GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in LIHC

Liver Hepatocellular Carcinoma

14 July 2016 | awg_lihc__2016_07_14

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 LIHC. Broad Institute of MIT and Harvard. doi:10.7908/C1BP029X

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 "LIHC.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: 705
Number of samples: 423
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 ] 129
pheno.type: 2 - 5 :[ clus2 ] 91
pheno.type: 3 - 5 :[ clus3 ] 50
pheno.type: 4 - 5 :[ clus4 ] 74
pheno.type: 5 - 5 :[ clus5 ] 79

For the expression subtypes of 17705 genes in 424 samples, GSEA found enriched gene sets in each cluster using 423 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG SPLICEOSOME, REACTOME METABOLISM OF NON CODING RNA, REACTOME CELL CYCLE, REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA, REACTOME CELL CYCLE CHECKPOINTS, REACTOME CYCLIN E ASSOCIATED EVENTS DURING G1 S TRANSITION , REACTOME MRNA PROCESSING, REACTOME M G1 TRANSITION, REACTOME G1 S TRANSITION, REACTOME TRANSPORT OF MATURE MRNA DERIVED FROM AN INTRONLESS TRANSCRIPT

And common core enriched genes are CDC6, CDT1, E2F1, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MCM8

clus2

Top enriched gene sets are KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG CYSTEINE AND METHIONINE METABOLISM, KEGG LYSINE DEGRADATION, KEGG PYRUVATE METABOLISM, KEGG DNA REPLICATION, KEGG BASE EXCISION REPAIR, KEGG NUCLEOTIDE EXCISION REPAIR, KEGG OOCYTE MEIOSIS, PID FANCONI PATHWAY, PID E2F PATHWAY

And common core enriched genes are DDB2, ERCC4, GTF2H3, LIG1, PCNA, POLD2, POLD3, POLE, POLE2, RFC3

clus3

Top enriched gene sets are KEGG PURINE METABOLISM, KEGG O GLYCAN BIOSYNTHESIS, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG GLYCEROLIPID METABOLISM, KEGG INOSITOL PHOSPHATE METABOLISM, KEGG GLYCEROPHOSPHOLIPID METABOLISM, KEGG ETHER LIPID METABOLISM, KEGG ARACHIDONIC ACID METABOLISM, KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES, KEGG MAPK SIGNALING PATHWAY

And common core enriched genes are ADCY2, ADCY3, ADCY4, ADCY5, ADCY7, CAMK4, ITPR3, PDE1A, PDE1B, PRKAR1B

clus4

Top enriched gene sets are KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS, KEGG FATTY ACID METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS, KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RNA POLYMERASE, KEGG ENDOMETRIAL CANCER, REACTOME BILE ACID AND BILE SALT METABOLISM, REACTOME MITOCHONDRIAL PROTEIN IMPORT, REACTOME RNA POL I TRANSCRIPTION

And common core enriched genes are EHMT2, ERCC2, GTF2H4, H3F3A, HIST1H2AC, HIST1H2AD, HIST1H2AE, HIST1H2BC, HIST1H2BD, HIST1H2BE

clus5

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG HISTIDINE METABOLISM, KEGG TRYPTOPHAN METABOLISM, KEGG SELENOAMINO ACID METABOLISM, KEGG PROPANOATE METABOLISM, KEGG COMPLEMENT AND COAGULATION CASCADES, KEGG PRION DISEASES, BIOCARTA VIP PATHWAY, BIOCARTA NFAT PATHWAY, BIOCARTA IL1R PATHWAY

And common core enriched genes are ALDH2, CYP1A1, CYP1A2, MAP2K1, NCAM1, ADH1A, ADH1B, ADH1C, ADH4, ADH6

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 SPLICEOSOME	114	genes.ES.table	0.43	1.7	0.071	0.5	0.84	0.68	0.48	0.36	0.23	0.13
REACTOME METABOLISM OF NON CODING RNA	47	genes.ES.table	0.5	1.7	0.035	0.6	0.68	0.77	0.46	0.42	0.22	0.15
REACTOME CELL CYCLE	374	genes.ES.table	0.57	1.7	0.053	0.52	0.84	0.4	0.23	0.31	0.24	0.14
REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA	126	genes.ES.table	0.44	1.7	0.045	0.57	0.83	0.7	0.48	0.36	0.26	0.16
REACTOME CELL CYCLE CHECKPOINTS	105	genes.ES.table	0.6	1.7	0.016	0.5	0.69	0.26	0.15	0.22	0.2	0.13
REACTOME CYCLIN E ASSOCIATED EVENTS DURING G1 S TRANSITION	62	genes.ES.table	0.46	1.7	0.05	0.54	0.83	0.081	0.044	0.077	0.24	0.15
REACTOME MRNA PROCESSING	145	genes.ES.table	0.42	1.8	0.039	0.73	0.64	0.67	0.47	0.36	0.26	0.19
REACTOME M G1 TRANSITION	72	genes.ES.table	0.66	1.8	0	1	0.49	0.31	0.16	0.26	0	0.42
REACTOME G1 S TRANSITION	100	genes.ES.table	0.63	1.8	0.012	0.91	0.59	0.3	0.15	0.26	0.3	0.23
REACTOME TRANSPORT OF MATURE MRNA DERIVED FROM AN INTRONLESS TRANSCRIPT	33	genes.ES.table	0.52	1.7	0.035	0.45	0.85	0.76	0.46	0.41	0.21	0.11

genes ES table in pathway: KEGG SPLICEOSOME

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	MCM10	MCM10	MCM10	81	0.62	0.062	YES
2	CDC45	CDC45	CDC45	175	0.56	0.12	YES
3	CDT1	CDT1	CDT1	224	0.53	0.17	YES
4	E2F2	E2F2	E2F2	236	0.53	0.23	YES
5	CDC6	CDC6	CDC6	242	0.52	0.28	YES
6	CDC7	CDC7	CDC7	526	0.43	0.32	YES
7	E2F1	E2F1	E2F1	659	0.4	0.35	YES
8	MCM2	MCM2	MCM2	811	0.37	0.38	YES
9	POLE2	POLE2	POLE2	921	0.36	0.41	YES
10	DBF4	DBF4	DBF4	1036	0.34	0.44	YES
11	MCM8	MCM8	MCM8	1321	0.31	0.46	YES
12	GMNN	GMNN	GMNN	1456	0.29	0.48	YES
13	MCM4	MCM4	MCM4	1667	0.28	0.5	YES
14	PRIM2	PRIM2	PRIM2	1689	0.27	0.53	YES
15	MCM6	MCM6	MCM6	1808	0.27	0.55	YES
16	MCM3	MCM3	MCM3	2264	0.23	0.55	YES
17	PRIM1	PRIM1	PRIM1	2297	0.23	0.58	YES
18	POLA1	POLA1	POLA1	2306	0.23	0.6	YES
19	POLA2	POLA2	POLA2	2558	0.21	0.61	YES
20	MCM5	MCM5	MCM5	2585	0.21	0.63	YES
21	MCM7	MCM7	MCM7	2615	0.21	0.65	YES
22	E2F3	E2F3	E2F3	2773	0.2	0.66	YES
23	PSMA8	PSMA8	PSMA8	3956	0.15	0.61	NO
24	RPS27A	RPS27A	RPS27A	4575	0.13	0.59	NO
25	CDK2	CDK2	CDK2	5028	0.12	0.58	NO
26	RPA1	RPA1	RPA1	6256	0.087	0.52	NO
27	UBA52	UBA52	UBA52	7044	0.068	0.48	NO
28	RPA4	RPA4	RPA4	7749	0.055	0.45	NO
29	PSMD14	PSMD14	PSMD14	7750	0.054	0.45	NO
30	PSMC4	PSMC4	PSMC4	7851	0.052	0.45	NO
31	RPA2	RPA2	RPA2	8346	0.043	0.43	NO
32	POLE	POLE	POLE	8387	0.042	0.43	NO
33	PSMB4	PSMB4	PSMB4	8610	0.038	0.42	NO
34	PSMD13	PSMD13	PSMD13	8682	0.036	0.42	NO
35	PSMA4	PSMA4	PSMA4	8683	0.036	0.43	NO
36	PSMD10	PSMD10	PSMD10	8827	0.034	0.42	NO
37	PSMD4	PSMD4	PSMD4	8972	0.031	0.42	NO
38	PSMB3	PSMB3	PSMB3	9055	0.03	0.42	NO
39	PSMB5	PSMB5	PSMB5	9195	0.027	0.41	NO
40	PSMD2	PSMD2	PSMD2	9321	0.025	0.41	NO
41	PSMD8	PSMD8	PSMD8	9329	0.024	0.41	NO
42	PSMA1	PSMA1	PSMA1	9426	0.023	0.41	NO
43	PSMC5	PSMC5	PSMC5	9975	0.012	0.38	NO
44	PSMD1	PSMD1	PSMD1	10124	0.0093	0.37	NO
45	PSMD11	PSMD11	PSMD11	10386	0.0042	0.36	NO
46	PSMD5	PSMD5	PSMD5	10499	0.0017	0.35	NO
47	PSMB1	PSMB1	PSMB1	10589	-0.00021	0.34	NO
48	PSMD9	PSMD9	PSMD9	10714	-0.0026	0.34	NO
49	PSME4	PSME4	PSME4	10752	-0.0032	0.34	NO
50	PSMB6	PSMB6	PSMB6	10793	-0.004	0.33	NO
51	PSMC3	PSMC3	PSMC3	10906	-0.006	0.33	NO
52	PSMD3	PSMD3	PSMD3	10952	-0.007	0.33	NO
53	PSMC1	PSMC1	PSMC1	10960	-0.0071	0.33	NO
54	PSMA6	PSMA6	PSMA6	11090	-0.0097	0.32	NO
55	RPA3	RPA3	RPA3	11137	-0.01	0.32	NO
56	PSMC6	PSMC6	PSMC6	11211	-0.012	0.32	NO
57	PSMB9	PSMB9	PSMB9	11222	-0.012	0.32	NO
58	PSMA7	PSMA7	PSMA7	11250	-0.013	0.32	NO
59	PSMB7	PSMB7	PSMB7	11253	-0.013	0.32	NO
60	PSMB2	PSMB2	PSMB2	11379	-0.016	0.31	NO
61	PSMD6	PSMD6	PSMD6	11439	-0.017	0.31	NO
62	PSMF1	PSMF1	PSMF1	11440	-0.017	0.31	NO
63	PSMA5	PSMA5	PSMA5	11648	-0.022	0.3	NO
64	PSMB10	PSMB10	PSMB10	11789	-0.025	0.3	NO
65	PSME2	PSME2	PSME2	11915	-0.028	0.29	NO
66	PSMA3	PSMA3	PSMA3	12108	-0.032	0.29	NO
67	PSMC2	PSMC2	PSMC2	12214	-0.035	0.28	NO
68	PSMD12	PSMD12	PSMD12	12238	-0.036	0.29	NO
69	PSMD7	PSMD7	PSMD7	12264	-0.036	0.29	NO
70	PSME1	PSME1	PSME1	12450	-0.041	0.28	NO
71	PSMA2	PSMA2	PSMA2	12520	-0.043	0.28	NO
72	PSMB8	PSMB8	PSMB8	13957	-0.087	0.21	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 SPLICEOSOME.

Figure S2. 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: REACTOME METABOLISM OF NON CODING RNA

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	UBE2C	UBE2C	UBE2C	43	0.67	0.1	YES
2	BUB1B	BUB1B	BUB1B	70	0.63	0.2	YES
3	CDC20	CDC20	CDC20	100	0.61	0.29	YES
4	PTTG1	PTTG1	PTTG1	152	0.57	0.38	YES
5	CDK1	CDK1	CDK1	153	0.57	0.46	YES
6	CCNB1	CCNB1	CCNB1	193	0.55	0.55	YES
7	MAD2L1	MAD2L1	MAD2L1	455	0.45	0.6	YES
8	ANAPC7	ANAPC7	ANAPC7	3810	0.16	0.43	NO
9	PSMA8	PSMA8	PSMA8	3956	0.15	0.45	NO
10	ANAPC4	ANAPC4	ANAPC4	4131	0.14	0.46	NO
11	RPS27A	RPS27A	RPS27A	4575	0.13	0.46	NO
12	UBE2D1	UBE2D1	UBE2D1	4675	0.13	0.47	NO
13	ANAPC1	ANAPC1	ANAPC1	5414	0.11	0.44	NO
14	UBE2E1	UBE2E1	UBE2E1	5617	0.1	0.45	NO
15	BUB3	BUB3	BUB3	6170	0.089	0.43	NO
16	UBA52	UBA52	UBA52	7044	0.068	0.39	NO
17	ANAPC5	ANAPC5	ANAPC5	7486	0.06	0.38	NO
18	PSMD14	PSMD14	PSMD14	7750	0.054	0.37	NO
19	CDC16	CDC16	CDC16	7806	0.053	0.38	NO
20	PSMC4	PSMC4	PSMC4	7851	0.052	0.38	NO
21	ANAPC11	ANAPC11	ANAPC11	8072	0.049	0.38	NO
22	CDC27	CDC27	CDC27	8088	0.048	0.38	NO
23	PSMB4	PSMB4	PSMB4	8610	0.038	0.36	NO
24	CDC23	CDC23	CDC23	8632	0.038	0.36	NO
25	PSMD13	PSMD13	PSMD13	8682	0.036	0.37	NO
26	PSMA4	PSMA4	PSMA4	8683	0.036	0.37	NO
27	PSMD10	PSMD10	PSMD10	8827	0.034	0.37	NO
28	PSMD4	PSMD4	PSMD4	8972	0.031	0.37	NO
29	PSMB3	PSMB3	PSMB3	9055	0.03	0.37	NO
30	CDC26	CDC26	CDC26	9123	0.028	0.37	NO
31	PSMB5	PSMB5	PSMB5	9195	0.027	0.37	NO
32	PSMD2	PSMD2	PSMD2	9321	0.025	0.36	NO
33	PSMD8	PSMD8	PSMD8	9329	0.024	0.37	NO
34	PSMA1	PSMA1	PSMA1	9426	0.023	0.36	NO
35	PSMC5	PSMC5	PSMC5	9975	0.012	0.34	NO
36	PSMD1	PSMD1	PSMD1	10124	0.0093	0.33	NO
37	PSMD11	PSMD11	PSMD11	10386	0.0042	0.32	NO
38	PSMD5	PSMD5	PSMD5	10499	0.0017	0.31	NO
39	PSMB1	PSMB1	PSMB1	10589	-0.00021	0.3	NO
40	PSMD9	PSMD9	PSMD9	10714	-0.0026	0.3	NO
41	PSME4	PSME4	PSME4	10752	-0.0032	0.3	NO
42	PSMB6	PSMB6	PSMB6	10793	-0.004	0.29	NO
43	PSMC3	PSMC3	PSMC3	10906	-0.006	0.29	NO
44	PSMD3	PSMD3	PSMD3	10952	-0.007	0.29	NO
45	PSMC1	PSMC1	PSMC1	10960	-0.0071	0.29	NO
46	PSMA6	PSMA6	PSMA6	11090	-0.0097	0.28	NO
47	PSMC6	PSMC6	PSMC6	11211	-0.012	0.28	NO
48	PSMB9	PSMB9	PSMB9	11222	-0.012	0.28	NO
49	PSMA7	PSMA7	PSMA7	11250	-0.013	0.28	NO
50	PSMB7	PSMB7	PSMB7	11253	-0.013	0.28	NO
51	PSMB2	PSMB2	PSMB2	11379	-0.016	0.28	NO
52	PSMD6	PSMD6	PSMD6	11439	-0.017	0.28	NO
53	PSMF1	PSMF1	PSMF1	11440	-0.017	0.28	NO
54	ANAPC2	ANAPC2	ANAPC2	11624	-0.021	0.27	NO
55	PSMA5	PSMA5	PSMA5	11648	-0.022	0.27	NO
56	PSMB10	PSMB10	PSMB10	11789	-0.025	0.27	NO
57	PSME2	PSME2	PSME2	11915	-0.028	0.27	NO
58	PSMA3	PSMA3	PSMA3	12108	-0.032	0.26	NO
59	PSMC2	PSMC2	PSMC2	12214	-0.035	0.26	NO
60	PSMD12	PSMD12	PSMD12	12238	-0.036	0.26	NO
61	PSMD7	PSMD7	PSMD7	12264	-0.036	0.27	NO
62	PSME1	PSME1	PSME1	12450	-0.041	0.26	NO
63	PSMA2	PSMA2	PSMA2	12520	-0.043	0.27	NO
64	ANAPC10	ANAPC10	ANAPC10	13877	-0.084	0.2	NO
65	PSMB8	PSMB8	PSMB8	13957	-0.087	0.21	NO

Figure S3. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: REACTOME METABOLISM OF NON CODING RNA.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME METABOLISM OF NON CODING RNA, 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 CELL CYCLE

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	AURKB	AURKB	AURKB	24	0.7	0.072	YES
2	UBE2C	UBE2C	UBE2C	43	0.67	0.14	YES
3	BUB1B	BUB1B	BUB1B	70	0.63	0.2	YES
4	CDC20	CDC20	CDC20	100	0.61	0.27	YES
5	PLK1	PLK1	PLK1	101	0.61	0.33	YES
6	PTTG1	PTTG1	PTTG1	152	0.57	0.39	YES
7	CDK1	CDK1	CDK1	153	0.57	0.45	YES
8	CCNB1	CCNB1	CCNB1	193	0.55	0.5	YES
9	CCNA2	CCNA2	CCNA2	371	0.47	0.54	YES
10	MAD2L1	MAD2L1	MAD2L1	455	0.45	0.58	YES
11	AURKA	AURKA	AURKA	733	0.38	0.61	YES
12	FBXO5	FBXO5	FBXO5	1545	0.29	0.59	NO
13	SKP2	SKP2	SKP2	2667	0.21	0.55	NO
14	ANAPC7	ANAPC7	ANAPC7	3810	0.16	0.5	NO
15	PSMA8	PSMA8	PSMA8	3956	0.15	0.51	NO
16	ANAPC4	ANAPC4	ANAPC4	4131	0.14	0.51	NO
17	CCNA1	CCNA1	CCNA1	4469	0.13	0.51	NO
18	RPS27A	RPS27A	RPS27A	4575	0.13	0.51	NO
19	UBE2D1	UBE2D1	UBE2D1	4675	0.13	0.52	NO
20	CDK2	CDK2	CDK2	5028	0.12	0.51	NO
21	ANAPC1	ANAPC1	ANAPC1	5414	0.11	0.5	NO
22	UBE2E1	UBE2E1	UBE2E1	5617	0.1	0.5	NO
23	BTRC	BTRC	BTRC	6084	0.091	0.48	NO
24	BUB3	BUB3	BUB3	6170	0.089	0.49	NO
25	UBA52	UBA52	UBA52	7044	0.068	0.45	NO
26	CDC14A	CDC14A	CDC14A	7074	0.068	0.45	NO
27	ANAPC5	ANAPC5	ANAPC5	7486	0.06	0.44	NO
28	PSMD14	PSMD14	PSMD14	7750	0.054	0.43	NO
29	CDC16	CDC16	CDC16	7806	0.053	0.43	NO
30	PSMC4	PSMC4	PSMC4	7851	0.052	0.43	NO
31	ANAPC11	ANAPC11	ANAPC11	8072	0.049	0.42	NO
32	CDC27	CDC27	CDC27	8088	0.048	0.43	NO
33	PSMB4	PSMB4	PSMB4	8610	0.038	0.4	NO
34	CDC23	CDC23	CDC23	8632	0.038	0.41	NO
35	PSMD13	PSMD13	PSMD13	8682	0.036	0.41	NO
36	PSMA4	PSMA4	PSMA4	8683	0.036	0.41	NO
37	PSMD10	PSMD10	PSMD10	8827	0.034	0.41	NO
38	PSMD4	PSMD4	PSMD4	8972	0.031	0.4	NO
39	PSMB3	PSMB3	PSMB3	9055	0.03	0.4	NO
40	CDC26	CDC26	CDC26	9123	0.028	0.4	NO
41	PSMB5	PSMB5	PSMB5	9195	0.027	0.4	NO
42	PSMD2	PSMD2	PSMD2	9321	0.025	0.39	NO
43	PSMD8	PSMD8	PSMD8	9329	0.024	0.4	NO
44	PSMA1	PSMA1	PSMA1	9426	0.023	0.39	NO
45	PSMC5	PSMC5	PSMC5	9975	0.012	0.36	NO
46	PSMD1	PSMD1	PSMD1	10124	0.0093	0.36	NO
47	PSMD11	PSMD11	PSMD11	10386	0.0042	0.34	NO
48	SKP1	SKP1	SKP1	10481	0.0021	0.34	NO
49	PSMD5	PSMD5	PSMD5	10499	0.0017	0.33	NO
50	PSMB1	PSMB1	PSMB1	10589	-0.00021	0.33	NO
51	PSMD9	PSMD9	PSMD9	10714	-0.0026	0.32	NO
52	PSME4	PSME4	PSME4	10752	-0.0032	0.32	NO
53	PSMB6	PSMB6	PSMB6	10793	-0.004	0.32	NO
54	PSMC3	PSMC3	PSMC3	10906	-0.006	0.31	NO
55	PSMD3	PSMD3	PSMD3	10952	-0.007	0.31	NO
56	PSMC1	PSMC1	PSMC1	10960	-0.0071	0.31	NO
57	PSMA6	PSMA6	PSMA6	11090	-0.0097	0.3	NO
58	PSMC6	PSMC6	PSMC6	11211	-0.012	0.3	NO
59	PSMB9	PSMB9	PSMB9	11222	-0.012	0.3	NO
60	PSMA7	PSMA7	PSMA7	11250	-0.013	0.3	NO
61	PSMB7	PSMB7	PSMB7	11253	-0.013	0.3	NO
62	PSMB2	PSMB2	PSMB2	11379	-0.016	0.3	NO
63	PSMD6	PSMD6	PSMD6	11439	-0.017	0.3	NO
64	PSMF1	PSMF1	PSMF1	11440	-0.017	0.3	NO
65	ANAPC2	ANAPC2	ANAPC2	11624	-0.021	0.29	NO
66	PSMA5	PSMA5	PSMA5	11648	-0.022	0.29	NO
67	PSMB10	PSMB10	PSMB10	11789	-0.025	0.28	NO
68	PSME2	PSME2	PSME2	11915	-0.028	0.28	NO
69	PSMA3	PSMA3	PSMA3	12108	-0.032	0.27	NO
70	PSMC2	PSMC2	PSMC2	12214	-0.035	0.27	NO
71	PSMD12	PSMD12	PSMD12	12238	-0.036	0.27	NO
72	PSMD7	PSMD7	PSMD7	12264	-0.036	0.28	NO
73	PSME1	PSME1	PSME1	12450	-0.041	0.27	NO
74	PSMA2	PSMA2	PSMA2	12520	-0.043	0.27	NO
75	CUL1	CUL1	CUL1	13147	-0.06	0.24	NO
76	ANAPC10	ANAPC10	ANAPC10	13877	-0.084	0.21	NO
77	PSMB8	PSMB8	PSMB8	13957	-0.087	0.21	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: REACTOME CELL CYCLE.

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

genes ES table in pathway: REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA

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	CDC25A	CDC25A	CDC25A	73	0.63	0.039	YES
2	MCM10	MCM10	MCM10	81	0.62	0.08	YES
3	CDK1	CDK1	CDK1	153	0.57	0.12	YES
4	CDC45	CDC45	CDC45	175	0.56	0.15	YES
5	CCNB1	CCNB1	CCNB1	193	0.55	0.19	YES
6	CCNE1	CCNE1	CCNE1	201	0.55	0.22	YES
7	CDT1	CDT1	CDT1	224	0.53	0.26	YES
8	CDC6	CDC6	CDC6	242	0.52	0.29	YES
9	CCNA2	CCNA2	CCNA2	371	0.47	0.32	YES
10	PKMYT1	PKMYT1	PKMYT1	441	0.45	0.34	YES
11	RRM2	RRM2	RRM2	485	0.44	0.37	YES
12	CDC7	CDC7	CDC7	526	0.43	0.4	YES
13	E2F1	E2F1	E2F1	659	0.4	0.42	YES
14	CCNE2	CCNE2	CCNE2	770	0.38	0.44	YES
15	MCM2	MCM2	MCM2	811	0.37	0.46	YES
16	POLE2	POLE2	POLE2	921	0.36	0.48	YES
17	DBF4	DBF4	DBF4	1036	0.34	0.5	YES
18	TYMS	TYMS	TYMS	1053	0.34	0.52	YES
19	MCM8	MCM8	MCM8	1321	0.31	0.52	YES
20	FBXO5	FBXO5	FBXO5	1545	0.29	0.53	YES
21	MCM4	MCM4	MCM4	1667	0.28	0.54	YES
22	PRIM2	PRIM2	PRIM2	1689	0.27	0.56	YES
23	MCM6	MCM6	MCM6	1808	0.27	0.57	YES
24	MCM3	MCM3	MCM3	2264	0.23	0.56	YES
25	PRIM1	PRIM1	PRIM1	2297	0.23	0.57	YES
26	POLA1	POLA1	POLA1	2306	0.23	0.59	YES
27	POLA2	POLA2	POLA2	2558	0.21	0.59	YES
28	MCM5	MCM5	MCM5	2585	0.21	0.6	YES
29	MCM7	MCM7	MCM7	2615	0.21	0.61	YES
30	SKP2	SKP2	SKP2	2667	0.21	0.62	YES
31	PPP2R3B	PPP2R3B	PPP2R3B	3573	0.17	0.58	NO
32	CKS1B	CKS1B	CKS1B	3775	0.16	0.58	NO
33	CDK7	CDK7	CDK7	4043	0.15	0.58	NO
34	CCNA1	CCNA1	CCNA1	4469	0.13	0.56	NO
35	RPS27A	RPS27A	RPS27A	4575	0.13	0.57	NO
36	CDK2	CDK2	CDK2	5028	0.12	0.55	NO
37	PPP2R1A	PPP2R1A	PPP2R1A	5097	0.11	0.55	NO
38	PCNA	PCNA	PCNA	5407	0.11	0.54	NO
39	TFDP1	TFDP1	TFDP1	5722	0.099	0.53	NO
40	RPA1	RPA1	RPA1	6256	0.087	0.51	NO
41	UBA52	UBA52	UBA52	7044	0.068	0.47	NO
42	RPA4	RPA4	RPA4	7749	0.055	0.43	NO
43	PSMD14	PSMD14	PSMD14	7750	0.054	0.43	NO
44	PSMC4	PSMC4	PSMC4	7851	0.052	0.43	NO
45	RPA2	RPA2	RPA2	8346	0.043	0.41	NO
46	POLE	POLE	POLE	8387	0.042	0.41	NO
47	PSMB4	PSMB4	PSMB4	8610	0.038	0.4	NO
48	PSMD13	PSMD13	PSMD13	8682	0.036	0.4	NO
49	PSMA4	PSMA4	PSMA4	8683	0.036	0.4	NO
50	PSMD10	PSMD10	PSMD10	8827	0.034	0.39	NO
51	PSMD4	PSMD4	PSMD4	8972	0.031	0.39	NO
52	PSMB3	PSMB3	PSMB3	9055	0.03	0.38	NO
53	PSMB5	PSMB5	PSMB5	9195	0.027	0.38	NO
54	PSMD2	PSMD2	PSMD2	9321	0.025	0.37	NO
55	PSMD8	PSMD8	PSMD8	9329	0.024	0.37	NO
56	PSMA1	PSMA1	PSMA1	9426	0.023	0.37	NO
57	MAX	MAX	MAX	9812	0.015	0.35	NO
58	WEE1	WEE1	WEE1	9914	0.013	0.34	NO
59	PSMC5	PSMC5	PSMC5	9975	0.012	0.34	NO
60	PPP2CA	PPP2CA	PPP2CA	10007	0.011	0.34	NO
61	PSMD1	PSMD1	PSMD1	10124	0.0093	0.34	NO
62	MNAT1	MNAT1	MNAT1	10188	0.0082	0.33	NO
63	PSMD11	PSMD11	PSMD11	10386	0.0042	0.32	NO
64	SKP1	SKP1	SKP1	10481	0.0021	0.32	NO
65	PSMD5	PSMD5	PSMD5	10499	0.0017	0.32	NO
66	PSMB1	PSMB1	PSMB1	10589	-0.00021	0.31	NO
67	PSMD9	PSMD9	PSMD9	10714	-0.0026	0.3	NO
68	PSMB6	PSMB6	PSMB6	10793	-0.004	0.3	NO
69	PSMC3	PSMC3	PSMC3	10906	-0.006	0.29	NO
70	PSMD3	PSMD3	PSMD3	10952	-0.007	0.29	NO
71	PSMC1	PSMC1	PSMC1	10960	-0.0071	0.29	NO
72	PSMA6	PSMA6	PSMA6	11090	-0.0097	0.28	NO
73	RPA3	RPA3	RPA3	11137	-0.01	0.28	NO
74	PSMC6	PSMC6	PSMC6	11211	-0.012	0.28	NO
75	PSMB9	PSMB9	PSMB9	11222	-0.012	0.28	NO
76	PSMA7	PSMA7	PSMA7	11250	-0.013	0.28	NO
77	PSMB7	PSMB7	PSMB7	11253	-0.013	0.28	NO
78	PSMB2	PSMB2	PSMB2	11379	-0.016	0.27	NO
79	PSMD6	PSMD6	PSMD6	11439	-0.017	0.27	NO
80	PSMF1	PSMF1	PSMF1	11440	-0.017	0.27	NO
81	PSMA5	PSMA5	PSMA5	11648	-0.022	0.26	NO
82	PSMB10	PSMB10	PSMB10	11789	-0.025	0.26	NO
83	DHFR	DHFR	DHFR	11814	-0.026	0.26	NO
84	MYC	MYC	MYC	11822	-0.026	0.26	NO
85	PSME2	PSME2	PSME2	11915	-0.028	0.25	NO
86	PSMA3	PSMA3	PSMA3	12108	-0.032	0.24	NO
87	PSMC2	PSMC2	PSMC2	12214	-0.035	0.24	NO
88	PSMD12	PSMD12	PSMD12	12238	-0.036	0.24	NO
89	PSMD7	PSMD7	PSMD7	12264	-0.036	0.24	NO
90	RB1	RB1	RB1	12317	-0.038	0.24	NO
91	PSME1	PSME1	PSME1	12450	-0.041	0.24	NO
92	PSMA2	PSMA2	PSMA2	12520	-0.043	0.24	NO
93	CUL1	CUL1	CUL1	13147	-0.06	0.21	NO
94	CDKN1B	CDKN1B	CDKN1B	13369	-0.066	0.2	NO
95	PPP2R1B	PPP2R1B	PPP2R1B	13453	-0.07	0.2	NO
96	PSMB8	PSMB8	PSMB8	13957	-0.087	0.18	NO
97	CCNH	CCNH	CCNH	13999	-0.089	0.18	NO
98	PPP2CB	PPP2CB	PPP2CB	14275	-0.099	0.17	NO
99	CDKN1A	CDKN1A	CDKN1A	15574	-0.17	0.11	NO
100	TK2	TK2	TK2	15823	-0.19	0.11	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: REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA.

Figure S8. 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 CELL CYCLE CHECKPOINTS

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	CDT1	CDT1	CDT1	224	0.53	0.082	YES
2	E2F2	E2F2	E2F2	236	0.53	0.17	YES
3	CDC6	CDC6	CDC6	242	0.52	0.27	YES
4	E2F1	E2F1	E2F1	659	0.4	0.31	YES
5	MCM2	MCM2	MCM2	811	0.37	0.37	YES
6	MCM8	MCM8	MCM8	1321	0.31	0.4	YES
7	GMNN	GMNN	GMNN	1456	0.29	0.44	YES
8	MCM4	MCM4	MCM4	1667	0.28	0.48	YES
9	MCM6	MCM6	MCM6	1808	0.27	0.52	YES
10	MCM3	MCM3	MCM3	2264	0.23	0.53	YES
11	MCM5	MCM5	MCM5	2585	0.21	0.55	YES
12	MCM7	MCM7	MCM7	2615	0.21	0.58	YES
13	E2F3	E2F3	E2F3	2773	0.2	0.61	YES
14	PSMA8	PSMA8	PSMA8	3956	0.15	0.57	NO
15	RPS27A	RPS27A	RPS27A	4575	0.13	0.56	NO
16	UBA52	UBA52	UBA52	7044	0.068	0.43	NO
17	PSMD14	PSMD14	PSMD14	7750	0.054	0.4	NO
18	PSMC4	PSMC4	PSMC4	7851	0.052	0.4	NO
19	PSMB4	PSMB4	PSMB4	8610	0.038	0.37	NO
20	PSMD13	PSMD13	PSMD13	8682	0.036	0.37	NO
21	PSMA4	PSMA4	PSMA4	8683	0.036	0.38	NO
22	PSMD10	PSMD10	PSMD10	8827	0.034	0.38	NO
23	PSMD4	PSMD4	PSMD4	8972	0.031	0.37	NO
24	PSMB3	PSMB3	PSMB3	9055	0.03	0.37	NO
25	PSMB5	PSMB5	PSMB5	9195	0.027	0.37	NO
26	PSMD2	PSMD2	PSMD2	9321	0.025	0.37	NO
27	PSMD8	PSMD8	PSMD8	9329	0.024	0.37	NO
28	PSMA1	PSMA1	PSMA1	9426	0.023	0.37	NO
29	PSMC5	PSMC5	PSMC5	9975	0.012	0.34	NO
30	PSMD1	PSMD1	PSMD1	10124	0.0093	0.33	NO
31	PSMD11	PSMD11	PSMD11	10386	0.0042	0.32	NO
32	PSMD5	PSMD5	PSMD5	10499	0.0017	0.31	NO
33	PSMB1	PSMB1	PSMB1	10589	-0.00021	0.31	NO
34	PSMD9	PSMD9	PSMD9	10714	-0.0026	0.3	NO
35	PSME4	PSME4	PSME4	10752	-0.0032	0.3	NO
36	PSMB6	PSMB6	PSMB6	10793	-0.004	0.3	NO
37	PSMC3	PSMC3	PSMC3	10906	-0.006	0.29	NO
38	PSMD3	PSMD3	PSMD3	10952	-0.007	0.29	NO
39	PSMC1	PSMC1	PSMC1	10960	-0.0071	0.29	NO
40	PSMA6	PSMA6	PSMA6	11090	-0.0097	0.29	NO
41	PSMC6	PSMC6	PSMC6	11211	-0.012	0.28	NO
42	PSMB9	PSMB9	PSMB9	11222	-0.012	0.28	NO
43	PSMA7	PSMA7	PSMA7	11250	-0.013	0.28	NO
44	PSMB7	PSMB7	PSMB7	11253	-0.013	0.29	NO
45	PSMB2	PSMB2	PSMB2	11379	-0.016	0.28	NO
46	PSMD6	PSMD6	PSMD6	11439	-0.017	0.28	NO
47	PSMF1	PSMF1	PSMF1	11440	-0.017	0.29	NO
48	PSMA5	PSMA5	PSMA5	11648	-0.022	0.28	NO
49	PSMB10	PSMB10	PSMB10	11789	-0.025	0.27	NO
50	PSME2	PSME2	PSME2	11915	-0.028	0.27	NO
51	PSMA3	PSMA3	PSMA3	12108	-0.032	0.27	NO
52	PSMC2	PSMC2	PSMC2	12214	-0.035	0.27	NO
53	PSMD12	PSMD12	PSMD12	12238	-0.036	0.27	NO
54	PSMD7	PSMD7	PSMD7	12264	-0.036	0.28	NO
55	PSME1	PSME1	PSME1	12450	-0.041	0.27	NO
56	PSMA2	PSMA2	PSMA2	12520	-0.043	0.28	NO
57	PSMB8	PSMB8	PSMB8	13957	-0.087	0.21	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: REACTOME CELL CYCLE CHECKPOINTS.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME CELL CYCLE CHECKPOINTS, 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 CYCLIN E ASSOCIATED EVENTS DURING G1 S TRANSITION

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	GTF2H2B	GTF2H2B	GTF2H2B	1719	0.27	-0.074	YES
2	SNRPD1	SNRPD1	SNRPD1	2300	0.23	-0.087	YES
3	ZNF473	ZNF473	ZNF473	2645	0.21	-0.089	YES
4	SF3A2	SF3A2	SF3A2	2719	0.2	-0.075	YES
5	SNRPA1	SNRPA1	SNRPA1	2769	0.2	-0.06	YES
6	LSM11	LSM11	LSM11	2964	0.19	-0.054	YES
7	THOC4	THOC4	THOC4	2988	0.19	-0.039	YES
8	NUP210	NUP210	NUP210	3139	0.18	-0.031	YES
9	SNRPB	SNRPB	SNRPB	3161	0.18	-0.016	YES
10	NUP37	NUP37	NUP37	3315	0.18	-0.0097	YES
11	SNRPE	SNRPE	SNRPE	3429	0.17	-0.0012	YES
12	LSM2	LSM2	LSM2	3432	0.17	0.014	YES
13	SNRPF	SNRPF	SNRPF	3496	0.17	0.025	YES
14	SNRPD2	SNRPD2	SNRPD2	3583	0.16	0.034	YES
15	SNRPA	SNRPA	SNRPA	3716	0.16	0.041	YES
16	CDK7	CDK7	CDK7	4043	0.15	0.035	YES
17	NUP43	NUP43	NUP43	4081	0.15	0.046	YES
18	POLR2H	POLR2H	POLR2H	4111	0.14	0.057	YES
19	NUP62	NUP62	NUP62	4207	0.14	0.064	YES
20	UPF3B	UPF3B	UPF3B	4239	0.14	0.074	YES
21	HNRNPA1	HNRNPA1	HNRNPA1	4254	0.14	0.086	YES
22	NUP205	NUP205	NUP205	4310	0.14	0.095	YES
23	NUP93	NUP93	NUP93	4314	0.14	0.11	YES
24	NUP107	NUP107	NUP107	4336	0.14	0.12	YES
25	SF3B4	SF3B4	SF3B4	4387	0.14	0.13	YES
26	NUP188	NUP188	NUP188	4405	0.14	0.14	YES
27	NCBP2	NCBP2	NCBP2	4411	0.14	0.15	YES
28	GTF2H2	GTF2H2	GTF2H2	4566	0.13	0.15	YES
29	RAE1	RAE1	RAE1	4573	0.13	0.16	YES
30	SNRPG	SNRPG	SNRPG	4777	0.12	0.16	YES
31	NUP155	NUP155	NUP155	5015	0.12	0.16	YES
32	SNRNP70	SNRNP70	SNRNP70	5021	0.12	0.17	YES
33	RBMX	RBMX	RBMX	5029	0.12	0.18	YES
34	FUS	FUS	FUS	5052	0.12	0.19	YES
35	CCAR1	CCAR1	CCAR1	5140	0.11	0.19	YES
36	NUP85	NUP85	NUP85	5247	0.11	0.2	YES
37	U2AF1	U2AF1	U2AF1	5337	0.11	0.2	YES
38	CPSF1	CPSF1	CPSF1	5367	0.11	0.21	YES
39	NHP2L1	NHP2L1	NHP2L1	5433	0.11	0.21	YES
40	TXNL4A	TXNL4A	TXNL4A	5481	0.1	0.22	YES
41	POLR2D	POLR2D	POLR2D	5518	0.1	0.23	YES
42	HNRNPA0	HNRNPA0	HNRNPA0	5581	0.1	0.23	YES
43	TPR	TPR	TPR	5661	0.1	0.24	YES
44	EFTUD2	EFTUD2	EFTUD2	5676	0.1	0.24	YES
45	HNRNPUL1	HNRNPUL1	HNRNPUL1	5733	0.099	0.25	YES
46	SUPT5H	SUPT5H	SUPT5H	5802	0.097	0.26	YES
47	SLBP	SLBP	SLBP	5821	0.097	0.26	YES
48	SNRPB2	SNRPB2	SNRPB2	5828	0.097	0.27	YES
49	U2AF2	U2AF2	U2AF2	5871	0.096	0.28	YES
50	HNRNPH1	HNRNPH1	HNRNPH1	5896	0.095	0.28	YES
51	RBM8A	RBM8A	RBM8A	5955	0.094	0.29	YES
52	HNRNPA3	HNRNPA3	HNRNPA3	6039	0.092	0.29	YES
53	GTF2F2	GTF2F2	GTF2F2	6102	0.091	0.3	YES
54	CSTF2	CSTF2	CSTF2	6107	0.091	0.3	YES
55	RNMT	RNMT	RNMT	6134	0.09	0.31	YES
56	NUP133	NUP133	NUP133	6138	0.09	0.32	YES
57	PHF5A	PHF5A	PHF5A	6294	0.086	0.32	YES
58	POLR2G	POLR2G	POLR2G	6312	0.085	0.32	YES
59	CPSF3	CPSF3	CPSF3	6363	0.084	0.33	YES
60	PRPF4	PRPF4	PRPF4	6428	0.082	0.33	YES
61	SNRNP40	SNRNP40	SNRNP40	6463	0.082	0.34	YES
62	NUP50	NUP50	NUP50	6496	0.081	0.34	YES
63	HNRNPU	HNRNPU	HNRNPU	6528	0.08	0.35	YES
64	DHX9	DHX9	DHX9	6552	0.079	0.35	YES
65	HNRNPL	HNRNPL	HNRNPL	6711	0.076	0.35	YES
66	PTBP1	PTBP1	PTBP1	6719	0.076	0.36	YES
67	GTF2H1	GTF2H1	GTF2H1	6723	0.076	0.36	YES
68	PRPF6	PRPF6	PRPF6	6734	0.076	0.37	YES
69	HNRNPD	HNRNPD	HNRNPD	6878	0.072	0.37	YES
70	PABPN1	PABPN1	PABPN1	6885	0.072	0.37	YES
71	RNPS1	RNPS1	RNPS1	6960	0.07	0.37	YES
72	ERCC2	ERCC2	ERCC2	7193	0.065	0.37	YES
73	AAAS	AAAS	AAAS	7198	0.065	0.37	YES
74	GTF2F1	GTF2F1	GTF2F1	7313	0.063	0.37	YES
75	POM121	POM121	POM121	7391	0.061	0.37	YES
76	SNRPD3	SNRPD3	SNRPD3	7417	0.061	0.38	YES
77	HNRNPM	HNRNPM	HNRNPM	7434	0.06	0.38	YES
78	POLR2I	POLR2I	POLR2I	7441	0.06	0.38	YES
79	NUP214	NUP214	NUP214	7496	0.059	0.39	YES
80	HNRNPC	HNRNPC	HNRNPC	7566	0.058	0.39	YES
81	CD2BP2	CD2BP2	CD2BP2	7584	0.058	0.39	YES
82	NUPL2	NUPL2	NUPL2	7626	0.057	0.4	YES
83	RBM5	RBM5	RBM5	7642	0.057	0.4	YES
84	ERCC3	ERCC3	ERCC3	7677	0.056	0.4	YES
85	SF3B5	SF3B5	SF3B5	7828	0.053	0.4	YES
86	METTL3	METTL3	METTL3	7895	0.052	0.4	YES
87	POLR2J	POLR2J	POLR2J	7932	0.051	0.4	YES
88	DDX23	DDX23	DDX23	7969	0.05	0.4	YES
89	NXF1	NXF1	NXF1	7971	0.05	0.41	YES
90	SEH1L	SEH1L	SEH1L	8106	0.048	0.4	YES
91	CSTF3	CSTF3	CSTF3	8116	0.048	0.41	YES
92	NUP35	NUP35	NUP35	8140	0.047	0.41	YES
93	SF3A3	SF3A3	SF3A3	8162	0.047	0.41	YES
94	YBX1	YBX1	YBX1	8222	0.046	0.42	YES
95	GTF2H4	GTF2H4	GTF2H4	8298	0.044	0.41	YES
96	POLR2B	POLR2B	POLR2B	8323	0.044	0.42	YES
97	SF3B14	SF3B14	SF3B14	8364	0.043	0.42	YES
98	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	8446	0.041	0.42	NO
99	CPSF7	CPSF7	CPSF7	8506	0.04	0.42	NO
100	POLR2K	POLR2K	POLR2K	8595	0.038	0.42	NO
101	HNRNPR	HNRNPR	HNRNPR	8698	0.036	0.41	NO
102	SNRNP200	SNRNP200	SNRNP200	8747	0.035	0.41	NO
103	POLR2F	POLR2F	POLR2F	8864	0.033	0.41	NO
104	SF3B2	SF3B2	SF3B2	8921	0.032	0.41	NO
105	PAPOLA	PAPOLA	PAPOLA	8927	0.032	0.41	NO
106	DNAJC8	DNAJC8	DNAJC8	9016	0.03	0.41	NO
107	MAGOH	MAGOH	MAGOH	9042	0.03	0.41	NO
108	SF3B3	SF3B3	SF3B3	9067	0.03	0.41	NO
109	SF3B1	SF3B1	SF3B1	9112	0.029	0.41	NO
110	NUPL1	NUPL1	NUPL1	9322	0.024	0.4	NO
111	NCBP1	NCBP1	NCBP1	9714	0.017	0.38	NO
112	PCBP2	PCBP2	PCBP2	9955	0.012	0.37	NO
113	HNRNPK	HNRNPK	HNRNPK	9971	0.012	0.37	NO
114	POLR2A	POLR2A	POLR2A	10165	0.0085	0.36	NO
115	PRPF8	PRPF8	PRPF8	10183	0.0082	0.36	NO
116	MNAT1	MNAT1	MNAT1	10188	0.0082	0.36	NO
117	ADAR	ADAR	ADAR	10197	0.008	0.36	NO
118	PCF11	PCF11	PCF11	10237	0.0071	0.36	NO
119	NUDT21	NUDT21	NUDT21	10302	0.0058	0.35	NO
120	EIF4E	EIF4E	EIF4E	10372	0.0045	0.35	NO
121	SMC1A	SMC1A	SMC1A	10401	0.0039	0.35	NO
122	POLR2L	POLR2L	POLR2L	10403	0.0038	0.35	NO
123	NUP88	NUP88	NUP88	10493	0.0018	0.34	NO
124	HNRNPF	HNRNPF	HNRNPF	10571	0.0002	0.34	NO
125	CPSF2	CPSF2	CPSF2	10581	-0.000074	0.34	NO
126	NUP153	NUP153	NUP153	10598	-0.00037	0.34	NO
127	SF3A1	SF3A1	SF3A1	10666	-0.0016	0.34	NO
128	RNGTT	RNGTT	RNGTT	10681	-0.002	0.34	NO
129	NUP54	NUP54	NUP54	10729	-0.0028	0.33	NO
130	RANBP2	RANBP2	RANBP2	10797	-0.004	0.33	NO
131	DHX38	DHX38	DHX38	10869	-0.0053	0.32	NO
132	CSTF1	CSTF1	CSTF1	11005	-0.008	0.32	NO
133	LSM10	LSM10	LSM10	11445	-0.018	0.3	NO
134	ADARB1	ADARB1	ADARB1	11465	-0.018	0.3	NO
135	PCBP1	PCBP1	PCBP1	11555	-0.02	0.29	NO
136	CLP1	CLP1	CLP1	11681	-0.022	0.29	NO
137	POLR2E	POLR2E	POLR2E	11994	-0.03	0.27	NO
138	NFX1	NFX1	NFX1	12119	-0.033	0.27	NO
139	GTF2H3	GTF2H3	GTF2H3	12254	-0.036	0.26	NO
140	SRRM1	SRRM1	SRRM1	12292	-0.037	0.26	NO
141	POLR2C	POLR2C	POLR2C	13096	-0.059	0.22	NO
142	HNRNPH2	HNRNPH2	HNRNPH2	13117	-0.06	0.23	NO
143	CDC40	CDC40	CDC40	13422	-0.068	0.22	NO
144	CCNH	CCNH	CCNH	13999	-0.089	0.19	NO
145	A1CF	A1CF	A1CF	16190	-0.22	0.086	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 CYCLIN E ASSOCIATED EVENTS DURING G1 S TRANSITION .

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME CYCLIN E ASSOCIATED EVENTS DURING G1 S TRANSITION , 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 MRNA PROCESSING

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	CDC25A	CDC25A	CDC25A	73	0.63	0.043	YES
2	CDC45	CDC45	CDC45	175	0.56	0.079	YES
3	GINS1	GINS1	GINS1	187	0.55	0.12	YES
4	CCNE1	CCNE1	CCNE1	201	0.55	0.16	YES
5	CDT1	CDT1	CDT1	224	0.53	0.2	YES
6	CDC6	CDC6	CDC6	242	0.52	0.24	YES
7	CCNA2	CCNA2	CCNA2	371	0.47	0.26	YES
8	DNA2	DNA2	DNA2	649	0.4	0.28	YES
9	GINS4	GINS4	GINS4	658	0.4	0.31	YES
10	CCNE2	CCNE2	CCNE2	770	0.38	0.33	YES
11	MCM2	MCM2	MCM2	811	0.37	0.35	YES
12	POLE2	POLE2	POLE2	921	0.36	0.37	YES
13	MCM8	MCM8	MCM8	1321	0.31	0.37	YES
14	GINS2	GINS2	GINS2	1345	0.3	0.4	YES
15	RFC4	RFC4	RFC4	1347	0.3	0.42	YES
16	MCM4	MCM4	MCM4	1667	0.28	0.42	YES
17	PRIM2	PRIM2	PRIM2	1689	0.27	0.44	YES
18	MCM6	MCM6	MCM6	1808	0.27	0.45	YES
19	POLD1	POLD1	POLD1	1895	0.26	0.47	YES
20	FEN1	FEN1	FEN1	2055	0.25	0.48	YES
21	MCM3	MCM3	MCM3	2264	0.23	0.48	YES
22	PRIM1	PRIM1	PRIM1	2297	0.23	0.5	YES
23	LIG1	LIG1	LIG1	2298	0.23	0.51	YES
24	POLA1	POLA1	POLA1	2306	0.23	0.53	YES
25	POLA2	POLA2	POLA2	2558	0.21	0.53	YES
26	MCM5	MCM5	MCM5	2585	0.21	0.55	YES
27	MCM7	MCM7	MCM7	2615	0.21	0.56	YES
28	SKP2	SKP2	SKP2	2667	0.21	0.57	YES
29	CDK4	CDK4	CDK4	2802	0.2	0.58	YES
30	POLD3	POLD3	POLD3	3283	0.18	0.57	YES
31	CDC25B	CDC25B	CDC25B	3436	0.17	0.57	YES
32	CKS1B	CKS1B	CKS1B	3775	0.16	0.56	YES
33	PSMA8	PSMA8	PSMA8	3956	0.15	0.56	YES
34	RFC2	RFC2	RFC2	3995	0.15	0.57	YES
35	CDK7	CDK7	CDK7	4043	0.15	0.58	YES
36	CCNA1	CCNA1	CCNA1	4469	0.13	0.57	NO
37	RPS27A	RPS27A	RPS27A	4575	0.13	0.57	NO
38	RFC3	RFC3	RFC3	4796	0.12	0.57	NO
39	RFC5	RFC5	RFC5	4810	0.12	0.58	NO
40	CDK2	CDK2	CDK2	5028	0.12	0.57	NO
41	PCNA	PCNA	PCNA	5407	0.11	0.56	NO
42	RPA1	RPA1	RPA1	6256	0.087	0.52	NO
43	UBA52	UBA52	UBA52	7044	0.068	0.48	NO
44	PSMD14	PSMD14	PSMD14	7750	0.054	0.44	NO
45	PSMC4	PSMC4	PSMC4	7851	0.052	0.44	NO
46	RPA2	RPA2	RPA2	8346	0.043	0.41	NO
47	POLE	POLE	POLE	8387	0.042	0.42	NO
48	PSMB4	PSMB4	PSMB4	8610	0.038	0.4	NO
49	PSMD13	PSMD13	PSMD13	8682	0.036	0.4	NO
50	PSMA4	PSMA4	PSMA4	8683	0.036	0.41	NO
51	PSMD10	PSMD10	PSMD10	8827	0.034	0.4	NO
52	PSMD4	PSMD4	PSMD4	8972	0.031	0.4	NO
53	PSMB3	PSMB3	PSMB3	9055	0.03	0.39	NO
54	PSMB5	PSMB5	PSMB5	9195	0.027	0.39	NO
55	PSMD2	PSMD2	PSMD2	9321	0.025	0.38	NO
56	PSMD8	PSMD8	PSMD8	9329	0.024	0.38	NO
57	PSMA1	PSMA1	PSMA1	9426	0.023	0.38	NO
58	MAX	MAX	MAX	9812	0.015	0.36	NO
59	WEE1	WEE1	WEE1	9914	0.013	0.35	NO
60	PSMC5	PSMC5	PSMC5	9975	0.012	0.35	NO
61	PSMD1	PSMD1	PSMD1	10124	0.0093	0.34	NO
62	MNAT1	MNAT1	MNAT1	10188	0.0082	0.34	NO
63	PSMD11	PSMD11	PSMD11	10386	0.0042	0.33	NO
64	SKP1	SKP1	SKP1	10481	0.0021	0.32	NO
65	PSMD5	PSMD5	PSMD5	10499	0.0017	0.32	NO
66	PSMB1	PSMB1	PSMB1	10589	-0.00021	0.32	NO
67	PSMD9	PSMD9	PSMD9	10714	-0.0026	0.31	NO
68	PSME4	PSME4	PSME4	10752	-0.0032	0.31	NO
69	PSMB6	PSMB6	PSMB6	10793	-0.004	0.31	NO
70	PSMC3	PSMC3	PSMC3	10906	-0.006	0.3	NO
71	PSMD3	PSMD3	PSMD3	10952	-0.007	0.3	NO
72	PSMC1	PSMC1	PSMC1	10960	-0.0071	0.3	NO
73	PSMA6	PSMA6	PSMA6	11090	-0.0097	0.29	NO
74	RPA3	RPA3	RPA3	11137	-0.01	0.29	NO
75	PSMC6	PSMC6	PSMC6	11211	-0.012	0.29	NO
76	PSMB9	PSMB9	PSMB9	11222	-0.012	0.29	NO
77	PSMA7	PSMA7	PSMA7	11250	-0.013	0.29	NO
78	PSMB7	PSMB7	PSMB7	11253	-0.013	0.29	NO
79	POLD2	POLD2	POLD2	11263	-0.014	0.29	NO
80	PSMB2	PSMB2	PSMB2	11379	-0.016	0.28	NO
81	PSMD6	PSMD6	PSMD6	11439	-0.017	0.28	NO
82	PSMF1	PSMF1	PSMF1	11440	-0.017	0.28	NO
83	PSMA5	PSMA5	PSMA5	11648	-0.022	0.27	NO
84	PSMB10	PSMB10	PSMB10	11789	-0.025	0.27	NO
85	MYC	MYC	MYC	11822	-0.026	0.27	NO
86	PSME2	PSME2	PSME2	11915	-0.028	0.26	NO
87	PSMA3	PSMA3	PSMA3	12108	-0.032	0.26	NO
88	PSMC2	PSMC2	PSMC2	12214	-0.035	0.25	NO
89	PSMD12	PSMD12	PSMD12	12238	-0.036	0.25	NO
90	PSMD7	PSMD7	PSMD7	12264	-0.036	0.26	NO
91	RB1	RB1	RB1	12317	-0.038	0.26	NO
92	PSME1	PSME1	PSME1	12450	-0.041	0.25	NO
93	PSMA2	PSMA2	PSMA2	12520	-0.043	0.25	NO
94	CCND1	CCND1	CCND1	12962	-0.055	0.23	NO
95	CUL1	CUL1	CUL1	13147	-0.06	0.22	NO
96	POLD4	POLD4	POLD4	13345	-0.066	0.22	NO
97	CDKN1B	CDKN1B	CDKN1B	13369	-0.066	0.22	NO
98	PSMB8	PSMB8	PSMB8	13957	-0.087	0.19	NO
99	CCNH	CCNH	CCNH	13999	-0.089	0.2	NO
100	CDKN1A	CDKN1A	CDKN1A	15574	-0.17	0.12	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 MRNA PROCESSING.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME MRNA PROCESSING, 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 M G1 TRANSITION

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	SNRPD1	SNRPD1	SNRPD1	2300	0.23	-0.077	YES
2	GEMIN7	GEMIN7	GEMIN7	3016	0.19	-0.073	YES
3	NUP210	NUP210	NUP210	3139	0.18	-0.036	YES
4	SNRPB	SNRPB	SNRPB	3161	0.18	0.0056	YES
5	NUP37	NUP37	NUP37	3315	0.18	0.038	YES
6	SNRPE	SNRPE	SNRPE	3429	0.17	0.072	YES
7	SNRPF	SNRPF	SNRPF	3496	0.17	0.11	YES
8	SNRPD2	SNRPD2	SNRPD2	3583	0.16	0.14	YES
9	NUP43	NUP43	NUP43	4081	0.15	0.15	YES
10	NUP62	NUP62	NUP62	4207	0.14	0.17	YES
11	NUP205	NUP205	NUP205	4310	0.14	0.2	YES
12	NUP93	NUP93	NUP93	4314	0.14	0.23	YES
13	NUP107	NUP107	NUP107	4336	0.14	0.26	YES
14	NUP188	NUP188	NUP188	4405	0.14	0.29	YES
15	NCBP2	NCBP2	NCBP2	4411	0.14	0.32	YES
16	RAE1	RAE1	RAE1	4573	0.13	0.35	YES
17	SNRPG	SNRPG	SNRPG	4777	0.12	0.36	YES
18	NUP155	NUP155	NUP155	5015	0.12	0.38	YES
19	NUP85	NUP85	NUP85	5247	0.11	0.39	YES
20	SMN1	SMN1	SMN1	5639	0.1	0.39	YES
21	TPR	TPR	TPR	5661	0.1	0.41	YES
22	WDR77	WDR77	WDR77	5822	0.097	0.43	YES
23	NUP133	NUP133	NUP133	6138	0.09	0.43	YES
24	NUP50	NUP50	NUP50	6496	0.081	0.43	YES
25	TGS1	TGS1	TGS1	6819	0.074	0.43	YES
26	AAAS	AAAS	AAAS	7198	0.065	0.42	YES
27	GEMIN4	GEMIN4	GEMIN4	7215	0.064	0.44	YES
28	DDX20	DDX20	DDX20	7370	0.062	0.44	YES
29	POM121	POM121	POM121	7391	0.061	0.46	YES
30	SNRPD3	SNRPD3	SNRPD3	7417	0.061	0.47	YES
31	GEMIN6	GEMIN6	GEMIN6	7450	0.06	0.48	YES
32	NUP214	NUP214	NUP214	7496	0.059	0.49	YES
33	NUPL2	NUPL2	NUPL2	7626	0.057	0.5	YES
34	SMN2	SMN2	SMN2	7782	0.054	0.5	YES
35	SEH1L	SEH1L	SEH1L	8106	0.048	0.5	YES
36	NUP35	NUP35	NUP35	8140	0.047	0.5	YES
37	GEMIN5	GEMIN5	GEMIN5	8735	0.036	0.48	NO
38	NUPL1	NUPL1	NUPL1	9322	0.024	0.45	NO
39	SNUPN	SNUPN	SNUPN	9487	0.022	0.45	NO
40	NCBP1	NCBP1	NCBP1	9714	0.017	0.44	NO
41	CLNS1A	CLNS1A	CLNS1A	9733	0.016	0.44	NO
42	NUP88	NUP88	NUP88	10493	0.0018	0.4	NO
43	PRMT5	PRMT5	PRMT5	10592	-0.00022	0.39	NO
44	NUP153	NUP153	NUP153	10598	-0.00037	0.39	NO
45	NUP54	NUP54	NUP54	10729	-0.0028	0.39	NO
46	RANBP2	RANBP2	RANBP2	10797	-0.004	0.38	NO
47	PHAX	PHAX	PHAX	12143	-0.033	0.31	NO

Figure S15. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: REACTOME M G1 TRANSITION.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME M G1 TRANSITION, 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 G1 S TRANSITION

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	MYBL2	MYBL2	MYBL2	17	0.73	0.037	YES
2	CDC25A	CDC25A	CDC25A	73	0.63	0.068	YES
3	MCM10	MCM10	MCM10	81	0.62	0.1	YES
4	CDK1	CDK1	CDK1	153	0.57	0.12	YES
5	CDC45	CDC45	CDC45	175	0.56	0.15	YES
6	CCNB1	CCNB1	CCNB1	193	0.55	0.18	YES
7	CCNE1	CCNE1	CCNE1	201	0.55	0.21	YES
8	CDT1	CDT1	CDT1	224	0.53	0.24	YES
9	E2F2	E2F2	E2F2	236	0.53	0.26	YES
10	CDC6	CDC6	CDC6	242	0.52	0.29	YES
11	CCNA2	CCNA2	CCNA2	371	0.47	0.31	YES
12	PKMYT1	PKMYT1	PKMYT1	441	0.45	0.33	YES
13	RRM2	RRM2	RRM2	485	0.44	0.35	YES
14	CDC7	CDC7	CDC7	526	0.43	0.37	YES
15	LIN9	LIN9	LIN9	651	0.4	0.38	YES
16	E2F1	E2F1	E2F1	659	0.4	0.4	YES
17	CCNE2	CCNE2	CCNE2	770	0.38	0.42	YES
18	MCM2	MCM2	MCM2	811	0.37	0.43	YES
19	POLE2	POLE2	POLE2	921	0.36	0.45	YES
20	DBF4	DBF4	DBF4	1036	0.34	0.46	YES
21	TYMS	TYMS	TYMS	1053	0.34	0.47	YES
22	RBL1	RBL1	RBL1	1081	0.33	0.49	YES
23	MCM8	MCM8	MCM8	1321	0.31	0.49	YES
24	FBXO5	FBXO5	FBXO5	1545	0.29	0.49	YES
25	MCM4	MCM4	MCM4	1667	0.28	0.5	YES
26	PRIM2	PRIM2	PRIM2	1689	0.27	0.52	YES
27	MCM6	MCM6	MCM6	1808	0.27	0.52	YES
28	E2F5	E2F5	E2F5	2174	0.24	0.51	YES
29	MCM3	MCM3	MCM3	2264	0.23	0.52	YES
30	PRIM1	PRIM1	PRIM1	2297	0.23	0.53	YES
31	POLA1	POLA1	POLA1	2306	0.23	0.54	YES
32	POLA2	POLA2	POLA2	2558	0.21	0.54	YES
33	MCM5	MCM5	MCM5	2585	0.21	0.55	YES
34	MCM7	MCM7	MCM7	2615	0.21	0.56	YES
35	SKP2	SKP2	SKP2	2667	0.21	0.57	YES
36	E2F3	E2F3	E2F3	2773	0.2	0.57	YES
37	CDK4	CDK4	CDK4	2802	0.2	0.58	YES
38	CCND2	CCND2	CCND2	2875	0.2	0.59	YES
39	CDKN2A	CDKN2A	CDKN2A	3060	0.19	0.59	NO
40	CDKN2C	CDKN2C	CDKN2C	3442	0.17	0.57	NO
41	PPP2R3B	PPP2R3B	PPP2R3B	3573	0.17	0.57	NO
42	CDKN2D	CDKN2D	CDKN2D	3714	0.16	0.57	NO
43	CKS1B	CKS1B	CKS1B	3775	0.16	0.58	NO
44	CDK7	CDK7	CDK7	4043	0.15	0.57	NO
45	CCNA1	CCNA1	CCNA1	4469	0.13	0.56	NO
46	RPS27A	RPS27A	RPS27A	4575	0.13	0.56	NO
47	HDAC1	HDAC1	HDAC1	4877	0.12	0.55	NO
48	CDK2	CDK2	CDK2	5028	0.12	0.54	NO
49	PPP2R1A	PPP2R1A	PPP2R1A	5097	0.11	0.55	NO
50	PCNA	PCNA	PCNA	5407	0.11	0.53	NO
51	E2F4	E2F4	E2F4	5603	0.1	0.53	NO
52	TFDP1	TFDP1	TFDP1	5722	0.099	0.52	NO
53	RPA1	RPA1	RPA1	6256	0.087	0.5	NO
54	LIN37	LIN37	LIN37	6467	0.081	0.49	NO
55	UBA52	UBA52	UBA52	7044	0.068	0.46	NO
56	RPA4	RPA4	RPA4	7749	0.055	0.42	NO
57	PSMD14	PSMD14	PSMD14	7750	0.054	0.43	NO
58	PSMC4	PSMC4	PSMC4	7851	0.052	0.42	NO
59	RPA2	RPA2	RPA2	8346	0.043	0.4	NO
60	POLE	POLE	POLE	8387	0.042	0.4	NO
61	PSMB4	PSMB4	PSMB4	8610	0.038	0.39	NO
62	PSMD13	PSMD13	PSMD13	8682	0.036	0.39	NO
63	PSMA4	PSMA4	PSMA4	8683	0.036	0.39	NO
64	PSMD10	PSMD10	PSMD10	8827	0.034	0.38	NO
65	CDKN2B	CDKN2B	CDKN2B	8941	0.032	0.38	NO
66	PSMD4	PSMD4	PSMD4	8972	0.031	0.38	NO
67	PSMB3	PSMB3	PSMB3	9055	0.03	0.37	NO
68	PSMB5	PSMB5	PSMB5	9195	0.027	0.37	NO
69	RBBP4	RBBP4	RBBP4	9301	0.025	0.36	NO
70	PSMD2	PSMD2	PSMD2	9321	0.025	0.36	NO
71	PSMD8	PSMD8	PSMD8	9329	0.024	0.36	NO
72	PSMA1	PSMA1	PSMA1	9426	0.023	0.36	NO
73	CCND3	CCND3	CCND3	9607	0.019	0.35	NO
74	MAX	MAX	MAX	9812	0.015	0.34	NO
75	WEE1	WEE1	WEE1	9914	0.013	0.34	NO
76	CDK6	CDK6	CDK6	9959	0.012	0.33	NO
77	PSMC5	PSMC5	PSMC5	9975	0.012	0.33	NO
78	PPP2CA	PPP2CA	PPP2CA	10007	0.011	0.33	NO
79	PSMD1	PSMD1	PSMD1	10124	0.0093	0.32	NO
80	MNAT1	MNAT1	MNAT1	10188	0.0082	0.32	NO
81	PSMD11	PSMD11	PSMD11	10386	0.0042	0.31	NO
82	SKP1	SKP1	SKP1	10481	0.0021	0.31	NO
83	PSMD5	PSMD5	PSMD5	10499	0.0017	0.3	NO
84	PSMB1	PSMB1	PSMB1	10589	-0.00021	0.3	NO
85	PSMD9	PSMD9	PSMD9	10714	-0.0026	0.29	NO
86	PSMB6	PSMB6	PSMB6	10793	-0.004	0.29	NO
87	PSMC3	PSMC3	PSMC3	10906	-0.006	0.28	NO
88	PSMD3	PSMD3	PSMD3	10952	-0.007	0.28	NO
89	PSMC1	PSMC1	PSMC1	10960	-0.0071	0.28	NO
90	DYRK1A	DYRK1A	DYRK1A	10981	-0.0076	0.28	NO
91	PSMA6	PSMA6	PSMA6	11090	-0.0097	0.27	NO
92	RPA3	RPA3	RPA3	11137	-0.01	0.27	NO
93	PSMC6	PSMC6	PSMC6	11211	-0.012	0.27	NO
94	PSMB9	PSMB9	PSMB9	11222	-0.012	0.27	NO
95	PSMA7	PSMA7	PSMA7	11250	-0.013	0.27	NO
96	PSMB7	PSMB7	PSMB7	11253	-0.013	0.27	NO
97	PSMB2	PSMB2	PSMB2	11379	-0.016	0.26	NO
98	PSMD6	PSMD6	PSMD6	11439	-0.017	0.26	NO
99	PSMF1	PSMF1	PSMF1	11440	-0.017	0.26	NO
100	PSMA5	PSMA5	PSMA5	11648	-0.022	0.25	NO
101	PSMB10	PSMB10	PSMB10	11789	-0.025	0.24	NO
102	DHFR	DHFR	DHFR	11814	-0.026	0.24	NO
103	MYC	MYC	MYC	11822	-0.026	0.24	NO
104	PSME2	PSME2	PSME2	11915	-0.028	0.24	NO
105	PPP2R2A	PPP2R2A	PPP2R2A	12043	-0.031	0.24	NO
106	PSMA3	PSMA3	PSMA3	12108	-0.032	0.23	NO
107	PSMC2	PSMC2	PSMC2	12214	-0.035	0.23	NO
108	PSMD12	PSMD12	PSMD12	12238	-0.036	0.23	NO
109	PSMD7	PSMD7	PSMD7	12264	-0.036	0.23	NO
110	RB1	RB1	RB1	12317	-0.038	0.23	NO
111	PSME1	PSME1	PSME1	12450	-0.041	0.22	NO
112	PSMA2	PSMA2	PSMA2	12520	-0.043	0.22	NO
113	CCND1	CCND1	CCND1	12962	-0.055	0.2	NO
114	CUL1	CUL1	CUL1	13147	-0.06	0.19	NO
115	CDKN1B	CDKN1B	CDKN1B	13369	-0.066	0.18	NO
116	PPP2R1B	PPP2R1B	PPP2R1B	13453	-0.07	0.18	NO
117	LIN54	LIN54	LIN54	13617	-0.074	0.18	NO
118	PSMB8	PSMB8	PSMB8	13957	-0.087	0.16	NO
119	CCNH	CCNH	CCNH	13999	-0.089	0.16	NO
120	PPP2CB	PPP2CB	PPP2CB	14275	-0.099	0.15	NO
121	CDKN1A	CDKN1A	CDKN1A	15574	-0.17	0.089	NO
122	LIN52	LIN52	LIN52	15577	-0.17	0.098	NO
123	TK2	TK2	TK2	15823	-0.19	0.093	NO
124	RBL2	RBL2	RBL2	16435	-0.25	0.072	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 G1 S TRANSITION.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME G1 S TRANSITION, 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 TRANSPORT OF MATURE MRNA DERIVED FROM AN INTRONLESS TRANSCRIPT

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	UBE2C	UBE2C	UBE2C	43	0.67	0.04	YES
2	BUB1B	BUB1B	BUB1B	70	0.63	0.079	YES
3	CDC25A	CDC25A	CDC25A	73	0.63	0.12	YES
4	MCM10	MCM10	MCM10	81	0.62	0.16	YES
5	CCNB2	CCNB2	CCNB2	99	0.61	0.2	YES
6	CDC20	CDC20	CDC20	100	0.61	0.24	YES
7	CDK1	CDK1	CDK1	153	0.57	0.27	YES
8	CDC45	CDC45	CDC45	175	0.56	0.3	YES
9	CCNB1	CCNB1	CCNB1	193	0.55	0.34	YES
10	CCNE1	CCNE1	CCNE1	201	0.55	0.37	YES
11	CDC25C	CDC25C	CDC25C	211	0.54	0.41	YES
12	CDC6	CDC6	CDC6	242	0.52	0.44	YES
13	MAD2L1	MAD2L1	MAD2L1	455	0.45	0.46	YES
14	CDC7	CDC7	CDC7	526	0.43	0.48	YES
15	CHEK1	CHEK1	CHEK1	756	0.38	0.49	YES
16	CCNE2	CCNE2	CCNE2	770	0.38	0.51	YES
17	MCM2	MCM2	MCM2	811	0.37	0.54	YES
18	DBF4	DBF4	DBF4	1036	0.34	0.54	YES
19	MCM8	MCM8	MCM8	1321	0.31	0.55	YES
20	RFC4	RFC4	RFC4	1347	0.3	0.56	YES
21	MCM4	MCM4	MCM4	1667	0.28	0.56	YES
22	MCM6	MCM6	MCM6	1808	0.27	0.57	YES
23	CHEK2	CHEK2	CHEK2	2206	0.24	0.57	YES
24	MCM3	MCM3	MCM3	2264	0.23	0.58	YES
25	RAD9A	RAD9A	RAD9A	2329	0.23	0.59	YES
26	MCM5	MCM5	MCM5	2585	0.21	0.59	YES
27	MCM7	MCM7	MCM7	2615	0.21	0.6	YES
28	ANAPC7	ANAPC7	ANAPC7	3810	0.16	0.54	NO
29	PSMA8	PSMA8	PSMA8	3956	0.15	0.54	NO
30	RFC2	RFC2	RFC2	3995	0.15	0.55	NO
31	ANAPC4	ANAPC4	ANAPC4	4131	0.14	0.55	NO
32	RPS27A	RPS27A	RPS27A	4575	0.13	0.54	NO
33	UBE2D1	UBE2D1	UBE2D1	4675	0.13	0.54	NO
34	RAD1	RAD1	RAD1	4741	0.12	0.54	NO
35	RFC3	RFC3	RFC3	4796	0.12	0.55	NO
36	RFC5	RFC5	RFC5	4810	0.12	0.55	NO
37	CDK2	CDK2	CDK2	5028	0.12	0.55	NO
38	ANAPC1	ANAPC1	ANAPC1	5414	0.11	0.53	NO
39	UBE2E1	UBE2E1	UBE2E1	5617	0.1	0.53	NO
40	RFWD2	RFWD2	RFWD2	5648	0.1	0.53	NO
41	BUB3	BUB3	BUB3	6170	0.089	0.51	NO
42	RPA1	RPA1	RPA1	6256	0.087	0.51	NO
43	TP53	TP53	TP53	6402	0.083	0.51	NO
44	ATRIP	ATRIP	ATRIP	6747	0.075	0.49	NO
45	UBA52	UBA52	UBA52	7044	0.068	0.48	NO
46	MAD1L1	MAD1L1	MAD1L1	7484	0.06	0.46	NO
47	ANAPC5	ANAPC5	ANAPC5	7486	0.06	0.46	NO
48	ATR	ATR	ATR	7644	0.057	0.46	NO
49	PSMD14	PSMD14	PSMD14	7750	0.054	0.46	NO
50	CDC16	CDC16	CDC16	7806	0.053	0.46	NO
51	PSMC4	PSMC4	PSMC4	7851	0.052	0.46	NO
52	ANAPC11	ANAPC11	ANAPC11	8072	0.049	0.45	NO
53	CDC27	CDC27	CDC27	8088	0.048	0.45	NO
54	RPA2	RPA2	RPA2	8346	0.043	0.44	NO
55	PSMB4	PSMB4	PSMB4	8610	0.038	0.42	NO
56	CDC23	CDC23	CDC23	8632	0.038	0.43	NO
57	PSMD13	PSMD13	PSMD13	8682	0.036	0.43	NO
58	PSMA4	PSMA4	PSMA4	8683	0.036	0.43	NO
59	PSMD10	PSMD10	PSMD10	8827	0.034	0.42	NO
60	PSMD4	PSMD4	PSMD4	8972	0.031	0.42	NO
61	PSMB3	PSMB3	PSMB3	9055	0.03	0.41	NO
62	CDC26	CDC26	CDC26	9123	0.028	0.41	NO
63	PSMB5	PSMB5	PSMB5	9195	0.027	0.41	NO
64	PSMD2	PSMD2	PSMD2	9321	0.025	0.4	NO
65	PSMD8	PSMD8	PSMD8	9329	0.024	0.4	NO
66	PSMA1	PSMA1	PSMA1	9426	0.023	0.4	NO
67	ATM	ATM	ATM	9738	0.016	0.38	NO
68	WEE1	WEE1	WEE1	9914	0.013	0.38	NO
69	PSMC5	PSMC5	PSMC5	9975	0.012	0.37	NO
70	PSMD1	PSMD1	PSMD1	10124	0.0093	0.36	NO
71	PSMD11	PSMD11	PSMD11	10386	0.0042	0.35	NO
72	PSMD5	PSMD5	PSMD5	10499	0.0017	0.34	NO
73	PSMB1	PSMB1	PSMB1	10589	-0.00021	0.34	NO
74	PSMD9	PSMD9	PSMD9	10714	-0.0026	0.33	NO
75	PSME4	PSME4	PSME4	10752	-0.0032	0.33	NO
76	PSMB6	PSMB6	PSMB6	10793	-0.004	0.33	NO
77	PSMC3	PSMC3	PSMC3	10906	-0.006	0.32	NO
78	PSMD3	PSMD3	PSMD3	10952	-0.007	0.32	NO
79	PSMC1	PSMC1	PSMC1	10960	-0.0071	0.32	NO
80	PSMA6	PSMA6	PSMA6	11090	-0.0097	0.31	NO
81	RPA3	RPA3	RPA3	11137	-0.01	0.31	NO
82	PSMC6	PSMC6	PSMC6	11211	-0.012	0.31	NO
83	PSMB9	PSMB9	PSMB9	11222	-0.012	0.31	NO
84	PSMA7	PSMA7	PSMA7	11250	-0.013	0.31	NO
85	PSMB7	PSMB7	PSMB7	11253	-0.013	0.31	NO
86	PSMB2	PSMB2	PSMB2	11379	-0.016	0.3	NO
87	PSMD6	PSMD6	PSMD6	11439	-0.017	0.3	NO
88	PSMF1	PSMF1	PSMF1	11440	-0.017	0.3	NO
89	ANAPC2	ANAPC2	ANAPC2	11624	-0.021	0.29	NO
90	PSMA5	PSMA5	PSMA5	11648	-0.022	0.29	NO
91	HUS1	HUS1	HUS1	11714	-0.023	0.29	NO
92	PSMB10	PSMB10	PSMB10	11789	-0.025	0.29	NO
93	RAD17	RAD17	RAD17	11899	-0.027	0.28	NO
94	PSME2	PSME2	PSME2	11915	-0.028	0.28	NO
95	PSMA3	PSMA3	PSMA3	12108	-0.032	0.27	NO
96	PSMC2	PSMC2	PSMC2	12214	-0.035	0.27	NO
97	PSMD12	PSMD12	PSMD12	12238	-0.036	0.27	NO
98	PSMD7	PSMD7	PSMD7	12264	-0.036	0.27	NO
99	PSME1	PSME1	PSME1	12450	-0.041	0.26	NO
100	PSMA2	PSMA2	PSMA2	12520	-0.043	0.26	NO
101	MDM2	MDM2	MDM2	13368	-0.066	0.22	NO
102	CDKN1B	CDKN1B	CDKN1B	13369	-0.066	0.22	NO
103	ANAPC10	ANAPC10	ANAPC10	13877	-0.084	0.2	NO
104	PSMB8	PSMB8	PSMB8	13957	-0.087	0.2	NO
105	CDKN1A	CDKN1A	CDKN1A	15574	-0.17	0.12	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 TRANSPORT OF MATURE MRNA DERIVED FROM AN INTRONLESS TRANSCRIPT.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME TRANSPORT OF MATURE MRNA DERIVED FROM AN INTRONLESS TRANSCRIPT, 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 GLYCINE SERINE AND THREONINE METABOLISM	31	genes.ES.table	0.74	1.6	0.037	0.54	0.96	0.48	0.097	0.44	0.29	0.16
KEGG CYSTEINE AND METHIONINE METABOLISM	34	genes.ES.table	0.53	1.6	0.027	0.57	0.93	0.29	0.14	0.25	0.29	0.17
KEGG LYSINE DEGRADATION	44	genes.ES.table	0.51	1.7	0.043	1	0.73	0.43	0.27	0.32	0.6	0.34
KEGG PYRUVATE METABOLISM	39	genes.ES.table	0.51	1.6	0.031	0.77	0.91	0.41	0.19	0.34	0.38	0.24
KEGG DNA REPLICATION	36	genes.ES.table	0.66	1.6	0.064	0.49	0.96	0.67	0.24	0.51	0.26	0.14
KEGG BASE EXCISION REPAIR	33	genes.ES.table	0.5	1.6	0.067	0.61	0.93	0.39	0.24	0.3	0.3	0.18
KEGG NUCLEOTIDE EXCISION REPAIR	44	genes.ES.table	0.46	1.7	0.04	1	0.74	0.46	0.32	0.31	0.42	0.27
KEGG OOCYTE MEIOSIS	107	genes.ES.table	0.47	1.6	0.034	0.75	0.92	0.23	0.077	0.22	0.37	0.22
PID FANCONI PATHWAY	46	genes.ES.table	0.69	1.7	0.02	0.79	0.84	0.5	0.15	0.43	0.32	0.22
PID E2F PATHWAY	70	genes.ES.table	0.56	1.6	0.06	0.54	0.94	0.39	0.15	0.33	0.28	0.17

genes ES table in pathway: KEGG GLYCINE SERINE AND THREONINE 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	POLE2	POLE2	POLE2	76	0.45	0.058	YES
2	BRIP1	BRIP1	BRIP1	175	0.38	0.11	YES
3	FANCA	FANCA	FANCA	670	0.25	0.11	YES
4	RAD51	RAD51	RAD51	677	0.25	0.15	YES
5	FANCD2	FANCD2	FANCD2	701	0.25	0.18	YES
6	FANCE	FANCE	FANCE	823	0.23	0.21	YES
7	FANCB	FANCB	FANCB	845	0.23	0.24	YES
8	BRCA2	BRCA2	BRCA2	912	0.22	0.26	YES
9	UBE2T	UBE2T	UBE2T	1022	0.21	0.29	YES
10	FANCM	FANCM	FANCM	1454	0.17	0.29	YES
11	RFC4	RFC4	RFC4	1498	0.16	0.31	YES
12	FANCC	FANCC	FANCC	1499	0.16	0.33	YES
13	BRCA1	BRCA1	BRCA1	1510	0.16	0.35	YES
14	C19orf40	C19orf40	C19orf40	1562	0.16	0.37	YES
15	RFC5	RFC5	RFC5	1623	0.16	0.39	YES
16	FEN1	FEN1	FEN1	1732	0.15	0.4	YES
17	ERCC4	ERCC4	ERCC4	1839	0.14	0.42	YES
18	RFC3	RFC3	RFC3	2072	0.13	0.42	YES
19	RPA3	RPA3	RPA3	2426	0.11	0.42	YES
20	LIG1	LIG1	LIG1	2547	0.11	0.42	YES
21	FANCG	FANCG	FANCG	2555	0.1	0.44	YES
22	PALB2	PALB2	PALB2	2616	0.1	0.45	YES
23	MAD2L2	MAD2L2	MAD2L2	2655	0.1	0.46	YES
24	POLE	POLE	POLE	2743	0.097	0.47	YES
25	PCNA	PCNA	PCNA	3110	0.086	0.46	YES
26	ALKBH2	ALKBH2	ALKBH2	3350	0.079	0.46	YES
27	USP1	USP1	USP1	3422	0.077	0.46	YES
28	POLD3	POLD3	POLD3	3540	0.074	0.47	YES
29	OGG1	OGG1	OGG1	3627	0.072	0.47	YES
30	ALKBH3	ALKBH3	ALKBH3	3654	0.07	0.48	YES
31	ERCC8	ERCC8	ERCC8	3732	0.069	0.49	YES
32	GTF2H3	GTF2H3	GTF2H3	3830	0.067	0.49	YES
33	LIG4	LIG4	LIG4	3880	0.066	0.5	YES
34	XPC	XPC	XPC	3925	0.064	0.5	YES
35	POLD2	POLD2	POLD2	4182	0.059	0.5	YES
36	MUTYH	MUTYH	MUTYH	4204	0.058	0.5	YES
37	MDC1	MDC1	MDC1	4387	0.055	0.5	YES
38	DDB2	DDB2	DDB2	4431	0.054	0.51	YES
39	RFC2	RFC2	RFC2	4751	0.048	0.5	NO
40	POLD4	POLD4	POLD4	5032	0.043	0.49	NO
41	RAD50	RAD50	RAD50	5067	0.042	0.49	NO
42	POLD1	POLD1	POLD1	5176	0.04	0.49	NO
43	NTHL1	NTHL1	NTHL1	5366	0.038	0.48	NO
44	XRCC4	XRCC4	XRCC4	5402	0.037	0.49	NO
45	CCNH	CCNH	CCNH	5484	0.036	0.49	NO
46	REV3L	REV3L	REV3L	5690	0.033	0.48	NO
47	C17orf70	C17orf70	C17orf70	5956	0.029	0.47	NO
48	GTF2H4	GTF2H4	GTF2H4	6428	0.023	0.44	NO
49	MPG	MPG	MPG	6585	0.021	0.44	NO
50	XRCC1	XRCC1	XRCC1	6736	0.019	0.43	NO
51	POLR2L	POLR2L	POLR2L	6867	0.017	0.43	NO
52	FANCF	FANCF	FANCF	6901	0.017	0.43	NO
53	POLR2E	POLR2E	POLR2E	7113	0.014	0.42	NO
54	MRE11A	MRE11A	MRE11A	7167	0.013	0.42	NO
55	TCEA1	TCEA1	TCEA1	7210	0.013	0.42	NO
56	DDB1	DDB1	DDB1	7235	0.013	0.42	NO
57	XAB2	XAB2	XAB2	7472	0.0099	0.41	NO
58	LIG3	LIG3	LIG3	7486	0.0097	0.41	NO
59	ERCC5	ERCC5	ERCC5	7549	0.009	0.4	NO
60	REV1	REV1	REV1	7597	0.0083	0.4	NO
61	MBD4	MBD4	MBD4	7773	0.0063	0.39	NO
62	FANCL	FANCL	FANCL	7787	0.0061	0.39	NO
63	POLR2I	POLR2I	POLR2I	7947	0.0043	0.38	NO
64	RPA2	RPA2	RPA2	8195	0.0016	0.37	NO
65	POLR2D	POLR2D	POLR2D	8245	0.001	0.37	NO
66	RAD23B	RAD23B	RAD23B	8261	0.00086	0.37	NO
67	POLH	POLH	POLH	8400	-0.00086	0.36	NO
68	H2AFX	H2AFX	H2AFX	8435	-0.0012	0.36	NO
69	XRCC5	XRCC5	XRCC5	8639	-0.0036	0.35	NO
70	POLR2C	POLR2C	POLR2C	8700	-0.0044	0.34	NO
71	TDG	TDG	TDG	8725	-0.0047	0.34	NO
72	ERCC3	ERCC3	ERCC3	8932	-0.007	0.33	NO
73	CCNO	CCNO	CCNO	9038	-0.0081	0.33	NO
74	ATR	ATR	ATR	9164	-0.0096	0.32	NO
75	POLR2K	POLR2K	POLR2K	9210	-0.01	0.32	NO
76	POLR2G	POLR2G	POLR2G	9342	-0.012	0.32	NO
77	ERCC6	ERCC6	ERCC6	9394	-0.012	0.31	NO
78	ATM	ATM	ATM	9537	-0.014	0.31	NO
79	SMUG1	SMUG1	SMUG1	9643	-0.015	0.3	NO
80	GTF2H1	GTF2H1	GTF2H1	9666	-0.016	0.3	NO
81	POLR2B	POLR2B	POLR2B	9961	-0.019	0.29	NO
82	MNAT1	MNAT1	MNAT1	9987	-0.019	0.29	NO
83	PRKDC	PRKDC	PRKDC	10079	-0.02	0.29	NO
84	POLR2J	POLR2J	POLR2J	10228	-0.022	0.28	NO
85	APEX1	APEX1	APEX1	10229	-0.022	0.29	NO
86	ERCC2	ERCC2	ERCC2	10243	-0.022	0.29	NO
87	TDP1	TDP1	TDP1	10270	-0.023	0.29	NO
88	POLR2F	POLR2F	POLR2F	10274	-0.023	0.3	NO
89	RPA1	RPA1	RPA1	10359	-0.024	0.29	NO
90	ERCC1	ERCC1	ERCC1	11036	-0.034	0.26	NO
91	XRCC6	XRCC6	XRCC6	11117	-0.036	0.26	NO
92	RAD52	RAD52	RAD52	11127	-0.036	0.26	NO
93	UBA52	UBA52	UBA52	11394	-0.04	0.26	NO
94	MGMT	MGMT	MGMT	11467	-0.042	0.26	NO
95	NBN	NBN	NBN	11542	-0.043	0.26	NO
96	GTF2H2B	GTF2H2B	GTF2H2B	11685	-0.046	0.26	NO
97	XPA	XPA	XPA	11829	-0.049	0.26	NO
98	POLR2H	POLR2H	POLR2H	12376	-0.059	0.23	NO
99	TP53BP1	TP53BP1	TP53BP1	12517	-0.063	0.23	NO
100	GTF2H2	GTF2H2	GTF2H2	12558	-0.064	0.24	NO
101	ZBTB32	ZBTB32	ZBTB32	12721	-0.068	0.24	NO
102	CDK7	CDK7	CDK7	12840	-0.071	0.24	NO
103	POLB	POLB	POLB	12942	-0.074	0.25	NO
104	RPS27A	RPS27A	RPS27A	12974	-0.075	0.26	NO
105	POLR2A	POLR2A	POLR2A	13211	-0.082	0.26	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 GLYCINE SERINE AND THREONINE METABOLISM.

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

genes ES table in pathway: KEGG CYSTEINE AND METHIONINE METABOLISM

Table 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	BBOX1	BBOX1	BBOX1	232	0.36	0.1	YES
2	AADAT	AADAT	AADAT	603	0.26	0.17	YES
3	AASS	AASS	AASS	675	0.25	0.25	YES
4	PIPOX	PIPOX	PIPOX	1081	0.2	0.3	YES
5	EHHADH	EHHADH	EHHADH	1725	0.15	0.31	YES
6	ALDH7A1	ALDH7A1	ALDH7A1	1962	0.13	0.34	YES
7	SUV39H1	SUV39H1	SUV39H1	2400	0.11	0.35	YES
8	SETD7	SETD7	SETD7	2526	0.11	0.38	YES
9	OGDHL	OGDHL	OGDHL	2712	0.099	0.4	YES
10	SUV420H2	SUV420H2	SUV420H2	3178	0.084	0.4	YES
11	ALDH9A1	ALDH9A1	ALDH9A1	3241	0.082	0.43	YES
12	PLOD1	PLOD1	PLOD1	3267	0.081	0.45	YES
13	ACAT2	ACAT2	ACAT2	3289	0.08	0.48	YES
14	GCDH	GCDH	GCDH	3668	0.07	0.48	YES
15	OGDH	OGDH	OGDH	4059	0.061	0.48	YES
16	ALDH2	ALDH2	ALDH2	4111	0.06	0.5	YES
17	HADH	HADH	HADH	4451	0.054	0.5	YES
18	WHSC1	WHSC1	WHSC1	4527	0.052	0.51	YES
19	SETD2	SETD2	SETD2	4735	0.048	0.51	YES
20	DOT1L	DOT1L	DOT1L	5269	0.039	0.5	NO
21	ACAT1	ACAT1	ACAT1	5616	0.034	0.49	NO
22	PLOD3	PLOD3	PLOD3	5867	0.03	0.48	NO
23	PLOD2	PLOD2	PLOD2	5964	0.029	0.49	NO
24	SETD1A	SETD1A	SETD1A	6132	0.026	0.49	NO
25	ASH1L	ASH1L	ASH1L	6364	0.024	0.48	NO
26	SUV420H1	SUV420H1	SUV420H1	6583	0.021	0.48	NO
27	NSD1	NSD1	NSD1	7092	0.014	0.45	NO
28	HADHA	HADHA	HADHA	7108	0.014	0.46	NO
29	SUV39H2	SUV39H2	SUV39H2	7528	0.0093	0.44	NO
30	WHSC1L1	WHSC1L1	WHSC1L1	7536	0.0092	0.44	NO
31	AASDH	AASDH	AASDH	8013	0.0037	0.41	NO
32	TMLHE	TMLHE	TMLHE	8393	-0.00082	0.39	NO
33	SETMAR	SETMAR	SETMAR	8778	-0.0054	0.37	NO
34	SETDB1	SETDB1	SETDB1	9435	-0.013	0.34	NO
35	EHMT2	EHMT2	EHMT2	9572	-0.014	0.34	NO
36	DLST	DLST	DLST	9836	-0.017	0.33	NO
37	ECHS1	ECHS1	ECHS1	9837	-0.017	0.33	NO
38	SETD1B	SETD1B	SETD1B	9910	-0.018	0.33	NO
39	AASDHPPT	AASDHPPT	AASDHPPT	10426	-0.025	0.31	NO
40	EHMT1	EHMT1	EHMT1	10552	-0.027	0.32	NO
41	SETD8	SETD8	SETD8	11239	-0.038	0.29	NO
42	ALDH1B1	ALDH1B1	ALDH1B1	11875	-0.049	0.27	NO
43	ALDH3A2	ALDH3A2	ALDH3A2	12533	-0.063	0.25	NO
44	SETDB2	SETDB2	SETDB2	14338	-0.12	0.19	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 CYSTEINE AND METHIONINE METABOLISM.

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

genes ES table in pathway: KEGG LYSINE DEGRADATION

Table 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	POLE2	POLE2	POLE2	76	0.45	0.17	YES
2	RFC4	RFC4	RFC4	1498	0.16	0.15	YES
3	RFC5	RFC5	RFC5	1623	0.16	0.2	YES
4	ERCC4	ERCC4	ERCC4	1839	0.14	0.24	YES
5	RFC3	RFC3	RFC3	2072	0.13	0.28	YES
6	RPA3	RPA3	RPA3	2426	0.11	0.3	YES
7	LIG1	LIG1	LIG1	2547	0.11	0.34	YES
8	POLE	POLE	POLE	2743	0.097	0.36	YES
9	PCNA	PCNA	PCNA	3110	0.086	0.38	YES
10	POLD3	POLD3	POLD3	3540	0.074	0.38	YES
11	ERCC8	ERCC8	ERCC8	3732	0.069	0.4	YES
12	GTF2H3	GTF2H3	GTF2H3	3830	0.067	0.42	YES
13	XPC	XPC	XPC	3925	0.064	0.44	YES
14	POLD2	POLD2	POLD2	4182	0.059	0.44	YES
15	DDB2	DDB2	DDB2	4431	0.054	0.45	YES
16	RFC2	RFC2	RFC2	4751	0.048	0.45	YES
17	POLD4	POLD4	POLD4	5032	0.043	0.45	YES
18	POLD1	POLD1	POLD1	5176	0.04	0.46	YES
19	CCNH	CCNH	CCNH	5484	0.036	0.46	YES
20	RFC1	RFC1	RFC1	5614	0.034	0.46	YES
21	GTF2H4	GTF2H4	GTF2H4	6428	0.023	0.42	NO
22	RAD23A	RAD23A	RAD23A	6732	0.019	0.41	NO
23	DDB1	DDB1	DDB1	7235	0.013	0.39	NO
24	POLE3	POLE3	POLE3	7244	0.013	0.39	NO
25	ERCC5	ERCC5	ERCC5	7549	0.009	0.38	NO
26	RPA2	RPA2	RPA2	8195	0.0016	0.34	NO
27	CUL4B	CUL4B	CUL4B	8220	0.0013	0.34	NO
28	RAD23B	RAD23B	RAD23B	8261	0.00086	0.34	NO
29	ERCC3	ERCC3	ERCC3	8932	-0.007	0.31	NO
30	CUL4A	CUL4A	CUL4A	9079	-0.0088	0.3	NO
31	ERCC6	ERCC6	ERCC6	9394	-0.012	0.29	NO
32	GTF2H1	GTF2H1	GTF2H1	9666	-0.016	0.28	NO
33	MNAT1	MNAT1	MNAT1	9987	-0.019	0.27	NO
34	ERCC2	ERCC2	ERCC2	10243	-0.022	0.26	NO
35	RPA1	RPA1	RPA1	10359	-0.024	0.26	NO
36	GTF2H5	GTF2H5	GTF2H5	10452	-0.026	0.27	NO
37	POLE4	POLE4	POLE4	10678	-0.029	0.27	NO
38	ERCC1	ERCC1	ERCC1	11036	-0.034	0.26	NO
39	RBX1	RBX1	RBX1	11150	-0.036	0.27	NO
40	CETN2	CETN2	CETN2	11392	-0.04	0.27	NO
41	RPA4	RPA4	RPA4	11481	-0.042	0.28	NO
42	XPA	XPA	XPA	11829	-0.049	0.28	NO
43	GTF2H2	GTF2H2	GTF2H2	12558	-0.064	0.26	NO
44	CDK7	CDK7	CDK7	12840	-0.071	0.28	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 LYSINE DEGRADATION.

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

genes ES table in pathway: KEGG PYRUVATE METABOLISM

Table S14. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	POLE2	POLE2	POLE2	76	0.45	0.19	YES
2	RFC4	RFC4	RFC4	1498	0.16	0.18	YES
3	RFC5	RFC5	RFC5	1623	0.16	0.24	YES
4	ERCC4	ERCC4	ERCC4	1839	0.14	0.29	YES
5	RFC3	RFC3	RFC3	2072	0.13	0.33	YES
6	RPA3	RPA3	RPA3	2426	0.11	0.36	YES
7	LIG1	LIG1	LIG1	2547	0.11	0.4	YES
8	POLE	POLE	POLE	2743	0.097	0.43	YES
9	PCNA	PCNA	PCNA	3110	0.086	0.44	YES
10	POLD3	POLD3	POLD3	3540	0.074	0.45	YES
11	GTF2H3	GTF2H3	GTF2H3	3830	0.067	0.46	YES
12	XPC	XPC	XPC	3925	0.064	0.49	YES
13	POLD2	POLD2	POLD2	4182	0.059	0.5	YES
14	DDB2	DDB2	DDB2	4431	0.054	0.51	YES
15	RFC2	RFC2	RFC2	4751	0.048	0.51	YES
16	POLD4	POLD4	POLD4	5032	0.043	0.51	YES
17	POLD1	POLD1	POLD1	5176	0.04	0.52	YES
18	CCNH	CCNH	CCNH	5484	0.036	0.52	NO
19	GTF2H4	GTF2H4	GTF2H4	6428	0.023	0.48	NO
20	DDB1	DDB1	DDB1	7235	0.013	0.44	NO
21	ERCC5	ERCC5	ERCC5	7549	0.009	0.42	NO
22	RPA2	RPA2	RPA2	8195	0.0016	0.38	NO
23	RAD23B	RAD23B	RAD23B	8261	0.00086	0.38	NO
24	ERCC3	ERCC3	ERCC3	8932	-0.007	0.35	NO
25	GTF2H1	GTF2H1	GTF2H1	9666	-0.016	0.31	NO
26	MNAT1	MNAT1	MNAT1	9987	-0.019	0.3	NO
27	ERCC2	ERCC2	ERCC2	10243	-0.022	0.3	NO
28	RPA1	RPA1	RPA1	10359	-0.024	0.3	NO
29	ERCC1	ERCC1	ERCC1	11036	-0.034	0.28	NO
30	GTF2H2B	GTF2H2B	GTF2H2B	11685	-0.046	0.26	NO
31	XPA	XPA	XPA	11829	-0.049	0.27	NO
32	GTF2H2	GTF2H2	GTF2H2	12558	-0.064	0.26	NO
33	CDK7	CDK7	CDK7	12840	-0.071	0.28	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 PYRUVATE METABOLISM.

Figure S28. 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 DNA REPLICATION

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	PFKFB1	PFKFB1	PFKFB1	130	0.41	0.14	YES
2	ALDOB	ALDOB	ALDOB	396	0.3	0.23	YES
3	FBP2	FBP2	FBP2	744	0.24	0.3	YES
4	ALDOC	ALDOC	ALDOC	869	0.23	0.38	YES
5	FBP1	FBP1	FBP1	1185	0.19	0.43	YES
6	PCK2	PCK2	PCK2	1369	0.18	0.48	YES
7	PCK1	PCK1	PCK1	1487	0.16	0.53	YES
8	SLC25A10	SLC25A10	SLC25A10	1746	0.15	0.57	YES
9	ENO3	ENO3	ENO3	2711	0.099	0.55	NO
10	MDH1	MDH1	MDH1	5018	0.043	0.44	NO
11	GOT2	GOT2	GOT2	6339	0.024	0.37	NO
12	PRKACB	PRKACB	PRKACB	6458	0.022	0.37	NO
13	GPI	GPI	GPI	6602	0.02	0.37	NO
14	PC	PC	PC	6679	0.02	0.38	NO
15	PGK1	PGK1	PGK1	7604	0.0083	0.33	NO
16	TPI1	TPI1	TPI1	7703	0.007	0.32	NO
17	ENO1	ENO1	ENO1	7785	0.0062	0.32	NO
18	SLC25A13	SLC25A13	SLC25A13	7904	0.0049	0.32	NO
19	GOT1	GOT1	GOT1	7923	0.0047	0.32	NO
20	SLC25A11	SLC25A11	SLC25A11	9806	-0.017	0.22	NO
21	SLC25A1	SLC25A1	SLC25A1	9973	-0.019	0.21	NO
22	PRKACA	PRKACA	PRKACA	10396	-0.025	0.2	NO
23	PGAM1	PGAM1	PGAM1	10434	-0.025	0.21	NO
24	PGAM2	PGAM2	PGAM2	10581	-0.028	0.21	NO
25	GAPDHS	GAPDHS	GAPDHS	10797	-0.031	0.21	NO
26	GAPDH	GAPDH	GAPDH	10892	-0.032	0.21	NO
27	ALDOA	ALDOA	ALDOA	11626	-0.045	0.19	NO
28	MDH2	MDH2	MDH2	12264	-0.057	0.17	NO
29	SLC25A12	SLC25A12	SLC25A12	12873	-0.072	0.16	NO
30	ENO2	ENO2	ENO2	16974	-0.3	0.041	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 DNA REPLICATION.

Figure S30. 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 BASE EXCISION REPAIR

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	BRIP1	BRIP1	BRIP1	175	0.38	0.067	YES
2	FANCA	FANCA	FANCA	670	0.25	0.09	YES
3	FANCD2	FANCD2	FANCD2	701	0.25	0.14	YES
4	FANCE	FANCE	FANCE	823	0.23	0.18	YES
5	FANCI	FANCI	FANCI	833	0.23	0.22	YES
6	FANCB	FANCB	FANCB	845	0.23	0.27	YES
7	BRCA2	BRCA2	BRCA2	912	0.22	0.31	YES
8	UBE2T	UBE2T	UBE2T	1022	0.21	0.35	YES
9	XRCC3	XRCC3	XRCC3	1114	0.2	0.38	YES
10	BLM	BLM	BLM	1223	0.19	0.41	YES
11	FANCM	FANCM	FANCM	1454	0.17	0.44	YES
12	RFC4	RFC4	RFC4	1498	0.16	0.46	YES
13	FANCC	FANCC	FANCC	1499	0.16	0.5	YES
14	BRCA1	BRCA1	BRCA1	1510	0.16	0.53	YES
15	C19orf40	C19orf40	C19orf40	1562	0.16	0.56	YES
16	RFC5	RFC5	RFC5	1623	0.16	0.59	YES
17	RFC3	RFC3	RFC3	2072	0.13	0.59	YES
18	RMI1	RMI1	RMI1	2293	0.12	0.6	YES
19	CHEK1	CHEK1	CHEK1	2509	0.11	0.61	YES
20	FANCG	FANCG	FANCG	2555	0.1	0.63	YES
21	RAD9A	RAD9A	RAD9A	2568	0.1	0.65	YES
22	TOPBP1	TOPBP1	TOPBP1	2591	0.1	0.67	YES
23	PALB2	PALB2	PALB2	2616	0.1	0.69	YES
24	APITD1	APITD1	APITD1	3408	0.077	0.66	NO
25	USP1	USP1	USP1	3422	0.077	0.67	NO
26	ATRIP	ATRIP	ATRIP	3874	0.066	0.66	NO
27	RAD1	RAD1	RAD1	3990	0.063	0.67	NO
28	RAD17	RAD17	RAD17	4327	0.056	0.66	NO
29	RFC2	RFC2	RFC2	4751	0.048	0.64	NO
30	RAD50	RAD50	RAD50	5067	0.042	0.64	NO
31	HUS1	HUS1	HUS1	5142	0.041	0.64	NO
32	FBXW11	FBXW11	FBXW11	5237	0.04	0.64	NO
33	C17orf70	C17orf70	C17orf70	5956	0.029	0.61	NO
34	FANCF	FANCF	FANCF	6901	0.017	0.56	NO
35	MRE11A	MRE11A	MRE11A	7167	0.013	0.54	NO
36	FANCL	FANCL	FANCL	7787	0.0061	0.51	NO
37	RPA2	RPA2	RPA2	8195	0.0016	0.49	NO
38	TOP3A	TOP3A	TOP3A	8266	0.00077	0.48	NO
39	H2AFX	H2AFX	H2AFX	8435	-0.0012	0.47	NO
40	ATR	ATR	ATR	9164	-0.0096	0.44	NO
41	ATM	ATM	ATM	9537	-0.014	0.42	NO
42	RPA1	RPA1	RPA1	10359	-0.024	0.38	NO
43	WDR48	WDR48	WDR48	10629	-0.028	0.37	NO
44	HES1	HES1	HES1	11212	-0.037	0.34	NO
45	NBN	NBN	NBN	11542	-0.043	0.33	NO
46	SSPO	SSPO	SSPO	13521	-0.09	0.24	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 BASE EXCISION REPAIR.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG BASE 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 NUCLEOTIDE EXCISION REPAIR

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	POLE2	POLE2	POLE2	76	0.45	0.16	YES
2	RFC4	RFC4	RFC4	1498	0.16	0.14	YES
3	RFC5	RFC5	RFC5	1623	0.16	0.19	YES
4	ERCC4	ERCC4	ERCC4	1839	0.14	0.23	YES
5	RFC3	RFC3	RFC3	2072	0.13	0.27	YES
6	RPA3	RPA3	RPA3	2426	0.11	0.29	YES
7	LIG1	LIG1	LIG1	2547	0.11	0.32	YES
8	POLE	POLE	POLE	2743	0.097	0.35	YES
9	PCNA	PCNA	PCNA	3110	0.086	0.36	YES
10	POLD3	POLD3	POLD3	3540	0.074	0.36	YES
11	ERCC8	ERCC8	ERCC8	3732	0.069	0.38	YES
12	GTF2H3	GTF2H3	GTF2H3	3830	0.067	0.4	YES
13	XPC	XPC	XPC	3925	0.064	0.41	YES
14	POLD2	POLD2	POLD2	4182	0.059	0.42	YES
15	DDB2	DDB2	DDB2	4431	0.054	0.43	YES
16	RFC2	RFC2	RFC2	4751	0.048	0.43	YES
17	POLD4	POLD4	POLD4	5032	0.043	0.43	YES
18	POLD1	POLD1	POLD1	5176	0.04	0.43	YES
19	CCNH	CCNH	CCNH	5484	0.036	0.43	NO
20	GTF2H4	GTF2H4	GTF2H4	6428	0.023	0.38	NO
21	POLR2L	POLR2L	POLR2L	6867	0.017	0.37	NO
22	POLR2E	POLR2E	POLR2E	7113	0.014	0.36	NO
23	TCEA1	TCEA1	TCEA1	7210	0.013	0.36	NO
24	DDB1	DDB1	DDB1	7235	0.013	0.36	NO
25	XAB2	XAB2	XAB2	7472	0.0099	0.35	NO
26	ERCC5	ERCC5	ERCC5	7549	0.009	0.35	NO
27	POLR2I	POLR2I	POLR2I	7947	0.0043	0.33	NO
28	RPA2	RPA2	RPA2	8195	0.0016	0.32	NO
29	POLR2D	POLR2D	POLR2D	8245	0.001	0.31	NO
30	RAD23B	RAD23B	RAD23B	8261	0.00086	0.31	NO
31	POLR2C	POLR2C	POLR2C	8700	-0.0044	0.29	NO
32	ERCC3	ERCC3	ERCC3	8932	-0.007	0.28	NO
33	POLR2K	POLR2K	POLR2K	9210	-0.01	0.27	NO
34	POLR2G	POLR2G	POLR2G	9342	-0.012	0.26	NO
35	ERCC6	ERCC6	ERCC6	9394	-0.012	0.26	NO
36	GTF2H1	GTF2H1	GTF2H1	9666	-0.016	0.26	NO
37	POLR2B	POLR2B	POLR2B	9961	-0.019	0.25	NO
38	MNAT1	MNAT1	MNAT1	9987	-0.019	0.25	NO
39	POLR2J	POLR2J	POLR2J	10228	-0.022	0.25	NO
40	ERCC2	ERCC2	ERCC2	10243	-0.022	0.25	NO
41	POLR2F	POLR2F	POLR2F	10274	-0.023	0.26	NO
42	RPA1	RPA1	RPA1	10359	-0.024	0.26	NO
43	ERCC1	ERCC1	ERCC1	11036	-0.034	0.24	NO
44	GTF2H2B	GTF2H2B	GTF2H2B	11685	-0.046	0.22	NO
45	XPA	XPA	XPA	11829	-0.049	0.23	NO
46	POLR2H	POLR2H	POLR2H	12376	-0.059	0.22	NO
47	GTF2H2	GTF2H2	GTF2H2	12558	-0.064	0.23	NO
48	CDK7	CDK7	CDK7	12840	-0.071	0.24	NO
49	POLR2A	POLR2A	POLR2A	13211	-0.082	0.25	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 NUCLEOTIDE EXCISION REPAIR.

Figure S34. 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 OOCYTE MEIOSIS

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	POLE2	POLE2	POLE2	76	0.45	0.059	YES
2	GINS2	GINS2	GINS2	325	0.32	0.09	YES
3	CCNA2	CCNA2	CCNA2	326	0.32	0.14	YES
4	CDC45	CDC45	CDC45	330	0.32	0.18	YES
5	GINS4	GINS4	GINS4	423	0.3	0.22	YES
6	CDC6	CDC6	CDC6	472	0.29	0.25	YES
7	GINS1	GINS1	GINS1	585	0.27	0.28	YES
8	CDT1	CDT1	CDT1	697	0.25	0.31	YES
9	MCM2	MCM2	MCM2	872	0.23	0.34	YES
10	PRIM1	PRIM1	PRIM1	1159	0.2	0.35	YES
11	DNA2	DNA2	DNA2	1228	0.19	0.37	YES
12	MCM8	MCM8	MCM8	1248	0.19	0.4	YES
13	POLA2	POLA2	POLA2	1484	0.16	0.4	YES
14	RFC4	RFC4	RFC4	1498	0.16	0.43	YES
15	RFC5	RFC5	RFC5	1623	0.16	0.44	YES
16	FEN1	FEN1	FEN1	1732	0.15	0.46	YES
17	CDKN1A	CDKN1A	CDKN1A	1891	0.14	0.47	YES
18	RFC3	RFC3	RFC3	2072	0.13	0.47	YES
19	MCM5	MCM5	MCM5	2308	0.12	0.48	YES
20	MCM6	MCM6	MCM6	2329	0.12	0.49	YES
21	PRIM2	PRIM2	PRIM2	2388	0.11	0.5	YES
22	RPA3	RPA3	RPA3	2426	0.11	0.52	YES
23	LIG1	LIG1	LIG1	2547	0.11	0.53	YES
24	MCM7	MCM7	MCM7	2647	0.1	0.54	YES
25	POLE	POLE	POLE	2743	0.097	0.54	YES
26	PSMB9	PSMB9	PSMB9	2921	0.092	0.55	YES
27	CDK2	CDK2	CDK2	3097	0.086	0.55	YES
28	PCNA	PCNA	PCNA	3110	0.086	0.56	YES
29	PSMB8	PSMB8	PSMB8	3338	0.079	0.56	YES
30	MCM4	MCM4	MCM4	3392	0.078	0.56	YES
31	MCM3	MCM3	MCM3	3444	0.076	0.57	YES
32	POLD3	POLD3	POLD3	3540	0.074	0.58	YES
33	POLA1	POLA1	POLA1	4042	0.062	0.56	NO
34	POLD2	POLD2	POLD2	4182	0.059	0.56	NO
35	CDKN1B	CDKN1B	CDKN1B	4315	0.056	0.56	NO
36	PSMC3	PSMC3	PSMC3	4510	0.053	0.56	NO
37	RFC2	RFC2	RFC2	4751	0.048	0.55	NO
38	PSMD2	PSMD2	PSMD2	4834	0.047	0.55	NO
39	PSMD12	PSMD12	PSMD12	4892	0.046	0.55	NO
40	PSME4	PSME4	PSME4	5001	0.043	0.55	NO
41	PSME1	PSME1	PSME1	5028	0.043	0.56	NO
42	POLD4	POLD4	POLD4	5032	0.043	0.56	NO
43	POLD1	POLD1	POLD1	5176	0.04	0.56	NO
44	PSMC4	PSMC4	PSMC4	5311	0.039	0.56	NO
45	PSMC5	PSMC5	PSMC5	5593	0.034	0.55	NO
46	PSMD10	PSMD10	PSMD10	5819	0.031	0.54	NO
47	PSMD3	PSMD3	PSMD3	5919	0.029	0.54	NO
48	PSMA8	PSMA8	PSMA8	5959	0.029	0.54	NO
49	PSMD11	PSMD11	PSMD11	6129	0.026	0.53	NO
50	PSMA6	PSMA6	PSMA6	6141	0.026	0.54	NO
51	PSMB2	PSMB2	PSMB2	6204	0.026	0.54	NO
52	PSMD9	PSMD9	PSMD9	6303	0.024	0.54	NO
53	PSMA7	PSMA7	PSMA7	6441	0.023	0.53	NO
54	PSMC2	PSMC2	PSMC2	6728	0.019	0.52	NO
55	PSMA1	PSMA1	PSMA1	6870	0.017	0.51	NO
56	PSMD13	PSMD13	PSMD13	6907	0.017	0.51	NO
57	PSMA4	PSMA4	PSMA4	6974	0.016	0.51	NO
58	PSMD8	PSMD8	PSMD8	7010	0.015	0.51	NO
59	PSME2	PSME2	PSME2	7026	0.015	0.51	NO
60	PSMC6	PSMC6	PSMC6	7358	0.011	0.49	NO
61	PSMA5	PSMA5	PSMA5	7396	0.011	0.49	NO
62	PSMD14	PSMD14	PSMD14	7927	0.0046	0.46	NO
63	PSMD6	PSMD6	PSMD6	8015	0.0037	0.46	NO
64	PSMA3	PSMA3	PSMA3	8055	0.0032	0.46	NO
65	RPA2	RPA2	RPA2	8195	0.0016	0.45	NO
66	PSMB4	PSMB4	PSMB4	8414	-0.001	0.44	NO
67	PSMA2	PSMA2	PSMA2	8454	-0.0015	0.44	NO
68	PSMD1	PSMD1	PSMD1	8577	-0.0029	0.43	NO
69	PSMB3	PSMB3	PSMB3	8657	-0.0039	0.42	NO
70	PSMD7	PSMD7	PSMD7	8682	-0.0042	0.42	NO
71	PSMB1	PSMB1	PSMB1	8801	-0.0056	0.42	NO
72	PSMC1	PSMC1	PSMC1	9123	-0.0092	0.4	NO
73	PSMB7	PSMB7	PSMB7	9386	-0.012	0.39	NO
74	PSMB10	PSMB10	PSMB10	9696	-0.016	0.37	NO
75	PSMB5	PSMB5	PSMB5	9894	-0.018	0.36	NO
76	PSMD4	PSMD4	PSMD4	9902	-0.018	0.37	NO
77	RPA1	RPA1	RPA1	10359	-0.024	0.34	NO
78	PSMF1	PSMF1	PSMF1	10440	-0.026	0.34	NO
79	UBA52	UBA52	UBA52	11394	-0.04	0.3	NO
80	PSMD5	PSMD5	PSMD5	11807	-0.048	0.28	NO
81	PSMB6	PSMB6	PSMB6	12025	-0.052	0.27	NO
82	RPS27A	RPS27A	RPS27A	12974	-0.075	0.23	NO
83	CCNA1	CCNA1	CCNA1	13920	-0.1	0.19	NO
84	RB1	RB1	RB1	15271	-0.17	0.14	NO

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

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

genes ES table in pathway: PID FANCONI PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACOT12	ACOT12	ACOT12	459	0.29	0.058	YES
2	ACACB	ACACB	ACACB	592	0.27	0.13	YES
3	PKLR	PKLR	PKLR	809	0.23	0.18	YES
4	PCK2	PCK2	PCK2	1369	0.18	0.2	YES
5	PCK1	PCK1	PCK1	1487	0.16	0.24	YES
6	ME3	ME3	ME3	1785	0.14	0.27	YES
7	HAGH	HAGH	HAGH	1787	0.14	0.31	YES
8	LDHC	LDHC	LDHC	1838	0.14	0.35	YES
9	ACSS2	ACSS2	ACSS2	1899	0.14	0.39	YES
10	ALDH7A1	ALDH7A1	ALDH7A1	1962	0.13	0.42	YES
11	LDHAL6B	LDHAL6B	LDHAL6B	2269	0.12	0.44	YES
12	ME1	ME1	ME1	2585	0.1	0.45	YES
13	ACYP1	ACYP1	ACYP1	2606	0.1	0.48	YES
14	LDHD	LDHD	LDHD	2826	0.095	0.49	YES
15	ALDH9A1	ALDH9A1	ALDH9A1	3241	0.082	0.49	YES
16	ACAT2	ACAT2	ACAT2	3289	0.08	0.52	YES
17	ALDH2	ALDH2	ALDH2	4111	0.06	0.49	NO
18	MDH1	MDH1	MDH1	5018	0.043	0.45	NO
19	ACYP2	ACYP2	ACYP2	5208	0.04	0.45	NO
20	ACAT1	ACAT1	ACAT1	5616	0.034	0.43	NO
21	GRHPR	GRHPR	GRHPR	5758	0.032	0.44	NO
22	ACACA	ACACA	ACACA	6596	0.021	0.39	NO
23	PC	PC	PC	6679	0.02	0.4	NO
24	LDHAL6A	LDHAL6A	LDHAL6A	6896	0.017	0.39	NO
25	PDHB	PDHB	PDHB	7577	0.0086	0.35	NO
26	GLO1	GLO1	GLO1	7661	0.0075	0.35	NO
27	DLD	DLD	DLD	8088	0.0029	0.33	NO
28	DLAT	DLAT	DLAT	8109	0.0027	0.33	NO
29	PDHA1	PDHA1	PDHA1	8239	0.0012	0.32	NO
30	ME2	ME2	ME2	8481	-0.0017	0.31	NO
31	AKR1B1	AKR1B1	AKR1B1	10153	-0.021	0.22	NO
32	LDHA	LDHA	LDHA	10203	-0.022	0.22	NO
33	ALDH1B1	ALDH1B1	ALDH1B1	11875	-0.049	0.14	NO
34	MDH2	MDH2	MDH2	12264	-0.057	0.14	NO
35	ALDH3A2	ALDH3A2	ALDH3A2	12533	-0.063	0.14	NO
36	PKM2	PKM2	PKM2	13295	-0.084	0.12	NO
37	ACSS1	ACSS1	ACSS1	13808	-0.1	0.12	NO
38	LDHB	LDHB	LDHB	15257	-0.16	0.085	NO
39	HAGHL	HAGHL	HAGHL	15545	-0.18	0.12	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: PID FANCONI PATHWAY.

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: PID FANCONI 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 E2F PATHWAY

Table S20. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CDC25C	CDC25C	CDC25C	136	0.4	0.028	YES
2	SGOL1	SGOL1	SGOL1	242	0.35	0.053	YES
3	FBXO43	FBXO43	FBXO43	377	0.31	0.073	YES
4	IGF1	IGF1	IGF1	411	0.3	0.097	YES
5	SPDYC	SPDYC	SPDYC	515	0.28	0.12	YES
6	CCNB2	CCNB2	CCNB2	531	0.28	0.14	YES
7	BUB1	BUB1	BUB1	577	0.27	0.16	YES
8	PKMYT1	PKMYT1	PKMYT1	589	0.27	0.18	YES
9	ESPL1	ESPL1	ESPL1	652	0.26	0.2	YES
10	CCNE2	CCNE2	CCNE2	654	0.26	0.22	YES
11	CDC20	CDC20	CDC20	655	0.26	0.25	YES
12	AR	AR	AR	716	0.25	0.27	YES
13	SMC1B	SMC1B	SMC1B	726	0.25	0.29	YES
14	PTTG1	PTTG1	PTTG1	798	0.24	0.3	YES
15	PLK1	PLK1	PLK1	916	0.22	0.32	YES
16	CCNE1	CCNE1	CCNE1	941	0.22	0.34	YES
17	AURKA	AURKA	AURKA	960	0.22	0.35	YES
18	MAD2L1	MAD2L1	MAD2L1	990	0.21	0.37	YES
19	CCNB1	CCNB1	CCNB1	1042	0.21	0.38	YES
20	CDK1	CDK1	CDK1	1059	0.2	0.4	YES
21	ADCY1	ADCY1	ADCY1	1074	0.2	0.42	YES
22	PLCZ1	PLCZ1	PLCZ1	1172	0.19	0.43	YES
23	CHP2	CHP2	CHP2	1272	0.18	0.44	YES
24	CALML6	CALML6	CALML6	1328	0.18	0.45	YES
25	RPS6KA1	RPS6KA1	RPS6KA1	1367	0.18	0.47	YES
26	PTTG2	PTTG2	PTTG2	1624	0.16	0.47	NO
27	CALML3	CALML3	CALML3	2163	0.12	0.45	NO
28	ADCY9	ADCY9	ADCY9	2403	0.11	0.44	NO
29	MAD2L2	MAD2L2	MAD2L2	2655	0.1	0.44	NO
30	SMC1A	SMC1A	SMC1A	3018	0.089	0.42	NO
31	CDK2	CDK2	CDK2	3097	0.086	0.43	NO
32	FBXO5	FBXO5	FBXO5	3449	0.076	0.42	NO
33	PPP2R1B	PPP2R1B	PPP2R1B	4230	0.058	0.38	NO
34	STAG3	STAG3	STAG3	4525	0.052	0.36	NO
35	PPP2R5B	PPP2R5B	PPP2R5B	4728	0.049	0.36	NO
36	ANAPC11	ANAPC11	ANAPC11	4969	0.044	0.35	NO
37	FBXW11	FBXW11	FBXW11	5237	0.04	0.34	NO
38	CDC23	CDC23	CDC23	5696	0.033	0.31	NO
39	PPP1CB	PPP1CB	PPP1CB	5872	0.03	0.3	NO
40	PPP2R5D	PPP2R5D	PPP2R5D	6009	0.028	0.3	NO
41	PPP2R5A	PPP2R5A	PPP2R5A	6010	0.028	0.3	NO
42	ITPR1	ITPR1	ITPR1	6191	0.026	0.29	NO
43	PRKACB	PRKACB	PRKACB	6458	0.022	0.28	NO
44	PPP2R5E	PPP2R5E	PPP2R5E	6474	0.022	0.28	NO
45	MAP2K1	MAP2K1	MAP2K1	6498	0.022	0.28	NO
46	ADCY6	ADCY6	ADCY6	6615	0.02	0.28	NO
47	PPP2CA	PPP2CA	PPP2CA	6632	0.02	0.28	NO
48	CHP	CHP	CHP	6795	0.018	0.27	NO
49	PPP1CC	PPP1CC	PPP1CC	6827	0.018	0.27	NO
50	RPS6KA6	RPS6KA6	RPS6KA6	7053	0.015	0.26	NO
51	PPP1CA	PPP1CA	PPP1CA	7152	0.014	0.26	NO
52	ANAPC2	ANAPC2	ANAPC2	7240	0.013	0.25	NO
53	ANAPC5	ANAPC5	ANAPC5	7401	0.011	0.24	NO
54	ANAPC7	ANAPC7	ANAPC7	7591	0.0084	0.23	NO
55	YWHAB	YWHAB	YWHAB	7651	0.0076	0.23	NO
56	CDC27	CDC27	CDC27	7691	0.0072	0.23	NO
57	SKP1	SKP1	SKP1	7872	0.0052	0.22	NO
58	PGR	PGR	PGR	8011	0.0037	0.21	NO
59	MAPK3	MAPK3	MAPK3	8096	0.0028	0.21	NO
60	MAPK1	MAPK1	MAPK1	8583	-0.003	0.18	NO
61	CAMK2G	CAMK2G	CAMK2G	8620	-0.0034	0.18	NO
62	PPP2CB	PPP2CB	PPP2CB	8714	-0.0046	0.17	NO
63	YWHAQ	YWHAQ	YWHAQ	8721	-0.0046	0.17	NO
64	CALM1	CALM1	CALM1	8824	-0.0058	0.17	NO
65	ANAPC13	ANAPC13	ANAPC13	8862	-0.0062	0.17	NO
66	ANAPC10	ANAPC10	ANAPC10	8879	-0.0064	0.17	NO
67	PPP3R1	PPP3R1	PPP3R1	9074	-0.0087	0.16	NO
68	CUL1	CUL1	CUL1	9288	-0.011	0.14	NO
69	PPP3CC	PPP3CC	PPP3CC	9397	-0.012	0.14	NO
70	CALM2	CALM2	CALM2	9441	-0.013	0.14	NO
71	CAMK2D	CAMK2D	CAMK2D	9563	-0.014	0.13	NO
72	RPS6KA3	RPS6KA3	RPS6KA3	9782	-0.017	0.12	NO
73	SPDYA	SPDYA	SPDYA	9864	-0.018	0.12	NO
74	ANAPC4	ANAPC4	ANAPC4	9947	-0.019	0.12	NO
75	YWHAG	YWHAG	YWHAG	9980	-0.019	0.12	NO
76	PPP2R5C	PPP2R5C	PPP2R5C	10004	-0.019	0.12	NO
77	PPP3CA	PPP3CA	PPP3CA	10036	-0.02	0.12	NO
78	ADCY4	ADCY4	ADCY4	10098	-0.02	0.11	NO
79	PRKACA	PRKACA	PRKACA	10396	-0.025	0.099	NO
80	ANAPC1	ANAPC1	ANAPC1	10559	-0.027	0.092	NO
81	YWHAH	YWHAH	YWHAH	10675	-0.029	0.088	NO
82	ITPR2	ITPR2	ITPR2	10727	-0.03	0.088	NO
83	MAPK12	MAPK12	MAPK12	10896	-0.032	0.081	NO
84	CDC26	CDC26	CDC26	11126	-0.036	0.071	NO
85	RBX1	RBX1	RBX1	11150	-0.036	0.073	NO
86	SMC3	SMC3	SMC3	11227	-0.037	0.072	NO
87	SLK	SLK	SLK	11264	-0.038	0.074	NO
88	CDC16	CDC16	CDC16	11723	-0.047	0.052	NO
89	RPS6KA2	RPS6KA2	RPS6KA2	12051	-0.053	0.038	NO
90	PPP2R1A	PPP2R1A	PPP2R1A	12388	-0.059	0.024	NO
91	CALM3	CALM3	CALM3	12496	-0.062	0.023	NO
92	YWHAE	YWHAE	YWHAE	12522	-0.063	0.027	NO
93	PPP3CB	PPP3CB	PPP3CB	12763	-0.069	0.02	NO
94	CAMK2B	CAMK2B	CAMK2B	13655	-0.095	-0.023	NO
95	ADCY3	ADCY3	ADCY3	13856	-0.1	-0.025	NO
96	YWHAZ	YWHAZ	YWHAZ	13973	-0.11	-0.022	NO
97	ADCY2	ADCY2	ADCY2	14222	-0.12	-0.026	NO
98	BTRC	BTRC	BTRC	14459	-0.12	-0.028	NO
99	ITPR3	ITPR3	ITPR3	15304	-0.17	-0.062	NO
100	CAMK2A	CAMK2A	CAMK2A	15981	-0.21	-0.082	NO
101	REC8	REC8	REC8	16071	-0.22	-0.068	NO
102	ADCY5	ADCY5	ADCY5	16217	-0.23	-0.056	NO
103	ADCY7	ADCY7	ADCY7	16272	-0.23	-0.039	NO
104	PRKX	PRKX	PRKX	17094	-0.31	-0.058	NO
105	CPEB1	CPEB1	CPEB1	17196	-0.33	-0.034	NO
106	ADCY8	ADCY8	ADCY8	17306	-0.35	-0.0095	NO
107	IGF1R	IGF1R	IGF1R	17329	-0.36	0.021	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: PID E2F PATHWAY.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: PID E2F PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

Table 5. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus3. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG PURINE METABOLISM	154	genes.ES.table	0.34	1.4	0.017	0.18	0.99	0.22	0.2	0.18	0.13	0.004
KEGG O GLYCAN BIOSYNTHESIS	27	genes.ES.table	0.62	1.5	0.027	0.14	0.97	0.48	0.22	0.37	0.088	0.004
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	43	genes.ES.table	0.45	1.6	0.058	0.13	0.91	0.44	0.34	0.29	0.063	0.004
KEGG GLYCEROLIPID METABOLISM	43	genes.ES.table	0.4	1.4	0.081	0.23	1	0.35	0.24	0.27	0.19	0.004
KEGG INOSITOL PHOSPHATE METABOLISM	54	genes.ES.table	0.47	1.6	0.02	0.13	0.95	0.39	0.29	0.28	0.074	0.004
KEGG GLYCEROPHOSPHOLIPID METABOLISM	70	genes.ES.table	0.48	1.7	0.0021	0.12	0.72	0.57	0.35	0.37	0.043	0.016
KEGG ETHER LIPID METABOLISM	27	genes.ES.table	0.56	1.5	0.017	0.14	0.96	0.56	0.27	0.4	0.078	0.004
KEGG ARACHIDONIC ACID METABOLISM	49	genes.ES.table	0.63	1.6	0.021	0.13	0.94	0.43	0.18	0.35	0.069	0.004
KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES	25	genes.ES.table	0.57	1.5	0.044	0.18	0.99	0.44	0.2	0.35	0.12	0.005
KEGG MAPK SIGNALING PATHWAY	241	genes.ES.table	0.52	1.9	0	0.18	0.36	0.31	0.19	0.25	0	0.041

genes ES table in pathway: KEGG PURINE 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	PDE1A	PDE1A	PDE1A	34	0.71	0.069	YES
2	PLCB4	PLCB4	PLCB4	147	0.58	0.12	YES
3	ADCY4	ADCY4	ADCY4	307	0.49	0.16	YES
4	PLA2G4A	PLA2G4A	PLA2G4A	504	0.42	0.19	YES
5	ADCY5	ADCY5	ADCY5	627	0.39	0.22	YES
6	POMC	POMC	POMC	757	0.37	0.25	YES
7	ADCY2	ADCY2	ADCY2	824	0.36	0.29	YES
8	GNAZ	GNAZ	GNAZ	1044	0.33	0.31	YES
9	ADCY3	ADCY3	ADCY3	1273	0.3	0.32	YES
10	PDE4D	PDE4D	PDE4D	1485	0.28	0.34	YES
11	GNB3	GNB3	GNB3	1491	0.28	0.37	YES
12	GNGT2	GNGT2	GNGT2	1558	0.27	0.39	YES
13	GNB4	GNB4	GNB4	1743	0.25	0.4	YES
14	PLCB2	PLCB2	PLCB2	1912	0.24	0.42	YES
15	CAMK4	CAMK4	CAMK4	1930	0.24	0.44	YES
16	PDE1B	PDE1B	PDE1B	2194	0.22	0.45	YES
17	GNAL	GNAL	GNAL	2233	0.22	0.47	YES
18	ITPR3	ITPR3	ITPR3	2243	0.22	0.49	YES
19	ADCY7	ADCY7	ADCY7	2266	0.21	0.51	YES
20	GNG11	GNG11	GNG11	2532	0.2	0.51	YES
21	PDE4B	PDE4B	PDE4B	2567	0.19	0.53	YES
22	PDE4C	PDE4C	PDE4C	2666	0.19	0.54	YES
23	PPP1R1B	PPP1R1B	PPP1R1B	2735	0.18	0.56	YES
24	PRKAR1B	PRKAR1B	PRKAR1B	2774	0.18	0.57	YES
25	PRKAR2B	PRKAR2B	PRKAR2B	2798	0.18	0.59	YES
26	GNG2	GNG2	GNG2	2886	0.17	0.6	YES
27	GNAO1	GNAO1	GNAO1	2889	0.17	0.62	YES
28	GNG12	GNG12	GNG12	4354	0.1	0.55	NO
29	GNB5	GNB5	GNB5	4702	0.094	0.54	NO
30	GNG7	GNG7	GNG7	5481	0.07	0.5	NO
31	ADCY9	ADCY9	ADCY9	5780	0.062	0.49	NO
32	PPP2R1B	PPP2R1B	PPP2R1B	6330	0.05	0.46	NO
33	PRKACA	PRKACA	PRKACA	6411	0.049	0.46	NO
34	ADCY6	ADCY6	ADCY6	6558	0.046	0.46	NO
35	PLCB3	PLCB3	PLCB3	6610	0.045	0.46	NO
36	PPP2R1A	PPP2R1A	PPP2R1A	7085	0.037	0.44	NO
37	GNB2	GNB2	GNB2	7696	0.028	0.41	NO
38	CALM1	CALM1	CALM1	7718	0.027	0.41	NO
39	PPP2CB	PPP2CB	PPP2CB	7836	0.026	0.4	NO
40	PRKCD	PRKCD	PRKCD	7899	0.025	0.4	NO
41	ADRBK1	ADRBK1	ADRBK1	8194	0.021	0.39	NO
42	GNAI2	GNAI2	GNAI2	8298	0.019	0.38	NO
43	PPP3CB	PPP3CB	PPP3CB	8327	0.019	0.38	NO
44	GNG5	GNG5	GNG5	8457	0.017	0.38	NO
45	GNB1	GNB1	GNB1	8752	0.014	0.36	NO
46	CALM2	CALM2	CALM2	8956	0.011	0.35	NO
47	PPP3CA	PPP3CA	PPP3CA	9033	0.01	0.35	NO
48	GNAT1	GNAT1	GNAT1	9424	0.0055	0.33	NO
49	PPP1CA	PPP1CA	PPP1CA	9452	0.0052	0.33	NO
50	CDK5	CDK5	CDK5	9889	-0.00018	0.3	NO
51	PPP2CA	PPP2CA	PPP2CA	9977	-0.0013	0.3	NO
52	CREB1	CREB1	CREB1	10284	-0.0049	0.28	NO
53	CALM3	CALM3	CALM3	10590	-0.0083	0.26	NO
54	PRKACB	PRKACB	PRKACB	10791	-0.01	0.26	NO
55	GNAI3	GNAI3	GNAI3	11994	-0.025	0.19	NO
56	PRKAR1A	PRKAR1A	PRKAR1A	12113	-0.027	0.18	NO
57	PPP3R1	PPP3R1	PPP3R1	12371	-0.03	0.17	NO
58	ADCY1	ADCY1	ADCY1	12388	-0.03	0.18	NO
59	MAPK1	MAPK1	MAPK1	12600	-0.033	0.17	NO
60	PLCB1	PLCB1	PLCB1	12675	-0.034	0.17	NO
61	GNG10	GNG10	GNG10	13394	-0.045	0.13	NO
62	PPP2R5D	PPP2R5D	PPP2R5D	14408	-0.064	0.079	NO
63	GNG4	GNG4	GNG4	14483	-0.065	0.081	NO
64	ITPR2	ITPR2	ITPR2	14625	-0.068	0.08	NO
65	PRKAR2A	PRKAR2A	PRKAR2A	15347	-0.089	0.048	NO
66	GNAT2	GNAT2	GNAT2	15570	-0.097	0.045	NO
67	GNAI1	GNAI1	GNAI1	15748	-0.1	0.045	NO
68	PRKCA	PRKCA	PRKCA	16244	-0.13	0.03	NO
69	GNG3	GNG3	GNG3	16275	-0.13	0.041	NO
70	ADCY8	ADCY8	ADCY8	16675	-0.15	0.034	NO
71	GNGT1	GNGT1	GNGT1	17375	-0.24	0.018	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 PURINE METABOLISM.

Figure S42. 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 O GLYCAN 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	CTSK	CTSK	CTSK	244	0.52	0.054	YES
2	ATP6V0D2	ATP6V0D2	ATP6V0D2	1003	0.33	0.054	YES
3	ACP5	ACP5	ACP5	1694	0.26	0.048	YES
4	DNASE2B	DNASE2B	DNASE2B	2014	0.23	0.06	YES
5	CTSS	CTSS	CTSS	2353	0.21	0.068	YES
6	LAPTM5	LAPTM5	LAPTM5	2858	0.18	0.062	YES
7	ATP6V1H	ATP6V1H	ATP6V1H	2960	0.17	0.078	YES
8	AP1M2	AP1M2	AP1M2	3273	0.15	0.08	YES
9	LAPTM4B	LAPTM4B	LAPTM4B	3436	0.15	0.09	YES
10	ARSG	ARSG	ARSG	3561	0.14	0.1	YES
11	TCIRG1	TCIRG1	TCIRG1	3602	0.14	0.12	YES
12	ABCB9	ABCB9	ABCB9	3644	0.14	0.13	YES
13	SORT1	SORT1	SORT1	3724	0.13	0.14	YES
14	LAMP3	LAMP3	LAMP3	3829	0.13	0.16	YES
15	CD68	CD68	CD68	3899	0.12	0.17	YES
16	GLA	GLA	GLA	3990	0.12	0.18	YES
17	AGA	AGA	AGA	4024	0.12	0.19	YES
18	ASAH1	ASAH1	ASAH1	4092	0.12	0.2	YES
19	CLTB	CLTB	CLTB	4290	0.11	0.21	YES
20	CTSA	CTSA	CTSA	4418	0.1	0.21	YES
21	CLN3	CLN3	CLN3	4497	0.1	0.22	YES
22	CTSW	CTSW	CTSW	4500	0.1	0.23	YES
23	AP1S2	AP1S2	AP1S2	4571	0.098	0.24	YES
24	AP3M2	AP3M2	AP3M2	4578	0.097	0.25	YES
25	CTSC	CTSC	CTSC	4632	0.096	0.26	YES
26	IDS	IDS	IDS	4954	0.086	0.26	YES
27	ATP6V0D1	ATP6V0D1	ATP6V0D1	4955	0.086	0.27	YES
28	GNPTG	GNPTG	GNPTG	4960	0.085	0.28	YES
29	ARSA	ARSA	ARSA	4994	0.084	0.29	YES
30	GBA	GBA	GBA	5010	0.084	0.3	YES
31	ATP6V0B	ATP6V0B	ATP6V0B	5030	0.083	0.31	YES
32	IDUA	IDUA	IDUA	5065	0.082	0.32	YES
33	CLTCL1	CLTCL1	CLTCL1	5139	0.08	0.32	YES
34	CTSD	CTSD	CTSD	5255	0.076	0.33	YES
35	PSAPL1	PSAPL1	PSAPL1	5370	0.073	0.33	YES
36	NPC2	NPC2	NPC2	5371	0.073	0.34	YES
37	MAN2B1	MAN2B1	MAN2B1	5425	0.071	0.34	YES
38	CTSE	CTSE	CTSE	5548	0.068	0.35	YES
39	NAGPA	NAGPA	NAGPA	5590	0.067	0.35	YES
40	GALNS	GALNS	GALNS	5699	0.065	0.36	YES
41	ABCA2	ABCA2	ABCA2	5837	0.061	0.36	YES
42	LAMP1	LAMP1	LAMP1	5966	0.058	0.36	YES
43	ATP6V0C	ATP6V0C	ATP6V0C	6028	0.057	0.36	YES
44	CTNS	CTNS	CTNS	6034	0.057	0.37	YES
45	CTSZ	CTSZ	CTSZ	6042	0.057	0.37	YES
46	HEXB	HEXB	HEXB	6074	0.056	0.38	YES
47	ARSB	ARSB	ARSB	6077	0.056	0.39	YES
48	AP3B2	AP3B2	AP3B2	6099	0.055	0.39	YES
49	CTSH	CTSH	CTSH	6116	0.055	0.4	YES
50	PPT1	PPT1	PPT1	6213	0.053	0.4	YES
51	LGMN	LGMN	LGMN	6492	0.047	0.39	YES
52	LAMP2	LAMP2	LAMP2	6620	0.045	0.39	YES
53	AP1S1	AP1S1	AP1S1	6624	0.045	0.39	YES
54	AP4M1	AP4M1	AP4M1	6643	0.044	0.4	YES
55	CTSL1	CTSL1	CTSL1	6696	0.043	0.4	YES
56	SLC17A5	SLC17A5	SLC17A5	6717	0.043	0.41	YES
57	GNPTAB	GNPTAB	GNPTAB	6926	0.04	0.4	YES
58	PSAP	PSAP	PSAP	6969	0.039	0.4	YES
59	ATP6AP1	ATP6AP1	ATP6AP1	7022	0.038	0.4	YES
60	SUMF1	SUMF1	SUMF1	7044	0.038	0.41	YES
61	CD63	CD63	CD63	7046	0.038	0.41	YES
62	DNASE2	DNASE2	DNASE2	7129	0.037	0.41	YES
63	AP1B1	AP1B1	AP1B1	7163	0.036	0.42	YES
64	ATP6V0A1	ATP6V0A1	ATP6V0A1	7182	0.036	0.42	YES
65	MCOLN1	MCOLN1	MCOLN1	7186	0.036	0.42	YES
66	GM2A	GM2A	GM2A	7385	0.032	0.42	NO
67	CTSB	CTSB	CTSB	7440	0.032	0.42	NO
68	SGSH	SGSH	SGSH	7441	0.032	0.42	NO
69	PLA2G15	PLA2G15	PLA2G15	7505	0.031	0.42	NO
70	NAPSA	NAPSA	NAPSA	7699	0.028	0.41	NO
71	LIPA	LIPA	LIPA	7831	0.026	0.41	NO
72	CLTA	CLTA	CLTA	8161	0.021	0.39	NO
73	AP4B1	AP4B1	AP4B1	8176	0.021	0.4	NO
74	AP1S3	AP1S3	AP1S3	8360	0.019	0.39	NO
75	MANBA	MANBA	MANBA	8438	0.018	0.39	NO
76	SMPD1	SMPD1	SMPD1	8443	0.018	0.39	NO
77	TPP1	TPP1	TPP1	8545	0.016	0.38	NO
78	AP1G1	AP1G1	AP1G1	8613	0.016	0.38	NO
79	AP1M1	AP1M1	AP1M1	8616	0.016	0.38	NO
80	CLN5	CLN5	CLN5	8685	0.015	0.38	NO
81	GNS	GNS	GNS	8789	0.014	0.38	NO
82	NAGLU	NAGLU	NAGLU	8855	0.013	0.38	NO
83	CTSF	CTSF	CTSF	8921	0.012	0.37	NO
84	AP3B1	AP3B1	AP3B1	8984	0.011	0.37	NO
85	GGA2	GGA2	GGA2	9037	0.01	0.37	NO
86	IGF2R	IGF2R	IGF2R	9058	0.01	0.37	NO
87	HEXA	HEXA	HEXA	9185	0.0085	0.36	NO
88	CTSO	CTSO	CTSO	9383	0.0061	0.35	NO
89	GLB1	GLB1	GLB1	9406	0.0058	0.35	NO
90	M6PR	M6PR	M6PR	9535	0.0041	0.35	NO
91	ACP2	ACP2	ACP2	9663	0.0027	0.34	NO
92	NEU1	NEU1	NEU1	9798	0.00096	0.33	NO
93	SCARB2	SCARB2	SCARB2	9874	-0.000011	0.33	NO
94	FUCA1	FUCA1	FUCA1	10281	-0.0049	0.31	NO
95	AP3S2	AP3S2	AP3S2	10468	-0.0068	0.3	NO
96	MFSD8	MFSD8	MFSD8	10615	-0.0086	0.29	NO
97	CD164	CD164	CD164	10663	-0.0091	0.29	NO
98	GUSB	GUSB	GUSB	10706	-0.0095	0.29	NO
99	SLC11A2	SLC11A2	SLC11A2	10929	-0.012	0.28	NO
100	AP3M1	AP3M1	AP3M1	10952	-0.012	0.28	NO
101	AP3D1	AP3D1	AP3D1	11265	-0.016	0.26	NO
102	ENTPD4	ENTPD4	ENTPD4	11281	-0.016	0.26	NO
103	AP4E1	AP4E1	AP4E1	11376	-0.018	0.26	NO
104	CLTC	CLTC	CLTC	11458	-0.018	0.26	NO
105	GAA	GAA	GAA	11556	-0.02	0.25	NO
106	ATP6V0A2	ATP6V0A2	ATP6V0A2	11750	-0.022	0.24	NO
107	LAPTM4A	LAPTM4A	LAPTM4A	11765	-0.022	0.25	NO
108	NAGA	NAGA	NAGA	12131	-0.027	0.23	NO
109	HGSNAT	HGSNAT	HGSNAT	12565	-0.032	0.21	NO
110	GGA1	GGA1	GGA1	12589	-0.033	0.21	NO
111	NPC1	NPC1	NPC1	12674	-0.034	0.21	NO
112	AP3S1	AP3S1	AP3S1	12797	-0.036	0.21	NO
113	SLC11A1	SLC11A1	SLC11A1	13047	-0.039	0.2	NO
114	CTSL2	CTSL2	CTSL2	13369	-0.044	0.19	NO
115	AP4S1	AP4S1	AP4S1	13693	-0.05	0.18	NO
116	HYAL1	HYAL1	HYAL1	13907	-0.054	0.17	NO
117	ATP6V0A4	ATP6V0A4	ATP6V0A4	13925	-0.054	0.18	NO
118	GGA3	GGA3	GGA3	14274	-0.061	0.16	NO
119	GALC	GALC	GALC	14381	-0.063	0.17	NO
120	PPT2	PPT2	PPT2	14959	-0.077	0.14	NO
121	CTSG	CTSG	CTSG	15208	-0.084	0.14	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 O GLYCAN BIOSYNTHESIS.

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

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

Table 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	PDE1A	PDE1A	PDE1A	34	0.71	0.035	YES
2	NTRK2	NTRK2	NTRK2	141	0.58	0.059	YES
3	NGFR	NGFR	NGFR	143	0.58	0.089	YES
4	ADCY4	ADCY4	ADCY4	307	0.49	0.1	YES
5	NGF	NGF	NGF	582	0.4	0.11	YES
6	ADCY5	ADCY5	ADCY5	627	0.39	0.13	YES
7	PCSK5	PCSK5	PCSK5	702	0.38	0.14	YES
8	MAPK11	MAPK11	MAPK11	726	0.38	0.16	YES
9	ARHGEF4	ARHGEF4	ARHGEF4	734	0.37	0.18	YES
10	MAPK12	MAPK12	MAPK12	740	0.37	0.2	YES
11	ADCY2	ADCY2	ADCY2	824	0.36	0.21	YES
12	ARHGEF16	ARHGEF16	ARHGEF16	835	0.36	0.23	YES
13	LINGO1	LINGO1	LINGO1	1014	0.33	0.24	YES
14	ADCY3	ADCY3	ADCY3	1273	0.3	0.24	YES
15	ABR	ABR	ABR	1372	0.29	0.25	YES
16	ARHGEF3	ARHGEF3	ARHGEF3	1388	0.29	0.26	YES
17	RASGRF2	RASGRF2	RASGRF2	1548	0.27	0.27	YES
18	OBSCN	OBSCN	OBSCN	1585	0.27	0.28	YES
19	MEF2C	MEF2C	MEF2C	1599	0.27	0.29	YES
20	FGD3	FGD3	FGD3	1604	0.27	0.31	YES
21	PREX1	PREX1	PREX1	1717	0.26	0.31	YES
22	RPS6KA2	RPS6KA2	RPS6KA2	1812	0.25	0.32	YES
23	VAV1	VAV1	VAV1	1856	0.25	0.33	YES
24	ARHGEF17	ARHGEF17	ARHGEF17	1872	0.24	0.34	YES
25	CAMK4	CAMK4	CAMK4	1930	0.24	0.35	YES
26	DUSP4	DUSP4	DUSP4	2011	0.23	0.36	YES
27	NTRK1	NTRK1	NTRK1	2096	0.23	0.37	YES
28	PDE1B	PDE1B	PDE1B	2194	0.22	0.37	YES
29	ITPR3	ITPR3	ITPR3	2243	0.22	0.38	YES
30	AKT3	AKT3	AKT3	2254	0.21	0.39	YES
31	ADCY7	ADCY7	ADCY7	2266	0.21	0.4	YES
32	TIAM2	TIAM2	TIAM2	2367	0.2	0.41	YES
33	ARHGAP4	ARHGAP4	ARHGAP4	2585	0.19	0.4	YES
34	FGD2	FGD2	FGD2	2727	0.18	0.4	YES
35	SHC3	SHC3	SHC3	2760	0.18	0.41	YES
36	PRKAR1B	PRKAR1B	PRKAR1B	2774	0.18	0.42	YES
37	FURIN	FURIN	FURIN	2786	0.18	0.43	YES
38	PRKAR2B	PRKAR2B	PRKAR2B	2798	0.18	0.44	YES
39	FGD1	FGD1	FGD1	2826	0.18	0.45	YES
40	ARHGEF6	ARHGEF6	ARHGEF6	2936	0.17	0.45	YES
41	TIAM1	TIAM1	TIAM1	2998	0.17	0.45	YES
42	PSEN2	PSEN2	PSEN2	3244	0.16	0.45	YES
43	DUSP7	DUSP7	DUSP7	3679	0.13	0.43	YES
44	MAPK13	MAPK13	MAPK13	3704	0.13	0.44	YES
45	PLEKHG2	PLEKHG2	PLEKHG2	3817	0.13	0.44	YES
46	MAPKAPK2	MAPKAPK2	MAPKAPK2	3862	0.13	0.44	YES
47	SQSTM1	SQSTM1	SQSTM1	3926	0.12	0.44	YES
48	DNM1	DNM1	DNM1	4014	0.12	0.44	YES
49	ADORA2A	ADORA2A	ADORA2A	4032	0.12	0.45	YES
50	RIPK2	RIPK2	RIPK2	4083	0.12	0.45	YES
51	SHC1	SHC1	SHC1	4228	0.11	0.45	YES
52	ARHGEF2	ARHGEF2	ARHGEF2	4382	0.1	0.45	YES
53	IRAK1	IRAK1	IRAK1	4400	0.1	0.45	YES
54	APH1B	APH1B	APH1B	4423	0.1	0.46	YES
55	MAPK3	MAPK3	MAPK3	4501	0.1	0.46	YES
56	NR4A1	NR4A1	NR4A1	4543	0.099	0.46	YES
57	RALGDS	RALGDS	RALGDS	4560	0.098	0.46	YES
58	VAV3	VAV3	VAV3	4988	0.084	0.44	NO
59	THEM4	THEM4	THEM4	4999	0.084	0.45	NO
60	SRC	SRC	SRC	5013	0.084	0.45	NO
61	SMPD2	SMPD2	SMPD2	5454	0.07	0.43	NO
62	TSC2	TSC2	TSC2	5584	0.067	0.42	NO
63	RALB	RALB	RALB	5700	0.065	0.42	NO
64	ADCY9	ADCY9	ADCY9	5780	0.062	0.42	NO
65	STAT3	STAT3	STAT3	6045	0.057	0.41	NO
66	PRKCE	PRKCE	PRKCE	6122	0.055	0.41	NO
67	MAG	MAG	MAG	6252	0.052	0.4	NO
68	PPP2R1B	PPP2R1B	PPP2R1B	6330	0.05	0.4	NO
69	RIT1	RIT1	RIT1	6386	0.049	0.4	NO
70	PRKACA	PRKACA	PRKACA	6411	0.049	0.4	NO
71	CDKN1A	CDKN1A	CDKN1A	6420	0.049	0.4	NO
72	TRIB3	TRIB3	TRIB3	6480	0.047	0.4	NO
73	ARHGEF11	ARHGEF11	ARHGEF11	6541	0.046	0.4	NO
74	ADCY6	ADCY6	ADCY6	6558	0.046	0.4	NO
75	RAPGEF1	RAPGEF1	RAPGEF1	6583	0.046	0.4	NO
76	MCF2	MCF2	MCF2	6599	0.045	0.4	NO
77	RPS6KA1	RPS6KA1	RPS6KA1	6615	0.045	0.41	NO
78	MAPK7	MAPK7	MAPK7	6699	0.043	0.4	NO
79	RAC1	RAC1	RAC1	6728	0.043	0.4	NO
80	MAP2K2	MAP2K2	MAP2K2	6751	0.042	0.4	NO
81	PDPK1	PDPK1	PDPK1	6778	0.042	0.41	NO
82	MEF2A	MEF2A	MEF2A	6826	0.041	0.4	NO
83	YWHAB	YWHAB	YWHAB	6919	0.04	0.4	NO
84	AKAP13	AKAP13	AKAP13	7006	0.038	0.4	NO
85	MLST8	MLST8	MLST8	7008	0.038	0.4	NO
86	PPP2R1A	PPP2R1A	PPP2R1A	7085	0.037	0.4	NO
87	SHC2	SHC2	SHC2	7329	0.033	0.39	NO
88	IKBKB	IKBKB	IKBKB	7500	0.031	0.38	NO
89	RAP1A	RAP1A	RAP1A	7632	0.029	0.37	NO
90	CALM1	CALM1	CALM1	7718	0.027	0.37	NO
91	BAD	BAD	BAD	7752	0.027	0.37	NO
92	RHOA	RHOA	RHOA	7763	0.027	0.37	NO
93	PPP2CB	PPP2CB	PPP2CB	7836	0.026	0.37	NO
94	PRKCD	PRKCD	PRKCD	7899	0.025	0.36	NO
95	CRK	CRK	CRK	7927	0.024	0.36	NO
96	AKT1	AKT1	AKT1	7977	0.024	0.36	NO
97	TRIO	TRIO	TRIO	8126	0.022	0.36	NO
98	PSENEN	PSENEN	PSENEN	8148	0.021	0.36	NO
99	ADCYAP1	ADCYAP1	ADCYAP1	8151	0.021	0.36	NO
100	CLTA	CLTA	CLTA	8161	0.021	0.36	NO
101	ADRBK1	ADRBK1	ADRBK1	8194	0.021	0.36	NO
102	HDAC1	HDAC1	HDAC1	8267	0.02	0.35	NO
103	NCSTN	NCSTN	NCSTN	8324	0.019	0.35	NO
104	HRAS	HRAS	HRAS	8335	0.019	0.35	NO
105	ADAM17	ADAM17	ADAM17	8380	0.018	0.35	NO
106	ARHGEF12	ARHGEF12	ARHGEF12	8415	0.018	0.35	NO
107	DNM2	DNM2	DNM2	8426	0.018	0.35	NO
108	PSEN1	PSEN1	PSEN1	8535	0.016	0.34	NO
109	ARHGEF1	ARHGEF1	ARHGEF1	8603	0.016	0.34	NO
110	MAPKAPK3	MAPKAPK3	MAPKAPK3	8609	0.016	0.34	NO
111	AP2S1	AP2S1	AP2S1	8643	0.015	0.34	NO
112	CHUK	CHUK	CHUK	8772	0.014	0.33	NO
113	DNAL4	DNAL4	DNAL4	8888	0.012	0.33	NO
114	NFKBIA	NFKBIA	NFKBIA	8926	0.012	0.33	NO
115	MTOR	MTOR	MTOR	8931	0.012	0.33	NO
116	CALM2	CALM2	CALM2	8956	0.011	0.32	NO
117	AP2A2	AP2A2	AP2A2	8981	0.011	0.32	NO
118	CASP3	CASP3	CASP3	9083	0.0098	0.32	NO
119	AKT1S1	AKT1S1	AKT1S1	9091	0.0097	0.32	NO
120	CASP2	CASP2	CASP2	9124	0.0093	0.32	NO
121	APH1A	APH1A	APH1A	9190	0.0084	0.32	NO
122	KALRN	KALRN	KALRN	9209	0.0081	0.31	NO
123	MAP2K5	MAP2K5	MAP2K5	9225	0.008	0.31	NO
124	ITSN1	ITSN1	ITSN1	9350	0.0064	0.31	NO
125	PRDM4	PRDM4	PRDM4	9479	0.0048	0.3	NO
126	RPS6KA3	RPS6KA3	RPS6KA3	9536	0.0041	0.3	NO
127	KRAS	KRAS	KRAS	9599	0.0034	0.29	NO
128	AP2A1	AP2A1	AP2A1	9688	0.0024	0.29	NO
129	DUSP3	DUSP3	DUSP3	9802	0.00091	0.28	NO
130	UBA52	UBA52	UBA52	9817	0.00075	0.28	NO
131	PIK3R2	PIK3R2	PIK3R2	9870	0.000095	0.28	NO
132	NGEF	NGEF	NGEF	9915	-0.0006	0.28	NO
133	RPS6KB2	RPS6KB2	RPS6KB2	9957	-0.00098	0.27	NO
134	PPP2CA	PPP2CA	PPP2CA	9977	-0.0013	0.27	NO
135	GSK3A	GSK3A	GSK3A	10123	-0.0032	0.26	NO
136	HDAC3	HDAC3	HDAC3	10159	-0.0036	0.26	NO
137	TRAF6	TRAF6	TRAF6	10189	-0.0038	0.26	NO
138	FOXO3	FOXO3	FOXO3	10192	-0.0038	0.26	NO
139	RTN4	RTN4	RTN4	10215	-0.0041	0.26	NO
140	PTEN	PTEN	PTEN	10272	-0.0048	0.26	NO
141	CREB1	CREB1	CREB1	10284	-0.0049	0.26	NO
142	RELA	RELA	RELA	10292	-0.005	0.26	NO
143	DUSP6	DUSP6	DUSP6	10556	-0.0079	0.24	NO
144	BCL2L11	BCL2L11	BCL2L11	10562	-0.0079	0.24	NO
145	CALM3	CALM3	CALM3	10590	-0.0083	0.24	NO
146	PLCG1	PLCG1	PLCG1	10775	-0.01	0.23	NO
147	PRKACB	PRKACB	PRKACB	10791	-0.01	0.23	NO
148	MAGED1	MAGED1	MAGED1	10880	-0.012	0.23	NO
149	RALA	RALA	RALA	10902	-0.012	0.23	NO
150	PIK3CB	PIK3CB	PIK3CB	11074	-0.014	0.22	NO
151	ARHGEF18	ARHGEF18	ARHGEF18	11215	-0.016	0.21	NO
152	MAPKAP1	MAPKAP1	MAPKAP1	11239	-0.016	0.21	NO
153	CLTC	CLTC	CLTC	11458	-0.018	0.2	NO
154	AP2M1	AP2M1	AP2M1	11476	-0.019	0.2	NO
155	KIDINS220	KIDINS220	KIDINS220	11662	-0.021	0.19	NO
156	RASGRF1	RASGRF1	RASGRF1	11672	-0.021	0.19	NO
157	RPS27A	RPS27A	RPS27A	11726	-0.022	0.19	NO
158	PCSK6	PCSK6	PCSK6	11774	-0.022	0.18	NO
159	HDAC2	HDAC2	HDAC2	11791	-0.022	0.18	NO
160	CASP9	CASP9	CASP9	11807	-0.023	0.19	NO
161	AATF	AATF	AATF	11837	-0.023	0.18	NO
162	GRB2	GRB2	GRB2	11985	-0.025	0.18	NO
163	PRKAR1A	PRKAR1A	PRKAR1A	12113	-0.027	0.17	NO
164	ELK1	ELK1	ELK1	12261	-0.028	0.16	NO
165	YWHAE	YWHAE	YWHAE	12335	-0.03	0.16	NO
166	ADCY1	ADCY1	ADCY1	12388	-0.03	0.16	NO
167	SOS2	SOS2	SOS2	12400	-0.03	0.16	NO
168	RICTOR	RICTOR	RICTOR	12413	-0.03	0.16	NO
169	NGFRAP1	NGFRAP1	NGFRAP1	12450	-0.031	0.16	NO
170	ARHGDIA	ARHGDIA	ARHGDIA	12491	-0.032	0.16	NO
171	MAPK1	MAPK1	MAPK1	12600	-0.033	0.16	NO
172	RAF1	RAF1	RAF1	12663	-0.034	0.16	NO
173	FGD4	FGD4	FGD4	12676	-0.034	0.16	NO
174	AP2B1	AP2B1	AP2B1	12784	-0.036	0.15	NO
175	MAPK14	MAPK14	MAPK14	12804	-0.036	0.15	NO
176	MAP2K1	MAP2K1	MAP2K1	12901	-0.037	0.15	NO
177	ARHGEF9	ARHGEF9	ARHGEF9	12958	-0.038	0.15	NO
178	OMG	OMG	OMG	13200	-0.042	0.14	NO
179	CDK1	CDK1	CDK1	13224	-0.042	0.14	NO
180	SOS1	SOS1	SOS1	13234	-0.042	0.14	NO
181	IRS2	IRS2	IRS2	13506	-0.047	0.13	NO
182	PRKCI	PRKCI	PRKCI	13516	-0.047	0.13	NO
183	AKT2	AKT2	AKT2	13574	-0.048	0.13	NO
184	FRS2	FRS2	FRS2	13650	-0.049	0.13	NO
185	CDKN1B	CDKN1B	CDKN1B	13663	-0.049	0.13	NO
186	FOXO1	FOXO1	FOXO1	13768	-0.051	0.12	NO
187	MDM2	MDM2	MDM2	13858	-0.053	0.12	NO
188	NRAS	NRAS	NRAS	14116	-0.058	0.11	NO
189	PPP2R5D	PPP2R5D	PPP2R5D	14408	-0.064	0.097	NO
190	PIK3CA	PIK3CA	PIK3CA	14556	-0.067	0.092	NO
191	ITPR2	ITPR2	ITPR2	14625	-0.068	0.091	NO
192	FOXO4	FOXO4	FOXO4	14693	-0.07	0.091	NO
193	MYD88	MYD88	MYD88	14798	-0.072	0.089	NO
194	MAPK8	MAPK8	MAPK8	14940	-0.076	0.085	NO
195	ATF1	ATF1	ATF1	15061	-0.08	0.082	NO
196	BRAF	BRAF	BRAF	15217	-0.085	0.078	NO
197	ECT2	ECT2	ECT2	15286	-0.086	0.078	NO
198	ITGB3BP	ITGB3BP	ITGB3BP	15295	-0.087	0.082	NO
199	PRKAR2A	PRKAR2A	PRKAR2A	15347	-0.089	0.084	NO
200	NET1	NET1	NET1	15547	-0.096	0.078	NO
201	SH3GL2	SH3GL2	SH3GL2	15577	-0.097	0.081	NO
202	PIK3R1	PIK3R1	PIK3R1	15708	-0.1	0.079	NO
203	IRS1	IRS1	IRS1	16089	-0.12	0.063	NO
204	PRKCA	PRKCA	PRKCA	16244	-0.13	0.061	NO
205	RPS6KA5	RPS6KA5	RPS6KA5	16270	-0.13	0.066	NO
206	PHLPP1	PHLPP1	PHLPP1	16434	-0.14	0.064	NO
207	ADCY8	ADCY8	ADCY8	16675	-0.15	0.058	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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

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

genes ES table in pathway: KEGG GLYCEROLIPID METABOLISM

Table S24. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PDE1A	PDE1A	PDE1A	34	0.71	0.044	YES
2	THBS2	THBS2	THBS2	103	0.62	0.08	YES
3	COL5A1	COL5A1	COL5A1	149	0.58	0.11	YES
4	COL1A1	COL1A1	COL1A1	303	0.49	0.14	YES
5	ADCY4	ADCY4	ADCY4	307	0.49	0.17	YES
6	SPP1	SPP1	SPP1	313	0.48	0.2	YES
7	PLAT	PLAT	PLAT	342	0.48	0.23	YES
8	PDGFRA	PDGFRA	PDGFRA	376	0.46	0.26	YES
9	COL1A2	COL1A2	COL1A2	427	0.44	0.28	YES
10	COL3A1	COL3A1	COL3A1	457	0.43	0.31	YES
11	ADCY5	ADCY5	ADCY5	627	0.39	0.32	YES
12	COL4A4	COL4A4	COL4A4	643	0.39	0.35	YES
13	COL6A3	COL6A3	COL6A3	647	0.39	0.37	YES
14	ADCY2	ADCY2	ADCY2	824	0.36	0.38	YES
15	PDGFA	PDGFA	PDGFA	832	0.36	0.41	YES
16	COL6A2	COL6A2	COL6A2	866	0.35	0.43	YES
17	COL9A1	COL9A1	COL9A1	905	0.35	0.45	YES
18	ADCY3	ADCY3	ADCY3	1273	0.3	0.45	YES
19	COL6A1	COL6A1	COL6A1	1358	0.29	0.46	YES
20	PDGFRB	PDGFRB	PDGFRB	1635	0.26	0.46	YES
21	COL4A2	COL4A2	COL4A2	1781	0.25	0.47	YES
22	CAMK4	CAMK4	CAMK4	1930	0.24	0.48	YES
23	COL4A1	COL4A1	COL4A1	2042	0.23	0.48	YES
24	PDE1B	PDE1B	PDE1B	2194	0.22	0.49	YES
25	ITPR3	ITPR3	ITPR3	2243	0.22	0.5	YES
26	AKT3	AKT3	AKT3	2254	0.21	0.52	YES
27	ADCY7	ADCY7	ADCY7	2266	0.21	0.53	YES
28	COL4A3	COL4A3	COL4A3	2392	0.2	0.53	YES
29	COL5A2	COL5A2	COL5A2	2497	0.2	0.54	YES
30	PDGFB	PDGFB	PDGFB	2653	0.19	0.54	YES
31	PRKAR1B	PRKAR1B	PRKAR1B	2774	0.18	0.55	YES
32	FURIN	FURIN	FURIN	2786	0.18	0.56	YES
33	PRKAR2B	PRKAR2B	PRKAR2B	2798	0.18	0.57	YES
34	THBS1	THBS1	THBS1	3902	0.12	0.52	NO
35	PDGFD	PDGFD	PDGFD	3955	0.12	0.52	NO
36	MAPK3	MAPK3	MAPK3	4501	0.1	0.5	NO
37	NR4A1	NR4A1	NR4A1	4543	0.099	0.5	NO
38	NCK2	NCK2	NCK2	4978	0.084	0.48	NO
39	THEM4	THEM4	THEM4	4999	0.084	0.48	NO
40	SRC	SRC	SRC	5013	0.084	0.49	NO
41	COL9A2	COL9A2	COL9A2	5213	0.077	0.48	NO
42	TSC2	TSC2	TSC2	5584	0.067	0.47	NO
43	STAT5A	STAT5A	STAT5A	5591	0.067	0.47	NO
44	ADCY9	ADCY9	ADCY9	5780	0.062	0.46	NO
45	BCAR1	BCAR1	BCAR1	5939	0.059	0.46	NO
46	STAT6	STAT6	STAT6	6008	0.057	0.46	NO
47	STAT3	STAT3	STAT3	6045	0.057	0.46	NO
48	PRKCE	PRKCE	PRKCE	6122	0.055	0.46	NO
49	PRKACA	PRKACA	PRKACA	6411	0.049	0.45	NO
50	CDKN1A	CDKN1A	CDKN1A	6420	0.049	0.45	NO
51	TRIB3	TRIB3	TRIB3	6480	0.047	0.45	NO
52	ADCY6	ADCY6	ADCY6	6558	0.046	0.45	NO
53	RAPGEF1	RAPGEF1	RAPGEF1	6583	0.046	0.45	NO
54	THBS3	THBS3	THBS3	6614	0.045	0.45	NO
55	MAP2K2	MAP2K2	MAP2K2	6751	0.042	0.44	NO
56	PDPK1	PDPK1	PDPK1	6778	0.042	0.45	NO
57	YWHAB	YWHAB	YWHAB	6919	0.04	0.44	NO
58	MLST8	MLST8	MLST8	7008	0.038	0.44	NO
59	PLG	PLG	PLG	7256	0.034	0.43	NO
60	COL4A5	COL4A5	COL4A5	7406	0.032	0.42	NO
61	STAT1	STAT1	STAT1	7636	0.029	0.41	NO
62	CALM1	CALM1	CALM1	7718	0.027	0.41	NO
63	BAD	BAD	BAD	7752	0.027	0.41	NO
64	PRKCD	PRKCD	PRKCD	7899	0.025	0.4	NO
65	CRK	CRK	CRK	7927	0.024	0.4	NO
66	AKT1	AKT1	AKT1	7977	0.024	0.4	NO
67	NCK1	NCK1	NCK1	7981	0.024	0.4	NO
68	ADRBK1	ADRBK1	ADRBK1	8194	0.021	0.39	NO
69	HRAS	HRAS	HRAS	8335	0.019	0.38	NO
70	CHUK	CHUK	CHUK	8772	0.014	0.36	NO
71	MTOR	MTOR	MTOR	8931	0.012	0.35	NO
72	CALM2	CALM2	CALM2	8956	0.011	0.35	NO
73	AKT1S1	AKT1S1	AKT1S1	9091	0.0097	0.34	NO
74	KRAS	KRAS	KRAS	9599	0.0034	0.31	NO
75	PIK3R2	PIK3R2	PIK3R2	9870	0.000095	0.3	NO
76	RPS6KB2	RPS6KB2	RPS6KB2	9957	-0.00098	0.29	NO
77	GSK3A	GSK3A	GSK3A	10123	-0.0032	0.28	NO
78	FOXO3	FOXO3	FOXO3	10192	-0.0038	0.28	NO
79	PTEN	PTEN	PTEN	10272	-0.0048	0.28	NO
80	CREB1	CREB1	CREB1	10284	-0.0049	0.28	NO
81	CALM3	CALM3	CALM3	10590	-0.0083	0.26	NO
82	PLCG1	PLCG1	PLCG1	10775	-0.01	0.25	NO
83	PRKACB	PRKACB	PRKACB	10791	-0.01	0.25	NO
84	RASA1	RASA1	RASA1	10904	-0.012	0.24	NO
85	PIK3CB	PIK3CB	PIK3CB	11074	-0.014	0.23	NO
86	MAPKAP1	MAPKAP1	MAPKAP1	11239	-0.016	0.23	NO
87	CASP9	CASP9	CASP9	11807	-0.023	0.2	NO
88	GRB2	GRB2	GRB2	11985	-0.025	0.19	NO
89	PRKAR1A	PRKAR1A	PRKAR1A	12113	-0.027	0.18	NO
90	ADCY1	ADCY1	ADCY1	12388	-0.03	0.17	NO
91	RICTOR	RICTOR	RICTOR	12413	-0.03	0.17	NO
92	MAPK1	MAPK1	MAPK1	12600	-0.033	0.16	NO
93	RAF1	RAF1	RAF1	12663	-0.034	0.16	NO
94	MAP2K1	MAP2K1	MAP2K1	12901	-0.037	0.15	NO
95	CDK1	CDK1	CDK1	13224	-0.042	0.13	NO
96	SOS1	SOS1	SOS1	13234	-0.042	0.13	NO
97	STAT5B	STAT5B	STAT5B	13348	-0.044	0.13	NO
98	AKT2	AKT2	AKT2	13574	-0.048	0.12	NO
99	CDKN1B	CDKN1B	CDKN1B	13663	-0.049	0.12	NO
100	FOXO1	FOXO1	FOXO1	13768	-0.051	0.12	NO
101	MDM2	MDM2	MDM2	13858	-0.053	0.11	NO
102	NRAS	NRAS	NRAS	14116	-0.058	0.1	NO
103	CRKL	CRKL	CRKL	14382	-0.063	0.092	NO
104	PIK3CA	PIK3CA	PIK3CA	14556	-0.067	0.087	NO
105	ITPR2	ITPR2	ITPR2	14625	-0.068	0.087	NO
106	FOXO4	FOXO4	FOXO4	14693	-0.07	0.088	NO
107	COL2A1	COL2A1	COL2A1	14823	-0.073	0.085	NO
108	PDGFC	PDGFC	PDGFC	15274	-0.086	0.065	NO
109	PRKAR2A	PRKAR2A	PRKAR2A	15347	-0.089	0.067	NO
110	PIK3R1	PIK3R1	PIK3R1	15708	-0.1	0.053	NO
111	COL9A3	COL9A3	COL9A3	15778	-0.1	0.056	NO
112	PRKCA	PRKCA	PRKCA	16244	-0.13	0.038	NO
113	THBS4	THBS4	THBS4	16390	-0.13	0.038	NO
114	PHLPP1	PHLPP1	PHLPP1	16434	-0.14	0.044	NO
115	ADCY8	ADCY8	ADCY8	16675	-0.15	0.04	NO
116	GRB7	GRB7	GRB7	17486	-0.27	0.012	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 GLYCEROLIPID METABOLISM.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCEROLIPID 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 INOSITOL PHOSPHATE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	JAG2	JAG2	JAG2	446	0.44	0.064	YES
2	HES5	HES5	HES5	488	0.42	0.15	YES
3	NOTCH3	NOTCH3	NOTCH3	637	0.39	0.22	YES
4	DLL1	DLL1	DLL1	756	0.37	0.29	YES
5	LFNG	LFNG	LFNG	1011	0.33	0.34	YES
6	DTX4	DTX4	DTX4	1882	0.24	0.34	YES
7	NOTCH4	NOTCH4	NOTCH4	2118	0.22	0.37	YES
8	MFNG	MFNG	MFNG	2137	0.22	0.42	YES
9	JAG1	JAG1	JAG1	2203	0.22	0.46	YES
10	NUMBL	NUMBL	NUMBL	2403	0.2	0.48	YES
11	DTX3	DTX3	DTX3	2565	0.19	0.52	YES
12	CTBP2	CTBP2	CTBP2	2770	0.18	0.54	YES
13	PSEN2	PSEN2	PSEN2	3244	0.16	0.55	YES
14	DLL4	DLL4	DLL4	3352	0.15	0.57	YES
15	MAML2	MAML2	MAML2	3830	0.13	0.57	YES
16	NOTCH1	NOTCH1	NOTCH1	4023	0.12	0.58	YES
17	DTX1	DTX1	DTX1	5784	0.062	0.49	NO
18	PTCRA	PTCRA	PTCRA	5922	0.059	0.5	NO
19	NCOR2	NCOR2	NCOR2	6822	0.041	0.46	NO
20	DTX2	DTX2	DTX2	6933	0.04	0.46	NO
21	PSENEN	PSENEN	PSENEN	8148	0.021	0.39	NO
22	HDAC1	HDAC1	HDAC1	8267	0.02	0.39	NO
23	NCSTN	NCSTN	NCSTN	8324	0.019	0.39	NO
24	ADAM17	ADAM17	ADAM17	8380	0.018	0.39	NO
25	DVL1	DVL1	DVL1	8521	0.017	0.39	NO
26	PSEN1	PSEN1	PSEN1	8535	0.016	0.39	NO
27	RBPJ	RBPJ	RBPJ	8568	0.016	0.39	NO
28	NUMB	NUMB	NUMB	8701	0.015	0.39	NO
29	APH1A	APH1A	APH1A	9190	0.0084	0.36	NO
30	DTX3L	DTX3L	DTX3L	9386	0.006	0.35	NO
31	MAML1	MAML1	MAML1	9478	0.0048	0.35	NO
32	CIR1	CIR1	CIR1	9857	0.00028	0.33	NO
33	CTBP1	CTBP1	CTBP1	10460	-0.0067	0.29	NO
34	DVL2	DVL2	DVL2	10703	-0.0094	0.28	NO
35	NOTCH2	NOTCH2	NOTCH2	10795	-0.01	0.28	NO
36	HES1	HES1	HES1	10836	-0.011	0.28	NO
37	CREBBP	CREBBP	CREBBP	11739	-0.022	0.23	NO
38	HDAC2	HDAC2	HDAC2	11791	-0.022	0.23	NO
39	SNW1	SNW1	SNW1	12107	-0.026	0.22	NO
40	KAT2B	KAT2B	KAT2B	13113	-0.04	0.17	NO
41	KAT2A	KAT2A	KAT2A	13152	-0.041	0.18	NO
42	DVL3	DVL3	DVL3	13456	-0.046	0.17	NO
43	MAML3	MAML3	MAML3	13745	-0.051	0.16	NO
44	EP300	EP300	EP300	14305	-0.061	0.14	NO
45	RFNG	RFNG	RFNG	15093	-0.08	0.12	NO
46	DLL3	DLL3	DLL3	16630	-0.15	0.06	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 INOSITOL PHOSPHATE METABOLISM.

Figure S50. 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 GLYCEROPHOSPHOLIPID METABOLISM

Table S26. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GJC2	GJC2	GJC2	52	0.68	0.092	YES
2	GJA5	GJA5	GJA5	179	0.56	0.16	YES
3	GJC1	GJC1	GJC1	654	0.39	0.19	YES
4	GJA4	GJA4	GJA4	852	0.35	0.23	YES
5	DNAJC6	DNAJC6	DNAJC6	1662	0.26	0.22	YES
6	DAB2	DAB2	DAB2	1965	0.24	0.23	YES
7	CHMP4C	CHMP4C	CHMP4C	2964	0.17	0.2	YES
8	TPD52	TPD52	TPD52	3034	0.17	0.22	YES
9	AP1M2	AP1M2	AP1M2	3273	0.15	0.22	YES
10	GJA1	GJA1	GJA1	3520	0.14	0.23	YES
11	SORT1	SORT1	SORT1	3724	0.13	0.24	YES
12	VPS28	VPS28	VPS28	3808	0.13	0.25	YES
13	DNM1	DNM1	DNM1	4014	0.12	0.26	YES
14	DTNBP1	DTNBP1	DTNBP1	4208	0.11	0.26	YES
15	CLTB	CLTB	CLTB	4290	0.11	0.27	YES
16	YIPF6	YIPF6	YIPF6	4465	0.1	0.28	YES
17	AP1S2	AP1S2	AP1S2	4571	0.098	0.28	YES
18	CPD	CPD	CPD	4683	0.094	0.29	YES
19	FTL	FTL	FTL	4933	0.086	0.29	YES
20	SRC	SRC	SRC	5013	0.084	0.29	YES
21	CLTCL1	CLTCL1	CLTCL1	5139	0.08	0.3	YES
22	STX4	STX4	STX4	5293	0.075	0.3	YES
23	HSPA8	HSPA8	HSPA8	5307	0.075	0.31	YES
24	SAR1B	SAR1B	SAR1B	5321	0.074	0.32	YES
25	FTH1	FTH1	FTH1	5364	0.073	0.33	YES
26	MYO6	MYO6	MYO6	5605	0.067	0.32	YES
27	VAMP8	VAMP8	VAMP8	5698	0.065	0.33	YES
28	VPS4A	VPS4A	VPS4A	6006	0.058	0.32	YES
29	BLOC1S3	BLOC1S3	BLOC1S3	6041	0.057	0.32	YES
30	CTSZ	CTSZ	CTSZ	6042	0.057	0.33	YES
31	ARF1	ARF1	ARF1	6055	0.057	0.34	YES
32	ARRB1	ARRB1	ARRB1	6227	0.053	0.34	YES
33	GJB1	GJB1	GJB1	6326	0.051	0.34	YES
34	SNX9	SNX9	SNX9	6364	0.05	0.34	YES
35	VAMP2	VAMP2	VAMP2	6536	0.046	0.34	YES
36	AP1S1	AP1S1	AP1S1	6624	0.045	0.34	YES
37	VPS37C	VPS37C	VPS37C	6654	0.044	0.34	YES
38	GJB2	GJB2	GJB2	6749	0.042	0.34	YES
39	CHMP4B	CHMP4B	CHMP4B	7103	0.037	0.33	YES
40	DNASE2	DNASE2	DNASE2	7129	0.037	0.33	YES
41	AP1B1	AP1B1	AP1B1	7163	0.036	0.34	YES
42	BLOC1S1	BLOC1S1	BLOC1S1	7249	0.034	0.34	YES
43	SNAPIN	SNAPIN	SNAPIN	7261	0.034	0.34	YES
44	GAK	GAK	GAK	7263	0.034	0.34	YES
45	COPE	COPE	COPE	7383	0.032	0.34	YES
46	OCRL	OCRL	OCRL	7407	0.032	0.34	YES
47	RAB5C	RAB5C	RAB5C	7413	0.032	0.35	YES
48	SNAP23	SNAP23	SNAP23	7464	0.031	0.35	YES
49	VPS4B	VPS4B	VPS4B	7590	0.029	0.35	NO
50	CHMP2A	CHMP2A	CHMP2A	7720	0.027	0.34	NO
51	SEC31A	SEC31A	SEC31A	7769	0.027	0.34	NO
52	TGOLN2	TGOLN2	TGOLN2	7916	0.024	0.34	NO
53	NAPA	NAPA	NAPA	7941	0.024	0.34	NO
54	VPS37A	VPS37A	VPS37A	8035	0.023	0.34	NO
55	SEC24D	SEC24D	SEC24D	8061	0.023	0.34	NO
56	CHMP5	CHMP5	CHMP5	8142	0.021	0.34	NO
57	CLTA	CLTA	CLTA	8161	0.021	0.34	NO
58	AP4B1	AP4B1	AP4B1	8176	0.021	0.34	NO
59	CHMP2B	CHMP2B	CHMP2B	8206	0.02	0.34	NO
60	SEC24B	SEC24B	SEC24B	8253	0.02	0.35	NO
61	GJB5	GJB5	GJB5	8369	0.018	0.34	NO
62	DNM2	DNM2	DNM2	8426	0.018	0.34	NO
63	HIP1R	HIP1R	HIP1R	8458	0.017	0.34	NO
64	SNX2	SNX2	SNX2	8540	0.016	0.34	NO
65	VPS25	VPS25	VPS25	8584	0.016	0.34	NO
66	AP1G1	AP1G1	AP1G1	8613	0.016	0.34	NO
67	AP1M1	AP1M1	AP1M1	8616	0.016	0.34	NO
68	TJP1	TJP1	TJP1	8680	0.015	0.34	NO
69	CHMP4A	CHMP4A	CHMP4A	8706	0.014	0.34	NO
70	GNS	GNS	GNS	8789	0.014	0.34	NO
71	PICALM	PICALM	PICALM	8822	0.013	0.34	NO
72	VPS36	VPS36	VPS36	8973	0.011	0.33	NO
73	AP3B1	AP3B1	AP3B1	8984	0.011	0.33	NO
74	NECAP1	NECAP1	NECAP1	9017	0.011	0.33	NO
75	IGF2R	IGF2R	IGF2R	9058	0.01	0.33	NO
76	COPZ1	COPZ1	COPZ1	9065	0.01	0.33	NO
77	COPA	COPA	COPA	9150	0.0089	0.33	NO
78	VAMP7	VAMP7	VAMP7	9161	0.0088	0.33	NO
79	CNO	CNO	CNO	9181	0.0086	0.33	NO
80	SEC24C	SEC24C	SEC24C	9253	0.0076	0.33	NO
81	CHMP7	CHMP7	CHMP7	9384	0.0061	0.32	NO
82	M6PR	M6PR	M6PR	9535	0.0041	0.31	NO
83	TPD52L1	TPD52L1	TPD52L1	9702	0.0021	0.3	NO
84	UBA52	UBA52	UBA52	9817	0.00075	0.3	NO
85	PLDN	PLDN	PLDN	9994	-0.0015	0.29	NO
86	COPG	COPG	COPG	10005	-0.0016	0.29	NO
87	TXNDC5	TXNDC5	TXNDC5	10045	-0.0022	0.28	NO
88	PIK3C2A	PIK3C2A	PIK3C2A	10179	-0.0036	0.28	NO
89	TFRC	TFRC	TFRC	10236	-0.0044	0.27	NO
90	ARFGAP1	ARFGAP1	ARFGAP1	10493	-0.0071	0.26	NO
91	TSG101	TSG101	TSG101	10557	-0.0079	0.26	NO
92	SNF8	SNF8	SNF8	10695	-0.0094	0.25	NO
93	COPB1	COPB1	COPB1	10772	-0.01	0.25	NO
94	STAM2	STAM2	STAM2	11073	-0.014	0.23	NO
95	STAM	STAM	STAM	11102	-0.014	0.23	NO
96	AP4E1	AP4E1	AP4E1	11376	-0.018	0.22	NO
97	CLTC	CLTC	CLTC	11458	-0.018	0.22	NO
98	AP2M1	AP2M1	AP2M1	11476	-0.019	0.22	NO
99	COPB2	COPB2	COPB2	11481	-0.019	0.22	NO
100	GJB3	GJB3	GJB3	11500	-0.019	0.22	NO
101	ARCN1	ARCN1	ARCN1	11564	-0.02	0.22	NO
102	SEC13	SEC13	SEC13	11608	-0.02	0.22	NO
103	GBF1	GBF1	GBF1	11688	-0.021	0.22	NO
104	RPS27A	RPS27A	RPS27A	11726	-0.022	0.22	NO
105	GJA3	GJA3	GJA3	12014	-0.026	0.21	NO
106	CHMP6	CHMP6	CHMP6	12285	-0.029	0.2	NO
107	GJD4	GJD4	GJD4	12332	-0.03	0.2	NO
108	TBC1D8B	TBC1D8B	TBC1D8B	12681	-0.034	0.18	NO
109	GJB4	GJB4	GJB4	12712	-0.035	0.19	NO
110	SEC23A	SEC23A	SEC23A	12716	-0.035	0.19	NO
111	SNX5	SNX5	SNX5	12720	-0.035	0.2	NO
112	AP3S1	AP3S1	AP3S1	12797	-0.036	0.2	NO
113	GJA9	GJA9	GJA9	12869	-0.037	0.2	NO
114	VTA1	VTA1	VTA1	12979	-0.038	0.2	NO
115	PUM1	PUM1	PUM1	13018	-0.039	0.2	NO
116	SH3D19	SH3D19	SH3D19	13166	-0.041	0.2	NO
117	HGS	HGS	HGS	13565	-0.048	0.18	NO
118	PREB	PREB	PREB	13580	-0.048	0.19	NO
119	GJB6	GJB6	GJB6	13627	-0.048	0.19	NO
120	GJA10	GJA10	GJA10	13875	-0.053	0.19	NO
121	VPS37D	VPS37D	VPS37D	14177	-0.059	0.18	NO
122	VPS37B	VPS37B	VPS37B	14601	-0.068	0.16	NO
123	SH3GL2	SH3GL2	SH3GL2	15577	-0.097	0.12	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 GLYCEROPHOSPHOLIPID METABOLISM.

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

genes ES table in pathway: KEGG ETHER LIPID METABOLISM

Table S27. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DNM3	DNM3	DNM3	170	0.56	0.027	YES
2	PDGFRA	PDGFRA	PDGFRA	376	0.46	0.046	YES
3	IL2RA	IL2RA	IL2RA	879	0.35	0.041	YES
4	ACAP1	ACAP1	ACAP1	881	0.35	0.064	YES
5	CCR5	CCR5	CCR5	886	0.35	0.086	YES
6	F2R	F2R	F2R	1021	0.33	0.1	YES
7	ARAP3	ARAP3	ARAP3	1205	0.31	0.11	YES
8	RAB31	RAB31	RAB31	1259	0.3	0.13	YES
9	EHD2	EHD2	EHD2	1339	0.3	0.14	YES
10	IL2RG	IL2RG	IL2RG	1422	0.28	0.16	YES
11	IGF1R	IGF1R	IGF1R	1461	0.28	0.17	YES
12	IQSEC2	IQSEC2	IQSEC2	1632	0.26	0.18	YES
13	DNAJC6	DNAJC6	DNAJC6	1662	0.26	0.2	YES
14	EHD3	EHD3	EHD3	1745	0.25	0.21	YES
15	EGF	EGF	EGF	1837	0.25	0.22	YES
16	DAB2	DAB2	DAB2	1965	0.24	0.23	YES
17	NTRK1	NTRK1	NTRK1	2096	0.23	0.24	YES
18	AGAP2	AGAP2	AGAP2	2219	0.22	0.24	YES
19	HSPA2	HSPA2	HSPA2	2362	0.2	0.25	YES
20	KDR	KDR	KDR	2378	0.2	0.26	YES
21	CXCR4	CXCR4	CXCR4	2385	0.2	0.27	YES
22	GRK5	GRK5	GRK5	2469	0.2	0.28	YES
23	PIP5K1B	PIP5K1B	PIP5K1B	2695	0.18	0.28	YES
24	FGFR2	FGFR2	FGFR2	2765	0.18	0.29	YES
25	CHMP4C	CHMP4C	CHMP4C	2964	0.17	0.29	YES
26	CSF1R	CSF1R	CSF1R	3026	0.17	0.3	YES
27	HSPA6	HSPA6	HSPA6	3133	0.16	0.3	YES
28	HLA-G	HLA-G	HLA-G	3160	0.16	0.31	YES
29	PSD	PSD	PSD	3261	0.16	0.32	YES
30	ASAP1	ASAP1	ASAP1	3375	0.15	0.32	YES
31	RAB11FIP5	RAB11FIP5	RAB11FIP5	3407	0.15	0.33	YES
32	KIT	KIT	KIT	3423	0.15	0.34	YES
33	HLA-F	HLA-F	HLA-F	3497	0.14	0.34	YES
34	FLT1	FLT1	FLT1	3792	0.13	0.33	YES
35	VPS28	VPS28	VPS28	3808	0.13	0.34	YES
36	CXCR1	CXCR1	CXCR1	3821	0.13	0.35	YES
37	PLD2	PLD2	PLD2	3823	0.13	0.36	YES
38	RAB11FIP1	RAB11FIP1	RAB11FIP1	3827	0.13	0.36	YES
39	HLA-B	HLA-B	HLA-B	3872	0.12	0.37	YES
40	CXCR2	CXCR2	CXCR2	3928	0.12	0.38	YES
41	IL2RB	IL2RB	IL2RB	3958	0.12	0.38	YES
42	ASAP3	ASAP3	ASAP3	3996	0.12	0.39	YES
43	DNM1	DNM1	DNM1	4014	0.12	0.39	YES
44	ARRB2	ARRB2	ARRB2	4069	0.12	0.4	YES
45	RET	RET	RET	4074	0.12	0.41	YES
46	SH3KBP1	SH3KBP1	SH3KBP1	4257	0.11	0.4	YES
47	PIP5K1C	PIP5K1C	PIP5K1C	4260	0.11	0.41	YES
48	CLTB	CLTB	CLTB	4290	0.11	0.42	YES
49	PLD1	PLD1	PLD1	4520	0.099	0.41	YES
50	EHD4	EHD4	EHD4	4598	0.097	0.41	YES
51	CBLB	CBLB	CBLB	4769	0.092	0.41	YES
52	AGAP1	AGAP1	AGAP1	4872	0.088	0.41	YES
53	SRC	SRC	SRC	5013	0.084	0.4	YES
54	CBL	CBL	CBL	5132	0.08	0.4	YES
55	CLTCL1	CLTCL1	CLTCL1	5139	0.08	0.41	YES
56	RAB11FIP4	RAB11FIP4	RAB11FIP4	5143	0.08	0.41	YES
57	HLA-C	HLA-C	HLA-C	5146	0.08	0.42	YES
58	HLA-A	HLA-A	HLA-A	5220	0.077	0.42	YES
59	HSPA8	HSPA8	HSPA8	5307	0.075	0.42	YES
60	HLA-E	HLA-E	HLA-E	5358	0.073	0.42	YES
61	FAM125B	FAM125B	FAM125B	5391	0.072	0.42	YES
62	SMURF1	SMURF1	SMURF1	5506	0.069	0.42	NO
63	VPS45	VPS45	VPS45	5859	0.061	0.41	NO
64	VPS4A	VPS4A	VPS4A	6006	0.058	0.4	NO
65	FAM125A	FAM125A	FAM125A	6010	0.057	0.4	NO
66	GIT2	GIT2	GIT2	6038	0.057	0.41	NO
67	RUFY1	RUFY1	RUFY1	6109	0.055	0.41	NO
68	GIT1	GIT1	GIT1	6123	0.055	0.41	NO
69	ARAP1	ARAP1	ARAP1	6178	0.054	0.41	NO
70	ARRB1	ARRB1	ARRB1	6227	0.053	0.41	NO
71	WWP1	WWP1	WWP1	6264	0.052	0.41	NO
72	CBLC	CBLC	CBLC	6460	0.048	0.4	NO
73	PSD4	PSD4	PSD4	6494	0.047	0.41	NO
74	ARAP2	ARAP2	ARAP2	6556	0.046	0.41	NO
75	RAB11FIP3	RAB11FIP3	RAB11FIP3	6653	0.044	0.4	NO
76	VPS37C	VPS37C	VPS37C	6654	0.044	0.41	NO
77	ARFGAP3	ARFGAP3	ARFGAP3	6816	0.041	0.4	NO
78	CDC42	CDC42	CDC42	6984	0.039	0.39	NO
79	CHMP4B	CHMP4B	CHMP4B	7103	0.037	0.39	NO
80	EGFR	EGFR	EGFR	7289	0.034	0.38	NO
81	RAB5C	RAB5C	RAB5C	7413	0.032	0.38	NO
82	VPS4B	VPS4B	VPS4B	7590	0.029	0.37	NO
83	PRKCZ	PRKCZ	PRKCZ	7713	0.028	0.36	NO
84	CHMP2A	CHMP2A	CHMP2A	7720	0.027	0.36	NO
85	RAB11A	RAB11A	RAB11A	7761	0.027	0.36	NO
86	VPS37A	VPS37A	VPS37A	8035	0.023	0.35	NO
87	RAB22A	RAB22A	RAB22A	8042	0.023	0.35	NO
88	CHMP5	CHMP5	CHMP5	8142	0.021	0.35	NO
89	CLTA	CLTA	CLTA	8161	0.021	0.35	NO
90	ADRBK1	ADRBK1	ADRBK1	8194	0.021	0.34	NO
91	CHMP2B	CHMP2B	CHMP2B	8206	0.02	0.35	NO
92	HRAS	HRAS	HRAS	8335	0.019	0.34	NO
93	DNM2	DNM2	DNM2	8426	0.018	0.34	NO
94	GRK6	GRK6	GRK6	8445	0.018	0.34	NO
95	SH3GLB1	SH3GLB1	SH3GLB1	8491	0.017	0.34	NO
96	IQSEC1	IQSEC1	IQSEC1	8500	0.017	0.34	NO
97	VPS25	VPS25	VPS25	8584	0.016	0.33	NO
98	IQSEC3	IQSEC3	IQSEC3	8611	0.016	0.33	NO
99	AP2S1	AP2S1	AP2S1	8643	0.015	0.33	NO
100	CHMP4A	CHMP4A	CHMP4A	8706	0.014	0.33	NO
101	EHD1	EHD1	EHD1	8797	0.013	0.32	NO
102	ACAP2	ACAP2	ACAP2	8932	0.012	0.32	NO
103	VPS36	VPS36	VPS36	8973	0.011	0.32	NO
104	AP2A2	AP2A2	AP2A2	8981	0.011	0.32	NO
105	RABEP1	RABEP1	RABEP1	9006	0.011	0.32	NO
106	SMAP2	SMAP2	SMAP2	9042	0.01	0.31	NO
107	FGFR4	FGFR4	FGFR4	9088	0.0097	0.31	NO
108	DNM1L	DNM1L	DNM1L	9096	0.0096	0.31	NO
109	SMAP1	SMAP1	SMAP1	9252	0.0076	0.3	NO
110	EPN3	EPN3	EPN3	9259	0.0075	0.3	NO
111	PIP5K1A	PIP5K1A	PIP5K1A	9276	0.0073	0.3	NO
112	ARF6	ARF6	ARF6	9284	0.0072	0.3	NO
113	RAB4A	RAB4A	RAB4A	9337	0.0065	0.3	NO
114	CHMP1B	CHMP1B	CHMP1B	9423	0.0055	0.3	NO
115	LDLRAP1	LDLRAP1	LDLRAP1	9458	0.0051	0.3	NO
116	PDCD6IP	PDCD6IP	PDCD6IP	9468	0.005	0.3	NO
117	SH3GLB2	SH3GLB2	SH3GLB2	9602	0.0033	0.29	NO
118	EPS15	EPS15	EPS15	9616	0.0031	0.29	NO
119	AP2A1	AP2A1	AP2A1	9688	0.0024	0.28	NO
120	TRAF6	TRAF6	TRAF6	10189	-0.0038	0.26	NO
121	STAMBP	STAMBP	STAMBP	10203	-0.004	0.25	NO
122	TFRC	TFRC	TFRC	10236	-0.0044	0.25	NO
123	PARD6G	PARD6G	PARD6G	10285	-0.0049	0.25	NO
124	EPN1	EPN1	EPN1	10299	-0.0051	0.25	NO
125	ARFGAP1	ARFGAP1	ARFGAP1	10493	-0.0071	0.24	NO
126	TSG101	TSG101	TSG101	10557	-0.0079	0.24	NO
127	SNF8	SNF8	SNF8	10695	-0.0094	0.23	NO
128	HSPA1A	HSPA1A	HSPA1A	11021	-0.013	0.21	NO
129	SH3GL1	SH3GL1	SH3GL1	11022	-0.013	0.21	NO
130	RAB5A	RAB5A	RAB5A	11053	-0.014	0.21	NO
131	FGFR3	FGFR3	FGFR3	11065	-0.014	0.21	NO
132	STAM2	STAM2	STAM2	11073	-0.014	0.21	NO
133	ADRBK2	ADRBK2	ADRBK2	11100	-0.014	0.21	NO
134	STAM	STAM	STAM	11102	-0.014	0.21	NO
135	ACAP3	ACAP3	ACAP3	11159	-0.015	0.21	NO
136	HSPA1B	HSPA1B	HSPA1B	11337	-0.017	0.2	NO
137	CLTC	CLTC	CLTC	11458	-0.018	0.2	NO
138	AP2M1	AP2M1	AP2M1	11476	-0.019	0.2	NO
139	EPN2	EPN2	EPN2	11522	-0.019	0.19	NO
140	PARD6B	PARD6B	PARD6B	11910	-0.024	0.17	NO
141	NEDD4	NEDD4	NEDD4	12019	-0.026	0.17	NO
142	CHMP6	CHMP6	CHMP6	12285	-0.029	0.16	NO
143	ASAP2	ASAP2	ASAP2	12570	-0.033	0.14	NO
144	RAB11B	RAB11B	RAB11B	12593	-0.033	0.14	NO
145	ARFGAP2	ARFGAP2	ARFGAP2	12693	-0.034	0.14	NO
146	PIP4K2B	PIP4K2B	PIP4K2B	12721	-0.035	0.14	NO
147	AP2B1	AP2B1	AP2B1	12784	-0.036	0.14	NO
148	MET	MET	MET	12881	-0.037	0.14	NO
149	ERBB4	ERBB4	ERBB4	12913	-0.038	0.14	NO
150	ZFYVE20	ZFYVE20	ZFYVE20	12938	-0.038	0.14	NO
151	VTA1	VTA1	VTA1	12979	-0.038	0.14	NO
152	RNF41	RNF41	RNF41	13177	-0.041	0.13	NO
153	USP8	USP8	USP8	13298	-0.043	0.13	NO
154	RAB5B	RAB5B	RAB5B	13347	-0.044	0.13	NO
155	PRKCI	PRKCI	PRKCI	13516	-0.047	0.12	NO
156	RAB11FIP2	RAB11FIP2	RAB11FIP2	13558	-0.048	0.12	NO
157	HGS	HGS	HGS	13565	-0.048	0.12	NO
158	ERBB3	ERBB3	ERBB3	13785	-0.051	0.11	NO
159	PSD3	PSD3	PSD3	13796	-0.052	0.12	NO
160	MDM2	MDM2	MDM2	13858	-0.053	0.12	NO
161	LDLR	LDLR	LDLR	13921	-0.054	0.12	NO
162	PSD2	PSD2	PSD2	13962	-0.055	0.12	NO
163	VPS37D	VPS37D	VPS37D	14177	-0.059	0.11	NO
164	GRK4	GRK4	GRK4	14232	-0.06	0.11	NO
165	EEA1	EEA1	EEA1	14280	-0.061	0.11	NO
166	PARD6A	PARD6A	PARD6A	14328	-0.062	0.11	NO
167	NEDD4L	NEDD4L	NEDD4L	14469	-0.065	0.11	NO
168	VPS37B	VPS37B	VPS37B	14601	-0.068	0.11	NO
169	SMURF2	SMURF2	SMURF2	14696	-0.07	0.11	NO
170	ITCH	ITCH	ITCH	14709	-0.07	0.11	NO
171	PARD3	PARD3	PARD3	14776	-0.072	0.11	NO
172	PIKFYVE	PIKFYVE	PIKFYVE	14961	-0.077	0.1	NO
173	ADRB2	ADRB2	ADRB2	15116	-0.081	0.1	NO
174	SH3GL2	SH3GL2	SH3GL2	15577	-0.097	0.082	NO
175	ADRB1	ADRB1	ADRB1	16359	-0.13	0.046	NO
176	HSPA1L	HSPA1L	HSPA1L	16767	-0.16	0.034	NO
177	SH3GL3	SH3GL3	SH3GL3	17537	-0.29	0.0088	NO

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

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ETHER LIPID METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG ARACHIDONIC ACID METABOLISM

Table S28. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	JAM2	JAM2	JAM2	119	0.61	0.077	YES
2	MAPK10	MAPK10	MAPK10	318	0.48	0.13	YES
3	MAPK11	MAPK11	MAPK11	726	0.38	0.16	YES
4	MAPK12	MAPK12	MAPK12	740	0.37	0.21	YES
5	PTPRZ1	PTPRZ1	PTPRZ1	797	0.36	0.26	YES
6	CXCL1	CXCL1	CXCL1	935	0.34	0.3	YES
7	ATP6V0D2	ATP6V0D2	ATP6V0D2	1003	0.33	0.34	YES
8	IL8	IL8	IL8	1041	0.33	0.38	YES
9	JAM3	JAM3	JAM3	1098	0.32	0.42	YES
10	LYN	LYN	LYN	2587	0.19	0.36	YES
11	NOD1	NOD1	NOD1	2688	0.18	0.38	YES
12	ATP6V1H	ATP6V1H	ATP6V1H	2960	0.17	0.39	YES
13	ATP6V1B1	ATP6V1B1	ATP6V1B1	2974	0.17	0.42	YES
14	CCL5	CCL5	CCL5	3416	0.15	0.41	YES
15	TCIRG1	TCIRG1	TCIRG1	3602	0.14	0.42	YES
16	MAPK13	MAPK13	MAPK13	3704	0.13	0.43	YES
17	ATP6V1C1	ATP6V1C1	ATP6V1C1	3814	0.13	0.44	YES
18	CXCR1	CXCR1	CXCR1	3821	0.13	0.46	YES
19	IKBKG	IKBKG	IKBKG	3851	0.13	0.48	YES
20	PLCG2	PLCG2	PLCG2	3874	0.12	0.49	YES
21	CXCR2	CXCR2	CXCR2	3928	0.12	0.51	YES
22	HBEGF	HBEGF	HBEGF	4426	0.1	0.49	YES
23	F11R	F11R	F11R	4552	0.098	0.5	YES
24	ATP6V1E2	ATP6V1E2	ATP6V1E2	4631	0.096	0.51	YES
25	ATP6V0D1	ATP6V0D1	ATP6V0D1	4955	0.086	0.5	YES
26	SRC	SRC	SRC	5013	0.084	0.51	YES
27	ATP6V0B	ATP6V0B	ATP6V0B	5030	0.083	0.52	YES
28	ATP6V1C2	ATP6V1C2	ATP6V1C2	5242	0.077	0.52	NO
29	ATP6V0E1	ATP6V0E1	ATP6V0E1	5570	0.068	0.51	NO
30	ATP6V1E1	ATP6V1E1	ATP6V1E1	5654	0.065	0.51	NO
31	ATP6V0C	ATP6V0C	ATP6V0C	6028	0.057	0.5	NO
32	ATP6V1F	ATP6V1F	ATP6V1F	6032	0.057	0.51	NO
33	GIT1	GIT1	GIT1	6123	0.055	0.51	NO
34	NFKB1	NFKB1	NFKB1	6198	0.053	0.51	NO
35	IGSF5	IGSF5	IGSF5	6333	0.05	0.51	NO
36	PAK1	PAK1	PAK1	6655	0.044	0.5	NO
37	RAC1	RAC1	RAC1	6728	0.043	0.5	NO
38	CDC42	CDC42	CDC42	6984	0.039	0.49	NO
39	ATP6AP1	ATP6AP1	ATP6AP1	7022	0.038	0.5	NO
40	ATP6V1D	ATP6V1D	ATP6V1D	7137	0.036	0.49	NO
41	ATP6V0A1	ATP6V0A1	ATP6V0A1	7182	0.036	0.5	NO
42	EGFR	EGFR	EGFR	7289	0.034	0.5	NO
43	IKBKB	IKBKB	IKBKB	7500	0.031	0.49	NO
44	ATP6V1B2	ATP6V1B2	ATP6V1B2	7650	0.028	0.48	NO
45	ATP6V1G1	ATP6V1G1	ATP6V1G1	7770	0.027	0.48	NO
46	ADAM17	ADAM17	ADAM17	8380	0.018	0.45	NO
47	MAPK9	MAPK9	MAPK9	8638	0.015	0.44	NO
48	TJP1	TJP1	TJP1	8680	0.015	0.44	NO
49	ATP6V0E2	ATP6V0E2	ATP6V0E2	8763	0.014	0.43	NO
50	CHUK	CHUK	CHUK	8772	0.014	0.43	NO
51	NFKBIA	NFKBIA	NFKBIA	8926	0.012	0.43	NO
52	CSK	CSK	CSK	9021	0.01	0.42	NO
53	CASP3	CASP3	CASP3	9083	0.0098	0.42	NO
54	ATP6V1A	ATP6V1A	ATP6V1A	9401	0.0058	0.4	NO
55	ADAM10	ADAM10	ADAM10	9699	0.0023	0.39	NO
56	RELA	RELA	RELA	10292	-0.005	0.35	NO
57	PLCG1	PLCG1	PLCG1	10775	-0.01	0.33	NO
58	MAP2K4	MAP2K4	MAP2K4	11616	-0.02	0.28	NO
59	ATP6V0A2	ATP6V0A2	ATP6V0A2	11750	-0.022	0.28	NO
60	MAP3K14	MAP3K14	MAP3K14	11857	-0.023	0.28	NO
61	MAPK14	MAPK14	MAPK14	12804	-0.036	0.23	NO
62	MET	MET	MET	12881	-0.037	0.23	NO
63	PTPN11	PTPN11	PTPN11	13754	-0.051	0.19	NO
64	ATP6V0A4	ATP6V0A4	ATP6V0A4	13925	-0.054	0.18	NO
65	ATP6V1G2	ATP6V1G2	ATP6V1G2	14677	-0.07	0.15	NO
66	JUN	JUN	JUN	14808	-0.073	0.15	NO
67	MAPK8	MAPK8	MAPK8	14940	-0.076	0.16	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 ARACHIDONIC ACID METABOLISM.

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

genes ES table in pathway: KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES

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	PDE1A	PDE1A	PDE1A	34	0.71	0.11	YES
2	PLCB4	PLCB4	PLCB4	147	0.58	0.19	YES
3	ADCY4	ADCY4	ADCY4	307	0.49	0.26	YES
4	PLA2G4A	PLA2G4A	PLA2G4A	504	0.42	0.32	YES
5	ADCY5	ADCY5	ADCY5	627	0.39	0.37	YES
6	ADCY2	ADCY2	ADCY2	824	0.36	0.42	YES
7	GNAZ	GNAZ	GNAZ	1044	0.33	0.46	YES
8	ADCY3	ADCY3	ADCY3	1273	0.3	0.49	YES
9	PLCB2	PLCB2	PLCB2	1912	0.24	0.49	YES
10	CAMK4	CAMK4	CAMK4	1930	0.24	0.53	YES
11	PDE1B	PDE1B	PDE1B	2194	0.22	0.55	YES
12	ITPR3	ITPR3	ITPR3	2243	0.22	0.58	YES
13	ADCY7	ADCY7	ADCY7	2266	0.21	0.61	YES
14	PRKAR1B	PRKAR1B	PRKAR1B	2774	0.18	0.61	YES
15	PRKAR2B	PRKAR2B	PRKAR2B	2798	0.18	0.64	YES
16	GNAO1	GNAO1	GNAO1	2889	0.17	0.66	YES
17	ADCY9	ADCY9	ADCY9	5780	0.062	0.51	NO
18	PRKACA	PRKACA	PRKACA	6411	0.049	0.48	NO
19	ADCY6	ADCY6	ADCY6	6558	0.046	0.48	NO
20	PLCB3	PLCB3	PLCB3	6610	0.045	0.48	NO
21	CALM1	CALM1	CALM1	7718	0.027	0.42	NO
22	PRKCD	PRKCD	PRKCD	7899	0.025	0.42	NO
23	ADRBK1	ADRBK1	ADRBK1	8194	0.021	0.4	NO
24	GNAI2	GNAI2	GNAI2	8298	0.019	0.4	NO
25	CALM2	CALM2	CALM2	8956	0.011	0.37	NO
26	GNAT1	GNAT1	GNAT1	9424	0.0055	0.34	NO
27	CREB1	CREB1	CREB1	10284	-0.0049	0.29	NO
28	CALM3	CALM3	CALM3	10590	-0.0083	0.28	NO
29	PRKACB	PRKACB	PRKACB	10791	-0.01	0.27	NO
30	GNAI3	GNAI3	GNAI3	11994	-0.025	0.2	NO
31	PRKAR1A	PRKAR1A	PRKAR1A	12113	-0.027	0.2	NO
32	ADCY1	ADCY1	ADCY1	12388	-0.03	0.19	NO
33	MAPK1	MAPK1	MAPK1	12600	-0.033	0.18	NO
34	PLCB1	PLCB1	PLCB1	12675	-0.034	0.18	NO
35	ITPR2	ITPR2	ITPR2	14625	-0.068	0.084	NO
36	PRKAR2A	PRKAR2A	PRKAR2A	15347	-0.089	0.057	NO
37	GNAT2	GNAT2	GNAT2	15570	-0.097	0.06	NO
38	GNAI1	GNAI1	GNAI1	15748	-0.1	0.066	NO
39	PRKCA	PRKCA	PRKCA	16244	-0.13	0.058	NO
40	ADCY8	ADCY8	ADCY8	16675	-0.15	0.058	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 GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES.

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

genes ES table in pathway: KEGG MAPK SIGNALING PATHWAY

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	NGFR	NGFR	NGFR	143	0.58	0.068	YES
2	NGF	NGF	NGF	582	0.4	0.096	YES
3	ARHGEF4	ARHGEF4	ARHGEF4	734	0.37	0.14	YES
4	ARHGEF16	ARHGEF16	ARHGEF16	835	0.36	0.18	YES
5	LINGO1	LINGO1	LINGO1	1014	0.33	0.21	YES
6	ABR	ABR	ABR	1372	0.29	0.23	YES
7	ARHGEF3	ARHGEF3	ARHGEF3	1388	0.29	0.26	YES
8	RASGRF2	RASGRF2	RASGRF2	1548	0.27	0.29	YES
9	OBSCN	OBSCN	OBSCN	1585	0.27	0.32	YES
10	FGD3	FGD3	FGD3	1604	0.27	0.36	YES
11	PREX1	PREX1	PREX1	1717	0.26	0.38	YES
12	VAV1	VAV1	VAV1	1856	0.25	0.41	YES
13	ARHGEF17	ARHGEF17	ARHGEF17	1872	0.24	0.44	YES
14	TIAM2	TIAM2	TIAM2	2367	0.2	0.44	YES
15	ARHGAP4	ARHGAP4	ARHGAP4	2585	0.19	0.45	YES
16	FGD2	FGD2	FGD2	2727	0.18	0.47	YES
17	FGD1	FGD1	FGD1	2826	0.18	0.48	YES
18	ARHGEF6	ARHGEF6	ARHGEF6	2936	0.17	0.5	YES
19	TIAM1	TIAM1	TIAM1	2998	0.17	0.52	YES
20	PSEN2	PSEN2	PSEN2	3244	0.16	0.52	YES
21	PLEKHG2	PLEKHG2	PLEKHG2	3817	0.13	0.51	YES
22	SQSTM1	SQSTM1	SQSTM1	3926	0.12	0.52	YES
23	RIPK2	RIPK2	RIPK2	4083	0.12	0.53	YES
24	ARHGEF2	ARHGEF2	ARHGEF2	4382	0.1	0.52	YES
25	IRAK1	IRAK1	IRAK1	4400	0.1	0.54	YES
26	APH1B	APH1B	APH1B	4423	0.1	0.55	YES
27	VAV3	VAV3	VAV3	4988	0.084	0.53	NO
28	SMPD2	SMPD2	SMPD2	5454	0.07	0.51	NO
29	MAG	MAG	MAG	6252	0.052	0.47	NO
30	ARHGEF11	ARHGEF11	ARHGEF11	6541	0.046	0.46	NO
31	MCF2	MCF2	MCF2	6599	0.045	0.46	NO
32	RAC1	RAC1	RAC1	6728	0.043	0.46	NO
33	AKAP13	AKAP13	AKAP13	7006	0.038	0.45	NO
34	IKBKB	IKBKB	IKBKB	7500	0.031	0.43	NO
35	BAD	BAD	BAD	7752	0.027	0.42	NO
36	RHOA	RHOA	RHOA	7763	0.027	0.42	NO
37	TRIO	TRIO	TRIO	8126	0.022	0.4	NO
38	PSENEN	PSENEN	PSENEN	8148	0.021	0.4	NO
39	HDAC1	HDAC1	HDAC1	8267	0.02	0.4	NO
40	NCSTN	NCSTN	NCSTN	8324	0.019	0.4	NO
41	ADAM17	ADAM17	ADAM17	8380	0.018	0.4	NO
42	ARHGEF12	ARHGEF12	ARHGEF12	8415	0.018	0.4	NO
43	PSEN1	PSEN1	PSEN1	8535	0.016	0.39	NO
44	ARHGEF1	ARHGEF1	ARHGEF1	8603	0.016	0.39	NO
45	NFKBIA	NFKBIA	NFKBIA	8926	0.012	0.37	NO
46	CASP3	CASP3	CASP3	9083	0.0098	0.37	NO
47	CASP2	CASP2	CASP2	9124	0.0093	0.37	NO
48	APH1A	APH1A	APH1A	9190	0.0084	0.36	NO
49	KALRN	KALRN	KALRN	9209	0.0081	0.36	NO
50	ITSN1	ITSN1	ITSN1	9350	0.0064	0.36	NO
51	PRDM4	PRDM4	PRDM4	9479	0.0048	0.35	NO
52	UBA52	UBA52	UBA52	9817	0.00075	0.33	NO
53	NGEF	NGEF	NGEF	9915	-0.0006	0.32	NO
54	HDAC3	HDAC3	HDAC3	10159	-0.0036	0.31	NO
55	TRAF6	TRAF6	TRAF6	10189	-0.0038	0.31	NO
56	RTN4	RTN4	RTN4	10215	-0.0041	0.31	NO
57	RELA	RELA	RELA	10292	-0.005	0.31	NO
58	BCL2L11	BCL2L11	BCL2L11	10562	-0.0079	0.29	NO
59	MAGED1	MAGED1	MAGED1	10880	-0.012	0.28	NO
60	ARHGEF18	ARHGEF18	ARHGEF18	11215	-0.016	0.26	NO
61	RASGRF1	RASGRF1	RASGRF1	11672	-0.021	0.24	NO
62	RPS27A	RPS27A	RPS27A	11726	-0.022	0.24	NO
63	HDAC2	HDAC2	HDAC2	11791	-0.022	0.23	NO
64	AATF	AATF	AATF	11837	-0.023	0.24	NO
65	YWHAE	YWHAE	YWHAE	12335	-0.03	0.21	NO
66	SOS2	SOS2	SOS2	12400	-0.03	0.21	NO
67	NGFRAP1	NGFRAP1	NGFRAP1	12450	-0.031	0.21	NO
68	ARHGDIA	ARHGDIA	ARHGDIA	12491	-0.032	0.21	NO
69	FGD4	FGD4	FGD4	12676	-0.034	0.21	NO
70	ARHGEF9	ARHGEF9	ARHGEF9	12958	-0.038	0.2	NO
71	OMG	OMG	OMG	13200	-0.042	0.19	NO
72	SOS1	SOS1	SOS1	13234	-0.042	0.19	NO
73	PRKCI	PRKCI	PRKCI	13516	-0.047	0.18	NO
74	MYD88	MYD88	MYD88	14798	-0.072	0.12	NO
75	MAPK8	MAPK8	MAPK8	14940	-0.076	0.12	NO
76	ECT2	ECT2	ECT2	15286	-0.086	0.11	NO
77	ITGB3BP	ITGB3BP	ITGB3BP	15295	-0.087	0.12	NO
78	NET1	NET1	NET1	15547	-0.096	0.12	NO

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

Figure S60. 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

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 PENTOSE AND GLUCURONATE INTERCONVERSIONS	27	genes.ES.table	0.65	1.4	0.15	0.92	1	0.52	0.1	0.47	0.73	0.34
KEGG FATTY ACID METABOLISM	40	genes.ES.table	0.62	1.4	0.15	1	0.99	0.42	0.14	0.37	1	0.57
KEGG STEROID HORMONE BIOSYNTHESIS	52	genes.ES.table	0.61	1.4	0.13	1	1	0.54	0.1	0.48	0.94	0.47
KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM	39	genes.ES.table	0.61	1.5	0.1	1	0.98	0.51	0.13	0.45	1	0.83
KEGG AMINOACYL TRNA BIOSYNTHESIS	41	genes.ES.table	0.37	1.4	0.13	1	0.99	1	0.63	0.37	1	0.61
KEGG RNA POLYMERASE	29	genes.ES.table	0.41	1.4	0.13	1	0.99	0.52	0.28	0.38	1	0.62
KEGG ENDOMETRIAL CANCER	52	genes.ES.table	0.35	1.4	0.11	0.96	1	0.077	0.017	0.076	0.77	0.37
REACTOME BILE ACID AND BILE SALT METABOLISM	26	genes.ES.table	0.68	1.4	0.13	1	1	0.54	0.11	0.48	0.96	0.48
REACTOME MITOCHONDRIAL PROTEIN IMPORT	49	genes.ES.table	0.47	1.5	0.14	1	0.97	0.33	0.18	0.27	1	0.91
REACTOME RNA POL I TRANSCRIPTION	73	genes.ES.table	0.59	1.5	0.11	1	0.98	0.52	0.17	0.43	1	0.77

genes ES table in pathway: KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS

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	TIMM17A	TIMM17A	TIMM17A	920	0.2	0.02	YES
2	TIMM8A	TIMM8A	TIMM8A	969	0.19	0.086	YES
3	SAMM50	SAMM50	SAMM50	1035	0.18	0.15	YES
4	LDHD	LDHD	LDHD	1125	0.17	0.21	YES
5	FXN	FXN	FXN	1398	0.14	0.24	YES
6	SLC25A13	SLC25A13	SLC25A13	1793	0.11	0.26	YES
7	SLC25A12	SLC25A12	SLC25A12	1921	0.11	0.29	YES
8	BCS1L	BCS1L	BCS1L	1946	0.1	0.33	YES
9	DNAJC19	DNAJC19	DNAJC19	1980	0.1	0.37	YES
10	TOMM20	TOMM20	TOMM20	2308	0.088	0.38	YES
11	PMPCB	PMPCB	PMPCB	2811	0.071	0.38	YES
12	MTX1	MTX1	MTX1	2869	0.069	0.4	YES
13	CS	CS	CS	3063	0.063	0.41	YES
14	TAZ	TAZ	TAZ	3221	0.058	0.43	YES
15	TOMM7	TOMM7	TOMM7	3255	0.058	0.44	YES
16	TIMM9	TIMM9	TIMM9	3257	0.058	0.47	YES
17	GRPEL1	GRPEL1	GRPEL1	3682	0.048	0.46	NO
18	SLC25A4	SLC25A4	SLC25A4	4222	0.037	0.44	NO
19	TOMM70A	TOMM70A	TOMM70A	4353	0.035	0.45	NO
20	ATP5G1	ATP5G1	ATP5G1	4512	0.032	0.45	NO
21	HSPD1	HSPD1	HSPD1	4679	0.029	0.45	NO
22	CHCHD4	CHCHD4	CHCHD4	4751	0.028	0.46	NO
23	PMPCA	PMPCA	PMPCA	5208	0.02	0.44	NO
24	COX17	COX17	COX17	5444	0.016	0.43	NO
25	GRPEL2	GRPEL2	GRPEL2	5748	0.012	0.42	NO
26	TIMM10	TIMM10	TIMM10	5838	0.01	0.42	NO
27	HSPA9	HSPA9	HSPA9	5840	0.01	0.42	NO
28	GFER	GFER	GFER	5844	0.01	0.42	NO
29	TIMM8B	TIMM8B	TIMM8B	5860	0.0098	0.43	NO
30	IDH3G	IDH3G	IDH3G	6086	0.0064	0.42	NO
31	TOMM22	TOMM22	TOMM22	6111	0.0059	0.42	NO
32	CYC1	CYC1	CYC1	6246	0.0039	0.41	NO
33	FXC1	FXC1	FXC1	6981	-0.007	0.37	NO
34	TIMM13	TIMM13	TIMM13	7013	-0.0075	0.37	NO
35	TIMM50	TIMM50	TIMM50	7080	-0.0086	0.37	NO
36	TOMM5	TOMM5	TOMM5	7713	-0.018	0.34	NO
37	TIMM17B	TIMM17B	TIMM17B	7784	-0.019	0.35	NO
38	ATP5B	ATP5B	ATP5B	8372	-0.028	0.32	NO
39	C18orf55	C18orf55	C18orf55	8403	-0.028	0.33	NO
40	VDAC1	VDAC1	VDAC1	8659	-0.032	0.33	NO
41	TIMM22	TIMM22	TIMM22	8863	-0.036	0.33	NO
42	SLC25A6	SLC25A6	SLC25A6	9052	-0.039	0.34	NO
43	TOMM40	TOMM40	TOMM40	9098	-0.04	0.35	NO
44	HSCB	HSCB	HSCB	9239	-0.043	0.36	NO
45	ATP5A1	ATP5A1	ATP5A1	9455	-0.047	0.36	NO
46	TIMM44	TIMM44	TIMM44	9577	-0.05	0.37	NO
47	ACO2	ACO2	ACO2	9656	-0.051	0.39	NO
48	MTX2	MTX2	MTX2	9667	-0.051	0.4	NO
49	COQ2	COQ2	COQ2	12372	-0.14	0.3	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 PENTOSE AND GLUCURONATE INTERCONVERSIONS.

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG FATTY ACID METABOLISM

Table 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	HIST1H2AE	HIST1H2AE	HIST1H2AE	216	0.41	0.027	YES
2	HIST1H3E	HIST1H3E	HIST1H3E	219	0.41	0.066	YES
3	HIST1H2BN	HIST1H2BN	HIST1H2BN	239	0.4	0.1	YES
4	HIST1H3H	HIST1H3H	HIST1H3H	370	0.33	0.12	YES
5	HIST1H4I	HIST1H4I	HIST1H4I	483	0.28	0.14	YES
6	HIST2H4A	HIST2H4A	HIST2H4A	495	0.28	0.17	YES
7	HIST1H4J	HIST1H4J	HIST1H4J	533	0.27	0.19	YES
8	HIST1H2BL	HIST1H2BL	HIST1H2BL	573	0.26	0.22	YES
9	HIST1H2BD	HIST1H2BD	HIST1H2BD	575	0.26	0.24	YES
10	HIST1H2AC	HIST1H2AC	HIST1H2AC	713	0.23	0.25	YES
11	HIST1H2BE	HIST1H2BE	HIST1H2BE	740	0.23	0.27	YES
12	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	806	0.21	0.29	YES
13	HIST1H2BC	HIST1H2BC	HIST1H2BC	831	0.21	0.31	YES
14	HIST1H4H	HIST1H4H	HIST1H4H	835	0.21	0.33	YES
15	HIST1H2BG	HIST1H2BG	HIST1H2BG	865	0.2	0.34	YES
16	HIST1H3D	HIST1H3D	HIST1H3D	916	0.2	0.36	YES
17	HIST1H3B	HIST1H3B	HIST1H3B	930	0.19	0.38	YES
18	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	987	0.18	0.39	YES
19	KAT2B	KAT2B	KAT2B	1021	0.18	0.41	YES
20	HIST1H3A	HIST1H3A	HIST1H3A	1046	0.18	0.42	YES
21	HIST1H2BK	HIST1H2BK	HIST1H2BK	1257	0.15	0.43	YES
22	HIST2H3C	HIST2H3C	HIST2H3C	1509	0.13	0.42	YES
23	TAF1A	TAF1A	TAF1A	1587	0.13	0.43	YES
24	HIST2H2BE	HIST2H2BE	HIST2H2BE	1607	0.12	0.44	YES
25	POLR1C	POLR1C	POLR1C	1737	0.12	0.45	YES
26	HIST1H4B	HIST1H4B	HIST1H4B	1772	0.11	0.45	YES
27	HIST1H4E	HIST1H4E	HIST1H4E	1812	0.11	0.46	YES
28	HIST1H2BF	HIST1H2BF	HIST1H2BF	1888	0.11	0.47	YES
29	HIST2H3D	HIST2H3D	HIST2H3D	1953	0.1	0.48	YES
30	POLRMT	POLRMT	POLRMT	2068	0.099	0.48	YES
31	MNAT1	MNAT1	MNAT1	2175	0.094	0.48	YES
32	POLR1D	POLR1D	POLR1D	2269	0.09	0.48	YES
33	GTF3C5	GTF3C5	GTF3C5	2523	0.08	0.48	YES
34	GTF2H4	GTF2H4	GTF2H4	2641	0.076	0.48	YES
35	HIST1H2AD	HIST1H2AD	HIST1H2AD	2650	0.076	0.48	YES
36	POLR3A	POLR3A	POLR3A	2841	0.07	0.48	YES
37	TFB2M	TFB2M	TFB2M	2865	0.069	0.48	YES
38	EHMT2	EHMT2	EHMT2	2868	0.069	0.49	YES
39	ERCC2	ERCC2	ERCC2	2873	0.069	0.5	YES
40	HIST1H2BO	HIST1H2BO	HIST1H2BO	2958	0.066	0.5	YES
41	POLR1A	POLR1A	POLR1A	3057	0.063	0.5	YES
42	H3F3A	H3F3A	H3F3A	3081	0.063	0.5	YES
43	POLR1B	POLR1B	POLR1B	3679	0.048	0.47	NO
44	POLR2K	POLR2K	POLR2K	3718	0.047	0.48	NO
45	POLR3E	POLR3E	POLR3E	3860	0.044	0.47	NO
46	POLR2F	POLR2F	POLR2F	3927	0.043	0.47	NO
47	HIST1H3J	HIST1H3J	HIST1H3J	4019	0.041	0.47	NO
48	RRN3	RRN3	RRN3	4219	0.037	0.46	NO
49	POLR2L	POLR2L	POLR2L	4556	0.031	0.45	NO
50	POLR3GL	POLR3GL	POLR3GL	4609	0.03	0.45	NO
51	HIST1H4D	HIST1H4D	HIST1H4D	4732	0.028	0.44	NO
52	UBTF	UBTF	UBTF	4922	0.025	0.44	NO
53	MBD2	MBD2	MBD2	4927	0.025	0.44	NO
54	ERCC3	ERCC3	ERCC3	5757	0.011	0.39	NO
55	GTF3C3	GTF3C3	GTF3C3	5773	0.011	0.39	NO
56	CBX3	CBX3	CBX3	5780	0.011	0.39	NO
57	POLR3C	POLR3C	POLR3C	5932	0.0088	0.38	NO
58	CDK7	CDK7	CDK7	5997	0.0078	0.38	NO
59	TFAM	TFAM	TFAM	6085	0.0064	0.38	NO
60	SSB	SSB	SSB	6089	0.0064	0.38	NO
61	SNAPC4	SNAPC4	SNAPC4	6338	0.0023	0.36	NO
62	CCNH	CCNH	CCNH	6403	0.0015	0.36	NO
63	HIST1H3C	HIST1H3C	HIST1H3C	6460	0.00046	0.36	NO
64	POLR3F	POLR3F	POLR3F	6463	0.00042	0.36	NO
65	POLR3K	POLR3K	POLR3K	6497	-0.00012	0.36	NO
66	POLR2E	POLR2E	POLR2E	6505	-0.00027	0.35	NO
67	TAF1C	TAF1C	TAF1C	6516	-0.00047	0.35	NO
68	POLR3H	POLR3H	POLR3H	6602	-0.0019	0.35	NO
69	SNAPC2	SNAPC2	SNAPC2	6724	-0.0035	0.34	NO
70	POLR2H	POLR2H	POLR2H	6831	-0.0051	0.34	NO
71	GTF3C2	GTF3C2	GTF3C2	6838	-0.0052	0.34	NO
72	ZNF143	ZNF143	ZNF143	6979	-0.0069	0.33	NO
73	BRF2	BRF2	BRF2	7099	-0.0088	0.32	NO
74	HIST1H3G	HIST1H3G	HIST1H3G	7115	-0.009	0.32	NO
75	SNAPC3	SNAPC3	SNAPC3	7532	-0.015	0.3	NO
76	GTF3C4	GTF3C4	GTF3C4	7830	-0.02	0.29	NO
77	NFIB	NFIB	NFIB	8096	-0.024	0.27	NO
78	H3F3B	H3F3B	H3F3B	8325	-0.027	0.26	NO
79	GTF2H3	GTF2H3	GTF2H3	8406	-0.028	0.26	NO
80	HIST1H2AB	HIST1H2AB	HIST1H2AB	8414	-0.028	0.26	NO
81	MAPK3	MAPK3	MAPK3	8444	-0.029	0.26	NO
82	BRF1	BRF1	BRF1	8517	-0.03	0.26	NO
83	H2AFZ	H2AFZ	H2AFZ	9197	-0.042	0.23	NO
84	SNAPC5	SNAPC5	SNAPC5	9715	-0.052	0.2	NO
85	HIST1H2BH	HIST1H2BH	HIST1H2BH	9907	-0.056	0.2	NO
86	GTF2H1	GTF2H1	GTF2H1	10021	-0.059	0.2	NO
87	TBP	TBP	TBP	10106	-0.062	0.2	NO
88	HIST1H4C	HIST1H4C	HIST1H4C	10219	-0.065	0.2	NO
89	POU2F1	POU2F1	POU2F1	10483	-0.072	0.19	NO
90	H2AFX	H2AFX	H2AFX	10766	-0.079	0.18	NO
91	PTRF	PTRF	PTRF	10873	-0.082	0.18	NO
92	ERCC6	ERCC6	ERCC6	10957	-0.084	0.19	NO
93	HIST1H3I	HIST1H3I	HIST1H3I	10996	-0.085	0.19	NO
94	SNAPC1	SNAPC1	SNAPC1	11228	-0.093	0.19	NO
95	POLR3D	POLR3D	POLR3D	11318	-0.096	0.19	NO
96	HIST2H2AC	HIST2H2AC	HIST2H2AC	11367	-0.097	0.2	NO
97	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	11515	-0.1	0.2	NO
98	HIST4H4	HIST4H4	HIST4H4	12096	-0.12	0.18	NO
99	HIST1H4A	HIST1H4A	HIST1H4A	12138	-0.12	0.19	NO
100	MTERF	MTERF	MTERF	12251	-0.13	0.19	NO
101	GTF2H2	GTF2H2	GTF2H2	12742	-0.15	0.18	NO
102	TAF1B	TAF1B	TAF1B	12846	-0.16	0.19	NO
103	POLR3B	POLR3B	POLR3B	12957	-0.16	0.2	NO
104	GTF2H2B	GTF2H2B	GTF2H2B	13270	-0.18	0.2	NO
105	HIST3H2BB	HIST3H2BB	HIST3H2BB	14687	-0.26	0.14	NO
106	LZTS1	LZTS1	LZTS1	15406	-0.31	0.13	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 FATTY ACID METABOLISM.

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

genes ES table in pathway: KEGG STEROID HORMONE BIOSYNTHESIS

Table 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	UGT1A5	UGT1A5	UGT1A5	70	0.65	0.094	YES
2	UGT1A3	UGT1A3	UGT1A3	75	0.64	0.19	YES
3	UGT1A4	UGT1A4	UGT1A4	105	0.57	0.27	YES
4	UGT1A1	UGT1A1	UGT1A1	237	0.4	0.33	YES
5	UGT1A9	UGT1A9	UGT1A9	319	0.35	0.37	YES
6	UGT1A6	UGT1A6	UGT1A6	442	0.3	0.41	YES
7	ALAS1	ALAS1	ALAS1	646	0.24	0.44	YES
8	UGT2B28	UGT2B28	UGT2B28	763	0.22	0.46	YES
9	UGT2B11	UGT2B11	UGT2B11	939	0.19	0.48	YES
10	UGT2B10	UGT2B10	UGT2B10	1003	0.18	0.51	YES
11	UGT1A8	UGT1A8	UGT1A8	1145	0.17	0.52	YES
12	ALAD	ALAD	ALAD	1390	0.14	0.53	YES
13	MMAB	MMAB	MMAB	1530	0.13	0.54	YES
14	BLVRB	BLVRB	BLVRB	1557	0.13	0.56	YES
15	PPOX	PPOX	PPOX	1608	0.12	0.58	YES
16	UGT2B7	UGT2B7	UGT2B7	1735	0.12	0.59	YES
17	UGT2B4	UGT2B4	UGT2B4	1803	0.11	0.6	YES
18	HMOX2	HMOX2	HMOX2	2189	0.094	0.59	YES
19	UGT2B15	UGT2B15	UGT2B15	2324	0.088	0.6	YES
20	EARS2	EARS2	EARS2	2343	0.087	0.61	YES
21	UROS	UROS	UROS	3352	0.056	0.56	NO
22	FECH	FECH	FECH	3909	0.043	0.54	NO
23	COX15	COX15	COX15	4403	0.034	0.51	NO
24	HMBS	HMBS	HMBS	4748	0.028	0.5	NO
25	EPRS	EPRS	EPRS	4926	0.025	0.49	NO
26	UROD	UROD	UROD	5466	0.016	0.46	NO
27	HCCS	HCCS	HCCS	6069	0.0067	0.43	NO
28	UGT1A7	UGT1A7	UGT1A7	7424	-0.013	0.36	NO
29	FTH1	FTH1	FTH1	7442	-0.014	0.36	NO
30	COX10	COX10	COX10	7953	-0.021	0.33	NO
31	CPOX	CPOX	CPOX	9347	-0.045	0.26	NO
32	GUSB	GUSB	GUSB	9840	-0.055	0.24	NO
33	UGT1A10	UGT1A10	UGT1A10	12123	-0.12	0.13	NO
34	ALAS2	ALAS2	ALAS2	12375	-0.14	0.14	NO
35	HMOX1	HMOX1	HMOX1	12703	-0.15	0.14	NO
36	CP	CP	CP	12747	-0.15	0.16	NO
37	UGT2A1	UGT2A1	UGT2A1	14090	-0.22	0.12	NO
38	UGT2A3	UGT2A3	UGT2A3	14991	-0.28	0.11	NO
39	BLVRA	BLVRA	BLVRA	15172	-0.3	0.14	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: KEGG STEROID HORMONE BIOSYNTHESIS.

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

genes ES table in pathway: KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM

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	HIST1H2AE	HIST1H2AE	HIST1H2AE	216	0.41	0.034	YES
2	HIST1H3E	HIST1H3E	HIST1H3E	219	0.41	0.079	YES
3	HIST1H2BN	HIST1H2BN	HIST1H2BN	239	0.4	0.12	YES
4	HIST1H3H	HIST1H3H	HIST1H3H	370	0.33	0.15	YES
5	HIST1H4I	HIST1H4I	HIST1H4I	483	0.28	0.18	YES
6	HIST2H4A	HIST2H4A	HIST2H4A	495	0.28	0.21	YES
7	HIST1H4J	HIST1H4J	HIST1H4J	533	0.27	0.23	YES
8	HIST1H2BL	HIST1H2BL	HIST1H2BL	573	0.26	0.26	YES
9	HIST1H2BD	HIST1H2BD	HIST1H2BD	575	0.26	0.29	YES
10	HIST1H2AC	HIST1H2AC	HIST1H2AC	713	0.23	0.31	YES
11	HIST1H2BE	HIST1H2BE	HIST1H2BE	740	0.23	0.33	YES
12	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	806	0.21	0.35	YES
13	HIST1H2BC	HIST1H2BC	HIST1H2BC	831	0.21	0.37	YES
14	HIST1H4H	HIST1H4H	HIST1H4H	835	0.21	0.39	YES
15	HIST1H2BG	HIST1H2BG	HIST1H2BG	865	0.2	0.42	YES
16	HIST1H3D	HIST1H3D	HIST1H3D	916	0.2	0.43	YES
17	HIST1H3B	HIST1H3B	HIST1H3B	930	0.19	0.45	YES
18	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	987	0.18	0.47	YES
19	KAT2B	KAT2B	KAT2B	1021	0.18	0.49	YES
20	HIST1H3A	HIST1H3A	HIST1H3A	1046	0.18	0.51	YES
21	HIST1H2BK	HIST1H2BK	HIST1H2BK	1257	0.15	0.51	YES
22	HIST2H3C	HIST2H3C	HIST2H3C	1509	0.13	0.51	YES
23	TAF1A	TAF1A	TAF1A	1587	0.13	0.52	YES
24	HIST2H2BE	HIST2H2BE	HIST2H2BE	1607	0.12	0.54	YES
25	POLR1C	POLR1C	POLR1C	1737	0.12	0.54	YES
26	HIST1H4B	HIST1H4B	HIST1H4B	1772	0.11	0.55	YES
27	HIST1H4E	HIST1H4E	HIST1H4E	1812	0.11	0.56	YES
28	HIST1H2BF	HIST1H2BF	HIST1H2BF	1888	0.11	0.57	YES
29	HIST2H3D	HIST2H3D	HIST2H3D	1953	0.1	0.58	YES
30	MNAT1	MNAT1	MNAT1	2175	0.094	0.58	YES
31	POLR1D	POLR1D	POLR1D	2269	0.09	0.58	YES
32	GTF2H4	GTF2H4	GTF2H4	2641	0.076	0.57	YES
33	HIST1H2AD	HIST1H2AD	HIST1H2AD	2650	0.076	0.58	YES
34	EHMT2	EHMT2	EHMT2	2868	0.069	0.57	YES
35	ERCC2	ERCC2	ERCC2	2873	0.069	0.58	YES
36	HIST1H2BO	HIST1H2BO	HIST1H2BO	2958	0.066	0.58	YES
37	POLR1A	POLR1A	POLR1A	3057	0.063	0.58	YES
38	H3F3A	H3F3A	H3F3A	3081	0.063	0.59	YES
39	POLR1B	POLR1B	POLR1B	3679	0.048	0.56	NO
40	POLR2K	POLR2K	POLR2K	3718	0.047	0.56	NO
41	HIST1H3J	HIST1H3J	HIST1H3J	4019	0.041	0.55	NO
42	RRN3	RRN3	RRN3	4219	0.037	0.54	NO
43	HIST1H4D	HIST1H4D	HIST1H4D	4732	0.028	0.52	NO
44	UBTF	UBTF	UBTF	4922	0.025	0.51	NO
45	MBD2	MBD2	MBD2	4927	0.025	0.51	NO
46	ERCC3	ERCC3	ERCC3	5757	0.011	0.47	NO
47	CBX3	CBX3	CBX3	5780	0.011	0.47	NO
48	CDK7	CDK7	CDK7	5997	0.0078	0.45	NO
49	CCNH	CCNH	CCNH	6403	0.0015	0.43	NO
50	HIST1H3C	HIST1H3C	HIST1H3C	6460	0.00046	0.43	NO
51	TAF1C	TAF1C	TAF1C	6516	-0.00047	0.42	NO
52	POLR2H	POLR2H	POLR2H	6831	-0.0051	0.41	NO
53	HIST1H3G	HIST1H3G	HIST1H3G	7115	-0.009	0.39	NO
54	H3F3B	H3F3B	H3F3B	8325	-0.027	0.33	NO
55	GTF2H3	GTF2H3	GTF2H3	8406	-0.028	0.33	NO
56	HIST1H2AB	HIST1H2AB	HIST1H2AB	8414	-0.028	0.33	NO
57	MAPK3	MAPK3	MAPK3	8444	-0.029	0.33	NO
58	H2AFZ	H2AFZ	H2AFZ	9197	-0.042	0.29	NO
59	HIST1H2BH	HIST1H2BH	HIST1H2BH	9907	-0.056	0.26	NO
60	GTF2H1	GTF2H1	GTF2H1	10021	-0.059	0.26	NO
61	HIST1H4C	HIST1H4C	HIST1H4C	10219	-0.065	0.25	NO
62	H2AFX	H2AFX	H2AFX	10766	-0.079	0.23	NO
63	PTRF	PTRF	PTRF	10873	-0.082	0.24	NO
64	ERCC6	ERCC6	ERCC6	10957	-0.084	0.24	NO
65	HIST1H3I	HIST1H3I	HIST1H3I	10996	-0.085	0.25	NO
66	HIST2H2AC	HIST2H2AC	HIST2H2AC	11367	-0.097	0.24	NO
67	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	11515	-0.1	0.24	NO
68	HIST4H4	HIST4H4	HIST4H4	12096	-0.12	0.22	NO
69	HIST1H4A	HIST1H4A	HIST1H4A	12138	-0.12	0.23	NO
70	GTF2H2	GTF2H2	GTF2H2	12742	-0.15	0.22	NO
71	TAF1B	TAF1B	TAF1B	12846	-0.16	0.23	NO
72	GTF2H2B	GTF2H2B	GTF2H2B	13270	-0.18	0.22	NO
73	HIST3H2BB	HIST3H2BB	HIST3H2BB	14687	-0.26	0.17	NO

Figure S67. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM.

Figure S68. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PORPHYRIN AND CHLOROPHYLL 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 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	RDBP	RDBP	RDBP	1750	0.12	0.0095	YES
2	TCEB1	TCEB1	TCEB1	2928	0.067	0.006	YES
3	POLR2C	POLR2C	POLR2C	3567	0.05	0.017	YES
4	POLR2K	POLR2K	POLR2K	3718	0.047	0.054	YES
5	TCEB2	TCEB2	TCEB2	3792	0.046	0.092	YES
6	POLR2F	POLR2F	POLR2F	3927	0.043	0.12	YES
7	SUPT4H1	SUPT4H1	SUPT4H1	3995	0.042	0.16	YES
8	POLR2J	POLR2J	POLR2J	4255	0.036	0.18	YES
9	TCEA1	TCEA1	TCEA1	4350	0.035	0.21	YES
10	TH1L	TH1L	TH1L	4436	0.033	0.23	YES
11	POLR2L	POLR2L	POLR2L	4556	0.031	0.26	YES
12	WHSC2	WHSC2	WHSC2	4716	0.028	0.27	YES
13	GTF2F2	GTF2F2	GTF2F2	5203	0.02	0.26	YES
14	POLR2E	POLR2E	POLR2E	6505	-0.00027	0.19	YES
15	GTF2F1	GTF2F1	GTF2F1	6771	-0.0043	0.18	YES
16	POLR2H	POLR2H	POLR2H	6831	-0.0051	0.18	YES
17	CTDP1	CTDP1	CTDP1	6875	-0.0056	0.18	YES
18	CDK9	CDK9	CDK9	6896	-0.0059	0.19	YES
19	SUPT16H	SUPT16H	SUPT16H	7289	-0.011	0.18	YES
20	COBRA1	COBRA1	COBRA1	7528	-0.015	0.18	YES
21	POLR2G	POLR2G	POLR2G	7630	-0.016	0.19	YES
22	TCEB3	TCEB3	TCEB3	7701	-0.018	0.2	YES
23	POLR2B	POLR2B	POLR2B	7843	-0.02	0.21	YES
24	POLR2I	POLR2I	POLR2I	7904	-0.021	0.23	YES
25	POLR2A	POLR2A	POLR2A	8241	-0.026	0.23	YES
26	SUPT5H	SUPT5H	SUPT5H	8275	-0.027	0.26	YES
27	POLR2D	POLR2D	POLR2D	8339	-0.028	0.28	YES
28	SSRP1	SSRP1	SSRP1	9046	-0.039	0.28	YES
29	CCNT2	CCNT2	CCNT2	9457	-0.047	0.3	YES
30	ELL	ELL	ELL	10980	-0.085	0.29	YES
31	CCNT1	CCNT1	CCNT1	11263	-0.094	0.36	YES

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

Figure S70. 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 RNA POLYMERASE

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	HIST1H2AE	HIST1H2AE	HIST1H2AE	216	0.41	0.045	YES
2	HIST1H3E	HIST1H3E	HIST1H3E	219	0.41	0.1	YES
3	HIST1H2BN	HIST1H2BN	HIST1H2BN	239	0.4	0.16	YES
4	HIST1H3H	HIST1H3H	HIST1H3H	370	0.33	0.19	YES
5	HIST1H4I	HIST1H4I	HIST1H4I	483	0.28	0.23	YES
6	HIST2H4A	HIST2H4A	HIST2H4A	495	0.28	0.26	YES
7	HIST1H4J	HIST1H4J	HIST1H4J	533	0.27	0.3	YES
8	HIST1H2BL	HIST1H2BL	HIST1H2BL	573	0.26	0.33	YES
9	HIST1H2BD	HIST1H2BD	HIST1H2BD	575	0.26	0.37	YES
10	HIST1H2AC	HIST1H2AC	HIST1H2AC	713	0.23	0.39	YES
11	HIST1H2BE	HIST1H2BE	HIST1H2BE	740	0.23	0.42	YES
12	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	806	0.21	0.45	YES
13	HIST1H2BC	HIST1H2BC	HIST1H2BC	831	0.21	0.48	YES
14	HIST1H4H	HIST1H4H	HIST1H4H	835	0.21	0.5	YES
15	HIST1H2BG	HIST1H2BG	HIST1H2BG	865	0.2	0.53	YES
16	HIST1H3D	HIST1H3D	HIST1H3D	916	0.2	0.55	YES
17	HIST1H3B	HIST1H3B	HIST1H3B	930	0.19	0.58	YES
18	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	987	0.18	0.6	YES
19	HIST1H3A	HIST1H3A	HIST1H3A	1046	0.18	0.62	YES
20	HIST1H2BK	HIST1H2BK	HIST1H2BK	1257	0.15	0.63	YES
21	HIST2H3C	HIST2H3C	HIST2H3C	1509	0.13	0.64	YES
22	HIST2H2BE	HIST2H2BE	HIST2H2BE	1607	0.12	0.65	YES
23	HIST1H4B	HIST1H4B	HIST1H4B	1772	0.11	0.66	YES
24	HIST1H4E	HIST1H4E	HIST1H4E	1812	0.11	0.67	YES
25	HIST1H2BF	HIST1H2BF	HIST1H2BF	1888	0.11	0.68	YES
26	HIST2H3D	HIST2H3D	HIST2H3D	1953	0.1	0.69	YES
27	HIST1H2AD	HIST1H2AD	HIST1H2AD	2650	0.076	0.66	NO
28	HIST1H2BO	HIST1H2BO	HIST1H2BO	2958	0.066	0.65	NO
29	H3F3A	H3F3A	H3F3A	3081	0.063	0.65	NO
30	HIST1H3J	HIST1H3J	HIST1H3J	4019	0.041	0.61	NO
31	HIST1H4D	HIST1H4D	HIST1H4D	4732	0.028	0.57	NO
32	UBTF	UBTF	UBTF	4922	0.025	0.56	NO
33	MBD2	MBD2	MBD2	4927	0.025	0.57	NO
34	HIST1H3C	HIST1H3C	HIST1H3C	6460	0.00046	0.48	NO
35	HIST1H3G	HIST1H3G	HIST1H3G	7115	-0.009	0.44	NO
36	H3F3B	H3F3B	H3F3B	8325	-0.027	0.38	NO
37	HIST1H2AB	HIST1H2AB	HIST1H2AB	8414	-0.028	0.38	NO
38	MAPK3	MAPK3	MAPK3	8444	-0.029	0.38	NO
39	H2AFZ	H2AFZ	H2AFZ	9197	-0.042	0.34	NO
40	HIST1H2BH	HIST1H2BH	HIST1H2BH	9907	-0.056	0.31	NO
41	HIST1H4C	HIST1H4C	HIST1H4C	10219	-0.065	0.3	NO
42	H2AFX	H2AFX	H2AFX	10766	-0.079	0.28	NO
43	HIST1H3I	HIST1H3I	HIST1H3I	10996	-0.085	0.28	NO
44	HIST2H2AC	HIST2H2AC	HIST2H2AC	11367	-0.097	0.27	NO
45	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	11515	-0.1	0.28	NO
46	HIST4H4	HIST4H4	HIST4H4	12096	-0.12	0.26	NO
47	HIST1H4A	HIST1H4A	HIST1H4A	12138	-0.12	0.28	NO
48	HIST3H2BB	HIST3H2BB	HIST3H2BB	14687	-0.26	0.17	NO

Figure S71. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RNA POLYMERASE.

Figure S72. 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 ENDOMETRIAL CANCER

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	POLR3G	POLR3G	POLR3G	1201	0.16	0.048	YES
2	POLR1C	POLR1C	POLR1C	1737	0.12	0.1	YES
3	POLR1D	POLR1D	POLR1D	2269	0.09	0.14	YES
4	POLR2J2	POLR2J2	POLR2J2	2437	0.083	0.19	YES
5	POLR3A	POLR3A	POLR3A	2841	0.07	0.22	YES
6	POLR1A	POLR1A	POLR1A	3057	0.063	0.25	YES
7	POLR2C	POLR2C	POLR2C	3567	0.05	0.26	YES
8	ZNRD1	ZNRD1	ZNRD1	3602	0.05	0.29	YES
9	POLR1B	POLR1B	POLR1B	3679	0.048	0.32	YES
10	POLR2K	POLR2K	POLR2K	3718	0.047	0.35	YES
11	POLR2F	POLR2F	POLR2F	3927	0.043	0.37	YES
12	POLR2J	POLR2J	POLR2J	4255	0.036	0.38	YES
13	POLR2L	POLR2L	POLR2L	4556	0.031	0.38	YES
14	POLR3GL	POLR3GL	POLR3GL	4609	0.03	0.4	YES
15	POLR2J3	POLR2J3	POLR2J3	4868	0.026	0.41	YES
16	POLR3C	POLR3C	POLR3C	5932	0.0088	0.35	NO
17	POLR3F	POLR3F	POLR3F	6463	0.00042	0.32	NO
18	POLR3K	POLR3K	POLR3K	6497	-0.00012	0.32	NO
19	POLR2E	POLR2E	POLR2E	6505	-0.00027	0.32	NO
20	POLR3H	POLR3H	POLR3H	6602	-0.0019	0.32	NO
21	POLR2H	POLR2H	POLR2H	6831	-0.0051	0.31	NO
22	POLR2G	POLR2G	POLR2G	7630	-0.016	0.28	NO
23	POLR2B	POLR2B	POLR2B	7843	-0.02	0.28	NO
24	POLR2I	POLR2I	POLR2I	7904	-0.021	0.29	NO
25	POLR2A	POLR2A	POLR2A	8241	-0.026	0.29	NO
26	POLR2D	POLR2D	POLR2D	8339	-0.028	0.3	NO
27	POLR1E	POLR1E	POLR1E	9793	-0.054	0.26	NO
28	POLR3D	POLR3D	POLR3D	11318	-0.096	0.24	NO
29	POLR3B	POLR3B	POLR3B	12957	-0.16	0.27	NO

Figure S73. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG ENDOMETRIAL CANCER.

Figure S74. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ENDOMETRIAL CANCER, 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 BILE ACID AND BILE SALT METABOLISM

Table S38. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	FARS2	FARS2	FARS2	1097	0.17	0.022	YES
2	NARS2	NARS2	NARS2	1295	0.15	0.085	YES
3	PSTK	PSTK	PSTK	1934	0.1	0.1	YES
4	EARS2	EARS2	EARS2	2343	0.087	0.12	YES
5	VARS	VARS	VARS	2506	0.081	0.15	YES
6	PARS2	PARS2	PARS2	2630	0.076	0.18	YES
7	HARS2	HARS2	HARS2	2818	0.07	0.2	YES
8	KARS	KARS	KARS	3137	0.061	0.22	YES
9	TARS2	TARS2	TARS2	3186	0.059	0.24	YES
10	HARS	HARS	HARS	3194	0.059	0.27	YES
11	AARS	AARS	AARS	3262	0.058	0.29	YES
12	IARS2	IARS2	IARS2	3357	0.056	0.32	YES
13	RARS	RARS	RARS	3376	0.055	0.34	YES
14	SEPSECS	SEPSECS	SEPSECS	3647	0.049	0.35	YES
15	AARS2	AARS2	AARS2	4120	0.039	0.34	YES
16	FARSB	FARSB	FARSB	4276	0.036	0.35	YES
17	QARS	QARS	QARS	4388	0.034	0.36	YES
18	DARS	DARS	DARS	4866	0.026	0.35	YES
19	EPRS	EPRS	EPRS	4926	0.025	0.36	YES
20	MTFMT	MTFMT	MTFMT	4977	0.024	0.36	YES
21	FARSA	FARSA	FARSA	5488	0.015	0.34	YES
22	NARS	NARS	NARS	5734	0.012	0.34	YES
23	VARS2	VARS2	VARS2	6133	0.0057	0.32	YES
24	IARS	IARS	IARS	6483	0.000036	0.3	YES
25	YARS2	YARS2	YARS2	6621	-0.0021	0.29	YES
26	DARS2	DARS2	DARS2	6859	-0.0054	0.28	YES
27	LARS	LARS	LARS	7062	-0.0083	0.27	YES
28	LARS2	LARS2	LARS2	7283	-0.011	0.26	YES
29	WARS2	WARS2	WARS2	8350	-0.028	0.22	YES
30	GARS	GARS	GARS	8603	-0.031	0.22	YES
31	MARS	MARS	MARS	8776	-0.034	0.22	YES
32	TARSL2	TARSL2	TARSL2	8909	-0.037	0.24	YES
33	CARS2	CARS2	CARS2	9250	-0.043	0.24	YES
34	WARS	WARS	WARS	9352	-0.045	0.25	YES
35	YARS	YARS	YARS	9397	-0.046	0.27	YES
36	RARS2	RARS2	RARS2	9553	-0.049	0.29	YES
37	SARS	SARS	SARS	9603	-0.05	0.31	YES
38	SARS2	SARS2	SARS2	10199	-0.064	0.31	YES
39	CARS	CARS	CARS	10572	-0.074	0.32	YES
40	TARS	TARS	TARS	10623	-0.075	0.36	YES
41	MARS2	MARS2	MARS2	11169	-0.091	0.37	YES

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: REACTOME BILE ACID AND BILE SALT METABOLISM.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME BILE ACID AND BILE SALT 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: REACTOME MITOCHONDRIAL PROTEIN IMPORT

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	ACSL6	ACSL6	ACSL6	47	0.72	0.15	YES
2	ACSL5	ACSL5	ACSL5	212	0.42	0.22	YES
3	ADH1B	ADH1B	ADH1B	315	0.35	0.29	YES
4	ADH6	ADH6	ADH6	351	0.34	0.36	YES
5	ADH4	ADH4	ADH4	376	0.32	0.43	YES
6	EHHADH	EHHADH	EHHADH	914	0.2	0.44	YES
7	ADH1C	ADH1C	ADH1C	915	0.2	0.48	YES
8	ALDH3A2	ALDH3A2	ALDH3A2	949	0.19	0.52	YES
9	HADH	HADH	HADH	1731	0.12	0.5	YES
10	ACADL	ACADL	ACADL	1964	0.1	0.5	YES
11	ADH7	ADH7	ADH7	2010	0.1	0.52	YES
12	ALDH1B1	ALDH1B1	ALDH1B1	2059	0.1	0.54	YES
13	CPT1C	CPT1C	CPT1C	2075	0.099	0.56	YES
14	ALDH2	ALDH2	ALDH2	2118	0.097	0.58	YES
15	ADH5	ADH5	ADH5	2152	0.096	0.6	YES
16	GCDH	GCDH	GCDH	2196	0.093	0.61	YES
17	ACAA1	ACAA1	ACAA1	2416	0.084	0.62	YES
18	ALDH7A1	ALDH7A1	ALDH7A1	3410	0.054	0.57	NO
19	ACADSB	ACADSB	ACADSB	3511	0.052	0.58	NO
20	ECHS1	ECHS1	ECHS1	3535	0.051	0.59	NO
21	CPT2	CPT2	CPT2	3699	0.048	0.59	NO
22	ACOX1	ACOX1	ACOX1	3904	0.043	0.58	NO
23	ADH1A	ADH1A	ADH1A	4691	0.029	0.55	NO
24	ALDH9A1	ALDH9A1	ALDH9A1	5042	0.023	0.53	NO
25	ACADM	ACADM	ACADM	5106	0.022	0.53	NO
26	ACSL3	ACSL3	ACSL3	5284	0.019	0.52	NO
27	ACADVL	ACADVL	ACADVL	5570	0.014	0.51	NO
28	ACAA2	ACAA2	ACAA2	6541	-0.00094	0.46	NO
29	HADHA	HADHA	HADHA	6790	-0.0046	0.44	NO
30	CYP4A11	CYP4A11	CYP4A11	7497	-0.014	0.41	NO
31	ACAT1	ACAT1	ACAT1	7521	-0.015	0.41	NO
32	HADHB	HADHB	HADHB	7548	-0.015	0.41	NO
33	CYP4A22	CYP4A22	CYP4A22	8552	-0.031	0.36	NO
34	ACSL1	ACSL1	ACSL1	8704	-0.033	0.36	NO
35	ACAT2	ACAT2	ACAT2	9286	-0.044	0.33	NO
36	ACOX3	ACOX3	ACOX3	9990	-0.058	0.31	NO
37	CPT1A	CPT1A	CPT1A	10319	-0.067	0.3	NO
38	CPT1B	CPT1B	CPT1B	10679	-0.077	0.3	NO
39	ACADS	ACADS	ACADS	11873	-0.12	0.25	NO
40	ACSL4	ACSL4	ACSL4	15998	-0.36	0.096	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: REACTOME MITOCHONDRIAL PROTEIN IMPORT.

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

genes ES table in pathway: REACTOME RNA POL I TRANSCRIPTION

Table 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	HIST1H2AE	HIST1H2AE	HIST1H2AE	216	0.41	0.018	YES
2	HIST1H3E	HIST1H3E	HIST1H3E	219	0.41	0.048	YES
3	HIST1H2BN	HIST1H2BN	HIST1H2BN	239	0.4	0.076	YES
4	HIST1H3H	HIST1H3H	HIST1H3H	370	0.33	0.092	YES
5	HIST1H4I	HIST1H4I	HIST1H4I	483	0.28	0.11	YES
6	HIST2H4A	HIST2H4A	HIST2H4A	495	0.28	0.13	YES
7	HIST1H4J	HIST1H4J	HIST1H4J	533	0.27	0.14	YES
8	HIST1H2BL	HIST1H2BL	HIST1H2BL	573	0.26	0.16	YES
9	HIST1H2BD	HIST1H2BD	HIST1H2BD	575	0.26	0.18	YES
10	HIST1H2AC	HIST1H2AC	HIST1H2AC	713	0.23	0.19	YES
11	HIST1H2BE	HIST1H2BE	HIST1H2BE	740	0.23	0.2	YES
12	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	806	0.21	0.22	YES
13	HIST1H2BC	HIST1H2BC	HIST1H2BC	831	0.21	0.23	YES
14	HIST1H4H	HIST1H4H	HIST1H4H	835	0.21	0.24	YES
15	HIST1H2BG	HIST1H2BG	HIST1H2BG	865	0.2	0.26	YES
16	HIST1H3D	HIST1H3D	HIST1H3D	916	0.2	0.27	YES
17	HIST1H3B	HIST1H3B	HIST1H3B	930	0.19	0.28	YES
18	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	987	0.18	0.29	YES
19	KAT2B	KAT2B	KAT2B	1021	0.18	0.3	YES
20	HIST1H3A	HIST1H3A	HIST1H3A	1046	0.18	0.32	YES
21	HIST1H2BK	HIST1H2BK	HIST1H2BK	1257	0.15	0.31	YES
22	HIST2H3C	HIST2H3C	HIST2H3C	1509	0.13	0.31	YES
23	TAF1A	TAF1A	TAF1A	1587	0.13	0.32	YES
24	HIST2H2BE	HIST2H2BE	HIST2H2BE	1607	0.12	0.32	YES
25	POLR1C	POLR1C	POLR1C	1737	0.12	0.32	YES
26	RDBP	RDBP	RDBP	1750	0.12	0.33	YES
27	HIST1H4B	HIST1H4B	HIST1H4B	1772	0.11	0.34	YES
28	HIST1H4E	HIST1H4E	HIST1H4E	1812	0.11	0.34	YES
29	HIST1H2BF	HIST1H2BF	HIST1H2BF	1888	0.11	0.35	YES
30	HIST2H3D	HIST2H3D	HIST2H3D	1953	0.1	0.35	YES
31	POLRMT	POLRMT	POLRMT	2068	0.099	0.35	YES
32	MNAT1	MNAT1	MNAT1	2175	0.094	0.35	YES
33	POLR1D	POLR1D	POLR1D	2269	0.09	0.36	YES
34	GTF3C5	GTF3C5	GTF3C5	2523	0.08	0.35	YES
35	GTF2H4	GTF2H4	GTF2H4	2641	0.076	0.34	YES
36	HIST1H2AD	HIST1H2AD	HIST1H2AD	2650	0.076	0.35	YES
37	GTF2B	GTF2B	GTF2B	2826	0.07	0.34	YES
38	POLR3A	POLR3A	POLR3A	2841	0.07	0.35	YES
39	GTF2E1	GTF2E1	GTF2E1	2862	0.069	0.35	YES
40	TFB2M	TFB2M	TFB2M	2865	0.069	0.36	YES
41	EHMT2	EHMT2	EHMT2	2868	0.069	0.36	YES
42	ERCC2	ERCC2	ERCC2	2873	0.069	0.37	YES
43	TCEB1	TCEB1	TCEB1	2928	0.067	0.37	YES
44	HIST1H2BO	HIST1H2BO	HIST1H2BO	2958	0.066	0.37	YES
45	POLR1A	POLR1A	POLR1A	3057	0.063	0.37	YES
46	H3F3A	H3F3A	H3F3A	3081	0.063	0.38	YES
47	CPSF1	CPSF1	CPSF1	3348	0.056	0.36	NO
48	TAF1	TAF1	TAF1	3349	0.056	0.37	NO
49	DHX38	DHX38	DHX38	3459	0.053	0.37	NO
50	POLR2C	POLR2C	POLR2C	3567	0.05	0.36	NO
51	TAF9	TAF9	TAF9	3626	0.049	0.36	NO
52	POLR1B	POLR1B	POLR1B	3679	0.048	0.36	NO
53	POLR2K	POLR2K	POLR2K	3718	0.047	0.37	NO
54	TCEB2	TCEB2	TCEB2	3792	0.046	0.36	NO
55	CSTF2	CSTF2	CSTF2	3836	0.045	0.36	NO
56	POLR3E	POLR3E	POLR3E	3860	0.044	0.37	NO
57	POLR2F	POLR2F	POLR2F	3927	0.043	0.37	NO
58	SUPT4H1	SUPT4H1	SUPT4H1	3995	0.042	0.37	NO
59	HIST1H3J	HIST1H3J	HIST1H3J	4019	0.041	0.37	NO
60	TAF12	TAF12	TAF12	4068	0.04	0.37	NO
61	MAGOH	MAGOH	MAGOH	4177	0.038	0.36	NO
62	RRN3	RRN3	RRN3	4219	0.037	0.36	NO
63	POLR2J	POLR2J	POLR2J	4255	0.036	0.36	NO
64	CLP1	CLP1	CLP1	4292	0.036	0.37	NO
65	TCEA1	TCEA1	TCEA1	4350	0.035	0.36	NO
66	TAF6	TAF6	TAF6	4417	0.033	0.36	NO
67	TH1L	TH1L	TH1L	4436	0.033	0.36	NO
68	POLR2L	POLR2L	POLR2L	4556	0.031	0.36	NO
69	POLR3GL	POLR3GL	POLR3GL	4609	0.03	0.36	NO
70	WHSC2	WHSC2	WHSC2	4716	0.028	0.36	NO
71	HIST1H4D	HIST1H4D	HIST1H4D	4732	0.028	0.36	NO
72	NFX1	NFX1	NFX1	4878	0.026	0.35	NO
73	UBTF	UBTF	UBTF	4922	0.025	0.35	NO
74	MBD2	MBD2	MBD2	4927	0.025	0.35	NO
75	TAF10	TAF10	TAF10	4943	0.024	0.35	NO
76	NUDT21	NUDT21	NUDT21	5032	0.023	0.35	NO
77	GTF2F2	GTF2F2	GTF2F2	5203	0.02	0.34	NO
78	CSTF1	CSTF1	CSTF1	5215	0.02	0.34	NO
79	GTF2A1	GTF2A1	GTF2A1	5265	0.019	0.34	NO
80	SNRPD3	SNRPD3	SNRPD3	5266	0.019	0.34	NO
81	RNPS1	RNPS1	RNPS1	5717	0.012	0.32	NO
82	ERCC3	ERCC3	ERCC3	5757	0.011	0.32	NO
83	GTF3C3	GTF3C3	GTF3C3	5773	0.011	0.32	NO
84	CBX3	CBX3	CBX3	5780	0.011	0.32	NO
85	SNRPE	SNRPE	SNRPE	5883	0.0095	0.31	NO
86	CPSF3	CPSF3	CPSF3	5914	0.0091	0.31	NO
87	POLR3C	POLR3C	POLR3C	5932	0.0088	0.31	NO
88	CDK7	CDK7	CDK7	5997	0.0078	0.31	NO
89	LSM11	LSM11	LSM11	6027	0.0073	0.3	NO
90	TFAM	TFAM	TFAM	6085	0.0064	0.3	NO
91	SSB	SSB	SSB	6089	0.0064	0.3	NO
92	RNMT	RNMT	RNMT	6221	0.0043	0.3	NO
93	TAF11	TAF11	TAF11	6236	0.004	0.3	NO
94	LSM10	LSM10	LSM10	6322	0.0025	0.29	NO
95	SNAPC4	SNAPC4	SNAPC4	6338	0.0023	0.29	NO
96	PCF11	PCF11	PCF11	6393	0.0016	0.29	NO
97	CCNH	CCNH	CCNH	6403	0.0015	0.29	NO
98	HIST1H3C	HIST1H3C	HIST1H3C	6460	0.00046	0.28	NO
99	POLR3F	POLR3F	POLR3F	6463	0.00042	0.28	NO
100	PABPN1	PABPN1	PABPN1	6465	0.00037	0.28	NO
101	POLR3K	POLR3K	POLR3K	6497	-0.00012	0.28	NO
102	POLR2E	POLR2E	POLR2E	6505	-0.00027	0.28	NO
103	TAF1C	TAF1C	TAF1C	6516	-0.00047	0.28	NO
104	U2AF2	U2AF2	U2AF2	6571	-0.0014	0.28	NO
105	POLR3H	POLR3H	POLR3H	6602	-0.0019	0.28	NO
106	SNAPC2	SNAPC2	SNAPC2	6724	-0.0035	0.27	NO
107	GTF2F1	GTF2F1	GTF2F1	6771	-0.0043	0.27	NO
108	POLR2H	POLR2H	POLR2H	6831	-0.0051	0.26	NO
109	GTF3C2	GTF3C2	GTF3C2	6838	-0.0052	0.26	NO
110	CTDP1	CTDP1	CTDP1	6875	-0.0056	0.26	NO
111	CDK9	CDK9	CDK9	6896	-0.0059	0.26	NO
112	ZNF143	ZNF143	ZNF143	6979	-0.0069	0.26	NO
113	BRF2	BRF2	BRF2	7099	-0.0088	0.25	NO
114	HIST1H3G	HIST1H3G	HIST1H3G	7115	-0.009	0.25	NO
115	SRRM1	SRRM1	SRRM1	7152	-0.0096	0.25	NO
116	SUPT16H	SUPT16H	SUPT16H	7289	-0.011	0.24	NO
117	SNRPB	SNRPB	SNRPB	7378	-0.013	0.24	NO
118	COBRA1	COBRA1	COBRA1	7528	-0.015	0.23	NO
119	SNAPC3	SNAPC3	SNAPC3	7532	-0.015	0.23	NO
120	ZNF473	ZNF473	ZNF473	7547	-0.015	0.23	NO
121	CSTF3	CSTF3	CSTF3	7622	-0.016	0.23	NO
122	POLR2G	POLR2G	POLR2G	7630	-0.016	0.23	NO
123	TCEB3	TCEB3	TCEB3	7701	-0.018	0.23	NO
124	TAF13	TAF13	TAF13	7802	-0.019	0.22	NO
125	GTF3C4	GTF3C4	GTF3C4	7830	-0.02	0.22	NO
126	POLR2B	POLR2B	POLR2B	7843	-0.02	0.22	NO
127	POLR2I	POLR2I	POLR2I	7904	-0.021	0.22	NO
128	SNRPG	SNRPG	SNRPG	8092	-0.024	0.21	NO
129	NFIB	NFIB	NFIB	8096	-0.024	0.21	NO
130	SLBP	SLBP	SLBP	8097	-0.024	0.22	NO
131	CPSF2	CPSF2	CPSF2	8128	-0.024	0.22	NO
132	NCBP1	NCBP1	NCBP1	8177	-0.025	0.22	NO
133	POLR2A	POLR2A	POLR2A	8241	-0.026	0.21	NO
134	SUPT5H	SUPT5H	SUPT5H	8275	-0.027	0.21	NO
135	H3F3B	H3F3B	H3F3B	8325	-0.027	0.21	NO
136	POLR2D	POLR2D	POLR2D	8339	-0.028	0.21	NO
137	GTF2A2	GTF2A2	GTF2A2	8360	-0.028	0.22	NO
138	GTF2H3	GTF2H3	GTF2H3	8406	-0.028	0.21	NO
139	HIST1H2AB	HIST1H2AB	HIST1H2AB	8414	-0.028	0.22	NO
140	MAPK3	MAPK3	MAPK3	8444	-0.029	0.22	NO
141	CPSF7	CPSF7	CPSF7	8476	-0.029	0.22	NO
142	BRF1	BRF1	BRF1	8517	-0.03	0.22	NO
143	UPF3B	UPF3B	UPF3B	8796	-0.035	0.2	NO
144	CDC40	CDC40	CDC40	8913	-0.037	0.2	NO
145	RBM8A	RBM8A	RBM8A	8943	-0.037	0.2	NO
146	SSRP1	SSRP1	SSRP1	9046	-0.039	0.2	NO
147	TAF5	TAF5	TAF5	9175	-0.042	0.19	NO
148	H2AFZ	H2AFZ	H2AFZ	9197	-0.042	0.2	NO
149	CCNT2	CCNT2	CCNT2	9457	-0.047	0.18	NO
150	RNGTT	RNGTT	RNGTT	9574	-0.05	0.18	NO
151	PAPOLA	PAPOLA	PAPOLA	9696	-0.052	0.18	NO
152	SNAPC5	SNAPC5	SNAPC5	9715	-0.052	0.18	NO
153	HIST1H2BH	HIST1H2BH	HIST1H2BH	9907	-0.056	0.17	NO
154	THOC4	THOC4	THOC4	9924	-0.057	0.18	NO
155	GTF2H1	GTF2H1	GTF2H1	10021	-0.059	0.18	NO
156	TAF4	TAF4	TAF4	10072	-0.061	0.18	NO
157	TBP	TBP	TBP	10106	-0.062	0.18	NO
158	HIST1H4C	HIST1H4C	HIST1H4C	10219	-0.065	0.18	NO
159	POU2F1	POU2F1	POU2F1	10483	-0.072	0.17	NO
160	NCBP2	NCBP2	NCBP2	10493	-0.072	0.17	NO
161	SNRPF	SNRPF	SNRPF	10736	-0.078	0.16	NO
162	H2AFX	H2AFX	H2AFX	10766	-0.079	0.17	NO
163	PTRF	PTRF	PTRF	10873	-0.082	0.17	NO
164	ERCC6	ERCC6	ERCC6	10957	-0.084	0.17	NO
165	ELL	ELL	ELL	10980	-0.085	0.18	NO
166	HIST1H3I	HIST1H3I	HIST1H3I	10996	-0.085	0.18	NO
167	SNAPC1	SNAPC1	SNAPC1	11228	-0.093	0.18	NO
168	CCNT1	CCNT1	CCNT1	11263	-0.094	0.18	NO
169	POLR3D	POLR3D	POLR3D	11318	-0.096	0.18	NO
170	U2AF1	U2AF1	U2AF1	11340	-0.096	0.19	NO
171	HIST2H2AC	HIST2H2AC	HIST2H2AC	11367	-0.097	0.2	NO
172	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	11515	-0.1	0.19	NO
173	HIST4H4	HIST4H4	HIST4H4	12096	-0.12	0.17	NO
174	HIST1H4A	HIST1H4A	HIST1H4A	12138	-0.12	0.18	NO
175	MTERF	MTERF	MTERF	12251	-0.13	0.18	NO
176	GTF2E2	GTF2E2	GTF2E2	12711	-0.15	0.16	NO
177	GTF2H2	GTF2H2	GTF2H2	12742	-0.15	0.17	NO
178	TAF1B	TAF1B	TAF1B	12846	-0.16	0.18	NO
179	POLR3B	POLR3B	POLR3B	12957	-0.16	0.18	NO
180	GTF2H2B	GTF2H2B	GTF2H2B	13270	-0.18	0.18	NO
181	HIST3H2BB	HIST3H2BB	HIST3H2BB	14687	-0.26	0.12	NO
182	LZTS1	LZTS1	LZTS1	15406	-0.31	0.1	NO
183	TAF4B	TAF4B	TAF4B	16492	-0.41	0.068	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: REACTOME RNA POL I TRANSCRIPTION.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus5 enriched pathways

Table 7. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus5. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG GLYCOLYSIS GLUCONEOGENESIS	60	genes.ES.table	0.52	1.6	0.0096	1	0.93	0.28	0.1	0.26	0.59	0.33
KEGG HISTIDINE METABOLISM	29	genes.ES.table	0.63	1.6	0.029	0.98	0.93	0.66	0.23	0.5	0.54	0.3
KEGG TRYPTOPHAN METABOLISM	39	genes.ES.table	0.67	1.7	0.011	1	0.85	0.62	0.18	0.51	1	0.72
KEGG SELENOAMINO ACID METABOLISM	26	genes.ES.table	0.49	1.6	0.03	0.92	0.94	0.31	0.19	0.25	0.51	0.29
KEGG PROPANOATE METABOLISM	32	genes.ES.table	0.63	1.6	0.033	1	0.91	0.69	0.23	0.53	0.66	0.36
KEGG COMPLEMENT AND COAGULATION CASCADES	68	genes.ES.table	0.69	1.6	0.037	0.96	0.94	0.81	0.23	0.62	0.53	0.3
KEGG PRION DISEASES	34	genes.ES.table	0.65	1.6	0.0084	1	0.88	0.53	0.17	0.44	1	0.62
BIOCARTA VIP PATHWAY	25	genes.ES.table	0.62	1.6	0.023	1	0.9	0.64	0.3	0.45	0.83	0.44
BIOCARTA NFAT PATHWAY	48	genes.ES.table	0.51	1.6	0.012	1	0.93	0.54	0.29	0.39	0.57	0.31
BIOCARTA IL1R PATHWAY	31	genes.ES.table	0.57	1.6	0.016	1	0.89	0.42	0.21	0.33	1	0.5

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

Table S41. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ITGA9	ITGA9	ITGA9	153	0.76	0.12	YES
2	NCAM1	NCAM1	NCAM1	236	0.68	0.23	YES
3	RPS6KA6	RPS6KA6	RPS6KA6	653	0.5	0.3	YES
4	L1CAM	L1CAM	L1CAM	1140	0.39	0.34	YES
5	SH3GL2	SH3GL2	SH3GL2	1491	0.33	0.37	YES
6	ITGB3	ITGB3	ITGB3	1565	0.32	0.42	YES
7	FGFR1	FGFR1	FGFR1	1716	0.31	0.47	YES
8	RPS6KA5	RPS6KA5	RPS6KA5	1952	0.28	0.5	YES
9	EGFR	EGFR	EGFR	2558	0.23	0.51	YES
10	MAP2K1	MAP2K1	MAP2K1	2700	0.22	0.54	YES
11	ITGA2B	ITGA2B	ITGA2B	2776	0.21	0.57	YES
12	RPS6KA2	RPS6KA2	RPS6KA2	3664	0.16	0.55	NO
13	NRP1	NRP1	NRP1	7177	0.025	0.35	NO
14	AP2A2	AP2A2	AP2A2	7682	0.012	0.32	NO
15	RPS6KA1	RPS6KA1	RPS6KA1	7963	0.0041	0.31	NO
16	RPS6KA3	RPS6KA3	RPS6KA3	8492	-0.0088	0.28	NO
17	ITGB1	ITGB1	ITGB1	8810	-0.016	0.26	NO
18	MAPK1	MAPK1	MAPK1	8909	-0.018	0.26	NO
19	CSNK2A2	CSNK2A2	CSNK2A2	9263	-0.026	0.25	NO
20	AP2S1	AP2S1	AP2S1	9517	-0.032	0.24	NO
21	CLTC	CLTC	CLTC	9588	-0.034	0.24	NO
22	AP2A1	AP2A1	AP2A1	9880	-0.041	0.23	NO
23	AP2B1	AP2B1	AP2B1	9889	-0.041	0.24	NO
24	RAC1	RAC1	RAC1	10364	-0.053	0.22	NO
25	AP2M1	AP2M1	AP2M1	10454	-0.055	0.22	NO
26	CSNK2A1	CSNK2A1	CSNK2A1	11644	-0.083	0.17	NO
27	ITGAV	ITGAV	ITGAV	11956	-0.09	0.17	NO
28	ITGA5	ITGA5	ITGA5	12269	-0.099	0.17	NO
29	CSNK2B	CSNK2B	CSNK2B	12724	-0.11	0.16	NO
30	CLTA	CLTA	CLTA	13047	-0.12	0.16	NO
31	MAP2K2	MAP2K2	MAP2K2	13117	-0.13	0.18	NO
32	RPS6KA4	RPS6KA4	RPS6KA4	13250	-0.13	0.2	NO
33	PAK1	PAK1	PAK1	13994	-0.16	0.18	NO
34	MAPK3	MAPK3	MAPK3	14125	-0.16	0.2	NO

Figure S81. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS.

Figure S82. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG HISTIDINE 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	CYP1A2	CYP1A2	CYP1A2	48	1	0.083	YES
2	AADAT	AADAT	AADAT	78	0.89	0.16	YES
3	INMT	INMT	INMT	97	0.85	0.23	YES
4	IDO2	IDO2	IDO2	203	0.71	0.28	YES
5	KMO	KMO	KMO	456	0.56	0.31	YES
6	TDO2	TDO2	TDO2	521	0.54	0.36	YES
7	OGDHL	OGDHL	OGDHL	654	0.5	0.39	YES
8	CYP1A1	CYP1A1	CYP1A1	850	0.45	0.42	YES
9	AOX1	AOX1	AOX1	1043	0.4	0.44	YES
10	EHHADH	EHHADH	EHHADH	1244	0.37	0.46	YES
11	ACMSD	ACMSD	ACMSD	1419	0.34	0.48	YES
12	HAAO	HAAO	HAAO	1440	0.34	0.51	YES
13	ABP1	ABP1	ABP1	1495	0.33	0.53	YES
14	GCDH	GCDH	GCDH	1660	0.31	0.55	YES
15	ALDH2	ALDH2	ALDH2	1772	0.3	0.57	YES
16	ALDH1B1	ALDH1B1	ALDH1B1	1815	0.3	0.59	YES
17	CAT	CAT	CAT	1906	0.28	0.61	YES
18	ACAT1	ACAT1	ACAT1	1931	0.28	0.63	YES
19	KYNU	KYNU	KYNU	2252	0.26	0.64	YES
20	ECHS1	ECHS1	ECHS1	2748	0.21	0.62	YES
21	DDC	DDC	DDC	2906	0.2	0.63	YES
22	MAOB	MAOB	MAOB	2967	0.2	0.65	YES
23	HADH	HADH	HADH	2988	0.2	0.66	YES
24	ALDH9A1	ALDH9A1	ALDH9A1	3112	0.19	0.67	YES
25	MAOA	MAOA	MAOA	3691	0.15	0.65	NO
26	ACAT2	ACAT2	ACAT2	3729	0.15	0.66	NO
27	ALDH7A1	ALDH7A1	ALDH7A1	4081	0.14	0.65	NO
28	ALDH3A2	ALDH3A2	ALDH3A2	5027	0.092	0.61	NO
29	HADHA	HADHA	HADHA	5470	0.077	0.59	NO
30	AFMID	AFMID	AFMID	5552	0.074	0.59	NO
31	CYP1B1	CYP1B1	CYP1B1	6111	0.056	0.56	NO
32	OGDH	OGDH	OGDH	8001	0.0032	0.46	NO
33	WARS2	WARS2	WARS2	9334	-0.028	0.38	NO
34	WARS	WARS	WARS	9382	-0.029	0.38	NO
35	ASMT	ASMT	ASMT	12980	-0.12	0.19	NO
36	IDO1	IDO1	IDO1	13163	-0.13	0.19	NO
37	AANAT	AANAT	AANAT	14445	-0.18	0.13	NO
38	TPH1	TPH1	TPH1	15031	-0.21	0.12	NO
39	IL4I1	IL4I1	IL4I1	16662	-0.38	0.058	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 HISTIDINE METABOLISM.

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

genes ES table in pathway: KEGG TRYPTOPHAN METABOLISM

Table S43. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CYP26A1	CYP26A1	CYP26A1	36	1	0.041	YES
2	CYP1A2	CYP1A2	CYP1A2	48	1	0.082	YES
3	PTGS2	PTGS2	PTGS2	86	0.86	0.12	YES
4	CYP39A1	CYP39A1	CYP39A1	105	0.83	0.15	YES
5	CYP3A43	CYP3A43	CYP3A43	193	0.72	0.17	YES
6	CYP3A4	CYP3A4	CYP3A4	204	0.71	0.2	YES
7	PTGIS	PTGIS	PTGIS	217	0.7	0.23	YES
8	CYP2C19	CYP2C19	CYP2C19	224	0.69	0.26	YES
9	CYP2B6	CYP2B6	CYP2B6	249	0.67	0.28	YES
10	CYP2C8	CYP2C8	CYP2C8	261	0.66	0.31	YES
11	FMO2	FMO2	FMO2	274	0.65	0.34	YES
12	ADH4	ADH4	ADH4	301	0.63	0.36	YES
13	CYP2A6	CYP2A6	CYP2A6	343	0.61	0.38	YES
14	CYP8B1	CYP8B1	CYP8B1	405	0.58	0.4	YES
15	CYP4A11	CYP4A11	CYP4A11	472	0.56	0.42	YES
16	ADH1C	ADH1C	ADH1C	523	0.54	0.44	YES
17	ADH1B	ADH1B	ADH1B	641	0.5	0.46	YES
18	CYP4F2	CYP4F2	CYP4F2	675	0.49	0.48	YES
19	CYP2C9	CYP2C9	CYP2C9	681	0.49	0.5	YES
20	CYP2E1	CYP2E1	CYP2E1	690	0.49	0.51	YES
21	ADH1A	ADH1A	ADH1A	774	0.47	0.53	YES
22	CYP2A13	CYP2A13	CYP2A13	849	0.45	0.54	YES
23	CYP1A1	CYP1A1	CYP1A1	850	0.45	0.56	YES
24	FMO3	FMO3	FMO3	1135	0.39	0.56	YES
25	TBXAS1	TBXAS1	TBXAS1	1211	0.37	0.57	YES
26	ADH6	ADH6	ADH6	1269	0.36	0.58	YES
27	CYP2C18	CYP2C18	CYP2C18	1322	0.36	0.6	YES
28	CYP11A1	CYP11A1	CYP11A1	1346	0.36	0.61	YES
29	CYP2J2	CYP2J2	CYP2J2	1375	0.35	0.62	YES
30	CYP4F12	CYP4F12	CYP4F12	1540	0.33	0.63	YES
31	CYP2U1	CYP2U1	CYP2U1	1576	0.32	0.64	YES
32	CYP7B1	CYP7B1	CYP7B1	1577	0.32	0.65	YES
33	CYP4F3	CYP4F3	CYP4F3	1581	0.32	0.66	YES
34	PTGS1	PTGS1	PTGS1	1590	0.32	0.68	YES
35	CYP46A1	CYP46A1	CYP46A1	1717	0.31	0.68	YES
36	CYP3A7	CYP3A7	CYP3A7	1752	0.3	0.69	YES
37	ADH7	ADH7	ADH7	1765	0.3	0.7	YES
38	ALDH2	ALDH2	ALDH2	1772	0.3	0.72	YES
39	POMC	POMC	POMC	1879	0.29	0.72	YES
40	CYP27A1	CYP27A1	CYP27A1	2740	0.22	0.68	NO
41	MAOB	MAOB	MAOB	2967	0.2	0.68	NO
42	CYP4F11	CYP4F11	CYP4F11	3037	0.19	0.68	NO
43	CYP26B1	CYP26B1	CYP26B1	3415	0.17	0.67	NO
44	CYP3A5	CYP3A5	CYP3A5	3529	0.16	0.67	NO
45	CYP2D6	CYP2D6	CYP2D6	3635	0.16	0.67	NO
46	MAOA	MAOA	MAOA	3691	0.15	0.67	NO
47	PAOX	PAOX	PAOX	4497	0.12	0.63	NO
48	CYP2S1	CYP2S1	CYP2S1	4828	0.1	0.62	NO
49	ALDH1A1	ALDH1A1	ALDH1A1	5316	0.082	0.59	NO
50	ACSS2	ACSS2	ACSS2	5709	0.068	0.57	NO
51	CYP7A1	CYP7A1	CYP7A1	5997	0.06	0.56	NO
52	CYP1B1	CYP1B1	CYP1B1	6111	0.056	0.55	NO
53	CYP51A1	CYP51A1	CYP51A1	8127	0.00018	0.44	NO
54	CYP21A2	CYP21A2	CYP21A2	9844	-0.04	0.34	NO
55	CYP4B1	CYP4B1	CYP4B1	10471	-0.055	0.31	NO
56	ACSS1	ACSS1	ACSS1	10722	-0.061	0.3	NO
57	CYP26C1	CYP26C1	CYP26C1	12259	-0.099	0.22	NO
58	FMO1	FMO1	FMO1	13005	-0.12	0.18	NO
59	CYP17A1	CYP17A1	CYP17A1	13987	-0.16	0.13	NO
60	CYP2R1	CYP2R1	CYP2R1	14680	-0.19	0.098	NO
61	SMOX	SMOX	SMOX	14933	-0.21	0.092	NO
62	CYP27B1	CYP27B1	CYP27B1	17087	-0.47	-0.01	NO
63	CYP19A1	CYP19A1	CYP19A1	17187	-0.5	0.0045	NO
64	CYP2W1	CYP2W1	CYP2W1	17361	-0.58	0.019	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 TRYPTOPHAN METABOLISM.

Figure S86. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG TRYPTOPHAN 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 SELENOAMINO ACID 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	C7	C7	C7	139	0.79	0.079	YES
2	C9	C9	C9	233	0.68	0.15	YES
3	NCAM1	NCAM1	NCAM1	236	0.68	0.22	YES
4	C6	C6	C6	465	0.56	0.27	YES
5	EGR1	EGR1	EGR1	483	0.55	0.33	YES
6	IL1B	IL1B	IL1B	522	0.54	0.39	YES
7	NCAM2	NCAM2	NCAM2	587	0.52	0.44	YES
8	C8A	C8A	C8A	750	0.47	0.48	YES
9	IL6	IL6	IL6	878	0.44	0.52	YES
10	C8B	C8B	C8B	1199	0.38	0.55	YES
11	FYN	FYN	FYN	2096	0.27	0.53	YES
12	C1QC	C1QC	C1QC	2337	0.25	0.54	YES
13	C1QB	C1QB	C1QB	2379	0.24	0.56	YES
14	PRNP	PRNP	PRNP	2582	0.23	0.58	YES
15	C1QA	C1QA	C1QA	2639	0.22	0.6	YES
16	MAP2K1	MAP2K1	MAP2K1	2700	0.22	0.62	YES
17	CCL5	CCL5	CCL5	2836	0.21	0.63	YES
18	C5	C5	C5	2963	0.2	0.65	YES
19	C8G	C8G	C8G	4078	0.14	0.6	NO
20	SOD1	SOD1	SOD1	4375	0.12	0.6	NO
21	PRKACB	PRKACB	PRKACB	5035	0.092	0.57	NO
22	PRKACA	PRKACA	PRKACA	5923	0.062	0.53	NO
23	PRKX	PRKX	PRKX	6134	0.056	0.52	NO
24	NOTCH1	NOTCH1	NOTCH1	6751	0.037	0.49	NO
25	ELK1	ELK1	ELK1	7853	0.0071	0.43	NO
26	MAPK1	MAPK1	MAPK1	8909	-0.018	0.37	NO
27	HSPA5	HSPA5	HSPA5	10285	-0.051	0.3	NO
28	IL1A	IL1A	IL1A	11780	-0.086	0.22	NO
29	HSPA1A	HSPA1A	HSPA1A	12643	-0.11	0.19	NO
30	MAP2K2	MAP2K2	MAP2K2	13117	-0.13	0.17	NO
31	MAPK3	MAPK3	MAPK3	14125	-0.16	0.13	NO
32	BAX	BAX	BAX	14414	-0.18	0.14	NO
33	STIP1	STIP1	STIP1	14876	-0.2	0.13	NO
34	LAMC1	LAMC1	LAMC1	15439	-0.24	0.13	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 SELENOAMINO ACID METABOLISM.

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

genes ES table in pathway: KEGG PROPANOATE 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	CYP26A1	CYP26A1	CYP26A1	36	1	0.024	YES
2	CYP1A2	CYP1A2	CYP1A2	48	1	0.048	YES
3	NAT2	NAT2	NAT2	72	0.9	0.069	YES
4	PTGS2	PTGS2	PTGS2	86	0.86	0.089	YES
5	CYP39A1	CYP39A1	CYP39A1	105	0.83	0.11	YES
6	GSTM5	GSTM5	GSTM5	123	0.81	0.13	YES
7	CYP3A43	CYP3A43	CYP3A43	193	0.72	0.14	YES
8	CYP3A4	CYP3A4	CYP3A4	204	0.71	0.16	YES
9	PTGIS	PTGIS	PTGIS	217	0.7	0.17	YES
10	CYP2C19	CYP2C19	CYP2C19	224	0.69	0.19	YES
11	CYP2B6	CYP2B6	CYP2B6	249	0.67	0.21	YES
12	CYP2C8	CYP2C8	CYP2C8	261	0.66	0.22	YES
13	FMO2	FMO2	FMO2	274	0.65	0.24	YES
14	ADH4	ADH4	ADH4	301	0.63	0.25	YES
15	GLYAT	GLYAT	GLYAT	306	0.63	0.27	YES
16	SULT1B1	SULT1B1	SULT1B1	330	0.62	0.28	YES
17	CYP2A6	CYP2A6	CYP2A6	343	0.61	0.29	YES
18	CYP8B1	CYP8B1	CYP8B1	405	0.58	0.3	YES
19	GGT5	GGT5	GGT5	419	0.58	0.32	YES
20	CYP4A11	CYP4A11	CYP4A11	472	0.56	0.33	YES
21	NNMT	NNMT	NNMT	506	0.54	0.34	YES
22	ADH1C	ADH1C	ADH1C	523	0.54	0.35	YES
23	ADH1B	ADH1B	ADH1B	641	0.5	0.36	YES
24	SULT1E1	SULT1E1	SULT1E1	673	0.49	0.37	YES
25	CYP4F2	CYP4F2	CYP4F2	675	0.49	0.38	YES
26	CYP2C9	CYP2C9	CYP2C9	681	0.49	0.39	YES
27	CYP2E1	CYP2E1	CYP2E1	690	0.49	0.4	YES
28	UGT2B7	UGT2B7	UGT2B7	696	0.48	0.42	YES
29	UGT1A5	UGT1A5	UGT1A5	732	0.48	0.43	YES
30	UGT2B10	UGT2B10	UGT2B10	770	0.47	0.44	YES
31	ADH1A	ADH1A	ADH1A	774	0.47	0.45	YES
32	UGT1A4	UGT1A4	UGT1A4	796	0.46	0.46	YES
33	UGT1A3	UGT1A3	UGT1A3	835	0.45	0.47	YES
34	CYP2A13	CYP2A13	CYP2A13	849	0.45	0.48	YES
35	CYP1A1	CYP1A1	CYP1A1	850	0.45	0.49	YES
36	NAT1	NAT1	NAT1	901	0.43	0.5	YES
37	SULT1A2	SULT1A2	SULT1A2	955	0.42	0.5	YES
38	UGT1A1	UGT1A1	UGT1A1	1022	0.41	0.51	YES
39	SULT1C4	SULT1C4	SULT1C4	1078	0.4	0.52	YES
40	GSTA2	GSTA2	GSTA2	1080	0.4	0.52	YES
41	FMO3	FMO3	FMO3	1135	0.39	0.53	YES
42	TBXAS1	TBXAS1	TBXAS1	1211	0.37	0.54	YES
43	SULT2A1	SULT2A1	SULT2A1	1259	0.37	0.54	YES
44	ADH6	ADH6	ADH6	1269	0.36	0.55	YES
45	CYP2C18	CYP2C18	CYP2C18	1322	0.36	0.56	YES
46	CYP11A1	CYP11A1	CYP11A1	1346	0.36	0.56	YES
47	MAT1A	MAT1A	MAT1A	1371	0.35	0.57	YES
48	CYP2J2	CYP2J2	CYP2J2	1375	0.35	0.58	YES
49	UGT2B28	UGT2B28	UGT2B28	1418	0.34	0.59	YES
50	ACSM2B	ACSM2B	ACSM2B	1456	0.34	0.59	YES
51	CYP4F12	CYP4F12	CYP4F12	1540	0.33	0.6	YES
52	CYP2U1	CYP2U1	CYP2U1	1576	0.32	0.6	YES
53	CYP7B1	CYP7B1	CYP7B1	1577	0.32	0.61	YES
54	CYP4F3	CYP4F3	CYP4F3	1581	0.32	0.62	YES
55	PTGS1	PTGS1	PTGS1	1590	0.32	0.62	YES
56	GSTA1	GSTA1	GSTA1	1685	0.31	0.63	YES
57	CYP46A1	CYP46A1	CYP46A1	1717	0.31	0.63	YES
58	CYP3A7	CYP3A7	CYP3A7	1752	0.3	0.64	YES
59	ADH7	ADH7	ADH7	1765	0.3	0.64	YES
60	ALDH2	ALDH2	ALDH2	1772	0.3	0.65	YES
61	SLC35D1	SLC35D1	SLC35D1	1773	0.3	0.66	YES
62	SULT1A1	SULT1A1	SULT1A1	1800	0.3	0.66	YES
63	POMC	POMC	POMC	1879	0.29	0.67	YES
64	PAPSS2	PAPSS2	PAPSS2	2177	0.26	0.66	NO
65	UGT2A1	UGT2A1	UGT2A1	2186	0.26	0.66	NO
66	UGP2	UGP2	UGP2	2374	0.24	0.66	NO
67	GSTM1	GSTM1	GSTM1	2421	0.24	0.66	NO
68	UGT1A9	UGT1A9	UGT1A9	2460	0.24	0.66	NO
69	CYP27A1	CYP27A1	CYP27A1	2740	0.22	0.66	NO
70	MAOB	MAOB	MAOB	2967	0.2	0.65	NO
71	CYP4F11	CYP4F11	CYP4F11	3037	0.19	0.65	NO
72	GSTP1	GSTP1	GSTP1	3162	0.18	0.64	NO
73	MGST1	MGST1	MGST1	3166	0.18	0.65	NO
74	GGT1	GGT1	GGT1	3334	0.17	0.64	NO
75	TPMT	TPMT	TPMT	3370	0.17	0.65	NO
76	COMT	COMT	COMT	3392	0.17	0.65	NO
77	CYP26B1	CYP26B1	CYP26B1	3415	0.17	0.65	NO
78	CYP3A5	CYP3A5	CYP3A5	3529	0.16	0.65	NO
79	CYP2D6	CYP2D6	CYP2D6	3635	0.16	0.65	NO
80	MAOA	MAOA	MAOA	3691	0.15	0.65	NO
81	UGT1A6	UGT1A6	UGT1A6	3723	0.15	0.65	NO
82	GCLC	GCLC	GCLC	3770	0.15	0.65	NO
83	PAOX	PAOX	PAOX	4497	0.12	0.61	NO
84	UGT2B4	UGT2B4	UGT2B4	4760	0.1	0.6	NO
85	CYP2S1	CYP2S1	CYP2S1	4828	0.1	0.6	NO
86	MGST2	MGST2	MGST2	4877	0.099	0.6	NO
87	CNDP2	CNDP2	CNDP2	5014	0.093	0.59	NO
88	ALDH1A1	ALDH1A1	ALDH1A1	5316	0.082	0.58	NO
89	UGT1A8	UGT1A8	UGT1A8	5339	0.082	0.58	NO
90	GSTM4	GSTM4	GSTM4	5438	0.078	0.57	NO
91	GCLM	GCLM	GCLM	5588	0.073	0.57	NO
92	GSTO1	GSTO1	GSTO1	5594	0.072	0.57	NO
93	ACSS2	ACSS2	ACSS2	5709	0.068	0.56	NO
94	CYP7A1	CYP7A1	CYP7A1	5997	0.06	0.55	NO
95	CYP1B1	CYP1B1	CYP1B1	6111	0.056	0.55	NO
96	MAT2B	MAT2B	MAT2B	6524	0.043	0.52	NO
97	MAT2A	MAT2A	MAT2A	7994	0.0034	0.44	NO
98	CYP51A1	CYP51A1	CYP51A1	8127	0.00018	0.43	NO
99	AHCY	AHCY	AHCY	8370	-0.0055	0.42	NO
100	GGT7	GGT7	GGT7	8962	-0.019	0.38	NO
101	OPLAH	OPLAH	OPLAH	9257	-0.026	0.37	NO
102	UGDH	UGDH	UGDH	9460	-0.03	0.36	NO
103	GSS	GSS	GSS	9520	-0.032	0.36	NO
104	MGST3	MGST3	MGST3	9618	-0.035	0.35	NO
105	GSTO2	GSTO2	GSTO2	9732	-0.038	0.35	NO
106	CYP21A2	CYP21A2	CYP21A2	9844	-0.04	0.34	NO
107	CYP4B1	CYP4B1	CYP4B1	10471	-0.055	0.31	NO
108	ACSS1	ACSS1	ACSS1	10722	-0.061	0.29	NO
109	BPNT1	BPNT1	BPNT1	10889	-0.065	0.28	NO
110	SULT2B1	SULT2B1	SULT2B1	12127	-0.095	0.22	NO
111	CYP26C1	CYP26C1	CYP26C1	12259	-0.099	0.21	NO
112	SULT1A3	SULT1A3	SULT1A3	12855	-0.12	0.18	NO
113	ACSM1	ACSM1	ACSM1	12902	-0.12	0.18	NO
114	FMO1	FMO1	FMO1	13005	-0.12	0.18	NO
115	UGT1A7	UGT1A7	UGT1A7	13049	-0.12	0.18	NO
116	MTR	MTR	MTR	13057	-0.12	0.18	NO
117	GGCT	GGCT	GGCT	13080	-0.12	0.18	NO
118	PAPSS1	PAPSS1	PAPSS1	13580	-0.14	0.16	NO
119	UGT2B11	UGT2B11	UGT2B11	13599	-0.14	0.16	NO
120	GSTA4	GSTA4	GSTA4	13947	-0.16	0.14	NO
121	CYP17A1	CYP17A1	CYP17A1	13987	-0.16	0.15	NO
122	CYP2R1	CYP2R1	CYP2R1	14680	-0.19	0.11	NO
123	SMOX	SMOX	SMOX	14933	-0.21	0.1	NO
124	SULT4A1	SULT4A1	SULT4A1	15190	-0.22	0.094	NO
125	SULT1C2	SULT1C2	SULT1C2	16793	-0.41	0.013	NO
126	CYP27B1	CYP27B1	CYP27B1	17087	-0.47	0.0076	NO
127	CYP19A1	CYP19A1	CYP19A1	17187	-0.5	0.014	NO
128	CYP2W1	CYP2W1	CYP2W1	17361	-0.58	0.019	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 PROPANOATE METABOLISM.

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

genes ES table in pathway: KEGG COMPLEMENT AND COAGULATION CASCADES

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	IL1B	IL1B	IL1B	522	0.54	0.077	YES
2	IL1RAP	IL1RAP	IL1RAP	819	0.45	0.15	YES
3	IL6	IL6	IL6	878	0.44	0.23	YES
4	IRAK3	IRAK3	IRAK3	920	0.43	0.32	YES
5	IL1RN	IL1RN	IL1RN	1101	0.39	0.38	YES
6	JUN	JUN	JUN	2066	0.27	0.38	YES
7	MAPK8	MAPK8	MAPK8	2348	0.25	0.42	YES
8	MAP2K3	MAP2K3	MAP2K3	2674	0.22	0.44	YES
9	TNF	TNF	TNF	2786	0.21	0.48	YES
10	IL1R1	IL1R1	IL1R1	2801	0.21	0.52	YES
11	MYD88	MYD88	MYD88	2821	0.21	0.56	YES
12	TGFB3	TGFB3	TGFB3	3528	0.16	0.55	YES
13	TRAF6	TRAF6	TRAF6	3683	0.15	0.57	YES
14	NFKBIA	NFKBIA	NFKBIA	4332	0.12	0.56	NO
15	NFKB1	NFKB1	NFKB1	4680	0.11	0.56	NO
16	TOLLIP	TOLLIP	TOLLIP	6020	0.059	0.5	NO
17	CHUK	CHUK	CHUK	6403	0.047	0.48	NO
18	ECSIT	ECSIT	ECSIT	6881	0.033	0.46	NO
19	MAP3K14	MAP3K14	MAP3K14	7017	0.03	0.46	NO
20	MAPK14	MAPK14	MAPK14	7621	0.013	0.43	NO
21	IKBKB	IKBKB	IKBKB	7905	0.0056	0.41	NO
22	MAP3K7	MAP3K7	MAP3K7	8394	-0.0061	0.39	NO
23	TGFB1	TGFB1	TGFB1	8646	-0.012	0.38	NO
24	RELA	RELA	RELA	8734	-0.014	0.37	NO
25	MAP3K1	MAP3K1	MAP3K1	9437	-0.03	0.34	NO
26	IRAK2	IRAK2	IRAK2	10406	-0.054	0.3	NO
27	TGFB2	TGFB2	TGFB2	11363	-0.075	0.26	NO
28	TAB1	TAB1	TAB1	11728	-0.084	0.25	NO
29	IL1A	IL1A	IL1A	11780	-0.086	0.27	NO
30	MAP2K6	MAP2K6	MAP2K6	12813	-0.12	0.23	NO
31	IRAK1	IRAK1	IRAK1	15215	-0.23	0.14	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 COMPLEMENT AND COAGULATION CASCADES.

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

genes ES table in pathway: KEGG PRION DISEASES

Table 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	ESR1	ESR1	ESR1	56	0.96	0.14	YES
2	CXCL12	CXCL12	CXCL12	155	0.76	0.25	YES
3	GHR	GHR	GHR	281	0.65	0.33	YES
4	NRG1	NRG1	NRG1	290	0.64	0.43	YES
5	PGR	PGR	PGR	367	0.6	0.51	YES
6	ERBB4	ERBB4	ERBB4	1031	0.41	0.54	YES
7	NRG4	NRG4	NRG4	1932	0.28	0.53	YES
8	NCOR1	NCOR1	NCOR1	2455	0.24	0.53	YES
9	HBEGF	HBEGF	HBEGF	2566	0.23	0.56	YES
10	TAB2	TAB2	TAB2	3450	0.17	0.53	YES
11	JAK2	JAK2	JAK2	3495	0.16	0.56	YES
12	EREG	EREG	EREG	3512	0.16	0.58	YES
13	WWOX	WWOX	WWOX	4458	0.12	0.54	NO
14	BTC	BTC	BTC	4784	0.1	0.54	NO
15	GFAP	GFAP	GFAP	4927	0.096	0.55	NO
16	S100B	S100B	S100B	5962	0.061	0.5	NO
17	STAT5B	STAT5B	STAT5B	6550	0.043	0.47	NO
18	PRLR	PRLR	PRLR	7186	0.025	0.44	NO
19	CUL1	CUL1	CUL1	7440	0.018	0.43	NO
20	PSEN1	PSEN1	PSEN1	7577	0.015	0.42	NO
21	YAP1	YAP1	YAP1	7601	0.014	0.42	NO
22	BTRC	BTRC	BTRC	8413	-0.0069	0.38	NO
23	STAT5A	STAT5A	STAT5A	8509	-0.0092	0.37	NO
24	ADAM17	ADAM17	ADAM17	9167	-0.024	0.34	NO
25	APH1B	APH1B	APH1B	9264	-0.026	0.34	NO
26	SKP1	SKP1	SKP1	9926	-0.042	0.3	NO
27	APH1A	APH1A	APH1A	11068	-0.069	0.25	NO
28	RBX1	RBX1	RBX1	11395	-0.076	0.24	NO
29	PSENEN	PSENEN	PSENEN	11435	-0.077	0.25	NO
30	NCSTN	NCSTN	NCSTN	11843	-0.088	0.24	NO
31	SH2B1	SH2B1	SH2B1	12331	-0.1	0.23	NO
32	PSEN2	PSEN2	PSEN2	12689	-0.11	0.23	NO
33	NRG2	NRG2	NRG2	16644	-0.38	0.059	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 PRION DISEASES.

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

genes ES table in pathway: BIOCARTA VIP 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	PRKAR2B	PRKAR2B	PRKAR2B	154	0.76	0.15	YES
2	EGR2	EGR2	EGR2	163	0.75	0.3	YES
3	EGR3	EGR3	EGR3	198	0.71	0.44	YES
4	VIPR2	VIPR2	VIPR2	1037	0.41	0.48	YES
5	NFATC2	NFATC2	NFATC2	1387	0.35	0.53	YES
6	MYC	MYC	MYC	2074	0.27	0.55	YES
7	NFATC1	NFATC1	NFATC1	2484	0.24	0.57	YES
8	PRKAR1B	PRKAR1B	PRKAR1B	3627	0.16	0.54	YES
9	PRKAR2A	PRKAR2A	PRKAR2A	4019	0.14	0.54	YES
10	NFKBIA	NFKBIA	NFKBIA	4332	0.12	0.55	YES
11	PPP3CA	PPP3CA	PPP3CA	4539	0.11	0.56	YES
12	NFKB1	NFKB1	NFKB1	4680	0.11	0.57	YES
13	PPP3CC	PPP3CC	PPP3CC	4694	0.11	0.6	YES
14	CALM1	CALM1	CALM1	4973	0.095	0.6	YES
15	PRKACB	PRKACB	PRKACB	5035	0.092	0.62	YES
16	GNAQ	GNAQ	GNAQ	5247	0.085	0.62	YES
17	CHUK	CHUK	CHUK	6403	0.047	0.56	NO
18	PRKAR1A	PRKAR1A	PRKAR1A	7053	0.028	0.53	NO
19	PPP3CB	PPP3CB	PPP3CB	8315	-0.0042	0.46	NO
20	RELA	RELA	RELA	8734	-0.014	0.44	NO
21	VIP	VIP	VIP	8932	-0.019	0.44	NO
22	CALM2	CALM2	CALM2	9094	-0.022	0.43	NO
23	MAP3K1	MAP3K1	MAP3K1	9437	-0.03	0.42	NO
24	CALM3	CALM3	CALM3	10518	-0.056	0.37	NO
25	PLCG1	PLCG1	PLCG1	14630	-0.19	0.17	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 VIP PATHWAY.

Figure S96. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA VIP 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 NFAT PATHWAY

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	F9	F9	F9	449	0.57	0.042	YES
2	F3	F3	F3	655	0.5	0.089	YES
3	THBD	THBD	THBD	701	0.48	0.14	YES
4	KLKB1	KLKB1	KLKB1	794	0.46	0.19	YES
5	PF4	PF4	PF4	844	0.45	0.24	YES
6	GP5	GP5	GP5	918	0.43	0.29	YES
7	F8	F8	F8	971	0.42	0.34	YES
8	F11	F11	F11	1201	0.38	0.37	YES
9	GP1BA	GP1BA	GP1BA	1568	0.32	0.38	YES
10	F12	F12	F12	1723	0.3	0.41	YES
11	PF4V1	PF4V1	PF4V1	1791	0.3	0.44	YES
12	F13B	F13B	F13B	1835	0.29	0.48	YES
13	FGB	FGB	FGB	2023	0.27	0.5	YES
14	FGG	FGG	FGG	2136	0.26	0.52	YES
15	SERPINC1	SERPINC1	SERPINC1	2142	0.26	0.55	YES
16	PROS1	PROS1	PROS1	2304	0.25	0.57	YES
17	GP9	GP9	GP9	2311	0.25	0.6	YES
18	FGA	FGA	FGA	2325	0.25	0.63	YES
19	F7	F7	F7	2530	0.23	0.65	YES
20	A2M	A2M	A2M	2551	0.23	0.67	YES
21	F2	F2	F2	2685	0.22	0.69	YES
22	SERPING1	SERPING1	SERPING1	2782	0.21	0.71	YES
23	KNG1	KNG1	KNG1	2874	0.2	0.73	YES
24	PROC	PROC	PROC	2998	0.2	0.75	YES
25	PRCP	PRCP	PRCP	3466	0.17	0.74	NO
26	TFPI	TFPI	TFPI	4565	0.11	0.69	NO
27	F10	F10	F10	4712	0.11	0.7	NO
28	F5	F5	F5	5726	0.068	0.65	NO
29	C1QBP	C1QBP	C1QBP	6924	0.032	0.58	NO
30	F13A1	F13A1	F13A1	11729	-0.085	0.32	NO
31	VWF	VWF	VWF	13561	-0.14	0.23	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: BIOCARTA NFAT PATHWAY.

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

genes ES table in pathway: BIOCARTA IL1R PATHWAY

Table 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	GDF2	GDF2	GDF2	2	1.6	0.3	YES
2	ID1	ID1	ID1	516	0.54	0.38	YES
3	SMAD9	SMAD9	SMAD9	915	0.43	0.44	YES
4	INHBA	INHBA	INHBA	1312	0.36	0.49	YES
5	ENG	ENG	ENG	2429	0.24	0.47	YES
6	SMAD7	SMAD7	SMAD7	2732	0.22	0.5	YES
7	SMAD1	SMAD1	SMAD1	3240	0.18	0.5	YES
8	TGFB3	TGFB3	TGFB3	3528	0.16	0.52	YES
9	BMPR2	BMPR2	BMPR2	3558	0.16	0.55	YES
10	TGFBR2	TGFBR2	TGFBR2	4233	0.13	0.53	NO
11	ACVR2A	ACVR2A	ACVR2A	4576	0.11	0.54	NO
12	ACVR1	ACVR1	ACVR1	6019	0.059	0.46	NO
13	SMAD4	SMAD4	SMAD4	6153	0.055	0.47	NO
14	ACVR2B	ACVR2B	ACVR2B	8041	0.0025	0.36	NO
15	TGFBR1	TGFBR1	TGFBR1	8131	-6e-06	0.36	NO
16	CAV1	CAV1	CAV1	8297	-0.0038	0.35	NO
17	ARRB2	ARRB2	ARRB2	8478	-0.0086	0.34	NO
18	TGFB1	TGFB1	TGFB1	8646	-0.012	0.33	NO
19	MAPK1	MAPK1	MAPK1	8909	-0.018	0.32	NO
20	SMAD5	SMAD5	SMAD5	9950	-0.043	0.27	NO
21	PPP1CA	PPP1CA	PPP1CA	11466	-0.078	0.2	NO
22	FKBP1A	FKBP1A	FKBP1A	12422	-0.1	0.17	NO
23	CSNK2B	CSNK2B	CSNK2B	12724	-0.11	0.17	NO
24	ACVRL1	ACVRL1	ACVRL1	13007	-0.12	0.18	NO
25	MAPK3	MAPK3	MAPK3	14125	-0.16	0.15	NO
26	TLX2	TLX2	TLX2	15833	-0.28	0.1	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: BIOCARTA IL1R PATHWAY.

Figure S100. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

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 = LIHC.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = LIHC.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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