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

Kidney Renal Clear Cell Carcinoma (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 KIRC-TP. Broad Institute of MIT and Harvard. doi:10.7908/C16T0M13

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 "KIRC-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: 717
Number of samples: 533
Original number of Gene Sets: 1320
Maximum gene set size: 933

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 5 :[ clus1 ] 85
pheno.type: 2 - 5 :[ clus2 ] 172
pheno.type: 3 - 5 :[ clus3 ] 82
pheno.type: 4 - 5 :[ clus4 ] 154
pheno.type: 5 - 5 :[ clus5 ] 40

For the expression subtypes of 18278 genes in 534 samples, GSEA found enriched gene sets in each cluster using 533 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG OXIDATIVE PHOSPHORYLATION, KEGG ALZHEIMERS DISEASE, KEGG PARKINSONS DISEASE, KEGG VIBRIO CHOLERAE INFECTION, KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION, SIG PIP3 SIGNALING IN CARDIAC MYOCTES, PID PI3KCIAKTPATHWAY, REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT, REACTOME TRANS GOLGI NETWORK VESICLE BUDDING, REACTOME MITOCHONDRIAL PROTEIN IMPORT

And common core enriched genes are ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V1A, ATP6V1B1, ATP6V1C2, ATP6V1D

clus2

Top enriched gene sets are KEGG FATTY ACID METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG LYSINE DEGRADATION, KEGG HISTIDINE METABOLISM, KEGG TRYPTOPHAN METABOLISM, KEGG PROPANOATE METABOLISM, KEGG PPAR SIGNALING PATHWAY, KEGG PEROXISOME, KEGG ADIPOCYTOKINE SIGNALING PATHWAY, BIOCARTA AT1R PATHWAY

And common core enriched genes are EHHADH, ACAT1, ALDH1B1, ALDH2, ALDH3A2, ALDH7A1, ALDH9A1, HADHA, MLYCD, ABAT

clus3

Top enriched gene sets are KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE, KEGG MAPK SIGNALING PATHWAY, KEGG CALCIUM SIGNALING PATHWAY, KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION, KEGG MTOR SIGNALING PATHWAY, KEGG VASCULAR SMOOTH MUSCLE CONTRACTION, KEGG WNT SIGNALING PATHWAY, KEGG NOTCH SIGNALING PATHWAY, KEGG HEDGEHOG SIGNALING PATHWAY, KEGG TGF BETA SIGNALING PATHWAY

And common core enriched genes are PIK3CA, PIK3R1, PLCG1, SHC1, ADCY1, ADCY3, ADCY4, ADCY8, AKT3, CALM1

clus4

Top enriched gene sets are KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG P53 SIGNALING PATHWAY, KEGG CYTOSOLIC DNA SENSING PATHWAY, PID AURORA B PATHWAY, PID E2F PATHWAY, PID INTEGRIN2 PATHWAY, REACTOME ANTIGEN PROCESSING CROSS PRESENTATION, REACTOME ORC1 REMOVAL FROM CHROMATIN, REACTOME ACTIVATION OF NF KAPPAB IN B CELLS, REACTOME MHC CLASS II ANTIGEN PRESENTATION

And common core enriched genes are CD4, PSMA1, PSMA2, PSMA4, PSMA5, PSMA7, PSMA8, PSMB10, PSMB2, PSMB3

clus5

Top enriched gene sets are KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT, KEGG NOTCH SIGNALING PATHWAY, KEGG RIG I LIKE RECEPTOR SIGNALING PATHWAY, KEGG OLFACTORY TRANSDUCTION, KEGG TASTE TRANSDUCTION, SIG CD40PATHWAYMAP, PID RHOA REG PATHWAY, PID HDAC CLASSI PATHWAY, REACTOME MEIOSIS, REACTOME SIGNALING BY FGFR1 MUTANTS

And common core enriched genes are ACD, HIST1H2AD, HIST1H2AE, HIST1H2BD, HIST1H2BE, HIST1H2BF, HIST1H2BG, HIST1H2BH, HIST1H2BJ, HIST1H2BL

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 OXIDATIVE PHOSPHORYLATION	113	genes.ES.table	0.66	1.9	0.0093	0.26	0.39	0.78	0.23	0.61	0	0.07
KEGG ALZHEIMERS DISEASE	155	genes.ES.table	0.37	1.6	0.052	0.5	0.92	0.52	0.23	0.4	0.33	0.15
KEGG PARKINSONS DISEASE	110	genes.ES.table	0.5	1.7	0.091	0.46	0.84	0.64	0.23	0.5	0.25	0.14
KEGG VIBRIO CHOLERAE INFECTION	52	genes.ES.table	0.6	2	0	0.1	0.14	0.36	0.17	0.3	0	0.032
KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION	67	genes.ES.table	0.42	1.6	0.019	0.51	0.9	0.25	0.17	0.21	0.32	0.16
SIG PIP3 SIGNALING IN CARDIAC MYOCTES	66	genes.ES.table	0.4	1.7	0.01	0.46	0.78	0.14	0.1	0.12	0.22	0.15
PID PI3KCIAKTPATHWAY	35	genes.ES.table	0.49	2.1	0.0021	0.14	0.1	0.43	0.27	0.31	0	0.051
REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT	115	genes.ES.table	0.61	1.8	0.03	0.49	0.62	0.75	0.23	0.58	0.18	0.15
REACTOME TRANS GOLGI NETWORK VESICLE BUDDING	59	genes.ES.table	0.36	1.6	0.054	0.47	0.87	0.051	0.041	0.049	0.28	0.14
REACTOME MITOCHONDRIAL PROTEIN IMPORT	49	genes.ES.table	0.62	1.8	0.034	0.46	0.64	0.71	0.3	0.5	0.18	0.14

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

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	SLC2A4	SLC2A4	SLC2A4	500	0.37	0.17	YES
2	SFN	SFN	SFN	1823	0.16	0.18	YES
3	HSP90AA1	HSP90AA1	HSP90AA1	2236	0.13	0.23	YES
4	TBC1D4	TBC1D4	TBC1D4	2771	0.1	0.26	YES
5	GSK3B	GSK3B	GSK3B	3344	0.085	0.27	YES
6	FOXO1	FOXO1	FOXO1	3368	0.084	0.32	YES
7	MAPKAP1	MAPKAP1	MAPKAP1	3462	0.081	0.35	YES
8	RAF1	RAF1	RAF1	3832	0.071	0.37	YES
9	CHUK	CHUK	CHUK	4540	0.053	0.36	YES
10	AKT2	AKT2	AKT2	4662	0.051	0.38	YES
11	KPNA1	KPNA1	KPNA1	4723	0.05	0.4	YES
12	YWHAB	YWHAB	YWHAB	4825	0.048	0.42	YES
13	BCL2L1	BCL2L1	BCL2L1	4891	0.047	0.45	YES
14	MLST8	MLST8	MLST8	4902	0.046	0.47	YES
15	MTOR	MTOR	MTOR	4903	0.046	0.5	YES
16	AKT1	AKT1	AKT1	5567	0.035	0.48	NO
17	PRKDC	PRKDC	PRKDC	6184	0.026	0.46	NO
18	YWHAE	YWHAE	YWHAE	6617	0.019	0.44	NO
19	PRKACA	PRKACA	PRKACA	6788	0.016	0.44	NO
20	GSK3A	GSK3A	GSK3A	6934	0.014	0.44	NO
21	RICTOR	RICTOR	RICTOR	6961	0.014	0.45	NO
22	FOXO4	FOXO4	FOXO4	6988	0.014	0.45	NO
23	CDKN1A	CDKN1A	CDKN1A	7351	0.0086	0.44	NO
24	BAD	BAD	BAD	7761	0.0033	0.42	NO
25	PDPK1	PDPK1	PDPK1	7787	0.003	0.42	NO
26	SRC	SRC	SRC	7993	0.0002	0.41	NO
27	YWHAQ	YWHAQ	YWHAQ	8143	-0.0018	0.4	NO
28	YWHAZ	YWHAZ	YWHAZ	8882	-0.011	0.36	NO
29	CASP9	CASP9	CASP9	9173	-0.015	0.36	NO
30	YWHAG	YWHAG	YWHAG	9234	-0.016	0.36	NO
31	YWHAH	YWHAH	YWHAH	9910	-0.025	0.34	NO
32	AKT3	AKT3	AKT3	10601	-0.036	0.32	NO
33	MAP3K5	MAP3K5	MAP3K5	10677	-0.037	0.34	NO
34	FOXO3	FOXO3	FOXO3	11288	-0.047	0.33	NO
35	CDKN1B	CDKN1B	CDKN1B	13638	-0.1	0.25	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 OXIDATIVE PHOSPHORYLATION.

Figure S2. 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 ALZHEIMERS DISEASE

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	ATP6V0A4	ATP6V0A4	ATP6V0A4	5	0.99	0.13	YES
2	ATP6V1B1	ATP6V1B1	ATP6V1B1	42	0.8	0.24	YES
3	CFTR	CFTR	CFTR	63	0.72	0.34	YES
4	ATP6V0D2	ATP6V0D2	ATP6V0D2	108	0.64	0.42	YES
5	ATP6V1C2	ATP6V1C2	ATP6V1C2	515	0.37	0.45	YES
6	PLCG2	PLCG2	PLCG2	948	0.27	0.46	YES
7	ATP6V0E2	ATP6V0E2	ATP6V0E2	1116	0.24	0.48	YES
8	ATP6V1A	ATP6V1A	ATP6V1A	1369	0.2	0.5	YES
9	KCNQ1	KCNQ1	KCNQ1	1549	0.18	0.51	YES
10	ATP6V1H	ATP6V1H	ATP6V1H	1647	0.18	0.53	YES
11	ATP6V1D	ATP6V1D	ATP6V1D	1732	0.17	0.55	YES
12	ATP6V0B	ATP6V0B	ATP6V0B	1852	0.16	0.56	YES
13	PRKCA	PRKCA	PRKCA	2098	0.14	0.57	YES
14	ATP6V0C	ATP6V0C	ATP6V0C	2103	0.14	0.59	YES
15	ATP6V0D1	ATP6V0D1	ATP6V0D1	2607	0.11	0.57	YES
16	ATP6V1F	ATP6V1F	ATP6V1F	2832	0.1	0.58	YES
17	ATP6V0A2	ATP6V0A2	ATP6V0A2	2974	0.097	0.58	YES
18	ATP6V1E1	ATP6V1E1	ATP6V1E1	3004	0.096	0.59	YES
19	ATP6V1G2	ATP6V1G2	ATP6V1G2	3065	0.094	0.6	YES
20	ATP6V1G1	ATP6V1G1	ATP6V1G1	3586	0.078	0.58	NO
21	ATP6AP1	ATP6AP1	ATP6AP1	3655	0.076	0.59	NO
22	GNAS	GNAS	GNAS	4260	0.059	0.56	NO
23	ATP6V0E1	ATP6V0E1	ATP6V0E1	4410	0.056	0.56	NO
24	SLC12A2	SLC12A2	SLC12A2	4421	0.056	0.57	NO
25	PRKCG	PRKCG	PRKCG	4456	0.055	0.58	NO
26	ATP6V1C1	ATP6V1C1	ATP6V1C1	5410	0.038	0.53	NO
27	TJP2	TJP2	TJP2	5561	0.035	0.53	NO
28	ACTG1	ACTG1	ACTG1	5655	0.034	0.53	NO
29	TJP1	TJP1	TJP1	5793	0.032	0.52	NO
30	KDELR1	KDELR1	KDELR1	5881	0.031	0.52	NO
31	PRKACB	PRKACB	PRKACB	6482	0.021	0.49	NO
32	PRKACA	PRKACA	PRKACA	6788	0.016	0.48	NO
33	MUC2	MUC2	MUC2	6953	0.014	0.47	NO
34	SEC61B	SEC61B	SEC61B	7112	0.012	0.46	NO
35	ACTB	ACTB	ACTB	7293	0.0094	0.46	NO
36	SEC61A1	SEC61A1	SEC61A1	7988	0.00027	0.42	NO
37	PRKX	PRKX	PRKX	8112	-0.0013	0.41	NO
38	ARF1	ARF1	ARF1	8367	-0.0044	0.4	NO
39	ATP6V1E2	ATP6V1E2	ATP6V1E2	9258	-0.016	0.35	NO
40	KDELR2	KDELR2	KDELR2	10074	-0.027	0.31	NO
41	ATP6V1B2	ATP6V1B2	ATP6V1B2	10647	-0.037	0.28	NO
42	ATP6V0A1	ATP6V0A1	ATP6V0A1	10728	-0.038	0.28	NO
43	PLCG1	PLCG1	PLCG1	11134	-0.044	0.27	NO
44	PDIA4	PDIA4	PDIA4	12076	-0.064	0.22	NO
45	ADCY9	ADCY9	ADCY9	12153	-0.065	0.23	NO
46	KDELR3	KDELR3	KDELR3	12187	-0.066	0.24	NO
47	SEC61G	SEC61G	SEC61G	12578	-0.075	0.22	NO
48	ERO1L	ERO1L	ERO1L	12702	-0.078	0.23	NO
49	ADCY3	ADCY3	ADCY3	13439	-0.097	0.2	NO
50	TCIRG1	TCIRG1	TCIRG1	13457	-0.098	0.21	NO
51	SEC61A2	SEC61A2	SEC61A2	13662	-0.1	0.22	NO
52	PRKCB	PRKCB	PRKCB	16904	-0.27	0.074	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 ALZHEIMERS DISEASE.

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

genes ES table in pathway: KEGG PARKINSONS DISEASE

Table S3. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ATP6V0A4	ATP6V0A4	ATP6V0A4	5	0.99	0.088	YES
2	FGF9	FGF9	FGF9	7	0.96	0.17	YES
3	ATP6V1B1	ATP6V1B1	ATP6V1B1	42	0.8	0.24	YES
4	ATP6V0D2	ATP6V0D2	ATP6V0D2	108	0.64	0.3	YES
5	ATP6V1C2	ATP6V1C2	ATP6V1C2	515	0.37	0.3	YES
6	FGF7	FGF7	FGF7	706	0.32	0.32	YES
7	CAB39L	CAB39L	CAB39L	965	0.26	0.33	YES
8	FGF1	FGF1	FGF1	1002	0.26	0.35	YES
9	IRS1	IRS1	IRS1	1203	0.22	0.36	YES
10	ATP6V1A	ATP6V1A	ATP6V1A	1369	0.2	0.37	YES
11	ATP6V1H	ATP6V1H	ATP6V1H	1647	0.18	0.37	YES
12	ATP6V1D	ATP6V1D	ATP6V1D	1732	0.17	0.38	YES
13	PDE3B	PDE3B	PDE3B	1800	0.16	0.39	YES
14	IRS2	IRS2	IRS2	1820	0.16	0.4	YES
15	ATP6V0B	ATP6V0B	ATP6V0B	1852	0.16	0.42	YES
16	FGF18	FGF18	FGF18	1916	0.15	0.43	YES
17	ATP6V0C	ATP6V0C	ATP6V0C	2103	0.14	0.43	YES
18	ATP6V0D1	ATP6V0D1	ATP6V0D1	2607	0.11	0.41	YES
19	EIF4E	EIF4E	EIF4E	2703	0.11	0.42	YES
20	ATP6V1F	ATP6V1F	ATP6V1F	2832	0.1	0.42	YES
21	PRKAG2	PRKAG2	PRKAG2	2939	0.098	0.42	YES
22	ATP6V0A2	ATP6V0A2	ATP6V0A2	2974	0.097	0.43	YES
23	ATP6V1E1	ATP6V1E1	ATP6V1E1	3004	0.096	0.43	YES
24	PPM1A	PPM1A	PPM1A	3005	0.096	0.44	YES
25	ATP6V1G2	ATP6V1G2	ATP6V1G2	3065	0.094	0.45	YES
26	PRKAB1	PRKAB1	PRKAB1	3133	0.091	0.45	YES
27	RHEB	RHEB	RHEB	3185	0.09	0.46	YES
28	ATP6V1G1	ATP6V1G1	ATP6V1G1	3586	0.078	0.44	NO
29	FGF23	FGF23	FGF23	3607	0.077	0.45	NO
30	RAF1	RAF1	RAF1	3832	0.071	0.44	NO
31	SHC3	SHC3	SHC3	4246	0.06	0.42	NO
32	ATP6V0E1	ATP6V0E1	ATP6V0E1	4410	0.056	0.42	NO
33	AKT2	AKT2	AKT2	4662	0.051	0.41	NO
34	PRKAG1	PRKAG1	PRKAG1	4664	0.051	0.42	NO
35	CAB39	CAB39	CAB39	4732	0.05	0.42	NO
36	FGFR1	FGFR1	FGFR1	4790	0.049	0.42	NO
37	YWHAB	YWHAB	YWHAB	4825	0.048	0.42	NO
38	MLST8	MLST8	MLST8	4902	0.046	0.42	NO
39	MTOR	MTOR	MTOR	4903	0.046	0.42	NO
40	THEM4	THEM4	THEM4	5176	0.042	0.41	NO
41	PIK3R4	PIK3R4	PIK3R4	5253	0.04	0.41	NO
42	ATP6V1C1	ATP6V1C1	ATP6V1C1	5410	0.038	0.41	NO
43	RPTOR	RPTOR	RPTOR	5417	0.037	0.41	NO
44	KRAS	KRAS	KRAS	5767	0.032	0.39	NO
45	PIK3R2	PIK3R2	PIK3R2	6052	0.028	0.38	NO
46	FGFR2	FGFR2	FGFR2	6266	0.024	0.37	NO
47	PRKAB2	PRKAB2	PRKAB2	6520	0.02	0.36	NO
48	PIK3CA	PIK3CA	PIK3CA	6546	0.02	0.36	NO
49	KLB	KLB	KLB	6550	0.02	0.36	NO
50	MAP2K2	MAP2K2	MAP2K2	7025	0.013	0.34	NO
51	FRS2	FRS2	FRS2	7057	0.013	0.34	NO
52	EIF4G1	EIF4G1	EIF4G1	7184	0.011	0.33	NO
53	PIK3C3	PIK3C3	PIK3C3	7380	0.0082	0.32	NO
54	TSC1	TSC1	TSC1	7550	0.0061	0.31	NO
55	TSC2	TSC2	TSC2	7595	0.0054	0.31	NO
56	MAP2K1	MAP2K1	MAP2K1	7598	0.0054	0.31	NO
57	STK11	STK11	STK11	7601	0.0054	0.31	NO
58	RPS6	RPS6	RPS6	7633	0.005	0.31	NO
59	PDPK1	PDPK1	PDPK1	7787	0.003	0.3	NO
60	FGF8	FGF8	FGF8	7824	0.0025	0.3	NO
61	CRK	CRK	CRK	7984	0.00034	0.29	NO
62	STRADA	STRADA	STRADA	8250	-0.0031	0.27	NO
63	SHC2	SHC2	SHC2	8699	-0.0087	0.25	NO
64	PRKAA1	PRKAA1	PRKAA1	9230	-0.016	0.22	NO
65	ATP6V1E2	ATP6V1E2	ATP6V1E2	9258	-0.016	0.22	NO
66	EIF4B	EIF4B	EIF4B	9555	-0.02	0.21	NO
67	GRB2	GRB2	GRB2	9568	-0.02	0.21	NO
68	HRAS	HRAS	HRAS	9804	-0.023	0.2	NO
69	MAPK3	MAPK3	MAPK3	10607	-0.036	0.16	NO
70	RPS6KB1	RPS6KB1	RPS6KB1	10624	-0.036	0.16	NO
71	ATP6V1B2	ATP6V1B2	ATP6V1B2	10647	-0.037	0.16	NO
72	FGF17	FGF17	FGF17	10843	-0.04	0.15	NO
73	PIK3CB	PIK3CB	PIK3CB	10847	-0.04	0.16	NO
74	KL	KL	KL	11242	-0.046	0.14	NO
75	GAB1	GAB1	GAB1	11253	-0.046	0.14	NO
76	PRKAA2	PRKAA2	PRKAA2	11719	-0.056	0.12	NO
77	SOS1	SOS1	SOS1	11807	-0.058	0.12	NO
78	EEF2K	EEF2K	EEF2K	11833	-0.058	0.13	NO
79	FGF2	FGF2	FGF2	12158	-0.065	0.12	NO
80	MAPK1	MAPK1	MAPK1	12274	-0.068	0.12	NO
81	NRAS	NRAS	NRAS	12572	-0.075	0.1	NO
82	GRB10	GRB10	GRB10	12676	-0.078	0.11	NO
83	STRADB	STRADB	STRADB	13377	-0.096	0.076	NO
84	TCIRG1	TCIRG1	TCIRG1	13457	-0.098	0.081	NO
85	PIK3R1	PIK3R1	PIK3R1	13813	-0.11	0.071	NO
86	DOK1	DOK1	DOK1	13947	-0.11	0.074	NO
87	SHC1	SHC1	SHC1	14166	-0.12	0.072	NO
88	INSR	INSR	INSR	14480	-0.13	0.067	NO
89	CDK1	CDK1	CDK1	14630	-0.14	0.071	NO
90	FGF20	FGF20	FGF20	14660	-0.14	0.082	NO
91	FGF5	FGF5	FGF5	15583	-0.18	0.047	NO
92	TRIB3	TRIB3	TRIB3	16045	-0.2	0.04	NO
93	FGFR4	FGFR4	FGFR4	16260	-0.22	0.047	NO
94	FGFR3	FGFR3	FGFR3	16420	-0.23	0.059	NO
95	EIF4EBP1	EIF4EBP1	EIF4EBP1	16496	-0.23	0.075	NO
96	TLR9	TLR9	TLR9	16658	-0.24	0.088	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 PARKINSONS DISEASE.

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

genes ES table in pathway: KEGG VIBRIO CHOLERAE INFECTION

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	ATP6V0A4	ATP6V0A4	ATP6V0A4	5	0.99	0.065	YES
2	ATP6V1B1	ATP6V1B1	ATP6V1B1	42	0.8	0.12	YES
3	ATP6V0D2	ATP6V0D2	ATP6V0D2	108	0.64	0.15	YES
4	ATP12A	ATP12A	ATP12A	208	0.54	0.18	YES
5	ATP4B	ATP4B	ATP4B	505	0.37	0.19	YES
6	ATP6V1C2	ATP6V1C2	ATP6V1C2	515	0.37	0.21	YES
7	COX7A1	COX7A1	COX7A1	1027	0.25	0.2	YES
8	ATP6V0E2	ATP6V0E2	ATP6V0E2	1116	0.24	0.21	YES
9	COX6B2	COX6B2	COX6B2	1234	0.22	0.22	YES
10	UQCRHL	UQCRHL	UQCRHL	1265	0.22	0.23	YES
11	NDUFA4	NDUFA4	NDUFA4	1308	0.21	0.24	YES
12	ATP6V1A	ATP6V1A	ATP6V1A	1369	0.2	0.26	YES
13	UQCRC1	UQCRC1	UQCRC1	1378	0.2	0.27	YES
14	UQCRFS1	UQCRFS1	UQCRFS1	1395	0.2	0.28	YES
15	UQCRH	UQCRH	UQCRH	1435	0.2	0.29	YES
16	COX5A	COX5A	COX5A	1584	0.18	0.29	YES
17	NDUFS8	NDUFS8	NDUFS8	1616	0.18	0.3	YES
18	ATP6V1H	ATP6V1H	ATP6V1H	1647	0.18	0.31	YES
19	COX7B	COX7B	COX7B	1693	0.17	0.32	YES
20	ATP6V1D	ATP6V1D	ATP6V1D	1732	0.17	0.33	YES
21	PPA2	PPA2	PPA2	1848	0.16	0.34	YES
22	ATP6V0B	ATP6V0B	ATP6V0B	1852	0.16	0.34	YES
23	NDUFA6	NDUFA6	NDUFA6	1892	0.16	0.35	YES
24	ATP5G1	ATP5G1	ATP5G1	1896	0.15	0.36	YES
25	NDUFB1	NDUFB1	NDUFB1	1953	0.15	0.37	YES
26	NDUFA3	NDUFA3	NDUFA3	1962	0.15	0.38	YES
27	ATP5A1	ATP5A1	ATP5A1	2016	0.14	0.39	YES
28	ATP6V0C	ATP6V0C	ATP6V0C	2103	0.14	0.39	YES
29	NDUFB2	NDUFB2	NDUFB2	2115	0.14	0.4	YES
30	COX10	COX10	COX10	2161	0.14	0.4	YES
31	COX6A1	COX6A1	COX6A1	2186	0.13	0.41	YES
32	COX7A2	COX7A2	COX7A2	2195	0.13	0.42	YES
33	COX6C	COX6C	COX6C	2197	0.13	0.43	YES
34	NDUFB9	NDUFB9	NDUFB9	2235	0.13	0.44	YES
35	NDUFA9	NDUFA9	NDUFA9	2286	0.13	0.44	YES
36	NDUFB5	NDUFB5	NDUFB5	2295	0.13	0.45	YES
37	ATP5B	ATP5B	ATP5B	2317	0.13	0.46	YES
38	UQCRC2	UQCRC2	UQCRC2	2356	0.12	0.46	YES
39	COX8A	COX8A	COX8A	2436	0.12	0.47	YES
40	UQCR10	UQCR10	UQCR10	2440	0.12	0.47	YES
41	NDUFA8	NDUFA8	NDUFA8	2454	0.12	0.48	YES
42	ATP5L	ATP5L	ATP5L	2481	0.12	0.49	YES
43	UQCR11	UQCR11	UQCR11	2565	0.12	0.49	YES
44	NDUFC2	NDUFC2	NDUFC2	2586	0.11	0.5	YES
45	ATP6V0D1	ATP6V0D1	ATP6V0D1	2607	0.11	0.5	YES
46	ATP5J2	ATP5J2	ATP5J2	2633	0.11	0.51	YES
47	COX4I1	COX4I1	COX4I1	2694	0.11	0.51	YES
48	NDUFS1	NDUFS1	NDUFS1	2702	0.11	0.52	YES
49	COX5B	COX5B	COX5B	2761	0.11	0.52	YES
50	NDUFS3	NDUFS3	NDUFS3	2821	0.1	0.53	YES
51	ATP6V1F	ATP6V1F	ATP6V1F	2832	0.1	0.53	YES
52	COX17	COX17	COX17	2833	0.1	0.54	YES
53	COX6B1	COX6B1	COX6B1	2847	0.1	0.55	YES
54	NDUFV1	NDUFV1	NDUFV1	2900	0.1	0.55	YES
55	SDHD	SDHD	SDHD	2914	0.099	0.56	YES
56	ATP5E	ATP5E	ATP5E	2950	0.098	0.56	YES
57	NDUFB7	NDUFB7	NDUFB7	2955	0.098	0.57	YES
58	ATP6V0A2	ATP6V0A2	ATP6V0A2	2974	0.097	0.57	YES
59	ATP6V1E1	ATP6V1E1	ATP6V1E1	3004	0.096	0.58	YES
60	ATP5I	ATP5I	ATP5I	3056	0.094	0.58	YES
61	NDUFS6	NDUFS6	NDUFS6	3059	0.094	0.58	YES
62	ATP6V1G2	ATP6V1G2	ATP6V1G2	3065	0.094	0.59	YES
63	NDUFS7	NDUFS7	NDUFS7	3077	0.094	0.6	YES
64	ATP5D	ATP5D	ATP5D	3144	0.091	0.6	YES
65	COX7C	COX7C	COX7C	3165	0.09	0.6	YES
66	NDUFAB1	NDUFAB1	NDUFAB1	3187	0.09	0.61	YES
67	NDUFA5	NDUFA5	NDUFA5	3201	0.089	0.61	YES
68	NDUFA1	NDUFA1	NDUFA1	3385	0.083	0.61	YES
69	ATP5G3	ATP5G3	ATP5G3	3421	0.082	0.61	YES
70	NDUFB6	NDUFB6	NDUFB6	3542	0.079	0.61	YES
71	ATP5H	ATP5H	ATP5H	3546	0.079	0.62	YES
72	ATP5J	ATP5J	ATP5J	3553	0.079	0.62	YES
73	ATP6V1G1	ATP6V1G1	ATP6V1G1	3586	0.078	0.62	YES
74	NDUFA7	NDUFA7	NDUFA7	3613	0.077	0.63	YES
75	NDUFB8	NDUFB8	NDUFB8	3616	0.077	0.63	YES
76	ATP6AP1	ATP6AP1	ATP6AP1	3655	0.076	0.64	YES
77	UQCRQ	UQCRQ	UQCRQ	3657	0.076	0.64	YES
78	CYC1	CYC1	CYC1	3699	0.074	0.64	YES
79	NDUFB3	NDUFB3	NDUFB3	3729	0.074	0.65	YES
80	NDUFA11	NDUFA11	NDUFA11	3769	0.073	0.65	YES
81	UQCRB	UQCRB	UQCRB	3791	0.072	0.65	YES
82	NDUFS2	NDUFS2	NDUFS2	3820	0.071	0.66	YES
83	NDUFB10	NDUFB10	NDUFB10	3921	0.069	0.65	YES
84	NDUFA10	NDUFA10	NDUFA10	4059	0.065	0.65	YES
85	ATP5O	ATP5O	ATP5O	4080	0.064	0.65	YES
86	SDHA	SDHA	SDHA	4100	0.064	0.66	YES
87	COX7A2L	COX7A2L	COX7A2L	4134	0.063	0.66	YES
88	ATP5F1	ATP5F1	ATP5F1	4149	0.062	0.66	YES
89	ATP5C1	ATP5C1	ATP5C1	4248	0.06	0.66	NO
90	ATP6V0E1	ATP6V0E1	ATP6V0E1	4410	0.056	0.66	NO
91	SDHC	SDHC	SDHC	4442	0.055	0.66	NO
92	NDUFB4	NDUFB4	NDUFB4	4720	0.05	0.65	NO
93	NDUFS4	NDUFS4	NDUFS4	4835	0.048	0.64	NO
94	LHPP	LHPP	LHPP	4847	0.047	0.64	NO
95	NDUFV2	NDUFV2	NDUFV2	5035	0.044	0.64	NO
96	NDUFS5	NDUFS5	NDUFS5	5188	0.041	0.63	NO
97	NDUFA2	NDUFA2	NDUFA2	5369	0.038	0.62	NO
98	ATP6V1C1	ATP6V1C1	ATP6V1C1	5410	0.038	0.62	NO
99	COX11	COX11	COX11	5637	0.034	0.62	NO
100	SDHB	SDHB	SDHB	6002	0.028	0.6	NO
101	COX15	COX15	COX15	7385	0.0081	0.52	NO
102	ATP5G2	ATP5G2	ATP5G2	7409	0.0078	0.52	NO
103	PPA1	PPA1	PPA1	7758	0.0034	0.5	NO
104	NDUFV3	NDUFV3	NDUFV3	8072	-0.00086	0.48	NO
105	ATP6V1E2	ATP6V1E2	ATP6V1E2	9258	-0.016	0.42	NO
106	NDUFC1	NDUFC1	NDUFC1	9449	-0.018	0.41	NO
107	ATP6V1B2	ATP6V1B2	ATP6V1B2	10647	-0.037	0.35	NO
108	ATP6V0A1	ATP6V0A1	ATP6V0A1	10728	-0.038	0.34	NO
109	TCIRG1	TCIRG1	TCIRG1	13457	-0.098	0.2	NO
110	COX4I2	COX4I2	COX4I2	13556	-0.1	0.2	NO
111	COX8C	COX8C	COX8C	14869	-0.15	0.14	NO
112	COX6A2	COX6A2	COX6A2	16926	-0.27	0.044	NO
113	NDUFA4L2	NDUFA4L2	NDUFA4L2	18072	-0.45	0.01	NO

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

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

genes ES table in pathway: KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION

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	NNT	NNT	NNT	1126	0.23	-0.043	YES
2	PDP2	PDP2	PDP2	1154	0.23	-0.026	YES
3	UQCRHL	UQCRHL	UQCRHL	1265	0.22	-0.014	YES
4	NDUFA4	NDUFA4	NDUFA4	1308	0.21	0.00094	YES
5	UQCRC1	UQCRC1	UQCRC1	1378	0.2	0.014	YES
6	UQCRFS1	UQCRFS1	UQCRFS1	1395	0.2	0.029	YES
7	PDP1	PDP1	PDP1	1402	0.2	0.045	YES
8	CYCS	CYCS	CYCS	1432	0.2	0.06	YES
9	UQCRH	UQCRH	UQCRH	1435	0.2	0.075	YES
10	COX5A	COX5A	COX5A	1584	0.18	0.082	YES
11	NDUFS8	NDUFS8	NDUFS8	1616	0.18	0.095	YES
12	IDH3A	IDH3A	IDH3A	1619	0.18	0.11	YES
13	PDHB	PDHB	PDHB	1683	0.17	0.12	YES
14	COX7B	COX7B	COX7B	1693	0.17	0.13	YES
15	PDHA1	PDHA1	PDHA1	1843	0.16	0.14	YES
16	SUCLG1	SUCLG1	SUCLG1	1875	0.16	0.15	YES
17	NDUFA6	NDUFA6	NDUFA6	1892	0.16	0.16	YES
18	ATP5G1	ATP5G1	ATP5G1	1896	0.15	0.17	YES
19	NDUFB1	NDUFB1	NDUFB1	1953	0.15	0.18	YES
20	NDUFA3	NDUFA3	NDUFA3	1962	0.15	0.19	YES
21	ATP5A1	ATP5A1	ATP5A1	2016	0.14	0.2	YES
22	NDUFB2	NDUFB2	NDUFB2	2115	0.14	0.21	YES
23	LDHB	LDHB	LDHB	2157	0.14	0.22	YES
24	COX6A1	COX6A1	COX6A1	2186	0.13	0.23	YES
25	PDHX	PDHX	PDHX	2188	0.13	0.24	YES
26	COX6C	COX6C	COX6C	2197	0.13	0.25	YES
27	NDUFB9	NDUFB9	NDUFB9	2235	0.13	0.26	YES
28	NDUFA9	NDUFA9	NDUFA9	2286	0.13	0.26	YES
29	NDUFB5	NDUFB5	NDUFB5	2295	0.13	0.27	YES
30	ATP5B	ATP5B	ATP5B	2317	0.13	0.28	YES
31	UQCRC2	UQCRC2	UQCRC2	2356	0.12	0.29	YES
32	DLD	DLD	DLD	2373	0.12	0.3	YES
33	SUCLG2	SUCLG2	SUCLG2	2374	0.12	0.31	YES
34	COX8A	COX8A	COX8A	2436	0.12	0.32	YES
35	NDUFA8	NDUFA8	NDUFA8	2454	0.12	0.33	YES
36	ATP5L	ATP5L	ATP5L	2481	0.12	0.33	YES
37	UQCR11	UQCR11	UQCR11	2565	0.12	0.34	YES
38	FH	FH	FH	2567	0.12	0.35	YES
39	NDUFC2	NDUFC2	NDUFC2	2586	0.11	0.36	YES
40	L2HGDH	L2HGDH	L2HGDH	2611	0.11	0.36	YES
41	ATP5J2	ATP5J2	ATP5J2	2633	0.11	0.37	YES
42	COX4I1	COX4I1	COX4I1	2694	0.11	0.38	YES
43	NDUFS1	NDUFS1	NDUFS1	2702	0.11	0.39	YES
44	COX5B	COX5B	COX5B	2761	0.11	0.39	YES
45	DLAT	DLAT	DLAT	2807	0.1	0.4	YES
46	NDUFS3	NDUFS3	NDUFS3	2821	0.1	0.41	YES
47	COX6B1	COX6B1	COX6B1	2847	0.1	0.41	YES
48	NDUFA13	NDUFA13	NDUFA13	2863	0.1	0.42	YES
49	ADHFE1	ADHFE1	ADHFE1	2878	0.1	0.43	YES
50	NDUFV1	NDUFV1	NDUFV1	2900	0.1	0.44	YES
51	SDHD	SDHD	SDHD	2914	0.099	0.44	YES
52	ATP5E	ATP5E	ATP5E	2950	0.098	0.45	YES
53	NDUFB7	NDUFB7	NDUFB7	2955	0.098	0.46	YES
54	DLST	DLST	DLST	2961	0.098	0.46	YES
55	SUCLA2	SUCLA2	SUCLA2	2973	0.097	0.47	YES
56	ATP5I	ATP5I	ATP5I	3056	0.094	0.47	YES
57	NDUFS6	NDUFS6	NDUFS6	3059	0.094	0.48	YES
58	NDUFS7	NDUFS7	NDUFS7	3077	0.094	0.49	YES
59	ATP5D	ATP5D	ATP5D	3144	0.091	0.49	YES
60	COX7C	COX7C	COX7C	3165	0.09	0.5	YES
61	NDUFAB1	NDUFAB1	NDUFAB1	3187	0.09	0.5	YES
62	NDUFA5	NDUFA5	NDUFA5	3201	0.089	0.51	YES
63	CS	CS	CS	3266	0.087	0.52	YES
64	IDH2	IDH2	IDH2	3284	0.086	0.52	YES
65	NDUFA12	NDUFA12	NDUFA12	3294	0.086	0.53	YES
66	OGDH	OGDH	OGDH	3365	0.084	0.53	YES
67	NDUFA1	NDUFA1	NDUFA1	3385	0.083	0.54	YES
68	BSG	BSG	BSG	3471	0.081	0.54	YES
69	MDH2	MDH2	MDH2	3490	0.08	0.54	YES
70	NDUFB6	NDUFB6	NDUFB6	3542	0.079	0.55	YES
71	ATP5H	ATP5H	ATP5H	3546	0.079	0.55	YES
72	ATP5J	ATP5J	ATP5J	3553	0.079	0.56	YES
73	NDUFA7	NDUFA7	NDUFA7	3613	0.077	0.56	YES
74	NDUFB8	NDUFB8	NDUFB8	3616	0.077	0.57	YES
75	UQCRQ	UQCRQ	UQCRQ	3657	0.076	0.57	YES
76	CYC1	CYC1	CYC1	3699	0.074	0.58	YES
77	NDUFB3	NDUFB3	NDUFB3	3729	0.074	0.58	YES
78	NDUFA11	NDUFA11	NDUFA11	3769	0.073	0.58	YES
79	UQCRB	UQCRB	UQCRB	3791	0.072	0.59	YES
80	NDUFS2	NDUFS2	NDUFS2	3820	0.071	0.59	YES
81	NDUFB10	NDUFB10	NDUFB10	3921	0.069	0.59	YES
82	NDUFA10	NDUFA10	NDUFA10	4059	0.065	0.59	YES
83	ATP5O	ATP5O	ATP5O	4080	0.064	0.6	YES
84	SDHA	SDHA	SDHA	4100	0.064	0.6	YES
85	COX7A2L	COX7A2L	COX7A2L	4134	0.063	0.6	YES
86	ATP5F1	ATP5F1	ATP5F1	4149	0.062	0.61	YES
87	ATP5C1	ATP5C1	ATP5C1	4248	0.06	0.61	NO
88	IDH3G	IDH3G	IDH3G	4348	0.057	0.61	NO
89	SDHC	SDHC	SDHC	4442	0.055	0.6	NO
90	NDUFB4	NDUFB4	NDUFB4	4720	0.05	0.59	NO
91	NDUFS4	NDUFS4	NDUFS4	4835	0.048	0.59	NO
92	ACO2	ACO2	ACO2	4885	0.047	0.59	NO
93	NDUFV2	NDUFV2	NDUFV2	5035	0.044	0.59	NO
94	ETFA	ETFA	ETFA	5078	0.043	0.59	NO
95	IDH3B	IDH3B	IDH3B	5115	0.043	0.59	NO
96	NDUFS5	NDUFS5	NDUFS5	5188	0.041	0.59	NO
97	NDUFA2	NDUFA2	NDUFA2	5369	0.038	0.58	NO
98	ETFDH	ETFDH	ETFDH	5883	0.031	0.56	NO
99	SDHB	SDHB	SDHB	6002	0.028	0.55	NO
100	SLC16A8	SLC16A8	SLC16A8	7086	0.012	0.5	NO
101	ETFB	ETFB	ETFB	7194	0.011	0.49	NO
102	NDUFV3	NDUFV3	NDUFV3	8072	-0.00086	0.44	NO
103	PDPR	PDPR	PDPR	9390	-0.018	0.37	NO
104	NDUFC1	NDUFC1	NDUFC1	9449	-0.018	0.37	NO
105	IDH1	IDH1	IDH1	10102	-0.028	0.34	NO
106	UCP2	UCP2	UCP2	10258	-0.03	0.33	NO
107	PDK2	PDK2	PDK2	10654	-0.037	0.31	NO
108	PDK3	PDK3	PDK3	11780	-0.057	0.25	NO
109	D2HGDH	D2HGDH	D2HGDH	13066	-0.088	0.19	NO
110	SLC16A1	SLC16A1	SLC16A1	14597	-0.14	0.12	NO
111	LDHA	LDHA	LDHA	14783	-0.15	0.12	NO
112	UCP3	UCP3	UCP3	15739	-0.19	0.081	NO
113	PDK1	PDK1	PDK1	16088	-0.21	0.078	NO
114	PDK4	PDK4	PDK4	16462	-0.23	0.077	NO
115	SLC16A3	SLC16A3	SLC16A3	16990	-0.27	0.07	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: KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: SIG PIP3 SIGNALING IN CARDIAC MYOCTES

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	LDHD	LDHD	LDHD	416	0.41	0.087	YES
2	COQ2	COQ2	COQ2	1095	0.24	0.12	YES
3	SLC25A4	SLC25A4	SLC25A4	1660	0.17	0.13	YES
4	FXC1	FXC1	FXC1	1748	0.17	0.17	YES
5	TIMM8A	TIMM8A	TIMM8A	1880	0.16	0.2	YES
6	ATP5G1	ATP5G1	ATP5G1	1896	0.15	0.25	YES
7	FXN	FXN	FXN	2008	0.14	0.28	YES
8	ATP5A1	ATP5A1	ATP5A1	2016	0.14	0.32	YES
9	CHCHD4	CHCHD4	CHCHD4	2249	0.13	0.34	YES
10	ATP5B	ATP5B	ATP5B	2317	0.13	0.37	YES
11	SLC25A12	SLC25A12	SLC25A12	2339	0.12	0.4	YES
12	COX17	COX17	COX17	2833	0.1	0.4	YES
13	CS	CS	CS	3266	0.087	0.4	YES
14	TIMM17B	TIMM17B	TIMM17B	3428	0.082	0.42	YES
15	PMPCB	PMPCB	PMPCB	3448	0.082	0.44	YES
16	TIMM50	TIMM50	TIMM50	3503	0.08	0.46	YES
17	PMPCA	PMPCA	PMPCA	3559	0.078	0.48	YES
18	CYC1	CYC1	CYC1	3699	0.074	0.49	YES
19	GFER	GFER	GFER	3991	0.067	0.49	YES
20	TIMM10	TIMM10	TIMM10	4152	0.062	0.5	YES
21	TIMM13	TIMM13	TIMM13	4192	0.061	0.51	YES
22	IDH3G	IDH3G	IDH3G	4348	0.057	0.52	YES
23	TIMM17A	TIMM17A	TIMM17A	4370	0.057	0.53	YES
24	DNAJC19	DNAJC19	DNAJC19	4472	0.055	0.54	YES
25	TOMM40	TOMM40	TOMM40	4688	0.05	0.54	YES
26	MTX2	MTX2	MTX2	4713	0.05	0.56	YES
27	C18orf55	C18orf55	C18orf55	4737	0.049	0.57	YES
28	TIMM22	TIMM22	TIMM22	4853	0.047	0.57	YES
29	ACO2	ACO2	ACO2	4885	0.047	0.59	YES
30	TOMM22	TOMM22	TOMM22	5021	0.044	0.59	YES
31	TIMM8B	TIMM8B	TIMM8B	5045	0.044	0.6	YES
32	TIMM9	TIMM9	TIMM9	5094	0.043	0.61	YES
33	SLC25A6	SLC25A6	SLC25A6	5381	0.038	0.6	YES
34	TOMM5	TOMM5	TOMM5	5428	0.037	0.61	YES
35	TIMM44	TIMM44	TIMM44	5463	0.037	0.62	YES
36	SAMM50	SAMM50	SAMM50	5702	0.033	0.62	NO
37	HSPA9	HSPA9	HSPA9	5886	0.03	0.61	NO
38	GRPEL1	GRPEL1	GRPEL1	7406	0.0079	0.53	NO
39	HSPD1	HSPD1	HSPD1	7727	0.0038	0.52	NO
40	SLC25A13	SLC25A13	SLC25A13	7766	0.0033	0.52	NO
41	GRPEL2	GRPEL2	GRPEL2	8282	-0.0034	0.49	NO
42	VDAC1	VDAC1	VDAC1	8313	-0.0038	0.49	NO
43	MTX1	MTX1	MTX1	8493	-0.0062	0.48	NO
44	TOMM70A	TOMM70A	TOMM70A	8758	-0.0095	0.47	NO
45	TOMM7	TOMM7	TOMM7	9482	-0.019	0.43	NO
46	TOMM20	TOMM20	TOMM20	9562	-0.02	0.43	NO
47	BCS1L	BCS1L	BCS1L	11014	-0.042	0.36	NO
48	HSCB	HSCB	HSCB	11692	-0.055	0.34	NO
49	TAZ	TAZ	TAZ	12204	-0.066	0.33	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: SIG PIP3 SIGNALING IN CARDIAC MYOCTES.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: SIG PIP3 SIGNALING IN CARDIAC MYOCTES, 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 PI3KCIAKTPATHWAY

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	SH3GL2	SH3GL2	SH3GL2	65	0.72	0.21	YES
2	L1CAM	L1CAM	L1CAM	148	0.59	0.37	YES
3	RPS6KA6	RPS6KA6	RPS6KA6	203	0.54	0.53	YES
4	AP2B1	AP2B1	AP2B1	4200	0.061	0.33	NO
5	CLTA	CLTA	CLTA	4487	0.054	0.33	NO
6	FGFR1	FGFR1	FGFR1	4790	0.049	0.32	NO
7	CSNK2A1	CSNK2A1	CSNK2A1	5217	0.041	0.31	NO
8	CLTC	CLTC	CLTC	5593	0.035	0.3	NO
9	CSNK2A2	CSNK2A2	CSNK2A2	5801	0.032	0.3	NO
10	ITGB3	ITGB3	ITGB3	6339	0.023	0.28	NO
11	RPS6KA1	RPS6KA1	RPS6KA1	6556	0.02	0.27	NO
12	AP2S1	AP2S1	AP2S1	6951	0.014	0.25	NO
13	MAP2K2	MAP2K2	MAP2K2	7025	0.013	0.25	NO
14	MAP2K1	MAP2K1	MAP2K1	7598	0.0054	0.22	NO
15	AP2A2	AP2A2	AP2A2	7618	0.0052	0.22	NO
16	RAC1	RAC1	RAC1	7792	0.0029	0.22	NO
17	AP2M1	AP2M1	AP2M1	8099	-0.0012	0.2	NO
18	RPS6KA4	RPS6KA4	RPS6KA4	8648	-0.0081	0.17	NO
19	ITGAV	ITGAV	ITGAV	9431	-0.018	0.13	NO
20	CSNK2B	CSNK2B	CSNK2B	9626	-0.02	0.13	NO
21	RPS6KA3	RPS6KA3	RPS6KA3	9929	-0.025	0.12	NO
22	NCAM1	NCAM1	NCAM1	9938	-0.025	0.13	NO
23	PAK1	PAK1	PAK1	10181	-0.029	0.12	NO
24	MAPK3	MAPK3	MAPK3	10607	-0.036	0.11	NO
25	ITGA2B	ITGA2B	ITGA2B	11501	-0.051	0.075	NO
26	ITGB1	ITGB1	ITGB1	11533	-0.052	0.089	NO
27	RPS6KA2	RPS6KA2	RPS6KA2	11551	-0.052	0.1	NO
28	AP2A1	AP2A1	AP2A1	12148	-0.065	0.089	NO
29	MAPK1	MAPK1	MAPK1	12274	-0.068	0.1	NO
30	ITGA9	ITGA9	ITGA9	12872	-0.082	0.094	NO
31	RPS6KA5	RPS6KA5	RPS6KA5	15137	-0.16	0.016	NO
32	EGFR	EGFR	EGFR	15370	-0.17	0.053	NO
33	NRP1	NRP1	NRP1	15450	-0.18	0.1	NO
34	ITGA5	ITGA5	ITGA5	15680	-0.19	0.14	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 PI3KCIAKTPATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: PID PI3KCIAKTPATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT

Table 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	SH3GL2	SH3GL2	SH3GL2	65	0.72	0.21	YES
2	TPD52L1	TPD52L1	TPD52L1	326	0.46	0.32	YES
3	AP1M2	AP1M2	AP1M2	743	0.31	0.39	YES
4	SORT1	SORT1	SORT1	2764	0.11	0.31	YES
5	CPD	CPD	CPD	3342	0.085	0.31	YES
6	NAPA	NAPA	NAPA	3998	0.067	0.29	YES
7	GAK	GAK	GAK	4023	0.066	0.31	YES
8	HSPA8	HSPA8	HSPA8	4107	0.063	0.32	YES
9	OCRL	OCRL	OCRL	4275	0.059	0.33	YES
10	DNAJC6	DNAJC6	DNAJC6	4394	0.056	0.34	YES
11	YIPF6	YIPF6	YIPF6	4398	0.056	0.36	YES
12	CLTA	CLTA	CLTA	4487	0.054	0.37	YES
13	RAB5C	RAB5C	RAB5C	4603	0.052	0.38	YES
14	VAMP7	VAMP7	VAMP7	4616	0.052	0.39	YES
15	VAMP2	VAMP2	VAMP2	5005	0.044	0.38	YES
16	BLOC1S1	BLOC1S1	BLOC1S1	5022	0.044	0.39	YES
17	CLTC	CLTC	CLTC	5593	0.035	0.37	NO
18	HIP1R	HIP1R	HIP1R	5848	0.031	0.37	NO
19	PICALM	PICALM	PICALM	6003	0.028	0.37	NO
20	AP1B1	AP1B1	AP1B1	6354	0.023	0.35	NO
21	AP1G1	AP1G1	AP1G1	6399	0.022	0.36	NO
22	PIK3C2A	PIK3C2A	PIK3C2A	6657	0.018	0.35	NO
23	TFRC	TFRC	TFRC	6708	0.018	0.35	NO
24	AP3B1	AP3B1	AP3B1	6730	0.017	0.36	NO
25	TPD52	TPD52	TPD52	7300	0.0093	0.33	NO
26	IGF2R	IGF2R	IGF2R	7325	0.009	0.33	NO
27	AP1S1	AP1S1	AP1S1	7465	0.007	0.32	NO
28	VAMP8	VAMP8	VAMP8	7566	0.0058	0.32	NO
29	SNX2	SNX2	SNX2	7657	0.0047	0.32	NO
30	SH3D19	SH3D19	SH3D19	7708	0.0041	0.31	NO
31	AP4E1	AP4E1	AP4E1	7838	0.0023	0.31	NO
32	BLOC1S3	BLOC1S3	BLOC1S3	7891	0.0017	0.3	NO
33	SNAPIN	SNAPIN	SNAPIN	8151	-0.0019	0.29	NO
34	SNX5	SNX5	SNX5	8183	-0.0023	0.29	NO
35	SNX9	SNX9	SNX9	8184	-0.0023	0.29	NO
36	PUM1	PUM1	PUM1	8223	-0.0028	0.29	NO
37	ARF1	ARF1	ARF1	8367	-0.0044	0.28	NO
38	FTL	FTL	FTL	8852	-0.011	0.26	NO
39	TGOLN2	TGOLN2	TGOLN2	9076	-0.013	0.25	NO
40	CNO	CNO	CNO	9079	-0.014	0.26	NO
41	NECAP1	NECAP1	NECAP1	9377	-0.017	0.24	NO
42	PLDN	PLDN	PLDN	9521	-0.019	0.24	NO
43	FTH1	FTH1	FTH1	10434	-0.033	0.2	NO
44	AP1S2	AP1S2	AP1S2	11146	-0.045	0.18	NO
45	AP1M1	AP1M1	AP1M1	11570	-0.052	0.17	NO
46	DNM2	DNM2	DNM2	11632	-0.054	0.18	NO
47	ARRB1	ARRB1	ARRB1	12015	-0.062	0.18	NO
48	TXNDC5	TXNDC5	TXNDC5	12424	-0.072	0.18	NO
49	AP4B1	AP4B1	AP4B1	12478	-0.073	0.19	NO
50	DTNBP1	DTNBP1	DTNBP1	12685	-0.078	0.2	NO
51	AP3S1	AP3S1	AP3S1	14687	-0.14	0.14	NO
52	TBC1D8B	TBC1D8B	TBC1D8B	16033	-0.2	0.12	NO

Figure S15. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT.

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

genes ES table in pathway: REACTOME TRANS GOLGI NETWORK VESICLE BUDDING

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	SH3GL2	SH3GL2	SH3GL2	65	0.72	0.2	YES
2	L1CAM	L1CAM	L1CAM	148	0.59	0.37	YES
3	RPS6KA6	RPS6KA6	RPS6KA6	203	0.54	0.52	YES
4	AP2B1	AP2B1	AP2B1	4200	0.061	0.32	NO
5	CLTA	CLTA	CLTA	4487	0.054	0.32	NO
6	KIAA1598	KIAA1598	KIAA1598	5270	0.04	0.29	NO
7	CLTC	CLTC	CLTC	5593	0.035	0.28	NO
8	RPS6KA1	RPS6KA1	RPS6KA1	6556	0.02	0.24	NO
9	AP2S1	AP2S1	AP2S1	6951	0.014	0.22	NO
10	EZR	EZR	EZR	7433	0.0075	0.2	NO
11	AP2A2	AP2A2	AP2A2	7618	0.0052	0.19	NO
12	SRC	SRC	SRC	7993	0.0002	0.17	NO
13	AP2M1	AP2M1	AP2M1	8099	-0.0012	0.16	NO
14	RPS6KA4	RPS6KA4	RPS6KA4	8648	-0.0081	0.13	NO
15	RPS6KA3	RPS6KA3	RPS6KA3	9929	-0.025	0.071	NO
16	NUMB	NUMB	NUMB	10032	-0.026	0.073	NO
17	RDX	RDX	RDX	10379	-0.032	0.063	NO
18	RPS6KA2	RPS6KA2	RPS6KA2	11551	-0.052	0.014	NO
19	DNM2	DNM2	DNM2	11632	-0.054	0.025	NO
20	AP2A1	AP2A1	AP2A1	12148	-0.065	0.016	NO
21	MAPK1	MAPK1	MAPK1	12274	-0.068	0.029	NO
22	MSN	MSN	MSN	12348	-0.07	0.045	NO
23	DNM1	DNM1	DNM1	13501	-0.099	0.011	NO
24	RPS6KA5	RPS6KA5	RPS6KA5	15137	-0.16	-0.032	NO
25	DPYSL2	DPYSL2	DPYSL2	15186	-0.16	0.012	NO
26	KIF4A	KIF4A	KIF4A	15940	-0.2	0.028	NO
27	KIF4B	KIF4B	KIF4B	17575	-0.34	0.038	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 TRANS GOLGI NETWORK VESICLE BUDDING.

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

genes ES table in pathway: REACTOME MITOCHONDRIAL PROTEIN IMPORT

Table 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	PAK6	PAK6	PAK6	31	0.83	0.12	YES
2	ERBB4	ERBB4	ERBB4	49	0.77	0.23	YES
3	PAK7	PAK7	PAK7	243	0.5	0.3	YES
4	SLC2A4	SLC2A4	SLC2A4	500	0.37	0.34	YES
5	PARD6A	PARD6A	PARD6A	1066	0.25	0.34	YES
6	IRS1	IRS1	IRS1	1203	0.22	0.37	YES
7	IGF1	IGF1	IGF1	1721	0.17	0.36	YES
8	IRS2	IRS2	IRS2	1820	0.16	0.38	YES
9	SFN	SFN	SFN	1823	0.16	0.4	YES
10	SOS2	SOS2	SOS2	3158	0.09	0.34	NO
11	GSK3B	GSK3B	GSK3B	3344	0.085	0.35	NO
12	EBP	EBP	EBP	3509	0.08	0.35	NO
13	PAK4	PAK4	PAK4	3898	0.069	0.34	NO
14	PPP1R13B	PPP1R13B	PPP1R13B	4123	0.063	0.33	NO
15	CYTH3	CYTH3	CYTH3	4446	0.055	0.32	NO
16	AKT2	AKT2	AKT2	4662	0.051	0.32	NO
17	YWHAB	YWHAB	YWHAB	4825	0.048	0.32	NO
18	BCL2L1	BCL2L1	BCL2L1	4891	0.047	0.32	NO
19	MTOR	MTOR	MTOR	4903	0.046	0.33	NO
20	AKT1	AKT1	AKT1	5567	0.035	0.3	NO
21	GADD45A	GADD45A	GADD45A	5724	0.033	0.29	NO
22	PIK3CA	PIK3CA	PIK3CA	6546	0.02	0.25	NO
23	RPS6KA1	RPS6KA1	RPS6KA1	6556	0.02	0.25	NO
24	YWHAE	YWHAE	YWHAE	6617	0.019	0.25	NO
25	GSK3A	GSK3A	GSK3A	6934	0.014	0.24	NO
26	TSC1	TSC1	TSC1	7550	0.0061	0.2	NO
27	TSC2	TSC2	TSC2	7595	0.0054	0.2	NO
28	INPPL1	INPPL1	INPPL1	7621	0.0052	0.2	NO
29	BAD	BAD	BAD	7761	0.0033	0.2	NO
30	CREB3	CREB3	CREB3	7854	0.0022	0.19	NO
31	CDC42	CDC42	CDC42	7983	0.00039	0.18	NO
32	YWHAQ	YWHAQ	YWHAQ	8143	-0.0018	0.17	NO
33	PTPN1	PTPN1	PTPN1	8383	-0.0048	0.16	NO
34	MET	MET	MET	8516	-0.0065	0.16	NO
35	PTEN	PTEN	PTEN	8564	-0.007	0.15	NO
36	PTK2	PTK2	PTK2	8569	-0.0071	0.16	NO
37	PAK2	PAK2	PAK2	8814	-0.01	0.14	NO
38	YWHAZ	YWHAZ	YWHAZ	8882	-0.011	0.14	NO
39	NOLC1	NOLC1	NOLC1	9077	-0.013	0.13	NO
40	YWHAG	YWHAG	YWHAG	9234	-0.016	0.13	NO
41	GRB2	GRB2	GRB2	9568	-0.02	0.11	NO
42	PARD3	PARD3	PARD3	9843	-0.024	0.099	NO
43	CDK2	CDK2	CDK2	9880	-0.024	0.1	NO
44	YWHAH	YWHAH	YWHAH	9910	-0.025	0.1	NO
45	RPS6KA3	RPS6KA3	RPS6KA3	9929	-0.025	0.1	NO
46	PAK1	PAK1	PAK1	10181	-0.029	0.096	NO
47	AKT3	AKT3	AKT3	10601	-0.036	0.078	NO
48	RPS6KB1	RPS6KB1	RPS6KB1	10624	-0.036	0.082	NO
49	CREB1	CREB1	CREB1	11007	-0.042	0.067	NO
50	GAB1	GAB1	GAB1	11253	-0.046	0.061	NO
51	FOXO3	FOXO3	FOXO3	11288	-0.047	0.066	NO
52	RPS6KA2	RPS6KA2	RPS6KA2	11551	-0.052	0.059	NO
53	F2RL2	F2RL2	F2RL2	11598	-0.053	0.064	NO
54	SOS1	SOS1	SOS1	11807	-0.058	0.061	NO
55	IFI27	IFI27	IFI27	11919	-0.06	0.064	NO
56	IGFBP1	IGFBP1	IGFBP1	12926	-0.084	0.021	NO
57	PAK3	PAK3	PAK3	13613	-0.1	-0.0018	NO
58	CDKN1B	CDKN1B	CDKN1B	13638	-0.1	0.012	NO
59	SHC1	SHC1	SHC1	14166	-0.12	0.00094	NO
60	PIK3CD	PIK3CD	PIK3CD	14632	-0.14	-0.0042	NO
61	PREX1	PREX1	PREX1	15073	-0.16	-0.0053	NO
62	PDK1	PDK1	PDK1	16088	-0.21	-0.031	NO
63	MYC	MYC	MYC	16451	-0.23	-0.017	NO
64	CDKN2A	CDKN2A	CDKN2A	16617	-0.24	0.0092	NO
65	CREB5	CREB5	CREB5	16831	-0.26	0.036	NO
66	PIK3R5	PIK3R5	PIK3R5	17195	-0.29	0.058	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 MITOCHONDRIAL PROTEIN IMPORT.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG FATTY ACID METABOLISM	39	genes.ES.table	0.55	1.5	0.071	1	0.97	0.44	0.16	0.37	1	0.55
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	44	genes.ES.table	0.59	1.6	0.061	1	0.89	0.73	0.24	0.56	0.76	0.43
KEGG LYSINE DEGRADATION	44	genes.ES.table	0.42	1.6	0.049	1	0.88	0.34	0.2	0.27	0.91	0.48
KEGG HISTIDINE METABOLISM	29	genes.ES.table	0.62	1.5	0.049	1	0.97	0.48	0.14	0.42	1	0.56
KEGG TRYPTOPHAN METABOLISM	39	genes.ES.table	0.49	1.3	0.1	1	1	0.56	0.2	0.45	1	0.6
KEGG PROPANOATE METABOLISM	32	genes.ES.table	0.61	1.7	0.045	1	0.8	0.62	0.21	0.49	0.71	0.4
KEGG PPAR SIGNALING PATHWAY	65	genes.ES.table	0.58	1.6	0.023	1	0.95	0.34	0.099	0.31	0.96	0.49
KEGG PEROXISOME	76	genes.ES.table	0.54	1.7	0.033	1	0.77	0.41	0.16	0.35	0.97	0.49
KEGG ADIPOCYTOKINE SIGNALING PATHWAY	64	genes.ES.table	0.38	1.4	0.079	1	0.99	0.25	0.15	0.21	1	0.6
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.38	1.5	0.079	1	0.98	0.22	0.18	0.18	1	0.52

genes ES table in pathway: KEGG FATTY ACID METABOLISM

Table S11. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	RXRG	RXRG	RXRG	663	0.24	0.1	YES
2	NR4A1	NR4A1	NR4A1	840	0.2	0.21	YES
3	BCL2	BCL2	BCL2	1148	0.16	0.29	YES
4	NR1H4	NR1H4	NR1H4	1505	0.13	0.35	YES
5	THRA	THRA	THRA	1560	0.13	0.42	YES
6	RARB	RARB	RARB	1773	0.12	0.48	YES
7	THRB	THRB	THRB	1982	0.11	0.53	YES
8	PPARG	PPARG	PPARG	2253	0.096	0.57	YES
9	PPARA	PPARA	PPARA	2346	0.093	0.62	YES
10	RARA	RARA	RARA	3914	0.052	0.56	NO
11	FAM120B	FAM120B	FAM120B	4363	0.043	0.56	NO
12	NCOA1	NCOA1	NCOA1	4372	0.043	0.59	NO
13	MED1	MED1	MED1	6161	0.018	0.5	NO
14	ABCA1	ABCA1	ABCA1	6296	0.017	0.5	NO
15	SREBF1	SREBF1	SREBF1	6632	0.012	0.49	NO
16	RXRB	RXRB	RXRB	6927	0.0089	0.48	NO
17	VDR	VDR	VDR	7034	0.0077	0.48	NO
18	RARG	RARG	RARG	7198	0.006	0.48	NO
19	RXRA	RXRA	RXRA	7546	0.0022	0.46	NO
20	NR1H3	NR1H3	NR1H3	8662	-0.012	0.4	NO
21	RPS6KB1	RPS6KB1	RPS6KB1	8880	-0.014	0.4	NO
22	NCOR2	NCOR2	NCOR2	9377	-0.02	0.38	NO
23	PPARD	PPARD	PPARD	9476	-0.022	0.39	NO
24	NR1H2	NR1H2	NR1H2	10752	-0.038	0.34	NO
25	TNF	TNF	TNF	11542	-0.049	0.33	NO
26	TGFB1	TGFB1	TGFB1	12447	-0.065	0.32	NO

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

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

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HAO2	HAO2	HAO2	14	0.7	0.089	YES
2	SLC27A2	SLC27A2	SLC27A2	43	0.55	0.16	YES
3	DAO	DAO	DAO	163	0.41	0.2	YES
4	EHHADH	EHHADH	EHHADH	466	0.28	0.22	YES
5	AGXT	AGXT	AGXT	571	0.26	0.25	YES
6	PXMP2	PXMP2	PXMP2	620	0.24	0.28	YES
7	EPHX2	EPHX2	EPHX2	757	0.22	0.3	YES
8	DDO	DDO	DDO	846	0.2	0.32	YES
9	FAR2	FAR2	FAR2	855	0.2	0.34	YES
10	PEX11A	PEX11A	PEX11A	1061	0.18	0.36	YES
11	PECR	PECR	PECR	1107	0.17	0.37	YES
12	NOS2	NOS2	NOS2	1223	0.16	0.39	YES
13	ACOX2	ACOX2	ACOX2	1262	0.15	0.4	YES
14	NUDT12	NUDT12	NUDT12	1442	0.14	0.41	YES
15	ACSL1	ACSL1	ACSL1	1484	0.14	0.43	YES
16	MLYCD	MLYCD	MLYCD	1811	0.12	0.42	YES
17	CAT	CAT	CAT	1955	0.11	0.43	YES
18	PHYH	PHYH	PHYH	2021	0.11	0.44	YES
19	AGPS	AGPS	AGPS	2092	0.1	0.45	YES
20	ABCD3	ABCD3	ABCD3	2097	0.1	0.46	YES
21	CRAT	CRAT	CRAT	2136	0.1	0.47	YES
22	PEX11G	PEX11G	PEX11G	2364	0.092	0.47	YES
23	MPV17L	MPV17L	MPV17L	2392	0.092	0.48	YES
24	PAOX	PAOX	PAOX	2470	0.089	0.49	YES
25	PEX1	PEX1	PEX1	2472	0.089	0.5	YES
26	DHRS4	DHRS4	DHRS4	2506	0.088	0.51	YES
27	PEX3	PEX3	PEX3	2756	0.08	0.51	YES
28	AMACR	AMACR	AMACR	2769	0.079	0.52	YES
29	ABCD2	ABCD2	ABCD2	2815	0.078	0.52	YES
30	ECH1	ECH1	ECH1	2825	0.078	0.53	YES
31	DECR2	DECR2	DECR2	2829	0.078	0.54	YES
32	ACOX1	ACOX1	ACOX1	3359	0.063	0.52	NO
33	PEX7	PEX7	PEX7	3361	0.063	0.53	NO
34	PIPOX	PIPOX	PIPOX	3551	0.059	0.53	NO
35	ACSL6	ACSL6	ACSL6	3953	0.051	0.51	NO
36	HMGCL	HMGCL	HMGCL	4061	0.049	0.51	NO
37	ABCD4	ABCD4	ABCD4	4153	0.048	0.51	NO
38	SCP2	SCP2	SCP2	4159	0.047	0.52	NO
39	PEX11B	PEX11B	PEX11B	4268	0.045	0.52	NO
40	PEX26	PEX26	PEX26	4332	0.044	0.52	NO
41	PEX10	PEX10	PEX10	4495	0.041	0.52	NO
42	PMVK	PMVK	PMVK	4527	0.041	0.52	NO
43	PEX19	PEX19	PEX19	4641	0.039	0.52	NO
44	PEX5	PEX5	PEX5	4676	0.038	0.52	NO
45	PEX12	PEX12	PEX12	4764	0.037	0.52	NO
46	PEX13	PEX13	PEX13	5800	0.023	0.47	NO
47	SLC25A17	SLC25A17	SLC25A17	6386	0.016	0.44	NO
48	HSD17B4	HSD17B4	HSD17B4	6623	0.013	0.43	NO
49	ACAA1	ACAA1	ACAA1	6706	0.012	0.42	NO
50	CROT	CROT	CROT	7270	0.0051	0.39	NO
51	GNPAT	GNPAT	GNPAT	7719	0.00032	0.37	NO
52	ACSL3	ACSL3	ACSL3	7836	-0.0012	0.36	NO
53	SOD1	SOD1	SOD1	7880	-0.0018	0.36	NO
54	IDH2	IDH2	IDH2	8840	-0.014	0.31	NO
55	PEX2	PEX2	PEX2	9335	-0.02	0.28	NO
56	GSTK1	GSTK1	GSTK1	9833	-0.026	0.26	NO
57	PEX14	PEX14	PEX14	10177	-0.03	0.24	NO
58	HACL1	HACL1	HACL1	10368	-0.033	0.24	NO
59	ABCD1	ABCD1	ABCD1	10547	-0.035	0.23	NO
60	PEX6	PEX6	PEX6	10664	-0.037	0.23	NO
61	FAR1	FAR1	FAR1	11214	-0.044	0.21	NO
62	MPV17	MPV17	MPV17	11428	-0.047	0.2	NO
63	PRDX1	PRDX1	PRDX1	11661	-0.051	0.2	NO
64	PRDX5	PRDX5	PRDX5	11821	-0.054	0.19	NO
65	ACSL5	ACSL5	ACSL5	11838	-0.054	0.2	NO
66	PXMP4	PXMP4	PXMP4	12118	-0.059	0.19	NO
67	MVK	MVK	MVK	12483	-0.066	0.18	NO
68	PEX16	PEX16	PEX16	12544	-0.067	0.18	NO
69	NUDT19	NUDT19	NUDT19	12565	-0.068	0.19	NO
70	ACSL4	ACSL4	ACSL4	12951	-0.076	0.18	NO
71	SOD2	SOD2	SOD2	13040	-0.078	0.19	NO
72	IDH1	IDH1	IDH1	13743	-0.096	0.16	NO
73	ACOT8	ACOT8	ACOT8	13857	-0.1	0.17	NO
74	ACOX3	ACOX3	ACOX3	13946	-0.1	0.18	NO
75	BAAT	BAAT	BAAT	14741	-0.13	0.15	NO
76	XDH	XDH	XDH	17450	-0.35	0.044	NO

Figure S23. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

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

genes ES table in pathway: KEGG LYSINE DEGRADATION

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ALDH6A1	ALDH6A1	ALDH6A1	241	0.37	0.093	YES
2	EHHADH	EHHADH	EHHADH	466	0.28	0.16	YES
3	ABAT	ABAT	ABAT	730	0.22	0.21	YES
4	ALDH3A2	ALDH3A2	ALDH3A2	797	0.21	0.27	YES
5	HIBCH	HIBCH	HIBCH	803	0.21	0.33	YES
6	ACAT1	ACAT1	ACAT1	956	0.19	0.38	YES
7	ACADM	ACADM	ACADM	1125	0.17	0.42	YES
8	PCCA	PCCA	PCCA	1279	0.15	0.45	YES
9	MUT	MUT	MUT	1547	0.13	0.48	YES
10	ACSS3	ACSS3	ACSS3	1599	0.13	0.51	YES
11	MLYCD	MLYCD	MLYCD	1811	0.12	0.53	YES
12	ALDH9A1	ALDH9A1	ALDH9A1	2098	0.1	0.55	YES
13	LDHAL6A	LDHAL6A	LDHAL6A	2403	0.091	0.56	YES
14	ALDH7A1	ALDH7A1	ALDH7A1	2499	0.088	0.58	YES
15	SUCLA2	SUCLA2	SUCLA2	2617	0.084	0.6	YES
16	ALDH1B1	ALDH1B1	ALDH1B1	2837	0.078	0.61	YES
17	ALDH2	ALDH2	ALDH2	3504	0.06	0.59	YES
18	HADHA	HADHA	HADHA	3729	0.055	0.59	YES
19	ACSS1	ACSS1	ACSS1	3793	0.054	0.6	YES
20	MCEE	MCEE	MCEE	3894	0.052	0.61	YES
21	LDHA	LDHA	LDHA	4775	0.037	0.57	NO
22	ECHS1	ECHS1	ECHS1	5476	0.027	0.55	NO
23	SUCLG1	SUCLG1	SUCLG1	7405	0.0039	0.44	NO
24	ACACB	ACACB	ACACB	7417	0.0038	0.44	NO
25	SUCLG2	SUCLG2	SUCLG2	8207	-0.0059	0.4	NO
26	LDHC	LDHC	LDHC	8870	-0.014	0.37	NO
27	ACSS2	ACSS2	ACSS2	9556	-0.023	0.34	NO
28	LDHB	LDHB	LDHB	10552	-0.035	0.29	NO
29	PCCB	PCCB	PCCB	11847	-0.054	0.24	NO
30	ACAT2	ACAT2	ACAT2	12031	-0.057	0.24	NO
31	ACACA	ACACA	ACACA	13498	-0.09	0.19	NO
32	LDHAL6B	LDHAL6B	LDHAL6B	16530	-0.25	0.095	NO

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

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

genes ES table in pathway: KEGG HISTIDINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	BBOX1	BBOX1	BBOX1	164	0.41	0.12	YES
2	EHHADH	EHHADH	EHHADH	466	0.28	0.2	YES
3	ALDH3A2	ALDH3A2	ALDH3A2	797	0.21	0.24	YES
4	ACAT1	ACAT1	ACAT1	956	0.19	0.3	YES
5	OGDHL	OGDHL	OGDHL	1613	0.13	0.3	YES
6	ALDH9A1	ALDH9A1	ALDH9A1	2098	0.1	0.31	YES
7	AASS	AASS	AASS	2369	0.092	0.32	YES
8	ALDH7A1	ALDH7A1	ALDH7A1	2499	0.088	0.34	YES
9	ALDH1B1	ALDH1B1	ALDH1B1	2837	0.078	0.35	YES
10	TMLHE	TMLHE	TMLHE	2973	0.073	0.36	YES
11	ASH1L	ASH1L	ASH1L	3208	0.067	0.37	YES
12	ALDH2	ALDH2	ALDH2	3504	0.06	0.38	YES
13	PIPOX	PIPOX	PIPOX	3551	0.059	0.39	YES
14	HADHA	HADHA	HADHA	3729	0.055	0.4	YES
15	AASDH	AASDH	AASDH	3752	0.055	0.42	YES
16	SUV420H1	SUV420H1	SUV420H1	4113	0.048	0.41	NO
17	AASDHPPT	AASDHPPT	AASDHPPT	4403	0.043	0.41	NO
18	DLST	DLST	DLST	5109	0.032	0.38	NO
19	ECHS1	ECHS1	ECHS1	5476	0.027	0.37	NO
20	OGDH	OGDH	OGDH	5488	0.027	0.38	NO
21	SETD7	SETD7	SETD7	5703	0.024	0.38	NO
22	HADH	HADH	HADH	5781	0.023	0.38	NO
23	AADAT	AADAT	AADAT	7096	0.0069	0.31	NO
24	SETDB1	SETDB1	SETDB1	7301	0.0048	0.3	NO
25	NSD1	NSD1	NSD1	7335	0.0045	0.3	NO
26	DOT1L	DOT1L	DOT1L	7510	0.0026	0.29	NO
27	SUV39H2	SUV39H2	SUV39H2	7690	0.00068	0.28	NO
28	EHMT1	EHMT1	EHMT1	7884	-0.0018	0.27	NO
29	WHSC1L1	WHSC1L1	WHSC1L1	8059	-0.0042	0.26	NO
30	SETD1B	SETD1B	SETD1B	8560	-0.01	0.24	NO
31	SETDB2	SETDB2	SETDB2	8857	-0.014	0.23	NO
32	SETD2	SETD2	SETD2	8894	-0.015	0.23	NO
33	SETD1A	SETD1A	SETD1A	9062	-0.016	0.22	NO
34	EHMT2	EHMT2	EHMT2	9727	-0.025	0.2	NO
35	WHSC1	WHSC1	WHSC1	10382	-0.033	0.17	NO
36	PLOD3	PLOD3	PLOD3	10481	-0.034	0.18	NO
37	SUV39H1	SUV39H1	SUV39H1	10689	-0.037	0.18	NO
38	PLOD1	PLOD1	PLOD1	11247	-0.044	0.16	NO
39	GCDH	GCDH	GCDH	11299	-0.045	0.17	NO
40	ACAT2	ACAT2	ACAT2	12031	-0.057	0.15	NO
41	SETD8	SETD8	SETD8	13163	-0.081	0.11	NO
42	PLOD2	PLOD2	PLOD2	14019	-0.11	0.1	NO
43	SUV420H2	SUV420H2	SUV420H2	15766	-0.19	0.067	NO
44	SETMAR	SETMAR	SETMAR	16154	-0.22	0.12	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 HISTIDINE METABOLISM.

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

genes ES table in pathway: KEGG TRYPTOPHAN METABOLISM

Table 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	HMGCS2	HMGCS2	HMGCS2	107	0.46	0.082	YES
2	ALDH6A1	ALDH6A1	ALDH6A1	241	0.37	0.14	YES
3	AOX1	AOX1	AOX1	403	0.3	0.19	YES
4	EHHADH	EHHADH	EHHADH	466	0.28	0.24	YES
5	ABAT	ABAT	ABAT	730	0.22	0.27	YES
6	ACAA2	ACAA2	ACAA2	733	0.22	0.32	YES
7	ALDH3A2	ALDH3A2	ALDH3A2	797	0.21	0.35	YES
8	HIBCH	HIBCH	HIBCH	803	0.21	0.39	YES
9	ACAT1	ACAT1	ACAT1	956	0.19	0.42	YES
10	ACADM	ACADM	ACADM	1125	0.17	0.44	YES
11	PCCA	PCCA	PCCA	1279	0.15	0.46	YES
12	ACADSB	ACADSB	ACADSB	1405	0.14	0.48	YES
13	AUH	AUH	AUH	1409	0.14	0.51	YES
14	MUT	MUT	MUT	1547	0.13	0.53	YES
15	ALDH9A1	ALDH9A1	ALDH9A1	2098	0.1	0.52	YES
16	ALDH7A1	ALDH7A1	ALDH7A1	2499	0.088	0.51	YES
17	IVD	IVD	IVD	2709	0.081	0.52	YES
18	ALDH1B1	ALDH1B1	ALDH1B1	2837	0.078	0.52	YES
19	BCKDHB	BCKDHB	BCKDHB	3341	0.064	0.51	YES
20	DBT	DBT	DBT	3488	0.06	0.51	YES
21	ALDH2	ALDH2	ALDH2	3504	0.06	0.52	YES
22	HMGCS1	HMGCS1	HMGCS1	3521	0.06	0.53	YES
23	HIBADH	HIBADH	HIBADH	3619	0.057	0.54	YES
24	HADHB	HADHB	HADHB	3620	0.057	0.55	YES
25	MCCC1	MCCC1	MCCC1	3677	0.056	0.56	YES
26	HADHA	HADHA	HADHA	3729	0.055	0.57	YES
27	MCEE	MCEE	MCEE	3894	0.052	0.57	YES
28	ACADS	ACADS	ACADS	3959	0.05	0.57	YES
29	HMGCL	HMGCL	HMGCL	4061	0.049	0.58	YES
30	OXCT1	OXCT1	OXCT1	4216	0.046	0.58	YES
31	BCKDHA	BCKDHA	BCKDHA	4312	0.045	0.58	YES
32	ACAD8	ACAD8	ACAD8	4344	0.044	0.59	YES
33	MCCC2	MCCC2	MCCC2	4822	0.036	0.57	NO
34	ECHS1	ECHS1	ECHS1	5476	0.027	0.54	NO
35	HADH	HADH	HADH	5781	0.023	0.53	NO
36	DLD	DLD	DLD	5916	0.022	0.52	NO
37	ACAA1	ACAA1	ACAA1	6706	0.012	0.48	NO
38	IL4I1	IL4I1	IL4I1	8905	-0.015	0.36	NO
39	BCAT2	BCAT2	BCAT2	9890	-0.027	0.32	NO
40	HSD17B10	HSD17B10	HSD17B10	11503	-0.048	0.24	NO
41	PCCB	PCCB	PCCB	11847	-0.054	0.23	NO
42	ACAT2	ACAT2	ACAT2	12031	-0.057	0.23	NO
43	BCAT1	BCAT1	BCAT1	16293	-0.23	0.038	NO
44	OXCT2	OXCT2	OXCT2	17505	-0.36	0.041	NO

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

Figure S30. 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 PROPANOATE METABOLISM

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	RPS6KA5	RPS6KA5	RPS6KA5	997	0.18	0.072	YES
2	MAPK8	MAPK8	MAPK8	1271	0.15	0.16	YES
3	MAPK1	MAPK1	MAPK1	2487	0.088	0.16	YES
4	MAPK10	MAPK10	MAPK10	2507	0.088	0.22	YES
5	ATF2	ATF2	ATF2	2616	0.084	0.27	YES
6	DUSP6	DUSP6	DUSP6	2828	0.078	0.32	YES
7	RPS6KA2	RPS6KA2	RPS6KA2	2948	0.074	0.36	YES
8	MEF2C	MEF2C	MEF2C	3187	0.067	0.4	YES
9	PPP2R1B	PPP2R1B	PPP2R1B	3469	0.061	0.42	YES
10	MEF2A	MEF2A	MEF2A	4154	0.048	0.42	YES
11	DUSP3	DUSP3	DUSP3	4630	0.039	0.42	YES
12	DUSP7	DUSP7	DUSP7	4666	0.038	0.44	YES
13	FOS	FOS	FOS	4765	0.037	0.46	YES
14	PPP2CB	PPP2CB	PPP2CB	5394	0.028	0.45	YES
15	CREB1	CREB1	CREB1	5395	0.028	0.47	YES
16	MAPK3	MAPK3	MAPK3	5559	0.026	0.48	YES
17	MAPK14	MAPK14	MAPK14	6416	0.016	0.44	NO
18	PPP2CA	PPP2CA	PPP2CA	6654	0.012	0.44	NO
19	RPS6KA3	RPS6KA3	RPS6KA3	6819	0.01	0.44	NO
20	JUN	JUN	JUN	7060	0.0074	0.43	NO
21	MAPK9	MAPK9	MAPK9	7120	0.0066	0.43	NO
22	PPP2R5D	PPP2R5D	PPP2R5D	7226	0.0057	0.43	NO
23	ATF1	ATF1	ATF1	7236	0.0056	0.43	NO
24	MAPKAPK2	MAPKAPK2	MAPKAPK2	7834	-0.0012	0.4	NO
25	PPP2R1A	PPP2R1A	PPP2R1A	9438	-0.021	0.33	NO
26	MAPK7	MAPK7	MAPK7	9875	-0.026	0.32	NO
27	DUSP4	DUSP4	DUSP4	10238	-0.031	0.32	NO
28	MAPK11	MAPK11	MAPK11	10417	-0.034	0.34	NO
29	RPS6KA1	RPS6KA1	RPS6KA1	11667	-0.051	0.3	NO
30	ELK1	ELK1	ELK1	13212	-0.082	0.28	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 PROPANOATE METABOLISM.

Figure S32. 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 PPAR SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CYP4A11	CYP4A11	CYP4A11	2	0.79	0.08	YES
2	CYP4A22	CYP4A22	CYP4A22	26	0.63	0.14	YES
3	PCK1	PCK1	PCK1	39	0.56	0.2	YES
4	SLC27A2	SLC27A2	SLC27A2	43	0.55	0.25	YES
5	HMGCS2	HMGCS2	HMGCS2	107	0.46	0.3	YES
6	AQP7	AQP7	AQP7	124	0.44	0.34	YES
7	ACADL	ACADL	ACADL	196	0.39	0.38	YES
8	FABP4	FABP4	FABP4	246	0.36	0.41	YES
9	EHHADH	EHHADH	EHHADH	466	0.28	0.43	YES
10	CD36	CD36	CD36	512	0.27	0.45	YES
11	RXRG	RXRG	RXRG	663	0.24	0.47	YES
12	FABP1	FABP1	FABP1	758	0.22	0.48	YES
13	GK	GK	GK	812	0.21	0.5	YES
14	CYP27A1	CYP27A1	CYP27A1	924	0.19	0.52	YES
15	ACADM	ACADM	ACADM	1125	0.17	0.52	YES
16	CPT2	CPT2	CPT2	1149	0.16	0.54	YES
17	ACOX2	ACOX2	ACOX2	1262	0.15	0.55	YES
18	ACSL1	ACSL1	ACSL1	1484	0.14	0.55	YES
19	PCK2	PCK2	PCK2	1487	0.14	0.56	YES
20	LPL	LPL	LPL	1548	0.13	0.57	YES
21	ANGPTL4	ANGPTL4	ANGPTL4	1760	0.12	0.57	YES
22	CPT1A	CPT1A	CPT1A	1810	0.12	0.58	YES
23	PPARG	PPARG	PPARG	2253	0.096	0.57	NO
24	PPARA	PPARA	PPARA	2346	0.093	0.57	NO
25	FABP2	FABP2	FABP2	3104	0.069	0.54	NO
26	FABP7	FABP7	FABP7	3138	0.068	0.54	NO
27	PLIN1	PLIN1	PLIN1	3226	0.066	0.54	NO
28	ACOX1	ACOX1	ACOX1	3359	0.063	0.54	NO
29	FABP3	FABP3	FABP3	3646	0.057	0.53	NO
30	ACSL6	ACSL6	ACSL6	3953	0.051	0.52	NO
31	PDPK1	PDPK1	PDPK1	4127	0.048	0.52	NO
32	SCP2	SCP2	SCP2	4159	0.047	0.52	NO
33	SCD	SCD	SCD	6244	0.018	0.41	NO
34	ILK	ILK	ILK	6541	0.014	0.39	NO
35	ACAA1	ACAA1	ACAA1	6706	0.012	0.38	NO
36	SORBS1	SORBS1	SORBS1	6893	0.0093	0.37	NO
37	RXRB	RXRB	RXRB	6927	0.0089	0.37	NO
38	RXRA	RXRA	RXRA	7546	0.0022	0.34	NO
39	SCD5	SCD5	SCD5	7676	0.00081	0.33	NO
40	ACSL3	ACSL3	ACSL3	7836	-0.0012	0.32	NO
41	NR1H3	NR1H3	NR1H3	8662	-0.012	0.28	NO
42	APOA2	APOA2	APOA2	8835	-0.014	0.27	NO
43	UBC	UBC	UBC	8846	-0.014	0.27	NO
44	FADS2	FADS2	FADS2	9190	-0.018	0.26	NO
45	PPARD	PPARD	PPARD	9476	-0.022	0.24	NO
46	OLR1	OLR1	OLR1	9821	-0.026	0.23	NO
47	CYP8B1	CYP8B1	CYP8B1	10076	-0.029	0.22	NO
48	SLC27A1	SLC27A1	SLC27A1	10759	-0.038	0.18	NO
49	ACSL5	ACSL5	ACSL5	11838	-0.054	0.13	NO
50	CPT1B	CPT1B	CPT1B	12266	-0.062	0.11	NO
51	SLC27A4	SLC27A4	SLC27A4	12698	-0.07	0.094	NO
52	FABP6	FABP6	FABP6	12878	-0.074	0.091	NO
53	CYP7A1	CYP7A1	CYP7A1	12888	-0.074	0.098	NO
54	ACSL4	ACSL4	ACSL4	12951	-0.076	0.1	NO
55	DBI	DBI	DBI	13155	-0.081	0.1	NO
56	CPT1C	CPT1C	CPT1C	13257	-0.084	0.1	NO
57	ACOX3	ACOX3	ACOX3	13946	-0.1	0.075	NO
58	FABP5	FABP5	FABP5	14508	-0.12	0.057	NO
59	MMP1	MMP1	MMP1	14557	-0.13	0.067	NO
60	ADIPOQ	ADIPOQ	ADIPOQ	14580	-0.13	0.079	NO
61	APOA1	APOA1	APOA1	15303	-0.16	0.056	NO
62	APOC3	APOC3	APOC3	15682	-0.18	0.054	NO
63	SLC27A5	SLC27A5	SLC27A5	15868	-0.2	0.064	NO
64	ME1	ME1	ME1	16422	-0.24	0.057	NO
65	PLTP	PLTP	PLTP	17812	-0.43	0.024	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 PPAR SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG PEROXISOME

Table 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	AMDHD1	AMDHD1	AMDHD1	36	0.58	0.12	YES
2	DDC	DDC	DDC	73	0.49	0.22	YES
3	FTCD	FTCD	FTCD	109	0.46	0.31	YES
4	ASPA	ASPA	ASPA	199	0.39	0.38	YES
5	ABP1	ABP1	ABP1	399	0.3	0.43	YES
6	CNDP1	CNDP1	CNDP1	446	0.29	0.49	YES
7	ACY3	ACY3	ACY3	580	0.25	0.53	YES
8	ALDH3A2	ALDH3A2	ALDH3A2	797	0.21	0.56	YES
9	MAOB	MAOB	MAOB	1008	0.18	0.59	YES
10	HDC	HDC	HDC	1294	0.15	0.61	YES
11	HNMT	HNMT	HNMT	1558	0.13	0.62	YES
12	ALDH9A1	ALDH9A1	ALDH9A1	2098	0.1	0.61	YES
13	LCMT2	LCMT2	LCMT2	2486	0.088	0.61	YES
14	ALDH7A1	ALDH7A1	ALDH7A1	2499	0.088	0.62	YES
15	ALDH1B1	ALDH1B1	ALDH1B1	2837	0.078	0.62	NO
16	ALDH2	ALDH2	ALDH2	3504	0.06	0.6	NO
17	METTL2B	METTL2B	METTL2B	6867	0.0096	0.41	NO
18	ALDH3B1	ALDH3B1	ALDH3B1	6961	0.0085	0.41	NO
19	TRMT11	TRMT11	TRMT11	7126	0.0066	0.4	NO
20	HEMK1	HEMK1	HEMK1	8079	-0.0044	0.35	NO
21	HAL	HAL	HAL	8261	-0.0067	0.34	NO
22	MAOA	MAOA	MAOA	9675	-0.024	0.27	NO
23	ALDH3A1	ALDH3A1	ALDH3A1	9852	-0.026	0.27	NO
24	LCMT1	LCMT1	LCMT1	10915	-0.04	0.22	NO
25	WBSCR22	WBSCR22	WBSCR22	12730	-0.071	0.13	NO
26	UROC1	UROC1	UROC1	13341	-0.086	0.12	NO
27	METTL6	METTL6	METTL6	13568	-0.091	0.12	NO
28	ALDH3B2	ALDH3B2	ALDH3B2	16042	-0.21	0.03	NO
29	ALDH1A3	ALDH1A3	ALDH1A3	17880	-0.45	0.021	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 PEROXISOME.

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

genes ES table in pathway: KEGG ADIPOCYTOKINE 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	CYP4A11	CYP4A11	CYP4A11	2	0.79	0.13	YES
2	CYP4A22	CYP4A22	CYP4A22	26	0.63	0.23	YES
3	ADH6	ADH6	ADH6	54	0.53	0.32	YES
4	ACADL	ACADL	ACADL	196	0.39	0.37	YES
5	EHHADH	EHHADH	EHHADH	466	0.28	0.4	YES
6	ACAA2	ACAA2	ACAA2	733	0.22	0.43	YES
7	ALDH3A2	ALDH3A2	ALDH3A2	797	0.21	0.46	YES
8	ACAT1	ACAT1	ACAT1	956	0.19	0.48	YES
9	ACADM	ACADM	ACADM	1125	0.17	0.5	YES
10	CPT2	CPT2	CPT2	1149	0.16	0.52	YES
11	ACADSB	ACADSB	ACADSB	1405	0.14	0.53	YES
12	ACSL1	ACSL1	ACSL1	1484	0.14	0.55	YES
13	CPT1A	CPT1A	CPT1A	1810	0.12	0.55	YES
14	ALDH9A1	ALDH9A1	ALDH9A1	2098	0.1	0.55	YES
15	ALDH7A1	ALDH7A1	ALDH7A1	2499	0.088	0.55	YES
16	ADH5	ADH5	ADH5	2657	0.083	0.55	YES
17	ALDH1B1	ALDH1B1	ALDH1B1	2837	0.078	0.55	YES
18	ACOX1	ACOX1	ACOX1	3359	0.063	0.54	NO
19	ALDH2	ALDH2	ALDH2	3504	0.06	0.54	NO
20	HADHB	HADHB	HADHB	3620	0.057	0.54	NO
21	HADHA	HADHA	HADHA	3729	0.055	0.54	NO
22	ACSL6	ACSL6	ACSL6	3953	0.051	0.54	NO
23	ACADS	ACADS	ACADS	3959	0.05	0.55	NO
24	ACADVL	ACADVL	ACADVL	5216	0.031	0.48	NO
25	ECHS1	ECHS1	ECHS1	5476	0.027	0.48	NO
26	HADH	HADH	HADH	5781	0.023	0.46	NO
27	ACAA1	ACAA1	ACAA1	6706	0.012	0.41	NO
28	ACSL3	ACSL3	ACSL3	7836	-0.0012	0.35	NO
29	GCDH	GCDH	GCDH	11299	-0.045	0.17	NO
30	ACSL5	ACSL5	ACSL5	11838	-0.054	0.15	NO
31	ACAT2	ACAT2	ACAT2	12031	-0.057	0.15	NO
32	CPT1B	CPT1B	CPT1B	12266	-0.062	0.14	NO
33	ACSL4	ACSL4	ACSL4	12951	-0.076	0.12	NO
34	CPT1C	CPT1C	CPT1C	13257	-0.084	0.12	NO
35	ACOX3	ACOX3	ACOX3	13946	-0.1	0.096	NO
36	ADH1B	ADH1B	ADH1B	14917	-0.14	0.066	NO
37	ADH1A	ADH1A	ADH1A	16008	-0.21	0.04	NO
38	ADH4	ADH4	ADH4	16014	-0.21	0.074	NO
39	ADH1C	ADH1C	ADH1C	17029	-0.3	0.068	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 ADIPOCYTOKINE SIGNALING PATHWAY.

Figure S38. 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

genes ES table in pathway: BIOCARTA AT1R 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	AGTR1	AGTR1	AGTR1	53	0.54	0.25	YES
2	AGT	AGT	AGT	914	0.19	0.29	YES
3	MAPK8	MAPK8	MAPK8	1271	0.15	0.34	YES
4	MAPK1	MAPK1	MAPK1	2487	0.088	0.32	YES
5	ATF2	ATF2	ATF2	2616	0.084	0.35	YES
6	EGFR	EGFR	EGFR	2705	0.081	0.38	YES
7	MEF2C	MEF2C	MEF2C	3187	0.067	0.38	YES
8	MEF2A	MEF2A	MEF2A	4154	0.048	0.35	NO
9	SOS1	SOS1	SOS1	4818	0.036	0.33	NO
10	CALM1	CALM1	CALM1	4857	0.036	0.35	NO
11	CALM3	CALM3	CALM3	5266	0.03	0.34	NO
12	PAK1	PAK1	PAK1	5464	0.027	0.34	NO
13	MAPK3	MAPK3	MAPK3	5559	0.026	0.35	NO
14	GNAQ	GNAQ	GNAQ	5562	0.026	0.36	NO
15	MAP2K4	MAP2K4	MAP2K4	5686	0.024	0.37	NO
16	MAP3K1	MAP3K1	MAP3K1	5777	0.023	0.37	NO
17	PTK2	PTK2	PTK2	6113	0.019	0.36	NO
18	MEF2D	MEF2D	MEF2D	6543	0.014	0.34	NO
19	JUN	JUN	JUN	7060	0.0074	0.32	NO
20	PRKCB	PRKCB	PRKCB	7381	0.0041	0.3	NO
21	MAP2K1	MAP2K1	MAP2K1	9463	-0.022	0.2	NO
22	GRB2	GRB2	GRB2	9661	-0.024	0.2	NO
23	RAC1	RAC1	RAC1	10519	-0.035	0.17	NO
24	HRAS	HRAS	HRAS	10851	-0.04	0.17	NO
25	RAF1	RAF1	RAF1	11192	-0.044	0.17	NO
26	SRC	SRC	SRC	11296	-0.045	0.19	NO
27	CALM2	CALM2	CALM2	11823	-0.054	0.18	NO
28	PTK2B	PTK2B	PTK2B	12625	-0.069	0.17	NO
29	MAP2K2	MAP2K2	MAP2K2	12631	-0.069	0.2	NO
30	PRKCA	PRKCA	PRKCA	12718	-0.071	0.23	NO
31	SHC1	SHC1	SHC1	12923	-0.075	0.25	NO
32	ELK1	ELK1	ELK1	13212	-0.082	0.28	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: BIOCARTA AT1R PATHWAY.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AT1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE	25	genes.ES.table	0.54	1.4	0.083	0.22	0.99	0.56	0.24	0.42	0.16	0.003
KEGG MAPK SIGNALING PATHWAY	247	genes.ES.table	0.43	1.6	0.0041	0.15	0.87	0.33	0.21	0.26	0.083	0.004
KEGG CALCIUM SIGNALING PATHWAY	168	genes.ES.table	0.58	1.7	0	0.14	0.84	0.47	0.19	0.38	0.069	0.006
KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION	223	genes.ES.table	0.56	1.5	0.0021	0.19	0.97	0.5	0.2	0.41	0.13	0.003
KEGG MTOR SIGNALING PATHWAY	50	genes.ES.table	0.38	1.6	0.02	0.14	0.89	0.38	0.34	0.25	0.083	0.003
KEGG VASCULAR SMOOTH MUSCLE CONTRACTION	107	genes.ES.table	0.56	1.7	0.002	0.15	0.78	0.43	0.19	0.35	0.067	0.013
KEGG WNT SIGNALING PATHWAY	146	genes.ES.table	0.5	1.7	0.0082	0.14	0.81	0.42	0.27	0.31	0.066	0.01
KEGG NOTCH SIGNALING PATHWAY	46	genes.ES.table	0.5	1.7	0.018	0.14	0.81	0.37	0.2	0.3	0.067	0.01
KEGG HEDGEHOG SIGNALING PATHWAY	54	genes.ES.table	0.57	1.5	0.033	0.21	0.98	0.39	0.13	0.34	0.15	0.003
KEGG TGF BETA SIGNALING PATHWAY	85	genes.ES.table	0.59	1.8	0	0.13	0.64	0.44	0.18	0.36	0.051	0.017

genes ES table in pathway: KEGG GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE

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	PIK3CG	PIK3CG	PIK3CG	1306	0.21	0.036	YES
2	NOS3	NOS3	NOS3	1421	0.2	0.13	YES
3	FLT4	FLT4	FLT4	1787	0.17	0.2	YES
4	KDR	KDR	KDR	1890	0.16	0.28	YES
5	FLT1	FLT1	FLT1	2421	0.13	0.32	YES
6	PIK3CA	PIK3CA	PIK3CA	2892	0.12	0.36	YES
7	HIF1A	HIF1A	HIF1A	3251	0.1	0.39	YES
8	SHC1	SHC1	SHC1	3962	0.083	0.39	YES
9	VHL	VHL	VHL	4099	0.079	0.43	YES
10	PTK2	PTK2	PTK2	4536	0.07	0.44	YES
11	EIF2B2	EIF2B2	EIF2B2	4576	0.069	0.47	YES
12	PLCG1	PLCG1	PLCG1	4753	0.065	0.5	YES
13	PRKCB	PRKCB	PRKCB	4838	0.063	0.52	YES
14	VEGFA	VEGFA	VEGFA	5041	0.059	0.54	YES
15	EIF2S1	EIF2S1	EIF2S1	5144	0.057	0.57	YES
16	ARNT	ARNT	ARNT	5345	0.054	0.58	YES
17	PIK3R1	PIK3R1	PIK3R1	5512	0.051	0.6	YES
18	PXN	PXN	PXN	5520	0.051	0.63	YES
19	EIF2S3	EIF2S3	EIF2S3	8630	0.013	0.47	NO
20	EIF2B4	EIF2B4	EIF2B4	8712	0.012	0.47	NO
21	EIF2B3	EIF2B3	EIF2B3	8716	0.012	0.47	NO
22	EIF2S2	EIF2S2	EIF2S2	9371	0.0051	0.44	NO
23	EIF1	EIF1	EIF1	10102	-0.0026	0.4	NO
24	EIF1AX	EIF1AX	EIF1AX	10446	-0.0064	0.39	NO
25	PRKCA	PRKCA	PRKCA	10479	-0.0067	0.39	NO
26	EIF2B1	EIF2B1	EIF2B1	10557	-0.0075	0.39	NO
27	ELAVL1	ELAVL1	ELAVL1	10728	-0.0096	0.38	NO
28	EIF2B5	EIF2B5	EIF2B5	11916	-0.024	0.33	NO
29	HRAS	HRAS	HRAS	12579	-0.033	0.31	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 GLYCOSAMINOGLYCAN BIOSYNTHESIS HEPARAN SULFATE.

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

genes ES table in pathway: KEGG MAPK SIGNALING PATHWAY

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	SERPINE1	SERPINE1	SERPINE1	988	0.24	0.053	YES
2	CDKN2B	CDKN2B	CDKN2B	1277	0.21	0.13	YES
3	CCNT1	CCNT1	CCNT1	1871	0.16	0.17	YES
4	SKIL	SKIL	SKIL	1960	0.16	0.24	YES
5	JUNB	JUNB	JUNB	2089	0.15	0.3	YES
6	SMAD7	SMAD7	SMAD7	2847	0.12	0.31	YES
7	SMURF2	SMURF2	SMURF2	2930	0.11	0.36	YES
8	MYC	MYC	MYC	2969	0.11	0.4	YES
9	CDK8	CDK8	CDK8	3012	0.11	0.45	YES
10	SKI	SKI	SKI	3085	0.11	0.5	YES
11	WWTR1	WWTR1	WWTR1	3140	0.11	0.54	YES
12	RBL1	RBL1	RBL1	3328	0.1	0.58	YES
13	HDAC1	HDAC1	HDAC1	4937	0.061	0.52	NO
14	SMAD2	SMAD2	SMAD2	6024	0.044	0.48	NO
15	TGIF2	TGIF2	TGIF2	6261	0.04	0.48	NO
16	SMAD4	SMAD4	SMAD4	6527	0.037	0.48	NO
17	TFDP1	TFDP1	TFDP1	7164	0.029	0.46	NO
18	USP9X	USP9X	USP9X	7316	0.028	0.46	NO
19	TRIM33	TRIM33	TRIM33	7582	0.025	0.46	NO
20	NCOR2	NCOR2	NCOR2	7891	0.021	0.46	NO
21	SP1	SP1	SP1	8065	0.019	0.45	NO
22	NCOR1	NCOR1	NCOR1	8069	0.019	0.46	NO
23	RPS27A	RPS27A	RPS27A	8353	0.016	0.45	NO
24	CCNT2	CCNT2	CCNT2	8372	0.016	0.46	NO
25	PPM1A	PPM1A	PPM1A	8735	0.012	0.44	NO
26	UBE2D1	UBE2D1	UBE2D1	8938	0.0098	0.44	NO
27	PARP1	PARP1	PARP1	8967	0.0095	0.44	NO
28	UBA52	UBA52	UBA52	9038	0.0086	0.44	NO
29	CDK9	CDK9	CDK9	9545	0.0033	0.42	NO
30	CCNC	CCNC	CCNC	10193	-0.0037	0.38	NO
31	UBE2D3	UBE2D3	UBE2D3	10717	-0.0094	0.36	NO
32	E2F4	E2F4	E2F4	11098	-0.014	0.34	NO
33	MEN1	MEN1	MEN1	11157	-0.014	0.34	NO
34	SMAD3	SMAD3	SMAD3	11205	-0.015	0.35	NO
35	TGIF1	TGIF1	TGIF1	11379	-0.017	0.35	NO
36	E2F5	E2F5	E2F5	14579	-0.066	0.2	NO

Figure S43. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG MAPK SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG CALCIUM SIGNALING PATHWAY

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	ADCY1	ADCY1	ADCY1	240	0.38	0.029	YES
2	CAMK4	CAMK4	CAMK4	389	0.34	0.058	YES
3	NTRK2	NTRK2	NTRK2	484	0.31	0.088	YES
4	NGF	NGF	NGF	599	0.29	0.11	YES
5	ADCYAP1R1	ADCYAP1R1	ADCYAP1R1	671	0.28	0.14	YES
6	PDE1A	PDE1A	PDE1A	685	0.28	0.17	YES
7	SHC3	SHC3	SHC3	883	0.25	0.19	YES
8	ADCY4	ADCY4	ADCY4	1031	0.23	0.2	YES
9	RPS6KA2	RPS6KA2	RPS6KA2	1484	0.19	0.2	YES
10	RPS6KA5	RPS6KA5	RPS6KA5	1567	0.19	0.22	YES
11	ADCYAP1	ADCYAP1	ADCYAP1	1735	0.17	0.23	YES
12	DUSP7	DUSP7	DUSP7	1758	0.17	0.25	YES
13	MEF2C	MEF2C	MEF2C	1808	0.17	0.26	YES
14	PRKAR2A	PRKAR2A	PRKAR2A	1818	0.17	0.28	YES
15	PDE1B	PDE1B	PDE1B	2259	0.14	0.27	YES
16	ADCY3	ADCY3	ADCY3	2295	0.14	0.28	YES
17	NTRK1	NTRK1	NTRK1	2514	0.13	0.29	YES
18	DUSP6	DUSP6	DUSP6	2543	0.13	0.3	YES
19	AKT3	AKT3	AKT3	2621	0.13	0.31	YES
20	FOXO1	FOXO1	FOXO1	2667	0.12	0.32	YES
21	IRS1	IRS1	IRS1	2769	0.12	0.33	YES
22	PIK3CA	PIK3CA	PIK3CA	2892	0.12	0.34	YES
23	PHLPP1	PHLPP1	PHLPP1	3117	0.11	0.34	YES
24	PRKAR2B	PRKAR2B	PRKAR2B	3130	0.11	0.35	YES
25	ADORA2A	ADORA2A	ADORA2A	3367	0.099	0.34	YES
26	MAPK11	MAPK11	MAPK11	3478	0.096	0.35	YES
27	SHC2	SHC2	SHC2	3501	0.096	0.36	YES
28	DUSP4	DUSP4	DUSP4	3570	0.094	0.36	YES
29	IRS2	IRS2	IRS2	3586	0.093	0.37	YES
30	FOXO4	FOXO4	FOXO4	3928	0.083	0.36	YES
31	SHC1	SHC1	SHC1	3962	0.083	0.37	YES
32	CREB1	CREB1	CREB1	4132	0.079	0.37	YES
33	BRAF	BRAF	BRAF	4148	0.078	0.38	YES
34	NR4A1	NR4A1	NR4A1	4337	0.074	0.38	YES
35	CRK	CRK	CRK	4422	0.072	0.38	YES
36	CALM1	CALM1	CALM1	4493	0.071	0.38	YES
37	ADCY8	ADCY8	ADCY8	4687	0.066	0.38	YES
38	FOXO3	FOXO3	FOXO3	4703	0.066	0.39	YES
39	RALA	RALA	RALA	4710	0.066	0.4	YES
40	PTEN	PTEN	PTEN	4734	0.065	0.4	YES
41	PLCG1	PLCG1	PLCG1	4753	0.065	0.41	YES
42	ITPR2	ITPR2	ITPR2	4986	0.06	0.4	YES
43	RAPGEF1	RAPGEF1	RAPGEF1	5102	0.058	0.4	YES
44	RALGDS	RALGDS	RALGDS	5259	0.055	0.4	YES
45	SOS1	SOS1	SOS1	5299	0.055	0.4	YES
46	TRIB3	TRIB3	TRIB3	5381	0.054	0.4	YES
47	MAPK3	MAPK3	MAPK3	5425	0.053	0.41	YES
48	ELK1	ELK1	ELK1	5474	0.052	0.41	YES
49	MEF2A	MEF2A	MEF2A	5477	0.052	0.42	YES
50	PIK3R1	PIK3R1	PIK3R1	5512	0.051	0.42	YES
51	STAT3	STAT3	STAT3	5566	0.05	0.42	YES
52	CDKN1B	CDKN1B	CDKN1B	5697	0.048	0.42	YES
53	PRKACB	PRKACB	PRKACB	5713	0.048	0.43	YES
54	MTOR	MTOR	MTOR	5788	0.047	0.43	YES
55	NRAS	NRAS	NRAS	5791	0.047	0.43	YES
56	RHOA	RHOA	RHOA	5836	0.046	0.44	YES
57	KIDINS220	KIDINS220	KIDINS220	5918	0.045	0.44	YES
58	ATF1	ATF1	ATF1	6002	0.044	0.44	YES
59	AKT1	AKT1	AKT1	6015	0.044	0.44	YES
60	MAP2K5	MAP2K5	MAP2K5	6250	0.041	0.43	NO
61	CDK1	CDK1	CDK1	6265	0.04	0.44	NO
62	RAP1A	RAP1A	RAP1A	6395	0.038	0.43	NO
63	ADCY2	ADCY2	ADCY2	6581	0.036	0.43	NO
64	PPP2R5D	PPP2R5D	PPP2R5D	6829	0.033	0.42	NO
65	MAP2K1	MAP2K1	MAP2K1	6871	0.033	0.42	NO
66	AP2A1	AP2A1	AP2A1	6927	0.032	0.42	NO
67	ADCY7	ADCY7	ADCY7	6977	0.031	0.42	NO
68	PRKAR1A	PRKAR1A	PRKAR1A	7006	0.031	0.42	NO
69	FRS2	FRS2	FRS2	7028	0.031	0.42	NO
70	PRKACA	PRKACA	PRKACA	7491	0.026	0.4	NO
71	RPS6KA3	RPS6KA3	RPS6KA3	7510	0.025	0.4	NO
72	YWHAB	YWHAB	YWHAB	7583	0.025	0.4	NO
73	RALB	RALB	RALB	7665	0.024	0.4	NO
74	MAPK14	MAPK14	MAPK14	7700	0.023	0.4	NO
75	ADCY5	ADCY5	ADCY5	7709	0.023	0.4	NO
76	TSC2	TSC2	TSC2	7845	0.022	0.4	NO
77	CLTC	CLTC	CLTC	7882	0.021	0.4	NO
78	CDKN1A	CDKN1A	CDKN1A	7965	0.02	0.4	NO
79	RAF1	RAF1	RAF1	8310	0.016	0.38	NO
80	ADRBK1	ADRBK1	ADRBK1	8337	0.016	0.38	NO
81	KRAS	KRAS	KRAS	8394	0.016	0.38	NO
82	ADCY6	ADCY6	ADCY6	8463	0.015	0.38	NO
83	AP2A2	AP2A2	AP2A2	8487	0.014	0.38	NO
84	MAPK12	MAPK12	MAPK12	8545	0.014	0.37	NO
85	MAPK1	MAPK1	MAPK1	8689	0.012	0.37	NO
86	MAPK7	MAPK7	MAPK7	8747	0.012	0.36	NO
87	PRKCE	PRKCE	PRKCE	9094	0.0079	0.35	NO
88	AP2S1	AP2S1	AP2S1	9224	0.0066	0.34	NO
89	AP2M1	AP2M1	AP2M1	9232	0.0065	0.34	NO
90	CASP9	CASP9	CASP9	9260	0.0062	0.34	NO
91	ADCY9	ADCY9	ADCY9	9308	0.0058	0.34	NO
92	MDM2	MDM2	MDM2	9493	0.0038	0.33	NO
93	DNM1	DNM1	DNM1	9556	0.0032	0.32	NO
94	PPP2CB	PPP2CB	PPP2CB	9873	-0.0003	0.31	NO
95	AP2B1	AP2B1	AP2B1	9931	-0.00097	0.3	NO
96	CHUK	CHUK	CHUK	10007	-0.0017	0.3	NO
97	ITPR3	ITPR3	ITPR3	10077	-0.0024	0.3	NO
98	PDPK1	PDPK1	PDPK1	10122	-0.0028	0.3	NO
99	RICTOR	RICTOR	RICTOR	10181	-0.0036	0.29	NO
100	MAPKAP1	MAPKAP1	MAPKAP1	10351	-0.0054	0.28	NO
101	RIT1	RIT1	RIT1	10406	-0.006	0.28	NO
102	PRKCA	PRKCA	PRKCA	10479	-0.0067	0.28	NO
103	CALM2	CALM2	CALM2	10491	-0.0069	0.28	NO
104	GRB2	GRB2	GRB2	10764	-0.0099	0.26	NO
105	MAPKAPK2	MAPKAPK2	MAPKAPK2	10782	-0.01	0.26	NO
106	CALM3	CALM3	CALM3	10872	-0.011	0.26	NO
107	PPP2R1A	PPP2R1A	PPP2R1A	11050	-0.013	0.25	NO
108	GSK3A	GSK3A	GSK3A	11174	-0.015	0.25	NO
109	PRKAR1B	PRKAR1B	PRKAR1B	11253	-0.016	0.24	NO
110	DNM2	DNM2	DNM2	11304	-0.016	0.24	NO
111	PPP2R1B	PPP2R1B	PPP2R1B	11660	-0.021	0.23	NO
112	MAP2K2	MAP2K2	MAP2K2	11728	-0.022	0.22	NO
113	PIK3R2	PIK3R2	PIK3R2	11871	-0.024	0.22	NO
114	DNAL4	DNAL4	DNAL4	12299	-0.029	0.2	NO
115	CLTA	CLTA	CLTA	12530	-0.033	0.19	NO
116	PIK3CB	PIK3CB	PIK3CB	12549	-0.033	0.19	NO
117	HRAS	HRAS	HRAS	12579	-0.033	0.2	NO
118	DUSP3	DUSP3	DUSP3	12958	-0.038	0.18	NO
119	AKT2	AKT2	AKT2	13029	-0.039	0.18	NO
120	AKT1S1	AKT1S1	AKT1S1	13138	-0.041	0.18	NO
121	PPP2CA	PPP2CA	PPP2CA	13186	-0.042	0.18	NO
122	PRKCG	PRKCG	PRKCG	13502	-0.047	0.17	NO
123	MAPK13	MAPK13	MAPK13	13574	-0.048	0.17	NO
124	MLST8	MLST8	MLST8	13643	-0.049	0.17	NO
125	RPS6KB2	RPS6KB2	RPS6KB2	13896	-0.053	0.16	NO
126	BAD	BAD	BAD	14073	-0.056	0.16	NO
127	SRC	SRC	SRC	14810	-0.071	0.13	NO
128	PRKCD	PRKCD	PRKCD	14855	-0.072	0.13	NO
129	RPS6KA1	RPS6KA1	RPS6KA1	14930	-0.074	0.14	NO
130	THEM4	THEM4	THEM4	15546	-0.088	0.11	NO
131	MAPKAPK3	MAPKAPK3	MAPKAPK3	16155	-0.11	0.09	NO
132	SH3GL2	SH3GL2	SH3GL2	17814	-0.23	0.024	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 CALCIUM SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION

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	ADAM12	ADAM12	ADAM12	30	0.54	0.077	YES
2	ADCY1	ADCY1	ADCY1	240	0.38	0.12	YES
3	CAMK4	CAMK4	CAMK4	389	0.34	0.16	YES
4	PDE1A	PDE1A	PDE1A	685	0.28	0.19	YES
5	ADCY4	ADCY4	ADCY4	1031	0.23	0.2	YES
6	SPRY1	SPRY1	SPRY1	1492	0.19	0.21	YES
7	PRKAR2A	PRKAR2A	PRKAR2A	1818	0.17	0.21	YES
8	PDE1B	PDE1B	PDE1B	2259	0.14	0.21	YES
9	ADCY3	ADCY3	ADCY3	2295	0.14	0.23	YES
10	AKT3	AKT3	AKT3	2621	0.13	0.23	YES
11	FOXO1	FOXO1	FOXO1	2667	0.12	0.24	YES
12	LRIG1	LRIG1	LRIG1	2743	0.12	0.26	YES
13	ADAM17	ADAM17	ADAM17	2867	0.12	0.27	YES
14	CBL	CBL	CBL	2887	0.12	0.28	YES
15	PIK3CA	PIK3CA	PIK3CA	2892	0.12	0.3	YES
16	SPRY2	SPRY2	SPRY2	2903	0.12	0.32	YES
17	PHLPP1	PHLPP1	PHLPP1	3117	0.11	0.32	YES
18	PRKAR2B	PRKAR2B	PRKAR2B	3130	0.11	0.34	YES
19	SH3KBP1	SH3KBP1	SH3KBP1	3712	0.089	0.32	YES
20	GAB1	GAB1	GAB1	3823	0.086	0.32	YES
21	FOXO4	FOXO4	FOXO4	3928	0.083	0.33	YES
22	SHC1	SHC1	SHC1	3962	0.083	0.34	YES
23	ADAM10	ADAM10	ADAM10	3987	0.082	0.35	YES
24	EGFR	EGFR	EGFR	4058	0.08	0.36	YES
25	CREB1	CREB1	CREB1	4132	0.079	0.37	YES
26	NR4A1	NR4A1	NR4A1	4337	0.074	0.37	YES
27	PAG1	PAG1	PAG1	4363	0.073	0.38	YES
28	CALM1	CALM1	CALM1	4493	0.071	0.38	YES
29	ADCY8	ADCY8	ADCY8	4687	0.066	0.38	YES
30	FOXO3	FOXO3	FOXO3	4703	0.066	0.39	YES
31	PTEN	PTEN	PTEN	4734	0.065	0.4	YES
32	PLCG1	PLCG1	PLCG1	4753	0.065	0.4	YES
33	ITPR2	ITPR2	ITPR2	4986	0.06	0.4	YES
34	SOS1	SOS1	SOS1	5299	0.055	0.39	YES
35	TRIB3	TRIB3	TRIB3	5381	0.054	0.4	YES
36	MAPK3	MAPK3	MAPK3	5425	0.053	0.4	YES
37	PIK3R1	PIK3R1	PIK3R1	5512	0.051	0.4	YES
38	CDKN1B	CDKN1B	CDKN1B	5697	0.048	0.4	YES
39	PRKACB	PRKACB	PRKACB	5713	0.048	0.41	YES
40	MTOR	MTOR	MTOR	5788	0.047	0.41	YES
41	NRAS	NRAS	NRAS	5791	0.047	0.42	YES
42	AKT1	AKT1	AKT1	6015	0.044	0.41	NO
43	CDK1	CDK1	CDK1	6265	0.04	0.4	NO
44	ADCY2	ADCY2	ADCY2	6581	0.036	0.39	NO
45	MAP2K1	MAP2K1	MAP2K1	6871	0.033	0.38	NO
46	AP2A1	AP2A1	AP2A1	6927	0.032	0.38	NO
47	ADCY7	ADCY7	ADCY7	6977	0.031	0.38	NO
48	PRKAR1A	PRKAR1A	PRKAR1A	7006	0.031	0.39	NO
49	CDC42	CDC42	CDC42	7113	0.03	0.38	NO
50	PRKACA	PRKACA	PRKACA	7491	0.026	0.37	NO
51	YWHAB	YWHAB	YWHAB	7583	0.025	0.37	NO
52	ADCY5	ADCY5	ADCY5	7709	0.023	0.36	NO
53	TSC2	TSC2	TSC2	7845	0.022	0.36	NO
54	EPS15	EPS15	EPS15	7861	0.022	0.36	NO
55	CLTC	CLTC	CLTC	7882	0.021	0.36	NO
56	CDKN1A	CDKN1A	CDKN1A	7965	0.02	0.36	NO
57	RAF1	RAF1	RAF1	8310	0.016	0.34	NO
58	CDC37	CDC37	CDC37	8315	0.016	0.35	NO
59	ADRBK1	ADRBK1	ADRBK1	8337	0.016	0.35	NO
60	RPS27A	RPS27A	RPS27A	8353	0.016	0.35	NO
61	KRAS	KRAS	KRAS	8394	0.016	0.35	NO
62	ADCY6	ADCY6	ADCY6	8463	0.015	0.35	NO
63	AP2A2	AP2A2	AP2A2	8487	0.014	0.35	NO
64	MAPK1	MAPK1	MAPK1	8689	0.012	0.34	NO
65	UBA52	UBA52	UBA52	9038	0.0086	0.32	NO
66	PRKCE	PRKCE	PRKCE	9094	0.0079	0.32	NO
67	AP2S1	AP2S1	AP2S1	9224	0.0066	0.31	NO
68	AP2M1	AP2M1	AP2M1	9232	0.0065	0.32	NO
69	STAM2	STAM2	STAM2	9245	0.0064	0.32	NO
70	CASP9	CASP9	CASP9	9260	0.0062	0.32	NO
71	ADCY9	ADCY9	ADCY9	9308	0.0058	0.31	NO
72	EPS15L1	EPS15L1	EPS15L1	9340	0.0056	0.31	NO
73	CSK	CSK	CSK	9465	0.0042	0.31	NO
74	MDM2	MDM2	MDM2	9493	0.0038	0.3	NO
75	STAM	STAM	STAM	9869	-0.00026	0.28	NO
76	AP2B1	AP2B1	AP2B1	9931	-0.00097	0.28	NO
77	CHUK	CHUK	CHUK	10007	-0.0017	0.28	NO
78	ITPR3	ITPR3	ITPR3	10077	-0.0024	0.27	NO
79	PDPK1	PDPK1	PDPK1	10122	-0.0028	0.27	NO
80	RICTOR	RICTOR	RICTOR	10181	-0.0036	0.27	NO
81	MAPKAP1	MAPKAP1	MAPKAP1	10351	-0.0054	0.26	NO
82	HSP90AA1	HSP90AA1	HSP90AA1	10395	-0.0058	0.26	NO
83	PRKCA	PRKCA	PRKCA	10479	-0.0067	0.26	NO
84	CALM2	CALM2	CALM2	10491	-0.0069	0.26	NO
85	GRB2	GRB2	GRB2	10764	-0.0099	0.24	NO
86	CALM3	CALM3	CALM3	10872	-0.011	0.24	NO
87	GSK3A	GSK3A	GSK3A	11174	-0.015	0.22	NO
88	PRKAR1B	PRKAR1B	PRKAR1B	11253	-0.016	0.22	NO
89	MAP2K2	MAP2K2	MAP2K2	11728	-0.022	0.2	NO
90	HGS	HGS	HGS	12071	-0.026	0.18	NO
91	CLTA	CLTA	CLTA	12530	-0.033	0.16	NO
92	HRAS	HRAS	HRAS	12579	-0.033	0.17	NO
93	EPN1	EPN1	EPN1	12743	-0.035	0.16	NO
94	AKT2	AKT2	AKT2	13029	-0.039	0.15	NO
95	AKT1S1	AKT1S1	AKT1S1	13138	-0.041	0.15	NO
96	PRKCG	PRKCG	PRKCG	13502	-0.047	0.14	NO
97	MLST8	MLST8	MLST8	13643	-0.049	0.14	NO
98	RPS6KB2	RPS6KB2	RPS6KB2	13896	-0.053	0.13	NO
99	BAD	BAD	BAD	14073	-0.056	0.13	NO
100	SRC	SRC	SRC	14810	-0.071	0.1	NO
101	PRKCD	PRKCD	PRKCD	14855	-0.072	0.11	NO
102	THEM4	THEM4	THEM4	15546	-0.088	0.084	NO
103	EGF	EGF	EGF	17688	-0.21	-0.0024	NO
104	SH3GL2	SH3GL2	SH3GL2	17814	-0.23	0.024	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 NEUROACTIVE LIGAND RECEPTOR INTERACTION.

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

genes ES table in pathway: KEGG MTOR SIGNALING PATHWAY

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	PDGFRA	PDGFRA	PDGFRA	9	0.57	0.051	YES
2	COL5A1	COL5A1	COL5A1	145	0.42	0.082	YES
3	THBS2	THBS2	THBS2	154	0.42	0.12	YES
4	COL1A1	COL1A1	COL1A1	227	0.38	0.15	YES
5	COL6A3	COL6A3	COL6A3	237	0.38	0.18	YES
6	ADCY1	ADCY1	ADCY1	240	0.38	0.22	YES
7	CAMK4	CAMK4	CAMK4	389	0.34	0.24	YES
8	COL3A1	COL3A1	COL3A1	432	0.33	0.27	YES
9	COL1A2	COL1A2	COL1A2	454	0.32	0.3	YES
10	COL5A2	COL5A2	COL5A2	531	0.3	0.32	YES
11	PDE1A	PDE1A	PDE1A	685	0.28	0.34	YES
12	ADCY4	ADCY4	ADCY4	1031	0.23	0.34	YES
13	PDGFRB	PDGFRB	PDGFRB	1035	0.23	0.36	YES
14	COL4A5	COL4A5	COL4A5	1134	0.22	0.37	YES
15	COL6A2	COL6A2	COL6A2	1290	0.21	0.38	YES
16	COL4A1	COL4A1	COL4A1	1514	0.19	0.39	YES
17	PLAT	PLAT	PLAT	1706	0.18	0.39	YES
18	COL4A2	COL4A2	COL4A2	1732	0.17	0.41	YES
19	PRKAR2A	PRKAR2A	PRKAR2A	1818	0.17	0.42	YES
20	COL6A1	COL6A1	COL6A1	1891	0.16	0.43	YES
21	THBS4	THBS4	THBS4	1985	0.16	0.44	YES
22	PDGFB	PDGFB	PDGFB	1989	0.16	0.45	YES
23	PDGFD	PDGFD	PDGFD	2135	0.15	0.46	YES
24	PDE1B	PDE1B	PDE1B	2259	0.14	0.46	YES
25	ADCY3	ADCY3	ADCY3	2295	0.14	0.47	YES
26	AKT3	AKT3	AKT3	2621	0.13	0.47	YES
27	THBS1	THBS1	THBS1	2644	0.13	0.48	YES
28	FOXO1	FOXO1	FOXO1	2667	0.12	0.49	YES
29	PIK3CA	PIK3CA	PIK3CA	2892	0.12	0.49	YES
30	PHLPP1	PHLPP1	PHLPP1	3117	0.11	0.48	YES
31	PRKAR2B	PRKAR2B	PRKAR2B	3130	0.11	0.49	YES
32	PDGFA	PDGFA	PDGFA	3539	0.095	0.48	YES
33	COL2A1	COL2A1	COL2A1	3554	0.094	0.49	YES
34	FOXO4	FOXO4	FOXO4	3928	0.083	0.47	YES
35	CREB1	CREB1	CREB1	4132	0.079	0.47	YES
36	NR4A1	NR4A1	NR4A1	4337	0.074	0.46	YES
37	CRK	CRK	CRK	4422	0.072	0.47	YES
38	CALM1	CALM1	CALM1	4493	0.071	0.47	YES
39	PDGFC	PDGFC	PDGFC	4679	0.066	0.46	YES
40	ADCY8	ADCY8	ADCY8	4687	0.066	0.47	YES
41	FOXO3	FOXO3	FOXO3	4703	0.066	0.48	YES
42	PTEN	PTEN	PTEN	4734	0.065	0.48	YES
43	PLCG1	PLCG1	PLCG1	4753	0.065	0.48	YES
44	COL9A1	COL9A1	COL9A1	4929	0.061	0.48	YES
45	COL9A3	COL9A3	COL9A3	4963	0.061	0.48	YES
46	ITPR2	ITPR2	ITPR2	4986	0.06	0.49	YES
47	NCK2	NCK2	NCK2	4991	0.06	0.49	YES
48	RAPGEF1	RAPGEF1	RAPGEF1	5102	0.058	0.49	YES
49	SOS1	SOS1	SOS1	5299	0.055	0.49	YES
50	TRIB3	TRIB3	TRIB3	5381	0.054	0.49	YES
51	MAPK3	MAPK3	MAPK3	5425	0.053	0.49	YES
52	PIK3R1	PIK3R1	PIK3R1	5512	0.051	0.49	YES
53	STAT3	STAT3	STAT3	5566	0.05	0.49	YES
54	CDKN1B	CDKN1B	CDKN1B	5697	0.048	0.49	YES
55	PRKACB	PRKACB	PRKACB	5713	0.048	0.49	YES
56	MTOR	MTOR	MTOR	5788	0.047	0.49	YES
57	NRAS	NRAS	NRAS	5791	0.047	0.5	YES
58	AKT1	AKT1	AKT1	6015	0.044	0.49	NO
59	COL9A2	COL9A2	COL9A2	6166	0.042	0.48	NO
60	CDK1	CDK1	CDK1	6265	0.04	0.48	NO
61	ADCY2	ADCY2	ADCY2	6581	0.036	0.47	NO
62	FURIN	FURIN	FURIN	6799	0.034	0.46	NO
63	MAP2K1	MAP2K1	MAP2K1	6871	0.033	0.46	NO
64	ADCY7	ADCY7	ADCY7	6977	0.031	0.46	NO
65	PRKAR1A	PRKAR1A	PRKAR1A	7006	0.031	0.46	NO
66	RASA1	RASA1	RASA1	7022	0.031	0.46	NO
67	THBS3	THBS3	THBS3	7121	0.03	0.46	NO
68	CRKL	CRKL	CRKL	7456	0.026	0.44	NO
69	PRKACA	PRKACA	PRKACA	7491	0.026	0.44	NO
70	YWHAB	YWHAB	YWHAB	7583	0.025	0.44	NO
71	STAT5B	STAT5B	STAT5B	7690	0.024	0.43	NO
72	ADCY5	ADCY5	ADCY5	7709	0.023	0.43	NO
73	NCK1	NCK1	NCK1	7715	0.023	0.44	NO
74	TSC2	TSC2	TSC2	7845	0.022	0.43	NO
75	CDKN1A	CDKN1A	CDKN1A	7965	0.02	0.43	NO
76	RAF1	RAF1	RAF1	8310	0.016	0.41	NO
77	ADRBK1	ADRBK1	ADRBK1	8337	0.016	0.41	NO
78	KRAS	KRAS	KRAS	8394	0.016	0.41	NO
79	ADCY6	ADCY6	ADCY6	8463	0.015	0.4	NO
80	MAPK1	MAPK1	MAPK1	8689	0.012	0.39	NO
81	PRKCE	PRKCE	PRKCE	9094	0.0079	0.37	NO
82	CASP9	CASP9	CASP9	9260	0.0062	0.36	NO
83	BCAR1	BCAR1	BCAR1	9303	0.0059	0.36	NO
84	ADCY9	ADCY9	ADCY9	9308	0.0058	0.36	NO
85	MDM2	MDM2	MDM2	9493	0.0038	0.35	NO
86	CHUK	CHUK	CHUK	10007	-0.0017	0.32	NO
87	ITPR3	ITPR3	ITPR3	10077	-0.0024	0.32	NO
88	PDPK1	PDPK1	PDPK1	10122	-0.0028	0.32	NO
89	RICTOR	RICTOR	RICTOR	10181	-0.0036	0.32	NO
90	MAPKAP1	MAPKAP1	MAPKAP1	10351	-0.0054	0.31	NO
91	PRKCA	PRKCA	PRKCA	10479	-0.0067	0.3	NO
92	CALM2	CALM2	CALM2	10491	-0.0069	0.3	NO
93	GRB2	GRB2	GRB2	10764	-0.0099	0.29	NO
94	CALM3	CALM3	CALM3	10872	-0.011	0.28	NO
95	GSK3A	GSK3A	GSK3A	11174	-0.015	0.27	NO
96	PRKAR1B	PRKAR1B	PRKAR1B	11253	-0.016	0.26	NO
97	STAT5A	STAT5A	STAT5A	11355	-0.017	0.26	NO
98	STAT1	STAT1	STAT1	11641	-0.02	0.24	NO
99	MAP2K2	MAP2K2	MAP2K2	11728	-0.022	0.24	NO
100	PIK3R2	PIK3R2	PIK3R2	11871	-0.024	0.24	NO
101	SPP1	SPP1	SPP1	11997	-0.025	0.23	NO
102	STAT6	STAT6	STAT6	12013	-0.025	0.23	NO
103	PIK3CB	PIK3CB	PIK3CB	12549	-0.033	0.21	NO
104	HRAS	HRAS	HRAS	12579	-0.033	0.21	NO
105	PLG	PLG	PLG	12952	-0.038	0.19	NO
106	AKT2	AKT2	AKT2	13029	-0.039	0.19	NO
107	AKT1S1	AKT1S1	AKT1S1	13138	-0.041	0.19	NO
108	PRKCG	PRKCG	PRKCG	13502	-0.047	0.17	NO
109	MLST8	MLST8	MLST8	13643	-0.049	0.17	NO
110	RPS6KB2	RPS6KB2	RPS6KB2	13896	-0.053	0.16	NO
111	BAD	BAD	BAD	14073	-0.056	0.16	NO
112	SRC	SRC	SRC	14810	-0.071	0.12	NO
113	PRKCD	PRKCD	PRKCD	14855	-0.072	0.12	NO
114	THEM4	THEM4	THEM4	15546	-0.088	0.095	NO
115	COL4A4	COL4A4	COL4A4	17099	-0.16	0.024	NO
116	COL4A3	COL4A3	COL4A3	17656	-0.21	0.012	NO
117	GRB7	GRB7	GRB7	17820	-0.23	0.024	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 MTOR SIGNALING PATHWAY.

Figure S50. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG MTOR 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 VASCULAR SMOOTH MUSCLE CONTRACTION

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	PDGFRA	PDGFRA	PDGFRA	9	0.57	0.024	YES
2	ITGA11	ITGA11	ITGA11	17	0.55	0.047	YES
3	LAMA2	LAMA2	LAMA2	52	0.5	0.066	YES
4	COL11A1	COL11A1	COL11A1	64	0.49	0.086	YES
5	COMP	COMP	COMP	109	0.45	0.1	YES
6	COL5A1	COL5A1	COL5A1	145	0.42	0.12	YES
7	THBS2	THBS2	THBS2	154	0.42	0.14	YES
8	ITGA9	ITGA9	ITGA9	222	0.38	0.15	YES
9	COL1A1	COL1A1	COL1A1	227	0.38	0.16	YES
10	COL6A3	COL6A3	COL6A3	237	0.38	0.18	YES
11	ITGA10	ITGA10	ITGA10	365	0.34	0.19	YES
12	SHC4	SHC4	SHC4	367	0.34	0.2	YES
13	HGF	HGF	HGF	424	0.33	0.21	YES
14	COL3A1	COL3A1	COL3A1	432	0.33	0.23	YES
15	ITGA8	ITGA8	ITGA8	434	0.33	0.24	YES
16	COL1A2	COL1A2	COL1A2	454	0.32	0.25	YES
17	FLNC	FLNC	FLNC	494	0.31	0.26	YES
18	PGF	PGF	PGF	506	0.31	0.28	YES
19	COL5A2	COL5A2	COL5A2	531	0.3	0.29	YES
20	COL5A3	COL5A3	COL5A3	540	0.3	0.3	YES
21	LAMC3	LAMC3	LAMC3	545	0.3	0.31	YES
22	TNC	TNC	TNC	569	0.3	0.32	YES
23	TNXB	TNXB	TNXB	632	0.28	0.33	YES
24	SHC3	SHC3	SHC3	883	0.25	0.33	YES
25	VEGFC	VEGFC	VEGFC	1017	0.23	0.33	YES
26	PDGFRB	PDGFRB	PDGFRB	1035	0.23	0.34	YES
27	MYLK2	MYLK2	MYLK2	1038	0.23	0.35	YES
28	IGF1	IGF1	IGF1	1050	0.23	0.36	YES
29	FN1	FN1	FN1	1153	0.22	0.36	YES
30	LAMB4	LAMB4	LAMB4	1171	0.22	0.37	YES
31	COL6A2	COL6A2	COL6A2	1290	0.21	0.38	YES
32	PIK3CG	PIK3CG	PIK3CG	1306	0.21	0.38	YES
33	LAMA4	LAMA4	LAMA4	1311	0.21	0.39	YES
34	ITGB3	ITGB3	ITGB3	1429	0.2	0.39	YES
35	ITGA5	ITGA5	ITGA5	1467	0.19	0.4	YES
36	RELN	RELN	RELN	1501	0.19	0.41	YES
37	COL4A1	COL4A1	COL4A1	1514	0.19	0.41	YES
38	TNR	TNR	TNR	1545	0.19	0.42	YES
39	ITGA7	ITGA7	ITGA7	1585	0.18	0.42	YES
40	ITGA1	ITGA1	ITGA1	1612	0.18	0.43	YES
41	IBSP	IBSP	IBSP	1633	0.18	0.44	YES
42	COL4A2	COL4A2	COL4A2	1732	0.17	0.44	YES
43	FLT4	FLT4	FLT4	1787	0.17	0.44	YES
44	VWF	VWF	VWF	1819	0.17	0.45	YES
45	ITGA2	ITGA2	ITGA2	1840	0.17	0.46	YES
46	KDR	KDR	KDR	1890	0.16	0.46	YES
47	COL6A1	COL6A1	COL6A1	1891	0.16	0.47	YES
48	THBS4	THBS4	THBS4	1985	0.16	0.47	YES
49	PDGFB	PDGFB	PDGFB	1989	0.16	0.48	YES
50	ROCK2	ROCK2	ROCK2	2072	0.15	0.48	YES
51	ITGA4	ITGA4	ITGA4	2121	0.15	0.48	YES
52	PDGFD	PDGFD	PDGFD	2135	0.15	0.49	YES
53	CAV1	CAV1	CAV1	2155	0.15	0.49	YES
54	FYN	FYN	FYN	2170	0.15	0.5	YES
55	VCL	VCL	VCL	2234	0.14	0.5	YES
56	ACTN1	ACTN1	ACTN1	2236	0.14	0.5	YES
57	LAMC1	LAMC1	LAMC1	2305	0.14	0.51	YES
58	FLT1	FLT1	FLT1	2421	0.13	0.51	YES
59	ACTN3	ACTN3	ACTN3	2422	0.13	0.51	YES
60	FLNA	FLNA	FLNA	2541	0.13	0.51	YES
61	CCND2	CCND2	CCND2	2563	0.13	0.52	YES
62	MYL9	MYL9	MYL9	2572	0.13	0.52	YES
63	COL6A6	COL6A6	COL6A6	2597	0.13	0.52	YES
64	AKT3	AKT3	AKT3	2621	0.13	0.53	YES
65	THBS1	THBS1	THBS1	2644	0.13	0.53	YES
66	PIK3R3	PIK3R3	PIK3R3	2738	0.12	0.53	YES
67	ACTN2	ACTN2	ACTN2	2800	0.12	0.54	YES
68	LAMB1	LAMB1	LAMB1	2864	0.12	0.54	YES
69	PIK3CA	PIK3CA	PIK3CA	2892	0.12	0.54	YES
70	ITGB1	ITGB1	ITGB1	2994	0.11	0.54	YES
71	ITGA2B	ITGA2B	ITGA2B	3003	0.11	0.54	YES
72	PARVA	PARVA	PARVA	3010	0.11	0.55	YES
73	VTN	VTN	VTN	3165	0.11	0.54	YES
74	MYLK	MYLK	MYLK	3224	0.1	0.55	YES
75	CTNNB1	CTNNB1	CTNNB1	3232	0.1	0.55	YES
76	TNN	TNN	TNN	3321	0.1	0.55	YES
77	ROCK1	ROCK1	ROCK1	3381	0.099	0.55	YES
78	DOCK1	DOCK1	DOCK1	3414	0.098	0.55	YES
79	ITGB5	ITGB5	ITGB5	3448	0.097	0.55	YES
80	SHC2	SHC2	SHC2	3501	0.096	0.56	YES
81	PDGFA	PDGFA	PDGFA	3539	0.095	0.56	YES
82	COL2A1	COL2A1	COL2A1	3554	0.094	0.56	YES
83	MAPK8	MAPK8	MAPK8	3701	0.09	0.56	NO
84	COL4A6	COL4A6	COL4A6	3916	0.084	0.55	NO
85	SHC1	SHC1	SHC1	3962	0.083	0.55	NO
86	EGFR	EGFR	EGFR	4058	0.08	0.55	NO
87	BRAF	BRAF	BRAF	4148	0.078	0.55	NO
88	PPP1R12A	PPP1R12A	PPP1R12A	4282	0.075	0.54	NO
89	LAMB2	LAMB2	LAMB2	4320	0.074	0.54	NO
90	CRK	CRK	CRK	4422	0.072	0.54	NO
91	TLN1	TLN1	TLN1	4452	0.072	0.54	NO
92	PTK2	PTK2	PTK2	4536	0.07	0.54	NO
93	PDGFC	PDGFC	PDGFC	4679	0.066	0.53	NO
94	PTEN	PTEN	PTEN	4734	0.065	0.53	NO
95	PIK3R5	PIK3R5	PIK3R5	4794	0.064	0.53	NO
96	PIP5K1C	PIP5K1C	PIP5K1C	4835	0.063	0.53	NO
97	PRKCB	PRKCB	PRKCB	4838	0.063	0.54	NO
98	ITGA6	ITGA6	ITGA6	4881	0.062	0.54	NO
99	MYL2	MYL2	MYL2	4941	0.061	0.54	NO
100	VEGFA	VEGFA	VEGFA	5041	0.059	0.53	NO
101	RAPGEF1	RAPGEF1	RAPGEF1	5102	0.058	0.53	NO
102	SOS1	SOS1	SOS1	5299	0.055	0.52	NO
103	SOS2	SOS2	SOS2	5334	0.054	0.52	NO
104	ARHGAP5	ARHGAP5	ARHGAP5	5353	0.054	0.52	NO
105	FLNB	FLNB	FLNB	5397	0.053	0.52	NO
106	MAPK3	MAPK3	MAPK3	5425	0.053	0.53	NO
107	ELK1	ELK1	ELK1	5474	0.052	0.53	NO
108	PIK3R1	PIK3R1	PIK3R1	5512	0.051	0.53	NO
109	PXN	PXN	PXN	5520	0.051	0.53	NO
110	VASP	VASP	VASP	5740	0.048	0.52	NO
111	RHOA	RHOA	RHOA	5836	0.046	0.51	NO
112	ZYX	ZYX	ZYX	5886	0.045	0.51	NO
113	VAV1	VAV1	VAV1	5912	0.045	0.51	NO
114	AKT1	AKT1	AKT1	6015	0.044	0.51	NO
115	ITGAV	ITGAV	ITGAV	6093	0.043	0.51	NO
116	LAMB3	LAMB3	LAMB3	6160	0.042	0.51	NO
117	JUN	JUN	JUN	6320	0.04	0.5	NO
118	RAP1A	RAP1A	RAP1A	6395	0.038	0.5	NO
119	IGF1R	IGF1R	IGF1R	6660	0.035	0.48	NO
120	CAV2	CAV2	CAV2	6720	0.034	0.48	NO
121	PARVB	PARVB	PARVB	6745	0.034	0.48	NO
122	COL11A2	COL11A2	COL11A2	6772	0.034	0.48	NO
123	MAP2K1	MAP2K1	MAP2K1	6871	0.033	0.48	NO
124	MYL12A	MYL12A	MYL12A	6881	0.032	0.48	NO
125	MAPK10	MAPK10	MAPK10	6965	0.031	0.48	NO
126	CDC42	CDC42	CDC42	7113	0.03	0.47	NO
127	THBS3	THBS3	THBS3	7121	0.03	0.47	NO
128	FIGF	FIGF	FIGF	7283	0.028	0.46	NO
129	ACTN4	ACTN4	ACTN4	7362	0.027	0.46	NO
130	CRKL	CRKL	CRKL	7456	0.026	0.45	NO
131	ACTG1	ACTG1	ACTG1	7717	0.023	0.44	NO
132	PPP1CC	PPP1CC	PPP1CC	7765	0.023	0.44	NO
133	CCND3	CCND3	CCND3	7779	0.022	0.44	NO
134	PAK2	PAK2	PAK2	7803	0.022	0.44	NO
135	GSK3B	GSK3B	GSK3B	7819	0.022	0.44	NO
136	ILK	ILK	ILK	8037	0.019	0.43	NO
137	PPP1CB	PPP1CB	PPP1CB	8144	0.018	0.42	NO
138	LAMA5	LAMA5	LAMA5	8154	0.018	0.42	NO
139	RAF1	RAF1	RAF1	8310	0.016	0.42	NO
140	PIK3CD	PIK3CD	PIK3CD	8314	0.016	0.42	NO
141	RAC2	RAC2	RAC2	8438	0.015	0.41	NO
142	RAP1B	RAP1B	RAP1B	8634	0.013	0.4	NO
143	ACTB	ACTB	ACTB	8675	0.013	0.4	NO
144	MAPK1	MAPK1	MAPK1	8689	0.012	0.4	NO
145	LAMA3	LAMA3	LAMA3	8853	0.011	0.39	NO
146	XIAP	XIAP	XIAP	8962	0.0096	0.38	NO
147	RAC1	RAC1	RAC1	9015	0.0089	0.38	NO
148	ITGB4	ITGB4	ITGB4	9204	0.0068	0.37	NO
149	CAPN2	CAPN2	CAPN2	9210	0.0067	0.37	NO
150	BCAR1	BCAR1	BCAR1	9303	0.0059	0.37	NO
151	BCL2	BCL2	BCL2	9338	0.0056	0.36	NO
152	CCND1	CCND1	CCND1	9649	0.0023	0.35	NO
153	PAK3	PAK3	PAK3	9685	0.0018	0.34	NO
154	BIRC2	BIRC2	BIRC2	9707	0.0016	0.34	NO
155	PDPK1	PDPK1	PDPK1	10122	-0.0028	0.32	NO
156	PRKCA	PRKCA	PRKCA	10479	-0.0067	0.3	NO
157	PARVG	PARVG	PARVG	10593	-0.008	0.3	NO
158	GRB2	GRB2	GRB2	10764	-0.0099	0.29	NO
159	MYL12B	MYL12B	MYL12B	11264	-0.016	0.26	NO
160	MAPK9	MAPK9	MAPK9	11463	-0.018	0.25	NO
161	PIK3R2	PIK3R2	PIK3R2	11871	-0.024	0.23	NO
162	SPP1	SPP1	SPP1	11997	-0.025	0.22	NO
163	PIK3CB	PIK3CB	PIK3CB	12549	-0.033	0.19	NO
164	HRAS	HRAS	HRAS	12579	-0.033	0.19	NO
165	LAMC2	LAMC2	LAMC2	12992	-0.039	0.17	NO
166	AKT2	AKT2	AKT2	13029	-0.039	0.17	NO
167	VAV2	VAV2	VAV2	13057	-0.04	0.17	NO
168	ITGA3	ITGA3	ITGA3	13111	-0.04	0.17	NO
169	PPP1CA	PPP1CA	PPP1CA	13148	-0.041	0.17	NO
170	RASGRF1	RASGRF1	RASGRF1	13245	-0.043	0.17	NO
171	DIAPH1	DIAPH1	DIAPH1	13322	-0.044	0.16	NO
172	VEGFB	VEGFB	VEGFB	13387	-0.045	0.16	NO
173	PAK1	PAK1	PAK1	13413	-0.045	0.16	NO
174	PRKCG	PRKCG	PRKCG	13502	-0.047	0.16	NO
175	TLN2	TLN2	TLN2	13521	-0.047	0.16	NO
176	BAD	BAD	BAD	14073	-0.056	0.13	NO
177	BIRC3	BIRC3	BIRC3	14251	-0.06	0.13	NO
178	MYLK3	MYLK3	MYLK3	14307	-0.061	0.13	NO
179	LAMA1	LAMA1	LAMA1	14658	-0.068	0.11	NO
180	PAK4	PAK4	PAK4	14744	-0.07	0.11	NO
181	SRC	SRC	SRC	14810	-0.071	0.11	NO
182	ITGB6	ITGB6	ITGB6	14979	-0.075	0.1	NO
183	MYLPF	MYLPF	MYLPF	15551	-0.088	0.073	NO
184	MET	MET	MET	15592	-0.089	0.074	NO
185	VAV3	VAV3	VAV3	15699	-0.093	0.072	NO
186	ITGB8	ITGB8	ITGB8	15735	-0.094	0.075	NO
187	ERBB2	ERBB2	ERBB2	16189	-0.11	0.054	NO
188	RAC3	RAC3	RAC3	16228	-0.11	0.057	NO
189	MYL5	MYL5	MYL5	16679	-0.13	0.037	NO
190	PAK6	PAK6	PAK6	16958	-0.15	0.028	NO
191	ITGB7	ITGB7	ITGB7	17084	-0.16	0.028	NO
192	COL4A4	COL4A4	COL4A4	17099	-0.16	0.034	NO
193	PAK7	PAK7	PAK7	17505	-0.19	0.02	NO
194	EGF	EGF	EGF	17688	-0.21	0.018	NO
195	CHAD	CHAD	CHAD	18103	-0.31	0.0086	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 VASCULAR SMOOTH MUSCLE CONTRACTION.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VASCULAR SMOOTH MUSCLE CONTRACTION, 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 WNT SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CNTN1	CNTN1	CNTN1	203	0.39	0.037	YES
2	HEYL	HEYL	HEYL	859	0.25	0.032	YES
3	TLE2	TLE2	TLE2	918	0.24	0.058	YES
4	NOTCH3	NOTCH3	NOTCH3	1156	0.22	0.072	YES
5	DLL4	DLL4	DLL4	1183	0.22	0.098	YES
6	HEY1	HEY1	HEY1	1192	0.22	0.12	YES
7	HES5	HES5	HES5	1235	0.21	0.15	YES
8	HEY2	HEY2	HEY2	1318	0.2	0.17	YES
9	MAMLD1	MAMLD1	MAMLD1	1496	0.19	0.18	YES
10	EIF2C2	EIF2C2	EIF2C2	1536	0.19	0.2	YES
11	MAML3	MAML3	MAML3	1702	0.18	0.22	YES
12	DLL1	DLL1	DLL1	1768	0.17	0.23	YES
13	NOTCH4	NOTCH4	NOTCH4	1793	0.17	0.25	YES
14	JAG2	JAG2	JAG2	1911	0.16	0.26	YES
15	ARRB1	ARRB1	ARRB1	1978	0.16	0.28	YES
16	HDAC9	HDAC9	HDAC9	2156	0.15	0.29	YES
17	HES1	HES1	HES1	2312	0.14	0.3	YES
18	MAML2	MAML2	MAML2	2343	0.14	0.31	YES
19	TLE4	TLE4	TLE4	2468	0.13	0.32	YES
20	JAG1	JAG1	JAG1	2527	0.13	0.34	YES
21	MIB1	MIB1	MIB1	2708	0.12	0.34	YES
22	ADAM17	ADAM17	ADAM17	2867	0.12	0.34	YES
23	HDAC4	HDAC4	HDAC4	2893	0.12	0.36	YES
24	LFNG	LFNG	LFNG	2895	0.12	0.37	YES
25	MYC	MYC	MYC	2969	0.11	0.38	YES
26	ATP2A3	ATP2A3	ATP2A3	2987	0.11	0.39	YES
27	CDK8	CDK8	CDK8	3012	0.11	0.41	YES
28	NOTCH2	NOTCH2	NOTCH2	3083	0.11	0.42	YES
29	HIF1A	HIF1A	HIF1A	3251	0.1	0.42	YES
30	MFNG	MFNG	MFNG	3330	0.1	0.43	YES
31	TNRC6C	TNRC6C	TNRC6C	3657	0.091	0.42	YES
32	DTX1	DTX1	DTX1	3724	0.089	0.43	YES
33	TLE1	TLE1	TLE1	3789	0.087	0.44	YES
34	ADAM10	ADAM10	ADAM10	3987	0.082	0.43	YES
35	ST3GAL6	ST3GAL6	ST3GAL6	4256	0.076	0.43	YES
36	HDAC7	HDAC7	HDAC7	4293	0.075	0.44	YES
37	EIF2C4	EIF2C4	EIF2C4	4371	0.073	0.44	YES
38	EIF2C1	EIF2C1	EIF2C1	4412	0.072	0.45	YES
39	HDAC2	HDAC2	HDAC2	4531	0.07	0.45	YES
40	EIF2C3	EIF2C3	EIF2C3	4609	0.068	0.45	YES
41	MAML1	MAML1	MAML1	4723	0.066	0.46	YES
42	HDAC1	HDAC1	HDAC1	4937	0.061	0.45	NO
43	TNRC6B	TNRC6B	TNRC6B	5248	0.056	0.44	NO
44	HDAC5	HDAC5	HDAC5	5307	0.055	0.44	NO
45	SNW1	SNW1	SNW1	5382	0.054	0.45	NO
46	CREBBP	CREBBP	CREBBP	5671	0.049	0.44	NO
47	EP300	EP300	EP300	5807	0.046	0.44	NO
48	SEL1L	SEL1L	SEL1L	6107	0.042	0.42	NO
49	FBXW7	FBXW7	FBXW7	6216	0.041	0.42	NO
50	JUN	JUN	JUN	6320	0.04	0.42	NO
51	RAB6A	RAB6A	RAB6A	6641	0.035	0.41	NO
52	FURIN	FURIN	FURIN	6799	0.034	0.4	NO
53	NEURL	NEURL	NEURL	6835	0.033	0.41	NO
54	B4GALT1	B4GALT1	B4GALT1	6905	0.032	0.41	NO
55	TP53	TP53	TP53	6994	0.031	0.4	NO
56	ATP2A2	ATP2A2	ATP2A2	7047	0.03	0.41	NO
57	APH1B	APH1B	APH1B	7155	0.029	0.4	NO
58	TFDP1	TFDP1	TFDP1	7164	0.029	0.41	NO
59	TLE3	TLE3	TLE3	7350	0.027	0.4	NO
60	PSEN1	PSEN1	PSEN1	7534	0.025	0.39	NO
61	RBPJ	RBPJ	RBPJ	7723	0.023	0.38	NO
62	NCOR2	NCOR2	NCOR2	7891	0.021	0.38	NO
63	KAT2B	KAT2B	KAT2B	8029	0.02	0.37	NO
64	NCOR1	NCOR1	NCOR1	8069	0.019	0.37	NO
65	TBL1XR1	TBL1XR1	TBL1XR1	8080	0.019	0.38	NO
66	ST3GAL3	ST3GAL3	ST3GAL3	8147	0.018	0.37	NO
67	E2F3	E2F3	E2F3	8255	0.017	0.37	NO
68	TBL1X	TBL1X	TBL1X	8281	0.017	0.37	NO
69	RPS27A	RPS27A	RPS27A	8353	0.016	0.37	NO
70	NUMB	NUMB	NUMB	8524	0.014	0.36	NO
71	NCSTN	NCSTN	NCSTN	8734	0.012	0.35	NO
72	TMED2	TMED2	TMED2	8906	0.01	0.34	NO
73	DTX4	DTX4	DTX4	8919	0.01	0.34	NO
74	UBA52	UBA52	UBA52	9038	0.0086	0.34	NO
75	CUL1	CUL1	CUL1	9172	0.007	0.33	NO
76	POFUT1	POFUT1	POFUT1	9514	0.0036	0.31	NO
77	ARRB2	ARRB2	ARRB2	9588	0.0029	0.31	NO
78	CCND1	CCND1	CCND1	9649	0.0023	0.31	NO
79	APH1A	APH1A	APH1A	9839	0.00016	0.3	NO
80	MIB2	MIB2	MIB2	10022	-0.0019	0.29	NO
81	CCNC	CCNC	CCNC	10193	-0.0037	0.28	NO
82	HDAC3	HDAC3	HDAC3	10271	-0.0047	0.27	NO
83	TNRC6A	TNRC6A	TNRC6A	10466	-0.0066	0.26	NO
84	DTX2	DTX2	DTX2	11770	-0.022	0.2	NO
85	SKP1	SKP1	SKP1	12319	-0.029	0.17	NO
86	MOV10	MOV10	MOV10	12420	-0.031	0.17	NO
87	HDAC8	HDAC8	HDAC8	12464	-0.032	0.17	NO
88	PSEN2	PSEN2	PSEN2	13248	-0.043	0.13	NO
89	KAT2A	KAT2A	KAT2A	13988	-0.055	0.096	NO
90	RFNG	RFNG	RFNG	14135	-0.058	0.095	NO
91	RBX1	RBX1	RBX1	14373	-0.062	0.09	NO
92	HDAC6	HDAC6	HDAC6	14639	-0.067	0.084	NO
93	E2F1	E2F1	E2F1	15325	-0.083	0.056	NO
94	HDAC10	HDAC10	HDAC10	15998	-0.1	0.032	NO
95	PSENEN	PSENEN	PSENEN	16327	-0.12	0.028	NO
96	DLK1	DLK1	DLK1	16441	-0.12	0.036	NO
97	HDAC11	HDAC11	HDAC11	16615	-0.13	0.042	NO
98	ATP2A1	ATP2A1	ATP2A1	17355	-0.18	0.023	NO
99	DNER	DNER	DNER	17740	-0.22	0.028	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 WNT SIGNALING PATHWAY.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG WNT 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 NOTCH SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ITGA1	ITGA1	ITGA1	1612	0.18	-0.019	YES
2	ACTA1	ACTA1	ACTA1	1983	0.16	0.02	YES
3	CAV1	CAV1	CAV1	2155	0.15	0.066	YES
4	FYN	FYN	FYN	2170	0.15	0.12	YES
5	VCL	VCL	VCL	2234	0.14	0.17	YES
6	ACTN1	ACTN1	ACTN1	2236	0.14	0.22	YES
7	PPP1R12B	PPP1R12B	PPP1R12B	2378	0.14	0.27	YES
8	ACTN3	ACTN3	ACTN3	2422	0.13	0.32	YES
9	ACTN2	ACTN2	ACTN2	2800	0.12	0.34	YES
10	ITGB1	ITGB1	ITGB1	2994	0.11	0.37	YES
11	ROCK1	ROCK1	ROCK1	3381	0.099	0.39	YES
12	MAPK8	MAPK8	MAPK8	3701	0.09	0.41	YES
13	SHC1	SHC1	SHC1	3962	0.083	0.42	YES
14	TLN1	TLN1	TLN1	4452	0.072	0.42	YES
15	PTK2	PTK2	PTK2	4536	0.07	0.44	YES
16	RAPGEF1	RAPGEF1	RAPGEF1	5102	0.058	0.44	YES
17	SOS1	SOS1	SOS1	5299	0.055	0.45	YES
18	MAPK3	MAPK3	MAPK3	5425	0.053	0.46	YES
19	PXN	PXN	PXN	5520	0.051	0.47	YES
20	RHOA	RHOA	RHOA	5836	0.046	0.47	YES
21	ZYX	ZYX	ZYX	5886	0.045	0.49	YES
22	TNS1	TNS1	TNS1	5905	0.045	0.5	YES
23	JUN	JUN	JUN	6320	0.04	0.5	YES
24	RAP1A	RAP1A	RAP1A	6395	0.038	0.51	YES
25	MAP2K1	MAP2K1	MAP2K1	6871	0.033	0.49	NO
26	CRKL	CRKL	CRKL	7456	0.026	0.47	NO
27	RAF1	RAF1	RAF1	8310	0.016	0.43	NO
28	MAPK1	MAPK1	MAPK1	8689	0.012	0.41	NO
29	BCAR1	BCAR1	BCAR1	9303	0.0059	0.38	NO
30	CSK	CSK	CSK	9465	0.0042	0.38	NO
31	BCR	BCR	BCR	9813	0.00045	0.36	NO
32	GRB2	GRB2	GRB2	10764	-0.0099	0.31	NO
33	CAPN1	CAPN1	CAPN1	11435	-0.018	0.28	NO
34	MAP2K2	MAP2K2	MAP2K2	11728	-0.022	0.27	NO
35	CAPNS1	CAPNS1	CAPNS1	11943	-0.024	0.27	NO
36	HRAS	HRAS	HRAS	12579	-0.033	0.24	NO
37	SRC	SRC	SRC	14810	-0.071	0.15	NO
38	CAPNS2	CAPNS2	CAPNS2	16071	-0.1	0.12	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 NOTCH SIGNALING PATHWAY.

Figure S56. 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 HEDGEHOG SIGNALING PATHWAY

Table S29. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PDGFRA	PDGFRA	PDGFRA	9	0.57	0.093	YES
2	ADCY1	ADCY1	ADCY1	240	0.38	0.14	YES
3	CAMK4	CAMK4	CAMK4	389	0.34	0.19	YES
4	PDE1A	PDE1A	PDE1A	685	0.28	0.22	YES
5	ADCY4	ADCY4	ADCY4	1031	0.23	0.24	YES
6	PDGFRB	PDGFRB	PDGFRB	1035	0.23	0.28	YES
7	PRKAR2A	PRKAR2A	PRKAR2A	1818	0.17	0.26	YES
8	PDGFB	PDGFB	PDGFB	1989	0.16	0.28	YES
9	PDE1B	PDE1B	PDE1B	2259	0.14	0.28	YES
10	ADCY3	ADCY3	ADCY3	2295	0.14	0.3	YES
11	AKT3	AKT3	AKT3	2621	0.13	0.31	YES
12	FOXO1	FOXO1	FOXO1	2667	0.12	0.32	YES
13	PIK3CA	PIK3CA	PIK3CA	2892	0.12	0.33	YES
14	PHLPP1	PHLPP1	PHLPP1	3117	0.11	0.34	YES
15	PRKAR2B	PRKAR2B	PRKAR2B	3130	0.11	0.35	YES
16	PDGFA	PDGFA	PDGFA	3539	0.095	0.35	YES
17	FOXO4	FOXO4	FOXO4	3928	0.083	0.34	YES
18	CREB1	CREB1	CREB1	4132	0.079	0.34	YES
19	NR4A1	NR4A1	NR4A1	4337	0.074	0.34	YES
20	CRK	CRK	CRK	4422	0.072	0.35	YES
21	CALM1	CALM1	CALM1	4493	0.071	0.36	YES
22	ADCY8	ADCY8	ADCY8	4687	0.066	0.36	YES
23	FOXO3	FOXO3	FOXO3	4703	0.066	0.37	YES
24	PTEN	PTEN	PTEN	4734	0.065	0.38	YES
25	PLCG1	PLCG1	PLCG1	4753	0.065	0.38	YES
26	ITPR2	ITPR2	ITPR2	4986	0.06	0.38	YES
27	NCK2	NCK2	NCK2	4991	0.06	0.39	YES
28	RAPGEF1	RAPGEF1	RAPGEF1	5102	0.058	0.4	YES
29	SOS1	SOS1	SOS1	5299	0.055	0.39	YES
30	TRIB3	TRIB3	TRIB3	5381	0.054	0.4	YES
31	MAPK3	MAPK3	MAPK3	5425	0.053	0.4	YES
32	PIK3R1	PIK3R1	PIK3R1	5512	0.051	0.41	YES
33	STAT3	STAT3	STAT3	5566	0.05	0.41	YES
34	CDKN1B	CDKN1B	CDKN1B	5697	0.048	0.41	YES
35	PRKACB	PRKACB	PRKACB	5713	0.048	0.42	YES
36	MTOR	MTOR	MTOR	5788	0.047	0.42	YES
37	NRAS	NRAS	NRAS	5791	0.047	0.43	YES
38	AKT1	AKT1	AKT1	6015	0.044	0.43	NO
39	CDK1	CDK1	CDK1	6265	0.04	0.42	NO
40	ADCY2	ADCY2	ADCY2	6581	0.036	0.41	NO
41	MAP2K1	MAP2K1	MAP2K1	6871	0.033	0.4	NO
42	ADCY7	ADCY7	ADCY7	6977	0.031	0.4	NO
43	PRKAR1A	PRKAR1A	PRKAR1A	7006	0.031	0.4	NO
44	RASA1	RASA1	RASA1	7022	0.031	0.4	NO
45	CRKL	CRKL	CRKL	7456	0.026	0.38	NO
46	PRKACA	PRKACA	PRKACA	7491	0.026	0.39	NO
47	YWHAB	YWHAB	YWHAB	7583	0.025	0.39	NO
48	STAT5B	STAT5B	STAT5B	7690	0.024	0.38	NO
49	ADCY5	ADCY5	ADCY5	7709	0.023	0.39	NO
50	NCK1	NCK1	NCK1	7715	0.023	0.39	NO
51	TSC2	TSC2	TSC2	7845	0.022	0.39	NO
52	CDKN1A	CDKN1A	CDKN1A	7965	0.02	0.38	NO
53	RAF1	RAF1	RAF1	8310	0.016	0.37	NO
54	ADRBK1	ADRBK1	ADRBK1	8337	0.016	0.37	NO
55	KRAS	KRAS	KRAS	8394	0.016	0.37	NO
56	ADCY6	ADCY6	ADCY6	8463	0.015	0.37	NO
57	MAPK1	MAPK1	MAPK1	8689	0.012	0.36	NO
58	PRKCE	PRKCE	PRKCE	9094	0.0079	0.34	NO
59	CASP9	CASP9	CASP9	9260	0.0062	0.33	NO
60	BCAR1	BCAR1	BCAR1	9303	0.0059	0.33	NO
61	ADCY9	ADCY9	ADCY9	9308	0.0058	0.33	NO
62	MDM2	MDM2	MDM2	9493	0.0038	0.32	NO
63	CHUK	CHUK	CHUK	10007	-0.0017	0.29	NO
64	ITPR3	ITPR3	ITPR3	10077	-0.0024	0.29	NO
65	PDPK1	PDPK1	PDPK1	10122	-0.0028	0.28	NO
66	RICTOR	RICTOR	RICTOR	10181	-0.0036	0.28	NO
67	MAPKAP1	MAPKAP1	MAPKAP1	10351	-0.0054	0.27	NO
68	PRKCA	PRKCA	PRKCA	10479	-0.0067	0.27	NO
69	CALM2	CALM2	CALM2	10491	-0.0069	0.27	NO
70	GRB2	GRB2	GRB2	10764	-0.0099	0.25	NO
71	CALM3	CALM3	CALM3	10872	-0.011	0.25	NO
72	GSK3A	GSK3A	GSK3A	11174	-0.015	0.24	NO
73	PRKAR1B	PRKAR1B	PRKAR1B	11253	-0.016	0.23	NO
74	STAT5A	STAT5A	STAT5A	11355	-0.017	0.23	NO
75	STAT1	STAT1	STAT1	11641	-0.02	0.22	NO
76	MAP2K2	MAP2K2	MAP2K2	11728	-0.022	0.22	NO
77	PIK3R2	PIK3R2	PIK3R2	11871	-0.024	0.21	NO
78	STAT6	STAT6	STAT6	12013	-0.025	0.21	NO
79	PIK3CB	PIK3CB	PIK3CB	12549	-0.033	0.19	NO
80	HRAS	HRAS	HRAS	12579	-0.033	0.19	NO
81	AKT2	AKT2	AKT2	13029	-0.039	0.17	NO
82	AKT1S1	AKT1S1	AKT1S1	13138	-0.041	0.17	NO
83	PRKCG	PRKCG	PRKCG	13502	-0.047	0.16	NO
84	MLST8	MLST8	MLST8	13643	-0.049	0.16	NO
85	RPS6KB2	RPS6KB2	RPS6KB2	13896	-0.053	0.16	NO
86	BAD	BAD	BAD	14073	-0.056	0.16	NO
87	SRC	SRC	SRC	14810	-0.071	0.13	NO
88	PRKCD	PRKCD	PRKCD	14855	-0.072	0.14	NO
89	THEM4	THEM4	THEM4	15546	-0.088	0.11	NO
90	GRB7	GRB7	GRB7	17820	-0.23	0.024	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 HEDGEHOG SIGNALING PATHWAY.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG HEDGEHOG 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 TGF BETA SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ADCY1	ADCY1	ADCY1	240	0.38	0.13	YES
2	NFATC2	NFATC2	NFATC2	722	0.27	0.21	YES
3	NFATC4	NFATC4	NFATC4	773	0.26	0.31	YES
4	PRKAR2A	PRKAR2A	PRKAR2A	1818	0.17	0.32	YES
5	FOS	FOS	FOS	1909	0.16	0.38	YES
6	GNAI1	GNAI1	GNAI1	2838	0.12	0.37	YES
7	PRKAR2B	PRKAR2B	PRKAR2B	3130	0.11	0.39	YES
8	PPP3CA	PPP3CA	PPP3CA	3162	0.11	0.43	YES
9	CREB1	CREB1	CREB1	4132	0.079	0.41	YES
10	NFATC1	NFATC1	NFATC1	4195	0.077	0.44	YES
11	CALM1	CALM1	CALM1	4493	0.071	0.45	YES
12	PLCG1	PLCG1	PLCG1	4753	0.065	0.46	YES
13	PRKCB	PRKCB	PRKCB	4838	0.063	0.48	YES
14	PPP3CC	PPP3CC	PPP3CC	4860	0.063	0.5	YES
15	GNB1	GNB1	GNB1	5220	0.056	0.5	YES
16	PPP3CB	PPP3CB	PPP3CB	5250	0.056	0.52	YES
17	MAPK3	MAPK3	MAPK3	5425	0.053	0.53	YES
18	ELK1	ELK1	ELK1	5474	0.052	0.55	YES
19	PRKACB	PRKACB	PRKACB	5713	0.048	0.56	YES
20	GNAQ	GNAQ	GNAQ	5921	0.045	0.56	YES
21	NFATC3	NFATC3	NFATC3	6218	0.041	0.56	YES
22	JUN	JUN	JUN	6320	0.04	0.57	YES
23	MAP2K1	MAP2K1	MAP2K1	6871	0.033	0.55	NO
24	PRKAR1A	PRKAR1A	PRKAR1A	7006	0.031	0.56	NO
25	GNGT1	GNGT1	GNGT1	7409	0.026	0.55	NO
26	RPS6KA3	RPS6KA3	RPS6KA3	7510	0.025	0.55	NO
27	RAF1	RAF1	RAF1	8310	0.016	0.51	NO
28	GNAS	GNAS	GNAS	8944	0.0098	0.48	NO
29	PRKCA	PRKCA	PRKCA	10479	-0.0067	0.4	NO
30	CALM2	CALM2	CALM2	10491	-0.0069	0.4	NO
31	CALM3	CALM3	CALM3	10872	-0.011	0.39	NO
32	PRKAR1B	PRKAR1B	PRKAR1B	11253	-0.016	0.37	NO
33	HRAS	HRAS	HRAS	12579	-0.033	0.31	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 TGF BETA SIGNALING PATHWAY.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus4 enriched pathways

Table 6. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus4. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	44	genes.ES.table	0.53	1.8	0.026	1	0.64	0.52	0.3	0.37	0.84	0.47
KEGG P53 SIGNALING PATHWAY	67	genes.ES.table	0.53	1.7	0.016	0.78	0.83	0.25	0.13	0.22	0.41	0.25
KEGG CYTOSOLIC DNA SENSING PATHWAY	45	genes.ES.table	0.58	1.7	0.018	0.91	0.83	0.33	0.16	0.28	0.48	0.28
PID AURORA B PATHWAY	39	genes.ES.table	0.74	1.7	0.004	1	0.76	0.38	0.083	0.35	0.61	0.36
PID E2F PATHWAY	69	genes.ES.table	0.54	1.7	0.025	0.84	0.83	0.25	0.14	0.21	0.44	0.26
PID INTEGRIN2 PATHWAY	29	genes.ES.table	0.69	1.6	0.014	0.74	0.87	0.62	0.16	0.52	0.41	0.24
REACTOME ANTIGEN PROCESSING CROSS PRESENTATION	72	genes.ES.table	0.47	1.7	0.049	0.77	0.85	0.6	0.36	0.38	0.42	0.25
REACTOME ORC1 REMOVAL FROM CHROMATIN	59	genes.ES.table	0.51	1.7	0.062	0.95	0.79	0.58	0.36	0.37	0.46	0.29
REACTOME ACTIVATION OF NF KAPPAB IN B CELLS	61	genes.ES.table	0.42	1.7	0.055	0.76	0.84	0.51	0.36	0.33	0.39	0.24
REACTOME MHC CLASS II ANTIGEN PRESENTATION	89	genes.ES.table	0.45	1.6	0.034	0.7	0.88	0.39	0.25	0.3	0.39	0.23

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CD8B	CD8B	CD8B	552	0.34	0.013	YES
2	CD28	CD28	CD28	712	0.32	0.044	YES
3	RCC1	RCC1	RCC1	943	0.28	0.067	YES
4	LCK	LCK	LCK	1147	0.25	0.088	YES
5	APOBEC3G	APOBEC3G	APOBEC3G	1332	0.24	0.11	YES
6	PSMA8	PSMA8	PSMA8	1581	0.22	0.12	YES
7	DOCK2	DOCK2	DOCK2	1662	0.21	0.14	YES
8	CD247	CD247	CD247	1773	0.2	0.16	YES
9	HCK	HCK	HCK	1818	0.2	0.19	YES
10	PSMB10	PSMB10	PSMB10	1945	0.19	0.2	YES
11	NUP210	NUP210	NUP210	1998	0.18	0.22	YES
12	HMGA1	HMGA1	HMGA1	2035	0.18	0.24	YES
13	CD4	CD4	CD4	2645	0.14	0.23	YES
14	AP1M2	AP1M2	AP1M2	3089	0.13	0.22	YES
15	PSMB9	PSMB9	PSMB9	3151	0.12	0.23	YES
16	PSMD14	PSMD14	PSMD14	3340	0.12	0.24	YES
17	PSMA5	PSMA5	PSMA5	3406	0.11	0.25	YES
18	PSME2	PSME2	PSME2	3498	0.11	0.26	YES
19	AP1M1	AP1M1	AP1M1	3798	0.1	0.25	YES
20	PSMB3	PSMB3	PSMB3	3979	0.094	0.26	YES
21	TCEB1	TCEB1	TCEB1	4086	0.091	0.26	YES
22	BANF1	BANF1	BANF1	4211	0.088	0.26	YES
23	TCEB2	TCEB2	TCEB2	4283	0.086	0.27	YES
24	AP2S1	AP2S1	AP2S1	4469	0.081	0.27	YES
25	AP2A1	AP2A1	AP2A1	4519	0.08	0.28	YES
26	PSMB4	PSMB4	PSMB4	4606	0.078	0.28	YES
27	RAN	RAN	RAN	4634	0.077	0.29	YES
28	PSMB2	PSMB2	PSMB2	4675	0.076	0.3	YES
29	RBX1	RBX1	RBX1	4740	0.075	0.31	YES
30	NUP37	NUP37	NUP37	4747	0.075	0.32	YES
31	PSMC4	PSMC4	PSMC4	4886	0.072	0.32	YES
32	NUPL2	NUPL2	NUPL2	4919	0.071	0.32	YES
33	PSMA7	PSMA7	PSMA7	5338	0.062	0.31	YES
34	NUP62	NUP62	NUP62	5447	0.06	0.31	YES
35	PSMB8	PSMB8	PSMB8	5451	0.06	0.32	YES
36	PPIA	PPIA	PPIA	5506	0.059	0.32	YES
37	PSMC2	PSMC2	PSMC2	5508	0.059	0.33	YES
38	RANGAP1	RANGAP1	RANGAP1	5520	0.059	0.34	YES
39	PSMD4	PSMD4	PSMD4	5525	0.058	0.34	YES
40	PSMD7	PSMD7	PSMD7	5570	0.058	0.35	YES
41	PSMD13	PSMD13	PSMD13	5641	0.057	0.35	YES
42	PSMA4	PSMA4	PSMA4	5646	0.056	0.36	YES
43	PSME4	PSME4	PSME4	5663	0.056	0.36	YES
44	RAE1	RAE1	RAE1	5682	0.056	0.37	YES
45	PSMA1	PSMA1	PSMA1	5693	0.056	0.38	YES
46	AAAS	AAAS	AAAS	5906	0.052	0.37	YES
47	HLA-A	HLA-A	HLA-A	5912	0.052	0.38	YES
48	PSMD8	PSMD8	PSMD8	5933	0.051	0.38	YES
49	AP1B1	AP1B1	AP1B1	5935	0.051	0.39	YES
50	PSMA2	PSMA2	PSMA2	6013	0.05	0.39	YES
51	PSMB6	PSMB6	PSMB6	6090	0.049	0.4	YES
52	NUP93	NUP93	NUP93	6177	0.047	0.4	YES
53	AP1S1	AP1S1	AP1S1	6212	0.047	0.4	YES
54	AP2M1	AP2M1	AP2M1	6279	0.046	0.4	YES
55	PSMD9	PSMD9	PSMD9	6286	0.046	0.41	YES
56	RANBP1	RANBP1	RANBP1	6379	0.044	0.41	YES
57	PSMD2	PSMD2	PSMD2	6527	0.042	0.4	NO
58	UBA52	UBA52	UBA52	6586	0.041	0.41	NO
59	NUP107	NUP107	NUP107	6783	0.037	0.4	NO
60	RAC1	RAC1	RAC1	7167	0.032	0.38	NO
61	PSMC5	PSMC5	PSMC5	7226	0.031	0.38	NO
62	PSMD1	PSMD1	PSMD1	7275	0.03	0.39	NO
63	ARF1	ARF1	ARF1	7317	0.03	0.39	NO
64	PSMD3	PSMD3	PSMD3	7330	0.03	0.39	NO
65	PSMC3	PSMC3	PSMC3	7444	0.028	0.39	NO
66	PACS1	PACS1	PACS1	7608	0.026	0.38	NO
67	RPS27A	RPS27A	RPS27A	7637	0.025	0.38	NO
68	PSMF1	PSMF1	PSMF1	7677	0.025	0.38	NO
69	PSMB1	PSMB1	PSMB1	7946	0.021	0.37	NO
70	PSMD10	PSMD10	PSMD10	8053	0.02	0.37	NO
71	PAK2	PAK2	PAK2	8079	0.02	0.37	NO
72	PSMD11	PSMD11	PSMD11	8085	0.02	0.37	NO
73	POM121	POM121	POM121	8196	0.018	0.37	NO
74	SLC25A6	SLC25A6	SLC25A6	8205	0.018	0.37	NO
75	B2M	B2M	B2M	8691	0.011	0.35	NO
76	ELMO1	ELMO1	ELMO1	8833	0.0095	0.34	NO
77	PSMC1	PSMC1	PSMC1	8857	0.0092	0.34	NO
78	PSMD12	PSMD12	PSMD12	8951	0.0081	0.34	NO
79	NPM1	NPM1	NPM1	9060	0.0069	0.33	NO
80	KPNB1	KPNB1	KPNB1	9082	0.0067	0.33	NO
81	ATP6V1H	ATP6V1H	ATP6V1H	9094	0.0065	0.33	NO
82	PSMA6	PSMA6	PSMA6	9098	0.0065	0.33	NO
83	XPO1	XPO1	XPO1	9102	0.0064	0.33	NO
84	PSME1	PSME1	PSME1	9110	0.0063	0.33	NO
85	NUP50	NUP50	NUP50	9117	0.0062	0.33	NO
86	PSMA3	PSMA3	PSMA3	9175	0.0055	0.33	NO
87	NUP85	NUP85	NUP85	9193	0.0052	0.33	NO
88	PSMB5	PSMB5	PSMB5	9342	0.0032	0.32	NO
89	PSMD6	PSMD6	PSMD6	9575	0.00057	0.31	NO
90	NUP88	NUP88	NUP88	9761	-0.0016	0.3	NO
91	SLC25A5	SLC25A5	SLC25A5	9879	-0.003	0.29	NO
92	SKP1	SKP1	SKP1	10040	-0.0051	0.28	NO
93	TPR	TPR	TPR	10250	-0.0074	0.27	NO
94	NUP43	NUP43	NUP43	10259	-0.0075	0.27	NO
95	PSMB7	PSMB7	PSMB7	10453	-0.0096	0.26	NO
96	CDK9	CDK9	CDK9	10706	-0.013	0.25	NO
97	NUP205	NUP205	NUP205	10765	-0.013	0.25	NO
98	KPNA1	KPNA1	KPNA1	10948	-0.016	0.24	NO
99	NUPL1	NUPL1	NUPL1	11223	-0.02	0.23	NO
100	AP1S2	AP1S2	AP1S2	11407	-0.022	0.22	NO
101	NUP155	NUP155	NUP155	11494	-0.023	0.22	NO
102	AP2B1	AP2B1	AP2B1	11575	-0.024	0.22	NO
103	AP1G1	AP1G1	AP1G1	11774	-0.027	0.21	NO
104	AP2A2	AP2A2	AP2A2	12434	-0.037	0.18	NO
105	NUP35	NUP35	NUP35	12509	-0.038	0.18	NO
106	NUP54	NUP54	NUP54	12806	-0.043	0.17	NO
107	NUP133	NUP133	NUP133	12835	-0.043	0.18	NO
108	RANBP2	RANBP2	RANBP2	13016	-0.046	0.17	NO
109	PSMD5	PSMD5	PSMD5	13285	-0.05	0.16	NO
110	NUP188	NUP188	NUP188	13394	-0.052	0.16	NO
111	NUP214	NUP214	NUP214	13454	-0.053	0.17	NO
112	PSMC6	PSMC6	PSMC6	13553	-0.055	0.17	NO
113	NUP153	NUP153	NUP153	13741	-0.058	0.16	NO
114	SEH1L	SEH1L	SEH1L	13788	-0.059	0.17	NO
115	BTRC	BTRC	BTRC	13803	-0.059	0.18	NO
116	CUL5	CUL5	CUL5	14724	-0.078	0.14	NO
117	SLC25A4	SLC25A4	SLC25A4	15502	-0.1	0.1	NO
118	PSIP1	PSIP1	PSIP1	15548	-0.1	0.12	NO
119	FYN	FYN	FYN	15712	-0.11	0.12	NO
120	CCNT1	CCNT1	CCNT1	16636	-0.16	0.089	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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

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

genes ES table in pathway: KEGG P53 SIGNALING PATHWAY

Table S32. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GFPT2	GFPT2	GFPT2	9	0.74	0.17	YES
2	HK3	HK3	HK3	754	0.31	0.2	YES
3	NPL	NPL	NPL	906	0.29	0.26	YES
4	CHIT1	CHIT1	CHIT1	987	0.27	0.31	YES
5	GALK1	GALK1	GALK1	1830	0.2	0.31	YES
6	HK2	HK2	HK2	1938	0.19	0.35	YES
7	PMM2	PMM2	PMM2	2516	0.15	0.35	YES
8	GALE	GALE	GALE	2597	0.15	0.38	YES
9	GMPPB	GMPPB	GMPPB	2778	0.14	0.4	YES
10	GCK	GCK	GCK	2889	0.13	0.43	YES
11	TSTA3	TSTA3	TSTA3	2912	0.13	0.46	YES
12	GMPPA	GMPPA	GMPPA	3361	0.12	0.46	YES
13	CMAS	CMAS	CMAS	4160	0.089	0.44	YES
14	PGM1	PGM1	PGM1	4203	0.088	0.45	YES
15	NAGK	NAGK	NAGK	4525	0.08	0.45	YES
16	UGDH	UGDH	UGDH	4636	0.077	0.47	YES
17	GMDS	GMDS	GMDS	4681	0.076	0.48	YES
18	GNPDA1	GNPDA1	GNPDA1	4943	0.07	0.48	YES
19	UGP2	UGP2	UGP2	5200	0.065	0.48	YES
20	NANS	NANS	NANS	5318	0.063	0.49	YES
21	HEXA	HEXA	HEXA	5412	0.061	0.5	YES
22	HK1	HK1	HK1	5421	0.061	0.51	YES
23	CYB5R3	CYB5R3	CYB5R3	5431	0.06	0.53	YES
24	AMDHD2	AMDHD2	AMDHD2	6368	0.044	0.48	NO
25	HEXB	HEXB	HEXB	6652	0.04	0.48	NO
26	UAP1	UAP1	UAP1	6705	0.039	0.48	NO
27	GPI	GPI	GPI	6764	0.038	0.49	NO
28	PGM3	PGM3	PGM3	6921	0.035	0.49	NO
29	RENBP	RENBP	RENBP	8121	0.019	0.43	NO
30	GFPT1	GFPT1	GFPT1	8125	0.019	0.43	NO
31	FUK	FUK	FUK	8270	0.017	0.43	NO
32	CYB5R1	CYB5R1	CYB5R1	10476	-0.0099	0.31	NO
33	MPI	MPI	MPI	10763	-0.013	0.3	NO
34	NANP	NANP	NANP	11164	-0.019	0.28	NO
35	CHIA	CHIA	CHIA	11211	-0.02	0.28	NO
36	UXS1	UXS1	UXS1	11253	-0.02	0.28	NO
37	PGM2	PGM2	PGM2	11521	-0.024	0.27	NO
38	GALK2	GALK2	GALK2	11722	-0.026	0.27	NO
39	FPGT	FPGT	FPGT	12138	-0.032	0.25	NO
40	GNPDA2	GNPDA2	GNPDA2	12186	-0.033	0.26	NO
41	GALT	GALT	GALT	13947	-0.062	0.18	NO
42	GNPNAT1	GNPNAT1	GNPNAT1	14143	-0.066	0.18	NO
43	PMM1	PMM1	PMM1	14474	-0.073	0.18	NO
44	GNE	GNE	GNE	16081	-0.12	0.12	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 P53 SIGNALING PATHWAY.

Figure S64. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG P53 SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG CYTOSOLIC DNA SENSING PATHWAY

Table S33. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SAA1	SAA1	SAA1	2	0.93	0.035	YES
2	LBP	LBP	LBP	14	0.67	0.06	YES
3	AIM2	AIM2	AIM2	47	0.57	0.08	YES
4	CRP	CRP	CRP	121	0.48	0.094	YES
5	MBL2	MBL2	MBL2	189	0.44	0.11	YES
6	C2	C2	C2	231	0.42	0.12	YES
7	ZBP1	ZBP1	ZBP1	240	0.42	0.14	YES
8	NOD2	NOD2	NOD2	263	0.42	0.15	YES
9	C1S	C1S	C1S	279	0.41	0.17	YES
10	C8G	C8G	C8G	305	0.4	0.18	YES
11	LY96	LY96	LY96	346	0.39	0.19	YES
12	CFHR3	CFHR3	CFHR3	356	0.39	0.21	YES
13	IKBKE	IKBKE	IKBKE	442	0.37	0.22	YES
14	TLR6	TLR6	TLR6	563	0.34	0.22	YES
15	CCR6	CCR6	CCR6	586	0.34	0.23	YES
16	CARD9	CARD9	CARD9	597	0.34	0.25	YES
17	PYCARD	PYCARD	PYCARD	612	0.33	0.26	YES
18	MEFV	MEFV	MEFV	629	0.33	0.27	YES
19	TLR10	TLR10	TLR10	684	0.32	0.28	YES
20	PSTPIP1	PSTPIP1	PSTPIP1	695	0.32	0.29	YES
21	IFNB1	IFNB1	IFNB1	728	0.31	0.3	YES
22	C9	C9	C9	792	0.3	0.31	YES
23	C3	C3	C3	858	0.29	0.32	YES
24	S100B	S100B	S100B	887	0.29	0.33	YES
25	CFB	CFB	CFB	931	0.28	0.33	YES
26	TLR8	TLR8	TLR8	974	0.28	0.34	YES
27	CFD	CFD	CFD	1006	0.27	0.35	YES
28	NLRC4	NLRC4	NLRC4	1041	0.27	0.36	YES
29	TLR9	TLR9	TLR9	1046	0.27	0.37	YES
30	C4BPA	C4BPA	C4BPA	1062	0.26	0.38	YES
31	CD180	CD180	CD180	1083	0.26	0.39	YES
32	BIRC3	BIRC3	BIRC3	1092	0.26	0.4	YES
33	CR1	CR1	CR1	1127	0.26	0.4	YES
34	TICAM2	TICAM2	TICAM2	1166	0.25	0.41	YES
35	CFH	CFH	CFH	1189	0.25	0.42	YES
36	LY86	LY86	LY86	1256	0.25	0.43	YES
37	TLR7	TLR7	TLR7	1341	0.24	0.43	YES
38	TLR2	TLR2	TLR2	1363	0.24	0.44	YES
39	CDK1	CDK1	CDK1	1537	0.22	0.44	YES
40	CCR2	CCR2	CCR2	1553	0.22	0.44	YES
41	C1QB	C1QB	C1QB	1598	0.22	0.45	YES
42	TLR5	TLR5	TLR5	1600	0.22	0.46	YES
43	BTK	BTK	BTK	1708	0.21	0.46	YES
44	C1QC	C1QC	C1QC	1748	0.2	0.46	YES
45	IRF7	IRF7	IRF7	1851	0.2	0.47	YES
46	C1QA	C1QA	C1QA	1882	0.19	0.47	YES
47	CD14	CD14	CD14	2028	0.18	0.47	YES
48	RIPK2	RIPK2	RIPK2	2271	0.17	0.46	YES
49	TMEM189-UBE2V1	TMEM189-UBE2V1	TMEM189-UBE2V1	2285	0.17	0.47	YES
50	CASP4	CASP4	CASP4	2356	0.16	0.47	YES
51	UNC93B1	UNC93B1	UNC93B1	2481	0.15	0.47	YES
52	CFI	CFI	CFI	2486	0.15	0.48	YES
53	CD4	CD4	CD4	2645	0.14	0.47	YES
54	CTSS	CTSS	CTSS	2646	0.14	0.48	YES
55	NLRP3	NLRP3	NLRP3	2666	0.14	0.48	YES
56	CASP1	CASP1	CASP1	2682	0.14	0.49	YES
57	TLR1	TLR1	TLR1	2695	0.14	0.49	YES
58	P2RX7	P2RX7	P2RX7	2930	0.13	0.48	NO
59	CASP8	CASP8	CASP8	3317	0.12	0.47	NO
60	RIPK3	RIPK3	RIPK3	3389	0.11	0.47	NO
61	IRAK1	IRAK1	IRAK1	3463	0.11	0.47	NO
62	ISG15	ISG15	ISG15	3604	0.11	0.46	NO
63	PROS1	PROS1	PROS1	3855	0.098	0.46	NO
64	HSP90B1	HSP90B1	HSP90B1	3883	0.097	0.46	NO
65	CAPZA1	CAPZA1	CAPZA1	3898	0.097	0.46	NO
66	LGALS3	LGALS3	LGALS3	3978	0.094	0.46	NO
67	PANX1	PANX1	PANX1	3982	0.094	0.46	NO
68	RPS6KA1	RPS6KA1	RPS6KA1	4018	0.093	0.46	NO
69	DHX58	DHX58	DHX58	4130	0.09	0.46	NO
70	IRF1	IRF1	IRF1	4146	0.09	0.46	NO
71	CTSB	CTSB	CTSB	4172	0.089	0.47	NO
72	CTSK	CTSK	CTSK	4217	0.088	0.47	NO
73	DUSP4	DUSP4	DUSP4	4243	0.087	0.47	NO
74	C4A	C4A	C4A	4454	0.082	0.46	NO
75	RNF135	RNF135	RNF135	4478	0.081	0.46	NO
76	MYD88	MYD88	MYD88	4538	0.08	0.46	NO
77	UBA7	UBA7	UBA7	4574	0.079	0.46	NO
78	CNPY3	CNPY3	CNPY3	4624	0.078	0.46	NO
79	UBE2L6	UBE2L6	UBE2L6	4641	0.077	0.46	NO
80	FADD	FADD	FADD	4730	0.075	0.46	NO
81	EEA1	EEA1	EEA1	4738	0.075	0.46	NO
82	MAPK13	MAPK13	MAPK13	4744	0.075	0.47	NO
83	ART1	ART1	ART1	4878	0.072	0.46	NO
84	IKBKG	IKBKG	IKBKG	4911	0.071	0.46	NO
85	NFKB2	NFKB2	NFKB2	4926	0.071	0.47	NO
86	DDOST	DDOST	DDOST	5165	0.066	0.46	NO
87	ELK1	ELK1	ELK1	5187	0.065	0.46	NO
88	IRF3	IRF3	IRF3	5213	0.065	0.46	NO
89	BCL2L1	BCL2L1	BCL2L1	5289	0.063	0.46	NO
90	UBE2D1	UBE2D1	UBE2D1	5319	0.063	0.46	NO
91	MAP2K2	MAP2K2	MAP2K2	5601	0.057	0.44	NO
92	DNM2	DNM2	DNM2	5668	0.056	0.44	NO
93	ATG12	ATG12	ATG12	5706	0.055	0.44	NO
94	CYLD	CYLD	CYLD	5807	0.053	0.44	NO
95	TICAM1	TICAM1	TICAM1	5970	0.051	0.43	NO
96	DEFB1	DEFB1	DEFB1	6033	0.05	0.43	NO
97	PRKCSH	PRKCSH	PRKCSH	6080	0.049	0.43	NO
98	IRF2	IRF2	IRF2	6228	0.046	0.42	NO
99	TBK1	TBK1	TBK1	6255	0.046	0.42	NO
100	NLRC5	NLRC5	NLRC5	6321	0.045	0.42	NO
101	MAPK9	MAPK9	MAPK9	6482	0.042	0.41	NO
102	JUN	JUN	JUN	6495	0.042	0.42	NO
103	UBA52	UBA52	UBA52	6586	0.041	0.41	NO
104	TNFAIP3	TNFAIP3	TNFAIP3	6617	0.04	0.41	NO
105	TRAF3	TRAF3	TRAF3	6702	0.039	0.41	NO
106	TRAF2	TRAF2	TRAF2	6789	0.037	0.4	NO
107	UBE2D2	UBE2D2	UBE2D2	6950	0.035	0.4	NO
108	NFKBIB	NFKBIB	NFKBIB	7112	0.032	0.39	NO
109	MAPK7	MAPK7	MAPK7	7124	0.032	0.39	NO
110	IRAK4	IRAK4	IRAK4	7359	0.029	0.38	NO
111	RPS6KA3	RPS6KA3	RPS6KA3	7421	0.028	0.38	NO
112	TLR3	TLR3	TLR3	7434	0.028	0.38	NO
113	DDX58	DDX58	DDX58	7445	0.028	0.38	NO
114	CASP9	CASP9	CASP9	7498	0.027	0.38	NO
115	CTSL1	CTSL1	CTSL1	7521	0.027	0.38	NO
116	CASP2	CASP2	CASP2	7562	0.026	0.37	NO
117	OTUD5	OTUD5	OTUD5	7626	0.026	0.37	NO
118	RPS27A	RPS27A	RPS27A	7637	0.025	0.37	NO
119	MAPKAPK2	MAPKAPK2	MAPKAPK2	7856	0.022	0.36	NO
120	TANK	TANK	TANK	7883	0.022	0.36	NO
121	BIRC2	BIRC2	BIRC2	7909	0.022	0.36	NO
122	TXN	TXN	TXN	7954	0.021	0.36	NO
123	CASP10	CASP10	CASP10	8006	0.02	0.36	NO
124	MAPK11	MAPK11	MAPK11	8347	0.016	0.34	NO
125	MAP2K1	MAP2K1	MAP2K1	8389	0.016	0.34	NO
126	PPP2R1A	PPP2R1A	PPP2R1A	8408	0.016	0.34	NO
127	MAPK14	MAPK14	MAPK14	8425	0.015	0.34	NO
128	AGER	AGER	AGER	8569	0.013	0.33	NO
129	NLRX1	NLRX1	NLRX1	8969	0.0079	0.31	NO
130	TAX1BP1	TAX1BP1	TAX1BP1	9038	0.0072	0.3	NO
131	LGMN	LGMN	LGMN	9112	0.0062	0.3	NO
132	MAPKAPK3	MAPKAPK3	MAPKAPK3	9123	0.0061	0.3	NO
133	NLRP1	NLRP1	NLRP1	9158	0.0057	0.3	NO
134	PPP2CA	PPP2CA	PPP2CA	9292	0.0038	0.29	NO
135	UBE2N	UBE2N	UBE2N	9481	0.0016	0.28	NO
136	TAB3	TAB3	TAB3	9716	-0.00095	0.27	NO
137	TAB1	TAB1	TAB1	9903	-0.0033	0.26	NO
138	RELA	RELA	RELA	9920	-0.0036	0.26	NO
139	RIPK1	RIPK1	RIPK1	10186	-0.0068	0.24	NO
140	PIN1	PIN1	PIN1	10206	-0.007	0.24	NO
141	DAK	DAK	DAK	10236	-0.0072	0.24	NO
142	ATG5	ATG5	ATG5	10286	-0.0078	0.24	NO
143	CD55	CD55	CD55	10391	-0.0089	0.23	NO
144	UBE2K	UBE2K	UBE2K	10461	-0.0098	0.23	NO
145	HSP90AB1	HSP90AB1	HSP90AB1	10556	-0.011	0.22	NO
146	MAP2K4	MAP2K4	MAP2K4	10557	-0.011	0.22	NO
147	MAP2K7	MAP2K7	MAP2K7	10806	-0.014	0.21	NO
148	TAB2	TAB2	TAB2	10820	-0.014	0.21	NO
149	IKBKB	IKBKB	IKBKB	10857	-0.014	0.21	NO
150	NOD1	NOD1	NOD1	10950	-0.016	0.2	NO
151	CAPZA2	CAPZA2	CAPZA2	11020	-0.017	0.2	NO
152	ATF1	ATF1	ATF1	11086	-0.018	0.2	NO
153	PCBP2	PCBP2	PCBP2	11089	-0.018	0.2	NO
154	MAVS	MAVS	MAVS	11116	-0.018	0.2	NO
155	DUSP3	DUSP3	DUSP3	11133	-0.018	0.2	NO
156	IFIH1	IFIH1	IFIH1	11146	-0.019	0.2	NO
157	UBE2D3	UBE2D3	UBE2D3	11190	-0.02	0.2	NO
158	HMGB1	HMGB1	HMGB1	11317	-0.021	0.19	NO
159	MAP3K7	MAP3K7	MAP3K7	11379	-0.022	0.19	NO
160	SIKE1	SIKE1	SIKE1	11682	-0.026	0.17	NO
161	C5	C5	C5	11703	-0.026	0.17	NO
162	MAP2K3	MAP2K3	MAP2K3	11877	-0.029	0.16	NO
163	PPP2R5D	PPP2R5D	PPP2R5D	11969	-0.03	0.16	NO
164	PELI1	PELI1	PELI1	12115	-0.032	0.15	NO
165	MAPK1	MAPK1	MAPK1	12294	-0.035	0.14	NO
166	ECSIT	ECSIT	ECSIT	12350	-0.036	0.14	NO
167	MAP3K1	MAP3K1	MAP3K1	12363	-0.036	0.14	NO
168	TXNIP	TXNIP	TXNIP	12417	-0.037	0.14	NO
169	PPP2CB	PPP2CB	PPP2CB	12693	-0.041	0.13	NO
170	RNF125	RNF125	RNF125	12765	-0.042	0.12	NO
171	MAPK3	MAPK3	MAPK3	12864	-0.044	0.12	NO
172	TRIM25	TRIM25	TRIM25	12899	-0.044	0.12	NO
173	CREB1	CREB1	CREB1	12976	-0.045	0.12	NO
174	CD46	CD46	CD46	13012	-0.046	0.12	NO
175	CREBBP	CREBBP	CREBBP	13021	-0.046	0.12	NO
176	S100A12	S100A12	S100A12	13063	-0.046	0.12	NO
177	SIGIRR	SIGIRR	SIGIRR	13075	-0.046	0.12	NO
178	PELI3	PELI3	PELI3	13169	-0.048	0.12	NO
179	HERC5	HERC5	HERC5	13171	-0.048	0.12	NO
180	APP	APP	APP	13199	-0.049	0.12	NO
181	CHUK	CHUK	CHUK	13258	-0.05	0.12	NO
182	ATF2	ATF2	ATF2	13443	-0.053	0.11	NO
183	MAP2K6	MAP2K6	MAP2K6	13519	-0.054	0.11	NO
184	EP300	EP300	EP300	13575	-0.055	0.11	NO
185	TLR4	TLR4	TLR4	13780	-0.059	0.096	NO
186	PIK3R4	PIK3R4	PIK3R4	13827	-0.06	0.096	NO
187	DEFA1B	DEFA1B	DEFA1B	14018	-0.064	0.088	NO
188	MEF2A	MEF2A	MEF2A	14194	-0.068	0.081	NO
189	TIRAP	TIRAP	TIRAP	14507	-0.074	0.066	NO
190	MEF2C	MEF2C	MEF2C	14708	-0.078	0.058	NO
191	NFKBIA	NFKBIA	NFKBIA	14800	-0.08	0.056	NO
192	FOS	FOS	FOS	14891	-0.082	0.054	NO
193	IRAK2	IRAK2	IRAK2	15006	-0.085	0.051	NO
194	PIK3C3	PIK3C3	PIK3C3	15008	-0.085	0.055	NO
195	PPP2R1B	PPP2R1B	PPP2R1B	15015	-0.086	0.058	NO
196	DUSP7	DUSP7	DUSP7	15079	-0.088	0.057	NO
197	PLCG2	PLCG2	PLCG2	15091	-0.088	0.06	NO
198	IRAK3	IRAK3	IRAK3	15220	-0.092	0.056	NO
199	ZFYVE20	ZFYVE20	ZFYVE20	15301	-0.095	0.056	NO
200	C4BPB	C4BPB	C4BPB	15445	-0.099	0.051	NO
201	IFNA21	IFNA21	IFNA21	15487	-0.1	0.053	NO
202	DUSP6	DUSP6	DUSP6	16097	-0.12	0.024	NO
203	C7	C7	C7	16149	-0.13	0.026	NO
204	MAPK12	MAPK12	MAPK12	16308	-0.14	0.022	NO
205	C6	C6	C6	16529	-0.15	0.016	NO
206	BCL2	BCL2	BCL2	16550	-0.15	0.02	NO
207	PELI2	PELI2	PELI2	16762	-0.16	0.015	NO
208	TRAF6	TRAF6	TRAF6	16785	-0.17	0.02	NO
209	RPS6KA2	RPS6KA2	RPS6KA2	16802	-0.17	0.026	NO
210	MAPK10	MAPK10	MAPK10	16805	-0.17	0.032	NO
211	MAPK8	MAPK8	MAPK8	16891	-0.17	0.034	NO
212	IFNA5	IFNA5	IFNA5	17138	-0.19	0.027	NO
213	RPS6KA5	RPS6KA5	RPS6KA5	17195	-0.2	0.032	NO
214	DNM1	DNM1	DNM1	17287	-0.21	0.034	NO
215	MASP2	MASP2	MASP2	17471	-0.23	0.033	NO
216	MASP1	MASP1	MASP1	17760	-0.28	0.028	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 CYTOSOLIC DNA SENSING PATHWAY.

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

genes ES table in pathway: PID AURORA B 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	CDC45	CDC45	CDC45	984	0.28	-0.0062	YES
2	CCNA2	CCNA2	CCNA2	1393	0.23	0.012	YES
3	CDC6	CDC6	CDC6	1515	0.22	0.044	YES
4	PSMA8	PSMA8	PSMA8	1581	0.22	0.078	YES
5	CDT1	CDT1	CDT1	1601	0.22	0.11	YES
6	CCNA1	CCNA1	CCNA1	1733	0.2	0.14	YES
7	PSMB10	PSMB10	PSMB10	1945	0.19	0.16	YES
8	DNA2	DNA2	DNA2	2143	0.18	0.18	YES
9	GINS2	GINS2	GINS2	2418	0.16	0.2	YES
10	POLD4	POLD4	POLD4	2428	0.16	0.22	YES
11	GINS1	GINS1	GINS1	2773	0.14	0.23	YES
12	PSMB9	PSMB9	PSMB9	3151	0.12	0.23	YES
13	PSMD14	PSMD14	PSMD14	3340	0.12	0.24	YES
14	PSMA5	PSMA5	PSMA5	3406	0.11	0.26	YES
15	PSME2	PSME2	PSME2	3498	0.11	0.27	YES
16	RFC4	RFC4	RFC4	3795	0.1	0.27	YES
17	GINS4	GINS4	GINS4	3862	0.098	0.28	YES
18	POLA2	POLA2	POLA2	3894	0.097	0.3	YES
19	POLD1	POLD1	POLD1	3902	0.096	0.32	YES
20	PSMB3	PSMB3	PSMB3	3979	0.094	0.33	YES
21	RFC2	RFC2	RFC2	4319	0.085	0.32	YES
22	MCM6	MCM6	MCM6	4328	0.085	0.34	YES
23	MCM2	MCM2	MCM2	4371	0.084	0.35	YES
24	PSMB4	PSMB4	PSMB4	4606	0.078	0.35	YES
25	PSMB2	PSMB2	PSMB2	4675	0.076	0.36	YES
26	RPA3	RPA3	RPA3	4761	0.074	0.37	YES
27	PSMC4	PSMC4	PSMC4	4886	0.072	0.38	YES
28	MCM8	MCM8	MCM8	4987	0.069	0.38	YES
29	LIG1	LIG1	LIG1	5068	0.068	0.39	YES
30	PCNA	PCNA	PCNA	5081	0.068	0.4	YES
31	POLE	POLE	POLE	5140	0.066	0.41	YES
32	RFC5	RFC5	RFC5	5284	0.063	0.41	YES
33	PSMA7	PSMA7	PSMA7	5338	0.062	0.42	YES
34	MCM4	MCM4	MCM4	5418	0.061	0.42	YES
35	PSMB8	PSMB8	PSMB8	5451	0.06	0.43	YES
36	PSMC2	PSMC2	PSMC2	5508	0.059	0.44	YES
37	PSMD4	PSMD4	PSMD4	5525	0.058	0.45	YES
38	PSMD7	PSMD7	PSMD7	5570	0.058	0.46	YES
39	MCM5	MCM5	MCM5	5598	0.057	0.47	YES
40	POLD2	POLD2	POLD2	5620	0.057	0.48	YES
41	PSMD13	PSMD13	PSMD13	5641	0.057	0.48	YES
42	PSMA4	PSMA4	PSMA4	5646	0.056	0.49	YES
43	PSME4	PSME4	PSME4	5663	0.056	0.5	YES
44	PSMA1	PSMA1	PSMA1	5693	0.056	0.51	YES
45	PSMD8	PSMD8	PSMD8	5933	0.051	0.51	YES
46	PSMA2	PSMA2	PSMA2	6013	0.05	0.51	YES
47	PSMB6	PSMB6	PSMB6	6090	0.049	0.52	YES
48	PSMD9	PSMD9	PSMD9	6286	0.046	0.51	YES
49	FEN1	FEN1	FEN1	6406	0.044	0.51	YES
50	POLD3	POLD3	POLD3	6418	0.043	0.52	YES
51	PSMD2	PSMD2	PSMD2	6527	0.042	0.52	YES
52	UBA52	UBA52	UBA52	6586	0.041	0.53	YES
53	PSMC5	PSMC5	PSMC5	7226	0.031	0.5	NO
54	PSMD1	PSMD1	PSMD1	7275	0.03	0.5	NO
55	PSMD3	PSMD3	PSMD3	7330	0.03	0.5	NO
56	PSMC3	PSMC3	PSMC3	7444	0.028	0.5	NO
57	PRIM2	PRIM2	PRIM2	7485	0.028	0.5	NO
58	RPS27A	RPS27A	RPS27A	7637	0.025	0.5	NO
59	PSMF1	PSMF1	PSMF1	7677	0.025	0.5	NO
60	PSMB1	PSMB1	PSMB1	7946	0.021	0.49	NO
61	CDK2	CDK2	CDK2	7980	0.021	0.49	NO
62	PSMD10	PSMD10	PSMD10	8053	0.02	0.49	NO
63	PSMD11	PSMD11	PSMD11	8085	0.02	0.49	NO
64	PSMC1	PSMC1	PSMC1	8857	0.0092	0.45	NO
65	PSMD12	PSMD12	PSMD12	8951	0.0081	0.45	NO
66	RPA2	RPA2	RPA2	9063	0.0069	0.44	NO
67	PSMA6	PSMA6	PSMA6	9098	0.0065	0.44	NO
68	PSME1	PSME1	PSME1	9110	0.0063	0.44	NO
69	PSMA3	PSMA3	PSMA3	9175	0.0055	0.44	NO
70	PSMB5	PSMB5	PSMB5	9342	0.0032	0.43	NO
71	PSMD6	PSMD6	PSMD6	9575	0.00057	0.42	NO
72	RB1	RB1	RB1	9824	-0.0022	0.41	NO
73	PRIM1	PRIM1	PRIM1	9925	-0.0036	0.4	NO
74	PSMB7	PSMB7	PSMB7	10453	-0.0096	0.37	NO
75	POLA1	POLA1	POLA1	10488	-0.01	0.37	NO
76	MCM7	MCM7	MCM7	10511	-0.01	0.37	NO
77	RPA1	RPA1	RPA1	10623	-0.012	0.37	NO
78	CDKN1A	CDKN1A	CDKN1A	10846	-0.014	0.36	NO
79	MCM3	MCM3	MCM3	11124	-0.018	0.35	NO
80	CDKN1B	CDKN1B	CDKN1B	12291	-0.035	0.29	NO
81	PSMD5	PSMD5	PSMD5	13285	-0.05	0.24	NO
82	POLE2	POLE2	POLE2	13426	-0.053	0.25	NO
83	PSMC6	PSMC6	PSMC6	13553	-0.055	0.25	NO
84	RFC3	RFC3	RFC3	13881	-0.061	0.24	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 AURORA B PATHWAY.

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

genes ES table in pathway: PID E2F PATHWAY

Table 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	XDH	XDH	XDH	316	0.4	0.046	YES
2	RRM2	RRM2	RRM2	611	0.33	0.082	YES
3	AMPD1	AMPD1	AMPD1	867	0.29	0.11	YES
4	ADA	ADA	ADA	959	0.28	0.15	YES
5	TK1	TK1	TK1	1261	0.24	0.18	YES
6	NME1-NME2	NME1-NME2	NME1-NME2	1293	0.24	0.21	YES
7	IMPDH1	IMPDH1	IMPDH1	1710	0.21	0.22	YES
8	TYMP	TYMP	TYMP	1753	0.2	0.25	YES
9	NME1	NME1	NME1	2194	0.17	0.25	YES
10	GPX1	GPX1	GPX1	2434	0.16	0.26	YES
11	NME4	NME4	NME4	2492	0.15	0.29	YES
12	NT5M	NT5M	NT5M	2726	0.14	0.3	YES
13	AMPD3	AMPD3	AMPD3	2898	0.13	0.31	YES
14	GLRX	GLRX	GLRX	2904	0.13	0.33	YES
15	DTYMK	DTYMK	DTYMK	3002	0.13	0.34	YES
16	CDA	CDA	CDA	3114	0.12	0.36	YES
17	APRT	APRT	APRT	3383	0.11	0.36	YES
18	ATIC	ATIC	ATIC	3438	0.11	0.37	YES
19	NME2	NME2	NME2	3709	0.1	0.38	YES
20	UCK2	UCK2	UCK2	3725	0.1	0.39	YES
21	AMPD2	AMPD2	AMPD2	3769	0.1	0.4	YES
22	NT5C3	NT5C3	NT5C3	3871	0.097	0.41	YES
23	DPYS	DPYS	DPYS	3975	0.094	0.42	YES
24	DGUOK	DGUOK	DGUOK	3976	0.094	0.44	YES
25	UPP2	UPP2	UPP2	4065	0.092	0.45	YES
26	AK5	AK5	AK5	4187	0.089	0.46	YES
27	NT5C1B	NT5C1B	NT5C1B	4304	0.085	0.46	YES
28	CAD	CAD	CAD	4398	0.083	0.47	YES
29	TXNRD1	TXNRD1	TXNRD1	4456	0.082	0.48	YES
30	GUK1	GUK1	GUK1	4651	0.077	0.48	YES
31	TK2	TK2	TK2	4964	0.07	0.48	NO
32	DHODH	DHODH	DHODH	5090	0.067	0.48	NO
33	DPYD	DPYD	DPYD	5597	0.057	0.46	NO
34	HPRT1	HPRT1	HPRT1	5609	0.057	0.47	NO
35	AK2	AK2	AK2	5671	0.056	0.47	NO
36	NT5C	NT5C	NT5C	5826	0.053	0.47	NO
37	PAICS	PAICS	PAICS	5901	0.052	0.48	NO
38	UPP1	UPP1	UPP1	6306	0.045	0.46	NO
39	CMPK1	CMPK1	CMPK1	6544	0.041	0.46	NO
40	RRM2B	RRM2B	RRM2B	6616	0.04	0.46	NO
41	GMPS	GMPS	GMPS	7020	0.034	0.44	NO
42	AGXT2	AGXT2	AGXT2	7106	0.032	0.44	NO
43	DCTD	DCTD	DCTD	7528	0.027	0.42	NO
44	GDA	GDA	GDA	7629	0.025	0.42	NO
45	TXN	TXN	TXN	7954	0.021	0.41	NO
46	GART	GART	GART	7975	0.021	0.41	NO
47	CTPS	CTPS	CTPS	8189	0.018	0.4	NO
48	CTPS2	CTPS2	CTPS2	8381	0.016	0.39	NO
49	PPAT	PPAT	PPAT	8520	0.014	0.39	NO
50	DUT	DUT	DUT	8536	0.014	0.39	NO
51	RRM1	RRM1	RRM1	8712	0.011	0.38	NO
52	UMPS	UMPS	UMPS	8866	0.0091	0.37	NO
53	IMPDH2	IMPDH2	IMPDH2	8986	0.0077	0.37	NO
54	UPB1	UPB1	UPB1	9023	0.0074	0.37	NO
55	GSR	GSR	GSR	9126	0.0061	0.36	NO
56	NT5C2	NT5C2	NT5C2	9297	0.0037	0.35	NO
57	GMPR	GMPR	GMPR	9411	0.0024	0.35	NO
58	PFAS	PFAS	PFAS	9439	0.0022	0.35	NO
59	TYMS	TYMS	TYMS	9443	0.0021	0.35	NO
60	ADSS	ADSS	ADSS	10128	-0.0061	0.31	NO
61	ADK	ADK	ADK	10345	-0.0084	0.3	NO
62	DCK	DCK	DCK	10433	-0.0094	0.3	NO
63	ADSL	ADSL	ADSL	10830	-0.014	0.28	NO
64	UCK1	UCK1	UCK1	13849	-0.06	0.12	NO
65	ADAL	ADAL	ADAL	13883	-0.061	0.13	NO
66	NT5C1A	NT5C1A	NT5C1A	14071	-0.065	0.13	NO
67	CAT	CAT	CAT	14450	-0.072	0.12	NO
68	PNP	PNP	PNP	14455	-0.073	0.13	NO
69	GMPR2	GMPR2	GMPR2	14731	-0.079	0.13	NO
70	NT5E	NT5E	NT5E	14818	-0.08	0.14	NO
71	AK1	AK1	AK1	16324	-0.14	0.074	NO
72	ADSSL1	ADSSL1	ADSSL1	17277	-0.21	0.054	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 E2F PATHWAY.

Figure S70. Get High-res Image For the top 5 core enriched genes in the pathway: PID E2F PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID INTEGRIN2 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CENPA	CENPA	CENPA	127	0.48	0.072	YES
2	AURKB	AURKB	AURKB	183	0.45	0.14	YES
3	KIF20A	KIF20A	KIF20A	210	0.43	0.21	YES
4	BUB1	BUB1	BUB1	211	0.43	0.28	YES
5	BIRC5	BIRC5	BIRC5	217	0.43	0.36	YES
6	KIF2C	KIF2C	KIF2C	555	0.34	0.39	YES
7	CDCA8	CDCA8	CDCA8	679	0.32	0.44	YES
8	SGOL1	SGOL1	SGOL1	777	0.3	0.49	YES
9	NCAPG	NCAPG	NCAPG	893	0.29	0.53	YES
10	NCAPH	NCAPH	NCAPH	898	0.29	0.57	YES
11	AURKA	AURKA	AURKA	1044	0.27	0.61	YES
12	KIF23	KIF23	KIF23	1207	0.25	0.64	YES
13	SEPT1	SEPT1	SEPT1	1247	0.25	0.68	YES
14	NDC80	NDC80	NDC80	1334	0.24	0.72	YES
15	AURKC	AURKC	AURKC	1516	0.22	0.74	YES
16	RACGAP1	RACGAP1	RACGAP1	3826	0.098	0.63	NO
17	NCAPD2	NCAPD2	NCAPD2	4812	0.073	0.59	NO
18	VIM	VIM	VIM	4945	0.07	0.6	NO
19	SMC4	SMC4	SMC4	5817	0.053	0.56	NO
20	CBX5	CBX5	CBX5	6810	0.037	0.51	NO
21	STMN1	STMN1	STMN1	7048	0.033	0.5	NO
22	PPP1CC	PPP1CC	PPP1CC	7249	0.031	0.49	NO
23	NSUN2	NSUN2	NSUN2	7898	0.022	0.46	NO
24	INCENP	INCENP	INCENP	8138	0.019	0.45	NO
25	NPM1	NPM1	NPM1	9060	0.0069	0.4	NO
26	PSMA3	PSMA3	PSMA3	9175	0.0055	0.4	NO
27	DES	DES	DES	10037	-0.005	0.35	NO
28	NCL	NCL	NCL	10091	-0.0057	0.35	NO
29	RASA1	RASA1	RASA1	10144	-0.0062	0.35	NO
30	EVI5	EVI5	EVI5	11096	-0.018	0.3	NO
31	MYLK	MYLK	MYLK	11278	-0.02	0.29	NO
32	PPP2R5D	PPP2R5D	PPP2R5D	11969	-0.03	0.26	NO
33	RHOA	RHOA	RHOA	12368	-0.036	0.24	NO
34	PEBP1	PEBP1	PEBP1	12441	-0.037	0.24	NO
35	KLHL13	KLHL13	KLHL13	13013	-0.046	0.22	NO
36	CUL3	CUL3	CUL3	13080	-0.047	0.22	NO
37	SMC2	SMC2	SMC2	13306	-0.05	0.22	NO
38	KLHL9	KLHL9	KLHL9	16306	-0.14	0.079	NO
39	TACC1	TACC1	TACC1	16876	-0.17	0.076	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 INTEGRIN2 PATHWAY.

Figure S72. Get High-res Image For the top 5 core enriched genes in the pathway: PID INTEGRIN2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: REACTOME ANTIGEN PROCESSING CROSS PRESENTATION

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	CD8B	CD8B	CD8B	552	0.34	0.000085	YES
2	CD28	CD28	CD28	712	0.32	0.019	YES
3	CCR5	CCR5	CCR5	847	0.29	0.038	YES
4	RCC1	RCC1	RCC1	943	0.28	0.058	YES
5	LCK	LCK	LCK	1147	0.25	0.069	YES
6	APOBEC3G	APOBEC3G	APOBEC3G	1332	0.24	0.08	YES
7	PSMA8	PSMA8	PSMA8	1581	0.22	0.086	YES
8	DOCK2	DOCK2	DOCK2	1662	0.21	0.1	YES
9	TAF10	TAF10	TAF10	1663	0.21	0.12	YES
10	CD247	CD247	CD247	1773	0.2	0.13	YES
11	HCK	HCK	HCK	1818	0.2	0.15	YES
12	PSMB10	PSMB10	PSMB10	1945	0.19	0.16	YES
13	NUP210	NUP210	NUP210	1998	0.18	0.17	YES
14	HMGA1	HMGA1	HMGA1	2035	0.18	0.18	YES
15	CD4	CD4	CD4	2645	0.14	0.16	YES
16	AP1M2	AP1M2	AP1M2	3089	0.13	0.15	YES
17	POLR2J	POLR2J	POLR2J	3113	0.12	0.16	YES
18	PSMB9	PSMB9	PSMB9	3151	0.12	0.17	YES
19	PSMD14	PSMD14	PSMD14	3340	0.12	0.17	YES
20	PSMA5	PSMA5	PSMA5	3406	0.11	0.18	YES
21	PSME2	PSME2	PSME2	3498	0.11	0.18	YES
22	POLR2L	POLR2L	POLR2L	3739	0.1	0.18	YES
23	AP1M1	AP1M1	AP1M1	3798	0.1	0.18	YES
24	CXCR4	CXCR4	CXCR4	3888	0.097	0.18	YES
25	POLR2H	POLR2H	POLR2H	3969	0.094	0.19	YES
26	PSMB3	PSMB3	PSMB3	3979	0.094	0.2	YES
27	TCEB1	TCEB1	TCEB1	4086	0.091	0.2	YES
28	BANF1	BANF1	BANF1	4211	0.088	0.2	YES
29	CDK7	CDK7	CDK7	4242	0.087	0.21	YES
30	TCEB2	TCEB2	TCEB2	4283	0.086	0.21	YES
31	AP2S1	AP2S1	AP2S1	4469	0.081	0.21	YES
32	AP2A1	AP2A1	AP2A1	4519	0.08	0.21	YES
33	GTF2H2B	GTF2H2B	GTF2H2B	4547	0.079	0.22	YES
34	PSMB4	PSMB4	PSMB4	4606	0.078	0.22	YES
35	RAN	RAN	RAN	4634	0.077	0.23	YES
36	PSMB2	PSMB2	PSMB2	4675	0.076	0.23	YES
37	RBX1	RBX1	RBX1	4740	0.075	0.24	YES
38	NUP37	NUP37	NUP37	4747	0.075	0.24	YES
39	PSMC4	PSMC4	PSMC4	4886	0.072	0.24	YES
40	NUPL2	NUPL2	NUPL2	4919	0.071	0.24	YES
41	LIG1	LIG1	LIG1	5068	0.068	0.24	YES
42	PSMA7	PSMA7	PSMA7	5338	0.062	0.23	YES
43	NUP62	NUP62	NUP62	5447	0.06	0.23	YES
44	PSMB8	PSMB8	PSMB8	5451	0.06	0.24	YES
45	XRCC4	XRCC4	XRCC4	5487	0.059	0.24	YES
46	PPIA	PPIA	PPIA	5506	0.059	0.24	YES
47	PSMC2	PSMC2	PSMC2	5508	0.059	0.25	YES
48	RANGAP1	RANGAP1	RANGAP1	5520	0.059	0.26	YES
49	VPS28	VPS28	VPS28	5522	0.059	0.26	YES
50	PSMD4	PSMD4	PSMD4	5525	0.058	0.26	YES
51	PSMD7	PSMD7	PSMD7	5570	0.058	0.27	YES
52	PSMD13	PSMD13	PSMD13	5641	0.057	0.27	YES
53	PSMA4	PSMA4	PSMA4	5646	0.056	0.27	YES
54	PSME4	PSME4	PSME4	5663	0.056	0.28	YES
55	RAE1	RAE1	RAE1	5682	0.056	0.28	YES
56	PSMA1	PSMA1	PSMA1	5693	0.056	0.29	YES
57	AAAS	AAAS	AAAS	5906	0.052	0.28	YES
58	HLA-A	HLA-A	HLA-A	5912	0.052	0.28	YES
59	POLR2G	POLR2G	POLR2G	5932	0.052	0.29	YES
60	PSMD8	PSMD8	PSMD8	5933	0.051	0.29	YES
61	AP1B1	AP1B1	AP1B1	5935	0.051	0.3	YES
62	GTF2E2	GTF2E2	GTF2E2	5948	0.051	0.3	YES
63	PSMA2	PSMA2	PSMA2	6013	0.05	0.3	YES
64	PSMB6	PSMB6	PSMB6	6090	0.049	0.3	YES
65	TAF12	TAF12	TAF12	6172	0.048	0.3	YES
66	NUP93	NUP93	NUP93	6177	0.047	0.3	YES
67	AP1S1	AP1S1	AP1S1	6212	0.047	0.31	YES
68	AP2M1	AP2M1	AP2M1	6279	0.046	0.31	YES
69	PSMD9	PSMD9	PSMD9	6286	0.046	0.31	YES
70	POLR2I	POLR2I	POLR2I	6300	0.045	0.32	YES
71	RANBP1	RANBP1	RANBP1	6379	0.044	0.31	YES
72	FEN1	FEN1	FEN1	6406	0.044	0.32	YES
73	PSMD2	PSMD2	PSMD2	6527	0.042	0.31	YES
74	NMT1	NMT1	NMT1	6543	0.041	0.32	YES
75	UBA52	UBA52	UBA52	6586	0.041	0.32	YES
76	CCNH	CCNH	CCNH	6589	0.041	0.32	YES
77	NUP107	NUP107	NUP107	6783	0.037	0.31	NO
78	RAC1	RAC1	RAC1	7167	0.032	0.3	NO
79	PSMC5	PSMC5	PSMC5	7226	0.031	0.3	NO
80	PSMD1	PSMD1	PSMD1	7275	0.03	0.3	NO
81	ARF1	ARF1	ARF1	7317	0.03	0.3	NO
82	PSMD3	PSMD3	PSMD3	7330	0.03	0.3	NO
83	POLR2F	POLR2F	POLR2F	7340	0.03	0.3	NO
84	POLR2K	POLR2K	POLR2K	7370	0.029	0.3	NO
85	PSMC3	PSMC3	PSMC3	7444	0.028	0.3	NO
86	PACS1	PACS1	PACS1	7608	0.026	0.29	NO
87	RPS27A	RPS27A	RPS27A	7637	0.025	0.29	NO
88	PSMF1	PSMF1	PSMF1	7677	0.025	0.29	NO
89	TCEA1	TCEA1	TCEA1	7768	0.024	0.29	NO
90	POLR2E	POLR2E	POLR2E	7836	0.022	0.29	NO
91	PSMB1	PSMB1	PSMB1	7946	0.021	0.28	NO
92	WHSC2	WHSC2	WHSC2	8002	0.02	0.28	NO
93	PSMD10	PSMD10	PSMD10	8053	0.02	0.28	NO
94	PAK2	PAK2	PAK2	8079	0.02	0.28	NO
95	PSMD11	PSMD11	PSMD11	8085	0.02	0.28	NO
96	TAF6	TAF6	TAF6	8088	0.019	0.29	NO
97	POM121	POM121	POM121	8196	0.018	0.28	NO
98	SLC25A6	SLC25A6	SLC25A6	8205	0.018	0.28	NO
99	TAF4	TAF4	TAF4	8322	0.016	0.28	NO
100	NCBP2	NCBP2	NCBP2	8419	0.015	0.27	NO
101	POLR2D	POLR2D	POLR2D	8545	0.014	0.27	NO
102	TH1L	TH1L	TH1L	8597	0.013	0.27	NO
103	GTF2A2	GTF2A2	GTF2A2	8661	0.012	0.26	NO
104	B2M	B2M	B2M	8691	0.011	0.26	NO
105	SUPT4H1	SUPT4H1	SUPT4H1	8813	0.0097	0.26	NO
106	ELMO1	ELMO1	ELMO1	8833	0.0095	0.26	NO
107	GTF2E1	GTF2E1	GTF2E1	8851	0.0093	0.26	NO
108	PSMC1	PSMC1	PSMC1	8857	0.0092	0.26	NO
109	GTF2H2	GTF2H2	GTF2H2	8910	0.0086	0.26	NO
110	PSMD12	PSMD12	PSMD12	8951	0.0081	0.25	NO
111	SUPT5H	SUPT5H	SUPT5H	8966	0.0079	0.25	NO
112	ELL	ELL	ELL	8987	0.0077	0.25	NO
113	NPM1	NPM1	NPM1	9060	0.0069	0.25	NO
114	KPNB1	KPNB1	KPNB1	9082	0.0067	0.25	NO
115	ATP6V1H	ATP6V1H	ATP6V1H	9094	0.0065	0.25	NO
116	PSMA6	PSMA6	PSMA6	9098	0.0065	0.25	NO
117	XPO1	XPO1	XPO1	9102	0.0064	0.25	NO
118	PSME1	PSME1	PSME1	9110	0.0063	0.25	NO
119	SSRP1	SSRP1	SSRP1	9115	0.0062	0.25	NO
120	NUP50	NUP50	NUP50	9117	0.0062	0.25	NO
121	PSMA3	PSMA3	PSMA3	9175	0.0055	0.25	NO
122	NUP85	NUP85	NUP85	9193	0.0052	0.25	NO
123	CTDP1	CTDP1	CTDP1	9199	0.0051	0.25	NO
124	PSMB5	PSMB5	PSMB5	9342	0.0032	0.24	NO
125	VPS37A	VPS37A	VPS37A	9395	0.0027	0.24	NO
126	GTF2F1	GTF2F1	GTF2F1	9430	0.0023	0.24	NO
127	PSMD6	PSMD6	PSMD6	9575	0.00057	0.23	NO
128	XRCC5	XRCC5	XRCC5	9652	-0.00029	0.22	NO
129	RDBP	RDBP	RDBP	9691	-0.00066	0.22	NO
130	GTF2H1	GTF2H1	GTF2H1	9709	-0.00086	0.22	NO
131	NUP88	NUP88	NUP88	9761	-0.0016	0.22	NO
132	TAF9	TAF9	TAF9	9776	-0.0018	0.22	NO
133	SLC25A5	SLC25A5	SLC25A5	9879	-0.003	0.21	NO
134	XRCC6	XRCC6	XRCC6	9975	-0.0041	0.21	NO
135	SKP1	SKP1	SKP1	10040	-0.0051	0.2	NO
136	TPR	TPR	TPR	10250	-0.0074	0.19	NO
137	NUP43	NUP43	NUP43	10259	-0.0075	0.19	NO
138	PSMB7	PSMB7	PSMB7	10453	-0.0096	0.18	NO
139	CDK9	CDK9	CDK9	10706	-0.013	0.17	NO
140	NUP205	NUP205	NUP205	10765	-0.013	0.17	NO
141	ERCC3	ERCC3	ERCC3	10836	-0.014	0.17	NO
142	POLR2C	POLR2C	POLR2C	10870	-0.015	0.17	NO
143	KPNA1	KPNA1	KPNA1	10948	-0.016	0.16	NO
144	GTF2F2	GTF2F2	GTF2F2	10965	-0.016	0.16	NO
145	TSG101	TSG101	TSG101	10982	-0.016	0.16	NO
146	VPS37C	VPS37C	VPS37C	11128	-0.018	0.16	NO
147	NUPL1	NUPL1	NUPL1	11223	-0.02	0.16	NO
148	GTF2B	GTF2B	GTF2B	11402	-0.022	0.15	NO
149	AP1S2	AP1S2	AP1S2	11407	-0.022	0.15	NO
150	NUP155	NUP155	NUP155	11494	-0.023	0.15	NO
151	POLR2B	POLR2B	POLR2B	11515	-0.024	0.15	NO
152	ERCC2	ERCC2	ERCC2	11555	-0.024	0.15	NO
153	AP2B1	AP2B1	AP2B1	11575	-0.024	0.15	NO
154	AP1G1	AP1G1	AP1G1	11774	-0.027	0.14	NO
155	LIG4	LIG4	LIG4	11917	-0.029	0.13	NO
156	TAF1	TAF1	TAF1	11997	-0.03	0.13	NO
157	RNGTT	RNGTT	RNGTT	12026	-0.031	0.13	NO
158	CCNT2	CCNT2	CCNT2	12146	-0.033	0.13	NO
159	GTF2H4	GTF2H4	GTF2H4	12366	-0.036	0.12	NO
160	NMT2	NMT2	NMT2	12394	-0.036	0.12	NO
161	AP2A2	AP2A2	AP2A2	12434	-0.037	0.12	NO
162	NUP35	NUP35	NUP35	12509	-0.038	0.12	NO
163	TCEB3	TCEB3	TCEB3	12556	-0.039	0.12	NO
164	RNMT	RNMT	RNMT	12710	-0.041	0.12	NO
165	POLR2A	POLR2A	POLR2A	12752	-0.042	0.12	NO
166	TBP	TBP	TBP	12760	-0.042	0.12	NO
167	NUP54	NUP54	NUP54	12806	-0.043	0.12	NO
168	NUP133	NUP133	NUP133	12835	-0.043	0.13	NO
169	RANBP2	RANBP2	RANBP2	13016	-0.046	0.12	NO
170	TAF11	TAF11	TAF11	13212	-0.049	0.12	NO
171	GTF2H3	GTF2H3	GTF2H3	13245	-0.049	0.12	NO
172	PSMD5	PSMD5	PSMD5	13285	-0.05	0.12	NO
173	TAF13	TAF13	TAF13	13352	-0.051	0.12	NO
174	NUP188	NUP188	NUP188	13394	-0.052	0.12	NO
175	NUP214	NUP214	NUP214	13454	-0.053	0.12	NO
176	PSMC6	PSMC6	PSMC6	13553	-0.055	0.12	NO
177	NCBP1	NCBP1	NCBP1	13611	-0.056	0.13	NO
178	NUP153	NUP153	NUP153	13741	-0.058	0.12	NO
179	SUPT16H	SUPT16H	SUPT16H	13772	-0.059	0.13	NO
180	SEH1L	SEH1L	SEH1L	13788	-0.059	0.13	NO
181	BTRC	BTRC	BTRC	13803	-0.059	0.14	NO
182	TAF4B	TAF4B	TAF4B	13850	-0.06	0.14	NO
183	TAF5	TAF5	TAF5	13952	-0.062	0.14	NO
184	COBRA1	COBRA1	COBRA1	14117	-0.066	0.14	NO
185	CUL5	CUL5	CUL5	14724	-0.078	0.11	NO
186	VPS37B	VPS37B	VPS37B	14896	-0.082	0.11	NO
187	MNAT1	MNAT1	MNAT1	15348	-0.096	0.091	NO
188	SLC25A4	SLC25A4	SLC25A4	15502	-0.1	0.092	NO
189	PSIP1	PSIP1	PSIP1	15548	-0.1	0.098	NO
190	FYN	FYN	FYN	15712	-0.11	0.099	NO
191	CCNT1	CCNT1	CCNT1	16636	-0.16	0.062	NO
192	GTF2A1	GTF2A1	GTF2A1	16673	-0.16	0.074	NO
193	VPS37D	VPS37D	VPS37D	16683	-0.16	0.087	NO

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

Figure S74. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME ANTIGEN PROCESSING CROSS PRESENTATION, 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 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	CCNE1	CCNE1	CCNE1	409	0.38	0.03	YES
2	CDC45	CDC45	CDC45	984	0.28	0.037	YES
3	CCNA2	CCNA2	CCNA2	1393	0.23	0.047	YES
4	CDC6	CDC6	CDC6	1515	0.22	0.072	YES
5	PSMA8	PSMA8	PSMA8	1581	0.22	0.098	YES
6	CDT1	CDT1	CDT1	1601	0.22	0.13	YES
7	CCNA1	CCNA1	CCNA1	1733	0.2	0.15	YES
8	PSMB10	PSMB10	PSMB10	1945	0.19	0.16	YES
9	DNA2	DNA2	DNA2	2143	0.18	0.18	YES
10	CDC25A	CDC25A	CDC25A	2305	0.16	0.19	YES
11	CCNE2	CCNE2	CCNE2	2379	0.16	0.21	YES
12	GINS2	GINS2	GINS2	2418	0.16	0.23	YES
13	POLD4	POLD4	POLD4	2428	0.16	0.25	YES
14	GINS1	GINS1	GINS1	2773	0.14	0.25	YES
15	CDC25B	CDC25B	CDC25B	3118	0.12	0.25	YES
16	PSMB9	PSMB9	PSMB9	3151	0.12	0.27	YES
17	PSMD14	PSMD14	PSMD14	3340	0.12	0.27	YES
18	PSMA5	PSMA5	PSMA5	3406	0.11	0.28	YES
19	PSME2	PSME2	PSME2	3498	0.11	0.3	YES
20	RFC4	RFC4	RFC4	3795	0.1	0.29	YES
21	GINS4	GINS4	GINS4	3862	0.098	0.3	YES
22	POLA2	POLA2	POLA2	3894	0.097	0.31	YES
23	POLD1	POLD1	POLD1	3902	0.096	0.33	YES
24	PSMB3	PSMB3	PSMB3	3979	0.094	0.34	YES
25	CDK7	CDK7	CDK7	4242	0.087	0.33	YES
26	RFC2	RFC2	RFC2	4319	0.085	0.34	YES
27	MCM6	MCM6	MCM6	4328	0.085	0.35	YES
28	MCM2	MCM2	MCM2	4371	0.084	0.36	YES
29	PSMB4	PSMB4	PSMB4	4606	0.078	0.36	YES
30	PSMB2	PSMB2	PSMB2	4675	0.076	0.37	YES
31	RPA3	RPA3	RPA3	4761	0.074	0.37	YES
32	PSMC4	PSMC4	PSMC4	4886	0.072	0.38	YES
33	MCM8	MCM8	MCM8	4987	0.069	0.38	YES
34	LIG1	LIG1	LIG1	5068	0.068	0.39	YES
35	PCNA	PCNA	PCNA	5081	0.068	0.4	YES
36	POLE	POLE	POLE	5140	0.066	0.4	YES
37	RFC5	RFC5	RFC5	5284	0.063	0.4	YES
38	PSMA7	PSMA7	PSMA7	5338	0.062	0.41	YES
39	MCM4	MCM4	MCM4	5418	0.061	0.41	YES
40	PSMB8	PSMB8	PSMB8	5451	0.06	0.42	YES
41	PSMC2	PSMC2	PSMC2	5508	0.059	0.42	YES
42	PSMD4	PSMD4	PSMD4	5525	0.058	0.43	YES
43	PSMD7	PSMD7	PSMD7	5570	0.058	0.44	YES
44	MCM5	MCM5	MCM5	5598	0.057	0.44	YES
45	POLD2	POLD2	POLD2	5620	0.057	0.45	YES
46	PSMD13	PSMD13	PSMD13	5641	0.057	0.46	YES
47	PSMA4	PSMA4	PSMA4	5646	0.056	0.46	YES
48	PSME4	PSME4	PSME4	5663	0.056	0.47	YES
49	PSMA1	PSMA1	PSMA1	5693	0.056	0.48	YES
50	CDK4	CDK4	CDK4	5734	0.055	0.48	YES
51	CKS1B	CKS1B	CKS1B	5815	0.053	0.49	YES
52	PSMD8	PSMD8	PSMD8	5933	0.051	0.49	YES
53	PSMA2	PSMA2	PSMA2	6013	0.05	0.49	YES
54	PSMB6	PSMB6	PSMB6	6090	0.049	0.49	YES
55	CUL1	CUL1	CUL1	6261	0.046	0.49	YES
56	PSMD9	PSMD9	PSMD9	6286	0.046	0.49	YES
57	FEN1	FEN1	FEN1	6406	0.044	0.49	YES
58	POLD3	POLD3	POLD3	6418	0.043	0.5	YES
59	PSMD2	PSMD2	PSMD2	6527	0.042	0.5	YES
60	UBA52	UBA52	UBA52	6586	0.041	0.5	YES
61	CCNH	CCNH	CCNH	6589	0.041	0.51	YES
62	PSMC5	PSMC5	PSMC5	7226	0.031	0.48	NO
63	PSMD1	PSMD1	PSMD1	7275	0.03	0.48	NO
64	PSMD3	PSMD3	PSMD3	7330	0.03	0.48	NO
65	PSMC3	PSMC3	PSMC3	7444	0.028	0.48	NO
66	PRIM2	PRIM2	PRIM2	7485	0.028	0.48	NO
67	RPS27A	RPS27A	RPS27A	7637	0.025	0.47	NO
68	PSMF1	PSMF1	PSMF1	7677	0.025	0.48	NO
69	PSMB1	PSMB1	PSMB1	7946	0.021	0.46	NO
70	CDK2	CDK2	CDK2	7980	0.021	0.46	NO
71	PSMD10	PSMD10	PSMD10	8053	0.02	0.46	NO
72	PSMD11	PSMD11	PSMD11	8085	0.02	0.46	NO
73	MYC	MYC	MYC	8710	0.011	0.43	NO
74	PSMC1	PSMC1	PSMC1	8857	0.0092	0.42	NO
75	PSMD12	PSMD12	PSMD12	8951	0.0081	0.42	NO
76	RPA2	RPA2	RPA2	9063	0.0069	0.42	NO
77	PSMA6	PSMA6	PSMA6	9098	0.0065	0.42	NO
78	PSME1	PSME1	PSME1	9110	0.0063	0.42	NO
79	PSMA3	PSMA3	PSMA3	9175	0.0055	0.41	NO
80	MAX	MAX	MAX	9176	0.0055	0.41	NO
81	PSMB5	PSMB5	PSMB5	9342	0.0032	0.4	NO
82	PSMD6	PSMD6	PSMD6	9575	0.00057	0.39	NO
83	RB1	RB1	RB1	9824	-0.0022	0.38	NO
84	PRIM1	PRIM1	PRIM1	9925	-0.0036	0.37	NO
85	SKP1	SKP1	SKP1	10040	-0.0051	0.37	NO
86	PSMB7	PSMB7	PSMB7	10453	-0.0096	0.35	NO
87	SKP2	SKP2	SKP2	10468	-0.0098	0.35	NO
88	POLA1	POLA1	POLA1	10488	-0.01	0.35	NO
89	MCM7	MCM7	MCM7	10511	-0.01	0.35	NO
90	RPA1	RPA1	RPA1	10623	-0.012	0.34	NO
91	CDKN1A	CDKN1A	CDKN1A	10846	-0.014	0.33	NO
92	MCM3	MCM3	MCM3	11124	-0.018	0.32	NO
93	CDKN1B	CDKN1B	CDKN1B	12291	-0.035	0.26	NO
94	PSMD5	PSMD5	PSMD5	13285	-0.05	0.21	NO
95	POLE2	POLE2	POLE2	13426	-0.053	0.21	NO
96	PSMC6	PSMC6	PSMC6	13553	-0.055	0.21	NO
97	RFC3	RFC3	RFC3	13881	-0.061	0.2	NO
98	CCND1	CCND1	CCND1	14808	-0.08	0.16	NO
99	WEE1	WEE1	WEE1	15023	-0.086	0.16	NO
100	MNAT1	MNAT1	MNAT1	15348	-0.096	0.16	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 ORC1 REMOVAL FROM CHROMATIN.

Figure S76. 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 ACTIVATION OF NF KAPPAB IN B CELLS

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	CCNA2	CCNA2	CCNA2	1393	0.23	-0.014	YES
2	CDC6	CDC6	CDC6	1515	0.22	0.04	YES
3	PSMA8	PSMA8	PSMA8	1581	0.22	0.094	YES
4	CDT1	CDT1	CDT1	1601	0.22	0.15	YES
5	CCNA1	CCNA1	CCNA1	1733	0.2	0.2	YES
6	PSMB10	PSMB10	PSMB10	1945	0.19	0.24	YES
7	PSMB9	PSMB9	PSMB9	3151	0.12	0.21	YES
8	PSMD14	PSMD14	PSMD14	3340	0.12	0.23	YES
9	PSMA5	PSMA5	PSMA5	3406	0.11	0.25	YES
10	PSME2	PSME2	PSME2	3498	0.11	0.28	YES
11	PSMB3	PSMB3	PSMB3	3979	0.094	0.28	YES
12	MCM6	MCM6	MCM6	4328	0.085	0.28	YES
13	MCM2	MCM2	MCM2	4371	0.084	0.3	YES
14	PSMB4	PSMB4	PSMB4	4606	0.078	0.31	YES
15	PSMB2	PSMB2	PSMB2	4675	0.076	0.33	YES
16	PSMC4	PSMC4	PSMC4	4886	0.072	0.34	YES
17	MCM8	MCM8	MCM8	4987	0.069	0.35	YES
18	PSMA7	PSMA7	PSMA7	5338	0.062	0.35	YES
19	MCM4	MCM4	MCM4	5418	0.061	0.36	YES
20	PSMB8	PSMB8	PSMB8	5451	0.06	0.37	YES
21	PSMC2	PSMC2	PSMC2	5508	0.059	0.38	YES
22	PSMD4	PSMD4	PSMD4	5525	0.058	0.4	YES
23	PSMD7	PSMD7	PSMD7	5570	0.058	0.41	YES
24	MCM5	MCM5	MCM5	5598	0.057	0.43	YES
25	PSMD13	PSMD13	PSMD13	5641	0.057	0.44	YES
26	PSMA4	PSMA4	PSMA4	5646	0.056	0.46	YES
27	PSME4	PSME4	PSME4	5663	0.056	0.47	YES
28	PSMA1	PSMA1	PSMA1	5693	0.056	0.48	YES
29	PSMD8	PSMD8	PSMD8	5933	0.051	0.48	YES
30	PSMA2	PSMA2	PSMA2	6013	0.05	0.49	YES
31	PSMB6	PSMB6	PSMB6	6090	0.049	0.5	YES
32	PSMD9	PSMD9	PSMD9	6286	0.046	0.5	YES
33	PSMD2	PSMD2	PSMD2	6527	0.042	0.5	YES
34	UBA52	UBA52	UBA52	6586	0.041	0.51	YES
35	PSMC5	PSMC5	PSMC5	7226	0.031	0.48	NO
36	PSMD1	PSMD1	PSMD1	7275	0.03	0.49	NO
37	PSMD3	PSMD3	PSMD3	7330	0.03	0.49	NO
38	PSMC3	PSMC3	PSMC3	7444	0.028	0.5	NO
39	RPS27A	RPS27A	RPS27A	7637	0.025	0.49	NO
40	PSMF1	PSMF1	PSMF1	7677	0.025	0.5	NO
41	PSMB1	PSMB1	PSMB1	7946	0.021	0.49	NO
42	CDK2	CDK2	CDK2	7980	0.021	0.49	NO
43	PSMD10	PSMD10	PSMD10	8053	0.02	0.49	NO
44	PSMD11	PSMD11	PSMD11	8085	0.02	0.5	NO
45	PSMC1	PSMC1	PSMC1	8857	0.0092	0.46	NO
46	PSMD12	PSMD12	PSMD12	8951	0.0081	0.45	NO
47	PSMA6	PSMA6	PSMA6	9098	0.0065	0.45	NO
48	PSME1	PSME1	PSME1	9110	0.0063	0.45	NO
49	PSMA3	PSMA3	PSMA3	9175	0.0055	0.44	NO
50	PSMB5	PSMB5	PSMB5	9342	0.0032	0.44	NO
51	PSMD6	PSMD6	PSMD6	9575	0.00057	0.42	NO
52	RB1	RB1	RB1	9824	-0.0022	0.41	NO
53	PSMB7	PSMB7	PSMB7	10453	-0.0096	0.38	NO
54	MCM7	MCM7	MCM7	10511	-0.01	0.38	NO
55	CDKN1A	CDKN1A	CDKN1A	10846	-0.014	0.36	NO
56	MCM3	MCM3	MCM3	11124	-0.018	0.35	NO
57	CDKN1B	CDKN1B	CDKN1B	12291	-0.035	0.3	NO
58	PSMD5	PSMD5	PSMD5	13285	-0.05	0.26	NO
59	PSMC6	PSMC6	PSMC6	13553	-0.055	0.26	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 ACTIVATION OF NF KAPPAB IN B CELLS.

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME ACTIVATION OF NF KAPPAB IN B CELLS, 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 MHC CLASS II ANTIGEN PRESENTATION

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	UNC5A	UNC5A	UNC5A	879	0.29	0.036	YES
2	PSMA8	PSMA8	PSMA8	1581	0.22	0.061	YES
3	PSMB10	PSMB10	PSMB10	1945	0.19	0.096	YES
4	DCC	DCC	DCC	2161	0.17	0.14	YES
5	DAPK2	DAPK2	DAPK2	2231	0.17	0.18	YES
6	PSMB9	PSMB9	PSMB9	3151	0.12	0.17	YES
7	PSMD14	PSMD14	PSMD14	3340	0.12	0.19	YES
8	PSMA5	PSMA5	PSMA5	3406	0.11	0.22	YES
9	PSME2	PSME2	PSME2	3498	0.11	0.25	YES
10	CASP3	CASP3	CASP3	3885	0.097	0.25	YES
11	PSMB3	PSMB3	PSMB3	3979	0.094	0.28	YES
12	PSMB4	PSMB4	PSMB4	4606	0.078	0.26	YES
13	PSMB2	PSMB2	PSMB2	4675	0.076	0.28	YES
14	PSMC4	PSMC4	PSMC4	4886	0.072	0.29	YES
15	MAGED1	MAGED1	MAGED1	5109	0.067	0.3	YES
16	PSMA7	PSMA7	PSMA7	5338	0.062	0.3	YES
17	PSMB8	PSMB8	PSMB8	5451	0.06	0.32	YES
18	PSMC2	PSMC2	PSMC2	5508	0.059	0.33	YES
19	PSMD4	PSMD4	PSMD4	5525	0.058	0.34	YES
20	PSMD7	PSMD7	PSMD7	5570	0.058	0.36	YES
21	PSMD13	PSMD13	PSMD13	5641	0.057	0.37	YES
22	PSMA4	PSMA4	PSMA4	5646	0.056	0.39	YES
23	PSME4	PSME4	PSME4	5663	0.056	0.4	YES
24	PSMA1	PSMA1	PSMA1	5693	0.056	0.42	YES
25	PSMD8	PSMD8	PSMD8	5933	0.051	0.42	YES
26	PSMA2	PSMA2	PSMA2	6013	0.05	0.43	YES
27	PSMB6	PSMB6	PSMB6	6090	0.049	0.44	YES
28	PSMD9	PSMD9	PSMD9	6286	0.046	0.44	YES
29	PSMD2	PSMD2	PSMD2	6527	0.042	0.44	YES
30	UBA52	UBA52	UBA52	6586	0.041	0.45	YES
31	PSMC5	PSMC5	PSMC5	7226	0.031	0.42	NO
32	PSMD1	PSMD1	PSMD1	7275	0.03	0.43	NO
33	PSMD3	PSMD3	PSMD3	7330	0.03	0.44	NO
34	PSMC3	PSMC3	PSMC3	7444	0.028	0.44	NO
35	CASP9	CASP9	CASP9	7498	0.027	0.44	NO
36	RPS27A	RPS27A	RPS27A	7637	0.025	0.44	NO
37	PSMF1	PSMF1	PSMF1	7677	0.025	0.45	NO
38	PSMB1	PSMB1	PSMB1	7946	0.021	0.44	NO
39	PSMD10	PSMD10	PSMD10	8053	0.02	0.44	NO
40	PAK2	PAK2	PAK2	8079	0.02	0.44	NO
41	PSMD11	PSMD11	PSMD11	8085	0.02	0.45	NO
42	DAPK3	DAPK3	DAPK3	8379	0.016	0.44	NO
43	PSMC1	PSMC1	PSMC1	8857	0.0092	0.42	NO
44	PSMD12	PSMD12	PSMD12	8951	0.0081	0.41	NO
45	PSMA6	PSMA6	PSMA6	9098	0.0065	0.41	NO
46	PSME1	PSME1	PSME1	9110	0.0063	0.41	NO
47	PSMA3	PSMA3	PSMA3	9175	0.0055	0.41	NO
48	PSMB5	PSMB5	PSMB5	9342	0.0032	0.4	NO
49	PSMD6	PSMD6	PSMD6	9575	0.00057	0.38	NO
50	PSMB7	PSMB7	PSMB7	10453	-0.0096	0.34	NO
51	DAPK1	DAPK1	DAPK1	11052	-0.017	0.31	NO
52	ARHGAP10	ARHGAP10	ARHGAP10	12028	-0.031	0.27	NO
53	PSMD5	PSMD5	PSMD5	13285	-0.05	0.21	NO
54	PSMC6	PSMC6	PSMC6	13553	-0.055	0.21	NO
55	UNC5B	UNC5B	UNC5B	14509	-0.074	0.18	NO
56	APPL1	APPL1	APPL1	14756	-0.079	0.19	NO

Figure S79. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: REACTOME MHC CLASS II ANTIGEN PRESENTATION.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus5 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT	38	genes.ES.table	0.42	1.6	0.037	1	0.91	0.32	0.3	0.22	1	0.74
KEGG NOTCH SIGNALING PATHWAY	46	genes.ES.table	0.39	1.3	0.17	1	1	0.28	0.25	0.21	1	0.82
KEGG RIG I LIKE RECEPTOR SIGNALING PATHWAY	61	genes.ES.table	0.36	1.3	0.16	1	1	0.28	0.26	0.21	1	0.8
KEGG OLFACTORY TRANSDUCTION	72	genes.ES.table	0.56	1.4	0.04	1	0.99	0.39	0.17	0.32	1	0.74
KEGG TASTE TRANSDUCTION	37	genes.ES.table	0.66	1.5	0.017	1	0.97	0.49	0.14	0.42	1	0.8
SIG CD40PATHWAYMAP	33	genes.ES.table	0.36	1.3	0.17	1	1	0.46	0.32	0.31	1	0.85
PID RHOA REG PATHWAY	44	genes.ES.table	0.38	1.3	0.16	1	1	0.3	0.27	0.22	1	0.85
PID HDAC CLASSI PATHWAY	65	genes.ES.table	0.33	1.6	0.03	1	0.86	0.31	0.37	0.2	1	0.79
REACTOME MEIOSIS	96	genes.ES.table	0.59	1.5	0.075	1	0.98	0.42	0.2	0.33	1	0.78
REACTOME SIGNALING BY FGFR1 MUTANTS	26	genes.ES.table	0.47	1.5	0.055	1	0.99	0.12	0.04	0.11	1	0.74

genes ES table in pathway: KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SSPO	SSPO	SSPO	101	0.66	0.15	YES
2	GATA1	GATA1	GATA1	2252	0.22	0.079	YES
3	SIRT4	SIRT4	SIRT4	2473	0.21	0.12	YES
4	HDAC10	HDAC10	HDAC10	2649	0.2	0.15	YES
5	SIN3B	SIN3B	SIN3B	2848	0.18	0.18	YES
6	ZFPM1	ZFPM1	ZFPM1	3205	0.17	0.2	YES
7	SIRT7	SIRT7	SIRT7	3324	0.16	0.23	YES
8	SMAD7	SMAD7	SMAD7	3474	0.15	0.26	YES
9	GATA2	GATA2	GATA2	3916	0.14	0.27	YES
10	SIRT6	SIRT6	SIRT6	3954	0.14	0.3	YES
11	HDAC7	HDAC7	HDAC7	4121	0.13	0.32	YES
12	NR2C1	NR2C1	NR2C1	4301	0.12	0.33	YES
13	NFKBIA	NFKBIA	NFKBIA	4747	0.11	0.33	YES
14	HDAC5	HDAC5	HDAC5	5943	0.075	0.29	YES
15	SIRT3	SIRT3	SIRT3	6025	0.074	0.3	YES
16	FKBP3	FKBP3	FKBP3	6135	0.071	0.31	YES
17	PPARG	PPARG	PPARG	6335	0.066	0.31	YES
18	SAP30	SAP30	SAP30	6529	0.062	0.32	YES
19	HDAC6	HDAC6	HDAC6	6558	0.062	0.33	YES
20	MBD3	MBD3	MBD3	6704	0.059	0.34	YES
21	SIRT2	SIRT2	SIRT2	7508	0.044	0.3	NO
22	HDAC1	HDAC1	HDAC1	7589	0.043	0.31	NO
23	GATAD2B	GATAD2B	GATAD2B	7640	0.042	0.31	NO
24	MBD2	MBD2	MBD2	7660	0.042	0.32	NO
25	RELA	RELA	RELA	8092	0.034	0.31	NO
26	MTA2	MTA2	MTA2	8127	0.034	0.31	NO
27	XPO1	XPO1	XPO1	8211	0.032	0.31	NO
28	HDAC8	HDAC8	HDAC8	8231	0.032	0.32	NO
29	SAP18	SAP18	SAP18	8425	0.029	0.32	NO
30	SIRT5	SIRT5	SIRT5	8432	0.028	0.32	NO
31	MXD1	MXD1	MXD1	8514	0.027	0.32	NO
32	MAX	MAX	MAX	9065	0.019	0.3	NO
33	UBE2I	UBE2I	UBE2I	9435	0.013	0.28	NO
34	SMURF1	SMURF1	SMURF1	9547	0.011	0.28	NO
35	RANGAP1	RANGAP1	RANGAP1	9560	0.011	0.28	NO
36	SIRT1	SIRT1	SIRT1	9572	0.011	0.28	NO
37	TNFRSF1A	TNFRSF1A	TNFRSF1A	9583	0.011	0.28	NO
38	HDAC4	HDAC4	HDAC4	9778	0.0076	0.28	NO
39	PRKACA	PRKACA	PRKACA	9899	0.0056	0.27	NO
40	NCOR2	NCOR2	NCOR2	9924	0.0054	0.27	NO
41	SUMO1	SUMO1	SUMO1	9989	0.0045	0.27	NO
42	WDR77	WDR77	WDR77	10078	0.0027	0.26	NO
43	CHD3	CHD3	CHD3	10088	0.0026	0.26	NO
44	YY1	YY1	YY1	10150	0.0017	0.26	NO
45	CREBBP	CREBBP	CREBBP	10483	-0.0036	0.24	NO
46	SMG5	SMG5	SMG5	10490	-0.0037	0.24	NO
47	HDAC11	HDAC11	HDAC11	10546	-0.0049	0.24	NO
48	GATAD2A	GATAD2A	GATAD2A	10620	-0.006	0.24	NO
49	RBBP7	RBBP7	RBBP7	11074	-0.012	0.22	NO
50	HDAC9	HDAC9	HDAC9	11121	-0.013	0.22	NO
51	HDAC3	HDAC3	HDAC3	12027	-0.026	0.17	NO
52	TNF	TNF	TNF	12140	-0.028	0.17	NO
53	KAT2B	KAT2B	KAT2B	12507	-0.033	0.16	NO
54	SIN3A	SIN3A	SIN3A	12564	-0.034	0.17	NO
55	RBBP4	RBBP4	RBBP4	12620	-0.035	0.17	NO
56	HDAC2	HDAC2	HDAC2	12794	-0.038	0.17	NO
57	STAT3	STAT3	STAT3	13106	-0.042	0.16	NO
58	CHD4	CHD4	CHD4	13137	-0.042	0.17	NO
59	EP300	EP300	EP300	13387	-0.047	0.17	NO
60	PRMT5	PRMT5	PRMT5	13615	-0.051	0.17	NO
61	TFCP2	TFCP2	TFCP2	14046	-0.059	0.16	NO
62	NFKB1	NFKB1	NFKB1	14460	-0.066	0.15	NO
63	RAN	RAN	RAN	14781	-0.072	0.15	NO
64	RANBP2	RANBP2	RANBP2	15391	-0.087	0.14	NO
65	NCOR1	NCOR1	NCOR1	15781	-0.098	0.14	NO

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

Figure S82. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT, 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 NOTCH SIGNALING PATHWAY

Table S42. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	STX1B	STX1B	STX1B	569	0.46	0.089	YES
2	VAMP1	VAMP1	VAMP1	833	0.39	0.18	YES
3	STX1A	STX1A	STX1A	1024	0.36	0.26	YES
4	SNAP25	SNAP25	SNAP25	1089	0.35	0.35	YES
5	STX19	STX19	STX19	1661	0.27	0.39	YES
6	TSNARE1	TSNARE1	TSNARE1	2442	0.21	0.4	YES
7	USE1	USE1	USE1	3453	0.16	0.39	YES
8	STX16	STX16	STX16	3789	0.14	0.4	YES
9	STX10	STX10	STX10	4578	0.11	0.39	YES
10	STX2	STX2	STX2	4665	0.11	0.42	YES
11	STX4	STX4	STX4	5055	0.098	0.42	YES
12	VAMP5	VAMP5	VAMP5	5427	0.088	0.42	YES
13	VAMP4	VAMP4	VAMP4	5896	0.077	0.42	NO
14	VAMP2	VAMP2	VAMP2	6589	0.061	0.4	NO
15	STX8	STX8	STX8	6850	0.056	0.4	NO
16	STX3	STX3	STX3	8604	0.026	0.31	NO
17	BNIP1	BNIP1	BNIP1	8695	0.024	0.31	NO
18	STX17	STX17	STX17	9038	0.019	0.29	NO
19	BET1L	BET1L	BET1L	9483	0.012	0.27	NO
20	STX7	STX7	STX7	10430	-0.0028	0.22	NO
21	STX5	STX5	STX5	10468	-0.0035	0.22	NO
22	BET1	BET1	BET1	10767	-0.0083	0.21	NO
23	VTI1B	VTI1B	VTI1B	11581	-0.019	0.17	NO
24	VAMP8	VAMP8	VAMP8	11665	-0.02	0.17	NO
25	STX11	STX11	STX11	11942	-0.025	0.16	NO
26	STX18	STX18	STX18	11972	-0.025	0.16	NO
27	SNAP29	SNAP29	SNAP29	12402	-0.032	0.15	NO
28	STX12	STX12	STX12	12426	-0.032	0.16	NO
29	STX6	STX6	STX6	12467	-0.033	0.16	NO
30	GOSR1	GOSR1	GOSR1	12729	-0.037	0.16	NO
31	SNAP23	SNAP23	SNAP23	12736	-0.037	0.17	NO
32	VTI1A	VTI1A	VTI1A	13801	-0.054	0.12	NO
33	VAMP3	VAMP3	VAMP3	14414	-0.065	0.11	NO
34	YKT6	YKT6	YKT6	14436	-0.065	0.12	NO
35	SNAP47	SNAP47	SNAP47	14493	-0.066	0.14	NO
36	SEC22B	SEC22B	SEC22B	14911	-0.076	0.13	NO
37	VAMP7	VAMP7	VAMP7	15639	-0.094	0.12	NO
38	GOSR2	GOSR2	GOSR2	15706	-0.096	0.14	NO

Figure S83. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG NOTCH SIGNALING PATHWAY.

Figure S84. 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 RIG I LIKE RECEPTOR SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	REC8	REC8	REC8	547	0.47	0.021	YES
2	TEX12	TEX12	TEX12	627	0.44	0.065	YES
3	HIST4H4	HIST4H4	HIST4H4	865	0.39	0.094	YES
4	SYCP2	SYCP2	SYCP2	917	0.38	0.13	YES
5	HIST2H2AC	HIST2H2AC	HIST2H2AC	1094	0.34	0.16	YES
6	HIST1H4E	HIST1H4E	HIST1H4E	1192	0.33	0.19	YES
7	HIST1H4B	HIST1H4B	HIST1H4B	1217	0.33	0.22	YES
8	HIST1H2BO	HIST1H2BO	HIST1H2BO	1263	0.32	0.26	YES
9	HIST1H4I	HIST1H4I	HIST1H4I	1344	0.31	0.29	YES
10	HIST1H2BE	HIST1H2BE	HIST1H2BE	1422	0.3	0.32	YES
11	HIST1H4C	HIST1H4C	HIST1H4C	1519	0.29	0.34	YES
12	STAG3	STAG3	STAG3	1761	0.26	0.36	YES
13	HIST1H4J	HIST1H4J	HIST1H4J	1764	0.26	0.39	YES
14	HIST1H2BG	HIST1H2BG	HIST1H2BG	1978	0.25	0.4	YES
15	HIST1H2BF	HIST1H2BF	HIST1H2BF	2033	0.24	0.42	YES
16	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	2074	0.24	0.45	YES
17	HIST1H2BM	HIST1H2BM	HIST1H2BM	2180	0.23	0.47	YES
18	SMC1B	SMC1B	SMC1B	2300	0.22	0.48	YES
19	HIST1H2BL	HIST1H2BL	HIST1H2BL	2340	0.22	0.51	YES
20	HIST1H2AE	HIST1H2AE	HIST1H2AE	2495	0.21	0.52	YES
21	HIST3H2BB	HIST3H2BB	HIST3H2BB	2547	0.2	0.54	YES
22	SYCP3	SYCP3	SYCP3	2671	0.2	0.55	YES
23	HIST3H3	HIST3H3	HIST3H3	2871	0.18	0.56	YES
24	HIST1H4A	HIST1H4A	HIST1H4A	2942	0.18	0.58	YES
25	HIST1H2AD	HIST1H2AD	HIST1H2AD	3067	0.17	0.59	YES
26	HIST1H2BH	HIST1H2BH	HIST1H2BH	3073	0.17	0.61	YES
27	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	3226	0.16	0.62	YES
28	HIST1H4D	HIST1H4D	HIST1H4D	3329	0.16	0.63	YES
29	HIST1H2BD	HIST1H2BD	HIST1H2BD	3596	0.15	0.63	YES
30	ACD	ACD	ACD	3696	0.14	0.64	YES
31	HIST2H2BE	HIST2H2BE	HIST2H2BE	3710	0.14	0.66	YES
32	FKBP6	FKBP6	FKBP6	4064	0.13	0.65	NO
33	HIST1H2BK	HIST1H2BK	HIST1H2BK	5337	0.091	0.59	NO
34	HIST1H4H	HIST1H4H	HIST1H4H	6250	0.068	0.55	NO
35	LMNA	LMNA	LMNA	6356	0.066	0.55	NO
36	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	6736	0.058	0.54	NO
37	H2AFX	H2AFX	H2AFX	7902	0.037	0.48	NO
38	HIST2H4A	HIST2H4A	HIST2H4A	8210	0.032	0.46	NO
39	DIDO1	DIDO1	DIDO1	8301	0.031	0.46	NO
40	HIST1H2AC	HIST1H2AC	HIST1H2AC	8562	0.026	0.45	NO
41	HIST1H2BN	HIST1H2BN	HIST1H2BN	8564	0.026	0.45	NO
42	SYNE1	SYNE1	SYNE1	9030	0.019	0.43	NO
43	UBE2I	UBE2I	UBE2I	9435	0.013	0.41	NO
44	TERF2IP	TERF2IP	TERF2IP	9479	0.012	0.41	NO
45	SYNE2	SYNE2	SYNE2	9855	0.0064	0.39	NO
46	TINF2	TINF2	TINF2	10053	0.0034	0.38	NO
47	ATR	ATR	ATR	10206	0.0008	0.37	NO
48	SUN2	SUN2	SUN2	10314	-0.00085	0.36	NO
49	H2AFZ	H2AFZ	H2AFZ	11927	-0.025	0.28	NO
50	SMC3	SMC3	SMC3	12490	-0.033	0.25	NO
51	LMNB1	LMNB1	LMNB1	12840	-0.038	0.24	NO
52	TERF2	TERF2	TERF2	13025	-0.041	0.23	NO
53	TERF1	TERF1	TERF1	13142	-0.043	0.23	NO
54	POT1	POT1	POT1	13367	-0.047	0.22	NO
55	HIST1H2BC	HIST1H2BC	HIST1H2BC	13493	-0.049	0.22	NO
56	STAG2	STAG2	STAG2	13516	-0.049	0.22	NO
57	RAD21	RAD21	RAD21	13620	-0.051	0.22	NO
58	HSPA2	HSPA2	HSPA2	14021	-0.058	0.21	NO
59	BRCA1	BRCA1	BRCA1	14261	-0.062	0.2	NO
60	STAG1	STAG1	STAG1	15323	-0.085	0.15	NO
61	SMC1A	SMC1A	SMC1A	15387	-0.087	0.16	NO

Figure S85. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RIG I LIKE RECEPTOR SIGNALING PATHWAY.

Figure S86. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RIG I LIKE RECEPTOR SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG OLFACTORY TRANSDUCTION

Table S44. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TAS2R5	TAS2R5	TAS2R5	139	0.63	0.065	YES
2	TAS2R20	TAS2R20	TAS2R20	233	0.57	0.13	YES
3	TAS2R10	TAS2R10	TAS2R10	335	0.54	0.18	YES
4	TAS2R14	TAS2R14	TAS2R14	392	0.51	0.24	YES
5	CACNA1A	CACNA1A	CACNA1A	496	0.48	0.29	YES
6	GNG3	GNG3	GNG3	571	0.46	0.34	YES
7	TAS2R19	TAS2R19	TAS2R19	661	0.43	0.38	YES
8	GNB3	GNB3	GNB3	770	0.41	0.42	YES
9	TAS2R4	TAS2R4	TAS2R4	780	0.4	0.47	YES
10	TRPM5	TRPM5	TRPM5	829	0.39	0.51	YES
11	TAS2R31	TAS2R31	TAS2R31	1157	0.34	0.53	YES
12	TAS2R1	TAS2R1	TAS2R1	1236	0.33	0.57	YES
13	TAS2R13	TAS2R13	TAS2R13	1359	0.31	0.6	YES
14	ADCY4	ADCY4	ADCY4	1823	0.26	0.6	YES
15	TAS2R50	TAS2R50	TAS2R50	1881	0.26	0.63	YES
16	TAS1R1	TAS1R1	TAS1R1	2049	0.24	0.64	YES
17	TAS2R43	TAS2R43	TAS2R43	2437	0.21	0.65	YES
18	PLCB2	PLCB2	PLCB2	2599	0.2	0.66	YES
19	TAS2R46	TAS2R46	TAS2R46	3628	0.15	0.62	NO
20	TAS1R3	TAS1R3	TAS1R3	4371	0.12	0.6	NO
21	SCNN1B	SCNN1B	SCNN1B	5701	0.082	0.53	NO
22	TAS2R3	TAS2R3	TAS2R3	6950	0.054	0.47	NO
23	GRM4	GRM4	GRM4	7529	0.044	0.44	NO
24	ADCY6	ADCY6	ADCY6	7977	0.036	0.42	NO
25	ITPR3	ITPR3	ITPR3	8342	0.03	0.41	NO
26	GNAS	GNAS	GNAS	8406	0.029	0.41	NO
27	CACNA1B	CACNA1B	CACNA1B	9231	0.016	0.36	NO
28	PRKACA	PRKACA	PRKACA	9899	0.0056	0.33	NO
29	PRKX	PRKX	PRKX	10498	-0.0038	0.3	NO
30	GNB1	GNB1	GNB1	13459	-0.048	0.14	NO
31	SCNN1G	SCNN1G	SCNN1G	13788	-0.054	0.13	NO
32	PRKACB	PRKACB	PRKACB	15529	-0.091	0.041	NO
33	ADCY8	ADCY8	ADCY8	16150	-0.11	0.02	NO
34	PDE1A	PDE1A	PDE1A	16723	-0.14	0.0044	NO
35	KCNB1	KCNB1	KCNB1	17034	-0.16	0.0058	NO
36	SCNN1A	SCNN1A	SCNN1A	17577	-0.21	0.00054	NO
37	ACCN1	ACCN1	ACCN1	18094	-0.32	0.009	NO

Figure S87. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG OLFACTORY TRANSDUCTION.

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

genes ES table in pathway: KEGG TASTE TRANSDUCTION

Table S45. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MSH4	MSH4	MSH4	269	0.56	0.028	YES
2	MSH5	MSH5	MSH5	494	0.48	0.052	YES
3	REC8	REC8	REC8	547	0.47	0.085	YES
4	TEX12	TEX12	TEX12	627	0.44	0.12	YES
5	HIST4H4	HIST4H4	HIST4H4	865	0.39	0.13	YES
6	SYCP2	SYCP2	SYCP2	917	0.38	0.16	YES
7	HIST2H2AC	HIST2H2AC	HIST2H2AC	1094	0.34	0.17	YES
8	HIST1H4E	HIST1H4E	HIST1H4E	1192	0.33	0.19	YES
9	HIST1H4B	HIST1H4B	HIST1H4B	1217	0.33	0.22	YES
10	HIST1H2BO	HIST1H2BO	HIST1H2BO	1263	0.32	0.24	YES
11	HIST1H4I	HIST1H4I	HIST1H4I	1344	0.31	0.26	YES
12	HIST1H2BE	HIST1H2BE	HIST1H2BE	1422	0.3	0.28	YES
13	TEX15	TEX15	TEX15	1469	0.29	0.3	YES
14	HIST1H4C	HIST1H4C	HIST1H4C	1519	0.29	0.32	YES
15	STAG3	STAG3	STAG3	1761	0.26	0.32	YES
16	HIST1H4J	HIST1H4J	HIST1H4J	1764	0.26	0.34	YES
17	DMC1	DMC1	DMC1	1887	0.25	0.36	YES
18	HIST1H2BG	HIST1H2BG	HIST1H2BG	1978	0.25	0.37	YES
19	HIST1H3J	HIST1H3J	HIST1H3J	2023	0.24	0.39	YES
20	HIST1H2BF	HIST1H2BF	HIST1H2BF	2033	0.24	0.41	YES
21	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	2074	0.24	0.42	YES
22	HIST1H2BM	HIST1H2BM	HIST1H2BM	2180	0.23	0.43	YES
23	SMC1B	SMC1B	SMC1B	2300	0.22	0.44	YES
24	HIST1H2BL	HIST1H2BL	HIST1H2BL	2340	0.22	0.46	YES
25	HIST1H3H	HIST1H3H	HIST1H3H	2392	0.21	0.47	YES
26	HIST1H2AE	HIST1H2AE	HIST1H2AE	2495	0.21	0.48	YES
27	HIST3H2BB	HIST3H2BB	HIST3H2BB	2547	0.2	0.49	YES
28	SYCP3	SYCP3	SYCP3	2671	0.2	0.5	YES
29	HIST2H3C	HIST2H3C	HIST2H3C	2721	0.19	0.52	YES
30	HIST3H3	HIST3H3	HIST3H3	2871	0.18	0.52	YES
31	HIST1H4A	HIST1H4A	HIST1H4A	2942	0.18	0.53	YES
32	HIST1H2AD	HIST1H2AD	HIST1H2AD	3067	0.17	0.54	YES
33	HIST1H2BH	HIST1H2BH	HIST1H2BH	3073	0.17	0.55	YES
34	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	3226	0.16	0.55	YES
35	HIST1H4D	HIST1H4D	HIST1H4D	3329	0.16	0.56	YES
36	HIST1H2BD	HIST1H2BD	HIST1H2BD	3596	0.15	0.56	YES
37	MLH3	MLH3	MLH3	3672	0.15	0.56	YES
38	ACD	ACD	ACD	3696	0.14	0.57	YES
39	HIST2H2BE	HIST2H2BE	HIST2H2BE	3710	0.14	0.58	YES
40	HIST1H3D	HIST1H3D	HIST1H3D	3726	0.14	0.6	YES
41	FKBP6	FKBP6	FKBP6	4064	0.13	0.59	NO
42	ATM	ATM	ATM	4284	0.12	0.58	NO
43	HIST1H2BK	HIST1H2BK	HIST1H2BK	5337	0.091	0.53	NO
44	HIST1H3C	HIST1H3C	HIST1H3C	5597	0.084	0.52	NO
45	H3F3A	H3F3A	H3F3A	5939	0.075	0.51	NO
46	HIST1H4H	HIST1H4H	HIST1H4H	6250	0.068	0.5	NO
47	LMNA	LMNA	LMNA	6356	0.066	0.5	NO
48	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	6736	0.058	0.48	NO
49	HIST1H3B	HIST1H3B	HIST1H3B	7409	0.046	0.45	NO
50	HIST1H3F	HIST1H3F	HIST1H3F	7548	0.044	0.44	NO
51	H2AFX	H2AFX	H2AFX	7902	0.037	0.43	NO
52	HIST1H3A	HIST1H3A	HIST1H3A	8066	0.035	0.42	NO
53	HIST2H4A	HIST2H4A	HIST2H4A	8210	0.032	0.42	NO
54	DIDO1	DIDO1	DIDO1	8301	0.031	0.41	NO
55	HIST1H2AC	HIST1H2AC	HIST1H2AC	8562	0.026	0.4	NO
56	HIST1H2BN	HIST1H2BN	HIST1H2BN	8564	0.026	0.4	NO
57	CDK2	CDK2	CDK2	8947	0.021	0.38	NO
58	HIST1H3E	HIST1H3E	HIST1H3E	8978	0.02	0.38	NO
59	SYNE1	SYNE1	SYNE1	9030	0.019	0.38	NO
60	H3F3B	H3F3B	H3F3B	9179	0.017	0.38	NO
61	UBE2I	UBE2I	UBE2I	9435	0.013	0.36	NO
62	HIST2H3D	HIST2H3D	HIST2H3D	9436	0.013	0.36	NO
63	TERF2IP	TERF2IP	TERF2IP	9479	0.012	0.36	NO
64	TOP3A	TOP3A	TOP3A	9609	0.01	0.36	NO
65	RPA2	RPA2	RPA2	9663	0.0094	0.35	NO
66	MRE11A	MRE11A	MRE11A	9676	0.0091	0.35	NO
67	SYNE2	SYNE2	SYNE2	9855	0.0064	0.34	NO
68	TINF2	TINF2	TINF2	10053	0.0034	0.34	NO
69	ATR	ATR	ATR	10206	0.0008	0.33	NO
70	SUN2	SUN2	SUN2	10314	-0.00085	0.32	NO
71	MND1	MND1	MND1	11787	-0.022	0.24	NO
72	H2AFZ	H2AFZ	H2AFZ	11927	-0.025	0.24	NO
73	SMC3	SMC3	SMC3	12490	-0.033	0.21	NO
74	LMNB1	LMNB1	LMNB1	12840	-0.038	0.19	NO
75	TERF2	TERF2	TERF2	13025	-0.041	0.18	NO
76	RBBP8	RBBP8	RBBP8	13051	-0.041	0.18	NO
77	TERF1	TERF1	TERF1	13142	-0.043	0.18	NO
78	MLH1	MLH1	MLH1	13205	-0.044	0.18	NO
79	BLM	BLM	BLM	13215	-0.044	0.19	NO
80	CDK4	CDK4	CDK4	13303	-0.046	0.18	NO
81	POT1	POT1	POT1	13367	-0.047	0.18	NO
82	HIST1H2BC	HIST1H2BC	HIST1H2BC	13493	-0.049	0.18	NO
83	STAG2	STAG2	STAG2	13516	-0.049	0.18	NO
84	RAD51C	RAD51C	RAD51C	13572	-0.05	0.18	NO
85	RAD21	RAD21	RAD21	13620	-0.051	0.19	NO
86	HSPA2	HSPA2	HSPA2	14021	-0.058	0.17	NO
87	HIST1H3G	HIST1H3G	HIST1H3G	14198	-0.061	0.16	NO
88	BRCA1	BRCA1	BRCA1	14261	-0.062	0.16	NO
89	RAD50	RAD50	RAD50	14505	-0.067	0.16	NO
90	RPA1	RPA1	RPA1	14710	-0.071	0.15	NO
91	RPA3	RPA3	RPA3	14745	-0.071	0.16	NO
92	NBN	NBN	NBN	15276	-0.084	0.13	NO
93	STAG1	STAG1	STAG1	15323	-0.085	0.14	NO
94	SMC1A	SMC1A	SMC1A	15387	-0.087	0.14	NO
95	RAD51	RAD51	RAD51	16397	-0.12	0.093	NO
96	BRCA2	BRCA2	BRCA2	16407	-0.12	0.1	NO

Figure S89. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG TASTE TRANSDUCTION.

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

genes ES table in pathway: SIG CD40PATHWAYMAP

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HIST4H4	HIST4H4	HIST4H4	865	0.39	0.012	YES
2	HIST2H2AC	HIST2H2AC	HIST2H2AC	1094	0.34	0.053	YES
3	HIST1H4E	HIST1H4E	HIST1H4E	1192	0.33	0.098	YES
4	HIST1H4B	HIST1H4B	HIST1H4B	1217	0.33	0.15	YES
5	HIST1H2BO	HIST1H2BO	HIST1H2BO	1263	0.32	0.2	YES
6	HIST1H4I	HIST1H4I	HIST1H4I	1344	0.31	0.24	YES
7	HIST1H2BE	HIST1H2BE	HIST1H2BE	1422	0.3	0.28	YES
8	HIST1H4C	HIST1H4C	HIST1H4C	1519	0.29	0.32	YES
9	HIST1H4J	HIST1H4J	HIST1H4J	1764	0.26	0.35	YES
10	HIST1H2BG	HIST1H2BG	HIST1H2BG	1978	0.25	0.37	YES
11	HIST1H2BF	HIST1H2BF	HIST1H2BF	2033	0.24	0.41	YES
12	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	2074	0.24	0.44	YES
13	HIST1H2BM	HIST1H2BM	HIST1H2BM	2180	0.23	0.47	YES
14	HIST1H2BL	HIST1H2BL	HIST1H2BL	2340	0.22	0.5	YES
15	HIST1H2AE	HIST1H2AE	HIST1H2AE	2495	0.21	0.52	YES
16	HIST3H2BB	HIST3H2BB	HIST3H2BB	2547	0.2	0.55	YES
17	HIST3H3	HIST3H3	HIST3H3	2871	0.18	0.56	YES
18	HIST1H4A	HIST1H4A	HIST1H4A	2942	0.18	0.58	YES
19	HIST1H2AD	HIST1H2AD	HIST1H2AD	3067	0.17	0.6	YES
20	HIST1H2BH	HIST1H2BH	HIST1H2BH	3073	0.17	0.63	YES
21	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	3226	0.16	0.65	YES
22	HIST1H4D	HIST1H4D	HIST1H4D	3329	0.16	0.66	YES
23	HIST1H2BD	HIST1H2BD	HIST1H2BD	3596	0.15	0.67	YES
24	ACD	ACD	ACD	3696	0.14	0.69	YES
25	HIST2H2BE	HIST2H2BE	HIST2H2BE	3710	0.14	0.71	YES
26	HIST1H2BK	HIST1H2BK	HIST1H2BK	5337	0.091	0.64	NO
27	HIST1H4H	HIST1H4H	HIST1H4H	6250	0.068	0.6	NO
28	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	6736	0.058	0.58	NO
29	H2AFX	H2AFX	H2AFX	7902	0.037	0.52	NO
30	HIST2H4A	HIST2H4A	HIST2H4A	8210	0.032	0.51	NO
31	HIST1H2AC	HIST1H2AC	HIST1H2AC	8562	0.026	0.49	NO
32	HIST1H2BN	HIST1H2BN	HIST1H2BN	8564	0.026	0.5	NO
33	TERF2IP	TERF2IP	TERF2IP	9479	0.012	0.45	NO
34	TINF2	TINF2	TINF2	10053	0.0034	0.42	NO
35	H2AFZ	H2AFZ	H2AFZ	11927	-0.025	0.32	NO
36	TERF2	TERF2	TERF2	13025	-0.041	0.27	NO
37	TERF1	TERF1	TERF1	13142	-0.043	0.27	NO
38	POT1	POT1	POT1	13367	-0.047	0.26	NO
39	HIST1H2BC	HIST1H2BC	HIST1H2BC	13493	-0.049	0.26	NO

Figure S91. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: SIG CD40PATHWAYMAP.

Figure S92. Get High-res Image For the top 5 core enriched genes in the pathway: SIG CD40PATHWAYMAP, 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 RHOA REG PATHWAY

Table S47. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	FGF17	FGF17	FGF17	38	0.73	0.23	YES
2	FGF23	FGF23	FGF23	554	0.46	0.35	YES
3	FGF8	FGF8	FGF8	740	0.41	0.47	YES
4	FGFR1OP	FGFR1OP	FGFR1OP	2780	0.19	0.42	NO
5	FGF20	FGF20	FGF20	3154	0.17	0.45	NO
6	ZMYM2	ZMYM2	ZMYM2	5145	0.096	0.37	NO
7	PLCG1	PLCG1	PLCG1	5503	0.087	0.38	NO
8	CPSF6	CPSF6	CPSF6	7053	0.052	0.31	NO
9	FGFR1	FGFR1	FGFR1	8074	0.034	0.27	NO
10	FGF2	FGF2	FGF2	8761	0.023	0.24	NO
11	STAT5B	STAT5B	STAT5B	9249	0.016	0.22	NO
12	FGFR1OP2	FGFR1OP2	FGFR1OP2	9441	0.013	0.21	NO
13	FGF1	FGF1	FGF1	10634	-0.0063	0.14	NO
14	STAT5A	STAT5A	STAT5A	11195	-0.014	0.12	NO
15	MYO18A	MYO18A	MYO18A	11940	-0.025	0.086	NO
16	TRIM24	TRIM24	TRIM24	12376	-0.031	0.072	NO
17	BCR	BCR	BCR	12390	-0.032	0.082	NO
18	STAT3	STAT3	STAT3	13106	-0.042	0.056	NO
19	GAB2	GAB2	GAB2	13680	-0.052	0.041	NO
20	GRB2	GRB2	GRB2	13869	-0.055	0.048	NO
21	CUX1	CUX1	CUX1	14653	-0.07	0.027	NO
22	FGF5	FGF5	FGF5	14773	-0.072	0.043	NO
23	PIK3R1	PIK3R1	PIK3R1	14782	-0.072	0.066	NO
24	STAT1	STAT1	STAT1	15826	-0.1	0.04	NO
25	FGF9	FGF9	FGF9	16839	-0.14	0.031	NO
26	PIK3CA	PIK3CA	PIK3CA	16867	-0.15	0.076	NO

Figure S93. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID RHOA REG PATHWAY.

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

genes ES table in pathway: PID HDAC CLASSI PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DNA2	DNA2	DNA2	480	0.49	0.03	YES
2	HIST4H4	HIST4H4	HIST4H4	865	0.39	0.053	YES
3	HIST2H2AC	HIST2H2AC	HIST2H2AC	1094	0.34	0.081	YES
4	HIST1H4E	HIST1H4E	HIST1H4E	1192	0.33	0.11	YES
5	HIST1H4B	HIST1H4B	HIST1H4B	1217	0.33	0.15	YES
6	HIST1H2BO	HIST1H2BO	HIST1H2BO	1263	0.32	0.18	YES
7	HIST1H4I	HIST1H4I	HIST1H4I	1344	0.31	0.22	YES
8	HIST1H2BE	HIST1H2BE	HIST1H2BE	1422	0.3	0.25	YES
9	HIST1H4C	HIST1H4C	HIST1H4C	1519	0.29	0.28	YES
10	TERT	TERT	TERT	1682	0.27	0.3	YES
11	HIST1H4J	HIST1H4J	HIST1H4J	1764	0.26	0.32	YES
12	HIST1H2BG	HIST1H2BG	HIST1H2BG	1978	0.25	0.34	YES
13	HIST1H2BF	HIST1H2BF	HIST1H2BF	2033	0.24	0.36	YES
14	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	2074	0.24	0.39	YES
15	HIST1H2BM	HIST1H2BM	HIST1H2BM	2180	0.23	0.41	YES
16	HIST1H2BL	HIST1H2BL	HIST1H2BL	2340	0.22	0.43	YES
17	HIST1H2AE	HIST1H2AE	HIST1H2AE	2495	0.21	0.44	YES
18	HIST3H2BB	HIST3H2BB	HIST3H2BB	2547	0.2	0.46	YES
19	HIST3H3	HIST3H3	HIST3H3	2871	0.18	0.47	YES
20	HIST1H4A	HIST1H4A	HIST1H4A	2942	0.18	0.48	YES
21	HIST1H2AD	HIST1H2AD	HIST1H2AD	3067	0.17	0.5	YES
22	HIST1H2BH	HIST1H2BH	HIST1H2BH	3073	0.17	0.52	YES
23	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	3226	0.16	0.53	YES
24	HIST1H4D	HIST1H4D	HIST1H4D	3329	0.16	0.54	YES
25	HIST1H2BD	HIST1H2BD	HIST1H2BD	3596	0.15	0.54	YES
26	ACD	ACD	ACD	3696	0.14	0.55	YES
27	HIST2H2BE	HIST2H2BE	HIST2H2BE	3710	0.14	0.57	YES
28	POLE	POLE	POLE	3816	0.14	0.58	YES
29	LIG1	LIG1	LIG1	4286	0.12	0.57	NO
30	HIST1H2BK	HIST1H2BK	HIST1H2BK	5337	0.091	0.52	NO
31	POLD1	POLD1	POLD1	5343	0.09	0.53	NO
32	WRAP53	WRAP53	WRAP53	5971	0.075	0.5	NO
33	HIST1H4H	HIST1H4H	HIST1H4H	6250	0.068	0.5	NO
34	RFC4	RFC4	RFC4	6679	0.06	0.48	NO
35	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	6736	0.058	0.48	NO
36	RFC2	RFC2	RFC2	7601	0.043	0.44	NO
37	POLE2	POLE2	POLE2	7827	0.039	0.43	NO
38	H2AFX	H2AFX	H2AFX	7902	0.037	0.43	NO
39	RUVBL2	RUVBL2	RUVBL2	8007	0.036	0.43	NO
40	POLD4	POLD4	POLD4	8097	0.034	0.43	NO
41	HIST2H4A	HIST2H4A	HIST2H4A	8210	0.032	0.43	NO
42	HIST1H2AC	HIST1H2AC	HIST1H2AC	8562	0.026	0.41	NO
43	HIST1H2BN	HIST1H2BN	HIST1H2BN	8564	0.026	0.42	NO
44	NHP2	NHP2	NHP2	9263	0.016	0.38	NO
45	TERF2IP	TERF2IP	TERF2IP	9479	0.012	0.37	NO
46	RPA2	RPA2	RPA2	9663	0.0094	0.36	NO
47	TINF2	TINF2	TINF2	10053	0.0034	0.34	NO
48	POLD3	POLD3	POLD3	10741	-0.0078	0.3	NO
49	POLD2	POLD2	POLD2	11177	-0.014	0.28	NO
50	DKC1	DKC1	DKC1	11909	-0.024	0.24	NO
51	POLA2	POLA2	POLA2	11925	-0.024	0.24	NO
52	H2AFZ	H2AFZ	H2AFZ	11927	-0.025	0.25	NO
53	RFC3	RFC3	RFC3	12243	-0.03	0.23	NO
54	TERF2	TERF2	TERF2	13025	-0.041	0.2	NO
55	RFC5	RFC5	RFC5	13088	-0.042	0.2	NO
56	TERF1	TERF1	TERF1	13142	-0.043	0.2	NO
57	RUVBL1	RUVBL1	RUVBL1	13243	-0.044	0.2	NO
58	POT1	POT1	POT1	13367	-0.047	0.2	NO
59	HIST1H2BC	HIST1H2BC	HIST1H2BC	13493	-0.049	0.2	NO
60	PCNA	PCNA	PCNA	14197	-0.061	0.16	NO
61	PRIM2	PRIM2	PRIM2	14631	-0.069	0.15	NO
62	RPA1	RPA1	RPA1	14710	-0.071	0.15	NO
63	RPA3	RPA3	RPA3	14745	-0.071	0.16	NO
64	FEN1	FEN1	FEN1	14858	-0.074	0.16	NO
65	POLA1	POLA1	POLA1	15977	-0.1	0.11	NO
66	PRIM1	PRIM1	PRIM1	16434	-0.12	0.1	NO

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

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

genes ES table in pathway: REACTOME MEIOSIS

Table S49. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AGER	AGER	AGER	88	0.66	0.12	YES
2	IFNA5	IFNA5	IFNA5	785	0.4	0.17	YES
3	IFNA21	IFNA21	IFNA21	844	0.39	0.24	YES
4	IRF7	IRF7	IRF7	1746	0.26	0.24	YES
5	S100A12	S100A12	S100A12	2145	0.23	0.26	YES
6	IRF3	IRF3	IRF3	2581	0.2	0.28	YES
7	ISG15	ISG15	ISG15	2933	0.18	0.3	YES
8	NFKB2	NFKB2	NFKB2	3307	0.16	0.31	YES
9	IKBKB	IKBKB	IKBKB	3982	0.13	0.3	YES
10	NLRC5	NLRC5	NLRC5	4101	0.13	0.31	YES
11	DHX58	DHX58	DHX58	4506	0.12	0.32	YES
12	TRAF2	TRAF2	TRAF2	4521	0.12	0.34	YES
13	NFKBIA	NFKBIA	NFKBIA	4747	0.11	0.34	YES
14	UBA7	UBA7	UBA7	4875	0.1	0.36	YES
15	NFKBIB	NFKBIB	NFKBIB	5891	0.077	0.32	NO
16	CASP10	CASP10	CASP10	6379	0.065	0.3	NO
17	IKBKG	IKBKG	IKBKG	6392	0.065	0.32	NO
18	HMGB1	HMGB1	HMGB1	6807	0.057	0.3	NO
19	PIN1	PIN1	PIN1	7531	0.044	0.27	NO
20	TANK	TANK	TANK	7670	0.041	0.27	NO
21	IRF1	IRF1	IRF1	7901	0.037	0.27	NO
22	RNF135	RNF135	RNF135	8059	0.035	0.27	NO
23	RELA	RELA	RELA	8092	0.034	0.27	NO
24	DAK	DAK	DAK	8248	0.032	0.27	NO
25	RPS27A	RPS27A	RPS27A	8269	0.031	0.27	NO
26	RNF125	RNF125	RNF125	8297	0.031	0.28	NO
27	MAVS	MAVS	MAVS	8543	0.027	0.27	NO
28	OTUD5	OTUD5	OTUD5	8557	0.027	0.27	NO
29	UBE2D2	UBE2D2	UBE2D2	8739	0.024	0.27	NO
30	ATG12	ATG12	ATG12	8900	0.021	0.26	NO
31	UBA52	UBA52	UBA52	9080	0.019	0.26	NO
32	TNFAIP3	TNFAIP3	TNFAIP3	9403	0.014	0.24	NO
33	SIKE1	SIKE1	SIKE1	9406	0.014	0.24	NO
34	RIPK1	RIPK1	RIPK1	9465	0.012	0.24	NO
35	TRIM25	TRIM25	TRIM25	9704	0.0087	0.23	NO
36	IFNB1	IFNB1	IFNB1	9732	0.0083	0.23	NO
37	CREBBP	CREBBP	CREBBP	10483	-0.0036	0.19	NO
38	HERC5	HERC5	HERC5	10617	-0.006	0.19	NO
39	MAP3K1	MAP3K1	MAP3K1	10821	-0.0089	0.18	NO
40	PCBP2	PCBP2	PCBP2	10864	-0.0095	0.18	NO
41	IRF2	IRF2	IRF2	11013	-0.012	0.17	NO
42	CASP8	CASP8	CASP8	11031	-0.012	0.17	NO
43	TBK1	TBK1	TBK1	12006	-0.026	0.12	NO
44	DDX58	DDX58	DDX58	12156	-0.028	0.12	NO
45	UBE2D3	UBE2D3	UBE2D3	12619	-0.035	0.1	NO
46	CYLD	CYLD	CYLD	12807	-0.038	0.1	NO
47	UBE2K	UBE2K	UBE2K	12839	-0.038	0.11	NO
48	APP	APP	APP	12930	-0.039	0.11	NO
49	ATG5	ATG5	ATG5	13068	-0.041	0.11	NO
50	UBE2D1	UBE2D1	UBE2D1	13379	-0.047	0.1	NO
51	EP300	EP300	EP300	13387	-0.047	0.11	NO
52	FADD	FADD	FADD	13401	-0.047	0.12	NO
53	NLRX1	NLRX1	NLRX1	13446	-0.048	0.12	NO
54	TRAF3	TRAF3	TRAF3	13506	-0.049	0.13	NO
55	S100B	S100B	S100B	13561	-0.05	0.14	NO
56	UBE2L6	UBE2L6	UBE2L6	13649	-0.051	0.14	NO
57	TRAF6	TRAF6	TRAF6	13840	-0.055	0.14	NO
58	IFIH1	IFIH1	IFIH1	14395	-0.064	0.13	NO
59	TAX1BP1	TAX1BP1	TAX1BP1	14670	-0.07	0.12	NO
60	CHUK	CHUK	CHUK	15341	-0.086	0.1	NO
61	IKBKE	IKBKE	IKBKE	15782	-0.098	0.099	NO
62	SAA1	SAA1	SAA1	17371	-0.19	0.049	NO

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

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

genes ES table in pathway: REACTOME SIGNALING BY FGFR1 MUTANTS

Table S50. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MSH4	MSH4	MSH4	269	0.56	0.04	YES
2	MSH5	MSH5	MSH5	494	0.48	0.076	YES
3	HIST4H4	HIST4H4	HIST4H4	865	0.39	0.093	YES
4	HIST2H2AC	HIST2H2AC	HIST2H2AC	1094	0.34	0.12	YES
5	HIST1H4E	HIST1H4E	HIST1H4E	1192	0.33	0.14	YES
6	HIST1H4B	HIST1H4B	HIST1H4B	1217	0.33	0.17	YES
7	HIST1H2BO	HIST1H2BO	HIST1H2BO	1263	0.32	0.2	YES
8	HIST1H4I	HIST1H4I	HIST1H4I	1344	0.31	0.23	YES
9	HIST1H2BE	HIST1H2BE	HIST1H2BE	1422	0.3	0.25	YES
10	TEX15	TEX15	TEX15	1469	0.29	0.28	YES
11	HIST1H4C	HIST1H4C	HIST1H4C	1519	0.29	0.31	YES
12	HIST1H4J	HIST1H4J	HIST1H4J	1764	0.26	0.32	YES
13	DMC1	DMC1	DMC1	1887	0.25	0.34	YES
14	HIST1H2BG	HIST1H2BG	HIST1H2BG	1978	0.25	0.36	YES
15	HIST1H3J	HIST1H3J	HIST1H3J	2023	0.24	0.38	YES
16	HIST1H2BF	HIST1H2BF	HIST1H2BF	2033	0.24	0.4	YES
17	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	2074	0.24	0.42	YES
18	HIST1H2BM	HIST1H2BM	HIST1H2BM	2180	0.23	0.44	YES
19	HIST1H2BL	HIST1H2BL	HIST1H2BL	2340	0.22	0.45	YES
20	HIST1H3H	HIST1H3H	HIST1H3H	2392	0.21	0.47	YES
21	HIST1H2AE	HIST1H2AE	HIST1H2AE	2495	0.21	0.48	YES
22	HIST3H2BB	HIST3H2BB	HIST3H2BB	2547	0.2	0.5	YES
23	HIST2H3C	HIST2H3C	HIST2H3C	2721	0.19	0.51	YES
24	HIST3H3	HIST3H3	HIST3H3	2871	0.18	0.52	YES
25	HIST1H4A	HIST1H4A	HIST1H4A	2942	0.18	0.54	YES
26	HIST1H2AD	HIST1H2AD	HIST1H2AD	3067	0.17	0.55	YES
27	HIST1H2BH	HIST1H2BH	HIST1H2BH	3073	0.17	0.56	YES
28	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	3226	0.16	0.57	YES
29	HIST1H4D	HIST1H4D	HIST1H4D	3329	0.16	0.58	YES
30	HIST1H2BD	HIST1H2BD	HIST1H2BD	3596	0.15	0.58	YES
31	MLH3	MLH3	MLH3	3672	0.15	0.59	YES
32	HIST2H2BE	HIST2H2BE	HIST2H2BE	3710	0.14	0.6	YES
33	HIST1H3D	HIST1H3D	HIST1H3D	3726	0.14	0.62	YES
34	ATM	ATM	ATM	4284	0.12	0.6	NO
35	HIST1H2BK	HIST1H2BK	HIST1H2BK	5337	0.091	0.55	NO
36	HIST1H3C	HIST1H3C	HIST1H3C	5597	0.084	0.54	NO
37	H3F3A	H3F3A	H3F3A	5939	0.075	0.53	NO
38	HIST1H4H	HIST1H4H	HIST1H4H	6250	0.068	0.52	NO
39	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	6736	0.058	0.5	NO
40	HIST1H3B	HIST1H3B	HIST1H3B	7409	0.046	0.47	NO
41	HIST1H3F	HIST1H3F	HIST1H3F	7548	0.044	0.46	NO
42	H2AFX	H2AFX	H2AFX	7902	0.037	0.45	NO
43	HIST1H3A	HIST1H3A	HIST1H3A	8066	0.035	0.44	NO
44	HIST2H4A	HIST2H4A	HIST2H4A	8210	0.032	0.44	NO
45	HIST1H2AC	HIST1H2AC	HIST1H2AC	8562	0.026	0.42	NO
46	HIST1H2BN	HIST1H2BN	HIST1H2BN	8564	0.026	0.42	NO
47	CDK2	CDK2	CDK2	8947	0.021	0.41	NO
48	HIST1H3E	HIST1H3E	HIST1H3E	8978	0.02	0.41	NO
49	H3F3B	H3F3B	H3F3B	9179	0.017	0.4	NO
50	HIST2H3D	HIST2H3D	HIST2H3D	9436	0.013	0.38	NO
51	TOP3A	TOP3A	TOP3A	9609	0.01	0.38	NO
52	RPA2	RPA2	RPA2	9663	0.0094	0.37	NO
53	MRE11A	MRE11A	MRE11A	9676	0.0091	0.37	NO
54	MND1	MND1	MND1	11787	-0.022	0.26	NO
55	H2AFZ	H2AFZ	H2AFZ	11927	-0.025	0.26	NO
56	RBBP8	RBBP8	RBBP8	13051	-0.041	0.2	NO
57	MLH1	MLH1	MLH1	13205	-0.044	0.19	NO
58	BLM	BLM	BLM	13215	-0.044	0.2	NO
59	CDK4	CDK4	CDK4	13303	-0.046	0.2	NO
60	HIST1H2BC	HIST1H2BC	HIST1H2BC	13493	-0.049	0.19	NO
61	RAD51C	RAD51C	RAD51C	13572	-0.05	0.19	NO
62	HIST1H3G	HIST1H3G	HIST1H3G	14198	-0.061	0.16	NO
63	BRCA1	BRCA1	BRCA1	14261	-0.062	0.17	NO
64	RAD50	RAD50	RAD50	14505	-0.067	0.16	NO
65	RPA1	RPA1	RPA1	14710	-0.071	0.16	NO
66	RPA3	RPA3	RPA3	14745	-0.071	0.16	NO
67	NBN	NBN	NBN	15276	-0.084	0.14	NO
68	RAD51	RAD51	RAD51	16397	-0.12	0.09	NO
69	BRCA2	BRCA2	BRCA2	16407	-0.12	0.1	NO

Figure S99. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: REACTOME SIGNALING BY FGFR1 MUTANTS.

Figure S100. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME SIGNALING BY FGFR1 MUTANTS, 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 = KIRC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = KIRC-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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