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

Thyroid 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 THCA-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1K64HJ9

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 "THCA-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: 705
Number of samples: 501
Original number of Gene Sets: 1320
Maximum gene set size: 933

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 4 :[ clus1 ] 158
pheno.type: 2 - 4 :[ clus2 ] 169
pheno.type: 3 - 4 :[ clus3 ] 59
pheno.type: 4 - 4 :[ clus4 ] 115

For the expression subtypes of 17991 genes in 502 samples, GSEA found enriched gene sets in each cluster using 501 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG DNA REPLICATION, KEGG LYSOSOME, KEGG CHRONIC MYELOID LEUKEMIA, BIOCARTA G1 PATHWAY, ST PHOSPHOINOSITIDE 3 KINASE PATHWAY, PID TNFPATHWAY, PID ECADHERIN NASCENTAJ PATHWAY, PID BARD1PATHWAY, REACTOME ORC1 REMOVAL FROM CHROMATIN, REACTOME ANTIVIRAL MECHANISM BY IFN STIMULATED GENES

And common core enriched genes are DDX58, HERC5, ISG15, STAT1, UBE2L6, ABI1, ARF6, CCND1, CDH1, CRK

clus2

Top enriched gene sets are KEGG OXIDATIVE PHOSPHORYLATION, KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG LYSINE DEGRADATION, KEGG ARGININE AND PROLINE METABOLISM, KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS, KEGG PROPANOATE METABOLISM, KEGG BUTANOATE METABOLISM, KEGG INSULIN SIGNALING PATHWAY, KEGG ADIPOCYTOKINE SIGNALING PATHWAY

And common core enriched genes are ACAT1, ALDH1B1, ALDH2, ALDH7A1, ALDH9A1, ECHS1, EHHADH, HADH, OGDH, ABAT

clus3

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG FATTY ACID METABOLISM, KEGG PURINE METABOLISM, KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, KEGG CYSTEINE AND METHIONINE METABOLISM, KEGG HISTIDINE METABOLISM, KEGG TYROSINE METABOLISM, KEGG TRYPTOPHAN METABOLISM, KEGG GLUTATHIONE METABOLISM

And common core enriched genes are PSMA8, PSMB9, B2M, HLA-A, PSMB10, PSMB8, PSME2, AP1S2, APOBEC3G, CD247

clus4

Top enriched gene sets are KEGG NOTCH SIGNALING PATHWAY, KEGG ADHERENS JUNCTION, KEGG THYROID CANCER, PID LKB1 PATHWAY, PID AJDISS 2PATHWAY, PID TRKRPATHWAY, PID NCADHERINPATHWAY, REACTOME CELL CELL COMMUNICATION, REACTOME NEGATIVE REGULATION OF FGFR SIGNALING, REACTOME ACTIVATED NOTCH1 TRANSMITS SIGNAL TO THE NUCLEUS

And common core enriched genes are CDH2, CLDN1, CLDN10, CLDN11, CLDN15, CLDN16, CLDN19, CLDN2, CLDN5, CLDN6

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	0.55	1.6	0.081	0.58	0.89	0.44	0.23	0.34	0.36	0.17
KEGG LYSOSOME	120	genes.ES.table	0.43	1.7	0.052	0.66	0.78	0.42	0.25	0.32	0.34	0.19
KEGG CHRONIC MYELOID LEUKEMIA	73	genes.ES.table	0.45	1.6	0.034	0.59	0.87	0.29	0.19	0.23	0.35	0.18
BIOCARTA G1 PATHWAY	28	genes.ES.table	0.59	1.6	0.014	0.68	0.84	0.32	0.16	0.27	0.38	0.2
ST PHOSPHOINOSITIDE 3 KINASE PATHWAY	37	genes.ES.table	0.55	1.6	0.024	0.6	0.88	0.38	0.21	0.3	0.36	0.18
PID TNFPATHWAY	46	genes.ES.table	0.53	1.8	0.014	0.78	0.52	0.54	0.28	0.4	0.25	0.22
PID ECADHERIN NASCENTAJ PATHWAY	39	genes.ES.table	0.56	2	0.0019	0.21	0.095	0.64	0.3	0.45	0	0.064
PID BARD1PATHWAY	29	genes.ES.table	0.63	1.7	0.014	0.73	0.71	0.62	0.27	0.45	0.35	0.21
REACTOME ORC1 REMOVAL FROM CHROMATIN	59	genes.ES.table	0.49	1.6	0.085	0.58	0.89	0.2	0.17	0.17	0.36	0.18
REACTOME ANTIVIRAL MECHANISM BY IFN STIMULATED GENES	65	genes.ES.table	0.46	1.8	0.028	1	0.48	0.52	0.3	0.37	0	0.27

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	ITGB7	ITGB7	ITGB7	1306	0.2	0.02	YES
2	TIAM1	TIAM1	TIAM1	1577	0.17	0.086	YES
3	PIK3CA	PIK3CA	PIK3CA	2003	0.14	0.13	YES
4	IQGAP1	IQGAP1	IQGAP1	2148	0.13	0.18	YES
5	ARF6	ARF6	ARF6	2380	0.12	0.22	YES
6	CCND1	CCND1	CCND1	2713	0.098	0.25	YES
7	CTTN	CTTN	CTTN	2796	0.094	0.29	YES
8	PIK3R1	PIK3R1	PIK3R1	3011	0.085	0.32	YES
9	NCKAP1	NCKAP1	NCKAP1	3115	0.081	0.35	YES
10	MLLT4	MLLT4	MLLT4	3216	0.078	0.38	YES
11	ENAH	ENAH	ENAH	3413	0.07	0.4	YES
12	JUP	JUP	JUP	3621	0.064	0.42	YES
13	ABI1	ABI1	ABI1	3668	0.063	0.45	YES
14	CTNNA1	CTNNA1	CTNNA1	4327	0.048	0.43	YES
15	KLHL20	KLHL20	KLHL20	4501	0.045	0.44	YES
16	CTNNB1	CTNNB1	CTNNB1	4732	0.04	0.45	YES
17	CDH1	CDH1	CDH1	4744	0.04	0.47	YES
18	CSNK2A2	CSNK2A2	CSNK2A2	4876	0.037	0.48	YES
19	SRC	SRC	SRC	4946	0.036	0.49	YES
20	CRK	CRK	CRK	5093	0.034	0.5	YES
21	CYFIP2	CYFIP2	CYFIP2	5134	0.033	0.51	YES
22	RAP1A	RAP1A	RAP1A	5164	0.033	0.53	YES
23	TJP1	TJP1	TJP1	5177	0.032	0.54	YES
24	CSNK2A1	CSNK2A1	CSNK2A1	5212	0.032	0.55	YES
25	WASF2	WASF2	WASF2	5332	0.03	0.56	YES
26	CDC42	CDC42	CDC42	5918	0.021	0.54	NO
27	RHOA	RHOA	RHOA	6027	0.019	0.54	NO
28	RAC1	RAC1	RAC1	6376	0.015	0.53	NO
29	CSNK2B	CSNK2B	CSNK2B	6735	0.011	0.51	NO
30	CTNND1	CTNND1	CTNND1	7058	0.0069	0.5	NO
31	RAP1B	RAP1B	RAP1B	7222	0.0051	0.49	NO
32	VAV2	VAV2	VAV2	7349	0.0036	0.49	NO
33	NME1	NME1	NME1	7835	-0.0017	0.46	NO
34	AP1M1	AP1M1	AP1M1	8455	-0.0091	0.43	NO
35	AKT1	AKT1	AKT1	8784	-0.013	0.42	NO
36	PIP5K1C	PIP5K1C	PIP5K1C	9380	-0.02	0.4	NO
37	RAPGEF1	RAPGEF1	RAPGEF1	9717	-0.024	0.39	NO
38	DLG1	DLG1	DLG1	10680	-0.037	0.35	NO
39	ITGAE	ITGAE	ITGAE	14065	-0.12	0.22	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 LYSOSOME

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	IFIT1	IFIT1	IFIT1	1323	0.2	-0.0071	YES
2	STAT1	STAT1	STAT1	1548	0.17	0.039	YES
3	HERC5	HERC5	HERC5	1748	0.15	0.08	YES
4	MX1	MX1	MX1	1855	0.15	0.12	YES
5	ISG15	ISG15	ISG15	1918	0.14	0.17	YES
6	EIF2AK2	EIF2AK2	EIF2AK2	2121	0.13	0.2	YES
7	UBE2L6	UBE2L6	UBE2L6	2575	0.1	0.21	YES
8	NUP155	NUP155	NUP155	2889	0.09	0.22	YES
9	DDX58	DDX58	DDX58	3370	0.072	0.22	YES
10	KPNA2	KPNA2	KPNA2	3536	0.067	0.24	YES
11	JAK1	JAK1	JAK1	3878	0.058	0.24	YES
12	KPNA1	KPNA1	KPNA1	3886	0.058	0.26	YES
13	NUP93	NUP93	NUP93	3942	0.057	0.27	YES
14	NUP188	NUP188	NUP188	4010	0.055	0.29	YES
15	EIF4G1	EIF4G1	EIF4G1	4186	0.051	0.29	YES
16	NUP133	NUP133	NUP133	4315	0.048	0.3	YES
17	SEH1L	SEH1L	SEH1L	4503	0.045	0.31	YES
18	MX2	MX2	MX2	4631	0.042	0.32	YES
19	NUPL1	NUPL1	NUPL1	4648	0.042	0.33	YES
20	ARIH1	ARIH1	ARIH1	4772	0.039	0.34	YES
21	NUP85	NUP85	NUP85	4789	0.039	0.35	YES
22	KPNA3	KPNA3	KPNA3	4802	0.039	0.36	YES
23	NEDD4	NEDD4	NEDD4	4805	0.038	0.37	YES
24	EIF4A3	EIF4A3	EIF4A3	4900	0.037	0.38	YES
25	FLNB	FLNB	FLNB	4977	0.036	0.39	YES
26	NUP62	NUP62	NUP62	4989	0.036	0.4	YES
27	UBE2E1	UBE2E1	UBE2E1	5027	0.035	0.41	YES
28	NUP107	NUP107	NUP107	5065	0.034	0.42	YES
29	UBA52	UBA52	UBA52	5090	0.034	0.43	YES
30	EIF4A1	EIF4A1	EIF4A1	5101	0.034	0.44	YES
31	KPNA4	KPNA4	KPNA4	5125	0.033	0.45	YES
32	EIF4A2	EIF4A2	EIF4A2	5280	0.03	0.45	YES
33	TPR	TPR	TPR	5349	0.03	0.46	YES
34	KPNB1	KPNB1	KPNB1	5395	0.029	0.46	YES
35	NUP153	NUP153	NUP153	6191	0.017	0.43	NO
36	NUP54	NUP54	NUP54	6338	0.016	0.42	NO
37	NUP43	NUP43	NUP43	6504	0.014	0.42	NO
38	RPS27A	RPS27A	RPS27A	6554	0.013	0.42	NO
39	PIN1	PIN1	PIN1	6924	0.0085	0.4	NO
40	UBA7	UBA7	UBA7	6961	0.008	0.4	NO
41	NUP214	NUP214	NUP214	7123	0.006	0.4	NO
42	NUP205	NUP205	NUP205	7229	0.005	0.39	NO
43	EIF4G2	EIF4G2	EIF4G2	7253	0.0047	0.39	NO
44	IRF3	IRF3	IRF3	7294	0.0041	0.39	NO
45	RANBP2	RANBP2	RANBP2	7303	0.0041	0.39	NO
46	USP18	USP18	USP18	7475	0.0022	0.38	NO
47	MAPK3	MAPK3	MAPK3	7882	-0.0022	0.36	NO
48	PPM1B	PPM1B	PPM1B	8297	-0.0072	0.34	NO
49	EIF4E3	EIF4E3	EIF4E3	8505	-0.0098	0.33	NO
50	RAE1	RAE1	RAE1	8546	-0.01	0.33	NO
51	POM121	POM121	POM121	8552	-0.01	0.34	NO
52	EIF4E2	EIF4E2	EIF4E2	8839	-0.014	0.33	NO
53	NUP50	NUP50	NUP50	8861	-0.014	0.33	NO
54	TRIM25	TRIM25	TRIM25	9651	-0.024	0.29	NO
55	EIF4E	EIF4E	EIF4E	9654	-0.024	0.3	NO
56	UBE2N	UBE2N	UBE2N	9704	-0.024	0.31	NO
57	NUPL2	NUPL2	NUPL2	9807	-0.025	0.31	NO
58	NUP210	NUP210	NUP210	9968	-0.028	0.31	NO
59	NUP37	NUP37	NUP37	10145	-0.03	0.31	NO
60	EIF4G3	EIF4G3	EIF4G3	10820	-0.039	0.29	NO
61	PLCG1	PLCG1	PLCG1	11980	-0.059	0.24	NO
62	NUP88	NUP88	NUP88	11987	-0.059	0.26	NO
63	AAAS	AAAS	AAAS	12060	-0.061	0.28	NO
64	NUP35	NUP35	NUP35	12209	-0.064	0.29	NO
65	KPNA5	KPNA5	KPNA5	13176	-0.088	0.27	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 LYSOSOME.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LYSOSOME, 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 CHRONIC MYELOID LEUKEMIA

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	BIRC3	BIRC3	BIRC3	304	0.42	0.13	YES
2	MAP3K5	MAP3K5	MAP3K5	976	0.24	0.17	YES
3	STAT1	STAT1	STAT1	1548	0.17	0.2	YES
4	CAV1	CAV1	CAV1	1627	0.16	0.25	YES
5	NRK	NRK	NRK	1930	0.14	0.28	YES
6	BAG4	BAG4	BAG4	2272	0.12	0.3	YES
7	MAP3K7	MAP3K7	MAP3K7	3005	0.086	0.29	YES
8	MAP3K1	MAP3K1	MAP3K1	3019	0.085	0.32	YES
9	TNFRSF1B	TNFRSF1B	TNFRSF1B	3073	0.083	0.35	YES
10	TNIK	TNIK	TNIK	3142	0.08	0.37	YES
11	SQSTM1	SQSTM1	SQSTM1	3601	0.065	0.37	YES
12	PRKCI	PRKCI	PRKCI	3925	0.057	0.37	YES
13	MAP2K3	MAP2K3	MAP2K3	3935	0.057	0.39	YES
14	MAP4K4	MAP4K4	MAP4K4	3950	0.056	0.41	YES
15	TXN	TXN	TXN	4022	0.055	0.42	YES
16	FADD	FADD	FADD	4107	0.053	0.43	YES
17	NFKB1	NFKB1	NFKB1	4127	0.052	0.45	YES
18	TNFRSF1A	TNFRSF1A	TNFRSF1A	4155	0.052	0.47	YES
19	NSMAF	NSMAF	NSMAF	4181	0.051	0.48	YES
20	RELA	RELA	RELA	4256	0.049	0.5	YES
21	BIRC2	BIRC2	BIRC2	4359	0.047	0.51	YES
22	TNF	TNF	TNF	4633	0.042	0.5	YES
23	ADAM17	ADAM17	ADAM17	4675	0.041	0.52	YES
24	GNB2L1	GNB2L1	GNB2L1	4737	0.04	0.53	YES
25	CHUK	CHUK	CHUK	4936	0.036	0.53	YES
26	MAP3K3	MAP3K3	MAP3K3	5241	0.031	0.52	NO
27	MAP4K3	MAP4K3	MAP4K3	5696	0.024	0.5	NO
28	TAB1	TAB1	TAB1	5708	0.024	0.51	NO
29	MAP4K5	MAP4K5	MAP4K5	6686	0.012	0.46	NO
30	MAP2K7	MAP2K7	MAP2K7	6806	0.0099	0.46	NO
31	TNFAIP3	TNFAIP3	TNFAIP3	6830	0.0096	0.46	NO
32	SMPD1	SMPD1	SMPD1	7809	-0.0014	0.41	NO
33	TRADD	TRADD	TRADD	7996	-0.0037	0.4	NO
34	TAB2	TAB2	TAB2	8147	-0.0055	0.39	NO
35	CASP8	CASP8	CASP8	8189	-0.0059	0.39	NO
36	PRKCZ	PRKCZ	PRKCZ	8377	-0.0081	0.38	NO
37	CYLD	CYLD	CYLD	8393	-0.0083	0.38	NO
38	RIPK1	RIPK1	RIPK1	9231	-0.018	0.34	NO
39	TRAF1	TRAF1	TRAF1	9716	-0.024	0.33	NO
40	SMPD2	SMPD2	SMPD2	10009	-0.028	0.32	NO
41	MADD	MADD	MADD	10909	-0.041	0.28	NO
42	IKBKB	IKBKB	IKBKB	11113	-0.044	0.29	NO
43	TRAF2	TRAF2	TRAF2	11234	-0.046	0.3	NO
44	IKBKG	IKBKG	IKBKG	12054	-0.06	0.27	NO
45	RFFL	RFFL	RFFL	12332	-0.066	0.28	NO
46	MAP4K2	MAP4K2	MAP4K2	13762	-0.1	0.24	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 CHRONIC MYELOID LEUKEMIA.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CHRONIC MYELOID LEUKEMIA, 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 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	HERC5	HERC5	HERC5	1748	0.15	0.023	YES
2	NLRC5	NLRC5	NLRC5	1904	0.14	0.13	YES
3	ISG15	ISG15	ISG15	1918	0.14	0.24	YES
4	RNF125	RNF125	RNF125	1927	0.14	0.35	YES
5	IFIH1	IFIH1	IFIH1	2220	0.12	0.43	YES
6	UBE2L6	UBE2L6	UBE2L6	2575	0.1	0.49	YES
7	DDX58	DDX58	DDX58	3370	0.072	0.5	YES
8	UBE2D1	UBE2D1	UBE2D1	3520	0.067	0.55	YES
9	ATG12	ATG12	ATG12	4654	0.042	0.52	NO
10	UBA52	UBA52	UBA52	5090	0.034	0.52	NO
11	TBK1	TBK1	TBK1	6018	0.02	0.48	NO
12	NLRX1	NLRX1	NLRX1	6020	0.02	0.5	NO
13	ATG5	ATG5	ATG5	6305	0.016	0.5	NO
14	TRAF3	TRAF3	TRAF3	6319	0.016	0.51	NO
15	TAX1BP1	TAX1BP1	TAX1BP1	6325	0.016	0.52	NO
16	RPS27A	RPS27A	RPS27A	6554	0.013	0.52	NO
17	TNFAIP3	TNFAIP3	TNFAIP3	6830	0.0096	0.51	NO
18	PIN1	PIN1	PIN1	6924	0.0085	0.51	NO
19	UBA7	UBA7	UBA7	6961	0.008	0.52	NO
20	OTUD5	OTUD5	OTUD5	7275	0.0044	0.5	NO
21	IRF3	IRF3	IRF3	7294	0.0041	0.5	NO
22	UBE2D3	UBE2D3	UBE2D3	7528	0.0016	0.49	NO
23	PCBP2	PCBP2	PCBP2	7900	-0.0024	0.47	NO
24	UBE2K	UBE2K	UBE2K	8157	-0.0056	0.46	NO
25	MAVS	MAVS	MAVS	8293	-0.0071	0.46	NO
26	CYLD	CYLD	CYLD	8393	-0.0083	0.46	NO
27	IKBKE	IKBKE	IKBKE	8847	-0.014	0.45	NO
28	RNF135	RNF135	RNF135	9554	-0.022	0.43	NO
29	TRIM25	TRIM25	TRIM25	9651	-0.024	0.44	NO
30	UBE2D2	UBE2D2	UBE2D2	10076	-0.029	0.44	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 G1 PATHWAY.

Figure S8. 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: ST PHOSPHOINOSITIDE 3 KINASE 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	PMAIP1	PMAIP1	PMAIP1	105	0.57	0.24	YES
2	BID	BID	BID	1015	0.23	0.3	YES
3	E2F1	E2F1	E2F1	1188	0.21	0.38	YES
4	BCL2L1	BCL2L1	BCL2L1	1515	0.18	0.44	YES
5	BBC3	BBC3	BBC3	1659	0.16	0.5	YES
6	BAX	BAX	BAX	3252	0.076	0.45	NO
7	CASP7	CASP7	CASP7	4872	0.038	0.37	NO
8	CASP3	CASP3	CASP3	6151	0.018	0.31	NO
9	APAF1	APAF1	APAF1	6327	0.016	0.31	NO
10	TP53	TP53	TP53	6435	0.014	0.31	NO
11	MAPK8	MAPK8	MAPK8	6449	0.014	0.31	NO
12	YWHAB	YWHAB	YWHAB	6486	0.014	0.32	NO
13	XIAP	XIAP	XIAP	6779	0.01	0.31	NO
14	PPP3R1	PPP3R1	PPP3R1	6997	0.0076	0.3	NO
15	NMT1	NMT1	NMT1	7323	0.0038	0.28	NO
16	DYNLL1	DYNLL1	DYNLL1	7415	0.0029	0.28	NO
17	BCL2L11	BCL2L11	BCL2L11	7942	-0.003	0.25	NO
18	CASP8	CASP8	CASP8	8189	-0.0059	0.24	NO
19	TFDP1	TFDP1	TFDP1	8587	-0.011	0.22	NO
20	AKT1	AKT1	AKT1	8784	-0.013	0.22	NO
21	DYNLL2	DYNLL2	DYNLL2	9347	-0.02	0.19	NO
22	GZMB	GZMB	GZMB	10586	-0.036	0.14	NO
23	DIABLO	DIABLO	DIABLO	10694	-0.037	0.15	NO
24	BAK1	BAK1	BAK1	11323	-0.048	0.14	NO
25	CYCS	CYCS	CYCS	12535	-0.071	0.099	NO
26	BMF	BMF	BMF	12692	-0.075	0.12	NO
27	BAD	BAD	BAD	12971	-0.082	0.14	NO
28	CASP9	CASP9	CASP9	13648	-0.1	0.15	NO
29	BCL2	BCL2	BCL2	15582	-0.2	0.13	NO

Figure S9. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: ST PHOSPHOINOSITIDE 3 KINASE PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: ST PHOSPHOINOSITIDE 3 KINASE 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 TNFPATHWAY

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	RAD51	RAD51	RAD51	768	0.28	0.088	YES
2	FANCA	FANCA	FANCA	897	0.25	0.2	YES
3	FANCD2	FANCD2	FANCD2	1314	0.2	0.27	YES
4	BARD1	BARD1	BARD1	1526	0.17	0.34	YES
5	FANCE	FANCE	FANCE	1797	0.15	0.4	YES
6	RBBP8	RBBP8	RBBP8	2189	0.12	0.43	YES
7	CCNE1	CCNE1	CCNE1	2686	0.099	0.45	YES
8	CDK2	CDK2	CDK2	2858	0.092	0.48	YES
9	PCNA	PCNA	PCNA	3292	0.074	0.5	YES
10	PRKDC	PRKDC	PRKDC	3437	0.07	0.52	YES
11	MRE11A	MRE11A	MRE11A	3833	0.059	0.52	YES
12	TOPBP1	TOPBP1	TOPBP1	3868	0.058	0.55	YES
13	NBN	NBN	NBN	4055	0.054	0.57	YES
14	RAD50	RAD50	RAD50	4221	0.05	0.58	YES
15	XRCC6	XRCC6	XRCC6	4253	0.05	0.6	YES
16	NPM1	NPM1	NPM1	4283	0.049	0.62	YES
17	XRCC5	XRCC5	XRCC5	4641	0.042	0.62	YES
18	FANCG	FANCG	FANCG	4899	0.037	0.63	YES
19	TP53	TP53	TP53	6435	0.014	0.55	NO
20	FANCL	FANCL	FANCL	7047	0.007	0.52	NO
21	UBE2D3	UBE2D3	UBE2D3	7528	0.0016	0.49	NO
22	BRCA1	BRCA1	BRCA1	7808	-0.0014	0.48	NO
23	UBE2L3	UBE2L3	UBE2L3	8084	-0.0047	0.46	NO
24	ATM	ATM	ATM	8259	-0.0068	0.46	NO
25	CSTF1	CSTF1	CSTF1	9310	-0.019	0.41	NO
26	EWSR1	EWSR1	EWSR1	9658	-0.024	0.4	NO
27	FANCF	FANCF	FANCF	10058	-0.029	0.39	NO
28	ATR	ATR	ATR	10129	-0.03	0.4	NO
29	FANCC	FANCC	FANCC	12902	-0.08	0.28	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 TNFPATHWAY.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: PID TNFPATHWAY, 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 ECADHERIN NASCENTAJ 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	CCNA1	CCNA1	CCNA1	24	0.74	0.13	YES
2	CDC45	CDC45	CDC45	477	0.36	0.17	YES
3	POLE2	POLE2	POLE2	677	0.3	0.21	YES
4	CDT1	CDT1	CDT1	1023	0.23	0.23	YES
5	MCM4	MCM4	MCM4	1101	0.22	0.27	YES
6	GINS1	GINS1	GINS1	1341	0.2	0.29	YES
7	CDC6	CDC6	CDC6	1475	0.18	0.31	YES
8	PSMB9	PSMB9	PSMB9	1601	0.17	0.34	YES
9	POLD1	POLD1	POLD1	1920	0.14	0.34	YES
10	PSMB8	PSMB8	PSMB8	1928	0.14	0.37	YES
11	PRIM2	PRIM2	PRIM2	1936	0.14	0.39	YES
12	MCM6	MCM6	MCM6	2002	0.14	0.41	YES
13	MCM2	MCM2	MCM2	2038	0.14	0.43	YES
14	CDKN1A	CDKN1A	CDKN1A	2100	0.13	0.45	YES
15	GINS2	GINS2	GINS2	2223	0.12	0.47	YES
16	MCM5	MCM5	MCM5	2520	0.11	0.47	YES
17	GINS4	GINS4	GINS4	2690	0.099	0.48	YES
18	PRIM1	PRIM1	PRIM1	2828	0.093	0.49	YES
19	CDK2	CDK2	CDK2	2858	0.092	0.5	YES
20	MCM8	MCM8	MCM8	3105	0.082	0.5	YES
21	RFC3	RFC3	RFC3	3110	0.081	0.52	YES
22	PCNA	PCNA	PCNA	3292	0.074	0.52	YES
23	FEN1	FEN1	FEN1	3500	0.068	0.52	YES
24	POLA2	POLA2	POLA2	3757	0.061	0.52	YES
25	CCNA2	CCNA2	CCNA2	3786	0.06	0.53	YES
26	RFC4	RFC4	RFC4	3839	0.059	0.53	YES
27	POLE	POLE	POLE	3899	0.058	0.54	YES
28	RPA3	RPA3	RPA3	4110	0.053	0.54	YES
29	PSMD2	PSMD2	PSMD2	4235	0.05	0.54	YES
30	PSMA5	PSMA5	PSMA5	4333	0.048	0.54	YES
31	PSMD11	PSMD11	PSMD11	4698	0.041	0.53	NO
32	UBA52	UBA52	UBA52	5090	0.034	0.51	NO
33	PSMD1	PSMD1	PSMD1	5387	0.029	0.5	NO
34	POLA1	POLA1	POLA1	5408	0.029	0.51	NO
35	PSMA7	PSMA7	PSMA7	5472	0.028	0.51	NO
36	PSMD8	PSMD8	PSMD8	5477	0.028	0.51	NO
37	MCM3	MCM3	MCM3	5582	0.026	0.51	NO
38	MCM7	MCM7	MCM7	5645	0.025	0.51	NO
39	RFC5	RFC5	RFC5	5677	0.024	0.52	NO
40	PSMB5	PSMB5	PSMB5	5736	0.024	0.52	NO
41	LIG1	LIG1	LIG1	5818	0.022	0.52	NO
42	PSMC6	PSMC6	PSMC6	5828	0.022	0.52	NO
43	PSMB10	PSMB10	PSMB10	5893	0.021	0.52	NO
44	PSMA6	PSMA6	PSMA6	6090	0.018	0.51	NO
45	PSMA1	PSMA1	PSMA1	6142	0.018	0.51	NO
46	RPA1	RPA1	RPA1	6244	0.017	0.51	NO
47	PSMB2	PSMB2	PSMB2	6527	0.013	0.5	NO
48	RPS27A	RPS27A	RPS27A	6554	0.013	0.5	NO
49	PSMD7	PSMD7	PSMD7	6655	0.012	0.49	NO
50	RFC2	RFC2	RFC2	6691	0.011	0.49	NO
51	PSMD14	PSMD14	PSMD14	6714	0.011	0.49	NO
52	PSME1	PSME1	PSME1	6867	0.0093	0.49	NO
53	POLD4	POLD4	POLD4	6925	0.0085	0.48	NO
54	PSMA2	PSMA2	PSMA2	7008	0.0074	0.48	NO
55	POLD3	POLD3	POLD3	7014	0.0073	0.48	NO
56	PSMD5	PSMD5	PSMD5	7067	0.0068	0.48	NO
57	CDKN1B	CDKN1B	CDKN1B	7330	0.0037	0.47	NO
58	RB1	RB1	RB1	7546	0.0014	0.46	NO
59	PSMD4	PSMD4	PSMD4	7577	0.0011	0.45	NO
60	PSMD10	PSMD10	PSMD10	7667	0.00016	0.45	NO
61	PSMC2	PSMC2	PSMC2	7863	-0.0019	0.44	NO
62	PSMD12	PSMD12	PSMD12	7871	-0.002	0.44	NO
63	RPA2	RPA2	RPA2	8043	-0.0043	0.43	NO
64	PSMB4	PSMB4	PSMB4	8156	-0.0056	0.42	NO
65	PSMB7	PSMB7	PSMB7	8288	-0.007	0.42	NO
66	DNA2	DNA2	DNA2	8324	-0.0074	0.42	NO
67	PSMA3	PSMA3	PSMA3	8526	-0.01	0.41	NO
68	PSMD6	PSMD6	PSMD6	8621	-0.011	0.4	NO
69	PSMB1	PSMB1	PSMB1	8844	-0.014	0.4	NO
70	PSMD3	PSMD3	PSMD3	8856	-0.014	0.4	NO
71	PSMA4	PSMA4	PSMA4	8976	-0.016	0.39	NO
72	PSMD9	PSMD9	PSMD9	9297	-0.019	0.38	NO
73	PSMC1	PSMC1	PSMC1	9518	-0.022	0.37	NO
74	PSMC3	PSMC3	PSMC3	9623	-0.023	0.37	NO
75	PSMD13	PSMD13	PSMD13	9688	-0.024	0.37	NO
76	PSMB3	PSMB3	PSMB3	9707	-0.024	0.37	NO
77	PSME2	PSME2	PSME2	9835	-0.026	0.37	NO
78	PSME4	PSME4	PSME4	9916	-0.027	0.37	NO
79	PSMC4	PSMC4	PSMC4	9932	-0.027	0.37	NO
80	PSMF1	PSMF1	PSMF1	10002	-0.028	0.38	NO
81	PSMB6	PSMB6	PSMB6	10222	-0.031	0.37	NO
82	PSMC5	PSMC5	PSMC5	10923	-0.041	0.34	NO
83	POLD2	POLD2	POLD2	11956	-0.059	0.29	NO
84	PSMA8	PSMA8	PSMA8	16264	-0.26	0.095	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 ECADHERIN NASCENTAJ PATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: PID ECADHERIN NASCENTAJ 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 BARD1PATHWAY

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	CCNA1	CCNA1	CCNA1	24	0.74	0.11	YES
2	CDC45	CDC45	CDC45	477	0.36	0.14	YES
3	POLE2	POLE2	POLE2	677	0.3	0.17	YES
4	CDT1	CDT1	CDT1	1023	0.23	0.18	YES
5	MCM4	MCM4	MCM4	1101	0.22	0.21	YES
6	CCNE2	CCNE2	CCNE2	1153	0.22	0.24	YES
7	GINS1	GINS1	GINS1	1341	0.2	0.26	YES
8	CDC6	CDC6	CDC6	1475	0.18	0.28	YES
9	PSMB9	PSMB9	PSMB9	1601	0.17	0.3	YES
10	POLD1	POLD1	POLD1	1920	0.14	0.3	YES
11	PSMB8	PSMB8	PSMB8	1928	0.14	0.32	YES
12	PRIM2	PRIM2	PRIM2	1936	0.14	0.34	YES
13	MCM6	MCM6	MCM6	2002	0.14	0.36	YES
14	MCM2	MCM2	MCM2	2038	0.14	0.37	YES
15	CDKN1A	CDKN1A	CDKN1A	2100	0.13	0.39	YES
16	GINS2	GINS2	GINS2	2223	0.12	0.4	YES
17	CDC25B	CDC25B	CDC25B	2314	0.12	0.41	YES
18	MCM5	MCM5	MCM5	2520	0.11	0.42	YES
19	CCNE1	CCNE1	CCNE1	2686	0.099	0.42	YES
20	GINS4	GINS4	GINS4	2690	0.099	0.44	YES
21	CCND1	CCND1	CCND1	2713	0.098	0.45	YES
22	CDK7	CDK7	CDK7	2801	0.094	0.46	YES
23	CKS1B	CKS1B	CKS1B	2803	0.094	0.47	YES
24	PRIM1	PRIM1	PRIM1	2828	0.093	0.49	YES
25	CDK2	CDK2	CDK2	2858	0.092	0.5	YES
26	MCM8	MCM8	MCM8	3105	0.082	0.5	YES
27	RFC3	RFC3	RFC3	3110	0.081	0.51	YES
28	PCNA	PCNA	PCNA	3292	0.074	0.51	YES
29	FEN1	FEN1	FEN1	3500	0.068	0.51	YES
30	POLA2	POLA2	POLA2	3757	0.061	0.5	YES
31	CCNA2	CCNA2	CCNA2	3786	0.06	0.51	YES
32	RFC4	RFC4	RFC4	3839	0.059	0.52	YES
33	POLE	POLE	POLE	3899	0.058	0.52	YES
34	RPA3	RPA3	RPA3	4110	0.053	0.52	NO
35	PSMD2	PSMD2	PSMD2	4235	0.05	0.52	NO
36	PSMA5	PSMA5	PSMA5	4333	0.048	0.52	NO
37	PSMD11	PSMD11	PSMD11	4698	0.041	0.5	NO
38	CDK4	CDK4	CDK4	4720	0.04	0.51	NO
39	MYC	MYC	MYC	4759	0.04	0.51	NO
40	UBA52	UBA52	UBA52	5090	0.034	0.5	NO
41	PSMD1	PSMD1	PSMD1	5387	0.029	0.49	NO
42	POLA1	POLA1	POLA1	5408	0.029	0.49	NO
43	PSMA7	PSMA7	PSMA7	5472	0.028	0.49	NO
44	PSMD8	PSMD8	PSMD8	5477	0.028	0.49	NO
45	MCM3	MCM3	MCM3	5582	0.026	0.49	NO
46	MCM7	MCM7	MCM7	5645	0.025	0.49	NO
47	RFC5	RFC5	RFC5	5677	0.024	0.49	NO
48	PSMB5	PSMB5	PSMB5	5736	0.024	0.5	NO
49	LIG1	LIG1	LIG1	5818	0.022	0.49	NO
50	PSMC6	PSMC6	PSMC6	5828	0.022	0.5	NO
51	PSMB10	PSMB10	PSMB10	5893	0.021	0.5	NO
52	PSMA6	PSMA6	PSMA6	6090	0.018	0.49	NO
53	PSMA1	PSMA1	PSMA1	6142	0.018	0.49	NO
54	RPA1	RPA1	RPA1	6244	0.017	0.48	NO
55	CCNH	CCNH	CCNH	6335	0.016	0.48	NO
56	PSMB2	PSMB2	PSMB2	6527	0.013	0.47	NO
57	RPS27A	RPS27A	RPS27A	6554	0.013	0.47	NO
58	PSMD7	PSMD7	PSMD7	6655	0.012	0.47	NO
59	RFC2	RFC2	RFC2	6691	0.011	0.47	NO
60	PSMD14	PSMD14	PSMD14	6714	0.011	0.47	NO
61	PSME1	PSME1	PSME1	6867	0.0093	0.46	NO
62	WEE1	WEE1	WEE1	6898	0.0088	0.46	NO
63	POLD4	POLD4	POLD4	6925	0.0085	0.46	NO
64	PSMA2	PSMA2	PSMA2	7008	0.0074	0.46	NO
65	POLD3	POLD3	POLD3	7014	0.0073	0.46	NO
66	PSMD5	PSMD5	PSMD5	7067	0.0068	0.46	NO
67	CDKN1B	CDKN1B	CDKN1B	7330	0.0037	0.44	NO
68	RB1	RB1	RB1	7546	0.0014	0.43	NO
69	PSMD4	PSMD4	PSMD4	7577	0.0011	0.43	NO
70	PSMD10	PSMD10	PSMD10	7667	0.00016	0.42	NO
71	SKP1	SKP1	SKP1	7673	0.000074	0.42	NO
72	PSMC2	PSMC2	PSMC2	7863	-0.0019	0.41	NO
73	PSMD12	PSMD12	PSMD12	7871	-0.002	0.41	NO
74	RPA2	RPA2	RPA2	8043	-0.0043	0.4	NO
75	PSMB4	PSMB4	PSMB4	8156	-0.0056	0.4	NO
76	PSMB7	PSMB7	PSMB7	8288	-0.007	0.39	NO
77	CUL1	CUL1	CUL1	8304	-0.0072	0.39	NO
78	DNA2	DNA2	DNA2	8324	-0.0074	0.39	NO
79	MNAT1	MNAT1	MNAT1	8343	-0.0076	0.39	NO
80	MAX	MAX	MAX	8407	-0.0084	0.39	NO
81	PSMA3	PSMA3	PSMA3	8526	-0.01	0.39	NO
82	PSMD6	PSMD6	PSMD6	8621	-0.011	0.38	NO
83	PSMB1	PSMB1	PSMB1	8844	-0.014	0.37	NO
84	PSMD3	PSMD3	PSMD3	8856	-0.014	0.37	NO
85	PSMA4	PSMA4	PSMA4	8976	-0.016	0.37	NO
86	PSMD9	PSMD9	PSMD9	9297	-0.019	0.35	NO
87	PSMC1	PSMC1	PSMC1	9518	-0.022	0.34	NO
88	PSMC3	PSMC3	PSMC3	9623	-0.023	0.34	NO
89	PSMD13	PSMD13	PSMD13	9688	-0.024	0.34	NO
90	PSMB3	PSMB3	PSMB3	9707	-0.024	0.34	NO
91	PSME2	PSME2	PSME2	9835	-0.026	0.34	NO
92	PSME4	PSME4	PSME4	9916	-0.027	0.34	NO
93	PSMC4	PSMC4	PSMC4	9932	-0.027	0.34	NO
94	PSMF1	PSMF1	PSMF1	10002	-0.028	0.34	NO
95	PSMB6	PSMB6	PSMB6	10222	-0.031	0.34	NO
96	PSMC5	PSMC5	PSMC5	10923	-0.041	0.3	NO
97	POLD2	POLD2	POLD2	11956	-0.059	0.26	NO
98	SKP2	SKP2	SKP2	13319	-0.092	0.19	NO
99	CDC25A	CDC25A	CDC25A	15451	-0.19	0.1	NO
100	PSMA8	PSMA8	PSMA8	16264	-0.26	0.096	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 BARD1PATHWAY.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: PID BARD1PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: REACTOME ORC1 REMOVAL FROM CHROMATIN

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	CTSE	CTSE	CTSE	354	0.4	0.025	YES
2	NAPSA	NAPSA	NAPSA	448	0.37	0.062	YES
3	NPC1	NPC1	NPC1	778	0.28	0.074	YES
4	CTSL2	CTSL2	CTSL2	840	0.27	0.1	YES
5	CTSC	CTSC	CTSC	852	0.26	0.13	YES
6	ATP6V0D2	ATP6V0D2	ATP6V0D2	866	0.26	0.16	YES
7	ACP5	ACP5	ACP5	891	0.26	0.19	YES
8	SLC11A1	SLC11A1	SLC11A1	990	0.24	0.21	YES
9	CTSK	CTSK	CTSK	1198	0.21	0.22	YES
10	CTSH	CTSH	CTSH	1367	0.19	0.23	YES
11	CTSS	CTSS	CTSS	1418	0.18	0.25	YES
12	CD68	CD68	CD68	1469	0.18	0.27	YES
13	DNASE2B	DNASE2B	DNASE2B	1536	0.17	0.28	YES
14	LAMP3	LAMP3	LAMP3	1822	0.15	0.28	YES
15	IGF2R	IGF2R	IGF2R	1824	0.15	0.3	YES
16	SLC17A5	SLC17A5	SLC17A5	1929	0.14	0.31	YES
17	IDS	IDS	IDS	2110	0.13	0.31	YES
18	CTSA	CTSA	CTSA	2559	0.1	0.3	YES
19	HEXB	HEXB	HEXB	2797	0.094	0.3	YES
20	CTSD	CTSD	CTSD	2934	0.088	0.3	YES
21	AP3S1	AP3S1	AP3S1	2959	0.088	0.31	YES
22	PSAP	PSAP	PSAP	2985	0.086	0.32	YES
23	TCIRG1	TCIRG1	TCIRG1	2987	0.086	0.33	YES
24	LAPTM5	LAPTM5	LAPTM5	3072	0.083	0.33	YES
25	TPP1	TPP1	TPP1	3086	0.082	0.34	YES
26	GM2A	GM2A	GM2A	3133	0.081	0.35	YES
27	CTSB	CTSB	CTSB	3284	0.075	0.35	YES
28	MANBA	MANBA	MANBA	3303	0.074	0.35	YES
29	AP4E1	AP4E1	AP4E1	3332	0.073	0.36	YES
30	ENTPD4	ENTPD4	ENTPD4	3440	0.07	0.36	YES
31	NAGA	NAGA	NAGA	3460	0.069	0.37	YES
32	LAMP2	LAMP2	LAMP2	3489	0.068	0.38	YES
33	MAN2B1	MAN2B1	MAN2B1	3567	0.066	0.38	YES
34	AP1S3	AP1S3	AP1S3	3823	0.059	0.37	YES
35	NPC2	NPC2	NPC2	3844	0.059	0.38	YES
36	LIPA	LIPA	LIPA	3846	0.059	0.38	YES
37	GGA3	GGA3	GGA3	3851	0.059	0.39	YES
38	HGSNAT	HGSNAT	HGSNAT	3856	0.059	0.4	YES
39	FUCA1	FUCA1	FUCA1	3871	0.058	0.4	YES
40	CLTA	CLTA	CLTA	4007	0.055	0.4	YES
41	ATP6V0A2	ATP6V0A2	ATP6V0A2	4030	0.055	0.4	YES
42	SCARB2	SCARB2	SCARB2	4100	0.053	0.41	YES
43	LAPTM4B	LAPTM4B	LAPTM4B	4141	0.052	0.41	YES
44	AP1S1	AP1S1	AP1S1	4148	0.052	0.42	YES
45	ARSB	ARSB	ARSB	4249	0.05	0.42	YES
46	LAMP1	LAMP1	LAMP1	4329	0.048	0.42	YES
47	PPT1	PPT1	PPT1	4392	0.047	0.42	YES
48	GLB1	GLB1	GLB1	4434	0.046	0.42	YES
49	GNPTAB	GNPTAB	GNPTAB	4456	0.046	0.43	YES
50	ARSA	ARSA	ARSA	4471	0.045	0.43	YES
51	ASAH1	ASAH1	ASAH1	4513	0.044	0.43	YES
52	CTNS	CTNS	CTNS	4672	0.041	0.43	NO
53	CLTC	CLTC	CLTC	4796	0.039	0.43	NO
54	NEU1	NEU1	NEU1	4877	0.037	0.43	NO
55	SLC11A2	SLC11A2	SLC11A2	4964	0.036	0.42	NO
56	GBA	GBA	GBA	5075	0.034	0.42	NO
57	AP1M2	AP1M2	AP1M2	5231	0.032	0.42	NO
58	MCOLN1	MCOLN1	MCOLN1	5378	0.029	0.41	NO
59	GGA2	GGA2	GGA2	5621	0.025	0.4	NO
60	ABCB9	ABCB9	ABCB9	5628	0.025	0.4	NO
61	NAGPA	NAGPA	NAGPA	5635	0.025	0.41	NO
62	M6PR	M6PR	M6PR	5704	0.024	0.41	NO
63	AP4M1	AP4M1	AP4M1	5799	0.022	0.4	NO
64	CD63	CD63	CD63	5871	0.022	0.4	NO
65	LAPTM4A	LAPTM4A	LAPTM4A	5917	0.021	0.4	NO
66	AGA	AGA	AGA	6021	0.02	0.4	NO
67	AP1S2	AP1S2	AP1S2	6040	0.019	0.4	NO
68	GNS	GNS	GNS	6075	0.019	0.4	NO
69	GUSB	GUSB	GUSB	6163	0.018	0.4	NO
70	AP3D1	AP3D1	AP3D1	6471	0.014	0.38	NO
71	AP3M1	AP3M1	AP3M1	6495	0.014	0.38	NO
72	HEXA	HEXA	HEXA	6701	0.011	0.37	NO
73	GGA1	GGA1	GGA1	6728	0.011	0.37	NO
74	ATP6AP1	ATP6AP1	ATP6AP1	6954	0.0082	0.36	NO
75	CLN3	CLN3	CLN3	7013	0.0074	0.36	NO
76	AP1G1	AP1G1	AP1G1	7056	0.007	0.36	NO
77	MFSD8	MFSD8	MFSD8	7061	0.0069	0.36	NO
78	AP1B1	AP1B1	AP1B1	7121	0.0061	0.35	NO
79	CTSL1	CTSL1	CTSL1	7727	-0.00046	0.32	NO
80	SMPD1	SMPD1	SMPD1	7809	-0.0014	0.31	NO
81	ATP6V0A1	ATP6V0A1	ATP6V0A1	7814	-0.0014	0.31	NO
82	ATP6V0C	ATP6V0C	ATP6V0C	7954	-0.0031	0.31	NO
83	CTSG	CTSG	CTSG	7985	-0.0036	0.3	NO
84	ACP2	ACP2	ACP2	8005	-0.0038	0.3	NO
85	SUMF1	SUMF1	SUMF1	8192	-0.006	0.3	NO
86	SORT1	SORT1	SORT1	8228	-0.0064	0.29	NO
87	GALNS	GALNS	GALNS	8274	-0.0069	0.29	NO
88	AP1M1	AP1M1	AP1M1	8455	-0.0091	0.28	NO
89	ATP6V1H	ATP6V1H	ATP6V1H	8521	-0.01	0.28	NO
90	GAA	GAA	GAA	8556	-0.01	0.28	NO
91	GNPTG	GNPTG	GNPTG	8965	-0.016	0.26	NO
92	CLTB	CLTB	CLTB	9190	-0.018	0.25	NO
93	AP3B1	AP3B1	AP3B1	9218	-0.018	0.25	NO
94	SGSH	SGSH	SGSH	9395	-0.02	0.24	NO
95	DNASE2	DNASE2	DNASE2	9894	-0.027	0.22	NO
96	ATP6V0D1	ATP6V0D1	ATP6V0D1	9934	-0.027	0.22	NO
97	PLA2G15	PLA2G15	PLA2G15	10249	-0.031	0.2	NO
98	CD164	CD164	CD164	10272	-0.032	0.2	NO
99	CTSO	CTSO	CTSO	10428	-0.034	0.2	NO
100	CTSZ	CTSZ	CTSZ	10505	-0.035	0.2	NO
101	CTSF	CTSF	CTSF	10590	-0.036	0.2	NO
102	NAGLU	NAGLU	NAGLU	10644	-0.037	0.2	NO
103	CTSW	CTSW	CTSW	10647	-0.037	0.2	NO
104	AP3S2	AP3S2	AP3S2	11449	-0.05	0.16	NO
105	ATP6V0A4	ATP6V0A4	ATP6V0A4	11468	-0.05	0.17	NO
106	GALC	GALC	GALC	11766	-0.055	0.16	NO
107	ATP6V0B	ATP6V0B	ATP6V0B	11937	-0.059	0.16	NO
108	ABCA2	ABCA2	ABCA2	12021	-0.06	0.16	NO
109	AP3M2	AP3M2	AP3M2	12176	-0.063	0.16	NO
110	AP3B2	AP3B2	AP3B2	12253	-0.065	0.16	NO
111	CLN5	CLN5	CLN5	13026	-0.083	0.13	NO
112	LGMN	LGMN	LGMN	13415	-0.095	0.12	NO
113	GLA	GLA	GLA	13684	-0.1	0.11	NO
114	PPT2	PPT2	PPT2	14114	-0.12	0.1	NO
115	AP4B1	AP4B1	AP4B1	14416	-0.13	0.099	NO
116	CLTCL1	CLTCL1	CLTCL1	14430	-0.13	0.11	NO
117	AP4S1	AP4S1	AP4S1	14777	-0.15	0.11	NO
118	ARSG	ARSG	ARSG	15367	-0.19	0.099	NO
119	IDUA	IDUA	IDUA	15504	-0.2	0.11	NO
120	HYAL1	HYAL1	HYAL1	15751	-0.22	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: REACTOME ORC1 REMOVAL FROM CHROMATIN.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME ORC1 REMOVAL FROM CHROMATIN, 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 ANTIVIRAL MECHANISM BY IFN STIMULATED GENES

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	EIF3C	EIF3C	EIF3C	1619	0.17	-0.011	YES
2	RPS27	RPS27	RPS27	1916	0.14	0.041	YES
3	EIF4EBP1	EIF4EBP1	EIF4EBP1	2170	0.13	0.087	YES
4	RPS2	RPS2	RPS2	3443	0.07	0.049	YES
5	PABPC1	PABPC1	PABPC1	3581	0.065	0.073	YES
6	EIF3H	EIF3H	EIF3H	3675	0.063	0.098	YES
7	RPS12	RPS12	RPS12	3682	0.063	0.13	YES
8	RPS5	RPS5	RPS5	3705	0.062	0.16	YES
9	EIF3A	EIF3A	EIF3A	3855	0.059	0.18	YES
10	EIF3D	EIF3D	EIF3D	3984	0.056	0.2	YES
11	RPS29	RPS29	RPS29	4017	0.055	0.22	YES
12	RPS4X	RPS4X	RPS4X	4101	0.053	0.24	YES
13	EIF4G1	EIF4G1	EIF4G1	4186	0.051	0.26	YES
14	RPS8	RPS8	RPS8	4216	0.05	0.28	YES
15	EIF2S2	EIF2S2	EIF2S2	4386	0.047	0.3	YES
16	EIF4B	EIF4B	EIF4B	4490	0.045	0.31	YES
17	RPS9	RPS9	RPS9	4511	0.044	0.33	YES
18	EIF3F	EIF3F	EIF3F	4697	0.041	0.34	YES
19	EIF2S3	EIF2S3	EIF2S3	4721	0.04	0.36	YES
20	RPS15A	RPS15A	RPS15A	4857	0.038	0.37	YES
21	EIF4A1	EIF4A1	EIF4A1	5101	0.034	0.37	YES
22	RPS18	RPS18	RPS18	5104	0.034	0.39	YES
23	RPS19	RPS19	RPS19	5237	0.031	0.4	YES
24	RPS17	RPS17	RPS17	5242	0.031	0.41	YES
25	EIF4A2	EIF4A2	EIF4A2	5280	0.03	0.42	YES
26	EIF3E	EIF3E	EIF3E	5360	0.029	0.43	YES
27	RPS10	RPS10	RPS10	5446	0.028	0.44	YES
28	RPS23	RPS23	RPS23	5586	0.026	0.44	YES
29	EIF3G	EIF3G	EIF3G	5636	0.025	0.45	YES
30	RPS3A	RPS3A	RPS3A	5648	0.025	0.46	YES
31	RPS3	RPS3	RPS3	5699	0.024	0.47	YES
32	RPS26	RPS26	RPS26	5746	0.023	0.48	YES
33	RPS16	RPS16	RPS16	5770	0.023	0.49	YES
34	RPS13	RPS13	RPS13	5785	0.023	0.5	YES
35	RPS15	RPS15	RPS15	5921	0.021	0.5	YES
36	RPS25	RPS25	RPS25	5935	0.021	0.51	YES
37	RPS21	RPS21	RPS21	5936	0.021	0.52	YES
38	RPS7	RPS7	RPS7	5957	0.02	0.53	YES
39	RPS20	RPS20	RPS20	6032	0.019	0.54	YES
40	RPS14	RPS14	RPS14	6186	0.017	0.54	YES
41	RPS6	RPS6	RPS6	6229	0.017	0.54	YES
42	RPS24	RPS24	RPS24	6230	0.017	0.55	YES
43	EIF3B	EIF3B	EIF3B	6348	0.015	0.55	YES
44	EIF3I	EIF3I	EIF3I	6458	0.014	0.55	YES
45	RPS27A	RPS27A	RPS27A	6554	0.013	0.55	YES
46	RPSA	RPSA	RPSA	6555	0.013	0.56	YES
47	RPS11	RPS11	RPS11	6584	0.013	0.56	YES
48	EIF2S1	EIF2S1	EIF2S1	6695	0.011	0.56	NO
49	RPS4Y1	RPS4Y1	RPS4Y1	6886	0.009	0.56	NO
50	EIF3J	EIF3J	EIF3J	7041	0.007	0.55	NO
51	EIF4H	EIF4H	EIF4H	7895	-0.0024	0.51	NO
52	EIF3K	EIF3K	EIF3K	8029	-0.0041	0.5	NO
53	FAU	FAU	FAU	8062	-0.0045	0.5	NO
54	RPS28	RPS28	RPS28	9004	-0.016	0.46	NO
55	EIF1AX	EIF1AX	EIF1AX	9520	-0.022	0.44	NO
56	EIF4E	EIF4E	EIF4E	9654	-0.024	0.44	NO
57	RPSAP9	RPSAP9	RPSAP9	11291	-0.047	0.37	NO

Figure S19. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: REACTOME ANTIVIRAL MECHANISM BY IFN STIMULATED GENES.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME ANTIVIRAL MECHANISM BY IFN STIMULATED GENES, 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 OXIDATIVE PHOSPHORYLATION	113	genes.ES.table	0.52	1.5	0.14	1	0.98	0.74	0.32	0.51	0.84	0.43
KEGG GLYCINE SERINE AND THREONINE METABOLISM	29	genes.ES.table	0.58	1.4	0.072	1	0.99	0.59	0.22	0.46	0.87	0.43
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	44	genes.ES.table	0.5	1.5	0.12	1	0.97	0.82	0.3	0.57	0.94	0.47
KEGG LYSINE DEGRADATION	44	genes.ES.table	0.49	1.8	0.019	1	0.53	0.48	0.28	0.34	0.34	0.29
KEGG ARGININE AND PROLINE METABOLISM	52	genes.ES.table	0.48	1.5	0.041	1	0.98	0.44	0.22	0.35	0.89	0.45
KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS	25	genes.ES.table	0.41	1.4	0.14	1	1	0.64	0.42	0.37	0.81	0.38
KEGG PROPANOATE METABOLISM	32	genes.ES.table	0.62	1.7	0.018	0.82	0.64	0.81	0.3	0.57	0.32	0.23
KEGG BUTANOATE METABOLISM	31	genes.ES.table	0.65	1.7	0.0064	0.67	0.71	0.74	0.28	0.54	0.27	0.2
KEGG INSULIN SIGNALING PATHWAY	128	genes.ES.table	0.36	1.5	0.031	1	0.98	0.15	0.14	0.13	0.8	0.41
KEGG ADIPOCYTOKINE SIGNALING PATHWAY	64	genes.ES.table	0.39	1.4	0.079	1	1	0.27	0.16	0.22	0.83	0.4

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

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	OGDHL	OGDHL	OGDHL	110	0.77	0.17	YES
2	ALDH1B1	ALDH1B1	ALDH1B1	1443	0.26	0.15	YES
3	ALDH2	ALDH2	ALDH2	1554	0.25	0.2	YES
4	SETMAR	SETMAR	SETMAR	2191	0.19	0.21	YES
5	ACAT1	ACAT1	ACAT1	2270	0.18	0.25	YES
6	EHHADH	EHHADH	EHHADH	2392	0.17	0.28	YES
7	AASS	AASS	AASS	2726	0.15	0.3	YES
8	ALDH9A1	ALDH9A1	ALDH9A1	2746	0.15	0.33	YES
9	AADAT	AADAT	AADAT	2805	0.15	0.36	YES
10	SETD8	SETD8	SETD8	2954	0.14	0.38	YES
11	OGDH	OGDH	OGDH	3396	0.12	0.39	YES
12	GCDH	GCDH	GCDH	3531	0.11	0.4	YES
13	ALDH7A1	ALDH7A1	ALDH7A1	3765	0.1	0.42	YES
14	ECHS1	ECHS1	ECHS1	4088	0.094	0.42	YES
15	SUV420H1	SUV420H1	SUV420H1	4252	0.089	0.43	YES
16	SETDB2	SETDB2	SETDB2	4367	0.086	0.44	YES
17	AASDH	AASDH	AASDH	4672	0.077	0.44	YES
18	PLOD1	PLOD1	PLOD1	4676	0.077	0.46	YES
19	HADH	HADH	HADH	4919	0.071	0.46	YES
20	WHSC1	WHSC1	WHSC1	5023	0.068	0.47	YES
21	TMLHE	TMLHE	TMLHE	5036	0.068	0.49	YES
22	HADHA	HADHA	HADHA	5325	0.062	0.49	NO
23	SUV39H2	SUV39H2	SUV39H2	6029	0.048	0.46	NO
24	NSD1	NSD1	NSD1	6587	0.038	0.44	NO
25	SETD2	SETD2	SETD2	6996	0.031	0.42	NO
26	DLST	DLST	DLST	7091	0.03	0.42	NO
27	SETD1B	SETD1B	SETD1B	7371	0.026	0.41	NO
28	EHMT1	EHMT1	EHMT1	7439	0.025	0.41	NO
29	SUV39H1	SUV39H1	SUV39H1	7807	0.02	0.4	NO
30	DOT1L	DOT1L	DOT1L	7926	0.018	0.4	NO
31	PLOD3	PLOD3	PLOD3	8027	0.016	0.39	NO
32	SETD1A	SETD1A	SETD1A	8051	0.016	0.4	NO
33	AASDHPPT	AASDHPPT	AASDHPPT	8555	0.0094	0.37	NO
34	PLOD2	PLOD2	PLOD2	8716	0.0069	0.36	NO
35	WHSC1L1	WHSC1L1	WHSC1L1	9560	-0.0054	0.32	NO
36	SETDB1	SETDB1	SETDB1	10005	-0.011	0.29	NO
37	ALDH3A2	ALDH3A2	ALDH3A2	10274	-0.015	0.28	NO
38	ACAT2	ACAT2	ACAT2	10306	-0.016	0.28	NO
39	ASH1L	ASH1L	ASH1L	10781	-0.023	0.26	NO
40	BBOX1	BBOX1	BBOX1	11179	-0.029	0.25	NO
41	EHMT2	EHMT2	EHMT2	11324	-0.032	0.25	NO
42	SUV420H2	SUV420H2	SUV420H2	12324	-0.051	0.2	NO
43	SETD7	SETD7	SETD7	13956	-0.11	0.14	NO
44	PIPOX	PIPOX	PIPOX	16786	-0.38	0.066	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 OXIDATIVE PHOSPHORYLATION.

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

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

Table S12. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACACB	ACACB	ACACB	848	0.38	0.049	YES
2	ALDH1B1	ALDH1B1	ALDH1B1	1443	0.26	0.084	YES
3	ALDH2	ALDH2	ALDH2	1554	0.25	0.14	YES
4	LDHAL6A	LDHAL6A	LDHAL6A	1764	0.22	0.19	YES
5	ALDH6A1	ALDH6A1	ALDH6A1	1814	0.22	0.24	YES
6	ACAT1	ACAT1	ACAT1	2270	0.18	0.26	YES
7	EHHADH	EHHADH	EHHADH	2392	0.17	0.3	YES
8	ACSS1	ACSS1	ACSS1	2578	0.16	0.33	YES
9	ALDH9A1	ALDH9A1	ALDH9A1	2746	0.15	0.36	YES
10	SUCLG1	SUCLG1	SUCLG1	3044	0.14	0.38	YES
11	ACADM	ACADM	ACADM	3246	0.13	0.4	YES
12	ABAT	ABAT	ABAT	3326	0.12	0.43	YES
13	LDHB	LDHB	LDHB	3451	0.12	0.45	YES
14	MLYCD	MLYCD	MLYCD	3497	0.12	0.48	YES
15	ALDH7A1	ALDH7A1	ALDH7A1	3765	0.1	0.49	YES
16	PCCB	PCCB	PCCB	3786	0.1	0.51	YES
17	PCCA	PCCA	PCCA	3870	0.1	0.54	YES
18	LDHC	LDHC	LDHC	3978	0.097	0.55	YES
19	ECHS1	ECHS1	ECHS1	4088	0.094	0.57	YES
20	SUCLA2	SUCLA2	SUCLA2	4189	0.091	0.59	YES
21	ACSS2	ACSS2	ACSS2	4872	0.072	0.57	YES
22	ACACA	ACACA	ACACA	5041	0.068	0.58	YES
23	HIBCH	HIBCH	HIBCH	5080	0.067	0.59	YES
24	SUCLG2	SUCLG2	SUCLG2	5281	0.063	0.6	YES
25	HADHA	HADHA	HADHA	5325	0.062	0.61	YES
26	MCEE	MCEE	MCEE	5443	0.059	0.62	YES
27	MUT	MUT	MUT	6076	0.047	0.6	NO
28	ACSS3	ACSS3	ACSS3	9167	0.00031	0.42	NO
29	ALDH3A2	ALDH3A2	ALDH3A2	10274	-0.015	0.37	NO
30	ACAT2	ACAT2	ACAT2	10306	-0.016	0.37	NO
31	LDHAL6B	LDHAL6B	LDHAL6B	13977	-0.11	0.19	NO
32	LDHA	LDHA	LDHA	14115	-0.12	0.22	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 GLYCINE SERINE AND THREONINE METABOLISM.

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

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

Table S13. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HMGCS2	HMGCS2	HMGCS2	461	0.5	0.082	YES
2	ACSM5	ACSM5	ACSM5	496	0.48	0.18	YES
3	OXCT2	OXCT2	OXCT2	979	0.34	0.23	YES
4	ALDH1B1	ALDH1B1	ALDH1B1	1443	0.26	0.26	YES
5	ACSM3	ACSM3	ACSM3	1503	0.26	0.31	YES
6	ALDH2	ALDH2	ALDH2	1554	0.25	0.37	YES
7	BDH1	BDH1	BDH1	1669	0.24	0.41	YES
8	ACAT1	ACAT1	ACAT1	2270	0.18	0.42	YES
9	EHHADH	EHHADH	EHHADH	2392	0.17	0.45	YES
10	ACADS	ACADS	ACADS	2399	0.17	0.48	YES
11	AACS	AACS	AACS	2680	0.16	0.5	YES
12	ALDH9A1	ALDH9A1	ALDH9A1	2746	0.15	0.53	YES
13	L2HGDH	L2HGDH	L2HGDH	2824	0.15	0.56	YES
14	PDHA1	PDHA1	PDHA1	3228	0.13	0.56	YES
15	ABAT	ABAT	ABAT	3326	0.12	0.58	YES
16	HMGCS1	HMGCS1	HMGCS1	3627	0.11	0.59	YES
17	ALDH7A1	ALDH7A1	ALDH7A1	3765	0.1	0.6	YES
18	GAD1	GAD1	GAD1	3818	0.1	0.62	YES
19	ACSM2A	ACSM2A	ACSM2A	3997	0.096	0.64	YES
20	ECHS1	ECHS1	ECHS1	4088	0.094	0.65	YES
21	OXCT1	OXCT1	OXCT1	4477	0.083	0.65	YES
22	HADH	HADH	HADH	4919	0.071	0.64	YES
23	AKR1B10	AKR1B10	AKR1B10	4948	0.07	0.65	YES
24	HADHA	HADHA	HADHA	5325	0.062	0.64	NO
25	HMGCL	HMGCL	HMGCL	5723	0.054	0.63	NO
26	ALDH5A1	ALDH5A1	ALDH5A1	5867	0.051	0.64	NO
27	PDHB	PDHB	PDHB	6271	0.044	0.62	NO
28	BDH2	BDH2	BDH2	8225	0.013	0.52	NO
29	ALDH3A2	ALDH3A2	ALDH3A2	10274	-0.015	0.4	NO
30	ACAT2	ACAT2	ACAT2	10306	-0.016	0.41	NO
31	ACSM1	ACSM1	ACSM1	13662	-0.094	0.24	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 VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

Figure S26. 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 LYSINE DEGRADATION

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	PYGM	PYGM	PYGM	42	0.92	0.11	YES
2	PFKFB1	PFKFB1	PFKFB1	318	0.57	0.16	YES
3	GYS2	GYS2	GYS2	361	0.55	0.22	YES
4	ENO3	ENO3	ENO3	460	0.5	0.28	YES
5	PFKFB2	PFKFB2	PFKFB2	1128	0.32	0.28	YES
6	PRKACB	PRKACB	PRKACB	1150	0.31	0.32	YES
7	GYG2	GYG2	GYG2	1268	0.29	0.34	YES
8	PGAM2	PGAM2	PGAM2	1521	0.26	0.36	YES
9	PHKG1	PHKG1	PHKG1	1605	0.25	0.39	YES
10	GAPDHS	GAPDHS	GAPDHS	1678	0.24	0.41	YES
11	PCK1	PCK1	PCK1	2277	0.18	0.4	YES
12	PHKB	PHKB	PHKB	2484	0.16	0.41	YES
13	PFKM	PFKM	PFKM	2563	0.16	0.42	YES
14	AGL	AGL	AGL	2624	0.16	0.44	YES
15	GOT1	GOT1	GOT1	2841	0.15	0.44	YES
16	ALDOB	ALDOB	ALDOB	3137	0.13	0.44	YES
17	SLC25A10	SLC25A10	SLC25A10	3163	0.13	0.46	YES
18	ENO2	ENO2	ENO2	3577	0.11	0.45	YES
19	GOT2	GOT2	GOT2	3596	0.11	0.46	YES
20	MDH2	MDH2	MDH2	3920	0.099	0.45	NO
21	SLC25A13	SLC25A13	SLC25A13	4458	0.083	0.43	NO
22	GYS1	GYS1	GYS1	4908	0.071	0.42	NO
23	SLC25A11	SLC25A11	SLC25A11	5056	0.068	0.42	NO
24	SLC25A1	SLC25A1	SLC25A1	5101	0.067	0.42	NO
25	PPP2R5D	PPP2R5D	PPP2R5D	5353	0.061	0.42	NO
26	PPP2R1B	PPP2R1B	PPP2R1B	5358	0.061	0.42	NO
27	ALDOA	ALDOA	ALDOA	5472	0.058	0.42	NO
28	SLC25A12	SLC25A12	SLC25A12	5522	0.057	0.43	NO
29	PGK1	PGK1	PGK1	5643	0.055	0.43	NO
30	UGP2	UGP2	UGP2	5646	0.055	0.43	NO
31	GAPDH	GAPDH	GAPDH	6241	0.044	0.41	NO
32	TPI1	TPI1	TPI1	6249	0.044	0.41	NO
33	GPI	GPI	GPI	6469	0.04	0.4	NO
34	GBE1	GBE1	GBE1	6822	0.034	0.39	NO
35	PPP2CA	PPP2CA	PPP2CA	7264	0.027	0.37	NO
36	MDH1	MDH1	MDH1	7320	0.026	0.37	NO
37	PRKACA	PRKACA	PRKACA	7846	0.019	0.34	NO
38	PHKG2	PHKG2	PHKG2	8169	0.014	0.32	NO
39	CALM1	CALM1	CALM1	8355	0.012	0.31	NO
40	CALM3	CALM3	CALM3	8710	0.007	0.3	NO
41	PGM2	PGM2	PGM2	8799	0.0058	0.29	NO
42	PCK2	PCK2	PCK2	9151	0.00047	0.27	NO
43	PGAM1	PGAM1	PGAM1	9432	-0.0034	0.26	NO
44	PPP2R1A	PPP2R1A	PPP2R1A	10309	-0.016	0.21	NO
45	PPP2CB	PPP2CB	PPP2CB	10725	-0.022	0.19	NO
46	PKLR	PKLR	PKLR	11249	-0.031	0.16	NO
47	PFKP	PFKP	PFKP	11355	-0.032	0.16	NO
48	FBP1	FBP1	FBP1	11573	-0.036	0.15	NO
49	PFKL	PFKL	PFKL	11619	-0.037	0.16	NO
50	PHKA1	PHKA1	PHKA1	11642	-0.037	0.16	NO
51	ENO1	ENO1	ENO1	12035	-0.045	0.14	NO
52	PGM1	PGM1	PGM1	12266	-0.05	0.14	NO
53	PHKA2	PHKA2	PHKA2	12321	-0.051	0.14	NO
54	PFKFB4	PFKFB4	PFKFB4	12491	-0.056	0.14	NO
55	GYG1	GYG1	GYG1	12829	-0.065	0.12	NO
56	PYGB	PYGB	PYGB	13014	-0.071	0.12	NO
57	CALM2	CALM2	CALM2	13176	-0.076	0.12	NO
58	PKM2	PKM2	PKM2	14358	-0.13	0.072	NO
59	PYGL	PYGL	PYGL	15076	-0.18	0.054	NO
60	PC	PC	PC	15971	-0.26	0.036	NO
61	PFKFB3	PFKFB3	PFKFB3	16294	-0.31	0.055	NO
62	ALDOC	ALDOC	ALDOC	16380	-0.32	0.089	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 LYSINE DEGRADATION.

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

genes ES table in pathway: KEGG ARGININE AND PROLINE METABOLISM

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	ADHFE1	ADHFE1	ADHFE1	2326	0.18	-0.11	YES
2	NDUFB1	NDUFB1	NDUFB1	2435	0.17	-0.1	YES
3	NNT	NNT	NNT	2482	0.17	-0.092	YES
4	ETFDH	ETFDH	ETFDH	2507	0.16	-0.079	YES
5	CYCS	CYCS	CYCS	2523	0.16	-0.064	YES
6	PDK4	PDK4	PDK4	2533	0.16	-0.05	YES
7	UCP3	UCP3	UCP3	2695	0.15	-0.045	YES
8	COX7B	COX7B	COX7B	2714	0.15	-0.032	YES
9	COX8A	COX8A	COX8A	2716	0.15	-0.018	YES
10	NDUFB2	NDUFB2	NDUFB2	2743	0.15	-0.0058	YES
11	ATP5G1	ATP5G1	ATP5G1	2802	0.15	0.0045	YES
12	L2HGDH	L2HGDH	L2HGDH	2824	0.15	0.017	YES
13	COX6A1	COX6A1	COX6A1	3030	0.14	0.018	YES
14	SUCLG1	SUCLG1	SUCLG1	3044	0.14	0.03	YES
15	ATP5H	ATP5H	ATP5H	3081	0.13	0.04	YES
16	NDUFA3	NDUFA3	NDUFA3	3101	0.13	0.051	YES
17	NDUFA5	NDUFA5	NDUFA5	3118	0.13	0.062	YES
18	COX6C	COX6C	COX6C	3140	0.13	0.073	YES
19	NDUFA1	NDUFA1	NDUFA1	3182	0.13	0.082	YES
20	D2HGDH	D2HGDH	D2HGDH	3191	0.13	0.094	YES
21	PDHA1	PDHA1	PDHA1	3228	0.13	0.1	YES
22	NDUFA8	NDUFA8	NDUFA8	3251	0.13	0.11	YES
23	FH	FH	FH	3273	0.13	0.12	YES
24	COX5B	COX5B	COX5B	3321	0.12	0.13	YES
25	CYC1	CYC1	CYC1	3362	0.12	0.14	YES
26	OGDH	OGDH	OGDH	3396	0.12	0.15	YES
27	LDHB	LDHB	LDHB	3451	0.12	0.16	YES
28	UQCRHL	UQCRHL	UQCRHL	3465	0.12	0.17	YES
29	ATP5I	ATP5I	ATP5I	3509	0.11	0.18	YES
30	ATP5J	ATP5J	ATP5J	3519	0.11	0.19	YES
31	NDUFA2	NDUFA2	NDUFA2	3520	0.11	0.2	YES
32	ATP5D	ATP5D	ATP5D	3618	0.11	0.2	YES
33	ETFB	ETFB	ETFB	3666	0.11	0.21	YES
34	NDUFV2	NDUFV2	NDUFV2	3675	0.11	0.22	YES
35	UQCRQ	UQCRQ	UQCRQ	3688	0.11	0.23	YES
36	NDUFA12	NDUFA12	NDUFA12	3739	0.11	0.23	YES
37	DLD	DLD	DLD	3766	0.1	0.24	YES
38	NDUFB3	NDUFB3	NDUFB3	3778	0.1	0.25	YES
39	NDUFB7	NDUFB7	NDUFB7	3796	0.1	0.26	YES
40	ATP5B	ATP5B	ATP5B	3815	0.1	0.27	YES
41	ATP5J2	ATP5J2	ATP5J2	3819	0.1	0.28	YES
42	UQCR11	UQCR11	UQCR11	3883	0.1	0.28	YES
43	MDH2	MDH2	MDH2	3920	0.099	0.29	YES
44	SDHD	SDHD	SDHD	3957	0.098	0.3	YES
45	NDUFC2	NDUFC2	NDUFC2	4019	0.096	0.3	YES
46	NDUFA6	NDUFA6	NDUFA6	4025	0.095	0.31	YES
47	NDUFS7	NDUFS7	NDUFS7	4070	0.094	0.32	YES
48	UQCRH	UQCRH	UQCRH	4081	0.094	0.32	YES
49	ATP5O	ATP5O	ATP5O	4162	0.091	0.33	YES
50	SUCLA2	SUCLA2	SUCLA2	4189	0.091	0.34	YES
51	COX5A	COX5A	COX5A	4230	0.09	0.34	YES
52	NDUFA7	NDUFA7	NDUFA7	4262	0.089	0.35	YES
53	IDH3B	IDH3B	IDH3B	4293	0.088	0.35	YES
54	ATP5E	ATP5E	ATP5E	4316	0.087	0.36	YES
55	ATP5C1	ATP5C1	ATP5C1	4331	0.087	0.37	YES
56	NDUFV3	NDUFV3	NDUFV3	4377	0.085	0.37	YES
57	COX4I1	COX4I1	COX4I1	4401	0.084	0.38	YES
58	NDUFS6	NDUFS6	NDUFS6	4460	0.083	0.38	YES
59	NDUFB6	NDUFB6	NDUFB6	4565	0.08	0.39	YES
60	NDUFB5	NDUFB5	NDUFB5	4600	0.079	0.39	YES
61	NDUFC1	NDUFC1	NDUFC1	4642	0.078	0.4	YES
62	PDPR	PDPR	PDPR	4650	0.077	0.4	YES
63	ATP5F1	ATP5F1	ATP5F1	4680	0.077	0.41	YES
64	NDUFB10	NDUFB10	NDUFB10	4691	0.076	0.41	YES
65	ATP5A1	ATP5A1	ATP5A1	4736	0.075	0.42	YES
66	NDUFS3	NDUFS3	NDUFS3	4761	0.075	0.42	YES
67	UQCRFS1	UQCRFS1	UQCRFS1	4812	0.074	0.43	YES
68	NDUFS2	NDUFS2	NDUFS2	4818	0.074	0.44	YES
69	COX6B1	COX6B1	COX6B1	4830	0.073	0.44	YES
70	ACO2	ACO2	ACO2	4842	0.073	0.45	YES
71	UQCRC2	UQCRC2	UQCRC2	4867	0.072	0.45	YES
72	SDHC	SDHC	SDHC	4927	0.071	0.46	YES
73	IDH3A	IDH3A	IDH3A	5073	0.067	0.45	YES
74	COX7C	COX7C	COX7C	5081	0.067	0.46	YES
75	NDUFA4	NDUFA4	NDUFA4	5098	0.067	0.46	YES
76	NDUFB8	NDUFB8	NDUFB8	5099	0.067	0.47	YES
77	UQCRB	UQCRB	UQCRB	5230	0.064	0.47	YES
78	NDUFA9	NDUFA9	NDUFA9	5257	0.063	0.47	YES
79	SUCLG2	SUCLG2	SUCLG2	5281	0.063	0.48	YES
80	ETFA	ETFA	ETFA	5301	0.062	0.48	YES
81	BSG	BSG	BSG	5342	0.061	0.49	YES
82	NDUFA10	NDUFA10	NDUFA10	5413	0.06	0.49	YES
83	NDUFB4	NDUFB4	NDUFB4	5421	0.059	0.49	YES
84	NDUFA13	NDUFA13	NDUFA13	5424	0.059	0.5	YES
85	NDUFS8	NDUFS8	NDUFS8	5485	0.058	0.5	YES
86	NDUFV1	NDUFV1	NDUFV1	5588	0.056	0.5	YES
87	SDHA	SDHA	SDHA	5665	0.055	0.5	YES
88	NDUFB9	NDUFB9	NDUFB9	5865	0.051	0.49	NO
89	NDUFS4	NDUFS4	NDUFS4	5938	0.049	0.49	NO
90	ATP5L	ATP5L	ATP5L	6083	0.047	0.49	NO
91	DLAT	DLAT	DLAT	6270	0.044	0.48	NO
92	PDHB	PDHB	PDHB	6271	0.044	0.49	NO
93	SDHB	SDHB	SDHB	6446	0.04	0.48	NO
94	UQCRC1	UQCRC1	UQCRC1	6460	0.04	0.48	NO
95	PDHX	PDHX	PDHX	6530	0.039	0.48	NO
96	NDUFS1	NDUFS1	NDUFS1	6568	0.038	0.48	NO
97	NDUFAB1	NDUFAB1	NDUFAB1	6594	0.038	0.49	NO
98	CS	CS	CS	6765	0.035	0.48	NO
99	DLST	DLST	DLST	7091	0.03	0.47	NO
100	NDUFA11	NDUFA11	NDUFA11	7141	0.029	0.47	NO
101	IDH2	IDH2	IDH2	7238	0.028	0.46	NO
102	IDH3G	IDH3G	IDH3G	7462	0.024	0.45	NO
103	UCP1	UCP1	UCP1	7577	0.023	0.45	NO
104	COX7A2L	COX7A2L	COX7A2L	9338	-0.002	0.35	NO
105	NDUFS5	NDUFS5	NDUFS5	9871	-0.0093	0.32	NO
106	PDP2	PDP2	PDP2	10709	-0.022	0.28	NO
107	PDK2	PDK2	PDK2	10844	-0.024	0.27	NO
108	SLC16A1	SLC16A1	SLC16A1	11879	-0.041	0.22	NO
109	IDH1	IDH1	IDH1	13350	-0.082	0.14	NO
110	SLC16A8	SLC16A8	SLC16A8	13419	-0.085	0.15	NO
111	PDK1	PDK1	PDK1	13539	-0.089	0.15	NO
112	LDHA	LDHA	LDHA	14115	-0.12	0.13	NO
113	PDP1	PDP1	PDP1	14698	-0.15	0.11	NO
114	UCP2	UCP2	UCP2	15224	-0.19	0.094	NO
115	SLC16A3	SLC16A3	SLC16A3	16071	-0.28	0.072	NO
116	PDK3	PDK3	PDK3	16718	-0.37	0.07	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 ARGININE AND PROLINE METABOLISM.

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

genes ES table in pathway: KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS

Table 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	LDHD	LDHD	LDHD	192	0.66	0.18	YES
2	TIMM17B	TIMM17B	TIMM17B	1655	0.24	0.17	YES
3	ATP5G1	ATP5G1	ATP5G1	2802	0.15	0.15	YES
4	SLC25A4	SLC25A4	SLC25A4	3160	0.13	0.16	YES
5	FXN	FXN	FXN	3224	0.13	0.2	YES
6	CYC1	CYC1	CYC1	3362	0.12	0.22	YES
7	ATP5B	ATP5B	ATP5B	3815	0.1	0.23	YES
8	COX17	COX17	COX17	3888	0.1	0.25	YES
9	MTX2	MTX2	MTX2	4099	0.093	0.27	YES
10	C18orf55	C18orf55	C18orf55	4108	0.093	0.3	YES
11	TIMM13	TIMM13	TIMM13	4181	0.091	0.32	YES
12	SLC25A13	SLC25A13	SLC25A13	4458	0.083	0.33	YES
13	GRPEL2	GRPEL2	GRPEL2	4539	0.081	0.34	YES
14	ATP5A1	ATP5A1	ATP5A1	4736	0.075	0.36	YES
15	TIMM17A	TIMM17A	TIMM17A	4809	0.074	0.37	YES
16	ACO2	ACO2	ACO2	4842	0.073	0.39	YES
17	DNAJC19	DNAJC19	DNAJC19	4983	0.069	0.4	YES
18	MTX1	MTX1	MTX1	5020	0.068	0.42	YES
19	HSPA9	HSPA9	HSPA9	5280	0.063	0.43	YES
20	TIMM8B	TIMM8B	TIMM8B	5387	0.06	0.44	YES
21	SLC25A12	SLC25A12	SLC25A12	5522	0.057	0.45	YES
22	TOMM5	TOMM5	TOMM5	5623	0.055	0.46	YES
23	FXC1	FXC1	FXC1	5690	0.054	0.47	YES
24	GRPEL1	GRPEL1	GRPEL1	5901	0.05	0.47	YES
25	TOMM40	TOMM40	TOMM40	6095	0.047	0.47	YES
26	CHCHD4	CHCHD4	CHCHD4	6207	0.045	0.48	YES
27	BCS1L	BCS1L	BCS1L	6273	0.044	0.49	YES
28	TOMM70A	TOMM70A	TOMM70A	6297	0.043	0.5	YES
29	TIMM22	TIMM22	TIMM22	6382	0.042	0.51	YES
30	PMPCA	PMPCA	PMPCA	6503	0.039	0.51	YES
31	TIMM44	TIMM44	TIMM44	6535	0.039	0.52	YES
32	TIMM50	TIMM50	TIMM50	6639	0.037	0.53	YES
33	TIMM10	TIMM10	TIMM10	6710	0.036	0.53	YES
34	CS	CS	CS	6765	0.035	0.54	YES
35	TOMM7	TOMM7	TOMM7	6823	0.034	0.55	YES
36	SAMM50	SAMM50	SAMM50	6952	0.032	0.55	YES
37	TIMM9	TIMM9	TIMM9	7300	0.027	0.54	YES
38	PMPCB	PMPCB	PMPCB	7389	0.026	0.54	YES
39	TAZ	TAZ	TAZ	7435	0.025	0.55	YES
40	IDH3G	IDH3G	IDH3G	7462	0.024	0.55	YES
41	TOMM22	TOMM22	TOMM22	8784	0.0059	0.48	NO
42	SLC25A6	SLC25A6	SLC25A6	9160	0.00041	0.46	NO
43	TIMM8A	TIMM8A	TIMM8A	9168	0.00031	0.46	NO
44	GFER	GFER	GFER	9601	-0.0059	0.44	NO
45	HSPD1	HSPD1	HSPD1	9679	-0.0069	0.43	NO
46	TOMM20	TOMM20	TOMM20	9855	-0.0091	0.42	NO
47	VDAC1	VDAC1	VDAC1	10055	-0.012	0.42	NO
48	HSCB	HSCB	HSCB	10577	-0.02	0.4	NO
49	COQ2	COQ2	COQ2	12742	-0.062	0.29	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 GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS.

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

genes ES table in pathway: KEGG PROPANOATE METABOLISM

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	HMGCS2	HMGCS2	HMGCS2	461	0.5	0.046	YES
2	AOX1	AOX1	AOX1	627	0.44	0.099	YES
3	OXCT2	OXCT2	OXCT2	979	0.34	0.13	YES
4	ALDH1B1	ALDH1B1	ALDH1B1	1443	0.26	0.14	YES
5	ALDH2	ALDH2	ALDH2	1554	0.25	0.17	YES
6	ALDH6A1	ALDH6A1	ALDH6A1	1814	0.22	0.19	YES
7	ACADSB	ACADSB	ACADSB	2091	0.19	0.2	YES
8	BCAT2	BCAT2	BCAT2	2177	0.19	0.22	YES
9	ACAT1	ACAT1	ACAT1	2270	0.18	0.24	YES
10	ACAD8	ACAD8	ACAD8	2314	0.18	0.26	YES
11	MCCC2	MCCC2	MCCC2	2349	0.17	0.29	YES
12	EHHADH	EHHADH	EHHADH	2392	0.17	0.31	YES
13	ACADS	ACADS	ACADS	2399	0.17	0.34	YES
14	ALDH9A1	ALDH9A1	ALDH9A1	2746	0.15	0.34	YES
15	DBT	DBT	DBT	2953	0.14	0.35	YES
16	BCKDHB	BCKDHB	BCKDHB	3112	0.13	0.36	YES
17	IVD	IVD	IVD	3220	0.13	0.37	YES
18	HSD17B10	HSD17B10	HSD17B10	3245	0.13	0.38	YES
19	ACADM	ACADM	ACADM	3246	0.13	0.4	YES
20	ABAT	ABAT	ABAT	3326	0.12	0.42	YES
21	HMGCS1	HMGCS1	HMGCS1	3627	0.11	0.42	YES
22	ALDH7A1	ALDH7A1	ALDH7A1	3765	0.1	0.42	YES
23	DLD	DLD	DLD	3766	0.1	0.44	YES
24	PCCB	PCCB	PCCB	3786	0.1	0.45	YES
25	PCCA	PCCA	PCCA	3870	0.1	0.46	YES
26	HIBADH	HIBADH	HIBADH	4002	0.096	0.47	YES
27	ECHS1	ECHS1	ECHS1	4088	0.094	0.48	YES
28	HADHB	HADHB	HADHB	4204	0.091	0.48	YES
29	BCKDHA	BCKDHA	BCKDHA	4224	0.09	0.5	YES
30	OXCT1	OXCT1	OXCT1	4477	0.083	0.49	YES
31	AUH	AUH	AUH	4886	0.072	0.48	YES
32	HADH	HADH	HADH	4919	0.071	0.49	YES
33	HIBCH	HIBCH	HIBCH	5080	0.067	0.49	YES
34	HADHA	HADHA	HADHA	5325	0.062	0.48	YES
35	MCCC1	MCCC1	MCCC1	5346	0.061	0.49	YES
36	MCEE	MCEE	MCEE	5443	0.059	0.5	YES
37	HMGCL	HMGCL	HMGCL	5723	0.054	0.49	NO
38	MUT	MUT	MUT	6076	0.047	0.48	NO
39	ACAA1	ACAA1	ACAA1	6218	0.045	0.47	NO
40	ALDH3A2	ALDH3A2	ALDH3A2	10274	-0.015	0.25	NO
41	ACAT2	ACAT2	ACAT2	10306	-0.016	0.25	NO
42	ACAA2	ACAA2	ACAA2	13840	-0.1	0.067	NO
43	BCAT1	BCAT1	BCAT1	17354	-0.51	-0.056	NO
44	IL4I1	IL4I1	IL4I1	17656	-0.63	0.018	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 PROPANOATE METABOLISM.

Figure S34. 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 BUTANOATE METABOLISM

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	SLC2A4	SLC2A4	SLC2A4	123	0.74	0.2	YES
2	GHR	GHR	GHR	566	0.46	0.3	YES
3	HNF1A	HNF1A	HNF1A	803	0.39	0.4	YES
4	IRS1	IRS1	IRS1	956	0.35	0.49	YES
5	PRKCA	PRKCA	PRKCA	1429	0.27	0.54	YES
6	RPS6KA1	RPS6KA1	RPS6KA1	4065	0.094	0.42	NO
7	SRF	SRF	SRF	5317	0.062	0.37	NO
8	SOS1	SOS1	SOS1	6348	0.042	0.32	NO
9	PRKCB	PRKCB	PRKCB	6648	0.037	0.32	NO
10	PLCG1	PLCG1	PLCG1	6834	0.034	0.31	NO
11	INSR	INSR	INSR	6930	0.032	0.32	NO
12	MAPK3	MAPK3	MAPK3	7407	0.025	0.3	NO
13	RAF1	RAF1	RAF1	7899	0.018	0.28	NO
14	HRAS	HRAS	HRAS	8157	0.014	0.27	NO
15	STAT5B	STAT5B	STAT5B	10116	-0.013	0.16	NO
16	SOCS1	SOCS1	SOCS1	10123	-0.013	0.16	NO
17	MAP2K1	MAP2K1	MAP2K1	10138	-0.013	0.17	NO
18	GRB2	GRB2	GRB2	10621	-0.02	0.14	NO
19	GH1	GH1	GH1	11881	-0.041	0.087	NO
20	SHC1	SHC1	SHC1	12833	-0.065	0.052	NO
21	JAK2	JAK2	JAK2	12997	-0.07	0.063	NO
22	PTPN6	PTPN6	PTPN6	13202	-0.077	0.073	NO
23	MAPK1	MAPK1	MAPK1	13273	-0.079	0.091	NO
24	PIK3R1	PIK3R1	PIK3R1	13741	-0.097	0.092	NO
25	STAT5A	STAT5A	STAT5A	14664	-0.15	0.082	NO
26	PIK3CA	PIK3CA	PIK3CA	14717	-0.15	0.12	NO
27	PIK3CG	PIK3CG	PIK3CG	15498	-0.22	0.14	NO

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

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

genes ES table in pathway: KEGG INSULIN SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CKMT2	CKMT2	CKMT2	310	0.57	0.056	YES
2	AGMAT	AGMAT	AGMAT	516	0.47	0.1	YES
3	GATM	GATM	GATM	769	0.4	0.14	YES
4	CKMT1B	CKMT1B	CKMT1B	907	0.36	0.18	YES
5	ALDH4A1	ALDH4A1	ALDH4A1	945	0.35	0.22	YES
6	MAOB	MAOB	MAOB	1073	0.33	0.26	YES
7	CKB	CKB	CKB	1251	0.3	0.28	YES
8	ALDH1B1	ALDH1B1	ALDH1B1	1443	0.26	0.31	YES
9	NOS1	NOS1	NOS1	1450	0.26	0.34	YES
10	ALDH2	ALDH2	ALDH2	1554	0.25	0.37	YES
11	CKMT1A	CKMT1A	CKMT1A	1677	0.24	0.39	YES
12	SAT2	SAT2	SAT2	2508	0.16	0.37	YES
13	ARG1	ARG1	ARG1	2554	0.16	0.38	YES
14	GAMT	GAMT	GAMT	2631	0.16	0.4	YES
15	P4HA3	P4HA3	P4HA3	2639	0.16	0.42	YES
16	ALDH9A1	ALDH9A1	ALDH9A1	2746	0.15	0.43	YES
17	GOT1	GOT1	GOT1	2841	0.15	0.45	YES
18	CPS1	CPS1	CPS1	2978	0.14	0.46	YES
19	NAGS	NAGS	NAGS	3128	0.13	0.47	YES
20	GOT2	GOT2	GOT2	3596	0.11	0.45	YES
21	PYCRL	PYCRL	PYCRL	3659	0.11	0.46	YES
22	ALDH7A1	ALDH7A1	ALDH7A1	3765	0.1	0.47	YES
23	MAOA	MAOA	MAOA	3884	0.1	0.48	YES
24	ARG2	ARG2	ARG2	4492	0.082	0.46	NO
25	ASL	ASL	ASL	4630	0.078	0.46	NO
26	PYCR1	PYCR1	PYCR1	4633	0.078	0.47	NO
27	OAT	OAT	OAT	4984	0.069	0.46	NO
28	GLUL	GLUL	GLUL	5815	0.052	0.42	NO
29	ALDH18A1	ALDH18A1	ALDH18A1	6706	0.036	0.37	NO
30	AMD1	AMD1	AMD1	6833	0.034	0.37	NO
31	NOS3	NOS3	NOS3	7244	0.028	0.35	NO
32	ACY1	ACY1	ACY1	7534	0.024	0.34	NO
33	ADC	ADC	ADC	8868	0.0046	0.26	NO
34	NOS2	NOS2	NOS2	9255	-0.00078	0.24	NO
35	ALDH3A2	ALDH3A2	ALDH3A2	10274	-0.015	0.19	NO
36	P4HA1	P4HA1	P4HA1	10517	-0.019	0.18	NO
37	PYCR2	PYCR2	PYCR2	11323	-0.032	0.13	NO
38	GLUD1	GLUD1	GLUD1	12133	-0.047	0.095	NO
39	ASS1	ASS1	ASS1	12155	-0.048	0.1	NO
40	SMS	SMS	SMS	12506	-0.056	0.088	NO
41	ABP1	ABP1	ABP1	12682	-0.061	0.086	NO
42	DAO	DAO	DAO	12934	-0.068	0.08	NO
43	SRM	SRM	SRM	13026	-0.071	0.084	NO
44	LAP3	LAP3	LAP3	13400	-0.084	0.074	NO
45	GLUD2	GLUD2	GLUD2	13530	-0.089	0.079	NO
46	SAT1	SAT1	SAT1	13569	-0.09	0.088	NO
47	ODC1	ODC1	ODC1	13899	-0.1	0.083	NO
48	P4HA2	P4HA2	P4HA2	14630	-0.14	0.061	NO
49	GLS	GLS	GLS	15141	-0.18	0.056	NO
50	CKM	CKM	CKM	15567	-0.22	0.061	NO
51	PRODH	PRODH	PRODH	15857	-0.25	0.077	NO
52	GLS2	GLS2	GLS2	16385	-0.32	0.088	NO

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

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG INSULIN 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 ADIPOCYTOKINE SIGNALING 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	ATP4A	ATP4A	ATP4A	227	0.63	0.04	YES
2	COX4I2	COX4I2	COX4I2	788	0.39	0.041	YES
3	ATP6V1G2	ATP6V1G2	ATP6V1G2	911	0.36	0.065	YES
4	COX7A1	COX7A1	COX7A1	1104	0.32	0.081	YES
5	ATP6V0E2	ATP6V0E2	ATP6V0E2	1253	0.3	0.097	YES
6	NDUFA4L2	NDUFA4L2	NDUFA4L2	1984	0.2	0.073	YES
7	ATP6V1E2	ATP6V1E2	ATP6V1E2	2352	0.17	0.067	YES
8	ATP6V1B1	ATP6V1B1	ATP6V1B1	2376	0.17	0.08	YES
9	NDUFB1	NDUFB1	NDUFB1	2435	0.17	0.091	YES
10	COX7B	COX7B	COX7B	2714	0.15	0.088	YES
11	COX10	COX10	COX10	2715	0.15	0.1	YES
12	COX8A	COX8A	COX8A	2716	0.15	0.11	YES
13	NDUFB2	NDUFB2	NDUFB2	2743	0.15	0.12	YES
14	ATP5G1	ATP5G1	ATP5G1	2802	0.15	0.14	YES
15	COX6A1	COX6A1	COX6A1	3030	0.14	0.13	YES
16	ATP5H	ATP5H	ATP5H	3081	0.13	0.14	YES
17	NDUFA3	NDUFA3	NDUFA3	3101	0.13	0.15	YES
18	NDUFA5	NDUFA5	NDUFA5	3118	0.13	0.16	YES
19	ATP4B	ATP4B	ATP4B	3139	0.13	0.17	YES
20	COX6C	COX6C	COX6C	3140	0.13	0.18	YES
21	NDUFA1	NDUFA1	NDUFA1	3182	0.13	0.19	YES
22	ATP6V1C2	ATP6V1C2	ATP6V1C2	3195	0.13	0.2	YES
23	NDUFA8	NDUFA8	NDUFA8	3251	0.13	0.21	YES
24	COX8C	COX8C	COX8C	3265	0.13	0.22	YES
25	COX5B	COX5B	COX5B	3321	0.12	0.23	YES
26	CYC1	CYC1	CYC1	3362	0.12	0.23	YES
27	UQCRHL	UQCRHL	UQCRHL	3465	0.12	0.24	YES
28	ATP5I	ATP5I	ATP5I	3509	0.11	0.25	YES
29	ATP5J	ATP5J	ATP5J	3519	0.11	0.26	YES
30	NDUFA2	NDUFA2	NDUFA2	3520	0.11	0.26	YES
31	ATP5D	ATP5D	ATP5D	3618	0.11	0.27	YES
32	NDUFV2	NDUFV2	NDUFV2	3675	0.11	0.27	YES
33	UQCRQ	UQCRQ	UQCRQ	3688	0.11	0.28	YES
34	NDUFB3	NDUFB3	NDUFB3	3778	0.1	0.29	YES
35	NDUFB7	NDUFB7	NDUFB7	3796	0.1	0.29	YES
36	ATP5B	ATP5B	ATP5B	3815	0.1	0.3	YES
37	ATP5J2	ATP5J2	ATP5J2	3819	0.1	0.31	YES
38	UQCR10	UQCR10	UQCR10	3829	0.1	0.32	YES
39	UQCR11	UQCR11	UQCR11	3883	0.1	0.32	YES
40	COX17	COX17	COX17	3888	0.1	0.33	YES
41	SDHD	SDHD	SDHD	3957	0.098	0.34	YES
42	NDUFC2	NDUFC2	NDUFC2	4019	0.096	0.34	YES
43	NDUFA6	NDUFA6	NDUFA6	4025	0.095	0.35	YES
44	NDUFS7	NDUFS7	NDUFS7	4070	0.094	0.35	YES
45	UQCRH	UQCRH	UQCRH	4081	0.094	0.36	YES
46	COX15	COX15	COX15	4138	0.092	0.37	YES
47	ATP5G3	ATP5G3	ATP5G3	4159	0.092	0.37	YES
48	ATP5O	ATP5O	ATP5O	4162	0.091	0.38	YES
49	COX5A	COX5A	COX5A	4230	0.09	0.38	YES
50	NDUFA7	NDUFA7	NDUFA7	4262	0.089	0.39	YES
51	ATP6V0B	ATP6V0B	ATP6V0B	4301	0.088	0.39	YES
52	ATP5E	ATP5E	ATP5E	4316	0.087	0.4	YES
53	ATP5C1	ATP5C1	ATP5C1	4331	0.087	0.41	YES
54	NDUFV3	NDUFV3	NDUFV3	4377	0.085	0.41	YES
55	COX4I1	COX4I1	COX4I1	4401	0.084	0.42	YES
56	NDUFS6	NDUFS6	NDUFS6	4460	0.083	0.42	YES
57	COX11	COX11	COX11	4549	0.08	0.42	YES
58	NDUFB6	NDUFB6	NDUFB6	4565	0.08	0.43	YES
59	COX7A2	COX7A2	COX7A2	4568	0.08	0.44	YES
60	NDUFB5	NDUFB5	NDUFB5	4600	0.079	0.44	YES
61	NDUFC1	NDUFC1	NDUFC1	4642	0.078	0.44	YES
62	ATP5F1	ATP5F1	ATP5F1	4680	0.077	0.45	YES
63	NDUFB10	NDUFB10	NDUFB10	4691	0.076	0.46	YES
64	ATP5A1	ATP5A1	ATP5A1	4736	0.075	0.46	YES
65	NDUFS3	NDUFS3	NDUFS3	4761	0.075	0.46	YES
66	ATP6V1H	ATP6V1H	ATP6V1H	4778	0.074	0.47	YES
67	UQCRFS1	UQCRFS1	UQCRFS1	4812	0.074	0.47	YES
68	LHPP	LHPP	LHPP	4813	0.074	0.48	YES
69	NDUFS2	NDUFS2	NDUFS2	4818	0.074	0.49	YES
70	COX6B1	COX6B1	COX6B1	4830	0.073	0.49	YES
71	UQCRC2	UQCRC2	UQCRC2	4867	0.072	0.5	YES
72	SDHC	SDHC	SDHC	4927	0.071	0.5	YES
73	ATP6V0D1	ATP6V0D1	ATP6V0D1	5039	0.068	0.5	YES
74	COX7C	COX7C	COX7C	5081	0.067	0.5	YES
75	NDUFA4	NDUFA4	NDUFA4	5098	0.067	0.5	YES
76	NDUFB8	NDUFB8	NDUFB8	5099	0.067	0.51	YES
77	UQCRB	UQCRB	UQCRB	5230	0.064	0.51	YES
78	NDUFA9	NDUFA9	NDUFA9	5257	0.063	0.51	YES
79	NDUFA10	NDUFA10	NDUFA10	5413	0.06	0.51	YES
80	NDUFB4	NDUFB4	NDUFB4	5421	0.059	0.51	YES
81	NDUFS8	NDUFS8	NDUFS8	5485	0.058	0.52	YES
82	ATP5G2	ATP5G2	ATP5G2	5506	0.057	0.52	YES
83	NDUFV1	NDUFV1	NDUFV1	5588	0.056	0.52	YES
84	SDHA	SDHA	SDHA	5665	0.055	0.52	YES
85	ATP6V1D	ATP6V1D	ATP6V1D	5834	0.051	0.51	NO
86	NDUFB9	NDUFB9	NDUFB9	5865	0.051	0.52	NO
87	NDUFS4	NDUFS4	NDUFS4	5938	0.049	0.52	NO
88	ATP6V0E1	ATP6V0E1	ATP6V0E1	6081	0.047	0.51	NO
89	ATP5L	ATP5L	ATP5L	6083	0.047	0.52	NO
90	SDHB	SDHB	SDHB	6446	0.04	0.5	NO
91	UQCRC1	UQCRC1	UQCRC1	6460	0.04	0.5	NO
92	NDUFS1	NDUFS1	NDUFS1	6568	0.038	0.5	NO
93	NDUFAB1	NDUFAB1	NDUFAB1	6594	0.038	0.5	NO
94	PPA2	PPA2	PPA2	6676	0.037	0.5	NO
95	ATP6AP1	ATP6AP1	ATP6AP1	6995	0.031	0.48	NO
96	NDUFA11	NDUFA11	NDUFA11	7141	0.029	0.48	NO
97	ATP6V1C1	ATP6V1C1	ATP6V1C1	7635	0.022	0.45	NO
98	ATP6V0C	ATP6V0C	ATP6V0C	8020	0.016	0.43	NO
99	ATP6V1G1	ATP6V1G1	ATP6V1G1	9071	0.0015	0.38	NO
100	ATP6V0A1	ATP6V0A1	ATP6V0A1	9295	-0.0013	0.36	NO
101	COX7A2L	COX7A2L	COX7A2L	9338	-0.002	0.36	NO
102	ATP6V1F	ATP6V1F	ATP6V1F	9700	-0.007	0.34	NO
103	NDUFS5	NDUFS5	NDUFS5	9871	-0.0093	0.33	NO
104	ATP6V0A4	ATP6V0A4	ATP6V0A4	11430	-0.034	0.25	NO
105	ATP6V1A	ATP6V1A	ATP6V1A	11458	-0.034	0.25	NO
106	ATP6V1E1	ATP6V1E1	ATP6V1E1	11877	-0.041	0.23	NO
107	ATP6V0A2	ATP6V0A2	ATP6V0A2	12906	-0.068	0.18	NO
108	PPA1	PPA1	PPA1	13401	-0.084	0.16	NO
109	ATP12A	ATP12A	ATP12A	13467	-0.087	0.16	NO
110	ATP6V1B2	ATP6V1B2	ATP6V1B2	14119	-0.12	0.13	NO
111	TCIRG1	TCIRG1	TCIRG1	15324	-0.2	0.082	NO
112	ATP6V0D2	ATP6V0D2	ATP6V0D2	16565	-0.35	0.042	NO
113	COX6B2	COX6B2	COX6B2	17075	-0.44	0.05	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype 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.
KEGG GLYCOLYSIS GLUCONEOGENESIS	55	genes.ES.table	0.42	1.3	0.15	0.21	1	0.31	0.27	0.22	0.17
KEGG FRUCTOSE AND MANNOSE METABOLISM	33	genes.ES.table	0.44	1.4	0.071	0.11	0.99	0.27	0.25	0.2	0.086
KEGG FATTY ACID METABOLISM	37	genes.ES.table	0.44	1.3	0.21	0.22	1	0.16	0.14	0.14	0.19
KEGG PURINE METABOLISM	154	genes.ES.table	0.42	1.7	0	0.042	0.68	0.23	0.26	0.18	0.019
KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM	29	genes.ES.table	0.49	1.5	0.038	0.098	0.98	0.1	0.041	0.099	0.072
KEGG CYSTEINE AND METHIONINE METABOLISM	33	genes.ES.table	0.45	1.4	0.092	0.15	1	0.3	0.27	0.22	0.11
KEGG HISTIDINE METABOLISM	29	genes.ES.table	0.53	1.4	0.085	0.14	1	0.38	0.23	0.29	0.11
KEGG TYROSINE METABOLISM	39	genes.ES.table	0.53	1.4	0.058	0.14	1	0.28	0.19	0.23	0.11
KEGG TRYPTOPHAN METABOLISM	39	genes.ES.table	0.62	1.6	0.0043	0.051	0.86	0.28	0.14	0.24	0.028
KEGG GLUTATHIONE METABOLISM	46	genes.ES.table	0.39	1.2	0.19	0.22	1	0.065	0.06	0.061	0.19

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

Table S21. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ASB2	ASB2	ASB2	169	0.87	0.038	YES
2	NCF4	NCF4	NCF4	583	0.64	0.05	YES
3	FCGR1A	FCGR1A	FCGR1A	620	0.63	0.082	YES
4	NCF2	NCF2	NCF2	684	0.6	0.11	YES
5	UBE2C	UBE2C	UBE2C	699	0.6	0.14	YES
6	CYBB	CYBB	CYBB	826	0.56	0.17	YES
7	PSMA8	PSMA8	PSMA8	909	0.54	0.19	YES
8	MRC1	MRC1	MRC1	992	0.52	0.21	YES
9	FCGR1B	FCGR1B	FCGR1B	1052	0.5	0.24	YES
10	FBXO17	FBXO17	FBXO17	1054	0.5	0.26	YES
11	SPSB4	SPSB4	SPSB4	1153	0.47	0.28	YES
12	CD207	CD207	CD207	1230	0.46	0.31	YES
13	PSMB9	PSMB9	PSMB9	1307	0.44	0.32	YES
14	HLA-G	HLA-G	HLA-G	1756	0.36	0.32	YES
15	CDC20	CDC20	CDC20	1800	0.35	0.34	YES
16	KLHL13	KLHL13	KLHL13	1897	0.33	0.35	YES
17	HLA-F	HLA-F	HLA-F	1911	0.33	0.36	YES
18	TAP1	TAP1	TAP1	1983	0.32	0.38	YES
19	TAP2	TAP2	TAP2	2164	0.29	0.38	YES
20	SOCS3	SOCS3	SOCS3	2483	0.25	0.38	YES
21	CTSS	CTSS	CTSS	2639	0.23	0.38	YES
22	SOCS1	SOCS1	SOCS1	2688	0.23	0.39	YES
23	PSMB10	PSMB10	PSMB10	2841	0.21	0.4	YES
24	FBXO27	FBXO27	FBXO27	2912	0.2	0.4	YES
25	UBE2L6	UBE2L6	UBE2L6	2913	0.2	0.41	YES
26	HLA-B	HLA-B	HLA-B	2932	0.2	0.42	YES
27	HLA-C	HLA-C	HLA-C	3069	0.19	0.43	YES
28	PSMB8	PSMB8	PSMB8	3225	0.18	0.43	YES
29	TRIM9	TRIM9	TRIM9	3278	0.17	0.43	YES
30	TRIM21	TRIM21	TRIM21	3309	0.17	0.44	YES
31	B2M	B2M	B2M	3410	0.16	0.44	YES
32	SPSB1	SPSB1	SPSB1	3447	0.16	0.45	YES
33	ERAP1	ERAP1	ERAP1	3536	0.16	0.46	YES
34	HLA-A	HLA-A	HLA-A	3615	0.15	0.46	YES
35	MRC2	MRC2	MRC2	3616	0.15	0.47	YES
36	PSME2	PSME2	PSME2	3636	0.15	0.48	YES
37	FBXO6	FBXO6	FBXO6	3640	0.15	0.48	YES
38	DTX3L	DTX3L	DTX3L	4133	0.12	0.46	NO
39	ASB13	ASB13	ASB13	4227	0.12	0.46	NO
40	UBA7	UBA7	UBA7	4356	0.11	0.46	NO
41	LNPEP	LNPEP	LNPEP	4391	0.11	0.46	NO
42	UBE2J1	UBE2J1	UBE2J1	4628	0.096	0.46	NO
43	SMURF2	SMURF2	SMURF2	4647	0.095	0.46	NO
44	SKP2	SKP2	SKP2	4675	0.094	0.46	NO
45	UBE2D1	UBE2D1	UBE2D1	4830	0.088	0.46	NO
46	PSME1	PSME1	PSME1	4860	0.087	0.46	NO
47	CYBA	CYBA	CYBA	4948	0.084	0.46	NO
48	UBA6	UBA6	UBA6	5020	0.081	0.46	NO
49	SEC23A	SEC23A	SEC23A	5134	0.078	0.46	NO
50	UBE2S	UBE2S	UBE2S	5372	0.069	0.45	NO
51	RNF138	RNF138	RNF138	5386	0.069	0.46	NO
52	TRIM36	TRIM36	TRIM36	5393	0.069	0.46	NO
53	PSMA4	PSMA4	PSMA4	5410	0.068	0.46	NO
54	FBXO2	FBXO2	FBXO2	5482	0.066	0.46	NO
55	SEC24D	SEC24D	SEC24D	5502	0.066	0.46	NO
56	CBLB	CBLB	CBLB	5513	0.065	0.47	NO
57	SMURF1	SMURF1	SMURF1	5569	0.063	0.47	NO
58	RNF34	RNF34	RNF34	5705	0.06	0.46	NO
59	ATG7	ATG7	ATG7	5802	0.057	0.46	NO
60	UBA3	UBA3	UBA3	5848	0.056	0.46	NO
61	UBE2N	UBE2N	UBE2N	5981	0.053	0.46	NO
62	TRIM63	TRIM63	TRIM63	5983	0.053	0.46	NO
63	KLHL20	KLHL20	KLHL20	6053	0.051	0.46	NO
64	PSMA3	PSMA3	PSMA3	6156	0.049	0.45	NO
65	ASB9	ASB9	ASB9	6162	0.049	0.46	NO
66	PSMA5	PSMA5	PSMA5	6365	0.045	0.45	NO
67	ASB12	ASB12	ASB12	6390	0.044	0.45	NO
68	VHL	VHL	VHL	6482	0.042	0.45	NO
69	UBE2E2	UBE2E2	UBE2E2	6483	0.042	0.45	NO
70	PSMA6	PSMA6	PSMA6	6509	0.042	0.45	NO
71	PSMB2	PSMB2	PSMB2	6656	0.039	0.44	NO
72	PSMD11	PSMD11	PSMD11	6680	0.039	0.44	NO
73	PSMD1	PSMD1	PSMD1	6886	0.035	0.43	NO
74	PSMD7	PSMD7	PSMD7	6901	0.035	0.44	NO
75	PSMD5	PSMD5	PSMD5	6976	0.034	0.43	NO
76	PSMA1	PSMA1	PSMA1	7037	0.033	0.43	NO
77	UBE2G1	UBE2G1	UBE2G1	7046	0.033	0.43	NO
78	TRIM11	TRIM11	TRIM11	7075	0.032	0.43	NO
79	UBE2L3	UBE2L3	UBE2L3	7111	0.032	0.43	NO
80	PSMC2	PSMC2	PSMC2	7116	0.032	0.43	NO
81	PSMA2	PSMA2	PSMA2	7223	0.03	0.43	NO
82	UBE3C	UBE3C	UBE3C	7322	0.028	0.43	NO
83	FBXW7	FBXW7	FBXW7	7375	0.028	0.42	NO
84	RNF6	RNF6	RNF6	7435	0.027	0.42	NO
85	ANAPC1	ANAPC1	ANAPC1	7462	0.027	0.42	NO
86	RBX1	RBX1	RBX1	7482	0.026	0.42	NO
87	ITGAV	ITGAV	ITGAV	7512	0.026	0.42	NO
88	PSMD12	PSMD12	PSMD12	7647	0.024	0.42	NO
89	PSMA7	PSMA7	PSMA7	7667	0.024	0.42	NO
90	PSME4	PSME4	PSME4	7736	0.023	0.41	NO
91	PSMD13	PSMD13	PSMD13	7764	0.023	0.41	NO
92	ASB3	ASB3	ASB3	7777	0.023	0.41	NO
93	TRIM32	TRIM32	TRIM32	7822	0.022	0.41	NO
94	WSB1	WSB1	WSB1	7853	0.022	0.41	NO
95	SEC31A	SEC31A	SEC31A	8036	0.02	0.4	NO
96	UBR2	UBR2	UBR2	8066	0.019	0.4	NO
97	TPP2	TPP2	TPP2	8069	0.019	0.4	NO
98	CDC26	CDC26	CDC26	8071	0.019	0.4	NO
99	ASB7	ASB7	ASB7	8088	0.019	0.4	NO
100	ASB16	ASB16	ASB16	8127	0.018	0.4	NO
101	CUL2	CUL2	CUL2	8189	0.018	0.4	NO
102	PSMB3	PSMB3	PSMB3	8242	0.017	0.4	NO
103	UBE2A	UBE2A	UBE2A	8246	0.017	0.4	NO
104	ITGB5	ITGB5	ITGB5	8302	0.017	0.4	NO
105	UBR1	UBR1	UBR1	8365	0.016	0.4	NO
106	PSMB4	PSMB4	PSMB4	8403	0.015	0.39	NO
107	UBE2W	UBE2W	UBE2W	8439	0.015	0.39	NO
108	ANAPC10	ANAPC10	ANAPC10	8500	0.014	0.39	NO
109	UBE2E1	UBE2E1	UBE2E1	8602	0.013	0.38	NO
110	CDC27	CDC27	CDC27	8605	0.013	0.39	NO
111	PSMD14	PSMD14	PSMD14	8607	0.013	0.39	NO
112	RNF4	RNF4	RNF4	8664	0.012	0.38	NO
113	CD36	CD36	CD36	8798	0.011	0.38	NO
114	TRIP12	TRIP12	TRIP12	8808	0.011	0.38	NO
115	WWP1	WWP1	WWP1	8843	0.011	0.38	NO
116	PSMB1	PSMB1	PSMB1	8909	0.01	0.37	NO
117	UBE2G2	UBE2G2	UBE2G2	8911	0.01	0.37	NO
118	UBA52	UBA52	UBA52	9051	0.0087	0.37	NO
119	ANAPC4	ANAPC4	ANAPC4	9058	0.0086	0.37	NO
120	RBCK1	RBCK1	RBCK1	9210	0.0072	0.36	NO
121	UBE2J2	UBE2J2	UBE2J2	9215	0.0071	0.36	NO
122	UBE2Z	UBE2Z	UBE2Z	9218	0.0071	0.36	NO
123	CUL1	CUL1	CUL1	9242	0.0069	0.36	NO
124	UBE2Q1	UBE2Q1	UBE2Q1	9243	0.0069	0.36	NO
125	NEDD4	NEDD4	NEDD4	9258	0.0067	0.36	NO
126	HECTD3	HECTD3	HECTD3	9272	0.0066	0.36	NO
127	PSMD3	PSMD3	PSMD3	9287	0.0065	0.36	NO
128	PSMD4	PSMD4	PSMD4	9326	0.0061	0.36	NO
129	SAR1B	SAR1B	SAR1B	9347	0.0059	0.35	NO
130	SEC13	SEC13	SEC13	9354	0.0059	0.35	NO
131	GAN	GAN	GAN	9381	0.0056	0.35	NO
132	UBE2Q2	UBE2Q2	UBE2Q2	9395	0.0054	0.35	NO
133	UBE2V2	UBE2V2	UBE2V2	9414	0.0053	0.35	NO
134	PSMD2	PSMD2	PSMD2	9438	0.005	0.35	NO
135	PSMF1	PSMF1	PSMF1	9454	0.0048	0.35	NO
136	SEC61A2	SEC61A2	SEC61A2	9520	0.0042	0.35	NO
137	SEC61B	SEC61B	SEC61B	9536	0.0041	0.35	NO
138	BLMH	BLMH	BLMH	9548	0.0039	0.34	NO
139	KLHL9	KLHL9	KLHL9	9585	0.0036	0.34	NO
140	PSMD6	PSMD6	PSMD6	9630	0.0031	0.34	NO
141	UBE2F	UBE2F	UBE2F	9741	0.0022	0.34	NO
142	RNF220	RNF220	RNF220	9761	0.002	0.33	NO
143	SEC61A1	SEC61A1	SEC61A1	9815	0.0016	0.33	NO
144	UBA2	UBA2	UBA2	9856	0.001	0.33	NO
145	ASB6	ASB6	ASB6	9874	0.00088	0.33	NO
146	PSMC6	PSMC6	PSMC6	9878	0.00086	0.33	NO
147	PSMB6	PSMB6	PSMB6	9986	-0.00029	0.32	NO
148	UBE2H	UBE2H	UBE2H	10013	-0.0005	0.32	NO
149	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.32	NO
150	UBE2B	UBE2B	UBE2B	10177	-0.002	0.31	NO
151	HUWE1	HUWE1	HUWE1	10198	-0.0022	0.31	NO
152	NPEPPS	NPEPPS	NPEPPS	10224	-0.0023	0.31	NO
153	VPRBP	VPRBP	VPRBP	10244	-0.0026	0.31	NO
154	UBE2D3	UBE2D3	UBE2D3	10318	-0.0033	0.3	NO
155	MKRN1	MKRN1	MKRN1	10333	-0.0034	0.3	NO
156	PSMC4	PSMC4	PSMC4	10346	-0.0036	0.3	NO
157	RNF25	RNF25	RNF25	10362	-0.0038	0.3	NO
158	ANAPC5	ANAPC5	ANAPC5	10586	-0.0059	0.29	NO
159	UBE2K	UBE2K	UBE2K	10593	-0.0059	0.29	NO
160	TCEB1	TCEB1	TCEB1	10691	-0.0067	0.28	NO
161	TRIM37	TRIM37	TRIM37	10714	-0.007	0.28	NO
162	PSMC1	PSMC1	PSMC1	10749	-0.0073	0.28	NO
163	ANAPC7	ANAPC7	ANAPC7	10783	-0.0076	0.28	NO
164	SEC24B	SEC24B	SEC24B	10805	-0.0079	0.28	NO
165	ANAPC2	ANAPC2	ANAPC2	10815	-0.0079	0.28	NO
166	PSMD10	PSMD10	PSMD10	10860	-0.0083	0.28	NO
167	SEC24C	SEC24C	SEC24C	10864	-0.0084	0.28	NO
168	PSMC5	PSMC5	PSMC5	10973	-0.0094	0.27	NO
169	UBE2R2	UBE2R2	UBE2R2	10974	-0.0094	0.27	NO
170	UBE2D2	UBE2D2	UBE2D2	11014	-0.0098	0.27	NO
171	CUL3	CUL3	CUL3	11039	-0.01	0.27	NO
172	PDIA3	PDIA3	PDIA3	11062	-0.01	0.27	NO
173	SEC61G	SEC61G	SEC61G	11116	-0.011	0.27	NO
174	UBE3A	UBE3A	UBE3A	11196	-0.012	0.26	NO
175	ASB8	ASB8	ASB8	11262	-0.012	0.26	NO
176	FBXW11	FBXW11	FBXW11	11326	-0.013	0.26	NO
177	PSMC3	PSMC3	PSMC3	11355	-0.013	0.26	NO
178	HSPA5	HSPA5	HSPA5	11529	-0.014	0.25	NO
179	PSMB7	PSMB7	PSMB7	11552	-0.015	0.25	NO
180	CALR	CALR	CALR	11575	-0.015	0.25	NO
181	UBE4A	UBE4A	UBE4A	11659	-0.016	0.24	NO
182	UBR4	UBR4	UBR4	11762	-0.016	0.24	NO
183	CDC16	CDC16	CDC16	11805	-0.017	0.24	NO
184	CDC23	CDC23	CDC23	11807	-0.017	0.24	NO
185	UBA1	UBA1	UBA1	11915	-0.018	0.23	NO
186	CUL5	CUL5	CUL5	11916	-0.018	0.24	NO
187	KEAP1	KEAP1	KEAP1	11966	-0.018	0.23	NO
188	FBXO4	FBXO4	FBXO4	12013	-0.018	0.23	NO
189	BTRC	BTRC	BTRC	12032	-0.019	0.23	NO
190	LRSAM1	LRSAM1	LRSAM1	12215	-0.02	0.22	NO
191	RNF41	RNF41	RNF41	12264	-0.021	0.22	NO
192	UBE2E3	UBE2E3	UBE2E3	12337	-0.022	0.22	NO
193	HERC2	HERC2	HERC2	12382	-0.022	0.22	NO
194	PSMB5	PSMB5	PSMB5	12404	-0.022	0.22	NO
195	LRRC41	LRRC41	LRRC41	12500	-0.023	0.21	NO
196	PSMD9	PSMD9	PSMD9	12646	-0.025	0.2	NO
197	PSMD8	PSMD8	PSMD8	12657	-0.025	0.21	NO
198	CUL7	CUL7	CUL7	12754	-0.026	0.2	NO
199	PJA2	PJA2	PJA2	12985	-0.028	0.19	NO
200	ARIH2	ARIH2	ARIH2	13062	-0.029	0.19	NO
201	RNF123	RNF123	RNF123	13199	-0.031	0.18	NO
202	UBE2O	UBE2O	UBE2O	13360	-0.032	0.18	NO
203	UBE3B	UBE3B	UBE3B	13458	-0.034	0.17	NO
204	UBA5	UBA5	UBA5	13553	-0.035	0.17	NO
205	SKP1	SKP1	SKP1	13659	-0.036	0.16	NO
206	PJA1	PJA1	PJA1	13680	-0.036	0.16	NO
207	SAE1	SAE1	SAE1	13818	-0.038	0.16	NO
208	SPSB2	SPSB2	SPSB2	13822	-0.038	0.16	NO
209	RCHY1	RCHY1	RCHY1	13890	-0.039	0.16	NO
210	TCEB2	TCEB2	TCEB2	13902	-0.039	0.16	NO
211	ANAPC11	ANAPC11	ANAPC11	13915	-0.039	0.16	NO
212	DET1	DET1	DET1	13940	-0.039	0.16	NO
213	ANAPC13	ANAPC13	ANAPC13	13996	-0.04	0.16	NO
214	CDC34	CDC34	CDC34	14128	-0.042	0.16	NO
215	UBE2M	UBE2M	UBE2M	14247	-0.044	0.15	NO
216	CANX	CANX	CANX	14312	-0.044	0.15	NO
217	ASB1	ASB1	ASB1	14343	-0.045	0.15	NO
218	FBXW8	FBXW8	FBXW8	14364	-0.045	0.15	NO
219	DZIP3	DZIP3	DZIP3	14516	-0.047	0.15	NO
220	UBOX5	UBOX5	UBOX5	14555	-0.048	0.15	NO
221	FBXO3	FBXO3	FBXO3	14598	-0.049	0.15	NO
222	RNF144B	RNF144B	RNF144B	14746	-0.051	0.14	NO
223	ZBTB16	ZBTB16	ZBTB16	14841	-0.053	0.14	NO
224	UBE2D4	UBE2D4	UBE2D4	15146	-0.058	0.13	NO
225	FBXO44	FBXO44	FBXO44	15418	-0.064	0.11	NO
226	STUB1	STUB1	STUB1	15420	-0.064	0.12	NO
227	RNF182	RNF182	RNF182	16816	-0.11	0.045	NO
228	ASB4	ASB4	ASB4	17412	-0.16	0.02	NO
229	PARK2	PARK2	PARK2	17686	-0.2	0.016	NO

Figure S41. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS.

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

Table S22. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CD28	CD28	CD28	85	0.97	0.064	YES
2	CD247	CD247	CD247	124	0.92	0.13	YES
3	LCK	LCK	LCK	230	0.82	0.18	YES
4	CCR5	CCR5	CCR5	302	0.77	0.23	YES
5	DOCK2	DOCK2	DOCK2	337	0.75	0.28	YES
6	CD8B	CD8B	CD8B	532	0.66	0.32	YES
7	HCK	HCK	HCK	615	0.63	0.36	YES
8	PSMA8	PSMA8	PSMA8	909	0.54	0.38	YES
9	CXCR4	CXCR4	CXCR4	1176	0.47	0.4	YES
10	PSMB9	PSMB9	PSMB9	1307	0.44	0.42	YES
11	CD4	CD4	CD4	1371	0.42	0.45	YES
12	APOBEC3G	APOBEC3G	APOBEC3G	1728	0.36	0.45	YES
13	AP1S2	AP1S2	AP1S2	2745	0.22	0.41	YES
14	PSMB10	PSMB10	PSMB10	2841	0.21	0.42	YES
15	NUP210	NUP210	NUP210	2872	0.21	0.43	YES
16	PSMB8	PSMB8	PSMB8	3225	0.18	0.43	YES
17	B2M	B2M	B2M	3410	0.16	0.43	YES
18	TAF4B	TAF4B	TAF4B	3415	0.16	0.44	YES
19	RCC1	RCC1	RCC1	3503	0.16	0.44	YES
20	HLA-A	HLA-A	HLA-A	3615	0.15	0.45	YES
21	PSME2	PSME2	PSME2	3636	0.15	0.46	YES
22	ELMO1	ELMO1	ELMO1	3915	0.13	0.45	NO
23	TAF5	TAF5	TAF5	4273	0.11	0.44	NO
24	GTF2E1	GTF2E1	GTF2E1	4278	0.11	0.45	NO
25	PSME1	PSME1	PSME1	4860	0.087	0.42	NO
26	XRCC4	XRCC4	XRCC4	4928	0.084	0.42	NO
27	ELL	ELL	ELL	5011	0.082	0.42	NO
28	FEN1	FEN1	FEN1	5041	0.081	0.43	NO
29	RNGTT	RNGTT	RNGTT	5081	0.08	0.43	NO
30	NUP62	NUP62	NUP62	5152	0.077	0.43	NO
31	NUP107	NUP107	NUP107	5261	0.073	0.43	NO
32	NUP50	NUP50	NUP50	5316	0.071	0.44	NO
33	PSMA4	PSMA4	PSMA4	5410	0.068	0.43	NO
34	NUP93	NUP93	NUP93	5665	0.06	0.42	NO
35	POLR2D	POLR2D	POLR2D	5696	0.06	0.43	NO
36	AP1M1	AP1M1	AP1M1	5899	0.055	0.42	NO
37	CCNT1	CCNT1	CCNT1	5906	0.055	0.42	NO
38	NUP153	NUP153	NUP153	6058	0.051	0.42	NO
39	TAF13	TAF13	TAF13	6141	0.049	0.42	NO
40	PSMA3	PSMA3	PSMA3	6156	0.049	0.42	NO
41	GTF2A1	GTF2A1	GTF2A1	6213	0.048	0.42	NO
42	GTF2H2	GTF2H2	GTF2H2	6247	0.047	0.42	NO
43	NMT2	NMT2	NMT2	6306	0.046	0.42	NO
44	PSMA5	PSMA5	PSMA5	6365	0.045	0.42	NO
45	PAK2	PAK2	PAK2	6370	0.045	0.42	NO
46	FYN	FYN	FYN	6389	0.044	0.43	NO
47	NUP155	NUP155	NUP155	6428	0.043	0.43	NO
48	TAF4	TAF4	TAF4	6493	0.042	0.43	NO
49	PSMA6	PSMA6	PSMA6	6509	0.042	0.43	NO
50	PSMB2	PSMB2	PSMB2	6656	0.039	0.42	NO
51	AP2A2	AP2A2	AP2A2	6668	0.039	0.42	NO
52	PSMD11	PSMD11	PSMD11	6680	0.039	0.43	NO
53	AP1B1	AP1B1	AP1B1	6797	0.037	0.42	NO
54	NCBP1	NCBP1	NCBP1	6835	0.036	0.42	NO
55	PSMD1	PSMD1	PSMD1	6886	0.035	0.42	NO
56	PSMD7	PSMD7	PSMD7	6901	0.035	0.42	NO
57	NUP85	NUP85	NUP85	6971	0.034	0.42	NO
58	PSMD5	PSMD5	PSMD5	6976	0.034	0.43	NO
59	PSMA1	PSMA1	PSMA1	7037	0.033	0.42	NO
60	RAN	RAN	RAN	7061	0.032	0.43	NO
61	HMGA1	HMGA1	HMGA1	7085	0.032	0.43	NO
62	TAF12	TAF12	TAF12	7115	0.032	0.43	NO
63	PSMC2	PSMC2	PSMC2	7116	0.032	0.43	NO
64	NUP205	NUP205	NUP205	7131	0.031	0.43	NO
65	PSMA2	PSMA2	PSMA2	7223	0.03	0.43	NO
66	RANBP1	RANBP1	RANBP1	7264	0.029	0.43	NO
67	NUP37	NUP37	NUP37	7324	0.028	0.43	NO
68	AP2S1	AP2S1	AP2S1	7377	0.028	0.43	NO
69	PSIP1	PSIP1	PSIP1	7464	0.027	0.42	NO
70	RBX1	RBX1	RBX1	7482	0.026	0.42	NO
71	CCNT2	CCNT2	CCNT2	7487	0.026	0.42	NO
72	TPR	TPR	TPR	7494	0.026	0.43	NO
73	XPO1	XPO1	XPO1	7518	0.026	0.43	NO
74	RANGAP1	RANGAP1	RANGAP1	7601	0.025	0.42	NO
75	LIG4	LIG4	LIG4	7618	0.024	0.42	NO
76	PSMD12	PSMD12	PSMD12	7647	0.024	0.42	NO
77	PSMA7	PSMA7	PSMA7	7667	0.024	0.43	NO
78	CTDP1	CTDP1	CTDP1	7708	0.024	0.42	NO
79	GTF2H3	GTF2H3	GTF2H3	7735	0.023	0.43	NO
80	PSME4	PSME4	PSME4	7736	0.023	0.43	NO
81	PSMD13	PSMD13	PSMD13	7764	0.023	0.43	NO
82	NUPL2	NUPL2	NUPL2	7938	0.021	0.42	NO
83	NUP54	NUP54	NUP54	8060	0.019	0.41	NO
84	KPNB1	KPNB1	KPNB1	8079	0.019	0.41	NO
85	NUP35	NUP35	NUP35	8141	0.018	0.41	NO
86	POLR2B	POLR2B	POLR2B	8148	0.018	0.41	NO
87	SLC25A5	SLC25A5	SLC25A5	8202	0.018	0.41	NO
88	PSMB3	PSMB3	PSMB3	8242	0.017	0.41	NO
89	NUP88	NUP88	NUP88	8296	0.017	0.41	NO
90	PACS1	PACS1	PACS1	8303	0.017	0.41	NO
91	GTF2B	GTF2B	GTF2B	8399	0.015	0.4	NO
92	PSMB4	PSMB4	PSMB4	8403	0.015	0.41	NO
93	GTF2H2B	GTF2H2B	GTF2H2B	8472	0.014	0.4	NO
94	TBP	TBP	TBP	8562	0.014	0.4	NO
95	GTF2F2	GTF2F2	GTF2F2	8587	0.013	0.4	NO
96	PSMD14	PSMD14	PSMD14	8607	0.013	0.4	NO
97	RAC1	RAC1	RAC1	8644	0.013	0.4	NO
98	GTF2E2	GTF2E2	GTF2E2	8701	0.012	0.4	NO
99	PPIA	PPIA	PPIA	8795	0.011	0.39	NO
100	POLR2G	POLR2G	POLR2G	8865	0.011	0.39	NO
101	SUPT16H	SUPT16H	SUPT16H	8890	0.01	0.39	NO
102	CDK9	CDK9	CDK9	8908	0.01	0.39	NO
103	PSMB1	PSMB1	PSMB1	8909	0.01	0.39	NO
104	GTF2A2	GTF2A2	GTF2A2	8915	0.01	0.39	NO
105	POLR2K	POLR2K	POLR2K	8984	0.0094	0.38	NO
106	VPS37C	VPS37C	VPS37C	9007	0.0092	0.38	NO
107	UBA52	UBA52	UBA52	9051	0.0087	0.38	NO
108	XRCC6	XRCC6	XRCC6	9113	0.0081	0.38	NO
109	SUPT4H1	SUPT4H1	SUPT4H1	9206	0.0072	0.38	NO
110	PSMD3	PSMD3	PSMD3	9287	0.0065	0.37	NO
111	ERCC3	ERCC3	ERCC3	9293	0.0064	0.37	NO
112	PSMD4	PSMD4	PSMD4	9326	0.0061	0.37	NO
113	PSMD2	PSMD2	PSMD2	9438	0.005	0.36	NO
114	PSMF1	PSMF1	PSMF1	9454	0.0048	0.36	NO
115	XRCC5	XRCC5	XRCC5	9487	0.0045	0.36	NO
116	NUPL1	NUPL1	NUPL1	9491	0.0045	0.36	NO
117	PSMD6	PSMD6	PSMD6	9630	0.0031	0.35	NO
118	AP2M1	AP2M1	AP2M1	9636	0.0031	0.35	NO
119	NUP43	NUP43	NUP43	9645	0.003	0.35	NO
120	KPNA1	KPNA1	KPNA1	9675	0.0027	0.35	NO
121	TAF9	TAF9	TAF9	9728	0.0023	0.35	NO
122	RAE1	RAE1	RAE1	9777	0.0019	0.35	NO
123	AP2A1	AP2A1	AP2A1	9779	0.0019	0.35	NO
124	TAF1	TAF1	TAF1	9847	0.0011	0.34	NO
125	NUP214	NUP214	NUP214	9857	0.001	0.34	NO
126	PSMC6	PSMC6	PSMC6	9878	0.00086	0.34	NO
127	AAAS	AAAS	AAAS	9929	0.00034	0.34	NO
128	NUP188	NUP188	NUP188	9930	0.00033	0.34	NO
129	PSMB6	PSMB6	PSMB6	9986	-0.00029	0.34	NO
130	LIG1	LIG1	LIG1	10074	-0.0011	0.33	NO
131	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.33	NO
132	AP1G1	AP1G1	AP1G1	10109	-0.0014	0.33	NO
133	NCBP2	NCBP2	NCBP2	10199	-0.0022	0.32	NO
134	NMT1	NMT1	NMT1	10294	-0.0031	0.32	NO
135	PSMC4	PSMC4	PSMC4	10346	-0.0036	0.32	NO
136	BANF1	BANF1	BANF1	10370	-0.0038	0.32	NO
137	TAF10	TAF10	TAF10	10372	-0.0038	0.32	NO
138	GTF2H1	GTF2H1	GTF2H1	10517	-0.0053	0.31	NO
139	SEH1L	SEH1L	SEH1L	10610	-0.006	0.3	NO
140	POM121	POM121	POM121	10622	-0.0061	0.3	NO
141	TCEB1	TCEB1	TCEB1	10691	-0.0067	0.3	NO
142	PSMC1	PSMC1	PSMC1	10749	-0.0073	0.3	NO
143	POLR2A	POLR2A	POLR2A	10801	-0.0078	0.3	NO
144	TCEB3	TCEB3	TCEB3	10818	-0.008	0.3	NO
145	PSMD10	PSMD10	PSMD10	10860	-0.0083	0.29	NO
146	PSMC5	PSMC5	PSMC5	10973	-0.0094	0.29	NO
147	VPS37A	VPS37A	VPS37A	11065	-0.01	0.28	NO
148	SUPT5H	SUPT5H	SUPT5H	11097	-0.01	0.28	NO
149	SSRP1	SSRP1	SSRP1	11109	-0.011	0.28	NO
150	RANBP2	RANBP2	RANBP2	11131	-0.011	0.28	NO
151	ARF1	ARF1	ARF1	11181	-0.011	0.28	NO
152	PSMC3	PSMC3	PSMC3	11355	-0.013	0.27	NO
153	PSMB7	PSMB7	PSMB7	11552	-0.015	0.26	NO
154	COBRA1	COBRA1	COBRA1	11567	-0.015	0.26	NO
155	POLR2F	POLR2F	POLR2F	11604	-0.015	0.26	NO
156	TAF11	TAF11	TAF11	11666	-0.016	0.26	NO
157	POLR2E	POLR2E	POLR2E	11734	-0.016	0.26	NO
158	POLR2H	POLR2H	POLR2H	11814	-0.017	0.25	NO
159	MNAT1	MNAT1	MNAT1	11857	-0.017	0.25	NO
160	CUL5	CUL5	CUL5	11916	-0.018	0.25	NO
161	BTRC	BTRC	BTRC	12032	-0.019	0.24	NO
162	TCEA1	TCEA1	TCEA1	12083	-0.019	0.24	NO
163	RNMT	RNMT	RNMT	12118	-0.019	0.24	NO
164	TSG101	TSG101	TSG101	12152	-0.02	0.24	NO
165	POLR2J	POLR2J	POLR2J	12155	-0.02	0.24	NO
166	CDK7	CDK7	CDK7	12179	-0.02	0.24	NO
167	VPS37B	VPS37B	VPS37B	12240	-0.021	0.24	NO
168	AP2B1	AP2B1	AP2B1	12255	-0.021	0.24	NO
169	PSMB5	PSMB5	PSMB5	12404	-0.022	0.24	NO
170	RDBP	RDBP	RDBP	12457	-0.023	0.23	NO
171	SLC25A6	SLC25A6	SLC25A6	12501	-0.024	0.23	NO
172	NUP133	NUP133	NUP133	12598	-0.024	0.23	NO
173	PSMD9	PSMD9	PSMD9	12646	-0.025	0.23	NO
174	PSMD8	PSMD8	PSMD8	12657	-0.025	0.23	NO
175	CCNH	CCNH	CCNH	12671	-0.025	0.23	NO
176	TAF6	TAF6	TAF6	12821	-0.027	0.22	NO
177	AP1S1	AP1S1	AP1S1	12990	-0.028	0.22	NO
178	GTF2F1	GTF2F1	GTF2F1	13262	-0.031	0.2	NO
179	WHSC2	WHSC2	WHSC2	13293	-0.032	0.2	NO
180	NPM1	NPM1	NPM1	13323	-0.032	0.2	NO
181	SKP1	SKP1	SKP1	13659	-0.036	0.19	NO
182	POLR2L	POLR2L	POLR2L	13681	-0.036	0.19	NO
183	GTF2H4	GTF2H4	GTF2H4	13763	-0.037	0.19	NO
184	VPS28	VPS28	VPS28	13875	-0.038	0.18	NO
185	TCEB2	TCEB2	TCEB2	13902	-0.039	0.18	NO
186	TH1L	TH1L	TH1L	14262	-0.044	0.17	NO
187	POLR2C	POLR2C	POLR2C	14372	-0.045	0.16	NO
188	POLR2I	POLR2I	POLR2I	14846	-0.053	0.14	NO
189	ATP6V1H	ATP6V1H	ATP6V1H	15622	-0.068	0.1	NO
190	ERCC2	ERCC2	ERCC2	16055	-0.08	0.085	NO
191	AP1M2	AP1M2	AP1M2	16399	-0.092	0.072	NO
192	SLC25A4	SLC25A4	SLC25A4	16831	-0.11	0.056	NO
193	VPS37D	VPS37D	VPS37D	16905	-0.12	0.06	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 FRUCTOSE AND MANNOSE METABOLISM.

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

genes ES table in pathway: KEGG FATTY ACID METABOLISM

Table 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	IFNG	IFNG	IFNG	253	0.8	0.14	YES
2	PIF1	PIF1	PIF1	385	0.73	0.27	YES
3	IL2	IL2	IL2	571	0.65	0.38	YES
4	WT1	WT1	WT1	1511	0.4	0.4	YES
5	BLM	BLM	BLM	1600	0.38	0.47	YES
6	IRF1	IRF1	IRF1	1768	0.35	0.52	YES
7	MYC	MYC	MYC	2140	0.29	0.56	YES
8	IFNAR2	IFNAR2	IFNAR2	2968	0.2	0.55	NO
9	NR2F2	NR2F2	NR2F2	4044	0.13	0.51	NO
10	ATM	ATM	ATM	4182	0.12	0.53	NO
11	TGFB1	TGFB1	TGFB1	4438	0.1	0.53	NO
12	MXD1	MXD1	MXD1	5420	0.068	0.49	NO
13	NFKB1	NFKB1	NFKB1	5568	0.064	0.49	NO
14	ZNFX1	ZNFX1	ZNFX1	5720	0.059	0.5	NO
15	WRN	WRN	WRN	6076	0.051	0.49	NO
16	NBN	NBN	NBN	6447	0.043	0.47	NO
17	TINF2	TINF2	TINF2	6591	0.04	0.47	NO
18	SP1	SP1	SP1	6620	0.04	0.48	NO
19	MAX	MAX	MAX	6781	0.037	0.48	NO
20	MRE11A	MRE11A	MRE11A	6921	0.035	0.48	NO
21	SAP30	SAP30	SAP30	7244	0.03	0.46	NO
22	ESR1	ESR1	ESR1	7265	0.029	0.47	NO
23	FOS	FOS	FOS	7557	0.025	0.46	NO
24	RBBP4	RBBP4	RBBP4	7637	0.024	0.46	NO
25	HSP90AA1	HSP90AA1	HSP90AA1	7659	0.024	0.46	NO
26	CDKN1B	CDKN1B	CDKN1B	7713	0.024	0.46	NO
27	HUS1	HUS1	HUS1	7805	0.022	0.46	NO
28	ACD	ACD	ACD	7892	0.022	0.46	NO
29	HNRNPC	HNRNPC	HNRNPC	8146	0.018	0.45	NO
30	HDAC2	HDAC2	HDAC2	8193	0.018	0.45	NO
31	TERF1	TERF1	TERF1	8224	0.018	0.45	NO
32	RAD1	RAD1	RAD1	8253	0.017	0.45	NO
33	SP3	SP3	SP3	8751	0.012	0.43	NO
34	XRCC6	XRCC6	XRCC6	9113	0.0081	0.41	NO
35	PINX1	PINX1	PINX1	9255	0.0068	0.4	NO
36	RPS6KB1	RPS6KB1	RPS6KB1	9265	0.0066	0.4	NO
37	SIN3B	SIN3B	SIN3B	9338	0.006	0.4	NO
38	MTOR	MTOR	MTOR	9430	0.0051	0.4	NO
39	NCL	NCL	NCL	9466	0.0047	0.4	NO
40	XRCC5	XRCC5	XRCC5	9487	0.0045	0.4	NO
41	TERF2	TERF2	TERF2	9696	0.0026	0.38	NO
42	DKC1	DKC1	DKC1	9735	0.0022	0.38	NO
43	SIN3A	SIN3A	SIN3A	10231	-0.0024	0.36	NO
44	PTGES3	PTGES3	PTGES3	10331	-0.0034	0.35	NO
45	PARP2	PARP2	PARP2	10354	-0.0037	0.35	NO
46	MAPK1	MAPK1	MAPK1	10407	-0.0042	0.35	NO
47	TERF2IP	TERF2IP	TERF2IP	10575	-0.0058	0.34	NO
48	TNKS	TNKS	TNKS	10698	-0.0068	0.33	NO
49	JUN	JUN	JUN	10935	-0.0089	0.32	NO
50	AKT1	AKT1	AKT1	11079	-0.01	0.32	NO
51	RAD50	RAD50	RAD50	11081	-0.01	0.32	NO
52	ABL1	ABL1	ABL1	11137	-0.011	0.32	NO
53	UBE3A	UBE3A	UBE3A	11196	-0.012	0.32	NO
54	RBBP7	RBBP7	RBBP7	11210	-0.012	0.32	NO
55	SMG6	SMG6	SMG6	11483	-0.014	0.3	NO
56	SMG5	SMG5	SMG5	11538	-0.014	0.3	NO
57	SAP18	SAP18	SAP18	11569	-0.015	0.3	NO
58	RAD9A	RAD9A	RAD9A	11800	-0.017	0.3	NO
59	E2F1	E2F1	E2F1	12148	-0.02	0.28	NO
60	EGF	EGF	EGF	12182	-0.02	0.28	NO
61	POT1	POT1	POT1	12485	-0.023	0.27	NO
62	EGFR	EGFR	EGFR	12628	-0.025	0.27	NO
63	SMAD3	SMAD3	SMAD3	13310	-0.032	0.23	NO
64	YWHAE	YWHAE	YWHAE	13473	-0.034	0.23	NO
65	HDAC1	HDAC1	HDAC1	13505	-0.034	0.24	NO
66	CCND1	CCND1	CCND1	13617	-0.035	0.24	NO
67	MAPK3	MAPK3	MAPK3	13684	-0.036	0.24	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 FATTY ACID METABOLISM.

Figure S46. 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 PURINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CD19	CD19	CD19	50	1	0.069	YES
2	CD79A	CD79A	CD79A	59	1	0.14	YES
3	BLK	BLK	BLK	117	0.93	0.2	YES
4	CD79B	CD79B	CD79B	198	0.85	0.26	YES
5	BTK	BTK	BTK	231	0.82	0.31	YES
6	VAV1	VAV1	VAV1	341	0.75	0.36	YES
7	RASGRP1	RASGRP1	RASGRP1	355	0.74	0.41	YES
8	PRKCB	PRKCB	PRKCB	537	0.66	0.45	YES
9	CARD11	CARD11	CARD11	557	0.65	0.49	YES
10	PSMA8	PSMA8	PSMA8	909	0.54	0.51	YES
11	PSMB9	PSMB9	PSMB9	1307	0.44	0.52	YES
12	PIK3CD	PIK3CD	PIK3CD	1368	0.43	0.55	YES
13	PIK3AP1	PIK3AP1	PIK3AP1	1755	0.36	0.55	YES
14	REL	REL	REL	1898	0.33	0.56	YES
15	PLCG2	PLCG2	PLCG2	2054	0.3	0.58	YES
16	NFKBIE	NFKBIE	NFKBIE	2607	0.24	0.56	NO
17	PSMB10	PSMB10	PSMB10	2841	0.21	0.56	NO
18	PSMB8	PSMB8	PSMB8	3225	0.18	0.56	NO
19	PSME2	PSME2	PSME2	3636	0.15	0.54	NO
20	SH3KBP1	SH3KBP1	SH3KBP1	3657	0.15	0.55	NO
21	LYN	LYN	LYN	3685	0.15	0.56	NO
22	RASGRP3	RASGRP3	RASGRP3	3725	0.14	0.57	NO
23	NFKBIA	NFKBIA	NFKBIA	3969	0.13	0.56	NO
24	MALT1	MALT1	MALT1	4440	0.1	0.55	NO
25	PSME1	PSME1	PSME1	4860	0.087	0.53	NO
26	BCL10	BCL10	BCL10	4942	0.084	0.53	NO
27	NRAS	NRAS	NRAS	5231	0.074	0.52	NO
28	PSMA4	PSMA4	PSMA4	5410	0.068	0.51	NO
29	CBL	CBL	CBL	5492	0.066	0.51	NO
30	CBLB	CBLB	CBLB	5513	0.065	0.52	NO
31	KRAS	KRAS	KRAS	5529	0.065	0.52	NO
32	GRB2	GRB2	GRB2	5755	0.058	0.51	NO
33	IKBKG	IKBKG	IKBKG	5908	0.055	0.51	NO
34	PSMA3	PSMA3	PSMA3	6156	0.049	0.5	NO
35	NCK1	NCK1	NCK1	6311	0.046	0.49	NO
36	PSMA5	PSMA5	PSMA5	6365	0.045	0.49	NO
37	PIK3R1	PIK3R1	PIK3R1	6384	0.044	0.49	NO
38	FYN	FYN	FYN	6389	0.044	0.5	NO
39	RICTOR	RICTOR	RICTOR	6458	0.043	0.5	NO
40	PSMA6	PSMA6	PSMA6	6509	0.042	0.5	NO
41	SHC1	SHC1	SHC1	6625	0.04	0.49	NO
42	ITPR2	ITPR2	ITPR2	6637	0.04	0.49	NO
43	PSMB2	PSMB2	PSMB2	6656	0.039	0.5	NO
44	SOS1	SOS1	SOS1	6678	0.039	0.5	NO
45	PSMD11	PSMD11	PSMD11	6680	0.039	0.5	NO
46	PSMD1	PSMD1	PSMD1	6886	0.035	0.49	NO
47	PSMD7	PSMD7	PSMD7	6901	0.035	0.49	NO
48	PSMD5	PSMD5	PSMD5	6976	0.034	0.49	NO
49	PSMA1	PSMA1	PSMA1	7037	0.033	0.49	NO
50	PSMC2	PSMC2	PSMC2	7116	0.032	0.49	NO
51	PSMA2	PSMA2	PSMA2	7223	0.03	0.48	NO
52	CALM1	CALM1	CALM1	7274	0.029	0.48	NO
53	IKBKB	IKBKB	IKBKB	7353	0.028	0.48	NO
54	PTEN	PTEN	PTEN	7432	0.027	0.48	NO
55	CREB1	CREB1	CREB1	7508	0.026	0.48	NO
56	PSMD12	PSMD12	PSMD12	7647	0.024	0.47	NO
57	PSMA7	PSMA7	PSMA7	7667	0.024	0.47	NO
58	CDKN1B	CDKN1B	CDKN1B	7713	0.024	0.47	NO
59	RELA	RELA	RELA	7719	0.024	0.47	NO
60	FOXO3	FOXO3	FOXO3	7733	0.023	0.47	NO
61	PSME4	PSME4	PSME4	7736	0.023	0.47	NO
62	CHUK	CHUK	CHUK	7759	0.023	0.47	NO
63	PSMD13	PSMD13	PSMD13	7764	0.023	0.48	NO
64	SYK	SYK	SYK	7895	0.022	0.47	NO
65	MAP3K7	MAP3K7	MAP3K7	7995	0.02	0.47	NO
66	PSMB3	PSMB3	PSMB3	8242	0.017	0.45	NO
67	CALM3	CALM3	CALM3	8320	0.016	0.45	NO
68	PSMB4	PSMB4	PSMB4	8403	0.015	0.45	NO
69	ORAI1	ORAI1	ORAI1	8538	0.014	0.44	NO
70	PSMD14	PSMD14	PSMD14	8607	0.013	0.44	NO
71	MDM2	MDM2	MDM2	8726	0.012	0.43	NO
72	PSMB1	PSMB1	PSMB1	8909	0.01	0.42	NO
73	UBA52	UBA52	UBA52	9051	0.0087	0.41	NO
74	PLCG1	PLCG1	PLCG1	9080	0.0085	0.41	NO
75	CUL1	CUL1	CUL1	9242	0.0069	0.4	NO
76	PSMD3	PSMD3	PSMD3	9287	0.0065	0.4	NO
77	RPS6KB2	RPS6KB2	RPS6KB2	9294	0.0064	0.4	NO
78	PSMD4	PSMD4	PSMD4	9326	0.0061	0.4	NO
79	MTOR	MTOR	MTOR	9430	0.0051	0.4	NO
80	PSMD2	PSMD2	PSMD2	9438	0.005	0.4	NO
81	PSMF1	PSMF1	PSMF1	9454	0.0048	0.4	NO
82	PSMD6	PSMD6	PSMD6	9630	0.0031	0.39	NO
83	CDKN1A	CDKN1A	CDKN1A	9722	0.0023	0.38	NO
84	PSMC6	PSMC6	PSMC6	9878	0.00086	0.37	NO
85	PSMB6	PSMB6	PSMB6	9986	-0.00029	0.37	NO
86	CALM2	CALM2	CALM2	10048	-0.00084	0.36	NO
87	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.36	NO
88	PSMC4	PSMC4	PSMC4	10346	-0.0036	0.35	NO
89	BLNK	BLNK	BLNK	10654	-0.0064	0.33	NO
90	PSMC1	PSMC1	PSMC1	10749	-0.0073	0.33	NO
91	NFKBIB	NFKBIB	NFKBIB	10857	-0.0083	0.32	NO
92	PSMD10	PSMD10	PSMD10	10860	-0.0083	0.32	NO
93	PSMC5	PSMC5	PSMC5	10973	-0.0094	0.32	NO
94	MAPKAP1	MAPKAP1	MAPKAP1	10989	-0.0096	0.32	NO
95	AKT1	AKT1	AKT1	11079	-0.01	0.31	NO
96	FBXW11	FBXW11	FBXW11	11326	-0.013	0.3	NO
97	ITPR3	ITPR3	ITPR3	11336	-0.013	0.3	NO
98	PSMC3	PSMC3	PSMC3	11355	-0.013	0.3	NO
99	PSMB7	PSMB7	PSMB7	11552	-0.015	0.29	NO
100	GSK3A	GSK3A	GSK3A	11806	-0.017	0.28	NO
101	BTRC	BTRC	BTRC	12032	-0.019	0.26	NO
102	AKT3	AKT3	AKT3	12067	-0.019	0.26	NO
103	FOXO1	FOXO1	FOXO1	12080	-0.019	0.26	NO
104	HRAS	HRAS	HRAS	12189	-0.02	0.26	NO
105	PSMB5	PSMB5	PSMB5	12404	-0.022	0.25	NO
106	PSMD9	PSMD9	PSMD9	12646	-0.025	0.24	NO
107	PSMD8	PSMD8	PSMD8	12657	-0.025	0.24	NO
108	CASP9	CASP9	CASP9	12720	-0.026	0.24	NO
109	PDPK1	PDPK1	PDPK1	12992	-0.028	0.22	NO
110	AKT1S1	AKT1S1	AKT1S1	13504	-0.034	0.2	NO
111	SKP1	SKP1	SKP1	13659	-0.036	0.19	NO
112	FOXO4	FOXO4	FOXO4	13845	-0.038	0.18	NO
113	NR4A1	NR4A1	NR4A1	14272	-0.044	0.16	NO
114	THEM4	THEM4	THEM4	14828	-0.052	0.14	NO
115	PHLPP1	PHLPP1	PHLPP1	15354	-0.062	0.11	NO
116	TSC2	TSC2	TSC2	15445	-0.064	0.11	NO
117	STIM1	STIM1	STIM1	15624	-0.068	0.1	NO
118	BAD	BAD	BAD	15714	-0.07	0.1	NO
119	MLST8	MLST8	MLST8	15777	-0.072	0.11	NO
120	AKT2	AKT2	AKT2	16561	-0.099	0.069	NO
121	TRIB3	TRIB3	TRIB3	17267	-0.14	0.039	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 PURINE METABOLISM.

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

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CD28	CD28	CD28	85	0.97	0.086	YES
2	CD247	CD247	CD247	124	0.92	0.17	YES
3	LCK	LCK	LCK	230	0.82	0.24	YES
4	DOCK2	DOCK2	DOCK2	337	0.75	0.3	YES
5	CD8B	CD8B	CD8B	532	0.66	0.36	YES
6	HCK	HCK	HCK	615	0.63	0.41	YES
7	PSMA8	PSMA8	PSMA8	909	0.54	0.44	YES
8	PSMB9	PSMB9	PSMB9	1307	0.44	0.46	YES
9	CD4	CD4	CD4	1371	0.42	0.5	YES
10	APOBEC3G	APOBEC3G	APOBEC3G	1728	0.36	0.51	YES
11	AP1S2	AP1S2	AP1S2	2745	0.22	0.48	YES
12	PSMB10	PSMB10	PSMB10	2841	0.21	0.49	YES
13	NUP210	NUP210	NUP210	2872	0.21	0.51	YES
14	PSMB8	PSMB8	PSMB8	3225	0.18	0.51	YES
15	B2M	B2M	B2M	3410	0.16	0.51	YES
16	RCC1	RCC1	RCC1	3503	0.16	0.52	YES
17	HLA-A	HLA-A	HLA-A	3615	0.15	0.53	YES
18	PSME2	PSME2	PSME2	3636	0.15	0.54	YES
19	ELMO1	ELMO1	ELMO1	3915	0.13	0.54	NO
20	PSME1	PSME1	PSME1	4860	0.087	0.49	NO
21	NUP62	NUP62	NUP62	5152	0.077	0.48	NO
22	NUP107	NUP107	NUP107	5261	0.073	0.48	NO
23	NUP50	NUP50	NUP50	5316	0.071	0.49	NO
24	PSMA4	PSMA4	PSMA4	5410	0.068	0.49	NO
25	NUP93	NUP93	NUP93	5665	0.06	0.48	NO
26	AP1M1	AP1M1	AP1M1	5899	0.055	0.47	NO
27	CCNT1	CCNT1	CCNT1	5906	0.055	0.48	NO
28	NUP153	NUP153	NUP153	6058	0.051	0.47	NO
29	PSMA3	PSMA3	PSMA3	6156	0.049	0.47	NO
30	PSMA5	PSMA5	PSMA5	6365	0.045	0.47	NO
31	PAK2	PAK2	PAK2	6370	0.045	0.47	NO
32	FYN	FYN	FYN	6389	0.044	0.47	NO
33	NUP155	NUP155	NUP155	6428	0.043	0.47	NO
34	PSMA6	PSMA6	PSMA6	6509	0.042	0.47	NO
35	PSMB2	PSMB2	PSMB2	6656	0.039	0.47	NO
36	AP2A2	AP2A2	AP2A2	6668	0.039	0.47	NO
37	PSMD11	PSMD11	PSMD11	6680	0.039	0.48	NO
38	AP1B1	AP1B1	AP1B1	6797	0.037	0.47	NO
39	PSMD1	PSMD1	PSMD1	6886	0.035	0.47	NO
40	PSMD7	PSMD7	PSMD7	6901	0.035	0.47	NO
41	NUP85	NUP85	NUP85	6971	0.034	0.47	NO
42	PSMD5	PSMD5	PSMD5	6976	0.034	0.48	NO
43	PSMA1	PSMA1	PSMA1	7037	0.033	0.48	NO
44	RAN	RAN	RAN	7061	0.032	0.48	NO
45	HMGA1	HMGA1	HMGA1	7085	0.032	0.48	NO
46	PSMC2	PSMC2	PSMC2	7116	0.032	0.48	NO
47	NUP205	NUP205	NUP205	7131	0.031	0.48	NO
48	PSMA2	PSMA2	PSMA2	7223	0.03	0.48	NO
49	RANBP1	RANBP1	RANBP1	7264	0.029	0.48	NO
50	NUP37	NUP37	NUP37	7324	0.028	0.48	NO
51	AP2S1	AP2S1	AP2S1	7377	0.028	0.48	NO
52	PSIP1	PSIP1	PSIP1	7464	0.027	0.48	NO
53	RBX1	RBX1	RBX1	7482	0.026	0.48	NO
54	TPR	TPR	TPR	7494	0.026	0.48	NO
55	XPO1	XPO1	XPO1	7518	0.026	0.48	NO
56	RANGAP1	RANGAP1	RANGAP1	7601	0.025	0.48	NO
57	PSMD12	PSMD12	PSMD12	7647	0.024	0.48	NO
58	PSMA7	PSMA7	PSMA7	7667	0.024	0.48	NO
59	PSME4	PSME4	PSME4	7736	0.023	0.48	NO
60	PSMD13	PSMD13	PSMD13	7764	0.023	0.48	NO
61	NUPL2	NUPL2	NUPL2	7938	0.021	0.47	NO
62	NUP54	NUP54	NUP54	8060	0.019	0.47	NO
63	KPNB1	KPNB1	KPNB1	8079	0.019	0.47	NO
64	NUP35	NUP35	NUP35	8141	0.018	0.46	NO
65	SLC25A5	SLC25A5	SLC25A5	8202	0.018	0.46	NO
66	PSMB3	PSMB3	PSMB3	8242	0.017	0.46	NO
67	NUP88	NUP88	NUP88	8296	0.017	0.46	NO
68	PACS1	PACS1	PACS1	8303	0.017	0.46	NO
69	PSMB4	PSMB4	PSMB4	8403	0.015	0.46	NO
70	PSMD14	PSMD14	PSMD14	8607	0.013	0.45	NO
71	RAC1	RAC1	RAC1	8644	0.013	0.45	NO
72	PPIA	PPIA	PPIA	8795	0.011	0.44	NO
73	CDK9	CDK9	CDK9	8908	0.01	0.44	NO
74	PSMB1	PSMB1	PSMB1	8909	0.01	0.44	NO
75	UBA52	UBA52	UBA52	9051	0.0087	0.43	NO
76	PSMD3	PSMD3	PSMD3	9287	0.0065	0.42	NO
77	PSMD4	PSMD4	PSMD4	9326	0.0061	0.42	NO
78	PSMD2	PSMD2	PSMD2	9438	0.005	0.41	NO
79	PSMF1	PSMF1	PSMF1	9454	0.0048	0.41	NO
80	NUPL1	NUPL1	NUPL1	9491	0.0045	0.41	NO
81	PSMD6	PSMD6	PSMD6	9630	0.0031	0.4	NO
82	AP2M1	AP2M1	AP2M1	9636	0.0031	0.4	NO
83	NUP43	NUP43	NUP43	9645	0.003	0.4	NO
84	KPNA1	KPNA1	KPNA1	9675	0.0027	0.4	NO
85	RAE1	RAE1	RAE1	9777	0.0019	0.39	NO
86	AP2A1	AP2A1	AP2A1	9779	0.0019	0.39	NO
87	NUP214	NUP214	NUP214	9857	0.001	0.39	NO
88	PSMC6	PSMC6	PSMC6	9878	0.00086	0.39	NO
89	AAAS	AAAS	AAAS	9929	0.00034	0.38	NO
90	NUP188	NUP188	NUP188	9930	0.00033	0.38	NO
91	PSMB6	PSMB6	PSMB6	9986	-0.00029	0.38	NO
92	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.38	NO
93	AP1G1	AP1G1	AP1G1	10109	-0.0014	0.38	NO
94	PSMC4	PSMC4	PSMC4	10346	-0.0036	0.36	NO
95	BANF1	BANF1	BANF1	10370	-0.0038	0.36	NO
96	SEH1L	SEH1L	SEH1L	10610	-0.006	0.35	NO
97	POM121	POM121	POM121	10622	-0.0061	0.35	NO
98	TCEB1	TCEB1	TCEB1	10691	-0.0067	0.34	NO
99	PSMC1	PSMC1	PSMC1	10749	-0.0073	0.34	NO
100	PSMD10	PSMD10	PSMD10	10860	-0.0083	0.34	NO
101	PSMC5	PSMC5	PSMC5	10973	-0.0094	0.33	NO
102	RANBP2	RANBP2	RANBP2	11131	-0.011	0.32	NO
103	ARF1	ARF1	ARF1	11181	-0.011	0.32	NO
104	PSMC3	PSMC3	PSMC3	11355	-0.013	0.31	NO
105	PSMB7	PSMB7	PSMB7	11552	-0.015	0.3	NO
106	CUL5	CUL5	CUL5	11916	-0.018	0.29	NO
107	BTRC	BTRC	BTRC	12032	-0.019	0.28	NO
108	AP2B1	AP2B1	AP2B1	12255	-0.021	0.27	NO
109	PSMB5	PSMB5	PSMB5	12404	-0.022	0.26	NO
110	SLC25A6	SLC25A6	SLC25A6	12501	-0.024	0.26	NO
111	NUP133	NUP133	NUP133	12598	-0.024	0.26	NO
112	PSMD9	PSMD9	PSMD9	12646	-0.025	0.26	NO
113	PSMD8	PSMD8	PSMD8	12657	-0.025	0.26	NO
114	AP1S1	AP1S1	AP1S1	12990	-0.028	0.24	NO
115	NPM1	NPM1	NPM1	13323	-0.032	0.23	NO
116	SKP1	SKP1	SKP1	13659	-0.036	0.21	NO
117	TCEB2	TCEB2	TCEB2	13902	-0.039	0.2	NO
118	ATP6V1H	ATP6V1H	ATP6V1H	15622	-0.068	0.11	NO
119	AP1M2	AP1M2	AP1M2	16399	-0.092	0.078	NO
120	SLC25A4	SLC25A4	SLC25A4	16831	-0.11	0.064	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 ALANINE ASPARTATE AND GLUTAMATE METABOLISM.

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

genes ES table in pathway: KEGG CYSTEINE AND METHIONINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ASB2	ASB2	ASB2	169	0.87	0.066	YES
2	UBE2C	UBE2C	UBE2C	699	0.6	0.088	YES
3	PSMA8	PSMA8	PSMA8	909	0.54	0.12	YES
4	FBXO17	FBXO17	FBXO17	1054	0.5	0.16	YES
5	SPSB4	SPSB4	SPSB4	1153	0.47	0.19	YES
6	PSMB9	PSMB9	PSMB9	1307	0.44	0.22	YES
7	CDC20	CDC20	CDC20	1800	0.35	0.23	YES
8	KLHL13	KLHL13	KLHL13	1897	0.33	0.25	YES
9	SOCS3	SOCS3	SOCS3	2483	0.25	0.24	YES
10	SOCS1	SOCS1	SOCS1	2688	0.23	0.25	YES
11	PSMB10	PSMB10	PSMB10	2841	0.21	0.26	YES
12	FBXO27	FBXO27	FBXO27	2912	0.2	0.27	YES
13	UBE2L6	UBE2L6	UBE2L6	2913	0.2	0.29	YES
14	PSMB8	PSMB8	PSMB8	3225	0.18	0.28	YES
15	TRIM9	TRIM9	TRIM9	3278	0.17	0.3	YES
16	TRIM21	TRIM21	TRIM21	3309	0.17	0.31	YES
17	SPSB1	SPSB1	SPSB1	3447	0.16	0.32	YES
18	PSME2	PSME2	PSME2	3636	0.15	0.32	YES
19	FBXO6	FBXO6	FBXO6	3640	0.15	0.33	YES
20	DTX3L	DTX3L	DTX3L	4133	0.12	0.32	YES
21	ASB13	ASB13	ASB13	4227	0.12	0.32	YES
22	UBA7	UBA7	UBA7	4356	0.11	0.32	YES
23	LNPEP	LNPEP	LNPEP	4391	0.11	0.33	YES
24	UBE2J1	UBE2J1	UBE2J1	4628	0.096	0.32	YES
25	SMURF2	SMURF2	SMURF2	4647	0.095	0.33	YES
26	SKP2	SKP2	SKP2	4675	0.094	0.34	YES
27	UBE2D1	UBE2D1	UBE2D1	4830	0.088	0.34	YES
28	PSME1	PSME1	PSME1	4860	0.087	0.34	YES
29	UBA6	UBA6	UBA6	5020	0.081	0.34	YES
30	UBE2S	UBE2S	UBE2S	5372	0.069	0.33	YES
31	RNF138	RNF138	RNF138	5386	0.069	0.33	YES
32	TRIM36	TRIM36	TRIM36	5393	0.069	0.34	YES
33	PSMA4	PSMA4	PSMA4	5410	0.068	0.34	YES
34	FBXO2	FBXO2	FBXO2	5482	0.066	0.34	YES
35	CBLB	CBLB	CBLB	5513	0.065	0.35	YES
36	SMURF1	SMURF1	SMURF1	5569	0.063	0.35	YES
37	RNF34	RNF34	RNF34	5705	0.06	0.35	YES
38	ATG7	ATG7	ATG7	5802	0.057	0.35	YES
39	UBA3	UBA3	UBA3	5848	0.056	0.35	YES
40	UBE2N	UBE2N	UBE2N	5981	0.053	0.35	YES
41	TRIM63	TRIM63	TRIM63	5983	0.053	0.35	YES
42	KLHL20	KLHL20	KLHL20	6053	0.051	0.35	YES
43	PSMA3	PSMA3	PSMA3	6156	0.049	0.35	YES
44	ASB9	ASB9	ASB9	6162	0.049	0.36	YES
45	PSMA5	PSMA5	PSMA5	6365	0.045	0.35	NO
46	ASB12	ASB12	ASB12	6390	0.044	0.35	NO
47	VHL	VHL	VHL	6482	0.042	0.35	NO
48	UBE2E2	UBE2E2	UBE2E2	6483	0.042	0.35	NO
49	PSMA6	PSMA6	PSMA6	6509	0.042	0.36	NO
50	PSMB2	PSMB2	PSMB2	6656	0.039	0.35	NO
51	PSMD11	PSMD11	PSMD11	6680	0.039	0.35	NO
52	PSMD1	PSMD1	PSMD1	6886	0.035	0.34	NO
53	PSMD7	PSMD7	PSMD7	6901	0.035	0.35	NO
54	PSMD5	PSMD5	PSMD5	6976	0.034	0.34	NO
55	PSMA1	PSMA1	PSMA1	7037	0.033	0.34	NO
56	UBE2G1	UBE2G1	UBE2G1	7046	0.033	0.35	NO
57	TRIM11	TRIM11	TRIM11	7075	0.032	0.35	NO
58	UBE2L3	UBE2L3	UBE2L3	7111	0.032	0.35	NO
59	PSMC2	PSMC2	PSMC2	7116	0.032	0.35	NO
60	PSMA2	PSMA2	PSMA2	7223	0.03	0.35	NO
61	UBE3C	UBE3C	UBE3C	7322	0.028	0.34	NO
62	FBXW7	FBXW7	FBXW7	7375	0.028	0.34	NO
63	RNF6	RNF6	RNF6	7435	0.027	0.34	NO
64	ANAPC1	ANAPC1	ANAPC1	7462	0.027	0.34	NO
65	RBX1	RBX1	RBX1	7482	0.026	0.34	NO
66	PSMD12	PSMD12	PSMD12	7647	0.024	0.34	NO
67	PSMA7	PSMA7	PSMA7	7667	0.024	0.34	NO
68	PSME4	PSME4	PSME4	7736	0.023	0.34	NO
69	PSMD13	PSMD13	PSMD13	7764	0.023	0.34	NO
70	ASB3	ASB3	ASB3	7777	0.023	0.34	NO
71	TRIM32	TRIM32	TRIM32	7822	0.022	0.34	NO
72	WSB1	WSB1	WSB1	7853	0.022	0.34	NO
73	UBR2	UBR2	UBR2	8066	0.019	0.33	NO
74	TPP2	TPP2	TPP2	8069	0.019	0.33	NO
75	CDC26	CDC26	CDC26	8071	0.019	0.33	NO
76	ASB7	ASB7	ASB7	8088	0.019	0.33	NO
77	ASB16	ASB16	ASB16	8127	0.018	0.33	NO
78	CUL2	CUL2	CUL2	8189	0.018	0.33	NO
79	PSMB3	PSMB3	PSMB3	8242	0.017	0.33	NO
80	UBE2A	UBE2A	UBE2A	8246	0.017	0.33	NO
81	UBR1	UBR1	UBR1	8365	0.016	0.32	NO
82	PSMB4	PSMB4	PSMB4	8403	0.015	0.32	NO
83	UBE2W	UBE2W	UBE2W	8439	0.015	0.32	NO
84	ANAPC10	ANAPC10	ANAPC10	8500	0.014	0.32	NO
85	UBE2E1	UBE2E1	UBE2E1	8602	0.013	0.32	NO
86	CDC27	CDC27	CDC27	8605	0.013	0.32	NO
87	PSMD14	PSMD14	PSMD14	8607	0.013	0.32	NO
88	RNF4	RNF4	RNF4	8664	0.012	0.32	NO
89	TRIP12	TRIP12	TRIP12	8808	0.011	0.31	NO
90	WWP1	WWP1	WWP1	8843	0.011	0.31	NO
91	PSMB1	PSMB1	PSMB1	8909	0.01	0.3	NO
92	UBE2G2	UBE2G2	UBE2G2	8911	0.01	0.31	NO
93	UBA52	UBA52	UBA52	9051	0.0087	0.3	NO
94	ANAPC4	ANAPC4	ANAPC4	9058	0.0086	0.3	NO
95	RBCK1	RBCK1	RBCK1	9210	0.0072	0.29	NO
96	UBE2J2	UBE2J2	UBE2J2	9215	0.0071	0.29	NO
97	UBE2Z	UBE2Z	UBE2Z	9218	0.0071	0.29	NO
98	CUL1	CUL1	CUL1	9242	0.0069	0.29	NO
99	UBE2Q1	UBE2Q1	UBE2Q1	9243	0.0069	0.29	NO
100	NEDD4	NEDD4	NEDD4	9258	0.0067	0.29	NO
101	HECTD3	HECTD3	HECTD3	9272	0.0066	0.29	NO
102	PSMD3	PSMD3	PSMD3	9287	0.0065	0.29	NO
103	PSMD4	PSMD4	PSMD4	9326	0.0061	0.29	NO
104	GAN	GAN	GAN	9381	0.0056	0.29	NO
105	UBE2Q2	UBE2Q2	UBE2Q2	9395	0.0054	0.29	NO
106	UBE2V2	UBE2V2	UBE2V2	9414	0.0053	0.29	NO
107	PSMD2	PSMD2	PSMD2	9438	0.005	0.29	NO
108	PSMF1	PSMF1	PSMF1	9454	0.0048	0.29	NO
109	BLMH	BLMH	BLMH	9548	0.0039	0.28	NO
110	KLHL9	KLHL9	KLHL9	9585	0.0036	0.28	NO
111	PSMD6	PSMD6	PSMD6	9630	0.0031	0.28	NO
112	UBE2F	UBE2F	UBE2F	9741	0.0022	0.27	NO
113	RNF220	RNF220	RNF220	9761	0.002	0.27	NO
114	UBA2	UBA2	UBA2	9856	0.001	0.26	NO
115	ASB6	ASB6	ASB6	9874	0.00088	0.26	NO
116	PSMC6	PSMC6	PSMC6	9878	0.00086	0.26	NO
117	PSMB6	PSMB6	PSMB6	9986	-0.00029	0.26	NO
118	UBE2H	UBE2H	UBE2H	10013	-0.0005	0.26	NO
119	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.25	NO
120	UBE2B	UBE2B	UBE2B	10177	-0.002	0.25	NO
121	HUWE1	HUWE1	HUWE1	10198	-0.0022	0.25	NO
122	NPEPPS	NPEPPS	NPEPPS	10224	-0.0023	0.24	NO
123	VPRBP	VPRBP	VPRBP	10244	-0.0026	0.24	NO
124	UBE2D3	UBE2D3	UBE2D3	10318	-0.0033	0.24	NO
125	MKRN1	MKRN1	MKRN1	10333	-0.0034	0.24	NO
126	PSMC4	PSMC4	PSMC4	10346	-0.0036	0.24	NO
127	RNF25	RNF25	RNF25	10362	-0.0038	0.24	NO
128	ANAPC5	ANAPC5	ANAPC5	10586	-0.0059	0.23	NO
129	UBE2K	UBE2K	UBE2K	10593	-0.0059	0.23	NO
130	TCEB1	TCEB1	TCEB1	10691	-0.0067	0.22	NO
131	TRIM37	TRIM37	TRIM37	10714	-0.007	0.22	NO
132	PSMC1	PSMC1	PSMC1	10749	-0.0073	0.22	NO
133	ANAPC7	ANAPC7	ANAPC7	10783	-0.0076	0.22	NO
134	ANAPC2	ANAPC2	ANAPC2	10815	-0.0079	0.22	NO
135	PSMD10	PSMD10	PSMD10	10860	-0.0083	0.22	NO
136	PSMC5	PSMC5	PSMC5	10973	-0.0094	0.21	NO
137	UBE2R2	UBE2R2	UBE2R2	10974	-0.0094	0.21	NO
138	UBE2D2	UBE2D2	UBE2D2	11014	-0.0098	0.21	NO
139	CUL3	CUL3	CUL3	11039	-0.01	0.21	NO
140	UBE3A	UBE3A	UBE3A	11196	-0.012	0.2	NO
141	ASB8	ASB8	ASB8	11262	-0.012	0.2	NO
142	FBXW11	FBXW11	FBXW11	11326	-0.013	0.2	NO
143	PSMC3	PSMC3	PSMC3	11355	-0.013	0.2	NO
144	PSMB7	PSMB7	PSMB7	11552	-0.015	0.19	NO
145	UBE4A	UBE4A	UBE4A	11659	-0.016	0.18	NO
146	UBR4	UBR4	UBR4	11762	-0.016	0.18	NO
147	CDC16	CDC16	CDC16	11805	-0.017	0.18	NO
148	CDC23	CDC23	CDC23	11807	-0.017	0.18	NO
149	UBA1	UBA1	UBA1	11915	-0.018	0.17	NO
150	CUL5	CUL5	CUL5	11916	-0.018	0.18	NO
151	KEAP1	KEAP1	KEAP1	11966	-0.018	0.17	NO
152	FBXO4	FBXO4	FBXO4	12013	-0.018	0.17	NO
153	BTRC	BTRC	BTRC	12032	-0.019	0.17	NO
154	LRSAM1	LRSAM1	LRSAM1	12215	-0.02	0.17	NO
155	RNF41	RNF41	RNF41	12264	-0.021	0.16	NO
156	UBE2E3	UBE2E3	UBE2E3	12337	-0.022	0.16	NO
157	HERC2	HERC2	HERC2	12382	-0.022	0.16	NO
158	PSMB5	PSMB5	PSMB5	12404	-0.022	0.16	NO
159	LRRC41	LRRC41	LRRC41	12500	-0.023	0.16	NO
160	PSMD9	PSMD9	PSMD9	12646	-0.025	0.15	NO
161	PSMD8	PSMD8	PSMD8	12657	-0.025	0.16	NO
162	CUL7	CUL7	CUL7	12754	-0.026	0.15	NO
163	PJA2	PJA2	PJA2	12985	-0.028	0.14	NO
164	ARIH2	ARIH2	ARIH2	13062	-0.029	0.14	NO
165	RNF123	RNF123	RNF123	13199	-0.031	0.14	NO
166	UBE2O	UBE2O	UBE2O	13360	-0.032	0.13	NO
167	UBE3B	UBE3B	UBE3B	13458	-0.034	0.13	NO
168	UBA5	UBA5	UBA5	13553	-0.035	0.12	NO
169	SKP1	SKP1	SKP1	13659	-0.036	0.12	NO
170	PJA1	PJA1	PJA1	13680	-0.036	0.12	NO
171	SAE1	SAE1	SAE1	13818	-0.038	0.12	NO
172	SPSB2	SPSB2	SPSB2	13822	-0.038	0.12	NO
173	RCHY1	RCHY1	RCHY1	13890	-0.039	0.12	NO
174	TCEB2	TCEB2	TCEB2	13902	-0.039	0.12	NO
175	ANAPC11	ANAPC11	ANAPC11	13915	-0.039	0.13	NO
176	DET1	DET1	DET1	13940	-0.039	0.13	NO
177	ANAPC13	ANAPC13	ANAPC13	13996	-0.04	0.13	NO
178	CDC34	CDC34	CDC34	14128	-0.042	0.12	NO
179	UBE2M	UBE2M	UBE2M	14247	-0.044	0.12	NO
180	ASB1	ASB1	ASB1	14343	-0.045	0.12	NO
181	FBXW8	FBXW8	FBXW8	14364	-0.045	0.12	NO
182	DZIP3	DZIP3	DZIP3	14516	-0.047	0.12	NO
183	UBOX5	UBOX5	UBOX5	14555	-0.048	0.12	NO
184	FBXO3	FBXO3	FBXO3	14598	-0.049	0.12	NO
185	RNF144B	RNF144B	RNF144B	14746	-0.051	0.12	NO
186	ZBTB16	ZBTB16	ZBTB16	14841	-0.053	0.12	NO
187	UBE2D4	UBE2D4	UBE2D4	15146	-0.058	0.11	NO
188	FBXO44	FBXO44	FBXO44	15418	-0.064	0.097	NO
189	STUB1	STUB1	STUB1	15420	-0.064	0.1	NO
190	RNF182	RNF182	RNF182	16816	-0.11	0.033	NO
191	ASB4	ASB4	ASB4	17412	-0.16	0.014	NO
192	PARK2	PARK2	PARK2	17686	-0.2	0.016	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 CYSTEINE AND METHIONINE METABOLISM.

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

genes ES table in pathway: KEGG HISTIDINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NOD2	NOD2	NOD2	227	0.82	0.098	YES
2	LY96	LY96	LY96	445	0.7	0.18	YES
3	S100B	S100B	S100B	468	0.69	0.27	YES
4	SAA1	SAA1	SAA1	780	0.58	0.33	YES
5	TICAM2	TICAM2	TICAM2	1301	0.44	0.36	YES
6	MAP2K6	MAP2K6	MAP2K6	1923	0.32	0.37	YES
7	TLR4	TLR4	TLR4	2196	0.28	0.4	YES
8	CDK1	CDK1	CDK1	2337	0.26	0.42	YES
9	TLR3	TLR3	TLR3	2342	0.26	0.46	YES
10	S100A12	S100A12	S100A12	2622	0.24	0.47	YES
11	CD14	CD14	CD14	2666	0.23	0.5	YES
12	RPS6KA5	RPS6KA5	RPS6KA5	3092	0.19	0.5	YES
13	NFKB2	NFKB2	NFKB2	3549	0.16	0.5	YES
14	DUSP4	DUSP4	DUSP4	3708	0.14	0.51	YES
15	IRAK2	IRAK2	IRAK2	3801	0.14	0.52	YES
16	NFKBIA	NFKBIA	NFKBIA	3969	0.13	0.53	YES
17	IRAK1	IRAK1	IRAK1	4165	0.12	0.54	YES
18	RIPK2	RIPK2	RIPK2	4295	0.11	0.55	YES
19	MAPK11	MAPK11	MAPK11	4327	0.11	0.56	YES
20	DUSP7	DUSP7	DUSP7	4501	0.1	0.56	YES
21	NOD1	NOD1	NOD1	4557	0.099	0.57	YES
22	MEF2C	MEF2C	MEF2C	4714	0.093	0.58	YES
23	MAP2K1	MAP2K1	MAP2K1	5735	0.059	0.53	NO
24	IKBKG	IKBKG	IKBKG	5908	0.055	0.52	NO
25	RPS6KA3	RPS6KA3	RPS6KA3	6626	0.04	0.49	NO
26	MEF2A	MEF2A	MEF2A	6820	0.036	0.48	NO
27	RIPK1	RIPK1	RIPK1	6951	0.034	0.48	NO
28	MAPKAPK2	MAPKAPK2	MAPKAPK2	6961	0.034	0.49	NO
29	TICAM1	TICAM1	TICAM1	7020	0.033	0.49	NO
30	DUSP6	DUSP6	DUSP6	7218	0.03	0.48	NO
31	MAPK7	MAPK7	MAPK7	7236	0.03	0.48	NO
32	IKBKB	IKBKB	IKBKB	7353	0.028	0.48	NO
33	CREB1	CREB1	CREB1	7508	0.026	0.48	NO
34	FOS	FOS	FOS	7557	0.025	0.48	NO
35	RPS6KA1	RPS6KA1	RPS6KA1	7657	0.024	0.47	NO
36	RELA	RELA	RELA	7719	0.024	0.47	NO
37	CHUK	CHUK	CHUK	7759	0.023	0.48	NO
38	ATF2	ATF2	ATF2	7894	0.022	0.47	NO
39	TRAF6	TRAF6	TRAF6	7943	0.021	0.47	NO
40	MAP3K7	MAP3K7	MAP3K7	7995	0.02	0.47	NO
41	PPP2R1B	PPP2R1B	PPP2R1B	8177	0.018	0.46	NO
42	ELK1	ELK1	ELK1	8257	0.017	0.46	NO
43	HMGB1	HMGB1	HMGB1	8451	0.015	0.45	NO
44	MAP2K3	MAP2K3	MAP2K3	8464	0.015	0.45	NO
45	TAB2	TAB2	TAB2	8656	0.012	0.44	NO
46	UBA52	UBA52	UBA52	9051	0.0087	0.42	NO
47	TAB3	TAB3	TAB3	9528	0.0041	0.4	NO
48	AGER	AGER	AGER	9659	0.0029	0.39	NO
49	PPP2R5D	PPP2R5D	PPP2R5D	10017	-0.00056	0.37	NO
50	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.37	NO
51	TAB1	TAB1	TAB1	10285	-0.003	0.36	NO
52	MAPKAPK3	MAPKAPK3	MAPKAPK3	10287	-0.0031	0.36	NO
53	MAPK1	MAPK1	MAPK1	10407	-0.0042	0.35	NO
54	PPP2CA	PPP2CA	PPP2CA	10514	-0.0052	0.34	NO
55	NFKBIB	NFKBIB	NFKBIB	10857	-0.0083	0.33	NO
56	JUN	JUN	JUN	10935	-0.0089	0.32	NO
57	ATF1	ATF1	ATF1	10949	-0.009	0.32	NO
58	MAP2K7	MAP2K7	MAP2K7	11191	-0.011	0.31	NO
59	MAP2K2	MAP2K2	MAP2K2	11291	-0.012	0.31	NO
60	MAPK14	MAPK14	MAPK14	11358	-0.013	0.31	NO
61	MAP2K4	MAP2K4	MAP2K4	12064	-0.019	0.27	NO
62	DUSP3	DUSP3	DUSP3	12788	-0.026	0.23	NO
63	APP	APP	APP	12930	-0.028	0.23	NO
64	PPP2R1A	PPP2R1A	PPP2R1A	13320	-0.032	0.21	NO
65	PPP2CB	PPP2CB	PPP2CB	13608	-0.035	0.2	NO
66	MAPK3	MAPK3	MAPK3	13684	-0.036	0.2	NO
67	MAPK8	MAPK8	MAPK8	14058	-0.041	0.18	NO
68	MAPK9	MAPK9	MAPK9	14059	-0.041	0.19	NO
69	RPS6KA2	RPS6KA2	RPS6KA2	14079	-0.041	0.2	NO
70	MAPK10	MAPK10	MAPK10	17433	-0.16	0.03	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 HISTIDINE METABOLISM.

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

genes ES table in pathway: KEGG TYROSINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TLR6	TLR6	TLR6	104	0.95	0.075	YES
2	NOD2	NOD2	NOD2	227	0.82	0.14	YES
3	BTK	BTK	BTK	231	0.82	0.21	YES
4	LY96	LY96	LY96	445	0.7	0.26	YES
5	S100B	S100B	S100B	468	0.69	0.31	YES
6	TLR1	TLR1	TLR1	658	0.62	0.36	YES
7	SAA1	SAA1	SAA1	780	0.58	0.4	YES
8	TICAM2	TICAM2	TICAM2	1301	0.44	0.41	YES
9	TLR2	TLR2	TLR2	1808	0.34	0.41	YES
10	IRAK3	IRAK3	IRAK3	1921	0.32	0.43	YES
11	MAP2K6	MAP2K6	MAP2K6	1923	0.32	0.46	YES
12	TLR4	TLR4	TLR4	2196	0.28	0.46	YES
13	CDK1	CDK1	CDK1	2337	0.26	0.48	YES
14	TLR3	TLR3	TLR3	2342	0.26	0.5	YES
15	S100A12	S100A12	S100A12	2622	0.24	0.51	YES
16	CD14	CD14	CD14	2666	0.23	0.52	YES
17	PELI1	PELI1	PELI1	2763	0.22	0.54	YES
18	RPS6KA5	RPS6KA5	RPS6KA5	3092	0.19	0.53	YES
19	MYD88	MYD88	MYD88	3212	0.18	0.54	YES
20	TRAF3	TRAF3	TRAF3	3274	0.18	0.55	YES
21	IRF7	IRF7	IRF7	3287	0.17	0.57	YES
22	NFKB2	NFKB2	NFKB2	3549	0.16	0.57	YES
23	DUSP4	DUSP4	DUSP4	3708	0.14	0.57	YES
24	IRAK2	IRAK2	IRAK2	3801	0.14	0.58	YES
25	PELI2	PELI2	PELI2	3952	0.13	0.58	YES
26	NFKBIA	NFKBIA	NFKBIA	3969	0.13	0.59	YES
27	IRAK1	IRAK1	IRAK1	4165	0.12	0.59	YES
28	RIPK2	RIPK2	RIPK2	4295	0.11	0.59	YES
29	MAPK11	MAPK11	MAPK11	4327	0.11	0.6	YES
30	DUSP7	DUSP7	DUSP7	4501	0.1	0.6	YES
31	NOD1	NOD1	NOD1	4557	0.099	0.6	YES
32	MEF2C	MEF2C	MEF2C	4714	0.093	0.6	NO
33	TBK1	TBK1	TBK1	5136	0.078	0.59	NO
34	MAP2K1	MAP2K1	MAP2K1	5735	0.059	0.56	NO
35	IKBKE	IKBKE	IKBKE	5803	0.057	0.56	NO
36	IKBKG	IKBKG	IKBKG	5908	0.055	0.56	NO
37	UBE2N	UBE2N	UBE2N	5981	0.053	0.56	NO
38	RPS6KA3	RPS6KA3	RPS6KA3	6626	0.04	0.52	NO
39	MEF2A	MEF2A	MEF2A	6820	0.036	0.52	NO
40	RIPK1	RIPK1	RIPK1	6951	0.034	0.51	NO
41	MAPKAPK2	MAPKAPK2	MAPKAPK2	6961	0.034	0.52	NO
42	IRF3	IRF3	IRF3	6966	0.034	0.52	NO
43	TICAM1	TICAM1	TICAM1	7020	0.033	0.52	NO
44	DUSP6	DUSP6	DUSP6	7218	0.03	0.51	NO
45	MAPK7	MAPK7	MAPK7	7236	0.03	0.51	NO
46	IKBKB	IKBKB	IKBKB	7353	0.028	0.51	NO
47	CREB1	CREB1	CREB1	7508	0.026	0.5	NO
48	FOS	FOS	FOS	7557	0.025	0.5	NO
49	RPS6KA1	RPS6KA1	RPS6KA1	7657	0.024	0.5	NO
50	RELA	RELA	RELA	7719	0.024	0.5	NO
51	CHUK	CHUK	CHUK	7759	0.023	0.5	NO
52	IRAK4	IRAK4	IRAK4	7882	0.022	0.49	NO
53	ATF2	ATF2	ATF2	7894	0.022	0.49	NO
54	TRAF6	TRAF6	TRAF6	7943	0.021	0.49	NO
55	MAP3K7	MAP3K7	MAP3K7	7995	0.02	0.49	NO
56	TIRAP	TIRAP	TIRAP	8134	0.018	0.48	NO
57	PPP2R1B	PPP2R1B	PPP2R1B	8177	0.018	0.48	NO
58	MAP3K1	MAP3K1	MAP3K1	8234	0.017	0.48	NO
59	ELK1	ELK1	ELK1	8257	0.017	0.48	NO
60	HMGB1	HMGB1	HMGB1	8451	0.015	0.47	NO
61	MAP2K3	MAP2K3	MAP2K3	8464	0.015	0.47	NO
62	TAB2	TAB2	TAB2	8656	0.012	0.46	NO
63	UBA52	UBA52	UBA52	9051	0.0087	0.44	NO
64	SIGIRR	SIGIRR	SIGIRR	9128	0.008	0.44	NO
65	TAB3	TAB3	TAB3	9528	0.0041	0.42	NO
66	AGER	AGER	AGER	9659	0.0029	0.41	NO
67	PPP2R5D	PPP2R5D	PPP2R5D	10017	-0.00056	0.39	NO
68	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.38	NO
69	TAB1	TAB1	TAB1	10285	-0.003	0.37	NO
70	MAPKAPK3	MAPKAPK3	MAPKAPK3	10287	-0.0031	0.37	NO
71	MAPK1	MAPK1	MAPK1	10407	-0.0042	0.37	NO
72	PPP2CA	PPP2CA	PPP2CA	10514	-0.0052	0.36	NO
73	NFKBIB	NFKBIB	NFKBIB	10857	-0.0083	0.34	NO
74	JUN	JUN	JUN	10935	-0.0089	0.34	NO
75	ATF1	ATF1	ATF1	10949	-0.009	0.34	NO
76	MAP2K7	MAP2K7	MAP2K7	11191	-0.011	0.33	NO
77	MAP2K2	MAP2K2	MAP2K2	11291	-0.012	0.32	NO
78	MAPK14	MAPK14	MAPK14	11358	-0.013	0.32	NO
79	MAP2K4	MAP2K4	MAP2K4	12064	-0.019	0.28	NO
80	DUSP3	DUSP3	DUSP3	12788	-0.026	0.24	NO
81	APP	APP	APP	12930	-0.028	0.24	NO
82	PPP2R1A	PPP2R1A	PPP2R1A	13320	-0.032	0.22	NO
83	PPP2CB	PPP2CB	PPP2CB	13608	-0.035	0.21	NO
84	MAPK3	MAPK3	MAPK3	13684	-0.036	0.21	NO
85	MAPK8	MAPK8	MAPK8	14058	-0.041	0.19	NO
86	MAPK9	MAPK9	MAPK9	14059	-0.041	0.19	NO
87	RPS6KA2	RPS6KA2	RPS6KA2	14079	-0.041	0.19	NO
88	PELI3	PELI3	PELI3	14796	-0.052	0.16	NO
89	ECSIT	ECSIT	ECSIT	15130	-0.058	0.14	NO
90	MAPK10	MAPK10	MAPK10	17433	-0.16	0.03	NO

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

Figure S56. 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 TRYPTOPHAN METABOLISM

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	TLR8	TLR8	TLR8	168	0.87	0.093	YES
2	NOD2	NOD2	NOD2	227	0.82	0.19	YES
3	TLR9	TLR9	TLR9	309	0.77	0.27	YES
4	TLR7	TLR7	TLR7	424	0.71	0.35	YES
5	S100B	S100B	S100B	468	0.69	0.43	YES
6	SAA1	SAA1	SAA1	780	0.58	0.48	YES
7	MAP2K6	MAP2K6	MAP2K6	1923	0.32	0.45	YES
8	CDK1	CDK1	CDK1	2337	0.26	0.46	YES
9	S100A12	S100A12	S100A12	2622	0.24	0.47	YES
10	PELI1	PELI1	PELI1	2763	0.22	0.49	YES
11	RPS6KA5	RPS6KA5	RPS6KA5	3092	0.19	0.49	YES
12	MYD88	MYD88	MYD88	3212	0.18	0.51	YES
13	NFKB2	NFKB2	NFKB2	3549	0.16	0.51	YES
14	DUSP4	DUSP4	DUSP4	3708	0.14	0.52	YES
15	IRAK2	IRAK2	IRAK2	3801	0.14	0.53	YES
16	PELI2	PELI2	PELI2	3952	0.13	0.53	YES
17	NFKBIA	NFKBIA	NFKBIA	3969	0.13	0.55	YES
18	IRAK1	IRAK1	IRAK1	4165	0.12	0.55	YES
19	RIPK2	RIPK2	RIPK2	4295	0.11	0.56	YES
20	MAPK11	MAPK11	MAPK11	4327	0.11	0.57	YES
21	DUSP7	DUSP7	DUSP7	4501	0.1	0.57	YES
22	NOD1	NOD1	NOD1	4557	0.099	0.58	YES
23	MEF2C	MEF2C	MEF2C	4714	0.093	0.58	YES
24	MAP2K1	MAP2K1	MAP2K1	5735	0.059	0.53	NO
25	IKBKG	IKBKG	IKBKG	5908	0.055	0.53	NO
26	UBE2N	UBE2N	UBE2N	5981	0.053	0.53	NO
27	RPS6KA3	RPS6KA3	RPS6KA3	6626	0.04	0.5	NO
28	MEF2A	MEF2A	MEF2A	6820	0.036	0.49	NO
29	MAPKAPK2	MAPKAPK2	MAPKAPK2	6961	0.034	0.49	NO
30	DUSP6	DUSP6	DUSP6	7218	0.03	0.48	NO
31	MAPK7	MAPK7	MAPK7	7236	0.03	0.48	NO
32	IKBKB	IKBKB	IKBKB	7353	0.028	0.48	NO
33	CREB1	CREB1	CREB1	7508	0.026	0.47	NO
34	FOS	FOS	FOS	7557	0.025	0.47	NO
35	RPS6KA1	RPS6KA1	RPS6KA1	7657	0.024	0.47	NO
36	RELA	RELA	RELA	7719	0.024	0.47	NO
37	CHUK	CHUK	CHUK	7759	0.023	0.47	NO
38	IRAK4	IRAK4	IRAK4	7882	0.022	0.46	NO
39	ATF2	ATF2	ATF2	7894	0.022	0.47	NO
40	TRAF6	TRAF6	TRAF6	7943	0.021	0.47	NO
41	MAP3K7	MAP3K7	MAP3K7	7995	0.02	0.47	NO
42	PPP2R1B	PPP2R1B	PPP2R1B	8177	0.018	0.46	NO
43	MAP3K1	MAP3K1	MAP3K1	8234	0.017	0.46	NO
44	ELK1	ELK1	ELK1	8257	0.017	0.46	NO
45	HMGB1	HMGB1	HMGB1	8451	0.015	0.45	NO
46	MAP2K3	MAP2K3	MAP2K3	8464	0.015	0.45	NO
47	TAB2	TAB2	TAB2	8656	0.012	0.44	NO
48	UBA52	UBA52	UBA52	9051	0.0087	0.42	NO
49	TAB3	TAB3	TAB3	9528	0.0041	0.39	NO
50	AGER	AGER	AGER	9659	0.0029	0.39	NO
51	PPP2R5D	PPP2R5D	PPP2R5D	10017	-0.00056	0.37	NO
52	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.36	NO
53	TAB1	TAB1	TAB1	10285	-0.003	0.35	NO
54	MAPKAPK3	MAPKAPK3	MAPKAPK3	10287	-0.0031	0.35	NO
55	MAPK1	MAPK1	MAPK1	10407	-0.0042	0.35	NO
56	PPP2CA	PPP2CA	PPP2CA	10514	-0.0052	0.34	NO
57	NFKBIB	NFKBIB	NFKBIB	10857	-0.0083	0.32	NO
58	JUN	JUN	JUN	10935	-0.0089	0.32	NO
59	ATF1	ATF1	ATF1	10949	-0.009	0.32	NO
60	MAP2K7	MAP2K7	MAP2K7	11191	-0.011	0.31	NO
61	MAP2K2	MAP2K2	MAP2K2	11291	-0.012	0.3	NO
62	MAPK14	MAPK14	MAPK14	11358	-0.013	0.3	NO
63	MAP2K4	MAP2K4	MAP2K4	12064	-0.019	0.26	NO
64	DUSP3	DUSP3	DUSP3	12788	-0.026	0.23	NO
65	APP	APP	APP	12930	-0.028	0.22	NO
66	PPP2R1A	PPP2R1A	PPP2R1A	13320	-0.032	0.2	NO
67	PPP2CB	PPP2CB	PPP2CB	13608	-0.035	0.19	NO
68	MAPK3	MAPK3	MAPK3	13684	-0.036	0.19	NO
69	MAPK8	MAPK8	MAPK8	14058	-0.041	0.18	NO
70	MAPK9	MAPK9	MAPK9	14059	-0.041	0.18	NO
71	RPS6KA2	RPS6KA2	RPS6KA2	14079	-0.041	0.18	NO
72	PELI3	PELI3	PELI3	14796	-0.052	0.15	NO
73	ECSIT	ECSIT	ECSIT	15130	-0.058	0.14	NO
74	MAPK10	MAPK10	MAPK10	17433	-0.16	0.03	NO

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

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

genes ES table in pathway: KEGG GLUTATHIONE METABOLISM

Table S30. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TLR6	TLR6	TLR6	104	0.95	0.087	YES
2	NOD2	NOD2	NOD2	227	0.82	0.16	YES
3	BTK	BTK	BTK	231	0.82	0.24	YES
4	LY96	LY96	LY96	445	0.7	0.3	YES
5	S100B	S100B	S100B	468	0.69	0.36	YES
6	TLR1	TLR1	TLR1	658	0.62	0.41	YES
7	SAA1	SAA1	SAA1	780	0.58	0.46	YES
8	TLR2	TLR2	TLR2	1808	0.34	0.44	YES
9	IRAK3	IRAK3	IRAK3	1921	0.32	0.46	YES
10	MAP2K6	MAP2K6	MAP2K6	1923	0.32	0.5	YES
11	TLR4	TLR4	TLR4	2196	0.28	0.51	YES
12	CDK1	CDK1	CDK1	2337	0.26	0.53	YES
13	S100A12	S100A12	S100A12	2622	0.24	0.53	YES
14	PELI1	PELI1	PELI1	2763	0.22	0.55	YES
15	RPS6KA5	RPS6KA5	RPS6KA5	3092	0.19	0.55	YES
16	MYD88	MYD88	MYD88	3212	0.18	0.56	YES
17	NFKB2	NFKB2	NFKB2	3549	0.16	0.56	YES
18	DUSP4	DUSP4	DUSP4	3708	0.14	0.56	YES
19	IRAK2	IRAK2	IRAK2	3801	0.14	0.57	YES
20	PELI2	PELI2	PELI2	3952	0.13	0.57	YES
21	NFKBIA	NFKBIA	NFKBIA	3969	0.13	0.58	YES
22	IRAK1	IRAK1	IRAK1	4165	0.12	0.58	YES
23	RIPK2	RIPK2	RIPK2	4295	0.11	0.59	YES
24	MAPK11	MAPK11	MAPK11	4327	0.11	0.6	YES
25	DUSP7	DUSP7	DUSP7	4501	0.1	0.6	YES
26	NOD1	NOD1	NOD1	4557	0.099	0.6	YES
27	MEF2C	MEF2C	MEF2C	4714	0.093	0.6	YES
28	MAP2K1	MAP2K1	MAP2K1	5735	0.059	0.55	NO
29	IKBKG	IKBKG	IKBKG	5908	0.055	0.55	NO
30	UBE2N	UBE2N	UBE2N	5981	0.053	0.55	NO
31	RPS6KA3	RPS6KA3	RPS6KA3	6626	0.04	0.52	NO
32	MEF2A	MEF2A	MEF2A	6820	0.036	0.51	NO
33	MAPKAPK2	MAPKAPK2	MAPKAPK2	6961	0.034	0.51	NO
34	DUSP6	DUSP6	DUSP6	7218	0.03	0.5	NO
35	MAPK7	MAPK7	MAPK7	7236	0.03	0.5	NO
36	IKBKB	IKBKB	IKBKB	7353	0.028	0.49	NO
37	CREB1	CREB1	CREB1	7508	0.026	0.49	NO
38	FOS	FOS	FOS	7557	0.025	0.49	NO
39	RPS6KA1	RPS6KA1	RPS6KA1	7657	0.024	0.48	NO
40	RELA	RELA	RELA	7719	0.024	0.48	NO
41	CHUK	CHUK	CHUK	7759	0.023	0.48	NO
42	IRAK4	IRAK4	IRAK4	7882	0.022	0.48	NO
43	ATF2	ATF2	ATF2	7894	0.022	0.48	NO
44	TRAF6	TRAF6	TRAF6	7943	0.021	0.48	NO
45	MAP3K7	MAP3K7	MAP3K7	7995	0.02	0.48	NO
46	TIRAP	TIRAP	TIRAP	8134	0.018	0.47	NO
47	PPP2R1B	PPP2R1B	PPP2R1B	8177	0.018	0.47	NO
48	MAP3K1	MAP3K1	MAP3K1	8234	0.017	0.47	NO
49	ELK1	ELK1	ELK1	8257	0.017	0.47	NO
50	HMGB1	HMGB1	HMGB1	8451	0.015	0.46	NO
51	MAP2K3	MAP2K3	MAP2K3	8464	0.015	0.46	NO
52	TAB2	TAB2	TAB2	8656	0.012	0.45	NO
53	UBA52	UBA52	UBA52	9051	0.0087	0.43	NO
54	SIGIRR	SIGIRR	SIGIRR	9128	0.008	0.43	NO
55	TAB3	TAB3	TAB3	9528	0.0041	0.41	NO
56	AGER	AGER	AGER	9659	0.0029	0.4	NO
57	PPP2R5D	PPP2R5D	PPP2R5D	10017	-0.00056	0.38	NO
58	RPS27A	RPS27A	RPS27A	10076	-0.0011	0.38	NO
59	TAB1	TAB1	TAB1	10285	-0.003	0.36	NO
60	MAPKAPK3	MAPKAPK3	MAPKAPK3	10287	-0.0031	0.36	NO
61	MAPK1	MAPK1	MAPK1	10407	-0.0042	0.36	NO
62	PPP2CA	PPP2CA	PPP2CA	10514	-0.0052	0.35	NO
63	NFKBIB	NFKBIB	NFKBIB	10857	-0.0083	0.34	NO
64	JUN	JUN	JUN	10935	-0.0089	0.33	NO
65	ATF1	ATF1	ATF1	10949	-0.009	0.33	NO
66	MAP2K7	MAP2K7	MAP2K7	11191	-0.011	0.32	NO
67	MAP2K2	MAP2K2	MAP2K2	11291	-0.012	0.32	NO
68	MAPK14	MAPK14	MAPK14	11358	-0.013	0.31	NO
69	MAP2K4	MAP2K4	MAP2K4	12064	-0.019	0.28	NO
70	DUSP3	DUSP3	DUSP3	12788	-0.026	0.24	NO
71	APP	APP	APP	12930	-0.028	0.23	NO
72	PPP2R1A	PPP2R1A	PPP2R1A	13320	-0.032	0.21	NO
73	PPP2CB	PPP2CB	PPP2CB	13608	-0.035	0.2	NO
74	MAPK3	MAPK3	MAPK3	13684	-0.036	0.2	NO
75	MAPK8	MAPK8	MAPK8	14058	-0.041	0.18	NO
76	MAPK9	MAPK9	MAPK9	14059	-0.041	0.19	NO
77	RPS6KA2	RPS6KA2	RPS6KA2	14079	-0.041	0.19	NO
78	PELI3	PELI3	PELI3	14796	-0.052	0.16	NO
79	ECSIT	ECSIT	ECSIT	15130	-0.058	0.14	NO
80	MAPK10	MAPK10	MAPK10	17433	-0.16	0.03	NO

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

Figure S60. 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

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 NOTCH SIGNALING PATHWAY	46	genes.ES.table	0.34	1.3	0.18	1	1	0.28	0.22	0.22	1	0.85
KEGG ADHERENS JUNCTION	73	genes.ES.table	0.36	1.3	0.17	1	1	0.33	0.22	0.26	1	0.86
KEGG THYROID CANCER	29	genes.ES.table	0.44	1.4	0.08	1	0.99	0.14	0.066	0.13	1	0.8
PID LKB1 PATHWAY	47	genes.ES.table	0.35	1.4	0.14	1	1	0.15	0.14	0.13	1	0.82
PID AJDISS 2PATHWAY	46	genes.ES.table	0.41	1.2	0.22	1	1	0.24	0.15	0.2	1	0.88
PID TRKRPATHWAY	61	genes.ES.table	0.45	1.6	0.038	1	0.94	0.082	0.038	0.079	1	0.74
PID NCADHERINPATHWAY	33	genes.ES.table	0.56	1.7	0	1	0.71	0.091	0.012	0.09	1	0.58
REACTOME CELL CELL COMMUNICATION	113	genes.ES.table	0.44	1.3	0.17	1	1	0.28	0.15	0.24	1	0.86
REACTOME NEGATIVE REGULATION OF FGFR SIGNALING	30	genes.ES.table	0.52	1.3	0.12	1	1	0.13	0.022	0.13	1	0.85
REACTOME ACTIVATED NOTCH1 TRANSMITS SIGNAL TO THE NUCLEUS	25	genes.ES.table	0.49	1.5	0.059	1	0.97	0.2	0.13	0.17	1	0.78

genes ES table in pathway: KEGG NOTCH SIGNALING PATHWAY

Table S31. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GRIA2	GRIA2	GRIA2	59	0.56	0.22	YES
2	GAP43	GAP43	GAP43	126	0.48	0.41	YES
3	CDH2	CDH2	CDH2	224	0.4	0.56	YES
4	GSN	GSN	GSN	2699	0.088	0.46	NO
5	GJA1	GJA1	GJA1	4064	0.054	0.41	NO
6	LRP5	LRP5	LRP5	4701	0.043	0.39	NO
7	CTNNB1	CTNNB1	CTNNB1	5396	0.034	0.36	NO
8	AXIN1	AXIN1	AXIN1	5405	0.034	0.38	NO
9	DAGLA	DAGLA	DAGLA	5828	0.029	0.36	NO
10	CTNNA1	CTNNA1	CTNNA1	5917	0.028	0.37	NO
11	PLCG1	PLCG1	PLCG1	6313	0.024	0.36	NO
12	CTTN	CTTN	CTTN	6783	0.019	0.34	NO
13	PIP5K1C	PIP5K1C	PIP5K1C	6810	0.019	0.35	NO
14	ROCK1	ROCK1	ROCK1	7128	0.016	0.34	NO
15	RAC1	RAC1	RAC1	7592	0.011	0.31	NO
16	JUP	JUP	JUP	7836	0.0092	0.3	NO
17	RHOA	RHOA	RHOA	7961	0.008	0.3	NO
18	DAGLB	DAGLB	DAGLB	8716	0.0013	0.26	NO
19	DCTN1	DCTN1	DCTN1	9731	-0.0079	0.2	NO
20	CDC42	CDC42	CDC42	9792	-0.0084	0.2	NO
21	PIK3R1	PIK3R1	PIK3R1	9836	-0.0088	0.21	NO
22	PIK3CA	PIK3CA	PIK3CA	10668	-0.017	0.17	NO
23	CTNND1	CTNND1	CTNND1	10771	-0.018	0.17	NO
24	MAPRE1	MAPRE1	MAPRE1	11172	-0.022	0.16	NO
25	CAMK2G	CAMK2G	CAMK2G	11334	-0.024	0.16	NO
26	FGFR1	FGFR1	FGFR1	11417	-0.025	0.16	NO
27	KIF5B	KIF5B	KIF5B	11687	-0.028	0.16	NO
28	PTPN11	PTPN11	PTPN11	12371	-0.037	0.13	NO
29	FER	FER	FER	12920	-0.045	0.12	NO
30	PTPN1	PTPN1	PTPN1	14005	-0.064	0.087	NO
31	MYL2	MYL2	MYL2	15397	-0.1	0.052	NO
32	CNR1	CNR1	CNR1	15550	-0.11	0.088	NO
33	MAPK8	MAPK8	MAPK8	15686	-0.12	0.13	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 NOTCH SIGNALING PATHWAY.

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG NOTCH 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 ADHERENS JUNCTION

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	CLDN6	CLDN6	CLDN6	85	0.52	0.077	YES
2	CLDN10	CLDN10	CLDN10	167	0.44	0.14	YES
3	CLDN2	CLDN2	CLDN2	170	0.44	0.21	YES
4	CDH2	CDH2	CDH2	224	0.4	0.27	YES
5	CDH3	CDH3	CDH3	358	0.34	0.32	YES
6	CDH15	CDH15	CDH15	630	0.27	0.34	YES
7	PVRL4	PVRL4	PVRL4	666	0.26	0.38	YES
8	CLDN9	CLDN9	CLDN9	724	0.25	0.42	YES
9	CADM1	CADM1	CADM1	980	0.21	0.44	YES
10	PARD6B	PARD6B	PARD6B	1217	0.18	0.45	YES
11	CLDN1	CLDN1	CLDN1	1300	0.17	0.48	YES
12	CDH8	CDH8	CDH8	1388	0.16	0.5	YES
13	CLDN16	CLDN16	CLDN16	1420	0.16	0.52	YES
14	CDH24	CDH24	CDH24	1567	0.15	0.54	YES
15	CDH4	CDH4	CDH4	1656	0.14	0.55	YES
16	CLDN11	CLDN11	CLDN11	1685	0.14	0.57	YES
17	CDH11	CDH11	CDH11	1686	0.14	0.6	YES
18	PVRL1	PVRL1	PVRL1	1901	0.13	0.6	YES
19	CLDN15	CLDN15	CLDN15	2099	0.11	0.61	YES
20	CLDN19	CLDN19	CLDN19	2120	0.11	0.63	YES
21	CLDN5	CLDN5	CLDN5	2201	0.11	0.64	YES
22	CDH13	CDH13	CDH13	2414	0.099	0.64	YES
23	PVRL2	PVRL2	PVRL2	3317	0.071	0.6	NO
24	CLDN3	CLDN3	CLDN3	4117	0.053	0.57	NO
25	CLDN4	CLDN4	CLDN4	4461	0.047	0.56	NO
26	INADL	INADL	INADL	4494	0.046	0.56	NO
27	PARD6A	PARD6A	PARD6A	5213	0.036	0.53	NO
28	F11R	F11R	F11R	5385	0.034	0.52	NO
29	CTNNB1	CTNNB1	CTNNB1	5396	0.034	0.53	NO
30	CLDN7	CLDN7	CLDN7	5599	0.032	0.52	NO
31	CDH5	CDH5	CDH5	5646	0.031	0.52	NO
32	CTNNA1	CTNNA1	CTNNA1	5917	0.028	0.51	NO
33	CDH12	CDH12	CDH12	6229	0.025	0.5	NO
34	MPP5	MPP5	MPP5	7442	0.013	0.43	NO
35	JUP	JUP	JUP	7836	0.0092	0.41	NO
36	PARD3	PARD3	PARD3	8227	0.0057	0.39	NO
37	CDH1	CDH1	CDH1	8696	0.0015	0.37	NO
38	CRB3	CRB3	CRB3	10064	-0.011	0.29	NO
39	PVRL3	PVRL3	PVRL3	10365	-0.014	0.28	NO
40	CTNND1	CTNND1	CTNND1	10771	-0.018	0.26	NO
41	PARD6G	PARD6G	PARD6G	11129	-0.022	0.24	NO
42	CDH10	CDH10	CDH10	11305	-0.024	0.24	NO
43	PRKCI	PRKCI	PRKCI	11523	-0.026	0.23	NO
44	CDH6	CDH6	CDH6	13348	-0.052	0.13	NO
45	PVR	PVR	PVR	14101	-0.066	0.1	NO
46	CADM2	CADM2	CADM2	14300	-0.071	0.1	NO
47	CLDN18	CLDN18	CLDN18	14452	-0.075	0.1	NO
48	CLDN14	CLDN14	CLDN14	14520	-0.077	0.11	NO
49	CLDN12	CLDN12	CLDN12	14768	-0.084	0.11	NO
50	CLDN20	CLDN20	CLDN20	15978	-0.13	0.066	NO
51	CLDN8	CLDN8	CLDN8	17495	-0.28	0.027	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 ADHERENS JUNCTION.

Figure S64. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ADHERENS JUNCTION, 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 THYROID CANCER

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	RASGRF1	RASGRF1	RASGRF1	35	0.63	0.13	YES
2	NGFR	NGFR	NGFR	38	0.61	0.25	YES
3	BDNF	BDNF	BDNF	120	0.48	0.35	YES
4	NTRK3	NTRK3	NTRK3	212	0.4	0.42	YES
5	TIAM1	TIAM1	TIAM1	690	0.26	0.45	YES
6	NTF3	NTF3	NTF3	2289	0.1	0.38	NO
7	RASA1	RASA1	RASA1	3248	0.073	0.34	NO
8	FRS3	FRS3	FRS3	3256	0.073	0.36	NO
9	GAB2	GAB2	GAB2	3854	0.058	0.34	NO
10	NTRK2	NTRK2	NTRK2	4298	0.05	0.32	NO
11	HRAS	HRAS	HRAS	4300	0.05	0.33	NO
12	MCF2L	MCF2L	MCF2L	4338	0.049	0.34	NO
13	CCND1	CCND1	CCND1	4807	0.041	0.32	NO
14	DNM1	DNM1	DNM1	4814	0.041	0.33	NO
15	SHC1	SHC1	SHC1	5245	0.036	0.32	NO
16	SH2B1	SH2B1	SH2B1	5448	0.033	0.31	NO
17	RIT1	RIT1	RIT1	5620	0.031	0.31	NO
18	CRKL	CRKL	CRKL	5775	0.03	0.3	NO
19	GAB1	GAB1	GAB1	5951	0.028	0.3	NO
20	NEDD4L	NEDD4L	NEDD4L	6120	0.026	0.3	NO
21	STAT3	STAT3	STAT3	6201	0.025	0.3	NO
22	PLCG1	PLCG1	PLCG1	6313	0.024	0.3	NO
23	ABL1	ABL1	ABL1	6416	0.023	0.3	NO
24	EHD4	EHD4	EHD4	6436	0.023	0.3	NO
25	FAIM	FAIM	FAIM	7074	0.016	0.27	NO
26	PRKCZ	PRKCZ	PRKCZ	7375	0.013	0.25	NO
27	RHOG	RHOG	RHOG	7377	0.013	0.26	NO
28	RAC1	RAC1	RAC1	7592	0.011	0.24	NO
29	RHOA	RHOA	RHOA	7961	0.008	0.23	NO
30	RAP1B	RAP1B	RAP1B	8508	0.0033	0.2	NO
31	GIPC1	GIPC1	GIPC1	9319	-0.0042	0.15	NO
32	GRB2	GRB2	GRB2	9336	-0.0043	0.15	NO
33	RGS19	RGS19	RGS19	9498	-0.0059	0.14	NO
34	MAPK3	MAPK3	MAPK3	9755	-0.0081	0.13	NO
35	CDC42	CDC42	CDC42	9792	-0.0084	0.13	NO
36	PIK3R1	PIK3R1	PIK3R1	9836	-0.0088	0.13	NO
37	FRS2	FRS2	FRS2	9870	-0.0091	0.13	NO
38	MAPK1	MAPK1	MAPK1	10177	-0.012	0.12	NO
39	PIK3CA	PIK3CA	PIK3CA	10668	-0.017	0.092	NO
40	RAPGEF1	RAPGEF1	RAPGEF1	10683	-0.017	0.095	NO
41	DOCK1	DOCK1	DOCK1	10884	-0.019	0.088	NO
42	RAP1A	RAP1A	RAP1A	11198	-0.023	0.075	NO
43	SQSTM1	SQSTM1	SQSTM1	11513	-0.026	0.063	NO
44	PRKCI	PRKCI	PRKCI	11523	-0.026	0.068	NO
45	SOS1	SOS1	SOS1	11578	-0.027	0.07	NO
46	MATK	MATK	MATK	11581	-0.027	0.076	NO
47	MAGED1	MAGED1	MAGED1	11624	-0.027	0.079	NO
48	CRK	CRK	CRK	12126	-0.034	0.058	NO
49	MAP2K1	MAP2K1	MAP2K1	12341	-0.037	0.053	NO
50	PTPN11	PTPN11	PTPN11	12371	-0.037	0.059	NO
51	KRAS	KRAS	KRAS	12724	-0.042	0.048	NO
52	DNAJA3	DNAJA3	DNAJA3	13130	-0.048	0.035	NO
53	NGF	NGF	NGF	13335	-0.052	0.034	NO
54	DYNLT1	DYNLT1	DYNLT1	14411	-0.074	-0.01	NO
55	NRAS	NRAS	NRAS	14649	-0.081	-0.0071	NO
56	ARHGAP32	ARHGAP32	ARHGAP32	14780	-0.085	0.003	NO
57	SHC3	SHC3	SHC3	15849	-0.12	-0.031	NO
58	SHC2	SHC2	SHC2	15908	-0.13	-0.008	NO
59	NTRK1	NTRK1	NTRK1	16501	-0.16	-0.008	NO
60	NTF4	NTF4	NTF4	16906	-0.19	0.0087	NO
61	ELMO1	ELMO1	ELMO1	17341	-0.25	0.035	NO

Figure S65. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG THYROID CANCER.

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

genes ES table in pathway: PID LKB1 PATHWAY

Table S34. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NEURL	NEURL	NEURL	81	0.52	0.27	YES
2	DTX1	DTX1	DTX1	875	0.22	0.34	YES
3	DTX4	DTX4	DTX4	922	0.22	0.45	YES
4	DLL1	DLL1	DLL1	1880	0.13	0.47	YES
5	DLL4	DLL4	DLL4	2345	0.1	0.49	YES
6	JAG2	JAG2	JAG2	3866	0.058	0.44	NO
7	MIB2	MIB2	MIB2	4723	0.043	0.41	NO
8	APH1B	APH1B	APH1B	6224	0.025	0.34	NO
9	PSEN2	PSEN2	PSEN2	6729	0.02	0.33	NO
10	PSENEN	PSENEN	PSENEN	7281	0.014	0.3	NO
11	MIB1	MIB1	MIB1	7569	0.012	0.29	NO
12	NCSTN	NCSTN	NCSTN	8465	0.0037	0.24	NO
13	RPS27A	RPS27A	RPS27A	8574	0.0027	0.24	NO
14	PSEN1	PSEN1	PSEN1	9149	-0.0026	0.21	NO
15	JAG1	JAG1	JAG1	9422	-0.0051	0.2	NO
16	UBA52	UBA52	UBA52	9631	-0.0071	0.19	NO
17	APH1A	APH1A	APH1A	9632	-0.0071	0.19	NO
18	ARRB2	ARRB2	ARRB2	9925	-0.0097	0.18	NO
19	DTX2	DTX2	DTX2	10611	-0.016	0.15	NO
20	ADAM10	ADAM10	ADAM10	12037	-0.032	0.09	NO
21	NUMB	NUMB	NUMB	12607	-0.04	0.079	NO
22	ADAM17	ADAM17	ADAM17	12679	-0.041	0.097	NO
23	ARRB1	ARRB1	ARRB1	13243	-0.05	0.092	NO
24	DNER	DNER	DNER	16297	-0.15	-0.00053	NO
25	CNTN1	CNTN1	CNTN1	16758	-0.18	0.068	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: PID LKB1 PATHWAY.

Figure S68. Get High-res Image For the top 5 core enriched genes in the pathway: PID LKB1 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 AJDISS 2PATHWAY

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	CLDN6	CLDN6	CLDN6	85	0.52	0.14	YES
2	CLDN10	CLDN10	CLDN10	167	0.44	0.26	YES
3	CLDN2	CLDN2	CLDN2	170	0.44	0.38	YES
4	CLDN9	CLDN9	CLDN9	724	0.25	0.42	YES
5	PARD6B	PARD6B	PARD6B	1217	0.18	0.44	YES
6	CLDN1	CLDN1	CLDN1	1300	0.17	0.48	YES
7	CLDN16	CLDN16	CLDN16	1420	0.16	0.52	YES
8	CLDN11	CLDN11	CLDN11	1685	0.14	0.54	YES
9	CLDN15	CLDN15	CLDN15	2099	0.11	0.55	YES
10	CLDN19	CLDN19	CLDN19	2120	0.11	0.58	YES
11	CLDN5	CLDN5	CLDN5	2201	0.11	0.61	YES
12	CLDN3	CLDN3	CLDN3	4117	0.053	0.52	NO
13	CLDN4	CLDN4	CLDN4	4461	0.047	0.51	NO
14	INADL	INADL	INADL	4494	0.046	0.52	NO
15	PARD6A	PARD6A	PARD6A	5213	0.036	0.49	NO
16	F11R	F11R	F11R	5385	0.034	0.49	NO
17	CLDN7	CLDN7	CLDN7	5599	0.032	0.49	NO
18	MPP5	MPP5	MPP5	7442	0.013	0.39	NO
19	PARD3	PARD3	PARD3	8227	0.0057	0.34	NO
20	CRB3	CRB3	CRB3	10064	-0.011	0.25	NO
21	PARD6G	PARD6G	PARD6G	11129	-0.022	0.19	NO
22	PRKCI	PRKCI	PRKCI	11523	-0.026	0.18	NO
23	CLDN18	CLDN18	CLDN18	14452	-0.075	0.036	NO
24	CLDN14	CLDN14	CLDN14	14520	-0.077	0.054	NO
25	CLDN12	CLDN12	CLDN12	14768	-0.084	0.063	NO
26	CLDN20	CLDN20	CLDN20	15978	-0.13	0.032	NO
27	CLDN8	CLDN8	CLDN8	17495	-0.28	0.026	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: PID AJDISS 2PATHWAY.

Figure S70. Get High-res Image For the top 5 core enriched genes in the pathway: PID AJDISS 2PATHWAY, 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 TRKRPATHWAY

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	CLDN6	CLDN6	CLDN6	85	0.52	0.06	YES
2	CLDN10	CLDN10	CLDN10	167	0.44	0.11	YES
3	CLDN2	CLDN2	CLDN2	170	0.44	0.16	YES
4	CDH2	CDH2	CDH2	224	0.4	0.21	YES
5	CDH3	CDH3	CDH3	358	0.34	0.25	YES
6	LAMB3	LAMB3	LAMB3	552	0.29	0.27	YES
7	CDH15	CDH15	CDH15	630	0.27	0.3	YES
8	PVRL4	PVRL4	PVRL4	666	0.26	0.33	YES
9	CLDN9	CLDN9	CLDN9	724	0.25	0.36	YES
10	CADM1	CADM1	CADM1	980	0.21	0.37	YES
11	PARD6B	PARD6B	PARD6B	1217	0.18	0.38	YES
12	CLDN1	CLDN1	CLDN1	1300	0.17	0.4	YES
13	CDH8	CDH8	CDH8	1388	0.16	0.41	YES
14	CLDN16	CLDN16	CLDN16	1420	0.16	0.43	YES
15	CDH24	CDH24	CDH24	1567	0.15	0.44	YES
16	CDH4	CDH4	CDH4	1656	0.14	0.46	YES
17	CLDN11	CLDN11	CLDN11	1685	0.14	0.47	YES
18	CDH11	CDH11	CDH11	1686	0.14	0.49	YES
19	PVRL1	PVRL1	PVRL1	1901	0.13	0.49	YES
20	CD151	CD151	CD151	2098	0.11	0.5	YES
21	CLDN15	CLDN15	CLDN15	2099	0.11	0.51	YES
22	CLDN19	CLDN19	CLDN19	2120	0.11	0.52	YES
23	CLDN5	CLDN5	CLDN5	2201	0.11	0.53	YES
24	CDH13	CDH13	CDH13	2414	0.099	0.53	YES
25	ITGB4	ITGB4	ITGB4	2461	0.097	0.54	YES
26	PVRL2	PVRL2	PVRL2	3317	0.071	0.5	NO
27	LIMS3	LIMS3	LIMS3	3738	0.061	0.49	NO
28	VASP	VASP	VASP	4069	0.054	0.48	NO
29	CLDN3	CLDN3	CLDN3	4117	0.053	0.48	NO
30	CLDN4	CLDN4	CLDN4	4461	0.047	0.47	NO
31	INADL	INADL	INADL	4494	0.046	0.47	NO
32	ACTN1	ACTN1	ACTN1	4562	0.045	0.47	NO
33	PARD6A	PARD6A	PARD6A	5213	0.036	0.44	NO
34	F11R	F11R	F11R	5385	0.034	0.44	NO
35	CTNNB1	CTNNB1	CTNNB1	5396	0.034	0.44	NO
36	CLDN7	CLDN7	CLDN7	5599	0.032	0.43	NO
37	CDH5	CDH5	CDH5	5646	0.031	0.43	NO
38	CTNNA1	CTNNA1	CTNNA1	5917	0.028	0.42	NO
39	CDH12	CDH12	CDH12	6229	0.025	0.41	NO
40	PLEC	PLEC	PLEC	6377	0.023	0.4	NO
41	FERMT2	FERMT2	FERMT2	6477	0.022	0.4	NO
42	TESK1	TESK1	TESK1	7208	0.015	0.36	NO
43	MPP5	MPP5	MPP5	7442	0.013	0.35	NO
44	JUP	JUP	JUP	7836	0.0092	0.33	NO
45	ILK	ILK	ILK	7944	0.0082	0.32	NO
46	PARD3	PARD3	PARD3	8227	0.0057	0.31	NO
47	CDH1	CDH1	CDH1	8696	0.0015	0.28	NO
48	CRB3	CRB3	CRB3	10064	-0.011	0.21	NO
49	PVRL3	PVRL3	PVRL3	10365	-0.014	0.19	NO
50	PARVB	PARVB	PARVB	10499	-0.015	0.19	NO
51	ITGB1	ITGB1	ITGB1	10594	-0.016	0.18	NO
52	CTNND1	CTNND1	CTNND1	10771	-0.018	0.18	NO
53	PARD6G	PARD6G	PARD6G	11129	-0.022	0.16	NO
54	CDH10	CDH10	CDH10	11305	-0.024	0.15	NO
55	PRKCI	PRKCI	PRKCI	11523	-0.026	0.14	NO
56	PARVA	PARVA	PARVA	12098	-0.033	0.12	NO
57	FLNC	FLNC	FLNC	12603	-0.04	0.093	NO
58	LAMA3	LAMA3	LAMA3	12902	-0.045	0.082	NO
59	RSU1	RSU1	RSU1	13329	-0.051	0.065	NO
60	CDH6	CDH6	CDH6	13348	-0.052	0.07	NO
61	FBLIM1	FBLIM1	FBLIM1	13874	-0.061	0.048	NO
62	PVR	PVR	PVR	14101	-0.066	0.044	NO
63	ARHGEF6	ARHGEF6	ARHGEF6	14205	-0.069	0.047	NO
64	LAMC2	LAMC2	LAMC2	14295	-0.071	0.051	NO
65	CADM2	CADM2	CADM2	14300	-0.071	0.06	NO
66	CLDN18	CLDN18	CLDN18	14452	-0.075	0.06	NO
67	CLDN14	CLDN14	CLDN14	14520	-0.077	0.066	NO
68	CLDN12	CLDN12	CLDN12	14768	-0.084	0.063	NO
69	CLDN20	CLDN20	CLDN20	15978	-0.13	0.012	NO
70	LIMS1	LIMS1	LIMS1	17023	-0.2	-0.021	NO
71	CLDN8	CLDN8	CLDN8	17495	-0.28	-0.012	NO
72	COL17A1	COL17A1	COL17A1	17570	-0.3	0.022	NO

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

Figure S72. Get High-res Image For the top 5 core enriched genes in the pathway: PID TRKRPATHWAY, 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 NCADHERINPATHWAY

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	RXRG	RXRG	RXRG	163	0.44	0.17	YES
2	RET	RET	RET	259	0.38	0.31	YES
3	TCF7	TCF7	TCF7	611	0.27	0.4	YES
4	LEF1	LEF1	LEF1	1183	0.18	0.44	YES
5	TCF7L2	TCF7L2	TCF7L2	3089	0.077	0.37	NO
6	MYC	MYC	MYC	4172	0.052	0.33	NO
7	HRAS	HRAS	HRAS	4300	0.05	0.34	NO
8	CCND1	CCND1	CCND1	4807	0.041	0.33	NO
9	CTNNB1	CTNNB1	CTNNB1	5396	0.034	0.31	NO
10	RXRB	RXRB	RXRB	6939	0.018	0.23	NO
11	TPM3	TPM3	TPM3	7660	0.011	0.19	NO
12	MAP2K2	MAP2K2	MAP2K2	8128	0.0065	0.17	NO
13	CDH1	CDH1	CDH1	8696	0.0015	0.14	NO
14	TP53	TP53	TP53	8903	-0.00031	0.13	NO
15	RXRA	RXRA	RXRA	9001	-0.0012	0.12	NO
16	MAPK3	MAPK3	MAPK3	9755	-0.0081	0.084	NO
17	PAX8	PAX8	PAX8	10121	-0.012	0.068	NO
18	MAPK1	MAPK1	MAPK1	10177	-0.012	0.069	NO
19	TPR	TPR	TPR	11281	-0.024	0.017	NO
20	TFG	TFG	TFG	11861	-0.03	-0.0031	NO
21	MAP2K1	MAP2K1	MAP2K1	12341	-0.037	-0.015	NO
22	KRAS	KRAS	KRAS	12724	-0.042	-0.02	NO
23	NCOA4	NCOA4	NCOA4	13290	-0.051	-0.032	NO
24	TCF7L1	TCF7L1	TCF7L1	13880	-0.062	-0.04	NO
25	CCDC6	CCDC6	CCDC6	14116	-0.067	-0.027	NO
26	NRAS	NRAS	NRAS	14649	-0.081	-0.024	NO
27	BRAF	BRAF	BRAF	14788	-0.085	0.0016	NO
28	NTRK1	NTRK1	NTRK1	16501	-0.16	-0.03	NO
29	PPARG	PPARG	PPARG	17491	-0.28	0.027	NO

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

Figure S74. Get High-res Image For the top 5 core enriched genes in the pathway: PID NCADHERINPATHWAY, 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 CELL COMMUNICATION

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	SLIT2	SLIT2	SLIT2	330	0.35	0.18	YES
2	SRGAP3	SRGAP3	SRGAP3	2139	0.11	0.15	YES
3	SRGAP2	SRGAP2	SRGAP2	2168	0.11	0.21	YES
4	CAP2	CAP2	CAP2	2555	0.093	0.24	YES
5	NCK2	NCK2	NCK2	2916	0.082	0.26	YES
6	PAK7	PAK7	PAK7	3079	0.077	0.3	YES
7	PAK1	PAK1	PAK1	3213	0.074	0.33	YES
8	ROBO2	ROBO2	ROBO2	3668	0.062	0.34	YES
9	ROBO1	ROBO1	ROBO1	3874	0.058	0.37	YES
10	PAK4	PAK4	PAK4	3903	0.057	0.4	YES
11	VASP	VASP	VASP	4069	0.054	0.42	YES
12	SRGAP1	SRGAP1	SRGAP1	4107	0.053	0.45	YES
13	CLASP1	CLASP1	CLASP1	4836	0.041	0.43	NO
14	ABL1	ABL1	ABL1	6416	0.023	0.35	NO
15	RAC1	RAC1	RAC1	7592	0.011	0.3	NO
16	CAP1	CAP1	CAP1	8908	-0.00034	0.22	NO
17	ENAH	ENAH	ENAH	9120	-0.0023	0.21	NO
18	EVL	EVL	EVL	9512	-0.006	0.19	NO
19	CDC42	CDC42	CDC42	9792	-0.0084	0.18	NO
20	PFN1	PFN1	PFN1	10218	-0.012	0.16	NO
21	PFN2	PFN2	PFN2	10231	-0.012	0.17	NO
22	PAK2	PAK2	PAK2	10515	-0.015	0.16	NO
23	ROBO3	ROBO3	ROBO3	11006	-0.021	0.15	NO
24	SOS1	SOS1	SOS1	11578	-0.027	0.13	NO
25	ABL2	ABL2	ABL2	12050	-0.032	0.12	NO
26	NCK1	NCK1	NCK1	12437	-0.038	0.12	NO
27	SOS2	SOS2	SOS2	13943	-0.063	0.077	NO
28	PAK6	PAK6	PAK6	14574	-0.078	0.086	NO
29	GPC1	GPC1	GPC1	16784	-0.18	0.066	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 CELL CELL COMMUNICATION.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME CELL CELL COMMUNICATION, 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 NEGATIVE REGULATION OF FGFR SIGNALING

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	FGF20	FGF20	FGF20	20	0.7	0.21	YES
2	FGF9	FGF9	FGF9	88	0.52	0.36	YES
3	FGFR3	FGFR3	FGFR3	264	0.38	0.47	YES
4	FGF1	FGF1	FGF1	2739	0.087	0.36	NO
5	FGF18	FGF18	FGF18	3778	0.06	0.32	NO
6	GAB2	GAB2	GAB2	3854	0.058	0.33	NO
7	HRAS	HRAS	HRAS	4300	0.05	0.32	NO
8	FGFR2	FGFR2	FGFR2	4399	0.048	0.33	NO
9	FGF2	FGF2	FGF2	4604	0.045	0.34	NO
10	STAT5A	STAT5A	STAT5A	5440	0.033	0.3	NO
11	STAT1	STAT1	STAT1	5642	0.031	0.3	NO
12	GAB1	GAB1	GAB1	5951	0.028	0.29	NO
13	STAT3	STAT3	STAT3	6201	0.025	0.28	NO
14	PLCG1	PLCG1	PLCG1	6313	0.024	0.28	NO
15	BCR	BCR	BCR	6786	0.019	0.26	NO
16	CPSF6	CPSF6	CPSF6	7274	0.014	0.24	NO
17	STAT5B	STAT5B	STAT5B	7440	0.013	0.24	NO
18	FGFR1OP2	FGFR1OP2	FGFR1OP2	7487	0.012	0.24	NO
19	ZMYM2	ZMYM2	ZMYM2	8533	0.0031	0.18	NO
20	GRB2	GRB2	GRB2	9336	-0.0043	0.14	NO
21	CUX1	CUX1	CUX1	9374	-0.0046	0.14	NO
22	PIK3R1	PIK3R1	PIK3R1	9836	-0.0088	0.11	NO
23	FRS2	FRS2	FRS2	9870	-0.0091	0.11	NO
24	FGF22	FGF22	FGF22	9964	-0.01	0.11	NO
25	PIK3CA	PIK3CA	PIK3CA	10668	-0.017	0.077	NO
26	MYO18A	MYO18A	MYO18A	10991	-0.021	0.066	NO
27	FGFR1	FGFR1	FGFR1	11417	-0.025	0.049	NO
28	SOS1	SOS1	SOS1	11578	-0.027	0.049	NO
29	FGFR1OP	FGFR1OP	FGFR1OP	12141	-0.034	0.028	NO
30	TRIM24	TRIM24	TRIM24	12408	-0.038	0.024	NO
31	KRAS	KRAS	KRAS	12724	-0.042	0.019	NO
32	NRAS	NRAS	NRAS	14649	-0.081	-0.063	NO
33	FGFR4	FGFR4	FGFR4	14990	-0.092	-0.054	NO
34	FGF17	FGF17	FGF17	17057	-0.21	-0.11	NO
35	FGF7	FGF7	FGF7	17230	-0.23	-0.046	NO
36	FGF10	FGF10	FGF10	17499	-0.29	0.026	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 NEGATIVE REGULATION OF FGFR SIGNALING.

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME NEGATIVE REGULATION OF FGFR SIGNALING, 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 ACTIVATED NOTCH1 TRANSMITS SIGNAL TO THE NUCLEUS

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	NEURL	NEURL	NEURL	81	0.52	0.11	YES
2	MAMLD1	MAMLD1	MAMLD1	454	0.31	0.16	YES
3	HEY2	HEY2	HEY2	658	0.26	0.21	YES
4	DTX1	DTX1	DTX1	875	0.22	0.25	YES
5	DTX4	DTX4	DTX4	922	0.22	0.29	YES
6	HEYL	HEYL	HEYL	1504	0.15	0.29	YES
7	DLL1	DLL1	DLL1	1880	0.13	0.3	YES
8	DLL4	DLL4	DLL4	2345	0.1	0.3	YES
9	HES5	HES5	HES5	2379	0.1	0.32	YES
10	MAML3	MAML3	MAML3	2418	0.099	0.34	YES
11	TLE4	TLE4	TLE4	2479	0.096	0.36	YES
12	TLE2	TLE2	TLE2	3111	0.076	0.34	NO
13	JAG2	JAG2	JAG2	3866	0.058	0.31	NO
14	HDAC8	HDAC8	HDAC8	3939	0.056	0.32	NO
15	MYC	MYC	MYC	4172	0.052	0.32	NO
16	HDAC7	HDAC7	HDAC7	4267	0.05	0.32	NO
17	MAML2	MAML2	MAML2	4295	0.05	0.33	NO
18	MIB2	MIB2	MIB2	4723	0.043	0.32	NO
19	SKP1	SKP1	SKP1	4913	0.04	0.32	NO
20	HDAC1	HDAC1	HDAC1	5060	0.038	0.32	NO
21	HDAC5	HDAC5	HDAC5	5589	0.032	0.29	NO
22	MAML1	MAML1	MAML1	5696	0.031	0.29	NO
23	KAT2A	KAT2A	KAT2A	6199	0.025	0.27	NO
24	APH1B	APH1B	APH1B	6224	0.025	0.28	NO
25	HDAC6	HDAC6	HDAC6	6530	0.022	0.26	NO
26	PSEN2	PSEN2	PSEN2	6729	0.02	0.26	NO
27	CREBBP	CREBBP	CREBBP	6805	0.019	0.26	NO
28	HDAC11	HDAC11	HDAC11	7115	0.016	0.24	NO
29	TBL1XR1	TBL1XR1	TBL1XR1	7209	0.015	0.24	NO
30	PSENEN	PSENEN	PSENEN	7281	0.014	0.24	NO
31	MIB1	MIB1	MIB1	7569	0.012	0.23	NO
32	RBX1	RBX1	RBX1	7627	0.011	0.23	NO
33	TLE3	TLE3	TLE3	7658	0.011	0.23	NO
34	RBPJ	RBPJ	RBPJ	8300	0.0052	0.19	NO
35	CUL1	CUL1	CUL1	8329	0.0048	0.19	NO
36	HIF1A	HIF1A	HIF1A	8369	0.0046	0.19	NO
37	NCSTN	NCSTN	NCSTN	8465	0.0037	0.19	NO
38	RPS27A	RPS27A	RPS27A	8574	0.0027	0.18	NO
39	EP300	EP300	EP300	8791	0.0006	0.17	NO
40	PSEN1	PSEN1	PSEN1	9149	-0.0026	0.15	NO
41	JAG1	JAG1	JAG1	9422	-0.0051	0.14	NO
42	HEY1	HEY1	HEY1	9575	-0.0066	0.13	NO
43	UBA52	UBA52	UBA52	9631	-0.0071	0.13	NO
44	APH1A	APH1A	APH1A	9632	-0.0071	0.13	NO
45	HDAC2	HDAC2	HDAC2	9744	-0.008	0.12	NO
46	NCOR1	NCOR1	NCOR1	9881	-0.0092	0.12	NO
47	ARRB2	ARRB2	ARRB2	9925	-0.0097	0.12	NO
48	NCOR2	NCOR2	NCOR2	10157	-0.012	0.11	NO
49	HDAC10	HDAC10	HDAC10	10235	-0.013	0.11	NO
50	SNW1	SNW1	SNW1	10417	-0.014	0.099	NO
51	DTX2	DTX2	DTX2	10611	-0.016	0.092	NO
52	HDAC3	HDAC3	HDAC3	10686	-0.017	0.092	NO
53	ADAM10	ADAM10	ADAM10	12037	-0.032	0.024	NO
54	KAT2B	KAT2B	KAT2B	12573	-0.04	0.0026	NO
55	NUMB	NUMB	NUMB	12607	-0.04	0.0098	NO
56	ADAM17	ADAM17	ADAM17	12679	-0.041	0.015	NO
57	FBXW7	FBXW7	FBXW7	12741	-0.042	0.021	NO
58	ARRB1	ARRB1	ARRB1	13243	-0.05	0.004	NO
59	TBL1X	TBL1X	TBL1X	13935	-0.063	-0.02	NO
60	CCNC	CCNC	CCNC	14594	-0.079	-0.04	NO
61	HDAC4	HDAC4	HDAC4	14801	-0.086	-0.032	NO
62	HDAC9	HDAC9	HDAC9	15003	-0.092	-0.023	NO
63	HES1	HES1	HES1	15977	-0.13	-0.048	NO
64	DNER	DNER	DNER	16297	-0.15	-0.032	NO
65	CDK8	CDK8	CDK8	16421	-0.16	-0.0045	NO
66	CNTN1	CNTN1	CNTN1	16758	-0.18	0.016	NO
67	TLE1	TLE1	TLE1	17232	-0.23	0.041	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 ACTIVATED NOTCH1 TRANSMITS SIGNAL TO THE NUCLEUS.

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME ACTIVATED NOTCH1 TRANSMITS SIGNAL TO THE NUCLEUS, 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 = THCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = THCA-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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