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

Lung Adenocarcinoma (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2016): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in LUAD-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1G73D55

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 "LUAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run. This pipeline has the following features:

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

Summary

Table 1. Get Full Table basic data info

basic data info
Number of Gene Sets: 714
Number of samples: 515
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 ] 132
pheno.type: 2 - 5 :[ clus2 ] 120
pheno.type: 3 - 5 :[ clus3 ] 90
pheno.type: 4 - 5 :[ clus4 ] 115
pheno.type: 5 - 5 :[ clus5 ] 58

For the expression subtypes of 18319 genes in 516 samples, GSEA found enriched gene sets in each cluster using 515 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG DNA REPLICATION, KEGG CELL CYCLE, KEGG PATHOGENIC ESCHERICHIA COLI INFECTION, BIOCARTA FAS PATHWAY, BIOCARTA VEGF PATHWAY, PID HDAC CLASSII PATHWAY, PID AVB3 OPN PATHWAY, PID ILK PATHWAY, PID TCPTP PATHWAY, PID TELOMERASEPATHWAY

And common core enriched genes are GRB2, CDK1, MAPK11, MAPK13, MAPK14, MAPKAPK2, MAPKAPK3, NGF, NRAS, NTRK1

clus2

Top enriched gene sets are KEGG FATTY ACID METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG ARACHIDONIC ACID METABOLISM, KEGG PROPANOATE METABOLISM, KEGG ALDOSTERONE REGULATED SODIUM REABSORPTION, KEGG VASOPRESSIN REGULATED WATER REABSORPTION, KEGG VIRAL MYOCARDITIS, BIOCARTA FCER1 PATHWAY, ST ADRENERGIC, ST WNT BETA CATENIN PATHWAY

And common core enriched genes are NEDD4L, ARRB2, ADCY9, AQP2, AQP3, AQP4, AVPR2, CREB3L1, DYNC2H1, VAMP2

clus3

Top enriched gene sets are KEGG DNA REPLICATION, KEGG SPLICEOSOME, KEGG PROTEASOME, KEGG NUCLEOTIDE EXCISION REPAIR, KEGG CELL CYCLE, KEGG P53 SIGNALING PATHWAY, KEGG UBIQUITIN MEDIATED PROTEOLYSIS, BIOCARTA G1 PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA PROTEASOME PATHWAY

And common core enriched genes are PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA8, PSMB1, PSMB10, PSMB2, PSMB3

clus4

Top enriched gene sets are KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RNA DEGRADATION, REACTOME METABOLISM OF NON CODING RNA, REACTOME CELL CYCLE, REACTOME MITOCHONDRIAL PROTEIN IMPORT, REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA, REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM, REACTOME RNA POL II TRANSCRIPTION, REACTOME RNA POL III TRANSCRIPTION, REACTOME RECRUITMENT OF MITOTIC CENTROSOME PROTEINS AND COMPLEXES

And common core enriched genes are PAPOLA, LSM2, CPSF1, CPSF2, CPSF3, CPSF7, CSTF1, CSTF2, CSTF3, GTF2F2

clus5

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG FATTY ACID METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS, KEGG TYROSINE METABOLISM, KEGG GLUTATHIONE METABOLISM, KEGG STARCH AND SUCROSE METABOLISM, KEGG GLYCEROPHOSPHOLIPID METABOLISM, KEGG LINOLEIC ACID METABOLISM, KEGG SPHINGOLIPID METABOLISM, KEGG RETINOL METABOLISM

And common core enriched genes are NRG1, NRG2, DNAH1, DNAH2, DNAH3, DNAI1, DNAI2, DNALI1, GRM5, PLCB4

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 DNA REPLICATION	36	genes.ES.table	0.62	1.5	0.1	1	0.98	0.56	0.27	0.41	1	0.59
KEGG CELL CYCLE	118	genes.ES.table	0.5	1.5	0.12	1	0.98	0.35	0.2	0.28	1	0.5
KEGG PATHOGENIC ESCHERICHIA COLI INFECTION	53	genes.ES.table	0.4	1.5	0.031	1	0.98	0.43	0.27	0.32	1	0.56
BIOCARTA FAS PATHWAY	30	genes.ES.table	0.44	1.6	0.089	1	0.96	0.57	0.33	0.38	1	0.68
BIOCARTA VEGF PATHWAY	29	genes.ES.table	0.44	1.6	0.074	1	0.96	0.14	0.1	0.12	1	0.6
PID HDAC CLASSII PATHWAY	34	genes.ES.table	0.4	1.5	0.072	1	0.98	0.12	0.13	0.1	1	0.54
PID AVB3 OPN PATHWAY	31	genes.ES.table	0.51	1.6	0.057	1	0.96	0.19	0.13	0.17	1	0.71
PID ILK PATHWAY	45	genes.ES.table	0.39	1.5	0.074	1	0.97	0.56	0.4	0.33	1	0.58
PID TCPTP PATHWAY	42	genes.ES.table	0.46	1.6	0.064	1	0.92	0.38	0.28	0.27	1	0.64
PID TELOMERASEPATHWAY	68	genes.ES.table	0.35	1.5	0.083	1	0.98	0.26	0.24	0.2	0.91	0.47

genes ES table in pathway: KEGG DNA REPLICATION

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	NGF	NGF	NGF	163	0.31	0.18	YES
2	SHC3	SHC3	SHC3	1658	0.13	0.18	YES
3	BRAF	BRAF	BRAF	2150	0.11	0.22	YES
4	CDK1	CDK1	CDK1	2261	0.1	0.27	YES
5	NTRK1	NTRK1	NTRK1	2465	0.095	0.32	YES
6	MAPKAPK3	MAPKAPK3	MAPKAPK3	2473	0.095	0.38	YES
7	SHC2	SHC2	SHC2	2918	0.082	0.41	YES
8	RALB	RALB	RALB	3801	0.061	0.4	YES
9	RALA	RALA	RALA	3868	0.06	0.43	YES
10	NRAS	NRAS	NRAS	4334	0.052	0.44	YES
11	GRB2	GRB2	GRB2	4560	0.048	0.45	YES
12	RAP1A	RAP1A	RAP1A	4622	0.047	0.48	YES
13	MAPKAPK2	MAPKAPK2	MAPKAPK2	4790	0.044	0.5	YES
14	MAPK13	MAPK13	MAPK13	5337	0.036	0.49	YES
15	RALGDS	RALGDS	RALGDS	6003	0.028	0.47	YES
16	FRS2	FRS2	FRS2	6028	0.028	0.49	YES
17	MAPK14	MAPK14	MAPK14	6043	0.028	0.5	YES
18	MAPK11	MAPK11	MAPK11	6228	0.026	0.51	YES
19	RIT1	RIT1	RIT1	6648	0.022	0.5	NO
20	MAP2K2	MAP2K2	MAP2K2	7480	0.014	0.46	NO
21	MAPK12	MAPK12	MAPK12	7734	0.011	0.46	NO
22	MAPK3	MAPK3	MAPK3	7882	0.01	0.45	NO
23	MAPK1	MAPK1	MAPK1	7915	0.0098	0.46	NO
24	SHC1	SHC1	SHC1	8487	0.0046	0.43	NO
25	KIDINS220	KIDINS220	KIDINS220	8718	0.0025	0.42	NO
26	PLCG1	PLCG1	PLCG1	8734	0.0023	0.42	NO
27	RAF1	RAF1	RAF1	8970	0.00017	0.4	NO
28	KRAS	KRAS	KRAS	9343	-0.0032	0.39	NO
29	YWHAB	YWHAB	YWHAB	9372	-0.0035	0.39	NO
30	SOS1	SOS1	SOS1	10189	-0.011	0.35	NO
31	SRC	SRC	SRC	10532	-0.014	0.34	NO
32	MAP2K1	MAP2K1	MAP2K1	10661	-0.015	0.34	NO
33	RAPGEF1	RAPGEF1	RAPGEF1	12741	-0.037	0.25	NO
34	CRK	CRK	CRK	12778	-0.037	0.27	NO
35	HRAS	HRAS	HRAS	13555	-0.049	0.26	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 DNA REPLICATION.

Figure S2. 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 CELL CYCLE

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	NGF	NGF	NGF	163	0.31	0.22	YES
2	SHC3	SHC3	SHC3	1658	0.13	0.23	YES
3	CDK1	CDK1	CDK1	2261	0.1	0.28	YES
4	NTRK1	NTRK1	NTRK1	2465	0.095	0.34	YES
5	MAPKAPK3	MAPKAPK3	MAPKAPK3	2473	0.095	0.41	YES
6	SHC2	SHC2	SHC2	2918	0.082	0.45	YES
7	RALB	RALB	RALB	3801	0.061	0.44	YES
8	RALA	RALA	RALA	3868	0.06	0.48	YES
9	NRAS	NRAS	NRAS	4334	0.052	0.5	YES
10	GRB2	GRB2	GRB2	4560	0.048	0.52	YES
11	MAPKAPK2	MAPKAPK2	MAPKAPK2	4790	0.044	0.54	YES
12	MAPK13	MAPK13	MAPK13	5337	0.036	0.54	YES
13	RALGDS	RALGDS	RALGDS	6003	0.028	0.52	YES
14	MAPK14	MAPK14	MAPK14	6043	0.028	0.54	YES
15	MAPK11	MAPK11	MAPK11	6228	0.026	0.55	YES
16	MAP2K2	MAP2K2	MAP2K2	7480	0.014	0.49	NO
17	MAPK12	MAPK12	MAPK12	7734	0.011	0.49	NO
18	MAPK3	MAPK3	MAPK3	7882	0.01	0.49	NO
19	MAPK1	MAPK1	MAPK1	7915	0.0098	0.49	NO
20	SHC1	SHC1	SHC1	8487	0.0046	0.46	NO
21	RAF1	RAF1	RAF1	8970	0.00017	0.44	NO
22	KRAS	KRAS	KRAS	9343	-0.0032	0.42	NO
23	YWHAB	YWHAB	YWHAB	9372	-0.0035	0.42	NO
24	SOS1	SOS1	SOS1	10189	-0.011	0.38	NO
25	SRC	SRC	SRC	10532	-0.014	0.38	NO
26	MAP2K1	MAP2K1	MAP2K1	10661	-0.015	0.38	NO
27	HRAS	HRAS	HRAS	13555	-0.049	0.26	NO

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

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

genes ES table in pathway: KEGG PATHOGENIC ESCHERICHIA COLI INFECTION

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	FCGR1A	FCGR1A	FCGR1A	415	0.24	0.0077	YES
2	ICAM1	ICAM1	ICAM1	428	0.23	0.037	YES
3	FCGR1B	FCGR1B	FCGR1B	433	0.23	0.067	YES
4	IRF5	IRF5	IRF5	713	0.19	0.076	YES
5	VCAM1	VCAM1	VCAM1	717	0.19	0.1	YES
6	GBP6	GBP6	GBP6	737	0.19	0.12	YES
7	IFIT1	IFIT1	IFIT1	1020	0.17	0.13	YES
8	PTAFR	PTAFR	PTAFR	1084	0.16	0.15	YES
9	IFNB1	IFNB1	IFNB1	1133	0.16	0.17	YES
10	HLA-DQA2	HLA-DQA2	HLA-DQA2	1176	0.16	0.18	YES
11	ISG15	ISG15	ISG15	1198	0.16	0.2	YES
12	IFNAR2	IFNAR2	IFNAR2	1249	0.15	0.22	YES
13	HLA-DRB5	HLA-DRB5	HLA-DRB5	1612	0.13	0.22	YES
14	HERC5	HERC5	HERC5	1766	0.12	0.22	YES
15	GBP1	GBP1	GBP1	1865	0.12	0.23	YES
16	KPNA2	KPNA2	KPNA2	1972	0.11	0.24	YES
17	NUP155	NUP155	NUP155	1999	0.11	0.26	YES
18	HLA-G	HLA-G	HLA-G	2010	0.11	0.27	YES
19	NUPL2	NUPL2	NUPL2	2072	0.11	0.28	YES
20	MX2	MX2	MX2	2201	0.1	0.29	YES
21	IFI27	IFI27	IFI27	2226	0.1	0.3	YES
22	IFIT2	IFIT2	IFIT2	2235	0.1	0.31	YES
23	GBP5	GBP5	GBP5	2324	0.1	0.32	YES
24	HLA-DQA1	HLA-DQA1	HLA-DQA1	2332	0.1	0.33	YES
25	IFNG	IFNG	IFNG	2351	0.1	0.34	YES
26	GBP2	GBP2	GBP2	2463	0.095	0.35	YES
27	MT2A	MT2A	MT2A	2468	0.095	0.36	YES
28	MX1	MX1	MX1	2508	0.094	0.37	YES
29	IFIT3	IFIT3	IFIT3	2751	0.087	0.37	YES
30	HLA-DRB1	HLA-DRB1	HLA-DRB1	2783	0.086	0.38	YES
31	SOCS1	SOCS1	SOCS1	2821	0.084	0.39	YES
32	IFI35	IFI35	IFI35	2839	0.084	0.4	YES
33	IFNGR2	IFNGR2	IFNGR2	2946	0.081	0.4	YES
34	HLA-DPA1	HLA-DPA1	HLA-DPA1	2956	0.081	0.41	YES
35	IFI6	IFI6	IFI6	3080	0.078	0.42	YES
36	EIF2AK2	EIF2AK2	EIF2AK2	3132	0.076	0.42	YES
37	IRF7	IRF7	IRF7	3189	0.075	0.43	YES
38	CIITA	CIITA	CIITA	3201	0.074	0.44	YES
39	OASL	OASL	OASL	3233	0.074	0.44	YES
40	DDX58	DDX58	DDX58	3284	0.072	0.45	YES
41	NUP85	NUP85	NUP85	3500	0.068	0.45	YES
42	NEDD4	NEDD4	NEDD4	3576	0.066	0.45	YES
43	GBP7	GBP7	GBP7	3632	0.065	0.46	YES
44	UBE2L6	UBE2L6	UBE2L6	3812	0.061	0.46	YES
45	NUP205	NUP205	NUP205	3903	0.059	0.46	YES
46	HLA-DPB1	HLA-DPB1	HLA-DPB1	3925	0.059	0.47	YES
47	HLA-B	HLA-B	HLA-B	4309	0.052	0.45	YES
48	OAS3	OAS3	OAS3	4317	0.052	0.46	YES
49	IFNAR1	IFNAR1	IFNAR1	4355	0.051	0.46	YES
50	XAF1	XAF1	XAF1	4430	0.05	0.46	YES
51	OAS2	OAS2	OAS2	4432	0.05	0.47	YES
52	PML	PML	PML	4502	0.049	0.47	YES
53	USP18	USP18	USP18	4626	0.047	0.47	YES
54	NUP210	NUP210	NUP210	4702	0.045	0.47	YES
55	STAT1	STAT1	STAT1	4772	0.044	0.48	YES
56	UBA7	UBA7	UBA7	4821	0.044	0.48	YES
57	NUP62	NUP62	NUP62	4862	0.043	0.48	YES
58	CD44	CD44	CD44	4865	0.043	0.49	YES
59	POM121	POM121	POM121	4870	0.043	0.49	YES
60	TYK2	TYK2	TYK2	5567	0.033	0.46	NO
61	HLA-A	HLA-A	HLA-A	5633	0.032	0.46	NO
62	HLA-F	HLA-F	HLA-F	5697	0.032	0.46	NO
63	HLA-C	HLA-C	HLA-C	5712	0.032	0.46	NO
64	PSMB8	PSMB8	PSMB8	5775	0.031	0.46	NO
65	NUP54	NUP54	NUP54	5945	0.029	0.46	NO
66	OAS1	OAS1	OAS1	6119	0.027	0.45	NO
67	CAMK2D	CAMK2D	CAMK2D	6202	0.026	0.45	NO
68	KPNA4	KPNA4	KPNA4	6287	0.026	0.45	NO
69	IRF9	IRF9	IRF9	6288	0.026	0.45	NO
70	IFNGR1	IFNGR1	IFNGR1	6297	0.026	0.46	NO
71	EIF4A3	EIF4A3	EIF4A3	6462	0.024	0.45	NO
72	EIF4E	EIF4E	EIF4E	6726	0.021	0.44	NO
73	JAK2	JAK2	JAK2	6794	0.02	0.44	NO
74	IRF1	IRF1	IRF1	6861	0.019	0.44	NO
75	NUP93	NUP93	NUP93	6901	0.019	0.44	NO
76	PTPN1	PTPN1	PTPN1	6931	0.019	0.44	NO
77	ADAR	ADAR	ADAR	6947	0.019	0.44	NO
78	NUP107	NUP107	NUP107	7088	0.017	0.43	NO
79	STAT2	STAT2	STAT2	7185	0.016	0.43	NO
80	IRF3	IRF3	IRF3	7466	0.014	0.42	NO
81	EIF4G1	EIF4G1	EIF4G1	7540	0.013	0.41	NO
82	NUP188	NUP188	NUP188	7639	0.012	0.41	NO
83	KPNB1	KPNB1	KPNB1	7816	0.011	0.4	NO
84	EGR1	EGR1	EGR1	7850	0.01	0.4	NO
85	MAPK3	MAPK3	MAPK3	7882	0.01	0.4	NO
86	NUP43	NUP43	NUP43	7901	0.0099	0.4	NO
87	UBE2E1	UBE2E1	UBE2E1	8107	0.0081	0.39	NO
88	SP100	SP100	SP100	8195	0.0072	0.39	NO
89	B2M	B2M	B2M	8341	0.0059	0.38	NO
90	EIF4G3	EIF4G3	EIF4G3	8549	0.004	0.37	NO
91	KPNA1	KPNA1	KPNA1	8634	0.0032	0.36	NO
92	FLNB	FLNB	FLNB	8717	0.0025	0.36	NO
93	PLCG1	PLCG1	PLCG1	8734	0.0023	0.36	NO
94	NUP37	NUP37	NUP37	8792	0.0017	0.36	NO
95	RNASEL	RNASEL	RNASEL	8805	0.0015	0.36	NO
96	NUP214	NUP214	NUP214	8843	0.0012	0.36	NO
97	PTPN6	PTPN6	PTPN6	8844	0.0012	0.36	NO
98	JAK1	JAK1	JAK1	8877	0.00094	0.35	NO
99	GBP4	GBP4	GBP4	9017	-0.00015	0.35	NO
100	IFITM3	IFITM3	IFITM3	9115	-0.00098	0.34	NO
101	PRKCD	PRKCD	PRKCD	9118	-0.00098	0.34	NO
102	PIN1	PIN1	PIN1	9138	-0.0012	0.34	NO
103	SUMO1	SUMO1	SUMO1	9445	-0.0042	0.32	NO
104	SOCS3	SOCS3	SOCS3	9446	-0.0042	0.32	NO
105	SEH1L	SEH1L	SEH1L	9454	-0.0042	0.32	NO
106	CAMK2A	CAMK2A	CAMK2A	9461	-0.0043	0.32	NO
107	RAE1	RAE1	RAE1	9481	-0.0045	0.32	NO
108	TPR	TPR	TPR	9488	-0.0046	0.32	NO
109	EIF4G2	EIF4G2	EIF4G2	9494	-0.0046	0.32	NO
110	UBA52	UBA52	UBA52	9657	-0.006	0.32	NO
111	EIF4A2	EIF4A2	EIF4A2	9708	-0.0065	0.32	NO
112	TRIM25	TRIM25	TRIM25	9734	-0.0068	0.31	NO
113	PTPN2	PTPN2	PTPN2	9793	-0.0073	0.31	NO
114	IRF2	IRF2	IRF2	10184	-0.011	0.29	NO
115	EIF4A1	EIF4A1	EIF4A1	10334	-0.012	0.28	NO
116	IFITM1	IFITM1	IFITM1	10576	-0.014	0.27	NO
117	IRF8	IRF8	IRF8	11009	-0.018	0.25	NO
118	IP6K2	IP6K2	IP6K2	11181	-0.02	0.24	NO
119	NUP153	NUP153	NUP153	11254	-0.021	0.24	NO
120	EIF4E2	EIF4E2	EIF4E2	11451	-0.023	0.24	NO
121	RPS27A	RPS27A	RPS27A	11655	-0.025	0.23	NO
122	UBE2N	UBE2N	UBE2N	11657	-0.025	0.23	NO
123	EIF4E3	EIF4E3	EIF4E3	11745	-0.026	0.23	NO
124	PPM1B	PPM1B	PPM1B	11850	-0.027	0.23	NO
125	NUP35	NUP35	NUP35	11963	-0.028	0.22	NO
126	NUPL1	NUPL1	NUPL1	12028	-0.029	0.22	NO
127	IFITM2	IFITM2	IFITM2	12307	-0.032	0.21	NO
128	KPNA3	KPNA3	KPNA3	12324	-0.032	0.22	NO
129	NUP133	NUP133	NUP133	12355	-0.032	0.22	NO
130	NUP50	NUP50	NUP50	12560	-0.035	0.21	NO
131	RANBP2	RANBP2	RANBP2	12793	-0.038	0.2	NO
132	IRF4	IRF4	IRF4	12825	-0.038	0.21	NO
133	AAAS	AAAS	AAAS	13592	-0.05	0.17	NO
134	NUP88	NUP88	NUP88	13722	-0.052	0.17	NO
135	IRF6	IRF6	IRF6	13837	-0.054	0.17	NO
136	ARIH1	ARIH1	ARIH1	14058	-0.058	0.17	NO
137	CAMK2B	CAMK2B	CAMK2B	14167	-0.06	0.17	NO
138	PIAS1	PIAS1	PIAS1	14542	-0.068	0.16	NO
139	KPNA5	KPNA5	KPNA5	16040	-0.12	0.091	NO
140	NCAM1	NCAM1	NCAM1	16154	-0.12	0.1	NO
141	ISG20	ISG20	ISG20	16409	-0.14	0.1	NO

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

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

genes ES table in pathway: BIOCARTA FAS PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MET	MET	MET	179	0.3	0.11	YES
2	EGFR	EGFR	EGFR	458	0.23	0.19	YES
3	CSF1	CSF1	CSF1	700	0.19	0.26	YES
4	VEGFA	VEGFA	VEGFA	1081	0.16	0.3	YES
5	KDR	KDR	KDR	1113	0.16	0.37	YES
6	CSF1R	CSF1R	CSF1R	1770	0.12	0.38	YES
7	KPNA2	KPNA2	KPNA2	1972	0.11	0.42	YES
8	PIK3CD	PIK3CD	PIK3CD	2257	0.1	0.44	YES
9	JAK3	JAK3	JAK3	3094	0.078	0.43	YES
10	EIF2AK2	EIF2AK2	EIF2AK2	3132	0.076	0.46	YES
11	EGF	EGF	EGF	3785	0.061	0.45	YES
12	PIK3R2	PIK3R2	PIK3R2	4559	0.048	0.42	YES
13	GRB2	GRB2	GRB2	4560	0.048	0.44	YES
14	STAT1	STAT1	STAT1	4772	0.044	0.45	YES
15	GAB1	GAB1	GAB1	5144	0.039	0.44	YES
16	STAT5A	STAT5A	STAT5A	5179	0.038	0.46	YES
17	PDGFRB	PDGFRB	PDGFRB	6380	0.024	0.4	NO
18	PIK3CB	PIK3CB	PIK3CB	6757	0.02	0.39	NO
19	PTPN1	PTPN1	PTPN1	6931	0.019	0.39	NO
20	PIK3CA	PIK3CA	PIK3CA	7037	0.018	0.39	NO
21	ATR	ATR	ATR	7071	0.017	0.4	NO
22	PIK3R1	PIK3R1	PIK3R1	7356	0.015	0.39	NO
23	KPNB1	KPNB1	KPNB1	7816	0.011	0.37	NO
24	SHC1	SHC1	SHC1	8487	0.0046	0.33	NO
25	JAK1	JAK1	JAK1	8877	0.00094	0.31	NO
26	CREBBP	CREBBP	CREBBP	9078	-0.00065	0.3	NO
27	PDGFB	PDGFB	PDGFB	9740	-0.0069	0.27	NO
28	PTPN2	PTPN2	PTPN2	9793	-0.0073	0.27	NO
29	ITGB1	ITGB1	ITGB1	9872	-0.0081	0.26	NO
30	PIK3R3	PIK3R3	PIK3R3	10062	-0.0098	0.26	NO
31	SOS1	SOS1	SOS1	10189	-0.011	0.26	NO
32	ITGA1	ITGA1	ITGA1	10276	-0.012	0.26	NO
33	SRC	SRC	SRC	10532	-0.014	0.25	NO
34	STAT5B	STAT5B	STAT5B	11010	-0.018	0.23	NO
35	LMAN1	LMAN1	LMAN1	11396	-0.022	0.22	NO
36	STAT3	STAT3	STAT3	11794	-0.026	0.21	NO
37	EIF2A	EIF2A	EIF2A	12569	-0.035	0.18	NO
38	STAT6	STAT6	STAT6	12679	-0.036	0.19	NO
39	INSR	INSR	INSR	14331	-0.063	0.12	NO
40	PIAS1	PIAS1	PIAS1	14542	-0.068	0.14	NO
41	RAB4A	RAB4A	RAB4A	14978	-0.079	0.15	NO
42	HGF	HGF	HGF	15130	-0.084	0.17	NO

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

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

genes ES table in pathway: BIOCARTA VEGF PATHWAY

Table S5. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PLAU	PLAU	PLAU	115	0.33	0.16	YES
2	ITGB3	ITGB3	ITGB3	171	0.3	0.3	YES
3	SPP1	SPP1	SPP1	369	0.24	0.41	YES
4	MMP9	MMP9	MMP9	695	0.19	0.49	YES
5	ITGAV	ITGAV	ITGAV	1623	0.13	0.5	YES
6	MMP2	MMP2	MMP2	2382	0.099	0.51	YES
7	RAC1	RAC1	RAC1	3468	0.068	0.48	NO
8	JUN	JUN	JUN	4426	0.05	0.45	NO
9	VAV3	VAV3	VAV3	4467	0.049	0.48	NO
10	CD44	CD44	CD44	4865	0.043	0.48	NO
11	PIP5K1A	PIP5K1A	PIP5K1A	5369	0.036	0.46	NO
12	RELA	RELA	RELA	6428	0.024	0.42	NO
13	CDC42	CDC42	CDC42	6733	0.021	0.41	NO
14	PIK3CA	PIK3CA	PIK3CA	7037	0.018	0.4	NO
15	RHOA	RHOA	RHOA	7278	0.016	0.4	NO
16	PIK3R1	PIK3R1	PIK3R1	7356	0.015	0.4	NO
17	NFKBIA	NFKBIA	NFKBIA	7409	0.014	0.41	NO
18	GSN	GSN	GSN	7713	0.012	0.4	NO
19	MAPK3	MAPK3	MAPK3	7882	0.01	0.39	NO
20	MAPK1	MAPK1	MAPK1	7915	0.0098	0.39	NO
21	MAP3K1	MAP3K1	MAP3K1	8036	0.0086	0.39	NO
22	SYK	SYK	SYK	9045	-0.00033	0.34	NO
23	MAP3K14	MAP3K14	MAP3K14	9416	-0.0038	0.32	NO
24	ILK	ILK	ILK	9430	-0.004	0.32	NO
25	NFKB1	NFKB1	NFKB1	9623	-0.0058	0.31	NO
26	BCAR1	BCAR1	BCAR1	10581	-0.014	0.27	NO
27	CHUK	CHUK	CHUK	12649	-0.036	0.17	NO
28	PTK2B	PTK2B	PTK2B	13794	-0.053	0.13	NO
29	MAPK8	MAPK8	MAPK8	13802	-0.053	0.16	NO
30	ROCK2	ROCK2	ROCK2	13972	-0.056	0.18	NO
31	FOS	FOS	FOS	16082	-0.12	0.12	NO

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

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA VEGF 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 HDAC CLASSII PATHWAY

Table S6. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	FAS	FAS	FAS	880	0.18	0.085	YES
2	CASP10	CASP10	CASP10	2534	0.093	0.065	YES
3	RIPK2	RIPK2	RIPK2	2574	0.092	0.13	YES
4	CFLAR	CFLAR	CFLAR	2745	0.087	0.19	YES
5	LMNB2	LMNB2	LMNB2	3443	0.069	0.2	YES
6	ARHGDIB	ARHGDIB	ARHGDIB	3669	0.064	0.24	YES
7	FADD	FADD	FADD	3997	0.058	0.26	YES
8	FAF1	FAF1	FAF1	4297	0.052	0.28	YES
9	JUN	JUN	JUN	4426	0.05	0.32	YES
10	LMNB1	LMNB1	LMNB1	4719	0.045	0.33	YES
11	LMNA	LMNA	LMNA	4931	0.042	0.35	YES
12	DFFA	DFFA	DFFA	5174	0.039	0.37	YES
13	CASP8	CASP8	CASP8	5388	0.036	0.38	YES
14	PAK1	PAK1	PAK1	5481	0.034	0.4	YES
15	FASLG	FASLG	FASLG	5696	0.032	0.42	YES
16	CASP6	CASP6	CASP6	5832	0.03	0.43	YES
17	SPTAN1	SPTAN1	SPTAN1	6117	0.027	0.44	YES
18	PAK2	PAK2	PAK2	6707	0.021	0.42	NO
19	PRKDC	PRKDC	PRKDC	7002	0.018	0.42	NO
20	PARP1	PARP1	PARP1	7295	0.015	0.41	NO
21	CASP3	CASP3	CASP3	7501	0.013	0.41	NO
22	MAP3K7	MAP3K7	MAP3K7	7960	0.0093	0.4	NO
23	MAP3K1	MAP3K1	MAP3K1	8036	0.0086	0.4	NO
24	MAP2K4	MAP2K4	MAP2K4	8724	0.0024	0.36	NO
25	PTPN13	PTPN13	PTPN13	10168	-0.011	0.29	NO
26	DAXX	DAXX	DAXX	11639	-0.024	0.23	NO
27	DFFB	DFFB	DFFB	12423	-0.033	0.21	NO
28	RB1	RB1	RB1	13362	-0.046	0.19	NO
29	CASP7	CASP7	CASP7	13543	-0.049	0.22	NO
30	MAPK8	MAPK8	MAPK8	13802	-0.053	0.25	NO

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

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: PID HDAC CLASSII 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 AVB3 OPN PATHWAY

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	ISG15	ISG15	ISG15	1198	0.16	0.064	YES
2	HERC5	HERC5	HERC5	1766	0.12	0.14	YES
3	IKBKE	IKBKE	IKBKE	2668	0.089	0.16	YES
4	IFIH1	IFIH1	IFIH1	2734	0.087	0.23	YES
5	RNF135	RNF135	RNF135	2845	0.084	0.29	YES
6	DDX58	DDX58	DDX58	3284	0.072	0.33	YES
7	TAX1BP1	TAX1BP1	TAX1BP1	3388	0.07	0.38	YES
8	UBE2L6	UBE2L6	UBE2L6	3812	0.061	0.41	YES
9	NLRC5	NLRC5	NLRC5	4451	0.05	0.42	YES
10	UBA7	UBA7	UBA7	4821	0.044	0.43	YES
11	UBE2D1	UBE2D1	UBE2D1	4929	0.042	0.46	YES
12	NLRX1	NLRX1	NLRX1	5652	0.032	0.45	NO
13	UBE2K	UBE2K	UBE2K	7096	0.017	0.38	NO
14	IRF3	IRF3	IRF3	7466	0.014	0.38	NO
15	TRAF3	TRAF3	TRAF3	8249	0.0067	0.34	NO
16	ATG5	ATG5	ATG5	8553	0.004	0.33	NO
17	OTUD5	OTUD5	OTUD5	8747	0.0022	0.32	NO
18	PIN1	PIN1	PIN1	9138	-0.0012	0.3	NO
19	UBE2D3	UBE2D3	UBE2D3	9236	-0.0021	0.29	NO
20	ATG12	ATG12	ATG12	9635	-0.0059	0.28	NO
21	UBA52	UBA52	UBA52	9657	-0.006	0.28	NO
22	TRIM25	TRIM25	TRIM25	9734	-0.0068	0.28	NO
23	TNFAIP3	TNFAIP3	TNFAIP3	9805	-0.0075	0.28	NO
24	CYLD	CYLD	CYLD	9831	-0.0077	0.29	NO
25	TBK1	TBK1	TBK1	10108	-0.01	0.28	NO
26	UBE2D2	UBE2D2	UBE2D2	10575	-0.014	0.27	NO
27	RPS27A	RPS27A	RPS27A	11655	-0.025	0.23	NO
28	PCBP2	PCBP2	PCBP2	12897	-0.039	0.2	NO
29	RNF125	RNF125	RNF125	13947	-0.056	0.18	NO
30	MAVS	MAVS	MAVS	14362	-0.064	0.22	NO

Figure S13. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID AVB3 OPN PATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: PID AVB3 OPN 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 ILK PATHWAY

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	VEGFA	VEGFA	VEGFA	1081	0.16	0.086	YES
2	KDR	KDR	KDR	1113	0.16	0.23	YES
3	PRKCA	PRKCA	PRKCA	1185	0.16	0.36	YES
4	NOS3	NOS3	NOS3	1849	0.12	0.44	YES
5	HIF1A	HIF1A	HIF1A	5244	0.038	0.28	NO
6	PIK3CG	PIK3CG	PIK3CG	5449	0.035	0.3	NO
7	PTK2	PTK2	PTK2	5452	0.035	0.34	NO
8	EIF2B3	EIF2B3	EIF2B3	5562	0.033	0.36	NO
9	EIF2S1	EIF2S1	EIF2S1	6689	0.021	0.32	NO
10	PIK3CA	PIK3CA	PIK3CA	7037	0.018	0.31	NO
11	EIF2B2	EIF2B2	EIF2B2	7144	0.017	0.32	NO
12	PIK3R1	PIK3R1	PIK3R1	7356	0.015	0.32	NO
13	FLT1	FLT1	FLT1	7528	0.013	0.33	NO
14	ELAVL1	ELAVL1	ELAVL1	7569	0.013	0.34	NO
15	EIF2B5	EIF2B5	EIF2B5	7579	0.013	0.35	NO
16	EIF2B1	EIF2B1	EIF2B1	8071	0.0083	0.33	NO
17	EIF2B4	EIF2B4	EIF2B4	8250	0.0067	0.32	NO
18	SHC1	SHC1	SHC1	8487	0.0046	0.32	NO
19	EIF2S2	EIF2S2	EIF2S2	8612	0.0034	0.31	NO
20	PLCG1	PLCG1	PLCG1	8734	0.0023	0.31	NO
21	EIF1AX	EIF1AX	EIF1AX	9055	-0.00044	0.29	NO
22	PXN	PXN	PXN	9307	-0.0028	0.28	NO
23	EIF1	EIF1	EIF1	9860	-0.008	0.26	NO
24	ARNT	ARNT	ARNT	10083	-0.01	0.25	NO
25	VHL	VHL	VHL	10430	-0.013	0.25	NO
26	EIF2S3	EIF2S3	EIF2S3	12814	-0.038	0.15	NO
27	HRAS	HRAS	HRAS	13555	-0.049	0.15	NO
28	FLT4	FLT4	FLT4	13764	-0.052	0.19	NO
29	PRKCB	PRKCB	PRKCB	14487	-0.066	0.21	NO

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

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: PID ILK 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 TCPTP PATHWAY

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	IFIT1	IFIT1	IFIT1	1020	0.17	0.0095	YES
2	ISG15	ISG15	ISG15	1198	0.16	0.061	YES
3	HERC5	HERC5	HERC5	1766	0.12	0.078	YES
4	KPNA2	KPNA2	KPNA2	1972	0.11	0.11	YES
5	NUP155	NUP155	NUP155	1999	0.11	0.15	YES
6	NUPL2	NUPL2	NUPL2	2072	0.11	0.19	YES
7	MX2	MX2	MX2	2201	0.1	0.23	YES
8	MX1	MX1	MX1	2508	0.094	0.25	YES
9	EIF2AK2	EIF2AK2	EIF2AK2	3132	0.076	0.24	YES
10	DDX58	DDX58	DDX58	3284	0.072	0.26	YES
11	NUP85	NUP85	NUP85	3500	0.068	0.28	YES
12	NEDD4	NEDD4	NEDD4	3576	0.066	0.3	YES
13	UBE2L6	UBE2L6	UBE2L6	3812	0.061	0.31	YES
14	NUP205	NUP205	NUP205	3903	0.059	0.33	YES
15	USP18	USP18	USP18	4626	0.047	0.31	YES
16	NUP210	NUP210	NUP210	4702	0.045	0.32	YES
17	STAT1	STAT1	STAT1	4772	0.044	0.34	YES
18	UBA7	UBA7	UBA7	4821	0.044	0.35	YES
19	NUP62	NUP62	NUP62	4862	0.043	0.36	YES
20	POM121	POM121	POM121	4870	0.043	0.38	YES
21	NUP54	NUP54	NUP54	5945	0.029	0.33	NO
22	KPNA4	KPNA4	KPNA4	6287	0.026	0.33	NO
23	EIF4A3	EIF4A3	EIF4A3	6462	0.024	0.32	NO
24	EIF4E	EIF4E	EIF4E	6726	0.021	0.32	NO
25	NUP93	NUP93	NUP93	6901	0.019	0.32	NO
26	NUP107	NUP107	NUP107	7088	0.017	0.31	NO
27	IRF3	IRF3	IRF3	7466	0.014	0.3	NO
28	EIF4G1	EIF4G1	EIF4G1	7540	0.013	0.3	NO
29	NUP188	NUP188	NUP188	7639	0.012	0.3	NO
30	KPNB1	KPNB1	KPNB1	7816	0.011	0.29	NO
31	MAPK3	MAPK3	MAPK3	7882	0.01	0.29	NO
32	NUP43	NUP43	NUP43	7901	0.0099	0.3	NO
33	UBE2E1	UBE2E1	UBE2E1	8107	0.0081	0.29	NO
34	EIF4G3	EIF4G3	EIF4G3	8549	0.004	0.27	NO
35	KPNA1	KPNA1	KPNA1	8634	0.0032	0.26	NO
36	FLNB	FLNB	FLNB	8717	0.0025	0.26	NO
37	PLCG1	PLCG1	PLCG1	8734	0.0023	0.26	NO
38	NUP37	NUP37	NUP37	8792	0.0017	0.26	NO
39	NUP214	NUP214	NUP214	8843	0.0012	0.26	NO
40	JAK1	JAK1	JAK1	8877	0.00094	0.25	NO
41	PIN1	PIN1	PIN1	9138	-0.0012	0.24	NO
42	SEH1L	SEH1L	SEH1L	9454	-0.0042	0.22	NO
43	RAE1	RAE1	RAE1	9481	-0.0045	0.22	NO
44	TPR	TPR	TPR	9488	-0.0046	0.23	NO
45	EIF4G2	EIF4G2	EIF4G2	9494	-0.0046	0.23	NO
46	UBA52	UBA52	UBA52	9657	-0.006	0.22	NO
47	EIF4A2	EIF4A2	EIF4A2	9708	-0.0065	0.22	NO
48	TRIM25	TRIM25	TRIM25	9734	-0.0068	0.22	NO
49	EIF4A1	EIF4A1	EIF4A1	10334	-0.012	0.19	NO
50	NUP153	NUP153	NUP153	11254	-0.021	0.15	NO
51	EIF4E2	EIF4E2	EIF4E2	11451	-0.023	0.15	NO
52	RPS27A	RPS27A	RPS27A	11655	-0.025	0.15	NO
53	UBE2N	UBE2N	UBE2N	11657	-0.025	0.16	NO
54	EIF4E3	EIF4E3	EIF4E3	11745	-0.026	0.16	NO
55	PPM1B	PPM1B	PPM1B	11850	-0.027	0.17	NO
56	NUP35	NUP35	NUP35	11963	-0.028	0.17	NO
57	NUPL1	NUPL1	NUPL1	12028	-0.029	0.18	NO
58	KPNA3	KPNA3	KPNA3	12324	-0.032	0.18	NO
59	NUP133	NUP133	NUP133	12355	-0.032	0.19	NO
60	NUP50	NUP50	NUP50	12560	-0.035	0.19	NO
61	RANBP2	RANBP2	RANBP2	12793	-0.038	0.19	NO
62	AAAS	AAAS	AAAS	13592	-0.05	0.17	NO
63	NUP88	NUP88	NUP88	13722	-0.052	0.18	NO
64	ARIH1	ARIH1	ARIH1	14058	-0.058	0.19	NO
65	KPNA5	KPNA5	KPNA5	16040	-0.12	0.12	NO

Figure S17. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID TCPTP PATHWAY.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: PID TCPTP 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 TELOMERASEPATHWAY

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	SPHK1	SPHK1	SPHK1	205	0.29	0.25	YES
2	FBXO6	FBXO6	FBXO6	1847	0.12	0.26	YES
3	FBXO4	FBXO4	FBXO4	1932	0.12	0.36	YES
4	CCT6A	CCT6A	CCT6A	3268	0.073	0.35	YES
5	CCT5	CCT5	CCT5	3853	0.06	0.38	YES
6	KIF13A	KIF13A	KIF13A	5220	0.038	0.34	NO
7	CCT4	CCT4	CCT4	6077	0.028	0.31	NO
8	CCT8	CCT8	CCT8	6994	0.018	0.28	NO
9	CCT3	CCT3	CCT3	7415	0.014	0.27	NO
10	CCT7	CCT7	CCT7	7822	0.011	0.26	NO
11	FBXW7	FBXW7	FBXW7	8157	0.0076	0.24	NO
12	FKBP9	FKBP9	FKBP9	8319	0.0061	0.24	NO
13	FBXL3	FBXL3	FBXL3	9165	-0.0014	0.2	NO
14	CCT2	CCT2	CCT2	9672	-0.0062	0.17	NO
15	TCP1	TCP1	TCP1	9834	-0.0077	0.17	NO
16	KIFC3	KIFC3	KIFC3	10622	-0.015	0.14	NO
17	FBXL5	FBXL5	FBXL5	10645	-0.015	0.15	NO
18	AP3M1	AP3M1	AP3M1	10739	-0.016	0.16	NO
19	FBXW2	FBXW2	FBXW2	11319	-0.022	0.15	NO
20	ARFGEF2	ARFGEF2	ARFGEF2	11549	-0.024	0.16	NO
21	USP11	USP11	USP11	11768	-0.026	0.17	NO
22	LONP2	LONP2	LONP2	11958	-0.028	0.18	NO
23	FBXW5	FBXW5	FBXW5	12837	-0.038	0.17	NO
24	NOP56	NOP56	NOP56	13147	-0.042	0.19	NO
25	XRN2	XRN2	XRN2	13404	-0.046	0.22	NO
26	FBXW4	FBXW4	FBXW4	13916	-0.055	0.24	NO

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

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: PID TELOMERASEPATHWAY, 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 FATTY ACID METABOLISM	40	genes.ES.table	0.52	1.5	0.047	1	0.98	0.48	0.25	0.36	0.93	0.48
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	44	genes.ES.table	0.48	1.7	0.038	1	0.84	0.61	0.28	0.44	1	0.62
KEGG ARACHIDONIC ACID METABOLISM	52	genes.ES.table	0.62	1.5	0.0083	1	0.98	0.44	0.18	0.36	0.98	0.5
KEGG PROPANOATE METABOLISM	32	genes.ES.table	0.46	1.5	0.076	1	0.98	0.44	0.22	0.34	0.9	0.46
KEGG ALDOSTERONE REGULATED SODIUM REABSORPTION	40	genes.ES.table	0.55	1.6	0.019	1	0.96	0.5	0.25	0.38	1	0.6
KEGG VASOPRESSIN REGULATED WATER REABSORPTION	42	genes.ES.table	0.51	1.9	0.0021	1	0.3	0.19	0.12	0.17	0	0.22
KEGG VIRAL MYOCARDITIS	66	genes.ES.table	0.55	1.5	0.079	1	0.98	0.46	0.2	0.36	0.91	0.47
BIOCARTA FCER1 PATHWAY	38	genes.ES.table	0.47	1.6	0.075	1	0.97	0.34	0.25	0.26	1	0.57
ST ADRENERGIC	35	genes.ES.table	0.53	1.5	0.037	1	0.98	0.37	0.18	0.3	1	0.51
ST WNT BETA CATENIN PATHWAY	31	genes.ES.table	0.51	1.5	0.086	1	0.99	0.32	0.2	0.26	0.89	0.46

genes ES table in pathway: KEGG FATTY ACID 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	AQP4	AQP4	AQP4	79	0.52	0.16	YES
2	AQP2	AQP2	AQP2	506	0.33	0.23	YES
3	AQP3	AQP3	AQP3	524	0.32	0.33	YES
4	ADCY9	ADCY9	ADCY9	1364	0.2	0.35	YES
5	AVPR2	AVPR2	AVPR2	1499	0.19	0.4	YES
6	CREB3L1	CREB3L1	CREB3L1	1749	0.17	0.44	YES
7	DYNC2H1	DYNC2H1	DYNC2H1	2129	0.15	0.46	YES
8	VAMP2	VAMP2	VAMP2	2141	0.15	0.51	YES
9	ARHGDIB	ARHGDIB	ARHGDIB	2876	0.12	0.5	NO
10	ADCY6	ADCY6	ADCY6	4417	0.071	0.44	NO
11	DCTN4	DCTN4	DCTN4	4806	0.062	0.44	NO
12	DYNC2LI1	DYNC2LI1	DYNC2LI1	5089	0.056	0.44	NO
13	DYNC1LI2	DYNC1LI2	DYNC1LI2	5642	0.047	0.43	NO
14	DYNLL2	DYNLL2	DYNLL2	5795	0.044	0.43	NO
15	DCTN6	DCTN6	DCTN6	6523	0.033	0.4	NO
16	DCTN1	DCTN1	DCTN1	6600	0.032	0.41	NO
17	RAB11B	RAB11B	RAB11B	6774	0.03	0.41	NO
18	RAB5B	RAB5B	RAB5B	7050	0.026	0.4	NO
19	CREB1	CREB1	CREB1	7272	0.023	0.4	NO
20	CREB3L4	CREB3L4	CREB3L4	7482	0.02	0.39	NO
21	PRKACB	PRKACB	PRKACB	7964	0.014	0.37	NO
22	PRKACA	PRKACA	PRKACA	8279	0.0097	0.35	NO
23	RAB5A	RAB5A	RAB5A	8631	0.0054	0.34	NO
24	CREB5	CREB5	CREB5	9207	-0.0016	0.3	NO
25	DCTN5	DCTN5	DCTN5	9677	-0.0076	0.28	NO
26	DYNC1LI1	DYNC1LI1	DYNC1LI1	9728	-0.0082	0.28	NO
27	RAB11A	RAB11A	RAB11A	9961	-0.011	0.27	NO
28	CREB3	CREB3	CREB3	10066	-0.012	0.27	NO
29	PRKX	PRKX	PRKX	10141	-0.013	0.27	NO
30	DYNC1H1	DYNC1H1	DYNC1H1	10239	-0.014	0.27	NO
31	RAB5C	RAB5C	RAB5C	10248	-0.014	0.27	NO
32	STX4	STX4	STX4	10401	-0.016	0.27	NO
33	GNAS	GNAS	GNAS	10936	-0.023	0.25	NO
34	CREB3L2	CREB3L2	CREB3L2	10973	-0.024	0.25	NO
35	DYNC1I2	DYNC1I2	DYNC1I2	11148	-0.026	0.25	NO
36	ARHGDIA	ARHGDIA	ARHGDIA	11193	-0.027	0.26	NO
37	NSF	NSF	NSF	11365	-0.029	0.26	NO
38	CREB3L3	CREB3L3	CREB3L3	11523	-0.031	0.26	NO
39	DCTN2	DCTN2	DCTN2	12173	-0.039	0.23	NO
40	ADCY3	ADCY3	ADCY3	13820	-0.068	0.16	NO
41	DYNLL1	DYNLL1	DYNLL1	15347	-0.11	0.11	NO
42	DYNC1I1	DYNC1I1	DYNC1I1	16417	-0.16	0.1	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 FATTY ACID METABOLISM.

Figure S22. 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 VALINE LEUCINE AND ISOLEUCINE DEGRADATION

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	ACADSB	ACADSB	ACADSB	922	0.25	0.0074	YES
2	PCCA	PCCA	PCCA	1223	0.22	0.041	YES
3	HMGCS2	HMGCS2	HMGCS2	1349	0.21	0.081	YES
4	ALDH6A1	ALDH6A1	ALDH6A1	1558	0.19	0.11	YES
5	ABAT	ABAT	ABAT	1637	0.18	0.15	YES
6	IVD	IVD	IVD	1674	0.18	0.19	YES
7	ACAD8	ACAD8	ACAD8	1845	0.17	0.22	YES
8	ALDH2	ALDH2	ALDH2	1947	0.16	0.25	YES
9	ACADS	ACADS	ACADS	2068	0.16	0.28	YES
10	MCEE	MCEE	MCEE	2349	0.14	0.3	YES
11	AOX1	AOX1	AOX1	2812	0.12	0.3	YES
12	ALDH3A2	ALDH3A2	ALDH3A2	2934	0.12	0.32	YES
13	BCKDHA	BCKDHA	BCKDHA	2992	0.11	0.34	YES
14	ACAA1	ACAA1	ACAA1	3004	0.11	0.37	YES
15	BCAT1	BCAT1	BCAT1	3027	0.11	0.39	YES
16	HADH	HADH	HADH	3246	0.1	0.4	YES
17	MCCC1	MCCC1	MCCC1	3641	0.091	0.4	YES
18	AUH	AUH	AUH	3705	0.09	0.42	YES
19	ACAT1	ACAT1	ACAT1	3811	0.086	0.44	YES
20	ALDH9A1	ALDH9A1	ALDH9A1	3970	0.082	0.44	YES
21	BCAT2	BCAT2	BCAT2	4019	0.081	0.46	YES
22	ALDH7A1	ALDH7A1	ALDH7A1	4041	0.08	0.48	YES
23	DBT	DBT	DBT	4732	0.064	0.46	YES
24	HIBCH	HIBCH	HIBCH	4890	0.061	0.46	YES
25	BCKDHB	BCKDHB	BCKDHB	4892	0.061	0.48	YES
26	ACAA2	ACAA2	ACAA2	5033	0.058	0.48	YES
27	HMGCL	HMGCL	HMGCL	5186	0.055	0.48	YES
28	ACADM	ACADM	ACADM	6252	0.037	0.44	NO
29	MUT	MUT	MUT	6257	0.037	0.44	NO
30	MCCC2	MCCC2	MCCC2	6406	0.035	0.44	NO
31	OXCT2	OXCT2	OXCT2	7007	0.026	0.42	NO
32	HADHB	HADHB	HADHB	7983	0.014	0.37	NO
33	HADHA	HADHA	HADHA	9076	-0.000046	0.31	NO
34	ECHS1	ECHS1	ECHS1	9492	-0.0052	0.28	NO
35	PCCB	PCCB	PCCB	11392	-0.029	0.19	NO
36	EHHADH	EHHADH	EHHADH	11696	-0.033	0.18	NO
37	HIBADH	HIBADH	HIBADH	13168	-0.056	0.11	NO
38	DLD	DLD	DLD	13270	-0.058	0.12	NO
39	HMGCS1	HMGCS1	HMGCS1	13739	-0.066	0.11	NO
40	ACAT2	ACAT2	ACAT2	13886	-0.069	0.12	NO
41	HSD17B10	HSD17B10	HSD17B10	13928	-0.07	0.13	NO
42	OXCT1	OXCT1	OXCT1	14295	-0.078	0.13	NO
43	ALDH1B1	ALDH1B1	ALDH1B1	16459	-0.16	0.046	NO
44	IL4I1	IL4I1	IL4I1	17246	-0.24	0.058	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 VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

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

genes ES table in pathway: KEGG ARACHIDONIC ACID METABOLISM

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	RASGRF1	RASGRF1	RASGRF1	107	0.49	0.097	YES
2	SHC3	SHC3	SHC3	485	0.34	0.15	YES
3	NTRK3	NTRK3	NTRK3	540	0.32	0.21	YES
4	NTRK2	NTRK2	NTRK2	688	0.29	0.26	YES
5	NTF4	NTF4	NTF4	1035	0.24	0.29	YES
6	NGFR	NGFR	NGFR	1343	0.21	0.32	YES
7	ELMO1	ELMO1	ELMO1	1838	0.17	0.33	YES
8	BDNF	BDNF	BDNF	1923	0.16	0.36	YES
9	NTRK1	NTRK1	NTRK1	1928	0.16	0.39	YES
10	NEDD4L	NEDD4L	NEDD4L	2095	0.15	0.41	YES
11	PRKCZ	PRKCZ	PRKCZ	2352	0.14	0.43	YES
12	PIK3R1	PIK3R1	PIK3R1	2685	0.13	0.44	YES
13	GAB1	GAB1	GAB1	2902	0.12	0.45	YES
14	SHC2	SHC2	SHC2	3404	0.099	0.44	NO
15	FRS3	FRS3	FRS3	3978	0.082	0.43	NO
16	MATK	MATK	MATK	4154	0.077	0.44	NO
17	GAB2	GAB2	GAB2	4403	0.071	0.44	NO
18	SH2B1	SH2B1	SH2B1	4638	0.066	0.44	NO
19	MCF2L	MCF2L	MCF2L	5062	0.057	0.43	NO
20	RASA1	RASA1	RASA1	5588	0.048	0.41	NO
21	SQSTM1	SQSTM1	SQSTM1	5952	0.042	0.4	NO
22	RAP1A	RAP1A	RAP1A	6214	0.038	0.39	NO
23	STAT3	STAT3	STAT3	6233	0.037	0.4	NO
24	DOCK1	DOCK1	DOCK1	6253	0.037	0.4	NO
25	CRK	CRK	CRK	6269	0.037	0.41	NO
26	CCND1	CCND1	CCND1	6387	0.035	0.41	NO
27	TIAM1	TIAM1	TIAM1	6995	0.026	0.38	NO
28	FRS2	FRS2	FRS2	7411	0.021	0.37	NO
29	MAPK1	MAPK1	MAPK1	7445	0.021	0.37	NO
30	RIT1	RIT1	RIT1	7821	0.016	0.35	NO
31	PRKCI	PRKCI	PRKCI	7853	0.016	0.35	NO
32	CDC42	CDC42	CDC42	7902	0.015	0.35	NO
33	EHD4	EHD4	EHD4	7955	0.014	0.35	NO
34	RHOA	RHOA	RHOA	8060	0.013	0.35	NO
35	ARHGAP32	ARHGAP32	ARHGAP32	8891	0.0019	0.3	NO
36	ABL1	ABL1	ABL1	8986	0.00084	0.3	NO
37	GIPC1	GIPC1	GIPC1	9100	-0.00033	0.29	NO
38	RAPGEF1	RAPGEF1	RAPGEF1	9145	-0.0009	0.29	NO
39	PLCG1	PLCG1	PLCG1	9210	-0.0017	0.29	NO
40	RHOG	RHOG	RHOG	9353	-0.0034	0.28	NO
41	MAPK3	MAPK3	MAPK3	9401	-0.004	0.28	NO
42	DNAJA3	DNAJA3	DNAJA3	9726	-0.0082	0.26	NO
43	MAP2K1	MAP2K1	MAP2K1	9896	-0.01	0.26	NO
44	MAGED1	MAGED1	MAGED1	10358	-0.016	0.24	NO
45	FAIM	FAIM	FAIM	10432	-0.017	0.23	NO
46	SOS1	SOS1	SOS1	10648	-0.019	0.23	NO
47	CRKL	CRKL	CRKL	10695	-0.02	0.23	NO
48	NTF3	NTF3	NTF3	10794	-0.021	0.23	NO
49	RGS19	RGS19	RGS19	10828	-0.022	0.23	NO
50	GRB2	GRB2	GRB2	11001	-0.024	0.23	NO
51	DYNLT1	DYNLT1	DYNLT1	11398	-0.029	0.21	NO
52	SHC1	SHC1	SHC1	11983	-0.037	0.19	NO
53	RAP1B	RAP1B	RAP1B	12091	-0.038	0.19	NO
54	PTPN11	PTPN11	PTPN11	12972	-0.053	0.15	NO
55	RAC1	RAC1	RAC1	13061	-0.054	0.16	NO
56	PIK3CA	PIK3CA	PIK3CA	13281	-0.058	0.16	NO
57	HRAS	HRAS	HRAS	13324	-0.059	0.17	NO
58	KRAS	KRAS	KRAS	13496	-0.062	0.17	NO
59	NGF	NGF	NGF	14428	-0.081	0.14	NO
60	NRAS	NRAS	NRAS	15067	-0.098	0.12	NO
61	DNM1	DNM1	DNM1	17432	-0.26	0.048	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 ARACHIDONIC ACID METABOLISM.

Figure S26. 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 PROPANOATE 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	ADRB2	ADRB2	ADRB2	218	0.42	0.13	YES
2	HGF	HGF	HGF	921	0.25	0.18	YES
3	GNA14	GNA14	GNA14	1540	0.19	0.2	YES
4	AGTR1	AGTR1	AGTR1	1647	0.18	0.26	YES
5	LHCGR	LHCGR	LHCGR	1690	0.18	0.32	YES
6	IPCEF1	IPCEF1	IPCEF1	1713	0.18	0.37	YES
7	ARRB1	ARRB1	ARRB1	2190	0.15	0.4	YES
8	CYTH3	CYTH3	CYTH3	3053	0.11	0.39	YES
9	GNAQ	GNAQ	GNAQ	3277	0.1	0.41	YES
10	EPHA2	EPHA2	EPHA2	3415	0.098	0.44	YES
11	EFNA1	EFNA1	EFNA1	3807	0.086	0.44	YES
12	ARAP2	ARAP2	ARAP2	4086	0.079	0.45	YES
13	KIF13B	KIF13B	KIF13B	4252	0.075	0.47	YES
14	EGF	EGF	EGF	4648	0.066	0.47	YES
15	IQSEC1	IQSEC1	IQSEC1	4746	0.063	0.49	YES
16	FBXO8	FBXO8	FBXO8	4815	0.062	0.5	YES
17	ACAP1	ACAP1	ACAP1	5073	0.057	0.51	YES
18	ARRB2	ARRB2	ARRB2	5153	0.056	0.52	YES
19	EGFR	EGFR	EGFR	5225	0.054	0.54	YES
20	GNA11	GNA11	GNA11	7116	0.025	0.44	NO
21	CYTH2	CYTH2	CYTH2	7222	0.024	0.44	NO
22	MET	MET	MET	7745	0.017	0.42	NO
23	ITGB3	ITGB3	ITGB3	8104	0.012	0.4	NO
24	GNA15	GNA15	GNA15	8179	0.011	0.4	NO
25	ADAP1	ADAP1	ADAP1	9355	-0.0034	0.34	NO
26	TSHR	TSHR	TSHR	10735	-0.02	0.27	NO
27	PXN	PXN	PXN	10939	-0.023	0.27	NO
28	USP6	USP6	USP6	11413	-0.029	0.25	NO
29	ACAP2	ACAP2	ACAP2	11665	-0.033	0.25	NO
30	ITGA2B	ITGA2B	ITGA2B	11847	-0.035	0.25	NO
31	SRC	SRC	SRC	12221	-0.04	0.24	NO
32	ARF6	ARF6	ARF6	12544	-0.045	0.24	NO
33	NCK1	NCK1	NCK1	13802	-0.068	0.2	NO
34	GIT1	GIT1	GIT1	14113	-0.073	0.2	NO
35	GULP1	GULP1	GULP1	14242	-0.076	0.22	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 PROPANOATE METABOLISM.

Figure S28. 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 ALDOSTERONE REGULATED SODIUM REABSORPTION

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	TGFBR3	TGFBR3	TGFBR3	666	0.29	0.051	YES
2	CAMK2A	CAMK2A	CAMK2A	827	0.27	0.12	YES
3	OCLN	OCLN	OCLN	1512	0.19	0.14	YES
4	NEDD4L	NEDD4L	NEDD4L	2095	0.15	0.16	YES
5	CAV1	CAV1	CAV1	2185	0.15	0.2	YES
6	DACT2	DACT2	DACT2	2187	0.15	0.24	YES
7	TGFBR2	TGFBR2	TGFBR2	2348	0.14	0.28	YES
8	YAP1	YAP1	YAP1	3583	0.093	0.24	YES
9	DAB2	DAB2	DAB2	3682	0.09	0.26	YES
10	TGFB2	TGFB2	TGFB2	3741	0.088	0.28	YES
11	PDPK1	PDPK1	PDPK1	3824	0.086	0.3	YES
12	ZFYVE9	ZFYVE9	ZFYVE9	3846	0.085	0.33	YES
13	SMAD7	SMAD7	SMAD7	4111	0.078	0.34	YES
14	PPP2CB	PPP2CB	PPP2CB	4236	0.075	0.35	YES
15	PPP1R15A	PPP1R15A	PPP1R15A	4421	0.071	0.36	YES
16	BAMBI	BAMBI	BAMBI	4835	0.062	0.36	YES
17	ARRB2	ARRB2	ARRB2	5153	0.056	0.36	YES
18	TGFB1	TGFB1	TGFB1	5305	0.053	0.37	YES
19	ZFYVE16	ZFYVE16	ZFYVE16	5499	0.05	0.37	YES
20	SPTBN1	SPTBN1	SPTBN1	5714	0.046	0.37	YES
21	SMAD4	SMAD4	SMAD4	5868	0.043	0.38	YES
22	TAB1	TAB1	TAB1	5885	0.043	0.39	YES
23	PPP2R2A	PPP2R2A	PPP2R2A	5970	0.042	0.4	YES
24	SMURF2	SMURF2	SMURF2	6304	0.036	0.39	NO
25	XIAP	XIAP	XIAP	6527	0.033	0.39	NO
26	RNF111	RNF111	RNF111	6783	0.03	0.38	NO
27	CTGF	CTGF	CTGF	6881	0.028	0.38	NO
28	SMAD2	SMAD2	SMAD2	7077	0.026	0.38	NO
29	PARD6A	PARD6A	PARD6A	7797	0.016	0.35	NO
30	RHOA	RHOA	RHOA	8060	0.013	0.34	NO
31	CTNNB1	CTNNB1	CTNNB1	8455	0.0075	0.32	NO
32	WWP1	WWP1	WWP1	8508	0.0069	0.32	NO
33	TGFBRAP1	TGFBRAP1	TGFBRAP1	8741	0.0039	0.31	NO
34	DAXX	DAXX	DAXX	8776	0.0034	0.3	NO
35	SMURF1	SMURF1	SMURF1	9269	-0.0024	0.28	NO
36	EIF2A	EIF2A	EIF2A	9742	-0.0083	0.26	NO
37	PML	PML	PML	10059	-0.012	0.24	NO
38	AXIN1	AXIN1	AXIN1	10292	-0.015	0.23	NO
39	YWHAE	YWHAE	YWHAE	10478	-0.017	0.23	NO
40	FKBP1A	FKBP1A	FKBP1A	10615	-0.019	0.23	NO
41	SOS1	SOS1	SOS1	10648	-0.019	0.23	NO
42	SMAD3	SMAD3	SMAD3	10745	-0.021	0.23	NO
43	TAB2	TAB2	TAB2	10797	-0.021	0.24	NO
44	PPP2CA	PPP2CA	PPP2CA	10835	-0.022	0.24	NO
45	DYNLRB1	DYNLRB1	DYNLRB1	10932	-0.023	0.24	NO
46	GRB2	GRB2	GRB2	11001	-0.024	0.24	NO
47	PPP1CA	PPP1CA	PPP1CA	11042	-0.025	0.25	NO
48	TGFBR1	TGFBR1	TGFBR1	11404	-0.029	0.24	NO
49	ITCH	ITCH	ITCH	11951	-0.036	0.22	NO
50	SHC1	SHC1	SHC1	11983	-0.037	0.23	NO
51	MAP3K7	MAP3K7	MAP3K7	12348	-0.042	0.22	NO
52	TGFB3	TGFB3	TGFB3	13748	-0.066	0.17	NO
53	RPS6KB1	RPS6KB1	RPS6KB1	14011	-0.071	0.17	NO
54	SKIL	SKIL	SKIL	14815	-0.091	0.16	NO
55	STRAP	STRAP	STRAP	15516	-0.12	0.15	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 ALDOSTERONE REGULATED SODIUM REABSORPTION.

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

genes ES table in pathway: KEGG VASOPRESSIN REGULATED WATER REABSORPTION

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	MAPK10	MAPK10	MAPK10	117	0.48	0.16	YES
2	C4BPA	C4BPA	C4BPA	184	0.44	0.32	YES
3	CD40LG	CD40LG	CD40LG	215	0.42	0.47	YES
4	FCAMR	FCAMR	FCAMR	813	0.27	0.53	YES
5	MAP3K1	MAP3K1	MAP3K1	3757	0.088	0.4	NO
6	JUN	JUN	JUN	4470	0.069	0.38	NO
7	MAPK9	MAPK9	MAPK9	4552	0.068	0.4	NO
8	TRAF6	TRAF6	TRAF6	4863	0.061	0.41	NO
9	MAP3K14	MAP3K14	MAP3K14	5106	0.056	0.42	NO
10	NFKB1	NFKB1	NFKB1	5307	0.053	0.42	NO
11	STAT5A	STAT5A	STAT5A	5721	0.046	0.42	NO
12	TRAF1	TRAF1	TRAF1	5761	0.045	0.43	NO
13	NFKBIA	NFKBIA	NFKBIA	5999	0.041	0.43	NO
14	CD40	CD40	CD40	6868	0.028	0.4	NO
15	MAPK14	MAPK14	MAPK14	7504	0.02	0.37	NO
16	MAP2K4	MAP2K4	MAP2K4	8160	0.012	0.34	NO
17	AKT1	AKT1	AKT1	8292	0.0095	0.33	NO
18	BIRC3	BIRC3	BIRC3	8703	0.0044	0.31	NO
19	MAPK11	MAPK11	MAPK11	9849	-0.0096	0.25	NO
20	BCL2L1	BCL2L1	BCL2L1	9949	-0.011	0.25	NO
21	TDP2	TDP2	TDP2	10213	-0.014	0.24	NO
22	RELA	RELA	RELA	11219	-0.027	0.2	NO
23	BIRC2	BIRC2	BIRC2	11467	-0.03	0.19	NO
24	TNFAIP3	TNFAIP3	TNFAIP3	12418	-0.043	0.16	NO
25	TRAF3	TRAF3	TRAF3	13765	-0.067	0.11	NO
26	CBLB	CBLB	CBLB	13809	-0.068	0.13	NO
27	JAK3	JAK3	JAK3	13871	-0.069	0.15	NO
28	TRAF2	TRAF2	TRAF2	14365	-0.08	0.15	NO
29	MAPK8	MAPK8	MAPK8	14729	-0.089	0.16	NO
30	MYC	MYC	MYC	14768	-0.09	0.19	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 VASOPRESSIN REGULATED WATER REABSORPTION.

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

genes ES table in pathway: KEGG VIRAL MYOCARDITIS

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	AQP5	AQP5	AQP5	392	0.36	0.11	YES
2	AQP3	AQP3	AQP3	524	0.32	0.22	YES
3	HGF	HGF	HGF	921	0.25	0.3	YES
4	CYFIP2	CYFIP2	CYFIP2	991	0.24	0.38	YES
5	MGAT3	MGAT3	MGAT3	1232	0.22	0.45	YES
6	EPHA2	EPHA2	EPHA2	3415	0.098	0.36	NO
7	PLEKHA7	PLEKHA7	PLEKHA7	3789	0.087	0.38	NO
8	EFNA1	EFNA1	EFNA1	3807	0.086	0.41	NO
9	EGF	EGF	EGF	4648	0.066	0.39	NO
10	MYO6	MYO6	MYO6	5169	0.055	0.38	NO
11	EGFR	EGFR	EGFR	5225	0.054	0.4	NO
12	CTNNA1	CTNNA1	CTNNA1	6342	0.036	0.35	NO
13	IGF1	IGF1	IGF1	6639	0.032	0.34	NO
14	MLLT4	MLLT4	MLLT4	7091	0.025	0.33	NO
15	KIFC3	KIFC3	KIFC3	7490	0.02	0.31	NO
16	MET	MET	MET	7745	0.017	0.31	NO
17	CTNND1	CTNND1	CTNND1	7805	0.016	0.31	NO
18	RHOA	RHOA	RHOA	8060	0.013	0.3	NO
19	DIAPH1	DIAPH1	DIAPH1	8074	0.013	0.3	NO
20	LIMA1	LIMA1	LIMA1	8194	0.011	0.3	NO
21	PIP5K1C	PIP5K1C	PIP5K1C	8452	0.0075	0.29	NO
22	CTNNB1	CTNNB1	CTNNB1	8455	0.0075	0.29	NO
23	ROCK1	ROCK1	ROCK1	8479	0.0072	0.29	NO
24	CDH1	CDH1	CDH1	8712	0.0043	0.28	NO
25	LPP	LPP	LPP	9889	-0.01	0.22	NO
26	EXOC3	EXOC3	EXOC3	10167	-0.013	0.21	NO
27	MYL2	MYL2	MYL2	10205	-0.014	0.22	NO
28	STX4	STX4	STX4	10401	-0.016	0.21	NO
29	VCL	VCL	VCL	10429	-0.017	0.22	NO
30	EXOC4	EXOC4	EXOC4	10954	-0.023	0.2	NO
31	IGF1R	IGF1R	IGF1R	11070	-0.025	0.2	NO
32	ABI1	ABI1	ABI1	11537	-0.031	0.18	NO
33	VASP	VASP	VASP	11596	-0.032	0.19	NO
34	NCKAP1	NCKAP1	NCKAP1	11608	-0.032	0.2	NO
35	ZYX	ZYX	ZYX	11759	-0.034	0.21	NO
36	ENAH	ENAH	ENAH	12182	-0.04	0.2	NO
37	ARF6	ARF6	ARF6	12544	-0.045	0.2	NO
38	PVRL2	PVRL2	PVRL2	13554	-0.063	0.16	NO
39	NCK1	NCK1	NCK1	13802	-0.068	0.18	NO
40	GIT1	GIT1	GIT1	14113	-0.073	0.19	NO
41	ACTN1	ACTN1	ACTN1	15558	-0.12	0.15	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 VIRAL MYOCARDITIS.

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

genes ES table in pathway: BIOCARTA FCER1 PATHWAY

Table 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	ATP1A2	ATP1A2	ATP1A2	65	0.54	0.11	YES
2	ATP1B2	ATP1B2	ATP1B2	219	0.42	0.18	YES
3	NR3C2	NR3C2	NR3C2	245	0.41	0.27	YES
4	SCNN1B	SCNN1B	SCNN1B	424	0.35	0.33	YES
5	SCNN1G	SCNN1G	SCNN1G	824	0.27	0.36	YES
6	HSD11B2	HSD11B2	HSD11B2	886	0.26	0.41	YES
7	ATP1A4	ATP1A4	ATP1A4	1200	0.22	0.44	YES
8	PRKCB	PRKCB	PRKCB	1717	0.18	0.45	YES
9	SGK1	SGK1	SGK1	1963	0.16	0.47	YES
10	NEDD4L	NEDD4L	NEDD4L	2095	0.15	0.49	YES
11	PIK3CG	PIK3CG	PIK3CG	2535	0.13	0.5	YES
12	PIK3R1	PIK3R1	PIK3R1	2685	0.13	0.52	YES
13	ATP1A1	ATP1A1	ATP1A1	3038	0.11	0.52	YES
14	PIK3R5	PIK3R5	PIK3R5	3046	0.11	0.54	YES
15	PDPK1	PDPK1	PDPK1	3824	0.086	0.52	YES
16	SLC9A3R2	SLC9A3R2	SLC9A3R2	3947	0.082	0.53	YES
17	FXYD4	FXYD4	FXYD4	4116	0.078	0.53	YES
18	KCNJ1	KCNJ1	KCNJ1	4237	0.075	0.54	YES
19	ATP1B1	ATP1B1	ATP1B1	4325	0.073	0.55	YES
20	IRS2	IRS2	IRS2	4536	0.068	0.55	YES
21	PIK3CD	PIK3CD	PIK3CD	5250	0.054	0.53	NO
22	SCNN1A	SCNN1A	SCNN1A	5789	0.045	0.51	NO
23	IGF1	IGF1	IGF1	6639	0.032	0.47	NO
24	PRKCA	PRKCA	PRKCA	6967	0.027	0.45	NO
25	MAPK1	MAPK1	MAPK1	7445	0.021	0.43	NO
26	SFN	SFN	SFN	8331	0.009	0.38	NO
27	MAPK3	MAPK3	MAPK3	9401	-0.004	0.33	NO
28	PIK3CB	PIK3CB	PIK3CB	9538	-0.0058	0.32	NO
29	PIK3R3	PIK3R3	PIK3R3	9771	-0.0086	0.31	NO
30	ATP1A3	ATP1A3	ATP1A3	10136	-0.013	0.29	NO
31	PIK3R2	PIK3R2	PIK3R2	10350	-0.016	0.28	NO
32	HSD11B1	HSD11B1	HSD11B1	10357	-0.016	0.29	NO
33	INSR	INSR	INSR	11385	-0.029	0.24	NO
34	FXYD2	FXYD2	FXYD2	12012	-0.037	0.21	NO
35	IRS4	IRS4	IRS4	12504	-0.044	0.19	NO
36	PIK3CA	PIK3CA	PIK3CA	13281	-0.058	0.16	NO
37	KRAS	KRAS	KRAS	13496	-0.062	0.16	NO
38	ATP1B3	ATP1B3	ATP1B3	14972	-0.096	0.1	NO
39	IRS1	IRS1	IRS1	16069	-0.14	0.071	NO
40	PRKCG	PRKCG	PRKCG	17345	-0.25	0.052	NO

Figure S35. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FCER1 PATHWAY.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: ST ADRENERGIC

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	FCER1A	FCER1A	FCER1A	38	0.57	0.2	YES
2	FOS	FOS	FOS	1382	0.2	0.2	YES
3	PRKCB	PRKCB	PRKCB	1717	0.18	0.24	YES
4	BTK	BTK	BTK	1973	0.16	0.29	YES
5	PIK3CG	PIK3CG	PIK3CG	2535	0.13	0.31	YES
6	NFATC3	NFATC3	NFATC3	2654	0.13	0.34	YES
7	PIK3R1	PIK3R1	PIK3R1	2685	0.13	0.39	YES
8	NFATC1	NFATC1	NFATC1	2894	0.12	0.42	YES
9	NFATC2	NFATC2	NFATC2	3378	0.099	0.43	YES
10	MAP3K1	MAP3K1	MAP3K1	3757	0.088	0.44	YES
11	PPP3CC	PPP3CC	PPP3CC	4397	0.071	0.43	YES
12	JUN	JUN	JUN	4470	0.069	0.45	YES
13	PPP3CA	PPP3CA	PPP3CA	4498	0.069	0.47	YES
14	SYK	SYK	SYK	5636	0.047	0.43	NO
15	VAV1	VAV1	VAV1	6642	0.031	0.38	NO
16	MAP2K7	MAP2K7	MAP2K7	6763	0.03	0.39	NO
17	MAPK1	MAPK1	MAPK1	7445	0.021	0.36	NO
18	PPP3CB	PPP3CB	PPP3CB	7646	0.018	0.35	NO
19	MAP2K4	MAP2K4	MAP2K4	8160	0.012	0.33	NO
20	RAF1	RAF1	RAF1	8175	0.011	0.33	NO
21	CALM1	CALM1	CALM1	8342	0.0089	0.32	NO
22	PLA2G4A	PLA2G4A	PLA2G4A	8473	0.0073	0.32	NO
23	PLCG1	PLCG1	PLCG1	9210	-0.0017	0.28	NO
24	MAPK3	MAPK3	MAPK3	9401	-0.004	0.27	NO
25	MAP2K1	MAP2K1	MAP2K1	9896	-0.01	0.25	NO
26	CALM2	CALM2	CALM2	10151	-0.013	0.24	NO
27	CALM3	CALM3	CALM3	10496	-0.017	0.23	NO
28	SOS1	SOS1	SOS1	10648	-0.019	0.23	NO
29	GRB2	GRB2	GRB2	11001	-0.024	0.22	NO
30	FCER1G	FCER1G	FCER1G	11321	-0.028	0.21	NO
31	LYN	LYN	LYN	11377	-0.029	0.22	NO
32	SHC1	SHC1	SHC1	11983	-0.037	0.2	NO
33	PIK3CA	PIK3CA	PIK3CA	13281	-0.058	0.14	NO
34	HRAS	HRAS	HRAS	13324	-0.059	0.16	NO
35	NFATC4	NFATC4	NFATC4	13458	-0.061	0.18	NO
36	PAK2	PAK2	PAK2	14293	-0.078	0.16	NO
37	ELK1	ELK1	ELK1	14349	-0.079	0.18	NO
38	MAPK8	MAPK8	MAPK8	14729	-0.089	0.2	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: ST ADRENERGIC.

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

genes ES table in pathway: ST WNT BETA CATENIN PATHWAY

Table 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	MAPK10	MAPK10	MAPK10	117	0.48	0.23	YES
2	TRPC6	TRPC6	TRPC6	614	0.3	0.35	YES
3	PRKCZ	PRKCZ	PRKCZ	2352	0.14	0.33	YES
4	PIK3R1	PIK3R1	PIK3R1	2685	0.13	0.37	YES
5	KIRREL	KIRREL	KIRREL	2988	0.11	0.41	YES
6	JUN	JUN	JUN	4470	0.069	0.37	YES
7	MAPK9	MAPK9	MAPK9	4552	0.068	0.4	YES
8	ARRB2	ARRB2	ARRB2	5153	0.056	0.39	YES
9	PIK3CD	PIK3CD	PIK3CD	5250	0.054	0.41	YES
10	F2RL2	F2RL2	F2RL2	5340	0.052	0.43	YES
11	TJP1	TJP1	TJP1	5430	0.051	0.45	YES
12	FYN	FYN	FYN	6891	0.028	0.39	NO
13	PARD6A	PARD6A	PARD6A	7797	0.016	0.35	NO
14	PRKCI	PRKCI	PRKCI	7853	0.016	0.35	NO
15	MAP2K4	MAP2K4	MAP2K4	8160	0.012	0.34	NO
16	NPHS1	NPHS1	NPHS1	8172	0.011	0.34	NO
17	BAD	BAD	BAD	8268	0.0099	0.34	NO
18	AKT1	AKT1	AKT1	8292	0.0095	0.35	NO
19	PLCG1	PLCG1	PLCG1	9210	-0.0017	0.3	NO
20	PIK3CB	PIK3CB	PIK3CB	9538	-0.0058	0.28	NO
21	PIK3R3	PIK3R3	PIK3R3	9771	-0.0086	0.28	NO
22	PIK3R2	PIK3R2	PIK3R2	10350	-0.016	0.25	NO
23	WASL	WASL	WASL	10677	-0.02	0.24	NO
24	CD2AP	CD2AP	CD2AP	10944	-0.023	0.24	NO
25	GRB2	GRB2	GRB2	11001	-0.024	0.25	NO
26	NCK2	NCK2	NCK2	11762	-0.034	0.22	NO
27	RAC1	RAC1	RAC1	13061	-0.054	0.18	NO
28	PIK3CA	PIK3CA	PIK3CA	13281	-0.058	0.2	NO
29	NCK1	NCK1	NCK1	13802	-0.068	0.2	NO
30	MAPK8	MAPK8	MAPK8	14729	-0.089	0.2	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: ST WNT BETA CATENIN PATHWAY.

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

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 DNA REPLICATION	36	genes.ES.table	0.62	1.6	0.097	0.25	0.96	0.64	0.24	0.48	0.15	0.031
KEGG SPLICEOSOME	114	genes.ES.table	0.4	1.6	0.094	0.25	0.96	0.71	0.41	0.42	0.15	0.031
KEGG PROTEASOME	43	genes.ES.table	0.63	1.8	0.018	0.14	0.61	0.67	0.27	0.49	0.049	0.028
KEGG NUCLEOTIDE EXCISION REPAIR	44	genes.ES.table	0.47	1.7	0.041	0.19	0.84	0.48	0.3	0.34	0.088	0.029
KEGG CELL CYCLE	118	genes.ES.table	0.59	1.8	0.023	0.15	0.66	0.42	0.2	0.34	0.055	0.028
KEGG P53 SIGNALING PATHWAY	67	genes.ES.table	0.46	1.6	0.029	0.22	0.93	0.33	0.15	0.28	0.12	0.028
KEGG UBIQUITIN MEDIATED PROTEOLYSIS	133	genes.ES.table	0.28	1.7	0.036	0.19	0.87	0.26	0.22	0.21	0.096	0.026
BIOCARTA G1 PATHWAY	28	genes.ES.table	0.64	1.8	0.0062	0.17	0.47	0.39	0.17	0.33	0	0.033
BIOCARTA HIVNEF PATHWAY	58	genes.ES.table	0.35	1.6	0.065	0.24	0.96	0.47	0.29	0.33	0.14	0.031
BIOCARTA PROTEASOME PATHWAY	28	genes.ES.table	0.62	1.6	0.033	0.23	0.93	0.86	0.34	0.57	0.12	0.028

genes ES table in pathway: KEGG DNA REPLICATION

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	PSMB9	PSMB9	PSMB9	1360	0.16	-0.029	YES
2	PSMD14	PSMD14	PSMD14	2349	0.1	-0.054	YES
3	PSMB8	PSMB8	PSMB8	2351	0.1	-0.026	YES
4	TNPO1	TNPO1	TNPO1	2437	0.097	-0.0025	YES
5	PSMA5	PSMA5	PSMA5	2588	0.091	0.015	YES
6	PSMB7	PSMB7	PSMB7	2657	0.088	0.037	YES
7	PSMB10	PSMB10	PSMB10	2660	0.088	0.062	YES
8	PSMA4	PSMA4	PSMA4	2827	0.083	0.077	YES
9	PSMC4	PSMC4	PSMC4	2908	0.081	0.096	YES
10	HSPA1B	HSPA1B	HSPA1B	2922	0.08	0.12	YES
11	PSMD12	PSMD12	PSMD12	3054	0.076	0.13	YES
12	PSMD11	PSMD11	PSMD11	3083	0.076	0.15	YES
13	PSMD1	PSMD1	PSMD1	3100	0.075	0.17	YES
14	EXOSC8	EXOSC8	EXOSC8	3150	0.074	0.19	YES
15	PSMD2	PSMD2	PSMD2	3170	0.073	0.21	YES
16	PSMA8	PSMA8	PSMA8	3186	0.073	0.23	YES
17	PSME2	PSME2	PSME2	3329	0.069	0.24	YES
18	PSMD9	PSMD9	PSMD9	3448	0.067	0.26	YES
19	PSMD7	PSMD7	PSMD7	3492	0.066	0.27	YES
20	PRKCA	PRKCA	PRKCA	3565	0.064	0.29	YES
21	ANP32A	ANP32A	ANP32A	3663	0.062	0.3	YES
22	YWHAZ	YWHAZ	YWHAZ	3672	0.062	0.32	YES
23	EIF4G1	EIF4G1	EIF4G1	3941	0.056	0.32	YES
24	PSMA2	PSMA2	PSMA2	3993	0.055	0.33	YES
25	PSMA3	PSMA3	PSMA3	4111	0.052	0.34	YES
26	DIS3	DIS3	DIS3	4164	0.052	0.35	YES
27	PSMD8	PSMD8	PSMD8	4205	0.051	0.37	YES
28	YWHAB	YWHAB	YWHAB	4223	0.051	0.38	YES
29	PSMB6	PSMB6	PSMB6	4256	0.05	0.39	YES
30	PSMB3	PSMB3	PSMB3	4713	0.043	0.38	YES
31	PSMA1	PSMA1	PSMA1	4724	0.043	0.39	YES
32	XPO1	XPO1	XPO1	4746	0.042	0.4	YES
33	MAPK11	MAPK11	MAPK11	4753	0.042	0.41	YES
34	PSMB5	PSMB5	PSMB5	4849	0.04	0.42	YES
35	PSMB2	PSMB2	PSMB2	4879	0.04	0.43	YES
36	PSMB1	PSMB1	PSMB1	4892	0.04	0.44	YES
37	PSMC2	PSMC2	PSMC2	4943	0.039	0.45	YES
38	XRN1	XRN1	XRN1	4979	0.038	0.46	YES
39	EXOSC3	EXOSC3	EXOSC3	5113	0.036	0.46	YES
40	PSMC5	PSMC5	PSMC5	5259	0.034	0.46	YES
41	HSPA8	HSPA8	HSPA8	5286	0.034	0.47	YES
42	RPS27A	RPS27A	RPS27A	5329	0.033	0.48	YES
43	EXOSC1	EXOSC1	EXOSC1	5346	0.033	0.49	YES
44	EXOSC9	EXOSC9	EXOSC9	5359	0.033	0.5	YES
45	EXOSC2	EXOSC2	EXOSC2	5461	0.032	0.5	YES
46	PSMD6	PSMD6	PSMD6	5603	0.029	0.5	YES
47	ZFP36	ZFP36	ZFP36	5690	0.028	0.5	YES
48	PSMC1	PSMC1	PSMC1	5752	0.027	0.51	YES
49	PSMA7	PSMA7	PSMA7	5871	0.026	0.51	YES
50	PSMC6	PSMC6	PSMC6	6214	0.021	0.5	NO
51	PSMD13	PSMD13	PSMD13	6478	0.017	0.49	NO
52	PSME1	PSME1	PSME1	6509	0.017	0.49	NO
53	HNRNPD	HNRNPD	HNRNPD	6533	0.017	0.49	NO
54	KHSRP	KHSRP	KHSRP	6573	0.016	0.5	NO
55	PSMD4	PSMD4	PSMD4	6627	0.016	0.5	NO
56	PSME4	PSME4	PSME4	6775	0.014	0.49	NO
57	PSMC3	PSMC3	PSMC3	6800	0.014	0.5	NO
58	UBA52	UBA52	UBA52	6969	0.012	0.49	NO
59	MAPK14	MAPK14	MAPK14	7241	0.0082	0.48	NO
60	PSMD5	PSMD5	PSMD5	7246	0.0082	0.48	NO
61	PSMD3	PSMD3	PSMD3	7386	0.0066	0.47	NO
62	PABPC1	PABPC1	PABPC1	7508	0.0051	0.47	NO
63	EXOSC7	EXOSC7	EXOSC7	7574	0.0043	0.47	NO
64	PSMF1	PSMF1	PSMF1	7692	0.0029	0.46	NO
65	PSMB4	PSMB4	PSMB4	7784	0.0016	0.46	NO
66	EXOSC5	EXOSC5	EXOSC5	7846	0.001	0.45	NO
67	PSMD10	PSMD10	PSMD10	8017	-0.0012	0.44	NO
68	DCP1A	DCP1A	DCP1A	8047	-0.0016	0.44	NO
69	ELAVL1	ELAVL1	ELAVL1	8050	-0.0016	0.44	NO
70	EXOSC6	EXOSC6	EXOSC6	8176	-0.0034	0.44	NO
71	NUP214	NUP214	NUP214	8674	-0.0097	0.41	NO
72	PSMA6	PSMA6	PSMA6	9209	-0.017	0.39	NO
73	MAPKAPK2	MAPKAPK2	MAPKAPK2	9330	-0.018	0.39	NO
74	EXOSC4	EXOSC4	EXOSC4	9463	-0.02	0.39	NO
75	PARN	PARN	PARN	9526	-0.021	0.39	NO
76	AKT1	AKT1	AKT1	10169	-0.03	0.36	NO
77	DCP2	DCP2	DCP2	10290	-0.032	0.36	NO
78	HSPB1	HSPB1	HSPB1	10907	-0.041	0.34	NO
79	TNFSF13	TNFSF13	TNFSF13	12231	-0.063	0.29	NO
80	ZFP36L1	ZFP36L1	ZFP36L1	12763	-0.075	0.28	NO
81	PRKCD	PRKCD	PRKCD	13062	-0.081	0.29	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 DNA REPLICATION.

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

genes ES table in pathway: KEGG SPLICEOSOME

Table 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	DSG3	DSG3	DSG3	76	0.49	0.042	YES
2	GZMB	GZMB	GZMB	261	0.35	0.065	YES
3	HIST1H1E	HIST1H1E	HIST1H1E	363	0.32	0.089	YES
4	HIST1H1D	HIST1H1D	HIST1H1D	542	0.27	0.1	YES
5	UNC5A	UNC5A	UNC5A	615	0.26	0.12	YES
6	DSG2	DSG2	DSG2	920	0.21	0.13	YES
7	HIST1H1B	HIST1H1B	HIST1H1B	944	0.2	0.15	YES
8	FASLG	FASLG	FASLG	1186	0.17	0.15	YES
9	DSG1	DSG1	DSG1	1286	0.16	0.16	YES
10	DSP	DSP	DSP	1318	0.16	0.17	YES
11	PLEC	PLEC	PLEC	1321	0.16	0.19	YES
12	PSMB9	PSMB9	PSMB9	1360	0.16	0.2	YES
13	PMAIP1	PMAIP1	PMAIP1	1560	0.14	0.2	YES
14	ARHGAP10	ARHGAP10	ARHGAP10	1809	0.13	0.2	YES
15	DNM1L	DNM1L	DNM1L	1910	0.12	0.21	YES
16	LMNB1	LMNB1	LMNB1	1972	0.12	0.22	YES
17	BID	BID	BID	1995	0.12	0.22	YES
18	HIST1H1C	HIST1H1C	HIST1H1C	2042	0.12	0.23	YES
19	STK24	STK24	STK24	2133	0.11	0.24	YES
20	TNFRSF1A	TNFRSF1A	TNFRSF1A	2322	0.1	0.24	YES
21	PSMD14	PSMD14	PSMD14	2349	0.1	0.25	YES
22	PSMB8	PSMB8	PSMB8	2351	0.1	0.26	YES
23	CASP9	CASP9	CASP9	2429	0.097	0.26	YES
24	PAK2	PAK2	PAK2	2537	0.093	0.26	YES
25	CYCS	CYCS	CYCS	2545	0.092	0.27	YES
26	BAK1	BAK1	BAK1	2573	0.092	0.28	YES
27	PSMA5	PSMA5	PSMA5	2588	0.091	0.29	YES
28	PSMB7	PSMB7	PSMB7	2657	0.088	0.29	YES
29	PSMB10	PSMB10	PSMB10	2660	0.088	0.3	YES
30	FAS	FAS	FAS	2764	0.085	0.3	YES
31	FADD	FADD	FADD	2795	0.084	0.31	YES
32	PSMA4	PSMA4	PSMA4	2827	0.083	0.31	YES
33	PSMC4	PSMC4	PSMC4	2908	0.081	0.32	YES
34	TNFRSF10B	TNFRSF10B	TNFRSF10B	3015	0.078	0.32	YES
35	BCL2L1	BCL2L1	BCL2L1	3016	0.078	0.33	YES
36	DYNLL1	DYNLL1	DYNLL1	3019	0.078	0.33	YES
37	PSMD12	PSMD12	PSMD12	3054	0.076	0.34	YES
38	PSMD11	PSMD11	PSMD11	3083	0.076	0.34	YES
39	PSMD1	PSMD1	PSMD1	3100	0.075	0.35	YES
40	PSMD2	PSMD2	PSMD2	3170	0.073	0.35	YES
41	PSMA8	PSMA8	PSMA8	3186	0.073	0.36	YES
42	PRKCQ	PRKCQ	PRKCQ	3262	0.07	0.36	YES
43	MST4	MST4	MST4	3326	0.069	0.36	YES
44	PSME2	PSME2	PSME2	3329	0.069	0.37	YES
45	KPNA1	KPNA1	KPNA1	3376	0.068	0.38	YES
46	PSMD9	PSMD9	PSMD9	3448	0.067	0.38	YES
47	PSMD7	PSMD7	PSMD7	3492	0.066	0.38	YES
48	BIRC2	BIRC2	BIRC2	3497	0.066	0.39	YES
49	TRAF2	TRAF2	TRAF2	3610	0.063	0.39	YES
50	E2F1	E2F1	E2F1	3670	0.062	0.39	YES
51	TJP2	TJP2	TJP2	3864	0.057	0.38	YES
52	KPNB1	KPNB1	KPNB1	3924	0.056	0.39	YES
53	PSMA2	PSMA2	PSMA2	3993	0.055	0.39	YES
54	TJP1	TJP1	TJP1	4033	0.054	0.39	YES
55	PSMA3	PSMA3	PSMA3	4111	0.052	0.39	YES
56	PSMD8	PSMD8	PSMD8	4205	0.051	0.39	YES
57	YWHAB	YWHAB	YWHAB	4223	0.051	0.4	YES
58	BCL2L11	BCL2L11	BCL2L11	4232	0.05	0.4	YES
59	PSMB6	PSMB6	PSMB6	4256	0.05	0.4	YES
60	DIABLO	DIABLO	DIABLO	4286	0.05	0.41	YES
61	MAPK8	MAPK8	MAPK8	4312	0.049	0.41	YES
62	PPP3R1	PPP3R1	PPP3R1	4426	0.047	0.41	YES
63	CASP3	CASP3	CASP3	4505	0.046	0.41	YES
64	CASP8	CASP8	CASP8	4670	0.043	0.4	YES
65	PSMB3	PSMB3	PSMB3	4713	0.043	0.4	YES
66	PSMA1	PSMA1	PSMA1	4724	0.043	0.41	YES
67	LMNA	LMNA	LMNA	4763	0.042	0.41	YES
68	PSMB5	PSMB5	PSMB5	4849	0.04	0.41	YES
69	PSMB2	PSMB2	PSMB2	4879	0.04	0.41	YES
70	PSMB1	PSMB1	PSMB1	4892	0.04	0.41	YES
71	HMGB1	HMGB1	HMGB1	4901	0.04	0.42	YES
72	PSMC2	PSMC2	PSMC2	4943	0.039	0.42	YES
73	TFDP1	TFDP1	TFDP1	5154	0.036	0.41	NO
74	GAS2	GAS2	GAS2	5208	0.035	0.41	NO
75	PSMC5	PSMC5	PSMC5	5259	0.034	0.41	NO
76	CASP7	CASP7	CASP7	5299	0.034	0.41	NO
77	RPS27A	RPS27A	RPS27A	5329	0.033	0.41	NO
78	FNTA	FNTA	FNTA	5467	0.031	0.41	NO
79	PSMD6	PSMD6	PSMD6	5603	0.029	0.4	NO
80	TNFSF10	TNFSF10	TNFSF10	5623	0.029	0.41	NO
81	PSMC1	PSMC1	PSMC1	5752	0.027	0.4	NO
82	NMT1	NMT1	NMT1	5798	0.026	0.4	NO
83	CFLAR	CFLAR	CFLAR	5828	0.026	0.4	NO
84	PSMA7	PSMA7	PSMA7	5871	0.026	0.4	NO
85	PKP1	PKP1	PKP1	5892	0.025	0.4	NO
86	UNC5B	UNC5B	UNC5B	5922	0.025	0.4	NO
87	HMGB2	HMGB2	HMGB2	5975	0.024	0.4	NO
88	CASP6	CASP6	CASP6	6145	0.022	0.4	NO
89	PSMC6	PSMC6	PSMC6	6214	0.021	0.4	NO
90	BCAP31	BCAP31	BCAP31	6365	0.019	0.39	NO
91	PSMD13	PSMD13	PSMD13	6478	0.017	0.38	NO
92	PSME1	PSME1	PSME1	6509	0.017	0.38	NO
93	PSMD4	PSMD4	PSMD4	6627	0.016	0.38	NO
94	LOC647859	LOC647859	LOC647859	6699	0.015	0.38	NO
95	PSME4	PSME4	PSME4	6775	0.014	0.37	NO
96	PSMC3	PSMC3	PSMC3	6800	0.014	0.37	NO
97	UBA52	UBA52	UBA52	6969	0.012	0.37	NO
98	BAX	BAX	BAX	7213	0.0086	0.35	NO
99	PSMD5	PSMD5	PSMD5	7246	0.0082	0.35	NO
100	ROCK1	ROCK1	ROCK1	7258	0.0081	0.35	NO
101	PSMD3	PSMD3	PSMD3	7386	0.0066	0.35	NO
102	SPTAN1	SPTAN1	SPTAN1	7487	0.0054	0.34	NO
103	ADD1	ADD1	ADD1	7520	0.0049	0.34	NO
104	PSMF1	PSMF1	PSMF1	7692	0.0029	0.33	NO
105	PSMB4	PSMB4	PSMB4	7784	0.0016	0.33	NO
106	PSMD10	PSMD10	PSMD10	8017	-0.0012	0.31	NO
107	DCC	DCC	DCC	8127	-0.0028	0.31	NO
108	DAPK3	DAPK3	DAPK3	8137	-0.0029	0.31	NO
109	RIPK1	RIPK1	RIPK1	8188	-0.0035	0.3	NO
110	VIM	VIM	VIM	8675	-0.0097	0.28	NO
111	APAF1	APAF1	APAF1	8831	-0.012	0.27	NO
112	PSMA6	PSMA6	PSMA6	9209	-0.017	0.25	NO
113	DBNL	DBNL	DBNL	9388	-0.019	0.24	NO
114	TRADD	TRADD	TRADD	9428	-0.02	0.24	NO
115	XIAP	XIAP	XIAP	9555	-0.021	0.24	NO
116	H1F0	H1F0	H1F0	9558	-0.021	0.24	NO
117	APC	APC	APC	9749	-0.024	0.23	NO
118	DFFA	DFFA	DFFA	9827	-0.025	0.23	NO
119	TNF	TNF	TNF	9944	-0.027	0.23	NO
120	AKT1	AKT1	AKT1	10169	-0.03	0.22	NO
121	CTNNB1	CTNNB1	CTNNB1	10259	-0.031	0.22	NO
122	GSN	GSN	GSN	10346	-0.032	0.21	NO
123	CDH1	CDH1	CDH1	10368	-0.033	0.22	NO
124	DAPK1	DAPK1	DAPK1	10390	-0.033	0.22	NO
125	ACIN1	ACIN1	ACIN1	10416	-0.034	0.22	NO
126	TP53	TP53	TP53	10613	-0.036	0.21	NO
127	APPL1	APPL1	APPL1	10657	-0.037	0.21	NO
128	SATB1	SATB1	SATB1	10797	-0.039	0.21	NO
129	DYNLL2	DYNLL2	DYNLL2	12085	-0.06	0.14	NO
130	PTK2	PTK2	PTK2	12349	-0.066	0.14	NO
131	MAGED1	MAGED1	MAGED1	12405	-0.067	0.14	NO
132	CASP10	CASP10	CASP10	12716	-0.074	0.13	NO
133	BBC3	BBC3	BBC3	12795	-0.075	0.13	NO
134	BAD	BAD	BAD	13007	-0.08	0.13	NO
135	PRKCD	PRKCD	PRKCD	13062	-0.081	0.13	NO
136	DFFB	DFFB	DFFB	13348	-0.088	0.12	NO
137	BMX	BMX	BMX	15002	-0.14	0.047	NO
138	BMF	BMF	BMF	15923	-0.18	0.014	NO
139	BCL2	BCL2	BCL2	16172	-0.2	0.018	NO
140	OCLN	OCLN	OCLN	16851	-0.24	0.0035	NO
141	MAPT	MAPT	MAPT	17943	-0.39	-0.02	NO
142	DAPK2	DAPK2	DAPK2	18052	-0.42	0.014	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 SPLICEOSOME.

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

genes ES table in pathway: KEGG PROTEASOME

Table 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	GJB3	GJB3	GJB3	3	0.88	0.11	YES
2	GJB4	GJB4	GJB4	36	0.57	0.17	YES
3	GJB5	GJB5	GJB5	66	0.5	0.23	YES
4	GJB2	GJB2	GJB2	75	0.49	0.29	YES
5	TPD52L1	TPD52L1	TPD52L1	946	0.2	0.27	YES
6	CLTB	CLTB	CLTB	1176	0.17	0.28	YES
7	GJB6	GJB6	GJB6	1243	0.17	0.29	YES
8	GJA3	GJA3	GJA3	1332	0.16	0.31	YES
9	TFRC	TFRC	TFRC	1729	0.13	0.3	YES
10	STAM	STAM	STAM	2057	0.11	0.3	YES
11	GJC2	GJC2	GJC2	2370	0.099	0.29	YES
12	GJA1	GJA1	GJA1	2627	0.089	0.29	YES
13	AP4E1	AP4E1	AP4E1	2682	0.088	0.3	YES
14	SNX9	SNX9	SNX9	2785	0.084	0.3	YES
15	AP3S1	AP3S1	AP3S1	2891	0.081	0.31	YES
16	GJA9	GJA9	GJA9	2960	0.079	0.31	YES
17	AP1S1	AP1S1	AP1S1	3092	0.075	0.31	YES
18	VTA1	VTA1	VTA1	3198	0.073	0.32	YES
19	AP2M1	AP2M1	AP2M1	3261	0.07	0.32	YES
20	COPZ1	COPZ1	COPZ1	3325	0.069	0.33	YES
21	M6PR	M6PR	M6PR	3443	0.067	0.33	YES
22	NECAP1	NECAP1	NECAP1	3455	0.067	0.34	YES
23	CPD	CPD	CPD	3512	0.065	0.34	YES
24	CNO	CNO	CNO	3538	0.065	0.35	YES
25	CHMP2B	CHMP2B	CHMP2B	3606	0.063	0.35	YES
26	SNF8	SNF8	SNF8	3653	0.062	0.36	YES
27	SNAP23	SNAP23	SNAP23	3798	0.059	0.36	YES
28	SEC23A	SEC23A	SEC23A	3848	0.057	0.36	YES
29	TJP1	TJP1	TJP1	4033	0.054	0.36	YES
30	CHMP4C	CHMP4C	CHMP4C	4145	0.052	0.36	YES
31	DNM1	DNM1	DNM1	4165	0.052	0.36	YES
32	GJC1	GJC1	GJC1	4243	0.05	0.36	YES
33	SRC	SRC	SRC	4339	0.049	0.36	YES
34	VPS37B	VPS37B	VPS37B	4354	0.048	0.37	YES
35	VPS4B	VPS4B	VPS4B	4429	0.047	0.37	YES
36	PICALM	PICALM	PICALM	4597	0.045	0.37	YES
37	PLDN	PLDN	PLDN	4750	0.042	0.36	YES
38	BLOC1S1	BLOC1S1	BLOC1S1	4825	0.041	0.36	YES
39	AP3B1	AP3B1	AP3B1	4856	0.04	0.37	YES
40	COPB2	COPB2	COPB2	4948	0.039	0.37	YES
41	CHMP5	CHMP5	CHMP5	4995	0.038	0.37	YES
42	GBF1	GBF1	GBF1	5011	0.038	0.37	YES
43	HGS	HGS	HGS	5150	0.036	0.37	YES
44	DAB2	DAB2	DAB2	5162	0.036	0.37	YES
45	YIPF6	YIPF6	YIPF6	5242	0.035	0.37	YES
46	COPG	COPG	COPG	5265	0.034	0.38	YES
47	HSPA8	HSPA8	HSPA8	5286	0.034	0.38	YES
48	RPS27A	RPS27A	RPS27A	5329	0.033	0.38	YES
49	PREB	PREB	PREB	5497	0.031	0.38	NO
50	TSG101	TSG101	TSG101	5529	0.03	0.38	NO
51	SEC13	SEC13	SEC13	5655	0.028	0.37	NO
52	TGOLN2	TGOLN2	TGOLN2	5822	0.026	0.37	NO
53	FTL	FTL	FTL	5872	0.026	0.37	NO
54	GAK	GAK	GAK	6036	0.023	0.36	NO
55	VPS25	VPS25	VPS25	6047	0.023	0.36	NO
56	FTH1	FTH1	FTH1	6127	0.022	0.36	NO
57	BLOC1S3	BLOC1S3	BLOC1S3	6270	0.02	0.36	NO
58	CHMP2A	CHMP2A	CHMP2A	6355	0.019	0.36	NO
59	COPB1	COPB1	COPB1	6389	0.018	0.36	NO
60	VPS37A	VPS37A	VPS37A	6553	0.016	0.35	NO
61	CHMP7	CHMP7	CHMP7	6601	0.016	0.35	NO
62	SEC24B	SEC24B	SEC24B	6714	0.015	0.34	NO
63	AP1G1	AP1G1	AP1G1	6788	0.014	0.34	NO
64	OCRL	OCRL	OCRL	6801	0.014	0.34	NO
65	VPS36	VPS36	VPS36	6834	0.013	0.34	NO
66	COPE	COPE	COPE	6860	0.013	0.34	NO
67	DNM2	DNM2	DNM2	6888	0.012	0.34	NO
68	ARCN1	ARCN1	ARCN1	6922	0.012	0.34	NO
69	UBA52	UBA52	UBA52	6969	0.012	0.34	NO
70	RAB5C	RAB5C	RAB5C	6991	0.011	0.34	NO
71	VPS4A	VPS4A	VPS4A	7141	0.0096	0.33	NO
72	VAMP7	VAMP7	VAMP7	7219	0.0086	0.33	NO
73	SAR1B	SAR1B	SAR1B	7347	0.007	0.32	NO
74	GNS	GNS	GNS	7412	0.0063	0.32	NO
75	SEC31A	SEC31A	SEC31A	7436	0.006	0.32	NO
76	STAM2	STAM2	STAM2	7455	0.0058	0.32	NO
77	CLTA	CLTA	CLTA	7506	0.0051	0.32	NO
78	ARF1	ARF1	ARF1	7605	0.0039	0.31	NO
79	SH3D19	SH3D19	SH3D19	7634	0.0036	0.31	NO
80	CLTC	CLTC	CLTC	7783	0.0016	0.3	NO
81	COPA	COPA	COPA	7841	0.001	0.3	NO
82	IGF2R	IGF2R	IGF2R	7948	-0.00026	0.3	NO
83	CHMP4B	CHMP4B	CHMP4B	7971	-0.00057	0.29	NO
84	CLTCL1	CLTCL1	CLTCL1	7975	-0.0006	0.29	NO
85	STX4	STX4	STX4	7998	-0.00092	0.29	NO
86	GJA5	GJA5	GJA5	8210	-0.0037	0.28	NO
87	SEC24C	SEC24C	SEC24C	8516	-0.0077	0.27	NO
88	TXNDC5	TXNDC5	TXNDC5	8683	-0.0098	0.26	NO
89	AP1B1	AP1B1	AP1B1	8717	-0.01	0.26	NO
90	CHMP4A	CHMP4A	CHMP4A	8768	-0.011	0.26	NO
91	SNX2	SNX2	SNX2	8811	-0.011	0.26	NO
92	SEC24D	SEC24D	SEC24D	8897	-0.012	0.25	NO
93	ARFGAP1	ARFGAP1	ARFGAP1	9267	-0.017	0.23	NO
94	GJD4	GJD4	GJD4	9291	-0.018	0.24	NO
95	VPS28	VPS28	VPS28	9381	-0.019	0.23	NO
96	SNX5	SNX5	SNX5	9424	-0.02	0.23	NO
97	PUM1	PUM1	PUM1	9746	-0.024	0.22	NO
98	GJB7	GJB7	GJB7	9778	-0.024	0.22	NO
99	PIK3C2A	PIK3C2A	PIK3C2A	9798	-0.025	0.22	NO
100	TPD52	TPD52	TPD52	9808	-0.025	0.22	NO
101	VPS37C	VPS37C	VPS37C	9816	-0.025	0.23	NO
102	NAPA	NAPA	NAPA	9845	-0.026	0.23	NO
103	DNASE2	DNASE2	DNASE2	10054	-0.029	0.22	NO
104	AP1M1	AP1M1	AP1M1	10546	-0.036	0.2	NO
105	AP1M2	AP1M2	AP1M2	10707	-0.038	0.19	NO
106	VAMP8	VAMP8	VAMP8	11355	-0.048	0.16	NO
107	HIP1R	HIP1R	HIP1R	11437	-0.049	0.16	NO
108	SNAPIN	SNAPIN	SNAPIN	11621	-0.052	0.16	NO
109	CTSZ	CTSZ	CTSZ	11695	-0.054	0.16	NO
110	AP1S2	AP1S2	AP1S2	12074	-0.06	0.15	NO
111	GJA4	GJA4	GJA4	12075	-0.06	0.16	NO
112	CHMP6	CHMP6	CHMP6	12195	-0.062	0.16	NO
113	TBC1D8B	TBC1D8B	TBC1D8B	12694	-0.073	0.14	NO
114	AP4B1	AP4B1	AP4B1	12781	-0.075	0.14	NO
115	VAMP2	VAMP2	VAMP2	13697	-0.097	0.1	NO
116	GJB1	GJB1	GJB1	13975	-0.1	0.1	NO
117	DNAJC6	DNAJC6	DNAJC6	14121	-0.11	0.11	NO
118	SORT1	SORT1	SORT1	14213	-0.11	0.12	NO
119	DTNBP1	DTNBP1	DTNBP1	14435	-0.12	0.12	NO
120	SH3GL2	SH3GL2	SH3GL2	14842	-0.13	0.11	NO
121	MYO6	MYO6	MYO6	15025	-0.14	0.12	NO
122	ARRB1	ARRB1	ARRB1	16891	-0.24	0.045	NO
123	VPS37D	VPS37D	VPS37D	17190	-0.27	0.061	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 PROTEASOME.

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

genes ES table in pathway: KEGG NUCLEOTIDE EXCISION REPAIR

Table 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	PSMB9	PSMB9	PSMB9	1360	0.16	-0.039	YES
2	TRIB3	TRIB3	TRIB3	1611	0.14	-0.022	YES
3	PSMD14	PSMD14	PSMD14	2349	0.1	-0.04	YES
4	PSMB8	PSMB8	PSMB8	2351	0.1	-0.018	YES
5	CARD11	CARD11	CARD11	2367	0.099	0.003	YES
6	CASP9	CASP9	CASP9	2429	0.097	0.021	YES
7	PSMA5	PSMA5	PSMA5	2588	0.091	0.033	YES
8	CDKN1A	CDKN1A	CDKN1A	2656	0.088	0.049	YES
9	PSMB7	PSMB7	PSMB7	2657	0.088	0.068	YES
10	PSMB10	PSMB10	PSMB10	2660	0.088	0.088	YES
11	AKT1S1	AKT1S1	AKT1S1	2782	0.084	0.1	YES
12	PSMA4	PSMA4	PSMA4	2827	0.083	0.12	YES
13	PSMC4	PSMC4	PSMC4	2908	0.081	0.13	YES
14	PSMD12	PSMD12	PSMD12	3054	0.076	0.14	YES
15	PSMD11	PSMD11	PSMD11	3083	0.076	0.15	YES
16	PSMD1	PSMD1	PSMD1	3100	0.075	0.17	YES
17	PSMD2	PSMD2	PSMD2	3170	0.073	0.18	YES
18	PSMA8	PSMA8	PSMA8	3186	0.073	0.2	YES
19	NRAS	NRAS	NRAS	3302	0.07	0.21	YES
20	PSME2	PSME2	PSME2	3329	0.069	0.22	YES
21	PSMD9	PSMD9	PSMD9	3448	0.067	0.23	YES
22	BCL10	BCL10	BCL10	3479	0.066	0.24	YES
23	PSMD7	PSMD7	PSMD7	3492	0.066	0.26	YES
24	FOXO1	FOXO1	FOXO1	3617	0.063	0.26	YES
25	MDM2	MDM2	MDM2	3671	0.062	0.27	YES
26	NFKBIB	NFKBIB	NFKBIB	3681	0.061	0.29	YES
27	KRAS	KRAS	KRAS	3750	0.06	0.3	YES
28	PSMA2	PSMA2	PSMA2	3993	0.055	0.3	YES
29	MAP3K7	MAP3K7	MAP3K7	4070	0.053	0.3	YES
30	NFKBIE	NFKBIE	NFKBIE	4096	0.053	0.31	YES
31	PSMA3	PSMA3	PSMA3	4111	0.052	0.32	YES
32	GSK3A	GSK3A	GSK3A	4142	0.052	0.33	YES
33	PSMD8	PSMD8	PSMD8	4205	0.051	0.34	YES
34	PSMB6	PSMB6	PSMB6	4256	0.05	0.35	YES
35	CHUK	CHUK	CHUK	4388	0.048	0.35	YES
36	PSMB3	PSMB3	PSMB3	4713	0.043	0.34	YES
37	PSMA1	PSMA1	PSMA1	4724	0.043	0.35	YES
38	PSMB5	PSMB5	PSMB5	4849	0.04	0.36	YES
39	PSMB2	PSMB2	PSMB2	4879	0.04	0.36	YES
40	PSMB1	PSMB1	PSMB1	4892	0.04	0.37	YES
41	PSMC2	PSMC2	PSMC2	4943	0.039	0.38	YES
42	HRAS	HRAS	HRAS	4997	0.038	0.38	YES
43	PSMC5	PSMC5	PSMC5	5259	0.034	0.38	YES
44	RPS27A	RPS27A	RPS27A	5329	0.033	0.38	YES
45	AKT3	AKT3	AKT3	5490	0.031	0.38	YES
46	PSMD6	PSMD6	PSMD6	5603	0.029	0.38	YES
47	PTEN	PTEN	PTEN	5631	0.029	0.38	YES
48	AKT2	AKT2	AKT2	5639	0.029	0.39	YES
49	PSMC1	PSMC1	PSMC1	5752	0.027	0.39	NO
50	PSMA7	PSMA7	PSMA7	5871	0.026	0.39	NO
51	PSMC6	PSMC6	PSMC6	6214	0.021	0.37	NO
52	RELA	RELA	RELA	6435	0.018	0.37	NO
53	PSMD13	PSMD13	PSMD13	6478	0.017	0.37	NO
54	PSME1	PSME1	PSME1	6509	0.017	0.37	NO
55	PSMD4	PSMD4	PSMD4	6627	0.016	0.37	NO
56	BTRC	BTRC	BTRC	6657	0.015	0.37	NO
57	RICTOR	RICTOR	RICTOR	6673	0.015	0.37	NO
58	CUL1	CUL1	CUL1	6690	0.015	0.37	NO
59	PSME4	PSME4	PSME4	6775	0.014	0.37	NO
60	PSMC3	PSMC3	PSMC3	6800	0.014	0.37	NO
61	MAPKAP1	MAPKAP1	MAPKAP1	6820	0.013	0.38	NO
62	RASGRP3	RASGRP3	RASGRP3	6950	0.012	0.37	NO
63	UBA52	UBA52	UBA52	6969	0.012	0.37	NO
64	MLST8	MLST8	MLST8	7169	0.0092	0.36	NO
65	CDKN1B	CDKN1B	CDKN1B	7228	0.0084	0.36	NO
66	PSMD5	PSMD5	PSMD5	7246	0.0082	0.36	NO
67	PSMD3	PSMD3	PSMD3	7386	0.0066	0.36	NO
68	SKP1	SKP1	SKP1	7573	0.0043	0.35	NO
69	PSMF1	PSMF1	PSMF1	7692	0.0029	0.34	NO
70	PSMB4	PSMB4	PSMB4	7784	0.0016	0.34	NO
71	MTOR	MTOR	MTOR	7912	0.0002	0.33	NO
72	PSMD10	PSMD10	PSMD10	8017	-0.0012	0.32	NO
73	IKBKG	IKBKG	IKBKG	8114	-0.0026	0.32	NO
74	THEM4	THEM4	THEM4	8849	-0.012	0.28	NO
75	FOXO3	FOXO3	FOXO3	8916	-0.013	0.28	NO
76	PSMA6	PSMA6	PSMA6	9209	-0.017	0.27	NO
77	RASGRP1	RASGRP1	RASGRP1	9358	-0.019	0.27	NO
78	MALT1	MALT1	MALT1	9382	-0.019	0.27	NO
79	RPS6KB2	RPS6KB2	RPS6KB2	9642	-0.023	0.26	NO
80	CREB1	CREB1	CREB1	10145	-0.03	0.24	NO
81	AKT1	AKT1	AKT1	10169	-0.03	0.24	NO
82	NR4A1	NR4A1	NR4A1	10867	-0.04	0.22	NO
83	FBXW11	FBXW11	FBXW11	10922	-0.041	0.22	NO
84	PDPK1	PDPK1	PDPK1	11876	-0.057	0.18	NO
85	PHLPP1	PHLPP1	PHLPP1	12305	-0.065	0.17	NO
86	BAD	BAD	BAD	13007	-0.08	0.15	NO
87	FOXO4	FOXO4	FOXO4	13016	-0.08	0.17	NO
88	NFKBIA	NFKBIA	NFKBIA	13256	-0.086	0.17	NO
89	TSC2	TSC2	TSC2	13268	-0.086	0.19	NO
90	PRKCB	PRKCB	PRKCB	13990	-0.11	0.18	NO
91	IKBKB	IKBKB	IKBKB	14811	-0.13	0.16	NO
92	REL	REL	REL	14984	-0.14	0.18	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 NUCLEOTIDE EXCISION REPAIR.

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

genes ES table in pathway: KEGG CELL CYCLE

Table 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	CCNA2	CCNA2	CCNA2	310	0.34	0.065	YES
2	CDC6	CDC6	CDC6	371	0.31	0.14	YES
3	CDT1	CDT1	CDT1	714	0.23	0.18	YES
4	PSMB9	PSMB9	PSMB9	1360	0.16	0.18	YES
5	MCM4	MCM4	MCM4	1573	0.14	0.2	YES
6	CCNA1	CCNA1	CCNA1	1651	0.14	0.23	YES
7	MCM8	MCM8	MCM8	2077	0.11	0.24	YES
8	CDK2	CDK2	CDK2	2140	0.11	0.26	YES
9	MCM2	MCM2	MCM2	2276	0.1	0.28	YES
10	MCM6	MCM6	MCM6	2283	0.1	0.3	YES
11	PSMD14	PSMD14	PSMD14	2349	0.1	0.32	YES
12	PSMB8	PSMB8	PSMB8	2351	0.1	0.35	YES
13	PSMA5	PSMA5	PSMA5	2588	0.091	0.36	YES
14	CDKN1A	CDKN1A	CDKN1A	2656	0.088	0.38	YES
15	PSMB7	PSMB7	PSMB7	2657	0.088	0.4	YES
16	PSMB10	PSMB10	PSMB10	2660	0.088	0.42	YES
17	PSMA4	PSMA4	PSMA4	2827	0.083	0.43	YES
18	MCM5	MCM5	MCM5	2839	0.083	0.45	YES
19	MCM7	MCM7	MCM7	2866	0.082	0.47	YES
20	PSMC4	PSMC4	PSMC4	2908	0.081	0.49	YES
21	PSMD12	PSMD12	PSMD12	3054	0.076	0.5	YES
22	PSMD11	PSMD11	PSMD11	3083	0.076	0.51	YES
23	PSMD1	PSMD1	PSMD1	3100	0.075	0.53	YES
24	RB1	RB1	RB1	3126	0.074	0.55	YES
25	PSMD2	PSMD2	PSMD2	3170	0.073	0.56	YES
26	PSMA8	PSMA8	PSMA8	3186	0.073	0.58	YES
27	PSME2	PSME2	PSME2	3329	0.069	0.59	YES
28	PSMD9	PSMD9	PSMD9	3448	0.067	0.6	YES
29	PSMD7	PSMD7	PSMD7	3492	0.066	0.61	YES
30	PSMA2	PSMA2	PSMA2	3993	0.055	0.6	YES
31	PSMA3	PSMA3	PSMA3	4111	0.052	0.61	YES
32	PSMD8	PSMD8	PSMD8	4205	0.051	0.61	YES
33	PSMB6	PSMB6	PSMB6	4256	0.05	0.62	YES
34	MCM3	MCM3	MCM3	4452	0.047	0.62	YES
35	PSMB3	PSMB3	PSMB3	4713	0.043	0.62	YES
36	PSMA1	PSMA1	PSMA1	4724	0.043	0.63	YES
37	PSMB5	PSMB5	PSMB5	4849	0.04	0.63	YES
38	PSMB2	PSMB2	PSMB2	4879	0.04	0.64	YES
39	PSMB1	PSMB1	PSMB1	4892	0.04	0.65	YES
40	PSMC2	PSMC2	PSMC2	4943	0.039	0.66	YES
41	PSMC5	PSMC5	PSMC5	5259	0.034	0.65	NO
42	RPS27A	RPS27A	RPS27A	5329	0.033	0.65	NO
43	PSMD6	PSMD6	PSMD6	5603	0.029	0.64	NO
44	PSMC1	PSMC1	PSMC1	5752	0.027	0.64	NO
45	PSMA7	PSMA7	PSMA7	5871	0.026	0.64	NO
46	PSMC6	PSMC6	PSMC6	6214	0.021	0.63	NO
47	PSMD13	PSMD13	PSMD13	6478	0.017	0.62	NO
48	PSME1	PSME1	PSME1	6509	0.017	0.62	NO
49	PSMD4	PSMD4	PSMD4	6627	0.016	0.62	NO
50	PSME4	PSME4	PSME4	6775	0.014	0.61	NO
51	PSMC3	PSMC3	PSMC3	6800	0.014	0.62	NO
52	UBA52	UBA52	UBA52	6969	0.012	0.61	NO
53	CDKN1B	CDKN1B	CDKN1B	7228	0.0084	0.6	NO
54	PSMD5	PSMD5	PSMD5	7246	0.0082	0.6	NO
55	PSMD3	PSMD3	PSMD3	7386	0.0066	0.59	NO
56	PSMF1	PSMF1	PSMF1	7692	0.0029	0.58	NO
57	PSMB4	PSMB4	PSMB4	7784	0.0016	0.57	NO
58	PSMD10	PSMD10	PSMD10	8017	-0.0012	0.56	NO
59	PSMA6	PSMA6	PSMA6	9209	-0.017	0.5	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 CELL CYCLE.

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

genes ES table in pathway: KEGG P53 SIGNALING PATHWAY

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	TAP1	TAP1	TAP1	1184	0.17	-0.0073	YES
2	TAP2	TAP2	TAP2	1331	0.16	0.038	YES
3	PSMB9	PSMB9	PSMB9	1360	0.16	0.09	YES
4	HLA-G	HLA-G	HLA-G	1789	0.13	0.11	YES
5	PSMD14	PSMD14	PSMD14	2349	0.1	0.11	YES
6	PSMB8	PSMB8	PSMB8	2351	0.1	0.14	YES
7	PSMA5	PSMA5	PSMA5	2588	0.091	0.16	YES
8	PSMB7	PSMB7	PSMB7	2657	0.088	0.19	YES
9	PSMB10	PSMB10	PSMB10	2660	0.088	0.22	YES
10	PSMA4	PSMA4	PSMA4	2827	0.083	0.24	YES
11	HLA-F	HLA-F	HLA-F	2874	0.082	0.26	YES
12	PSMC4	PSMC4	PSMC4	2908	0.081	0.29	YES
13	PSMD12	PSMD12	PSMD12	3054	0.076	0.3	YES
14	PSMD11	PSMD11	PSMD11	3083	0.076	0.33	YES
15	PSMD1	PSMD1	PSMD1	3100	0.075	0.35	YES
16	PSMD2	PSMD2	PSMD2	3170	0.073	0.37	YES
17	PSMA8	PSMA8	PSMA8	3186	0.073	0.4	YES
18	PSME2	PSME2	PSME2	3329	0.069	0.41	YES
19	PSMD9	PSMD9	PSMD9	3448	0.067	0.43	YES
20	PSMD7	PSMD7	PSMD7	3492	0.066	0.45	YES
21	SEC61G	SEC61G	SEC61G	3577	0.064	0.46	YES
22	B2M	B2M	B2M	3696	0.061	0.48	YES
23	PSMA2	PSMA2	PSMA2	3993	0.055	0.48	YES
24	PSMA3	PSMA3	PSMA3	4111	0.052	0.49	YES
25	PSMD8	PSMD8	PSMD8	4205	0.051	0.5	YES
26	PSMB6	PSMB6	PSMB6	4256	0.05	0.52	YES
27	PSMB3	PSMB3	PSMB3	4713	0.043	0.5	YES
28	PSMA1	PSMA1	PSMA1	4724	0.043	0.52	YES
29	PSMB5	PSMB5	PSMB5	4849	0.04	0.52	YES
30	PSMB2	PSMB2	PSMB2	4879	0.04	0.54	YES
31	PSMB1	PSMB1	PSMB1	4892	0.04	0.55	YES
32	SEC61A1	SEC61A1	SEC61A1	4927	0.039	0.56	YES
33	PSMC2	PSMC2	PSMC2	4943	0.039	0.57	YES
34	PDIA3	PDIA3	PDIA3	4954	0.039	0.58	YES
35	HLA-B	HLA-B	HLA-B	5122	0.036	0.59	YES
36	SEC61B	SEC61B	SEC61B	5226	0.035	0.59	YES
37	PSMC5	PSMC5	PSMC5	5259	0.034	0.6	YES
38	HLA-A	HLA-A	HLA-A	5303	0.034	0.61	YES
39	RPS27A	RPS27A	RPS27A	5329	0.033	0.62	YES
40	PSMD6	PSMD6	PSMD6	5603	0.029	0.62	NO
41	PSMC1	PSMC1	PSMC1	5752	0.027	0.62	NO
42	PSMA7	PSMA7	PSMA7	5871	0.026	0.62	NO
43	HLA-C	HLA-C	HLA-C	5985	0.024	0.62	NO
44	PSMC6	PSMC6	PSMC6	6214	0.021	0.62	NO
45	PSMD13	PSMD13	PSMD13	6478	0.017	0.61	NO
46	PSME1	PSME1	PSME1	6509	0.017	0.61	NO
47	PSMD4	PSMD4	PSMD4	6627	0.016	0.61	NO
48	PSME4	PSME4	PSME4	6775	0.014	0.61	NO
49	PSMC3	PSMC3	PSMC3	6800	0.014	0.61	NO
50	UBA52	UBA52	UBA52	6969	0.012	0.6	NO
51	PSMD5	PSMD5	PSMD5	7246	0.0082	0.59	NO
52	PSMD3	PSMD3	PSMD3	7386	0.0066	0.59	NO
53	PSMF1	PSMF1	PSMF1	7692	0.0029	0.57	NO
54	PSMB4	PSMB4	PSMB4	7784	0.0016	0.57	NO
55	PSMD10	PSMD10	PSMD10	8017	-0.0012	0.55	NO
56	CALR	CALR	CALR	8124	-0.0028	0.55	NO
57	SEC61A2	SEC61A2	SEC61A2	8638	-0.0093	0.52	NO
58	PSMA6	PSMA6	PSMA6	9209	-0.017	0.5	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 P53 SIGNALING PATHWAY.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG P53 SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG UBIQUITIN MEDIATED PROTEOLYSIS

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	NEDD4	NEDD4	NEDD4	1036	0.19	0.0017	YES
2	NUP37	NUP37	NUP37	1297	0.16	0.038	YES
3	KPNA2	KPNA2	KPNA2	1623	0.14	0.063	YES
4	STAT1	STAT1	STAT1	1742	0.13	0.096	YES
5	EIF2AK2	EIF2AK2	EIF2AK2	2159	0.11	0.11	YES
6	ISG15	ISG15	ISG15	2179	0.11	0.14	YES
7	KPNA4	KPNA4	KPNA4	2736	0.086	0.14	YES
8	UBE2L6	UBE2L6	UBE2L6	2741	0.086	0.16	YES
9	MX1	MX1	MX1	2820	0.083	0.18	YES
10	NUP107	NUP107	NUP107	2822	0.083	0.21	YES
11	DDX58	DDX58	DDX58	2890	0.081	0.23	YES
12	EIF4A3	EIF4A3	EIF4A3	2966	0.079	0.25	YES
13	KPNA3	KPNA3	KPNA3	3213	0.072	0.26	YES
14	FLNB	FLNB	FLNB	3288	0.07	0.28	YES
15	KPNA1	KPNA1	KPNA1	3376	0.068	0.29	YES
16	NUP205	NUP205	NUP205	3673	0.061	0.29	YES
17	IFIT1	IFIT1	IFIT1	3866	0.057	0.3	YES
18	KPNB1	KPNB1	KPNB1	3924	0.056	0.31	YES
19	EIF4G1	EIF4G1	EIF4G1	3941	0.056	0.33	YES
20	JAK1	JAK1	JAK1	4043	0.054	0.34	YES
21	NUP54	NUP54	NUP54	4077	0.053	0.36	YES
22	NUP50	NUP50	NUP50	4125	0.052	0.37	YES
23	AAAS	AAAS	AAAS	4185	0.051	0.38	YES
24	EIF4E	EIF4E	EIF4E	4242	0.05	0.39	YES
25	ARIH1	ARIH1	ARIH1	4270	0.05	0.41	YES
26	TRIM25	TRIM25	TRIM25	4311	0.049	0.42	YES
27	NUP62	NUP62	NUP62	4400	0.048	0.43	YES
28	EIF4A1	EIF4A1	EIF4A1	4439	0.047	0.44	YES
29	UBE2N	UBE2N	UBE2N	4464	0.047	0.46	YES
30	NUP35	NUP35	NUP35	4567	0.045	0.46	YES
31	NUP153	NUP153	NUP153	4574	0.045	0.48	YES
32	NUP155	NUP155	NUP155	4778	0.042	0.48	YES
33	NUP93	NUP93	NUP93	5270	0.034	0.46	YES
34	RPS27A	RPS27A	RPS27A	5329	0.033	0.47	YES
35	USP18	USP18	USP18	5339	0.033	0.48	YES
36	HERC5	HERC5	HERC5	5463	0.032	0.48	YES
37	UBE2E1	UBE2E1	UBE2E1	5756	0.027	0.48	NO
38	EIF4A2	EIF4A2	EIF4A2	6027	0.023	0.47	NO
39	EIF4E2	EIF4E2	EIF4E2	6419	0.018	0.45	NO
40	RAE1	RAE1	RAE1	6505	0.017	0.45	NO
41	MAPK3	MAPK3	MAPK3	6757	0.014	0.44	NO
42	NUP85	NUP85	NUP85	6822	0.013	0.44	NO
43	UBA52	UBA52	UBA52	6969	0.012	0.44	NO
44	NUP88	NUP88	NUP88	7032	0.011	0.44	NO
45	EIF4G2	EIF4G2	EIF4G2	7159	0.0093	0.43	NO
46	EIF4G3	EIF4G3	EIF4G3	7315	0.0074	0.43	NO
47	SEH1L	SEH1L	SEH1L	7542	0.0047	0.42	NO
48	NUP43	NUP43	NUP43	7597	0.004	0.42	NO
49	NUPL1	NUPL1	NUPL1	7902	0.00034	0.4	NO
50	NUP188	NUP188	NUP188	8036	-0.0015	0.39	NO
51	NUP214	NUP214	NUP214	8674	-0.0097	0.36	NO
52	POM121	POM121	POM121	8731	-0.01	0.36	NO
53	RANBP2	RANBP2	RANBP2	8797	-0.011	0.36	NO
54	TPR	TPR	TPR	8814	-0.012	0.36	NO
55	IRF3	IRF3	IRF3	8967	-0.013	0.36	NO
56	PPM1B	PPM1B	PPM1B	9017	-0.014	0.36	NO
57	NUP133	NUP133	NUP133	9919	-0.026	0.32	NO
58	NUP210	NUP210	NUP210	9933	-0.027	0.33	NO
59	PIN1	PIN1	PIN1	10210	-0.03	0.32	NO
60	NUPL2	NUPL2	NUPL2	10596	-0.036	0.31	NO
61	MX2	MX2	MX2	11049	-0.043	0.3	NO
62	UBA7	UBA7	UBA7	11134	-0.044	0.31	NO
63	EIF4E3	EIF4E3	EIF4E3	12805	-0.076	0.24	NO
64	KPNA5	KPNA5	KPNA5	13578	-0.094	0.23	NO
65	PLCG1	PLCG1	PLCG1	14103	-0.11	0.23	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 UBIQUITIN MEDIATED PROTEOLYSIS.

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

genes ES table in pathway: BIOCARTA G1 PATHWAY

Table 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	HMGA1	HMGA1	HMGA1	705	0.24	0.0021	YES
2	NUP37	NUP37	NUP37	1297	0.16	-0.002	YES
3	PSMB9	PSMB9	PSMB9	1360	0.16	0.022	YES
4	RAN	RAN	RAN	1996	0.12	0.0072	YES
5	PSMD14	PSMD14	PSMD14	2349	0.1	0.0051	YES
6	PSMB8	PSMB8	PSMB8	2351	0.1	0.022	YES
7	CCNT1	CCNT1	CCNT1	2462	0.096	0.033	YES
8	AP2S1	AP2S1	AP2S1	2527	0.093	0.045	YES
9	PAK2	PAK2	PAK2	2537	0.093	0.061	YES
10	PSMA5	PSMA5	PSMA5	2588	0.091	0.074	YES
11	PSMB7	PSMB7	PSMB7	2657	0.088	0.085	YES
12	PSMB10	PSMB10	PSMB10	2660	0.088	0.1	YES
13	CD8B	CD8B	CD8B	2750	0.086	0.11	YES
14	NUP107	NUP107	NUP107	2822	0.083	0.12	YES
15	PSMA4	PSMA4	PSMA4	2827	0.083	0.14	YES
16	PSMC4	PSMC4	PSMC4	2908	0.081	0.14	YES
17	PSMD12	PSMD12	PSMD12	3054	0.076	0.15	YES
18	CD247	CD247	CD247	3062	0.076	0.16	YES
19	PSMD11	PSMD11	PSMD11	3083	0.076	0.17	YES
20	AP1S1	AP1S1	AP1S1	3092	0.075	0.19	YES
21	PSMD1	PSMD1	PSMD1	3100	0.075	0.2	YES
22	PSMD2	PSMD2	PSMD2	3170	0.073	0.21	YES
23	PSMA8	PSMA8	PSMA8	3186	0.073	0.22	YES
24	AP2M1	AP2M1	AP2M1	3261	0.07	0.23	YES
25	PSME2	PSME2	PSME2	3329	0.069	0.24	YES
26	KPNA1	KPNA1	KPNA1	3376	0.068	0.25	YES
27	PSMD9	PSMD9	PSMD9	3448	0.067	0.25	YES
28	PSMD7	PSMD7	PSMD7	3492	0.066	0.26	YES
29	AP2A1	AP2A1	AP2A1	3505	0.066	0.27	YES
30	RANBP1	RANBP1	RANBP1	3585	0.064	0.28	YES
31	APOBEC3G	APOBEC3G	APOBEC3G	3586	0.064	0.29	YES
32	NUP205	NUP205	NUP205	3673	0.061	0.3	YES
33	B2M	B2M	B2M	3696	0.061	0.31	YES
34	RANGAP1	RANGAP1	RANGAP1	3747	0.06	0.31	YES
35	LCK	LCK	LCK	3765	0.059	0.32	YES
36	KPNB1	KPNB1	KPNB1	3924	0.056	0.32	YES
37	PSMA2	PSMA2	PSMA2	3993	0.055	0.33	YES
38	PACS1	PACS1	PACS1	4032	0.054	0.34	YES
39	NUP54	NUP54	NUP54	4077	0.053	0.34	YES
40	PSMA3	PSMA3	PSMA3	4111	0.052	0.35	YES
41	NUP50	NUP50	NUP50	4125	0.052	0.36	YES
42	AAAS	AAAS	AAAS	4185	0.051	0.36	YES
43	PSMD8	PSMD8	PSMD8	4205	0.051	0.37	YES
44	PSMB6	PSMB6	PSMB6	4256	0.05	0.38	YES
45	RAC1	RAC1	RAC1	4337	0.049	0.38	YES
46	NUP62	NUP62	NUP62	4400	0.048	0.39	YES
47	NUP35	NUP35	NUP35	4567	0.045	0.39	YES
48	NPM1	NPM1	NPM1	4568	0.045	0.39	YES
49	NUP153	NUP153	NUP153	4574	0.045	0.4	YES
50	PSMB3	PSMB3	PSMB3	4713	0.043	0.4	YES
51	PSMA1	PSMA1	PSMA1	4724	0.043	0.41	YES
52	XPO1	XPO1	XPO1	4746	0.042	0.41	YES
53	NUP155	NUP155	NUP155	4778	0.042	0.42	YES
54	RCC1	RCC1	RCC1	4827	0.041	0.42	YES
55	PSMB5	PSMB5	PSMB5	4849	0.04	0.43	YES
56	PSMB2	PSMB2	PSMB2	4879	0.04	0.44	YES
57	PSMB1	PSMB1	PSMB1	4892	0.04	0.44	YES
58	PSMC2	PSMC2	PSMC2	4943	0.039	0.44	YES
59	PSMC5	PSMC5	PSMC5	5259	0.034	0.43	YES
60	NUP93	NUP93	NUP93	5270	0.034	0.44	YES
61	HLA-A	HLA-A	HLA-A	5303	0.034	0.44	YES
62	RPS27A	RPS27A	RPS27A	5329	0.033	0.45	YES
63	AP2B1	AP2B1	AP2B1	5367	0.033	0.45	YES
64	PPIA	PPIA	PPIA	5546	0.03	0.45	NO
65	PSMD6	PSMD6	PSMD6	5603	0.029	0.45	NO
66	PSMC1	PSMC1	PSMC1	5752	0.027	0.44	NO
67	BANF1	BANF1	BANF1	5764	0.027	0.45	NO
68	PSMA7	PSMA7	PSMA7	5871	0.026	0.45	NO
69	SLC25A5	SLC25A5	SLC25A5	5998	0.024	0.44	NO
70	PSMC6	PSMC6	PSMC6	6214	0.021	0.44	NO
71	TCEB2	TCEB2	TCEB2	6254	0.02	0.44	NO
72	TCEB1	TCEB1	TCEB1	6364	0.019	0.44	NO
73	PSMD13	PSMD13	PSMD13	6478	0.017	0.43	NO
74	RAE1	RAE1	RAE1	6505	0.017	0.43	NO
75	PSME1	PSME1	PSME1	6509	0.017	0.44	NO
76	PSMD4	PSMD4	PSMD4	6627	0.016	0.43	NO
77	BTRC	BTRC	BTRC	6657	0.015	0.43	NO
78	PSME4	PSME4	PSME4	6775	0.014	0.43	NO
79	AP1G1	AP1G1	AP1G1	6788	0.014	0.43	NO
80	PSMC3	PSMC3	PSMC3	6800	0.014	0.43	NO
81	NUP85	NUP85	NUP85	6822	0.013	0.43	NO
82	UBA52	UBA52	UBA52	6969	0.012	0.43	NO
83	NUP88	NUP88	NUP88	7032	0.011	0.43	NO
84	PSMD5	PSMD5	PSMD5	7246	0.0082	0.42	NO
85	PSMD3	PSMD3	PSMD3	7386	0.0066	0.41	NO
86	SLC25A6	SLC25A6	SLC25A6	7489	0.0054	0.4	NO
87	SEH1L	SEH1L	SEH1L	7542	0.0047	0.4	NO
88	SKP1	SKP1	SKP1	7573	0.0043	0.4	NO
89	NUP43	NUP43	NUP43	7597	0.004	0.4	NO
90	ARF1	ARF1	ARF1	7605	0.0039	0.4	NO
91	PSMF1	PSMF1	PSMF1	7692	0.0029	0.4	NO
92	PSMB4	PSMB4	PSMB4	7784	0.0016	0.39	NO
93	NUPL1	NUPL1	NUPL1	7902	0.00034	0.39	NO
94	PSMD10	PSMD10	PSMD10	8017	-0.0012	0.38	NO
95	NUP188	NUP188	NUP188	8036	-0.0015	0.38	NO
96	RBX1	RBX1	RBX1	8110	-0.0026	0.38	NO
97	CDK9	CDK9	CDK9	8457	-0.0071	0.36	NO
98	NUP214	NUP214	NUP214	8674	-0.0097	0.35	NO
99	AP1B1	AP1B1	AP1B1	8717	-0.01	0.35	NO
100	POM121	POM121	POM121	8731	-0.01	0.35	NO
101	RANBP2	RANBP2	RANBP2	8797	-0.011	0.35	NO
102	TPR	TPR	TPR	8814	-0.012	0.35	NO
103	PSMA6	PSMA6	PSMA6	9209	-0.017	0.33	NO
104	HCK	HCK	HCK	9566	-0.021	0.31	NO
105	CUL5	CUL5	CUL5	9829	-0.025	0.3	NO
106	NUP133	NUP133	NUP133	9919	-0.026	0.3	NO
107	NUP210	NUP210	NUP210	9933	-0.027	0.31	NO
108	ATP6V1H	ATP6V1H	ATP6V1H	10102	-0.029	0.3	NO
109	CD4	CD4	CD4	10117	-0.029	0.31	NO
110	AP1M1	AP1M1	AP1M1	10546	-0.036	0.29	NO
111	NUPL2	NUPL2	NUPL2	10596	-0.036	0.29	NO
112	AP1M2	AP1M2	AP1M2	10707	-0.038	0.29	NO
113	DOCK2	DOCK2	DOCK2	10772	-0.039	0.3	NO
114	AP2A2	AP2A2	AP2A2	11512	-0.05	0.26	NO
115	PSIP1	PSIP1	PSIP1	11832	-0.056	0.26	NO
116	AP1S2	AP1S2	AP1S2	12074	-0.06	0.25	NO
117	CD28	CD28	CD28	12787	-0.075	0.23	NO
118	ELMO1	ELMO1	ELMO1	14453	-0.12	0.16	NO
119	FYN	FYN	FYN	14796	-0.13	0.16	NO
120	SLC25A4	SLC25A4	SLC25A4	15922	-0.18	0.13	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: BIOCARTA G1 PATHWAY.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA G1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA HIVNEF PATHWAY

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	CCNE1	CCNE1	CCNE1	361	0.32	0.094	YES
2	PSMB9	PSMB9	PSMB9	1360	0.16	0.096	YES
3	CDK2	CDK2	CDK2	2140	0.11	0.092	YES
4	PSMD14	PSMD14	PSMD14	2349	0.1	0.12	YES
5	PSMB8	PSMB8	PSMB8	2351	0.1	0.15	YES
6	PSMA5	PSMA5	PSMA5	2588	0.091	0.17	YES
7	CDKN1A	CDKN1A	CDKN1A	2656	0.088	0.2	YES
8	PSMB7	PSMB7	PSMB7	2657	0.088	0.23	YES
9	PSMB10	PSMB10	PSMB10	2660	0.088	0.26	YES
10	PSMA4	PSMA4	PSMA4	2827	0.083	0.28	YES
11	PSMC4	PSMC4	PSMC4	2908	0.081	0.31	YES
12	PSMD12	PSMD12	PSMD12	3054	0.076	0.33	YES
13	PSMD11	PSMD11	PSMD11	3083	0.076	0.35	YES
14	PSMD1	PSMD1	PSMD1	3100	0.075	0.38	YES
15	PSMD2	PSMD2	PSMD2	3170	0.073	0.4	YES
16	PSMA8	PSMA8	PSMA8	3186	0.073	0.42	YES
17	PSME2	PSME2	PSME2	3329	0.069	0.44	YES
18	PSMD9	PSMD9	PSMD9	3448	0.067	0.46	YES
19	PSMD7	PSMD7	PSMD7	3492	0.066	0.48	YES
20	MDM2	MDM2	MDM2	3671	0.062	0.49	YES
21	PSMA2	PSMA2	PSMA2	3993	0.055	0.49	YES
22	PSMA3	PSMA3	PSMA3	4111	0.052	0.51	YES
23	PSMD8	PSMD8	PSMD8	4205	0.051	0.52	YES
24	PSMB6	PSMB6	PSMB6	4256	0.05	0.53	YES
25	PSMB3	PSMB3	PSMB3	4713	0.043	0.52	YES
26	PSMA1	PSMA1	PSMA1	4724	0.043	0.54	YES
27	PSMB5	PSMB5	PSMB5	4849	0.04	0.55	YES
28	PSMB2	PSMB2	PSMB2	4879	0.04	0.56	YES
29	PSMB1	PSMB1	PSMB1	4892	0.04	0.57	YES
30	PSMC2	PSMC2	PSMC2	4943	0.039	0.58	YES
31	PSMC5	PSMC5	PSMC5	5259	0.034	0.58	YES
32	RPS27A	RPS27A	RPS27A	5329	0.033	0.59	YES
33	CCNE2	CCNE2	CCNE2	5474	0.031	0.59	YES
34	PSMD6	PSMD6	PSMD6	5603	0.029	0.59	YES
35	PSMC1	PSMC1	PSMC1	5752	0.027	0.6	YES
36	PSMA7	PSMA7	PSMA7	5871	0.026	0.6	YES
37	PSMC6	PSMC6	PSMC6	6214	0.021	0.59	NO
38	PSMD13	PSMD13	PSMD13	6478	0.017	0.58	NO
39	PSME1	PSME1	PSME1	6509	0.017	0.58	NO
40	PSMD4	PSMD4	PSMD4	6627	0.016	0.58	NO
41	PSME4	PSME4	PSME4	6775	0.014	0.58	NO
42	PSMC3	PSMC3	PSMC3	6800	0.014	0.58	NO
43	UBA52	UBA52	UBA52	6969	0.012	0.58	NO
44	CDKN1B	CDKN1B	CDKN1B	7228	0.0084	0.57	NO
45	PSMD5	PSMD5	PSMD5	7246	0.0082	0.57	NO
46	RFWD2	RFWD2	RFWD2	7318	0.0074	0.57	NO
47	PSMD3	PSMD3	PSMD3	7386	0.0066	0.57	NO
48	PSMF1	PSMF1	PSMF1	7692	0.0029	0.55	NO
49	PSMB4	PSMB4	PSMB4	7784	0.0016	0.55	NO
50	PSMD10	PSMD10	PSMD10	8017	-0.0012	0.53	NO
51	PSMA6	PSMA6	PSMA6	9209	-0.017	0.47	NO
52	ATM	ATM	ATM	10254	-0.031	0.43	NO
53	TP53	TP53	TP53	10613	-0.036	0.42	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: BIOCARTA HIVNEF PATHWAY.

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

genes ES table in pathway: BIOCARTA PROTEASOME 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	CDC25A	CDC25A	CDC25A	258	0.35	0.066	YES
2	CCNA2	CCNA2	CCNA2	310	0.34	0.14	YES
3	CCNE1	CCNE1	CCNE1	361	0.32	0.21	YES
4	PKMYT1	PKMYT1	PKMYT1	471	0.29	0.27	YES
5	CKS1B	CKS1B	CKS1B	1230	0.17	0.27	YES
6	PSMB9	PSMB9	PSMB9	1360	0.16	0.3	YES
7	CCNA1	CCNA1	CCNA1	1651	0.14	0.31	YES
8	MYC	MYC	MYC	1686	0.14	0.34	YES
9	SKP2	SKP2	SKP2	2027	0.12	0.35	YES
10	CDK2	CDK2	CDK2	2140	0.11	0.37	YES
11	PSMD14	PSMD14	PSMD14	2349	0.1	0.38	YES
12	PSMB8	PSMB8	PSMB8	2351	0.1	0.4	YES
13	PSMA5	PSMA5	PSMA5	2588	0.091	0.41	YES
14	CDKN1A	CDKN1A	CDKN1A	2656	0.088	0.42	YES
15	PSMB7	PSMB7	PSMB7	2657	0.088	0.44	YES
16	PSMB10	PSMB10	PSMB10	2660	0.088	0.47	YES
17	PSMA4	PSMA4	PSMA4	2827	0.083	0.48	YES
18	PSMC4	PSMC4	PSMC4	2908	0.081	0.49	YES
19	PSMD12	PSMD12	PSMD12	3054	0.076	0.5	YES
20	PSMD11	PSMD11	PSMD11	3083	0.076	0.52	YES
21	PSMD1	PSMD1	PSMD1	3100	0.075	0.53	YES
22	RB1	RB1	RB1	3126	0.074	0.55	YES
23	PSMD2	PSMD2	PSMD2	3170	0.073	0.56	YES
24	CDK7	CDK7	CDK7	3209	0.072	0.57	YES
25	PSME2	PSME2	PSME2	3329	0.069	0.58	YES
26	PSMD9	PSMD9	PSMD9	3448	0.067	0.59	YES
27	PSMD7	PSMD7	PSMD7	3492	0.066	0.61	YES
28	PSMA2	PSMA2	PSMA2	3993	0.055	0.59	YES
29	PSMA3	PSMA3	PSMA3	4111	0.052	0.6	YES
30	PSMD8	PSMD8	PSMD8	4205	0.051	0.6	YES
31	PSMB6	PSMB6	PSMB6	4256	0.05	0.61	YES
32	PSMB3	PSMB3	PSMB3	4713	0.043	0.6	YES
33	PSMA1	PSMA1	PSMA1	4724	0.043	0.61	YES
34	PSMB5	PSMB5	PSMB5	4849	0.04	0.61	YES
35	PSMB2	PSMB2	PSMB2	4879	0.04	0.62	YES
36	PSMB1	PSMB1	PSMB1	4892	0.04	0.62	YES
37	PSMC2	PSMC2	PSMC2	4943	0.039	0.63	YES
38	PSMC5	PSMC5	PSMC5	5259	0.034	0.62	NO
39	RPS27A	RPS27A	RPS27A	5329	0.033	0.62	NO
40	CCNE2	CCNE2	CCNE2	5474	0.031	0.62	NO
41	PSMD6	PSMD6	PSMD6	5603	0.029	0.62	NO
42	PSMC1	PSMC1	PSMC1	5752	0.027	0.62	NO
43	PSMA7	PSMA7	PSMA7	5871	0.026	0.62	NO
44	PSMC6	PSMC6	PSMC6	6214	0.021	0.61	NO
45	CCNH	CCNH	CCNH	6378	0.018	0.6	NO
46	PSMD13	PSMD13	PSMD13	6478	0.017	0.6	NO
47	PSME1	PSME1	PSME1	6509	0.017	0.6	NO
48	PSMD4	PSMD4	PSMD4	6627	0.016	0.6	NO
49	CUL1	CUL1	CUL1	6690	0.015	0.6	NO
50	PSMC3	PSMC3	PSMC3	6800	0.014	0.6	NO
51	MAX	MAX	MAX	6906	0.012	0.6	NO
52	UBA52	UBA52	UBA52	6969	0.012	0.59	NO
53	CDKN1B	CDKN1B	CDKN1B	7228	0.0084	0.58	NO
54	PSMD5	PSMD5	PSMD5	7246	0.0082	0.58	NO
55	PSMD3	PSMD3	PSMD3	7386	0.0066	0.58	NO
56	SKP1	SKP1	SKP1	7573	0.0043	0.57	NO
57	PSMF1	PSMF1	PSMF1	7692	0.0029	0.56	NO
58	PSMB4	PSMB4	PSMB4	7784	0.0016	0.56	NO
59	PSMD10	PSMD10	PSMD10	8017	-0.0012	0.54	NO
60	MNAT1	MNAT1	MNAT1	8780	-0.011	0.5	NO
61	PSMA6	PSMA6	PSMA6	9209	-0.017	0.48	NO
62	WEE1	WEE1	WEE1	11855	-0.056	0.35	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: BIOCARTA PROTEASOME PATHWAY.

Figure S60. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA PROTEASOME 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 AMINOACYL TRNA BIOSYNTHESIS	41	genes.ES.table	0.51	1.9	0.024	0.21	0.45	0.66	0.37	0.41	0	0.043
KEGG RNA DEGRADATION	57	genes.ES.table	0.51	2.1	0.004	0.13	0.074	0.49	0.33	0.33	0	0.039
REACTOME METABOLISM OF NON CODING RNA	47	genes.ES.table	0.53	1.8	0.032	0.22	0.68	0.6	0.33	0.4	0.074	0.042
REACTOME CELL CYCLE	379	genes.ES.table	0.54	1.7	0.043	0.24	0.77	0.47	0.25	0.36	0.1	0.044
REACTOME MITOCHONDRIAL PROTEIN IMPORT	49	genes.ES.table	0.55	1.8	0.044	0.23	0.67	0.63	0.32	0.43	0.074	0.044
REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA	126	genes.ES.table	0.52	2	0.0061	0.11	0.16	0.79	0.43	0.46	0	0.021
REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM	44	genes.ES.table	0.53	1.8	0.029	0.24	0.59	0.8	0.42	0.46	0.067	0.047
REACTOME RNA POL II TRANSCRIPTION	93	genes.ES.table	0.45	2	0.01	0.15	0.26	0.63	0.39	0.39	0	0.035
REACTOME RNA POL III TRANSCRIPTION	33	genes.ES.table	0.47	1.8	0.025	0.22	0.52	0.73	0.35	0.48	0.061	0.045
REACTOME RECRUITMENT OF MITOTIC CENTROSOME PROTEINS AND COMPLEXES	59	genes.ES.table	0.46	1.7	0.051	0.22	0.72	0.64	0.4	0.38	0.08	0.039

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

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	ENO3	ENO3	ENO3	2	0.81	0.25	YES
2	PNPT1	PNPT1	PNPT1	2227	0.13	0.16	YES
3	PAPOLB	PAPOLB	PAPOLB	2301	0.12	0.2	YES
4	HSPD1	HSPD1	HSPD1	2341	0.12	0.23	YES
5	PAPOLA	PAPOLA	PAPOLA	2455	0.12	0.26	YES
6	EXOSC3	EXOSC3	EXOSC3	2505	0.11	0.29	YES
7	LSM1	LSM1	LSM1	2849	0.1	0.3	YES
8	EXOSC8	EXOSC8	EXOSC8	2921	0.099	0.33	YES
9	EXOSC4	EXOSC4	EXOSC4	3052	0.095	0.35	YES
10	CNOT7	CNOT7	CNOT7	3258	0.089	0.37	YES
11	LSM2	LSM2	LSM2	3629	0.08	0.37	YES
12	ZCCHC7	ZCCHC7	ZCCHC7	3954	0.072	0.38	YES
13	HSPA9	HSPA9	HSPA9	4236	0.065	0.38	YES
14	CNOT2	CNOT2	CNOT2	4462	0.061	0.39	YES
15	EXOSC2	EXOSC2	EXOSC2	4481	0.061	0.4	YES
16	CNOT3	CNOT3	CNOT3	4505	0.061	0.42	YES
17	EXOSC1	EXOSC1	EXOSC1	4660	0.058	0.43	YES
18	MPHOSPH6	MPHOSPH6	MPHOSPH6	4703	0.058	0.45	YES
19	LSM7	LSM7	LSM7	4811	0.056	0.46	YES
20	NAA38	NAA38	NAA38	4926	0.054	0.47	YES
21	EXOSC6	EXOSC6	EXOSC6	5025	0.052	0.48	YES
22	RQCD1	RQCD1	RQCD1	5041	0.052	0.49	YES
23	EXOSC5	EXOSC5	EXOSC5	5319	0.047	0.49	YES
24	PAPD7	PAPD7	PAPD7	5447	0.045	0.5	YES
25	LSM4	LSM4	LSM4	5602	0.043	0.5	YES
26	EDC4	EDC4	EDC4	5839	0.04	0.5	YES
27	XRN2	XRN2	XRN2	5940	0.038	0.51	YES
28	PATL1	PATL1	PATL1	6080	0.036	0.51	YES
29	DCPS	DCPS	DCPS	7094	0.024	0.46	NO
30	EDC3	EDC3	EDC3	7214	0.022	0.46	NO
31	ENO2	ENO2	ENO2	7472	0.019	0.46	NO
32	C1D	C1D	C1D	7517	0.018	0.46	NO
33	LSM5	LSM5	LSM5	7552	0.018	0.46	NO
34	WDR61	WDR61	WDR61	7603	0.017	0.46	NO
35	LSM3	LSM3	LSM3	7764	0.015	0.46	NO
36	CNOT10	CNOT10	CNOT10	7842	0.014	0.46	NO
37	EXOSC9	EXOSC9	EXOSC9	7914	0.013	0.46	NO
38	EXOSC10	EXOSC10	EXOSC10	7928	0.013	0.46	NO
39	EXOSC7	EXOSC7	EXOSC7	8250	0.0091	0.45	NO
40	SKIV2L	SKIV2L	SKIV2L	8299	0.0085	0.45	NO
41	DDX6	DDX6	DDX6	8425	0.0067	0.44	NO
42	PAPOLG	PAPOLG	PAPOLG	8718	0.003	0.43	NO
43	TTC37	TTC37	TTC37	8725	0.0029	0.43	NO
44	CNOT1	CNOT1	CNOT1	8821	0.0018	0.43	NO
45	DCP1A	DCP1A	DCP1A	8935	0.00017	0.42	NO
46	XRN1	XRN1	XRN1	9137	-0.0027	0.41	NO
47	CNOT6	CNOT6	CNOT6	9495	-0.0072	0.39	NO
48	SKIV2L2	SKIV2L2	SKIV2L2	9514	-0.0074	0.39	NO
49	DCP1B	DCP1B	DCP1B	9957	-0.014	0.37	NO
50	CNOT6L	CNOT6L	CNOT6L	10298	-0.019	0.36	NO
51	DCP2	DCP2	DCP2	10488	-0.022	0.36	NO
52	LSM6	LSM6	LSM6	10685	-0.025	0.35	NO
53	ENO1	ENO1	ENO1	10814	-0.027	0.35	NO
54	CNOT4	CNOT4	CNOT4	10948	-0.03	0.36	NO
55	PARN	PARN	PARN	11036	-0.031	0.36	NO
56	DIS3	DIS3	DIS3	11402	-0.038	0.35	NO
57	CNOT8	CNOT8	CNOT8	13539	-0.086	0.26	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 AMINOACYL TRNA BIOSYNTHESIS.

Figure S62. 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 DEGRADATION

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	SNRPF	SNRPF	SNRPF	1656	0.16	-0.066	YES
2	SNRPD1	SNRPD1	SNRPD1	1999	0.14	-0.063	YES
3	NUP210	NUP210	NUP210	2104	0.13	-0.048	YES
4	TXNL4A	TXNL4A	TXNL4A	2119	0.13	-0.028	YES
5	RAE1	RAE1	RAE1	2317	0.12	-0.019	YES
6	SNRPA1	SNRPA1	SNRPA1	2352	0.12	-0.0024	YES
7	MNAT1	MNAT1	MNAT1	2369	0.12	0.016	YES
8	UPF3B	UPF3B	UPF3B	2435	0.12	0.03	YES
9	PAPOLA	PAPOLA	PAPOLA	2455	0.12	0.048	YES
10	SNRPB	SNRPB	SNRPB	2500	0.11	0.063	YES
11	METTL3	METTL3	METTL3	2507	0.11	0.081	YES
12	NUP107	NUP107	NUP107	2671	0.11	0.089	YES
13	SEH1L	SEH1L	SEH1L	2878	0.1	0.093	YES
14	PABPN1	PABPN1	PABPN1	2912	0.099	0.11	YES
15	SNRPE	SNRPE	SNRPE	2987	0.097	0.12	YES
16	SNRPG	SNRPG	SNRPG	3205	0.09	0.12	YES
17	CCAR1	CCAR1	CCAR1	3245	0.089	0.13	YES
18	CPSF1	CPSF1	CPSF1	3275	0.088	0.14	YES
19	NUP35	NUP35	NUP35	3412	0.085	0.15	YES
20	CSTF3	CSTF3	CSTF3	3510	0.082	0.16	YES
21	CSTF1	CSTF1	CSTF1	3511	0.082	0.17	YES
22	LSM2	LSM2	LSM2	3629	0.08	0.18	YES
23	POLR2H	POLR2H	POLR2H	3699	0.078	0.18	YES
24	NUP37	NUP37	NUP37	3765	0.076	0.19	YES
25	SNRPB2	SNRPB2	SNRPB2	3811	0.075	0.2	YES
26	POLR2K	POLR2K	POLR2K	3815	0.075	0.22	YES
27	NUP88	NUP88	NUP88	3981	0.071	0.22	YES
28	HNRNPA0	HNRNPA0	HNRNPA0	4309	0.064	0.21	YES
29	CPSF3	CPSF3	CPSF3	4333	0.063	0.22	YES
30	NUP155	NUP155	NUP155	4369	0.063	0.22	YES
31	SMC1A	SMC1A	SMC1A	4457	0.061	0.23	YES
32	AAAS	AAAS	AAAS	4474	0.061	0.24	YES
33	PCBP2	PCBP2	PCBP2	4650	0.058	0.24	YES
34	MAGOH	MAGOH	MAGOH	4670	0.058	0.25	YES
35	GTF2H4	GTF2H4	GTF2H4	4710	0.058	0.25	YES
36	THOC4	THOC4	THOC4	4766	0.056	0.26	YES
37	U2AF2	U2AF2	U2AF2	4778	0.056	0.27	YES
38	HNRNPA3	HNRNPA3	HNRNPA3	4941	0.054	0.27	YES
39	POLR2F	POLR2F	POLR2F	4989	0.053	0.27	YES
40	SNRPA	SNRPA	SNRPA	5051	0.052	0.28	YES
41	ZNF473	ZNF473	ZNF473	5088	0.051	0.28	YES
42	GTF2F2	GTF2F2	GTF2F2	5104	0.051	0.29	YES
43	FUS	FUS	FUS	5151	0.05	0.3	YES
44	CSTF2	CSTF2	CSTF2	5181	0.049	0.3	YES
45	POLR2D	POLR2D	POLR2D	5262	0.048	0.3	YES
46	NUP133	NUP133	NUP133	5279	0.048	0.31	YES
47	NUP85	NUP85	NUP85	5360	0.047	0.32	YES
48	NUP153	NUP153	NUP153	5396	0.046	0.32	YES
49	NFX1	NFX1	NFX1	5397	0.046	0.33	YES
50	NCBP1	NCBP1	NCBP1	5468	0.045	0.33	YES
51	POLR2G	POLR2G	POLR2G	5544	0.044	0.33	YES
52	PRPF4	PRPF4	PRPF4	5591	0.043	0.34	YES
53	NUP43	NUP43	NUP43	5618	0.043	0.34	YES
54	HNRNPL	HNRNPL	HNRNPL	5622	0.043	0.35	YES
55	SNRNP200	SNRNP200	SNRNP200	5643	0.043	0.36	YES
56	SLBP	SLBP	SLBP	5663	0.042	0.36	YES
57	RBMX	RBMX	RBMX	5679	0.042	0.37	YES
58	CPSF7	CPSF7	CPSF7	5702	0.042	0.37	YES
59	DHX9	DHX9	DHX9	5725	0.041	0.38	YES
60	SNRPD3	SNRPD3	SNRPD3	5767	0.041	0.38	YES
61	POLR2J	POLR2J	POLR2J	5856	0.04	0.38	YES
62	HNRNPD	HNRNPD	HNRNPD	5961	0.038	0.38	YES
63	HNRNPR	HNRNPR	HNRNPR	5965	0.038	0.39	YES
64	NUP205	NUP205	NUP205	5975	0.038	0.39	YES
65	HNRNPA1	HNRNPA1	HNRNPA1	5978	0.038	0.4	YES
66	RNMT	RNMT	RNMT	6048	0.037	0.4	YES
67	DDX23	DDX23	DDX23	6072	0.037	0.41	YES
68	CPSF2	CPSF2	CPSF2	6172	0.035	0.41	YES
69	SF3B3	SF3B3	SF3B3	6254	0.034	0.41	YES
70	SF3B4	SF3B4	SF3B4	6309	0.034	0.41	YES
71	HNRNPC	HNRNPC	HNRNPC	6318	0.033	0.41	YES
72	GTF2H2B	GTF2H2B	GTF2H2B	6340	0.033	0.42	YES
73	SF3B1	SF3B1	SF3B1	6341	0.033	0.42	YES
74	RANBP2	RANBP2	RANBP2	6372	0.033	0.43	YES
75	SNRNP70	SNRNP70	SNRNP70	6436	0.032	0.43	YES
76	PRPF6	PRPF6	PRPF6	6457	0.032	0.43	YES
77	NUP188	NUP188	NUP188	6474	0.032	0.44	YES
78	POLR2B	POLR2B	POLR2B	6570	0.03	0.44	YES
79	SF3B2	SF3B2	SF3B2	6586	0.03	0.44	YES
80	ERCC3	ERCC3	ERCC3	6596	0.03	0.44	YES
81	HNRNPH2	HNRNPH2	HNRNPH2	6601	0.03	0.45	YES
82	HNRNPM	HNRNPM	HNRNPM	6613	0.03	0.45	YES
83	SF3B14	SF3B14	SF3B14	6618	0.03	0.46	YES
84	PCBP1	PCBP1	PCBP1	6671	0.029	0.46	YES
85	SNRPD2	SNRPD2	SNRPD2	6733	0.028	0.46	YES
86	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	6781	0.028	0.46	YES
87	HNRNPU	HNRNPU	HNRNPU	6921	0.026	0.46	YES
88	RBM8A	RBM8A	RBM8A	6995	0.025	0.46	YES
89	HNRNPF	HNRNPF	HNRNPF	7004	0.025	0.46	YES
90	POLR2I	POLR2I	POLR2I	7031	0.025	0.46	YES
91	SF3B5	SF3B5	SF3B5	7108	0.024	0.46	YES
92	POLR2A	POLR2A	POLR2A	7216	0.022	0.46	YES
93	YBX1	YBX1	YBX1	7281	0.022	0.46	YES
94	EFTUD2	EFTUD2	EFTUD2	7347	0.021	0.46	YES
95	PCF11	PCF11	PCF11	7489	0.019	0.46	YES
96	NUP50	NUP50	NUP50	7494	0.019	0.46	YES
97	NCBP2	NCBP2	NCBP2	7507	0.019	0.46	YES
98	HNRNPK	HNRNPK	HNRNPK	7509	0.018	0.46	YES
99	NXF1	NXF1	NXF1	7568	0.018	0.46	YES
100	TPR	TPR	TPR	7586	0.018	0.46	YES
101	NUP93	NUP93	NUP93	7587	0.018	0.47	YES
102	RNPS1	RNPS1	RNPS1	7646	0.017	0.47	YES
103	NUPL2	NUPL2	NUPL2	7712	0.016	0.47	YES
104	RNGTT	RNGTT	RNGTT	7724	0.016	0.47	YES
105	NUP214	NUP214	NUP214	7770	0.015	0.47	YES
106	PTBP1	PTBP1	PTBP1	7780	0.015	0.47	YES
107	PRPF8	PRPF8	PRPF8	7791	0.015	0.47	YES
108	SF3A3	SF3A3	SF3A3	7850	0.014	0.47	NO
109	CLP1	CLP1	CLP1	8022	0.012	0.46	NO
110	HNRNPH1	HNRNPH1	HNRNPH1	8291	0.0086	0.45	NO
111	SF3A2	SF3A2	SF3A2	8332	0.0081	0.45	NO
112	GTF2H2	GTF2H2	GTF2H2	8466	0.0062	0.44	NO
113	RBM5	RBM5	RBM5	8500	0.0056	0.44	NO
114	CD2BP2	CD2BP2	CD2BP2	8513	0.0055	0.44	NO
115	U2AF1	U2AF1	U2AF1	8520	0.0055	0.44	NO
116	GTF2H1	GTF2H1	GTF2H1	8644	0.004	0.44	NO
117	NUDT21	NUDT21	NUDT21	8655	0.0037	0.44	NO
118	EIF4E	EIF4E	EIF4E	8706	0.0031	0.43	NO
119	ADAR	ADAR	ADAR	8714	0.003	0.43	NO
120	GTF2H3	GTF2H3	GTF2H3	8881	0.00085	0.42	NO
121	HNRNPUL1	HNRNPUL1	HNRNPUL1	8947	-0.000025	0.42	NO
122	PHF5A	PHF5A	PHF5A	8985	-0.00057	0.42	NO
123	SRRM1	SRRM1	SRRM1	9011	-0.001	0.42	NO
124	POLR2E	POLR2E	POLR2E	9031	-0.0013	0.42	NO
125	SNRNP40	SNRNP40	SNRNP40	9150	-0.0028	0.41	NO
126	DHX38	DHX38	DHX38	9378	-0.0056	0.4	NO
127	NHP2L1	NHP2L1	NHP2L1	9440	-0.0064	0.4	NO
128	SUPT5H	SUPT5H	SUPT5H	9526	-0.0075	0.39	NO
129	POM121	POM121	POM121	9740	-0.011	0.38	NO
130	DNAJC8	DNAJC8	DNAJC8	9763	-0.011	0.38	NO
131	NUP62	NUP62	NUP62	9825	-0.012	0.38	NO
132	NUP54	NUP54	NUP54	9855	-0.012	0.38	NO
133	POLR2C	POLR2C	POLR2C	9921	-0.013	0.38	NO
134	LSM10	LSM10	LSM10	10066	-0.015	0.38	NO
135	CDK7	CDK7	CDK7	10133	-0.016	0.38	NO
136	ERCC2	ERCC2	ERCC2	10137	-0.016	0.38	NO
137	SF3A1	SF3A1	SF3A1	10245	-0.018	0.37	NO
138	CDC40	CDC40	CDC40	10478	-0.022	0.36	NO
139	NUPL1	NUPL1	NUPL1	10874	-0.028	0.35	NO
140	LSM11	LSM11	LSM11	11125	-0.032	0.34	NO
141	GTF2F1	GTF2F1	GTF2F1	11709	-0.043	0.31	NO
142	POLR2L	POLR2L	POLR2L	11833	-0.046	0.31	NO
143	CCNH	CCNH	CCNH	12287	-0.055	0.3	NO
144	APOBEC1	APOBEC1	APOBEC1	13557	-0.086	0.24	NO
145	ADARB1	ADARB1	ADARB1	14747	-0.13	0.2	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 RNA DEGRADATION.

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

genes ES table in pathway: REACTOME METABOLISM OF NON CODING RNA

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	SNRPF	SNRPF	SNRPF	1656	0.16	-0.063	YES
2	SNRPD1	SNRPD1	SNRPD1	1999	0.14	-0.057	YES
3	NUP210	NUP210	NUP210	2104	0.13	-0.039	YES
4	TXNL4A	TXNL4A	TXNL4A	2119	0.13	-0.016	YES
5	RAE1	RAE1	RAE1	2317	0.12	-0.0057	YES
6	SNRPA1	SNRPA1	SNRPA1	2352	0.12	0.014	YES
7	UPF3B	UPF3B	UPF3B	2435	0.12	0.03	YES
8	PAPOLA	PAPOLA	PAPOLA	2455	0.12	0.05	YES
9	SNRPB	SNRPB	SNRPB	2500	0.11	0.067	YES
10	METTL3	METTL3	METTL3	2507	0.11	0.087	YES
11	NUP107	NUP107	NUP107	2671	0.11	0.097	YES
12	SEH1L	SEH1L	SEH1L	2878	0.1	0.1	YES
13	PABPN1	PABPN1	PABPN1	2912	0.099	0.12	YES
14	SNRPE	SNRPE	SNRPE	2987	0.097	0.13	YES
15	SNRPG	SNRPG	SNRPG	3205	0.09	0.14	YES
16	CCAR1	CCAR1	CCAR1	3245	0.089	0.15	YES
17	CPSF1	CPSF1	CPSF1	3275	0.088	0.16	YES
18	NUP35	NUP35	NUP35	3412	0.085	0.17	YES
19	CSTF3	CSTF3	CSTF3	3510	0.082	0.18	YES
20	CSTF1	CSTF1	CSTF1	3511	0.082	0.2	YES
21	LSM2	LSM2	LSM2	3629	0.08	0.2	YES
22	POLR2H	POLR2H	POLR2H	3699	0.078	0.21	YES
23	NUP37	NUP37	NUP37	3765	0.076	0.22	YES
24	SNRPB2	SNRPB2	SNRPB2	3811	0.075	0.23	YES
25	POLR2K	POLR2K	POLR2K	3815	0.075	0.25	YES
26	NUP88	NUP88	NUP88	3981	0.071	0.25	YES
27	HNRNPA0	HNRNPA0	HNRNPA0	4309	0.064	0.24	YES
28	CPSF3	CPSF3	CPSF3	4333	0.063	0.25	YES
29	NUP155	NUP155	NUP155	4369	0.063	0.26	YES
30	SMC1A	SMC1A	SMC1A	4457	0.061	0.27	YES
31	AAAS	AAAS	AAAS	4474	0.061	0.28	YES
32	PCBP2	PCBP2	PCBP2	4650	0.058	0.28	YES
33	MAGOH	MAGOH	MAGOH	4670	0.058	0.29	YES
34	THOC4	THOC4	THOC4	4766	0.056	0.29	YES
35	U2AF2	U2AF2	U2AF2	4778	0.056	0.3	YES
36	HNRNPA3	HNRNPA3	HNRNPA3	4941	0.054	0.3	YES
37	POLR2F	POLR2F	POLR2F	4989	0.053	0.31	YES
38	SNRPA	SNRPA	SNRPA	5051	0.052	0.32	YES
39	GTF2F2	GTF2F2	GTF2F2	5104	0.051	0.32	YES
40	FUS	FUS	FUS	5151	0.05	0.33	YES
41	CSTF2	CSTF2	CSTF2	5181	0.049	0.34	YES
42	POLR2D	POLR2D	POLR2D	5262	0.048	0.34	YES
43	NUP133	NUP133	NUP133	5279	0.048	0.35	YES
44	NUP85	NUP85	NUP85	5360	0.047	0.35	YES
45	NUP153	NUP153	NUP153	5396	0.046	0.36	YES
46	NFX1	NFX1	NFX1	5397	0.046	0.37	YES
47	NCBP1	NCBP1	NCBP1	5468	0.045	0.37	YES
48	POLR2G	POLR2G	POLR2G	5544	0.044	0.37	YES
49	PRPF4	PRPF4	PRPF4	5591	0.043	0.38	YES
50	NUP43	NUP43	NUP43	5618	0.043	0.38	YES
51	HNRNPL	HNRNPL	HNRNPL	5622	0.043	0.39	YES
52	SNRNP200	SNRNP200	SNRNP200	5643	0.043	0.4	YES
53	SLBP	SLBP	SLBP	5663	0.042	0.4	YES
54	RBMX	RBMX	RBMX	5679	0.042	0.41	YES
55	CPSF7	CPSF7	CPSF7	5702	0.042	0.42	YES
56	DHX9	DHX9	DHX9	5725	0.041	0.42	YES
57	SNRPD3	SNRPD3	SNRPD3	5767	0.041	0.43	YES
58	POLR2J	POLR2J	POLR2J	5856	0.04	0.43	YES
59	HNRNPD	HNRNPD	HNRNPD	5961	0.038	0.43	YES
60	HNRNPR	HNRNPR	HNRNPR	5965	0.038	0.44	YES
61	NUP205	NUP205	NUP205	5975	0.038	0.44	YES
62	HNRNPA1	HNRNPA1	HNRNPA1	5978	0.038	0.45	YES
63	DDX23	DDX23	DDX23	6072	0.037	0.45	YES
64	CPSF2	CPSF2	CPSF2	6172	0.035	0.45	YES
65	SF3B3	SF3B3	SF3B3	6254	0.034	0.46	YES
66	SF3B4	SF3B4	SF3B4	6309	0.034	0.46	YES
67	HNRNPC	HNRNPC	HNRNPC	6318	0.033	0.46	YES
68	SF3B1	SF3B1	SF3B1	6341	0.033	0.47	YES
69	RANBP2	RANBP2	RANBP2	6372	0.033	0.47	YES
70	SNRNP70	SNRNP70	SNRNP70	6436	0.032	0.47	YES
71	PRPF6	PRPF6	PRPF6	6457	0.032	0.48	YES
72	NUP188	NUP188	NUP188	6474	0.032	0.48	YES
73	POLR2B	POLR2B	POLR2B	6570	0.03	0.48	YES
74	SF3B2	SF3B2	SF3B2	6586	0.03	0.49	YES
75	HNRNPH2	HNRNPH2	HNRNPH2	6601	0.03	0.49	YES
76	HNRNPM	HNRNPM	HNRNPM	6613	0.03	0.5	YES
77	SF3B14	SF3B14	SF3B14	6618	0.03	0.5	YES
78	PCBP1	PCBP1	PCBP1	6671	0.029	0.5	YES
79	SNRPD2	SNRPD2	SNRPD2	6733	0.028	0.51	YES
80	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	6781	0.028	0.51	YES
81	HNRNPU	HNRNPU	HNRNPU	6921	0.026	0.5	YES
82	RBM8A	RBM8A	RBM8A	6995	0.025	0.51	YES
83	HNRNPF	HNRNPF	HNRNPF	7004	0.025	0.51	YES
84	POLR2I	POLR2I	POLR2I	7031	0.025	0.51	YES
85	SF3B5	SF3B5	SF3B5	7108	0.024	0.51	YES
86	POLR2A	POLR2A	POLR2A	7216	0.022	0.51	YES
87	YBX1	YBX1	YBX1	7281	0.022	0.51	YES
88	EFTUD2	EFTUD2	EFTUD2	7347	0.021	0.51	YES
89	PCF11	PCF11	PCF11	7489	0.019	0.51	YES
90	NUP50	NUP50	NUP50	7494	0.019	0.51	YES
91	NCBP2	NCBP2	NCBP2	7507	0.019	0.51	YES
92	HNRNPK	HNRNPK	HNRNPK	7509	0.018	0.52	YES
93	NXF1	NXF1	NXF1	7568	0.018	0.52	YES
94	TPR	TPR	TPR	7586	0.018	0.52	YES
95	NUP93	NUP93	NUP93	7587	0.018	0.52	YES
96	RNPS1	RNPS1	RNPS1	7646	0.017	0.52	YES
97	NUPL2	NUPL2	NUPL2	7712	0.016	0.52	YES
98	NUP214	NUP214	NUP214	7770	0.015	0.52	YES
99	PTBP1	PTBP1	PTBP1	7780	0.015	0.52	YES
100	PRPF8	PRPF8	PRPF8	7791	0.015	0.52	YES
101	SF3A3	SF3A3	SF3A3	7850	0.014	0.52	NO
102	CLP1	CLP1	CLP1	8022	0.012	0.52	NO
103	HNRNPH1	HNRNPH1	HNRNPH1	8291	0.0086	0.5	NO
104	SF3A2	SF3A2	SF3A2	8332	0.0081	0.5	NO
105	RBM5	RBM5	RBM5	8500	0.0056	0.49	NO
106	CD2BP2	CD2BP2	CD2BP2	8513	0.0055	0.49	NO
107	U2AF1	U2AF1	U2AF1	8520	0.0055	0.5	NO
108	NUDT21	NUDT21	NUDT21	8655	0.0037	0.49	NO
109	EIF4E	EIF4E	EIF4E	8706	0.0031	0.49	NO
110	HNRNPUL1	HNRNPUL1	HNRNPUL1	8947	-0.000025	0.47	NO
111	PHF5A	PHF5A	PHF5A	8985	-0.00057	0.47	NO
112	SRRM1	SRRM1	SRRM1	9011	-0.001	0.47	NO
113	POLR2E	POLR2E	POLR2E	9031	-0.0013	0.47	NO
114	SNRNP40	SNRNP40	SNRNP40	9150	-0.0028	0.46	NO
115	DHX38	DHX38	DHX38	9378	-0.0056	0.45	NO
116	NHP2L1	NHP2L1	NHP2L1	9440	-0.0064	0.45	NO
117	POM121	POM121	POM121	9740	-0.011	0.43	NO
118	DNAJC8	DNAJC8	DNAJC8	9763	-0.011	0.44	NO
119	NUP62	NUP62	NUP62	9825	-0.012	0.43	NO
120	NUP54	NUP54	NUP54	9855	-0.012	0.43	NO
121	POLR2C	POLR2C	POLR2C	9921	-0.013	0.43	NO
122	SF3A1	SF3A1	SF3A1	10245	-0.018	0.42	NO
123	CDC40	CDC40	CDC40	10478	-0.022	0.41	NO
124	NUPL1	NUPL1	NUPL1	10874	-0.028	0.39	NO
125	GTF2F1	GTF2F1	GTF2F1	11709	-0.043	0.36	NO
126	POLR2L	POLR2L	POLR2L	11833	-0.046	0.36	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: REACTOME METABOLISM OF NON CODING RNA.

Figure S66. 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 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	SNRPF	SNRPF	SNRPF	1656	0.16	-0.055	YES
2	TAF5	TAF5	TAF5	1705	0.16	-0.022	YES
3	TH1L	TH1L	TH1L	1898	0.14	-0.00022	YES
4	TAF4	TAF4	TAF4	2165	0.13	0.014	YES
5	TCEB1	TCEB1	TCEB1	2220	0.13	0.04	YES
6	MNAT1	MNAT1	MNAT1	2369	0.12	0.059	YES
7	UPF3B	UPF3B	UPF3B	2435	0.12	0.082	YES
8	PAPOLA	PAPOLA	PAPOLA	2455	0.12	0.11	YES
9	SNRPB	SNRPB	SNRPB	2500	0.11	0.13	YES
10	PABPN1	PABPN1	PABPN1	2912	0.099	0.13	YES
11	TAF11	TAF11	TAF11	2929	0.099	0.15	YES
12	SNRPE	SNRPE	SNRPE	2987	0.097	0.17	YES
13	SNRPG	SNRPG	SNRPG	3205	0.09	0.18	YES
14	CPSF1	CPSF1	CPSF1	3275	0.088	0.2	YES
15	CSTF3	CSTF3	CSTF3	3510	0.082	0.2	YES
16	CSTF1	CSTF1	CSTF1	3511	0.082	0.22	YES
17	POLR2H	POLR2H	POLR2H	3699	0.078	0.23	YES
18	POLR2K	POLR2K	POLR2K	3815	0.075	0.24	YES
19	TBP	TBP	TBP	4009	0.07	0.24	YES
20	CPSF3	CPSF3	CPSF3	4333	0.063	0.24	YES
21	SSRP1	SSRP1	SSRP1	4442	0.062	0.25	YES
22	SUPT16H	SUPT16H	SUPT16H	4453	0.062	0.26	YES
23	GTF2A1	GTF2A1	GTF2A1	4593	0.059	0.27	YES
24	MAGOH	MAGOH	MAGOH	4670	0.058	0.28	YES
25	GTF2H4	GTF2H4	GTF2H4	4710	0.058	0.28	YES
26	THOC4	THOC4	THOC4	4766	0.056	0.3	YES
27	U2AF2	U2AF2	U2AF2	4778	0.056	0.31	YES
28	POLR2F	POLR2F	POLR2F	4989	0.053	0.31	YES
29	TCEA1	TCEA1	TCEA1	5009	0.052	0.32	YES
30	GTF2A2	GTF2A2	GTF2A2	5064	0.052	0.33	YES
31	ZNF473	ZNF473	ZNF473	5088	0.051	0.34	YES
32	GTF2F2	GTF2F2	GTF2F2	5104	0.051	0.35	YES
33	CSTF2	CSTF2	CSTF2	5181	0.049	0.36	YES
34	GTF2E2	GTF2E2	GTF2E2	5252	0.048	0.36	YES
35	POLR2D	POLR2D	POLR2D	5262	0.048	0.37	YES
36	NFX1	NFX1	NFX1	5397	0.046	0.38	YES
37	TAF6	TAF6	TAF6	5422	0.046	0.38	YES
38	NCBP1	NCBP1	NCBP1	5468	0.045	0.39	YES
39	POLR2G	POLR2G	POLR2G	5544	0.044	0.4	YES
40	WHSC2	WHSC2	WHSC2	5630	0.043	0.4	YES
41	SLBP	SLBP	SLBP	5663	0.042	0.41	YES
42	CPSF7	CPSF7	CPSF7	5702	0.042	0.42	YES
43	SNRPD3	SNRPD3	SNRPD3	5767	0.041	0.42	YES
44	POLR2J	POLR2J	POLR2J	5856	0.04	0.43	YES
45	RNMT	RNMT	RNMT	6048	0.037	0.42	YES
46	CPSF2	CPSF2	CPSF2	6172	0.035	0.43	YES
47	GTF2H2B	GTF2H2B	GTF2H2B	6340	0.033	0.42	YES
48	TAF10	TAF10	TAF10	6347	0.033	0.43	YES
49	GTF2E1	GTF2E1	GTF2E1	6390	0.032	0.44	YES
50	TAF9	TAF9	TAF9	6540	0.031	0.44	YES
51	POLR2B	POLR2B	POLR2B	6570	0.03	0.44	YES
52	ERCC3	ERCC3	ERCC3	6596	0.03	0.45	YES
53	RDBP	RDBP	RDBP	6712	0.028	0.45	YES
54	CCNT2	CCNT2	CCNT2	6833	0.027	0.45	YES
55	RBM8A	RBM8A	RBM8A	6995	0.025	0.44	YES
56	POLR2I	POLR2I	POLR2I	7031	0.025	0.45	YES
57	CTDP1	CTDP1	CTDP1	7047	0.025	0.45	YES
58	TAF4B	TAF4B	TAF4B	7176	0.023	0.45	YES
59	POLR2A	POLR2A	POLR2A	7216	0.022	0.45	YES
60	PCF11	PCF11	PCF11	7489	0.019	0.44	NO
61	NCBP2	NCBP2	NCBP2	7507	0.019	0.44	NO
62	CCNT1	CCNT1	CCNT1	7564	0.018	0.45	NO
63	RNPS1	RNPS1	RNPS1	7646	0.017	0.44	NO
64	RNGTT	RNGTT	RNGTT	7724	0.016	0.44	NO
65	CLP1	CLP1	CLP1	8022	0.012	0.43	NO
66	TAF1	TAF1	TAF1	8383	0.0074	0.41	NO
67	GTF2H2	GTF2H2	GTF2H2	8466	0.0062	0.41	NO
68	U2AF1	U2AF1	U2AF1	8520	0.0055	0.41	NO
69	GTF2H1	GTF2H1	GTF2H1	8644	0.004	0.4	NO
70	NUDT21	NUDT21	NUDT21	8655	0.0037	0.4	NO
71	GTF2H3	GTF2H3	GTF2H3	8881	0.00085	0.39	NO
72	SRRM1	SRRM1	SRRM1	9011	-0.001	0.38	NO
73	POLR2E	POLR2E	POLR2E	9031	-0.0013	0.38	NO
74	DHX38	DHX38	DHX38	9378	-0.0056	0.36	NO
75	TCEB3	TCEB3	TCEB3	9426	-0.0063	0.36	NO
76	SUPT5H	SUPT5H	SUPT5H	9526	-0.0075	0.36	NO
77	COBRA1	COBRA1	COBRA1	9837	-0.012	0.35	NO
78	POLR2C	POLR2C	POLR2C	9921	-0.013	0.34	NO
79	LSM10	LSM10	LSM10	10066	-0.015	0.34	NO
80	CDK7	CDK7	CDK7	10133	-0.016	0.34	NO
81	ERCC2	ERCC2	ERCC2	10137	-0.016	0.34	NO
82	CDC40	CDC40	CDC40	10478	-0.022	0.33	NO
83	CDK9	CDK9	CDK9	10530	-0.022	0.33	NO
84	SUPT4H1	SUPT4H1	SUPT4H1	10609	-0.023	0.33	NO
85	GTF2B	GTF2B	GTF2B	10716	-0.025	0.33	NO
86	TAF12	TAF12	TAF12	10933	-0.029	0.33	NO
87	LSM11	LSM11	LSM11	11125	-0.032	0.32	NO
88	TCEB2	TCEB2	TCEB2	11218	-0.034	0.33	NO
89	GTF2F1	GTF2F1	GTF2F1	11709	-0.043	0.31	NO
90	POLR2L	POLR2L	POLR2L	11833	-0.046	0.31	NO
91	CCNH	CCNH	CCNH	12287	-0.055	0.3	NO
92	TAF13	TAF13	TAF13	12718	-0.065	0.29	NO
93	ELL	ELL	ELL	12841	-0.068	0.3	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: REACTOME CELL CYCLE.

Figure S68. 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 MITOCHONDRIAL PROTEIN IMPORT

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	SNRPF	SNRPF	SNRPF	1656	0.16	-0.053	YES
2	SNRPD1	SNRPD1	SNRPD1	1999	0.14	-0.039	YES
3	TXNL4A	TXNL4A	TXNL4A	2119	0.13	-0.014	YES
4	SNRPA1	SNRPA1	SNRPA1	2352	0.12	0.0017	YES
5	UPF3B	UPF3B	UPF3B	2435	0.12	0.025	YES
6	PAPOLA	PAPOLA	PAPOLA	2455	0.12	0.052	YES
7	SNRPB	SNRPB	SNRPB	2500	0.11	0.076	YES
8	PABPN1	PABPN1	PABPN1	2912	0.099	0.077	YES
9	SNRPE	SNRPE	SNRPE	2987	0.097	0.096	YES
10	SNRPG	SNRPG	SNRPG	3205	0.09	0.1	YES
11	CCAR1	CCAR1	CCAR1	3245	0.089	0.12	YES
12	CPSF1	CPSF1	CPSF1	3275	0.088	0.14	YES
13	CSTF3	CSTF3	CSTF3	3510	0.082	0.15	YES
14	CSTF1	CSTF1	CSTF1	3511	0.082	0.17	YES
15	LSM2	LSM2	LSM2	3629	0.08	0.18	YES
16	POLR2H	POLR2H	POLR2H	3699	0.078	0.2	YES
17	SNRPB2	SNRPB2	SNRPB2	3811	0.075	0.21	YES
18	POLR2K	POLR2K	POLR2K	3815	0.075	0.23	YES
19	HNRNPA0	HNRNPA0	HNRNPA0	4309	0.064	0.21	YES
20	CPSF3	CPSF3	CPSF3	4333	0.063	0.23	YES
21	SMC1A	SMC1A	SMC1A	4457	0.061	0.24	YES
22	PCBP2	PCBP2	PCBP2	4650	0.058	0.24	YES
23	MAGOH	MAGOH	MAGOH	4670	0.058	0.25	YES
24	THOC4	THOC4	THOC4	4766	0.056	0.26	YES
25	U2AF2	U2AF2	U2AF2	4778	0.056	0.27	YES
26	HNRNPA3	HNRNPA3	HNRNPA3	4941	0.054	0.28	YES
27	POLR2F	POLR2F	POLR2F	4989	0.053	0.29	YES
28	SNRPA	SNRPA	SNRPA	5051	0.052	0.3	YES
29	GTF2F2	GTF2F2	GTF2F2	5104	0.051	0.3	YES
30	FUS	FUS	FUS	5151	0.05	0.31	YES
31	CSTF2	CSTF2	CSTF2	5181	0.049	0.32	YES
32	POLR2D	POLR2D	POLR2D	5262	0.048	0.33	YES
33	NFX1	NFX1	NFX1	5397	0.046	0.33	YES
34	NCBP1	NCBP1	NCBP1	5468	0.045	0.34	YES
35	POLR2G	POLR2G	POLR2G	5544	0.044	0.35	YES
36	PRPF4	PRPF4	PRPF4	5591	0.043	0.36	YES
37	HNRNPL	HNRNPL	HNRNPL	5622	0.043	0.36	YES
38	SNRNP200	SNRNP200	SNRNP200	5643	0.043	0.37	YES
39	RBMX	RBMX	RBMX	5679	0.042	0.38	YES
40	CPSF7	CPSF7	CPSF7	5702	0.042	0.39	YES
41	DHX9	DHX9	DHX9	5725	0.041	0.4	YES
42	SNRPD3	SNRPD3	SNRPD3	5767	0.041	0.4	YES
43	POLR2J	POLR2J	POLR2J	5856	0.04	0.41	YES
44	HNRNPD	HNRNPD	HNRNPD	5961	0.038	0.41	YES
45	HNRNPR	HNRNPR	HNRNPR	5965	0.038	0.42	YES
46	HNRNPA1	HNRNPA1	HNRNPA1	5978	0.038	0.43	YES
47	DDX23	DDX23	DDX23	6072	0.037	0.43	YES
48	CPSF2	CPSF2	CPSF2	6172	0.035	0.44	YES
49	SF3B3	SF3B3	SF3B3	6254	0.034	0.44	YES
50	SF3B4	SF3B4	SF3B4	6309	0.034	0.44	YES
51	HNRNPC	HNRNPC	HNRNPC	6318	0.033	0.45	YES
52	SF3B1	SF3B1	SF3B1	6341	0.033	0.46	YES
53	SNRNP70	SNRNP70	SNRNP70	6436	0.032	0.46	YES
54	PRPF6	PRPF6	PRPF6	6457	0.032	0.47	YES
55	POLR2B	POLR2B	POLR2B	6570	0.03	0.47	YES
56	SF3B2	SF3B2	SF3B2	6586	0.03	0.48	YES
57	HNRNPH2	HNRNPH2	HNRNPH2	6601	0.03	0.48	YES
58	HNRNPM	HNRNPM	HNRNPM	6613	0.03	0.49	YES
59	SF3B14	SF3B14	SF3B14	6618	0.03	0.5	YES
60	PCBP1	PCBP1	PCBP1	6671	0.029	0.5	YES
61	SNRPD2	SNRPD2	SNRPD2	6733	0.028	0.5	YES
62	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	6781	0.028	0.51	YES
63	HNRNPU	HNRNPU	HNRNPU	6921	0.026	0.5	YES
64	RBM8A	RBM8A	RBM8A	6995	0.025	0.51	YES
65	HNRNPF	HNRNPF	HNRNPF	7004	0.025	0.51	YES
66	POLR2I	POLR2I	POLR2I	7031	0.025	0.52	YES
67	SF3B5	SF3B5	SF3B5	7108	0.024	0.52	YES
68	POLR2A	POLR2A	POLR2A	7216	0.022	0.52	YES
69	YBX1	YBX1	YBX1	7281	0.022	0.52	YES
70	EFTUD2	EFTUD2	EFTUD2	7347	0.021	0.52	YES
71	PCF11	PCF11	PCF11	7489	0.019	0.52	YES
72	NCBP2	NCBP2	NCBP2	7507	0.019	0.52	YES
73	HNRNPK	HNRNPK	HNRNPK	7509	0.018	0.52	YES
74	RNPS1	RNPS1	RNPS1	7646	0.017	0.52	NO
75	PTBP1	PTBP1	PTBP1	7780	0.015	0.52	NO
76	PRPF8	PRPF8	PRPF8	7791	0.015	0.52	NO
77	SF3A3	SF3A3	SF3A3	7850	0.014	0.52	NO
78	CLP1	CLP1	CLP1	8022	0.012	0.51	NO
79	HNRNPH1	HNRNPH1	HNRNPH1	8291	0.0086	0.5	NO
80	SF3A2	SF3A2	SF3A2	8332	0.0081	0.5	NO
81	RBM5	RBM5	RBM5	8500	0.0056	0.49	NO
82	CD2BP2	CD2BP2	CD2BP2	8513	0.0055	0.49	NO
83	U2AF1	U2AF1	U2AF1	8520	0.0055	0.5	NO
84	NUDT21	NUDT21	NUDT21	8655	0.0037	0.49	NO
85	HNRNPUL1	HNRNPUL1	HNRNPUL1	8947	-0.000025	0.47	NO
86	PHF5A	PHF5A	PHF5A	8985	-0.00057	0.47	NO
87	SRRM1	SRRM1	SRRM1	9011	-0.001	0.47	NO
88	POLR2E	POLR2E	POLR2E	9031	-0.0013	0.47	NO
89	SNRNP40	SNRNP40	SNRNP40	9150	-0.0028	0.46	NO
90	DHX38	DHX38	DHX38	9378	-0.0056	0.45	NO
91	NHP2L1	NHP2L1	NHP2L1	9440	-0.0064	0.45	NO
92	DNAJC8	DNAJC8	DNAJC8	9763	-0.011	0.44	NO
93	POLR2C	POLR2C	POLR2C	9921	-0.013	0.43	NO
94	SF3A1	SF3A1	SF3A1	10245	-0.018	0.42	NO
95	CDC40	CDC40	CDC40	10478	-0.022	0.41	NO
96	GTF2F1	GTF2F1	GTF2F1	11709	-0.043	0.35	NO
97	POLR2L	POLR2L	POLR2L	11833	-0.046	0.36	NO

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

Figure S70. 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 PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA

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	SNRPF	SNRPF	SNRPF	1656	0.16	-0.0024	YES
2	UPF3B	UPF3B	UPF3B	2435	0.12	0.02	YES
3	PAPOLA	PAPOLA	PAPOLA	2455	0.12	0.083	YES
4	SNRPB	SNRPB	SNRPB	2500	0.11	0.14	YES
5	PABPN1	PABPN1	PABPN1	2912	0.099	0.18	YES
6	SNRPE	SNRPE	SNRPE	2987	0.097	0.23	YES
7	SNRPG	SNRPG	SNRPG	3205	0.09	0.26	YES
8	CPSF1	CPSF1	CPSF1	3275	0.088	0.31	YES
9	CSTF3	CSTF3	CSTF3	3510	0.082	0.34	YES
10	CSTF1	CSTF1	CSTF1	3511	0.082	0.39	YES
11	CPSF3	CPSF3	CPSF3	4333	0.063	0.38	YES
12	MAGOH	MAGOH	MAGOH	4670	0.058	0.39	YES
13	THOC4	THOC4	THOC4	4766	0.056	0.42	YES
14	U2AF2	U2AF2	U2AF2	4778	0.056	0.45	YES
15	ZNF473	ZNF473	ZNF473	5088	0.051	0.46	YES
16	CSTF2	CSTF2	CSTF2	5181	0.049	0.48	YES
17	NFX1	NFX1	NFX1	5397	0.046	0.5	YES
18	NCBP1	NCBP1	NCBP1	5468	0.045	0.52	YES
19	SLBP	SLBP	SLBP	5663	0.042	0.53	YES
20	CPSF7	CPSF7	CPSF7	5702	0.042	0.55	YES
21	SNRPD3	SNRPD3	SNRPD3	5767	0.041	0.57	YES
22	CPSF2	CPSF2	CPSF2	6172	0.035	0.57	NO
23	RBM8A	RBM8A	RBM8A	6995	0.025	0.54	NO
24	PCF11	PCF11	PCF11	7489	0.019	0.52	NO
25	NCBP2	NCBP2	NCBP2	7507	0.019	0.53	NO
26	RNPS1	RNPS1	RNPS1	7646	0.017	0.53	NO
27	CLP1	CLP1	CLP1	8022	0.012	0.52	NO
28	U2AF1	U2AF1	U2AF1	8520	0.0055	0.49	NO
29	NUDT21	NUDT21	NUDT21	8655	0.0037	0.49	NO
30	SRRM1	SRRM1	SRRM1	9011	-0.001	0.47	NO
31	DHX38	DHX38	DHX38	9378	-0.0056	0.45	NO
32	LSM10	LSM10	LSM10	10066	-0.015	0.42	NO
33	CDC40	CDC40	CDC40	10478	-0.022	0.41	NO
34	LSM11	LSM11	LSM11	11125	-0.032	0.39	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: REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA.

Figure S72. 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 TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM

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	NARS2	NARS2	NARS2	1499	0.17	-0.00064	YES
2	MARS2	MARS2	MARS2	1738	0.15	0.06	YES
3	PSTK	PSTK	PSTK	1752	0.15	0.13	YES
4	DARS2	DARS2	DARS2	2114	0.13	0.18	YES
5	MARS	MARS	MARS	2526	0.11	0.21	YES
6	NARS	NARS	NARS	2969	0.097	0.23	YES
7	SARS2	SARS2	SARS2	3003	0.096	0.28	YES
8	TARS	TARS	TARS	3464	0.083	0.29	YES
9	PARS2	PARS2	PARS2	3742	0.077	0.31	YES
10	AARS	AARS	AARS	3932	0.072	0.34	YES
11	YARS2	YARS2	YARS2	3939	0.072	0.37	YES
12	FARSB	FARSB	FARSB	4806	0.056	0.35	YES
13	CARS	CARS	CARS	4939	0.054	0.37	YES
14	TARS2	TARS2	TARS2	5109	0.051	0.38	YES
15	LARS2	LARS2	LARS2	5297	0.048	0.39	YES
16	GARS	GARS	GARS	5318	0.047	0.42	YES
17	VARS	VARS	VARS	5443	0.045	0.43	YES
18	AARS2	AARS2	AARS2	5797	0.04	0.43	YES
19	EPRS	EPRS	EPRS	5842	0.04	0.45	YES
20	DARS	DARS	DARS	5864	0.039	0.46	YES
21	IARS	IARS	IARS	6127	0.036	0.47	YES
22	YARS	YARS	YARS	6286	0.034	0.48	YES
23	EARS2	EARS2	EARS2	6564	0.03	0.47	YES
24	RARS2	RARS2	RARS2	6607	0.03	0.49	YES
25	SEPSECS	SEPSECS	SEPSECS	6646	0.029	0.5	YES
26	TARSL2	TARSL2	TARSL2	6759	0.028	0.5	YES
27	IARS2	IARS2	IARS2	6821	0.027	0.51	YES
28	LARS	LARS	LARS	7129	0.024	0.51	NO
29	MTFMT	MTFMT	MTFMT	7416	0.02	0.5	NO
30	HARS	HARS	HARS	7714	0.016	0.49	NO
31	FARSA	FARSA	FARSA	7756	0.015	0.5	NO
32	VARS2	VARS2	VARS2	8147	0.01	0.48	NO
33	QARS	QARS	QARS	8311	0.0084	0.48	NO
34	HARS2	HARS2	HARS2	8545	0.0052	0.47	NO
35	WARS2	WARS2	WARS2	8635	0.0041	0.46	NO
36	KARS	KARS	KARS	8783	0.0023	0.46	NO
37	CARS2	CARS2	CARS2	9872	-0.012	0.4	NO
38	FARS2	FARS2	FARS2	10406	-0.02	0.38	NO
39	RARS	RARS	RARS	10434	-0.021	0.39	NO
40	WARS	WARS	WARS	11449	-0.038	0.36	NO
41	SARS	SARS	SARS	11573	-0.041	0.37	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: REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM.

Figure S74. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM, 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 II TRANSCRIPTION

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	PRKAA2	PRKAA2	PRKAA2	230	0.38	0.2	YES
2	PDE3B	PDE3B	PDE3B	464	0.3	0.36	YES
3	EIF4EBP1	EIF4EBP1	EIF4EBP1	1074	0.2	0.45	YES
4	PRKAB2	PRKAB2	PRKAB2	4398	0.062	0.3	NO
5	PRKAB1	PRKAB1	PRKAB1	4436	0.062	0.34	NO
6	PRKAG1	PRKAG1	PRKAG1	5126	0.05	0.33	NO
7	PPM1A	PPM1A	PPM1A	5322	0.047	0.34	NO
8	RHEB	RHEB	RHEB	5503	0.045	0.36	NO
9	TSC1	TSC1	TSC1	6082	0.036	0.35	NO
10	PRKAA1	PRKAA1	PRKAA1	6942	0.026	0.32	NO
11	RPTOR	RPTOR	RPTOR	7234	0.022	0.31	NO
12	RPS6	RPS6	RPS6	7411	0.02	0.32	NO
13	EIF4B	EIF4B	EIF4B	7495	0.019	0.32	NO
14	RPS6KB1	RPS6KB1	RPS6KB1	7541	0.018	0.33	NO
15	MLST8	MLST8	MLST8	7607	0.017	0.34	NO
16	MTOR	MTOR	MTOR	7630	0.017	0.34	NO
17	EIF4G1	EIF4G1	EIF4G1	8461	0.0063	0.3	NO
18	TSC2	TSC2	TSC2	8502	0.0056	0.3	NO
19	PRKAG2	PRKAG2	PRKAG2	8508	0.0056	0.31	NO
20	EIF4E	EIF4E	EIF4E	8706	0.0031	0.3	NO
21	AKT2	AKT2	AKT2	8914	0.00036	0.29	NO
22	EEF2K	EEF2K	EEF2K	9859	-0.012	0.24	NO
23	STRADA	STRADA	STRADA	12263	-0.054	0.14	NO
24	STRADB	STRADB	STRADB	12526	-0.06	0.16	NO
25	CAB39L	CAB39L	CAB39L	13091	-0.073	0.17	NO
26	CAB39	CAB39	CAB39	13665	-0.089	0.19	NO
27	STK11	STK11	STK11	14262	-0.11	0.22	NO

Figure S75. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: REACTOME RNA POL II TRANSCRIPTION.

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

genes ES table in pathway: REACTOME RNA POL III TRANSCRIPTION

Table 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	POU2F1	POU2F1	POU2F1	1021	0.21	0.048	YES
2	POLR3F	POLR3F	POLR3F	2473	0.12	0.025	YES
3	NFIB	NFIB	NFIB	2808	0.1	0.057	YES
4	POLR3A	POLR3A	POLR3A	3008	0.096	0.094	YES
5	BRF2	BRF2	BRF2	3356	0.086	0.12	YES
6	POLR2H	POLR2H	POLR2H	3699	0.078	0.14	YES
7	SSB	SSB	SSB	3735	0.077	0.17	YES
8	BRF1	BRF1	BRF1	3758	0.076	0.21	YES
9	POLR2K	POLR2K	POLR2K	3815	0.075	0.24	YES
10	TBP	TBP	TBP	4009	0.07	0.27	YES
11	POLR1C	POLR1C	POLR1C	4096	0.068	0.3	YES
12	GTF3C5	GTF3C5	GTF3C5	4286	0.064	0.32	YES
13	POLR3B	POLR3B	POLR3B	4942	0.054	0.31	YES
14	POLR2F	POLR2F	POLR2F	4989	0.053	0.33	YES
15	SNAPC3	SNAPC3	SNAPC3	4993	0.053	0.36	YES
16	SNAPC4	SNAPC4	SNAPC4	4997	0.053	0.38	YES
17	POLR3D	POLR3D	POLR3D	5036	0.052	0.4	YES
18	POLR3E	POLR3E	POLR3E	5320	0.047	0.41	YES
19	GTF3C3	GTF3C3	GTF3C3	5457	0.045	0.43	YES
20	POLR1D	POLR1D	POLR1D	5746	0.041	0.43	YES
21	LZTS1	LZTS1	LZTS1	5844	0.04	0.45	YES
22	GTF3C2	GTF3C2	GTF3C2	6142	0.036	0.45	YES
23	POLR3K	POLR3K	POLR3K	6174	0.035	0.46	YES
24	SNAPC5	SNAPC5	SNAPC5	6336	0.033	0.47	YES
25	POLR3H	POLR3H	POLR3H	7083	0.024	0.44	NO
26	ZNF143	ZNF143	ZNF143	7248	0.022	0.44	NO
27	SNAPC1	SNAPC1	SNAPC1	8347	0.0079	0.39	NO
28	POLR3C	POLR3C	POLR3C	8358	0.0077	0.39	NO
29	POLR2E	POLR2E	POLR2E	9031	-0.0013	0.35	NO
30	GTF3C4	GTF3C4	GTF3C4	9237	-0.0038	0.34	NO
31	POLR2L	POLR2L	POLR2L	11833	-0.046	0.22	NO
32	SNAPC2	SNAPC2	SNAPC2	14726	-0.12	0.13	NO
33	POLR3GL	POLR3GL	POLR3GL	15038	-0.14	0.18	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 RNA POL III TRANSCRIPTION.

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

genes ES table in pathway: REACTOME RECRUITMENT OF MITOTIC CENTROSOME PROTEINS AND COMPLEXES

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	NUP210	NUP210	NUP210	2104	0.13	-0.048	YES
2	RAE1	RAE1	RAE1	2317	0.12	0.0026	YES
3	UPF3B	UPF3B	UPF3B	2435	0.12	0.056	YES
4	NUP107	NUP107	NUP107	2671	0.11	0.097	YES
5	SEH1L	SEH1L	SEH1L	2878	0.1	0.14	YES
6	CPSF1	CPSF1	CPSF1	3275	0.088	0.16	YES
7	NUP35	NUP35	NUP35	3412	0.085	0.2	YES
8	NUP37	NUP37	NUP37	3765	0.076	0.21	YES
9	NUP88	NUP88	NUP88	3981	0.071	0.24	YES
10	CPSF3	CPSF3	CPSF3	4333	0.063	0.25	YES
11	NUP155	NUP155	NUP155	4369	0.063	0.28	YES
12	AAAS	AAAS	AAAS	4474	0.061	0.31	YES
13	MAGOH	MAGOH	MAGOH	4670	0.058	0.32	YES
14	THOC4	THOC4	THOC4	4766	0.056	0.35	YES
15	U2AF2	U2AF2	U2AF2	4778	0.056	0.38	YES
16	NUP133	NUP133	NUP133	5279	0.048	0.37	YES
17	NUP85	NUP85	NUP85	5360	0.047	0.39	YES
18	NUP153	NUP153	NUP153	5396	0.046	0.41	YES
19	NFX1	NFX1	NFX1	5397	0.046	0.44	YES
20	NCBP1	NCBP1	NCBP1	5468	0.045	0.46	YES
21	NUP43	NUP43	NUP43	5618	0.043	0.47	YES
22	SLBP	SLBP	SLBP	5663	0.042	0.49	YES
23	NUP205	NUP205	NUP205	5975	0.038	0.49	YES
24	CPSF2	CPSF2	CPSF2	6172	0.035	0.5	YES
25	RANBP2	RANBP2	RANBP2	6372	0.033	0.5	YES
26	NUP188	NUP188	NUP188	6474	0.032	0.51	YES
27	RBM8A	RBM8A	RBM8A	6995	0.025	0.5	YES
28	NUP50	NUP50	NUP50	7494	0.019	0.48	YES
29	NCBP2	NCBP2	NCBP2	7507	0.019	0.49	YES
30	NXF1	NXF1	NXF1	7568	0.018	0.5	YES
31	TPR	TPR	TPR	7586	0.018	0.5	YES
32	NUP93	NUP93	NUP93	7587	0.018	0.51	YES
33	RNPS1	RNPS1	RNPS1	7646	0.017	0.52	YES
34	NUPL2	NUPL2	NUPL2	7712	0.016	0.52	YES
35	NUP214	NUP214	NUP214	7770	0.015	0.53	YES
36	U2AF1	U2AF1	U2AF1	8520	0.0055	0.49	NO
37	EIF4E	EIF4E	EIF4E	8706	0.0031	0.48	NO
38	SRRM1	SRRM1	SRRM1	9011	-0.001	0.46	NO
39	DHX38	DHX38	DHX38	9378	-0.0056	0.45	NO
40	POM121	POM121	POM121	9740	-0.011	0.43	NO
41	NUP62	NUP62	NUP62	9825	-0.012	0.43	NO
42	NUP54	NUP54	NUP54	9855	-0.012	0.44	NO
43	CDC40	CDC40	CDC40	10478	-0.022	0.41	NO
44	NUPL1	NUPL1	NUPL1	10874	-0.028	0.41	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 RECRUITMENT OF MITOTIC CENTROSOME PROTEINS AND COMPLEXES.

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME RECRUITMENT OF MITOTIC CENTROSOME PROTEINS AND COMPLEXES, 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	0.49	1.6	0.016	0.24	0.9	0.15	0.085	0.14	0.13	0.04
KEGG FATTY ACID METABOLISM	40	genes.ES.table	0.67	1.9	0	0.33	0.34	0.15	0.041	0.14	0	0.086
KEGG STEROID HORMONE BIOSYNTHESIS	45	genes.ES.table	0.58	1.4	0.059	0.24	1	0.47	0.23	0.36	0.18	0.002
KEGG TYROSINE METABOLISM	41	genes.ES.table	0.63	1.7	0.002	0.23	0.82	0.32	0.17	0.26	0.11	0.041
KEGG GLUTATHIONE METABOLISM	48	genes.ES.table	0.49	1.5	0.061	0.23	0.99	0.1	0.046	0.1	0.15	0.01
KEGG STARCH AND SUCROSE METABOLISM	41	genes.ES.table	0.57	1.5	0.02	0.23	0.98	0.27	0.13	0.24	0.15	0.02
KEGG GLYCEROPHOSPHOLIPID METABOLISM	73	genes.ES.table	0.43	1.6	0.011	0.21	0.96	0.22	0.21	0.17	0.13	0.02
KEGG LINOLEIC ACID METABOLISM	26	genes.ES.table	0.67	1.5	0.051	0.23	0.99	0.54	0.18	0.44	0.16	0.005
KEGG SPHINGOLIPID METABOLISM	38	genes.ES.table	0.42	1.4	0.1	0.25	1	0.4	0.34	0.26	0.19	0.001
KEGG RETINOL METABOLISM	56	genes.ES.table	0.66	1.6	0.014	0.22	0.94	0.55	0.23	0.43	0.13	0.031

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	DNAI2	DNAI2	DNAI2	10	1.5	0.13	YES
2	DNAI1	DNAI1	DNAI1	42	1.4	0.25	YES
3	DNAH3	DNAH3	DNAH3	204	0.93	0.32	YES
4	DNAH1	DNAH1	DNAH1	511	0.45	0.34	YES
5	DNAH2	DNAH2	DNAH2	635	0.4	0.37	YES
6	PLCB4	PLCB4	PLCB4	689	0.38	0.4	YES
7	DNALI1	DNALI1	DNALI1	872	0.34	0.42	YES
8	GRM5	GRM5	GRM5	881	0.33	0.45	YES
9	COX4I2	COX4I2	COX4I2	1801	0.22	0.42	NO
10	COX6B2	COX6B2	COX6B2	2053	0.2	0.42	NO
11	COX7A1	COX7A1	COX7A1	2285	0.19	0.42	NO
12	IFT57	IFT57	IFT57	2363	0.18	0.44	NO
13	DNAL1	DNAL1	DNAL1	2577	0.17	0.44	NO
14	DNAL4	DNAL4	DNAL4	4231	0.11	0.36	NO
15	DLG4	DLG4	DLG4	4555	0.098	0.35	NO
16	PLCB2	PLCB2	PLCB2	4633	0.096	0.35	NO
17	CREB5	CREB5	CREB5	4765	0.093	0.35	NO
18	BBC3	BBC3	BBC3	4902	0.089	0.35	NO
19	TGM2	TGM2	TGM2	4925	0.089	0.36	NO
20	PPARG	PPARG	PPARG	5004	0.087	0.36	NO
21	POLR2J2	POLR2J2	POLR2J2	6517	0.056	0.29	NO
22	ITPR1	ITPR1	ITPR1	6518	0.056	0.29	NO
23	CREB3L1	CREB3L1	CREB3L1	6677	0.053	0.29	NO
24	PPARGC1A	PPARGC1A	PPARGC1A	6791	0.051	0.28	NO
25	CLTB	CLTB	CLTB	7381	0.042	0.26	NO
26	NDUFS7	NDUFS7	NDUFS7	7449	0.041	0.26	NO
27	NDUFA4L2	NDUFA4L2	NDUFA4L2	7774	0.036	0.24	NO
28	COX8C	COX8C	COX8C	7900	0.034	0.24	NO
29	NRF1	NRF1	NRF1	7942	0.034	0.24	NO
30	GNAQ	GNAQ	GNAQ	8001	0.033	0.24	NO
31	HIP1	HIP1	HIP1	8129	0.032	0.23	NO
32	BAX	BAX	BAX	8242	0.03	0.23	NO
33	BDNF	BDNF	BDNF	8418	0.028	0.22	NO
34	REST	REST	REST	8521	0.026	0.22	NO
35	TAF4B	TAF4B	TAF4B	8751	0.024	0.21	NO
36	SLC25A4	SLC25A4	SLC25A4	8860	0.023	0.2	NO
37	TP53	TP53	TP53	9046	0.021	0.2	NO
38	GPX1	GPX1	GPX1	9079	0.02	0.2	NO
39	POLR2E	POLR2E	POLR2E	9132	0.02	0.2	NO
40	AP2B1	AP2B1	AP2B1	9317	0.018	0.19	NO
41	NDUFB7	NDUFB7	NDUFB7	9452	0.016	0.18	NO
42	EP300	EP300	EP300	9497	0.016	0.18	NO
43	POLR2L	POLR2L	POLR2L	9799	0.013	0.16	NO
44	AP2A1	AP2A1	AP2A1	9885	0.012	0.16	NO
45	CASP9	CASP9	CASP9	9891	0.012	0.16	NO
46	TBPL1	TBPL1	TBPL1	9893	0.012	0.16	NO
47	UQCR10	UQCR10	UQCR10	10046	0.011	0.16	NO
48	POLR2J3	POLR2J3	POLR2J3	10207	0.0097	0.15	NO
49	ATP5D	ATP5D	ATP5D	10309	0.0089	0.14	NO
50	DCTN1	DCTN1	DCTN1	10388	0.0083	0.14	NO
51	CREBBP	CREBBP	CREBBP	10445	0.0077	0.14	NO
52	POLR2I	POLR2I	POLR2I	10450	0.0077	0.14	NO
53	CREB3	CREB3	CREB3	10515	0.0071	0.13	NO
54	UQCR11	UQCR11	UQCR11	10659	0.0058	0.13	NO
55	CLTCL1	CLTCL1	CLTCL1	10752	0.0049	0.12	NO
56	NDUFA6	NDUFA6	NDUFA6	10815	0.0043	0.12	NO
57	APAF1	APAF1	APAF1	10901	0.0036	0.11	NO
58	SIN3A	SIN3A	SIN3A	10923	0.0035	0.11	NO
59	CREB1	CREB1	CREB1	10961	0.0032	0.11	NO
60	HTT	HTT	HTT	11018	0.0026	0.11	NO
61	NDUFA5	NDUFA5	NDUFA5	11052	0.0024	0.11	NO
62	COX4I1	COX4I1	COX4I1	11267	0.00049	0.095	NO
63	AP2A2	AP2A2	AP2A2	11275	0.00046	0.095	NO
64	POLR2A	POLR2A	POLR2A	11305	0.00022	0.093	NO
65	SOD2	SOD2	SOD2	11325	0.000094	0.092	NO
66	NDUFA3	NDUFA3	NDUFA3	11379	-0.0004	0.089	NO
67	CREB3L3	CREB3L3	CREB3L3	11381	-0.00041	0.089	NO
68	NDUFB2	NDUFB2	NDUFB2	11573	-0.0021	0.079	NO
69	AP2M1	AP2M1	AP2M1	11658	-0.0028	0.074	NO
70	CLTA	CLTA	CLTA	11850	-0.0044	0.064	NO
71	SLC25A6	SLC25A6	SLC25A6	11851	-0.0044	0.065	NO
72	ATP5O	ATP5O	ATP5O	11854	-0.0044	0.065	NO
73	NDUFA2	NDUFA2	NDUFA2	11944	-0.0051	0.061	NO
74	PPID	PPID	PPID	11951	-0.0051	0.061	NO
75	CASP8	CASP8	CASP8	11972	-0.0054	0.06	NO
76	HAP1	HAP1	HAP1	12004	-0.0057	0.059	NO
77	NDUFA7	NDUFA7	NDUFA7	12184	-0.0072	0.05	NO
78	NDUFB10	NDUFB10	NDUFB10	12231	-0.0076	0.048	NO
79	NDUFV1	NDUFV1	NDUFV1	12384	-0.0089	0.04	NO
80	AP2S1	AP2S1	AP2S1	12480	-0.0098	0.036	NO
81	CASP3	CASP3	CASP3	12529	-0.01	0.034	NO
82	NDUFA10	NDUFA10	NDUFA10	12598	-0.011	0.031	NO
83	CREB3L2	CREB3L2	CREB3L2	12623	-0.011	0.031	NO
84	NDUFS3	NDUFS3	NDUFS3	12655	-0.011	0.03	NO
85	NDUFB1	NDUFB1	NDUFB1	12801	-0.013	0.023	NO
86	SP1	SP1	SP1	12842	-0.013	0.022	NO
87	POLR2F	POLR2F	POLR2F	12848	-0.013	0.023	NO
88	ATP5E	ATP5E	ATP5E	12866	-0.013	0.023	NO
89	PLCB3	PLCB3	PLCB3	12912	-0.014	0.022	NO
90	ATP5A1	ATP5A1	ATP5A1	12926	-0.014	0.022	NO
91	ATP5F1	ATP5F1	ATP5F1	12945	-0.014	0.022	NO
92	NDUFC2	NDUFC2	NDUFC2	13158	-0.016	0.012	NO
93	UQCRC2	UQCRC2	UQCRC2	13193	-0.016	0.012	NO
94	NDUFS8	NDUFS8	NDUFS8	13310	-0.017	0.0068	NO
95	CREB3L4	CREB3L4	CREB3L4	13353	-0.017	0.006	NO
96	SDHD	SDHD	SDHD	13359	-0.017	0.0072	NO
97	CLTC	CLTC	CLTC	13374	-0.017	0.0079	NO
98	NDUFS4	NDUFS4	NDUFS4	13504	-0.019	0.0024	NO
99	NDUFS5	NDUFS5	NDUFS5	13608	-0.019	-0.0016	NO
100	POLR2G	POLR2G	POLR2G	13623	-0.02	-0.00065	NO
101	DCTN4	DCTN4	DCTN4	13721	-0.02	-0.0042	NO
102	NDUFB5	NDUFB5	NDUFB5	13759	-0.021	-0.0045	NO
103	POLR2C	POLR2C	POLR2C	13774	-0.021	-0.0034	NO
104	VDAC3	VDAC3	VDAC3	13800	-0.021	-0.003	NO
105	SOD1	SOD1	SOD1	13818	-0.021	-0.002	NO
106	GRIN1	GRIN1	GRIN1	13857	-0.022	-0.0023	NO
107	NDUFAB1	NDUFAB1	NDUFAB1	13945	-0.022	-0.0051	NO
108	POLR2B	POLR2B	POLR2B	14088	-0.024	-0.011	NO
109	NDUFC1	NDUFC1	NDUFC1	14144	-0.024	-0.012	NO
110	ATP5G2	ATP5G2	ATP5G2	14157	-0.024	-0.01	NO
111	SDHA	SDHA	SDHA	14163	-0.024	-0.0084	NO
112	COX8A	COX8A	COX8A	14219	-0.025	-0.0093	NO
113	COX7C	COX7C	COX7C	14226	-0.025	-0.0074	NO
114	HDAC1	HDAC1	HDAC1	14242	-0.025	-0.0061	NO
115	ATP5J	ATP5J	ATP5J	14249	-0.025	-0.0042	NO
116	NDUFA1	NDUFA1	NDUFA1	14281	-0.026	-0.0037	NO
117	NDUFB6	NDUFB6	NDUFB6	14383	-0.026	-0.007	NO
118	UQCRC1	UQCRC1	UQCRC1	14485	-0.028	-0.01	NO
119	NDUFA8	NDUFA8	NDUFA8	14558	-0.028	-0.012	NO
120	DCTN2	DCTN2	DCTN2	14562	-0.028	-0.0093	NO
121	NDUFB8	NDUFB8	NDUFB8	14585	-0.029	-0.008	NO
122	NDUFV3	NDUFV3	NDUFV3	14599	-0.029	-0.0062	NO
123	TBP	TBP	TBP	14845	-0.032	-0.017	NO
124	NDUFA4	NDUFA4	NDUFA4	14876	-0.032	-0.016	NO
125	NDUFB3	NDUFB3	NDUFB3	15059	-0.034	-0.023	NO
126	NDUFS2	NDUFS2	NDUFS2	15246	-0.036	-0.03	NO
127	NDUFB4	NDUFB4	NDUFB4	15276	-0.037	-0.028	NO
128	COX7B	COX7B	COX7B	15291	-0.037	-0.026	NO
129	POLR2J	POLR2J	POLR2J	15293	-0.037	-0.023	NO
130	NDUFS6	NDUFS6	NDUFS6	15305	-0.037	-0.02	NO
131	COX6B1	COX6B1	COX6B1	15327	-0.037	-0.018	NO
132	RCOR1	RCOR1	RCOR1	15405	-0.038	-0.019	NO
133	SLC25A5	SLC25A5	SLC25A5	15417	-0.038	-0.016	NO
134	UQCRQ	UQCRQ	UQCRQ	15435	-0.039	-0.014	NO
135	SDHB	SDHB	SDHB	15458	-0.039	-0.012	NO
136	ATP5H	ATP5H	ATP5H	15653	-0.041	-0.019	NO
137	NDUFA9	NDUFA9	NDUFA9	15665	-0.042	-0.016	NO
138	UQCRFS1	UQCRFS1	UQCRFS1	15674	-0.042	-0.013	NO
139	COX7A2L	COX7A2L	COX7A2L	15710	-0.042	-0.011	NO
140	UQCRB	UQCRB	UQCRB	15747	-0.043	-0.0091	NO
141	SDHC	SDHC	SDHC	15781	-0.043	-0.0072	NO
142	COX5B	COX5B	COX5B	15903	-0.045	-0.0099	NO
143	NDUFV2	NDUFV2	NDUFV2	15917	-0.046	-0.0066	NO
144	HDAC2	HDAC2	HDAC2	15998	-0.047	-0.007	NO
145	ATP5B	ATP5B	ATP5B	16220	-0.051	-0.015	NO
146	VDAC1	VDAC1	VDAC1	16241	-0.051	-0.011	NO
147	ATP5G3	ATP5G3	ATP5G3	16254	-0.051	-0.0076	NO
148	ATP5G1	ATP5G1	ATP5G1	16256	-0.051	-0.0032	NO
149	COX5A	COX5A	COX5A	16377	-0.054	-0.0051	NO
150	ATP5C1	ATP5C1	ATP5C1	16395	-0.054	-0.0013	NO
151	POLR2H	POLR2H	POLR2H	16607	-0.06	-0.0078	NO
152	NDUFB9	NDUFB9	NDUFB9	16661	-0.061	-0.0054	NO
153	UQCRH	UQCRH	UQCRH	16690	-0.062	-0.0015	NO
154	VDAC2	VDAC2	VDAC2	16692	-0.062	0.0038	NO
155	NDUFS1	NDUFS1	NDUFS1	16757	-0.064	0.0059	NO
156	COX6C	COX6C	COX6C	16849	-0.067	0.0067	NO
157	COX6A1	COX6A1	COX6A1	16877	-0.068	0.011	NO
158	TFAM	TFAM	TFAM	16910	-0.069	0.015	NO
159	TAF4	TAF4	TAF4	16922	-0.07	0.021	NO
160	POLR2D	POLR2D	POLR2D	16931	-0.07	0.026	NO
161	CYCS	CYCS	CYCS	16970	-0.071	0.03	NO
162	COX7A2	COX7A2	COX7A2	17008	-0.072	0.035	NO
163	POLR2K	POLR2K	POLR2K	17044	-0.073	0.039	NO
164	UQCRHL	UQCRHL	UQCRHL	17279	-0.085	0.034	NO
165	CYC1	CYC1	CYC1	17424	-0.094	0.034	NO
166	PLCB1	PLCB1	PLCB1	17988	-0.16	0.017	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 FATTY ACID 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	MAPK10	MAPK10	MAPK10	396	0.54	0.18	YES
2	NRG2	NRG2	NRG2	489	0.46	0.35	YES
3	NRG1	NRG1	NRG1	1641	0.23	0.38	YES
4	JAK2	JAK2	JAK2	3827	0.12	0.3	YES
5	PIK3CD	PIK3CD	PIK3CD	4010	0.11	0.34	YES
6	CHRNE	CHRNE	CHRNE	4159	0.11	0.37	YES
7	PIK3R1	PIK3R1	PIK3R1	4307	0.1	0.4	YES
8	FOS	FOS	FOS	4682	0.095	0.41	YES
9	PIK3R3	PIK3R3	PIK3R3	4996	0.087	0.43	YES
10	CHRNA1	CHRNA1	CHRNA1	5229	0.082	0.45	YES
11	JUN	JUN	JUN	5243	0.082	0.48	YES
12	BAD	BAD	BAD	7126	0.046	0.39	NO
13	ERBB2	ERBB2	ERBB2	8828	0.023	0.31	NO
14	PRKACA	PRKACA	PRKACA	8885	0.023	0.31	NO
15	PIK3R2	PIK3R2	PIK3R2	9252	0.019	0.3	NO
16	DOCK7	DOCK7	DOCK7	9444	0.016	0.3	NO
17	MAPK3	MAPK3	MAPK3	9791	0.013	0.28	NO
18	STAT3	STAT3	STAT3	10375	0.0085	0.25	NO
19	MAPK1	MAPK1	MAPK1	10665	0.0057	0.24	NO
20	NF2	NF2	NF2	10891	0.0037	0.23	NO
21	CDC42	CDC42	CDC42	11071	0.0022	0.22	NO
22	MAP2K2	MAP2K2	MAP2K2	11159	0.0014	0.22	NO
23	USP8	USP8	USP8	11161	0.0013	0.22	NO
24	HRAS	HRAS	HRAS	11188	0.0011	0.22	NO
25	PIK3CA	PIK3CA	PIK3CA	11272	0.00046	0.21	NO
26	GRB2	GRB2	GRB2	11536	-0.0017	0.2	NO
27	AKT1	AKT1	AKT1	11648	-0.0027	0.19	NO
28	PPP3CB	PPP3CB	PPP3CB	11715	-0.0033	0.19	NO
29	MTOR	MTOR	MTOR	12043	-0.006	0.17	NO
30	RAC1	RAC1	RAC1	12142	-0.0068	0.17	NO
31	SOS1	SOS1	SOS1	12264	-0.0079	0.17	NO
32	ERBB3	ERBB3	ERBB3	12550	-0.01	0.16	NO
33	RAF1	RAF1	RAF1	12900	-0.013	0.14	NO
34	SRC	SRC	SRC	13054	-0.015	0.14	NO
35	PIK3CB	PIK3CB	PIK3CB	13151	-0.016	0.14	NO
36	RNF41	RNF41	RNF41	13624	-0.02	0.12	NO
37	NFATC4	NFATC4	NFATC4	14109	-0.024	0.1	NO
38	MAPK9	MAPK9	MAPK9	14301	-0.026	0.1	NO
39	SHC1	SHC1	SHC1	15471	-0.039	0.053	NO
40	MAP2K1	MAP2K1	MAP2K1	16014	-0.047	0.041	NO
41	PTPN11	PTPN11	PTPN11	16211	-0.05	0.049	NO
42	KRAS	KRAS	KRAS	16283	-0.052	0.065	NO
43	NRAS	NRAS	NRAS	16504	-0.057	0.074	NO
44	MAPK8	MAPK8	MAPK8	16773	-0.064	0.084	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 FATTY ACID METABOLISM.

Figure S84. 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 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	NGFR	NGFR	NGFR	332	0.62	0.11	YES
2	NTRK3	NTRK3	NTRK3	436	0.5	0.21	YES
3	NTF4	NTF4	NTF4	698	0.38	0.27	YES
4	NTF3	NTF3	NTF3	735	0.37	0.34	YES
5	NTRK2	NTRK2	NTRK2	761	0.36	0.42	YES
6	RASGRF1	RASGRF1	RASGRF1	1397	0.26	0.43	YES
7	MATK	MATK	MATK	1746	0.22	0.46	YES
8	NTRK1	NTRK1	NTRK1	1774	0.22	0.5	YES
9	SHC3	SHC3	SHC3	2552	0.17	0.5	YES
10	TIAM1	TIAM1	TIAM1	2584	0.17	0.53	YES
11	SHC2	SHC2	SHC2	3236	0.14	0.52	NO
12	PIK3R1	PIK3R1	PIK3R1	4307	0.1	0.49	NO
13	SH2B1	SH2B1	SH2B1	5271	0.081	0.45	NO
14	FAIM	FAIM	FAIM	5281	0.081	0.47	NO
15	DNM1	DNM1	DNM1	5615	0.072	0.46	NO
16	ELMO1	ELMO1	ELMO1	5994	0.065	0.46	NO
17	RGS19	RGS19	RGS19	6110	0.063	0.46	NO
18	EHD4	EHD4	EHD4	6298	0.059	0.47	NO
19	GAB1	GAB1	GAB1	6891	0.049	0.44	NO
20	RAPGEF1	RAPGEF1	RAPGEF1	6944	0.049	0.45	NO
21	GIPC1	GIPC1	GIPC1	6989	0.048	0.46	NO
22	ARHGAP32	ARHGAP32	ARHGAP32	7220	0.044	0.46	NO
23	PLCG1	PLCG1	PLCG1	7836	0.035	0.43	NO
24	RHOG	RHOG	RHOG	8018	0.033	0.42	NO
25	BDNF	BDNF	BDNF	8418	0.028	0.41	NO
26	MCF2L	MCF2L	MCF2L	8623	0.025	0.4	NO
27	RAP1A	RAP1A	RAP1A	9107	0.02	0.38	NO
28	PRKCZ	PRKCZ	PRKCZ	9294	0.018	0.37	NO
29	DYNLT1	DYNLT1	DYNLT1	9698	0.014	0.36	NO
30	MAPK3	MAPK3	MAPK3	9791	0.013	0.35	NO
31	CCND1	CCND1	CCND1	9981	0.012	0.34	NO
32	NEDD4L	NEDD4L	NEDD4L	10152	0.01	0.34	NO
33	RASA1	RASA1	RASA1	10277	0.0092	0.33	NO
34	STAT3	STAT3	STAT3	10375	0.0085	0.33	NO
35	NGF	NGF	NGF	10431	0.0078	0.33	NO
36	FRS3	FRS3	FRS3	10580	0.0065	0.32	NO
37	ABL1	ABL1	ABL1	10598	0.0064	0.32	NO
38	MAPK1	MAPK1	MAPK1	10665	0.0057	0.32	NO
39	CDC42	CDC42	CDC42	11071	0.0022	0.3	NO
40	HRAS	HRAS	HRAS	11188	0.0011	0.29	NO
41	PRKCI	PRKCI	PRKCI	11220	0.00086	0.29	NO
42	PIK3CA	PIK3CA	PIK3CA	11272	0.00046	0.29	NO
43	MAGED1	MAGED1	MAGED1	11279	0.00043	0.29	NO
44	GRB2	GRB2	GRB2	11536	-0.0017	0.27	NO
45	RHOA	RHOA	RHOA	11860	-0.0044	0.26	NO
46	CRKL	CRKL	CRKL	11864	-0.0044	0.26	NO
47	RAC1	RAC1	RAC1	12142	-0.0068	0.24	NO
48	RAP1B	RAP1B	RAP1B	12191	-0.0073	0.24	NO
49	SOS1	SOS1	SOS1	12264	-0.0079	0.24	NO
50	DOCK1	DOCK1	DOCK1	12265	-0.0079	0.24	NO
51	SQSTM1	SQSTM1	SQSTM1	13061	-0.015	0.2	NO
52	GAB2	GAB2	GAB2	13085	-0.015	0.2	NO
53	CRK	CRK	CRK	13423	-0.018	0.19	NO
54	SHC1	SHC1	SHC1	15471	-0.039	0.083	NO
55	FRS2	FRS2	FRS2	15485	-0.039	0.091	NO
56	MAP2K1	MAP2K1	MAP2K1	16014	-0.047	0.072	NO
57	DNAJA3	DNAJA3	DNAJA3	16090	-0.048	0.078	NO
58	PTPN11	PTPN11	PTPN11	16211	-0.05	0.081	NO
59	RIT1	RIT1	RIT1	16260	-0.052	0.089	NO
60	KRAS	KRAS	KRAS	16283	-0.052	0.099	NO
61	NRAS	NRAS	NRAS	16504	-0.057	0.098	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 STEROID HORMONE BIOSYNTHESIS.

Figure S86. 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 TYROSINE 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	ERBB4	ERBB4	ERBB4	373	0.56	0.18	YES
2	NRG2	NRG2	NRG2	489	0.46	0.34	YES
3	NRG4	NRG4	NRG4	1495	0.25	0.38	YES
4	BTC	BTC	BTC	1556	0.24	0.46	YES
5	NRG1	NRG1	NRG1	1641	0.23	0.55	YES
6	PIK3R1	PIK3R1	PIK3R1	4307	0.1	0.44	NO
7	FOXO1	FOXO1	FOXO1	5112	0.085	0.42	NO
8	CDKN1A	CDKN1A	CDKN1A	5422	0.077	0.44	NO
9	FOXO3	FOXO3	FOXO3	6434	0.057	0.4	NO
10	HBEGF	HBEGF	HBEGF	6923	0.049	0.39	NO
11	BAD	BAD	BAD	7126	0.046	0.4	NO
12	NR4A1	NR4A1	NR4A1	7163	0.045	0.41	NO
13	AKT3	AKT3	AKT3	8092	0.032	0.37	NO
14	FOXO4	FOXO4	FOXO4	8182	0.031	0.38	NO
15	PHLPP1	PHLPP1	PHLPP1	8221	0.03	0.39	NO
16	EREG	EREG	EREG	8464	0.027	0.39	NO
17	PDPK1	PDPK1	PDPK1	8581	0.026	0.39	NO
18	PTEN	PTEN	PTEN	9153	0.02	0.36	NO
19	CDKN1B	CDKN1B	CDKN1B	9870	0.013	0.33	NO
20	CASP9	CASP9	CASP9	9891	0.012	0.33	NO
21	TSC2	TSC2	TSC2	10471	0.0075	0.3	NO
22	AKT2	AKT2	AKT2	10811	0.0044	0.29	NO
23	CREB1	CREB1	CREB1	10961	0.0032	0.28	NO
24	PIK3CA	PIK3CA	PIK3CA	11272	0.00046	0.26	NO
25	AKT1	AKT1	AKT1	11648	-0.0027	0.24	NO
26	MTOR	MTOR	MTOR	12043	-0.006	0.22	NO
27	AKT1S1	AKT1S1	AKT1S1	12311	-0.0082	0.21	NO
28	MAPKAP1	MAPKAP1	MAPKAP1	12906	-0.014	0.19	NO
29	RICTOR	RICTOR	RICTOR	13248	-0.016	0.17	NO
30	MDM2	MDM2	MDM2	13355	-0.017	0.17	NO
31	GSK3A	GSK3A	GSK3A	13362	-0.017	0.18	NO
32	MLST8	MLST8	MLST8	14221	-0.025	0.14	NO
33	THEM4	THEM4	THEM4	14423	-0.027	0.14	NO
34	RPS6KB2	RPS6KB2	RPS6KB2	14701	-0.03	0.14	NO
35	CHUK	CHUK	CHUK	16088	-0.048	0.078	NO
36	TRIB3	TRIB3	TRIB3	17685	-0.12	0.034	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 TYROSINE METABOLISM.

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

genes ES table in pathway: KEGG GLUTATHIONE 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	ADH7	ADH7	ADH7	236	0.82	0.18	YES
2	ADH6	ADH6	ADH6	351	0.58	0.31	YES
3	ADH1B	ADH1B	ADH1B	562	0.43	0.4	YES
4	ADH1C	ADH1C	ADH1C	568	0.42	0.5	YES
5	ADH1A	ADH1A	ADH1A	651	0.39	0.58	YES
6	ACADL	ACADL	ACADL	745	0.37	0.67	YES
7	CYP4A11	CYP4A11	CYP4A11	1874	0.22	0.65	NO
8	ACSL6	ACSL6	ACSL6	2856	0.16	0.64	NO
9	CYP4A22	CYP4A22	CYP4A22	3402	0.14	0.64	NO
10	ALDH2	ALDH2	ALDH2	5318	0.08	0.55	NO
11	CPT1B	CPT1B	CPT1B	5577	0.073	0.56	NO
12	ADH4	ADH4	ADH4	6927	0.049	0.49	NO
13	GCDH	GCDH	GCDH	7248	0.044	0.49	NO
14	HADH	HADH	HADH	7592	0.038	0.48	NO
15	ACAA2	ACAA2	ACAA2	8120	0.032	0.46	NO
16	ALDH9A1	ALDH9A1	ALDH9A1	8546	0.026	0.44	NO
17	ACAA1	ACAA1	ACAA1	8875	0.023	0.42	NO
18	ALDH7A1	ALDH7A1	ALDH7A1	9213	0.019	0.41	NO
19	ACOX3	ACOX3	ACOX3	9396	0.017	0.4	NO
20	ACADS	ACADS	ACADS	9485	0.016	0.4	NO
21	EHHADH	EHHADH	EHHADH	9515	0.016	0.41	NO
22	ACSL5	ACSL5	ACSL5	9606	0.015	0.4	NO
23	CPT1A	CPT1A	CPT1A	10546	0.0068	0.36	NO
24	ACADVL	ACADVL	ACADVL	10753	0.0049	0.34	NO
25	ACADSB	ACADSB	ACADSB	11037	0.0025	0.33	NO
26	ACSL4	ACSL4	ACSL4	11278	0.00044	0.32	NO
27	ACSL1	ACSL1	ACSL1	11629	-0.0025	0.3	NO
28	ALDH3A2	ALDH3A2	ALDH3A2	11911	-0.0047	0.28	NO
29	HADHB	HADHB	HADHB	12173	-0.0071	0.27	NO
30	HADHA	HADHA	HADHA	12806	-0.013	0.24	NO
31	ACADM	ACADM	ACADM	13334	-0.017	0.22	NO
32	ACOX1	ACOX1	ACOX1	13458	-0.018	0.21	NO
33	ECHS1	ECHS1	ECHS1	13585	-0.019	0.21	NO
34	ADH5	ADH5	ADH5	13678	-0.02	0.21	NO
35	ALDH1B1	ALDH1B1	ALDH1B1	14066	-0.024	0.19	NO
36	CPT2	CPT2	CPT2	14141	-0.024	0.2	NO
37	ACAT1	ACAT1	ACAT1	14810	-0.031	0.17	NO
38	CPT1C	CPT1C	CPT1C	14934	-0.032	0.17	NO
39	ACAT2	ACAT2	ACAT2	14976	-0.033	0.17	NO
40	ACSL3	ACSL3	ACSL3	15596	-0.041	0.15	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 GLUTATHIONE METABOLISM.

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

genes ES table in pathway: KEGG STARCH AND SUCROSE METABOLISM

Table S46. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ERBB4	ERBB4	ERBB4	373	0.56	0.064	YES
2	MAPK10	MAPK10	MAPK10	396	0.54	0.14	YES
3	NRG2	NRG2	NRG2	489	0.46	0.21	YES
4	SHC4	SHC4	SHC4	812	0.35	0.24	YES
5	PAK7	PAK7	PAK7	1099	0.29	0.27	YES
6	NRG4	NRG4	NRG4	1495	0.25	0.29	YES
7	BTC	BTC	BTC	1556	0.24	0.32	YES
8	PRKCB	PRKCB	PRKCB	1559	0.24	0.36	YES
9	NRG1	NRG1	NRG1	1641	0.23	0.39	YES
10	NRG3	NRG3	NRG3	1818	0.22	0.41	YES
11	PIK3CG	PIK3CG	PIK3CG	2409	0.18	0.41	YES
12	SHC3	SHC3	SHC3	2552	0.17	0.43	YES
13	CAMK2A	CAMK2A	CAMK2A	2700	0.16	0.44	YES
14	PLCG2	PLCG2	PLCG2	2805	0.16	0.46	YES
15	PIK3R5	PIK3R5	PIK3R5	2835	0.16	0.48	YES
16	SHC2	SHC2	SHC2	3236	0.14	0.48	NO
17	STAT5A	STAT5A	STAT5A	3872	0.12	0.47	NO
18	PIK3CD	PIK3CD	PIK3CD	4010	0.11	0.48	NO
19	PIK3R1	PIK3R1	PIK3R1	4307	0.1	0.48	NO
20	PIK3R3	PIK3R3	PIK3R3	4996	0.087	0.45	NO
21	JUN	JUN	JUN	5243	0.082	0.45	NO
22	CDKN1A	CDKN1A	CDKN1A	5422	0.077	0.45	NO
23	PRKCA	PRKCA	PRKCA	5769	0.07	0.44	NO
24	CBLB	CBLB	CBLB	6821	0.051	0.39	NO
25	GAB1	GAB1	GAB1	6891	0.049	0.4	NO
26	HBEGF	HBEGF	HBEGF	6923	0.049	0.4	NO
27	NCK2	NCK2	NCK2	6950	0.049	0.41	NO
28	BAD	BAD	BAD	7126	0.046	0.41	NO
29	CAMK2D	CAMK2D	CAMK2D	7187	0.045	0.41	NO
30	TGFA	TGFA	TGFA	7736	0.037	0.38	NO
31	PLCG1	PLCG1	PLCG1	7836	0.035	0.38	NO
32	PRKCG	PRKCG	PRKCG	7902	0.034	0.39	NO
33	PAK6	PAK6	PAK6	8011	0.033	0.39	NO
34	AKT3	AKT3	AKT3	8092	0.032	0.39	NO
35	AREG	AREG	AREG	8110	0.032	0.39	NO
36	STAT5B	STAT5B	STAT5B	8195	0.031	0.39	NO
37	EREG	EREG	EREG	8464	0.027	0.38	NO
38	CBL	CBL	CBL	8714	0.024	0.37	NO
39	MAP2K7	MAP2K7	MAP2K7	8788	0.024	0.37	NO
40	ERBB2	ERBB2	ERBB2	8828	0.023	0.37	NO
41	PAK1	PAK1	PAK1	8861	0.023	0.37	NO
42	EGFR	EGFR	EGFR	9007	0.021	0.37	NO
43	PIK3R2	PIK3R2	PIK3R2	9252	0.019	0.36	NO
44	ARAF	ARAF	ARAF	9578	0.015	0.34	NO
45	SOS2	SOS2	SOS2	9741	0.014	0.33	NO
46	MAPK3	MAPK3	MAPK3	9791	0.013	0.33	NO
47	CDKN1B	CDKN1B	CDKN1B	9870	0.013	0.33	NO
48	ABL1	ABL1	ABL1	10598	0.0064	0.29	NO
49	MAPK1	MAPK1	MAPK1	10665	0.0057	0.29	NO
50	AKT2	AKT2	AKT2	10811	0.0044	0.28	NO
51	CAMK2G	CAMK2G	CAMK2G	10984	0.0029	0.27	NO
52	MAP2K2	MAP2K2	MAP2K2	11159	0.0014	0.26	NO
53	HRAS	HRAS	HRAS	11188	0.0011	0.26	NO
54	PAK3	PAK3	PAK3	11197	0.001	0.26	NO
55	PIK3CA	PIK3CA	PIK3CA	11272	0.00046	0.26	NO
56	NCK1	NCK1	NCK1	11453	-0.0011	0.25	NO
57	GRB2	GRB2	GRB2	11536	-0.0017	0.24	NO
58	AKT1	AKT1	AKT1	11648	-0.0027	0.24	NO
59	CRKL	CRKL	CRKL	11864	-0.0044	0.23	NO
60	MTOR	MTOR	MTOR	12043	-0.006	0.22	NO
61	MAP2K4	MAP2K4	MAP2K4	12082	-0.0063	0.22	NO
62	CAMK2B	CAMK2B	CAMK2B	12236	-0.0076	0.21	NO
63	SOS1	SOS1	SOS1	12264	-0.0079	0.21	NO
64	ELK1	ELK1	ELK1	12380	-0.0088	0.2	NO
65	PAK2	PAK2	PAK2	12429	-0.0093	0.2	NO
66	ERBB3	ERBB3	ERBB3	12550	-0.01	0.2	NO
67	PAK4	PAK4	PAK4	12860	-0.013	0.18	NO
68	RAF1	RAF1	RAF1	12900	-0.013	0.18	NO
69	SRC	SRC	SRC	13054	-0.015	0.18	NO
70	ABL2	ABL2	ABL2	13098	-0.015	0.18	NO
71	PIK3CB	PIK3CB	PIK3CB	13151	-0.016	0.18	NO
72	CBLC	CBLC	CBLC	13267	-0.017	0.17	NO
73	MYC	MYC	MYC	13317	-0.017	0.17	NO
74	CRK	CRK	CRK	13423	-0.018	0.17	NO
75	RPS6KB1	RPS6KB1	RPS6KB1	13891	-0.022	0.15	NO
76	GSK3B	GSK3B	GSK3B	14067	-0.024	0.14	NO
77	MAPK9	MAPK9	MAPK9	14301	-0.026	0.13	NO
78	RPS6KB2	RPS6KB2	RPS6KB2	14701	-0.03	0.12	NO
79	PTK2	PTK2	PTK2	14778	-0.031	0.12	NO
80	SHC1	SHC1	SHC1	15471	-0.039	0.084	NO
81	MAP2K1	MAP2K1	MAP2K1	16014	-0.047	0.061	NO
82	KRAS	KRAS	KRAS	16283	-0.052	0.054	NO
83	NRAS	NRAS	NRAS	16504	-0.057	0.051	NO
84	MAPK8	MAPK8	MAPK8	16773	-0.064	0.046	NO
85	BRAF	BRAF	BRAF	17135	-0.076	0.038	NO
86	EGF	EGF	EGF	17255	-0.083	0.044	NO
87	EIF4EBP1	EIF4EBP1	EIF4EBP1	17372	-0.09	0.051	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 STARCH AND SUCROSE METABOLISM.

Figure S92. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG STARCH AND SUCROSE 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 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	GLI1	GLI1	GLI1	939	0.32	0.051	YES
2	IFT172	IFT172	IFT172	1161	0.28	0.13	YES
3	GNAO1	GNAO1	GNAO1	1422	0.25	0.2	YES
4	GNAZ	GNAZ	GNAZ	2246	0.19	0.21	YES
5	IFT88	IFT88	IFT88	2398	0.18	0.26	YES
6	SHH	SHH	SHH	2479	0.18	0.31	YES
7	FOXA2	FOXA2	FOXA2	2576	0.17	0.36	YES
8	SMO	SMO	SMO	3117	0.15	0.38	YES
9	PTCH1	PTCH1	PTCH1	3391	0.14	0.4	YES
10	GLI3	GLI3	GLI3	3896	0.12	0.42	YES
11	GNG2	GNG2	GNG2	4206	0.11	0.43	YES
12	SSPO	SSPO	SSPO	4536	0.098	0.44	YES
13	GLI2	GLI2	GLI2	4543	0.098	0.48	YES
14	STK36	STK36	STK36	4609	0.096	0.5	YES
15	KIF3A	KIF3A	KIF3A	4793	0.092	0.52	YES
16	SUFU	SUFU	SUFU	6801	0.051	0.43	NO
17	LGALS3	LGALS3	LGALS3	6967	0.048	0.44	NO
18	CSNK1G2	CSNK1G2	CSNK1G2	7300	0.043	0.43	NO
19	GNAI2	GNAI2	GNAI2	7543	0.039	0.43	NO
20	ARRB2	ARRB2	ARRB2	8006	0.033	0.42	NO
21	PIAS1	PIAS1	PIAS1	8394	0.028	0.4	NO
22	SAP30	SAP30	SAP30	8855	0.023	0.38	NO
23	PRKACA	PRKACA	PRKACA	8885	0.023	0.39	NO
24	SIN3B	SIN3B	SIN3B	8932	0.022	0.39	NO
25	PRKCD	PRKCD	PRKCD	9014	0.021	0.4	NO
26	RAB23	RAB23	RAB23	9528	0.016	0.37	NO
27	FBXW11	FBXW11	FBXW11	9862	0.013	0.36	NO
28	CSNK1A1	CSNK1A1	CSNK1A1	10084	0.011	0.35	NO
29	MTSS1	MTSS1	MTSS1	10231	0.0095	0.35	NO
30	CREBBP	CREBBP	CREBBP	10445	0.0077	0.34	NO
31	SPOP	SPOP	SPOP	10701	0.0054	0.32	NO
32	SIN3A	SIN3A	SIN3A	10923	0.0035	0.31	NO
33	CSNK1G3	CSNK1G3	CSNK1G3	11129	0.0016	0.3	NO
34	GNAI1	GNAI1	GNAI1	11155	0.0014	0.3	NO
35	AKT1	AKT1	AKT1	11648	-0.0027	0.28	NO
36	CSNK1E	CSNK1E	CSNK1E	11746	-0.0036	0.27	NO
37	CSNK1G1	CSNK1G1	CSNK1G1	11822	-0.0041	0.27	NO
38	CSNK1D	CSNK1D	CSNK1D	11993	-0.0056	0.26	NO
39	GNAI3	GNAI3	GNAI3	12123	-0.0067	0.26	NO
40	SAP18	SAP18	SAP18	12873	-0.013	0.22	NO
41	GNB1	GNB1	GNB1	13130	-0.016	0.21	NO
42	GSK3B	GSK3B	GSK3B	14067	-0.024	0.17	NO
43	HDAC1	HDAC1	HDAC1	14242	-0.025	0.16	NO
44	RBBP7	RBBP7	RBBP7	14243	-0.025	0.17	NO
45	RBBP4	RBBP4	RBBP4	14274	-0.026	0.18	NO
46	XPO1	XPO1	XPO1	15201	-0.036	0.14	NO
47	HDAC2	HDAC2	HDAC2	15998	-0.047	0.11	NO
48	MAP2K1	MAP2K1	MAP2K1	16014	-0.047	0.12	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 GLYCEROPHOSPHOLIPID METABOLISM.

Figure S94. 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 LINOLEIC ACID METABOLISM

Table S48. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NGFR	NGFR	NGFR	332	0.62	0.046	YES
2	TP73	TP73	TP73	345	0.59	0.11	YES
3	MAPK10	MAPK10	MAPK10	396	0.54	0.16	YES
4	NTRK3	NTRK3	NTRK3	436	0.5	0.21	YES
5	NTF4	NTF4	NTF4	698	0.38	0.24	YES
6	NTF3	NTF3	NTF3	735	0.37	0.27	YES
7	NTRK2	NTRK2	NTRK2	761	0.36	0.31	YES
8	SHC4	SHC4	SHC4	812	0.35	0.34	YES
9	IRS4	IRS4	IRS4	1234	0.28	0.35	YES
10	CAMK4	CAMK4	CAMK4	1614	0.24	0.35	YES
11	NTRK1	NTRK1	NTRK1	1774	0.22	0.36	YES
12	PIK3CG	PIK3CG	PIK3CG	2409	0.18	0.35	YES
13	MAPK11	MAPK11	MAPK11	2438	0.18	0.36	YES
14	SHC3	SHC3	SHC3	2552	0.17	0.38	YES
15	CAMK2A	CAMK2A	CAMK2A	2700	0.16	0.39	YES
16	RPS6KA5	RPS6KA5	RPS6KA5	2747	0.16	0.4	YES
17	BCL2	BCL2	BCL2	2756	0.16	0.42	YES
18	PLCG2	PLCG2	PLCG2	2805	0.16	0.43	YES
19	PIK3R5	PIK3R5	PIK3R5	2835	0.16	0.44	YES
20	SHC2	SHC2	SHC2	3236	0.14	0.44	NO
21	IRAK3	IRAK3	IRAK3	3481	0.13	0.44	NO
22	PIK3CD	PIK3CD	PIK3CD	4010	0.11	0.42	NO
23	CALML6	CALML6	CALML6	4276	0.11	0.42	NO
24	PIK3R1	PIK3R1	PIK3R1	4307	0.1	0.43	NO
25	PIK3R3	PIK3R3	PIK3R3	4996	0.087	0.4	NO
26	MAP3K5	MAP3K5	MAP3K5	5001	0.087	0.41	NO
27	MAP3K3	MAP3K3	MAP3K3	5057	0.086	0.41	NO
28	SH2B3	SH2B3	SH2B3	5088	0.085	0.42	NO
29	JUN	JUN	JUN	5243	0.082	0.42	NO
30	SH2B1	SH2B1	SH2B1	5271	0.081	0.43	NO
31	FASLG	FASLG	FASLG	5468	0.076	0.42	NO
32	ARHGDIB	ARHGDIB	ARHGDIB	5894	0.067	0.41	NO
33	RPS6KA6	RPS6KA6	RPS6KA6	6023	0.064	0.41	NO
34	NFKBIE	NFKBIE	NFKBIE	6137	0.063	0.41	NO
35	FOXO3	FOXO3	FOXO3	6434	0.057	0.4	NO
36	CALML3	CALML3	CALML3	6460	0.057	0.4	NO
37	CALM1	CALM1	CALM1	6471	0.056	0.41	NO
38	MAP3K1	MAP3K1	MAP3K1	6482	0.056	0.41	NO
39	CALML5	CALML5	CALML5	6822	0.051	0.4	NO
40	GAB1	GAB1	GAB1	6891	0.049	0.4	NO
41	RAPGEF1	RAPGEF1	RAPGEF1	6944	0.049	0.4	NO
42	BAD	BAD	BAD	7126	0.046	0.4	NO
43	MAPK12	MAPK12	MAPK12	7180	0.045	0.4	NO
44	CAMK2D	CAMK2D	CAMK2D	7187	0.045	0.4	NO
45	RPS6KA1	RPS6KA1	RPS6KA1	7201	0.044	0.41	NO
46	IRS1	IRS1	IRS1	7341	0.042	0.4	NO
47	NFKB1	NFKB1	NFKB1	7484	0.04	0.4	NO
48	IKBKB	IKBKB	IKBKB	7754	0.036	0.39	NO
49	PLCG1	PLCG1	PLCG1	7836	0.035	0.39	NO
50	SORT1	SORT1	SORT1	7877	0.035	0.39	NO
51	AKT3	AKT3	AKT3	8092	0.032	0.38	NO
52	CSK	CSK	CSK	8142	0.031	0.38	NO
53	TRAF6	TRAF6	TRAF6	8151	0.031	0.38	NO
54	MAP2K5	MAP2K5	MAP2K5	8203	0.031	0.38	NO
55	IRAK4	IRAK4	IRAK4	8234	0.03	0.39	NO
56	BAX	BAX	BAX	8242	0.03	0.39	NO
57	BDNF	BDNF	BDNF	8418	0.028	0.38	NO
58	YWHAH	YWHAH	YWHAH	8484	0.027	0.38	NO
59	RPS6KA4	RPS6KA4	RPS6KA4	8731	0.024	0.37	NO
60	MAP2K7	MAP2K7	MAP2K7	8788	0.024	0.37	NO
61	RPS6KA2	RPS6KA2	RPS6KA2	8846	0.023	0.37	NO
62	MAPK7	MAPK7	MAPK7	8964	0.022	0.36	NO
63	PRKCD	PRKCD	PRKCD	9014	0.021	0.36	NO
64	TP53	TP53	TP53	9046	0.021	0.36	NO
65	RAP1A	RAP1A	RAP1A	9107	0.02	0.36	NO
66	RPS6KA3	RPS6KA3	RPS6KA3	9233	0.019	0.36	NO
67	PIK3R2	PIK3R2	PIK3R2	9252	0.019	0.36	NO
68	IRAK2	IRAK2	IRAK2	9323	0.018	0.36	NO
69	SH2B2	SH2B2	SH2B2	9333	0.018	0.36	NO
70	SOS2	SOS2	SOS2	9741	0.014	0.34	NO
71	MAPK3	MAPK3	MAPK3	9791	0.013	0.34	NO
72	KIDINS220	KIDINS220	KIDINS220	10032	0.011	0.32	NO
73	CALM3	CALM3	CALM3	10422	0.0079	0.3	NO
74	NGF	NGF	NGF	10431	0.0078	0.3	NO
75	ABL1	ABL1	ABL1	10598	0.0064	0.3	NO
76	MAPK1	MAPK1	MAPK1	10665	0.0057	0.29	NO
77	AKT2	AKT2	AKT2	10811	0.0044	0.29	NO
78	CAMK2G	CAMK2G	CAMK2G	10984	0.0029	0.28	NO
79	ARHGDIA	ARHGDIA	ARHGDIA	11055	0.0024	0.27	NO
80	CDC42	CDC42	CDC42	11071	0.0022	0.27	NO
81	YWHAB	YWHAB	YWHAB	11090	0.002	0.27	NO
82	MAP2K2	MAP2K2	MAP2K2	11159	0.0014	0.27	NO
83	NGFRAP1	NGFRAP1	NGFRAP1	11176	0.0012	0.27	NO
84	HRAS	HRAS	HRAS	11188	0.0011	0.27	NO
85	NFKBIB	NFKBIB	NFKBIB	11231	0.00076	0.26	NO
86	PIK3CA	PIK3CA	PIK3CA	11272	0.00046	0.26	NO
87	MAPKAPK2	MAPKAPK2	MAPKAPK2	11273	0.00046	0.26	NO
88	MAGED1	MAGED1	MAGED1	11279	0.00043	0.26	NO
89	GRB2	GRB2	GRB2	11536	-0.0017	0.25	NO
90	CALM2	CALM2	CALM2	11546	-0.0018	0.25	NO
91	AKT1	AKT1	AKT1	11648	-0.0027	0.24	NO
92	MAPK14	MAPK14	MAPK14	11777	-0.0038	0.24	NO
93	RHOA	RHOA	RHOA	11860	-0.0044	0.23	NO
94	CRKL	CRKL	CRKL	11864	-0.0044	0.23	NO
95	NFKBIA	NFKBIA	NFKBIA	12119	-0.0066	0.22	NO
96	RAC1	RAC1	RAC1	12142	-0.0068	0.22	NO
97	RAP1B	RAP1B	RAP1B	12191	-0.0073	0.22	NO
98	CAMK2B	CAMK2B	CAMK2B	12236	-0.0076	0.22	NO
99	SOS1	SOS1	SOS1	12264	-0.0079	0.21	NO
100	RELA	RELA	RELA	12536	-0.01	0.2	NO
101	RAF1	RAF1	RAF1	12900	-0.013	0.18	NO
102	PIK3CB	PIK3CB	PIK3CB	13151	-0.016	0.17	NO
103	PSEN1	PSEN1	PSEN1	13321	-0.017	0.16	NO
104	CRK	CRK	CRK	13423	-0.018	0.16	NO
105	YWHAE	YWHAE	YWHAE	13824	-0.021	0.14	NO
106	GSK3B	GSK3B	GSK3B	14067	-0.024	0.13	NO
107	ZNF274	ZNF274	ZNF274	14090	-0.024	0.13	NO
108	MAPK9	MAPK9	MAPK9	14301	-0.026	0.12	NO
109	PRDM4	PRDM4	PRDM4	14313	-0.026	0.12	NO
110	ATF4	ATF4	ATF4	14327	-0.026	0.12	NO
111	YWHAQ	YWHAQ	YWHAQ	15302	-0.037	0.074	NO
112	SHC1	SHC1	SHC1	15471	-0.039	0.069	NO
113	FRS2	FRS2	FRS2	15485	-0.039	0.073	NO
114	YWHAG	YWHAG	YWHAG	15915	-0.046	0.054	NO
115	MAP2K1	MAP2K1	MAP2K1	16014	-0.047	0.053	NO
116	PTPN11	PTPN11	PTPN11	16211	-0.05	0.048	NO
117	KRAS	KRAS	KRAS	16283	-0.052	0.049	NO
118	IRAK1	IRAK1	IRAK1	16311	-0.053	0.053	NO
119	YWHAZ	YWHAZ	YWHAZ	16329	-0.053	0.058	NO
120	NRAS	NRAS	NRAS	16504	-0.057	0.054	NO
121	MAPK13	MAPK13	MAPK13	16507	-0.057	0.06	NO
122	RIPK2	RIPK2	RIPK2	16511	-0.057	0.066	NO
123	MAPK8	MAPK8	MAPK8	16773	-0.064	0.058	NO
124	PDK1	PDK1	PDK1	16867	-0.068	0.06	NO
125	BRAF	BRAF	BRAF	17135	-0.076	0.053	NO
126	IRS2	IRS2	IRS2	17527	-0.1	0.042	NO

Figure S95. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG LINOLEIC ACID METABOLISM.

Figure S96. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LINOLEIC 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 SPHINGOLIPID METABOLISM

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	CLDN16	CLDN16	CLDN16	242	0.8	0.063	YES
2	CLDN8	CLDN8	CLDN8	400	0.53	0.1	YES
3	ACTN2	ACTN2	ACTN2	704	0.37	0.12	YES
4	CLDN9	CLDN9	CLDN9	1147	0.29	0.13	YES
5	VAV3	VAV3	VAV3	1292	0.27	0.14	YES
6	TXK	TXK	TXK	1554	0.24	0.15	YES
7	PRKCB	PRKCB	PRKCB	1559	0.24	0.18	YES
8	JAM2	JAM2	JAM2	1580	0.24	0.2	YES
9	CLDN18	CLDN18	CLDN18	1601	0.24	0.22	YES
10	ITK	ITK	ITK	1671	0.23	0.24	YES
11	CLDN10	CLDN10	CLDN10	2044	0.2	0.23	YES
12	MYL2	MYL2	MYL2	2239	0.19	0.24	YES
13	CLDN1	CLDN1	CLDN1	2332	0.18	0.25	YES
14	PIK3CG	PIK3CG	PIK3CG	2409	0.18	0.27	YES
15	CLDN19	CLDN19	CLDN19	2420	0.18	0.28	YES
16	MAPK11	MAPK11	MAPK11	2438	0.18	0.3	YES
17	NOX1	NOX1	NOX1	2501	0.18	0.31	YES
18	CXCL12	CXCL12	CXCL12	2581	0.17	0.32	YES
19	CLDN2	CLDN2	CLDN2	2658	0.17	0.34	YES
20	CTNNA2	CTNNA2	CTNNA2	2680	0.16	0.35	YES
21	CLDN5	CLDN5	CLDN5	2750	0.16	0.36	YES
22	PLCG2	PLCG2	PLCG2	2805	0.16	0.37	YES
23	PIK3R5	PIK3R5	PIK3R5	2835	0.16	0.39	YES
24	ITGAL	ITGAL	ITGAL	2954	0.15	0.4	YES
25	CLDN11	CLDN11	CLDN11	2969	0.15	0.41	YES
26	NCF1	NCF1	NCF1	3006	0.15	0.42	YES
27	NCF4	NCF4	NCF4	3059	0.15	0.43	YES
28	VAV1	VAV1	VAV1	3216	0.14	0.44	YES
29	CLDN20	CLDN20	CLDN20	3312	0.14	0.44	YES
30	RHOH	RHOH	RHOH	3396	0.14	0.45	YES
31	PTK2B	PTK2B	PTK2B	3669	0.12	0.45	YES
32	MYL9	MYL9	MYL9	3869	0.12	0.45	YES
33	RAPGEF3	RAPGEF3	RAPGEF3	3874	0.12	0.46	YES
34	ITGAM	ITGAM	ITGAM	3928	0.12	0.47	YES
35	ITGA4	ITGA4	ITGA4	3949	0.12	0.48	YES
36	JAM3	JAM3	JAM3	3959	0.12	0.49	YES
37	PIK3CD	PIK3CD	PIK3CD	4010	0.11	0.5	YES
38	MMP2	MMP2	MMP2	4089	0.11	0.5	YES
39	VCAM1	VCAM1	VCAM1	4152	0.11	0.51	YES
40	MMP9	MMP9	MMP9	4233	0.11	0.52	YES
41	CXCR4	CXCR4	CXCR4	4284	0.11	0.52	YES
42	PIK3R1	PIK3R1	PIK3R1	4307	0.1	0.53	YES
43	NCF2	NCF2	NCF2	4381	0.1	0.54	YES
44	RASSF5	RASSF5	RASSF5	4706	0.094	0.53	YES
45	ITGB2	ITGB2	ITGB2	4768	0.093	0.54	YES
46	CYBB	CYBB	CYBB	4865	0.09	0.54	YES
47	RAPGEF4	RAPGEF4	RAPGEF4	4879	0.09	0.55	YES
48	PIK3R3	PIK3R3	PIK3R3	4996	0.087	0.55	YES
49	RAC2	RAC2	RAC2	5129	0.084	0.55	YES
50	ESAM	ESAM	ESAM	5177	0.083	0.55	YES
51	MYLPF	MYLPF	MYLPF	5226	0.082	0.56	YES
52	CDH5	CDH5	CDH5	5401	0.078	0.56	YES
53	PECAM1	PECAM1	PECAM1	5545	0.074	0.56	YES
54	CLDN15	CLDN15	CLDN15	5585	0.073	0.56	YES
55	MYL5	MYL5	MYL5	5720	0.071	0.56	YES
56	PRKCA	PRKCA	PRKCA	5769	0.07	0.56	YES
57	ICAM1	ICAM1	ICAM1	6330	0.059	0.54	NO
58	EZR	EZR	EZR	6724	0.052	0.52	NO
59	CLDN23	CLDN23	CLDN23	6825	0.051	0.52	NO
60	CLDN3	CLDN3	CLDN3	7003	0.048	0.52	NO
61	MAPK12	MAPK12	MAPK12	7180	0.045	0.51	NO
62	SIPA1	SIPA1	SIPA1	7403	0.041	0.5	NO
63	GNAI2	GNAI2	GNAI2	7543	0.039	0.5	NO
64	MLLT4	MLLT4	MLLT4	7583	0.039	0.5	NO
65	BCAR1	BCAR1	BCAR1	7597	0.038	0.5	NO
66	CLDN4	CLDN4	CLDN4	7624	0.038	0.5	NO
67	CYBA	CYBA	CYBA	7756	0.036	0.5	NO
68	PLCG1	PLCG1	PLCG1	7836	0.035	0.5	NO
69	PRKCG	PRKCG	PRKCG	7902	0.034	0.5	NO
70	ACTN1	ACTN1	ACTN1	8323	0.029	0.48	NO
71	PXN	PXN	PXN	8326	0.029	0.48	NO
72	VCL	VCL	VCL	8769	0.024	0.46	NO
73	VASP	VASP	VASP	8777	0.024	0.46	NO
74	RAP1A	RAP1A	RAP1A	9107	0.02	0.45	NO
75	PIK3R2	PIK3R2	PIK3R2	9252	0.019	0.44	NO
76	THY1	THY1	THY1	9391	0.017	0.43	NO
77	ACTN4	ACTN4	ACTN4	9466	0.016	0.43	NO
78	CD99	CD99	CD99	9718	0.014	0.42	NO
79	CTNNA1	CTNNA1	CTNNA1	9850	0.013	0.41	NO
80	MSN	MSN	MSN	9914	0.012	0.41	NO
81	ACTB	ACTB	ACTB	10034	0.011	0.4	NO
82	MYL12A	MYL12A	MYL12A	10566	0.0066	0.38	NO
83	F11R	F11R	F11R	10962	0.0032	0.36	NO
84	MYL12B	MYL12B	MYL12B	10974	0.0031	0.36	NO
85	CTNNB1	CTNNB1	CTNNB1	10977	0.003	0.36	NO
86	CDC42	CDC42	CDC42	11071	0.0022	0.35	NO
87	GNAI1	GNAI1	GNAI1	11155	0.0014	0.35	NO
88	PIK3CA	PIK3CA	PIK3CA	11272	0.00046	0.34	NO
89	ROCK1	ROCK1	ROCK1	11418	-0.00072	0.33	NO
90	MAPK14	MAPK14	MAPK14	11777	-0.0038	0.31	NO
91	RHOA	RHOA	RHOA	11860	-0.0044	0.31	NO
92	ACTG1	ACTG1	ACTG1	11966	-0.0053	0.3	NO
93	GNAI3	GNAI3	GNAI3	12123	-0.0067	0.3	NO
94	RAC1	RAC1	RAC1	12142	-0.0068	0.3	NO
95	RAP1B	RAP1B	RAP1B	12191	-0.0073	0.29	NO
96	CTNND1	CTNND1	CTNND1	12352	-0.0086	0.28	NO
97	OCLN	OCLN	OCLN	12455	-0.0096	0.28	NO
98	VAV2	VAV2	VAV2	12726	-0.012	0.27	NO
99	CTNNA3	CTNNA3	CTNNA3	13112	-0.015	0.25	NO
100	PIK3CB	PIK3CB	PIK3CB	13151	-0.016	0.25	NO
101	ROCK2	ROCK2	ROCK2	13196	-0.016	0.24	NO
102	CLDN7	CLDN7	CLDN7	13856	-0.022	0.21	NO
103	PTK2	PTK2	PTK2	14778	-0.031	0.16	NO
104	CLDN6	CLDN6	CLDN6	15294	-0.037	0.14	NO
105	ACTN3	ACTN3	ACTN3	15311	-0.037	0.14	NO
106	ITGB1	ITGB1	ITGB1	15341	-0.038	0.14	NO
107	ARHGAP5	ARHGAP5	ARHGAP5	15345	-0.038	0.15	NO
108	PTPN11	PTPN11	PTPN11	16211	-0.05	0.1	NO
109	MAPK13	MAPK13	MAPK13	16507	-0.057	0.093	NO
110	CLDN14	CLDN14	CLDN14	16687	-0.062	0.089	NO

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

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

genes ES table in pathway: KEGG RETINOL METABOLISM

Table 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	ERBB4	ERBB4	ERBB4	373	0.56	0.072	YES
2	ADCY2	ADCY2	ADCY2	401	0.53	0.16	YES
3	NRG2	NRG2	NRG2	489	0.46	0.23	YES
4	NRG4	NRG4	NRG4	1495	0.25	0.22	YES
5	ADCY5	ADCY5	ADCY5	1518	0.24	0.26	YES
6	BTC	BTC	BTC	1556	0.24	0.3	YES
7	CAMK4	CAMK4	CAMK4	1614	0.24	0.33	YES
8	NRG1	NRG1	NRG1	1641	0.23	0.37	YES
9	MATK	MATK	MATK	1746	0.22	0.4	YES
10	PDE1B	PDE1B	PDE1B	2126	0.2	0.41	YES
11	ADCY4	ADCY4	ADCY4	2271	0.19	0.44	YES
12	PRKCE	PRKCE	PRKCE	3760	0.12	0.38	NO
13	PIK3R1	PIK3R1	PIK3R1	4307	0.1	0.36	NO
14	PDE1A	PDE1A	PDE1A	4482	0.1	0.37	NO
15	ADCY9	ADCY9	ADCY9	4657	0.095	0.38	NO
16	FOXO1	FOXO1	FOXO1	5112	0.085	0.36	NO
17	PRKAR2B	PRKAR2B	PRKAR2B	5123	0.084	0.38	NO
18	CDKN1A	CDKN1A	CDKN1A	5422	0.077	0.38	NO
19	PRKCA	PRKCA	PRKCA	5769	0.07	0.37	NO
20	FOXO3	FOXO3	FOXO3	6434	0.057	0.34	NO
21	CALM1	CALM1	CALM1	6471	0.056	0.35	NO
22	FYN	FYN	FYN	6857	0.05	0.34	NO
23	GAB1	GAB1	GAB1	6891	0.049	0.34	NO
24	HBEGF	HBEGF	HBEGF	6923	0.049	0.35	NO
25	BAD	BAD	BAD	7126	0.046	0.34	NO
26	NR4A1	NR4A1	NR4A1	7163	0.045	0.35	NO
27	PRKACB	PRKACB	PRKACB	7439	0.041	0.34	NO
28	ITPR2	ITPR2	ITPR2	7589	0.038	0.34	NO
29	PLCG1	PLCG1	PLCG1	7836	0.035	0.33	NO
30	PRKCG	PRKCG	PRKCG	7902	0.034	0.34	NO
31	AKT3	AKT3	AKT3	8092	0.032	0.33	NO
32	FOXO4	FOXO4	FOXO4	8182	0.031	0.33	NO
33	PHLPP1	PHLPP1	PHLPP1	8221	0.03	0.33	NO
34	EREG	EREG	EREG	8464	0.027	0.32	NO
35	PDPK1	PDPK1	PDPK1	8581	0.026	0.32	NO
36	PRKAR1B	PRKAR1B	PRKAR1B	8663	0.025	0.32	NO
37	ERBB2	ERBB2	ERBB2	8828	0.023	0.32	NO
38	PRKACA	PRKACA	PRKACA	8885	0.023	0.32	NO
39	EGFR	EGFR	EGFR	9007	0.021	0.32	NO
40	PRKCD	PRKCD	PRKCD	9014	0.021	0.32	NO
41	PTEN	PTEN	PTEN	9153	0.02	0.31	NO
42	ADCY6	ADCY6	ADCY6	9229	0.019	0.31	NO
43	PRKAR1A	PRKAR1A	PRKAR1A	9406	0.017	0.31	NO
44	MAPK3	MAPK3	MAPK3	9791	0.013	0.29	NO
45	STUB1	STUB1	STUB1	9795	0.013	0.29	NO
46	CDKN1B	CDKN1B	CDKN1B	9870	0.013	0.29	NO
47	CASP9	CASP9	CASP9	9891	0.012	0.29	NO
48	CDC37	CDC37	CDC37	10002	0.012	0.28	NO
49	ITPR3	ITPR3	ITPR3	10159	0.01	0.28	NO
50	CALM3	CALM3	CALM3	10422	0.0079	0.26	NO
51	TSC2	TSC2	TSC2	10471	0.0075	0.26	NO
52	MAPK1	MAPK1	MAPK1	10665	0.0057	0.25	NO
53	UBA52	UBA52	UBA52	10806	0.0044	0.25	NO
54	AKT2	AKT2	AKT2	10811	0.0044	0.25	NO
55	CREB1	CREB1	CREB1	10961	0.0032	0.24	NO
56	ADRBK1	ADRBK1	ADRBK1	10969	0.0031	0.24	NO
57	YWHAB	YWHAB	YWHAB	11090	0.002	0.23	NO
58	MAP2K2	MAP2K2	MAP2K2	11159	0.0014	0.23	NO
59	USP8	USP8	USP8	11161	0.0013	0.23	NO
60	HRAS	HRAS	HRAS	11188	0.0011	0.23	NO
61	PIK3CA	PIK3CA	PIK3CA	11272	0.00046	0.22	NO
62	HSP90AA1	HSP90AA1	HSP90AA1	11409	-0.00068	0.22	NO
63	GRB2	GRB2	GRB2	11536	-0.0017	0.21	NO
64	CALM2	CALM2	CALM2	11546	-0.0018	0.21	NO
65	AKT1	AKT1	AKT1	11648	-0.0027	0.2	NO
66	ADCY8	ADCY8	ADCY8	11931	-0.005	0.19	NO
67	MTOR	MTOR	MTOR	12043	-0.006	0.18	NO
68	SOS1	SOS1	SOS1	12264	-0.0079	0.17	NO
69	GRB7	GRB7	GRB7	12295	-0.0081	0.17	NO
70	AKT1S1	AKT1S1	AKT1S1	12311	-0.0082	0.17	NO
71	ADCY7	ADCY7	ADCY7	12387	-0.0089	0.17	NO
72	ADCY3	ADCY3	ADCY3	12394	-0.009	0.17	NO
73	PRKAR2A	PRKAR2A	PRKAR2A	12490	-0.0098	0.17	NO
74	ERBB3	ERBB3	ERBB3	12550	-0.01	0.17	NO
75	CUL5	CUL5	CUL5	12672	-0.011	0.16	NO
76	RAF1	RAF1	RAF1	12900	-0.013	0.15	NO
77	MAPKAP1	MAPKAP1	MAPKAP1	12906	-0.014	0.15	NO
78	RPS27A	RPS27A	RPS27A	12981	-0.014	0.15	NO
79	ADCY1	ADCY1	ADCY1	13032	-0.015	0.15	NO
80	SRC	SRC	SRC	13054	-0.015	0.15	NO
81	RICTOR	RICTOR	RICTOR	13248	-0.016	0.15	NO
82	MDM2	MDM2	MDM2	13355	-0.017	0.14	NO
83	GSK3A	GSK3A	GSK3A	13362	-0.017	0.14	NO
84	RNF41	RNF41	RNF41	13624	-0.02	0.13	NO
85	MLST8	MLST8	MLST8	14221	-0.025	0.11	NO
86	THEM4	THEM4	THEM4	14423	-0.027	0.099	NO
87	RPS6KB2	RPS6KB2	RPS6KB2	14701	-0.03	0.089	NO
88	SHC1	SHC1	SHC1	15471	-0.039	0.053	NO
89	MAP2K1	MAP2K1	MAP2K1	16014	-0.047	0.031	NO
90	YES1	YES1	YES1	16080	-0.048	0.036	NO
91	CHUK	CHUK	CHUK	16088	-0.048	0.044	NO
92	KRAS	KRAS	KRAS	16283	-0.052	0.042	NO
93	NRAS	NRAS	NRAS	16504	-0.057	0.039	NO
94	EGF	EGF	EGF	17255	-0.083	0.012	NO
95	TRIB3	TRIB3	TRIB3	17685	-0.12	0.0078	NO
96	CDK1	CDK1	CDK1	17940	-0.16	0.02	NO

Figure S99. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RETINOL METABOLISM.

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

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 = LUAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = LUAD-TP.mergedcluster.txt

GSEA analysis

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

Download Results

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

References

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

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