1I1	9822	0.018	0.27	NO
23	DCTN1	DCTN1	DCTN1	9836	0.017	0.28	NO
24	DYNLL2	DYNLL2	DYNLL2	9960	0.015	0.27	NO
25	RAB5C	RAB5C	RAB5C	10179	0.012	0.26	NO
26	RAB11B	RAB11B	RAB11B	10365	0.0087	0.25	NO
27	PRKACB	PRKACB	PRKACB	10454	0.0074	0.25	NO
28	RAB11A	RAB11A	RAB11A	10883	0.0006	0.23	NO
29	NSF	NSF	NSF	10915	0.000055	0.23	NO
30	PRKX	PRKX	PRKX	11110	-0.003	0.22	NO
31	DCTN4	DCTN4	DCTN4	11199	-0.0044	0.21	NO
32	GNAS	GNAS	GNAS	11761	-0.013	0.19	NO
33	RAB5B	RAB5B	RAB5B	11890	-0.015	0.18	NO
34	ADCY9	ADCY9	ADCY9	12931	-0.034	0.13	NO
35	RAB5A	RAB5A	RAB5A	13377	-0.042	0.12	NO
36	DYNC1H1	DYNC1H1	DYNC1H1	13393	-0.042	0.12	NO
37	DYNC1I2	DYNC1I2	DYNC1I2	13824	-0.05	0.11	NO
38	DYNC2H1	DYNC2H1	DYNC2H1	14003	-0.054	0.11	NO
39	CREB3L2	CREB3L2	CREB3L2	14062	-0.055	0.12	NO
40	CREB1	CREB1	CREB1	14824	-0.073	0.09	NO
41	ADCY6	ADCY6	ADCY6	16129	-0.12	0.042	NO
42	DYNC1LI2	DYNC1LI2	DYNC1LI2	16198	-0.12	0.06	NO
43	CREB5	CREB5	CREB5	16512	-0.13	0.067	NO
44	CREB3L3	CREB3L3	CREB3L3	18559	-0.37	0.026	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: KEGG ETHER LIPID METABOLISM.

Figure S88. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ETHER LIPID METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PYRUVATE METABOLISM

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	COX7A1	COX7A1	COX7A1	601	0.46	0.0087	YES
2	COX7B2	COX7B2	COX7B2	892	0.4	0.028	YES
3	COX6B2	COX6B2	COX6B2	1138	0.36	0.047	YES
4	COX8C	COX8C	COX8C	1200	0.35	0.074	YES
5	COX4I2	COX4I2	COX4I2	1728	0.29	0.071	YES
6	ATP6V0A4	ATP6V0A4	ATP6V0A4	1820	0.28	0.091	YES
7	ATP12A	ATP12A	ATP12A	2208	0.24	0.092	YES
8	ATP6V1E2	ATP6V1E2	ATP6V1E2	2830	0.2	0.076	YES
9	ATP4A	ATP4A	ATP4A	2950	0.19	0.087	YES
10	COX6A2	COX6A2	COX6A2	3192	0.18	0.09	YES
11	LHPP	LHPP	LHPP	3369	0.17	0.095	YES
12	NDUFS4	NDUFS4	NDUFS4	3586	0.16	0.098	YES
13	NDUFA3	NDUFA3	NDUFA3	3882	0.14	0.095	YES
14	NDUFB2	NDUFB2	NDUFB2	3938	0.14	0.1	YES
15	NDUFC1	NDUFC1	NDUFC1	3990	0.14	0.11	YES
16	NDUFB1	NDUFB1	NDUFB1	3998	0.14	0.13	YES
17	NDUFA2	NDUFA2	NDUFA2	4158	0.13	0.13	YES
18	PPA1	PPA1	PPA1	4248	0.13	0.14	YES
19	NDUFV2	NDUFV2	NDUFV2	4309	0.13	0.14	YES
20	NDUFB9	NDUFB9	NDUFB9	4343	0.13	0.15	YES
21	NDUFS7	NDUFS7	NDUFS7	4365	0.12	0.16	YES
22	ATP5H	ATP5H	ATP5H	4372	0.12	0.17	YES
23	NDUFAB1	NDUFAB1	NDUFAB1	4390	0.12	0.18	YES
24	UQCRQ	UQCRQ	UQCRQ	4485	0.12	0.19	YES
25	NDUFS6	NDUFS6	NDUFS6	4493	0.12	0.2	YES
26	COX6C	COX6C	COX6C	4516	0.12	0.21	YES
27	UQCR11	UQCR11	UQCR11	4541	0.12	0.22	YES
28	ATP5D	ATP5D	ATP5D	4625	0.12	0.22	YES
29	COX11	COX11	COX11	4663	0.12	0.23	YES
30	NDUFA8	NDUFA8	NDUFA8	4711	0.12	0.24	YES
31	COX7A2	COX7A2	COX7A2	4736	0.11	0.25	YES
32	NDUFC2	NDUFC2	NDUFC2	4744	0.11	0.26	YES
33	NDUFB7	NDUFB7	NDUFB7	4789	0.11	0.27	YES
34	NDUFB6	NDUFB6	NDUFB6	4827	0.11	0.27	YES
35	COX5B	COX5B	COX5B	4842	0.11	0.28	YES
36	NDUFS8	NDUFS8	NDUFS8	4860	0.11	0.29	YES
37	COX7C	COX7C	COX7C	4872	0.11	0.3	YES
38	UQCRHL	UQCRHL	UQCRHL	4878	0.11	0.31	YES
39	ATP6V0E2	ATP6V0E2	ATP6V0E2	4893	0.11	0.32	YES
40	COX5A	COX5A	COX5A	4955	0.11	0.32	YES
41	ATP6V1C2	ATP6V1C2	ATP6V1C2	5047	0.11	0.33	YES
42	NDUFS3	NDUFS3	NDUFS3	5105	0.1	0.34	YES
43	ATP6V0E1	ATP6V0E1	ATP6V0E1	5154	0.1	0.34	YES
44	SDHB	SDHB	SDHB	5167	0.1	0.35	YES
45	ATP5L	ATP5L	ATP5L	5195	0.1	0.36	YES
46	ATP6V1B1	ATP6V1B1	ATP6V1B1	5245	0.1	0.36	YES
47	ATP6V1F	ATP6V1F	ATP6V1F	5288	0.1	0.37	YES
48	NDUFA11	NDUFA11	NDUFA11	5298	0.099	0.38	YES
49	NDUFA5	NDUFA5	NDUFA5	5339	0.098	0.38	YES
50	NDUFB10	NDUFB10	NDUFB10	5437	0.096	0.39	YES
51	UQCRH	UQCRH	UQCRH	5513	0.094	0.39	YES
52	ATP5J2	ATP5J2	ATP5J2	5515	0.094	0.4	YES
53	SDHA	SDHA	SDHA	5728	0.089	0.4	YES
54	NDUFB3	NDUFB3	NDUFB3	5851	0.086	0.4	YES
55	ATP5E	ATP5E	ATP5E	5870	0.086	0.41	YES
56	NDUFA1	NDUFA1	NDUFA1	5957	0.084	0.41	YES
57	COX8A	COX8A	COX8A	6022	0.083	0.41	YES
58	COX17	COX17	COX17	6045	0.082	0.42	YES
59	COX6A1	COX6A1	COX6A1	6067	0.082	0.42	YES
60	NDUFA4	NDUFA4	NDUFA4	6093	0.082	0.43	YES
61	COX4I1	COX4I1	COX4I1	6163	0.08	0.43	YES
62	NDUFA7	NDUFA7	NDUFA7	6185	0.08	0.44	YES
63	NDUFS5	NDUFS5	NDUFS5	6192	0.079	0.45	YES
64	UQCRFS1	UQCRFS1	UQCRFS1	6273	0.078	0.45	YES
65	ATP5I	ATP5I	ATP5I	6338	0.076	0.45	YES
66	NDUFB8	NDUFB8	NDUFB8	6353	0.076	0.46	YES
67	ATP5O	ATP5O	ATP5O	6512	0.073	0.46	YES
68	COX6B1	COX6B1	COX6B1	6544	0.072	0.46	YES
69	SDHD	SDHD	SDHD	6643	0.07	0.46	YES
70	ATP6V1G2	ATP6V1G2	ATP6V1G2	6788	0.068	0.46	YES
71	ATP6V0B	ATP6V0B	ATP6V0B	6827	0.067	0.46	YES
72	UQCRB	UQCRB	UQCRB	6848	0.067	0.47	YES
73	NDUFV1	NDUFV1	NDUFV1	6880	0.066	0.47	YES
74	ATP5G3	ATP5G3	ATP5G3	6952	0.065	0.48	YES
75	ATP5F1	ATP5F1	ATP5F1	7148	0.061	0.47	YES
76	NDUFB5	NDUFB5	NDUFB5	7200	0.06	0.47	YES
77	NDUFB4	NDUFB4	NDUFB4	7229	0.06	0.48	YES
78	ATP6V1D	ATP6V1D	ATP6V1D	7252	0.059	0.48	YES
79	ATP6V1G1	ATP6V1G1	ATP6V1G1	7258	0.059	0.48	YES
80	ATP5C1	ATP5C1	ATP5C1	7263	0.059	0.49	YES
81	COX7B	COX7B	COX7B	7454	0.056	0.48	YES
82	NDUFA9	NDUFA9	NDUFA9	7627	0.053	0.48	YES
83	TCIRG1	TCIRG1	TCIRG1	7841	0.049	0.47	YES
84	UQCR10	UQCR10	UQCR10	7866	0.049	0.48	YES
85	ATP5G1	ATP5G1	ATP5G1	7930	0.048	0.48	YES
86	NDUFA10	NDUFA10	NDUFA10	7945	0.047	0.48	YES
87	COX7A2L	COX7A2L	COX7A2L	8032	0.046	0.48	YES
88	ATP6V0D1	ATP6V0D1	ATP6V0D1	8068	0.045	0.48	YES
89	ATP6V0C	ATP6V0C	ATP6V0C	8131	0.044	0.48	YES
90	ATP5A1	ATP5A1	ATP5A1	8177	0.043	0.48	YES
91	ATP5J	ATP5J	ATP5J	8212	0.043	0.49	YES
92	ATP6V1H	ATP6V1H	ATP6V1H	8276	0.041	0.49	YES
93	NDUFA6	NDUFA6	NDUFA6	8281	0.041	0.49	YES
94	ATP6V1E1	ATP6V1E1	ATP6V1E1	8312	0.041	0.49	YES
95	CYC1	CYC1	CYC1	8510	0.038	0.48	NO
96	NDUFV3	NDUFV3	NDUFV3	8615	0.036	0.48	NO
97	ATP6V0A1	ATP6V0A1	ATP6V0A1	8674	0.035	0.48	NO
98	PPA2	PPA2	PPA2	8760	0.034	0.48	NO
99	COX10	COX10	COX10	9105	0.029	0.47	NO
100	ATP5B	ATP5B	ATP5B	9326	0.025	0.46	NO
101	UQCRC1	UQCRC1	UQCRC1	9606	0.021	0.44	NO
102	NDUFS2	NDUFS2	NDUFS2	9617	0.021	0.44	NO
103	ATP5G2	ATP5G2	ATP5G2	9669	0.02	0.44	NO
104	UQCRC2	UQCRC2	UQCRC2	10011	0.015	0.43	NO
105	SDHC	SDHC	SDHC	10038	0.014	0.43	NO
106	COX15	COX15	COX15	10334	0.0094	0.41	NO
107	ATP6AP1	ATP6AP1	ATP6AP1	10472	0.0071	0.41	NO
108	ATP6V1B2	ATP6V1B2	ATP6V1B2	11307	-0.0058	0.36	NO
109	ATP6V0A2	ATP6V0A2	ATP6V0A2	11766	-0.013	0.34	NO
110	NDUFS1	NDUFS1	NDUFS1	12252	-0.021	0.32	NO
111	ATP6V1A	ATP6V1A	ATP6V1A	12465	-0.025	0.31	NO
112	ATP6V1C1	ATP6V1C1	ATP6V1C1	12893	-0.033	0.29	NO
113	NDUFA4L2	NDUFA4L2	NDUFA4L2	14313	-0.06	0.22	NO
114	ATP4B	ATP4B	ATP4B	16873	-0.15	0.095	NO
115	ATP6V0D2	ATP6V0D2	ATP6V0D2	17653	-0.22	0.074	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: KEGG PYRUVATE METABOLISM.

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

genes ES table in pathway: KEGG PROPANOATE 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	PDK4	PDK4	PDK4	798	0.41	0.0018	YES
2	SLC16A8	SLC16A8	SLC16A8	3319	0.17	-0.11	YES
3	UCP2	UCP2	UCP2	3489	0.16	-0.1	YES
4	NDUFS4	NDUFS4	NDUFS4	3586	0.16	-0.093	YES
5	UCP1	UCP1	UCP1	3734	0.15	-0.085	YES
6	NDUFA3	NDUFA3	NDUFA3	3882	0.14	-0.078	YES
7	NDUFB2	NDUFB2	NDUFB2	3938	0.14	-0.066	YES
8	NDUFC1	NDUFC1	NDUFC1	3990	0.14	-0.054	YES
9	NDUFB1	NDUFB1	NDUFB1	3998	0.14	-0.039	YES
10	PDK3	PDK3	PDK3	4051	0.14	-0.027	YES
11	NDUFA2	NDUFA2	NDUFA2	4158	0.13	-0.019	YES
12	ETFB	ETFB	ETFB	4243	0.13	-0.0096	YES
13	NDUFV2	NDUFV2	NDUFV2	4309	0.13	0.00037	YES
14	NDUFB9	NDUFB9	NDUFB9	4343	0.13	0.012	YES
15	NDUFS7	NDUFS7	NDUFS7	4365	0.12	0.024	YES
16	ATP5H	ATP5H	ATP5H	4372	0.12	0.037	YES
17	NDUFAB1	NDUFAB1	NDUFAB1	4390	0.12	0.049	YES
18	MDH2	MDH2	MDH2	4451	0.12	0.059	YES
19	UQCRQ	UQCRQ	UQCRQ	4485	0.12	0.07	YES
20	NDUFS6	NDUFS6	NDUFS6	4493	0.12	0.083	YES
21	COX6C	COX6C	COX6C	4516	0.12	0.094	YES
22	UQCR11	UQCR11	UQCR11	4541	0.12	0.11	YES
23	ATP5D	ATP5D	ATP5D	4625	0.12	0.11	YES
24	NDUFA8	NDUFA8	NDUFA8	4711	0.12	0.12	YES
25	NDUFC2	NDUFC2	NDUFC2	4744	0.11	0.13	YES
26	NDUFB7	NDUFB7	NDUFB7	4789	0.11	0.14	YES
27	NDUFB6	NDUFB6	NDUFB6	4827	0.11	0.15	YES
28	COX5B	COX5B	COX5B	4842	0.11	0.16	YES
29	NDUFS8	NDUFS8	NDUFS8	4860	0.11	0.17	YES
30	COX7C	COX7C	COX7C	4872	0.11	0.18	YES
31	UQCRHL	UQCRHL	UQCRHL	4878	0.11	0.2	YES
32	CYCS	CYCS	CYCS	4916	0.11	0.2	YES
33	COX5A	COX5A	COX5A	4955	0.11	0.22	YES
34	NDUFS3	NDUFS3	NDUFS3	5105	0.1	0.22	YES
35	SDHB	SDHB	SDHB	5167	0.1	0.22	YES
36	ATP5L	ATP5L	ATP5L	5195	0.1	0.24	YES
37	NDUFA11	NDUFA11	NDUFA11	5298	0.099	0.24	YES
38	NDUFA5	NDUFA5	NDUFA5	5339	0.098	0.25	YES
39	NDUFB10	NDUFB10	NDUFB10	5437	0.096	0.25	YES
40	UQCRH	UQCRH	UQCRH	5513	0.094	0.26	YES
41	ATP5J2	ATP5J2	ATP5J2	5515	0.094	0.27	YES
42	UCP3	UCP3	UCP3	5536	0.094	0.28	YES
43	NDUFA12	NDUFA12	NDUFA12	5652	0.091	0.28	YES
44	SDHA	SDHA	SDHA	5728	0.089	0.29	YES
45	NDUFA13	NDUFA13	NDUFA13	5837	0.086	0.29	YES
46	NDUFB3	NDUFB3	NDUFB3	5851	0.086	0.3	YES
47	ATP5E	ATP5E	ATP5E	5870	0.086	0.31	YES
48	NDUFA1	NDUFA1	NDUFA1	5957	0.084	0.31	YES
49	SLC16A3	SLC16A3	SLC16A3	5975	0.084	0.32	YES
50	LDHB	LDHB	LDHB	5983	0.084	0.33	YES
51	COX8A	COX8A	COX8A	6022	0.083	0.34	YES
52	COX6A1	COX6A1	COX6A1	6067	0.082	0.34	YES
53	ETFDH	ETFDH	ETFDH	6084	0.082	0.35	YES
54	NDUFA4	NDUFA4	NDUFA4	6093	0.082	0.36	YES
55	COX4I1	COX4I1	COX4I1	6163	0.08	0.36	YES
56	NDUFA7	NDUFA7	NDUFA7	6185	0.08	0.37	YES
57	NDUFS5	NDUFS5	NDUFS5	6192	0.079	0.38	YES
58	UQCRFS1	UQCRFS1	UQCRFS1	6273	0.078	0.38	YES
59	ATP5I	ATP5I	ATP5I	6338	0.076	0.39	YES
60	NDUFB8	NDUFB8	NDUFB8	6353	0.076	0.39	YES
61	PDK2	PDK2	PDK2	6432	0.075	0.4	YES
62	ATP5O	ATP5O	ATP5O	6512	0.073	0.4	YES
63	COX6B1	COX6B1	COX6B1	6544	0.072	0.41	YES
64	IDH3G	IDH3G	IDH3G	6617	0.071	0.41	YES
65	SDHD	SDHD	SDHD	6643	0.07	0.42	YES
66	UQCRB	UQCRB	UQCRB	6848	0.067	0.41	YES
67	ADHFE1	ADHFE1	ADHFE1	6876	0.066	0.42	YES
68	NDUFV1	NDUFV1	NDUFV1	6880	0.066	0.42	YES
69	ATP5F1	ATP5F1	ATP5F1	7148	0.061	0.42	YES
70	NDUFB5	NDUFB5	NDUFB5	7200	0.06	0.42	YES
71	NDUFB4	NDUFB4	NDUFB4	7229	0.06	0.43	YES
72	ATP5C1	ATP5C1	ATP5C1	7263	0.059	0.43	YES
73	ETFA	ETFA	ETFA	7406	0.056	0.43	YES
74	COX7B	COX7B	COX7B	7454	0.056	0.43	YES
75	IDH3A	IDH3A	IDH3A	7612	0.053	0.43	YES
76	NDUFA9	NDUFA9	NDUFA9	7627	0.053	0.44	YES
77	BSG	BSG	BSG	7919	0.048	0.42	YES
78	ATP5G1	ATP5G1	ATP5G1	7930	0.048	0.43	YES
79	NDUFA10	NDUFA10	NDUFA10	7945	0.047	0.43	YES
80	COX7A2L	COX7A2L	COX7A2L	8032	0.046	0.43	YES
81	ATP5A1	ATP5A1	ATP5A1	8177	0.043	0.43	YES
82	ATP5J	ATP5J	ATP5J	8212	0.043	0.43	YES
83	NDUFA6	NDUFA6	NDUFA6	8281	0.041	0.43	YES
84	LDHA	LDHA	LDHA	8339	0.04	0.44	YES
85	SUCLG1	SUCLG1	SUCLG1	8368	0.04	0.44	YES
86	SUCLA2	SUCLA2	SUCLA2	8480	0.038	0.44	YES
87	CYC1	CYC1	CYC1	8510	0.038	0.44	YES
88	IDH3B	IDH3B	IDH3B	8554	0.037	0.44	YES
89	OGDH	OGDH	OGDH	8561	0.037	0.44	YES
90	NDUFV3	NDUFV3	NDUFV3	8615	0.036	0.44	YES
91	DLD	DLD	DLD	8935	0.031	0.43	NO
92	ATP5B	ATP5B	ATP5B	9326	0.025	0.41	NO
93	UQCRC1	UQCRC1	UQCRC1	9606	0.021	0.4	NO
94	NDUFS2	NDUFS2	NDUFS2	9617	0.021	0.4	NO
95	FH	FH	FH	9709	0.019	0.4	NO
96	DLAT	DLAT	DLAT	9932	0.016	0.39	NO
97	UQCRC2	UQCRC2	UQCRC2	10011	0.015	0.39	NO
98	SDHC	SDHC	SDHC	10038	0.014	0.39	NO
99	PDHB	PDHB	PDHB	10459	0.0074	0.37	NO
100	PDHX	PDHX	PDHX	10482	0.007	0.37	NO
101	D2HGDH	D2HGDH	D2HGDH	10491	0.0067	0.37	NO
102	ACO2	ACO2	ACO2	11345	-0.0064	0.32	NO
103	PDHA1	PDHA1	PDHA1	11564	-0.0097	0.31	NO
104	CS	CS	CS	11662	-0.011	0.31	NO
105	IDH2	IDH2	IDH2	11749	-0.013	0.3	NO
106	SUCLG2	SUCLG2	SUCLG2	11769	-0.013	0.3	NO
107	NNT	NNT	NNT	12057	-0.018	0.29	NO
108	NDUFS1	NDUFS1	NDUFS1	12252	-0.021	0.28	NO
109	IDH1	IDH1	IDH1	12510	-0.026	0.27	NO
110	DLST	DLST	DLST	12710	-0.03	0.26	NO
111	SLC16A1	SLC16A1	SLC16A1	13205	-0.038	0.24	NO
112	PDP1	PDP1	PDP1	13629	-0.047	0.23	NO
113	PDK1	PDK1	PDK1	13697	-0.048	0.23	NO
114	L2HGDH	L2HGDH	L2HGDH	14882	-0.075	0.17	NO
115	PDP2	PDP2	PDP2	17325	-0.19	0.064	NO
116	PDPR	PDPR	PDPR	17953	-0.26	0.058	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 PROPANOATE METABOLISM.

Figure S92. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PROPANOATE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG VASOPRESSIN REGULATED WATER REABSORPTION

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	LDHC	LDHC	LDHC	424	0.52	0.12	YES
2	LDHAL6B	LDHAL6B	LDHAL6B	472	0.5	0.25	YES
3	LDHAL6A	LDHAL6A	LDHAL6A	544	0.48	0.38	YES
4	ACSS1	ACSS1	ACSS1	968	0.38	0.46	YES
5	ACAT1	ACAT1	ACAT1	2853	0.2	0.41	NO
6	ACSS3	ACSS3	ACSS3	4287	0.13	0.37	NO
7	MCEE	MCEE	MCEE	5027	0.11	0.36	NO
8	PCCA	PCCA	PCCA	5075	0.1	0.39	NO
9	ALDH2	ALDH2	ALDH2	5731	0.089	0.38	NO
10	LDHB	LDHB	LDHB	5983	0.084	0.39	NO
11	ECHS1	ECHS1	ECHS1	6272	0.078	0.39	NO
12	MLYCD	MLYCD	MLYCD	6361	0.076	0.41	NO
13	ALDH3A2	ALDH3A2	ALDH3A2	6664	0.07	0.41	NO
14	HIBCH	HIBCH	HIBCH	7222	0.06	0.4	NO
15	ACADM	ACADM	ACADM	7262	0.059	0.41	NO
16	PCCB	PCCB	PCCB	7340	0.058	0.42	NO
17	LDHA	LDHA	LDHA	8339	0.04	0.38	NO
18	SUCLG1	SUCLG1	SUCLG1	8368	0.04	0.39	NO
19	SUCLA2	SUCLA2	SUCLA2	8480	0.038	0.4	NO
20	HADHA	HADHA	HADHA	8991	0.03	0.38	NO
21	ALDH9A1	ALDH9A1	ALDH9A1	9205	0.027	0.38	NO
22	ALDH1B1	ALDH1B1	ALDH1B1	9904	0.016	0.34	NO
23	ABAT	ABAT	ABAT	10346	0.009	0.32	NO
24	ACSS2	ACSS2	ACSS2	10406	0.008	0.32	NO
25	ACAT2	ACAT2	ACAT2	10588	0.0051	0.31	NO
26	ACACB	ACACB	ACACB	11080	-0.0024	0.29	NO
27	SUCLG2	SUCLG2	SUCLG2	11769	-0.013	0.26	NO
28	ALDH7A1	ALDH7A1	ALDH7A1	11846	-0.014	0.26	NO
29	MUT	MUT	MUT	12705	-0.03	0.22	NO
30	ACACA	ACACA	ACACA	15602	-0.096	0.092	NO
31	ALDH6A1	ALDH6A1	ALDH6A1	16428	-0.13	0.083	NO
32	EHHADH	EHHADH	EHHADH	17448	-0.2	0.084	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 VASOPRESSIN REGULATED WATER REABSORPTION.

Figure S94. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VASOPRESSIN REGULATED WATER REABSORPTION, 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 PARKINSONS DISEASE

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	PLA2G2A	PLA2G2A	PLA2G2A	36	1.1	0.18	YES
2	ENPP6	ENPP6	ENPP6	80	0.9	0.33	YES
3	PLA2G5	PLA2G5	PLA2G5	103	0.82	0.47	YES
4	PLA2G1B	PLA2G1B	PLA2G1B	684	0.44	0.51	YES
5	PLA2G2D	PLA2G2D	PLA2G2D	1179	0.35	0.54	YES
6	PLA2G4A	PLA2G4A	PLA2G4A	1492	0.31	0.57	YES
7	PPAP2B	PPAP2B	PPAP2B	2053	0.26	0.59	YES
8	PLA2G2F	PLA2G2F	PLA2G2F	4201	0.13	0.5	NO
9	PLA2G7	PLA2G7	PLA2G7	4803	0.11	0.48	NO
10	PPAP2A	PPAP2A	PPAP2A	5222	0.1	0.48	NO
11	PLA2G4E	PLA2G4E	PLA2G4E	6455	0.074	0.42	NO
12	CHPT1	CHPT1	CHPT1	6498	0.074	0.44	NO
13	PAFAH1B3	PAFAH1B3	PAFAH1B3	7727	0.051	0.38	NO
14	PLA2G12A	PLA2G12A	PLA2G12A	8001	0.046	0.37	NO
15	LPCAT4	LPCAT4	LPCAT4	8447	0.039	0.36	NO
16	ENPP2	ENPP2	ENPP2	9504	0.022	0.3	NO
17	PLD1	PLD1	PLD1	11020	-0.0015	0.22	NO
18	PAFAH1B1	PAFAH1B1	PAFAH1B1	11040	-0.0017	0.22	NO
19	LPCAT1	LPCAT1	LPCAT1	11413	-0.0075	0.2	NO
20	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	12266	-0.022	0.16	NO
21	LPCAT2	LPCAT2	LPCAT2	12593	-0.027	0.15	NO
22	PAFAH2	PAFAH2	PAFAH2	12770	-0.031	0.15	NO
23	PLA2G6	PLA2G6	PLA2G6	13388	-0.042	0.12	NO
24	PLD2	PLD2	PLD2	13620	-0.046	0.12	NO
25	PLA2G10	PLA2G10	PLA2G10	14542	-0.066	0.08	NO
26	AGPS	AGPS	AGPS	14563	-0.066	0.09	NO
27	PPAP2C	PPAP2C	PPAP2C	14958	-0.077	0.081	NO
28	PLA2G3	PLA2G3	PLA2G3	16866	-0.15	0.0061	NO
29	PAFAH1B2	PAFAH1B2	PAFAH1B2	17154	-0.17	0.02	NO
30	PLA2G12B	PLA2G12B	PLA2G12B	18854	-0.49	0.01	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 PARKINSONS DISEASE.

Figure S96. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PARKINSONS DISEASE, 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 PRION DISEASES

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	GSTA1	GSTA1	GSTA1	33	1.2	0.15	YES
2	GSTA3	GSTA3	GSTA3	112	0.79	0.24	YES
3	GSTM5	GSTM5	GSTM5	121	0.78	0.34	YES
4	GSTM3	GSTM3	GSTM3	165	0.71	0.43	YES
5	GSTA2	GSTA2	GSTA2	547	0.48	0.47	YES
6	GGT5	GGT5	GGT5	1432	0.32	0.47	YES
7	GPX5	GPX5	GPX5	1664	0.29	0.49	YES
8	GPX3	GPX3	GPX3	1783	0.28	0.52	YES
9	GSTK1	GSTK1	GSTK1	3577	0.16	0.45	YES
10	GSTA4	GSTA4	GSTA4	3937	0.14	0.45	YES
11	MGST2	MGST2	MGST2	3963	0.14	0.47	YES
12	GSTZ1	GSTZ1	GSTZ1	4154	0.13	0.47	YES
13	GSTM2	GSTM2	GSTM2	4366	0.12	0.48	YES
14	GSTM4	GSTM4	GSTM4	4417	0.12	0.49	YES
15	G6PD	G6PD	G6PD	4822	0.11	0.48	YES
16	GSTT2	GSTT2	GSTT2	5107	0.1	0.48	YES
17	SRM	SRM	SRM	5150	0.1	0.49	YES
18	LAP3	LAP3	LAP3	5186	0.1	0.5	YES
19	GSTM1	GSTM1	GSTM1	5191	0.1	0.52	YES
20	MGST3	MGST3	MGST3	5204	0.1	0.53	YES
21	GSTT1	GSTT1	GSTT1	5578	0.093	0.52	YES
22	GSTO1	GSTO1	GSTO1	5650	0.091	0.53	YES
23	GSTO2	GSTO2	GSTO2	5832	0.086	0.53	YES
24	GPX1	GPX1	GPX1	6267	0.078	0.52	NO
25	GPX2	GPX2	GPX2	6366	0.076	0.52	NO
26	PGD	PGD	PGD	6496	0.074	0.53	NO
27	GPX4	GPX4	GPX4	6644	0.07	0.53	NO
28	GCLM	GCLM	GCLM	6957	0.064	0.52	NO
29	GSS	GSS	GSS	7910	0.048	0.48	NO
30	GGT6	GGT6	GGT6	8605	0.036	0.44	NO
31	MGST1	MGST1	MGST1	8667	0.035	0.44	NO
32	GPX7	GPX7	GPX7	9187	0.027	0.42	NO
33	GSTP1	GSTP1	GSTP1	9295	0.026	0.42	NO
34	GGCT	GGCT	GGCT	9691	0.02	0.4	NO
35	TXNDC12	TXNDC12	TXNDC12	9935	0.016	0.39	NO
36	OPLAH	OPLAH	OPLAH	10386	0.0084	0.37	NO
37	ODC1	ODC1	ODC1	10811	0.0018	0.34	NO
38	RRM1	RRM1	RRM1	11699	-0.012	0.3	NO
39	IDH2	IDH2	IDH2	11749	-0.013	0.3	NO
40	IDH1	IDH1	IDH1	12510	-0.026	0.26	NO
41	GSR	GSR	GSR	12800	-0.031	0.25	NO
42	GGT1	GGT1	GGT1	12843	-0.032	0.25	NO
43	RRM2B	RRM2B	RRM2B	13238	-0.039	0.24	NO
44	SMS	SMS	SMS	13775	-0.049	0.22	NO
45	RRM2	RRM2	RRM2	13826	-0.05	0.22	NO
46	GGT7	GGT7	GGT7	13921	-0.052	0.22	NO
47	GCLC	GCLC	GCLC	14144	-0.057	0.22	NO
48	GPX6	GPX6	GPX6	15609	-0.096	0.15	NO
49	ANPEP	ANPEP	ANPEP	17730	-0.23	0.07	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 PRION DISEASES.

Figure S98. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PRION DISEASES, 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 PATHOGENIC ESCHERICHIA COLI INFECTION

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	FAM153A	FAM153A	FAM153A	92	0.87	0.09	YES
2	RPS28	RPS28	RPS28	1233	0.34	0.068	YES
3	RPS27	RPS27	RPS27	1516	0.31	0.087	YES
4	RPSAP9	RPSAP9	RPSAP9	3144	0.18	0.021	YES
5	SEC11C	SEC11C	SEC11C	3429	0.16	0.024	YES
6	RPL3L	RPL3L	RPL3L	3712	0.15	0.025	YES
7	RPL39	RPL39	RPL39	3850	0.15	0.034	YES
8	RPL26L1	RPL26L1	RPL26L1	3935	0.14	0.045	YES
9	RPL38	RPL38	RPL38	4096	0.14	0.052	YES
10	RPL34	RPL34	RPL34	4238	0.13	0.058	YES
11	SSR4	SSR4	SSR4	4331	0.13	0.067	YES
12	RPL36A	RPL36A	RPL36A	4422	0.12	0.076	YES
13	SPCS2	SPCS2	SPCS2	4557	0.12	0.082	YES
14	RPL23A	RPL23A	RPL23A	4649	0.12	0.09	YES
15	RPS26	RPS26	RPS26	4684	0.12	0.1	YES
16	RPS14	RPS14	RPS14	4793	0.11	0.11	YES
17	RPS23	RPS23	RPS23	4834	0.11	0.12	YES
18	FAU	FAU	FAU	4968	0.11	0.12	YES
19	RPL18A	RPL18A	RPL18A	5052	0.1	0.13	YES
20	RPS13	RPS13	RPS13	5064	0.1	0.14	YES
21	RPS4Y1	RPS4Y1	RPS4Y1	5118	0.1	0.15	YES
22	RPL37	RPL37	RPL37	5123	0.1	0.16	YES
23	SEC61G	SEC61G	SEC61G	5158	0.1	0.17	YES
24	RPLP2	RPLP2	RPLP2	5213	0.1	0.18	YES
25	RPL26	RPL26	RPL26	5248	0.1	0.19	YES
26	RPS21	RPS21	RPS21	5408	0.097	0.19	YES
27	RPL27	RPL27	RPL27	5505	0.094	0.2	YES
28	RPSA	RPSA	RPSA	5525	0.094	0.2	YES
29	RPL28	RPL28	RPL28	5531	0.094	0.21	YES
30	RPL36	RPL36	RPL36	5639	0.091	0.22	YES
31	RPS27A	RPS27A	RPS27A	5683	0.09	0.23	YES
32	RPL35	RPL35	RPL35	5691	0.09	0.24	YES
33	RPS16	RPS16	RPS16	5757	0.089	0.24	YES
34	SEC61B	SEC61B	SEC61B	5787	0.088	0.25	YES
35	RPL12	RPL12	RPL12	5796	0.088	0.26	YES
36	RPL7A	RPL7A	RPL7A	5846	0.086	0.27	YES
37	RPS3	RPS3	RPS3	5949	0.084	0.27	YES
38	RPS5	RPS5	RPS5	5980	0.084	0.28	YES
39	RPL23	RPL23	RPL23	6010	0.083	0.28	YES
40	RPS29	RPS29	RPS29	6011	0.083	0.29	YES
41	LOC653566	LOC653566	LOC653566	6026	0.083	0.3	YES
42	RPS25	RPS25	RPS25	6044	0.082	0.31	YES
43	RPS9	RPS9	RPS9	6076	0.082	0.32	YES
44	RPS12	RPS12	RPS12	6150	0.08	0.32	YES
45	RPS3A	RPS3A	RPS3A	6206	0.079	0.33	YES
46	RPL18	RPL18	RPL18	6210	0.079	0.34	YES
47	RPS15	RPS15	RPS15	6251	0.078	0.34	YES
48	RPS19	RPS19	RPS19	6282	0.078	0.35	YES
49	RPL8	RPL8	RPL8	6303	0.077	0.36	YES
50	RPL11	RPL11	RPL11	6390	0.075	0.36	YES
51	RPS10	RPS10	RPS10	6408	0.075	0.37	YES
52	UBA52	UBA52	UBA52	6460	0.074	0.37	YES
53	RPL19	RPL19	RPL19	6529	0.073	0.38	YES
54	RPL31	RPL31	RPL31	6533	0.073	0.39	YES
55	RPL37A	RPL37A	RPL37A	6541	0.072	0.39	YES
56	RPL24	RPL24	RPL24	6553	0.072	0.4	YES
57	RPL10A	RPL10A	RPL10A	6620	0.071	0.4	YES
58	RPS6	RPS6	RPS6	6753	0.068	0.41	YES
59	RPS24	RPS24	RPS24	6819	0.067	0.41	YES
60	RPL27A	RPL27A	RPL27A	6863	0.066	0.42	YES
61	RPS18	RPS18	RPS18	6948	0.065	0.42	YES
62	SRPRB	SRPRB	SRPRB	6971	0.064	0.42	YES
63	RPS8	RPS8	RPS8	6973	0.064	0.43	YES
64	RPL14	RPL14	RPL14	6977	0.064	0.44	YES
65	RPL13	RPL13	RPL13	7011	0.063	0.44	YES
66	RPL13A	RPL13A	RPL13A	7016	0.063	0.45	YES
67	SRPR	SRPR	SRPR	7135	0.061	0.45	YES
68	SRP19	SRP19	SRP19	7146	0.061	0.46	YES
69	RPL21	RPL21	RPL21	7235	0.06	0.46	YES
70	RPL41	RPL41	RPL41	7246	0.059	0.46	YES
71	RPS15A	RPS15A	RPS15A	7266	0.059	0.47	YES
72	RPL17	RPL17	RPL17	7351	0.057	0.47	YES
73	RPL10	RPL10	RPL10	7371	0.057	0.48	YES
74	RPLP1	RPLP1	RPLP1	7381	0.057	0.48	YES
75	RPL30	RPL30	RPL30	7404	0.056	0.49	YES
76	RPL32	RPL32	RPL32	7418	0.056	0.49	YES
77	RPL35A	RPL35A	RPL35A	7529	0.055	0.49	YES
78	RPS20	RPS20	RPS20	7550	0.054	0.5	YES
79	RPS11	RPS11	RPS11	7562	0.054	0.5	YES
80	RPS4X	RPS4X	RPS4X	7564	0.054	0.51	YES
81	RPLP0	RPLP0	RPLP0	7588	0.054	0.51	YES
82	RPS7	RPS7	RPS7	7607	0.053	0.52	YES
83	RPL3	RPL3	RPL3	7641	0.053	0.52	YES
84	RPS17	RPS17	RPS17	7733	0.051	0.52	YES
85	RPL22	RPL22	RPL22	7901	0.048	0.52	NO
86	RPS2	RPS2	RPS2	7977	0.046	0.52	NO
87	RPL29	RPL29	RPL29	8109	0.044	0.52	NO
88	RPL5	RPL5	RPL5	8164	0.043	0.52	NO
89	RPL6	RPL6	RPL6	8295	0.041	0.52	NO
90	RPL4	RPL4	RPL4	8809	0.033	0.5	NO
91	SRP14	SRP14	SRP14	8818	0.033	0.5	NO
92	SRP54	SRP54	SRP54	8836	0.033	0.5	NO
93	SPCS1	SPCS1	SPCS1	8869	0.032	0.5	NO
94	DDOST	DDOST	DDOST	8896	0.032	0.5	NO
95	RPL15	RPL15	RPL15	9147	0.028	0.49	NO
96	RPL7	RPL7	RPL7	9194	0.027	0.5	NO
97	SRP68	SRP68	SRP68	9695	0.02	0.47	NO
98	RPN1	RPN1	RPN1	10088	0.013	0.45	NO
99	RPN2	RPN2	RPN2	10253	0.01	0.44	NO
100	SSR2	SSR2	SSR2	10335	0.0093	0.44	NO
101	RPL9	RPL9	RPL9	10500	0.0066	0.43	NO
102	SSR3	SSR3	SSR3	10527	0.0062	0.43	NO
103	SRP72	SRP72	SRP72	10553	0.0057	0.43	NO
104	SPCS3	SPCS3	SPCS3	10634	0.0045	0.43	NO
105	SEC11A	SEC11A	SEC11A	10672	0.0039	0.43	NO
106	SSR1	SSR1	SSR1	12183	-0.02	0.35	NO
107	SEC61A1	SEC61A1	SEC61A1	12192	-0.02	0.35	NO
108	SRP9	SRP9	SRP9	12375	-0.024	0.34	NO
109	SEC61A2	SEC61A2	SEC61A2	13330	-0.041	0.3	NO
110	TRAM1	TRAM1	TRAM1	13357	-0.042	0.3	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 PATHOGENIC ESCHERICHIA COLI INFECTION.

Figure S100. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PATHOGENIC ESCHERICHIA COLI INFECTION, 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 clus6 enriched pathways

Table 8. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus6. 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 ALANINE ASPARTATE AND GLUTAMATE METABOLISM	32	genes.ES.table	0.58	1.6	0.0081	0.72	0.84	0.38	0.18	0.31	0.28	0.18
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	44	genes.ES.table	0.54	1.9	0.0057	0.8	0.17	0.57	0.33	0.38	0	0.15
KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS	25	genes.ES.table	0.49	1.7	0.016	0.67	0.64	0.64	0.37	0.4	0.18	0.15
KEGG PPAR SIGNALING PATHWAY	68	genes.ES.table	0.6	1.7	0	0.66	0.66	0.43	0.18	0.35	0.18	0.15
KEGG PEROXISOME	76	genes.ES.table	0.49	1.8	0.012	0.57	0.51	0.45	0.26	0.33	0.12	0.13
ST WNT BETA CATENIN PATHWAY	33	genes.ES.table	0.6	1.7	0.014	0.66	0.77	0.21	0.076	0.2	0.22	0.16
PID HNF3BPATHWAY	44	genes.ES.table	0.8	1.8	0	0.7	0.35	0.48	0.078	0.44	0	0.14
PID P75NTRPATHWAY	69	genes.ES.table	0.46	1.6	0.012	0.75	0.83	0.26	0.22	0.2	0.28	0.18
PID SYNDECAN 4 PATHWAY	31	genes.ES.table	0.64	1.7	0.0058	0.68	0.76	0.39	0.18	0.32	0.22	0.16
REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION	25	genes.ES.table	0.71	1.8	0	0.52	0.41	0.24	0.034	0.23	0	0.12

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

Table S51. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HMGCS2	HMGCS2	HMGCS2	35	1.4	0.21	YES
2	ALDH1B1	ALDH1B1	ALDH1B1	1316	0.47	0.21	YES
3	EHHADH	EHHADH	EHHADH	1811	0.39	0.24	YES
4	BCAT2	BCAT2	BCAT2	2519	0.3	0.25	YES
5	ABAT	ABAT	ABAT	2750	0.28	0.28	YES
6	ACAA1	ACAA1	ACAA1	2769	0.28	0.32	YES
7	ALDH6A1	ALDH6A1	ALDH6A1	3090	0.25	0.34	YES
8	PCCA	PCCA	PCCA	3350	0.23	0.36	YES
9	ACAA2	ACAA2	ACAA2	3504	0.22	0.38	YES
10	HMGCS1	HMGCS1	HMGCS1	3683	0.21	0.4	YES
11	MCCC1	MCCC1	MCCC1	3942	0.19	0.42	YES
12	BCAT1	BCAT1	BCAT1	4093	0.18	0.43	YES
13	ALDH2	ALDH2	ALDH2	4194	0.18	0.45	YES
14	BCKDHB	BCKDHB	BCKDHB	4441	0.16	0.46	YES
15	ACADSB	ACADSB	ACADSB	4648	0.15	0.48	YES
16	ECHS1	ECHS1	ECHS1	4666	0.15	0.5	YES
17	ALDH3A2	ALDH3A2	ALDH3A2	4910	0.14	0.5	YES
18	HMGCL	HMGCL	HMGCL	4983	0.13	0.52	YES
19	HIBCH	HIBCH	HIBCH	5639	0.11	0.5	YES
20	HIBADH	HIBADH	HIBADH	5785	0.1	0.51	YES
21	MCEE	MCEE	MCEE	5791	0.1	0.52	YES
22	OXCT2	OXCT2	OXCT2	5802	0.1	0.54	YES
23	HADHA	HADHA	HADHA	6265	0.084	0.52	YES
24	ACAD8	ACAD8	ACAD8	6345	0.082	0.53	YES
25	ACAT1	ACAT1	ACAT1	6367	0.081	0.54	YES
26	HADH	HADH	HADH	6653	0.072	0.54	NO
27	MUT	MUT	MUT	7857	0.037	0.48	NO
28	DBT	DBT	DBT	8198	0.028	0.47	NO
29	ALDH7A1	ALDH7A1	ALDH7A1	8627	0.018	0.45	NO
30	BCKDHA	BCKDHA	BCKDHA	9085	0.0071	0.42	NO
31	AOX1	AOX1	AOX1	9142	0.006	0.42	NO
32	MCCC2	MCCC2	MCCC2	9215	0.0042	0.42	NO
33	IVD	IVD	IVD	9406	0.00026	0.41	NO
34	ACADS	ACADS	ACADS	9482	-0.0016	0.41	NO
35	HSD17B10	HSD17B10	HSD17B10	9726	-0.0069	0.39	NO
36	DLD	DLD	DLD	9932	-0.011	0.38	NO
37	HADHB	HADHB	HADHB	10031	-0.014	0.38	NO
38	ALDH9A1	ALDH9A1	ALDH9A1	10541	-0.025	0.36	NO
39	PCCB	PCCB	PCCB	10885	-0.033	0.35	NO
40	OXCT1	OXCT1	OXCT1	11723	-0.053	0.31	NO
41	ACADM	ACADM	ACADM	12509	-0.073	0.28	NO
42	ACAT2	ACAT2	ACAT2	13232	-0.092	0.25	NO
43	AUH	AUH	AUH	13765	-0.11	0.24	NO
44	IL4I1	IL4I1	IL4I1	16526	-0.24	0.13	NO

Figure S101. 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 S102. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION

Table S52. 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	FGF17	FGF17	FGF17	435	0.75	0.14	YES
2	FGF23	FGF23	FGF23	651	0.64	0.28	YES
3	FGF8	FGF8	FGF8	993	0.54	0.38	YES
4	FGF20	FGF20	FGF20	1190	0.49	0.48	YES
5	FGF5	FGF5	FGF5	1280	0.47	0.58	YES
6	FGF1	FGF1	FGF1	1451	0.44	0.67	YES
7	PIK3R1	PIK3R1	PIK3R1	4243	0.17	0.56	NO
8	CUX1	CUX1	CUX1	5872	0.097	0.5	NO
9	MYO18A	MYO18A	MYO18A	6110	0.089	0.5	NO
10	FGFR1	FGFR1	FGFR1	6691	0.071	0.49	NO
11	FGFR1OP2	FGFR1OP2	FGFR1OP2	7238	0.054	0.47	NO
12	GRB2	GRB2	GRB2	7340	0.051	0.48	NO
13	FGF4	FGF4	FGF4	8354	0.025	0.43	NO
14	FGF2	FGF2	FGF2	8388	0.024	0.43	NO
15	PLCG1	PLCG1	PLCG1	8675	0.017	0.42	NO
16	ZMYM2	ZMYM2	ZMYM2	9281	0.003	0.39	NO
17	CPSF6	CPSF6	CPSF6	9770	-0.0079	0.37	NO
18	BCR	BCR	BCR	9905	-0.011	0.36	NO
19	TRIM24	TRIM24	TRIM24	10428	-0.022	0.34	NO
20	PIK3CA	PIK3CA	PIK3CA	10501	-0.024	0.34	NO
21	STAT1	STAT1	STAT1	10875	-0.033	0.33	NO
22	FGF9	FGF9	FGF9	11848	-0.056	0.29	NO
23	STAT3	STAT3	STAT3	11902	-0.057	0.3	NO
24	STAT5B	STAT5B	STAT5B	12131	-0.063	0.3	NO
25	FGFR1OP	FGFR1OP	FGFR1OP	12338	-0.069	0.31	NO
26	STAT5A	STAT5A	STAT5A	13533	-0.1	0.27	NO
27	GAB2	GAB2	GAB2	13625	-0.1	0.28	NO

Figure S103. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

Figure S104. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS

Table S53. 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	SLC2A2	SLC2A2	SLC2A2	3	1.9	0.082	YES
2	PDX1	PDX1	PDX1	36	1.4	0.14	YES
3	HNF1A	HNF1A	HNF1A	56	1.3	0.2	YES
4	AFP	AFP	AFP	69	1.3	0.25	YES
5	FOXA2	FOXA2	FOXA2	75	1.3	0.31	YES
6	TTR	TTR	TTR	79	1.2	0.36	YES
7	F2	F2	F2	80	1.2	0.42	YES
8	HNF4A	HNF4A	HNF4A	110	1.2	0.46	YES
9	FOXA1	FOXA1	FOXA1	112	1.1	0.51	YES
10	APOA1	APOA1	APOA1	122	1.1	0.56	YES
11	HNF1B	HNF1B	HNF1B	190	0.98	0.6	YES
12	PKLR	PKLR	PKLR	228	0.93	0.64	YES
13	ALB	ALB	ALB	250	0.9	0.67	YES
14	FOXF1	FOXF1	FOXF1	584	0.67	0.68	YES
15	IGFBP1	IGFBP1	IGFBP1	787	0.6	0.7	YES
16	FOXA3	FOXA3	FOXA3	814	0.59	0.72	YES
17	NKX2-1	NKX2-1	NKX2-1	908	0.56	0.74	YES
18	ALDOB	ALDOB	ALDOB	930	0.56	0.77	YES
19	PCK1	PCK1	PCK1	1063	0.52	0.78	YES
20	BDH1	BDH1	BDH1	1294	0.47	0.79	YES
21	DLK1	DLK1	DLK1	1494	0.43	0.8	YES
22	KCNJ11	KCNJ11	KCNJ11	1945	0.37	0.79	NO
23	GCK	GCK	GCK	3610	0.21	0.71	NO
24	HMGCS1	HMGCS1	HMGCS1	3683	0.21	0.72	NO
25	ACADVL	ACADVL	ACADVL	5595	0.11	0.62	NO
26	AKT1	AKT1	AKT1	5809	0.099	0.61	NO
27	CEBPA	CEBPA	CEBPA	6537	0.075	0.58	NO
28	HADH	HADH	HADH	6653	0.072	0.58	NO
29	CEBPB	CEBPB	CEBPB	7329	0.052	0.54	NO
30	NF1	NF1	NF1	7807	0.038	0.52	NO
31	NR3C1	NR3C1	NR3C1	7889	0.036	0.52	NO
32	ALAS1	ALAS1	ALAS1	8216	0.028	0.5	NO
33	CPT1B	CPT1B	CPT1B	9016	0.009	0.46	NO
34	SP1	SP1	SP1	10212	-0.018	0.4	NO
35	TFRC	TFRC	TFRC	10814	-0.032	0.37	NO
36	CREB1	CREB1	CREB1	10857	-0.033	0.37	NO
37	CPT1C	CPT1C	CPT1C	12323	-0.068	0.29	NO
38	ACADM	ACADM	ACADM	12509	-0.073	0.28	NO
39	CEBPD	CEBPD	CEBPD	13389	-0.096	0.24	NO
40	UCP2	UCP2	UCP2	13797	-0.11	0.23	NO
41	TAT	TAT	TAT	14806	-0.14	0.18	NO
42	CPT1A	CPT1A	CPT1A	16710	-0.26	0.091	NO
43	ABCC8	ABCC8	ABCC8	16834	-0.27	0.096	NO
44	G6PC	G6PC	G6PC	18258	-0.48	0.042	NO

Figure S105. 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 GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS.

Figure S106. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR 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 PPAR SIGNALING PATHWAY

Table S54. 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	SEMA6D	SEMA6D	SEMA6D	843	0.58	0.12	YES
2	PGAP1	PGAP1	PGAP1	1467	0.44	0.2	YES
3	PIGF	PIGF	PIGF	2793	0.28	0.21	YES
4	PIGQ	PIGQ	PIGQ	3393	0.23	0.24	YES
5	PIGU	PIGU	PIGU	3482	0.22	0.3	YES
6	PIGS	PIGS	PIGS	3759	0.2	0.34	YES
7	PLAUR	PLAUR	PLAUR	4046	0.18	0.37	YES
8	PIGT	PIGT	PIGT	4616	0.15	0.39	YES
9	PIGX	PIGX	PIGX	4946	0.14	0.41	YES
10	PIGM	PIGM	PIGM	5507	0.11	0.41	YES
11	PIGK	PIGK	PIGK	5779	0.1	0.42	YES
12	PIGN	PIGN	PIGN	5807	0.099	0.45	YES
13	DPM3	DPM3	DPM3	5957	0.094	0.46	YES
14	GPAA1	GPAA1	GPAA1	6146	0.088	0.48	YES
15	DPM1	DPM1	DPM1	6385	0.08	0.49	YES
16	PIGC	PIGC	PIGC	6479	0.077	0.5	YES
17	PIGO	PIGO	PIGO	6959	0.063	0.5	YES
18	DPM2	DPM2	DPM2	7044	0.06	0.51	YES
19	PIGA	PIGA	PIGA	8583	0.019	0.43	NO
20	PIGV	PIGV	PIGV	9882	-0.01	0.37	NO
21	PIGW	PIGW	PIGW	10598	-0.027	0.34	NO
22	PIGH	PIGH	PIGH	10684	-0.029	0.34	NO
23	PIGG	PIGG	PIGG	10865	-0.033	0.34	NO
24	PIGP	PIGP	PIGP	11929	-0.058	0.3	NO
25	PIGB	PIGB	PIGB	13505	-0.099	0.25	NO
26	PIGL	PIGL	PIGL	15200	-0.16	0.2	NO

Figure S107. 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 PPAR SIGNALING PATHWAY.

Figure S108. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PPAR SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PEROXISOME

Table S55. 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	F7	F7	F7	53	1.4	0.16	YES
2	F2	F2	F2	80	1.2	0.32	YES
3	PROC	PROC	PROC	154	1	0.44	YES
4	F10	F10	F10	182	0.99	0.57	YES
5	ARSE	ARSE	ARSE	565	0.68	0.63	YES
6	PROZ	PROZ	PROZ	639	0.65	0.71	YES
7	ARSI	ARSI	ARSI	3408	0.23	0.59	NO
8	ARSH	ARSH	ARSH	4251	0.17	0.57	NO
9	ARSA	ARSA	ARSA	4569	0.15	0.57	NO
10	SUMF1	SUMF1	SUMF1	4686	0.15	0.58	NO
11	ARSJ	ARSJ	ARSJ	4807	0.14	0.6	NO
12	GGCX	GGCX	GGCX	4971	0.14	0.6	NO
13	ARSK	ARSK	ARSK	5475	0.11	0.59	NO
14	EIF5A2	EIF5A2	EIF5A2	5599	0.11	0.6	NO
15	PROS1	PROS1	PROS1	5978	0.093	0.59	NO
16	FURIN	FURIN	FURIN	6349	0.082	0.58	NO
17	ARSB	ARSB	ARSB	6685	0.071	0.57	NO
18	EIF5A	EIF5A	EIF5A	8069	0.032	0.5	NO
19	STS	STS	STS	8402	0.024	0.49	NO
20	SUMF2	SUMF2	SUMF2	8469	0.022	0.49	NO
21	VKORC1	VKORC1	VKORC1	8888	0.013	0.47	NO
22	ARSG	ARSG	ARSG	9214	0.0042	0.45	NO
23	DOHH	DOHH	DOHH	11776	-0.054	0.32	NO
24	DHPS	DHPS	DHPS	12735	-0.079	0.28	NO
25	ARSF	ARSF	ARSF	17911	-0.4	0.06	NO

Figure S109. 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 PEROXISOME.

Figure S110. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PEROXISOME, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: ST WNT BETA CATENIN PATHWAY

Table S56. 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	FABP1	FABP1	FABP1	17	1.6	0.063	YES
2	APOA2	APOA2	APOA2	31	1.4	0.12	YES
3	HMGCS2	HMGCS2	HMGCS2	35	1.4	0.18	YES
4	SULT2A1	SULT2A1	SULT2A1	50	1.4	0.23	YES
5	AGT	AGT	AGT	98	1.2	0.28	YES
6	APOA1	APOA1	APOA1	122	1.1	0.32	YES
7	ANKRD1	ANKRD1	ANKRD1	161	1	0.36	YES
8	APOA5	APOA5	APOA5	214	0.95	0.4	YES
9	PPARGC1A	PPARGC1A	PPARGC1A	384	0.79	0.42	YES
10	CYP4A11	CYP4A11	CYP4A11	750	0.61	0.43	YES
11	TEAD3	TEAD3	TEAD3	1475	0.44	0.41	YES
12	SMARCD3	SMARCD3	SMARCD3	1543	0.43	0.42	YES
13	CD36	CD36	CD36	1602	0.42	0.44	YES
14	FADS1	FADS1	FADS1	2123	0.35	0.42	YES
15	ABCB4	ABCB4	ABCB4	2190	0.34	0.44	YES
16	RXRA	RXRA	RXRA	2231	0.34	0.45	YES
17	MED12	MED12	MED12	2381	0.32	0.45	YES
18	G0S2	G0S2	G0S2	2505	0.3	0.46	YES
19	YAP1	YAP1	YAP1	2561	0.3	0.47	YES
20	WWTR1	WWTR1	WWTR1	2640	0.29	0.48	YES
21	CTGF	CTGF	CTGF	3002	0.26	0.47	NO
22	NPAS2	NPAS2	NPAS2	3481	0.22	0.45	NO
23	PPARA	PPARA	PPARA	3607	0.21	0.45	NO
24	MED30	MED30	MED30	3623	0.21	0.46	NO
25	HMGCS1	HMGCS1	HMGCS1	3683	0.21	0.47	NO
26	MED22	MED22	MED22	4582	0.15	0.42	NO
27	TEAD1	TEAD1	TEAD1	4625	0.15	0.43	NO
28	ME1	ME1	ME1	4679	0.15	0.43	NO
29	UGT1A9	UGT1A9	UGT1A9	4773	0.14	0.43	NO
30	MED14	MED14	MED14	4903	0.14	0.43	NO
31	TBL1XR1	TBL1XR1	TBL1XR1	5420	0.12	0.41	NO
32	RORA	RORA	RORA	5648	0.1	0.4	NO
33	MED16	MED16	MED16	5984	0.093	0.39	NO
34	MED8	MED8	MED8	6060	0.091	0.39	NO
35	CDK19	CDK19	CDK19	6264	0.084	0.38	NO
36	MED10	MED10	MED10	6467	0.078	0.37	NO
37	ESRRA	ESRRA	ESRRA	6793	0.068	0.36	NO
38	PLIN2	PLIN2	PLIN2	7168	0.056	0.34	NO
39	HDAC3	HDAC3	HDAC3	7350	0.051	0.33	NO
40	MED24	MED24	MED24	7448	0.048	0.33	NO
41	MED17	MED17	MED17	7620	0.044	0.32	NO
42	CCNC	CCNC	CCNC	7771	0.039	0.32	NO
43	MED11	MED11	MED11	7830	0.038	0.32	NO
44	MED27	MED27	MED27	7840	0.038	0.32	NO
45	PRIC285	PRIC285	PRIC285	8209	0.028	0.3	NO
46	ALAS1	ALAS1	ALAS1	8216	0.028	0.3	NO
47	MED13L	MED13L	MED13L	8436	0.023	0.29	NO
48	MED6	MED6	MED6	8451	0.022	0.29	NO
49	CDK8	CDK8	CDK8	8474	0.022	0.29	NO
50	MED19	MED19	MED19	8705	0.017	0.28	NO
51	TNFRSF21	TNFRSF21	TNFRSF21	8733	0.016	0.28	NO
52	NCOR1	NCOR1	NCOR1	8808	0.014	0.27	NO
53	NFYB	NFYB	NFYB	8980	0.01	0.26	NO
54	GLIPR1	GLIPR1	GLIPR1	9008	0.0092	0.26	NO
55	NCOA6	NCOA6	NCOA6	9151	0.0059	0.26	NO
56	CPT2	CPT2	CPT2	9220	0.0041	0.25	NO
57	MED1	MED1	MED1	9247	0.0036	0.25	NO
58	ABCA1	ABCA1	ABCA1	9345	0.0018	0.25	NO
59	MED31	MED31	MED31	9395	0.00052	0.24	NO
60	ACOX1	ACOX1	ACOX1	9577	-0.0037	0.23	NO
61	MED29	MED29	MED29	9637	-0.005	0.23	NO
62	PEX11A	PEX11A	PEX11A	9812	-0.0087	0.22	NO
63	SREBF2	SREBF2	SREBF2	10137	-0.016	0.21	NO
64	MED21	MED21	MED21	10451	-0.023	0.19	NO
65	CREBBP	CREBBP	CREBBP	10586	-0.026	0.18	NO
66	FHL2	FHL2	FHL2	10787	-0.031	0.18	NO
67	MED7	MED7	MED7	11023	-0.036	0.16	NO
68	SLC27A1	SLC27A1	SLC27A1	11106	-0.038	0.16	NO
69	MED18	MED18	MED18	11181	-0.04	0.16	NO
70	NRF1	NRF1	NRF1	11445	-0.047	0.15	NO
71	NFYA	NFYA	NFYA	11913	-0.057	0.12	NO
72	ACSL1	ACSL1	ACSL1	12308	-0.068	0.11	NO
73	MED20	MED20	MED20	12322	-0.068	0.11	NO
74	HMGCR	HMGCR	HMGCR	12438	-0.071	0.11	NO
75	ACADM	ACADM	ACADM	12509	-0.073	0.11	NO
76	MED25	MED25	MED25	12658	-0.077	0.1	NO
77	PPARG	PPARG	PPARG	12817	-0.08	0.096	NO
78	NCOA3	NCOA3	NCOA3	13071	-0.088	0.086	NO
79	MED4	MED4	MED4	13163	-0.09	0.085	NO
80	NCOA1	NCOA1	NCOA1	13404	-0.096	0.076	NO
81	MED9	MED9	MED9	13744	-0.11	0.063	NO
82	MED23	MED23	MED23	13886	-0.11	0.06	NO
83	TEAD2	TEAD2	TEAD2	14146	-0.12	0.051	NO
84	TBL1X	TBL1X	TBL1X	14209	-0.12	0.053	NO
85	TRIB3	TRIB3	TRIB3	14272	-0.12	0.055	NO
86	SREBF1	SREBF1	SREBF1	14442	-0.13	0.051	NO
87	EP300	EP300	EP300	14932	-0.15	0.031	NO
88	ANGPTL4	ANGPTL4	ANGPTL4	15268	-0.17	0.021	NO
89	TEAD4	TEAD4	TEAD4	15347	-0.17	0.024	NO
90	MED15	MED15	MED15	15425	-0.18	0.027	NO
91	ARNTL	ARNTL	ARNTL	15458	-0.18	0.032	NO
92	FDFT1	FDFT1	FDFT1	15605	-0.18	0.032	NO
93	NR1D1	NR1D1	NR1D1	15637	-0.19	0.038	NO
94	TXNRD1	TXNRD1	TXNRD1	15876	-0.2	0.034	NO
95	CYP7A1	CYP7A1	CYP7A1	16200	-0.22	0.026	NO
96	MED26	MED26	MED26	16309	-0.23	0.029	NO
97	GRHL1	GRHL1	GRHL1	16405	-0.24	0.034	NO
98	CPT1A	CPT1A	CPT1A	16710	-0.26	0.029	NO
99	CYP1A1	CYP1A1	CYP1A1	16944	-0.28	0.028	NO
100	TGS1	TGS1	TGS1	17032	-0.29	0.035	NO
101	TIAM2	TIAM2	TIAM2	17219	-0.31	0.038	NO
102	CLOCK	CLOCK	CLOCK	17837	-0.39	0.021	NO
103	NCOA2	NCOA2	NCOA2	17942	-0.4	0.032	NO
104	PPARGC1B	PPARGC1B	PPARGC1B	18738	-0.64	0.016	NO

Figure S111. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: ST WNT BETA CATENIN PATHWAY.

Figure S112. Get High-res Image For the top 5 core enriched genes in the pathway: ST WNT BETA CATENIN PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID HNF3BPATHWAY

Table S57. 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	AGXT	AGXT	AGXT	9	1.7	0.1	YES
2	ACOX2	ACOX2	ACOX2	240	0.91	0.15	YES
3	SLC27A2	SLC27A2	SLC27A2	279	0.88	0.2	YES
4	HAO2	HAO2	HAO2	421	0.76	0.24	YES
5	BAAT	BAAT	BAAT	1105	0.51	0.23	YES
6	EPHX2	EPHX2	EPHX2	1155	0.5	0.26	YES
7	NOS2	NOS2	NOS2	1398	0.45	0.27	YES
8	XDH	XDH	XDH	1425	0.45	0.3	YES
9	EHHADH	EHHADH	EHHADH	1811	0.39	0.3	YES
10	DAO	DAO	DAO	1878	0.38	0.32	YES
11	PXMP2	PXMP2	PXMP2	2107	0.35	0.33	YES
12	PHYH	PHYH	PHYH	2125	0.35	0.35	YES
13	PIPOX	PIPOX	PIPOX	2191	0.34	0.36	YES
14	FAR2	FAR2	FAR2	2340	0.32	0.38	YES
15	PEX11G	PEX11G	PEX11G	2402	0.32	0.39	YES
16	PAOX	PAOX	PAOX	2578	0.3	0.4	YES
17	CRAT	CRAT	CRAT	2720	0.28	0.41	YES
18	ACOX3	ACOX3	ACOX3	2766	0.28	0.42	YES
19	ACAA1	ACAA1	ACAA1	2769	0.28	0.44	YES
20	AMACR	AMACR	AMACR	2776	0.28	0.46	YES
21	CROT	CROT	CROT	2819	0.27	0.47	YES
22	ACSL5	ACSL5	ACSL5	3328	0.23	0.46	YES
23	DDO	DDO	DDO	3427	0.22	0.47	YES
24	MLYCD	MLYCD	MLYCD	3786	0.2	0.46	YES
25	GSTK1	GSTK1	GSTK1	3823	0.2	0.47	YES
26	AGPS	AGPS	AGPS	4106	0.18	0.47	YES
27	IDH2	IDH2	IDH2	4156	0.18	0.47	YES
28	IDH1	IDH1	IDH1	4372	0.16	0.47	YES
29	GNPAT	GNPAT	GNPAT	4432	0.16	0.48	YES
30	ABCD1	ABCD1	ABCD1	4455	0.16	0.49	YES
31	DECR2	DECR2	DECR2	4556	0.16	0.49	YES
32	PECR	PECR	PECR	4712	0.15	0.49	YES
33	PEX10	PEX10	PEX10	4834	0.14	0.49	YES
34	HMGCL	HMGCL	HMGCL	4983	0.13	0.49	YES
35	PEX6	PEX6	PEX6	5201	0.12	0.49	NO
36	NUDT12	NUDT12	NUDT12	5569	0.11	0.48	NO
37	PRDX5	PRDX5	PRDX5	5758	0.1	0.47	NO
38	ABCD3	ABCD3	ABCD3	5916	0.096	0.47	NO
39	PEX13	PEX13	PEX13	5953	0.094	0.48	NO
40	DHRS4	DHRS4	DHRS4	6717	0.07	0.44	NO
41	PEX19	PEX19	PEX19	6769	0.068	0.44	NO
42	SCP2	SCP2	SCP2	6770	0.068	0.44	NO
43	PXMP4	PXMP4	PXMP4	6891	0.065	0.44	NO
44	ECH1	ECH1	ECH1	7071	0.059	0.44	NO
45	FAR1	FAR1	FAR1	7397	0.05	0.42	NO
46	CAT	CAT	CAT	7545	0.046	0.42	NO
47	HACL1	HACL1	HACL1	8309	0.026	0.38	NO
48	PEX16	PEX16	PEX16	8453	0.022	0.37	NO
49	NUDT19	NUDT19	NUDT19	8803	0.014	0.35	NO
50	PMVK	PMVK	PMVK	8977	0.01	0.35	NO
51	PEX11B	PEX11B	PEX11B	9322	0.0023	0.33	NO
52	HSD17B4	HSD17B4	HSD17B4	9380	0.00082	0.32	NO
53	PEX7	PEX7	PEX7	9516	-0.0023	0.32	NO
54	ACOX1	ACOX1	ACOX1	9577	-0.0037	0.32	NO
55	PEX26	PEX26	PEX26	9769	-0.0078	0.3	NO
56	PEX11A	PEX11A	PEX11A	9812	-0.0087	0.3	NO
57	PEX14	PEX14	PEX14	10248	-0.018	0.28	NO
58	MPV17	MPV17	MPV17	10280	-0.019	0.28	NO
59	PEX12	PEX12	PEX12	11099	-0.038	0.24	NO
60	PEX5	PEX5	PEX5	11983	-0.059	0.2	NO
61	ACSL1	ACSL1	ACSL1	12308	-0.068	0.18	NO
62	ACOT8	ACOT8	ACOT8	12437	-0.071	0.18	NO
63	PEX1	PEX1	PEX1	12569	-0.075	0.18	NO
64	PRDX1	PRDX1	PRDX1	13103	-0.089	0.16	NO
65	ABCD4	ABCD4	ABCD4	13228	-0.092	0.16	NO
66	ACSL3	ACSL3	ACSL3	13591	-0.1	0.14	NO
67	PEX2	PEX2	PEX2	13742	-0.11	0.14	NO
68	PEX3	PEX3	PEX3	14208	-0.12	0.12	NO
69	MVK	MVK	MVK	14261	-0.12	0.13	NO
70	SLC25A17	SLC25A17	SLC25A17	14910	-0.15	0.1	NO
71	SOD1	SOD1	SOD1	14959	-0.15	0.11	NO
72	SOD2	SOD2	SOD2	15213	-0.16	0.11	NO
73	ACSL4	ACSL4	ACSL4	16147	-0.22	0.071	NO
74	MPV17L	MPV17L	MPV17L	17173	-0.3	0.035	NO
75	ABCD2	ABCD2	ABCD2	18145	-0.45	0.01	NO
76	ACSL6	ACSL6	ACSL6	18700	-0.62	0.018	NO

Figure S113. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID HNF3BPATHWAY.

Figure S114. Get High-res Image For the top 5 core enriched genes in the pathway: PID HNF3BPATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID P75NTRPATHWAY

Table S58. 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	APOC3	APOC3	APOC3	4	1.8	0.091	YES
2	APOA2	APOA2	APOA2	31	1.4	0.16	YES
3	AMN	AMN	AMN	34	1.4	0.23	YES
4	ABCG8	ABCG8	ABCG8	37	1.4	0.3	YES
5	MTTP	MTTP	MTTP	41	1.4	0.37	YES
6	APOB	APOB	APOB	51	1.4	0.44	YES
7	LIPC	LIPC	LIPC	102	1.2	0.49	YES
8	APOA1	APOA1	APOA1	122	1.1	0.55	YES
9	APOA5	APOA5	APOA5	214	0.95	0.59	YES
10	CUBN	CUBN	CUBN	222	0.93	0.63	YES
11	ALB	ALB	ALB	250	0.9	0.68	YES
12	PNLIPRP2	PNLIPRP2	PNLIPRP2	357	0.81	0.71	YES
13	APOC2	APOC2	APOC2	1214	0.49	0.69	NO
14	SDC1	SDC1	SDC1	1629	0.41	0.69	NO
15	HSPG2	HSPG2	HSPG2	2530	0.3	0.66	NO
16	SCARB1	SCARB1	SCARB1	2541	0.3	0.67	NO
17	LDLR	LDLR	LDLR	2553	0.3	0.68	NO
18	BMP1	BMP1	BMP1	2799	0.28	0.68	NO
19	LPL	LPL	LPL	3004	0.26	0.69	NO
20	LPA	LPA	LPA	3111	0.25	0.69	NO
21	ABCG5	ABCG5	ABCG5	3249	0.24	0.7	NO
22	CAV1	CAV1	CAV1	3647	0.21	0.69	NO
23	FABP4	FABP4	FABP4	3732	0.2	0.69	NO
24	P4HB	P4HB	P4HB	5806	0.099	0.59	NO
25	CLPS	CLPS	CLPS	6715	0.07	0.55	NO
26	PPP1CA	PPP1CA	PPP1CA	7260	0.053	0.52	NO
27	ABHD5	ABHD5	ABHD5	7270	0.053	0.52	NO
28	PPP1CC	PPP1CC	PPP1CC	7976	0.034	0.49	NO
29	PRKACA	PRKACA	PRKACA	8075	0.032	0.48	NO
30	LCAT	LCAT	LCAT	8116	0.03	0.48	NO
31	PRKACB	PRKACB	PRKACB	8125	0.03	0.48	NO
32	PPP1CB	PPP1CB	PPP1CB	8559	0.02	0.46	NO
33	A2M	A2M	A2M	8722	0.016	0.45	NO
34	ABCA1	ABCA1	ABCA1	9345	0.0018	0.42	NO
35	SAR1B	SAR1B	SAR1B	10080	-0.015	0.38	NO
36	APOE	APOE	APOE	10434	-0.023	0.37	NO
37	PLTP	PLTP	PLTP	10874	-0.033	0.34	NO
38	MGLL	MGLL	MGLL	11930	-0.058	0.29	NO
39	ABCG1	ABCG1	ABCG1	11997	-0.059	0.29	NO
40	PLIN1	PLIN1	PLIN1	14004	-0.12	0.19	NO
41	CETP	CETP	CETP	15426	-0.18	0.12	NO
42	LDLRAP1	LDLRAP1	LDLRAP1	17187	-0.3	0.047	NO
43	LIPE	LIPE	LIPE	18064	-0.43	0.023	NO
44	PRKACG	PRKACG	PRKACG	18608	-0.59	0.023	NO

Figure S115. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID P75NTRPATHWAY.

Figure S116. Get High-res Image For the top 5 core enriched genes in the pathway: PID P75NTRPATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID SYNDECAN 4 PATHWAY

Table S59. 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	PIGZ	PIGZ	PIGZ	493	0.72	0.18	YES
2	PGAP1	PGAP1	PGAP1	1467	0.44	0.25	YES
3	PIGF	PIGF	PIGF	2793	0.28	0.25	YES
4	PIGQ	PIGQ	PIGQ	3393	0.23	0.28	YES
5	PIGU	PIGU	PIGU	3482	0.22	0.34	YES
6	PIGS	PIGS	PIGS	3759	0.2	0.38	YES
7	PIGT	PIGT	PIGT	4616	0.15	0.38	YES
8	PIGX	PIGX	PIGX	4946	0.14	0.4	YES
9	PIGM	PIGM	PIGM	5507	0.11	0.4	YES
10	PIGK	PIGK	PIGK	5779	0.1	0.42	YES
11	PIGN	PIGN	PIGN	5807	0.099	0.44	YES
12	PIGY	PIGY	PIGY	5921	0.096	0.46	YES
13	GPAA1	GPAA1	GPAA1	6146	0.088	0.48	YES
14	PIGC	PIGC	PIGC	6479	0.077	0.48	YES
15	PIGO	PIGO	PIGO	6959	0.063	0.47	YES
16	DPM2	DPM2	DPM2	7044	0.06	0.49	YES
17	PIGA	PIGA	PIGA	8583	0.019	0.41	NO
18	PIGV	PIGV	PIGV	9882	-0.01	0.34	NO
19	PIGW	PIGW	PIGW	10598	-0.027	0.32	NO
20	PIGH	PIGH	PIGH	10684	-0.029	0.32	NO
21	PIGG	PIGG	PIGG	10865	-0.033	0.32	NO
22	PIGP	PIGP	PIGP	11929	-0.058	0.28	NO
23	GPLD1	GPLD1	GPLD1	12776	-0.08	0.26	NO
24	PIGB	PIGB	PIGB	13505	-0.099	0.25	NO
25	PIGL	PIGL	PIGL	15200	-0.16	0.2	NO

Figure S117. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID SYNDECAN 4 PATHWAY.

Figure S118. Get High-res Image For the top 5 core enriched genes in the pathway: PID SYNDECAN 4 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: REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION

Table S60. 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	APOC3	APOC3	APOC3	4	1.8	0.075	YES
2	FABP1	FABP1	FABP1	17	1.6	0.14	YES
3	APOA2	APOA2	APOA2	31	1.4	0.2	YES
4	HMGCS2	HMGCS2	HMGCS2	35	1.4	0.25	YES
5	APOA1	APOA1	APOA1	122	1.1	0.29	YES
6	APOA5	APOA5	APOA5	214	0.95	0.33	YES
7	ACOX2	ACOX2	ACOX2	240	0.91	0.36	YES
8	SLC27A2	SLC27A2	SLC27A2	279	0.88	0.4	YES
9	AQP7	AQP7	AQP7	353	0.82	0.43	YES
10	MMP1	MMP1	MMP1	407	0.77	0.45	YES
11	SLC27A6	SLC27A6	SLC27A6	470	0.73	0.48	YES
12	CYP4A11	CYP4A11	CYP4A11	750	0.61	0.49	YES
13	CYP8B1	CYP8B1	CYP8B1	1047	0.53	0.5	YES
14	PCK1	PCK1	PCK1	1063	0.52	0.52	YES
15	OLR1	OLR1	OLR1	1566	0.42	0.51	YES
16	CD36	CD36	CD36	1602	0.42	0.52	YES
17	UCP1	UCP1	UCP1	1610	0.42	0.54	YES
18	SCD5	SCD5	SCD5	1645	0.41	0.55	YES
19	FABP2	FABP2	FABP2	1766	0.39	0.56	YES
20	EHHADH	EHHADH	EHHADH	1811	0.39	0.58	YES
21	RXRA	RXRA	RXRA	2231	0.34	0.57	YES
22	ADIPOQ	ADIPOQ	ADIPOQ	2383	0.32	0.57	YES
23	PCK2	PCK2	PCK2	2411	0.31	0.58	YES
24	FADS2	FADS2	FADS2	2605	0.29	0.59	YES
25	ACOX3	ACOX3	ACOX3	2766	0.28	0.59	YES
26	ACAA1	ACAA1	ACAA1	2769	0.28	0.6	YES
27	LPL	LPL	LPL	3004	0.26	0.6	YES
28	CYP27A1	CYP27A1	CYP27A1	3152	0.25	0.6	YES
29	ACSL5	ACSL5	ACSL5	3328	0.23	0.6	YES
30	PPARA	PPARA	PPARA	3607	0.21	0.6	NO
31	FABP4	FABP4	FABP4	3732	0.2	0.6	NO
32	DBI	DBI	DBI	4585	0.15	0.56	NO
33	ME1	ME1	ME1	4679	0.15	0.56	NO
34	ILK	ILK	ILK	5426	0.12	0.52	NO
35	FABP7	FABP7	FABP7	5586	0.11	0.52	NO
36	PDPK1	PDPK1	PDPK1	6714	0.07	0.46	NO
37	SCP2	SCP2	SCP2	6770	0.068	0.46	NO
38	RXRB	RXRB	RXRB	7349	0.051	0.44	NO
39	UBC	UBC	UBC	8851	0.014	0.36	NO
40	CPT1B	CPT1B	CPT1B	9016	0.009	0.35	NO
41	CPT2	CPT2	CPT2	9220	0.0041	0.34	NO
42	ACOX1	ACOX1	ACOX1	9577	-0.0037	0.32	NO
43	SCD	SCD	SCD	9701	-0.0062	0.31	NO
44	RXRG	RXRG	RXRG	9848	-0.0095	0.31	NO
45	NR1H3	NR1H3	NR1H3	10267	-0.019	0.28	NO
46	PLTP	PLTP	PLTP	10874	-0.033	0.26	NO
47	SLC27A1	SLC27A1	SLC27A1	11106	-0.038	0.24	NO
48	SLC27A5	SLC27A5	SLC27A5	11393	-0.046	0.23	NO
49	ACSL1	ACSL1	ACSL1	12308	-0.068	0.19	NO
50	CPT1C	CPT1C	CPT1C	12323	-0.068	0.19	NO
51	ACADM	ACADM	ACADM	12509	-0.073	0.18	NO
52	SLC27A4	SLC27A4	SLC27A4	12594	-0.075	0.18	NO
53	PPARG	PPARG	PPARG	12817	-0.08	0.17	NO
54	ACSL3	ACSL3	ACSL3	13591	-0.1	0.13	NO
55	PLIN1	PLIN1	PLIN1	14004	-0.12	0.12	NO
56	ANGPTL4	ANGPTL4	ANGPTL4	15268	-0.17	0.058	NO
57	FABP3	FABP3	FABP3	15782	-0.19	0.039	NO
58	SORBS1	SORBS1	SORBS1	15812	-0.2	0.045	NO
59	FABP5	FABP5	FABP5	16062	-0.21	0.04	NO
60	ACSL4	ACSL4	ACSL4	16147	-0.22	0.045	NO
61	CYP7A1	CYP7A1	CYP7A1	16200	-0.22	0.051	NO
62	PPARD	PPARD	PPARD	16321	-0.23	0.054	NO
63	ACADL	ACADL	ACADL	16465	-0.24	0.056	NO
64	CPT1A	CPT1A	CPT1A	16710	-0.26	0.054	NO
65	GK2	GK2	GK2	17356	-0.32	0.033	NO
66	FABP6	FABP6	FABP6	17511	-0.34	0.039	NO
67	GK	GK	GK	17986	-0.41	0.031	NO
68	ACSL6	ACSL6	ACSL6	18700	-0.62	0.018	NO

Figure S119. 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: REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION.

Figure S120. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Methods & Data

Input

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