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

Stomach Adenocarcinoma (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 STAD-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1QJ7GRD

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 "STAD-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: 726
Number of samples: 415
Original number of Gene Sets: 1320
Maximum gene set size: 933

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 5 :[ clus1 ] 94
pheno.type: 2 - 5 :[ clus2 ] 95
pheno.type: 3 - 5 :[ clus3 ] 94
pheno.type: 4 - 5 :[ clus4 ] 82
pheno.type: 5 - 5 :[ clus5 ] 50

For the expression subtypes of 18694 genes in 416 samples, GSEA found enriched gene sets in each cluster using 415 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS, KEGG SPLICEOSOME, ST WNT BETA CATENIN PATHWAY, PID HNF3BPATHWAY, REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION, REACTOME METABOLISM OF STEROID HORMONES AND VITAMINS A AND D, REACTOME METABOLISM OF VITAMINS AND COFACTORS, REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA, REACTOME AMINO ACID TRANSPORT ACROSS THE PLASMA MEMBRANE

And common core enriched genes are F2, F10, F7, PROC, ENPP1, FASN, FLAD1, MOCS1, MOCS3, NFS1

clus2

Top enriched gene sets are KEGG PURINE METABOLISM, KEGG TYROSINE METABOLISM, KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE, KEGG ABC TRANSPORTERS, KEGG MAPK SIGNALING PATHWAY, KEGG ERBB SIGNALING PATHWAY, KEGG CALCIUM SIGNALING PATHWAY, KEGG CHEMOKINE SIGNALING PATHWAY, KEGG PHOSPHATIDYLINOSITOL SIGNALING SYSTEM, KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION

And common core enriched genes are AKT3, ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY7, ADCY8, ADCY9, CAMK4

clus3

Top enriched gene sets are KEGG PYRIMIDINE METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RIBOSOME, KEGG RNA DEGRADATION, KEGG RNA POLYMERASE, KEGG DNA REPLICATION, KEGG SPLICEOSOME, KEGG PROTEASOME, KEGG NUCLEOTIDE EXCISION REPAIR, KEGG CELL CYCLE

And common core enriched genes are CCNH, CDK7, MNAT1, CCNA2, CCNE2, CDK2, CDKN1A, CKS1B, PSMA1, PSMA2

clus4

Top enriched gene sets are KEGG INOSITOL PHOSPHATE METABOLISM, KEGG APOPTOSIS, BIOCARTA HIVNEF PATHWAY, BIOCARTA PYK2 PATHWAY, BIOCARTA STRESS PATHWAY, ST TUMOR NECROSIS FACTOR PATHWAY, ST INTERLEUKIN 4 PATHWAY, PID BCR 5PATHWAY, PID TRAIL PATHWAY, PID CDC42 PATHWAY

And common core enriched genes are MAP3K1, CHUK, CRADD, MAP3K14, NFKB1, TNF, TRADD, AP1B1, AP1G1, AP1M2

clus5

Top enriched gene sets are KEGG CITRATE CYCLE TCA CYCLE, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG PYRUVATE METABOLISM, KEGG BUTANOATE METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG PEROXISOME, BIOCARTA DEATH PATHWAY, REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX, REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT

And common core enriched genes are AARS2, CARS2, DARS, DARS2, EPRS, FARSA, FARSB, GARS, HARS2, IARS

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 GLYCINE SERINE AND THREONINE METABOLISM	31	genes.ES.table	0.63	1.6	0.0079	1	0.94	0.39	0.11	0.35	0.93	0.47
KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS	25	genes.ES.table	0.45	1.6	0.06	1	0.94	0.52	0.39	0.32	1	0.51
KEGG SPLICEOSOME	114	genes.ES.table	0.41	1.6	0.086	1	0.94	0.68	0.5	0.34	1	0.55
ST WNT BETA CATENIN PATHWAY	32	genes.ES.table	0.55	1.5	0.057	1	0.99	0.19	0.075	0.17	0.69	0.37
PID HNF3BPATHWAY	44	genes.ES.table	0.66	1.7	0.0079	1	0.87	0.48	0.19	0.39	1	0.55
REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION	25	genes.ES.table	0.6	1.7	0.0019	1	0.86	0.16	0.0064	0.16	1	0.67
REACTOME METABOLISM OF STEROID HORMONES AND VITAMINS A AND D	31	genes.ES.table	0.61	1.5	0.014	1	0.98	0.48	0.16	0.41	0.77	0.42
REACTOME METABOLISM OF VITAMINS AND COFACTORS	50	genes.ES.table	0.43	1.7	0.02	1	0.86	0.36	0.26	0.27	1	0.78
REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA	126	genes.ES.table	0.44	1.6	0.095	1	0.97	0.73	0.51	0.36	1	0.53
REACTOME AMINO ACID TRANSPORT ACROSS THE PLASMA MEMBRANE	31	genes.ES.table	0.6	1.6	0.023	1	0.97	0.48	0.23	0.38	0.95	0.48

genes ES table in pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM

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	QPRT	QPRT	QPRT	38	0.66	0.14	YES
2	SLC23A1	SLC23A1	SLC23A1	502	0.4	0.19	YES
3	MOCS3	MOCS3	MOCS3	1491	0.25	0.19	YES
4	SLC46A1	SLC46A1	SLC46A1	2070	0.21	0.2	YES
5	NMNAT2	NMNAT2	NMNAT2	2466	0.18	0.22	YES
6	SLC19A3	SLC19A3	SLC19A3	2586	0.18	0.25	YES
7	MOCS1	MOCS1	MOCS1	2630	0.17	0.28	YES
8	NMNAT3	NMNAT3	NMNAT3	2863	0.16	0.3	YES
9	NFS1	NFS1	NFS1	3108	0.15	0.32	YES
10	SLC5A6	SLC5A6	SLC5A6	3359	0.14	0.34	YES
11	SLC19A2	SLC19A2	SLC19A2	3949	0.12	0.33	YES
12	PPCDC	PPCDC	PPCDC	4013	0.12	0.35	YES
13	FLAD1	FLAD1	FLAD1	4066	0.12	0.37	YES
14	ENPP1	ENPP1	ENPP1	4392	0.11	0.38	YES
15	SLC19A1	SLC19A1	SLC19A1	4513	0.1	0.39	YES
16	FASN	FASN	FASN	4583	0.1	0.41	YES
17	SLC23A2	SLC23A2	SLC23A2	4759	0.096	0.42	YES
18	SLC2A1	SLC2A1	SLC2A1	4919	0.093	0.43	YES
19	PANK2	PANK2	PANK2	6257	0.066	0.37	NO
20	THTPA	THTPA	THTPA	6355	0.064	0.38	NO
21	AASDHPPT	AASDHPPT	AASDHPPT	6367	0.064	0.39	NO
22	PANK1	PANK1	PANK1	6381	0.064	0.4	NO
23	COASY	COASY	COASY	6425	0.063	0.42	NO
24	RFK	RFK	RFK	7338	0.048	0.38	NO
25	GSTO2	GSTO2	GSTO2	7551	0.045	0.37	NO
26	SLC25A32	SLC25A32	SLC25A32	8117	0.037	0.35	NO
27	PNPO	PNPO	PNPO	8605	0.03	0.33	NO
28	SHMT1	SHMT1	SHMT1	9873	0.014	0.27	NO
29	PANK4	PANK4	PANK4	10372	0.0075	0.24	NO
30	SLC25A16	SLC25A16	SLC25A16	10524	0.0055	0.23	NO
31	CYB5R3	CYB5R3	CYB5R3	10822	0.0014	0.22	NO
32	NAMPT	NAMPT	NAMPT	11040	-0.0017	0.21	NO
33	PDXK	PDXK	PDXK	11353	-0.0057	0.19	NO
34	CYB5A	CYB5A	CYB5A	11575	-0.0088	0.18	NO
35	NADK	NADK	NADK	11776	-0.011	0.17	NO
36	PPCS	PPCS	PPCS	11804	-0.012	0.17	NO
37	SLC2A3	SLC2A3	SLC2A3	12112	-0.016	0.16	NO
38	GSTO1	GSTO1	GSTO1	12412	-0.021	0.15	NO
39	MTHFD1	MTHFD1	MTHFD1	13558	-0.039	0.096	NO
40	GPHN	GPHN	GPHN	13582	-0.039	0.1	NO
41	MTHFR	MTHFR	MTHFR	13693	-0.041	0.1	NO
42	ACP5	ACP5	ACP5	13942	-0.046	0.1	NO
43	FPGS	FPGS	FPGS	14086	-0.049	0.1	NO
44	PANK3	PANK3	PANK3	14260	-0.053	0.1	NO
45	DHFR	DHFR	DHFR	14321	-0.054	0.11	NO
46	MOCS2	MOCS2	MOCS2	14325	-0.054	0.12	NO
47	NADSYN1	NADSYN1	NADSYN1	15671	-0.089	0.07	NO
48	NMNAT1	NMNAT1	NMNAT1	15847	-0.094	0.08	NO
49	MOCOS	MOCOS	MOCOS	15853	-0.094	0.1	NO
50	TPK1	TPK1	TPK1	18088	-0.25	0.032	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 GLYCINE SERINE AND THREONINE METABOLISM.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS

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	F7	F7	F7	22	0.71	0.17	YES
2	F2	F2	F2	33	0.67	0.33	YES
3	F10	F10	F10	101	0.57	0.47	YES
4	PROC	PROC	PROC	120	0.55	0.6	YES
5	PROZ	PROZ	PROZ	1795	0.23	0.56	NO
6	PROS1	PROS1	PROS1	3319	0.14	0.51	NO
7	ARSE	ARSE	ARSE	3502	0.13	0.54	NO
8	GGCX	GGCX	GGCX	3962	0.12	0.54	NO
9	EIF5A2	EIF5A2	EIF5A2	4431	0.11	0.54	NO
10	FURIN	FURIN	FURIN	5973	0.071	0.48	NO
11	SUMF2	SUMF2	SUMF2	6460	0.062	0.46	NO
12	DOHH	DOHH	DOHH	7923	0.039	0.4	NO
13	VKORC1	VKORC1	VKORC1	8454	0.032	0.38	NO
14	SUMF1	SUMF1	SUMF1	9379	0.02	0.33	NO
15	EIF5A	EIF5A	EIF5A	10246	0.009	0.29	NO
16	DHPS	DHPS	DHPS	11579	-0.0089	0.22	NO
17	ARSI	ARSI	ARSI	11600	-0.0092	0.22	NO
18	ARSK	ARSK	ARSK	12881	-0.028	0.16	NO
19	ARSA	ARSA	ARSA	13318	-0.035	0.14	NO
20	ARSH	ARSH	ARSH	13394	-0.036	0.14	NO
21	ARSB	ARSB	ARSB	13682	-0.041	0.14	NO
22	ARSG	ARSG	ARSG	15220	-0.076	0.076	NO
23	ARSF	ARSF	ARSF	15533	-0.085	0.079	NO
24	ARSJ	ARSJ	ARSJ	16907	-0.14	0.04	NO
25	STS	STS	STS	17935	-0.23	0.04	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 GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS.

Figure S4. 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 SPLICEOSOME

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	F2	F2	F2	33	0.67	0.085	YES
2	APOA1	APOA1	APOA1	59	0.62	0.16	YES
3	TTR	TTR	TTR	215	0.5	0.22	YES
4	NKX2-1	NKX2-1	NKX2-1	286	0.47	0.28	YES
5	FOXA2	FOXA2	FOXA2	369	0.44	0.33	YES
6	AFP	AFP	AFP	565	0.38	0.37	YES
7	PKLR	PKLR	PKLR	719	0.35	0.41	YES
8	IGFBP1	IGFBP1	IGFBP1	1008	0.31	0.43	YES
9	TAT	TAT	TAT	1127	0.29	0.46	YES
10	ALB	ALB	ALB	1156	0.29	0.5	YES
11	ABCC8	ABCC8	ABCC8	1312	0.27	0.52	YES
12	KCNJ11	KCNJ11	KCNJ11	1366	0.26	0.56	YES
13	GCK	GCK	GCK	1397	0.26	0.59	YES
14	G6PC	G6PC	G6PC	1568	0.25	0.61	YES
15	CPT1C	CPT1C	CPT1C	1758	0.23	0.63	YES
16	SLC2A2	SLC2A2	SLC2A2	1904	0.22	0.65	YES
17	CPT1B	CPT1B	CPT1B	2677	0.17	0.63	YES
18	HMGCS1	HMGCS1	HMGCS1	3015	0.16	0.63	YES
19	HNF1A	HNF1A	HNF1A	3252	0.14	0.64	YES
20	CEBPA	CEBPA	CEBPA	3460	0.14	0.65	YES
21	CEBPB	CEBPB	CEBPB	3524	0.13	0.66	YES
22	HNF4A	HNF4A	HNF4A	4053	0.12	0.65	NO
23	DLK1	DLK1	DLK1	4658	0.1	0.63	NO
24	NF1	NF1	NF1	7744	0.042	0.47	NO
25	HNF1B	HNF1B	HNF1B	7922	0.039	0.46	NO
26	FOXA1	FOXA1	FOXA1	8383	0.033	0.44	NO
27	PDX1	PDX1	PDX1	8621	0.03	0.43	NO
28	PCK1	PCK1	PCK1	9352	0.02	0.4	NO
29	TFRC	TFRC	TFRC	9471	0.018	0.39	NO
30	ACADM	ACADM	ACADM	10149	0.01	0.36	NO
31	AKT1	AKT1	AKT1	11005	-0.0012	0.31	NO
32	CREB1	CREB1	CREB1	11398	-0.0064	0.29	NO
33	UCP2	UCP2	UCP2	11430	-0.0069	0.29	NO
34	CEBPD	CEBPD	CEBPD	11875	-0.013	0.27	NO
35	ALAS1	ALAS1	ALAS1	11963	-0.014	0.27	NO
36	ACADVL	ACADVL	ACADVL	12448	-0.021	0.24	NO
37	BDH1	BDH1	BDH1	12777	-0.026	0.23	NO
38	SP1	SP1	SP1	13943	-0.046	0.17	NO
39	FOXA3	FOXA3	FOXA3	14214	-0.052	0.16	NO
40	CPT1A	CPT1A	CPT1A	14900	-0.067	0.14	NO
41	NR3C1	NR3C1	NR3C1	15241	-0.076	0.13	NO
42	HADH	HADH	HADH	16096	-0.1	0.095	NO
43	FOXF1	FOXF1	FOXF1	16816	-0.14	0.074	NO
44	ALDOB	ALDOB	ALDOB	17714	-0.2	0.052	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 SPLICEOSOME.

Figure S6. 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: ST WNT BETA CATENIN PATHWAY

Table S4. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	F7	F7	F7	22	0.71	0.1	YES
2	F2	F2	F2	33	0.67	0.2	YES
3	F10	F10	F10	101	0.57	0.28	YES
4	FGG	FGG	FGG	119	0.55	0.36	YES
5	PROC	PROC	PROC	120	0.55	0.44	YES
6	FGA	FGA	FGA	124	0.55	0.51	YES
7	FGB	FGB	FGB	189	0.51	0.58	YES
8	KNG1	KNG1	KNG1	263	0.47	0.65	YES
9	SERPINC1	SERPINC1	SERPINC1	790	0.34	0.67	YES
10	F11	F11	F11	1649	0.24	0.66	YES
11	F5	F5	F5	1728	0.23	0.69	YES
12	GP5	GP5	GP5	2608	0.18	0.67	NO
13	PROS1	PROS1	PROS1	3319	0.14	0.65	NO
14	GP9	GP9	GP9	4831	0.095	0.58	NO
15	PF4	PF4	PF4	10231	0.0092	0.29	NO
16	KLKB1	KLKB1	KLKB1	10286	0.0085	0.29	NO
17	PRCP	PRCP	PRCP	11160	-0.0032	0.24	NO
18	PF4V1	PF4V1	PF4V1	11474	-0.0075	0.23	NO
19	C1QBP	C1QBP	C1QBP	11865	-0.013	0.21	NO
20	F12	F12	F12	12165	-0.017	0.2	NO
21	TFPI	TFPI	TFPI	12244	-0.018	0.19	NO
22	THBD	THBD	THBD	12306	-0.019	0.19	NO
23	GP1BA	GP1BA	GP1BA	15881	-0.095	0.016	NO
24	A2M	A2M	A2M	16297	-0.11	0.0095	NO
25	SERPING1	SERPING1	SERPING1	16539	-0.12	0.014	NO
26	VWF	VWF	VWF	16645	-0.13	0.027	NO
27	F8	F8	F8	16730	-0.13	0.041	NO
28	F3	F3	F3	17607	-0.19	0.022	NO
29	F13A1	F13A1	F13A1	18012	-0.24	0.036	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: ST WNT BETA CATENIN PATHWAY.

Figure S8. 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 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	PRPF40B	PRPF40B	PRPF40B	1128	0.29	-0.0038	YES
2	SNRPA1	SNRPA1	SNRPA1	3807	0.12	-0.12	YES
3	SNRPB2	SNRPB2	SNRPB2	3857	0.12	-0.1	YES
4	HSPA1L	HSPA1L	HSPA1L	3904	0.12	-0.082	YES
5	PPIE	PPIE	PPIE	4007	0.12	-0.065	YES
6	PRPF6	PRPF6	PRPF6	4497	0.1	-0.071	YES
7	CTNNBL1	CTNNBL1	CTNNBL1	4548	0.1	-0.054	YES
8	SNRPC	SNRPC	SNRPC	4559	0.1	-0.034	YES
9	SNRPE	SNRPE	SNRPE	4600	0.1	-0.017	YES
10	SNRPB	SNRPB	SNRPB	4657	0.1	-0.00035	YES
11	SF3B4	SF3B4	SF3B4	4726	0.098	0.015	YES
12	SNRPD1	SNRPD1	SNRPD1	4743	0.097	0.033	YES
13	PPIL1	PPIL1	PPIL1	4866	0.094	0.044	YES
14	SNRPG	SNRPG	SNRPG	4949	0.092	0.058	YES
15	THOC1	THOC1	THOC1	4954	0.092	0.076	YES
16	LSM5	LSM5	LSM5	4979	0.091	0.092	YES
17	HSPA1A	HSPA1A	HSPA1A	5175	0.086	0.098	YES
18	PRPF3	PRPF3	PRPF3	5221	0.086	0.11	YES
19	PQBP1	PQBP1	PQBP1	5284	0.084	0.12	YES
20	CRNKL1	CRNKL1	CRNKL1	5427	0.081	0.13	YES
21	SNRPD3	SNRPD3	SNRPD3	5785	0.074	0.13	YES
22	MAGOH	MAGOH	MAGOH	5835	0.074	0.14	YES
23	PPIH	PPIH	PPIH	5849	0.073	0.15	YES
24	SNRPF	SNRPF	SNRPF	5930	0.072	0.16	YES
25	USP39	USP39	USP39	6039	0.07	0.17	YES
26	CWC15	CWC15	CWC15	6165	0.068	0.18	YES
27	RBM17	RBM17	RBM17	6219	0.067	0.19	YES
28	NCBP2	NCBP2	NCBP2	6285	0.066	0.2	YES
29	CCDC12	CCDC12	CCDC12	6551	0.061	0.19	YES
30	PUF60	PUF60	PUF60	6562	0.06	0.2	YES
31	BUD31	BUD31	BUD31	6592	0.06	0.22	YES
32	PRPF19	PRPF19	PRPF19	6806	0.056	0.22	YES
33	MAGOHB	MAGOHB	MAGOHB	7032	0.053	0.21	YES
34	RBM8A	RBM8A	RBM8A	7060	0.052	0.22	YES
35	PHF5A	PHF5A	PHF5A	7072	0.052	0.23	YES
36	EIF4A3	EIF4A3	EIF4A3	7167	0.051	0.24	YES
37	NHP2L1	NHP2L1	NHP2L1	7202	0.05	0.24	YES
38	SART1	SART1	SART1	7214	0.05	0.25	YES
39	LSM2	LSM2	LSM2	7219	0.05	0.26	YES
40	U2AF1	U2AF1	U2AF1	7332	0.048	0.27	YES
41	DHX16	DHX16	DHX16	7465	0.046	0.27	YES
42	LSM4	LSM4	LSM4	7502	0.046	0.28	YES
43	PRPF4	PRPF4	PRPF4	7539	0.045	0.28	YES
44	PRPF38A	PRPF38A	PRPF38A	7549	0.045	0.29	YES
45	THOC4	THOC4	THOC4	7589	0.044	0.3	YES
46	EFTUD2	EFTUD2	EFTUD2	7616	0.044	0.3	YES
47	PRPF31	PRPF31	PRPF31	7660	0.043	0.31	YES
48	SNRNP27	SNRNP27	SNRNP27	7663	0.043	0.32	YES
49	SMNDC1	SMNDC1	SMNDC1	7745	0.042	0.32	YES
50	TXNL4A	TXNL4A	TXNL4A	7755	0.042	0.33	YES
51	SNRNP200	SNRNP200	SNRNP200	7863	0.041	0.33	YES
52	HSPA1B	HSPA1B	HSPA1B	7880	0.04	0.34	YES
53	SF3B14	SF3B14	SF3B14	7883	0.04	0.35	YES
54	SF3B3	SF3B3	SF3B3	7889	0.04	0.35	YES
55	TRA2A	TRA2A	TRA2A	7907	0.04	0.36	YES
56	LSM6	LSM6	LSM6	7976	0.039	0.36	YES
57	SNRPA	SNRPA	SNRPA	7981	0.038	0.37	YES
58	SNRNP40	SNRNP40	SNRNP40	8127	0.037	0.37	YES
59	U2AF2	U2AF2	U2AF2	8138	0.036	0.38	YES
60	RBMX	RBMX	RBMX	8257	0.035	0.38	YES
61	RBM25	RBM25	RBM25	8542	0.031	0.37	YES
62	HSPA6	HSPA6	HSPA6	8610	0.03	0.37	YES
63	SNRPD2	SNRPD2	SNRPD2	8625	0.029	0.38	YES
64	SF3B2	SF3B2	SF3B2	8636	0.029	0.38	YES
65	CDC5L	CDC5L	CDC5L	8652	0.029	0.38	YES
66	HNRNPU	HNRNPU	HNRNPU	8654	0.029	0.39	YES
67	SNW1	SNW1	SNW1	8706	0.028	0.39	YES
68	PCBP1	PCBP1	PCBP1	8742	0.028	0.4	YES
69	HNRNPC	HNRNPC	HNRNPC	8783	0.027	0.4	YES
70	SNRNP70	SNRNP70	SNRNP70	8798	0.027	0.4	YES
71	HNRNPA3	HNRNPA3	HNRNPA3	8855	0.026	0.41	YES
72	THOC2	THOC2	THOC2	9087	0.023	0.4	YES
73	TRA2B	TRA2B	TRA2B	9100	0.023	0.4	YES
74	LSM3	LSM3	LSM3	9145	0.022	0.4	YES
75	ACIN1	ACIN1	ACIN1	9188	0.022	0.41	YES
76	PRPF40A	PRPF40A	PRPF40A	9207	0.022	0.41	YES
77	SF3A3	SF3A3	SF3A3	9254	0.021	0.41	YES
78	DDX23	DDX23	DDX23	9482	0.018	0.4	NO
79	PRPF38B	PRPF38B	PRPF38B	9794	0.015	0.39	NO
80	PRPF18	PRPF18	PRPF18	9803	0.015	0.39	NO
81	SF3A2	SF3A2	SF3A2	9806	0.014	0.39	NO
82	THOC3	THOC3	THOC3	9809	0.014	0.4	NO
83	CHERP	CHERP	CHERP	9851	0.014	0.4	NO
84	DDX46	DDX46	DDX46	9866	0.014	0.4	NO
85	ISY1	ISY1	ISY1	9932	0.013	0.4	NO
86	TCERG1	TCERG1	TCERG1	10211	0.0094	0.38	NO
87	WBP11	WBP11	WBP11	10228	0.0092	0.39	NO
88	HNRNPK	HNRNPK	HNRNPK	10329	0.008	0.38	NO
89	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	10333	0.008	0.38	NO
90	DDX42	DDX42	DDX42	10443	0.0064	0.38	NO
91	HNRNPM	HNRNPM	HNRNPM	10477	0.006	0.38	NO
92	SF3B5	SF3B5	SF3B5	10561	0.005	0.38	NO
93	HNRNPA1	HNRNPA1	HNRNPA1	10581	0.0048	0.38	NO
94	SF3B1	SF3B1	SF3B1	10724	0.0026	0.37	NO
95	LSM7	LSM7	LSM7	10867	0.00074	0.36	NO
96	DDX5	DDX5	DDX5	10875	0.00065	0.36	NO
97	DHX8	DHX8	DHX8	10968	-0.00072	0.36	NO
98	SYF2	SYF2	SYF2	11042	-0.0017	0.35	NO
99	BCAS2	BCAS2	BCAS2	11183	-0.0035	0.34	NO
100	PLRG1	PLRG1	PLRG1	11222	-0.004	0.34	NO
101	CDC40	CDC40	CDC40	11571	-0.0088	0.33	NO
102	NCBP1	NCBP1	NCBP1	11671	-0.01	0.32	NO
103	DHX15	DHX15	DHX15	11699	-0.01	0.32	NO
104	DHX38	DHX38	DHX38	11790	-0.012	0.32	NO
105	XAB2	XAB2	XAB2	11855	-0.012	0.32	NO
106	PRPF8	PRPF8	PRPF8	12145	-0.016	0.31	NO
107	SF3A1	SF3A1	SF3A1	12215	-0.017	0.31	NO
108	ZMAT2	ZMAT2	ZMAT2	12275	-0.018	0.31	NO
109	AQR	AQR	AQR	12623	-0.024	0.29	NO
110	NAA38	NAA38	NAA38	12644	-0.024	0.3	NO
111	SLU7	SLU7	SLU7	12825	-0.027	0.29	NO
112	RBM22	RBM22	RBM22	12899	-0.028	0.29	NO
113	HSPA8	HSPA8	HSPA8	12924	-0.029	0.3	NO
114	HSPA2	HSPA2	HSPA2	14594	-0.06	0.22	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: PID HNF3BPATHWAY.

Figure S10. 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: REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION

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	GPLD1	GPLD1	GPLD1	1142	0.29	0.088	YES
2	PIGZ	PIGZ	PIGZ	1637	0.24	0.18	YES
3	PIGM	PIGM	PIGM	2312	0.19	0.24	YES
4	PIGU	PIGU	PIGU	2997	0.16	0.29	YES
5	PIGT	PIGT	PIGT	3116	0.15	0.36	YES
6	PIGW	PIGW	PIGW	3845	0.12	0.38	YES
7	PIGC	PIGC	PIGC	4932	0.092	0.37	YES
8	GPAA1	GPAA1	GPAA1	5089	0.088	0.41	YES
9	PIGH	PIGH	PIGH	5518	0.08	0.43	YES
10	DPM2	DPM2	DPM2	6057	0.069	0.43	YES
11	PIGO	PIGO	PIGO	6805	0.056	0.42	YES
12	PIGX	PIGX	PIGX	6886	0.055	0.44	YES
13	PIGA	PIGA	PIGA	7279	0.049	0.45	YES
14	PIGP	PIGP	PIGP	8736	0.028	0.38	NO
15	PIGS	PIGS	PIGS	9177	0.022	0.37	NO
16	PIGG	PIGG	PIGG	10180	0.0098	0.32	NO
17	PIGK	PIGK	PIGK	10836	0.0012	0.29	NO
18	PGAP1	PGAP1	PGAP1	11006	-0.0012	0.28	NO
19	PIGV	PIGV	PIGV	12027	-0.014	0.23	NO
20	PIGF	PIGF	PIGF	12160	-0.016	0.24	NO
21	PIGQ	PIGQ	PIGQ	12257	-0.018	0.24	NO
22	PIGN	PIGN	PIGN	12801	-0.027	0.22	NO
23	PIGY	PIGY	PIGY	13008	-0.03	0.23	NO
24	PIGL	PIGL	PIGL	14562	-0.06	0.18	NO
25	PIGB	PIGB	PIGB	15667	-0.089	0.16	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: REACTOME PTM GAMMA CARBOXYLATION HYPUSINE FORMATION AND ARYLSULFATASE ACTIVATION.

Figure S12. 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

genes ES table in pathway: REACTOME METABOLISM OF STEROID HORMONES AND VITAMINS A AND D

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	GLDC	GLDC	GLDC	5	0.77	0.12	YES
2	CBS	CBS	CBS	98	0.57	0.21	YES
3	AGXT	AGXT	AGXT	415	0.42	0.26	YES
4	AGXT2	AGXT2	AGXT2	451	0.41	0.33	YES
5	PIPOX	PIPOX	PIPOX	461	0.41	0.39	YES
6	GAMT	GAMT	GAMT	509	0.4	0.45	YES
7	PHGDH	PHGDH	PHGDH	520	0.39	0.52	YES
8	DAO	DAO	DAO	1148	0.29	0.53	YES
9	PSPH	PSPH	PSPH	1669	0.24	0.54	YES
10	AMT	AMT	AMT	1860	0.22	0.56	YES
11	GLYCTK	GLYCTK	GLYCTK	1953	0.21	0.6	YES
12	GNMT	GNMT	GNMT	2013	0.21	0.62	YES
13	BHMT	BHMT	BHMT	2834	0.16	0.61	NO
14	ALAS2	ALAS2	ALAS2	3566	0.13	0.59	NO
15	SARDH	SARDH	SARDH	4430	0.11	0.56	NO
16	PSAT1	PSAT1	PSAT1	4442	0.11	0.58	NO
17	CHDH	CHDH	CHDH	5073	0.089	0.56	NO
18	AOC2	AOC2	AOC2	5963	0.071	0.52	NO
19	GCAT	GCAT	GCAT	7215	0.05	0.46	NO
20	CTH	CTH	CTH	8123	0.037	0.42	NO
21	SHMT2	SHMT2	SHMT2	9849	0.014	0.33	NO
22	SHMT1	SHMT1	SHMT1	9873	0.014	0.33	NO
23	ALAS1	ALAS1	ALAS1	11963	-0.014	0.22	NO
24	MAOB	MAOB	MAOB	12039	-0.015	0.22	NO
25	DLD	DLD	DLD	12889	-0.028	0.18	NO
26	GATM	GATM	GATM	13494	-0.038	0.15	NO
27	SRR	SRR	SRR	15771	-0.092	0.044	NO
28	MAOA	MAOA	MAOA	16893	-0.14	0.0063	NO
29	SDS	SDS	SDS	17387	-0.17	0.0078	NO
30	DMGDH	DMGDH	DMGDH	17512	-0.18	0.031	NO
31	AOC3	AOC3	AOC3	17642	-0.2	0.055	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: REACTOME METABOLISM OF STEROID HORMONES AND VITAMINS A AND D.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME METABOLISM OF STEROID HORMONES AND VITAMINS A AND D, 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 METABOLISM OF VITAMINS AND COFACTORS

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	NUP210	NUP210	NUP210	1723	0.23	-0.052	YES
2	RAE1	RAE1	RAE1	2111	0.2	-0.038	YES
3	UPF3B	UPF3B	UPF3B	2981	0.16	-0.057	YES
4	SNRPA1	SNRPA1	SNRPA1	3807	0.12	-0.08	YES
5	SNRPB2	SNRPB2	SNRPB2	3857	0.12	-0.061	YES
6	NUP155	NUP155	NUP155	3971	0.12	-0.046	YES
7	CSTF1	CSTF1	CSTF1	4078	0.12	-0.032	YES
8	POLR2I	POLR2I	POLR2I	4108	0.12	-0.013	YES
9	GTF2F2	GTF2F2	GTF2F2	4436	0.11	-0.012	YES
10	PRPF6	PRPF6	PRPF6	4497	0.1	0.0026	YES
11	SNRPE	SNRPE	SNRPE	4600	0.1	0.015	YES
12	SNRPB	SNRPB	SNRPB	4657	0.1	0.029	YES
13	SF3B4	SF3B4	SF3B4	4726	0.098	0.043	YES
14	SNRPD1	SNRPD1	SNRPD1	4743	0.097	0.059	YES
15	POLR2K	POLR2K	POLR2K	4806	0.095	0.072	YES
16	POLR2D	POLR2D	POLR2D	4835	0.095	0.087	YES
17	SNRPG	SNRPG	SNRPG	4949	0.092	0.097	YES
18	AAAS	AAAS	AAAS	5286	0.084	0.094	YES
19	POLR2F	POLR2F	POLR2F	5288	0.084	0.11	YES
20	PABPN1	PABPN1	PABPN1	5562	0.079	0.11	YES
21	NUPL2	NUPL2	NUPL2	5654	0.077	0.12	YES
22	NUP43	NUP43	NUP43	5655	0.077	0.13	YES
23	POLR2J	POLR2J	POLR2J	5664	0.077	0.14	YES
24	SNRPD3	SNRPD3	SNRPD3	5785	0.074	0.15	YES
25	MAGOH	MAGOH	MAGOH	5835	0.074	0.16	YES
26	POLR2G	POLR2G	POLR2G	5888	0.073	0.17	YES
27	SNRPF	SNRPF	SNRPF	5930	0.072	0.18	YES
28	NUP107	NUP107	NUP107	6025	0.07	0.19	YES
29	NCBP2	NCBP2	NCBP2	6285	0.066	0.18	YES
30	POLR2C	POLR2C	POLR2C	6338	0.064	0.19	YES
31	CSTF3	CSTF3	CSTF3	6373	0.064	0.2	YES
32	METTL3	METTL3	METTL3	6394	0.064	0.21	YES
33	CCAR1	CCAR1	CCAR1	6414	0.063	0.22	YES
34	POLR2H	POLR2H	POLR2H	6422	0.063	0.23	YES
35	FUS	FUS	FUS	6734	0.058	0.23	YES
36	NUP35	NUP35	NUP35	6927	0.054	0.22	YES
37	CPSF1	CPSF1	CPSF1	7011	0.053	0.23	YES
38	RBM8A	RBM8A	RBM8A	7060	0.052	0.24	YES
39	PHF5A	PHF5A	PHF5A	7072	0.052	0.24	YES
40	CLP1	CLP1	CLP1	7198	0.05	0.25	YES
41	NHP2L1	NHP2L1	NHP2L1	7202	0.05	0.26	YES
42	LSM2	LSM2	LSM2	7219	0.05	0.26	YES
43	CPSF3	CPSF3	CPSF3	7257	0.049	0.27	YES
44	U2AF1	U2AF1	U2AF1	7332	0.048	0.28	YES
45	CPSF7	CPSF7	CPSF7	7348	0.048	0.28	YES
46	DNAJC8	DNAJC8	DNAJC8	7476	0.046	0.28	YES
47	HNRNPL	HNRNPL	HNRNPL	7479	0.046	0.29	YES
48	PAPOLA	PAPOLA	PAPOLA	7501	0.046	0.3	YES
49	PRPF4	PRPF4	PRPF4	7539	0.045	0.3	YES
50	NUP133	NUP133	NUP133	7554	0.045	0.31	YES
51	THOC4	THOC4	THOC4	7589	0.044	0.32	YES
52	EFTUD2	EFTUD2	EFTUD2	7616	0.044	0.32	YES
53	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	7642	0.044	0.33	YES
54	HNRNPD	HNRNPD	HNRNPD	7681	0.043	0.34	YES
55	TXNL4A	TXNL4A	TXNL4A	7755	0.042	0.34	YES
56	NUP153	NUP153	NUP153	7806	0.041	0.34	YES
57	NUP93	NUP93	NUP93	7845	0.041	0.35	YES
58	SNRNP200	SNRNP200	SNRNP200	7863	0.041	0.36	YES
59	SF3B14	SF3B14	SF3B14	7883	0.04	0.36	YES
60	SF3B3	SF3B3	SF3B3	7889	0.04	0.37	YES
61	SNRPA	SNRPA	SNRPA	7981	0.038	0.37	YES
62	NUP37	NUP37	NUP37	8035	0.038	0.37	YES
63	NUP85	NUP85	NUP85	8100	0.037	0.38	YES
64	CSTF2	CSTF2	CSTF2	8104	0.037	0.38	YES
65	SNRNP40	SNRNP40	SNRNP40	8127	0.037	0.39	YES
66	U2AF2	U2AF2	U2AF2	8138	0.036	0.39	YES
67	PCBP2	PCBP2	PCBP2	8229	0.035	0.4	YES
68	SLBP	SLBP	SLBP	8254	0.035	0.4	YES
69	RBMX	RBMX	RBMX	8257	0.035	0.4	YES
70	SEH1L	SEH1L	SEH1L	8474	0.032	0.4	YES
71	DHX9	DHX9	DHX9	8561	0.03	0.4	YES
72	SNRPD2	SNRPD2	SNRPD2	8625	0.029	0.4	YES
73	SF3B2	SF3B2	SF3B2	8636	0.029	0.41	YES
74	HNRNPU	HNRNPU	HNRNPU	8654	0.029	0.41	YES
75	NUP62	NUP62	NUP62	8715	0.028	0.41	YES
76	PCBP1	PCBP1	PCBP1	8742	0.028	0.42	YES
77	HNRNPC	HNRNPC	HNRNPC	8783	0.027	0.42	YES
78	TPR	TPR	TPR	8793	0.027	0.42	YES
79	SNRNP70	SNRNP70	SNRNP70	8798	0.027	0.43	YES
80	NUP50	NUP50	NUP50	8838	0.027	0.43	YES
81	HNRNPA3	HNRNPA3	HNRNPA3	8855	0.026	0.43	YES
82	NXF1	NXF1	NXF1	8978	0.024	0.43	YES
83	NUPL1	NUPL1	NUPL1	9033	0.024	0.43	YES
84	PTBP1	PTBP1	PTBP1	9084	0.023	0.43	YES
85	HNRNPR	HNRNPR	HNRNPR	9140	0.022	0.43	YES
86	SF3A3	SF3A3	SF3A3	9254	0.021	0.43	YES
87	POM121	POM121	POM121	9264	0.021	0.44	YES
88	SMC1A	SMC1A	SMC1A	9446	0.019	0.43	YES
89	DDX23	DDX23	DDX23	9482	0.018	0.43	YES
90	POLR2L	POLR2L	POLR2L	9511	0.018	0.43	YES
91	NUP88	NUP88	NUP88	9530	0.018	0.43	YES
92	HNRNPUL1	HNRNPUL1	HNRNPUL1	9556	0.018	0.44	YES
93	SF3A2	SF3A2	SF3A2	9806	0.014	0.42	NO
94	CPSF2	CPSF2	CPSF2	10187	0.0097	0.41	NO
95	RNPS1	RNPS1	RNPS1	10196	0.0096	0.41	NO
96	YBX1	YBX1	YBX1	10214	0.0094	0.41	NO
97	HNRNPK	HNRNPK	HNRNPK	10329	0.008	0.4	NO
98	CD2BP2	CD2BP2	CD2BP2	10462	0.0062	0.4	NO
99	HNRNPM	HNRNPM	HNRNPM	10477	0.006	0.4	NO
100	NUP188	NUP188	NUP188	10553	0.0051	0.39	NO
101	SF3B5	SF3B5	SF3B5	10561	0.005	0.4	NO
102	HNRNPA1	HNRNPA1	HNRNPA1	10581	0.0048	0.4	NO
103	NFX1	NFX1	NFX1	10600	0.0046	0.39	NO
104	EIF4E	EIF4E	EIF4E	10616	0.0044	0.39	NO
105	HNRNPH2	HNRNPH2	HNRNPH2	10693	0.0031	0.39	NO
106	SF3B1	SF3B1	SF3B1	10724	0.0026	0.39	NO
107	POLR2E	POLR2E	POLR2E	10761	0.0021	0.39	NO
108	HNRNPH1	HNRNPH1	HNRNPH1	10778	0.0019	0.39	NO
109	NUP214	NUP214	NUP214	10816	0.0015	0.39	NO
110	HNRNPA0	HNRNPA0	HNRNPA0	10833	0.0013	0.38	NO
111	NUP54	NUP54	NUP54	11009	-0.0013	0.38	NO
112	NUP205	NUP205	NUP205	11198	-0.0037	0.37	NO
113	SRRM1	SRRM1	SRRM1	11477	-0.0075	0.35	NO
114	CDC40	CDC40	CDC40	11571	-0.0088	0.35	NO
115	NUDT21	NUDT21	NUDT21	11649	-0.0099	0.35	NO
116	NCBP1	NCBP1	NCBP1	11671	-0.01	0.35	NO
117	RANBP2	RANBP2	RANBP2	11716	-0.011	0.35	NO
118	HNRNPF	HNRNPF	HNRNPF	11777	-0.011	0.35	NO
119	DHX38	DHX38	DHX38	11790	-0.012	0.35	NO
120	RBM5	RBM5	RBM5	11808	-0.012	0.35	NO
121	POLR2A	POLR2A	POLR2A	11899	-0.013	0.35	NO
122	PRPF8	PRPF8	PRPF8	12145	-0.016	0.34	NO
123	SF3A1	SF3A1	SF3A1	12215	-0.017	0.34	NO
124	PCF11	PCF11	PCF11	12400	-0.02	0.33	NO
125	POLR2B	POLR2B	POLR2B	12555	-0.022	0.32	NO
126	GTF2F1	GTF2F1	GTF2F1	13269	-0.034	0.29	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: REACTOME METABOLISM OF VITAMINS AND COFACTORS.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME METABOLISM OF VITAMINS AND COFACTORS, 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 PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA

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	APOA1	APOA1	APOA1	59	0.62	0.12	YES
2	APOC3	APOC3	APOC3	60	0.62	0.25	YES
3	APOA2	APOA2	APOA2	211	0.5	0.35	YES
4	APOA5	APOA5	APOA5	270	0.47	0.44	YES
5	APOB	APOB	APOB	526	0.39	0.51	YES
6	LIPC	LIPC	LIPC	1015	0.31	0.54	YES
7	ALB	ALB	ALB	1156	0.29	0.6	YES
8	SCARB1	SCARB1	SCARB1	1673	0.24	0.62	YES
9	LPA	LPA	LPA	1960	0.21	0.64	YES
10	APOC2	APOC2	APOC2	3056	0.15	0.62	NO
11	MTTP	MTTP	MTTP	3202	0.15	0.64	NO
12	PLTP	PLTP	PLTP	4156	0.11	0.61	NO
13	LPL	LPL	LPL	7966	0.039	0.42	NO
14	P4HB	P4HB	P4HB	8401	0.033	0.4	NO
15	LCAT	LCAT	LCAT	10024	0.012	0.31	NO
16	LDLRAP1	LDLRAP1	LDLRAP1	10807	0.0016	0.27	NO
17	CUBN	CUBN	CUBN	10926	-0.000095	0.27	NO
18	BMP1	BMP1	BMP1	10949	-0.00044	0.26	NO
19	AMN	AMN	AMN	12893	-0.028	0.17	NO
20	SAR1B	SAR1B	SAR1B	13521	-0.038	0.14	NO
21	ABCA1	ABCA1	ABCA1	13716	-0.041	0.14	NO
22	APOE	APOE	APOE	14069	-0.049	0.13	NO
23	HSPG2	HSPG2	HSPG2	14596	-0.06	0.11	NO
24	SDC1	SDC1	SDC1	14745	-0.064	0.12	NO
25	ABCG1	ABCG1	ABCG1	15212	-0.075	0.11	NO
26	A2M	A2M	A2M	16297	-0.11	0.074	NO
27	CETP	CETP	CETP	16614	-0.12	0.083	NO
28	LDLR	LDLR	LDLR	16800	-0.13	0.1	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: REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA, 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 AMINO ACID TRANSPORT ACROSS THE PLASMA MEMBRANE

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	SLC38A3	SLC38A3	SLC38A3	57	0.62	0.14	YES
2	SLC7A10	SLC7A10	SLC7A10	131	0.54	0.26	YES
3	SLC16A10	SLC16A10	SLC16A10	174	0.52	0.38	YES
4	SLC7A2	SLC7A2	SLC7A2	1477	0.26	0.36	YES
5	SLC6A12	SLC6A12	SLC6A12	1528	0.25	0.42	YES
6	SLC7A9	SLC7A9	SLC7A9	1791	0.23	0.46	YES
7	SLC6A15	SLC6A15	SLC6A15	2142	0.2	0.48	YES
8	SLC7A5	SLC7A5	SLC7A5	3220	0.14	0.46	YES
9	SLC36A2	SLC36A2	SLC36A2	3517	0.13	0.47	YES
10	SLC43A2	SLC43A2	SLC43A2	3623	0.13	0.5	YES
11	SLC38A4	SLC38A4	SLC38A4	3658	0.13	0.52	YES
12	SLC1A5	SLC1A5	SLC1A5	3763	0.13	0.55	YES
13	SLC6A19	SLC6A19	SLC6A19	3777	0.13	0.58	YES
14	SLC3A2	SLC3A2	SLC3A2	4160	0.11	0.58	YES
15	SLC43A1	SLC43A1	SLC43A1	4217	0.11	0.6	YES
16	SLC3A1	SLC3A1	SLC3A1	5879	0.073	0.53	NO
17	SLC7A3	SLC7A3	SLC7A3	6354	0.064	0.52	NO
18	SLC7A7	SLC7A7	SLC7A7	6732	0.058	0.51	NO
19	SLC6A18	SLC6A18	SLC6A18	7579	0.045	0.48	NO
20	SLC7A6	SLC7A6	SLC7A6	9235	0.021	0.4	NO
21	SLC38A5	SLC38A5	SLC38A5	9493	0.018	0.38	NO
22	SLC1A4	SLC1A4	SLC1A4	10137	0.01	0.35	NO
23	SLC6A6	SLC6A6	SLC6A6	10421	0.0067	0.34	NO
24	SLC38A1	SLC38A1	SLC38A1	10554	0.0051	0.33	NO
25	SLC7A8	SLC7A8	SLC7A8	11789	-0.012	0.27	NO
26	SLC38A2	SLC38A2	SLC38A2	12549	-0.022	0.23	NO
27	SLC36A1	SLC36A1	SLC36A1	12967	-0.029	0.22	NO
28	SLC7A1	SLC7A1	SLC7A1	13379	-0.036	0.2	NO
29	SLC6A20	SLC6A20	SLC6A20	15530	-0.085	0.11	NO
30	SLC7A11	SLC7A11	SLC7A11	16228	-0.11	0.096	NO
31	SLC6A14	SLC6A14	SLC6A14	17115	-0.15	0.084	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: REACTOME AMINO ACID TRANSPORT ACROSS THE PLASMA MEMBRANE.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME AMINO ACID TRANSPORT ACROSS THE PLASMA MEMBRANE, 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 PURINE METABOLISM	155	genes.ES.table	0.39	1.6	0.01	0.18	0.97	0.17	0.13	0.15	0.095	0.015
KEGG TYROSINE METABOLISM	41	genes.ES.table	0.49	1.3	0.098	0.25	1	0.22	0.1	0.2	0.19	0.001
KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE	26	genes.ES.table	0.52	1.4	0.09	0.22	1	0.42	0.27	0.31	0.17	0.003
KEGG ABC TRANSPORTERS	44	genes.ES.table	0.59	1.6	0.015	0.18	0.97	0.25	0.12	0.22	0.1	0.015
KEGG MAPK SIGNALING PATHWAY	257	genes.ES.table	0.45	1.7	0	0.18	0.86	0.38	0.3	0.28	0.073	0.036
KEGG ERBB SIGNALING PATHWAY	87	genes.ES.table	0.4	1.5	0.023	0.17	0.98	0.22	0.19	0.18	0.097	0.009
KEGG CALCIUM SIGNALING PATHWAY	175	genes.ES.table	0.63	1.7	0	0.18	0.86	0.46	0.19	0.37	0.073	0.037
KEGG CHEMOKINE SIGNALING PATHWAY	185	genes.ES.table	0.48	1.4	0.13	0.22	1	0.38	0.23	0.3	0.17	0.002
KEGG PHOSPHATIDYLINOSITOL SIGNALING SYSTEM	76	genes.ES.table	0.41	1.5	0.052	0.18	1	0.47	0.32	0.32	0.12	0.005
KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION	245	genes.ES.table	0.58	1.5	0.0041	0.19	1	0.51	0.24	0.4	0.13	0.004

genes ES table in pathway: KEGG PURINE METABOLISM

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	ADCY5	ADCY5	ADCY5	160	0.85	0.037	YES
2	ADCY2	ADCY2	ADCY2	261	0.78	0.074	YES
3	ADCYAP1R1	ADCYAP1R1	ADCYAP1R1	314	0.74	0.11	YES
4	ADCYAP1	ADCYAP1	ADCYAP1	320	0.74	0.15	YES
5	PDE1A	PDE1A	PDE1A	342	0.72	0.19	YES
6	PDE1B	PDE1B	PDE1B	515	0.66	0.21	YES
7	NGF	NGF	NGF	624	0.62	0.24	YES
8	PRKAR2B	PRKAR2B	PRKAR2B	828	0.55	0.26	YES
9	NTRK1	NTRK1	NTRK1	953	0.52	0.28	YES
10	NTRK2	NTRK2	NTRK2	994	0.52	0.31	YES
11	AKT3	AKT3	AKT3	1032	0.51	0.33	YES
12	CAMK4	CAMK4	CAMK4	1118	0.49	0.35	YES
13	MEF2C	MEF2C	MEF2C	1496	0.42	0.36	YES
14	ADCY4	ADCY4	ADCY4	1577	0.41	0.37	YES
15	SHC2	SHC2	SHC2	2257	0.32	0.35	YES
16	MAPK11	MAPK11	MAPK11	2763	0.26	0.34	YES
17	PRKACB	PRKACB	PRKACB	2792	0.26	0.35	YES
18	SHC3	SHC3	SHC3	2952	0.25	0.36	YES
19	ADORA2A	ADORA2A	ADORA2A	3000	0.24	0.37	YES
20	ADCY9	ADCY9	ADCY9	3153	0.23	0.37	YES
21	SH3GL2	SH3GL2	SH3GL2	3411	0.21	0.37	YES
22	PIK3R1	PIK3R1	PIK3R1	3462	0.21	0.38	YES
23	ITPR2	ITPR2	ITPR2	3504	0.21	0.39	YES
24	RPS6KA5	RPS6KA5	RPS6KA5	3585	0.2	0.4	YES
25	MEF2A	MEF2A	MEF2A	3620	0.2	0.4	YES
26	IRS2	IRS2	IRS2	3649	0.2	0.41	YES
27	RPS6KA2	RPS6KA2	RPS6KA2	3709	0.19	0.42	YES
28	IRS1	IRS1	IRS1	3781	0.19	0.43	YES
29	DNM1	DNM1	DNM1	3847	0.18	0.43	YES
30	PRKCE	PRKCE	PRKCE	4134	0.16	0.43	YES
31	FOXO4	FOXO4	FOXO4	4292	0.15	0.43	YES
32	DUSP3	DUSP3	DUSP3	4358	0.15	0.43	YES
33	ADCY8	ADCY8	ADCY8	4557	0.14	0.43	YES
34	FOXO1	FOXO1	FOXO1	4563	0.14	0.44	YES
35	ADCY1	ADCY1	ADCY1	4693	0.13	0.44	YES
36	RAP1A	RAP1A	RAP1A	5026	0.12	0.42	YES
37	PIK3CA	PIK3CA	PIK3CA	5049	0.12	0.43	YES
38	RAPGEF1	RAPGEF1	RAPGEF1	5155	0.11	0.43	YES
39	MAP2K5	MAP2K5	MAP2K5	5197	0.11	0.43	YES
40	PRKCG	PRKCG	PRKCG	5226	0.11	0.44	YES
41	PTEN	PTEN	PTEN	5404	0.1	0.43	YES
42	PRKCA	PRKCA	PRKCA	5442	0.099	0.44	YES
43	ADCY7	ADCY7	ADCY7	5533	0.095	0.44	YES
44	NR4A1	NR4A1	NR4A1	5545	0.095	0.44	YES
45	KIDINS220	KIDINS220	KIDINS220	5553	0.094	0.44	YES
46	CDKN1B	CDKN1B	CDKN1B	5721	0.088	0.44	YES
47	ADCY3	ADCY3	ADCY3	5752	0.087	0.44	YES
48	PRKACA	PRKACA	PRKACA	5809	0.085	0.44	YES
49	MAPK12	MAPK12	MAPK12	5814	0.085	0.45	YES
50	PLCG1	PLCG1	PLCG1	5848	0.084	0.45	YES
51	MAPKAP1	MAPKAP1	MAPKAP1	6033	0.077	0.45	NO
52	SOS1	SOS1	SOS1	6105	0.075	0.45	NO
53	PRKAR2A	PRKAR2A	PRKAR2A	6208	0.072	0.44	NO
54	TSC2	TSC2	TSC2	6211	0.072	0.45	NO
55	BRAF	BRAF	BRAF	6609	0.06	0.43	NO
56	STAT3	STAT3	STAT3	6623	0.06	0.43	NO
57	PRKAR1A	PRKAR1A	PRKAR1A	6674	0.058	0.43	NO
58	CREB1	CREB1	CREB1	6736	0.057	0.43	NO
59	PDPK1	PDPK1	PDPK1	7090	0.047	0.42	NO
60	CALM1	CALM1	CALM1	7097	0.047	0.42	NO
61	RICTOR	RICTOR	RICTOR	7155	0.046	0.42	NO
62	MAPK7	MAPK7	MAPK7	7205	0.045	0.42	NO
63	AKT2	AKT2	AKT2	7332	0.042	0.41	NO
64	RPS6KA3	RPS6KA3	RPS6KA3	7337	0.041	0.42	NO
65	ELK1	ELK1	ELK1	7440	0.039	0.41	NO
66	AP2A2	AP2A2	AP2A2	7473	0.038	0.41	NO
67	FOXO3	FOXO3	FOXO3	7485	0.038	0.41	NO
68	MAPK14	MAPK14	MAPK14	7542	0.037	0.41	NO
69	FRS2	FRS2	FRS2	7782	0.032	0.4	NO
70	MAPK1	MAPK1	MAPK1	8166	0.024	0.38	NO
71	AP2A1	AP2A1	AP2A1	8328	0.021	0.38	NO
72	SHC1	SHC1	SHC1	8385	0.019	0.37	NO
73	DUSP6	DUSP6	DUSP6	8625	0.015	0.36	NO
74	MAPKAPK2	MAPKAPK2	MAPKAPK2	8859	0.011	0.35	NO
75	CRK	CRK	CRK	8934	0.0094	0.35	NO
76	RAF1	RAF1	RAF1	9003	0.0082	0.34	NO
77	RALGDS	RALGDS	RALGDS	9090	0.0066	0.34	NO
78	AP2M1	AP2M1	AP2M1	9180	0.0051	0.33	NO
79	RIT1	RIT1	RIT1	9248	0.0037	0.33	NO
80	PPP2CB	PPP2CB	PPP2CB	9249	0.0036	0.33	NO
81	AKT1	AKT1	AKT1	9288	0.0029	0.33	NO
82	MTOR	MTOR	MTOR	9314	0.0024	0.33	NO
83	RHOA	RHOA	RHOA	9354	0.0015	0.32	NO
84	PRKAR1B	PRKAR1B	PRKAR1B	9587	-0.0024	0.31	NO
85	MDM2	MDM2	MDM2	9639	-0.0032	0.31	NO
86	CALM3	CALM3	CALM3	9767	-0.0058	0.3	NO
87	BAD	BAD	BAD	9784	-0.0062	0.3	NO
88	ADCY6	ADCY6	ADCY6	9896	-0.0082	0.3	NO
89	CDKN1A	CDKN1A	CDKN1A	9949	-0.0091	0.3	NO
90	CALM2	CALM2	CALM2	9971	-0.0096	0.3	NO
91	CASP9	CASP9	CASP9	9989	-0.0099	0.29	NO
92	GRB2	GRB2	GRB2	10085	-0.011	0.29	NO
93	ATF1	ATF1	ATF1	10465	-0.018	0.27	NO
94	PPP2R1A	PPP2R1A	PPP2R1A	10580	-0.019	0.26	NO
95	AP2B1	AP2B1	AP2B1	10648	-0.02	0.26	NO
96	DUSP7	DUSP7	DUSP7	10697	-0.021	0.26	NO
97	THEM4	THEM4	THEM4	10796	-0.023	0.26	NO
98	MAP2K1	MAP2K1	MAP2K1	10906	-0.025	0.25	NO
99	PPP2R5D	PPP2R5D	PPP2R5D	10979	-0.026	0.25	NO
100	KRAS	KRAS	KRAS	10994	-0.027	0.25	NO
101	AKT1S1	AKT1S1	AKT1S1	11074	-0.028	0.25	NO
102	PIK3R2	PIK3R2	PIK3R2	11116	-0.029	0.25	NO
103	MAP2K2	MAP2K2	MAP2K2	11283	-0.031	0.24	NO
104	ADRBK1	ADRBK1	ADRBK1	11340	-0.032	0.24	NO
105	PPP2CA	PPP2CA	PPP2CA	11572	-0.036	0.23	NO
106	CLTC	CLTC	CLTC	11636	-0.036	0.23	NO
107	GSK3A	GSK3A	GSK3A	11704	-0.038	0.22	NO
108	MAPK3	MAPK3	MAPK3	11852	-0.04	0.22	NO
109	PHLPP1	PHLPP1	PHLPP1	12525	-0.051	0.19	NO
110	CHUK	CHUK	CHUK	12593	-0.052	0.18	NO
111	MLST8	MLST8	MLST8	12618	-0.053	0.19	NO
112	RALB	RALB	RALB	12673	-0.054	0.19	NO
113	YWHAB	YWHAB	YWHAB	12844	-0.057	0.18	NO
114	PIK3CB	PIK3CB	PIK3CB	13345	-0.066	0.16	NO
115	AP2S1	AP2S1	AP2S1	13564	-0.07	0.15	NO
116	MAPKAPK3	MAPKAPK3	MAPKAPK3	13598	-0.071	0.15	NO
117	DNAL4	DNAL4	DNAL4	13635	-0.071	0.15	NO
118	DNM2	DNM2	DNM2	13653	-0.072	0.16	NO
119	CLTA	CLTA	CLTA	13722	-0.073	0.16	NO
120	NRAS	NRAS	NRAS	14079	-0.08	0.14	NO
121	PRKACG	PRKACG	PRKACG	14345	-0.086	0.13	NO
122	HRAS	HRAS	HRAS	14495	-0.089	0.13	NO
123	DUSP4	DUSP4	DUSP4	14625	-0.092	0.13	NO
124	RALA	RALA	RALA	15022	-0.1	0.11	NO
125	PPP2R1B	PPP2R1B	PPP2R1B	15172	-0.11	0.11	NO
126	SRC	SRC	SRC	15271	-0.11	0.11	NO
127	RPS6KB2	RPS6KB2	RPS6KB2	15545	-0.12	0.1	NO
128	PRKCD	PRKCD	PRKCD	15704	-0.12	0.099	NO
129	RPS6KA1	RPS6KA1	RPS6KA1	15741	-0.12	0.1	NO
130	ITPR3	ITPR3	ITPR3	15966	-0.13	0.099	NO
131	MAPK13	MAPK13	MAPK13	17652	-0.23	0.02	NO
132	CDK1	CDK1	CDK1	18076	-0.27	0.012	NO
133	TRIB3	TRIB3	TRIB3	18564	-0.38	0.0059	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 PURINE METABOLISM.

Figure S22. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PURINE 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 TYROSINE METABOLISM

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	IGF1	IGF1	IGF1	205	0.82	0.094	YES
2	FIGF	FIGF	FIGF	420	0.68	0.17	YES
3	PRKAA2	PRKAA2	PRKAA2	923	0.53	0.21	YES
4	AKT3	AKT3	AKT3	1032	0.51	0.27	YES
5	RPS6KA6	RPS6KA6	RPS6KA6	1132	0.49	0.33	YES
6	PIK3CG	PIK3CG	PIK3CG	1485	0.42	0.36	YES
7	VEGFC	VEGFC	VEGFC	1671	0.39	0.4	YES
8	CAB39L	CAB39L	CAB39L	1767	0.38	0.45	YES
9	ULK2	ULK2	ULK2	2169	0.33	0.47	YES
10	PIK3R5	PIK3R5	PIK3R5	2199	0.33	0.51	YES
11	PIK3CD	PIK3CD	PIK3CD	2647	0.28	0.52	YES
12	PIK3R1	PIK3R1	PIK3R1	3462	0.21	0.51	NO
13	RPS6KA2	RPS6KA2	RPS6KA2	3709	0.19	0.52	NO
14	VEGFB	VEGFB	VEGFB	4164	0.16	0.51	NO
15	PIK3R3	PIK3R3	PIK3R3	4598	0.14	0.51	NO
16	PIK3CA	PIK3CA	PIK3CA	5049	0.12	0.5	NO
17	PGF	PGF	PGF	5515	0.096	0.49	NO
18	ULK1	ULK1	ULK1	5849	0.084	0.48	NO
19	TSC2	TSC2	TSC2	6211	0.072	0.47	NO
20	BRAF	BRAF	BRAF	6609	0.06	0.46	NO
21	PDPK1	PDPK1	PDPK1	7090	0.047	0.44	NO
22	RICTOR	RICTOR	RICTOR	7155	0.046	0.44	NO
23	RPTOR	RPTOR	RPTOR	7321	0.042	0.44	NO
24	AKT2	AKT2	AKT2	7332	0.042	0.44	NO
25	RPS6KA3	RPS6KA3	RPS6KA3	7337	0.041	0.44	NO
26	EIF4B	EIF4B	EIF4B	7701	0.033	0.43	NO
27	TSC1	TSC1	TSC1	7717	0.033	0.43	NO
28	MAPK1	MAPK1	MAPK1	8166	0.024	0.41	NO
29	STRADA	STRADA	STRADA	8271	0.022	0.41	NO
30	AKT1	AKT1	AKT1	9288	0.0029	0.36	NO
31	MTOR	MTOR	MTOR	9314	0.0024	0.35	NO
32	RPS6KB1	RPS6KB1	RPS6KB1	9510	-0.0011	0.34	NO
33	HIF1A	HIF1A	HIF1A	9991	-0.0099	0.32	NO
34	STK11	STK11	STK11	10167	-0.013	0.31	NO
35	CAB39	CAB39	CAB39	10226	-0.014	0.31	NO
36	RPS6	RPS6	RPS6	10364	-0.016	0.3	NO
37	DDIT4	DDIT4	DDIT4	10863	-0.024	0.28	NO
38	PRKAA1	PRKAA1	PRKAA1	11051	-0.028	0.27	NO
39	PIK3R2	PIK3R2	PIK3R2	11116	-0.029	0.28	NO
40	RHEB	RHEB	RHEB	11433	-0.033	0.26	NO
41	MAPK3	MAPK3	MAPK3	11852	-0.04	0.24	NO
42	MLST8	MLST8	MLST8	12618	-0.053	0.21	NO
43	ULK3	ULK3	ULK3	12985	-0.059	0.2	NO
44	EIF4E2	EIF4E2	EIF4E2	13125	-0.062	0.2	NO
45	PIK3CB	PIK3CB	PIK3CB	13345	-0.066	0.2	NO
46	EIF4E	EIF4E	EIF4E	14870	-0.098	0.13	NO
47	RPS6KB2	RPS6KB2	RPS6KB2	15545	-0.12	0.11	NO
48	RPS6KA1	RPS6KA1	RPS6KA1	15741	-0.12	0.11	NO
49	EIF4EBP1	EIF4EBP1	EIF4EBP1	16432	-0.15	0.094	NO
50	VEGFA	VEGFA	VEGFA	17374	-0.2	0.07	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: KEGG TYROSINE METABOLISM.

Figure S24. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG TYROSINE 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 GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE

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	ADCY5	ADCY5	ADCY5	160	0.85	0.061	YES
2	ADCY2	ADCY2	ADCY2	261	0.78	0.12	YES
3	PDE1A	PDE1A	PDE1A	342	0.72	0.17	YES
4	PDE1B	PDE1B	PDE1B	515	0.66	0.22	YES
5	PRKAR2B	PRKAR2B	PRKAR2B	828	0.55	0.25	YES
6	AKT3	AKT3	AKT3	1032	0.51	0.28	YES
7	CAMK4	CAMK4	CAMK4	1118	0.49	0.31	YES
8	ADCY4	ADCY4	ADCY4	1577	0.41	0.32	YES
9	PRKACB	PRKACB	PRKACB	2792	0.26	0.28	YES
10	LRIG1	LRIG1	LRIG1	3031	0.24	0.28	YES
11	ADCY9	ADCY9	ADCY9	3153	0.23	0.3	YES
12	SH3GL2	SH3GL2	SH3GL2	3411	0.21	0.3	YES
13	PIK3R1	PIK3R1	PIK3R1	3462	0.21	0.31	YES
14	ITPR2	ITPR2	ITPR2	3504	0.21	0.33	YES
15	GAB1	GAB1	GAB1	3561	0.2	0.34	YES
16	PRKCE	PRKCE	PRKCE	4134	0.16	0.32	YES
17	FOXO4	FOXO4	FOXO4	4292	0.15	0.33	YES
18	ADAM12	ADAM12	ADAM12	4303	0.15	0.34	YES
19	ADCY8	ADCY8	ADCY8	4557	0.14	0.34	YES
20	FOXO1	FOXO1	FOXO1	4563	0.14	0.35	YES
21	SPRY1	SPRY1	SPRY1	4588	0.14	0.36	YES
22	ADCY1	ADCY1	ADCY1	4693	0.13	0.36	YES
23	PIK3CA	PIK3CA	PIK3CA	5049	0.12	0.36	YES
24	PRKCG	PRKCG	PRKCG	5226	0.11	0.35	YES
25	CBL	CBL	CBL	5320	0.1	0.36	YES
26	PTEN	PTEN	PTEN	5404	0.1	0.36	YES
27	PRKCA	PRKCA	PRKCA	5442	0.099	0.37	YES
28	EGFR	EGFR	EGFR	5456	0.098	0.38	YES
29	ADCY7	ADCY7	ADCY7	5533	0.095	0.38	YES
30	NR4A1	NR4A1	NR4A1	5545	0.095	0.39	YES
31	CDKN1B	CDKN1B	CDKN1B	5721	0.088	0.38	YES
32	ADCY3	ADCY3	ADCY3	5752	0.087	0.39	YES
33	PRKACA	PRKACA	PRKACA	5809	0.085	0.39	YES
34	PLCG1	PLCG1	PLCG1	5848	0.084	0.4	YES
35	EPS15	EPS15	EPS15	5905	0.081	0.4	YES
36	MAPKAP1	MAPKAP1	MAPKAP1	6033	0.077	0.4	YES
37	SOS1	SOS1	SOS1	6105	0.075	0.4	YES
38	PRKAR2A	PRKAR2A	PRKAR2A	6208	0.072	0.4	YES
39	TSC2	TSC2	TSC2	6211	0.072	0.41	YES
40	PRKAR1A	PRKAR1A	PRKAR1A	6674	0.058	0.39	NO
41	CREB1	CREB1	CREB1	6736	0.057	0.39	NO
42	PAG1	PAG1	PAG1	6844	0.054	0.39	NO
43	PDPK1	PDPK1	PDPK1	7090	0.047	0.38	NO
44	CALM1	CALM1	CALM1	7097	0.047	0.38	NO
45	RICTOR	RICTOR	RICTOR	7155	0.046	0.38	NO
46	AKT2	AKT2	AKT2	7332	0.042	0.38	NO
47	AP2A2	AP2A2	AP2A2	7473	0.038	0.37	NO
48	FOXO3	FOXO3	FOXO3	7485	0.038	0.38	NO
49	SPRY2	SPRY2	SPRY2	7946	0.028	0.35	NO
50	MAPK1	MAPK1	MAPK1	8166	0.024	0.34	NO
51	STAM2	STAM2	STAM2	8295	0.021	0.34	NO
52	AP2A1	AP2A1	AP2A1	8328	0.021	0.34	NO
53	SHC1	SHC1	SHC1	8385	0.019	0.34	NO
54	EPS15L1	EPS15L1	EPS15L1	8634	0.015	0.32	NO
55	SH3KBP1	SH3KBP1	SH3KBP1	8798	0.012	0.32	NO
56	RAF1	RAF1	RAF1	9003	0.0082	0.31	NO
57	AP2M1	AP2M1	AP2M1	9180	0.0051	0.3	NO
58	AKT1	AKT1	AKT1	9288	0.0029	0.29	NO
59	MTOR	MTOR	MTOR	9314	0.0024	0.29	NO
60	PRKAR1B	PRKAR1B	PRKAR1B	9587	-0.0024	0.28	NO
61	MDM2	MDM2	MDM2	9639	-0.0032	0.27	NO
62	CALM3	CALM3	CALM3	9767	-0.0058	0.27	NO
63	BAD	BAD	BAD	9784	-0.0062	0.27	NO
64	CDC42	CDC42	CDC42	9840	-0.0072	0.26	NO
65	ADCY6	ADCY6	ADCY6	9896	-0.0082	0.26	NO
66	CDKN1A	CDKN1A	CDKN1A	9949	-0.0091	0.26	NO
67	CALM2	CALM2	CALM2	9971	-0.0096	0.26	NO
68	CASP9	CASP9	CASP9	9989	-0.0099	0.26	NO
69	ADAM17	ADAM17	ADAM17	10054	-0.011	0.26	NO
70	RPS27A	RPS27A	RPS27A	10077	-0.011	0.26	NO
71	GRB2	GRB2	GRB2	10085	-0.011	0.26	NO
72	UBA52	UBA52	UBA52	10288	-0.015	0.25	NO
73	AP2B1	AP2B1	AP2B1	10648	-0.02	0.23	NO
74	THEM4	THEM4	THEM4	10796	-0.023	0.22	NO
75	MAP2K1	MAP2K1	MAP2K1	10906	-0.025	0.22	NO
76	KRAS	KRAS	KRAS	10994	-0.027	0.22	NO
77	AKT1S1	AKT1S1	AKT1S1	11074	-0.028	0.22	NO
78	STAM	STAM	STAM	11187	-0.03	0.21	NO
79	MAP2K2	MAP2K2	MAP2K2	11283	-0.031	0.21	NO
80	ADRBK1	ADRBK1	ADRBK1	11340	-0.032	0.21	NO
81	CLTC	CLTC	CLTC	11636	-0.036	0.2	NO
82	CSK	CSK	CSK	11637	-0.036	0.2	NO
83	GSK3A	GSK3A	GSK3A	11704	-0.038	0.2	NO
84	MAPK3	MAPK3	MAPK3	11852	-0.04	0.19	NO
85	CDC37	CDC37	CDC37	12060	-0.044	0.19	NO
86	EGF	EGF	EGF	12353	-0.049	0.18	NO
87	PHLPP1	PHLPP1	PHLPP1	12525	-0.051	0.17	NO
88	CHUK	CHUK	CHUK	12593	-0.052	0.17	NO
89	MLST8	MLST8	MLST8	12618	-0.053	0.17	NO
90	ADAM10	ADAM10	ADAM10	12723	-0.055	0.17	NO
91	EPN1	EPN1	EPN1	12725	-0.055	0.18	NO
92	YWHAB	YWHAB	YWHAB	12844	-0.057	0.18	NO
93	HGS	HGS	HGS	13279	-0.064	0.16	NO
94	AP2S1	AP2S1	AP2S1	13564	-0.07	0.15	NO
95	CLTA	CLTA	CLTA	13722	-0.073	0.14	NO
96	NRAS	NRAS	NRAS	14079	-0.08	0.13	NO
97	PRKACG	PRKACG	PRKACG	14345	-0.086	0.12	NO
98	HRAS	HRAS	HRAS	14495	-0.089	0.12	NO
99	HSP90AA1	HSP90AA1	HSP90AA1	14530	-0.09	0.13	NO
100	SRC	SRC	SRC	15271	-0.11	0.099	NO
101	RPS6KB2	RPS6KB2	RPS6KB2	15545	-0.12	0.094	NO
102	PRKCD	PRKCD	PRKCD	15704	-0.12	0.096	NO
103	ITPR3	ITPR3	ITPR3	15966	-0.13	0.093	NO
104	CDK1	CDK1	CDK1	18076	-0.27	0.0013	NO
105	TRIB3	TRIB3	TRIB3	18564	-0.38	0.0059	NO

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

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

genes ES table in pathway: KEGG ABC TRANSPORTERS

Table 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	ESR1	ESR1	ESR1	393	0.7	0.1	YES
2	MAPT	MAPT	MAPT	541	0.65	0.21	YES
3	PRKAA2	PRKAA2	PRKAA2	923	0.53	0.28	YES
4	MAP2	MAP2	MAP2	1378	0.44	0.34	YES
5	SMARCD3	SMARCD3	SMARCD3	1380	0.44	0.41	YES
6	BRSK1	BRSK1	BRSK1	1866	0.36	0.45	YES
7	SIK3	SIK3	SIK3	4512	0.14	0.34	NO
8	SMAD4	SMAD4	SMAD4	5154	0.11	0.32	NO
9	SIK2	SIK2	SIK2	5339	0.1	0.33	NO
10	SIK1	SIK1	SIK1	5653	0.091	0.33	NO
11	PRKACA	PRKACA	PRKACA	5809	0.085	0.34	NO
12	TSC2	TSC2	TSC2	6211	0.072	0.33	NO
13	CREB1	CREB1	CREB1	6736	0.057	0.31	NO
14	RPTOR	RPTOR	RPTOR	7321	0.042	0.28	NO
15	TSC1	TSC1	TSC1	7717	0.033	0.27	NO
16	BRSK2	BRSK2	BRSK2	7944	0.028	0.26	NO
17	TP53	TP53	TP53	8022	0.027	0.26	NO
18	STRADA	STRADA	STRADA	8271	0.022	0.25	NO
19	MARK4	MARK4	MARK4	8468	0.018	0.24	NO
20	PRKAB1	PRKAB1	PRKAB1	9095	0.0065	0.21	NO
21	YWHAH	YWHAH	YWHAH	9245	0.0037	0.2	NO
22	MTOR	MTOR	MTOR	9314	0.0024	0.2	NO
23	YWHAQ	YWHAQ	YWHAQ	9697	-0.0044	0.18	NO
24	MYC	MYC	MYC	9862	-0.0077	0.18	NO
25	STK11	STK11	STK11	10167	-0.013	0.16	NO
26	CAB39	CAB39	CAB39	10226	-0.014	0.16	NO
27	GSK3B	GSK3B	GSK3B	10374	-0.016	0.16	NO
28	PRKAG1	PRKAG1	PRKAG1	10780	-0.023	0.14	NO
29	PRKAA1	PRKAA1	PRKAA1	11051	-0.028	0.13	NO
30	AKT1S1	AKT1S1	AKT1S1	11074	-0.028	0.13	NO
31	CTSD	CTSD	CTSD	11322	-0.031	0.12	NO
32	CRTC2	CRTC2	CRTC2	11357	-0.032	0.13	NO
33	YWHAG	YWHAG	YWHAG	11423	-0.033	0.13	NO
34	PSEN2	PSEN2	PSEN2	11459	-0.034	0.13	NO
35	CDC37	CDC37	CDC37	12060	-0.044	0.11	NO
36	MLST8	MLST8	MLST8	12618	-0.053	0.089	NO
37	YWHAB	YWHAB	YWHAB	12844	-0.057	0.087	NO
38	STK11IP	STK11IP	STK11IP	12964	-0.059	0.091	NO
39	YWHAZ	YWHAZ	YWHAZ	14238	-0.084	0.038	NO
40	MARK2	MARK2	MARK2	14389	-0.086	0.045	NO
41	YWHAE	YWHAE	YWHAE	14434	-0.088	0.058	NO
42	HSP90AA1	HSP90AA1	HSP90AA1	14530	-0.09	0.069	NO
43	STRADB	STRADB	STRADB	14741	-0.095	0.074	NO
44	MST4	MST4	MST4	15098	-0.1	0.074	NO
45	EZR	EZR	EZR	15431	-0.12	0.076	NO
46	ETV4	ETV4	ETV4	17874	-0.25	-0.011	NO
47	SFN	SFN	SFN	18304	-0.3	0.02	NO

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

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

genes ES table in pathway: KEGG MAPK SIGNALING PATHWAY

Table S15. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACTG2	ACTG2	ACTG2	114	0.87	0.13	YES
2	FLNC	FLNC	FLNC	117	0.87	0.27	YES
3	MYLK	MYLK	MYLK	564	0.64	0.35	YES
4	PAK3	PAK3	PAK3	676	0.6	0.44	YES
5	CFL2	CFL2	CFL2	846	0.55	0.52	YES
6	FLNA	FLNA	FLNA	1499	0.42	0.55	YES
7	ANGPTL2	ANGPTL2	ANGPTL2	1818	0.37	0.59	YES
8	WASF1	WASF1	WASF1	1974	0.35	0.64	YES
9	PFN2	PFN2	PFN2	4902	0.12	0.5	NO
10	ROCK1	ROCK1	ROCK1	6056	0.076	0.45	NO
11	PAK7	PAK7	PAK7	6362	0.067	0.45	NO
12	ROCK2	ROCK2	ROCK2	6777	0.055	0.44	NO
13	FSCN1	FSCN1	FSCN1	7185	0.045	0.42	NO
14	RPS4X	RPS4X	RPS4X	8992	0.0084	0.32	NO
15	GDI1	GDI1	GDI1	9027	0.0077	0.32	NO
16	RHO	RHO	RHO	9160	0.0054	0.32	NO
17	AKT1	AKT1	AKT1	9288	0.0029	0.31	NO
18	PFN1	PFN1	PFN1	9699	-0.0044	0.29	NO
19	CDC42	CDC42	CDC42	9840	-0.0072	0.28	NO
20	PAK2	PAK2	PAK2	10131	-0.012	0.27	NO
21	ACTR2	ACTR2	ACTR2	10159	-0.012	0.27	NO
22	WASL	WASL	WASL	10191	-0.013	0.27	NO
23	VASP	VASP	VASP	10233	-0.014	0.27	NO
24	LIMK1	LIMK1	LIMK1	11178	-0.03	0.23	NO
25	GDI2	GDI2	GDI2	11230	-0.03	0.23	NO
26	ACTG1	ACTG1	ACTG1	11592	-0.036	0.21	NO
27	ACTR3	ACTR3	ACTR3	11617	-0.036	0.22	NO
28	FSCN2	FSCN2	FSCN2	11689	-0.037	0.22	NO
29	CFL1	CFL1	CFL1	12664	-0.054	0.18	NO
30	PAK1	PAK1	PAK1	14234	-0.084	0.11	NO
31	PAK4	PAK4	PAK4	16207	-0.14	0.023	NO
32	MYLK2	MYLK2	MYLK2	16229	-0.14	0.045	NO
33	FSCN3	FSCN3	FSCN3	17262	-0.2	0.021	NO
34	PAK6	PAK6	PAK6	18474	-0.34	0.011	NO

Figure S29. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG MAPK SIGNALING PATHWAY.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG MAPK 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 ERBB SIGNALING 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	MYOCD	MYOCD	MYOCD	83	0.91	0.058	YES
2	MAPK10	MAPK10	MAPK10	149	0.85	0.11	YES
3	PPP2R2B	PPP2R2B	PPP2R2B	652	0.61	0.13	YES
4	TAGLN	TAGLN	TAGLN	855	0.55	0.15	YES
5	BLK	BLK	BLK	1192	0.47	0.17	YES
6	ACTA2	ACTA2	ACTA2	1287	0.46	0.19	YES
7	ITGB3	ITGB3	ITGB3	1388	0.44	0.22	YES
8	PIK3CG	PIK3CG	PIK3CG	1485	0.42	0.24	YES
9	PIK3R6	PIK3R6	PIK3R6	1634	0.4	0.26	YES
10	S1PR1	S1PR1	S1PR1	1652	0.4	0.28	YES
11	PIK3R5	PIK3R5	PIK3R5	2199	0.33	0.28	YES
12	SLA	SLA	SLA	2548	0.29	0.28	YES
13	PIK3CD	PIK3CD	PIK3CD	2647	0.28	0.29	YES
14	CYFIP2	CYFIP2	CYFIP2	2750	0.27	0.3	YES
15	PDGFRB	PDGFRB	PDGFRB	2885	0.25	0.32	YES
16	DOCK4	DOCK4	DOCK4	3092	0.24	0.32	YES
17	PIK3R1	PIK3R1	PIK3R1	3462	0.21	0.31	YES
18	GAB1	GAB1	GAB1	3561	0.2	0.32	YES
19	STAT5B	STAT5B	STAT5B	3566	0.2	0.34	YES
20	FYN	FYN	FYN	3593	0.2	0.35	YES
21	FGR	FGR	FGR	3602	0.2	0.36	YES
22	STAT5A	STAT5A	STAT5A	3922	0.18	0.36	YES
23	LRP1	LRP1	LRP1	3983	0.17	0.36	YES
24	HCK	HCK	HCK	4063	0.17	0.37	YES
25	ABL1	ABL1	ABL1	4088	0.17	0.38	YES
26	PRKCE	PRKCE	PRKCE	4134	0.16	0.39	YES
27	SRF	SRF	SRF	4262	0.16	0.39	YES
28	LCK	LCK	LCK	4427	0.15	0.4	YES
29	PIK3R3	PIK3R3	PIK3R3	4598	0.14	0.4	YES
30	SIPA1	SIPA1	SIPA1	4774	0.13	0.4	YES
31	KSR1	KSR1	KSR1	4841	0.12	0.4	YES
32	RAP1A	RAP1A	RAP1A	5026	0.12	0.4	YES
33	ITGAV	ITGAV	ITGAV	5029	0.12	0.4	YES
34	PIK3CA	PIK3CA	PIK3CA	5049	0.12	0.41	YES
35	RAPGEF1	RAPGEF1	RAPGEF1	5155	0.11	0.41	YES
36	CBL	CBL	CBL	5320	0.1	0.41	YES
37	JAK2	JAK2	JAK2	5361	0.1	0.42	YES
38	PTEN	PTEN	PTEN	5404	0.1	0.42	YES
39	PRKCA	PRKCA	PRKCA	5442	0.099	0.43	YES
40	WASF2	WASF2	WASF2	5525	0.096	0.43	YES
41	JUN	JUN	JUN	5808	0.085	0.42	NO
42	PLCG1	PLCG1	PLCG1	5848	0.084	0.42	NO
43	PLA2G4A	PLA2G4A	PLA2G4A	5945	0.079	0.42	NO
44	SOS1	SOS1	SOS1	6105	0.075	0.42	NO
45	MAP2K7	MAP2K7	MAP2K7	6294	0.069	0.41	NO
46	BRAF	BRAF	BRAF	6609	0.06	0.4	NO
47	STAT3	STAT3	STAT3	6623	0.06	0.4	NO
48	SLC9A3R2	SLC9A3R2	SLC9A3R2	6641	0.059	0.41	NO
49	RASA1	RASA1	RASA1	6682	0.058	0.41	NO
50	PDGFB	PDGFB	PDGFB	6695	0.058	0.41	NO
51	ARAP1	ARAP1	ARAP1	6788	0.055	0.41	NO
52	PAG1	PAG1	PAG1	6844	0.054	0.41	NO
53	NCK1	NCK1	NCK1	6871	0.053	0.41	NO
54	SPHK1	SPHK1	SPHK1	7139	0.046	0.4	NO
55	PIN1	PIN1	PIN1	7219	0.044	0.4	NO
56	DOK1	DOK1	DOK1	7292	0.043	0.4	NO
57	RPS6KA3	RPS6KA3	RPS6KA3	7337	0.041	0.4	NO
58	PTPN11	PTPN11	PTPN11	7377	0.041	0.4	NO
59	ELK1	ELK1	ELK1	7440	0.039	0.4	NO
60	GRB10	GRB10	GRB10	7655	0.034	0.39	NO
61	FOS	FOS	FOS	7690	0.033	0.39	NO
62	EIF2AK2	EIF2AK2	EIF2AK2	8049	0.026	0.37	NO
63	MAPK1	MAPK1	MAPK1	8166	0.024	0.37	NO
64	JUND	JUND	JUND	8207	0.023	0.37	NO
65	IQGAP1	IQGAP1	IQGAP1	8370	0.02	0.36	NO
66	SHC1	SHC1	SHC1	8385	0.019	0.36	NO
67	PTPRJ	PTPRJ	PTPRJ	8568	0.016	0.35	NO
68	PTPN1	PTPN1	PTPN1	8659	0.014	0.35	NO
69	MAP2K4	MAP2K4	MAP2K4	8745	0.013	0.35	NO
70	CRK	CRK	CRK	8934	0.0094	0.34	NO
71	RAF1	RAF1	RAF1	9003	0.0082	0.33	NO
72	NCK2	NCK2	NCK2	9172	0.0052	0.32	NO
73	YWHAH	YWHAH	YWHAH	9245	0.0037	0.32	NO
74	RHOA	RHOA	RHOA	9354	0.0015	0.32	NO
75	RAP1B	RAP1B	RAP1B	9438	0.0002	0.31	NO
76	EPS8	EPS8	EPS8	9612	-0.0029	0.3	NO
77	MAPK8	MAPK8	MAPK8	9647	-0.0034	0.3	NO
78	MAPK9	MAPK9	MAPK9	9668	-0.0038	0.3	NO
79	YWHAQ	YWHAQ	YWHAQ	9697	-0.0044	0.3	NO
80	RAB4A	RAB4A	RAB4A	9707	-0.0046	0.3	NO
81	MYC	MYC	MYC	9862	-0.0077	0.29	NO
82	ACTN4	ACTN4	ACTN4	9988	-0.0099	0.28	NO
83	GRB2	GRB2	GRB2	10085	-0.011	0.28	NO
84	ACTR2	ACTR2	ACTR2	10159	-0.012	0.28	NO
85	STAT1	STAT1	STAT1	10181	-0.013	0.28	NO
86	WASL	WASL	WASL	10191	-0.013	0.28	NO
87	NCKAP1	NCKAP1	NCKAP1	10366	-0.016	0.27	NO
88	PPP2R1A	PPP2R1A	PPP2R1A	10580	-0.019	0.26	NO
89	BAIAP2	BAIAP2	BAIAP2	10622	-0.02	0.26	NO
90	MAP2K1	MAP2K1	MAP2K1	10906	-0.025	0.24	NO
91	RAB5A	RAB5A	RAB5A	10991	-0.026	0.24	NO
92	KRAS	KRAS	KRAS	10994	-0.027	0.24	NO
93	ABI1	ABI1	ABI1	11056	-0.028	0.24	NO
94	USP6NL	USP6NL	USP6NL	11068	-0.028	0.24	NO
95	ARPC2	ARPC2	ARPC2	11102	-0.028	0.24	NO
96	PIK3R2	PIK3R2	PIK3R2	11116	-0.029	0.24	NO
97	ARPC1B	ARPC1B	ARPC1B	11209	-0.03	0.24	NO
98	MAP2K2	MAP2K2	MAP2K2	11283	-0.031	0.24	NO
99	YWHAG	YWHAG	YWHAG	11423	-0.033	0.23	NO
100	PPP2CA	PPP2CA	PPP2CA	11572	-0.036	0.23	NO
101	ACTR3	ACTR3	ACTR3	11617	-0.036	0.23	NO
102	CSK	CSK	CSK	11637	-0.036	0.23	NO
103	ARPC5	ARPC5	ARPC5	11780	-0.039	0.22	NO
104	MAPK3	MAPK3	MAPK3	11852	-0.04	0.22	NO
105	ARHGDIA	ARHGDIA	ARHGDIA	11854	-0.04	0.23	NO
106	ARPC4	ARPC4	ARPC4	12247	-0.046	0.21	NO
107	LYN	LYN	LYN	12568	-0.052	0.2	NO
108	RAC1	RAC1	RAC1	12692	-0.054	0.19	NO
109	YWHAB	YWHAB	YWHAB	12844	-0.057	0.19	NO
110	PIK3CB	PIK3CB	PIK3CB	13345	-0.066	0.16	NO
111	ARPC3	ARPC3	ARPC3	13376	-0.066	0.17	NO
112	MLLT4	MLLT4	MLLT4	13640	-0.071	0.16	NO
113	DNM2	DNM2	DNM2	13653	-0.072	0.16	NO
114	PTPN2	PTPN2	PTPN2	13830	-0.076	0.16	NO
115	CTTN	CTTN	CTTN	14029	-0.079	0.15	NO
116	NRAS	NRAS	NRAS	14079	-0.08	0.16	NO
117	BCAR1	BCAR1	BCAR1	14134	-0.082	0.16	NO
118	PAK1	PAK1	PAK1	14234	-0.084	0.16	NO
119	YWHAZ	YWHAZ	YWHAZ	14238	-0.084	0.16	NO
120	YWHAE	YWHAE	YWHAE	14434	-0.088	0.16	NO
121	YES1	YES1	YES1	14468	-0.088	0.16	NO
122	HRAS	HRAS	HRAS	14495	-0.089	0.17	NO
123	VAV2	VAV2	VAV2	15267	-0.11	0.14	NO
124	SRC	SRC	SRC	15271	-0.11	0.14	NO
125	PRKCD	PRKCD	PRKCD	15704	-0.12	0.13	NO
126	SLC9A3R1	SLC9A3R1	SLC9A3R1	17013	-0.18	0.069	NO
127	SFN	SFN	SFN	18304	-0.3	0.02	NO

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

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ERBB 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 CALCIUM SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IGF1	IGF1	IGF1	205	0.82	0.19	YES
2	PIK3CG	PIK3CG	PIK3CG	1485	0.42	0.22	YES
3	MEF2C	MEF2C	MEF2C	1496	0.42	0.32	YES
4	NFATC1	NFATC1	NFATC1	2546	0.29	0.34	YES
5	CAMK1	CAMK1	CAMK1	3263	0.22	0.35	YES
6	CAMK1G	CAMK1G	CAMK1G	3337	0.22	0.4	YES
7	PIK3R1	PIK3R1	PIK3R1	3462	0.21	0.44	YES
8	MEF2A	MEF2A	MEF2A	3620	0.2	0.48	YES
9	IGF1R	IGF1R	IGF1R	3880	0.18	0.51	YES
10	NFATC2	NFATC2	NFATC2	4324	0.15	0.53	YES
11	HDAC5	HDAC5	HDAC5	4356	0.15	0.56	YES
12	PPP3CC	PPP3CC	PPP3CC	4501	0.14	0.59	YES
13	PPP3CB	PPP3CB	PPP3CB	4635	0.14	0.61	YES
14	MEF2D	MEF2D	MEF2D	4661	0.13	0.64	YES
15	PIK3CA	PIK3CA	PIK3CA	5049	0.12	0.65	YES
16	INSR	INSR	INSR	6303	0.069	0.6	NO
17	CALM1	CALM1	CALM1	7097	0.047	0.57	NO
18	MAPK7	MAPK7	MAPK7	7205	0.045	0.57	NO
19	CABIN1	CABIN1	CABIN1	7418	0.04	0.57	NO
20	MAPK14	MAPK14	MAPK14	7542	0.037	0.58	NO
21	PPP3CA	PPP3CA	PPP3CA	7708	0.033	0.57	NO
22	YWHAH	YWHAH	YWHAH	9245	0.0037	0.49	NO
23	AKT1	AKT1	AKT1	9288	0.0029	0.49	NO
24	CALM3	CALM3	CALM3	9767	-0.0058	0.47	NO
25	CALM2	CALM2	CALM2	9971	-0.0096	0.46	NO
26	MAP2K6	MAP2K6	MAP2K6	11353	-0.032	0.39	NO

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

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CALCIUM 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 CHEMOKINE SIGNALING PATHWAY

Table S18. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NGFR	NGFR	NGFR	61	0.94	0.03	YES
2	ADCY5	ADCY5	ADCY5	160	0.85	0.054	YES
3	ADCY2	ADCY2	ADCY2	261	0.78	0.076	YES
4	ADCYAP1R1	ADCYAP1R1	ADCYAP1R1	314	0.74	0.099	YES
5	ADCYAP1	ADCYAP1	ADCYAP1	320	0.74	0.12	YES
6	PDE1A	PDE1A	PDE1A	342	0.72	0.15	YES
7	PDE1B	PDE1B	PDE1B	515	0.66	0.16	YES
8	NGF	NGF	NGF	624	0.62	0.18	YES
9	PRKAR2B	PRKAR2B	PRKAR2B	828	0.55	0.19	YES
10	NTRK1	NTRK1	NTRK1	953	0.52	0.2	YES
11	NTRK2	NTRK2	NTRK2	994	0.52	0.21	YES
12	AKT3	AKT3	AKT3	1032	0.51	0.23	YES
13	CAMK4	CAMK4	CAMK4	1118	0.49	0.24	YES
14	MEF2C	MEF2C	MEF2C	1496	0.42	0.24	YES
15	ADCY4	ADCY4	ADCY4	1577	0.41	0.25	YES
16	RASGRF2	RASGRF2	RASGRF2	1659	0.4	0.26	YES
17	ARHGEF6	ARHGEF6	ARHGEF6	1702	0.39	0.27	YES
18	SORCS3	SORCS3	SORCS3	1783	0.38	0.28	YES
19	MCF2	MCF2	MCF2	1814	0.37	0.29	YES
20	FGD2	FGD2	FGD2	1925	0.36	0.29	YES
21	ARHGEF4	ARHGEF4	ARHGEF4	2109	0.34	0.3	YES
22	SHC2	SHC2	SHC2	2257	0.32	0.3	YES
23	TIAM1	TIAM1	TIAM1	2288	0.32	0.31	YES
24	ARHGEF17	ARHGEF17	ARHGEF17	2380	0.3	0.31	YES
25	FGD1	FGD1	FGD1	2387	0.3	0.32	YES
26	VAV1	VAV1	VAV1	2681	0.27	0.32	YES
27	MAPK11	MAPK11	MAPK11	2763	0.26	0.32	YES
28	PRKACB	PRKACB	PRKACB	2792	0.26	0.33	YES
29	SHC3	SHC3	SHC3	2952	0.25	0.33	YES
30	ADORA2A	ADORA2A	ADORA2A	3000	0.24	0.34	YES
31	ADCY9	ADCY9	ADCY9	3153	0.23	0.34	YES
32	NGFRAP1	NGFRAP1	NGFRAP1	3281	0.22	0.34	YES
33	SH3GL2	SH3GL2	SH3GL2	3411	0.21	0.34	YES
34	PIK3R1	PIK3R1	PIK3R1	3462	0.21	0.34	YES
35	ITPR2	ITPR2	ITPR2	3504	0.21	0.35	YES
36	FGD3	FGD3	FGD3	3581	0.2	0.35	YES
37	RPS6KA5	RPS6KA5	RPS6KA5	3585	0.2	0.36	YES
38	MEF2A	MEF2A	MEF2A	3620	0.2	0.36	YES
39	MAG	MAG	MAG	3647	0.2	0.37	YES
40	IRS2	IRS2	IRS2	3649	0.2	0.38	YES
41	ARHGEF9	ARHGEF9	ARHGEF9	3655	0.2	0.38	YES
42	RPS6KA2	RPS6KA2	RPS6KA2	3709	0.19	0.38	YES
43	IRS1	IRS1	IRS1	3781	0.19	0.39	YES
44	DNM1	DNM1	DNM1	3847	0.18	0.39	YES
45	PREX1	PREX1	PREX1	3857	0.18	0.4	YES
46	PRKCE	PRKCE	PRKCE	4134	0.16	0.39	YES
47	OMG	OMG	OMG	4201	0.16	0.39	YES
48	FOXO4	FOXO4	FOXO4	4292	0.15	0.39	YES
49	APH1B	APH1B	APH1B	4327	0.15	0.39	YES
50	DUSP3	DUSP3	DUSP3	4358	0.15	0.4	YES
51	TRIO	TRIO	TRIO	4421	0.15	0.4	YES
52	ADCY8	ADCY8	ADCY8	4557	0.14	0.4	YES
53	FOXO1	FOXO1	FOXO1	4563	0.14	0.4	YES
54	PLEKHG2	PLEKHG2	PLEKHG2	4656	0.13	0.4	YES
55	ADCY1	ADCY1	ADCY1	4693	0.13	0.4	YES
56	RAP1A	RAP1A	RAP1A	5026	0.12	0.39	YES
57	PIK3CA	PIK3CA	PIK3CA	5049	0.12	0.39	YES
58	ITSN1	ITSN1	ITSN1	5055	0.12	0.4	YES
59	RAPGEF1	RAPGEF1	RAPGEF1	5155	0.11	0.4	YES
60	MAP2K5	MAP2K5	MAP2K5	5197	0.11	0.4	YES
61	ARHGEF3	ARHGEF3	ARHGEF3	5211	0.11	0.4	YES
62	PRKCG	PRKCG	PRKCG	5226	0.11	0.4	YES
63	TRAF6	TRAF6	TRAF6	5311	0.1	0.4	YES
64	PTEN	PTEN	PTEN	5404	0.1	0.4	YES
65	PCSK5	PCSK5	PCSK5	5414	0.1	0.4	YES
66	PRKCA	PRKCA	PRKCA	5442	0.099	0.4	YES
67	ADCY7	ADCY7	ADCY7	5533	0.095	0.4	YES
68	NR4A1	NR4A1	NR4A1	5545	0.095	0.41	YES
69	KIDINS220	KIDINS220	KIDINS220	5553	0.094	0.41	YES
70	CDKN1B	CDKN1B	CDKN1B	5721	0.088	0.4	YES
71	ADCY3	ADCY3	ADCY3	5752	0.087	0.4	YES
72	RTN4	RTN4	RTN4	5800	0.085	0.4	YES
73	PRKACA	PRKACA	PRKACA	5809	0.085	0.41	YES
74	MAPK12	MAPK12	MAPK12	5814	0.085	0.41	YES
75	PLCG1	PLCG1	PLCG1	5848	0.084	0.41	YES
76	ARHGAP4	ARHGAP4	ARHGAP4	5936	0.08	0.41	YES
77	SOS2	SOS2	SOS2	5938	0.08	0.41	YES
78	MAPKAP1	MAPKAP1	MAPKAP1	6033	0.077	0.41	YES
79	SOS1	SOS1	SOS1	6105	0.075	0.41	YES
80	ARHGEF2	ARHGEF2	ARHGEF2	6145	0.074	0.41	YES
81	PRKAR2A	PRKAR2A	PRKAR2A	6208	0.072	0.41	YES
82	TSC2	TSC2	TSC2	6211	0.072	0.41	YES
83	KALRN	KALRN	KALRN	6218	0.072	0.41	YES
84	RASGRF1	RASGRF1	RASGRF1	6248	0.071	0.41	YES
85	AKAP13	AKAP13	AKAP13	6414	0.066	0.41	NO
86	OBSCN	OBSCN	OBSCN	6583	0.061	0.4	NO
87	BRAF	BRAF	BRAF	6609	0.06	0.4	NO
88	STAT3	STAT3	STAT3	6623	0.06	0.4	NO
89	PRKAR1A	PRKAR1A	PRKAR1A	6674	0.058	0.4	NO
90	CREB1	CREB1	CREB1	6736	0.057	0.4	NO
91	NFKBIA	NFKBIA	NFKBIA	6744	0.056	0.4	NO
92	ARHGEF18	ARHGEF18	ARHGEF18	6874	0.052	0.4	NO
93	PDPK1	PDPK1	PDPK1	7090	0.047	0.39	NO
94	CALM1	CALM1	CALM1	7097	0.047	0.39	NO
95	IKBKB	IKBKB	IKBKB	7146	0.046	0.39	NO
96	RICTOR	RICTOR	RICTOR	7155	0.046	0.39	NO
97	MAPK7	MAPK7	MAPK7	7205	0.045	0.39	NO
98	AKT2	AKT2	AKT2	7332	0.042	0.38	NO
99	RPS6KA3	RPS6KA3	RPS6KA3	7337	0.041	0.38	NO
100	ARHGEF12	ARHGEF12	ARHGEF12	7396	0.04	0.38	NO
101	ELK1	ELK1	ELK1	7440	0.039	0.38	NO
102	AP2A2	AP2A2	AP2A2	7473	0.038	0.38	NO
103	FOXO3	FOXO3	FOXO3	7485	0.038	0.38	NO
104	MAPK14	MAPK14	MAPK14	7542	0.037	0.38	NO
105	FRS2	FRS2	FRS2	7782	0.032	0.37	NO
106	ABR	ABR	ABR	7791	0.031	0.37	NO
107	MAPK1	MAPK1	MAPK1	8166	0.024	0.35	NO
108	ARHGEF1	ARHGEF1	ARHGEF1	8189	0.023	0.35	NO
109	AP2A1	AP2A1	AP2A1	8328	0.021	0.34	NO
110	MAGED1	MAGED1	MAGED1	8376	0.02	0.34	NO
111	SHC1	SHC1	SHC1	8385	0.019	0.34	NO
112	VAV3	VAV3	VAV3	8623	0.015	0.33	NO
113	DUSP6	DUSP6	DUSP6	8625	0.015	0.33	NO
114	MAPKAPK2	MAPKAPK2	MAPKAPK2	8859	0.011	0.32	NO
115	CRK	CRK	CRK	8934	0.0094	0.31	NO
116	BCL2L11	BCL2L11	BCL2L11	8939	0.0092	0.31	NO
117	RAF1	RAF1	RAF1	9003	0.0082	0.31	NO
118	RELA	RELA	RELA	9063	0.0069	0.31	NO
119	RALGDS	RALGDS	RALGDS	9090	0.0066	0.3	NO
120	AP2M1	AP2M1	AP2M1	9180	0.0051	0.3	NO
121	RIT1	RIT1	RIT1	9248	0.0037	0.3	NO
122	PPP2CB	PPP2CB	PPP2CB	9249	0.0036	0.3	NO
123	AKT1	AKT1	AKT1	9288	0.0029	0.3	NO
124	MTOR	MTOR	MTOR	9314	0.0024	0.29	NO
125	ARHGEF11	ARHGEF11	ARHGEF11	9319	0.0023	0.29	NO
126	RHOA	RHOA	RHOA	9354	0.0015	0.29	NO
127	HDAC3	HDAC3	HDAC3	9560	-0.0018	0.28	NO
128	PRKAR1B	PRKAR1B	PRKAR1B	9587	-0.0024	0.28	NO
129	MDM2	MDM2	MDM2	9639	-0.0032	0.28	NO
130	MAPK8	MAPK8	MAPK8	9647	-0.0034	0.28	NO
131	CALM3	CALM3	CALM3	9767	-0.0058	0.27	NO
132	BAD	BAD	BAD	9784	-0.0062	0.27	NO
133	ADCY6	ADCY6	ADCY6	9896	-0.0082	0.26	NO
134	CDKN1A	CDKN1A	CDKN1A	9949	-0.0091	0.26	NO
135	CALM2	CALM2	CALM2	9971	-0.0096	0.26	NO
136	CASP9	CASP9	CASP9	9989	-0.0099	0.26	NO
137	ADAM17	ADAM17	ADAM17	10054	-0.011	0.26	NO
138	RPS27A	RPS27A	RPS27A	10077	-0.011	0.26	NO
139	GRB2	GRB2	GRB2	10085	-0.011	0.26	NO
140	FGD4	FGD4	FGD4	10248	-0.014	0.25	NO
141	SQSTM1	SQSTM1	SQSTM1	10263	-0.014	0.25	NO
142	UBA52	UBA52	UBA52	10288	-0.015	0.25	NO
143	ATF1	ATF1	ATF1	10465	-0.018	0.24	NO
144	PPP2R1A	PPP2R1A	PPP2R1A	10580	-0.019	0.23	NO
145	AP2B1	AP2B1	AP2B1	10648	-0.02	0.23	NO
146	DUSP7	DUSP7	DUSP7	10697	-0.021	0.23	NO
147	THEM4	THEM4	THEM4	10796	-0.023	0.22	NO
148	MAP2K1	MAP2K1	MAP2K1	10906	-0.025	0.22	NO
149	PPP2R5D	PPP2R5D	PPP2R5D	10979	-0.026	0.22	NO
150	KRAS	KRAS	KRAS	10994	-0.027	0.22	NO
151	MYD88	MYD88	MYD88	11003	-0.027	0.22	NO
152	AKT1S1	AKT1S1	AKT1S1	11074	-0.028	0.21	NO
153	PIK3R2	PIK3R2	PIK3R2	11116	-0.029	0.21	NO
154	MAP2K2	MAP2K2	MAP2K2	11283	-0.031	0.2	NO
155	PRDM4	PRDM4	PRDM4	11305	-0.031	0.2	NO
156	ADRBK1	ADRBK1	ADRBK1	11340	-0.032	0.2	NO
157	CASP2	CASP2	CASP2	11381	-0.032	0.2	NO
158	PSEN2	PSEN2	PSEN2	11459	-0.034	0.2	NO
159	PPP2CA	PPP2CA	PPP2CA	11572	-0.036	0.19	NO
160	CLTC	CLTC	CLTC	11636	-0.036	0.19	NO
161	GSK3A	GSK3A	GSK3A	11704	-0.038	0.19	NO
162	MAPK3	MAPK3	MAPK3	11852	-0.04	0.18	NO
163	ARHGDIA	ARHGDIA	ARHGDIA	11854	-0.04	0.18	NO
164	IRAK1	IRAK1	IRAK1	12231	-0.046	0.16	NO
165	TIAM2	TIAM2	TIAM2	12381	-0.049	0.16	NO
166	PHLPP1	PHLPP1	PHLPP1	12525	-0.051	0.15	NO
167	CHUK	CHUK	CHUK	12593	-0.052	0.15	NO
168	MLST8	MLST8	MLST8	12618	-0.053	0.15	NO
169	RALB	RALB	RALB	12673	-0.054	0.15	NO
170	RAC1	RAC1	RAC1	12692	-0.054	0.15	NO
171	NET1	NET1	NET1	12709	-0.054	0.15	NO
172	LINGO1	LINGO1	LINGO1	12795	-0.056	0.15	NO
173	YWHAB	YWHAB	YWHAB	12844	-0.057	0.15	NO
174	FURIN	FURIN	FURIN	12860	-0.057	0.15	NO
175	PSEN1	PSEN1	PSEN1	12918	-0.058	0.15	NO
176	APH1A	APH1A	APH1A	13001	-0.06	0.15	NO
177	PIK3CB	PIK3CB	PIK3CB	13345	-0.066	0.13	NO
178	AATF	AATF	AATF	13388	-0.067	0.13	NO
179	NCSTN	NCSTN	NCSTN	13490	-0.069	0.13	NO
180	AP2S1	AP2S1	AP2S1	13564	-0.07	0.13	NO
181	MAPKAPK3	MAPKAPK3	MAPKAPK3	13598	-0.071	0.13	NO
182	DNAL4	DNAL4	DNAL4	13635	-0.071	0.13	NO
183	DNM2	DNM2	DNM2	13653	-0.072	0.13	NO
184	CLTA	CLTA	CLTA	13722	-0.073	0.13	NO
185	HDAC2	HDAC2	HDAC2	13896	-0.077	0.12	NO
186	NRAS	NRAS	NRAS	14079	-0.08	0.12	NO
187	PSENEN	PSENEN	PSENEN	14287	-0.084	0.11	NO
188	PRKACG	PRKACG	PRKACG	14345	-0.086	0.11	NO
189	YWHAE	YWHAE	YWHAE	14434	-0.088	0.1	NO
190	HRAS	HRAS	HRAS	14495	-0.089	0.1	NO
191	PRKCI	PRKCI	PRKCI	14591	-0.091	0.1	NO
192	DUSP4	DUSP4	DUSP4	14625	-0.092	0.1	NO
193	HDAC1	HDAC1	HDAC1	14631	-0.092	0.11	NO
194	RIPK2	RIPK2	RIPK2	14667	-0.093	0.11	NO
195	RALA	RALA	RALA	15022	-0.1	0.092	NO
196	PPP2R1B	PPP2R1B	PPP2R1B	15172	-0.11	0.088	NO
197	SRC	SRC	SRC	15271	-0.11	0.087	NO
198	ITGB3BP	ITGB3BP	ITGB3BP	15414	-0.11	0.083	NO
199	RPS6KB2	RPS6KB2	RPS6KB2	15545	-0.12	0.08	NO
200	CASP3	CASP3	CASP3	15637	-0.12	0.08	NO
201	PRKCD	PRKCD	PRKCD	15704	-0.12	0.08	NO
202	RPS6KA1	RPS6KA1	RPS6KA1	15741	-0.12	0.083	NO
203	ITPR3	ITPR3	ITPR3	15966	-0.13	0.075	NO
204	SMPD2	SMPD2	SMPD2	16415	-0.15	0.056	NO
205	NGEF	NGEF	NGEF	17283	-0.2	0.016	NO
206	ECT2	ECT2	ECT2	17594	-0.22	0.0072	NO
207	MAPK13	MAPK13	MAPK13	17652	-0.23	0.012	NO
208	PCSK6	PCSK6	PCSK6	17906	-0.25	0.0072	NO
209	CDK1	CDK1	CDK1	18076	-0.27	0.0075	NO
210	ARHGEF16	ARHGEF16	ARHGEF16	18425	-0.33	0.00023	NO
211	TRIB3	TRIB3	TRIB3	18564	-0.38	0.006	NO

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

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CHEMOKINE 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 PHOSPHATIDYLINOSITOL SIGNALING SYSTEM

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	BMX	BMX	BMX	605	0.62	0.063	YES
2	KLF8	KLF8	KLF8	733	0.58	0.15	YES
3	ACTA1	ACTA1	ACTA1	1547	0.41	0.16	YES
4	ELMO1	ELMO1	ELMO1	2395	0.3	0.17	YES
5	ITGA5	ITGA5	ITGA5	2697	0.27	0.19	YES
6	ACTN1	ACTN1	ACTN1	3225	0.23	0.2	YES
7	TLN1	TLN1	TLN1	3228	0.23	0.23	YES
8	PIK3R1	PIK3R1	PIK3R1	3462	0.21	0.25	YES
9	FYN	FYN	FYN	3593	0.2	0.28	YES
10	VCL	VCL	VCL	3628	0.2	0.3	YES
11	PTPN21	PTPN21	PTPN21	3777	0.19	0.32	YES
12	GIT2	GIT2	GIT2	3915	0.18	0.34	YES
13	ETS1	ETS1	ETS1	3924	0.18	0.37	YES
14	RRAS	RRAS	RRAS	3959	0.17	0.4	YES
15	RAP1A	RAP1A	RAP1A	5026	0.12	0.36	YES
16	ITGAV	ITGAV	ITGAV	5029	0.12	0.38	YES
17	PIK3CA	PIK3CA	PIK3CA	5049	0.12	0.39	YES
18	RAPGEF1	RAPGEF1	RAPGEF1	5155	0.11	0.4	YES
19	DOCK1	DOCK1	DOCK1	5496	0.096	0.4	YES
20	ASAP1	ASAP1	ASAP1	5588	0.093	0.41	YES
21	ITGB1	ITGB1	ITGB1	5781	0.086	0.41	YES
22	JUN	JUN	JUN	5808	0.085	0.42	YES
23	PLCG1	PLCG1	PLCG1	5848	0.084	0.43	YES
24	SOS1	SOS1	SOS1	6105	0.075	0.43	YES
25	MMP14	MMP14	MMP14	6407	0.066	0.42	YES
26	ITGB5	ITGB5	ITGB5	6531	0.063	0.43	YES
27	BRAF	BRAF	BRAF	6609	0.06	0.43	YES
28	RASA1	RASA1	RASA1	6682	0.058	0.44	YES
29	ROCK2	ROCK2	ROCK2	6777	0.055	0.44	YES
30	NCK1	NCK1	NCK1	6871	0.053	0.44	YES
31	MAPK8IP3	MAPK8IP3	MAPK8IP3	8162	0.024	0.38	NO
32	MAPK1	MAPK1	MAPK1	8166	0.024	0.38	NO
33	ARHGEF7	ARHGEF7	ARHGEF7	8220	0.023	0.38	NO
34	RGNEF	RGNEF	RGNEF	8351	0.02	0.38	NO
35	MAP2K4	MAP2K4	MAP2K4	8745	0.013	0.36	NO
36	CRK	CRK	CRK	8934	0.0094	0.35	NO
37	RAF1	RAF1	RAF1	9003	0.0082	0.35	NO
38	ARHGAP26	ARHGAP26	ARHGAP26	9154	0.0055	0.34	NO
39	NCK2	NCK2	NCK2	9172	0.0052	0.34	NO
40	PXN	PXN	PXN	9205	0.0044	0.34	NO
41	ARHGEF11	ARHGEF11	ARHGEF11	9319	0.0023	0.34	NO
42	CAPN2	CAPN2	CAPN2	9330	0.0021	0.34	NO
43	RHOA	RHOA	RHOA	9354	0.0015	0.33	NO
44	RAP1B	RAP1B	RAP1B	9438	0.0002	0.33	NO
45	MAPK8	MAPK8	MAPK8	9647	-0.0034	0.32	NO
46	MAPK9	MAPK9	MAPK9	9668	-0.0038	0.32	NO
47	GRB2	GRB2	GRB2	10085	-0.011	0.3	NO
48	WASL	WASL	WASL	10191	-0.013	0.29	NO
49	MAP2K1	MAP2K1	MAP2K1	10906	-0.025	0.26	NO
50	PTK2	PTK2	PTK2	11957	-0.042	0.21	NO
51	SH3GL1	SH3GL1	SH3GL1	11968	-0.042	0.22	NO
52	RAC1	RAC1	RAC1	12692	-0.054	0.18	NO
53	BCAR1	BCAR1	BCAR1	14134	-0.082	0.12	NO
54	PAK1	PAK1	PAK1	14234	-0.084	0.13	NO
55	YES1	YES1	YES1	14468	-0.088	0.13	NO
56	SRC	SRC	SRC	15271	-0.11	0.1	NO
57	CCND1	CCND1	CCND1	15715	-0.12	0.098	NO
58	GRB7	GRB7	GRB7	18603	-0.4	0.0038	NO

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

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PHOSPHATIDYLINOSITOL SIGNALING SYSTEM, 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 NEUROACTIVE LIGAND RECEPTOR INTERACTION

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	CNR1	CNR1	CNR1	201	0.82	0.15	YES
2	GAP43	GAP43	GAP43	459	0.67	0.27	YES
3	FGFR1	FGFR1	FGFR1	1271	0.46	0.32	YES
4	CDH2	CDH2	CDH2	1556	0.41	0.38	YES
5	FER	FER	FER	2222	0.32	0.41	YES
6	GRIA2	GRIA2	GRIA2	2807	0.26	0.43	YES
7	GJA1	GJA1	GJA1	2844	0.26	0.48	YES
8	GSN	GSN	GSN	3066	0.24	0.52	YES
9	PIK3R1	PIK3R1	PIK3R1	3462	0.21	0.54	YES
10	PIP5K1C	PIP5K1C	PIP5K1C	3654	0.2	0.57	YES
11	CAMK2G	CAMK2G	CAMK2G	4747	0.13	0.54	NO
12	PIK3CA	PIK3CA	PIK3CA	5049	0.12	0.54	NO
13	PLCG1	PLCG1	PLCG1	5848	0.084	0.52	NO
14	ROCK1	ROCK1	ROCK1	6056	0.076	0.52	NO
15	PTPN11	PTPN11	PTPN11	7377	0.041	0.46	NO
16	DCTN1	DCTN1	DCTN1	7496	0.038	0.46	NO
17	PTPN1	PTPN1	PTPN1	8659	0.014	0.4	NO
18	MYL2	MYL2	MYL2	8757	0.013	0.4	NO
19	RHOA	RHOA	RHOA	9354	0.0015	0.36	NO
20	MAPK8	MAPK8	MAPK8	9647	-0.0034	0.35	NO
21	KIF5B	KIF5B	KIF5B	9746	-0.0053	0.34	NO
22	CTNNB1	CTNNB1	CTNNB1	9763	-0.0057	0.34	NO
23	CDC42	CDC42	CDC42	9840	-0.0072	0.34	NO
24	CTNNA1	CTNNA1	CTNNA1	10375	-0.016	0.32	NO
25	AXIN1	AXIN1	AXIN1	10457	-0.018	0.32	NO
26	MAPRE1	MAPRE1	MAPRE1	10544	-0.019	0.32	NO
27	RAC1	RAC1	RAC1	12692	-0.054	0.21	NO
28	CTNND1	CTNND1	CTNND1	12802	-0.056	0.22	NO
29	LRP5	LRP5	LRP5	12937	-0.058	0.22	NO
30	DAGLB	DAGLB	DAGLB	13006	-0.06	0.23	NO
31	CTTN	CTTN	CTTN	14029	-0.079	0.19	NO
32	DAGLA	DAGLA	DAGLA	14385	-0.086	0.19	NO
33	JUP	JUP	JUP	17483	-0.21	0.064	NO

Figure S39. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION, 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 PYRIMIDINE METABOLISM	98	genes.ES.table	0.35	1.5	0.065	0.16	0.99	0.36	0.16	0.3	0.1	0.003
KEGG AMINOACYL TRNA BIOSYNTHESIS	41	genes.ES.table	0.48	1.6	0.11	0.13	0.98	0.54	0.26	0.4	0.071	0.003
KEGG RIBOSOME	86	genes.ES.table	0.61	1.7	0.051	0.08	0.87	0.79	0.26	0.59	0.035	0.004
KEGG RNA DEGRADATION	57	genes.ES.table	0.36	1.4	0.15	0.22	1	0.47	0.24	0.36	0.15	0.004
KEGG RNA POLYMERASE	29	genes.ES.table	0.59	2	0.016	0.038	0.29	0.62	0.28	0.45	0	0.005
KEGG DNA REPLICATION	36	genes.ES.table	0.62	1.6	0.063	0.12	0.97	0.64	0.19	0.52	0.06	0.003
KEGG SPLICEOSOME	114	genes.ES.table	0.42	1.7	0.084	0.089	0.91	0.6	0.3	0.42	0.041	0.004
KEGG PROTEASOME	43	genes.ES.table	0.61	1.7	0.032	0.064	0.74	0.81	0.28	0.59	0.024	0.004
KEGG NUCLEOTIDE EXCISION REPAIR	44	genes.ES.table	0.57	2.1	0.004	0.036	0.13	0.5	0.19	0.4	0	0.009
KEGG CELL CYCLE	118	genes.ES.table	0.46	1.7	0.054	0.079	0.87	0.42	0.16	0.36	0.034	0.004

genes ES table in pathway: KEGG PYRIMIDINE METABOLISM

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	CDC25A	CDC25A	CDC25A	603	0.14	0.016	YES
2	PKMYT1	PKMYT1	PKMYT1	740	0.12	0.052	YES
3	CDK7	CDK7	CDK7	801	0.12	0.089	YES
4	CCNA2	CCNA2	CCNA2	839	0.12	0.13	YES
5	PSMB10	PSMB10	PSMB10	905	0.11	0.16	YES
6	PSMB9	PSMB9	PSMB9	1005	0.1	0.19	YES
7	PSME2	PSME2	PSME2	1091	0.098	0.22	YES
8	CKS1B	CKS1B	CKS1B	1436	0.081	0.23	YES
9	CDKN1A	CDKN1A	CDKN1A	1526	0.078	0.25	YES
10	PSMB7	PSMB7	PSMB7	1757	0.07	0.26	YES
11	PSMD9	PSMD9	PSMD9	1788	0.07	0.28	YES
12	MYC	MYC	MYC	1919	0.066	0.3	YES
13	PSMA5	PSMA5	PSMA5	1935	0.065	0.32	YES
14	PSME1	PSME1	PSME1	1943	0.065	0.34	YES
15	CCNE2	CCNE2	CCNE2	1978	0.064	0.36	YES
16	PSMA6	PSMA6	PSMA6	1979	0.064	0.39	YES
17	PSMD12	PSMD12	PSMD12	2014	0.063	0.41	YES
18	MNAT1	MNAT1	MNAT1	2020	0.062	0.43	YES
19	PSMB6	PSMB6	PSMB6	2194	0.058	0.44	YES
20	PSMA4	PSMA4	PSMA4	2261	0.056	0.45	YES
21	PSMA1	PSMA1	PSMA1	2335	0.055	0.47	YES
22	RB1	RB1	RB1	2501	0.052	0.48	YES
23	PSMB8	PSMB8	PSMB8	2625	0.05	0.49	YES
24	PSMD14	PSMD14	PSMD14	2631	0.049	0.5	YES
25	PSMB2	PSMB2	PSMB2	2641	0.049	0.52	YES
26	PSMD8	PSMD8	PSMD8	2684	0.048	0.54	YES
27	PSMD6	PSMD6	PSMD6	2692	0.048	0.55	YES
28	CCNH	CCNH	CCNH	2843	0.046	0.56	YES
29	PSMD2	PSMD2	PSMD2	2875	0.045	0.57	YES
30	SKP2	SKP2	SKP2	2907	0.045	0.59	YES
31	PSMD13	PSMD13	PSMD13	2997	0.044	0.6	YES
32	PSMA3	PSMA3	PSMA3	3111	0.042	0.61	YES
33	PSMA2	PSMA2	PSMA2	3158	0.041	0.62	YES
34	MAX	MAX	MAX	3346	0.038	0.62	YES
35	PSMB5	PSMB5	PSMB5	3503	0.036	0.62	YES
36	CDK2	CDK2	CDK2	3747	0.033	0.62	YES
37	PSMD11	PSMD11	PSMD11	3768	0.033	0.63	YES
38	PSMC4	PSMC4	PSMC4	3879	0.032	0.64	YES
39	PSMC1	PSMC1	PSMC1	3907	0.031	0.65	YES
40	PSMC5	PSMC5	PSMC5	3966	0.03	0.65	YES
41	SKP1	SKP1	SKP1	3981	0.03	0.66	YES
42	UBA52	UBA52	UBA52	4047	0.029	0.67	YES
43	PSMC6	PSMC6	PSMC6	4057	0.029	0.68	YES
44	PSMB3	PSMB3	PSMB3	4323	0.026	0.68	YES
45	PSMD5	PSMD5	PSMD5	4340	0.026	0.68	YES
46	PSMB1	PSMB1	PSMB1	4378	0.026	0.69	YES
47	PSMD3	PSMD3	PSMD3	4720	0.022	0.68	NO
48	PSMD10	PSMD10	PSMD10	4863	0.02	0.68	NO
49	PSMD7	PSMD7	PSMD7	4938	0.02	0.68	NO
50	PSMC2	PSMC2	PSMC2	5159	0.018	0.68	NO
51	PSMD1	PSMD1	PSMD1	5333	0.016	0.67	NO
52	RPS27A	RPS27A	RPS27A	5355	0.015	0.68	NO
53	PSMC3	PSMC3	PSMC3	5963	0.0089	0.65	NO
54	CUL1	CUL1	CUL1	6448	0.0041	0.62	NO
55	PSMB4	PSMB4	PSMB4	6659	0.0021	0.61	NO
56	CDKN1B	CDKN1B	CDKN1B	6673	0.002	0.61	NO
57	PSMD4	PSMD4	PSMD4	7513	-0.0065	0.57	NO
58	PSMA7	PSMA7	PSMA7	7576	-0.0071	0.57	NO
59	WEE1	WEE1	WEE1	7821	-0.0098	0.56	NO
60	CCNE1	CCNE1	CCNE1	8211	-0.014	0.54	NO
61	PSMF1	PSMF1	PSMF1	8235	-0.015	0.55	NO
62	CCNA1	CCNA1	CCNA1	10570	-0.045	0.44	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 PYRIMIDINE METABOLISM.

Figure S42. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PYRIMIDINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

Table 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	CCNA2	CCNA2	CCNA2	839	0.12	0.006	YES
2	PSMB10	PSMB10	PSMB10	905	0.11	0.051	YES
3	PSMB9	PSMB9	PSMB9	1005	0.1	0.091	YES
4	PSME2	PSME2	PSME2	1091	0.098	0.13	YES
5	CKS1B	CKS1B	CKS1B	1436	0.081	0.15	YES
6	CDKN1A	CDKN1A	CDKN1A	1526	0.078	0.18	YES
7	PSMB7	PSMB7	PSMB7	1757	0.07	0.2	YES
8	PSMD9	PSMD9	PSMD9	1788	0.07	0.22	YES
9	PSMA5	PSMA5	PSMA5	1935	0.065	0.25	YES
10	PSME1	PSME1	PSME1	1943	0.065	0.28	YES
11	CCNE2	CCNE2	CCNE2	1978	0.064	0.3	YES
12	PSMA6	PSMA6	PSMA6	1979	0.064	0.33	YES
13	PSMD12	PSMD12	PSMD12	2014	0.063	0.36	YES
14	PSMB6	PSMB6	PSMB6	2194	0.058	0.37	YES
15	PSMA4	PSMA4	PSMA4	2261	0.056	0.39	YES
16	PSMA1	PSMA1	PSMA1	2335	0.055	0.41	YES
17	PSMB8	PSMB8	PSMB8	2625	0.05	0.42	YES
18	PSMD14	PSMD14	PSMD14	2631	0.049	0.44	YES
19	PSMB2	PSMB2	PSMB2	2641	0.049	0.46	YES
20	PSMD8	PSMD8	PSMD8	2684	0.048	0.48	YES
21	PSMD6	PSMD6	PSMD6	2692	0.048	0.5	YES
22	PSMD2	PSMD2	PSMD2	2875	0.045	0.52	YES
23	SKP2	SKP2	SKP2	2907	0.045	0.53	YES
24	PSMD13	PSMD13	PSMD13	2997	0.044	0.55	YES
25	PSMA3	PSMA3	PSMA3	3111	0.042	0.56	YES
26	PSMA2	PSMA2	PSMA2	3158	0.041	0.58	YES
27	PSMB5	PSMB5	PSMB5	3503	0.036	0.57	YES
28	CDK2	CDK2	CDK2	3747	0.033	0.57	YES
29	PSMD11	PSMD11	PSMD11	3768	0.033	0.59	YES
30	PSMC4	PSMC4	PSMC4	3879	0.032	0.6	YES
31	PSMC1	PSMC1	PSMC1	3907	0.031	0.61	YES
32	PSMC5	PSMC5	PSMC5	3966	0.03	0.62	YES
33	SKP1	SKP1	SKP1	3981	0.03	0.63	YES
34	UBA52	UBA52	UBA52	4047	0.029	0.64	YES
35	PSMC6	PSMC6	PSMC6	4057	0.029	0.65	YES
36	PSMB3	PSMB3	PSMB3	4323	0.026	0.65	YES
37	PSMD5	PSMD5	PSMD5	4340	0.026	0.66	YES
38	PSMB1	PSMB1	PSMB1	4378	0.026	0.67	YES
39	PSMD3	PSMD3	PSMD3	4720	0.022	0.66	NO
40	PSMD10	PSMD10	PSMD10	4863	0.02	0.66	NO
41	PSMD7	PSMD7	PSMD7	4938	0.02	0.67	NO
42	PSMC2	PSMC2	PSMC2	5159	0.018	0.66	NO
43	PSMD1	PSMD1	PSMD1	5333	0.016	0.66	NO
44	RPS27A	RPS27A	RPS27A	5355	0.015	0.67	NO
45	PSMC3	PSMC3	PSMC3	5963	0.0089	0.64	NO
46	CUL1	CUL1	CUL1	6448	0.0041	0.62	NO
47	PSMB4	PSMB4	PSMB4	6659	0.0021	0.6	NO
48	CDKN1B	CDKN1B	CDKN1B	6673	0.002	0.6	NO
49	PSMD4	PSMD4	PSMD4	7513	-0.0065	0.56	NO
50	PSMA7	PSMA7	PSMA7	7576	-0.0071	0.56	NO
51	CCNE1	CCNE1	CCNE1	8211	-0.014	0.54	NO
52	PSMF1	PSMF1	PSMF1	8235	-0.015	0.54	NO
53	CCNA1	CCNA1	CCNA1	10570	-0.045	0.44	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 AMINOACYL TRNA BIOSYNTHESIS.

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

genes ES table in pathway: KEGG RIBOSOME

Table 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	CDK7	CDK7	CDK7	801	0.12	0.02	YES
2	DDB2	DDB2	DDB2	1025	0.1	0.062	YES
3	POLE2	POLE2	POLE2	1170	0.094	0.1	YES
4	RFC2	RFC2	RFC2	1314	0.086	0.14	YES
5	RFC4	RFC4	RFC4	1385	0.083	0.18	YES
6	PCNA	PCNA	PCNA	1395	0.083	0.22	YES
7	POLD2	POLD2	POLD2	1607	0.075	0.25	YES
8	RFC5	RFC5	RFC5	1669	0.073	0.29	YES
9	GTF2H3	GTF2H3	GTF2H3	1742	0.071	0.32	YES
10	LIG1	LIG1	LIG1	1886	0.066	0.35	YES
11	MNAT1	MNAT1	MNAT1	2020	0.062	0.38	YES
12	POLR2L	POLR2L	POLR2L	2044	0.062	0.41	YES
13	GTF2H2	GTF2H2	GTF2H2	2366	0.054	0.42	YES
14	POLD1	POLD1	POLD1	2377	0.054	0.45	YES
15	POLR2H	POLR2H	POLR2H	2435	0.053	0.47	YES
16	POLR2F	POLR2F	POLR2F	2591	0.05	0.49	YES
17	RPA3	RPA3	RPA3	2759	0.047	0.51	YES
18	CCNH	CCNH	CCNH	2843	0.046	0.53	YES
19	POLR2E	POLR2E	POLR2E	3008	0.043	0.54	YES
20	ERCC8	ERCC8	ERCC8	3147	0.041	0.55	YES
21	RAD23B	RAD23B	RAD23B	3456	0.037	0.56	YES
22	POLR2I	POLR2I	POLR2I	3508	0.036	0.57	YES
23	GTF2H4	GTF2H4	GTF2H4	3591	0.035	0.59	YES
24	RFC3	RFC3	RFC3	3954	0.03	0.58	YES
25	GTF2H2B	GTF2H2B	GTF2H2B	4269	0.027	0.58	YES
26	RPA2	RPA2	RPA2	4349	0.026	0.59	YES
27	POLR2A	POLR2A	POLR2A	4371	0.026	0.6	YES
28	TCEA1	TCEA1	TCEA1	4476	0.025	0.61	YES
29	POLR2D	POLR2D	POLR2D	4780	0.022	0.61	YES
30	POLR2G	POLR2G	POLR2G	4845	0.021	0.61	YES
31	RPA1	RPA1	RPA1	5209	0.017	0.6	YES
32	ERCC1	ERCC1	ERCC1	5217	0.017	0.61	YES
33	POLD4	POLD4	POLD4	5325	0.016	0.62	YES
34	POLE	POLE	POLE	5582	0.013	0.61	NO
35	XAB2	XAB2	XAB2	5590	0.013	0.61	NO
36	ERCC3	ERCC3	ERCC3	6172	0.0067	0.59	NO
37	GTF2H1	GTF2H1	GTF2H1	6254	0.0058	0.58	NO
38	ERCC2	ERCC2	ERCC2	6338	0.0052	0.58	NO
39	POLR2B	POLR2B	POLR2B	6464	0.0038	0.58	NO
40	POLR2C	POLR2C	POLR2C	6533	0.0031	0.58	NO
41	POLR2J	POLR2J	POLR2J	6646	0.0022	0.57	NO
42	XPC	XPC	XPC	6956	-0.00085	0.56	NO
43	XPA	XPA	XPA	6980	-0.0011	0.56	NO
44	DDB1	DDB1	DDB1	7498	-0.0063	0.53	NO
45	POLR2K	POLR2K	POLR2K	7791	-0.0093	0.52	NO
46	ERCC5	ERCC5	ERCC5	7894	-0.011	0.52	NO
47	POLD3	POLD3	POLD3	8301	-0.015	0.51	NO
48	ERCC6	ERCC6	ERCC6	9543	-0.03	0.46	NO
49	ERCC4	ERCC4	ERCC4	11705	-0.065	0.37	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 RIBOSOME.

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

genes ES table in pathway: KEGG RNA DEGRADATION

Table 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	CDC45	CDC45	CDC45	460	0.16	0.0043	YES
2	CDT1	CDT1	CDT1	520	0.15	0.029	YES
3	CDC25A	CDC25A	CDC25A	603	0.14	0.05	YES
4	MCM10	MCM10	MCM10	605	0.14	0.075	YES
5	CCNB1	CCNB1	CCNB1	620	0.14	0.1	YES
6	RRM2	RRM2	RRM2	644	0.14	0.12	YES
7	PKMYT1	PKMYT1	PKMYT1	740	0.12	0.14	YES
8	CDK7	CDK7	CDK7	801	0.12	0.16	YES
9	CCNA2	CCNA2	CCNA2	839	0.12	0.18	YES
10	TYMS	TYMS	TYMS	840	0.12	0.2	YES
11	CDC6	CDC6	CDC6	901	0.11	0.21	YES
12	PSMB10	PSMB10	PSMB10	905	0.11	0.23	YES
13	CDK1	CDK1	CDK1	943	0.11	0.25	YES
14	PSMB9	PSMB9	PSMB9	1005	0.1	0.26	YES
15	PSME2	PSME2	PSME2	1091	0.098	0.28	YES
16	POLE2	POLE2	POLE2	1170	0.094	0.29	YES
17	DHFR	DHFR	DHFR	1188	0.092	0.31	YES
18	TK2	TK2	TK2	1215	0.091	0.32	YES
19	MCM2	MCM2	MCM2	1219	0.09	0.34	YES
20	MCM4	MCM4	MCM4	1329	0.085	0.35	YES
21	PCNA	PCNA	PCNA	1395	0.083	0.36	YES
22	CKS1B	CKS1B	CKS1B	1436	0.081	0.37	YES
23	CDC7	CDC7	CDC7	1490	0.079	0.38	YES
24	MCM5	MCM5	MCM5	1523	0.078	0.39	YES
25	CDKN1A	CDKN1A	CDKN1A	1526	0.078	0.41	YES
26	PSMB7	PSMB7	PSMB7	1757	0.07	0.41	YES
27	FBXO5	FBXO5	FBXO5	1759	0.07	0.42	YES
28	PSMD9	PSMD9	PSMD9	1788	0.07	0.43	YES
29	MYC	MYC	MYC	1919	0.066	0.44	YES
30	PSMA5	PSMA5	PSMA5	1935	0.065	0.45	YES
31	PSME1	PSME1	PSME1	1943	0.065	0.46	YES
32	PRIM1	PRIM1	PRIM1	1954	0.064	0.47	YES
33	CCNE2	CCNE2	CCNE2	1978	0.064	0.48	YES
34	PSMA6	PSMA6	PSMA6	1979	0.064	0.49	YES
35	PSMD12	PSMD12	PSMD12	2014	0.063	0.5	YES
36	MNAT1	MNAT1	MNAT1	2020	0.062	0.51	YES
37	PSMB6	PSMB6	PSMB6	2194	0.058	0.51	YES
38	DBF4	DBF4	DBF4	2247	0.057	0.52	YES
39	PSMA4	PSMA4	PSMA4	2261	0.056	0.53	YES
40	TFDP1	TFDP1	TFDP1	2271	0.056	0.54	YES
41	PSMA1	PSMA1	PSMA1	2335	0.055	0.55	YES
42	RB1	RB1	RB1	2501	0.052	0.55	YES
43	PPP2CB	PPP2CB	PPP2CB	2504	0.052	0.56	YES
44	PSMB8	PSMB8	PSMB8	2625	0.05	0.56	YES
45	PSMD14	PSMD14	PSMD14	2631	0.049	0.57	YES
46	PSMB2	PSMB2	PSMB2	2641	0.049	0.57	YES
47	PSMD8	PSMD8	PSMD8	2684	0.048	0.58	YES
48	PSMD6	PSMD6	PSMD6	2692	0.048	0.59	YES
49	PRIM2	PRIM2	PRIM2	2707	0.048	0.6	YES
50	RPA3	RPA3	RPA3	2759	0.047	0.6	YES
51	MCM6	MCM6	MCM6	2820	0.046	0.61	YES
52	PPP2CA	PPP2CA	PPP2CA	2838	0.046	0.62	YES
53	CCNH	CCNH	CCNH	2843	0.046	0.62	YES
54	PSMD2	PSMD2	PSMD2	2875	0.045	0.63	YES
55	MCM3	MCM3	MCM3	2904	0.045	0.64	YES
56	SKP2	SKP2	SKP2	2907	0.045	0.64	YES
57	PSMD13	PSMD13	PSMD13	2997	0.044	0.65	YES
58	PSMA3	PSMA3	PSMA3	3111	0.042	0.65	YES
59	PSMA2	PSMA2	PSMA2	3158	0.041	0.65	YES
60	E2F1	E2F1	E2F1	3299	0.039	0.65	YES
61	MAX	MAX	MAX	3346	0.038	0.66	YES
62	MCM7	MCM7	MCM7	3418	0.037	0.66	YES
63	PPP2R3B	PPP2R3B	PPP2R3B	3436	0.037	0.67	YES
64	PSMB5	PSMB5	PSMB5	3503	0.036	0.67	YES
65	POLA2	POLA2	POLA2	3563	0.035	0.67	YES
66	CDK2	CDK2	CDK2	3747	0.033	0.67	YES
67	PSMD11	PSMD11	PSMD11	3768	0.033	0.67	YES
68	PSMC4	PSMC4	PSMC4	3879	0.032	0.67	YES
69	PSMC1	PSMC1	PSMC1	3907	0.031	0.68	YES
70	PSMC5	PSMC5	PSMC5	3966	0.03	0.68	YES
71	SKP1	SKP1	SKP1	3981	0.03	0.68	YES
72	UBA52	UBA52	UBA52	4047	0.029	0.69	YES
73	PSMC6	PSMC6	PSMC6	4057	0.029	0.69	YES
74	PSMB3	PSMB3	PSMB3	4323	0.026	0.68	YES
75	PSMD5	PSMD5	PSMD5	4340	0.026	0.68	YES
76	RPA2	RPA2	RPA2	4349	0.026	0.69	YES
77	PSMB1	PSMB1	PSMB1	4378	0.026	0.69	YES
78	PSMD3	PSMD3	PSMD3	4720	0.022	0.68	NO
79	PSMD10	PSMD10	PSMD10	4863	0.02	0.67	NO
80	PSMD7	PSMD7	PSMD7	4938	0.02	0.67	NO
81	PSMC2	PSMC2	PSMC2	5159	0.018	0.66	NO
82	RPA1	RPA1	RPA1	5209	0.017	0.67	NO
83	PSMD1	PSMD1	PSMD1	5333	0.016	0.66	NO
84	RPS27A	RPS27A	RPS27A	5355	0.015	0.66	NO
85	POLE	POLE	POLE	5582	0.013	0.65	NO
86	PPP2R1B	PPP2R1B	PPP2R1B	5813	0.01	0.64	NO
87	PSMC3	PSMC3	PSMC3	5963	0.0089	0.64	NO
88	PPP2R1A	PPP2R1A	PPP2R1A	6146	0.007	0.63	NO
89	CUL1	CUL1	CUL1	6448	0.0041	0.61	NO
90	POLA1	POLA1	POLA1	6594	0.0026	0.6	NO
91	PSMB4	PSMB4	PSMB4	6659	0.0021	0.6	NO
92	CDKN1B	CDKN1B	CDKN1B	6673	0.002	0.6	NO
93	PSMD4	PSMD4	PSMD4	7513	-0.0065	0.56	NO
94	PSMA7	PSMA7	PSMA7	7576	-0.0071	0.56	NO
95	WEE1	WEE1	WEE1	7821	-0.0098	0.54	NO
96	CCNE1	CCNE1	CCNE1	8211	-0.014	0.53	NO
97	PSMF1	PSMF1	PSMF1	8235	-0.015	0.53	NO
98	MCM8	MCM8	MCM8	9519	-0.03	0.46	NO
99	CCNA1	CCNA1	CCNA1	10570	-0.045	0.42	NO
100	RPA4	RPA4	RPA4	13774	-0.12	0.26	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 DEGRADATION.

Figure S48. 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 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	CDK7	CDK7	CDK7	801	0.12	0.056	YES
2	GTF2H3	GTF2H3	GTF2H3	1742	0.071	0.065	YES
3	MNAT1	MNAT1	MNAT1	2020	0.062	0.1	YES
4	POLR2L	POLR2L	POLR2L	2044	0.062	0.15	YES
5	GTF2H2	GTF2H2	GTF2H2	2366	0.054	0.18	YES
6	POLR2H	POLR2H	POLR2H	2435	0.053	0.22	YES
7	POLR2F	POLR2F	POLR2F	2591	0.05	0.26	YES
8	CCNH	CCNH	CCNH	2843	0.046	0.28	YES
9	WHSC2	WHSC2	WHSC2	2912	0.045	0.32	YES
10	POLR2E	POLR2E	POLR2E	3008	0.043	0.35	YES
11	GTF2F1	GTF2F1	GTF2F1	3437	0.037	0.35	YES
12	POLR2I	POLR2I	POLR2I	3508	0.036	0.38	YES
13	GTF2H4	GTF2H4	GTF2H4	3591	0.035	0.4	YES
14	TCEB2	TCEB2	TCEB2	3696	0.034	0.43	YES
15	TCEB1	TCEB1	TCEB1	3937	0.031	0.44	YES
16	COBRA1	COBRA1	COBRA1	4116	0.029	0.46	YES
17	GTF2H2B	GTF2H2B	GTF2H2B	4269	0.027	0.47	YES
18	POLR2A	POLR2A	POLR2A	4371	0.026	0.49	YES
19	TCEA1	TCEA1	TCEA1	4476	0.025	0.5	YES
20	SSRP1	SSRP1	SSRP1	4492	0.024	0.52	YES
21	POLR2D	POLR2D	POLR2D	4780	0.022	0.52	YES
22	POLR2G	POLR2G	POLR2G	4845	0.021	0.54	YES
23	NCBP2	NCBP2	NCBP2	5080	0.018	0.54	YES
24	RDBP	RDBP	RDBP	5279	0.016	0.54	YES
25	GTF2F2	GTF2F2	GTF2F2	5318	0.016	0.55	YES
26	SUPT4H1	SUPT4H1	SUPT4H1	5383	0.015	0.56	YES
27	CDK9	CDK9	CDK9	5555	0.013	0.56	YES
28	ERCC3	ERCC3	ERCC3	6172	0.0067	0.54	NO
29	NCBP1	NCBP1	NCBP1	6173	0.0067	0.54	NO
30	ELL	ELL	ELL	6244	0.006	0.55	NO
31	GTF2H1	GTF2H1	GTF2H1	6254	0.0058	0.55	NO
32	ERCC2	ERCC2	ERCC2	6338	0.0052	0.55	NO
33	SUPT16H	SUPT16H	SUPT16H	6400	0.0046	0.55	NO
34	POLR2B	POLR2B	POLR2B	6464	0.0038	0.55	NO
35	POLR2C	POLR2C	POLR2C	6533	0.0031	0.55	NO
36	POLR2J	POLR2J	POLR2J	6646	0.0022	0.54	NO
37	SUPT5H	SUPT5H	SUPT5H	7210	-0.0036	0.52	NO
38	CCNT1	CCNT1	CCNT1	7243	-0.0039	0.52	NO
39	POLR2K	POLR2K	POLR2K	7791	-0.0093	0.5	NO
40	CTDP1	CTDP1	CTDP1	7900	-0.011	0.5	NO
41	TCEB3	TCEB3	TCEB3	8281	-0.015	0.49	NO
42	TH1L	TH1L	TH1L	9964	-0.036	0.43	NO
43	CCNT2	CCNT2	CCNT2	10391	-0.042	0.44	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 RNA POLYMERASE.

Figure S50. 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 DNA REPLICATION

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	CDK7	CDK7	CDK7	801	0.12	0.076	YES
2	GTF2H3	GTF2H3	GTF2H3	1742	0.071	0.097	YES
3	MNAT1	MNAT1	MNAT1	2020	0.062	0.14	YES
4	POLR2L	POLR2L	POLR2L	2044	0.062	0.21	YES
5	GTF2H2	GTF2H2	GTF2H2	2366	0.054	0.24	YES
6	POLR2H	POLR2H	POLR2H	2435	0.053	0.29	YES
7	POLR2F	POLR2F	POLR2F	2591	0.05	0.34	YES
8	CCNH	CCNH	CCNH	2843	0.046	0.37	YES
9	WHSC2	WHSC2	WHSC2	2912	0.045	0.41	YES
10	POLR2E	POLR2E	POLR2E	3008	0.043	0.45	YES
11	GTF2F1	GTF2F1	GTF2F1	3437	0.037	0.46	YES
12	POLR2I	POLR2I	POLR2I	3508	0.036	0.49	YES
13	GTF2H4	GTF2H4	GTF2H4	3591	0.035	0.52	YES
14	COBRA1	COBRA1	COBRA1	4116	0.029	0.52	YES
15	GTF2H2B	GTF2H2B	GTF2H2B	4269	0.027	0.54	YES
16	POLR2A	POLR2A	POLR2A	4371	0.026	0.56	YES
17	POLR2D	POLR2D	POLR2D	4780	0.022	0.56	YES
18	POLR2G	POLR2G	POLR2G	4845	0.021	0.58	YES
19	NCBP2	NCBP2	NCBP2	5080	0.018	0.59	YES
20	RDBP	RDBP	RDBP	5279	0.016	0.59	YES
21	GTF2F2	GTF2F2	GTF2F2	5318	0.016	0.61	YES
22	SUPT4H1	SUPT4H1	SUPT4H1	5383	0.015	0.62	YES
23	ERCC3	ERCC3	ERCC3	6172	0.0067	0.58	NO
24	NCBP1	NCBP1	NCBP1	6173	0.0067	0.59	NO
25	GTF2H1	GTF2H1	GTF2H1	6254	0.0058	0.59	NO
26	ERCC2	ERCC2	ERCC2	6338	0.0052	0.59	NO
27	POLR2B	POLR2B	POLR2B	6464	0.0038	0.59	NO
28	POLR2C	POLR2C	POLR2C	6533	0.0031	0.59	NO
29	POLR2J	POLR2J	POLR2J	6646	0.0022	0.58	NO
30	SUPT5H	SUPT5H	SUPT5H	7210	-0.0036	0.56	NO
31	POLR2K	POLR2K	POLR2K	7791	-0.0093	0.54	NO
32	CTDP1	CTDP1	CTDP1	7900	-0.011	0.54	NO
33	TH1L	TH1L	TH1L	9964	-0.036	0.47	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 DNA REPLICATION.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG DNA REPLICATION, 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 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	CDC45	CDC45	CDC45	460	0.16	-0.00056	YES
2	CDT1	CDT1	CDT1	520	0.15	0.019	YES
3	CDC25A	CDC25A	CDC25A	603	0.14	0.036	YES
4	MCM10	MCM10	MCM10	605	0.14	0.057	YES
5	CCNB1	CCNB1	CCNB1	620	0.14	0.078	YES
6	RRM2	RRM2	RRM2	644	0.14	0.097	YES
7	PKMYT1	PKMYT1	PKMYT1	740	0.12	0.11	YES
8	CCND1	CCND1	CCND1	746	0.12	0.13	YES
9	CDK7	CDK7	CDK7	801	0.12	0.14	YES
10	CCNA2	CCNA2	CCNA2	839	0.12	0.16	YES
11	TYMS	TYMS	TYMS	840	0.12	0.18	YES
12	CDC6	CDC6	CDC6	901	0.11	0.19	YES
13	PSMB10	PSMB10	PSMB10	905	0.11	0.2	YES
14	CDK1	CDK1	CDK1	943	0.11	0.22	YES
15	E2F2	E2F2	E2F2	989	0.1	0.23	YES
16	PSMB9	PSMB9	PSMB9	1005	0.1	0.25	YES
17	PSME2	PSME2	PSME2	1091	0.098	0.26	YES
18	POLE2	POLE2	POLE2	1170	0.094	0.27	YES
19	DHFR	DHFR	DHFR	1188	0.092	0.28	YES
20	TK2	TK2	TK2	1215	0.091	0.29	YES
21	MCM2	MCM2	MCM2	1219	0.09	0.3	YES
22	PPP2R2A	PPP2R2A	PPP2R2A	1230	0.09	0.32	YES
23	MCM4	MCM4	MCM4	1329	0.085	0.32	YES
24	PCNA	PCNA	PCNA	1395	0.083	0.33	YES
25	CKS1B	CKS1B	CKS1B	1436	0.081	0.34	YES
26	CDC7	CDC7	CDC7	1490	0.079	0.35	YES
27	MCM5	MCM5	MCM5	1523	0.078	0.36	YES
28	CDKN1A	CDKN1A	CDKN1A	1526	0.078	0.38	YES
29	CDKN2D	CDKN2D	CDKN2D	1739	0.071	0.37	YES
30	PSMB7	PSMB7	PSMB7	1757	0.07	0.38	YES
31	FBXO5	FBXO5	FBXO5	1759	0.07	0.39	YES
32	PSMD9	PSMD9	PSMD9	1788	0.07	0.4	YES
33	MYC	MYC	MYC	1919	0.066	0.41	YES
34	PSMA5	PSMA5	PSMA5	1935	0.065	0.42	YES
35	PSME1	PSME1	PSME1	1943	0.065	0.42	YES
36	PRIM1	PRIM1	PRIM1	1954	0.064	0.43	YES
37	CCNE2	CCNE2	CCNE2	1978	0.064	0.44	YES
38	PSMA6	PSMA6	PSMA6	1979	0.064	0.45	YES
39	PSMD12	PSMD12	PSMD12	2014	0.063	0.46	YES
40	MNAT1	MNAT1	MNAT1	2020	0.062	0.47	YES
41	LIN54	LIN54	LIN54	2153	0.059	0.47	YES
42	PSMB6	PSMB6	PSMB6	2194	0.058	0.48	YES
43	DBF4	DBF4	DBF4	2247	0.057	0.48	YES
44	PSMA4	PSMA4	PSMA4	2261	0.056	0.49	YES
45	TFDP1	TFDP1	TFDP1	2271	0.056	0.5	YES
46	PSMA1	PSMA1	PSMA1	2335	0.055	0.5	YES
47	RB1	RB1	RB1	2501	0.052	0.5	YES
48	PPP2CB	PPP2CB	PPP2CB	2504	0.052	0.51	YES
49	LIN9	LIN9	LIN9	2619	0.05	0.51	YES
50	PSMB8	PSMB8	PSMB8	2625	0.05	0.52	YES
51	PSMD14	PSMD14	PSMD14	2631	0.049	0.52	YES
52	PSMB2	PSMB2	PSMB2	2641	0.049	0.53	YES
53	PSMD8	PSMD8	PSMD8	2684	0.048	0.54	YES
54	PSMD6	PSMD6	PSMD6	2692	0.048	0.54	YES
55	PRIM2	PRIM2	PRIM2	2707	0.048	0.55	YES
56	E2F5	E2F5	E2F5	2724	0.048	0.56	YES
57	RPA3	RPA3	RPA3	2759	0.047	0.56	YES
58	HDAC1	HDAC1	HDAC1	2760	0.047	0.57	YES
59	MCM6	MCM6	MCM6	2820	0.046	0.57	YES
60	PPP2CA	PPP2CA	PPP2CA	2838	0.046	0.58	YES
61	CCNH	CCNH	CCNH	2843	0.046	0.58	YES
62	PSMD2	PSMD2	PSMD2	2875	0.045	0.59	YES
63	MCM3	MCM3	MCM3	2904	0.045	0.6	YES
64	SKP2	SKP2	SKP2	2907	0.045	0.6	YES
65	PSMD13	PSMD13	PSMD13	2997	0.044	0.6	YES
66	PSMA3	PSMA3	PSMA3	3111	0.042	0.6	YES
67	PSMA2	PSMA2	PSMA2	3158	0.041	0.61	YES
68	E2F1	E2F1	E2F1	3299	0.039	0.6	YES
69	MAX	MAX	MAX	3346	0.038	0.61	YES
70	MCM7	MCM7	MCM7	3418	0.037	0.61	YES
71	PPP2R3B	PPP2R3B	PPP2R3B	3436	0.037	0.62	YES
72	PSMB5	PSMB5	PSMB5	3503	0.036	0.62	YES
73	POLA2	POLA2	POLA2	3563	0.035	0.62	YES
74	CDK2	CDK2	CDK2	3747	0.033	0.61	YES
75	PSMD11	PSMD11	PSMD11	3768	0.033	0.62	YES
76	PSMC4	PSMC4	PSMC4	3879	0.032	0.62	YES
77	PSMC1	PSMC1	PSMC1	3907	0.031	0.62	YES
78	PSMC5	PSMC5	PSMC5	3966	0.03	0.62	YES
79	SKP1	SKP1	SKP1	3981	0.03	0.62	YES
80	UBA52	UBA52	UBA52	4047	0.029	0.63	YES
81	PSMC6	PSMC6	PSMC6	4057	0.029	0.63	YES
82	CDK4	CDK4	CDK4	4210	0.028	0.63	YES
83	RBBP4	RBBP4	RBBP4	4217	0.028	0.63	YES
84	PSMB3	PSMB3	PSMB3	4323	0.026	0.63	YES
85	PSMD5	PSMD5	PSMD5	4340	0.026	0.63	YES
86	RPA2	RPA2	RPA2	4349	0.026	0.63	YES
87	PSMB1	PSMB1	PSMB1	4378	0.026	0.64	YES
88	CDKN2B	CDKN2B	CDKN2B	4474	0.025	0.64	NO
89	PSMD3	PSMD3	PSMD3	4720	0.022	0.62	NO
90	CDKN2C	CDKN2C	CDKN2C	4748	0.022	0.63	NO
91	E2F4	E2F4	E2F4	4835	0.021	0.63	NO
92	PSMD10	PSMD10	PSMD10	4863	0.02	0.63	NO
93	PSMD7	PSMD7	PSMD7	4938	0.02	0.63	NO
94	LIN37	LIN37	LIN37	4984	0.019	0.63	NO
95	PSMC2	PSMC2	PSMC2	5159	0.018	0.62	NO
96	RPA1	RPA1	RPA1	5209	0.017	0.62	NO
97	PSMD1	PSMD1	PSMD1	5333	0.016	0.62	NO
98	RPS27A	RPS27A	RPS27A	5355	0.015	0.62	NO
99	POLE	POLE	POLE	5582	0.013	0.61	NO
100	PPP2R1B	PPP2R1B	PPP2R1B	5813	0.01	0.6	NO
101	PSMC3	PSMC3	PSMC3	5963	0.0089	0.59	NO
102	PPP2R1A	PPP2R1A	PPP2R1A	6146	0.007	0.58	NO
103	CUL1	CUL1	CUL1	6448	0.0041	0.56	NO
104	POLA1	POLA1	POLA1	6594	0.0026	0.56	NO
105	PSMB4	PSMB4	PSMB4	6659	0.0021	0.55	NO
106	CDKN1B	CDKN1B	CDKN1B	6673	0.002	0.55	NO
107	MYBL2	MYBL2	MYBL2	6880	-0.000032	0.54	NO
108	RBL1	RBL1	RBL1	7465	-0.006	0.51	NO
109	PSMD4	PSMD4	PSMD4	7513	-0.0065	0.51	NO
110	PSMA7	PSMA7	PSMA7	7576	-0.0071	0.51	NO
111	WEE1	WEE1	WEE1	7821	-0.0098	0.5	NO
112	CCNE1	CCNE1	CCNE1	8211	-0.014	0.48	NO
113	PSMF1	PSMF1	PSMF1	8235	-0.015	0.48	NO
114	E2F3	E2F3	E2F3	8385	-0.016	0.47	NO
115	RBL2	RBL2	RBL2	8989	-0.023	0.44	NO
116	MCM8	MCM8	MCM8	9519	-0.03	0.42	NO
117	LIN52	LIN52	LIN52	9612	-0.031	0.42	NO
118	CDK6	CDK6	CDK6	10359	-0.042	0.38	NO
119	CCNA1	CCNA1	CCNA1	10570	-0.045	0.38	NO
120	CCND3	CCND3	CCND3	10575	-0.045	0.39	NO
121	DYRK1A	DYRK1A	DYRK1A	11239	-0.056	0.36	NO
122	CCND2	CCND2	CCND2	11965	-0.07	0.33	NO
123	CDKN2A	CDKN2A	CDKN2A	12616	-0.084	0.31	NO
124	RPA4	RPA4	RPA4	13774	-0.12	0.26	NO

Figure S53. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG SPLICEOSOME.

Figure S54. 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 PROTEASOME

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	CDK7	CDK7	CDK7	801	0.12	0.02	YES
2	DDB2	DDB2	DDB2	1025	0.1	0.063	YES
3	POLE2	POLE2	POLE2	1170	0.094	0.1	YES
4	RFC2	RFC2	RFC2	1314	0.086	0.14	YES
5	RFC4	RFC4	RFC4	1385	0.083	0.18	YES
6	PCNA	PCNA	PCNA	1395	0.083	0.23	YES
7	POLD2	POLD2	POLD2	1607	0.075	0.26	YES
8	RFC5	RFC5	RFC5	1669	0.073	0.29	YES
9	GTF2H3	GTF2H3	GTF2H3	1742	0.071	0.33	YES
10	LIG1	LIG1	LIG1	1886	0.066	0.35	YES
11	MNAT1	MNAT1	MNAT1	2020	0.062	0.38	YES
12	POLE3	POLE3	POLE3	2193	0.058	0.4	YES
13	RBX1	RBX1	RBX1	2313	0.056	0.42	YES
14	GTF2H2	GTF2H2	GTF2H2	2366	0.054	0.45	YES
15	POLD1	POLD1	POLD1	2377	0.054	0.48	YES
16	RPA3	RPA3	RPA3	2759	0.047	0.48	YES
17	CCNH	CCNH	CCNH	2843	0.046	0.5	YES
18	RAD23A	RAD23A	RAD23A	2845	0.046	0.53	YES
19	CETN2	CETN2	CETN2	3119	0.042	0.54	YES
20	ERCC8	ERCC8	ERCC8	3147	0.041	0.56	YES
21	RAD23B	RAD23B	RAD23B	3456	0.037	0.56	YES
22	GTF2H4	GTF2H4	GTF2H4	3591	0.035	0.57	YES
23	RFC3	RFC3	RFC3	3954	0.03	0.57	NO
24	RPA2	RPA2	RPA2	4349	0.026	0.56	NO
25	RPA1	RPA1	RPA1	5209	0.017	0.52	NO
26	ERCC1	ERCC1	ERCC1	5217	0.017	0.53	NO
27	POLD4	POLD4	POLD4	5325	0.016	0.54	NO
28	POLE	POLE	POLE	5582	0.013	0.53	NO
29	ERCC3	ERCC3	ERCC3	6172	0.0067	0.5	NO
30	RFC1	RFC1	RFC1	6201	0.0063	0.5	NO
31	GTF2H1	GTF2H1	GTF2H1	6254	0.0058	0.5	NO
32	ERCC2	ERCC2	ERCC2	6338	0.0052	0.5	NO
33	CUL4A	CUL4A	CUL4A	6851	0.00025	0.47	NO
34	XPC	XPC	XPC	6956	-0.00085	0.47	NO
35	XPA	XPA	XPA	6980	-0.0011	0.47	NO
36	DDB1	DDB1	DDB1	7498	-0.0063	0.44	NO
37	GTF2H5	GTF2H5	GTF2H5	7773	-0.0092	0.43	NO
38	ERCC5	ERCC5	ERCC5	7894	-0.011	0.43	NO
39	POLD3	POLD3	POLD3	8301	-0.015	0.42	NO
40	CUL4B	CUL4B	CUL4B	8457	-0.017	0.42	NO
41	POLE4	POLE4	POLE4	9287	-0.026	0.39	NO
42	ERCC6	ERCC6	ERCC6	9543	-0.03	0.39	NO
43	ERCC4	ERCC4	ERCC4	11705	-0.065	0.31	NO
44	RPA4	RPA4	RPA4	13774	-0.12	0.26	NO

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

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PROTEASOME, 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 NUCLEOTIDE EXCISION REPAIR

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	EIF4E	EIF4E	EIF4E	1417	0.082	-0.018	YES
2	EXOSC7	EXOSC7	EXOSC7	1685	0.073	0.019	YES
3	EIF4A1	EIF4A1	EIF4A1	1876	0.067	0.056	YES
4	EIF4A3	EIF4A3	EIF4A3	1976	0.064	0.096	YES
5	RQCD1	RQCD1	RQCD1	2299	0.056	0.12	YES
6	LSM4	LSM4	LSM4	2569	0.05	0.14	YES
7	EXOSC8	EXOSC8	EXOSC8	2614	0.05	0.17	YES
8	LSM6	LSM6	LSM6	2745	0.047	0.2	YES
9	EXOSC9	EXOSC9	EXOSC9	2756	0.047	0.23	YES
10	EXOSC2	EXOSC2	EXOSC2	2835	0.046	0.26	YES
11	CNOT6	CNOT6	CNOT6	2925	0.044	0.29	YES
12	LSM1	LSM1	LSM1	3090	0.042	0.31	YES
13	LSM3	LSM3	LSM3	3128	0.041	0.34	YES
14	LSM2	LSM2	LSM2	3174	0.041	0.36	YES
15	EXOSC3	EXOSC3	EXOSC3	3459	0.037	0.37	YES
16	CNOT8	CNOT8	CNOT8	3507	0.036	0.4	YES
17	CNOT7	CNOT7	CNOT7	3676	0.034	0.41	YES
18	LSM5	LSM5	LSM5	3845	0.032	0.42	YES
19	XRN1	XRN1	XRN1	4017	0.03	0.44	YES
20	EXOSC4	EXOSC4	EXOSC4	4167	0.028	0.45	YES
21	CNOT10	CNOT10	CNOT10	4258	0.027	0.46	YES
22	EXOSC5	EXOSC5	EXOSC5	4395	0.026	0.47	YES
23	EIF4A2	EIF4A2	EIF4A2	4488	0.024	0.48	YES
24	PATL1	PATL1	PATL1	4505	0.024	0.5	YES
25	C2orf29	C2orf29	C2orf29	4650	0.023	0.51	YES
26	DCPS	DCPS	DCPS	4786	0.021	0.52	YES
27	TNKS1BP1	TNKS1BP1	TNKS1BP1	4909	0.02	0.52	YES
28	PAIP1	PAIP1	PAIP1	5052	0.018	0.53	YES
29	EXOSC1	EXOSC1	EXOSC1	5091	0.018	0.54	YES
30	EIF4G1	EIF4G1	EIF4G1	5334	0.016	0.54	YES
31	DIS3	DIS3	DIS3	5415	0.015	0.55	YES
32	PABPC1	PABPC1	PABPC1	5617	0.013	0.54	NO
33	EIF4B	EIF4B	EIF4B	6373	0.0048	0.51	NO
34	DCP2	DCP2	DCP2	6417	0.0044	0.51	NO
35	EXOSC6	EXOSC6	EXOSC6	6861	0.00015	0.48	NO
36	DDX6	DDX6	DDX6	6946	-0.00072	0.48	NO
37	EDC4	EDC4	EDC4	7450	-0.0058	0.46	NO
38	CNOT2	CNOT2	CNOT2	7559	-0.007	0.46	NO
39	PARN	PARN	PARN	7562	-0.007	0.46	NO
40	CNOT4	CNOT4	CNOT4	8054	-0.012	0.44	NO
41	CNOT3	CNOT3	CNOT3	9410	-0.028	0.39	NO
42	DCP1A	DCP1A	DCP1A	9671	-0.032	0.4	NO
43	DCP1B	DCP1B	DCP1B	10260	-0.04	0.4	NO
44	EDC3	EDC3	EDC3	12368	-0.078	0.34	NO

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

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

genes ES table in pathway: KEGG CELL CYCLE

Table 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	CDK7	CDK7	CDK7	801	0.12	0.025	YES
2	POLE2	POLE2	POLE2	1170	0.094	0.059	YES
3	RFC2	RFC2	RFC2	1314	0.086	0.1	YES
4	RFC4	RFC4	RFC4	1385	0.083	0.14	YES
5	PCNA	PCNA	PCNA	1395	0.083	0.19	YES
6	POLD2	POLD2	POLD2	1607	0.075	0.22	YES
7	RFC5	RFC5	RFC5	1669	0.073	0.26	YES
8	GTF2H3	GTF2H3	GTF2H3	1742	0.071	0.3	YES
9	LIG1	LIG1	LIG1	1886	0.066	0.33	YES
10	MNAT1	MNAT1	MNAT1	2020	0.062	0.36	YES
11	POLR2L	POLR2L	POLR2L	2044	0.062	0.39	YES
12	GTF2H2	GTF2H2	GTF2H2	2366	0.054	0.41	YES
13	POLD1	POLD1	POLD1	2377	0.054	0.44	YES
14	POLR2H	POLR2H	POLR2H	2435	0.053	0.46	YES
15	POLR2F	POLR2F	POLR2F	2591	0.05	0.48	YES
16	RPA3	RPA3	RPA3	2759	0.047	0.5	YES
17	CCNH	CCNH	CCNH	2843	0.046	0.52	YES
18	POLR2E	POLR2E	POLR2E	3008	0.043	0.54	YES
19	ERCC8	ERCC8	ERCC8	3147	0.041	0.56	YES
20	POLR2I	POLR2I	POLR2I	3508	0.036	0.56	YES
21	GTF2H4	GTF2H4	GTF2H4	3591	0.035	0.57	YES
22	RFC3	RFC3	RFC3	3954	0.03	0.57	YES
23	GTF2H2B	GTF2H2B	GTF2H2B	4269	0.027	0.57	YES
24	RPA2	RPA2	RPA2	4349	0.026	0.58	YES
25	POLR2A	POLR2A	POLR2A	4371	0.026	0.6	YES
26	TCEA1	TCEA1	TCEA1	4476	0.025	0.6	YES
27	POLR2D	POLR2D	POLR2D	4780	0.022	0.6	YES
28	POLR2G	POLR2G	POLR2G	4845	0.021	0.61	YES
29	RPA1	RPA1	RPA1	5209	0.017	0.6	YES
30	ERCC1	ERCC1	ERCC1	5217	0.017	0.61	YES
31	POLD4	POLD4	POLD4	5325	0.016	0.61	YES
32	POLE	POLE	POLE	5582	0.013	0.6	YES
33	XAB2	XAB2	XAB2	5590	0.013	0.61	YES
34	ERCC3	ERCC3	ERCC3	6172	0.0067	0.58	NO
35	GTF2H1	GTF2H1	GTF2H1	6254	0.0058	0.58	NO
36	ERCC2	ERCC2	ERCC2	6338	0.0052	0.58	NO
37	POLR2B	POLR2B	POLR2B	6464	0.0038	0.58	NO
38	POLR2C	POLR2C	POLR2C	6533	0.0031	0.57	NO
39	POLR2J	POLR2J	POLR2J	6646	0.0022	0.57	NO
40	POLR2K	POLR2K	POLR2K	7791	-0.0093	0.52	NO
41	ERCC5	ERCC5	ERCC5	7894	-0.011	0.52	NO
42	POLD3	POLD3	POLD3	8301	-0.015	0.5	NO
43	ERCC6	ERCC6	ERCC6	9543	-0.03	0.45	NO
44	ERCC4	ERCC4	ERCC4	11705	-0.065	0.37	NO

Figure S59. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG CELL CYCLE.

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

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 INOSITOL PHOSPHATE METABOLISM	54	genes.ES.table	0.48	1.8	0.006	0.3	0.58	0.33	0.18	0.27	0.08	0.069
KEGG APOPTOSIS	86	genes.ES.table	0.46	1.7	0.028	0.39	0.78	0.57	0.32	0.39	0.15	0.086
BIOCARTA HIVNEF PATHWAY	58	genes.ES.table	0.5	2.1	0.0061	0.42	0.14	0.48	0.33	0.32	0	0.099
BIOCARTA PYK2 PATHWAY	28	genes.ES.table	0.42	1.8	0.0099	0.28	0.59	0.36	0.24	0.27	0.075	0.064
BIOCARTA STRESS PATHWAY	25	genes.ES.table	0.57	2	0.0019	0.21	0.18	0.44	0.24	0.34	0	0.041
ST TUMOR NECROSIS FACTOR PATHWAY	28	genes.ES.table	0.55	1.8	0.01	0.31	0.53	0.54	0.28	0.39	0.078	0.07
ST INTERLEUKIN 4 PATHWAY	25	genes.ES.table	0.59	1.9	0.0079	0.36	0.47	0.36	0.19	0.29	0	0.078
PID BCR 5PATHWAY	65	genes.ES.table	0.58	1.8	0.03	0.37	0.72	0.48	0.24	0.36	0.12	0.078
PID TRAIL PATHWAY	28	genes.ES.table	0.56	1.9	0.012	0.32	0.48	0.57	0.31	0.4	0	0.073
PID CDC42 PATHWAY	70	genes.ES.table	0.39	2	0.004	0.18	0.24	0.53	0.34	0.35	0	0.037

genes ES table in pathway: KEGG INOSITOL PHOSPHATE METABOLISM

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	BIRC3	BIRC3	BIRC3	627	0.22	0.069	YES
2	TNF	TNF	TNF	981	0.18	0.13	YES
3	CASP7	CASP7	CASP7	1424	0.14	0.17	YES
4	PRKCD	PRKCD	PRKCD	2192	0.098	0.18	YES
5	CFLAR	CFLAR	CFLAR	2200	0.098	0.22	YES
6	APAF1	APAF1	APAF1	2583	0.083	0.24	YES
7	FAS	FAS	FAS	2622	0.082	0.27	YES
8	TRADD	TRADD	TRADD	2725	0.079	0.3	YES
9	MAP3K14	MAP3K14	MAP3K14	3161	0.067	0.31	YES
10	FASLG	FASLG	FASLG	3264	0.064	0.33	YES
11	ARHGDIB	ARHGDIB	ARHGDIB	3629	0.056	0.34	YES
12	NFKB1	NFKB1	NFKB1	3658	0.056	0.36	YES
13	MDM2	MDM2	MDM2	3671	0.056	0.39	YES
14	TNFRSF1B	TNFRSF1B	TNFRSF1B	3713	0.055	0.41	YES
15	CRADD	CRADD	CRADD	3865	0.052	0.43	YES
16	MAP3K5	MAP3K5	MAP3K5	4011	0.049	0.44	YES
17	MAP3K1	MAP3K1	MAP3K1	4297	0.044	0.45	YES
18	CASP3	CASP3	CASP3	4353	0.043	0.46	YES
19	CHUK	CHUK	CHUK	4441	0.042	0.48	YES
20	CASP8	CASP8	CASP8	4717	0.038	0.48	YES
21	CASP9	CASP9	CASP9	5033	0.033	0.48	YES
22	FADD	FADD	FADD	5183	0.031	0.48	YES
23	NFKBIA	NFKBIA	NFKBIA	5559	0.027	0.48	YES
24	RB1	RB1	RB1	5616	0.026	0.49	YES
25	PSEN1	PSEN1	PSEN1	5780	0.024	0.49	YES
26	CYCS	CYCS	CYCS	5873	0.023	0.49	YES
27	RELA	RELA	RELA	6090	0.021	0.49	YES
28	TRAF1	TRAF1	TRAF1	6160	0.02	0.5	YES
29	ACTG1	ACTG1	ACTG1	6403	0.017	0.49	NO
30	PAK2	PAK2	PAK2	6470	0.017	0.5	NO
31	TNFRSF1A	TNFRSF1A	TNFRSF1A	6900	0.012	0.48	NO
32	BIRC2	BIRC2	BIRC2	7079	0.01	0.47	NO
33	RASA1	RASA1	RASA1	7097	0.01	0.48	NO
34	RIPK1	RIPK1	RIPK1	7350	0.0082	0.47	NO
35	CDK11A	CDK11A	CDK11A	7722	0.0044	0.45	NO
36	XIAP	XIAP	XIAP	7893	0.003	0.44	NO
37	MAPK8	MAPK8	MAPK8	7894	0.003	0.44	NO
38	DFFB	DFFB	DFFB	7898	0.003	0.44	NO
39	PRKDC	PRKDC	PRKDC	8286	-0.00034	0.42	NO
40	BAG4	BAG4	BAG4	8401	-0.0014	0.42	NO
41	LMNA	LMNA	LMNA	8592	-0.003	0.41	NO
42	NUMA1	NUMA1	NUMA1	8837	-0.0051	0.4	NO
43	TRAF2	TRAF2	TRAF2	8937	-0.006	0.4	NO
44	CDK11B	CDK11B	CDK11B	8977	-0.0063	0.4	NO
45	SPTAN1	SPTAN1	SPTAN1	9180	-0.0081	0.39	NO
46	BID	BID	BID	9225	-0.0085	0.39	NO
47	PSEN2	PSEN2	PSEN2	9295	-0.0091	0.39	NO
48	PARP1	PARP1	PARP1	9356	-0.0096	0.39	NO
49	CASP6	CASP6	CASP6	9373	-0.0098	0.4	NO
50	GSN	GSN	GSN	9476	-0.011	0.4	NO
51	PTK2	PTK2	PTK2	9654	-0.012	0.39	NO
52	MAP2K7	MAP2K7	MAP2K7	9850	-0.014	0.39	NO
53	DAXX	DAXX	DAXX	10532	-0.02	0.36	NO
54	LMNB1	LMNB1	LMNB1	10706	-0.022	0.36	NO
55	LMNB2	LMNB2	LMNB2	10768	-0.022	0.37	NO
56	CASP2	CASP2	CASP2	11180	-0.026	0.36	NO
57	DFFA	DFFA	DFFA	11894	-0.034	0.34	NO
58	BCL2	BCL2	BCL2	14047	-0.064	0.25	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 INOSITOL PHOSPHATE METABOLISM.

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG INOSITOL PHOSPHATE 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 APOPTOSIS

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	HIP1R	HIP1R	HIP1R	1259	0.15	-0.0095	YES
2	TBC1D8B	TBC1D8B	TBC1D8B	1344	0.15	0.042	YES
3	CPD	CPD	CPD	1434	0.14	0.091	YES
4	AP4B1	AP4B1	AP4B1	1976	0.11	0.1	YES
5	AP1M2	AP1M2	AP1M2	2255	0.096	0.13	YES
6	VAMP8	VAMP8	VAMP8	2376	0.091	0.15	YES
7	GAK	GAK	GAK	2569	0.084	0.18	YES
8	DNM2	DNM2	DNM2	2712	0.079	0.2	YES
9	SH3GL2	SH3GL2	SH3GL2	2966	0.072	0.21	YES
10	AP1G1	AP1G1	AP1G1	2980	0.072	0.24	YES
11	TFRC	TFRC	TFRC	3079	0.069	0.26	YES
12	TPD52	TPD52	TPD52	3103	0.068	0.28	YES
13	AP3B1	AP3B1	AP3B1	3554	0.058	0.28	YES
14	TXNDC5	TXNDC5	TXNDC5	3753	0.054	0.29	YES
15	NECAP1	NECAP1	NECAP1	3912	0.051	0.3	YES
16	TGOLN2	TGOLN2	TGOLN2	3931	0.051	0.32	YES
17	ARRB1	ARRB1	ARRB1	4236	0.045	0.32	YES
18	SNX2	SNX2	SNX2	4333	0.044	0.34	YES
19	AP1B1	AP1B1	AP1B1	4426	0.042	0.35	YES
20	CLTC	CLTC	CLTC	4579	0.04	0.35	YES
21	AP4E1	AP4E1	AP4E1	4769	0.037	0.36	YES
22	DNASE2	DNASE2	DNASE2	4833	0.036	0.37	YES
23	PIK3C2A	PIK3C2A	PIK3C2A	4918	0.035	0.38	YES
24	YIPF6	YIPF6	YIPF6	4980	0.034	0.39	YES
25	GBF1	GBF1	GBF1	5196	0.031	0.39	YES
26	NAPA	NAPA	NAPA	5272	0.03	0.39	YES
27	BLOC1S1	BLOC1S1	BLOC1S1	5484	0.027	0.39	YES
28	STX4	STX4	STX4	5611	0.026	0.4	YES
29	SNAP23	SNAP23	SNAP23	6158	0.02	0.38	NO
30	TPD52L1	TPD52L1	TPD52L1	6445	0.017	0.37	NO
31	CNO	CNO	CNO	6553	0.016	0.37	NO
32	ARF1	ARF1	ARF1	6960	0.012	0.35	NO
33	RAB5C	RAB5C	RAB5C	7072	0.011	0.35	NO
34	AP1S1	AP1S1	AP1S1	7344	0.0082	0.34	NO
35	PICALM	PICALM	PICALM	7348	0.0082	0.34	NO
36	BLOC1S3	BLOC1S3	BLOC1S3	7598	0.006	0.33	NO
37	VAMP7	VAMP7	VAMP7	8032	0.0019	0.3	NO
38	M6PR	M6PR	M6PR	8062	0.0017	0.3	NO
39	HSPA8	HSPA8	HSPA8	8361	-0.0011	0.29	NO
40	IGF2R	IGF2R	IGF2R	8483	-0.002	0.28	NO
41	GNS	GNS	GNS	8550	-0.0027	0.28	NO
42	OCRL	OCRL	OCRL	8716	-0.004	0.27	NO
43	CLTA	CLTA	CLTA	8783	-0.0046	0.27	NO
44	FTL	FTL	FTL	8942	-0.006	0.26	NO
45	SNX5	SNX5	SNX5	9349	-0.0095	0.25	NO
46	PUM1	PUM1	PUM1	9531	-0.011	0.24	NO
47	PLDN	PLDN	PLDN	9605	-0.012	0.24	NO
48	CTSZ	CTSZ	CTSZ	9828	-0.014	0.24	NO
49	SNX9	SNX9	SNX9	10503	-0.02	0.21	NO
50	SNAPIN	SNAPIN	SNAPIN	10783	-0.022	0.2	NO
51	AP3S1	AP3S1	AP3S1	12208	-0.037	0.14	NO
52	AP1M1	AP1M1	AP1M1	12221	-0.037	0.15	NO
53	SORT1	SORT1	SORT1	12332	-0.038	0.16	NO
54	FTH1	FTH1	FTH1	12893	-0.046	0.15	NO
55	DTNBP1	DTNBP1	DTNBP1	13037	-0.048	0.16	NO
56	VAMP2	VAMP2	VAMP2	13072	-0.048	0.18	NO
57	DNAJC6	DNAJC6	DNAJC6	14040	-0.064	0.15	NO
58	SH3D19	SH3D19	SH3D19	14400	-0.072	0.16	NO
59	AP1S2	AP1S2	AP1S2	17438	-0.19	0.066	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 APOPTOSIS.

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

genes ES table in pathway: BIOCARTA HIVNEF PATHWAY

Table 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	TNF	TNF	TNF	981	0.18	0.13	YES
2	LTA	LTA	LTA	2181	0.099	0.17	YES
3	TRADD	TRADD	TRADD	2725	0.079	0.22	YES
4	MAP2K3	MAP2K3	MAP2K3	2848	0.075	0.29	YES
5	MAP3K14	MAP3K14	MAP3K14	3161	0.067	0.35	YES
6	NFKB1	NFKB1	NFKB1	3658	0.056	0.38	YES
7	CRADD	CRADD	CRADD	3865	0.052	0.42	YES
8	MAP2K6	MAP2K6	MAP2K6	4288	0.044	0.44	YES
9	MAP3K1	MAP3K1	MAP3K1	4297	0.044	0.49	YES
10	IKBKB	IKBKB	IKBKB	4430	0.042	0.52	YES
11	CHUK	CHUK	CHUK	4441	0.042	0.57	YES
12	NFKBIA	NFKBIA	NFKBIA	5559	0.027	0.53	NO
13	RELA	RELA	RELA	6090	0.021	0.53	NO
14	TANK	TANK	TANK	6262	0.019	0.54	NO
15	IKBKG	IKBKG	IKBKG	6840	0.013	0.52	NO
16	TNFRSF1A	TNFRSF1A	TNFRSF1A	6900	0.012	0.53	NO
17	RIPK1	RIPK1	RIPK1	7350	0.0082	0.51	NO
18	MAPK8	MAPK8	MAPK8	7894	0.003	0.49	NO
19	MAP2K4	MAP2K4	MAP2K4	8605	-0.0031	0.45	NO
20	JUN	JUN	JUN	8713	-0.004	0.45	NO
21	TRAF2	TRAF2	TRAF2	8937	-0.006	0.45	NO
22	MAP4K2	MAP4K2	MAP4K2	9022	-0.0067	0.45	NO
23	MAPK14	MAPK14	MAPK14	10041	-0.016	0.41	NO
24	ATF1	ATF1	ATF1	11043	-0.025	0.38	NO
25	CASP2	CASP2	CASP2	11180	-0.026	0.4	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 HIVNEF PATHWAY.

Figure S66. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA HIVNEF PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA PYK2 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	HIP1R	HIP1R	HIP1R	1259	0.15	-0.0064	YES
2	TBC1D8B	TBC1D8B	TBC1D8B	1344	0.15	0.048	YES
3	CPD	CPD	CPD	1434	0.14	0.1	YES
4	AP4B1	AP4B1	AP4B1	1976	0.11	0.12	YES
5	AP1M2	AP1M2	AP1M2	2255	0.096	0.14	YES
6	VAMP8	VAMP8	VAMP8	2376	0.091	0.17	YES
7	GAK	GAK	GAK	2569	0.084	0.19	YES
8	DNM2	DNM2	DNM2	2712	0.079	0.22	YES
9	SH3GL2	SH3GL2	SH3GL2	2966	0.072	0.23	YES
10	AP1G1	AP1G1	AP1G1	2980	0.072	0.26	YES
11	TFRC	TFRC	TFRC	3079	0.069	0.28	YES
12	TPD52	TPD52	TPD52	3103	0.068	0.31	YES
13	AP3B1	AP3B1	AP3B1	3554	0.058	0.31	YES
14	TXNDC5	TXNDC5	TXNDC5	3753	0.054	0.32	YES
15	NECAP1	NECAP1	NECAP1	3912	0.051	0.33	YES
16	TGOLN2	TGOLN2	TGOLN2	3931	0.051	0.35	YES
17	ARRB1	ARRB1	ARRB1	4236	0.045	0.35	YES
18	SNX2	SNX2	SNX2	4333	0.044	0.36	YES
19	AP1B1	AP1B1	AP1B1	4426	0.042	0.38	YES
20	CLTC	CLTC	CLTC	4579	0.04	0.38	YES
21	AP4E1	AP4E1	AP4E1	4769	0.037	0.39	YES
22	PIK3C2A	PIK3C2A	PIK3C2A	4918	0.035	0.4	YES
23	YIPF6	YIPF6	YIPF6	4980	0.034	0.41	YES
24	NAPA	NAPA	NAPA	5272	0.03	0.4	NO
25	BLOC1S1	BLOC1S1	BLOC1S1	5484	0.027	0.4	NO
26	TPD52L1	TPD52L1	TPD52L1	6445	0.017	0.36	NO
27	CNO	CNO	CNO	6553	0.016	0.36	NO
28	ARF1	ARF1	ARF1	6960	0.012	0.34	NO
29	RAB5C	RAB5C	RAB5C	7072	0.011	0.34	NO
30	AP1S1	AP1S1	AP1S1	7344	0.0082	0.33	NO
31	PICALM	PICALM	PICALM	7348	0.0082	0.33	NO
32	BLOC1S3	BLOC1S3	BLOC1S3	7598	0.006	0.32	NO
33	VAMP7	VAMP7	VAMP7	8032	0.0019	0.3	NO
34	HSPA8	HSPA8	HSPA8	8361	-0.0011	0.28	NO
35	IGF2R	IGF2R	IGF2R	8483	-0.002	0.28	NO
36	OCRL	OCRL	OCRL	8716	-0.004	0.26	NO
37	CLTA	CLTA	CLTA	8783	-0.0046	0.26	NO
38	FTL	FTL	FTL	8942	-0.006	0.26	NO
39	SNX5	SNX5	SNX5	9349	-0.0095	0.24	NO
40	PUM1	PUM1	PUM1	9531	-0.011	0.23	NO
41	PLDN	PLDN	PLDN	9605	-0.012	0.23	NO
42	SNX9	SNX9	SNX9	10503	-0.02	0.19	NO
43	SNAPIN	SNAPIN	SNAPIN	10783	-0.022	0.19	NO
44	AP3S1	AP3S1	AP3S1	12208	-0.037	0.13	NO
45	AP1M1	AP1M1	AP1M1	12221	-0.037	0.14	NO
46	SORT1	SORT1	SORT1	12332	-0.038	0.15	NO
47	FTH1	FTH1	FTH1	12893	-0.046	0.14	NO
48	DTNBP1	DTNBP1	DTNBP1	13037	-0.048	0.15	NO
49	VAMP2	VAMP2	VAMP2	13072	-0.048	0.17	NO
50	DNAJC6	DNAJC6	DNAJC6	14040	-0.064	0.14	NO
51	SH3D19	SH3D19	SH3D19	14400	-0.072	0.15	NO
52	AP1S2	AP1S2	AP1S2	17438	-0.19	0.066	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 PYK2 PATHWAY.

Figure S68. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA PYK2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA STRESS PATHWAY

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	MYL2	MYL2	MYL2	1553	0.13	-0.035	YES
2	CDH1	CDH1	CDH1	1870	0.11	-0.011	YES
3	ARHGEF6	ARHGEF6	ARHGEF6	1985	0.11	0.022	YES
4	CDC42BPA	CDC42BPA	CDC42BPA	2067	0.1	0.055	YES
5	LIMK2	LIMK2	LIMK2	2307	0.094	0.076	YES
6	F2RL2	F2RL2	F2RL2	2434	0.089	0.1	YES
7	PLD1	PLD1	PLD1	2568	0.084	0.12	YES
8	MAP2K3	MAP2K3	MAP2K3	2848	0.075	0.14	YES
9	DLG1	DLG1	DLG1	2883	0.074	0.16	YES
10	SRC	SRC	SRC	2915	0.073	0.19	YES
11	CTNNA1	CTNNA1	CTNNA1	3155	0.067	0.2	YES
12	ARPC1B	ARPC1B	ARPC1B	3330	0.063	0.21	YES
13	BCAR1	BCAR1	BCAR1	3437	0.06	0.23	YES
14	MAP3K11	MAP3K11	MAP3K11	3605	0.057	0.24	YES
15	TIAM1	TIAM1	TIAM1	3667	0.056	0.26	YES
16	EPS8	EPS8	EPS8	3831	0.052	0.26	YES
17	TNK2	TNK2	TNK2	4000	0.05	0.27	YES
18	IQGAP3	IQGAP3	IQGAP3	4085	0.048	0.29	YES
19	PAK1	PAK1	PAK1	4147	0.047	0.3	YES
20	MAP2K6	MAP2K6	MAP2K6	4288	0.044	0.31	YES
21	MAP3K1	MAP3K1	MAP3K1	4297	0.044	0.32	YES
22	PRKCE	PRKCE	PRKCE	4385	0.043	0.34	YES
23	RAF1	RAF1	RAF1	4396	0.042	0.35	YES
24	ARPC4	ARPC4	ARPC4	4488	0.041	0.36	YES
25	APC	APC	APC	4610	0.039	0.37	YES
26	MAPK9	MAPK9	MAPK9	4744	0.037	0.37	YES
27	IQGAP1	IQGAP1	IQGAP1	4857	0.035	0.38	YES
28	ATF2	ATF2	ATF2	5199	0.031	0.37	YES
29	WASL	WASL	WASL	5302	0.03	0.38	YES
30	YES1	YES1	YES1	5465	0.028	0.38	YES
31	PAX6	PAX6	PAX6	5477	0.028	0.39	YES
32	MAPK3	MAPK3	MAPK3	5794	0.024	0.38	YES
33	ACTR3	ACTR3	ACTR3	6009	0.022	0.38	YES
34	ACTR2	ACTR2	ACTR2	6075	0.021	0.38	YES
35	MTOR	MTOR	MTOR	6110	0.02	0.39	YES
36	ARPC3	ARPC3	ARPC3	6233	0.019	0.39	YES
37	BRAF	BRAF	BRAF	6257	0.019	0.39	YES
38	PAK2	PAK2	PAK2	6470	0.017	0.39	NO
39	ARPC2	ARPC2	ARPC2	6496	0.016	0.39	NO
40	ARHGDIA	ARHGDIA	ARHGDIA	6646	0.015	0.39	NO
41	PRKCZ	PRKCZ	PRKCZ	6750	0.014	0.39	NO
42	CFL1	CFL1	CFL1	6787	0.013	0.39	NO
43	ARPC5	ARPC5	ARPC5	6867	0.013	0.39	NO
44	RAC1	RAC1	RAC1	7207	0.0094	0.38	NO
45	PIK3CA	PIK3CA	PIK3CA	7464	0.0073	0.37	NO
46	PAK4	PAK4	PAK4	7666	0.0051	0.36	NO
47	MAPK8	MAPK8	MAPK8	7894	0.003	0.35	NO
48	GSK3B	GSK3B	GSK3B	8204	0.00037	0.33	NO
49	RPS6KB1	RPS6KB1	RPS6KB1	8514	-0.0023	0.31	NO
50	MAP2K4	MAP2K4	MAP2K4	8605	-0.0031	0.31	NO
51	CDC42	CDC42	CDC42	8654	-0.0035	0.31	NO
52	JUN	JUN	JUN	8713	-0.004	0.31	NO
53	EXOC7	EXOC7	EXOC7	8801	-0.0048	0.3	NO
54	MAPK1	MAPK1	MAPK1	8979	-0.0063	0.3	NO
55	ARHGEF7	ARHGEF7	ARHGEF7	9800	-0.013	0.26	NO
56	MAP2K7	MAP2K7	MAP2K7	9850	-0.014	0.26	NO
57	MAPK14	MAPK14	MAPK14	10041	-0.016	0.26	NO
58	PARD6A	PARD6A	PARD6A	10961	-0.024	0.22	NO
59	CBL	CBL	CBL	11066	-0.025	0.22	NO
60	VAV2	VAV2	VAV2	11469	-0.029	0.21	NO
61	SEPT2	SEPT2	SEPT2	11779	-0.032	0.2	NO
62	RASGRF1	RASGRF1	RASGRF1	11811	-0.033	0.21	NO
63	BAIAP2	BAIAP2	BAIAP2	11821	-0.033	0.22	NO
64	DIAPH3	DIAPH3	DIAPH3	12464	-0.04	0.2	NO
65	LIMK1	LIMK1	LIMK1	12563	-0.041	0.21	NO
66	CTNNB1	CTNNB1	CTNNB1	12935	-0.046	0.21	NO
67	HRAS	HRAS	HRAS	13778	-0.059	0.19	NO
68	PIK3R1	PIK3R1	PIK3R1	14200	-0.068	0.19	NO
69	ENAH	ENAH	ENAH	14301	-0.07	0.21	NO
70	HES5	HES5	HES5	14539	-0.075	0.22	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: BIOCARTA STRESS PATHWAY.

Figure S70. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA STRESS 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: ST TUMOR NECROSIS FACTOR PATHWAY

Table S36. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HDAC9	HDAC9	HDAC9	371	0.28	0.079	YES
2	PPARG	PPARG	PPARG	891	0.19	0.12	YES
3	TNF	TNF	TNF	981	0.18	0.17	YES
4	ZFPM1	ZFPM1	ZFPM1	1273	0.15	0.21	YES
5	KAT2B	KAT2B	KAT2B	1693	0.12	0.23	YES
6	GATA1	GATA1	GATA1	2126	0.1	0.24	YES
7	MXD1	MXD1	MXD1	2141	0.1	0.28	YES
8	SIRT7	SIRT7	SIRT7	2258	0.096	0.31	YES
9	SMURF1	SMURF1	SMURF1	2304	0.094	0.34	YES
10	GATA2	GATA2	GATA2	2634	0.082	0.35	YES
11	NFKB1	NFKB1	NFKB1	3658	0.056	0.31	NO
12	SIRT6	SIRT6	SIRT6	5325	0.03	0.23	NO
13	NFKBIA	NFKBIA	NFKBIA	5559	0.027	0.23	NO
14	MBD2	MBD2	MBD2	5876	0.023	0.22	NO
15	RELA	RELA	RELA	6090	0.021	0.22	NO
16	NCOR1	NCOR1	NCOR1	6253	0.019	0.22	NO
17	RANBP2	RANBP2	RANBP2	6260	0.019	0.22	NO
18	WDR77	WDR77	WDR77	6602	0.015	0.21	NO
19	TNFRSF1A	TNFRSF1A	TNFRSF1A	6900	0.012	0.2	NO
20	HDAC10	HDAC10	HDAC10	7060	0.011	0.19	NO
21	SIRT2	SIRT2	SIRT2	7159	0.0097	0.19	NO
22	TFCP2	TFCP2	TFCP2	7377	0.008	0.18	NO
23	GATAD2A	GATAD2A	GATAD2A	7454	0.0074	0.18	NO
24	STAT3	STAT3	STAT3	7498	0.0071	0.18	NO
25	CREBBP	CREBBP	CREBBP	7609	0.0058	0.18	NO
26	EP300	EP300	EP300	7820	0.0036	0.17	NO
27	SMG5	SMG5	SMG5	8022	0.002	0.16	NO
28	CHD3	CHD3	CHD3	8322	-0.00075	0.14	NO
29	HDAC1	HDAC1	HDAC1	8721	-0.0041	0.12	NO
30	HDAC3	HDAC3	HDAC3	8945	-0.006	0.11	NO
31	NCOR2	NCOR2	NCOR2	8971	-0.0062	0.11	NO
32	SIRT1	SIRT1	SIRT1	9024	-0.0067	0.11	NO
33	XPO1	XPO1	XPO1	9036	-0.0068	0.11	NO
34	SIN3A	SIN3A	SIN3A	9122	-0.0076	0.11	NO
35	RANGAP1	RANGAP1	RANGAP1	9192	-0.0083	0.11	NO
36	HDAC6	HDAC6	HDAC6	9326	-0.0094	0.11	NO
37	MTA2	MTA2	MTA2	9359	-0.0096	0.11	NO
38	HDAC7	HDAC7	HDAC7	9538	-0.011	0.1	NO
39	YY1	YY1	YY1	9545	-0.011	0.1	NO
40	RBBP7	RBBP7	RBBP7	9739	-0.013	0.1	NO
41	HDAC8	HDAC8	HDAC8	10044	-0.016	0.089	NO
42	SUMO1	SUMO1	SUMO1	10075	-0.016	0.092	NO
43	GATAD2B	GATAD2B	GATAD2B	10130	-0.016	0.095	NO
44	SIRT5	SIRT5	SIRT5	10179	-0.017	0.099	NO
45	SAP30	SAP30	SAP30	10182	-0.017	0.1	NO
46	RAN	RAN	RAN	10295	-0.018	0.1	NO
47	SIN3B	SIN3B	SIN3B	11433	-0.029	0.054	NO
48	CHD4	CHD4	CHD4	11458	-0.029	0.062	NO
49	RBBP4	RBBP4	RBBP4	11734	-0.032	0.059	NO
50	MAX	MAX	MAX	11736	-0.032	0.07	NO
51	MBD3	MBD3	MBD3	11909	-0.034	0.073	NO
52	PRKACA	PRKACA	PRKACA	11925	-0.034	0.084	NO
53	NR2C1	NR2C1	NR2C1	12028	-0.035	0.09	NO
54	UBE2I	UBE2I	UBE2I	12326	-0.038	0.088	NO
55	PRMT5	PRMT5	PRMT5	12378	-0.039	0.099	NO
56	SSPO	SSPO	SSPO	12401	-0.039	0.11	NO
57	SAP18	SAP18	SAP18	12715	-0.043	0.11	NO
58	FKBP3	FKBP3	FKBP3	12887	-0.046	0.12	NO
59	SMAD7	SMAD7	SMAD7	12902	-0.046	0.13	NO
60	SIRT3	SIRT3	SIRT3	13283	-0.051	0.13	NO
61	HDAC2	HDAC2	HDAC2	14141	-0.066	0.11	NO
62	HDAC5	HDAC5	HDAC5	14808	-0.082	0.099	NO
63	HDAC11	HDAC11	HDAC11	14922	-0.085	0.12	NO
64	SIRT4	SIRT4	SIRT4	15679	-0.11	0.12	NO
65	HDAC4	HDAC4	HDAC4	15921	-0.12	0.15	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: ST TUMOR NECROSIS FACTOR PATHWAY.

Figure S72. Get High-res Image For the top 5 core enriched genes in the pathway: ST TUMOR NECROSIS FACTOR 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: ST INTERLEUKIN 4 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	NR0B2	NR0B2	NR0B2	146	0.38	0.2	YES
2	SERPINA4	SERPINA4	SERPINA4	159	0.37	0.4	YES
3	JAK2	JAK2	JAK2	977	0.18	0.45	YES
4	IL2RG	IL2RG	IL2RG	1667	0.13	0.49	YES
5	PI3	PI3	PI3	2101	0.1	0.52	YES
6	INPP5D	INPP5D	INPP5D	2746	0.078	0.53	YES
7	SRC	SRC	SRC	2915	0.073	0.56	YES
8	TYK2	TYK2	TYK2	3313	0.063	0.57	YES
9	PPP1R13B	PPP1R13B	PPP1R13B	3575	0.058	0.59	YES
10	JAK3	JAK3	JAK3	4372	0.043	0.57	NO
11	JAK1	JAK1	JAK1	4556	0.04	0.58	NO
12	IL4R	IL4R	IL4R	5872	0.023	0.52	NO
13	STAT6	STAT6	STAT6	5981	0.022	0.53	NO
14	GRB2	GRB2	GRB2	6193	0.02	0.53	NO
15	SOS2	SOS2	SOS2	7365	0.0081	0.47	NO
16	PIK3CA	PIK3CA	PIK3CA	7464	0.0073	0.47	NO
17	AKT1	AKT1	AKT1	7547	0.0066	0.47	NO
18	IARS	IARS	IARS	7569	0.0062	0.47	NO
19	SOS1	SOS1	SOS1	7962	0.0025	0.45	NO
20	RPS6KB1	RPS6KB1	RPS6KB1	8514	-0.0023	0.42	NO
21	IL13RA1	IL13RA1	IL13RA1	9579	-0.012	0.37	NO
22	SHC1	SHC1	SHC1	9901	-0.014	0.36	NO
23	CISH	CISH	CISH	11653	-0.031	0.28	NO
24	AKT2	AKT2	AKT2	12096	-0.036	0.28	NO
25	AKT3	AKT3	AKT3	16419	-0.14	0.12	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: ST INTERLEUKIN 4 PATHWAY.

Figure S74. Get High-res Image For the top 5 core enriched genes in the pathway: ST INTERLEUKIN 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: PID BCR 5PATHWAY

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	TNFRSF10C	TNFRSF10C	TNFRSF10C	1206	0.16	0.064	YES
2	CASP10	CASP10	CASP10	1363	0.14	0.17	YES
3	TNFSF10	TNFSF10	TNFSF10	1919	0.11	0.24	YES
4	CFLAR	CFLAR	CFLAR	2200	0.098	0.3	YES
5	TNFRSF10A	TNFRSF10A	TNFRSF10A	2373	0.091	0.37	YES
6	TRADD	TRADD	TRADD	2725	0.079	0.41	YES
7	PIK3CB	PIK3CB	PIK3CB	3365	0.062	0.43	YES
8	MAP3K1	MAP3K1	MAP3K1	4297	0.044	0.42	YES
9	IKBKB	IKBKB	IKBKB	4430	0.042	0.44	YES
10	PIK3CD	PIK3CD	PIK3CD	4439	0.042	0.48	YES
11	CHUK	CHUK	CHUK	4441	0.042	0.51	YES
12	CASP8	CASP8	CASP8	4717	0.038	0.53	YES
13	FADD	FADD	FADD	5183	0.031	0.53	YES
14	TNFRSF10B	TNFRSF10B	TNFRSF10B	5467	0.028	0.54	YES
15	PIK3R3	PIK3R3	PIK3R3	5613	0.026	0.55	YES
16	MAPK3	MAPK3	MAPK3	5794	0.024	0.56	YES
17	IKBKG	IKBKG	IKBKG	6840	0.013	0.51	NO
18	RIPK1	RIPK1	RIPK1	7350	0.0082	0.49	NO
19	PIK3CA	PIK3CA	PIK3CA	7464	0.0073	0.49	NO
20	MAPK8	MAPK8	MAPK8	7894	0.003	0.47	NO
21	SMPD1	SMPD1	SMPD1	8177	0.0006	0.46	NO
22	TNFRSF10D	TNFRSF10D	TNFRSF10D	8272	-0.00024	0.45	NO
23	MAP2K4	MAP2K4	MAP2K4	8605	-0.0031	0.44	NO
24	TRAF2	TRAF2	TRAF2	8937	-0.006	0.42	NO
25	MAPK1	MAPK1	MAPK1	8979	-0.0063	0.43	NO
26	DAP3	DAP3	DAP3	10191	-0.017	0.38	NO
27	PIK3R2	PIK3R2	PIK3R2	11309	-0.028	0.34	NO
28	PIK3R1	PIK3R1	PIK3R1	14200	-0.068	0.24	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 BCR 5PATHWAY.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: PID BCR 5PATHWAY, 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 TRAIL PATHWAY

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	BLNK	BLNK	BLNK	243	0.33	0.046	YES
2	BLK	BLK	BLK	277	0.31	0.099	YES
3	CD79A	CD79A	CD79A	316	0.3	0.15	YES
4	CD19	CD19	CD19	702	0.22	0.17	YES
5	CD79B	CD79B	CD79B	864	0.19	0.19	YES
6	CARD11	CARD11	CARD11	942	0.18	0.22	YES
7	BTK	BTK	BTK	1163	0.16	0.24	YES
8	RASGRP1	RASGRP1	RASGRP1	1673	0.13	0.23	YES
9	CBLB	CBLB	CBLB	1927	0.11	0.24	YES
10	VAV1	VAV1	VAV1	1943	0.11	0.26	YES
11	REL	REL	REL	1979	0.11	0.28	YES
12	PRKCB	PRKCB	PRKCB	2025	0.11	0.29	YES
13	BCL10	BCL10	BCL10	2124	0.1	0.3	YES
14	RASGRP3	RASGRP3	RASGRP3	2136	0.1	0.32	YES
15	ITPR3	ITPR3	ITPR3	2357	0.092	0.33	YES
16	LYN	LYN	LYN	2428	0.089	0.34	YES
17	SYK	SYK	SYK	2670	0.08	0.34	YES
18	NFKBIE	NFKBIE	NFKBIE	2671	0.08	0.36	YES
19	PSME4	PSME4	PSME4	2867	0.075	0.36	YES
20	NR4A1	NR4A1	NR4A1	2904	0.074	0.37	YES
21	PLCG2	PLCG2	PLCG2	3015	0.071	0.38	YES
22	SH3KBP1	SH3KBP1	SH3KBP1	3084	0.069	0.38	YES
23	PHLPP1	PHLPP1	PHLPP1	3174	0.066	0.39	YES
24	MDM2	MDM2	MDM2	3671	0.056	0.37	YES
25	PSMB10	PSMB10	PSMB10	3840	0.052	0.37	YES
26	KRAS	KRAS	KRAS	3883	0.052	0.38	YES
27	NRAS	NRAS	NRAS	3930	0.051	0.39	YES
28	IKBKB	IKBKB	IKBKB	4430	0.042	0.37	YES
29	NFKBIB	NFKBIB	NFKBIB	4434	0.042	0.38	YES
30	PIK3CD	PIK3CD	PIK3CD	4439	0.042	0.38	YES
31	CHUK	CHUK	CHUK	4441	0.042	0.39	YES
32	FBXW11	FBXW11	FBXW11	4493	0.041	0.4	YES
33	PSMC2	PSMC2	PSMC2	4890	0.035	0.38	NO
34	PIK3AP1	PIK3AP1	PIK3AP1	4924	0.034	0.38	NO
35	CASP9	CASP9	CASP9	5033	0.033	0.38	NO
36	RPS6KB2	RPS6KB2	RPS6KB2	5072	0.033	0.39	NO
37	PDPK1	PDPK1	PDPK1	5284	0.03	0.38	NO
38	PSMB8	PSMB8	PSMB8	5401	0.028	0.38	NO
39	PSMA5	PSMA5	PSMA5	5441	0.028	0.38	NO
40	NFKBIA	NFKBIA	NFKBIA	5559	0.027	0.38	NO
41	BAD	BAD	BAD	5652	0.026	0.38	NO
42	ORAI1	ORAI1	ORAI1	5992	0.022	0.37	NO
43	RELA	RELA	RELA	6090	0.021	0.37	NO
44	MTOR	MTOR	MTOR	6110	0.02	0.37	NO
45	PSME2	PSME2	PSME2	6128	0.02	0.37	NO
46	PSMD2	PSMD2	PSMD2	6134	0.02	0.38	NO
47	GRB2	GRB2	GRB2	6193	0.02	0.38	NO
48	PSMC4	PSMC4	PSMC4	6201	0.019	0.38	NO
49	PSMD9	PSMD9	PSMD9	6204	0.019	0.38	NO
50	TSC2	TSC2	TSC2	6592	0.015	0.36	NO
51	CDKN1A	CDKN1A	CDKN1A	6731	0.014	0.36	NO
52	IKBKG	IKBKG	IKBKG	6840	0.013	0.36	NO
53	PTEN	PTEN	PTEN	6995	0.011	0.35	NO
54	CALM3	CALM3	CALM3	7321	0.0083	0.33	NO
55	ITPR2	ITPR2	ITPR2	7458	0.0074	0.33	NO
56	PSMA4	PSMA4	PSMA4	7493	0.0071	0.33	NO
57	AKT1	AKT1	AKT1	7547	0.0066	0.32	NO
58	PSMB9	PSMB9	PSMB9	7676	0.0049	0.32	NO
59	GSK3A	GSK3A	GSK3A	7684	0.0048	0.32	NO
60	PSMA8	PSMA8	PSMA8	7688	0.0048	0.32	NO
61	PSMC5	PSMC5	PSMC5	7922	0.0028	0.31	NO
62	PSME1	PSME1	PSME1	7946	0.0026	0.31	NO
63	SOS1	SOS1	SOS1	7962	0.0025	0.31	NO
64	PSMB2	PSMB2	PSMB2	8045	0.0018	0.3	NO
65	PSMD11	PSMD11	PSMD11	8048	0.0018	0.3	NO
66	AKT1S1	AKT1S1	AKT1S1	8138	0.0011	0.3	NO
67	STIM1	STIM1	STIM1	8225	0.00017	0.29	NO
68	RICTOR	RICTOR	RICTOR	8337	-0.00087	0.29	NO
69	PSMA3	PSMA3	PSMA3	8373	-0.0012	0.29	NO
70	MLST8	MLST8	MLST8	8422	-0.0016	0.28	NO
71	PSMD8	PSMD8	PSMD8	8578	-0.0029	0.28	NO
72	PSMC6	PSMC6	PSMC6	8726	-0.0041	0.27	NO
73	PSMD12	PSMD12	PSMD12	8774	-0.0046	0.27	NO
74	NCK1	NCK1	NCK1	8829	-0.005	0.26	NO
75	RPS27A	RPS27A	RPS27A	8902	-0.0056	0.26	NO
76	PSMD6	PSMD6	PSMD6	8929	-0.0059	0.26	NO
77	PSMD10	PSMD10	PSMD10	9065	-0.0071	0.26	NO
78	PSMD1	PSMD1	PSMD1	9090	-0.0073	0.26	NO
79	PSMA2	PSMA2	PSMA2	9113	-0.0075	0.26	NO
80	PSMC1	PSMC1	PSMC1	9173	-0.0081	0.25	NO
81	UBA52	UBA52	UBA52	9280	-0.009	0.25	NO
82	PSMC3	PSMC3	PSMC3	9315	-0.0093	0.25	NO
83	PSMD14	PSMD14	PSMD14	9319	-0.0094	0.25	NO
84	CALM2	CALM2	CALM2	9333	-0.0094	0.25	NO
85	PSMB3	PSMB3	PSMB3	9393	-0.01	0.25	NO
86	FOXO1	FOXO1	FOXO1	9397	-0.01	0.25	NO
87	PSMD13	PSMD13	PSMD13	9398	-0.01	0.25	NO
88	PSMD7	PSMD7	PSMD7	9627	-0.012	0.24	NO
89	PSMA1	PSMA1	PSMA1	9761	-0.013	0.24	NO
90	PSMD3	PSMD3	PSMD3	9894	-0.014	0.23	NO
91	SHC1	SHC1	SHC1	9901	-0.014	0.24	NO
92	FYN	FYN	FYN	9933	-0.014	0.24	NO
93	PSMA7	PSMA7	PSMA7	9983	-0.015	0.24	NO
94	PSMB4	PSMB4	PSMB4	10262	-0.017	0.23	NO
95	CALM1	CALM1	CALM1	10275	-0.018	0.23	NO
96	FOXO4	FOXO4	FOXO4	10353	-0.018	0.23	NO
97	BTRC	BTRC	BTRC	10451	-0.019	0.22	NO
98	PSMD5	PSMD5	PSMD5	10488	-0.02	0.23	NO
99	PSMA6	PSMA6	PSMA6	10501	-0.02	0.23	NO
100	CUL1	CUL1	CUL1	10507	-0.02	0.23	NO
101	CREB1	CREB1	CREB1	10572	-0.02	0.23	NO
102	PSMD4	PSMD4	PSMD4	10752	-0.022	0.23	NO
103	SKP1	SKP1	SKP1	10926	-0.024	0.22	NO
104	PSMB5	PSMB5	PSMB5	10992	-0.024	0.22	NO
105	PSMB1	PSMB1	PSMB1	11023	-0.025	0.23	NO
106	CBL	CBL	CBL	11066	-0.025	0.23	NO
107	PSMB6	PSMB6	PSMB6	11558	-0.03	0.21	NO
108	PSMF1	PSMF1	PSMF1	11844	-0.033	0.2	NO
109	PSMB7	PSMB7	PSMB7	12044	-0.035	0.19	NO
110	AKT2	AKT2	AKT2	12096	-0.036	0.2	NO
111	MAPKAP1	MAPKAP1	MAPKAP1	12305	-0.038	0.19	NO
112	MAP3K7	MAP3K7	MAP3K7	12345	-0.039	0.2	NO
113	MALT1	MALT1	MALT1	12835	-0.045	0.18	NO
114	FOXO3	FOXO3	FOXO3	12988	-0.047	0.18	NO
115	HRAS	HRAS	HRAS	13778	-0.059	0.15	NO
116	THEM4	THEM4	THEM4	14138	-0.066	0.14	NO
117	PIK3R1	PIK3R1	PIK3R1	14200	-0.068	0.15	NO
118	CDKN1B	CDKN1B	CDKN1B	14326	-0.07	0.15	NO
119	PLCG1	PLCG1	PLCG1	15006	-0.087	0.13	NO
120	AKT3	AKT3	AKT3	16419	-0.14	0.081	NO
121	TRIB3	TRIB3	TRIB3	17804	-0.22	0.047	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 TRAIL PATHWAY.

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: PID TRAIL 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 CDC42 PATHWAY

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	BIRC3	BIRC3	BIRC3	627	0.22	0.14	YES
2	TNF	TNF	TNF	981	0.18	0.25	YES
3	CFLAR	CFLAR	CFLAR	2200	0.098	0.26	YES
4	NFKBIE	NFKBIE	NFKBIE	2671	0.08	0.29	YES
5	TRADD	TRADD	TRADD	2725	0.079	0.35	YES
6	NFKB1	NFKB1	NFKB1	3658	0.056	0.34	YES
7	TNFAIP3	TNFAIP3	TNFAIP3	3699	0.055	0.38	YES
8	TNFRSF1B	TNFRSF1B	TNFRSF1B	3713	0.055	0.42	YES
9	NFKB2	NFKB2	NFKB2	3889	0.051	0.45	YES
10	CASP3	CASP3	CASP3	4353	0.043	0.46	YES
11	NFKBIB	NFKBIB	NFKBIB	4434	0.042	0.48	YES
12	AGFG1	AGFG1	AGFG1	4634	0.039	0.5	YES
13	CASP8	CASP8	CASP8	4717	0.038	0.53	YES
14	RALBP1	RALBP1	RALBP1	5172	0.031	0.53	YES
15	FADD	FADD	FADD	5183	0.031	0.55	YES
16	NFKBIA	NFKBIA	NFKBIA	5559	0.027	0.55	NO
17	NR2C2	NR2C2	NR2C2	6432	0.017	0.52	NO
18	IKBKG	IKBKG	IKBKG	6840	0.013	0.5	NO
19	TNFRSF1A	TNFRSF1A	TNFRSF1A	6900	0.012	0.51	NO
20	BIRC2	BIRC2	BIRC2	7079	0.01	0.51	NO
21	RIPK1	RIPK1	RIPK1	7350	0.0082	0.5	NO
22	BAG4	BAG4	BAG4	8401	-0.0014	0.44	NO
23	MAP2K4	MAP2K4	MAP2K4	8605	-0.0031	0.44	NO
24	JUN	JUN	JUN	8713	-0.004	0.43	NO
25	TRAF2	TRAF2	TRAF2	8937	-0.006	0.43	NO
26	NFKBIL1	NFKBIL1	NFKBIL1	11303	-0.028	0.32	NO
27	MAP3K7	MAP3K7	MAP3K7	12345	-0.039	0.29	NO
28	MAP3K3	MAP3K3	MAP3K3	13925	-0.062	0.26	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 CDC42 PATHWAY.

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: PID CDC42 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 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 CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.65	2	0.0041	0.13	0.26	0.69	0.21	0.55	0	0.025
KEGG FRUCTOSE AND MANNOSE METABOLISM	34	genes.ES.table	0.66	2.1	0.002	0.19	0.11	0.44	0.13	0.38	0	0.055
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	44	genes.ES.table	0.51	1.8	0.024	0.41	0.62	0.57	0.22	0.44	0.12	0.099
KEGG PYRUVATE METABOLISM	38	genes.ES.table	0.53	1.8	0.006	0.37	0.63	0.47	0.18	0.39	0.11	0.095
KEGG BUTANOATE METABOLISM	31	genes.ES.table	0.57	1.7	0.012	0.53	0.92	0.52	0.18	0.42	0.26	0.14
KEGG AMINOACYL TRNA BIOSYNTHESIS	41	genes.ES.table	0.61	2	0.0041	0.24	0.21	0.68	0.26	0.51	0	0.06
KEGG PEROXISOME	76	genes.ES.table	0.54	2	0	0.15	0.25	0.34	0.14	0.3	0	0.035
BIOCARTA DEATH PATHWAY	33	genes.ES.table	0.47	1.7	0.049	0.44	0.78	0.39	0.22	0.31	0.17	0.11
REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX	49	genes.ES.table	0.58	1.7	0.074	0.54	0.91	0.86	0.31	0.59	0.26	0.15
REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT	115	genes.ES.table	0.47	1.7	0.09	0.55	0.87	0.61	0.25	0.46	0.24	0.15

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

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	ALDOB	ALDOB	ALDOB	66	0.53	0.16	YES
2	KHK	KHK	KHK	183	0.39	0.27	YES
3	PFKFB4	PFKFB4	PFKFB4	309	0.31	0.36	YES
4	SORD	SORD	SORD	759	0.19	0.39	YES
5	AKR1B10	AKR1B10	AKR1B10	850	0.18	0.44	YES
6	PFKFB2	PFKFB2	PFKFB2	1030	0.15	0.48	YES
7	FUK	FUK	FUK	1122	0.14	0.51	YES
8	FBP1	FBP1	FBP1	1405	0.12	0.54	YES
9	GMDS	GMDS	GMDS	1726	0.1	0.55	YES
10	TSTA3	TSTA3	TSTA3	2080	0.089	0.56	YES
11	PFKL	PFKL	PFKL	2185	0.085	0.58	YES
12	PMM1	PMM1	PMM1	2300	0.082	0.6	YES
13	TPI1	TPI1	TPI1	2372	0.08	0.62	YES
14	PMM2	PMM2	PMM2	2383	0.079	0.64	YES
15	ALDOC	ALDOC	ALDOC	2484	0.076	0.66	YES
16	MPI	MPI	MPI	5009	0.03	0.53	NO
17	PFKP	PFKP	PFKP	5176	0.027	0.53	NO
18	ALDOA	ALDOA	ALDOA	5364	0.025	0.53	NO
19	FPGT	FPGT	FPGT	5437	0.024	0.53	NO
20	MTMR6	MTMR6	MTMR6	5523	0.023	0.53	NO
21	GMPPA	GMPPA	GMPPA	5654	0.021	0.53	NO
22	PHPT1	PHPT1	PHPT1	6012	0.018	0.52	NO
23	MTMR1	MTMR1	MTMR1	6482	0.011	0.5	NO
24	FBP2	FBP2	FBP2	7293	0.0021	0.46	NO
25	PFKFB3	PFKFB3	PFKFB3	7809	-0.0036	0.43	NO
26	GMPPB	GMPPB	GMPPB	8075	-0.0067	0.42	NO
27	HK2	HK2	HK2	8125	-0.0073	0.42	NO
28	MTMR7	MTMR7	MTMR7	8459	-0.011	0.4	NO
29	PFKM	PFKM	PFKM	8781	-0.014	0.39	NO
30	HK3	HK3	HK3	9508	-0.024	0.36	NO
31	PFKFB1	PFKFB1	PFKFB1	9527	-0.024	0.36	NO
32	MTMR2	MTMR2	MTMR2	11048	-0.048	0.3	NO
33	HK1	HK1	HK1	14540	-0.14	0.15	NO
34	AKR1B1	AKR1B1	AKR1B1	16486	-0.23	0.12	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 CITRATE CYCLE TCA CYCLE.

Figure S82. 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 FRUCTOSE AND MANNOSE METABOLISM

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	MARS2	MARS2	MARS2	1221	0.14	-0.0051	YES
2	NARS2	NARS2	NARS2	1261	0.13	0.052	YES
3	SEPSECS	SEPSECS	SEPSECS	1360	0.12	0.1	YES
4	FARSB	FARSB	FARSB	1440	0.12	0.15	YES
5	PARS2	PARS2	PARS2	1494	0.12	0.2	YES
6	AARS2	AARS2	AARS2	1718	0.1	0.24	YES
7	DARS2	DARS2	DARS2	1857	0.098	0.27	YES
8	WARS2	WARS2	WARS2	2404	0.078	0.28	YES
9	NARS	NARS	NARS	2436	0.077	0.31	YES
10	QARS	QARS	QARS	2577	0.074	0.34	YES
11	CARS2	CARS2	CARS2	2713	0.07	0.36	YES
12	LARS2	LARS2	LARS2	2742	0.07	0.39	YES
13	KARS	KARS	KARS	2772	0.069	0.42	YES
14	EPRS	EPRS	EPRS	2844	0.067	0.45	YES
15	YARS2	YARS2	YARS2	3242	0.059	0.45	YES
16	IARS2	IARS2	IARS2	3617	0.052	0.46	YES
17	IARS	IARS	IARS	3735	0.049	0.47	YES
18	FARSA	FARSA	FARSA	3743	0.049	0.49	YES
19	MTFMT	MTFMT	MTFMT	3972	0.045	0.5	YES
20	RARS2	RARS2	RARS2	4022	0.044	0.52	YES
21	LARS	LARS	LARS	4273	0.04	0.52	YES
22	HARS2	HARS2	HARS2	4301	0.04	0.54	YES
23	PSTK	PSTK	PSTK	4388	0.038	0.55	YES
24	RARS	RARS	RARS	4394	0.038	0.57	YES
25	GARS	GARS	GARS	4407	0.038	0.58	YES
26	VARS	VARS	VARS	4770	0.033	0.58	YES
27	SARS	SARS	SARS	4773	0.033	0.6	YES
28	DARS	DARS	DARS	4836	0.032	0.61	YES
29	TARS	TARS	TARS	5754	0.02	0.57	NO
30	YARS	YARS	YARS	6076	0.016	0.56	NO
31	FARS2	FARS2	FARS2	6293	0.013	0.55	NO
32	SARS2	SARS2	SARS2	6354	0.013	0.55	NO
33	CARS	CARS	CARS	6356	0.013	0.56	NO
34	TARS2	TARS2	TARS2	6370	0.012	0.56	NO
35	EARS2	EARS2	EARS2	6429	0.012	0.56	NO
36	VARS2	VARS2	VARS2	6510	0.011	0.57	NO
37	HARS	HARS	HARS	7509	-0.0003	0.51	NO
38	AARS	AARS	AARS	8431	-0.011	0.47	NO
39	MARS	MARS	MARS	10272	-0.035	0.38	NO
40	TARSL2	TARSL2	TARSL2	12038	-0.068	0.32	NO
41	WARS	WARS	WARS	12576	-0.08	0.33	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 FRUCTOSE AND MANNOSE METABOLISM.

Figure S84. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

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

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	MARS2	MARS2	MARS2	1221	0.14	-0.0039	YES
2	NARS2	NARS2	NARS2	1261	0.13	0.054	YES
3	FARSB	FARSB	FARSB	1440	0.12	0.099	YES
4	PARS2	PARS2	PARS2	1494	0.12	0.15	YES
5	AARS2	AARS2	AARS2	1718	0.1	0.19	YES
6	DARS2	DARS2	DARS2	1857	0.098	0.22	YES
7	WARS2	WARS2	WARS2	2404	0.078	0.23	YES
8	NARS	NARS	NARS	2436	0.077	0.26	YES
9	AIMP2	AIMP2	AIMP2	2508	0.076	0.29	YES
10	QARS	QARS	QARS	2577	0.074	0.32	YES
11	CARS2	CARS2	CARS2	2713	0.07	0.35	YES
12	LARS2	LARS2	LARS2	2742	0.07	0.38	YES
13	KARS	KARS	KARS	2772	0.069	0.41	YES
14	EPRS	EPRS	EPRS	2844	0.067	0.44	YES
15	YARS2	YARS2	YARS2	3242	0.059	0.44	YES
16	PPA2	PPA2	PPA2	3256	0.059	0.47	YES
17	IARS2	IARS2	IARS2	3617	0.052	0.47	YES
18	PPA1	PPA1	PPA1	3733	0.05	0.49	YES
19	IARS	IARS	IARS	3735	0.049	0.51	YES
20	FARSA	FARSA	FARSA	3743	0.049	0.53	YES
21	RARS2	RARS2	RARS2	4022	0.044	0.54	YES
22	AIMP1	AIMP1	AIMP1	4098	0.043	0.56	YES
23	LARS	LARS	LARS	4273	0.04	0.56	YES
24	HARS2	HARS2	HARS2	4301	0.04	0.58	YES
25	RARS	RARS	RARS	4394	0.038	0.59	YES
26	GARS	GARS	GARS	4407	0.038	0.61	YES
27	VARS	VARS	VARS	4770	0.033	0.6	YES
28	SARS	SARS	SARS	4773	0.033	0.62	YES
29	DARS	DARS	DARS	4836	0.032	0.63	YES
30	TARS	TARS	TARS	5754	0.02	0.59	NO
31	YARS	YARS	YARS	6076	0.016	0.58	NO
32	FARS2	FARS2	FARS2	6293	0.013	0.58	NO
33	SARS2	SARS2	SARS2	6354	0.013	0.58	NO
34	CARS	CARS	CARS	6356	0.013	0.58	NO
35	TARS2	TARS2	TARS2	6370	0.012	0.59	NO
36	EARS2	EARS2	EARS2	6429	0.012	0.59	NO
37	VARS2	VARS2	VARS2	6510	0.011	0.59	NO
38	EEF1E1	EEF1E1	EEF1E1	6955	0.0057	0.57	NO
39	HARS	HARS	HARS	7509	-0.0003	0.54	NO
40	AARS	AARS	AARS	8431	-0.011	0.5	NO
41	MARS	MARS	MARS	10272	-0.035	0.41	NO
42	WARS	WARS	WARS	12576	-0.08	0.33	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 VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

Figure S86. 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 PYRUVATE 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	NOS2	NOS2	NOS2	7	0.8	0.11	YES
2	XDH	XDH	XDH	100	0.46	0.16	YES
3	ACSL6	ACSL6	ACSL6	213	0.37	0.21	YES
4	FAR2	FAR2	FAR2	218	0.37	0.25	YES
5	ACOX2	ACOX2	ACOX2	271	0.34	0.3	YES
6	EPHX2	EPHX2	EPHX2	322	0.31	0.34	YES
7	SLC27A2	SLC27A2	SLC27A2	567	0.23	0.35	YES
8	AMACR	AMACR	AMACR	696	0.2	0.37	YES
9	ACSL5	ACSL5	ACSL5	753	0.19	0.39	YES
10	AGXT	AGXT	AGXT	937	0.16	0.41	YES
11	PEX7	PEX7	PEX7	939	0.16	0.43	YES
12	IDH2	IDH2	IDH2	1017	0.15	0.44	YES
13	PEX6	PEX6	PEX6	1123	0.14	0.46	YES
14	DECR2	DECR2	DECR2	1198	0.14	0.47	YES
15	PXMP2	PXMP2	PXMP2	1482	0.12	0.47	YES
16	NUDT12	NUDT12	NUDT12	1530	0.11	0.48	YES
17	PEX11G	PEX11G	PEX11G	1679	0.11	0.49	YES
18	GSTK1	GSTK1	GSTK1	1803	0.1	0.5	YES
19	PEX1	PEX1	PEX1	1863	0.098	0.51	YES
20	PEX11A	PEX11A	PEX11A	1895	0.096	0.52	YES
21	HSD17B4	HSD17B4	HSD17B4	2196	0.085	0.51	YES
22	CRAT	CRAT	CRAT	2198	0.085	0.52	YES
23	DHRS4	DHRS4	DHRS4	2257	0.083	0.53	YES
24	SOD1	SOD1	SOD1	2378	0.079	0.54	YES
25	HMGCL	HMGCL	HMGCL	2534	0.075	0.54	YES
26	MLYCD	MLYCD	MLYCD	2618	0.073	0.54	YES
27	EHHADH	EHHADH	EHHADH	3354	0.056	0.51	NO
28	PEX11B	PEX11B	PEX11B	3419	0.055	0.52	NO
29	ABCD1	ABCD1	ABCD1	3481	0.054	0.52	NO
30	PEX2	PEX2	PEX2	3504	0.054	0.52	NO
31	IDH1	IDH1	IDH1	3636	0.051	0.52	NO
32	ABCD3	ABCD3	ABCD3	3681	0.05	0.53	NO
33	SCP2	SCP2	SCP2	3746	0.049	0.53	NO
34	PIPOX	PIPOX	PIPOX	3853	0.047	0.53	NO
35	NUDT19	NUDT19	NUDT19	3924	0.046	0.54	NO
36	MVK	MVK	MVK	3985	0.045	0.54	NO
37	PAOX	PAOX	PAOX	4100	0.043	0.54	NO
38	PRDX5	PRDX5	PRDX5	4140	0.043	0.54	NO
39	PEX5	PEX5	PEX5	4302	0.04	0.54	NO
40	ACOT8	ACOT8	ACOT8	4612	0.035	0.53	NO
41	HAO2	HAO2	HAO2	4725	0.033	0.52	NO
42	GNPAT	GNPAT	GNPAT	4756	0.033	0.53	NO
43	ABCD4	ABCD4	ABCD4	4828	0.032	0.53	NO
44	PEX16	PEX16	PEX16	4858	0.032	0.53	NO
45	PECR	PECR	PECR	5283	0.026	0.51	NO
46	PEX14	PEX14	PEX14	5475	0.023	0.5	NO
47	HACL1	HACL1	HACL1	5559	0.022	0.5	NO
48	ACAA1	ACAA1	ACAA1	5571	0.022	0.5	NO
49	PEX13	PEX13	PEX13	5873	0.019	0.49	NO
50	PHYH	PHYH	PHYH	6577	0.0099	0.46	NO
51	PEX10	PEX10	PEX10	6580	0.0098	0.46	NO
52	AGPS	AGPS	AGPS	6645	0.0091	0.45	NO
53	CAT	CAT	CAT	6921	0.006	0.44	NO
54	PEX26	PEX26	PEX26	7150	0.0035	0.43	NO
55	PRDX1	PRDX1	PRDX1	7681	-0.002	0.4	NO
56	PEX3	PEX3	PEX3	8005	-0.0059	0.38	NO
57	ACOX3	ACOX3	ACOX3	8112	-0.0071	0.38	NO
58	SOD2	SOD2	SOD2	8153	-0.0076	0.38	NO
59	PXMP4	PXMP4	PXMP4	8492	-0.011	0.36	NO
60	MPV17	MPV17	MPV17	8624	-0.013	0.36	NO
61	FAR1	FAR1	FAR1	8693	-0.013	0.35	NO
62	SLC25A17	SLC25A17	SLC25A17	9029	-0.017	0.34	NO
63	PEX19	PEX19	PEX19	9305	-0.021	0.32	NO
64	CROT	CROT	CROT	9496	-0.024	0.32	NO
65	BAAT	BAAT	BAAT	10221	-0.034	0.28	NO
66	ACOX1	ACOX1	ACOX1	10562	-0.04	0.27	NO
67	PMVK	PMVK	PMVK	11225	-0.051	0.24	NO
68	ACSL3	ACSL3	ACSL3	11706	-0.06	0.22	NO
69	PEX12	PEX12	PEX12	12090	-0.069	0.21	NO
70	ACSL4	ACSL4	ACSL4	12481	-0.078	0.2	NO
71	DAO	DAO	DAO	13475	-0.11	0.16	NO
72	MPV17L	MPV17L	MPV17L	13608	-0.11	0.17	NO
73	ECH1	ECH1	ECH1	14238	-0.13	0.15	NO
74	ACSL1	ACSL1	ACSL1	14331	-0.14	0.17	NO
75	DDO	DDO	DDO	16674	-0.24	0.074	NO
76	ABCD2	ABCD2	ABCD2	16885	-0.26	0.096	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 PYRUVATE METABOLISM.

Figure S88. 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 BUTANOATE 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	PCK1	PCK1	PCK1	70	0.52	0.2	YES
2	PCK2	PCK2	PCK2	657	0.21	0.25	YES
3	IDH2	IDH2	IDH2	1017	0.15	0.29	YES
4	SUCLG1	SUCLG1	SUCLG1	1161	0.14	0.34	YES
5	IDH3A	IDH3A	IDH3A	1313	0.13	0.38	YES
6	DLD	DLD	DLD	1740	0.1	0.4	YES
7	PDHA1	PDHA1	PDHA1	2106	0.088	0.41	YES
8	SUCLG2	SUCLG2	SUCLG2	2116	0.088	0.45	YES
9	SDHB	SDHB	SDHB	2266	0.082	0.47	YES
10	IDH3G	IDH3G	IDH3G	2278	0.082	0.5	YES
11	IDH3B	IDH3B	IDH3B	2287	0.082	0.54	YES
12	SUCLA2	SUCLA2	SUCLA2	2629	0.072	0.55	YES
13	SDHD	SDHD	SDHD	2952	0.065	0.55	YES
14	CS	CS	CS	2985	0.064	0.58	YES
15	MDH2	MDH2	MDH2	3041	0.063	0.6	YES
16	DLAT	DLAT	DLAT	3264	0.058	0.61	YES
17	DLST	DLST	DLST	3472	0.054	0.62	YES
18	FH	FH	FH	3586	0.052	0.63	YES
19	IDH1	IDH1	IDH1	3636	0.051	0.65	YES
20	SDHA	SDHA	SDHA	3951	0.046	0.65	YES
21	ACO2	ACO2	ACO2	4472	0.037	0.64	NO
22	OGDH	OGDH	OGDH	4727	0.033	0.64	NO
23	MDH1	MDH1	MDH1	4954	0.03	0.64	NO
24	ACO1	ACO1	ACO1	5220	0.027	0.63	NO
25	SDHC	SDHC	SDHC	5645	0.021	0.62	NO
26	ACLY	ACLY	ACLY	6083	0.016	0.6	NO
27	PDHB	PDHB	PDHB	6828	0.007	0.57	NO
28	PC	PC	PC	11469	-0.055	0.34	NO
29	OGDHL	OGDHL	OGDHL	13950	-0.12	0.25	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 BUTANOATE METABOLISM.

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

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	HMGCS2	HMGCS2	HMGCS2	588	0.23	0.042	YES
2	ACAA2	ACAA2	ACAA2	752	0.19	0.094	YES
3	ACADS	ACADS	ACADS	831	0.18	0.15	YES
4	HADH	HADH	HADH	1277	0.13	0.17	YES
5	BCKDHB	BCKDHB	BCKDHB	1337	0.13	0.2	YES
6	AUH	AUH	AUH	1579	0.11	0.23	YES
7	DLD	DLD	DLD	1740	0.1	0.25	YES
8	HIBCH	HIBCH	HIBCH	2032	0.091	0.27	YES
9	HADHA	HADHA	HADHA	2142	0.087	0.29	YES
10	ACAT2	ACAT2	ACAT2	2419	0.078	0.3	YES
11	HADHB	HADHB	HADHB	2449	0.077	0.32	YES
12	PCCA	PCCA	PCCA	2450	0.077	0.35	YES
13	HMGCL	HMGCL	HMGCL	2534	0.075	0.37	YES
14	ECHS1	ECHS1	ECHS1	2572	0.074	0.39	YES
15	HIBADH	HIBADH	HIBADH	2611	0.073	0.41	YES
16	MCCC1	MCCC1	MCCC1	2839	0.067	0.42	YES
17	MCCC2	MCCC2	MCCC2	3072	0.062	0.43	YES
18	ALDH2	ALDH2	ALDH2	3192	0.06	0.44	YES
19	ALDH1B1	ALDH1B1	ALDH1B1	3221	0.059	0.46	YES
20	MCEE	MCEE	MCEE	3278	0.058	0.47	YES
21	ABAT	ABAT	ABAT	3346	0.057	0.49	YES
22	EHHADH	EHHADH	EHHADH	3354	0.056	0.51	YES
23	MUT	MUT	MUT	3832	0.048	0.5	YES
24	PCCB	PCCB	PCCB	3941	0.046	0.5	YES
25	ACADSB	ACADSB	ACADSB	4114	0.043	0.51	YES
26	ALDH9A1	ALDH9A1	ALDH9A1	4430	0.038	0.51	NO
27	HSD17B10	HSD17B10	HSD17B10	5260	0.026	0.47	NO
28	ACAA1	ACAA1	ACAA1	5571	0.022	0.46	NO
29	ACADM	ACADM	ACADM	5947	0.018	0.45	NO
30	HMGCS1	HMGCS1	HMGCS1	7228	0.0028	0.38	NO
31	IVD	IVD	IVD	7386	0.0011	0.37	NO
32	ACAT1	ACAT1	ACAT1	7411	0.00079	0.37	NO
33	ALDH3A2	ALDH3A2	ALDH3A2	8485	-0.011	0.32	NO
34	BCAT2	BCAT2	BCAT2	8664	-0.013	0.31	NO
35	ALDH6A1	ALDH6A1	ALDH6A1	9036	-0.018	0.3	NO
36	ACAD8	ACAD8	ACAD8	9258	-0.021	0.29	NO
37	OXCT2	OXCT2	OXCT2	9453	-0.023	0.29	NO
38	ALDH7A1	ALDH7A1	ALDH7A1	10008	-0.03	0.27	NO
39	BCKDHA	BCKDHA	BCKDHA	10306	-0.035	0.26	NO
40	IL4I1	IL4I1	IL4I1	10754	-0.043	0.25	NO
41	DBT	DBT	DBT	11802	-0.062	0.22	NO
42	OXCT1	OXCT1	OXCT1	13776	-0.12	0.15	NO
43	BCAT1	BCAT1	BCAT1	15088	-0.17	0.13	NO
44	AOX1	AOX1	AOX1	15582	-0.19	0.17	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 AMINOACYL TRNA BIOSYNTHESIS.

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

genes ES table in pathway: KEGG PEROXISOME

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	PCK1	PCK1	PCK1	70	0.52	0.14	YES
2	PKLR	PKLR	PKLR	278	0.33	0.22	YES
3	ACSS2	ACSS2	ACSS2	424	0.28	0.29	YES
4	PCK2	PCK2	PCK2	657	0.21	0.34	YES
5	ME1	ME1	ME1	1062	0.15	0.36	YES
6	ACSS1	ACSS1	ACSS1	1555	0.11	0.37	YES
7	LDHC	LDHC	LDHC	1652	0.11	0.39	YES
8	DLD	DLD	DLD	1740	0.1	0.42	YES
9	ME2	ME2	ME2	1766	0.1	0.44	YES
10	ACYP1	ACYP1	ACYP1	1862	0.098	0.46	YES
11	PDHA1	PDHA1	PDHA1	2106	0.088	0.48	YES
12	ACAT2	ACAT2	ACAT2	2419	0.078	0.48	YES
13	LDHD	LDHD	LDHD	2969	0.064	0.47	YES
14	MDH2	MDH2	MDH2	3041	0.063	0.48	YES
15	ALDH2	ALDH2	ALDH2	3192	0.06	0.49	YES
16	ALDH1B1	ALDH1B1	ALDH1B1	3221	0.059	0.51	YES
17	DLAT	DLAT	DLAT	3264	0.058	0.52	YES
18	HAGHL	HAGHL	HAGHL	3444	0.055	0.53	YES
19	LDHA	LDHA	LDHA	3928	0.046	0.52	NO
20	ALDH9A1	ALDH9A1	ALDH9A1	4430	0.038	0.5	NO
21	MDH1	MDH1	MDH1	4954	0.03	0.48	NO
22	GLO1	GLO1	GLO1	5799	0.02	0.44	NO
23	GRHPR	GRHPR	GRHPR	6460	0.011	0.41	NO
24	PDHB	PDHB	PDHB	6828	0.007	0.39	NO
25	ACACA	ACACA	ACACA	7254	0.0026	0.37	NO
26	ACAT1	ACAT1	ACAT1	7411	0.00079	0.36	NO
27	PKM2	PKM2	PKM2	8291	-0.0089	0.31	NO
28	ALDH3A2	ALDH3A2	ALDH3A2	8485	-0.011	0.31	NO
29	LDHAL6B	LDHAL6B	LDHAL6B	9713	-0.026	0.25	NO
30	HAGH	HAGH	HAGH	9927	-0.029	0.24	NO
31	ALDH7A1	ALDH7A1	ALDH7A1	10008	-0.03	0.25	NO
32	ME3	ME3	ME3	10029	-0.031	0.26	NO
33	ACYP2	ACYP2	ACYP2	11117	-0.049	0.21	NO
34	PC	PC	PC	11469	-0.055	0.21	NO
35	LDHAL6A	LDHAL6A	LDHAL6A	12311	-0.074	0.18	NO
36	ACACB	ACACB	ACACB	12694	-0.083	0.19	NO
37	AKR1B1	AKR1B1	AKR1B1	16486	-0.23	0.049	NO
38	LDHB	LDHB	LDHB	16696	-0.24	0.11	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 PEROXISOME.

Figure S94. 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: BIOCARTA DEATH PATHWAY

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	A1CF	A1CF	A1CF	18	0.71	0.14	YES
2	APOBEC1	APOBEC1	APOBEC1	71	0.52	0.24	YES
3	GTF2F2	GTF2F2	GTF2F2	1985	0.093	0.16	YES
4	SEH1L	SEH1L	SEH1L	2258	0.083	0.16	YES
5	NCBP1	NCBP1	NCBP1	2414	0.078	0.16	YES
6	NUP37	NUP37	NUP37	2420	0.078	0.18	YES
7	NUPL1	NUPL1	NUPL1	2503	0.076	0.19	YES
8	METTL3	METTL3	METTL3	2585	0.073	0.2	YES
9	UPF3B	UPF3B	UPF3B	2622	0.072	0.21	YES
10	CPSF1	CPSF1	CPSF1	2838	0.067	0.22	YES
11	CSTF2	CSTF2	CSTF2	2936	0.065	0.22	YES
12	NUP88	NUP88	NUP88	2996	0.064	0.23	YES
13	CPSF3	CPSF3	CPSF3	3115	0.061	0.24	YES
14	NUP35	NUP35	NUP35	3123	0.061	0.25	YES
15	GTF2H2	GTF2H2	GTF2H2	3265	0.058	0.25	YES
16	SF3B14	SF3B14	SF3B14	3433	0.055	0.26	YES
17	SNRPA1	SNRPA1	SNRPA1	3574	0.052	0.26	YES
18	SNRPE	SNRPE	SNRPE	3710	0.05	0.26	YES
19	NUP54	NUP54	NUP54	3718	0.05	0.27	YES
20	CDK7	CDK7	CDK7	3806	0.048	0.28	YES
21	LSM2	LSM2	LSM2	3884	0.047	0.28	YES
22	PRPF4	PRPF4	PRPF4	3975	0.045	0.28	YES
23	CLP1	CLP1	CLP1	4064	0.044	0.29	YES
24	RBMX	RBMX	RBMX	4119	0.043	0.3	YES
25	GTF2H2B	GTF2H2B	GTF2H2B	4146	0.042	0.3	YES
26	SNRPF	SNRPF	SNRPF	4151	0.042	0.31	YES
27	EIF4E	EIF4E	EIF4E	4162	0.042	0.32	YES
28	RAE1	RAE1	RAE1	4179	0.042	0.32	YES
29	HNRNPF	HNRNPF	HNRNPF	4356	0.039	0.32	YES
30	NUP205	NUP205	NUP205	4365	0.039	0.33	YES
31	HNRNPA1	HNRNPA1	HNRNPA1	4370	0.039	0.34	YES
32	GTF2H3	GTF2H3	GTF2H3	4441	0.038	0.34	YES
33	SNRPB	SNRPB	SNRPB	4556	0.036	0.34	YES
34	NFX1	NFX1	NFX1	4566	0.036	0.35	YES
35	POLR2H	POLR2H	POLR2H	4567	0.036	0.36	YES
36	SNRPA	SNRPA	SNRPA	4580	0.036	0.36	YES
37	MAGOH	MAGOH	MAGOH	4795	0.032	0.36	YES
38	PAPOLA	PAPOLA	PAPOLA	4808	0.032	0.36	YES
39	SNRPB2	SNRPB2	SNRPB2	4824	0.032	0.37	YES
40	SNRPD3	SNRPD3	SNRPD3	4852	0.032	0.37	YES
41	SF3B3	SF3B3	SF3B3	4856	0.032	0.38	YES
42	NUPL2	NUPL2	NUPL2	4877	0.031	0.39	YES
43	SF3A2	SF3A2	SF3A2	5044	0.029	0.38	YES
44	POM121	POM121	POM121	5207	0.027	0.38	YES
45	PHF5A	PHF5A	PHF5A	5226	0.027	0.38	YES
46	CCAR1	CCAR1	CCAR1	5291	0.026	0.38	YES
47	EFTUD2	EFTUD2	EFTUD2	5328	0.026	0.39	YES
48	HNRNPC	HNRNPC	HNRNPC	5340	0.025	0.39	YES
49	RNMT	RNMT	RNMT	5409	0.024	0.39	YES
50	SNRPD2	SNRPD2	SNRPD2	5467	0.024	0.4	YES
51	NUDT21	NUDT21	NUDT21	5504	0.023	0.4	YES
52	CSTF3	CSTF3	CSTF3	5681	0.021	0.39	YES
53	DHX9	DHX9	DHX9	5696	0.021	0.4	YES
54	NHP2L1	NHP2L1	NHP2L1	5730	0.02	0.4	YES
55	SMC1A	SMC1A	SMC1A	5755	0.02	0.4	YES
56	RNPS1	RNPS1	RNPS1	5819	0.019	0.4	YES
57	U2AF1	U2AF1	U2AF1	5821	0.019	0.4	YES
58	NUP85	NUP85	NUP85	5853	0.019	0.41	YES
59	HNRNPR	HNRNPR	HNRNPR	5974	0.018	0.4	YES
60	HNRNPL	HNRNPL	HNRNPL	5976	0.018	0.41	YES
61	CDC40	CDC40	CDC40	5989	0.018	0.41	YES
62	NUP43	NUP43	NUP43	6065	0.017	0.41	YES
63	POLR2K	POLR2K	POLR2K	6075	0.016	0.41	YES
64	SF3A3	SF3A3	SF3A3	6103	0.016	0.42	YES
65	GTF2H1	GTF2H1	GTF2H1	6122	0.016	0.42	YES
66	NUP107	NUP107	NUP107	6136	0.016	0.42	YES
67	POLR2B	POLR2B	POLR2B	6140	0.016	0.42	YES
68	NUP214	NUP214	NUP214	6221	0.014	0.42	YES
69	NUP133	NUP133	NUP133	6248	0.014	0.42	YES
70	HNRNPA3	HNRNPA3	HNRNPA3	6255	0.014	0.42	YES
71	SLBP	SLBP	SLBP	6273	0.014	0.43	YES
72	SNRNP40	SNRNP40	SNRNP40	6292	0.013	0.43	YES
73	SF3B5	SF3B5	SF3B5	6302	0.013	0.43	YES
74	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	6333	0.013	0.43	YES
75	PTBP1	PTBP1	PTBP1	6355	0.013	0.43	YES
76	RNGTT	RNGTT	RNGTT	6385	0.012	0.43	YES
77	CPSF2	CPSF2	CPSF2	6407	0.012	0.44	YES
78	DHX38	DHX38	DHX38	6411	0.012	0.44	YES
79	HNRNPH1	HNRNPH1	HNRNPH1	6415	0.012	0.44	YES
80	HNRNPH2	HNRNPH2	HNRNPH2	6499	0.011	0.44	NO
81	NUP93	NUP93	NUP93	6504	0.011	0.44	NO
82	HNRNPK	HNRNPK	HNRNPK	6565	0.01	0.44	NO
83	CSTF1	CSTF1	CSTF1	6589	0.0097	0.44	NO
84	DNAJC8	DNAJC8	DNAJC8	6626	0.0094	0.44	NO
85	SNRPD1	SNRPD1	SNRPD1	6691	0.0086	0.44	NO
86	SF3B2	SF3B2	SF3B2	6710	0.0084	0.44	NO
87	HNRNPM	HNRNPM	HNRNPM	6780	0.0077	0.44	NO
88	PRPF6	PRPF6	PRPF6	6804	0.0074	0.44	NO
89	THOC4	THOC4	THOC4	6825	0.0071	0.44	NO
90	POLR2C	POLR2C	POLR2C	6842	0.0069	0.44	NO
91	SF3A1	SF3A1	SF3A1	6864	0.0067	0.44	NO
92	PCBP1	PCBP1	PCBP1	6896	0.0063	0.44	NO
93	POLR2D	POLR2D	POLR2D	6917	0.0061	0.44	NO
94	NXF1	NXF1	NXF1	6928	0.006	0.44	NO
95	CCNH	CCNH	CCNH	6977	0.0054	0.44	NO
96	YBX1	YBX1	YBX1	7072	0.0042	0.43	NO
97	SNRNP70	SNRNP70	SNRNP70	7088	0.0041	0.43	NO
98	SNRPG	SNRPG	SNRPG	7155	0.0035	0.43	NO
99	PCF11	PCF11	PCF11	7165	0.0034	0.43	NO
100	RANBP2	RANBP2	RANBP2	7200	0.0031	0.43	NO
101	SF3B1	SF3B1	SF3B1	7216	0.0029	0.43	NO
102	NUP188	NUP188	NUP188	7246	0.0027	0.43	NO
103	PABPN1	PABPN1	PABPN1	7270	0.0024	0.42	NO
104	POLR2E	POLR2E	POLR2E	7373	0.0012	0.42	NO
105	RBM5	RBM5	RBM5	7423	0.00067	0.42	NO
106	TXNL4A	TXNL4A	TXNL4A	7467	0.0002	0.42	NO
107	POLR2J	POLR2J	POLR2J	7470	0.00015	0.42	NO
108	GTF2F1	GTF2F1	GTF2F1	7555	-0.0008	0.41	NO
109	POLR2L	POLR2L	POLR2L	7607	-0.0012	0.41	NO
110	HNRNPD	HNRNPD	HNRNPD	7685	-0.0021	0.4	NO
111	NUP50	NUP50	NUP50	7759	-0.003	0.4	NO
112	SF3B4	SF3B4	SF3B4	7783	-0.0032	0.4	NO
113	ZNF473	ZNF473	ZNF473	7829	-0.0038	0.4	NO
114	TPR	TPR	TPR	7848	-0.004	0.4	NO
115	POLR2G	POLR2G	POLR2G	7897	-0.0046	0.4	NO
116	ERCC2	ERCC2	ERCC2	7925	-0.005	0.4	NO
117	HNRNPU	HNRNPU	HNRNPU	7974	-0.0055	0.4	NO
118	HNRNPUL1	HNRNPUL1	HNRNPUL1	8014	-0.006	0.39	NO
119	POLR2F	POLR2F	POLR2F	8036	-0.0062	0.39	NO
120	AAAS	AAAS	AAAS	8085	-0.0068	0.39	NO
121	CPSF7	CPSF7	CPSF7	8095	-0.0069	0.39	NO
122	DDX23	DDX23	DDX23	8138	-0.0074	0.39	NO
123	PRPF8	PRPF8	PRPF8	8252	-0.0085	0.39	NO
124	NUP62	NUP62	NUP62	8288	-0.0089	0.39	NO
125	NUP155	NUP155	NUP155	8312	-0.0092	0.39	NO
126	SNRNP200	SNRNP200	SNRNP200	8462	-0.011	0.38	NO
127	PCBP2	PCBP2	PCBP2	8498	-0.011	0.38	NO
128	ADAR	ADAR	ADAR	8618	-0.012	0.38	NO
129	HNRNPA0	HNRNPA0	HNRNPA0	8667	-0.013	0.38	NO
130	U2AF2	U2AF2	U2AF2	8904	-0.016	0.37	NO
131	LSM11	LSM11	LSM11	8960	-0.017	0.37	NO
132	POLR2I	POLR2I	POLR2I	8980	-0.017	0.37	NO
133	NUP153	NUP153	NUP153	9101	-0.018	0.37	NO
134	RBM8A	RBM8A	RBM8A	9140	-0.019	0.37	NO
135	GTF2H4	GTF2H4	GTF2H4	9301	-0.021	0.37	NO
136	ERCC3	ERCC3	ERCC3	9340	-0.022	0.37	NO
137	SUPT5H	SUPT5H	SUPT5H	9462	-0.023	0.37	NO
138	SRRM1	SRRM1	SRRM1	9546	-0.024	0.37	NO
139	CD2BP2	CD2BP2	CD2BP2	9741	-0.027	0.36	NO
140	FUS	FUS	FUS	10113	-0.032	0.35	NO
141	NCBP2	NCBP2	NCBP2	10173	-0.033	0.35	NO
142	POLR2A	POLR2A	POLR2A	10275	-0.035	0.35	NO
143	LSM10	LSM10	LSM10	12310	-0.074	0.26	NO
144	MNAT1	MNAT1	MNAT1	12647	-0.082	0.26	NO
145	ADARB1	ADARB1	ADARB1	14693	-0.15	0.18	NO
146	NUP210	NUP210	NUP210	15762	-0.2	0.16	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: BIOCARTA DEATH PATHWAY.

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

genes ES table in pathway: REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX

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	CYC1	CYC1	CYC1	1375	0.12	-0.024	YES
2	ATP5G1	ATP5G1	ATP5G1	1935	0.095	-0.017	YES
3	COQ2	COQ2	COQ2	2133	0.087	0.0074	YES
4	CHCHD4	CHCHD4	CHCHD4	2217	0.084	0.036	YES
5	IDH3G	IDH3G	IDH3G	2278	0.082	0.066	YES
6	GRPEL1	GRPEL1	GRPEL1	2359	0.08	0.094	YES
7	PMPCA	PMPCA	PMPCA	2500	0.076	0.12	YES
8	C18orf55	C18orf55	C18orf55	2561	0.074	0.14	YES
9	VDAC1	VDAC1	VDAC1	2699	0.071	0.16	YES
10	PMPCB	PMPCB	PMPCB	2729	0.07	0.19	YES
11	TIMM8A	TIMM8A	TIMM8A	2835	0.067	0.21	YES
12	HSPD1	HSPD1	HSPD1	2903	0.066	0.23	YES
13	LDHD	LDHD	LDHD	2969	0.064	0.26	YES
14	ATP5B	ATP5B	ATP5B	2976	0.064	0.28	YES
15	CS	CS	CS	2985	0.064	0.31	YES
16	FXN	FXN	FXN	3005	0.064	0.33	YES
17	TOMM40	TOMM40	TOMM40	3065	0.062	0.35	YES
18	BCS1L	BCS1L	BCS1L	3140	0.061	0.37	YES
19	TOMM22	TOMM22	TOMM22	3199	0.06	0.39	YES
20	ATP5A1	ATP5A1	ATP5A1	3280	0.058	0.41	YES
21	TAZ	TAZ	TAZ	3310	0.058	0.43	YES
22	TIMM9	TIMM9	TIMM9	3635	0.051	0.44	YES
23	TIMM13	TIMM13	TIMM13	3989	0.045	0.44	YES
24	TIMM44	TIMM44	TIMM44	4143	0.042	0.44	YES
25	SLC25A13	SLC25A13	SLC25A13	4170	0.042	0.46	YES
26	GFER	GFER	GFER	4182	0.042	0.48	YES
27	GRPEL2	GRPEL2	GRPEL2	4245	0.041	0.49	YES
28	SLC25A6	SLC25A6	SLC25A6	4260	0.041	0.5	YES
29	TIMM10	TIMM10	TIMM10	4321	0.04	0.52	YES
30	ACO2	ACO2	ACO2	4472	0.037	0.52	YES
31	MTX2	MTX2	MTX2	4502	0.037	0.54	YES
32	TOMM5	TOMM5	TOMM5	4628	0.035	0.54	YES
33	HSPA9	HSPA9	HSPA9	4720	0.033	0.55	YES
34	TOMM20	TOMM20	TOMM20	4838	0.032	0.56	YES
35	TOMM70A	TOMM70A	TOMM70A	4991	0.03	0.56	YES
36	TIMM17A	TIMM17A	TIMM17A	5614	0.022	0.54	NO
37	SLC25A4	SLC25A4	SLC25A4	6150	0.016	0.52	NO
38	TIMM50	TIMM50	TIMM50	6176	0.015	0.52	NO
39	FXC1	FXC1	FXC1	6604	0.0096	0.5	NO
40	HSCB	HSCB	HSCB	6634	0.0092	0.5	NO
41	TIMM8B	TIMM8B	TIMM8B	6826	0.0071	0.5	NO
42	SAMM50	SAMM50	SAMM50	6868	0.0066	0.5	NO
43	TIMM17B	TIMM17B	TIMM17B	7720	-0.0025	0.45	NO
44	TOMM7	TOMM7	TOMM7	7877	-0.0044	0.44	NO
45	TIMM22	TIMM22	TIMM22	10044	-0.031	0.34	NO
46	DNAJC19	DNAJC19	DNAJC19	10245	-0.034	0.34	NO
47	MTX1	MTX1	MTX1	10258	-0.034	0.36	NO
48	COX17	COX17	COX17	12825	-0.087	0.25	NO
49	SLC25A12	SLC25A12	SLC25A12	14765	-0.15	0.21	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: REACTOME FORMATION OF THE TERNARY COMPLEX AND SUBSEQUENTLY THE 43S COMPLEX.

Figure S98. 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 TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT

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	CASP6	CASP6	CASP6	484	0.26	0.096	YES
2	TNFRSF25	TNFRSF25	TNFRSF25	610	0.22	0.19	YES
3	GAS2	GAS2	GAS2	718	0.2	0.28	YES
4	DFFB	DFFB	DFFB	771	0.19	0.37	YES
5	CASP10	CASP10	CASP10	1076	0.15	0.42	YES
6	CYCS	CYCS	CYCS	2507	0.076	0.38	YES
7	CASP3	CASP3	CASP3	2540	0.075	0.42	YES
8	CASP7	CASP7	CASP7	3090	0.062	0.42	YES
9	TNFRSF10A	TNFRSF10A	TNFRSF10A	3406	0.056	0.42	YES
10	CASP8	CASP8	CASP8	3876	0.047	0.42	YES
11	APAF1	APAF1	APAF1	3969	0.045	0.44	YES
12	BID	BID	BID	3981	0.045	0.46	YES
13	TNFSF10	TNFSF10	TNFSF10	4159	0.042	0.47	YES
14	FADD	FADD	FADD	5119	0.028	0.43	NO
15	TRAF2	TRAF2	TRAF2	5381	0.025	0.43	NO
16	XIAP	XIAP	XIAP	5725	0.02	0.42	NO
17	RIPK1	RIPK1	RIPK1	6907	0.0062	0.36	NO
18	TNFRSF10B	TNFRSF10B	TNFRSF10B	7314	0.0019	0.34	NO
19	CHUK	CHUK	CHUK	7713	-0.0024	0.32	NO
20	NFKB1	NFKB1	NFKB1	7981	-0.0056	0.31	NO
21	SPTAN1	SPTAN1	SPTAN1	8171	-0.0078	0.3	NO
22	CASP9	CASP9	CASP9	8443	-0.011	0.29	NO
23	BIRC2	BIRC2	BIRC2	8962	-0.017	0.27	NO
24	RELA	RELA	RELA	9084	-0.018	0.28	NO
25	DFFA	DFFA	DFFA	9649	-0.026	0.26	NO
26	BCL2	BCL2	BCL2	9985	-0.03	0.25	NO
27	MAP3K14	MAP3K14	MAP3K14	10072	-0.031	0.26	NO
28	NFKBIA	NFKBIA	NFKBIA	10159	-0.033	0.28	NO
29	LMNA	LMNA	LMNA	10224	-0.034	0.29	NO
30	BIRC3	BIRC3	BIRC3	10620	-0.041	0.29	NO
31	TRADD	TRADD	TRADD	10914	-0.046	0.29	NO
32	CFLAR	CFLAR	CFLAR	12159	-0.07	0.26	NO
33	TNFSF12	TNFSF12	TNFSF12	15654	-0.19	0.16	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: REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT.

Figure S100. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT, 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 = STAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = STAD-TP.mergedcluster.txt

GSEA analysis

For the Gene Set Enrichment Analysis (GSEA), Broad GSEA-P-R.1.0 version is used with class2: canonical pathways geneses from MSigDB. Further details about statistics are available inThe Broad GSEA website.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References

[1] Subramanian, A. et al, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles., Proc. Natl. Acad. Sci. USA 102(43) (2005)

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