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

Rectum Adenocarcinoma (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2016): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in READ-TP. Broad Institute of MIT and Harvard. doi:10.7908/C10P0ZGT

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 "READ-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: 716
Number of samples: 166
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 ] 32
pheno.type: 2 - 5 :[ clus5 ] 58
pheno.type: 3 - 5 :[ clus2 ] 14
pheno.type: 4 - 5 :[ clus3 ] 34
pheno.type: 5 - 5 :[ clus4 ] 28

For the expression subtypes of 18106 genes in 167 samples, GSEA found enriched gene sets in each cluster using 166 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG ABC TRANSPORTERS, KEGG MAPK SIGNALING PATHWAY, KEGG ERBB SIGNALING PATHWAY, KEGG CALCIUM SIGNALING PATHWAY, KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION, KEGG CHEMOKINE SIGNALING PATHWAY, KEGG PHOSPHATIDYLINOSITOL SIGNALING SYSTEM, KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION, KEGG OOCYTE MEIOSIS, KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT

And common core enriched genes are FYN, PIK3CA, SOS1, ACTN1, BRAF, RAP1A, TLN1, ACTA1, ASAP1, DOCK1

clus2

Top enriched gene sets are KEGG INOSITOL PHOSPHATE METABOLISM, BIOCARTA HIVNEF PATHWAY, PID HDAC CLASSII PATHWAY, PID TRAIL PATHWAY, PID CDC42 PATHWAY, PID FASPATHWAY, PID NFAT 3PATHWAY, PID ERBB1 RECEPTOR PROXIMAL PATHWAY, PID CERAMIDE PATHWAY, PID AR TF PATHWAY

And common core enriched genes are PIK3C2A, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIP4K2A, PIP5K1B, PTEN, SYNJ1, SYNJ2

clus3

Top enriched gene sets are KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RNA DEGRADATION, BIOCARTA FAS PATHWAY, PID PLK1 PATHWAY, PID BARD1PATHWAY, PID P53REGULATIONPATHWAY, REACTOME METABOLISM OF NON CODING RNA, REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA, REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM, REACTOME CELL CYCLE MITOTIC

And common core enriched genes are NUP133, NUP37, NUP43, RANBP2, SEH1L, CDC40, CPSF2, CPSF3, EIF4E, NCBP1

clus4

Top enriched gene sets are KEGG LYSINE DEGRADATION, KEGG SELENOAMINO ACID METABOLISM, KEGG RNA DEGRADATION, KEGG SPLICEOSOME, KEGG PEROXISOME, PID ATM PATHWAY, REACTOME METABOLISM OF NON CODING RNA, REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA, REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM, REACTOME RNA POL II TRANSCRIPTION

And common core enriched genes are CDC40, CPSF3, CSTF2, CSTF3, MAGOH, NCBP2, NUDT21, PAPOLA, PCF11, UPF3B

clus5

Top enriched gene sets are KEGG PENTOSE PHOSPHATE PATHWAY, KEGG SYSTEMIC LUPUS ERYTHEMATOSUS, REACTOME MEIOSIS, REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S, REACTOME RNA POL I TRANSCRIPTION, REACTOME GLYCOLYSIS, REACTOME GLUCONEOGENESIS, REACTOME PREFOLDIN MEDIATED TRANSFER OF SUBSTRATE TO CCT TRIC, REACTOME 3 UTR MEDIATED TRANSLATIONAL REGULATION, REACTOME TRANSCRIPTION

And common core enriched genes are H2AFX, HIST1H2AB, HIST1H2AE, HIST1H2AJ, HIST1H2BC, HIST1H2BE, HIST1H2BF, HIST1H2BG, HIST1H2BH, HIST1H2BI

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 ABC TRANSPORTERS	43	genes.ES.table	0.51	1.4	0.048	0.21	0.99	0.21	0.095	0.19	0.15	0.004
KEGG MAPK SIGNALING PATHWAY	253	genes.ES.table	0.43	1.6	0.013	0.16	0.93	0.32	0.25	0.24	0.083	0.018
KEGG ERBB SIGNALING PATHWAY	86	genes.ES.table	0.37	1.5	0.053	0.19	0.99	0.3	0.28	0.22	0.13	0.009
KEGG CALCIUM SIGNALING PATHWAY	164	genes.ES.table	0.56	1.6	0.0084	0.16	0.92	0.39	0.17	0.33	0.082	0.018
KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION	236	genes.ES.table	0.53	1.3	0.13	0.25	1	0.51	0.25	0.38	0.19	0.002
KEGG CHEMOKINE SIGNALING PATHWAY	183	genes.ES.table	0.47	1.3	0.16	0.25	1	0.31	0.17	0.26	0.19	0.002
KEGG PHOSPHATIDYLINOSITOL SIGNALING SYSTEM	73	genes.ES.table	0.34	1.3	0.16	0.25	1	0.34	0.32	0.23	0.19	0.002
KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION	215	genes.ES.table	0.52	1.4	0.062	0.24	1	0.47	0.21	0.38	0.18	0.002
KEGG OOCYTE MEIOSIS	106	genes.ES.table	0.35	1.5	0.035	0.18	0.98	0.076	0.065	0.071	0.11	0.008
KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT	38	genes.ES.table	0.36	1.4	0.13	0.21	0.99	0.34	0.32	0.23	0.15	0.004

genes ES table in pathway: KEGG ABC TRANSPORTERS

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	KLF8	KLF8	KLF8	757	0.48	0.047	YES
2	ITGA5	ITGA5	ITGA5	1824	0.3	0.044	YES
3	ITGAV	ITGAV	ITGAV	2112	0.27	0.078	YES
4	ETS1	ETS1	ETS1	2283	0.25	0.12	YES
5	MMP14	MMP14	MMP14	2346	0.24	0.16	YES
6	FYN	FYN	FYN	2781	0.21	0.17	YES
7	ELMO1	ELMO1	ELMO1	2796	0.2	0.21	YES
8	PIK3CA	PIK3CA	PIK3CA	3029	0.18	0.23	YES
9	PTPN21	PTPN21	PTPN21	3209	0.17	0.25	YES
10	BMX	BMX	BMX	3329	0.17	0.28	YES
11	ASAP1	ASAP1	ASAP1	3419	0.16	0.3	YES
12	VCL	VCL	VCL	3672	0.15	0.32	YES
13	ITGB5	ITGB5	ITGB5	4164	0.13	0.31	YES
14	RAP1A	RAP1A	RAP1A	4200	0.13	0.34	YES
15	ITGB1	ITGB1	ITGB1	4432	0.12	0.34	YES
16	GIT2	GIT2	GIT2	4485	0.12	0.36	YES
17	ROCK2	ROCK2	ROCK2	4503	0.12	0.38	YES
18	SOS1	SOS1	SOS1	4554	0.12	0.4	YES
19	NCK1	NCK1	NCK1	4571	0.12	0.42	YES
20	ACTA1	ACTA1	ACTA1	4614	0.11	0.44	YES
21	TLN1	TLN1	TLN1	4655	0.11	0.46	YES
22	ACTN1	ACTN1	ACTN1	4737	0.11	0.48	YES
23	BRAF	BRAF	BRAF	4871	0.11	0.49	YES
24	DOCK1	DOCK1	DOCK1	4888	0.1	0.51	YES
25	WASL	WASL	WASL	5012	0.1	0.52	YES
26	RAPGEF1	RAPGEF1	RAPGEF1	5416	0.09	0.52	NO
27	PIK3R1	PIK3R1	PIK3R1	5625	0.084	0.52	NO
28	CCND1	CCND1	CCND1	6525	0.065	0.48	NO
29	RASA1	RASA1	RASA1	6962	0.057	0.47	NO
30	MAP2K1	MAP2K1	MAP2K1	7121	0.054	0.47	NO
31	JUN	JUN	JUN	7129	0.054	0.48	NO
32	PTK2	PTK2	PTK2	7175	0.053	0.49	NO
33	YES1	YES1	YES1	7194	0.053	0.5	NO
34	ARHGEF7	ARHGEF7	ARHGEF7	7429	0.048	0.49	NO
35	MAPK1	MAPK1	MAPK1	7905	0.039	0.47	NO
36	RAC1	RAC1	RAC1	7971	0.038	0.48	NO
37	CAPN2	CAPN2	CAPN2	7990	0.038	0.48	NO
38	PLCG1	PLCG1	PLCG1	8117	0.036	0.48	NO
39	MAPK9	MAPK9	MAPK9	8325	0.033	0.48	NO
40	RHOA	RHOA	RHOA	8528	0.029	0.47	NO
41	GRB2	GRB2	GRB2	8831	0.024	0.46	NO
42	PAK1	PAK1	PAK1	9079	0.02	0.45	NO
43	MAP2K4	MAP2K4	MAP2K4	9098	0.019	0.45	NO
44	NCK2	NCK2	NCK2	9123	0.019	0.45	NO
45	ARHGEF11	ARHGEF11	ARHGEF11	9256	0.017	0.45	NO
46	MAPK8	MAPK8	MAPK8	9558	0.012	0.43	NO
47	RAP1B	RAP1B	RAP1B	9837	0.0069	0.42	NO
48	PXN	PXN	PXN	10041	0.0038	0.41	NO
49	RGNEF	RGNEF	RGNEF	10075	0.0032	0.41	NO
50	CRK	CRK	CRK	10196	0.0011	0.4	NO
51	RAF1	RAF1	RAF1	10380	-0.0019	0.39	NO
52	SH3GL1	SH3GL1	SH3GL1	10744	-0.0079	0.37	NO
53	RRAS	RRAS	RRAS	10839	-0.0094	0.37	NO
54	ARHGAP26	ARHGAP26	ARHGAP26	10914	-0.011	0.37	NO
55	SRC	SRC	SRC	11311	-0.018	0.35	NO
56	GRB7	GRB7	GRB7	12203	-0.034	0.3	NO
57	BCAR1	BCAR1	BCAR1	12451	-0.038	0.3	NO
58	MAPK8IP3	MAPK8IP3	MAPK8IP3	14319	-0.079	0.21	NO

Figure S1. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG ABC TRANSPORTERS.

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

genes ES table in pathway: KEGG MAPK SIGNALING PATHWAY

Table 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	TNS1	TNS1	TNS1	704	0.49	0.074	YES
2	ACTN2	ACTN2	ACTN2	936	0.44	0.16	YES
3	PPP1R12B	PPP1R12B	PPP1R12B	1583	0.33	0.2	YES
4	ITGA1	ITGA1	ITGA1	2102	0.27	0.24	YES
5	CAV1	CAV1	CAV1	2148	0.26	0.3	YES
6	FYN	FYN	FYN	2781	0.21	0.31	YES
7	CAPNS2	CAPNS2	CAPNS2	2907	0.2	0.35	YES
8	ACTN3	ACTN3	ACTN3	3289	0.17	0.37	YES
9	ROCK1	ROCK1	ROCK1	3660	0.15	0.38	YES
10	VCL	VCL	VCL	3672	0.15	0.41	YES
11	RAP1A	RAP1A	RAP1A	4200	0.13	0.41	YES
12	ITGB1	ITGB1	ITGB1	4432	0.12	0.43	YES
13	SOS1	SOS1	SOS1	4554	0.12	0.45	YES
14	ACTA1	ACTA1	ACTA1	4614	0.11	0.47	YES
15	TLN1	TLN1	TLN1	4655	0.11	0.5	YES
16	ACTN1	ACTN1	ACTN1	4737	0.11	0.52	YES
17	RAPGEF1	RAPGEF1	RAPGEF1	5416	0.09	0.5	NO
18	MAP2K1	MAP2K1	MAP2K1	7121	0.054	0.42	NO
19	JUN	JUN	JUN	7129	0.054	0.43	NO
20	SHC1	SHC1	SHC1	7140	0.054	0.44	NO
21	PTK2	PTK2	PTK2	7175	0.053	0.45	NO
22	MAPK1	MAPK1	MAPK1	7905	0.039	0.42	NO
23	ZYX	ZYX	ZYX	8122	0.036	0.42	NO
24	RHOA	RHOA	RHOA	8528	0.029	0.4	NO
25	GRB2	GRB2	GRB2	8831	0.024	0.39	NO
26	MAPK8	MAPK8	MAPK8	9558	0.012	0.35	NO
27	CRKL	CRKL	CRKL	9673	0.0096	0.35	NO
28	PXN	PXN	PXN	10041	0.0038	0.33	NO
29	RAF1	RAF1	RAF1	10380	-0.0019	0.31	NO
30	SRC	SRC	SRC	11311	-0.018	0.26	NO
31	CAPN1	CAPN1	CAPN1	12166	-0.033	0.22	NO
32	BCAR1	BCAR1	BCAR1	12451	-0.038	0.22	NO
33	MAPK3	MAPK3	MAPK3	12548	-0.04	0.22	NO
34	CSK	CSK	CSK	13143	-0.052	0.2	NO
35	BCR	BCR	BCR	13851	-0.067	0.18	NO
36	CAPNS1	CAPNS1	CAPNS1	14077	-0.072	0.18	NO
37	HRAS	HRAS	HRAS	14517	-0.085	0.18	NO
38	MAP2K2	MAP2K2	MAP2K2	14966	-0.099	0.17	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 MAPK SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG ERBB SIGNALING PATHWAY

Table 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	LY96	LY96	LY96	348	0.62	0.17	YES
2	GJA1	GJA1	GJA1	1667	0.32	0.19	YES
3	GNAI1	GNAI1	GNAI1	2057	0.27	0.26	YES
4	TLR4	TLR4	TLR4	2089	0.27	0.34	YES
5	LEF1	LEF1	LEF1	2096	0.27	0.42	YES
6	FZD1	FZD1	FZD1	2141	0.27	0.5	YES
7	PIK3CA	PIK3CA	PIK3CA	3029	0.18	0.5	YES
8	CD14	CD14	CD14	3407	0.16	0.53	YES
9	APC	APC	APC	3427	0.16	0.58	YES
10	EIF2AK2	EIF2AK2	EIF2AK2	3446	0.16	0.63	YES
11	PIK3R1	PIK3R1	PIK3R1	5625	0.084	0.53	NO
12	CCND1	CCND1	CCND1	6525	0.065	0.5	NO
13	GSK3B	GSK3B	GSK3B	7748	0.042	0.45	NO
14	WNT1	WNT1	WNT1	8820	0.024	0.4	NO
15	NFKB1	NFKB1	NFKB1	9265	0.017	0.38	NO
16	RELA	RELA	RELA	9364	0.015	0.38	NO
17	CTNNB1	CTNNB1	CTNNB1	9731	0.0085	0.36	NO
18	MYD88	MYD88	MYD88	10495	-0.0039	0.32	NO
19	PDPK1	PDPK1	PDPK1	10578	-0.0054	0.32	NO
20	TIRAP	TIRAP	TIRAP	10729	-0.0077	0.31	NO
21	AKT1	AKT1	AKT1	11291	-0.017	0.28	NO
22	PPP2CA	PPP2CA	PPP2CA	11305	-0.018	0.29	NO
23	AXIN1	AXIN1	AXIN1	11671	-0.024	0.28	NO
24	TOLLIP	TOLLIP	TOLLIP	12824	-0.045	0.22	NO
25	IRAK1	IRAK1	IRAK1	13002	-0.048	0.23	NO
26	DVL1	DVL1	DVL1	14206	-0.076	0.19	NO
27	LBP	LBP	LBP	14800	-0.094	0.18	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 ERBB SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG CALCIUM SIGNALING PATHWAY

Table 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	PPP2R2B	PPP2R2B	PPP2R2B	213	0.69	0.04	YES
2	MYOCD	MYOCD	MYOCD	258	0.66	0.088	YES
3	MAPK10	MAPK10	MAPK10	581	0.53	0.11	YES
4	TAGLN	TAGLN	TAGLN	1263	0.38	0.1	YES
5	FGR	FGR	FGR	1312	0.37	0.13	YES
6	SPHK1	SPHK1	SPHK1	1351	0.37	0.15	YES
7	ITGB3	ITGB3	ITGB3	1369	0.36	0.18	YES
8	DOCK4	DOCK4	DOCK4	1396	0.36	0.2	YES
9	PIK3R6	PIK3R6	PIK3R6	1414	0.36	0.23	YES
10	PIK3CG	PIK3CG	PIK3CG	1484	0.34	0.25	YES
11	ACTA2	ACTA2	ACTA2	1683	0.32	0.27	YES
12	S1PR1	S1PR1	S1PR1	1730	0.31	0.29	YES
13	PIK3R5	PIK3R5	PIK3R5	1755	0.31	0.31	YES
14	SLA	SLA	SLA	1771	0.31	0.33	YES
15	PDGFRB	PDGFRB	PDGFRB	1809	0.3	0.35	YES
16	ITGAV	ITGAV	ITGAV	2112	0.27	0.36	YES
17	PIK3CD	PIK3CD	PIK3CD	2220	0.26	0.37	YES
18	HCK	HCK	HCK	2399	0.24	0.38	YES
19	JAK2	JAK2	JAK2	2541	0.23	0.39	YES
20	PDGFB	PDGFB	PDGFB	2708	0.21	0.4	YES
21	FYN	FYN	FYN	2781	0.21	0.41	YES
22	PIK3CA	PIK3CA	PIK3CA	3029	0.18	0.41	YES
23	EIF2AK2	EIF2AK2	EIF2AK2	3446	0.16	0.4	YES
24	PAG1	PAG1	PAG1	3649	0.15	0.4	YES
25	STAT1	STAT1	STAT1	3835	0.14	0.4	YES
26	RAP1A	RAP1A	RAP1A	4200	0.13	0.39	YES
27	FOS	FOS	FOS	4544	0.12	0.38	YES
28	SOS1	SOS1	SOS1	4554	0.12	0.38	YES
29	PLA2G4A	PLA2G4A	PLA2G4A	4558	0.12	0.39	YES
30	NCK1	NCK1	NCK1	4571	0.12	0.4	YES
31	CBL	CBL	CBL	4580	0.11	0.41	YES
32	GAB1	GAB1	GAB1	4618	0.11	0.42	YES
33	ACTR2	ACTR2	ACTR2	4857	0.11	0.41	YES
34	BRAF	BRAF	BRAF	4871	0.11	0.42	YES
35	WASL	WASL	WASL	5012	0.1	0.42	YES
36	PIK3R3	PIK3R3	PIK3R3	5110	0.099	0.42	YES
37	RAB5A	RAB5A	RAB5A	5157	0.097	0.42	YES
38	LRP1	LRP1	LRP1	5372	0.092	0.42	YES
39	RAPGEF1	RAPGEF1	RAPGEF1	5416	0.09	0.42	YES
40	PIK3R1	PIK3R1	PIK3R1	5625	0.084	0.42	YES
41	GRB10	GRB10	GRB10	5980	0.076	0.4	YES
42	PTPRJ	PTPRJ	PTPRJ	6089	0.074	0.4	YES
43	SLC9A3R2	SLC9A3R2	SLC9A3R2	6096	0.074	0.41	YES
44	IQGAP1	IQGAP1	IQGAP1	6130	0.073	0.41	YES
45	PTEN	PTEN	PTEN	6241	0.07	0.41	YES
46	YWHAG	YWHAG	YWHAG	6290	0.07	0.41	YES
47	VAV2	VAV2	VAV2	6334	0.069	0.42	YES
48	ARPC3	ARPC3	ARPC3	6554	0.064	0.41	YES
49	PTPN11	PTPN11	PTPN11	6566	0.064	0.41	YES
50	NCKAP1	NCKAP1	NCKAP1	6585	0.064	0.42	YES
51	NRAS	NRAS	NRAS	6607	0.064	0.42	YES
52	KRAS	KRAS	KRAS	6672	0.062	0.42	YES
53	STAT5B	STAT5B	STAT5B	6863	0.059	0.42	YES
54	PIK3CB	PIK3CB	PIK3CB	6912	0.058	0.42	YES
55	RASA1	RASA1	RASA1	6962	0.057	0.42	YES
56	ABL1	ABL1	ABL1	6965	0.057	0.42	YES
57	MAP2K1	MAP2K1	MAP2K1	7121	0.054	0.42	YES
58	JUN	JUN	JUN	7129	0.054	0.42	YES
59	SHC1	SHC1	SHC1	7140	0.054	0.43	YES
60	WASF2	WASF2	WASF2	7161	0.054	0.43	YES
61	YES1	YES1	YES1	7194	0.053	0.43	YES
62	YWHAZ	YWHAZ	YWHAZ	7200	0.053	0.44	YES
63	ABI1	ABI1	ABI1	7210	0.052	0.44	YES
64	RPS6KA3	RPS6KA3	RPS6KA3	7410	0.048	0.43	NO
65	MLLT4	MLLT4	MLLT4	7427	0.048	0.43	NO
66	PRKCE	PRKCE	PRKCE	7499	0.047	0.43	NO
67	ACTR3	ACTR3	ACTR3	7563	0.046	0.43	NO
68	ARAP1	ARAP1	ARAP1	7629	0.044	0.43	NO
69	ARPC5	ARPC5	ARPC5	7891	0.039	0.42	NO
70	MAPK1	MAPK1	MAPK1	7905	0.039	0.42	NO
71	RAC1	RAC1	RAC1	7971	0.038	0.42	NO
72	YWHAH	YWHAH	YWHAH	8106	0.036	0.42	NO
73	PLCG1	PLCG1	PLCG1	8117	0.036	0.42	NO
74	KSR1	KSR1	KSR1	8322	0.033	0.41	NO
75	MAPK9	MAPK9	MAPK9	8325	0.033	0.41	NO
76	RHOA	RHOA	RHOA	8528	0.029	0.4	NO
77	SRF	SRF	SRF	8621	0.028	0.4	NO
78	BAIAP2	BAIAP2	BAIAP2	8634	0.028	0.4	NO
79	STAT3	STAT3	STAT3	8788	0.025	0.4	NO
80	GRB2	GRB2	GRB2	8831	0.024	0.4	NO
81	STAT5A	STAT5A	STAT5A	8967	0.022	0.39	NO
82	YWHAB	YWHAB	YWHAB	8975	0.022	0.39	NO
83	USP6NL	USP6NL	USP6NL	8979	0.021	0.39	NO
84	PTPN2	PTPN2	PTPN2	8986	0.021	0.4	NO
85	PAK1	PAK1	PAK1	9079	0.02	0.39	NO
86	MAP2K4	MAP2K4	MAP2K4	9098	0.019	0.39	NO
87	NCK2	NCK2	NCK2	9123	0.019	0.39	NO
88	DOK1	DOK1	DOK1	9282	0.016	0.38	NO
89	MAPK8	MAPK8	MAPK8	9558	0.012	0.37	NO
90	SIPA1	SIPA1	SIPA1	9584	0.011	0.37	NO
91	CTTN	CTTN	CTTN	9693	0.0092	0.36	NO
92	ARPC2	ARPC2	ARPC2	9808	0.0074	0.36	NO
93	RAP1B	RAP1B	RAP1B	9837	0.0069	0.36	NO
94	MAP2K7	MAP2K7	MAP2K7	9865	0.0064	0.36	NO
95	EPS8	EPS8	EPS8	9974	0.0047	0.35	NO
96	PTPN1	PTPN1	PTPN1	10144	0.0021	0.34	NO
97	CRK	CRK	CRK	10196	0.0011	0.34	NO
98	YWHAQ	YWHAQ	YWHAQ	10362	-0.0017	0.33	NO
99	RAF1	RAF1	RAF1	10380	-0.0019	0.33	NO
100	ACTN4	ACTN4	ACTN4	10475	-0.0036	0.32	NO
101	LYN	LYN	LYN	10538	-0.0045	0.32	NO
102	ELK1	ELK1	ELK1	10617	-0.006	0.32	NO
103	YWHAE	YWHAE	YWHAE	10701	-0.0073	0.31	NO
104	ARPC4	ARPC4	ARPC4	10704	-0.0074	0.31	NO
105	PRKCD	PRKCD	PRKCD	10900	-0.01	0.3	NO
106	PRKCA	PRKCA	PRKCA	11274	-0.017	0.28	NO
107	PPP2CA	PPP2CA	PPP2CA	11305	-0.018	0.28	NO
108	SRC	SRC	SRC	11311	-0.018	0.28	NO
109	RAB4A	RAB4A	RAB4A	11331	-0.018	0.28	NO
110	ARPC1B	ARPC1B	ARPC1B	11461	-0.02	0.28	NO
111	LCK	LCK	LCK	12180	-0.033	0.24	NO
112	BCAR1	BCAR1	BCAR1	12451	-0.038	0.23	NO
113	MAPK3	MAPK3	MAPK3	12548	-0.04	0.23	NO
114	CSK	CSK	CSK	13143	-0.052	0.2	NO
115	ARHGDIA	ARHGDIA	ARHGDIA	13154	-0.052	0.2	NO
116	DNM2	DNM2	DNM2	13352	-0.056	0.19	NO
117	BLK	BLK	BLK	13371	-0.056	0.2	NO
118	CYFIP2	CYFIP2	CYFIP2	13795	-0.066	0.18	NO
119	PPP2R1A	PPP2R1A	PPP2R1A	13829	-0.067	0.18	NO
120	MYC	MYC	MYC	14108	-0.074	0.17	NO
121	SFN	SFN	SFN	14114	-0.074	0.18	NO
122	PIK3R2	PIK3R2	PIK3R2	14118	-0.074	0.18	NO
123	PIN1	PIN1	PIN1	14404	-0.081	0.17	NO
124	HRAS	HRAS	HRAS	14517	-0.085	0.17	NO
125	JUND	JUND	JUND	14716	-0.091	0.17	NO
126	MAP2K2	MAP2K2	MAP2K2	14966	-0.099	0.16	NO
127	SLC9A3R1	SLC9A3R1	SLC9A3R1	16107	-0.15	0.11	NO

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

Figure S8. 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 CYTOKINE CYTOKINE RECEPTOR INTERACTION

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	AKT3	AKT3	AKT3	522	0.55	0.021	YES
2	ITGA10	ITGA10	ITGA10	558	0.54	0.068	YES
3	RASGRF2	RASGRF2	RASGRF2	571	0.53	0.12	YES
4	MAPK10	MAPK10	MAPK10	581	0.53	0.16	YES
5	MRAS	MRAS	MRAS	742	0.48	0.2	YES
6	PAK3	PAK3	PAK3	788	0.47	0.24	YES
7	ITGA11	ITGA11	ITGA11	816	0.47	0.28	YES
8	MYLK	MYLK	MYLK	873	0.46	0.32	YES
9	ANGPTL2	ANGPTL2	ANGPTL2	1159	0.4	0.34	YES
10	ARHGEF6	ARHGEF6	ARHGEF6	1297	0.38	0.36	YES
11	ITGA4	ITGA4	ITGA4	1494	0.34	0.38	YES
12	ITGA7	ITGA7	ITGA7	1524	0.34	0.42	YES
13	ITGA5	ITGA5	ITGA5	1824	0.3	0.43	YES
14	WAS	WAS	WAS	1937	0.29	0.45	YES
15	ITGA1	ITGA1	ITGA1	2102	0.27	0.46	YES
16	CAV1	CAV1	CAV1	2148	0.26	0.48	YES
17	MAPK8IP2	MAPK8IP2	MAPK8IP2	2610	0.22	0.48	YES
18	FYN	FYN	FYN	2781	0.21	0.49	YES
19	PLCG2	PLCG2	PLCG2	2910	0.2	0.5	YES
20	PIK3CA	PIK3CA	PIK3CA	3029	0.18	0.51	YES
21	ASAP1	ASAP1	ASAP1	3419	0.16	0.5	YES
22	ITGA9	ITGA9	ITGA9	3482	0.16	0.51	YES
23	MAPK8IP1	MAPK8IP1	MAPK8IP1	3577	0.15	0.52	YES
24	ROCK1	ROCK1	ROCK1	3660	0.15	0.53	YES
25	SOS2	SOS2	SOS2	3891	0.14	0.53	YES
26	ROCK2	ROCK2	ROCK2	4503	0.12	0.51	YES
27	SOS1	SOS1	SOS1	4554	0.12	0.51	YES
28	TLN1	TLN1	TLN1	4655	0.11	0.52	YES
29	ACTN1	ACTN1	ACTN1	4737	0.11	0.52	YES
30	ACTR2	ACTR2	ACTR2	4857	0.11	0.53	YES
31	BRAF	BRAF	BRAF	4871	0.11	0.54	YES
32	DOCK1	DOCK1	DOCK1	4888	0.1	0.54	YES
33	TERF2IP	TERF2IP	TERF2IP	5446	0.09	0.52	NO
34	PAK2	PAK2	PAK2	5878	0.079	0.5	NO
35	RALA	RALA	RALA	5890	0.078	0.51	NO
36	ITGA8	ITGA8	ITGA8	6114	0.074	0.5	NO
37	PTEN	PTEN	PTEN	6241	0.07	0.5	NO
38	PIK3CB	PIK3CB	PIK3CB	6912	0.058	0.47	NO
39	MYLK2	MYLK2	MYLK2	6929	0.058	0.48	NO
40	ABL1	ABL1	ABL1	6965	0.057	0.48	NO
41	CDC42	CDC42	CDC42	7092	0.055	0.48	NO
42	SHC1	SHC1	SHC1	7140	0.054	0.48	NO
43	PTK2	PTK2	PTK2	7175	0.053	0.48	NO
44	ARHGEF7	ARHGEF7	ARHGEF7	7429	0.048	0.47	NO
45	ACTR3	ACTR3	ACTR3	7563	0.046	0.47	NO
46	ILK	ILK	ILK	7655	0.044	0.47	NO
47	MAPK1	MAPK1	MAPK1	7905	0.039	0.46	NO
48	PLCG1	PLCG1	PLCG1	8117	0.036	0.45	NO
49	ZYX	ZYX	ZYX	8122	0.036	0.45	NO
50	MAPK9	MAPK9	MAPK9	8325	0.033	0.45	NO
51	ITGA2	ITGA2	ITGA2	8431	0.031	0.44	NO
52	GRB2	GRB2	GRB2	8831	0.024	0.42	NO
53	PAK1	PAK1	PAK1	9079	0.02	0.41	NO
54	MAP2K4	MAP2K4	MAP2K4	9098	0.019	0.41	NO
55	ITGB3BP	ITGB3BP	ITGB3BP	9479	0.013	0.39	NO
56	MAPK8	MAPK8	MAPK8	9558	0.012	0.39	NO
57	MAP2K7	MAP2K7	MAP2K7	9865	0.0064	0.37	NO
58	TLN2	TLN2	TLN2	10021	0.004	0.36	NO
59	CSE1L	CSE1L	CSE1L	10186	0.0013	0.36	NO
60	CRK	CRK	CRK	10196	0.0011	0.35	NO
61	TNK2	TNK2	TNK2	10373	-0.0018	0.34	NO
62	RAF1	RAF1	RAF1	10380	-0.0019	0.34	NO
63	ARHGAP26	ARHGAP26	ARHGAP26	10914	-0.011	0.32	NO
64	AKT1	AKT1	AKT1	11291	-0.017	0.3	NO
65	SRC	SRC	SRC	11311	-0.018	0.3	NO
66	VASP	VASP	VASP	11547	-0.022	0.29	NO
67	ITGA6	ITGA6	ITGA6	11767	-0.026	0.28	NO
68	AKT2	AKT2	AKT2	11899	-0.028	0.27	NO
69	GRB7	GRB7	GRB7	12203	-0.034	0.26	NO
70	ITGA3	ITGA3	ITGA3	12208	-0.034	0.26	NO
71	BCAR1	BCAR1	BCAR1	12451	-0.038	0.25	NO
72	P4HB	P4HB	P4HB	12755	-0.044	0.24	NO
73	MAP3K11	MAP3K11	MAP3K11	12800	-0.044	0.24	NO
74	PAK6	PAK6	PAK6	12942	-0.047	0.24	NO
75	PAK4	PAK4	PAK4	13141	-0.052	0.23	NO
76	CDKN2A	CDKN2A	CDKN2A	14048	-0.072	0.18	NO
77	MAPK8IP3	MAPK8IP3	MAPK8IP3	14319	-0.079	0.18	NO
78	EPHB2	EPHB2	EPHB2	14761	-0.093	0.16	NO
79	PKLR	PKLR	PKLR	17185	-0.26	0.05	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 CYTOKINE CYTOKINE RECEPTOR INTERACTION.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CYTOKINE CYTOKINE 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 CHEMOKINE SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACTN2	ACTN2	ACTN2	936	0.44	0.0093	YES
2	SNAI2	SNAI2	SNAI2	995	0.43	0.065	YES
3	CTNNA3	CTNNA3	CTNNA3	1109	0.41	0.12	YES
4	SORBS1	SORBS1	SORBS1	1367	0.36	0.15	YES
5	FGFR1	FGFR1	FGFR1	1506	0.34	0.19	YES
6	PTPRM	PTPRM	PTPRM	1610	0.33	0.23	YES
7	WASF3	WASF3	WASF3	1781	0.31	0.26	YES
8	WAS	WAS	WAS	1937	0.29	0.3	YES
9	LEF1	LEF1	LEF1	2096	0.27	0.32	YES
10	TCF7L1	TCF7L1	TCF7L1	2444	0.24	0.34	YES
11	WASF1	WASF1	WASF1	2764	0.21	0.35	YES
12	FYN	FYN	FYN	2781	0.21	0.38	YES
13	TGFBR1	TGFBR1	TGFBR1	3016	0.19	0.39	YES
14	ACTN3	ACTN3	ACTN3	3289	0.17	0.4	YES
15	VCL	VCL	VCL	3672	0.15	0.4	YES
16	TGFBR2	TGFBR2	TGFBR2	4203	0.13	0.38	YES
17	EGFR	EGFR	EGFR	4274	0.12	0.4	YES
18	SNAI1	SNAI1	SNAI1	4552	0.12	0.4	YES
19	ACTN1	ACTN1	ACTN1	4737	0.11	0.4	YES
20	CTNNA2	CTNNA2	CTNNA2	4748	0.11	0.42	YES
21	WASL	WASL	WASL	5012	0.1	0.42	YES
22	IGF1R	IGF1R	IGF1R	5113	0.099	0.42	YES
23	TJP1	TJP1	TJP1	5208	0.096	0.43	YES
24	FER	FER	FER	5217	0.095	0.45	YES
25	PTPRB	PTPRB	PTPRB	5729	0.082	0.43	YES
26	PTPRJ	PTPRJ	PTPRJ	6089	0.074	0.42	YES
27	IQGAP1	IQGAP1	IQGAP1	6130	0.073	0.43	YES
28	SMAD2	SMAD2	SMAD2	6154	0.072	0.44	YES
29	MET	MET	MET	6165	0.072	0.44	YES
30	LMO7	LMO7	LMO7	6291	0.07	0.45	YES
31	EP300	EP300	EP300	6509	0.065	0.44	YES
32	SMAD4	SMAD4	SMAD4	6612	0.064	0.45	YES
33	SMAD3	SMAD3	SMAD3	6935	0.057	0.44	YES
34	CDC42	CDC42	CDC42	7092	0.055	0.44	YES
35	WASF2	WASF2	WASF2	7161	0.054	0.44	YES
36	MAP3K7	MAP3K7	MAP3K7	7167	0.053	0.45	YES
37	CSNK2A1	CSNK2A1	CSNK2A1	7187	0.053	0.45	YES
38	YES1	YES1	YES1	7194	0.053	0.46	YES
39	INSR	INSR	INSR	7371	0.049	0.46	YES
40	MLLT4	MLLT4	MLLT4	7427	0.048	0.46	YES
41	CREBBP	CREBBP	CREBBP	7520	0.046	0.46	YES
42	SSX2IP	SSX2IP	SSX2IP	7591	0.045	0.46	YES
43	MAPK1	MAPK1	MAPK1	7905	0.039	0.45	NO
44	RAC1	RAC1	RAC1	7971	0.038	0.46	NO
45	CTNND1	CTNND1	CTNND1	8095	0.036	0.45	NO
46	RHOA	RHOA	RHOA	8528	0.029	0.43	NO
47	BAIAP2	BAIAP2	BAIAP2	8634	0.028	0.43	NO
48	NLK	NLK	NLK	9114	0.019	0.41	NO
49	PARD3	PARD3	PARD3	9326	0.016	0.4	NO
50	CTNNB1	CTNNB1	CTNNB1	9731	0.0085	0.38	NO
51	CDH1	CDH1	CDH1	9754	0.0082	0.38	NO
52	TCF7	TCF7	TCF7	9894	0.0059	0.37	NO
53	PTPN1	PTPN1	PTPN1	10144	0.0021	0.36	NO
54	ACP1	ACP1	ACP1	10285	-0.00036	0.35	NO
55	ACTN4	ACTN4	ACTN4	10475	-0.0036	0.34	NO
56	CTNNA1	CTNNA1	CTNNA1	10480	-0.0037	0.34	NO
57	ACTB	ACTB	ACTB	10738	-0.0078	0.32	NO
58	TCF7L2	TCF7L2	TCF7L2	10766	-0.0083	0.32	NO
59	PVRL3	PVRL3	PVRL3	10886	-0.01	0.32	NO
60	RAC2	RAC2	RAC2	11109	-0.014	0.31	NO
61	PTPRF	PTPRF	PTPRF	11116	-0.014	0.31	NO
62	SRC	SRC	SRC	11311	-0.018	0.3	NO
63	ERBB2	ERBB2	ERBB2	11468	-0.02	0.3	NO
64	PTPN6	PTPN6	PTPN6	11622	-0.023	0.29	NO
65	FARP2	FARP2	FARP2	12229	-0.034	0.26	NO
66	CSNK2A2	CSNK2A2	CSNK2A2	12532	-0.039	0.25	NO
67	MAPK3	MAPK3	MAPK3	12548	-0.04	0.26	NO
68	PVRL1	PVRL1	PVRL1	12611	-0.041	0.26	NO
69	ACTG1	ACTG1	ACTG1	12921	-0.047	0.25	NO
70	PVRL2	PVRL2	PVRL2	13332	-0.056	0.23	NO
71	CSNK2B	CSNK2B	CSNK2B	13365	-0.056	0.24	NO
72	PVRL4	PVRL4	PVRL4	13664	-0.063	0.23	NO
73	RAC3	RAC3	RAC3	15322	-0.11	0.15	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: KEGG CHEMOKINE SIGNALING PATHWAY.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CHEMOKINE SIGNALING PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PHOSPHATIDYLINOSITOL SIGNALING SYSTEM

Table 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	THBS4	THBS4	THBS4	23	0.91	0.025	YES
2	COMP	COMP	COMP	200	0.7	0.035	YES
3	IGF1	IGF1	IGF1	321	0.64	0.047	YES
4	COL11A1	COL11A1	COL11A1	329	0.63	0.064	YES
5	SHC4	SHC4	SHC4	413	0.59	0.077	YES
6	VEGFC	VEGFC	VEGFC	430	0.58	0.093	YES
7	IBSP	IBSP	IBSP	435	0.58	0.11	YES
8	RELN	RELN	RELN	471	0.57	0.12	YES
9	THBS2	THBS2	THBS2	473	0.56	0.14	YES
10	SPP1	SPP1	SPP1	502	0.56	0.15	YES
11	HGF	HGF	HGF	517	0.55	0.17	YES
12	AKT3	AKT3	AKT3	522	0.55	0.18	YES
13	ITGA10	ITGA10	ITGA10	558	0.54	0.2	YES
14	MAPK10	MAPK10	MAPK10	581	0.53	0.21	YES
15	TNN	TNN	TNN	613	0.52	0.22	YES
16	PDGFC	PDGFC	PDGFC	624	0.51	0.24	YES
17	LAMA2	LAMA2	LAMA2	762	0.48	0.24	YES
18	TNXB	TNXB	TNXB	779	0.47	0.26	YES
19	PAK3	PAK3	PAK3	788	0.47	0.27	YES
20	ITGA11	ITGA11	ITGA11	816	0.47	0.28	YES
21	MYLK	MYLK	MYLK	873	0.46	0.29	YES
22	ACTN2	ACTN2	ACTN2	936	0.44	0.3	YES
23	COL6A6	COL6A6	COL6A6	1008	0.42	0.31	YES
24	TNC	TNC	TNC	1069	0.42	0.32	YES
25	FLNC	FLNC	FLNC	1087	0.41	0.33	YES
26	PRKCB	PRKCB	PRKCB	1247	0.38	0.33	YES
27	COL4A4	COL4A4	COL4A4	1308	0.37	0.34	YES
28	ITGB3	ITGB3	ITGB3	1369	0.36	0.35	YES
29	MYL9	MYL9	MYL9	1381	0.36	0.36	YES
30	COL5A2	COL5A2	COL5A2	1418	0.36	0.36	YES
31	FN1	FN1	FN1	1446	0.35	0.37	YES
32	PIK3CG	PIK3CG	PIK3CG	1484	0.34	0.38	YES
33	ITGA4	ITGA4	ITGA4	1494	0.34	0.39	YES
34	ITGA7	ITGA7	ITGA7	1524	0.34	0.4	YES
35	COL6A3	COL6A3	COL6A3	1652	0.32	0.4	YES
36	FLT4	FLT4	FLT4	1738	0.31	0.4	YES
37	PIK3R5	PIK3R5	PIK3R5	1755	0.31	0.41	YES
38	PDGFRB	PDGFRB	PDGFRB	1809	0.3	0.42	YES
39	ITGA5	ITGA5	ITGA5	1824	0.3	0.43	YES
40	COL5A1	COL5A1	COL5A1	1893	0.29	0.43	YES
41	PDGFD	PDGFD	PDGFD	1917	0.29	0.44	YES
42	COL1A2	COL1A2	COL1A2	1965	0.28	0.44	YES
43	FIGF	FIGF	FIGF	1971	0.28	0.45	YES
44	COL3A1	COL3A1	COL3A1	1984	0.28	0.46	YES
45	COL5A3	COL5A3	COL5A3	1993	0.28	0.47	YES
46	LAMA4	LAMA4	LAMA4	2033	0.28	0.47	YES
47	ITGA1	ITGA1	ITGA1	2102	0.27	0.48	YES
48	ITGAV	ITGAV	ITGAV	2112	0.27	0.48	YES
49	ITGB8	ITGB8	ITGB8	2142	0.27	0.49	YES
50	KDR	KDR	KDR	2143	0.27	0.5	YES
51	CAV1	CAV1	CAV1	2148	0.26	0.5	YES
52	CAV2	CAV2	CAV2	2173	0.26	0.51	YES
53	COL1A1	COL1A1	COL1A1	2216	0.26	0.52	YES
54	PIK3CD	PIK3CD	PIK3CD	2220	0.26	0.52	YES
55	PARVG	PARVG	PARVG	2231	0.26	0.53	YES
56	FLT1	FLT1	FLT1	2299	0.25	0.53	YES
57	FLNA	FLNA	FLNA	2300	0.25	0.54	YES
58	THBS1	THBS1	THBS1	2304	0.25	0.55	YES
59	COL6A1	COL6A1	COL6A1	2503	0.23	0.54	YES
60	PDGFRA	PDGFRA	PDGFRA	2523	0.23	0.55	YES
61	BCL2	BCL2	BCL2	2568	0.22	0.55	YES
62	COL6A2	COL6A2	COL6A2	2634	0.22	0.55	YES
63	TNR	TNR	TNR	2666	0.22	0.56	YES
64	PDGFB	PDGFB	PDGFB	2708	0.21	0.56	YES
65	FYN	FYN	FYN	2781	0.21	0.56	YES
66	COL4A2	COL4A2	COL4A2	2885	0.2	0.56	YES
67	COL4A1	COL4A1	COL4A1	2889	0.2	0.57	YES
68	LAMB2	LAMB2	LAMB2	2899	0.2	0.57	YES
69	THBS3	THBS3	THBS3	2973	0.19	0.58	YES
70	PIK3CA	PIK3CA	PIK3CA	3029	0.18	0.58	YES
71	BIRC3	BIRC3	BIRC3	3130	0.18	0.58	YES
72	LAMC1	LAMC1	LAMC1	3282	0.17	0.57	YES
73	ACTN3	ACTN3	ACTN3	3289	0.17	0.58	YES
74	VWF	VWF	VWF	3420	0.16	0.58	YES
75	PDGFA	PDGFA	PDGFA	3477	0.16	0.58	YES
76	ITGA9	ITGA9	ITGA9	3482	0.16	0.58	YES
77	PGF	PGF	PGF	3575	0.15	0.58	YES
78	VTN	VTN	VTN	3654	0.15	0.58	YES
79	ROCK1	ROCK1	ROCK1	3660	0.15	0.59	YES
80	VCL	VCL	VCL	3672	0.15	0.59	YES
81	LAMB1	LAMB1	LAMB1	3748	0.15	0.59	YES
82	MYLK3	MYLK3	MYLK3	3843	0.14	0.59	YES
83	MYL2	MYL2	MYL2	3855	0.14	0.59	YES
84	SOS2	SOS2	SOS2	3891	0.14	0.59	YES
85	ARHGAP5	ARHGAP5	ARHGAP5	4031	0.13	0.59	YES
86	PPP1R12A	PPP1R12A	PPP1R12A	4053	0.13	0.59	YES
87	VAV1	VAV1	VAV1	4071	0.13	0.6	YES
88	BIRC2	BIRC2	BIRC2	4092	0.13	0.6	YES
89	ITGB5	ITGB5	ITGB5	4164	0.13	0.6	YES
90	RAP1A	RAP1A	RAP1A	4200	0.13	0.6	YES
91	EGFR	EGFR	EGFR	4274	0.12	0.6	NO
92	ITGB1	ITGB1	ITGB1	4432	0.12	0.59	NO
93	ROCK2	ROCK2	ROCK2	4503	0.12	0.59	NO
94	SOS1	SOS1	SOS1	4554	0.12	0.59	NO
95	SHC3	SHC3	SHC3	4577	0.12	0.6	NO
96	TLN1	TLN1	TLN1	4655	0.11	0.59	NO
97	ACTN1	ACTN1	ACTN1	4737	0.11	0.59	NO
98	BRAF	BRAF	BRAF	4871	0.11	0.59	NO
99	DOCK1	DOCK1	DOCK1	4888	0.1	0.59	NO
100	PIK3R3	PIK3R3	PIK3R3	5110	0.099	0.58	NO
101	IGF1R	IGF1R	IGF1R	5113	0.099	0.58	NO
102	PARVA	PARVA	PARVA	5182	0.096	0.58	NO
103	RAPGEF1	RAPGEF1	RAPGEF1	5416	0.09	0.57	NO
104	PIK3R1	PIK3R1	PIK3R1	5625	0.084	0.56	NO
105	LAMA5	LAMA5	LAMA5	5646	0.084	0.56	NO
106	PPP1CB	PPP1CB	PPP1CB	5669	0.083	0.57	NO
107	LAMC2	LAMC2	LAMC2	5871	0.079	0.56	NO
108	PAK2	PAK2	PAK2	5878	0.079	0.56	NO
109	SHC2	SHC2	SHC2	5902	0.078	0.56	NO
110	ITGA8	ITGA8	ITGA8	6114	0.074	0.55	NO
111	MET	MET	MET	6165	0.072	0.55	NO
112	PTEN	PTEN	PTEN	6241	0.07	0.55	NO
113	VAV2	VAV2	VAV2	6334	0.069	0.54	NO
114	CCND1	CCND1	CCND1	6525	0.065	0.54	NO
115	VEGFB	VEGFB	VEGFB	6663	0.062	0.53	NO
116	LAMB4	LAMB4	LAMB4	6898	0.058	0.52	NO
117	PIK3CB	PIK3CB	PIK3CB	6912	0.058	0.52	NO
118	MYLK2	MYLK2	MYLK2	6929	0.058	0.52	NO
119	LAMA3	LAMA3	LAMA3	7018	0.056	0.52	NO
120	CDC42	CDC42	CDC42	7092	0.055	0.51	NO
121	MAP2K1	MAP2K1	MAP2K1	7121	0.054	0.51	NO
122	JUN	JUN	JUN	7129	0.054	0.52	NO
123	SHC1	SHC1	SHC1	7140	0.054	0.52	NO
124	PTK2	PTK2	PTK2	7175	0.053	0.52	NO
125	PIP5K1C	PIP5K1C	PIP5K1C	7179	0.053	0.52	NO
126	XIAP	XIAP	XIAP	7204	0.053	0.52	NO
127	ILK	ILK	ILK	7655	0.044	0.49	NO
128	GSK3B	GSK3B	GSK3B	7748	0.042	0.49	NO
129	VAV3	VAV3	VAV3	7791	0.041	0.49	NO
130	MAPK1	MAPK1	MAPK1	7905	0.039	0.48	NO
131	RAC1	RAC1	RAC1	7971	0.038	0.48	NO
132	CAPN2	CAPN2	CAPN2	7990	0.038	0.48	NO
133	ZYX	ZYX	ZYX	8122	0.036	0.47	NO
134	MAPK9	MAPK9	MAPK9	8325	0.033	0.46	NO
135	ITGA2	ITGA2	ITGA2	8431	0.031	0.46	NO
136	RHOA	RHOA	RHOA	8528	0.029	0.45	NO
137	VEGFA	VEGFA	VEGFA	8613	0.028	0.45	NO
138	LAMA1	LAMA1	LAMA1	8796	0.024	0.44	NO
139	GRB2	GRB2	GRB2	8831	0.024	0.44	NO
140	MYL12A	MYL12A	MYL12A	8880	0.023	0.44	NO
141	ITGB6	ITGB6	ITGB6	9008	0.021	0.43	NO
142	PAK1	PAK1	PAK1	9079	0.02	0.43	NO
143	FLNB	FLNB	FLNB	9421	0.014	0.41	NO
144	LAMB3	LAMB3	LAMB3	9472	0.013	0.41	NO
145	MAPK8	MAPK8	MAPK8	9558	0.012	0.4	NO
146	CRKL	CRKL	CRKL	9673	0.0096	0.4	NO
147	CTNNB1	CTNNB1	CTNNB1	9731	0.0085	0.39	NO
148	RAP1B	RAP1B	RAP1B	9837	0.0069	0.39	NO
149	TLN2	TLN2	TLN2	10021	0.004	0.38	NO
150	PXN	PXN	PXN	10041	0.0038	0.38	NO
151	DIAPH1	DIAPH1	DIAPH1	10120	0.0025	0.37	NO
152	CRK	CRK	CRK	10196	0.0011	0.37	NO
153	RAF1	RAF1	RAF1	10380	-0.0019	0.36	NO
154	LAMC3	LAMC3	LAMC3	10438	-0.0029	0.36	NO
155	ACTN4	ACTN4	ACTN4	10475	-0.0036	0.35	NO
156	CCND2	CCND2	CCND2	10558	-0.0049	0.35	NO
157	PDPK1	PDPK1	PDPK1	10578	-0.0054	0.35	NO
158	ITGB7	ITGB7	ITGB7	10588	-0.0055	0.35	NO
159	PPP1CC	PPP1CC	PPP1CC	10601	-0.0056	0.35	NO
160	ELK1	ELK1	ELK1	10617	-0.006	0.35	NO
161	ACTB	ACTB	ACTB	10738	-0.0078	0.34	NO
162	RAC2	RAC2	RAC2	11109	-0.014	0.32	NO
163	PRKCA	PRKCA	PRKCA	11274	-0.017	0.31	NO
164	AKT1	AKT1	AKT1	11291	-0.017	0.31	NO
165	SRC	SRC	SRC	11311	-0.018	0.31	NO
166	ERBB2	ERBB2	ERBB2	11468	-0.02	0.3	NO
167	VASP	VASP	VASP	11547	-0.022	0.3	NO
168	ITGA6	ITGA6	ITGA6	11767	-0.026	0.29	NO
169	AKT2	AKT2	AKT2	11899	-0.028	0.28	NO
170	CCND3	CCND3	CCND3	12063	-0.031	0.27	NO
171	ITGA3	ITGA3	ITGA3	12208	-0.034	0.26	NO
172	COL2A1	COL2A1	COL2A1	12291	-0.035	0.26	NO
173	BCAR1	BCAR1	BCAR1	12451	-0.038	0.25	NO
174	MAPK3	MAPK3	MAPK3	12548	-0.04	0.25	NO
175	PARVB	PARVB	PARVB	12859	-0.046	0.23	NO
176	ACTG1	ACTG1	ACTG1	12921	-0.047	0.23	NO
177	PAK6	PAK6	PAK6	12942	-0.047	0.23	NO
178	ITGB4	ITGB4	ITGB4	13012	-0.049	0.23	NO
179	MYL12B	MYL12B	MYL12B	13056	-0.05	0.23	NO
180	PAK4	PAK4	PAK4	13141	-0.052	0.22	NO
181	PPP1CA	PPP1CA	PPP1CA	13707	-0.064	0.19	NO
182	COL11A2	COL11A2	COL11A2	13728	-0.064	0.2	NO
183	CHAD	CHAD	CHAD	13900	-0.068	0.19	NO
184	RASGRF1	RASGRF1	RASGRF1	14004	-0.071	0.18	NO
185	PIK3R2	PIK3R2	PIK3R2	14118	-0.074	0.18	NO
186	ITGA2B	ITGA2B	ITGA2B	14320	-0.079	0.17	NO
187	HRAS	HRAS	HRAS	14517	-0.085	0.16	NO
188	BAD	BAD	BAD	14655	-0.089	0.16	NO
189	EGF	EGF	EGF	14755	-0.092	0.15	NO
190	RAC3	RAC3	RAC3	15322	-0.11	0.13	NO
191	PRKCG	PRKCG	PRKCG	15907	-0.14	0.097	NO
192	MYL5	MYL5	MYL5	15963	-0.14	0.098	NO
193	MYLPF	MYLPF	MYLPF	17418	-0.3	0.025	NO
194	COL4A6	COL4A6	COL4A6	17783	-0.43	0.017	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: KEGG PHOSPHATIDYLINOSITOL SIGNALING SYSTEM.

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

genes ES table in pathway: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION

Table 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	ADCY2	ADCY2	ADCY2	124	0.75	0.049	YES
2	PDE1A	PDE1A	PDE1A	240	0.68	0.093	YES
3	AKT3	AKT3	AKT3	522	0.55	0.12	YES
4	ADCYAP1	ADCYAP1	ADCYAP1	545	0.54	0.16	YES
5	PDE1B	PDE1B	PDE1B	728	0.49	0.18	YES
6	ADCY5	ADCY5	ADCY5	945	0.44	0.2	YES
7	PRKAR2B	PRKAR2B	PRKAR2B	970	0.43	0.24	YES
8	MEF2C	MEF2C	MEF2C	973	0.43	0.27	YES
9	NGF	NGF	NGF	1373	0.36	0.27	YES
10	MAPK11	MAPK11	MAPK11	1723	0.32	0.28	YES
11	CAMK4	CAMK4	CAMK4	1840	0.3	0.29	YES
12	NTRK1	NTRK1	NTRK1	2243	0.26	0.29	YES
13	NTRK2	NTRK2	NTRK2	2555	0.23	0.29	YES
14	RICTOR	RICTOR	RICTOR	2733	0.21	0.3	YES
15	RPS6KA2	RPS6KA2	RPS6KA2	3020	0.19	0.29	YES
16	PIK3CA	PIK3CA	PIK3CA	3029	0.18	0.31	YES
17	IRS1	IRS1	IRS1	3060	0.18	0.32	YES
18	MEF2A	MEF2A	MEF2A	3197	0.17	0.32	YES
19	DNM1	DNM1	DNM1	3237	0.17	0.33	YES
20	ADCY4	ADCY4	ADCY4	3323	0.17	0.34	YES
21	FOXO1	FOXO1	FOXO1	3417	0.16	0.35	YES
22	KIDINS220	KIDINS220	KIDINS220	3735	0.15	0.34	YES
23	MAPK12	MAPK12	MAPK12	4035	0.13	0.34	YES
24	RAP1A	RAP1A	RAP1A	4200	0.13	0.34	YES
25	PRKACB	PRKACB	PRKACB	4226	0.13	0.34	YES
26	ITPR2	ITPR2	ITPR2	4332	0.12	0.35	YES
27	FRS2	FRS2	FRS2	4381	0.12	0.35	YES
28	CREB1	CREB1	CREB1	4399	0.12	0.36	YES
29	RIT1	RIT1	RIT1	4539	0.12	0.36	YES
30	SOS1	SOS1	SOS1	4554	0.12	0.37	YES
31	SHC3	SHC3	SHC3	4577	0.12	0.38	YES
32	ADCY9	ADCY9	ADCY9	4663	0.11	0.38	YES
33	ADCY1	ADCY1	ADCY1	4685	0.11	0.39	YES
34	FOXO4	FOXO4	FOXO4	4816	0.11	0.39	YES
35	BRAF	BRAF	BRAF	4871	0.11	0.39	YES
36	ADORA2A	ADORA2A	ADORA2A	4976	0.1	0.4	YES
37	ADCY7	ADCY7	ADCY7	4991	0.1	0.4	YES
38	PRKAR1A	PRKAR1A	PRKAR1A	5071	0.1	0.41	YES
39	RAPGEF1	RAPGEF1	RAPGEF1	5416	0.09	0.39	NO
40	PIK3R1	PIK3R1	PIK3R1	5625	0.084	0.39	NO
41	RALA	RALA	RALA	5890	0.078	0.38	NO
42	SHC2	SHC2	SHC2	5902	0.078	0.38	NO
43	ATF1	ATF1	ATF1	6078	0.074	0.38	NO
44	PTEN	PTEN	PTEN	6241	0.07	0.38	NO
45	RALB	RALB	RALB	6285	0.07	0.38	NO
46	DUSP3	DUSP3	DUSP3	6519	0.065	0.37	NO
47	NRAS	NRAS	NRAS	6607	0.064	0.37	NO
48	RPS6KA5	RPS6KA5	RPS6KA5	6640	0.063	0.37	NO
49	KRAS	KRAS	KRAS	6672	0.062	0.38	NO
50	CDKN1B	CDKN1B	CDKN1B	6881	0.058	0.37	NO
51	PIK3CB	PIK3CB	PIK3CB	6912	0.058	0.37	NO
52	MAP2K1	MAP2K1	MAP2K1	7121	0.054	0.36	NO
53	SHC1	SHC1	SHC1	7140	0.054	0.37	NO
54	PPP2CB	PPP2CB	PPP2CB	7269	0.051	0.36	NO
55	RPS6KA3	RPS6KA3	RPS6KA3	7410	0.048	0.36	NO
56	PRKCE	PRKCE	PRKCE	7499	0.047	0.36	NO
57	DUSP7	DUSP7	DUSP7	7778	0.041	0.35	NO
58	SH3GL2	SH3GL2	SH3GL2	7807	0.041	0.35	NO
59	PRKACA	PRKACA	PRKACA	7818	0.04	0.35	NO
60	MAPK1	MAPK1	MAPK1	7905	0.039	0.35	NO
61	FOXO3	FOXO3	FOXO3	8028	0.037	0.34	NO
62	PLCG1	PLCG1	PLCG1	8117	0.036	0.34	NO
63	CALM2	CALM2	CALM2	8185	0.035	0.34	NO
64	MAPKAPK2	MAPKAPK2	MAPKAPK2	8202	0.034	0.34	NO
65	PPP2R1B	PPP2R1B	PPP2R1B	8327	0.032	0.34	NO
66	RALGDS	RALGDS	RALGDS	8518	0.029	0.33	NO
67	RHOA	RHOA	RHOA	8528	0.029	0.33	NO
68	MAPKAP1	MAPKAP1	MAPKAP1	8618	0.028	0.33	NO
69	STAT3	STAT3	STAT3	8788	0.025	0.32	NO
70	ADCY3	ADCY3	ADCY3	8812	0.024	0.32	NO
71	IRS2	IRS2	IRS2	8819	0.024	0.32	NO
72	GRB2	GRB2	GRB2	8831	0.024	0.32	NO
73	CALM1	CALM1	CALM1	8857	0.024	0.32	NO
74	CHUK	CHUK	CHUK	8866	0.023	0.33	NO
75	YWHAB	YWHAB	YWHAB	8975	0.022	0.32	NO
76	MTOR	MTOR	MTOR	9647	0.01	0.28	NO
77	CDK1	CDK1	CDK1	9662	0.0098	0.28	NO
78	MDM2	MDM2	MDM2	9787	0.0077	0.28	NO
79	AP2M1	AP2M1	AP2M1	9869	0.0062	0.28	NO
80	NR4A1	NR4A1	NR4A1	9897	0.0059	0.27	NO
81	MAPK7	MAPK7	MAPK7	9916	0.0055	0.27	NO
82	CLTC	CLTC	CLTC	9945	0.005	0.27	NO
83	DUSP6	DUSP6	DUSP6	10001	0.0044	0.27	NO
84	PHLPP1	PHLPP1	PHLPP1	10045	0.0036	0.27	NO
85	CRK	CRK	CRK	10196	0.0011	0.26	NO
86	RAF1	RAF1	RAF1	10380	-0.0019	0.25	NO
87	MAPK14	MAPK14	MAPK14	10405	-0.0023	0.25	NO
88	PDPK1	PDPK1	PDPK1	10578	-0.0054	0.24	NO
89	ELK1	ELK1	ELK1	10617	-0.006	0.24	NO
90	DNAL4	DNAL4	DNAL4	10888	-0.01	0.22	NO
91	PRKCD	PRKCD	PRKCD	10900	-0.01	0.22	NO
92	MAP2K5	MAP2K5	MAP2K5	11013	-0.012	0.22	NO
93	CASP9	CASP9	CASP9	11087	-0.014	0.21	NO
94	PRKCA	PRKCA	PRKCA	11274	-0.017	0.2	NO
95	AKT1	AKT1	AKT1	11291	-0.017	0.2	NO
96	PPP2CA	PPP2CA	PPP2CA	11305	-0.018	0.21	NO
97	SRC	SRC	SRC	11311	-0.018	0.21	NO
98	PPP2R5D	PPP2R5D	PPP2R5D	11372	-0.019	0.2	NO
99	THEM4	THEM4	THEM4	11549	-0.022	0.2	NO
100	TRIB3	TRIB3	TRIB3	11624	-0.023	0.2	NO
101	AKT2	AKT2	AKT2	11899	-0.028	0.18	NO
102	AP2A2	AP2A2	AP2A2	12060	-0.031	0.18	NO
103	ITPR3	ITPR3	ITPR3	12109	-0.032	0.17	NO
104	AP2B1	AP2B1	AP2B1	12126	-0.032	0.18	NO
105	CALM3	CALM3	CALM3	12377	-0.036	0.16	NO
106	MAPK3	MAPK3	MAPK3	12548	-0.04	0.16	NO
107	TSC2	TSC2	TSC2	12628	-0.041	0.16	NO
108	ADCY6	ADCY6	ADCY6	12724	-0.043	0.16	NO
109	GSK3A	GSK3A	GSK3A	12745	-0.043	0.16	NO
110	CLTA	CLTA	CLTA	13184	-0.053	0.14	NO
111	PRKAR2A	PRKAR2A	PRKAR2A	13225	-0.054	0.14	NO
112	ADRBK1	ADRBK1	ADRBK1	13294	-0.055	0.14	NO
113	DNM2	DNM2	DNM2	13352	-0.056	0.14	NO
114	AP2A1	AP2A1	AP2A1	13382	-0.057	0.14	NO
115	DUSP4	DUSP4	DUSP4	13513	-0.06	0.14	NO
116	MAPKAPK3	MAPKAPK3	MAPKAPK3	13685	-0.063	0.14	NO
117	PPP2R1A	PPP2R1A	PPP2R1A	13829	-0.067	0.13	NO
118	PRKAR1B	PRKAR1B	PRKAR1B	13879	-0.068	0.13	NO
119	MAPK13	MAPK13	MAPK13	13933	-0.069	0.14	NO
120	CDKN1A	CDKN1A	CDKN1A	14068	-0.072	0.13	NO
121	PIK3R2	PIK3R2	PIK3R2	14118	-0.074	0.14	NO
122	AP2S1	AP2S1	AP2S1	14178	-0.075	0.14	NO
123	HRAS	HRAS	HRAS	14517	-0.085	0.13	NO
124	BAD	BAD	BAD	14655	-0.089	0.13	NO
125	RPS6KA1	RPS6KA1	RPS6KA1	14750	-0.092	0.13	NO
126	AKT1S1	AKT1S1	AKT1S1	14817	-0.094	0.13	NO
127	MAP2K2	MAP2K2	MAP2K2	14966	-0.099	0.13	NO
128	PRKCG	PRKCG	PRKCG	15907	-0.14	0.088	NO
129	RPS6KB2	RPS6KB2	RPS6KB2	16093	-0.15	0.088	NO
130	PRKACG	PRKACG	PRKACG	16155	-0.15	0.096	NO
131	MLST8	MLST8	MLST8	16257	-0.16	0.1	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: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION.

Figure S16. 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 OOCYTE MEIOSIS

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	DOK5	DOK5	DOK5	55	0.83	0.16	YES
2	DOK6	DOK6	DOK6	152	0.73	0.31	YES
3	GFRA1	GFRA1	GFRA1	1125	0.41	0.34	YES
4	GDNF	GDNF	GDNF	1976	0.28	0.35	YES
5	RET	RET	RET	2226	0.26	0.38	YES
6	PDLIM7	PDLIM7	PDLIM7	2687	0.21	0.4	YES
7	PIK3CA	PIK3CA	PIK3CA	3029	0.18	0.42	YES
8	IRS1	IRS1	IRS1	3060	0.18	0.46	YES
9	SHANK3	SHANK3	SHANK3	3551	0.16	0.46	YES
10	RAP1A	RAP1A	RAP1A	4200	0.13	0.45	YES
11	FRS2	FRS2	FRS2	4381	0.12	0.47	YES
12	CREB1	CREB1	CREB1	4399	0.12	0.49	YES
13	SOS1	SOS1	SOS1	4554	0.12	0.5	YES
14	NCK1	NCK1	NCK1	4571	0.12	0.53	YES
15	GAB1	GAB1	GAB1	4618	0.11	0.55	YES
16	PIK3R1	PIK3R1	PIK3R1	5625	0.084	0.51	NO
17	GRB10	GRB10	GRB10	5980	0.076	0.5	NO
18	PTPN11	PTPN11	PTPN11	6566	0.064	0.48	NO
19	RASA1	RASA1	RASA1	6962	0.057	0.48	NO
20	JUN	JUN	JUN	7129	0.054	0.48	NO
21	SHC1	SHC1	SHC1	7140	0.054	0.49	NO
22	PTK2	PTK2	PTK2	7175	0.053	0.5	NO
23	PRKACA	PRKACA	PRKACA	7818	0.04	0.47	NO
24	MAPK1	MAPK1	MAPK1	7905	0.039	0.47	NO
25	RAC1	RAC1	RAC1	7971	0.038	0.48	NO
26	RHOA	RHOA	RHOA	8528	0.029	0.45	NO
27	IRS2	IRS2	IRS2	8819	0.024	0.44	NO
28	GRB2	GRB2	GRB2	8831	0.024	0.44	NO
29	DOK1	DOK1	DOK1	9282	0.016	0.42	NO
30	MAPK8	MAPK8	MAPK8	9558	0.012	0.41	NO
31	PXN	PXN	PXN	10041	0.0038	0.38	NO
32	CRK	CRK	CRK	10196	0.0011	0.38	NO
33	PRKCA	PRKCA	PRKCA	11274	-0.017	0.32	NO
34	SRC	SRC	SRC	11311	-0.018	0.32	NO
35	GRB7	GRB7	GRB7	12203	-0.034	0.28	NO
36	BCAR1	BCAR1	BCAR1	12451	-0.038	0.27	NO
37	MAPK3	MAPK3	MAPK3	12548	-0.04	0.27	NO
38	DOK4	DOK4	DOK4	14263	-0.077	0.2	NO
39	HRAS	HRAS	HRAS	14517	-0.085	0.2	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: KEGG OOCYTE MEIOSIS.

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

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

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	ADCY2	ADCY2	ADCY2	124	0.75	0.03	YES
2	PDE1A	PDE1A	PDE1A	240	0.68	0.057	YES
3	AKT3	AKT3	AKT3	522	0.55	0.069	YES
4	ADCYAP1	ADCYAP1	ADCYAP1	545	0.54	0.094	YES
5	RASGRF2	RASGRF2	RASGRF2	571	0.53	0.12	YES
6	NGFR	NGFR	NGFR	677	0.5	0.14	YES
7	PDE1B	PDE1B	PDE1B	728	0.49	0.16	YES
8	ADCY5	ADCY5	ADCY5	945	0.44	0.17	YES
9	PRKAR2B	PRKAR2B	PRKAR2B	970	0.43	0.19	YES
10	MEF2C	MEF2C	MEF2C	973	0.43	0.21	YES
11	TIAM1	TIAM1	TIAM1	1197	0.39	0.22	YES
12	ARHGEF6	ARHGEF6	ARHGEF6	1297	0.38	0.23	YES
13	NGF	NGF	NGF	1373	0.36	0.24	YES
14	MAPK11	MAPK11	MAPK11	1723	0.32	0.24	YES
15	SORCS3	SORCS3	SORCS3	1807	0.3	0.25	YES
16	CAMK4	CAMK4	CAMK4	1840	0.3	0.26	YES
17	PCSK5	PCSK5	PCSK5	1882	0.3	0.28	YES
18	ARHGEF17	ARHGEF17	ARHGEF17	1935	0.29	0.29	YES
19	NTRK1	NTRK1	NTRK1	2243	0.26	0.28	YES
20	TIAM2	TIAM2	TIAM2	2490	0.23	0.28	YES
21	NTRK2	NTRK2	NTRK2	2555	0.23	0.29	YES
22	RICTOR	RICTOR	RICTOR	2733	0.21	0.29	YES
23	FGD2	FGD2	FGD2	2817	0.2	0.29	YES
24	RPS6KA2	RPS6KA2	RPS6KA2	3020	0.19	0.29	YES
25	PIK3CA	PIK3CA	PIK3CA	3029	0.18	0.3	YES
26	IRS1	IRS1	IRS1	3060	0.18	0.31	YES
27	ITSN1	ITSN1	ITSN1	3166	0.18	0.31	YES
28	MCF2	MCF2	MCF2	3186	0.18	0.32	YES
29	MEF2A	MEF2A	MEF2A	3197	0.17	0.33	YES
30	DNM1	DNM1	DNM1	3237	0.17	0.33	YES
31	ADCY4	ADCY4	ADCY4	3323	0.17	0.34	YES
32	FOXO1	FOXO1	FOXO1	3417	0.16	0.34	YES
33	PLEKHG2	PLEKHG2	PLEKHG2	3502	0.16	0.34	YES
34	ARHGEF4	ARHGEF4	ARHGEF4	3579	0.15	0.35	YES
35	KIDINS220	KIDINS220	KIDINS220	3735	0.15	0.34	YES
36	SOS2	SOS2	SOS2	3891	0.14	0.34	YES
37	AKAP13	AKAP13	AKAP13	3892	0.14	0.35	YES
38	MAPK12	MAPK12	MAPK12	4035	0.13	0.35	YES
39	VAV1	VAV1	VAV1	4071	0.13	0.35	YES
40	RAP1A	RAP1A	RAP1A	4200	0.13	0.35	YES
41	PRKACB	PRKACB	PRKACB	4226	0.13	0.36	YES
42	ITPR2	ITPR2	ITPR2	4332	0.12	0.36	YES
43	FRS2	FRS2	FRS2	4381	0.12	0.36	YES
44	CREB1	CREB1	CREB1	4399	0.12	0.36	YES
45	RIT1	RIT1	RIT1	4539	0.12	0.36	YES
46	SOS1	SOS1	SOS1	4554	0.12	0.37	YES
47	SHC3	SHC3	SHC3	4577	0.12	0.37	YES
48	ADCY9	ADCY9	ADCY9	4663	0.11	0.37	YES
49	ADCY1	ADCY1	ADCY1	4685	0.11	0.38	YES
50	FOXO4	FOXO4	FOXO4	4816	0.11	0.38	YES
51	APH1B	APH1B	APH1B	4842	0.11	0.38	YES
52	BRAF	BRAF	BRAF	4871	0.11	0.38	YES
53	ARHGEF12	ARHGEF12	ARHGEF12	4969	0.1	0.38	YES
54	ADORA2A	ADORA2A	ADORA2A	4976	0.1	0.39	YES
55	ADCY7	ADCY7	ADCY7	4991	0.1	0.39	YES
56	PRKAR1A	PRKAR1A	PRKAR1A	5071	0.1	0.39	YES
57	ARHGEF3	ARHGEF3	ARHGEF3	5089	0.099	0.4	YES
58	BCL2L11	BCL2L11	BCL2L11	5291	0.094	0.39	NO
59	TRIO	TRIO	TRIO	5347	0.093	0.39	NO
60	RAPGEF1	RAPGEF1	RAPGEF1	5416	0.09	0.39	NO
61	ADAM17	ADAM17	ADAM17	5572	0.086	0.39	NO
62	PIK3R1	PIK3R1	PIK3R1	5625	0.084	0.39	NO
63	RALA	RALA	RALA	5890	0.078	0.38	NO
64	PRKCI	PRKCI	PRKCI	5896	0.078	0.38	NO
65	SHC2	SHC2	SHC2	5902	0.078	0.38	NO
66	ATF1	ATF1	ATF1	6078	0.074	0.38	NO
67	PTEN	PTEN	PTEN	6241	0.07	0.37	NO
68	RALB	RALB	RALB	6285	0.07	0.38	NO
69	DUSP3	DUSP3	DUSP3	6519	0.065	0.36	NO
70	RPS27A	RPS27A	RPS27A	6565	0.064	0.37	NO
71	NRAS	NRAS	NRAS	6607	0.064	0.37	NO
72	RPS6KA5	RPS6KA5	RPS6KA5	6640	0.063	0.37	NO
73	KRAS	KRAS	KRAS	6672	0.062	0.37	NO
74	OMG	OMG	OMG	6744	0.061	0.37	NO
75	NET1	NET1	NET1	6764	0.061	0.37	NO
76	CDKN1B	CDKN1B	CDKN1B	6881	0.058	0.37	NO
77	PIK3CB	PIK3CB	PIK3CB	6912	0.058	0.37	NO
78	NFKBIA	NFKBIA	NFKBIA	7084	0.055	0.36	NO
79	MAP2K1	MAP2K1	MAP2K1	7121	0.054	0.36	NO
80	SHC1	SHC1	SHC1	7140	0.054	0.36	NO
81	KALRN	KALRN	KALRN	7252	0.052	0.36	NO
82	PPP2CB	PPP2CB	PPP2CB	7269	0.051	0.36	NO
83	ECT2	ECT2	ECT2	7320	0.05	0.36	NO
84	PREX1	PREX1	PREX1	7324	0.05	0.36	NO
85	RPS6KA3	RPS6KA3	RPS6KA3	7410	0.048	0.36	NO
86	RTN4	RTN4	RTN4	7441	0.048	0.36	NO
87	PRKCE	PRKCE	PRKCE	7499	0.047	0.36	NO
88	TRAF6	TRAF6	TRAF6	7636	0.044	0.36	NO
89	DUSP7	DUSP7	DUSP7	7778	0.041	0.35	NO
90	VAV3	VAV3	VAV3	7791	0.041	0.35	NO
91	SH3GL2	SH3GL2	SH3GL2	7807	0.041	0.35	NO
92	PRKACA	PRKACA	PRKACA	7818	0.04	0.35	NO
93	HDAC2	HDAC2	HDAC2	7823	0.04	0.36	NO
94	MAPK1	MAPK1	MAPK1	7905	0.039	0.35	NO
95	ARHGEF2	ARHGEF2	ARHGEF2	7922	0.038	0.35	NO
96	RAC1	RAC1	RAC1	7971	0.038	0.35	NO
97	NGFRAP1	NGFRAP1	NGFRAP1	7996	0.037	0.35	NO
98	FOXO3	FOXO3	FOXO3	8028	0.037	0.35	NO
99	PLCG1	PLCG1	PLCG1	8117	0.036	0.35	NO
100	CALM2	CALM2	CALM2	8185	0.035	0.35	NO
101	MAPKAPK2	MAPKAPK2	MAPKAPK2	8202	0.034	0.35	NO
102	PPP2R1B	PPP2R1B	PPP2R1B	8327	0.032	0.34	NO
103	IKBKB	IKBKB	IKBKB	8423	0.031	0.34	NO
104	CASP2	CASP2	CASP2	8424	0.031	0.34	NO
105	RALGDS	RALGDS	RALGDS	8518	0.029	0.34	NO
106	RHOA	RHOA	RHOA	8528	0.029	0.34	NO
107	FGD4	FGD4	FGD4	8564	0.028	0.34	NO
108	PSEN1	PSEN1	PSEN1	8610	0.028	0.34	NO
109	MAPKAP1	MAPKAP1	MAPKAP1	8618	0.028	0.34	NO
110	STAT3	STAT3	STAT3	8788	0.025	0.33	NO
111	ADCY3	ADCY3	ADCY3	8812	0.024	0.33	NO
112	IRS2	IRS2	IRS2	8819	0.024	0.33	NO
113	GRB2	GRB2	GRB2	8831	0.024	0.33	NO
114	CALM1	CALM1	CALM1	8857	0.024	0.33	NO
115	CHUK	CHUK	CHUK	8866	0.023	0.33	NO
116	SQSTM1	SQSTM1	SQSTM1	8885	0.023	0.33	NO
117	ARHGEF9	ARHGEF9	ARHGEF9	8911	0.023	0.33	NO
118	RIPK2	RIPK2	RIPK2	8968	0.022	0.33	NO
119	YWHAB	YWHAB	YWHAB	8975	0.022	0.33	NO
120	LINGO1	LINGO1	LINGO1	9102	0.019	0.32	NO
121	ARHGEF11	ARHGEF11	ARHGEF11	9256	0.017	0.32	NO
122	RELA	RELA	RELA	9364	0.015	0.31	NO
123	ITGB3BP	ITGB3BP	ITGB3BP	9479	0.013	0.3	NO
124	MAPK8	MAPK8	MAPK8	9558	0.012	0.3	NO
125	NCSTN	NCSTN	NCSTN	9604	0.011	0.3	NO
126	MTOR	MTOR	MTOR	9647	0.01	0.3	NO
127	CDK1	CDK1	CDK1	9662	0.0098	0.3	NO
128	MDM2	MDM2	MDM2	9787	0.0077	0.29	NO
129	AP2M1	AP2M1	AP2M1	9869	0.0062	0.29	NO
130	NR4A1	NR4A1	NR4A1	9897	0.0059	0.28	NO
131	MAPK7	MAPK7	MAPK7	9916	0.0055	0.28	NO
132	FGD1	FGD1	FGD1	9922	0.0053	0.28	NO
133	CLTC	CLTC	CLTC	9945	0.005	0.28	NO
134	ARHGEF1	ARHGEF1	ARHGEF1	9993	0.0044	0.28	NO
135	DUSP6	DUSP6	DUSP6	10001	0.0044	0.28	NO
136	PHLPP1	PHLPP1	PHLPP1	10045	0.0036	0.28	NO
137	CASP3	CASP3	CASP3	10110	0.0027	0.28	NO
138	NGEF	NGEF	NGEF	10122	0.0025	0.28	NO
139	ARHGAP4	ARHGAP4	ARHGAP4	10143	0.0022	0.27	NO
140	ARHGEF18	ARHGEF18	ARHGEF18	10168	0.0018	0.27	NO
141	CRK	CRK	CRK	10196	0.0011	0.27	NO
142	RAF1	RAF1	RAF1	10380	-0.0019	0.26	NO
143	PRDM4	PRDM4	PRDM4	10383	-0.002	0.26	NO
144	MAPK14	MAPK14	MAPK14	10405	-0.0023	0.26	NO
145	FURIN	FURIN	FURIN	10446	-0.0031	0.26	NO
146	MYD88	MYD88	MYD88	10495	-0.0039	0.26	NO
147	PDPK1	PDPK1	PDPK1	10578	-0.0054	0.25	NO
148	ABR	ABR	ABR	10598	-0.0056	0.25	NO
149	ELK1	ELK1	ELK1	10617	-0.006	0.25	NO
150	YWHAE	YWHAE	YWHAE	10701	-0.0073	0.24	NO
151	MAGED1	MAGED1	MAGED1	10819	-0.0091	0.24	NO
152	DNAL4	DNAL4	DNAL4	10888	-0.01	0.24	NO
153	PRKCD	PRKCD	PRKCD	10900	-0.01	0.24	NO
154	MAP2K5	MAP2K5	MAP2K5	11013	-0.012	0.23	NO
155	CASP9	CASP9	CASP9	11087	-0.014	0.23	NO
156	AATF	AATF	AATF	11105	-0.014	0.23	NO
157	PRKCA	PRKCA	PRKCA	11274	-0.017	0.22	NO
158	AKT1	AKT1	AKT1	11291	-0.017	0.22	NO
159	APH1A	APH1A	APH1A	11304	-0.018	0.22	NO
160	PPP2CA	PPP2CA	PPP2CA	11305	-0.018	0.22	NO
161	SRC	SRC	SRC	11311	-0.018	0.22	NO
162	PPP2R5D	PPP2R5D	PPP2R5D	11372	-0.019	0.22	NO
163	THEM4	THEM4	THEM4	11549	-0.022	0.21	NO
164	TRIB3	TRIB3	TRIB3	11624	-0.023	0.2	NO
165	HDAC1	HDAC1	HDAC1	11652	-0.024	0.2	NO
166	AKT2	AKT2	AKT2	11899	-0.028	0.19	NO
167	AP2A2	AP2A2	AP2A2	12060	-0.031	0.18	NO
168	ITPR3	ITPR3	ITPR3	12109	-0.032	0.18	NO
169	AP2B1	AP2B1	AP2B1	12126	-0.032	0.18	NO
170	PSENEN	PSENEN	PSENEN	12267	-0.035	0.18	NO
171	CALM3	CALM3	CALM3	12377	-0.036	0.17	NO
172	MAPK3	MAPK3	MAPK3	12548	-0.04	0.17	NO
173	TSC2	TSC2	TSC2	12628	-0.041	0.16	NO
174	PSEN2	PSEN2	PSEN2	12717	-0.043	0.16	NO
175	ADCY6	ADCY6	ADCY6	12724	-0.043	0.16	NO
176	GSK3A	GSK3A	GSK3A	12745	-0.043	0.16	NO
177	FGD3	FGD3	FGD3	12849	-0.045	0.16	NO
178	HDAC3	HDAC3	HDAC3	12851	-0.045	0.16	NO
179	IRAK1	IRAK1	IRAK1	13002	-0.048	0.16	NO
180	ARHGDIA	ARHGDIA	ARHGDIA	13154	-0.052	0.15	NO
181	CLTA	CLTA	CLTA	13184	-0.053	0.15	NO
182	OBSCN	OBSCN	OBSCN	13216	-0.053	0.15	NO
183	PRKAR2A	PRKAR2A	PRKAR2A	13225	-0.054	0.16	NO
184	MAG	MAG	MAG	13247	-0.054	0.16	NO
185	ADRBK1	ADRBK1	ADRBK1	13294	-0.055	0.16	NO
186	DNM2	DNM2	DNM2	13352	-0.056	0.16	NO
187	AP2A1	AP2A1	AP2A1	13382	-0.057	0.16	NO
188	DUSP4	DUSP4	DUSP4	13513	-0.06	0.15	NO
189	MAPKAPK3	MAPKAPK3	MAPKAPK3	13685	-0.063	0.15	NO
190	PPP2R1A	PPP2R1A	PPP2R1A	13829	-0.067	0.14	NO
191	PRKAR1B	PRKAR1B	PRKAR1B	13879	-0.068	0.14	NO
192	MAPK13	MAPK13	MAPK13	13933	-0.069	0.14	NO
193	RASGRF1	RASGRF1	RASGRF1	14004	-0.071	0.14	NO
194	CDKN1A	CDKN1A	CDKN1A	14068	-0.072	0.14	NO
195	PIK3R2	PIK3R2	PIK3R2	14118	-0.074	0.14	NO
196	PCSK6	PCSK6	PCSK6	14174	-0.075	0.14	NO
197	AP2S1	AP2S1	AP2S1	14178	-0.075	0.15	NO
198	HRAS	HRAS	HRAS	14517	-0.085	0.13	NO
199	BAD	BAD	BAD	14655	-0.089	0.13	NO
200	RPS6KA1	RPS6KA1	RPS6KA1	14750	-0.092	0.13	NO
201	AKT1S1	AKT1S1	AKT1S1	14817	-0.094	0.13	NO
202	MAP2K2	MAP2K2	MAP2K2	14966	-0.099	0.13	NO
203	UBA52	UBA52	UBA52	15096	-0.1	0.12	NO
204	ARHGEF16	ARHGEF16	ARHGEF16	15501	-0.12	0.11	NO
205	PRKCG	PRKCG	PRKCG	15907	-0.14	0.092	NO
206	RPS6KB2	RPS6KB2	RPS6KB2	16093	-0.15	0.089	NO
207	SMPD2	SMPD2	SMPD2	16137	-0.15	0.094	NO
208	PRKACG	PRKACG	PRKACG	16155	-0.15	0.1	NO
209	MLST8	MLST8	MLST8	16257	-0.16	0.1	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: KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT.

Figure S20. 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

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 INOSITOL PHOSPHATE METABOLISM	52	genes.ES.table	0.5	2	0	0.61	0.28	0.42	0.24	0.32	0	0.12
BIOCARTA HIVNEF PATHWAY	58	genes.ES.table	0.42	1.9	0.01	0.4	0.38	0.5	0.36	0.32	0	0.075
PID HDAC CLASSII PATHWAY	34	genes.ES.table	0.56	1.9	0.0043	0.39	0.29	0.21	0.087	0.19	0	0.075
PID TRAIL PATHWAY	28	genes.ES.table	0.49	1.8	0.018	0.29	0.58	0.64	0.32	0.44	0.076	0.074
PID CDC42 PATHWAY	70	genes.ES.table	0.39	1.9	0.015	0.38	0.43	0.5	0.36	0.32	0	0.087
PID FASPATHWAY	38	genes.ES.table	0.53	1.9	0.0042	0.32	0.44	0.71	0.34	0.47	0	0.078
PID NFAT 3PATHWAY	54	genes.ES.table	0.45	1.8	0.013	0.3	0.53	0.37	0.28	0.27	0.071	0.074
PID ERBB1 RECEPTOR PROXIMAL PATHWAY	35	genes.ES.table	0.49	1.8	0.013	0.29	0.57	0.6	0.33	0.4	0.075	0.074
PID CERAMIDE PATHWAY	48	genes.ES.table	0.42	2	0.0042	0.91	0.27	0.44	0.32	0.3	0	0.16
PID AR TF PATHWAY	51	genes.ES.table	0.53	1.9	0.0066	0.41	0.42	0.47	0.3	0.33	0	0.086

genes ES table in pathway: KEGG INOSITOL PHOSPHATE 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	PIK3CG	PIK3CG	PIK3CG	200	0.52	0.13	YES
2	MTMR7	MTMR7	MTMR7	1091	0.25	0.14	YES
3	SYNJ1	SYNJ1	SYNJ1	1520	0.19	0.17	YES
4	PIK3R5	PIK3R5	PIK3R5	1612	0.19	0.22	YES
5	PIK3R6	PIK3R6	PIK3R6	1641	0.18	0.26	YES
6	MTM1	MTM1	MTM1	1807	0.17	0.3	YES
7	PIK3CD	PIK3CD	PIK3CD	1989	0.16	0.33	YES
8	PIP5K1B	PIP5K1B	PIP5K1B	2089	0.15	0.36	YES
9	PIKFYVE	PIKFYVE	PIKFYVE	2733	0.12	0.36	YES
10	PI4K2B	PI4K2B	PI4K2B	3469	0.098	0.34	YES
11	TPTE2	TPTE2	TPTE2	3621	0.094	0.36	YES
12	SYNJ2	SYNJ2	SYNJ2	3631	0.094	0.38	YES
13	PIK3CA	PIK3CA	PIK3CA	3678	0.093	0.41	YES
14	PIP4K2A	PIP4K2A	PIP4K2A	3907	0.087	0.42	YES
15	PIK3C2A	PIK3C2A	PIK3C2A	3932	0.086	0.44	YES
16	PIK3C3	PIK3C3	PIK3C3	4101	0.083	0.45	YES
17	MTMR6	MTMR6	MTMR6	4236	0.08	0.46	YES
18	PTEN	PTEN	PTEN	4332	0.078	0.48	YES
19	PIK3R3	PIK3R3	PIK3R3	4421	0.076	0.5	YES
20	PIK3CB	PIK3CB	PIK3CB	4437	0.076	0.52	YES
21	MTMR3	MTMR3	MTMR3	4530	0.074	0.53	YES
22	PIK3R4	PIK3R4	PIK3R4	5449	0.056	0.49	YES
23	PIK3R1	PIK3R1	PIK3R1	5695	0.053	0.49	YES
24	MTMR4	MTMR4	MTMR4	5696	0.053	0.51	YES
25	SACM1L	SACM1L	SACM1L	5752	0.051	0.52	YES
26	INPP4B	INPP4B	INPP4B	5759	0.051	0.53	YES
27	PIK3C2B	PIK3C2B	PIK3C2B	5870	0.05	0.54	YES
28	PI4KA	PI4KA	PI4KA	6433	0.041	0.52	NO
29	ARF3	ARF3	ARF3	7933	0.018	0.44	NO
30	PI4KB	PI4KB	PI4KB	8029	0.017	0.44	NO
31	PI4K2A	PI4K2A	PI4K2A	8451	0.011	0.42	NO
32	MTMR2	MTMR2	MTMR2	8511	0.01	0.42	NO
33	PITPNB	PITPNB	PITPNB	8853	0.0053	0.4	NO
34	FIG4	FIG4	FIG4	9097	0.002	0.39	NO
35	INPP5K	INPP5K	INPP5K	9135	0.0015	0.38	NO
36	PIP4K2B	PIP4K2B	PIP4K2B	9902	-0.01	0.34	NO
37	OCRL	OCRL	OCRL	9961	-0.011	0.34	NO
38	INPPL1	INPPL1	INPPL1	10483	-0.018	0.32	NO
39	MTMR14	MTMR14	MTMR14	10882	-0.024	0.3	NO
40	MTMR1	MTMR1	MTMR1	11023	-0.026	0.3	NO
41	ARF1	ARF1	ARF1	11197	-0.029	0.3	NO
42	PIP5K1C	PIP5K1C	PIP5K1C	11370	-0.032	0.3	NO
43	INPP5J	INPP5J	INPP5J	11951	-0.041	0.28	NO
44	VAC14	VAC14	VAC14	12416	-0.05	0.27	NO
45	PIK3R2	PIK3R2	PIK3R2	12709	-0.055	0.27	NO
46	INPP5E	INPP5E	INPP5E	15200	-0.12	0.16	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 INOSITOL PHOSPHATE METABOLISM.

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

genes ES table in pathway: BIOCARTA HIVNEF PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IGF1	IGF1	IGF1	1043	0.26	0.026	YES
2	BIRC3	BIRC3	BIRC3	1254	0.22	0.088	YES
3	BCL2	BCL2	BCL2	1408	0.21	0.15	YES
4	SMPD3	SMPD3	SMPD3	1604	0.19	0.2	YES
5	EGF	EGF	EGF	2289	0.14	0.21	YES
6	SMPD1	SMPD1	SMPD1	2657	0.12	0.23	YES
7	PDGFA	PDGFA	PDGFA	2763	0.12	0.26	YES
8	MAP3K1	MAP3K1	MAP3K1	3605	0.095	0.24	YES
9	KSR1	KSR1	KSR1	3692	0.092	0.27	YES
10	ASAH1	ASAH1	ASAH1	3934	0.086	0.28	YES
11	EIF2AK2	EIF2AK2	EIF2AK2	4013	0.085	0.31	YES
12	RB1	RB1	RB1	4451	0.076	0.31	YES
13	MAPK3	MAPK3	MAPK3	4650	0.071	0.32	YES
14	NFKB1	NFKB1	NFKB1	4759	0.069	0.34	YES
15	RIPK1	RIPK1	RIPK1	4818	0.067	0.36	YES
16	CASP8	CASP8	CASP8	4831	0.067	0.38	YES
17	MAP2K1	MAP2K1	MAP2K1	4988	0.064	0.39	YES
18	MAPK8	MAPK8	MAPK8	5067	0.063	0.41	YES
19	MAPK1	MAPK1	MAPK1	5534	0.055	0.4	YES
20	PAWR	PAWR	PAWR	5671	0.053	0.41	YES
21	CYCS	CYCS	CYCS	5760	0.051	0.42	YES
22	MAP4K4	MAP4K4	MAP4K4	6439	0.041	0.4	NO
23	BAG4	BAG4	BAG4	6474	0.04	0.41	NO
24	EIF2A	EIF2A	EIF2A	7028	0.032	0.39	NO
25	MAP2K4	MAP2K4	MAP2K4	7518	0.024	0.37	NO
26	CRADD	CRADD	CRADD	7701	0.022	0.37	NO
27	PRKCD	PRKCD	PRKCD	8131	0.015	0.35	NO
28	TNF	TNF	TNF	8213	0.014	0.35	NO
29	TNFRSF1A	TNFRSF1A	TNFRSF1A	8226	0.014	0.35	NO
30	MADD	MADD	MADD	8303	0.013	0.35	NO
31	RAF1	RAF1	RAF1	8377	0.012	0.35	NO
32	CTSD	CTSD	CTSD	8546	0.0094	0.34	NO
33	NSMAF	NSMAF	NSMAF	8585	0.009	0.35	NO
34	BAX	BAX	BAX	8765	0.0065	0.34	NO
35	SPHK2	SPHK2	SPHK2	9339	-0.0014	0.31	NO
36	AKT1	AKT1	AKT1	9581	-0.005	0.3	NO
37	MYC	MYC	MYC	9940	-0.011	0.28	NO
38	TRAF2	TRAF2	TRAF2	10284	-0.016	0.26	NO
39	RELA	RELA	RELA	10621	-0.02	0.25	NO
40	NFKBIA	NFKBIA	NFKBIA	10972	-0.026	0.24	NO
41	AIFM1	AIFM1	AIFM1	11330	-0.031	0.23	NO
42	MAP2K2	MAP2K2	MAP2K2	11467	-0.034	0.24	NO
43	PRKCZ	PRKCZ	PRKCZ	11701	-0.038	0.24	NO
44	BAD	BAD	BAD	11861	-0.04	0.24	NO
45	PRKRA	PRKRA	PRKRA	12195	-0.046	0.24	NO
46	FADD	FADD	FADD	12867	-0.058	0.22	NO
47	BID	BID	BID	14446	-0.096	0.16	NO
48	TRADD	TRADD	TRADD	15115	-0.12	0.16	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: BIOCARTA HIVNEF PATHWAY.

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

genes ES table in pathway: PID HDAC CLASSII PATHWAY

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	PIK3CG	PIK3CG	PIK3CG	200	0.52	0.099	YES
2	PLCE1	PLCE1	PLCE1	651	0.34	0.14	YES
3	PLCG2	PLCG2	PLCG2	968	0.27	0.18	YES
4	ITPKA	ITPKA	ITPKA	1067	0.25	0.23	YES
5	IPMK	IPMK	IPMK	1339	0.21	0.26	YES
6	IMPA1	IMPA1	IMPA1	1438	0.2	0.3	YES
7	SYNJ1	SYNJ1	SYNJ1	1520	0.19	0.33	YES
8	PIK3CD	PIK3CD	PIK3CD	1989	0.16	0.34	YES
9	PIP5K1B	PIP5K1B	PIP5K1B	2089	0.15	0.37	YES
10	PLCB1	PLCB1	PLCB1	2466	0.13	0.37	YES
11	PIKFYVE	PIKFYVE	PIKFYVE	2733	0.12	0.38	YES
12	INPP1	INPP1	INPP1	2916	0.12	0.4	YES
13	ALDH6A1	ALDH6A1	ALDH6A1	3289	0.1	0.4	YES
14	PLCD3	PLCD3	PLCD3	3393	0.1	0.41	YES
15	SYNJ2	SYNJ2	SYNJ2	3631	0.094	0.42	YES
16	PIK3CA	PIK3CA	PIK3CA	3678	0.093	0.44	YES
17	PIP4K2A	PIP4K2A	PIP4K2A	3907	0.087	0.44	YES
18	PIK3C2A	PIK3C2A	PIK3C2A	3932	0.086	0.46	YES
19	PIK3C3	PIK3C3	PIK3C3	4101	0.083	0.47	YES
20	PLCD1	PLCD1	PLCD1	4303	0.078	0.47	YES
21	PTEN	PTEN	PTEN	4332	0.078	0.49	YES
22	PIK3CB	PIK3CB	PIK3CB	4437	0.076	0.5	YES
23	MINPP1	MINPP1	MINPP1	5230	0.06	0.47	NO
24	PIP4K2C	PIP4K2C	PIP4K2C	5562	0.055	0.46	NO
25	INPP4B	INPP4B	INPP4B	5759	0.051	0.46	NO
26	PIK3C2B	PIK3C2B	PIK3C2B	5870	0.05	0.46	NO
27	PLCB4	PLCB4	PLCB4	5998	0.048	0.47	NO
28	PLCB2	PLCB2	PLCB2	6110	0.046	0.47	NO
29	IMPA2	IMPA2	IMPA2	6396	0.041	0.46	NO
30	PI4KA	PI4KA	PI4KA	6433	0.041	0.47	NO
31	ITPKB	ITPKB	ITPKB	6861	0.034	0.45	NO
32	PIP5K1A	PIP5K1A	PIP5K1A	6942	0.033	0.46	NO
33	INPP4A	INPP4A	INPP4A	7320	0.027	0.44	NO
34	IPPK	IPPK	IPPK	7763	0.02	0.42	NO
35	PI4KB	PI4KB	PI4KB	8029	0.017	0.41	NO
36	INPP5A	INPP5A	INPP5A	8240	0.014	0.4	NO
37	ITPK1	ITPK1	ITPK1	8493	0.01	0.39	NO
38	PLCB3	PLCB3	PLCB3	8558	0.0093	0.39	NO
39	INPP5K	INPP5K	INPP5K	9135	0.0015	0.35	NO
40	PIP4K2B	PIP4K2B	PIP4K2B	9902	-0.01	0.31	NO
41	OCRL	OCRL	OCRL	9961	-0.011	0.31	NO
42	PLCD4	PLCD4	PLCD4	10013	-0.012	0.31	NO
43	INPPL1	INPPL1	INPPL1	10483	-0.018	0.29	NO
44	PIP5K1C	PIP5K1C	PIP5K1C	11370	-0.032	0.25	NO
45	INPP5J	INPP5J	INPP5J	11951	-0.041	0.22	NO
46	PLCG1	PLCG1	PLCG1	12207	-0.046	0.22	NO
47	INPP5B	INPP5B	INPP5B	12231	-0.046	0.23	NO
48	TPI1	TPI1	TPI1	12790	-0.057	0.21	NO
49	CDIPT	CDIPT	CDIPT	13076	-0.062	0.21	NO
50	MIOX	MIOX	MIOX	14112	-0.087	0.17	NO
51	INPP5E	INPP5E	INPP5E	15200	-0.12	0.13	NO
52	ISYNA1	ISYNA1	ISYNA1	15385	-0.13	0.15	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: PID HDAC CLASSII PATHWAY.

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

genes ES table in pathway: PID TRAIL PATHWAY

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	PIK3CG	PIK3CG	PIK3CG	200	0.52	0.18	YES
2	SYNJ1	SYNJ1	SYNJ1	1520	0.19	0.17	YES
3	PIK3R5	PIK3R5	PIK3R5	1612	0.19	0.24	YES
4	PIK3R6	PIK3R6	PIK3R6	1641	0.18	0.3	YES
5	MTM1	MTM1	MTM1	1807	0.17	0.35	YES
6	PIK3CD	PIK3CD	PIK3CD	1989	0.16	0.4	YES
7	PIP5K1B	PIP5K1B	PIP5K1B	2089	0.15	0.45	YES
8	PI4K2B	PI4K2B	PI4K2B	3469	0.098	0.41	YES
9	SYNJ2	SYNJ2	SYNJ2	3631	0.094	0.43	YES
10	PIK3CA	PIK3CA	PIK3CA	3678	0.093	0.46	YES
11	PIP4K2A	PIP4K2A	PIP4K2A	3907	0.087	0.48	YES
12	PIK3C2A	PIK3C2A	PIK3C2A	3932	0.086	0.51	YES
13	MTMR6	MTMR6	MTMR6	4236	0.08	0.52	YES
14	PTEN	PTEN	PTEN	4332	0.078	0.55	YES
15	PIK3R3	PIK3R3	PIK3R3	4421	0.076	0.57	YES
16	PIK3CB	PIK3CB	PIK3CB	4437	0.076	0.6	YES
17	MTMR3	MTMR3	MTMR3	4530	0.074	0.62	YES
18	PIK3R1	PIK3R1	PIK3R1	5695	0.053	0.57	NO
19	INPP4B	INPP4B	INPP4B	5759	0.051	0.58	NO
20	PIK3C2B	PIK3C2B	PIK3C2B	5870	0.05	0.6	NO
21	PI4K2A	PI4K2A	PI4K2A	8451	0.011	0.46	NO
22	INPP5K	INPP5K	INPP5K	9135	0.0015	0.42	NO
23	PIP4K2B	PIP4K2B	PIP4K2B	9902	-0.01	0.38	NO
24	INPPL1	INPPL1	INPPL1	10483	-0.018	0.36	NO
25	MTMR14	MTMR14	MTMR14	10882	-0.024	0.34	NO
26	MTMR1	MTMR1	MTMR1	11023	-0.026	0.34	NO
27	PIP5K1C	PIP5K1C	PIP5K1C	11370	-0.032	0.34	NO
28	INPP5J	INPP5J	INPP5J	11951	-0.041	0.32	NO
29	PIK3R2	PIK3R2	PIK3R2	12709	-0.055	0.3	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: PID TRAIL PATHWAY.

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

genes ES table in pathway: PID CDC42 PATHWAY

Table 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	HDAC9	HDAC9	HDAC9	308	0.46	0.13	YES
2	GATA1	GATA1	GATA1	697	0.32	0.21	YES
3	CAMK4	CAMK4	CAMK4	752	0.31	0.3	YES
4	NR3C1	NR3C1	NR3C1	777	0.31	0.4	YES
5	GNG2	GNG2	GNG2	1096	0.25	0.46	YES
6	ESR1	ESR1	ESR1	1478	0.2	0.5	YES
7	MEF2C	MEF2C	MEF2C	1576	0.19	0.56	YES
8	RANBP2	RANBP2	RANBP2	4658	0.071	0.41	NO
9	BCOR	BCOR	BCOR	4931	0.065	0.42	NO
10	ANKRA2	ANKRA2	ANKRA2	5470	0.056	0.4	NO
11	SUMO1	SUMO1	SUMO1	6005	0.048	0.39	NO
12	XPO1	XPO1	XPO1	7353	0.026	0.32	NO
13	HSP90AA1	HSP90AA1	HSP90AA1	7464	0.025	0.32	NO
14	HDAC4	HDAC4	HDAC4	7762	0.02	0.31	NO
15	SRF	SRF	SRF	8329	0.012	0.29	NO
16	YWHAB	YWHAB	YWHAB	9145	0.0014	0.24	NO
17	GATA2	GATA2	GATA2	9223	0.00027	0.24	NO
18	GNB1	GNB1	GNB1	9419	-0.0026	0.23	NO
19	HDAC11	HDAC11	HDAC11	9643	-0.0059	0.22	NO
20	NCOR2	NCOR2	NCOR2	10089	-0.013	0.2	NO
21	UBE2I	UBE2I	UBE2I	10340	-0.016	0.19	NO
22	YWHAE	YWHAE	YWHAE	10536	-0.019	0.18	NO
23	BCL6	BCL6	BCL6	10954	-0.025	0.17	NO
24	HDAC5	HDAC5	HDAC5	11452	-0.033	0.15	NO
25	ADRBK1	ADRBK1	ADRBK1	11731	-0.038	0.15	NO
26	HDAC7	HDAC7	HDAC7	11872	-0.04	0.15	NO
27	TUBA1B	TUBA1B	TUBA1B	11943	-0.041	0.16	NO
28	HDAC6	HDAC6	HDAC6	12111	-0.044	0.17	NO
29	RAN	RAN	RAN	12514	-0.052	0.16	NO
30	HDAC3	HDAC3	HDAC3	12652	-0.054	0.17	NO
31	RFXANK	RFXANK	RFXANK	13508	-0.072	0.15	NO
32	RANGAP1	RANGAP1	RANGAP1	13619	-0.074	0.16	NO
33	TUBB2A	TUBB2A	TUBB2A	15359	-0.13	0.11	NO
34	HDAC10	HDAC10	HDAC10	15547	-0.14	0.14	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: PID CDC42 PATHWAY.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: PID CDC42 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID FASPATHWAY

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	TIAM1	TIAM1	TIAM1	878	0.29	0.076	YES
2	ITGB7	ITGB7	ITGB7	1759	0.18	0.1	YES
3	RAP1A	RAP1A	RAP1A	2683	0.12	0.11	YES
4	IQGAP1	IQGAP1	IQGAP1	3088	0.11	0.13	YES
5	KLHL20	KLHL20	KLHL20	3095	0.11	0.18	YES
6	PIK3CA	PIK3CA	PIK3CA	3678	0.093	0.19	YES
7	MLLT4	MLLT4	MLLT4	3990	0.085	0.21	YES
8	TJP1	TJP1	TJP1	4335	0.078	0.22	YES
9	CTNND1	CTNND1	CTNND1	4398	0.076	0.25	YES
10	RAPGEF1	RAPGEF1	RAPGEF1	4652	0.071	0.27	YES
11	CDH1	CDH1	CDH1	4679	0.07	0.3	YES
12	CRK	CRK	CRK	4716	0.07	0.33	YES
13	CDC42	CDC42	CDC42	5034	0.064	0.34	YES
14	DLG1	DLG1	DLG1	5154	0.061	0.36	YES
15	ARF6	ARF6	ARF6	5203	0.06	0.38	YES
16	ABI1	ABI1	ABI1	5576	0.054	0.38	YES
17	PIK3R1	PIK3R1	PIK3R1	5695	0.053	0.4	YES
18	RAP1B	RAP1B	RAP1B	5811	0.05	0.42	YES
19	NCKAP1	NCKAP1	NCKAP1	6016	0.048	0.43	YES
20	WASF2	WASF2	WASF2	6103	0.046	0.44	YES
21	CYFIP2	CYFIP2	CYFIP2	7932	0.018	0.35	NO
22	CTNNA1	CTNNA1	CTNNA1	8120	0.015	0.34	NO
23	SRC	SRC	SRC	8149	0.015	0.35	NO
24	CSNK2A1	CSNK2A1	CSNK2A1	8395	0.012	0.34	NO
25	VAV2	VAV2	VAV2	8896	0.0046	0.32	NO
26	RAC1	RAC1	RAC1	9404	-0.0024	0.29	NO
27	JUP	JUP	JUP	9474	-0.0035	0.29	NO
28	RHOA	RHOA	RHOA	9551	-0.0045	0.28	NO
29	AKT1	AKT1	AKT1	9581	-0.005	0.28	NO
30	CTNNB1	CTNNB1	CTNNB1	9613	-0.0054	0.29	NO
31	ITGAE	ITGAE	ITGAE	9797	-0.0083	0.28	NO
32	ENAH	ENAH	ENAH	10125	-0.014	0.27	NO
33	CTTN	CTTN	CTTN	10239	-0.015	0.27	NO
34	PIP5K1C	PIP5K1C	PIP5K1C	11370	-0.032	0.22	NO
35	CCND1	CCND1	CCND1	12019	-0.043	0.2	NO
36	CSNK2B	CSNK2B	CSNK2B	12122	-0.044	0.22	NO
37	AP1M1	AP1M1	AP1M1	13428	-0.07	0.17	NO
38	NME1	NME1	NME1	14137	-0.088	0.17	NO
39	CSNK2A2	CSNK2A2	CSNK2A2	14738	-0.1	0.19	NO

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

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: PID FASPATHWAY, 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 NFAT 3PATHWAY

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	FAS	FAS	FAS	913	0.28	0.024	YES
2	FASLG	FASLG	FASLG	1019	0.26	0.088	YES
3	BIRC3	BIRC3	BIRC3	1254	0.22	0.14	YES
4	CASP7	CASP7	CASP7	1280	0.22	0.19	YES
5	BCL2	BCL2	BCL2	1408	0.21	0.24	YES
6	GSN	GSN	GSN	2199	0.14	0.24	YES
7	CHUK	CHUK	CHUK	2745	0.12	0.24	YES
8	MAP3K5	MAP3K5	MAP3K5	3340	0.1	0.23	YES
9	PSEN1	PSEN1	PSEN1	3482	0.098	0.25	YES
10	MAP3K1	MAP3K1	MAP3K1	3605	0.095	0.27	YES
11	APAF1	APAF1	APAF1	3628	0.094	0.29	YES
12	CASP3	CASP3	CASP3	4027	0.085	0.29	YES
13	BIRC2	BIRC2	BIRC2	4162	0.081	0.31	YES
14	MAP3K14	MAP3K14	MAP3K14	4442	0.076	0.31	YES
15	RB1	RB1	RB1	4451	0.076	0.33	YES
16	NFKB1	NFKB1	NFKB1	4759	0.069	0.33	YES
17	RIPK1	RIPK1	RIPK1	4818	0.067	0.35	YES
18	CASP8	CASP8	CASP8	4831	0.067	0.37	YES
19	XIAP	XIAP	XIAP	5008	0.064	0.37	YES
20	MAPK8	MAPK8	MAPK8	5067	0.063	0.39	YES
21	CFLAR	CFLAR	CFLAR	5210	0.06	0.4	YES
22	RASA1	RASA1	RASA1	5293	0.059	0.41	YES
23	SPTAN1	SPTAN1	SPTAN1	5725	0.052	0.4	YES
24	CYCS	CYCS	CYCS	5760	0.051	0.41	YES
25	PAK2	PAK2	PAK2	6065	0.047	0.4	YES
26	MDM2	MDM2	MDM2	6361	0.042	0.4	YES
27	BAG4	BAG4	BAG4	6474	0.04	0.4	YES
28	TRAF1	TRAF1	TRAF1	6507	0.04	0.41	YES
29	CASP9	CASP9	CASP9	6601	0.038	0.42	YES
30	TNFRSF1B	TNFRSF1B	TNFRSF1B	7368	0.026	0.38	NO
31	PARP1	PARP1	PARP1	7513	0.024	0.38	NO
32	CRADD	CRADD	CRADD	7701	0.022	0.38	NO
33	PRKDC	PRKDC	PRKDC	7926	0.018	0.37	NO
34	MAP2K7	MAP2K7	MAP2K7	7967	0.017	0.37	NO
35	DAXX	DAXX	DAXX	8040	0.016	0.37	NO
36	PRKCD	PRKCD	PRKCD	8131	0.015	0.37	NO
37	TNF	TNF	TNF	8213	0.014	0.37	NO
38	TNFRSF1A	TNFRSF1A	TNFRSF1A	8226	0.014	0.37	NO
39	NUMA1	NUMA1	NUMA1	8420	0.011	0.36	NO
40	CASP6	CASP6	CASP6	8605	0.0086	0.36	NO
41	ARHGDIB	ARHGDIB	ARHGDIB	9186	0.0008	0.33	NO
42	CASP2	CASP2	CASP2	9331	-0.0013	0.32	NO
43	LMNA	LMNA	LMNA	9458	-0.0031	0.31	NO
44	LMNB1	LMNB1	LMNB1	9862	-0.0095	0.29	NO
45	CDK11B	CDK11B	CDK11B	10085	-0.013	0.28	NO
46	LMNB2	LMNB2	LMNB2	10104	-0.013	0.29	NO
47	TRAF2	TRAF2	TRAF2	10284	-0.016	0.28	NO
48	PTK2	PTK2	PTK2	10389	-0.017	0.28	NO
49	RELA	RELA	RELA	10621	-0.02	0.27	NO
50	PSEN2	PSEN2	PSEN2	10762	-0.022	0.27	NO
51	NFKBIA	NFKBIA	NFKBIA	10972	-0.026	0.26	NO
52	CDK11A	CDK11A	CDK11A	11534	-0.035	0.24	NO
53	ACTG1	ACTG1	ACTG1	12010	-0.042	0.23	NO
54	DFFA	DFFA	DFFA	12205	-0.046	0.23	NO
55	FADD	FADD	FADD	12867	-0.058	0.21	NO
56	DFFB	DFFB	DFFB	14078	-0.086	0.16	NO
57	BID	BID	BID	14446	-0.096	0.17	NO
58	TRADD	TRADD	TRADD	15115	-0.12	0.16	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: PID NFAT 3PATHWAY.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: PID NFAT 3PATHWAY, 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 ERBB1 RECEPTOR PROXIMAL PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SPDEF	SPDEF	SPDEF	306	0.46	0.083	YES
2	HOXB13	HOXB13	HOXB13	483	0.39	0.16	YES
3	PDE9A	PDE9A	PDE9A	763	0.31	0.21	YES
4	REL	REL	REL	773	0.31	0.27	YES
5	NR3C1	NR3C1	NR3C1	777	0.31	0.34	YES
6	KAT2B	KAT2B	KAT2B	850	0.29	0.4	YES
7	KLK3	KLK3	KLK3	1422	0.2	0.41	YES
8	NCOA2	NCOA2	NCOA2	1603	0.19	0.44	YES
9	TMPRSS2	TMPRSS2	TMPRSS2	1946	0.16	0.46	YES
10	FOXO1	FOXO1	FOXO1	2097	0.15	0.48	YES
11	SIRT1	SIRT1	SIRT1	2641	0.12	0.48	YES
12	SMARCA2	SMARCA2	SMARCA2	2732	0.12	0.5	YES
13	NCOA1	NCOA1	NCOA1	3124	0.11	0.5	YES
14	NR0B1	NR0B1	NR0B1	3752	0.091	0.48	YES
15	RCHY1	RCHY1	RCHY1	3894	0.087	0.5	YES
16	EP300	EP300	EP300	4337	0.078	0.49	YES
17	MAP2K6	MAP2K6	MAP2K6	4525	0.074	0.49	YES
18	APPBP2	APPBP2	APPBP2	4940	0.065	0.48	YES
19	NR2C2	NR2C2	NR2C2	5000	0.064	0.49	YES
20	MAPK8	MAPK8	MAPK8	5067	0.063	0.5	YES
21	RXRA	RXRA	RXRA	5139	0.062	0.51	YES
22	SENP1	SENP1	SENP1	5256	0.059	0.52	YES
23	CREBBP	CREBBP	CREBBP	5439	0.056	0.52	YES
24	AR	AR	AR	5471	0.056	0.53	YES
25	MAPK14	MAPK14	MAPK14	6186	0.044	0.5	NO
26	MDM2	MDM2	MDM2	6361	0.042	0.5	NO
27	HSP90AA1	HSP90AA1	HSP90AA1	7464	0.025	0.45	NO
28	MAP2K4	MAP2K4	MAP2K4	7518	0.024	0.45	NO
29	SMARCE1	SMARCE1	SMARCE1	7548	0.024	0.45	NO
30	DNAJA1	DNAJA1	DNAJA1	8010	0.017	0.43	NO
31	HDAC1	HDAC1	HDAC1	8076	0.016	0.43	NO
32	SRC	SRC	SRC	8149	0.015	0.43	NO
33	NR2C1	NR2C1	NR2C1	8394	0.012	0.42	NO
34	KLK2	KLK2	KLK2	8417	0.011	0.42	NO
35	GSK3B	GSK3B	GSK3B	8462	0.011	0.42	NO
36	RXRG	RXRG	RXRG	8769	0.0064	0.4	NO
37	GATA2	GATA2	GATA2	9223	0.00027	0.38	NO
38	CEBPA	CEBPA	CEBPA	9316	-0.0011	0.37	NO
39	EGR1	EGR1	EGR1	9660	-0.0063	0.36	NO
40	RXRB	RXRB	RXRB	9731	-0.0071	0.35	NO
41	TRIM24	TRIM24	TRIM24	9778	-0.008	0.35	NO
42	KAT5	KAT5	KAT5	11012	-0.026	0.29	NO
43	SMARCC1	SMARCC1	SMARCC1	11651	-0.037	0.26	NO
44	POU2F1	POU2F1	POU2F1	11670	-0.037	0.27	NO
45	HDAC7	HDAC7	HDAC7	11872	-0.04	0.27	NO
46	PKN1	PKN1	PKN1	12036	-0.043	0.27	NO
47	EHMT2	EHMT2	EHMT2	12666	-0.054	0.24	NO
48	ZMIZ2	ZMIZ2	ZMIZ2	12686	-0.055	0.25	NO
49	GNB2L1	GNB2L1	GNB2L1	13216	-0.065	0.24	NO
50	CARM1	CARM1	CARM1	13412	-0.07	0.24	NO
51	JUN	JUN	JUN	13628	-0.075	0.25	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: PID ERBB1 RECEPTOR PROXIMAL PATHWAY.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: PID ERBB1 RECEPTOR PROXIMAL 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 CERAMIDE 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	TIAM1	TIAM1	TIAM1	878	0.29	0.023	YES
2	ARHGEF6	ARHGEF6	ARHGEF6	1527	0.19	0.036	YES
3	APC	APC	APC	1766	0.17	0.066	YES
4	F2RL2	F2RL2	F2RL2	2242	0.14	0.076	YES
5	PLD1	PLD1	PLD1	2906	0.12	0.068	YES
6	MYL2	MYL2	MYL2	2919	0.12	0.096	YES
7	YES1	YES1	YES1	3017	0.11	0.12	YES
8	IQGAP1	IQGAP1	IQGAP1	3088	0.11	0.14	YES
9	MAP3K1	MAP3K1	MAP3K1	3605	0.095	0.14	YES
10	PIK3CA	PIK3CA	PIK3CA	3678	0.093	0.16	YES
11	WASL	WASL	WASL	3715	0.092	0.18	YES
12	ACTR2	ACTR2	ACTR2	3877	0.088	0.19	YES
13	PRKCE	PRKCE	PRKCE	3935	0.086	0.21	YES
14	RASGRF1	RASGRF1	RASGRF1	3964	0.086	0.23	YES
15	CDC42BPA	CDC42BPA	CDC42BPA	4196	0.081	0.24	YES
16	LIMK2	LIMK2	LIMK2	4316	0.078	0.25	YES
17	MAP2K6	MAP2K6	MAP2K6	4525	0.074	0.26	YES
18	MAPK3	MAPK3	MAPK3	4650	0.071	0.27	YES
19	CDH1	CDH1	CDH1	4679	0.07	0.28	YES
20	CDC42	CDC42	CDC42	5034	0.064	0.28	YES
21	MAPK8	MAPK8	MAPK8	5067	0.063	0.29	YES
22	CBL	CBL	CBL	5149	0.061	0.3	YES
23	DLG1	DLG1	DLG1	5154	0.061	0.32	YES
24	DIAPH3	DIAPH3	DIAPH3	5157	0.061	0.34	YES
25	MAPK1	MAPK1	MAPK1	5534	0.055	0.33	YES
26	PIK3R1	PIK3R1	PIK3R1	5695	0.053	0.33	YES
27	ARPC3	ARPC3	ARPC3	5751	0.051	0.34	YES
28	EPS8	EPS8	EPS8	5806	0.051	0.35	YES
29	PAK1	PAK1	PAK1	5919	0.049	0.36	YES
30	MAPK9	MAPK9	MAPK9	6028	0.047	0.36	YES
31	PAK2	PAK2	PAK2	6065	0.047	0.37	YES
32	MAPK14	MAPK14	MAPK14	6186	0.044	0.38	YES
33	ACTR3	ACTR3	ACTR3	6387	0.041	0.38	YES
34	ATF2	ATF2	ATF2	6408	0.041	0.39	YES
35	RPS6KB1	RPS6KB1	RPS6KB1	6509	0.04	0.39	YES
36	ARPC5	ARPC5	ARPC5	7048	0.031	0.37	NO
37	BRAF	BRAF	BRAF	7076	0.031	0.38	NO
38	MAP2K4	MAP2K4	MAP2K4	7518	0.024	0.36	NO
39	PAX6	PAX6	PAX6	7661	0.022	0.35	NO
40	ARPC2	ARPC2	ARPC2	7928	0.018	0.34	NO
41	MAP2K7	MAP2K7	MAP2K7	7967	0.017	0.35	NO
42	MTOR	MTOR	MTOR	8088	0.016	0.34	NO
43	CTNNA1	CTNNA1	CTNNA1	8120	0.015	0.34	NO
44	SRC	SRC	SRC	8149	0.015	0.35	NO
45	ARHGEF7	ARHGEF7	ARHGEF7	8308	0.013	0.34	NO
46	RAF1	RAF1	RAF1	8377	0.012	0.34	NO
47	GSK3B	GSK3B	GSK3B	8462	0.011	0.34	NO
48	VAV2	VAV2	VAV2	8896	0.0046	0.32	NO
49	ARPC4	ARPC4	ARPC4	9017	0.0031	0.31	NO
50	SEPT2	SEPT2	SEPT2	9074	0.0024	0.31	NO
51	CFL1	CFL1	CFL1	9085	0.0022	0.31	NO
52	RAC1	RAC1	RAC1	9404	-0.0024	0.29	NO
53	MAP2K3	MAP2K3	MAP2K3	9486	-0.0036	0.29	NO
54	TNK2	TNK2	TNK2	9575	-0.0049	0.28	NO
55	CTNNB1	CTNNB1	CTNNB1	9613	-0.0054	0.28	NO
56	BCAR1	BCAR1	BCAR1	9906	-0.01	0.27	NO
57	ENAH	ENAH	ENAH	10125	-0.014	0.26	NO
58	EXOC7	EXOC7	EXOC7	10222	-0.015	0.26	NO
59	MAP3K11	MAP3K11	MAP3K11	10856	-0.024	0.23	NO
60	ARPC1B	ARPC1B	ARPC1B	10987	-0.026	0.23	NO
61	ARHGDIA	ARHGDIA	ARHGDIA	11118	-0.028	0.23	NO
62	HES5	HES5	HES5	11139	-0.028	0.24	NO
63	PAK4	PAK4	PAK4	11234	-0.03	0.24	NO
64	PRKCZ	PRKCZ	PRKCZ	11701	-0.038	0.22	NO
65	IQGAP3	IQGAP3	IQGAP3	12225	-0.046	0.2	NO
66	LIMK1	LIMK1	LIMK1	13306	-0.067	0.16	NO
67	JUN	JUN	JUN	13628	-0.075	0.16	NO
68	BAIAP2	BAIAP2	BAIAP2	13673	-0.076	0.18	NO
69	HRAS	HRAS	HRAS	15203	-0.12	0.12	NO
70	PARD6A	PARD6A	PARD6A	15720	-0.15	0.13	NO

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

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: PID CERAMIDE 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 AR TF 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	TUSC3	TUSC3	TUSC3	725	0.32	0.022	YES
2	EDEM3	EDEM3	EDEM3	1446	0.2	0.02	YES
3	MGAT5	MGAT5	MGAT5	1523	0.19	0.054	YES
4	MGAT3	MGAT3	MGAT3	1598	0.19	0.086	YES
5	MAN2A1	MAN2A1	MAN2A1	1630	0.19	0.12	YES
6	MAN1A2	MAN1A2	MAN1A2	1631	0.19	0.16	YES
7	ST8SIA2	ST8SIA2	ST8SIA2	2002	0.16	0.17	YES
8	MGAT4A	MGAT4A	MGAT4A	2101	0.15	0.19	YES
9	ALG11	ALG11	ALG11	2104	0.15	0.22	YES
10	B4GALT4	B4GALT4	B4GALT4	2323	0.14	0.23	YES
11	ST8SIA3	ST8SIA3	ST8SIA3	2377	0.14	0.26	YES
12	MANEA	MANEA	MANEA	2379	0.14	0.28	YES
13	MAN1A1	MAN1A1	MAN1A1	2410	0.14	0.31	YES
14	MAN1C1	MAN1C1	MAN1C1	3201	0.11	0.28	YES
15	LMAN1	LMAN1	LMAN1	3206	0.11	0.3	YES
16	SEC24D	SEC24D	SEC24D	3238	0.1	0.32	YES
17	ALG6	ALG6	ALG6	3440	0.099	0.33	YES
18	EDEM1	EDEM1	EDEM1	3582	0.095	0.34	YES
19	ST6GAL1	ST6GAL1	ST6GAL1	4148	0.082	0.33	YES
20	DOLPP1	DOLPP1	DOLPP1	4185	0.081	0.34	YES
21	B4GALT1	B4GALT1	B4GALT1	4283	0.079	0.35	YES
22	UGGT2	UGGT2	UGGT2	4433	0.076	0.36	YES
23	PGM3	PGM3	PGM3	4667	0.07	0.36	YES
24	SEC24B	SEC24B	SEC24B	5121	0.062	0.34	YES
25	B4GALT5	B4GALT5	B4GALT5	5144	0.062	0.35	YES
26	MPI	MPI	MPI	5190	0.061	0.36	YES
27	SEC23A	SEC23A	SEC23A	5371	0.057	0.36	YES
28	MGAT2	MGAT2	MGAT2	5372	0.057	0.38	YES
29	ALG10	ALG10	ALG10	5424	0.057	0.38	YES
30	SEC31A	SEC31A	SEC31A	5710	0.052	0.38	YES
31	ALG10B	ALG10B	ALG10B	5790	0.051	0.38	YES
32	MCFD2	MCFD2	MCFD2	5929	0.049	0.38	YES
33	SAR1B	SAR1B	SAR1B	6034	0.047	0.39	YES
34	ALG14	ALG14	ALG14	6084	0.046	0.4	YES
35	PDIA3	PDIA3	PDIA3	6292	0.043	0.39	YES
36	ALG5	ALG5	ALG5	6323	0.043	0.4	YES
37	UGGT1	UGGT1	UGGT1	6420	0.041	0.4	YES
38	CANX	CANX	CANX	6838	0.034	0.38	NO
39	SEC24C	SEC24C	SEC24C	7634	0.022	0.34	NO
40	MLEC	MLEC	MLEC	7721	0.021	0.34	NO
41	ALG13	ALG13	ALG13	7775	0.02	0.34	NO
42	ALG2	ALG2	ALG2	7791	0.02	0.35	NO
43	STT3A	STT3A	STT3A	8441	0.011	0.31	NO
44	PMM2	PMM2	PMM2	8549	0.0094	0.31	NO
45	GNPNAT1	GNPNAT1	GNPNAT1	8792	0.0061	0.3	NO
46	ALG8	ALG8	ALG8	8840	0.0054	0.3	NO
47	GMPPB	GMPPB	GMPPB	9109	0.0019	0.28	NO
48	B4GALT6	B4GALT6	B4GALT6	9136	0.0015	0.28	NO
49	DPM1	DPM1	DPM1	9422	-0.0026	0.26	NO
50	GANAB	GANAB	GANAB	9513	-0.0041	0.26	NO
51	DOLK	DOLK	DOLK	9530	-0.0043	0.26	NO
52	FUT8	FUT8	FUT8	9669	-0.0064	0.25	NO
53	MOGS	MOGS	MOGS	9693	-0.0067	0.25	NO
54	B4GALT3	B4GALT3	B4GALT3	9757	-0.0076	0.25	NO
55	ST8SIA6	ST8SIA6	ST8SIA6	9859	-0.0094	0.25	NO
56	CALR	CALR	CALR	10484	-0.018	0.22	NO
57	ALG1	ALG1	ALG1	10627	-0.02	0.21	NO
58	MGAT1	MGAT1	MGAT1	10637	-0.021	0.22	NO
59	RPN2	RPN2	RPN2	10669	-0.021	0.22	NO
60	ALG9	ALG9	ALG9	10832	-0.024	0.22	NO
61	MGAT4B	MGAT4B	MGAT4B	10836	-0.024	0.22	NO
62	DAD1	DAD1	DAD1	10910	-0.025	0.22	NO
63	GMPPA	GMPPA	GMPPA	10958	-0.025	0.22	NO
64	PRKCSH	PRKCSH	PRKCSH	11008	-0.026	0.22	NO
65	DDOST	DDOST	DDOST	11022	-0.026	0.23	NO
66	MAN1B1	MAN1B1	MAN1B1	11029	-0.026	0.23	NO
67	SEC13	SEC13	SEC13	11084	-0.027	0.24	NO
68	DPAGT1	DPAGT1	DPAGT1	11499	-0.034	0.22	NO
69	PMM1	PMM1	PMM1	11721	-0.038	0.22	NO
70	RPN1	RPN1	RPN1	11786	-0.039	0.22	NO
71	PREB	PREB	PREB	12349	-0.049	0.2	NO
72	ALG12	ALG12	ALG12	12823	-0.058	0.18	NO
73	B4GALT2	B4GALT2	B4GALT2	13093	-0.063	0.18	NO
74	EDEM2	EDEM2	EDEM2	13388	-0.069	0.18	NO
75	ALG3	ALG3	ALG3	13649	-0.075	0.18	NO
76	DPM2	DPM2	DPM2	13650	-0.075	0.19	NO
77	DPM3	DPM3	DPM3	13979	-0.083	0.19	NO
78	GFPT2	GFPT2	GFPT2	14362	-0.094	0.19	NO
79	RFT1	RFT1	RFT1	14899	-0.11	0.18	NO

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

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: PID AR TF 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 AMINOACYL TRNA BIOSYNTHESIS	41	genes.ES.table	0.54	1.9	0.038	0.76	0.42	0.71	0.34	0.47	0	0.14
KEGG RNA DEGRADATION	57	genes.ES.table	0.44	1.7	0.049	0.41	0.76	0.51	0.26	0.38	0.14	0.096
BIOCARTA FAS PATHWAY	30	genes.ES.table	0.46	1.6	0.061	0.43	0.88	0.57	0.32	0.39	0.19	0.12
PID PLK1 PATHWAY	45	genes.ES.table	0.56	1.8	0.053	0.51	0.66	0.58	0.26	0.43	0.14	0.11
PID BARD1PATHWAY	29	genes.ES.table	0.56	1.7	0.06	0.4	0.83	0.72	0.35	0.47	0.15	0.1
PID P53REGULATIONPATHWAY	58	genes.ES.table	0.38	1.9	0.016	0.52	0.42	0.52	0.31	0.36	0	0.1
REACTOME METABOLISM OF NON CODING RNA	47	genes.ES.table	0.51	1.8	0.049	0.4	0.67	0.51	0.24	0.39	0.11	0.09
REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA	126	genes.ES.table	0.41	1.7	0.065	0.43	0.82	0.63	0.36	0.4	0.17	0.11
REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM	44	genes.ES.table	0.52	1.8	0.026	0.53	0.6	0.48	0.24	0.36	0.11	0.11
REACTOME CELL CYCLE MITOTIC	296	genes.ES.table	0.41	1.6	0.12	0.43	0.9	0.44	0.24	0.34	0.2	0.12

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

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	SNRPD1	SNRPD1	SNRPD1	999	0.14	-0.034	YES
2	SNRPE	SNRPE	SNRPE	1214	0.12	-0.026	YES
3	APOBEC1	APOBEC1	APOBEC1	1248	0.12	-0.0083	YES
4	RANBP2	RANBP2	RANBP2	1252	0.12	0.011	YES
5	SEH1L	SEH1L	SEH1L	1400	0.11	0.021	YES
6	RNGTT	RNGTT	RNGTT	1446	0.11	0.036	YES
7	MNAT1	MNAT1	MNAT1	1545	0.11	0.048	YES
8	NUP155	NUP155	NUP155	1830	0.097	0.047	YES
9	CPSF2	CPSF2	CPSF2	1854	0.096	0.061	YES
10	RBM8A	RBM8A	RBM8A	1881	0.095	0.075	YES
11	CCAR1	CCAR1	CCAR1	1904	0.094	0.089	YES
12	HNRNPR	HNRNPR	HNRNPR	1954	0.093	0.1	YES
13	POLR2A	POLR2A	POLR2A	2023	0.091	0.11	YES
14	NUP133	NUP133	NUP133	2110	0.089	0.12	YES
15	RNMT	RNMT	RNMT	2156	0.088	0.13	YES
16	SNRPB2	SNRPB2	SNRPB2	2161	0.088	0.15	YES
17	CSTF3	CSTF3	CSTF3	2346	0.083	0.15	YES
18	SNRPA1	SNRPA1	SNRPA1	2363	0.083	0.16	YES
19	SRRM1	SRRM1	SRRM1	2378	0.083	0.17	YES
20	UPF3B	UPF3B	UPF3B	2491	0.08	0.18	YES
21	NCBP1	NCBP1	NCBP1	2551	0.078	0.19	YES
22	CDC40	CDC40	CDC40	2630	0.076	0.2	YES
23	NUP37	NUP37	NUP37	2823	0.072	0.2	YES
24	HNRNPU	HNRNPU	HNRNPU	2837	0.072	0.21	YES
25	GTF2H3	GTF2H3	GTF2H3	2970	0.069	0.21	YES
26	PAPOLA	PAPOLA	PAPOLA	3067	0.068	0.22	YES
27	HNRNPC	HNRNPC	HNRNPC	3104	0.067	0.23	YES
28	SNRPF	SNRPF	SNRPF	3118	0.067	0.24	YES
29	POLR2B	POLR2B	POLR2B	3124	0.066	0.25	YES
30	NUP50	NUP50	NUP50	3190	0.065	0.25	YES
31	CDK7	CDK7	CDK7	3197	0.065	0.26	YES
32	HNRNPH1	HNRNPH1	HNRNPH1	3208	0.065	0.27	YES
33	HNRNPA1	HNRNPA1	HNRNPA1	3214	0.065	0.28	YES
34	TPR	TPR	TPR	3220	0.065	0.29	YES
35	HNRNPA3	HNRNPA3	HNRNPA3	3223	0.064	0.3	YES
36	SF3A3	SF3A3	SF3A3	3333	0.063	0.31	YES
37	HNRNPK	HNRNPK	HNRNPK	3554	0.058	0.3	YES
38	NUP54	NUP54	NUP54	3706	0.056	0.3	YES
39	NUP43	NUP43	NUP43	3744	0.055	0.31	YES
40	DHX9	DHX9	DHX9	3840	0.053	0.31	YES
41	NUP88	NUP88	NUP88	3961	0.051	0.32	YES
42	NUP153	NUP153	NUP153	4052	0.05	0.32	YES
43	HNRNPD	HNRNPD	HNRNPD	4068	0.05	0.32	YES
44	NUP107	NUP107	NUP107	4171	0.048	0.33	YES
45	PABPN1	PABPN1	PABPN1	4177	0.048	0.34	YES
46	SF3B1	SF3B1	SF3B1	4209	0.048	0.34	YES
47	EIF4E	EIF4E	EIF4E	4224	0.047	0.35	YES
48	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	4265	0.047	0.35	YES
49	NUP35	NUP35	NUP35	4270	0.046	0.36	YES
50	SF3B14	SF3B14	SF3B14	4276	0.046	0.37	YES
51	CPSF3	CPSF3	CPSF3	4281	0.046	0.37	YES
52	HNRNPF	HNRNPF	HNRNPF	4372	0.045	0.38	YES
53	ADAR	ADAR	ADAR	4758	0.04	0.36	YES
54	GTF2H4	GTF2H4	GTF2H4	4823	0.038	0.36	YES
55	RBMX	RBMX	RBMX	4933	0.037	0.36	YES
56	SNRPG	SNRPG	SNRPG	4971	0.036	0.37	YES
57	SNRNP40	SNRNP40	SNRNP40	5017	0.036	0.37	YES
58	MAGOH	MAGOH	MAGOH	5038	0.035	0.37	YES
59	TXNL4A	TXNL4A	TXNL4A	5089	0.034	0.38	YES
60	DDX23	DDX23	DDX23	5125	0.034	0.38	YES
61	HNRNPA0	HNRNPA0	HNRNPA0	5163	0.033	0.38	YES
62	LSM11	LSM11	LSM11	5228	0.032	0.38	YES
63	DNAJC8	DNAJC8	DNAJC8	5293	0.032	0.39	YES
64	NUP188	NUP188	NUP188	5453	0.029	0.38	YES
65	NUPL1	NUPL1	NUPL1	5581	0.027	0.38	YES
66	PRPF4	PRPF4	PRPF4	5611	0.027	0.38	YES
67	SNRPA	SNRPA	SNRPA	5612	0.027	0.39	YES
68	POLR2D	POLR2D	POLR2D	5631	0.026	0.39	YES
69	NUDT21	NUDT21	NUDT21	5688	0.026	0.39	YES
70	U2AF1	U2AF1	U2AF1	5814	0.024	0.39	YES
71	FUS	FUS	FUS	5832	0.023	0.39	YES
72	HNRNPM	HNRNPM	HNRNPM	5860	0.023	0.39	YES
73	POLR2K	POLR2K	POLR2K	5878	0.023	0.4	YES
74	SNRPD3	SNRPD3	SNRPD3	5890	0.023	0.4	YES
75	NUP205	NUP205	NUP205	5907	0.022	0.4	YES
76	CCNH	CCNH	CCNH	5918	0.022	0.4	YES
77	PRPF8	PRPF8	PRPF8	6027	0.021	0.4	YES
78	METTL3	METTL3	METTL3	6155	0.019	0.4	YES
79	SF3B3	SF3B3	SF3B3	6157	0.019	0.4	YES
80	HNRNPUL1	HNRNPUL1	HNRNPUL1	6171	0.019	0.4	YES
81	SNRNP70	SNRNP70	SNRNP70	6175	0.019	0.4	YES
82	LSM2	LSM2	LSM2	6224	0.018	0.4	YES
83	SNRPB	SNRPB	SNRPB	6285	0.017	0.4	YES
84	ZNF473	ZNF473	ZNF473	6304	0.017	0.41	YES
85	HNRNPL	HNRNPL	HNRNPL	6355	0.016	0.41	YES
86	PTBP1	PTBP1	PTBP1	6423	0.016	0.4	YES
87	GTF2F2	GTF2F2	GTF2F2	6508	0.014	0.4	YES
88	SMC1A	SMC1A	SMC1A	6519	0.014	0.4	YES
89	NUP62	NUP62	NUP62	6525	0.014	0.41	YES
90	AAAS	AAAS	AAAS	6549	0.014	0.41	YES
91	SLBP	SLBP	SLBP	6685	0.012	0.4	NO
92	PCF11	PCF11	PCF11	6696	0.012	0.4	NO
93	NUP214	NUP214	NUP214	6993	0.008	0.39	NO
94	NUP93	NUP93	NUP93	7028	0.0074	0.39	NO
95	SNRPD2	SNRPD2	SNRPD2	7087	0.0068	0.38	NO
96	YBX1	YBX1	YBX1	7184	0.0054	0.38	NO
97	CD2BP2	CD2BP2	CD2BP2	7278	0.0041	0.38	NO
98	PCBP2	PCBP2	PCBP2	7363	0.0028	0.37	NO
99	GTF2H1	GTF2H1	GTF2H1	7565	-0.00017	0.36	NO
100	NCBP2	NCBP2	NCBP2	7580	-0.00036	0.36	NO
101	SF3A1	SF3A1	SF3A1	7640	-0.0011	0.36	NO
102	EFTUD2	EFTUD2	EFTUD2	7684	-0.0017	0.35	NO
103	SUPT5H	SUPT5H	SUPT5H	7778	-0.0028	0.35	NO
104	HNRNPH2	HNRNPH2	HNRNPH2	7901	-0.0045	0.34	NO
105	NUPL2	NUPL2	NUPL2	7994	-0.0056	0.34	NO
106	NUP210	NUP210	NUP210	8122	-0.0074	0.33	NO
107	ADARB1	ADARB1	ADARB1	8151	-0.0078	0.33	NO
108	SF3B4	SF3B4	SF3B4	8204	-0.0087	0.33	NO
109	THOC4	THOC4	THOC4	8210	-0.0088	0.33	NO
110	RBM5	RBM5	RBM5	8242	-0.0093	0.33	NO
111	NFX1	NFX1	NFX1	8275	-0.0096	0.33	NO
112	NHP2L1	NHP2L1	NHP2L1	8339	-0.01	0.33	NO
113	U2AF2	U2AF2	U2AF2	8412	-0.012	0.33	NO
114	CPSF7	CPSF7	CPSF7	8498	-0.013	0.32	NO
115	SF3B2	SF3B2	SF3B2	8585	-0.014	0.32	NO
116	CSTF2	CSTF2	CSTF2	8589	-0.014	0.32	NO
117	ERCC2	ERCC2	ERCC2	8873	-0.018	0.31	NO
118	RNPS1	RNPS1	RNPS1	8996	-0.02	0.31	NO
119	SNRNP200	SNRNP200	SNRNP200	9014	-0.02	0.31	NO
120	GTF2F1	GTF2F1	GTF2F1	9119	-0.021	0.31	NO
121	SF3B5	SF3B5	SF3B5	9156	-0.022	0.31	NO
122	PCBP1	PCBP1	PCBP1	9161	-0.022	0.31	NO
123	NUP85	NUP85	NUP85	9244	-0.023	0.31	NO
124	GTF2H2	GTF2H2	GTF2H2	9305	-0.024	0.31	NO
125	CSTF1	CSTF1	CSTF1	9637	-0.029	0.3	NO
126	POLR2E	POLR2E	POLR2E	9664	-0.029	0.3	NO
127	DHX38	DHX38	DHX38	9740	-0.031	0.3	NO
128	NXF1	NXF1	NXF1	9751	-0.031	0.31	NO
129	ERCC3	ERCC3	ERCC3	9910	-0.033	0.3	NO
130	PHF5A	PHF5A	PHF5A	10039	-0.035	0.3	NO
131	GTF2H2B	GTF2H2B	GTF2H2B	10130	-0.037	0.3	NO
132	POLR2H	POLR2H	POLR2H	10269	-0.039	0.3	NO
133	RAE1	RAE1	RAE1	10340	-0.04	0.3	NO
134	POLR2L	POLR2L	POLR2L	10642	-0.046	0.29	NO
135	POM121	POM121	POM121	10664	-0.046	0.3	NO
136	SF3A2	SF3A2	SF3A2	10814	-0.048	0.3	NO
137	CLP1	CLP1	CLP1	10825	-0.048	0.31	NO
138	POLR2C	POLR2C	POLR2C	10884	-0.05	0.31	NO
139	LSM10	LSM10	LSM10	11256	-0.056	0.3	NO
140	CPSF1	CPSF1	CPSF1	11378	-0.059	0.3	NO
141	POLR2F	POLR2F	POLR2F	11407	-0.059	0.31	NO
142	A1CF	A1CF	A1CF	11866	-0.069	0.3	NO
143	POLR2I	POLR2I	POLR2I	12118	-0.075	0.29	NO
144	POLR2G	POLR2G	POLR2G	12328	-0.08	0.29	NO
145	POLR2J	POLR2J	POLR2J	12384	-0.081	0.3	NO
146	PRPF6	PRPF6	PRPF6	12605	-0.087	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 AMINOACYL TRNA BIOSYNTHESIS.

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

genes ES table in pathway: KEGG RNA DEGRADATION

Table 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	YARS2	YARS2	YARS2	1844	0.096	-0.041	YES
2	DARS2	DARS2	DARS2	1858	0.096	0.018	YES
3	NARS	NARS	NARS	2037	0.091	0.066	YES
4	EPRS	EPRS	EPRS	2112	0.089	0.12	YES
5	RARS	RARS	RARS	2150	0.088	0.17	YES
6	WARS2	WARS2	WARS2	2151	0.088	0.23	YES
7	SEPSECS	SEPSECS	SEPSECS	2399	0.082	0.26	YES
8	HARS2	HARS2	HARS2	2696	0.075	0.3	YES
9	MTFMT	MTFMT	MTFMT	3642	0.057	0.28	YES
10	TARS	TARS	TARS	3685	0.056	0.31	YES
11	IARS2	IARS2	IARS2	3998	0.051	0.33	YES
12	LARS	LARS	LARS	4366	0.045	0.33	YES
13	AARS2	AARS2	AARS2	4477	0.043	0.36	YES
14	SARS2	SARS2	SARS2	4793	0.039	0.36	YES
15	YARS	YARS	YARS	4834	0.038	0.38	YES
16	FARSB	FARSB	FARSB	5113	0.034	0.39	YES
17	MARS2	MARS2	MARS2	5251	0.032	0.4	YES
18	PSTK	PSTK	PSTK	5284	0.032	0.42	YES
19	RARS2	RARS2	RARS2	5290	0.032	0.44	YES
20	DARS	DARS	DARS	5509	0.028	0.45	YES
21	TARS2	TARS2	TARS2	5554	0.028	0.46	YES
22	IARS	IARS	IARS	5574	0.027	0.48	YES
23	EARS2	EARS2	EARS2	5710	0.025	0.49	YES
24	TARSL2	TARSL2	TARSL2	5891	0.023	0.49	YES
25	HARS	HARS	HARS	5976	0.022	0.5	YES
26	PARS2	PARS2	PARS2	5981	0.021	0.51	YES
27	QARS	QARS	QARS	6057	0.02	0.52	YES
28	LARS2	LARS2	LARS2	6070	0.02	0.53	YES
29	VARS2	VARS2	VARS2	6195	0.018	0.54	YES
30	KARS	KARS	KARS	6617	0.013	0.52	NO
31	VARS	VARS	VARS	7008	0.0077	0.51	NO
32	MARS	MARS	MARS	7164	0.0058	0.5	NO
33	FARS2	FARS2	FARS2	7188	0.0054	0.5	NO
34	GARS	GARS	GARS	7440	0.0017	0.49	NO
35	WARS	WARS	WARS	7741	-0.0023	0.48	NO
36	SARS	SARS	SARS	8637	-0.015	0.43	NO
37	FARSA	FARSA	FARSA	8807	-0.017	0.44	NO
38	CARS	CARS	CARS	9158	-0.022	0.43	NO
39	AARS	AARS	AARS	9286	-0.024	0.44	NO
40	NARS2	NARS2	NARS2	9755	-0.031	0.43	NO
41	CARS2	CARS2	CARS2	10770	-0.048	0.41	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 RNA DEGRADATION.

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

genes ES table in pathway: BIOCARTA FAS 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	MDM2	MDM2	MDM2	733	0.16	0.023	YES
2	SKP2	SKP2	SKP2	1401	0.11	0.031	YES
3	HIPK2	HIPK2	HIPK2	1733	0.1	0.052	YES
4	CSNK1G1	CSNK1G1	CSNK1G1	2088	0.09	0.068	YES
5	CCNG1	CCNG1	CCNG1	2186	0.087	0.097	YES
6	SMYD2	SMYD2	SMYD2	2294	0.084	0.12	YES
7	CCNA2	CCNA2	CCNA2	2463	0.081	0.15	YES
8	CHEK1	CHEK1	CHEK1	3357	0.062	0.12	YES
9	FBXO11	FBXO11	FBXO11	3384	0.062	0.15	YES
10	RPL11	RPL11	RPL11	3420	0.061	0.17	YES
11	DYRK2	DYRK2	DYRK2	3540	0.058	0.18	YES
12	TP53AIP1	TP53AIP1	TP53AIP1	3600	0.057	0.2	YES
13	CDK2	CDK2	CDK2	3617	0.057	0.22	YES
14	CSNK1A1	CSNK1A1	CSNK1A1	3637	0.057	0.25	YES
15	CSNK1G3	CSNK1G3	CSNK1G3	3733	0.055	0.26	YES
16	RPL5	RPL5	RPL5	3803	0.054	0.28	YES
17	PRMT5	PRMT5	PRMT5	3982	0.051	0.29	YES
18	MAPK8	MAPK8	MAPK8	4144	0.048	0.3	YES
19	SETD8	SETD8	SETD8	4432	0.044	0.3	YES
20	CHEK2	CHEK2	CHEK2	4617	0.041	0.31	YES
21	RFWD2	RFWD2	RFWD2	4663	0.041	0.32	YES
22	UBE2D1	UBE2D1	UBE2D1	4780	0.039	0.33	YES
23	RCHY1	RCHY1	RCHY1	4912	0.037	0.34	YES
24	MDM4	MDM4	MDM4	4966	0.036	0.35	YES
25	GSK3B	GSK3B	GSK3B	5157	0.033	0.35	YES
26	PPP2CA	PPP2CA	PPP2CA	5192	0.033	0.36	YES
27	PPM1D	PPM1D	PPM1D	5393	0.03	0.37	YES
28	PPP2R4	PPP2R4	PPP2R4	5494	0.029	0.37	YES
29	ATM	ATM	ATM	5655	0.026	0.37	YES
30	SETD7	SETD7	SETD7	5658	0.026	0.38	YES
31	RPL23	RPL23	RPL23	6134	0.019	0.36	NO
32	USP7	USP7	USP7	6271	0.017	0.36	NO
33	YY1	YY1	YY1	6372	0.016	0.36	NO
34	ATR	ATR	ATR	6638	0.013	0.36	NO
35	CSE1L	CSE1L	CSE1L	6644	0.013	0.36	NO
36	MAPK14	MAPK14	MAPK14	6908	0.0091	0.35	NO
37	TRIM28	TRIM28	TRIM28	7046	0.0072	0.34	NO
38	DAXX	DAXX	DAXX	7088	0.0068	0.34	NO
39	RASSF1	RASSF1	RASSF1	7097	0.0067	0.35	NO
40	HUWE1	HUWE1	HUWE1	7606	-0.00075	0.32	NO
41	EP300	EP300	EP300	7712	-0.0021	0.31	NO
42	AKT1	AKT1	AKT1	7738	-0.0023	0.31	NO
43	NEDD8	NEDD8	NEDD8	8379	-0.011	0.28	NO
44	MAPK9	MAPK9	MAPK9	8438	-0.012	0.28	NO
45	CSNK1E	CSNK1E	CSNK1E	8640	-0.015	0.28	NO
46	CREBBP	CREBBP	CREBBP	8918	-0.018	0.27	NO
47	CSNK1D	CSNK1D	CSNK1D	9303	-0.024	0.26	NO
48	CSNK1G2	CSNK1G2	CSNK1G2	9559	-0.028	0.26	NO
49	KAT2B	KAT2B	KAT2B	9867	-0.032	0.25	NO
50	TP53	TP53	TP53	9948	-0.033	0.26	NO
51	ABL1	ABL1	ABL1	10097	-0.036	0.27	NO
52	TTC5	TTC5	TTC5	10357	-0.04	0.27	NO
53	PRKCD	PRKCD	PRKCD	10479	-0.042	0.28	NO
54	PPP1R13L	PPP1R13L	PPP1R13L	10805	-0.048	0.28	NO
55	PIN1	PIN1	PIN1	11301	-0.057	0.27	NO
56	E4F1	E4F1	E4F1	11621	-0.064	0.28	NO
57	KAT5	KAT5	KAT5	12856	-0.093	0.25	NO
58	CDKN2A	CDKN2A	CDKN2A	13108	-0.1	0.28	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: BIOCARTA FAS PATHWAY.

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

genes ES table in pathway: PID PLK1 PATHWAY

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	NDC80	NDC80	NDC80	251	0.24	0.024	YES
2	CENPK	CENPK	CENPK	540	0.19	0.036	YES
3	CASC5	CASC5	CASC5	570	0.18	0.062	YES
4	SKA1	SKA1	SKA1	626	0.17	0.086	YES
5	NUF2	NUF2	NUF2	690	0.16	0.11	YES
6	ERCC6L	ERCC6L	ERCC6L	694	0.16	0.13	YES
7	SGOL2	SGOL2	SGOL2	698	0.16	0.16	YES
8	KIF18A	KIF18A	KIF18A	794	0.15	0.18	YES
9	ZWILCH	ZWILCH	ZWILCH	1001	0.14	0.18	YES
10	CCDC99	CCDC99	CCDC99	1014	0.14	0.2	YES
11	SGOL1	SGOL1	SGOL1	1040	0.13	0.22	YES
12	BUB1B	BUB1B	BUB1B	1200	0.12	0.24	YES
13	MLF1IP	MLF1IP	MLF1IP	1203	0.12	0.25	YES
14	RANBP2	RANBP2	RANBP2	1252	0.12	0.27	YES
15	SEH1L	SEH1L	SEH1L	1400	0.11	0.28	YES
16	MAD2L1	MAD2L1	MAD2L1	1480	0.11	0.29	YES
17	CENPI	CENPI	CENPI	1482	0.11	0.31	YES
18	CENPC1	CENPC1	CENPC1	1552	0.11	0.32	YES
19	AHCTF1	AHCTF1	AHCTF1	1646	0.1	0.33	YES
20	TAOK1	TAOK1	TAOK1	1709	0.1	0.34	YES
21	BUB1	BUB1	BUB1	1759	0.099	0.36	YES
22	KIF2A	KIF2A	KIF2A	1868	0.096	0.36	YES
23	MIS12	MIS12	MIS12	1919	0.094	0.38	YES
24	CENPQ	CENPQ	CENPQ	1923	0.094	0.39	YES
25	ITGB3BP	ITGB3BP	ITGB3BP	2035	0.091	0.4	YES
26	NUP133	NUP133	NUP133	2110	0.089	0.41	YES
27	SPC25	SPC25	SPC25	2123	0.088	0.42	YES
28	BIRC5	BIRC5	BIRC5	2132	0.088	0.43	YES
29	CENPL	CENPL	CENPL	2138	0.088	0.45	YES
30	XPO1	XPO1	XPO1	2141	0.088	0.46	YES
31	APITD1	APITD1	APITD1	2170	0.088	0.47	YES
32	CENPN	CENPN	CENPN	2173	0.088	0.49	YES
33	KIF2C	KIF2C	KIF2C	2207	0.086	0.5	YES
34	RCC2	RCC2	RCC2	2306	0.084	0.5	YES
35	CENPH	CENPH	CENPH	2546	0.078	0.5	YES
36	NSL1	NSL1	NSL1	2564	0.078	0.52	YES
37	CDCA8	CDCA8	CDCA8	2608	0.077	0.52	YES
38	ZWINT	ZWINT	ZWINT	2716	0.075	0.53	YES
39	PPP2R5A	PPP2R5A	PPP2R5A	2724	0.075	0.54	YES
40	CDC20	CDC20	CDC20	2773	0.073	0.55	YES
41	PPP2R5E	PPP2R5E	PPP2R5E	2802	0.073	0.56	YES
42	NUP37	NUP37	NUP37	2823	0.072	0.57	YES
43	CENPA	CENPA	CENPA	3088	0.067	0.56	YES
44	CENPO	CENPO	CENPO	3196	0.065	0.57	YES
45	PPP2CB	PPP2CB	PPP2CB	3249	0.064	0.57	YES
46	KNTC1	KNTC1	KNTC1	3328	0.063	0.58	YES
47	NUDC	NUDC	NUDC	3407	0.061	0.59	YES
48	PPP2R5C	PPP2R5C	PPP2R5C	3498	0.059	0.59	YES
49	AURKB	AURKB	AURKB	3721	0.055	0.59	YES
50	NUP43	NUP43	NUP43	3744	0.055	0.59	YES
51	PPP1CC	PPP1CC	PPP1CC	4091	0.049	0.58	NO
52	SKA2	SKA2	SKA2	4107	0.049	0.59	NO
53	NUP107	NUP107	NUP107	4171	0.048	0.59	NO
54	PAFAH1B1	PAFAH1B1	PAFAH1B1	4294	0.046	0.59	NO
55	CKAP5	CKAP5	CKAP5	4546	0.042	0.58	NO
56	PPP2R1B	PPP2R1B	PPP2R1B	4594	0.042	0.59	NO
57	CLIP1	CLIP1	CLIP1	4836	0.038	0.58	NO
58	ZW10	ZW10	ZW10	5149	0.034	0.57	NO
59	PPP2CA	PPP2CA	PPP2CA	5192	0.033	0.57	NO
60	BUB3	BUB3	BUB3	5668	0.026	0.55	NO
61	PMF1	PMF1	PMF1	6005	0.021	0.53	NO
62	RAD21	RAD21	RAD21	6298	0.017	0.52	NO
63	RANGAP1	RANGAP1	RANGAP1	6445	0.015	0.51	NO
64	SMC1A	SMC1A	SMC1A	6519	0.014	0.51	NO
65	STAG1	STAG1	STAG1	7111	0.0065	0.48	NO
66	SMC3	SMC3	SMC3	7180	0.0054	0.48	NO
67	NDEL1	NDEL1	NDEL1	7430	0.0019	0.46	NO
68	STAG2	STAG2	STAG2	7586	-0.00047	0.46	NO
69	B9D2	B9D2	B9D2	7794	-0.003	0.44	NO
70	PLK1	PLK1	PLK1	8492	-0.013	0.41	NO
71	CLASP1	CLASP1	CLASP1	8610	-0.014	0.4	NO
72	INCENP	INCENP	INCENP	8625	-0.014	0.4	NO
73	PPP2R1A	PPP2R1A	PPP2R1A	8689	-0.015	0.4	NO
74	SEC13	SEC13	SEC13	8727	-0.016	0.4	NO
75	PPP2R5D	PPP2R5D	PPP2R5D	8959	-0.019	0.39	NO
76	NUP85	NUP85	NUP85	9244	-0.023	0.38	NO
77	MAPRE1	MAPRE1	MAPRE1	9791	-0.032	0.36	NO
78	DSN1	DSN1	DSN1	10204	-0.038	0.34	NO
79	CENPM	CENPM	CENPM	10588	-0.044	0.32	NO
80	CENPP	CENPP	CENPP	11187	-0.055	0.3	NO
81	SPC24	SPC24	SPC24	11705	-0.066	0.28	NO
82	MAD1L1	MAD1L1	MAD1L1	12200	-0.077	0.27	NO
83	CENPT	CENPT	CENPT	13134	-0.1	0.23	NO
84	PPP2R5B	PPP2R5B	PPP2R5B	13271	-0.1	0.24	NO
85	RPS27	RPS27	RPS27	15431	-0.19	0.15	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: PID PLK1 PATHWAY.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: PID PLK1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID BARD1PATHWAY

Table 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	RANBP2	RANBP2	RANBP2	1252	0.12	-0.0085	YES
2	SEH1L	SEH1L	SEH1L	1400	0.11	0.04	YES
3	NUP155	NUP155	NUP155	1830	0.097	0.064	YES
4	CPSF2	CPSF2	CPSF2	1854	0.096	0.11	YES
5	RBM8A	RBM8A	RBM8A	1881	0.095	0.16	YES
6	NUP133	NUP133	NUP133	2110	0.089	0.19	YES
7	SRRM1	SRRM1	SRRM1	2378	0.083	0.21	YES
8	UPF3B	UPF3B	UPF3B	2491	0.08	0.25	YES
9	NCBP1	NCBP1	NCBP1	2551	0.078	0.28	YES
10	CDC40	CDC40	CDC40	2630	0.076	0.32	YES
11	NUP37	NUP37	NUP37	2823	0.072	0.34	YES
12	NUP50	NUP50	NUP50	3190	0.065	0.35	YES
13	TPR	TPR	TPR	3220	0.065	0.38	YES
14	NUP54	NUP54	NUP54	3706	0.056	0.38	YES
15	NUP43	NUP43	NUP43	3744	0.055	0.41	YES
16	NUP88	NUP88	NUP88	3961	0.051	0.42	YES
17	NUP153	NUP153	NUP153	4052	0.05	0.44	YES
18	NUP107	NUP107	NUP107	4171	0.048	0.46	YES
19	EIF4E	EIF4E	EIF4E	4224	0.047	0.48	YES
20	NUP35	NUP35	NUP35	4270	0.046	0.5	YES
21	CPSF3	CPSF3	CPSF3	4281	0.046	0.52	YES
22	MAGOH	MAGOH	MAGOH	5038	0.035	0.5	NO
23	NUP188	NUP188	NUP188	5453	0.029	0.49	NO
24	NUPL1	NUPL1	NUPL1	5581	0.027	0.5	NO
25	U2AF1	U2AF1	U2AF1	5814	0.024	0.5	NO
26	NUP205	NUP205	NUP205	5907	0.022	0.5	NO
27	NUP62	NUP62	NUP62	6525	0.014	0.47	NO
28	AAAS	AAAS	AAAS	6549	0.014	0.48	NO
29	SLBP	SLBP	SLBP	6685	0.012	0.48	NO
30	NUP214	NUP214	NUP214	6993	0.008	0.47	NO
31	NUP93	NUP93	NUP93	7028	0.0074	0.47	NO
32	NCBP2	NCBP2	NCBP2	7580	-0.00036	0.44	NO
33	NUPL2	NUPL2	NUPL2	7994	-0.0056	0.42	NO
34	NUP210	NUP210	NUP210	8122	-0.0074	0.41	NO
35	THOC4	THOC4	THOC4	8210	-0.0088	0.41	NO
36	NFX1	NFX1	NFX1	8275	-0.0096	0.41	NO
37	U2AF2	U2AF2	U2AF2	8412	-0.012	0.41	NO
38	RNPS1	RNPS1	RNPS1	8996	-0.02	0.39	NO
39	NUP85	NUP85	NUP85	9244	-0.023	0.39	NO
40	DHX38	DHX38	DHX38	9740	-0.031	0.38	NO
41	NXF1	NXF1	NXF1	9751	-0.031	0.39	NO
42	RAE1	RAE1	RAE1	10340	-0.04	0.38	NO
43	POM121	POM121	POM121	10664	-0.046	0.38	NO
44	CPSF1	CPSF1	CPSF1	11378	-0.059	0.37	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: PID BARD1PATHWAY.

Figure S50. Get High-res Image For the top 5 core enriched genes in the pathway: PID BARD1PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID P53REGULATIONPATHWAY

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	NDC80	NDC80	NDC80	251	0.24	0.063	YES
2	CENPE	CENPE	CENPE	299	0.23	0.13	YES
3	CLSPN	CLSPN	CLSPN	391	0.21	0.2	YES
4	ERCC6L	ERCC6L	ERCC6L	694	0.16	0.23	YES
5	ECT2	ECT2	ECT2	862	0.15	0.27	YES
6	SGOL1	SGOL1	SGOL1	1040	0.13	0.3	YES
7	BUB1B	BUB1B	BUB1B	1200	0.12	0.33	YES
8	MLF1IP	MLF1IP	MLF1IP	1203	0.12	0.37	YES
9	CDK1	CDK1	CDK1	1683	0.1	0.38	YES
10	BUB1	BUB1	BUB1	1759	0.099	0.4	YES
11	KIF2A	KIF2A	KIF2A	1868	0.096	0.43	YES
12	PPP1R12A	PPP1R12A	PPP1R12A	1997	0.092	0.45	YES
13	CDC25C	CDC25C	CDC25C	2367	0.083	0.46	YES
14	KIF20A	KIF20A	KIF20A	2642	0.076	0.46	YES
15	CDC20	CDC20	CDC20	2773	0.073	0.48	YES
16	ODF2	ODF2	ODF2	3121	0.066	0.48	YES
17	FBXO5	FBXO5	FBXO5	3170	0.066	0.5	YES
18	PLK1S1	PLK1S1	PLK1S1	3171	0.066	0.52	YES
19	CCNB1	CCNB1	CCNB1	3391	0.061	0.53	YES
20	NUDC	NUDC	NUDC	3407	0.061	0.55	YES
21	CDC25B	CDC25B	CDC25B	4074	0.049	0.52	YES
22	PRC1	PRC1	PRC1	4463	0.044	0.52	YES
23	CDC14B	CDC14B	CDC14B	4501	0.043	0.53	YES
24	FBXW11	FBXW11	FBXW11	4504	0.043	0.54	YES
25	ROCK2	ROCK2	ROCK2	4510	0.043	0.56	YES
26	PPP1CB	PPP1CB	PPP1CB	4645	0.041	0.56	YES
27	PPP2CA	PPP2CA	PPP2CA	5192	0.033	0.54	NO
28	RAB1A	RAB1A	RAB1A	5298	0.031	0.54	NO
29	RHOA	RHOA	RHOA	5920	0.022	0.52	NO
30	NINL	NINL	NINL	6113	0.02	0.51	NO
31	TPX2	TPX2	TPX2	6183	0.019	0.52	NO
32	AURKA	AURKA	AURKA	7426	0.0019	0.45	NO
33	STAG2	STAG2	STAG2	7586	-0.00047	0.44	NO
34	GOLGA2	GOLGA2	GOLGA2	7626	-0.00095	0.44	NO
35	WEE1	WEE1	WEE1	7857	-0.004	0.42	NO
36	GORASP1	GORASP1	GORASP1	8162	-0.008	0.41	NO
37	TPT1	TPT1	TPT1	8169	-0.0081	0.41	NO
38	PLK1	PLK1	PLK1	8492	-0.013	0.4	NO
39	INCENP	INCENP	INCENP	8625	-0.014	0.4	NO
40	PPP2R1A	PPP2R1A	PPP2R1A	8689	-0.015	0.4	NO
41	PAK1	PAK1	PAK1	9091	-0.021	0.38	NO
42	FZR1	FZR1	FZR1	10140	-0.037	0.34	NO
43	TUBG1	TUBG1	TUBG1	11262	-0.056	0.29	NO
44	SPC24	SPC24	SPC24	11705	-0.066	0.29	NO
45	SSPO	SSPO	SSPO	15829	-0.21	0.12	NO

Figure S51. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID P53REGULATIONPATHWAY.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: PID P53REGULATIONPATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

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

Table 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	EEF1E1	EEF1E1	EEF1E1	1352	0.12	-0.0056	YES
2	YARS2	YARS2	YARS2	1844	0.096	0.024	YES
3	DARS2	DARS2	DARS2	1858	0.096	0.08	YES
4	NARS	NARS	NARS	2037	0.091	0.12	YES
5	EPRS	EPRS	EPRS	2112	0.089	0.17	YES
6	RARS	RARS	RARS	2150	0.088	0.22	YES
7	WARS2	WARS2	WARS2	2151	0.088	0.28	YES
8	PPA2	PPA2	PPA2	2231	0.086	0.32	YES
9	HARS2	HARS2	HARS2	2696	0.075	0.34	YES
10	AIMP1	AIMP1	AIMP1	3485	0.059	0.33	YES
11	TARS	TARS	TARS	3685	0.056	0.35	YES
12	IARS2	IARS2	IARS2	3998	0.051	0.37	YES
13	LARS	LARS	LARS	4366	0.045	0.37	YES
14	AARS2	AARS2	AARS2	4477	0.043	0.39	YES
15	SARS2	SARS2	SARS2	4793	0.039	0.4	YES
16	YARS	YARS	YARS	4834	0.038	0.42	YES
17	FARSB	FARSB	FARSB	5113	0.034	0.42	YES
18	MARS2	MARS2	MARS2	5251	0.032	0.43	YES
19	RARS2	RARS2	RARS2	5290	0.032	0.45	YES
20	DARS	DARS	DARS	5509	0.028	0.46	YES
21	TARS2	TARS2	TARS2	5554	0.028	0.47	YES
22	IARS	IARS	IARS	5574	0.027	0.48	YES
23	EARS2	EARS2	EARS2	5710	0.025	0.49	YES
24	HARS	HARS	HARS	5976	0.022	0.49	YES
25	PARS2	PARS2	PARS2	5981	0.021	0.5	YES
26	QARS	QARS	QARS	6057	0.02	0.51	YES
27	PPA1	PPA1	PPA1	6063	0.02	0.52	YES
28	LARS2	LARS2	LARS2	6070	0.02	0.53	YES
29	VARS2	VARS2	VARS2	6195	0.018	0.54	YES
30	KARS	KARS	KARS	6617	0.013	0.52	NO
31	VARS	VARS	VARS	7008	0.0077	0.5	NO
32	MARS	MARS	MARS	7164	0.0058	0.5	NO
33	FARS2	FARS2	FARS2	7188	0.0054	0.5	NO
34	GARS	GARS	GARS	7440	0.0017	0.49	NO
35	WARS	WARS	WARS	7741	-0.0023	0.47	NO
36	AIMP2	AIMP2	AIMP2	8459	-0.012	0.44	NO
37	SARS	SARS	SARS	8637	-0.015	0.44	NO
38	FARSA	FARSA	FARSA	8807	-0.017	0.44	NO
39	CARS	CARS	CARS	9158	-0.022	0.43	NO
40	AARS	AARS	AARS	9286	-0.024	0.44	NO
41	NARS2	NARS2	NARS2	9755	-0.031	0.43	NO
42	CARS2	CARS2	CARS2	10770	-0.048	0.41	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: REACTOME METABOLISM OF NON CODING RNA.

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

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

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	SNRPD1	SNRPD1	SNRPD1	999	0.14	0.0021	YES
2	SNRPE	SNRPE	SNRPE	1214	0.12	0.042	YES
3	RANBP2	RANBP2	RANBP2	1252	0.12	0.092	YES
4	SEH1L	SEH1L	SEH1L	1400	0.11	0.13	YES
5	NUP155	NUP155	NUP155	1830	0.097	0.15	YES
6	NUP133	NUP133	NUP133	2110	0.089	0.17	YES
7	DDX20	DDX20	DDX20	2254	0.085	0.2	YES
8	GEMIN4	GEMIN4	GEMIN4	2300	0.084	0.23	YES
9	NCBP1	NCBP1	NCBP1	2551	0.078	0.25	YES
10	PHAX	PHAX	PHAX	2607	0.077	0.28	YES
11	NUP37	NUP37	NUP37	2823	0.072	0.3	YES
12	TGS1	TGS1	TGS1	3020	0.068	0.31	YES
13	SNRPF	SNRPF	SNRPF	3118	0.067	0.34	YES
14	NUP50	NUP50	NUP50	3190	0.065	0.36	YES
15	TPR	TPR	TPR	3220	0.065	0.38	YES
16	NUP54	NUP54	NUP54	3706	0.056	0.38	YES
17	NUP43	NUP43	NUP43	3744	0.055	0.4	YES
18	GEMIN5	GEMIN5	GEMIN5	3780	0.054	0.42	YES
19	NUP88	NUP88	NUP88	3961	0.051	0.44	YES
20	PRMT5	PRMT5	PRMT5	3982	0.051	0.46	YES
21	NUP153	NUP153	NUP153	4052	0.05	0.47	YES
22	NUP107	NUP107	NUP107	4171	0.048	0.48	YES
23	NUP35	NUP35	NUP35	4270	0.046	0.5	YES
24	GEMIN6	GEMIN6	GEMIN6	4439	0.044	0.51	YES
25	SNRPG	SNRPG	SNRPG	4971	0.036	0.49	NO
26	NUP188	NUP188	NUP188	5453	0.029	0.48	NO
27	NUPL1	NUPL1	NUPL1	5581	0.027	0.48	NO
28	SNRPD3	SNRPD3	SNRPD3	5890	0.023	0.48	NO
29	NUP205	NUP205	NUP205	5907	0.022	0.48	NO
30	SNRPB	SNRPB	SNRPB	6285	0.017	0.47	NO
31	GEMIN7	GEMIN7	GEMIN7	6451	0.015	0.47	NO
32	NUP62	NUP62	NUP62	6525	0.014	0.47	NO
33	AAAS	AAAS	AAAS	6549	0.014	0.48	NO
34	NUP214	NUP214	NUP214	6993	0.008	0.45	NO
35	NUP93	NUP93	NUP93	7028	0.0074	0.46	NO
36	SNRPD2	SNRPD2	SNRPD2	7087	0.0068	0.46	NO
37	WDR77	WDR77	WDR77	7323	0.0034	0.44	NO
38	NCBP2	NCBP2	NCBP2	7580	-0.00036	0.43	NO
39	SNUPN	SNUPN	SNUPN	7802	-0.0031	0.42	NO
40	NUPL2	NUPL2	NUPL2	7994	-0.0056	0.41	NO
41	NUP210	NUP210	NUP210	8122	-0.0074	0.41	NO
42	SMN2	SMN2	SMN2	8175	-0.0082	0.41	NO
43	CLNS1A	CLNS1A	CLNS1A	9040	-0.02	0.37	NO
44	NUP85	NUP85	NUP85	9244	-0.023	0.36	NO
45	RAE1	RAE1	RAE1	10340	-0.04	0.32	NO
46	POM121	POM121	POM121	10664	-0.046	0.32	NO
47	SMN1	SMN1	SMN1	15835	-0.21	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: REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM

Table 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	RANBP2	RANBP2	RANBP2	1252	0.12	0.01	YES
2	SEH1L	SEH1L	SEH1L	1400	0.11	0.076	YES
3	NUP155	NUP155	NUP155	1830	0.097	0.12	YES
4	CPSF2	CPSF2	CPSF2	1854	0.096	0.18	YES
5	NUP133	NUP133	NUP133	2110	0.089	0.22	YES
6	NCBP1	NCBP1	NCBP1	2551	0.078	0.25	YES
7	NUP37	NUP37	NUP37	2823	0.072	0.28	YES
8	NUP50	NUP50	NUP50	3190	0.065	0.3	YES
9	TPR	TPR	TPR	3220	0.065	0.34	YES
10	NUP54	NUP54	NUP54	3706	0.056	0.35	YES
11	NUP43	NUP43	NUP43	3744	0.055	0.38	YES
12	NUP88	NUP88	NUP88	3961	0.051	0.4	YES
13	NUP153	NUP153	NUP153	4052	0.05	0.43	YES
14	NUP107	NUP107	NUP107	4171	0.048	0.46	YES
15	EIF4E	EIF4E	EIF4E	4224	0.047	0.48	YES
16	NUP35	NUP35	NUP35	4270	0.046	0.51	YES
17	CPSF3	CPSF3	CPSF3	4281	0.046	0.54	YES
18	NUP188	NUP188	NUP188	5453	0.029	0.5	NO
19	NUPL1	NUPL1	NUPL1	5581	0.027	0.51	NO
20	NUP205	NUP205	NUP205	5907	0.022	0.5	NO
21	NUP62	NUP62	NUP62	6525	0.014	0.48	NO
22	AAAS	AAAS	AAAS	6549	0.014	0.48	NO
23	NUP214	NUP214	NUP214	6993	0.008	0.47	NO
24	NUP93	NUP93	NUP93	7028	0.0074	0.47	NO
25	NCBP2	NCBP2	NCBP2	7580	-0.00036	0.44	NO
26	NUPL2	NUPL2	NUPL2	7994	-0.0056	0.42	NO
27	NUP210	NUP210	NUP210	8122	-0.0074	0.42	NO
28	THOC4	THOC4	THOC4	8210	-0.0088	0.42	NO
29	NUP85	NUP85	NUP85	9244	-0.023	0.38	NO
30	NXF1	NXF1	NXF1	9751	-0.031	0.37	NO
31	RAE1	RAE1	RAE1	10340	-0.04	0.36	NO
32	POM121	POM121	POM121	10664	-0.046	0.37	NO
33	CPSF1	CPSF1	CPSF1	11378	-0.059	0.37	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: REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM.

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

genes ES table in pathway: REACTOME CELL CYCLE MITOTIC

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	CEP70	CEP70	CEP70	363	0.22	0.045	YES
2	CEP76	CEP76	CEP76	595	0.18	0.085	YES
3	CEP290	CEP290	CEP290	636	0.17	0.13	YES
4	PCM1	PCM1	PCM1	710	0.16	0.18	YES
5	CEP192	CEP192	CEP192	833	0.15	0.21	YES
6	CEP135	CEP135	CEP135	933	0.14	0.25	YES
7	PLK4	PLK4	PLK4	976	0.14	0.29	YES
8	NEK2	NEK2	NEK2	1106	0.13	0.32	YES
9	NEDD1	NEDD1	NEDD1	1541	0.11	0.33	YES
10	FGFR1OP	FGFR1OP	FGFR1OP	1590	0.11	0.36	YES
11	CDK1	CDK1	CDK1	1683	0.1	0.38	YES
12	CDK5RAP2	CDK5RAP2	CDK5RAP2	1859	0.096	0.4	YES
13	HSP90AA1	HSP90AA1	HSP90AA1	1970	0.093	0.42	YES
14	ALMS1	ALMS1	ALMS1	2099	0.089	0.44	YES
15	CEP72	CEP72	CEP72	2979	0.069	0.41	YES
16	YWHAE	YWHAE	YWHAE	3226	0.064	0.42	YES
17	SDCCAG8	SDCCAG8	SDCCAG8	3487	0.059	0.42	YES
18	PCNT	PCNT	PCNT	3729	0.055	0.43	YES
19	AKAP9	AKAP9	AKAP9	3830	0.053	0.44	YES
20	HAUS2	HAUS2	HAUS2	4121	0.049	0.43	YES
21	CEP63	CEP63	CEP63	4259	0.047	0.44	YES
22	PAFAH1B1	PAFAH1B1	PAFAH1B1	4294	0.046	0.45	YES
23	CKAP5	CKAP5	CKAP5	4546	0.042	0.45	YES
24	CENPJ	CENPJ	CENPJ	4837	0.038	0.45	YES
25	DYNC1H1	DYNC1H1	DYNC1H1	4910	0.037	0.45	YES
26	DYNC1I2	DYNC1I2	DYNC1I2	5065	0.035	0.46	YES
27	TUBB	TUBB	TUBB	5979	0.021	0.41	NO
28	NINL	NINL	NINL	6113	0.02	0.41	NO
29	DCTN2	DCTN2	DCTN2	6129	0.02	0.41	NO
30	CEP57	CEP57	CEP57	6405	0.016	0.4	NO
31	DYNLL1	DYNLL1	DYNLL1	7379	0.0026	0.35	NO
32	CETN2	CETN2	CETN2	7424	0.002	0.35	NO
33	OFD1	OFD1	OFD1	8018	-0.006	0.32	NO
34	YWHAG	YWHAG	YWHAG	8182	-0.0083	0.31	NO
35	ACTR1A	ACTR1A	ACTR1A	8399	-0.011	0.3	NO
36	DCTN1	DCTN1	DCTN1	8426	-0.012	0.3	NO
37	PLK1	PLK1	PLK1	8492	-0.013	0.3	NO
38	CLASP1	CLASP1	CLASP1	8610	-0.014	0.3	NO
39	CSNK1E	CSNK1E	CSNK1E	8640	-0.015	0.3	NO
40	PPP2R1A	PPP2R1A	PPP2R1A	8689	-0.015	0.31	NO
41	AZI1	AZI1	AZI1	9155	-0.022	0.29	NO
42	CSNK1D	CSNK1D	CSNK1D	9303	-0.024	0.29	NO
43	MAPRE1	MAPRE1	MAPRE1	9791	-0.032	0.27	NO
44	TUBA4A	TUBA4A	TUBA4A	9929	-0.033	0.27	NO
45	CEP164	CEP164	CEP164	10122	-0.036	0.27	NO
46	PRKACA	PRKACA	PRKACA	10191	-0.038	0.28	NO
47	TUBG1	TUBG1	TUBG1	11262	-0.056	0.24	NO
48	SSNA1	SSNA1	SSNA1	11456	-0.06	0.24	NO
49	CEP250	CEP250	CEP250	11915	-0.07	0.24	NO
50	PRKAR2B	PRKAR2B	PRKAR2B	12099	-0.074	0.25	NO
51	DCTN3	DCTN3	DCTN3	12965	-0.096	0.23	NO
52	TUBA1A	TUBA1A	TUBA1A	15160	-0.18	0.16	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: REACTOME CELL CYCLE MITOTIC.

Figure S60. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME CELL CYCLE MITOTIC, 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 LYSINE DEGRADATION	44	genes.ES.table	0.54	2.1	0.002	0.057	0.061	0.25	0.15	0.21	0	0.021
KEGG SELENOAMINO ACID METABOLISM	26	genes.ES.table	0.41	1.4	0.14	1	1	0.27	0.16	0.23	1	0.53
KEGG RNA DEGRADATION	57	genes.ES.table	0.41	1.6	0.067	0.8	0.9	0.47	0.26	0.35	0.38	0.23
KEGG SPLICEOSOME	114	genes.ES.table	0.35	1.6	0.11	0.83	0.96	0.37	0.24	0.28	0.46	0.26
KEGG PEROXISOME	76	genes.ES.table	0.45	1.6	0.043	0.76	0.92	0.25	0.14	0.22	0.37	0.22
PID ATM PATHWAY	34	genes.ES.table	0.53	1.6	0.065	0.82	0.94	0.53	0.26	0.4	0.43	0.24
REACTOME METABOLISM OF NON CODING RNA	47	genes.ES.table	0.39	1.3	0.2	1	1	0.57	0.31	0.4	1	0.52
REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA	126	genes.ES.table	0.42	1.7	0.055	1	0.8	0.55	0.36	0.35	0.38	0.27
REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM	44	genes.ES.table	0.47	1.6	0.066	0.83	0.95	0.52	0.35	0.34	0.46	0.25
REACTOME RNA POL II TRANSCRIPTION	93	genes.ES.table	0.3	1.4	0.17	1	1	0.34	0.24	0.26	1	0.54

genes ES table in pathway: KEGG LYSINE DEGRADATION

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	PIPOX	PIPOX	PIPOX	5	0.59	0.2	YES
2	AASS	AASS	AASS	285	0.25	0.27	YES
3	BBOX1	BBOX1	BBOX1	677	0.18	0.31	YES
4	OGDHL	OGDHL	OGDHL	724	0.17	0.36	YES
5	PLOD2	PLOD2	PLOD2	904	0.15	0.4	YES
6	AASDHPPT	AASDHPPT	AASDHPPT	988	0.15	0.45	YES
7	SETDB2	SETDB2	SETDB2	999	0.15	0.5	YES
8	ACAT1	ACAT1	ACAT1	1589	0.12	0.51	YES
9	WHSC1L1	WHSC1L1	WHSC1L1	2025	0.099	0.52	YES
10	SUV420H1	SUV420H1	SUV420H1	2467	0.087	0.52	YES
11	ALDH2	ALDH2	ALDH2	2634	0.082	0.54	YES
12	SETD2	SETD2	SETD2	3400	0.064	0.52	NO
13	ALDH7A1	ALDH7A1	ALDH7A1	3640	0.06	0.53	NO
14	ALDH3A2	ALDH3A2	ALDH3A2	4420	0.046	0.5	NO
15	EHHADH	EHHADH	EHHADH	5025	0.037	0.48	NO
16	ACAT2	ACAT2	ACAT2	5256	0.034	0.48	NO
17	SUV39H2	SUV39H2	SUV39H2	5346	0.032	0.48	NO
18	PLOD3	PLOD3	PLOD3	5427	0.031	0.49	NO
19	SETMAR	SETMAR	SETMAR	5656	0.028	0.48	NO
20	ALDH9A1	ALDH9A1	ALDH9A1	6094	0.021	0.47	NO
21	GCDH	GCDH	GCDH	6131	0.02	0.47	NO
22	ASH1L	ASH1L	ASH1L	6215	0.019	0.48	NO
23	AASDH	AASDH	AASDH	6489	0.015	0.46	NO
24	ALDH1B1	ALDH1B1	ALDH1B1	6761	0.011	0.45	NO
25	TMLHE	TMLHE	TMLHE	6888	0.0096	0.45	NO
26	EHMT2	EHMT2	EHMT2	7540	0.0012	0.41	NO
27	SUV39H1	SUV39H1	SUV39H1	7641	-0.00024	0.41	NO
28	SETD1A	SETD1A	SETD1A	7811	-0.0026	0.4	NO
29	HADH	HADH	HADH	7813	-0.0027	0.4	NO
30	NSD1	NSD1	NSD1	7904	-0.004	0.4	NO
31	HADHA	HADHA	HADHA	7973	-0.0049	0.4	NO
32	SETD1B	SETD1B	SETD1B	7988	-0.0051	0.4	NO
33	SETD8	SETD8	SETD8	8352	-0.01	0.38	NO
34	SETD7	SETD7	SETD7	8520	-0.012	0.38	NO
35	SETDB1	SETDB1	SETDB1	8789	-0.016	0.36	NO
36	ECHS1	ECHS1	ECHS1	9223	-0.022	0.35	NO
37	WHSC1	WHSC1	WHSC1	9251	-0.023	0.36	NO
38	OGDH	OGDH	OGDH	9280	-0.023	0.36	NO
39	PLOD1	PLOD1	PLOD1	9325	-0.024	0.37	NO
40	AADAT	AADAT	AADAT	9914	-0.032	0.35	NO
41	SUV420H2	SUV420H2	SUV420H2	10024	-0.034	0.35	NO
42	DOT1L	DOT1L	DOT1L	12674	-0.089	0.23	NO
43	DLST	DLST	DLST	12846	-0.094	0.26	NO
44	EHMT1	EHMT1	EHMT1	13045	-0.1	0.28	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 LYSINE DEGRADATION.

Figure S62. 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 SELENOAMINO ACID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	UPF3B	UPF3B	UPF3B	1050	0.14	0.082	YES
2	NCBP2	NCBP2	NCBP2	1281	0.13	0.2	YES
3	CDC40	CDC40	CDC40	1745	0.11	0.28	YES
4	CSTF3	CSTF3	CSTF3	2783	0.078	0.29	YES
5	PCF11	PCF11	PCF11	3244	0.068	0.33	YES
6	NUDT21	NUDT21	NUDT21	3344	0.066	0.39	YES
7	PAPOLA	PAPOLA	PAPOLA	4216	0.05	0.39	YES
8	MAGOH	MAGOH	MAGOH	4241	0.049	0.44	YES
9	CSTF2	CSTF2	CSTF2	4257	0.049	0.48	YES
10	CPSF3	CPSF3	CPSF3	4402	0.046	0.52	YES
11	CLP1	CLP1	CLP1	4895	0.039	0.53	YES
12	CPSF7	CPSF7	CPSF7	5267	0.033	0.55	YES
13	THOC4	THOC4	THOC4	5941	0.023	0.53	YES
14	CSTF1	CSTF1	CSTF1	6018	0.022	0.55	YES
15	NCBP1	NCBP1	NCBP1	6764	0.011	0.52	NO
16	PABPN1	PABPN1	PABPN1	6941	0.0089	0.52	NO
17	U2AF1	U2AF1	U2AF1	7019	0.0077	0.52	NO
18	CPSF2	CPSF2	CPSF2	7365	0.0037	0.5	NO
19	RBM8A	RBM8A	RBM8A	7585	0.00052	0.49	NO
20	U2AF2	U2AF2	U2AF2	7688	-0.00094	0.49	NO
21	SRRM1	SRRM1	SRRM1	8281	-0.009	0.46	NO
22	DHX38	DHX38	DHX38	8461	-0.012	0.46	NO
23	RNPS1	RNPS1	RNPS1	8719	-0.015	0.46	NO
24	CPSF1	CPSF1	CPSF1	9025	-0.02	0.47	NO
25	NFX1	NFX1	NFX1	10143	-0.036	0.44	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 SELENOAMINO ACID METABOLISM.

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

genes ES table in pathway: KEGG RNA DEGRADATION

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	GZMB	GZMB	GZMB	296	0.25	0.1	YES
2	PMAIP1	PMAIP1	PMAIP1	653	0.18	0.17	YES
3	TP53	TP53	TP53	1197	0.14	0.2	YES
4	YWHAB	YWHAB	YWHAB	1827	0.11	0.22	YES
5	XIAP	XIAP	XIAP	2239	0.092	0.24	YES
6	BBC3	BBC3	BBC3	2257	0.092	0.28	YES
7	CYCS	CYCS	CYCS	2261	0.092	0.33	YES
8	CASP8	CASP8	CASP8	2411	0.088	0.36	YES
9	BCL2L1	BCL2L1	BCL2L1	2619	0.082	0.39	YES
10	APAF1	APAF1	APAF1	3290	0.067	0.39	YES
11	DYNLL2	DYNLL2	DYNLL2	3747	0.058	0.39	YES
12	CASP3	CASP3	CASP3	3821	0.056	0.41	YES
13	E2F1	E2F1	E2F1	4197	0.05	0.42	YES
14	DIABLO	DIABLO	DIABLO	4337	0.048	0.43	YES
15	BMF	BMF	BMF	5033	0.037	0.41	NO
16	PPP3R1	PPP3R1	PPP3R1	5495	0.03	0.4	NO
17	NMT1	NMT1	NMT1	5606	0.028	0.41	NO
18	TFDP1	TFDP1	TFDP1	6683	0.012	0.35	NO
19	BID	BID	BID	8171	-0.0072	0.27	NO
20	DYNLL1	DYNLL1	DYNLL1	8467	-0.012	0.26	NO
21	BAX	BAX	BAX	8501	-0.012	0.27	NO
22	MAPK8	MAPK8	MAPK8	10113	-0.036	0.2	NO
23	BCL2L11	BCL2L11	BCL2L11	10875	-0.049	0.18	NO
24	BAD	BAD	BAD	11088	-0.053	0.19	NO
25	BCL2	BCL2	BCL2	11089	-0.053	0.22	NO
26	CASP9	CASP9	CASP9	11272	-0.057	0.23	NO
27	CASP7	CASP7	CASP7	12117	-0.075	0.22	NO
28	AKT1	AKT1	AKT1	12781	-0.092	0.23	NO
29	BAK1	BAK1	BAK1	13943	-0.13	0.23	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 RNA DEGRADATION.

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

genes ES table in pathway: KEGG SPLICEOSOME

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	UPF3B	UPF3B	UPF3B	1050	0.14	-0.03	YES
2	GTF2F2	GTF2F2	GTF2F2	1210	0.13	-0.012	YES
3	PRPF6	PRPF6	PRPF6	1217	0.13	0.013	YES
4	NCBP2	NCBP2	NCBP2	1281	0.13	0.035	YES
5	POLR2K	POLR2K	POLR2K	1377	0.12	0.055	YES
6	RAE1	RAE1	RAE1	1544	0.12	0.069	YES
7	NUPL1	NUPL1	NUPL1	1730	0.11	0.08	YES
8	CDC40	CDC40	CDC40	1745	0.11	0.1	YES
9	NUPL2	NUPL2	NUPL2	2011	0.099	0.11	YES
10	SNRPE	SNRPE	SNRPE	2091	0.097	0.12	YES
11	NUP107	NUP107	NUP107	2138	0.095	0.14	YES
12	SNRPA1	SNRPA1	SNRPA1	2219	0.093	0.15	YES
13	SNRPF	SNRPF	SNRPF	2429	0.088	0.16	YES
14	SF3B14	SF3B14	SF3B14	2434	0.088	0.17	YES
15	NUP35	NUP35	NUP35	2533	0.085	0.18	YES
16	SMC1A	SMC1A	SMC1A	2575	0.084	0.2	YES
17	CCAR1	CCAR1	CCAR1	2577	0.084	0.22	YES
18	SNRPG	SNRPG	SNRPG	2602	0.083	0.23	YES
19	CSTF3	CSTF3	CSTF3	2783	0.078	0.24	YES
20	HNRNPH2	HNRNPH2	HNRNPH2	2862	0.076	0.25	YES
21	PCF11	PCF11	PCF11	3244	0.068	0.24	YES
22	NUDT21	NUDT21	NUDT21	3344	0.066	0.25	YES
23	HNRNPD	HNRNPD	HNRNPD	3419	0.064	0.25	YES
24	SNRPB2	SNRPB2	SNRPB2	3427	0.064	0.27	YES
25	SNRPD3	SNRPD3	SNRPD3	3559	0.061	0.27	YES
26	SF3B2	SF3B2	SF3B2	3579	0.061	0.28	YES
27	POLR2J	POLR2J	POLR2J	3613	0.06	0.29	YES
28	NUP88	NUP88	NUP88	3865	0.056	0.29	YES
29	HNRNPR	HNRNPR	HNRNPR	3907	0.055	0.3	YES
30	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	3930	0.055	0.31	YES
31	NUP54	NUP54	NUP54	4014	0.053	0.31	YES
32	POLR2F	POLR2F	POLR2F	4015	0.053	0.32	YES
33	PAPOLA	PAPOLA	PAPOLA	4216	0.05	0.32	YES
34	MAGOH	MAGOH	MAGOH	4241	0.049	0.33	YES
35	CSTF2	CSTF2	CSTF2	4257	0.049	0.34	YES
36	TPR	TPR	TPR	4284	0.048	0.35	YES
37	HNRNPK	HNRNPK	HNRNPK	4304	0.048	0.36	YES
38	HNRNPA3	HNRNPA3	HNRNPA3	4339	0.048	0.36	YES
39	NUP37	NUP37	NUP37	4360	0.047	0.37	YES
40	CPSF3	CPSF3	CPSF3	4402	0.046	0.38	YES
41	HNRNPU	HNRNPU	HNRNPU	4861	0.039	0.36	YES
42	CLP1	CLP1	CLP1	4895	0.039	0.37	YES
43	SNRNP200	SNRNP200	SNRNP200	4983	0.037	0.37	YES
44	FUS	FUS	FUS	5068	0.036	0.37	YES
45	NHP2L1	NHP2L1	NHP2L1	5098	0.036	0.38	YES
46	POLR2C	POLR2C	POLR2C	5151	0.035	0.38	YES
47	RANBP2	RANBP2	RANBP2	5236	0.034	0.38	YES
48	CPSF7	CPSF7	CPSF7	5267	0.033	0.39	YES
49	SNRPD2	SNRPD2	SNRPD2	5364	0.032	0.39	YES
50	NUP153	NUP153	NUP153	5442	0.031	0.39	YES
51	NUP205	NUP205	NUP205	5528	0.03	0.39	YES
52	RBMX	RBMX	RBMX	5533	0.03	0.4	YES
53	NUP50	NUP50	NUP50	5579	0.029	0.4	YES
54	CD2BP2	CD2BP2	CD2BP2	5619	0.028	0.4	YES
55	NUP43	NUP43	NUP43	5684	0.027	0.41	YES
56	SLBP	SLBP	SLBP	5808	0.025	0.4	YES
57	DNAJC8	DNAJC8	DNAJC8	5886	0.024	0.4	YES
58	THOC4	THOC4	THOC4	5941	0.023	0.41	YES
59	GTF2F1	GTF2F1	GTF2F1	6006	0.022	0.41	YES
60	CSTF1	CSTF1	CSTF1	6018	0.022	0.41	YES
61	SF3A2	SF3A2	SF3A2	6076	0.021	0.41	YES
62	DDX23	DDX23	DDX23	6099	0.02	0.41	YES
63	SF3B3	SF3B3	SF3B3	6233	0.019	0.41	YES
64	NUP133	NUP133	NUP133	6254	0.018	0.41	YES
65	NUP210	NUP210	NUP210	6278	0.018	0.42	YES
66	HNRNPF	HNRNPF	HNRNPF	6408	0.016	0.41	YES
67	HNRNPUL1	HNRNPUL1	HNRNPUL1	6419	0.016	0.41	YES
68	POLR2D	POLR2D	POLR2D	6458	0.016	0.42	YES
69	HNRNPA0	HNRNPA0	HNRNPA0	6493	0.015	0.42	YES
70	POLR2B	POLR2B	POLR2B	6662	0.013	0.41	NO
71	POM121	POM121	POM121	6723	0.012	0.41	NO
72	HNRNPL	HNRNPL	HNRNPL	6756	0.012	0.41	NO
73	SF3A3	SF3A3	SF3A3	6763	0.011	0.41	NO
74	NCBP1	NCBP1	NCBP1	6764	0.011	0.41	NO
75	SNRPD1	SNRPD1	SNRPD1	6768	0.011	0.42	NO
76	DHX9	DHX9	DHX9	6881	0.0097	0.41	NO
77	PABPN1	PABPN1	PABPN1	6941	0.0089	0.41	NO
78	U2AF1	U2AF1	U2AF1	7019	0.0077	0.41	NO
79	AAAS	AAAS	AAAS	7029	0.0076	0.41	NO
80	SEH1L	SEH1L	SEH1L	7047	0.0074	0.41	NO
81	SF3B1	SF3B1	SF3B1	7140	0.0063	0.4	NO
82	PCBP1	PCBP1	PCBP1	7200	0.0056	0.4	NO
83	PRPF8	PRPF8	PRPF8	7316	0.0042	0.4	NO
84	CPSF2	CPSF2	CPSF2	7365	0.0037	0.39	NO
85	EFTUD2	EFTUD2	EFTUD2	7428	0.0027	0.39	NO
86	RBM8A	RBM8A	RBM8A	7585	0.00052	0.38	NO
87	HNRNPH1	HNRNPH1	HNRNPH1	7608	0.00022	0.38	NO
88	NUP93	NUP93	NUP93	7680	-0.00082	0.38	NO
89	POLR2E	POLR2E	POLR2E	7683	-0.00086	0.38	NO
90	U2AF2	U2AF2	U2AF2	7688	-0.00094	0.38	NO
91	NXF1	NXF1	NXF1	7692	-0.001	0.38	NO
92	SNRPA	SNRPA	SNRPA	7713	-0.0012	0.38	NO
93	HNRNPA1	HNRNPA1	HNRNPA1	7743	-0.0017	0.38	NO
94	EIF4E	EIF4E	EIF4E	7803	-0.0026	0.37	NO
95	POLR2H	POLR2H	POLR2H	7816	-0.0027	0.37	NO
96	HNRNPC	HNRNPC	HNRNPC	7870	-0.0035	0.37	NO
97	PTBP1	PTBP1	PTBP1	8017	-0.0054	0.36	NO
98	NUP85	NUP85	NUP85	8045	-0.0058	0.36	NO
99	SF3A1	SF3A1	SF3A1	8129	-0.0068	0.36	NO
100	PHF5A	PHF5A	PHF5A	8220	-0.0081	0.36	NO
101	HNRNPM	HNRNPM	HNRNPM	8245	-0.0084	0.36	NO
102	SRRM1	SRRM1	SRRM1	8281	-0.009	0.36	NO
103	PCBP2	PCBP2	PCBP2	8445	-0.011	0.35	NO
104	DHX38	DHX38	DHX38	8461	-0.012	0.35	NO
105	POLR2G	POLR2G	POLR2G	8537	-0.013	0.35	NO
106	RNPS1	RNPS1	RNPS1	8719	-0.015	0.34	NO
107	NUP214	NUP214	NUP214	8756	-0.016	0.34	NO
108	YBX1	YBX1	YBX1	8986	-0.019	0.33	NO
109	CPSF1	CPSF1	CPSF1	9025	-0.02	0.34	NO
110	SNRNP70	SNRNP70	SNRNP70	9262	-0.023	0.33	NO
111	SF3B4	SF3B4	SF3B4	9390	-0.025	0.32	NO
112	PRPF4	PRPF4	PRPF4	9877	-0.032	0.3	NO
113	NUP155	NUP155	NUP155	9973	-0.034	0.31	NO
114	NFX1	NFX1	NFX1	10143	-0.036	0.3	NO
115	RBM5	RBM5	RBM5	10448	-0.042	0.3	NO
116	LSM2	LSM2	LSM2	10654	-0.045	0.29	NO
117	NUP62	NUP62	NUP62	10712	-0.046	0.3	NO
118	POLR2L	POLR2L	POLR2L	10872	-0.049	0.3	NO
119	POLR2I	POLR2I	POLR2I	11184	-0.055	0.29	NO
120	POLR2A	POLR2A	POLR2A	11242	-0.056	0.3	NO
121	SF3B5	SF3B5	SF3B5	11336	-0.058	0.31	NO
122	METTL3	METTL3	METTL3	11439	-0.06	0.31	NO
123	TXNL4A	TXNL4A	TXNL4A	11734	-0.066	0.31	NO
124	SNRNP40	SNRNP40	SNRNP40	11948	-0.071	0.31	NO
125	SNRPB	SNRPB	SNRPB	12187	-0.076	0.31	NO
126	NUP188	NUP188	NUP188	12326	-0.079	0.32	NO

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

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

genes ES table in pathway: KEGG PEROXISOME

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	UPF3B	UPF3B	UPF3B	1050	0.14	0.031	YES
2	NCBP2	NCBP2	NCBP2	1281	0.13	0.098	YES
3	CDC40	CDC40	CDC40	1745	0.11	0.14	YES
4	SNRPE	SNRPE	SNRPE	2091	0.097	0.18	YES
5	SNRPF	SNRPF	SNRPF	2429	0.088	0.22	YES
6	SNRPG	SNRPG	SNRPG	2602	0.083	0.26	YES
7	CSTF3	CSTF3	CSTF3	2783	0.078	0.3	YES
8	PCF11	PCF11	PCF11	3244	0.068	0.31	YES
9	NUDT21	NUDT21	NUDT21	3344	0.066	0.35	YES
10	LSM11	LSM11	LSM11	3404	0.064	0.38	YES
11	SNRPD3	SNRPD3	SNRPD3	3559	0.061	0.41	YES
12	PAPOLA	PAPOLA	PAPOLA	4216	0.05	0.41	YES
13	MAGOH	MAGOH	MAGOH	4241	0.049	0.44	YES
14	CSTF2	CSTF2	CSTF2	4257	0.049	0.46	YES
15	CPSF3	CPSF3	CPSF3	4402	0.046	0.49	YES
16	CLP1	CLP1	CLP1	4895	0.039	0.48	NO
17	CPSF7	CPSF7	CPSF7	5267	0.033	0.48	NO
18	SLBP	SLBP	SLBP	5808	0.025	0.47	NO
19	THOC4	THOC4	THOC4	5941	0.023	0.48	NO
20	CSTF1	CSTF1	CSTF1	6018	0.022	0.48	NO
21	ZNF473	ZNF473	ZNF473	6721	0.012	0.45	NO
22	NCBP1	NCBP1	NCBP1	6764	0.011	0.46	NO
23	PABPN1	PABPN1	PABPN1	6941	0.0089	0.45	NO
24	U2AF1	U2AF1	U2AF1	7019	0.0077	0.45	NO
25	CPSF2	CPSF2	CPSF2	7365	0.0037	0.44	NO
26	RBM8A	RBM8A	RBM8A	7585	0.00052	0.42	NO
27	U2AF2	U2AF2	U2AF2	7688	-0.00094	0.42	NO
28	SRRM1	SRRM1	SRRM1	8281	-0.009	0.39	NO
29	DHX38	DHX38	DHX38	8461	-0.012	0.39	NO
30	RNPS1	RNPS1	RNPS1	8719	-0.015	0.38	NO
31	CPSF1	CPSF1	CPSF1	9025	-0.02	0.38	NO
32	NFX1	NFX1	NFX1	10143	-0.036	0.34	NO
33	SNRPB	SNRPB	SNRPB	12187	-0.076	0.27	NO
34	LSM10	LSM10	LSM10	12578	-0.086	0.3	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: KEGG PEROXISOME.

Figure S70. 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: PID ATM 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	CHMP4B	CHMP4B	CHMP4B	1579	0.12	0.027	YES
2	RPS27A	RPS27A	RPS27A	1662	0.11	0.13	YES
3	CHMP4C	CHMP4C	CHMP4C	2120	0.096	0.2	YES
4	VPS36	VPS36	VPS36	2661	0.082	0.25	YES
5	VTA1	VTA1	VTA1	3637	0.06	0.26	YES
6	STAM2	STAM2	STAM2	3859	0.056	0.3	YES
7	CHMP2B	CHMP2B	CHMP2B	4326	0.048	0.32	YES
8	TSG101	TSG101	TSG101	4589	0.044	0.35	YES
9	VPS37D	VPS37D	VPS37D	4606	0.043	0.39	YES
10	SNF8	SNF8	SNF8	5138	0.035	0.4	YES
11	VPS37A	VPS37A	VPS37A	5237	0.034	0.42	YES
12	CHMP2A	CHMP2A	CHMP2A	5423	0.031	0.44	YES
13	CHMP7	CHMP7	CHMP7	6356	0.017	0.41	NO
14	VPS25	VPS25	VPS25	6973	0.0084	0.38	NO
15	VPS4A	VPS4A	VPS4A	6986	0.0082	0.39	NO
16	VPS4B	VPS4B	VPS4B	7669	-0.00058	0.35	NO
17	VPS37C	VPS37C	VPS37C	7845	-0.0032	0.35	NO
18	STAM	STAM	STAM	7855	-0.0034	0.35	NO
19	HGS	HGS	HGS	8031	-0.0056	0.35	NO
20	CHMP5	CHMP5	CHMP5	8758	-0.016	0.32	NO
21	CHMP4A	CHMP4A	CHMP4A	8891	-0.018	0.33	NO
22	CHMP6	CHMP6	CHMP6	9119	-0.021	0.34	NO
23	UBA52	UBA52	UBA52	9232	-0.022	0.36	NO
24	VPS28	VPS28	VPS28	9731	-0.03	0.36	NO
25	VPS37B	VPS37B	VPS37B	13294	-0.11	0.26	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 ATM PATHWAY.

Figure S72. Get High-res Image For the top 5 core enriched genes in the pathway: PID ATM 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 METABOLISM OF NON CODING RNA

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	UPF3B	UPF3B	UPF3B	1050	0.14	-0.021	YES
2	GTF2F2	GTF2F2	GTF2F2	1210	0.13	0.0045	YES
3	PRPF6	PRPF6	PRPF6	1217	0.13	0.038	YES
4	NCBP2	NCBP2	NCBP2	1281	0.13	0.068	YES
5	POLR2K	POLR2K	POLR2K	1377	0.12	0.095	YES
6	CDC40	CDC40	CDC40	1745	0.11	0.1	YES
7	SNRPE	SNRPE	SNRPE	2091	0.097	0.11	YES
8	SNRPA1	SNRPA1	SNRPA1	2219	0.093	0.13	YES
9	SNRPF	SNRPF	SNRPF	2429	0.088	0.14	YES
10	SF3B14	SF3B14	SF3B14	2434	0.088	0.16	YES
11	SMC1A	SMC1A	SMC1A	2575	0.084	0.17	YES
12	CCAR1	CCAR1	CCAR1	2577	0.084	0.19	YES
13	SNRPG	SNRPG	SNRPG	2602	0.083	0.21	YES
14	CSTF3	CSTF3	CSTF3	2783	0.078	0.22	YES
15	HNRNPH2	HNRNPH2	HNRNPH2	2862	0.076	0.24	YES
16	PCF11	PCF11	PCF11	3244	0.068	0.24	YES
17	NUDT21	NUDT21	NUDT21	3344	0.066	0.25	YES
18	HNRNPD	HNRNPD	HNRNPD	3419	0.064	0.26	YES
19	SNRPB2	SNRPB2	SNRPB2	3427	0.064	0.28	YES
20	SNRPD3	SNRPD3	SNRPD3	3559	0.061	0.28	YES
21	SF3B2	SF3B2	SF3B2	3579	0.061	0.3	YES
22	POLR2J	POLR2J	POLR2J	3613	0.06	0.31	YES
23	HNRNPR	HNRNPR	HNRNPR	3907	0.055	0.31	YES
24	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	3930	0.055	0.32	YES
25	POLR2F	POLR2F	POLR2F	4015	0.053	0.33	YES
26	PAPOLA	PAPOLA	PAPOLA	4216	0.05	0.34	YES
27	MAGOH	MAGOH	MAGOH	4241	0.049	0.35	YES
28	CSTF2	CSTF2	CSTF2	4257	0.049	0.36	YES
29	HNRNPK	HNRNPK	HNRNPK	4304	0.048	0.37	YES
30	HNRNPA3	HNRNPA3	HNRNPA3	4339	0.048	0.38	YES
31	CPSF3	CPSF3	CPSF3	4402	0.046	0.39	YES
32	HNRNPU	HNRNPU	HNRNPU	4861	0.039	0.37	YES
33	CLP1	CLP1	CLP1	4895	0.039	0.38	YES
34	SNRNP200	SNRNP200	SNRNP200	4983	0.037	0.38	YES
35	FUS	FUS	FUS	5068	0.036	0.39	YES
36	NHP2L1	NHP2L1	NHP2L1	5098	0.036	0.4	YES
37	POLR2C	POLR2C	POLR2C	5151	0.035	0.4	YES
38	CPSF7	CPSF7	CPSF7	5267	0.033	0.4	YES
39	SNRPD2	SNRPD2	SNRPD2	5364	0.032	0.41	YES
40	RBMX	RBMX	RBMX	5533	0.03	0.41	YES
41	CD2BP2	CD2BP2	CD2BP2	5619	0.028	0.41	YES
42	DNAJC8	DNAJC8	DNAJC8	5886	0.024	0.4	YES
43	THOC4	THOC4	THOC4	5941	0.023	0.4	YES
44	GTF2F1	GTF2F1	GTF2F1	6006	0.022	0.4	YES
45	CSTF1	CSTF1	CSTF1	6018	0.022	0.41	YES
46	SF3A2	SF3A2	SF3A2	6076	0.021	0.41	YES
47	DDX23	DDX23	DDX23	6099	0.02	0.42	YES
48	SF3B3	SF3B3	SF3B3	6233	0.019	0.41	NO
49	HNRNPF	HNRNPF	HNRNPF	6408	0.016	0.41	NO
50	HNRNPUL1	HNRNPUL1	HNRNPUL1	6419	0.016	0.41	NO
51	POLR2D	POLR2D	POLR2D	6458	0.016	0.41	NO
52	HNRNPA0	HNRNPA0	HNRNPA0	6493	0.015	0.42	NO
53	POLR2B	POLR2B	POLR2B	6662	0.013	0.41	NO
54	HNRNPL	HNRNPL	HNRNPL	6756	0.012	0.41	NO
55	SF3A3	SF3A3	SF3A3	6763	0.011	0.41	NO
56	NCBP1	NCBP1	NCBP1	6764	0.011	0.41	NO
57	SNRPD1	SNRPD1	SNRPD1	6768	0.011	0.42	NO
58	DHX9	DHX9	DHX9	6881	0.0097	0.41	NO
59	PABPN1	PABPN1	PABPN1	6941	0.0089	0.41	NO
60	U2AF1	U2AF1	U2AF1	7019	0.0077	0.41	NO
61	SF3B1	SF3B1	SF3B1	7140	0.0063	0.4	NO
62	PCBP1	PCBP1	PCBP1	7200	0.0056	0.4	NO
63	PRPF8	PRPF8	PRPF8	7316	0.0042	0.4	NO
64	CPSF2	CPSF2	CPSF2	7365	0.0037	0.4	NO
65	EFTUD2	EFTUD2	EFTUD2	7428	0.0027	0.39	NO
66	RBM8A	RBM8A	RBM8A	7585	0.00052	0.38	NO
67	HNRNPH1	HNRNPH1	HNRNPH1	7608	0.00022	0.38	NO
68	POLR2E	POLR2E	POLR2E	7683	-0.00086	0.38	NO
69	U2AF2	U2AF2	U2AF2	7688	-0.00094	0.38	NO
70	SNRPA	SNRPA	SNRPA	7713	-0.0012	0.38	NO
71	HNRNPA1	HNRNPA1	HNRNPA1	7743	-0.0017	0.38	NO
72	POLR2H	POLR2H	POLR2H	7816	-0.0027	0.37	NO
73	HNRNPC	HNRNPC	HNRNPC	7870	-0.0035	0.37	NO
74	PTBP1	PTBP1	PTBP1	8017	-0.0054	0.36	NO
75	SF3A1	SF3A1	SF3A1	8129	-0.0068	0.36	NO
76	PHF5A	PHF5A	PHF5A	8220	-0.0081	0.36	NO
77	HNRNPM	HNRNPM	HNRNPM	8245	-0.0084	0.36	NO
78	SRRM1	SRRM1	SRRM1	8281	-0.009	0.36	NO
79	PCBP2	PCBP2	PCBP2	8445	-0.011	0.35	NO
80	DHX38	DHX38	DHX38	8461	-0.012	0.35	NO
81	POLR2G	POLR2G	POLR2G	8537	-0.013	0.35	NO
82	RNPS1	RNPS1	RNPS1	8719	-0.015	0.35	NO
83	YBX1	YBX1	YBX1	8986	-0.019	0.34	NO
84	CPSF1	CPSF1	CPSF1	9025	-0.02	0.34	NO
85	SNRNP70	SNRNP70	SNRNP70	9262	-0.023	0.33	NO
86	SF3B4	SF3B4	SF3B4	9390	-0.025	0.33	NO
87	PRPF4	PRPF4	PRPF4	9877	-0.032	0.31	NO
88	NFX1	NFX1	NFX1	10143	-0.036	0.31	NO
89	RBM5	RBM5	RBM5	10448	-0.042	0.3	NO
90	LSM2	LSM2	LSM2	10654	-0.045	0.3	NO
91	POLR2L	POLR2L	POLR2L	10872	-0.049	0.3	NO
92	POLR2I	POLR2I	POLR2I	11184	-0.055	0.3	NO
93	POLR2A	POLR2A	POLR2A	11242	-0.056	0.31	NO
94	SF3B5	SF3B5	SF3B5	11336	-0.058	0.32	NO
95	TXNL4A	TXNL4A	TXNL4A	11734	-0.066	0.32	NO
96	SNRNP40	SNRNP40	SNRNP40	11948	-0.071	0.32	NO
97	SNRPB	SNRPB	SNRPB	12187	-0.076	0.33	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 METABOLISM OF NON CODING RNA.

Figure S74. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME METABOLISM OF NON CODING RNA, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

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

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	C1D	C1D	C1D	484	0.21	0.036	YES
2	NAA38	NAA38	NAA38	796	0.16	0.068	YES
3	MPHOSPH6	MPHOSPH6	MPHOSPH6	1245	0.13	0.083	YES
4	PNPT1	PNPT1	PNPT1	1492	0.12	0.11	YES
5	LSM6	LSM6	LSM6	1616	0.12	0.13	YES
6	DIS3	DIS3	DIS3	1675	0.11	0.16	YES
7	LSM5	LSM5	LSM5	1762	0.11	0.19	YES
8	HSPD1	HSPD1	HSPD1	1765	0.11	0.22	YES
9	EXOSC9	EXOSC9	EXOSC9	2415	0.088	0.22	YES
10	CNOT6L	CNOT6L	CNOT6L	2420	0.088	0.24	YES
11	XRN1	XRN1	XRN1	3042	0.072	0.23	YES
12	LSM3	LSM3	LSM3	3052	0.072	0.25	YES
13	LSM1	LSM1	LSM1	3077	0.071	0.27	YES
14	CNOT4	CNOT4	CNOT4	3122	0.07	0.29	YES
15	HSPA9	HSPA9	HSPA9	3239	0.068	0.3	YES
16	DDX6	DDX6	DDX6	3304	0.066	0.32	YES
17	EXOSC8	EXOSC8	EXOSC8	3364	0.065	0.34	YES
18	PARN	PARN	PARN	3523	0.062	0.35	YES
19	DCP2	DCP2	DCP2	3591	0.061	0.36	YES
20	PAPOLG	PAPOLG	PAPOLG	3770	0.057	0.37	YES
21	EXOSC5	EXOSC5	EXOSC5	4044	0.053	0.37	YES
22	SKIV2L2	SKIV2L2	SKIV2L2	4157	0.051	0.38	YES
23	PAPOLA	PAPOLA	PAPOLA	4216	0.05	0.39	YES
24	CNOT6	CNOT6	CNOT6	4507	0.045	0.39	YES
25	ZCCHC7	ZCCHC7	ZCCHC7	4611	0.043	0.4	YES
26	CNOT2	CNOT2	CNOT2	4720	0.041	0.4	YES
27	PATL1	PATL1	PATL1	4736	0.041	0.41	YES
28	CNOT7	CNOT7	CNOT7	5486	0.03	0.38	NO
29	XRN2	XRN2	XRN2	5573	0.029	0.39	NO
30	CNOT1	CNOT1	CNOT1	5871	0.024	0.38	NO
31	DCP1B	DCP1B	DCP1B	5972	0.022	0.38	NO
32	EXOSC7	EXOSC7	EXOSC7	6731	0.012	0.34	NO
33	EXOSC1	EXOSC1	EXOSC1	6865	0.01	0.34	NO
34	DCP1A	DCP1A	DCP1A	6875	0.0098	0.34	NO
35	LSM4	LSM4	LSM4	7318	0.0042	0.31	NO
36	CNOT10	CNOT10	CNOT10	7368	0.0036	0.31	NO
37	TTC37	TTC37	TTC37	7602	0.00028	0.3	NO
38	ENO2	ENO2	ENO2	8026	-0.0055	0.28	NO
39	EXOSC10	EXOSC10	EXOSC10	8309	-0.0095	0.26	NO
40	PAPOLB	PAPOLB	PAPOLB	8353	-0.01	0.27	NO
41	CNOT8	CNOT8	CNOT8	8822	-0.017	0.24	NO
42	EXOSC3	EXOSC3	EXOSC3	8823	-0.017	0.25	NO
43	SKIV2L	SKIV2L	SKIV2L	8870	-0.017	0.25	NO
44	ENO1	ENO1	ENO1	9289	-0.023	0.24	NO
45	PAPD7	PAPD7	PAPD7	9813	-0.031	0.22	NO
46	EDC4	EDC4	EDC4	9845	-0.032	0.22	NO
47	LSM7	LSM7	LSM7	9963	-0.033	0.23	NO
48	EDC3	EDC3	EDC3	10202	-0.037	0.23	NO
49	EXOSC2	EXOSC2	EXOSC2	10263	-0.038	0.24	NO
50	LSM2	LSM2	LSM2	10654	-0.045	0.23	NO
51	WDR61	WDR61	WDR61	10680	-0.046	0.24	NO
52	CNOT3	CNOT3	CNOT3	10932	-0.05	0.24	NO
53	DCPS	DCPS	DCPS	11209	-0.055	0.24	NO
54	EXOSC4	EXOSC4	EXOSC4	11738	-0.066	0.23	NO
55	EXOSC6	EXOSC6	EXOSC6	13383	-0.11	0.18	NO
56	RQCD1	RQCD1	RQCD1	13963	-0.13	0.18	NO
57	ENO3	ENO3	ENO3	14322	-0.15	0.21	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 PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM

Table 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	PIPOX	PIPOX	PIPOX	5	0.59	0.089	YES
2	BAAT	BAAT	BAAT	39	0.42	0.15	YES
3	ACSL6	ACSL6	ACSL6	58	0.4	0.21	YES
4	DDO	DDO	DDO	83	0.37	0.26	YES
5	PECR	PECR	PECR	222	0.27	0.3	YES
6	AMACR	AMACR	AMACR	581	0.19	0.31	YES
7	CROT	CROT	CROT	632	0.18	0.33	YES
8	PEX12	PEX12	PEX12	746	0.17	0.35	YES
9	NUDT12	NUDT12	NUDT12	810	0.16	0.37	YES
10	ACSL4	ACSL4	ACSL4	1286	0.13	0.37	YES
11	ACOT8	ACOT8	ACOT8	1423	0.12	0.38	YES
12	PEX1	PEX1	PEX1	1453	0.12	0.4	YES
13	PRDX5	PRDX5	PRDX5	1491	0.12	0.41	YES
14	PXMP4	PXMP4	PXMP4	1578	0.12	0.42	YES
15	HAO2	HAO2	HAO2	1721	0.11	0.43	YES
16	FAR1	FAR1	FAR1	1973	0.1	0.43	YES
17	PEX3	PEX3	PEX3	2104	0.096	0.44	YES
18	AGXT	AGXT	AGXT	2346	0.09	0.44	YES
19	PHYH	PHYH	PHYH	2469	0.087	0.45	YES
20	PEX16	PEX16	PEX16	3154	0.07	0.42	NO
21	ACSL5	ACSL5	ACSL5	3231	0.068	0.43	NO
22	ACOX2	ACOX2	ACOX2	3414	0.064	0.43	NO
23	ACSL3	ACSL3	ACSL3	4028	0.053	0.4	NO
24	PEX13	PEX13	PEX13	4034	0.053	0.41	NO
25	HSD17B4	HSD17B4	HSD17B4	4142	0.051	0.41	NO
26	PEX7	PEX7	PEX7	4209	0.05	0.41	NO
27	NUDT19	NUDT19	NUDT19	4322	0.048	0.42	NO
28	SLC25A17	SLC25A17	SLC25A17	4487	0.045	0.41	NO
29	ACOX1	ACOX1	ACOX1	4725	0.041	0.41	NO
30	SCP2	SCP2	SCP2	4732	0.041	0.41	NO
31	PEX5	PEX5	PEX5	4766	0.041	0.42	NO
32	AGPS	AGPS	AGPS	4851	0.04	0.42	NO
33	GSTK1	GSTK1	GSTK1	4887	0.039	0.42	NO
34	EHHADH	EHHADH	EHHADH	5025	0.037	0.42	NO
35	SOD1	SOD1	SOD1	5125	0.036	0.42	NO
36	HACL1	HACL1	HACL1	5406	0.031	0.41	NO
37	FAR2	FAR2	FAR2	5638	0.028	0.4	NO
38	IDH1	IDH1	IDH1	5653	0.028	0.4	NO
39	CAT	CAT	CAT	6081	0.021	0.38	NO
40	PEX2	PEX2	PEX2	6118	0.02	0.38	NO
41	EPHX2	EPHX2	EPHX2	6244	0.018	0.38	NO
42	PRDX1	PRDX1	PRDX1	6253	0.018	0.38	NO
43	ACSL1	ACSL1	ACSL1	6391	0.016	0.38	NO
44	MPV17	MPV17	MPV17	6639	0.013	0.37	NO
45	GNPAT	GNPAT	GNPAT	6755	0.012	0.36	NO
46	MPV17L	MPV17L	MPV17L	7161	0.0061	0.34	NO
47	PEX11B	PEX11B	PEX11B	7213	0.0054	0.34	NO
48	ACOX3	ACOX3	ACOX3	7285	0.0045	0.33	NO
49	IDH2	IDH2	IDH2	7480	0.002	0.32	NO
50	ABCD3	ABCD3	ABCD3	7868	-0.0035	0.3	NO
51	SLC27A2	SLC27A2	SLC27A2	8173	-0.0073	0.29	NO
52	ABCD1	ABCD1	ABCD1	8225	-0.0082	0.29	NO
53	PEX10	PEX10	PEX10	8241	-0.0084	0.29	NO
54	PMVK	PMVK	PMVK	8302	-0.0094	0.28	NO
55	MLYCD	MLYCD	MLYCD	8472	-0.012	0.28	NO
56	PEX19	PEX19	PEX19	8569	-0.013	0.27	NO
57	DHRS4	DHRS4	DHRS4	8809	-0.017	0.26	NO
58	HMGCL	HMGCL	HMGCL	8865	-0.017	0.26	NO
59	DECR2	DECR2	DECR2	9000	-0.019	0.26	NO
60	ECH1	ECH1	ECH1	9017	-0.02	0.26	NO
61	SOD2	SOD2	SOD2	9381	-0.024	0.24	NO
62	PEX14	PEX14	PEX14	9401	-0.025	0.25	NO
63	PAOX	PAOX	PAOX	9775	-0.03	0.23	NO
64	MVK	MVK	MVK	9861	-0.032	0.23	NO
65	PEX11A	PEX11A	PEX11A	10431	-0.041	0.2	NO
66	ACAA1	ACAA1	ACAA1	10752	-0.047	0.19	NO
67	PEX6	PEX6	PEX6	11666	-0.064	0.15	NO
68	PEX26	PEX26	PEX26	11687	-0.065	0.16	NO
69	PXMP2	PXMP2	PXMP2	11859	-0.069	0.16	NO
70	PEX11G	PEX11G	PEX11G	12040	-0.073	0.16	NO
71	ABCD4	ABCD4	ABCD4	12814	-0.093	0.14	NO
72	CRAT	CRAT	CRAT	13074	-0.1	0.14	NO
73	XDH	XDH	XDH	14445	-0.15	0.083	NO
74	DAO	DAO	DAO	15719	-0.22	0.046	NO
75	NOS2	NOS2	NOS2	16465	-0.28	0.047	NO
76	ABCD2	ABCD2	ABCD2	16539	-0.28	0.086	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 TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM.

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

genes ES table in pathway: REACTOME RNA POL II TRANSCRIPTION

Table 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	MRE11A	MRE11A	MRE11A	981	0.15	0.017	YES
2	FAM175A	FAM175A	FAM175A	1007	0.15	0.087	YES
3	XRCC4	XRCC4	XRCC4	1247	0.13	0.14	YES
4	SMC3	SMC3	SMC3	1585	0.12	0.17	YES
5	DCLRE1C	DCLRE1C	DCLRE1C	1719	0.11	0.22	YES
6	YWHAB	YWHAB	YWHAB	1827	0.11	0.26	YES
7	RAD17	RAD17	RAD17	1968	0.1	0.31	YES
8	CHEK2	CHEK2	CHEK2	2002	0.1	0.35	YES
9	ATM	ATM	ATM	2243	0.092	0.38	YES
10	RAD50	RAD50	RAD50	2380	0.089	0.42	YES
11	SMC1A	SMC1A	SMC1A	2575	0.084	0.45	YES
12	NBN	NBN	NBN	2675	0.081	0.48	YES
13	BRCA1	BRCA1	BRCA1	2788	0.078	0.51	YES
14	UBE2N	UBE2N	UBE2N	4062	0.052	0.47	YES
15	BLM	BLM	BLM	4242	0.049	0.48	YES
16	RNF8	RNF8	RNF8	4295	0.048	0.5	YES
17	CDC25C	CDC25C	CDC25C	4565	0.044	0.51	YES
18	UIMC1	UIMC1	UIMC1	4615	0.043	0.53	YES
19	MDM2	MDM2	MDM2	5217	0.034	0.51	NO
20	CDC25A	CDC25A	CDC25A	5376	0.032	0.52	NO
21	RAD9A	RAD9A	RAD9A	5629	0.028	0.52	NO
22	TERF2	TERF2	TERF2	5939	0.023	0.51	NO
23	MDC1	MDC1	MDC1	6611	0.013	0.48	NO
24	RBBP8	RBBP8	RBBP8	6782	0.011	0.48	NO
25	RFWD2	RFWD2	RFWD2	7426	0.0027	0.44	NO
26	KAT5	KAT5	KAT5	7441	0.0025	0.44	NO
27	BID	BID	BID	8171	-0.0072	0.4	NO
28	CTBP1	CTBP1	CTBP1	8835	-0.017	0.38	NO
29	ABL1	ABL1	ABL1	9854	-0.032	0.34	NO
30	TP53BP1	TP53BP1	TP53BP1	9949	-0.033	0.35	NO
31	TRIM28	TRIM28	TRIM28	10362	-0.04	0.34	NO
32	TOP3A	TOP3A	TOP3A	10461	-0.042	0.36	NO
33	FANCD2	FANCD2	FANCD2	11761	-0.067	0.32	NO
34	H2AFX	H2AFX	H2AFX	11793	-0.067	0.35	NO

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

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

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 PENTOSE PHOSPHATE PATHWAY	27	genes.ES.table	0.49	1.5	0.078	1	0.98	0.56	0.33	0.37	0.73	0.4
KEGG SYSTEMIC LUPUS ERYTHEMATOSUS	117	genes.ES.table	0.69	1.6	0.016	1	0.93	0.44	0.12	0.39	0.82	0.44
REACTOME MEIOSIS	98	genes.ES.table	0.64	1.6	0.02	1	0.92	0.37	0.12	0.32	1	0.53
REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S	57	genes.ES.table	0.45	1.5	0.15	1	0.98	0.18	0.14	0.15	0.69	0.38
REACTOME RNA POL I TRANSCRIPTION	77	genes.ES.table	0.68	1.5	0.046	1	0.97	0.44	0.12	0.39	0.74	0.42
REACTOME GLYCOLYSIS	27	genes.ES.table	0.5	1.5	0.061	1	0.98	0.67	0.36	0.42	0.68	0.37
REACTOME GLUCONEOGENESIS	31	genes.ES.table	0.54	1.6	0.03	1	0.9	0.61	0.31	0.42	1	0.54
REACTOME PREFOLDIN MEDIATED TRANSFER OF SUBSTRATE TO CCT TRIC	25	genes.ES.table	0.48	1.5	0.08	1	0.98	0.16	0.064	0.15	0.7	0.39
REACTOME 3 UTR MEDIATED TRANSLATIONAL REGULATION	105	genes.ES.table	0.49	1.5	0.14	1	0.98	0.16	0.13	0.14	0.72	0.39
REACTOME TRANSCRIPTION	187	genes.ES.table	0.44	1.5	0.061	1	0.97	0.19	0.12	0.17	0.69	0.4

genes ES table in pathway: KEGG PENTOSE PHOSPHATE PATHWAY

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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.069	YES
2	FKBP6	FKBP6	FKBP6	33	1.4	0.13	YES
3	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.18	YES
4	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.23	YES
5	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.27	YES
6	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.3	YES
7	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.33	YES
8	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.35	YES
9	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.37	YES
10	STAG3	STAG3	STAG3	474	0.56	0.4	YES
11	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.41	YES
12	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.43	YES
13	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.44	YES
14	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.46	YES
15	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.48	YES
16	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.49	YES
17	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.5	YES
18	TERT	TERT	TERT	898	0.38	0.52	YES
19	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.53	YES
20	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.54	YES
21	REC8	REC8	REC8	1173	0.32	0.55	YES
22	HIST3H3	HIST3H3	HIST3H3	1280	0.3	0.56	YES
23	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.56	YES
24	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.57	YES
25	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.57	YES
26	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.58	YES
27	H2AFX	H2AFX	H2AFX	1736	0.24	0.59	YES
28	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.59	YES
29	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.59	YES
30	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.59	YES
31	POLD1	POLD1	POLD1	2193	0.2	0.6	YES
32	RUVBL2	RUVBL2	RUVBL2	2984	0.16	0.56	NO
33	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.55	NO
34	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.53	NO
35	ACD	ACD	ACD	4030	0.12	0.52	NO
36	POLD2	POLD2	POLD2	4888	0.097	0.48	NO
37	NHP2	NHP2	NHP2	5301	0.086	0.46	NO
38	POLA2	POLA2	POLA2	5449	0.083	0.45	NO
39	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.46	NO
40	OIP5	OIP5	OIP5	5707	0.075	0.45	NO
41	POLE2	POLE2	POLE2	6030	0.067	0.43	NO
42	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.43	NO
43	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.43	NO
44	RFC2	RFC2	RFC2	6249	0.062	0.43	NO
45	WRAP53	WRAP53	WRAP53	6384	0.059	0.42	NO
46	POLD4	POLD4	POLD4	6506	0.056	0.42	NO
47	LIG1	LIG1	LIG1	6521	0.056	0.42	NO
48	HSPA2	HSPA2	HSPA2	6555	0.055	0.42	NO
49	RUVBL1	RUVBL1	RUVBL1	6808	0.049	0.41	NO
50	TINF2	TINF2	TINF2	7803	0.027	0.35	NO
51	CENPO	CENPO	CENPO	8054	0.021	0.34	NO
52	PCNA	PCNA	PCNA	8121	0.02	0.34	NO
53	POLE	POLE	POLE	8156	0.019	0.34	NO
54	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.34	NO
55	PRIM2	PRIM2	PRIM2	8211	0.018	0.34	NO
56	CENPP	CENPP	CENPP	8337	0.015	0.33	NO
57	LMNA	LMNA	LMNA	8465	0.012	0.32	NO
58	FEN1	FEN1	FEN1	8647	0.0088	0.31	NO
59	RBBP7	RBBP7	RBBP7	8739	0.0066	0.31	NO
60	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.31	NO
61	UBE2I	UBE2I	UBE2I	8975	0.0012	0.3	NO
62	CENPA	CENPA	CENPA	10061	-0.022	0.24	NO
63	CENPI	CENPI	CENPI	10304	-0.027	0.22	NO
64	CENPN	CENPN	CENPN	10361	-0.028	0.22	NO
65	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.22	NO
66	LMNB1	LMNB1	LMNB1	10436	-0.03	0.22	NO
67	RFC5	RFC5	RFC5	10536	-0.032	0.22	NO
68	RPA1	RPA1	RPA1	10595	-0.033	0.22	NO
69	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.21	NO
70	SUN2	SUN2	SUN2	10819	-0.038	0.21	NO
71	TERF2	TERF2	TERF2	10869	-0.039	0.2	NO
72	RFC4	RFC4	RFC4	10906	-0.04	0.2	NO
73	RPA3	RPA3	RPA3	10933	-0.04	0.2	NO
74	RPA2	RPA2	RPA2	10961	-0.041	0.2	NO
75	DKC1	DKC1	DKC1	11165	-0.045	0.2	NO
76	DIDO1	DIDO1	DIDO1	11270	-0.047	0.19	NO
77	HJURP	HJURP	HJURP	11955	-0.063	0.16	NO
78	RBBP4	RBBP4	RBBP4	12000	-0.064	0.16	NO
79	SYCP2	SYCP2	SYCP2	12023	-0.064	0.16	NO
80	ATR	ATR	ATR	12578	-0.077	0.13	NO
81	SMC1A	SMC1A	SMC1A	12584	-0.077	0.13	NO
82	POLD3	POLD3	POLD3	12909	-0.084	0.12	NO
83	BRCA1	BRCA1	BRCA1	13129	-0.09	0.11	NO
84	TERF2IP	TERF2IP	TERF2IP	13192	-0.091	0.11	NO
85	DNA2	DNA2	DNA2	13215	-0.091	0.11	NO
86	RFC3	RFC3	RFC3	13251	-0.092	0.12	NO
87	POLA1	POLA1	POLA1	13273	-0.093	0.12	NO
88	PRIM1	PRIM1	PRIM1	13707	-0.1	0.1	NO
89	RAD21	RAD21	RAD21	13776	-0.11	0.1	NO
90	CENPH	CENPH	CENPH	14080	-0.11	0.088	NO
91	ITGB3BP	ITGB3BP	ITGB3BP	14278	-0.12	0.082	NO
92	POT1	POT1	POT1	14450	-0.12	0.078	NO
93	SYNE2	SYNE2	SYNE2	14506	-0.12	0.08	NO
94	STAG2	STAG2	STAG2	14736	-0.13	0.073	NO
95	MLF1IP	MLF1IP	MLF1IP	14784	-0.13	0.076	NO
96	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.07	NO
97	SMC1B	SMC1B	SMC1B	15028	-0.14	0.075	NO
98	STAG1	STAG1	STAG1	15097	-0.14	0.077	NO
99	CASC5	CASC5	CASC5	15324	-0.15	0.071	NO
100	SMARCA5	SMARCA5	SMARCA5	15402	-0.15	0.074	NO
101	NPM1	NPM1	NPM1	16448	-0.19	0.024	NO
102	TERF1	TERF1	TERF1	16565	-0.2	0.026	NO
103	SYNE1	SYNE1	SYNE1	16791	-0.21	0.022	NO
104	SMC3	SMC3	SMC3	16805	-0.21	0.03	NO
105	TEX12	TEX12	TEX12	16998	-0.22	0.029	NO
106	CENPK	CENPK	CENPK	17039	-0.22	0.037	NO
107	CENPQ	CENPQ	CENPQ	17159	-0.23	0.04	NO
108	RSF1	RSF1	RSF1	17549	-0.27	0.03	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 PENTOSE PHOSPHATE PATHWAY.

Figure S82. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PENTOSE PHOSPHATE 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 SYSTEMIC LUPUS ERYTHEMATOSUS

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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.092	YES
2	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.16	YES
3	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.23	YES
4	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.29	YES
5	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.33	YES
6	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.37	YES
7	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.4	YES
8	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.43	YES
9	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.45	YES
10	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.47	YES
11	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.5	YES
12	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.52	YES
13	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.55	YES
14	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.56	YES
15	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.58	YES
16	TERT	TERT	TERT	898	0.38	0.6	YES
17	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.62	YES
18	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.63	YES
19	HIST3H3	HIST3H3	HIST3H3	1280	0.3	0.64	YES
20	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.65	YES
21	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.66	YES
22	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.66	YES
23	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.68	YES
24	H2AFX	H2AFX	H2AFX	1736	0.24	0.69	YES
25	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.7	YES
26	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.7	YES
27	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.71	YES
28	POLD1	POLD1	POLD1	2193	0.2	0.71	YES
29	RUVBL2	RUVBL2	RUVBL2	2984	0.16	0.68	NO
30	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.67	NO
31	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.66	NO
32	ACD	ACD	ACD	4030	0.12	0.65	NO
33	POLD2	POLD2	POLD2	4888	0.097	0.6	NO
34	NHP2	NHP2	NHP2	5301	0.086	0.59	NO
35	POLA2	POLA2	POLA2	5449	0.083	0.58	NO
36	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.58	NO
37	POLE2	POLE2	POLE2	6030	0.067	0.56	NO
38	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.56	NO
39	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.56	NO
40	RFC2	RFC2	RFC2	6249	0.062	0.56	NO
41	WRAP53	WRAP53	WRAP53	6384	0.059	0.55	NO
42	POLD4	POLD4	POLD4	6506	0.056	0.55	NO
43	LIG1	LIG1	LIG1	6521	0.056	0.55	NO
44	RUVBL1	RUVBL1	RUVBL1	6808	0.049	0.54	NO
45	TINF2	TINF2	TINF2	7803	0.027	0.49	NO
46	PCNA	PCNA	PCNA	8121	0.02	0.47	NO
47	POLE	POLE	POLE	8156	0.019	0.47	NO
48	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.47	NO
49	PRIM2	PRIM2	PRIM2	8211	0.018	0.47	NO
50	FEN1	FEN1	FEN1	8647	0.0088	0.44	NO
51	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.44	NO
52	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.35	NO
53	RFC5	RFC5	RFC5	10536	-0.032	0.34	NO
54	RPA1	RPA1	RPA1	10595	-0.033	0.34	NO
55	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.34	NO
56	TERF2	TERF2	TERF2	10869	-0.039	0.33	NO
57	RFC4	RFC4	RFC4	10906	-0.04	0.33	NO
58	RPA3	RPA3	RPA3	10933	-0.04	0.33	NO
59	RPA2	RPA2	RPA2	10961	-0.041	0.33	NO
60	DKC1	DKC1	DKC1	11165	-0.045	0.32	NO
61	POLD3	POLD3	POLD3	12909	-0.084	0.23	NO
62	TERF2IP	TERF2IP	TERF2IP	13192	-0.091	0.22	NO
63	DNA2	DNA2	DNA2	13215	-0.091	0.23	NO
64	RFC3	RFC3	RFC3	13251	-0.092	0.23	NO
65	POLA1	POLA1	POLA1	13273	-0.093	0.23	NO
66	PRIM1	PRIM1	PRIM1	13707	-0.1	0.22	NO
67	POT1	POT1	POT1	14450	-0.12	0.18	NO
68	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.16	NO
69	TERF1	TERF1	TERF1	16565	-0.2	0.085	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 SYSTEMIC LUPUS ERYTHEMATOSUS.

Figure S84. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG SYSTEMIC LUPUS ERYTHEMATOSUS, 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 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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.083	YES
2	FKBP6	FKBP6	FKBP6	33	1.4	0.15	YES
3	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.22	YES
4	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.28	YES
5	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.33	YES
6	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.36	YES
7	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.4	YES
8	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.43	YES
9	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.46	YES
10	STAG3	STAG3	STAG3	474	0.56	0.48	YES
11	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.51	YES
12	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.52	YES
13	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.55	YES
14	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.57	YES
15	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.59	YES
16	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.6	YES
17	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.62	YES
18	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.63	YES
19	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.64	YES
20	REC8	REC8	REC8	1173	0.32	0.66	YES
21	HIST3H3	HIST3H3	HIST3H3	1280	0.3	0.67	YES
22	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.68	YES
23	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.68	YES
24	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.69	YES
25	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.7	YES
26	H2AFX	H2AFX	H2AFX	1736	0.24	0.71	YES
27	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.72	YES
28	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.72	YES
29	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.72	YES
30	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.67	NO
31	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.65	NO
32	ACD	ACD	ACD	4030	0.12	0.64	NO
33	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.56	NO
34	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.53	NO
35	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.53	NO
36	HSPA2	HSPA2	HSPA2	6555	0.055	0.51	NO
37	TINF2	TINF2	TINF2	7803	0.027	0.44	NO
38	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.42	NO
39	LMNA	LMNA	LMNA	8465	0.012	0.41	NO
40	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.39	NO
41	UBE2I	UBE2I	UBE2I	8975	0.0012	0.38	NO
42	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.3	NO
43	LMNB1	LMNB1	LMNB1	10436	-0.03	0.3	NO
44	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.29	NO
45	SUN2	SUN2	SUN2	10819	-0.038	0.29	NO
46	TERF2	TERF2	TERF2	10869	-0.039	0.29	NO
47	DIDO1	DIDO1	DIDO1	11270	-0.047	0.27	NO
48	SYCP2	SYCP2	SYCP2	12023	-0.064	0.23	NO
49	ATR	ATR	ATR	12578	-0.077	0.2	NO
50	SMC1A	SMC1A	SMC1A	12584	-0.077	0.2	NO
51	BRCA1	BRCA1	BRCA1	13129	-0.09	0.18	NO
52	TERF2IP	TERF2IP	TERF2IP	13192	-0.091	0.18	NO
53	RAD21	RAD21	RAD21	13776	-0.11	0.15	NO
54	POT1	POT1	POT1	14450	-0.12	0.12	NO
55	SYNE2	SYNE2	SYNE2	14506	-0.12	0.13	NO
56	STAG2	STAG2	STAG2	14736	-0.13	0.12	NO
57	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.11	NO
58	SMC1B	SMC1B	SMC1B	15028	-0.14	0.12	NO
59	STAG1	STAG1	STAG1	15097	-0.14	0.12	NO
60	TERF1	TERF1	TERF1	16565	-0.2	0.051	NO
61	SYNE1	SYNE1	SYNE1	16791	-0.21	0.05	NO
62	SMC3	SMC3	SMC3	16805	-0.21	0.06	NO
63	TEX12	TEX12	TEX12	16998	-0.22	0.061	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: REACTOME MEIOSIS.

Figure S86. 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 ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S

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	GAPDHS	GAPDHS	GAPDHS	210	0.84	0.18	YES
2	PGAM2	PGAM2	PGAM2	575	0.5	0.27	YES
3	PRKACG	PRKACG	PRKACG	1554	0.26	0.28	YES
4	PFKFB1	PFKFB1	PFKFB1	1849	0.23	0.32	YES
5	SLC25A10	SLC25A10	SLC25A10	2344	0.2	0.33	YES
6	SLC25A1	SLC25A1	SLC25A1	2422	0.19	0.37	YES
7	FBP2	FBP2	FBP2	2686	0.18	0.4	YES
8	PC	PC	PC	3520	0.14	0.38	YES
9	PGAM1	PGAM1	PGAM1	3644	0.14	0.41	YES
10	SLC25A11	SLC25A11	SLC25A11	3912	0.13	0.42	YES
11	ALDOC	ALDOC	ALDOC	4022	0.12	0.44	YES
12	ENO3	ENO3	ENO3	4252	0.12	0.46	YES
13	FBP1	FBP1	FBP1	4384	0.11	0.48	YES
14	PCK2	PCK2	PCK2	4385	0.11	0.5	YES
15	ALDOA	ALDOA	ALDOA	4646	0.1	0.51	YES
16	MDH2	MDH2	MDH2	4869	0.098	0.52	YES
17	ALDOB	ALDOB	ALDOB	5068	0.092	0.53	YES
18	GAPDH	GAPDH	GAPDH	5558	0.079	0.52	YES
19	TPI1	TPI1	TPI1	5563	0.079	0.54	YES
20	GPI	GPI	GPI	6004	0.068	0.53	NO
21	PGK1	PGK1	PGK1	6576	0.054	0.51	NO
22	GOT2	GOT2	GOT2	6907	0.047	0.5	NO
23	ENO1	ENO1	ENO1	7400	0.036	0.48	NO
24	GOT1	GOT1	GOT1	8175	0.019	0.45	NO
25	PCK1	PCK1	PCK1	9420	-0.0087	0.38	NO
26	PRKACA	PRKACA	PRKACA	10177	-0.024	0.34	NO
27	SLC25A12	SLC25A12	SLC25A12	10264	-0.026	0.34	NO
28	MDH1	MDH1	MDH1	11118	-0.044	0.31	NO
29	SLC25A13	SLC25A13	SLC25A13	12340	-0.071	0.26	NO
30	ENO2	ENO2	ENO2	13443	-0.097	0.22	NO
31	PRKACB	PRKACB	PRKACB	16061	-0.18	0.11	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: REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S.

Figure S88. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME ACTIVATION OF THE MRNA UPON BINDING OF THE CAP BINDING COMPLEX AND EIFS AND SUBSEQUENT BINDING TO 43S, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: REACTOME RNA POL I TRANSCRIPTION

Table 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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.062	YES
2	FKBP6	FKBP6	FKBP6	33	1.4	0.12	YES
3	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.16	YES
4	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.21	YES
5	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.24	YES
6	HIST2H3C	HIST2H3C	HIST2H3C	161	0.94	0.28	YES
7	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.31	YES
8	HIST2H3D	HIST2H3D	HIST2H3D	281	0.75	0.33	YES
9	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.36	YES
10	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.39	YES
11	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.4	YES
12	STAG3	STAG3	STAG3	474	0.56	0.42	YES
13	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.44	YES
14	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.45	YES
15	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.47	YES
16	HIST1H3H	HIST1H3H	HIST1H3H	686	0.45	0.48	YES
17	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.5	YES
18	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.52	YES
19	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.53	YES
20	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.54	YES
21	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.55	YES
22	HIST1H3D	HIST1H3D	HIST1H3D	1042	0.34	0.56	YES
23	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.57	YES
24	REC8	REC8	REC8	1173	0.32	0.57	YES
25	HIST3H3	HIST3H3	HIST3H3	1280	0.3	0.58	YES
26	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.59	YES
27	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.59	YES
28	HIST1H3B	HIST1H3B	HIST1H3B	1614	0.26	0.59	YES
29	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.6	YES
30	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.61	YES
31	H2AFX	H2AFX	H2AFX	1736	0.24	0.62	YES
32	HIST1H3G	HIST1H3G	HIST1H3G	1759	0.24	0.62	YES
33	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.63	YES
34	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.63	YES
35	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.63	YES
36	HIST1H3J	HIST1H3J	HIST1H3J	2168	0.21	0.64	YES
37	HIST1H3F	HIST1H3F	HIST1H3F	2548	0.18	0.62	NO
38	MSH5	MSH5	MSH5	2828	0.17	0.61	NO
39	MSH4	MSH4	MSH4	3118	0.16	0.6	NO
40	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.6	NO
41	HIST1H3A	HIST1H3A	HIST1H3A	3498	0.14	0.6	NO
42	HIST1H3I	HIST1H3I	HIST1H3I	3616	0.14	0.59	NO
43	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.59	NO
44	ACD	ACD	ACD	4030	0.12	0.58	NO
45	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.5	NO
46	H3F3A	H3F3A	H3F3A	6075	0.066	0.47	NO
47	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.47	NO
48	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.47	NO
49	CDK4	CDK4	CDK4	6236	0.062	0.47	NO
50	HSPA2	HSPA2	HSPA2	6555	0.055	0.46	NO
51	RAD51	RAD51	RAD51	6709	0.051	0.45	NO
52	HIST1H3C	HIST1H3C	HIST1H3C	6733	0.05	0.45	NO
53	TINF2	TINF2	TINF2	7803	0.027	0.39	NO
54	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.37	NO
55	LMNA	LMNA	LMNA	8465	0.012	0.36	NO
56	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.34	NO
57	UBE2I	UBE2I	UBE2I	8975	0.0012	0.33	NO
58	TOP3A	TOP3A	TOP3A	9525	-0.011	0.3	NO
59	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.25	NO
60	LMNB1	LMNB1	LMNB1	10436	-0.03	0.25	NO
61	HIST1H3E	HIST1H3E	HIST1H3E	10515	-0.031	0.25	NO
62	RPA1	RPA1	RPA1	10595	-0.033	0.24	NO
63	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.24	NO
64	SUN2	SUN2	SUN2	10819	-0.038	0.24	NO
65	TERF2	TERF2	TERF2	10869	-0.039	0.23	NO
66	DMC1	DMC1	DMC1	10904	-0.04	0.23	NO
67	RPA3	RPA3	RPA3	10933	-0.04	0.23	NO
68	RPA2	RPA2	RPA2	10961	-0.041	0.23	NO
69	MLH1	MLH1	MLH1	11079	-0.043	0.23	NO
70	DIDO1	DIDO1	DIDO1	11270	-0.047	0.22	NO
71	CDK2	CDK2	CDK2	11288	-0.048	0.22	NO
72	RAD51C	RAD51C	RAD51C	11689	-0.056	0.2	NO
73	SYCP2	SYCP2	SYCP2	12023	-0.064	0.18	NO
74	ATR	ATR	ATR	12578	-0.077	0.16	NO
75	SMC1A	SMC1A	SMC1A	12584	-0.077	0.16	NO
76	H3F3B	H3F3B	H3F3B	13106	-0.089	0.13	NO
77	BRCA1	BRCA1	BRCA1	13129	-0.09	0.14	NO
78	TERF2IP	TERF2IP	TERF2IP	13192	-0.091	0.14	NO
79	RAD21	RAD21	RAD21	13776	-0.11	0.11	NO
80	MLH3	MLH3	MLH3	14131	-0.11	0.093	NO
81	POT1	POT1	POT1	14450	-0.12	0.08	NO
82	SYNE2	SYNE2	SYNE2	14506	-0.12	0.082	NO
83	STAG2	STAG2	STAG2	14736	-0.13	0.074	NO
84	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.065	NO
85	SMC1B	SMC1B	SMC1B	15028	-0.14	0.069	NO
86	RAD50	RAD50	RAD50	15046	-0.14	0.074	NO
87	STAG1	STAG1	STAG1	15097	-0.14	0.076	NO
88	NBN	NBN	NBN	15997	-0.17	0.033	NO
89	BLM	BLM	BLM	16086	-0.18	0.035	NO
90	MRE11A	MRE11A	MRE11A	16133	-0.18	0.04	NO
91	TERF1	TERF1	TERF1	16565	-0.2	0.024	NO
92	SYNE1	SYNE1	SYNE1	16791	-0.21	0.019	NO
93	SMC3	SMC3	SMC3	16805	-0.21	0.027	NO
94	MND1	MND1	MND1	16899	-0.22	0.03	NO
95	RBBP8	RBBP8	RBBP8	16948	-0.22	0.036	NO
96	TEX12	TEX12	TEX12	16998	-0.22	0.042	NO
97	ATM	ATM	ATM	17010	-0.22	0.05	NO
98	BRCA2	BRCA2	BRCA2	17474	-0.26	0.034	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: REACTOME RNA POL I TRANSCRIPTION.

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

genes ES table in pathway: REACTOME GLYCOLYSIS

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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.079	YES
2	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.14	YES
3	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.2	YES
4	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.24	YES
5	HIST2H3C	HIST2H3C	HIST2H3C	161	0.94	0.29	YES
6	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.32	YES
7	HIST2H3D	HIST2H3D	HIST2H3D	281	0.75	0.36	YES
8	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.4	YES
9	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.43	YES
10	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.45	YES
11	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.47	YES
12	NPPA	NPPA	NPPA	629	0.47	0.49	YES
13	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.51	YES
14	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.53	YES
15	HIST1H3H	HIST1H3H	HIST1H3H	686	0.45	0.55	YES
16	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.57	YES
17	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.59	YES
18	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.61	YES
19	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.62	YES
20	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.64	YES
21	HIST1H3D	HIST1H3D	HIST1H3D	1042	0.34	0.65	YES
22	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.66	YES
23	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.66	YES
24	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.67	YES
25	HIST1H3B	HIST1H3B	HIST1H3B	1614	0.26	0.67	YES
26	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.68	YES
27	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.69	YES
28	H2AFX	H2AFX	H2AFX	1736	0.24	0.7	YES
29	HIST1H3G	HIST1H3G	HIST1H3G	1759	0.24	0.72	YES
30	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.73	YES
31	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.72	YES
32	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.73	YES
33	HIST1H3J	HIST1H3J	HIST1H3J	2168	0.21	0.74	YES
34	HIST1H3F	HIST1H3F	HIST1H3F	2548	0.18	0.72	NO
35	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.69	NO
36	CST3	CST3	CST3	3327	0.15	0.7	NO
37	HIST1H3A	HIST1H3A	HIST1H3A	3498	0.14	0.69	NO
38	HIST1H3I	HIST1H3I	HIST1H3I	3616	0.14	0.69	NO
39	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.7	NO
40	CALCA	CALCA	CALCA	5395	0.084	0.61	NO
41	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.6	NO
42	SAA1	SAA1	SAA1	5759	0.074	0.59	NO
43	H3F3A	H3F3A	H3F3A	6075	0.066	0.58	NO
44	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.58	NO
45	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.58	NO
46	HIST1H3C	HIST1H3C	HIST1H3C	6733	0.05	0.55	NO
47	MFGE8	MFGE8	MFGE8	6867	0.048	0.55	NO
48	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.48	NO
49	GSN	GSN	GSN	8498	0.012	0.46	NO
50	TGFBI	TGFBI	TGFBI	8730	0.0068	0.44	NO
51	SEMG1	SEMG1	SEMG1	8749	0.0064	0.44	NO
52	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.44	NO
53	B2M	B2M	B2M	9557	-0.012	0.4	NO
54	APOA1	APOA1	APOA1	10086	-0.022	0.37	NO
55	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.36	NO
56	HIST1H3E	HIST1H3E	HIST1H3E	10515	-0.031	0.35	NO
57	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.35	NO
58	HSPG2	HSPG2	HSPG2	11319	-0.048	0.31	NO
59	APP	APP	APP	11798	-0.059	0.29	NO
60	LTF	LTF	LTF	12015	-0.064	0.28	NO
61	ITM2B	ITM2B	ITM2B	12748	-0.081	0.24	NO
62	PRL	PRL	PRL	13018	-0.087	0.23	NO
63	H3F3B	H3F3B	H3F3B	13106	-0.089	0.23	NO
64	ODAM	ODAM	ODAM	14030	-0.11	0.19	NO
65	TTR	TTR	TTR	14719	-0.13	0.15	NO
66	LYZ	LYZ	LYZ	14923	-0.14	0.15	NO
67	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.15	NO
68	SNCA	SNCA	SNCA	15199	-0.14	0.15	NO
69	FGA	FGA	FGA	17265	-0.24	0.046	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: REACTOME GLYCOLYSIS.

Figure S92. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME GLYCOLYSIS, 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 GLUCONEOGENESIS

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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.052	YES
2	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.092	YES
3	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.13	YES
4	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.16	YES
5	HIST2H3C	HIST2H3C	HIST2H3C	161	0.94	0.19	YES
6	HIST3H2A	HIST3H2A	HIST3H2A	238	0.8	0.21	YES
7	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.24	YES
8	HIST2H3D	HIST2H3D	HIST2H3D	281	0.75	0.26	YES
9	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.28	YES
10	FCGR2C	FCGR2C	FCGR2C	314	0.71	0.31	YES
11	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.33	YES
12	H2AFB1	H2AFB1	H2AFB1	441	0.59	0.34	YES
13	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.36	YES
14	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.37	YES
15	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.38	YES
16	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.39	YES
17	HIST2H2BF	HIST2H2BF	HIST2H2BF	673	0.45	0.41	YES
18	HIST1H3H	HIST1H3H	HIST1H3H	686	0.45	0.42	YES
19	H3F3C	H3F3C	H3F3C	697	0.44	0.44	YES
20	FCGR3B	FCGR3B	FCGR3B	700	0.44	0.45	YES
21	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.46	YES
22	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.48	YES
23	FCGR1A	FCGR1A	FCGR1A	759	0.42	0.49	YES
24	HLA-DRB5	HLA-DRB5	HLA-DRB5	771	0.42	0.5	YES
25	C8G	C8G	C8G	793	0.41	0.52	YES
26	HLA-DQA2	HLA-DQA2	HLA-DQA2	811	0.4	0.53	YES
27	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.54	YES
28	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.55	YES
29	HIST1H2AG	HIST1H2AG	HIST1H2AG	886	0.38	0.56	YES
30	HIST1H2AM	HIST1H2AM	HIST1H2AM	908	0.38	0.57	YES
31	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.58	YES
32	HIST1H3D	HIST1H3D	HIST1H3D	1042	0.34	0.59	YES
33	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.6	YES
34	FCGR2B	FCGR2B	FCGR2B	1265	0.3	0.6	YES
35	HIST3H3	HIST3H3	HIST3H3	1280	0.3	0.6	YES
36	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.61	YES
37	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.61	YES
38	HIST1H3B	HIST1H3B	HIST1H3B	1614	0.26	0.61	YES
39	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.62	YES
40	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.62	YES
41	HIST1H2AL	HIST1H2AL	HIST1H2AL	1708	0.25	0.63	YES
42	H2AFX	H2AFX	H2AFX	1736	0.24	0.64	YES
43	HIST1H3G	HIST1H3G	HIST1H3G	1759	0.24	0.65	YES
44	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.65	YES
45	ELANE	ELANE	ELANE	1828	0.23	0.66	YES
46	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.66	YES
47	HLA-DRB1	HLA-DRB1	HLA-DRB1	1999	0.22	0.66	YES
48	HLA-DQB1	HLA-DQB1	HLA-DQB1	2039	0.22	0.67	YES
49	HIST1H2AH	HIST1H2AH	HIST1H2AH	2050	0.22	0.68	YES
50	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.68	YES
51	HIST1H3J	HIST1H3J	HIST1H3J	2168	0.21	0.68	YES
52	HIST1H2AK	HIST1H2AK	HIST1H2AK	2170	0.21	0.69	YES
53	HIST1H3F	HIST1H3F	HIST1H3F	2548	0.18	0.67	NO
54	C1QC	C1QC	C1QC	2671	0.18	0.67	NO
55	C1QB	C1QB	C1QB	2877	0.17	0.67	NO
56	HLA-DQA1	HLA-DQA1	HLA-DQA1	2937	0.16	0.67	NO
57	TNF	TNF	TNF	2992	0.16	0.67	NO
58	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.66	NO
59	H2AFJ	H2AFJ	H2AFJ	3466	0.14	0.66	NO
60	HIST1H3A	HIST1H3A	HIST1H3A	3498	0.14	0.66	NO
61	HIST1H3I	HIST1H3I	HIST1H3I	3616	0.14	0.66	NO
62	HLA-DMB	HLA-DMB	HLA-DMB	3676	0.14	0.66	NO
63	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.66	NO
64	HLA-DPB1	HLA-DPB1	HLA-DPB1	3815	0.13	0.66	NO
65	HIST2H2AB	HIST2H2AB	HIST2H2AB	3944	0.13	0.66	NO
66	C4A	C4A	C4A	4409	0.11	0.63	NO
67	CD80	CD80	CD80	5254	0.088	0.59	NO
68	SNRPB	SNRPB	SNRPB	5453	0.083	0.58	NO
69	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.58	NO
70	HLA-DMA	HLA-DMA	HLA-DMA	5621	0.078	0.58	NO
71	CD40	CD40	CD40	5645	0.077	0.58	NO
72	HLA-DPA1	HLA-DPA1	HLA-DPA1	5733	0.075	0.57	NO
73	C1QA	C1QA	C1QA	5918	0.07	0.57	NO
74	HLA-DRA	HLA-DRA	HLA-DRA	5919	0.07	0.57	NO
75	H3F3A	H3F3A	H3F3A	6075	0.066	0.56	NO
76	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.56	NO
77	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.56	NO
78	HIST1H3C	HIST1H3C	HIST1H3C	6733	0.05	0.53	NO
79	IL10	IL10	IL10	6843	0.048	0.53	NO
80	HLA-DOB	HLA-DOB	HLA-DOB	6885	0.047	0.53	NO
81	GRIN2B	GRIN2B	GRIN2B	7616	0.031	0.49	NO
82	H2AFY2	H2AFY2	H2AFY2	7692	0.03	0.48	NO
83	C9	C9	C9	8042	0.022	0.47	NO
84	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.46	NO
85	HLA-DOA	HLA-DOA	HLA-DOA	8338	0.015	0.45	NO
86	FCGR2A	FCGR2A	FCGR2A	8746	0.0064	0.43	NO
87	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.43	NO
88	H2AFY	H2AFY	H2AFY	8950	0.0018	0.42	NO
89	ACTN4	ACTN4	ACTN4	9248	-0.0048	0.4	NO
90	C2	C2	C2	9379	-0.0078	0.39	NO
91	TRIM21	TRIM21	TRIM21	9501	-0.011	0.39	NO
92	ACTN1	ACTN1	ACTN1	9799	-0.017	0.37	NO
93	ACTN3	ACTN3	ACTN3	9805	-0.017	0.37	NO
94	ACTN2	ACTN2	ACTN2	9878	-0.018	0.37	NO
95	C1R	C1R	C1R	10091	-0.022	0.36	NO
96	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.34	NO
97	H2AFV	H2AFV	H2AFV	10485	-0.031	0.34	NO
98	HIST1H3E	HIST1H3E	HIST1H3E	10515	-0.031	0.34	NO
99	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.33	NO
100	CTSG	CTSG	CTSG	11001	-0.042	0.31	NO
101	SNRPD3	SNRPD3	SNRPD3	11142	-0.044	0.31	NO
102	CD40LG	CD40LG	CD40LG	11204	-0.046	0.3	NO
103	C3	C3	C3	11287	-0.048	0.3	NO
104	C1S	C1S	C1S	11913	-0.062	0.27	NO
105	CD86	CD86	CD86	12228	-0.069	0.25	NO
106	FCGR3A	FCGR3A	FCGR3A	12914	-0.084	0.22	NO
107	H3F3B	H3F3B	H3F3B	13106	-0.089	0.21	NO
108	SNRPD1	SNRPD1	SNRPD1	13149	-0.09	0.21	NO
109	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.11	NO
110	CD28	CD28	CD28	15031	-0.14	0.12	NO
111	C5	C5	C5	15626	-0.16	0.088	NO
112	IFNG	IFNG	IFNG	16005	-0.17	0.072	NO
113	C7	C7	C7	16544	-0.2	0.049	NO
114	C6	C6	C6	17112	-0.23	0.025	NO
115	TROVE2	TROVE2	TROVE2	17180	-0.23	0.029	NO
116	SSB	SSB	SSB	17771	-0.31	0.006	NO
117	GRIN2A	GRIN2A	GRIN2A	17950	-0.36	0.0078	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: REACTOME GLUCONEOGENESIS.

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

genes ES table in pathway: REACTOME PREFOLDIN MEDIATED TRANSFER OF SUBSTRATE TO CCT TRIC

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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.098	YES
2	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.18	YES
3	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.25	YES
4	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.3	YES
5	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.35	YES
6	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.39	YES
7	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.43	YES
8	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.46	YES
9	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.48	YES
10	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.51	YES
11	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.53	YES
12	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.56	YES
13	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.58	YES
14	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.6	YES
15	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.62	YES
16	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.64	YES
17	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.65	YES
18	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.66	YES
19	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.67	YES
20	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.67	YES
21	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.69	YES
22	H2AFX	H2AFX	H2AFX	1736	0.24	0.7	YES
23	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.71	YES
24	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.71	YES
25	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.72	YES
26	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.67	NO
27	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.65	NO
28	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.56	NO
29	OIP5	OIP5	OIP5	5707	0.075	0.55	NO
30	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.53	NO
31	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.53	NO
32	RUVBL1	RUVBL1	RUVBL1	6808	0.049	0.5	NO
33	CENPO	CENPO	CENPO	8054	0.021	0.43	NO
34	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.42	NO
35	CENPP	CENPP	CENPP	8337	0.015	0.42	NO
36	RBBP7	RBBP7	RBBP7	8739	0.0066	0.4	NO
37	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.39	NO
38	CENPA	CENPA	CENPA	10061	-0.022	0.32	NO
39	CENPI	CENPI	CENPI	10304	-0.027	0.31	NO
40	CENPN	CENPN	CENPN	10361	-0.028	0.31	NO
41	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.31	NO
42	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.3	NO
43	HJURP	HJURP	HJURP	11955	-0.063	0.23	NO
44	RBBP4	RBBP4	RBBP4	12000	-0.064	0.23	NO
45	CENPH	CENPH	CENPH	14080	-0.11	0.12	NO
46	ITGB3BP	ITGB3BP	ITGB3BP	14278	-0.12	0.12	NO
47	MLF1IP	MLF1IP	MLF1IP	14784	-0.13	0.099	NO
48	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.095	NO
49	CASC5	CASC5	CASC5	15324	-0.15	0.087	NO
50	SMARCA5	SMARCA5	SMARCA5	15402	-0.15	0.092	NO
51	NPM1	NPM1	NPM1	16448	-0.19	0.046	NO
52	CENPK	CENPK	CENPK	17039	-0.22	0.027	NO
53	CENPQ	CENPQ	CENPQ	17159	-0.23	0.035	NO
54	RSF1	RSF1	RSF1	17549	-0.27	0.03	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: REACTOME PREFOLDIN MEDIATED TRANSFER OF SUBSTRATE TO CCT TRIC.

Figure S96. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME PREFOLDIN MEDIATED TRANSFER OF SUBSTRATE TO CCT TRIC, 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 3 UTR MEDIATED TRANSLATIONAL REGULATION

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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.1	YES
2	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.19	YES
3	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.27	YES
4	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.33	YES
5	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.37	YES
6	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.42	YES
7	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.46	YES
8	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.49	YES
9	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.52	YES
10	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.54	YES
11	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.57	YES
12	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.6	YES
13	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.63	YES
14	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.65	YES
15	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.67	YES
16	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.69	YES
17	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.7	YES
18	HIST3H3	HIST3H3	HIST3H3	1280	0.3	0.71	YES
19	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.73	YES
20	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.74	YES
21	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.75	YES
22	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.76	YES
23	H2AFX	H2AFX	H2AFX	1736	0.24	0.77	YES
24	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.79	YES
25	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.79	YES
26	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.8	YES
27	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.74	NO
28	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.73	NO
29	ACD	ACD	ACD	4030	0.12	0.72	NO
30	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.64	NO
31	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.61	NO
32	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.61	NO
33	TINF2	TINF2	TINF2	7803	0.027	0.52	NO
34	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.5	NO
35	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.47	NO
36	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.38	NO
37	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.37	NO
38	TERF2	TERF2	TERF2	10869	-0.039	0.36	NO
39	TERF2IP	TERF2IP	TERF2IP	13192	-0.091	0.24	NO
40	POT1	POT1	POT1	14450	-0.12	0.18	NO
41	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.16	NO
42	TERF1	TERF1	TERF1	16565	-0.2	0.084	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 3 UTR MEDIATED TRANSLATIONAL REGULATION.

Figure S98. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME 3 UTR MEDIATED TRANSLATIONAL REGULATION, 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 TRANSCRIPTION

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	HIST1H4K	HIST1H4K	HIST1H4K	9	1.6	0.062	YES
2	HIST1H2BO	HIST1H2BO	HIST1H2BO	46	1.3	0.11	YES
3	HIST2H2AC	HIST2H2AC	HIST2H2AC	66	1.2	0.16	YES
4	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	138	0.97	0.19	YES
5	HIST2H3C	HIST2H3C	HIST2H3C	161	0.94	0.23	YES
6	HIST1H2BN	HIST1H2BN	HIST1H2BN	245	0.79	0.25	YES
7	HIST2H3D	HIST2H3D	HIST2H3D	281	0.75	0.28	YES
8	HIST1H2BE	HIST1H2BE	HIST1H2BE	293	0.74	0.31	YES
9	HIST1H2BL	HIST1H2BL	HIST1H2BL	346	0.66	0.33	YES
10	HIST1H4J	HIST1H4J	HIST1H4J	463	0.57	0.35	YES
11	GTF2H2B	GTF2H2B	GTF2H2B	502	0.54	0.37	YES
12	HIST2H2AA3	HIST2H2AA3	HIST2H2AA3	541	0.52	0.38	YES
13	HIST2H4A	HIST2H4A	HIST2H4A	667	0.46	0.4	YES
14	HIST1H4I	HIST1H4I	HIST1H4I	672	0.45	0.41	YES
15	HIST1H3H	HIST1H3H	HIST1H3H	686	0.45	0.43	YES
16	HIST1H4B	HIST1H4B	HIST1H4B	729	0.43	0.44	YES
17	HIST1H4A	HIST1H4A	HIST1H4A	730	0.43	0.46	YES
18	HIST1H4E	HIST1H4E	HIST1H4E	840	0.39	0.47	YES
19	HIST1H2BH	HIST1H2BH	HIST1H2BH	865	0.38	0.48	YES
20	GTF2H2	GTF2H2	GTF2H2	899	0.38	0.5	YES
21	HIST3H2BB	HIST3H2BB	HIST3H2BB	980	0.36	0.51	YES
22	HIST1H3D	HIST1H3D	HIST1H3D	1042	0.34	0.52	YES
23	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	1111	0.33	0.53	YES
24	HIST1H2BG	HIST1H2BG	HIST1H2BG	1349	0.29	0.52	YES
25	HIST1H2AB	HIST1H2AB	HIST1H2AB	1460	0.27	0.53	YES
26	HIST1H3B	HIST1H3B	HIST1H3B	1614	0.26	0.53	YES
27	HIST1H2BF	HIST1H2BF	HIST1H2BF	1650	0.25	0.54	YES
28	HIST1H2BI	HIST1H2BI	HIST1H2BI	1706	0.25	0.54	YES
29	H2AFX	H2AFX	H2AFX	1736	0.24	0.55	YES
30	HIST1H3G	HIST1H3G	HIST1H3G	1759	0.24	0.56	YES
31	HIST1H2BC	HIST1H2BC	HIST1H2BC	1776	0.24	0.57	YES
32	HIST1H2AE	HIST1H2AE	HIST1H2AE	1984	0.22	0.57	YES
33	HIST1H4C	HIST1H4C	HIST1H4C	2115	0.21	0.57	YES
34	HIST1H3J	HIST1H3J	HIST1H3J	2168	0.21	0.57	YES
35	HIST1H3F	HIST1H3F	HIST1H3F	2548	0.18	0.56	NO
36	POLR2L	POLR2L	POLR2L	2556	0.18	0.56	NO
37	HIST1H4D	HIST1H4D	HIST1H4D	3249	0.15	0.53	NO
38	ERCC2	ERCC2	ERCC2	3360	0.15	0.53	NO
39	HIST1H3A	HIST1H3A	HIST1H3A	3498	0.14	0.53	NO
40	POLRMT	POLRMT	POLRMT	3515	0.14	0.54	NO
41	HIST1H3I	HIST1H3I	HIST1H3I	3616	0.14	0.54	NO
42	HIST1H2BK	HIST1H2BK	HIST1H2BK	3710	0.13	0.54	NO
43	POLR3K	POLR3K	POLR3K	4232	0.12	0.51	NO
44	MAPK3	MAPK3	MAPK3	4465	0.11	0.5	NO
45	POLR2H	POLR2H	POLR2H	4523	0.11	0.5	NO
46	POLR3H	POLR3H	POLR3H	4721	0.1	0.5	NO
47	POLR1C	POLR1C	POLR1C	4857	0.098	0.49	NO
48	POLR3E	POLR3E	POLR3E	5187	0.089	0.48	NO
49	POLR2F	POLR2F	POLR2F	5278	0.087	0.48	NO
50	POLR2E	POLR2E	POLR2E	5319	0.086	0.48	NO
51	TAF1C	TAF1C	TAF1C	5378	0.084	0.48	NO
52	BRF1	BRF1	BRF1	5391	0.084	0.48	NO
53	HIST1H4H	HIST1H4H	HIST1H4H	5491	0.082	0.48	NO
54	SNAPC4	SNAPC4	SNAPC4	5696	0.076	0.47	NO
55	SNAPC5	SNAPC5	SNAPC5	5708	0.075	0.47	NO
56	GTF2H4	GTF2H4	GTF2H4	5804	0.072	0.47	NO
57	SNAPC2	SNAPC2	SNAPC2	6072	0.066	0.46	NO
58	H3F3A	H3F3A	H3F3A	6075	0.066	0.46	NO
59	HIST1H2BD	HIST1H2BD	HIST1H2BD	6151	0.064	0.46	NO
60	HIST1H2BM	HIST1H2BM	HIST1H2BM	6159	0.064	0.46	NO
61	HIST1H3C	HIST1H3C	HIST1H3C	6733	0.05	0.43	NO
62	EHMT2	EHMT2	EHMT2	6850	0.048	0.42	NO
63	GTF3C5	GTF3C5	GTF3C5	6862	0.048	0.43	NO
64	ERCC3	ERCC3	ERCC3	7918	0.025	0.37	NO
65	BRF2	BRF2	BRF2	8015	0.022	0.36	NO
66	POLR3D	POLR3D	POLR3D	8152	0.019	0.36	NO
67	HIST1H2AC	HIST1H2AC	HIST1H2AC	8181	0.019	0.36	NO
68	POLR3C	POLR3C	POLR3C	8440	0.013	0.34	NO
69	H2AFZ	H2AFZ	H2AFZ	8763	0.0062	0.32	NO
70	POLR3A	POLR3A	POLR3A	9206	-0.0038	0.3	NO
71	GTF3C2	GTF3C2	GTF3C2	9273	-0.0053	0.3	NO
72	TBP	TBP	TBP	9281	-0.0055	0.3	NO
73	POLR3B	POLR3B	POLR3B	9885	-0.018	0.26	NO
74	ZNF143	ZNF143	ZNF143	10188	-0.024	0.25	NO
75	HIST1H2AD	HIST1H2AD	HIST1H2AD	10420	-0.029	0.24	NO
76	HIST1H3E	HIST1H3E	HIST1H3E	10515	-0.031	0.23	NO
77	POLR1B	POLR1B	POLR1B	10553	-0.032	0.23	NO
78	HIST2H2BE	HIST2H2BE	HIST2H2BE	10651	-0.034	0.23	NO
79	GTF3C3	GTF3C3	GTF3C3	11104	-0.044	0.2	NO
80	POLR1A	POLR1A	POLR1A	11420	-0.05	0.19	NO
81	GTF2H3	GTF2H3	GTF2H3	11488	-0.052	0.19	NO
82	SNAPC3	SNAPC3	SNAPC3	11539	-0.053	0.19	NO
83	CCNH	CCNH	CCNH	12142	-0.066	0.16	NO
84	GTF3C4	GTF3C4	GTF3C4	12362	-0.072	0.15	NO
85	GTF2H1	GTF2H1	GTF2H1	12404	-0.073	0.15	NO
86	POLR1D	POLR1D	POLR1D	12594	-0.077	0.14	NO
87	MNAT1	MNAT1	MNAT1	12655	-0.079	0.14	NO
88	UBTF	UBTF	UBTF	12664	-0.079	0.14	NO
89	H3F3B	H3F3B	H3F3B	13106	-0.089	0.12	NO
90	LZTS1	LZTS1	LZTS1	13335	-0.094	0.11	NO
91	PTRF	PTRF	PTRF	14079	-0.11	0.074	NO
92	TFB2M	TFB2M	TFB2M	14193	-0.12	0.073	NO
93	NFIB	NFIB	NFIB	14861	-0.14	0.041	NO
94	POLR3F	POLR3F	POLR3F	14938	-0.14	0.042	NO
95	HIST4H4	HIST4H4	HIST4H4	15010	-0.14	0.044	NO
96	POU2F1	POU2F1	POU2F1	15137	-0.14	0.042	NO
97	RRN3	RRN3	RRN3	15336	-0.15	0.037	NO
98	CDK7	CDK7	CDK7	15684	-0.16	0.024	NO
99	ERCC6	ERCC6	ERCC6	15698	-0.16	0.03	NO
100	MBD2	MBD2	MBD2	15725	-0.16	0.034	NO
101	POLR2K	POLR2K	POLR2K	16014	-0.17	0.025	NO
102	TFAM	TFAM	TFAM	16351	-0.19	0.014	NO
103	TAF1B	TAF1B	TAF1B	16819	-0.21	-0.0038	NO
104	CBX3	CBX3	CBX3	16964	-0.22	-0.0033	NO
105	POLR3GL	POLR3GL	POLR3GL	17029	-0.22	0.0019	NO
106	MTERF	MTERF	MTERF	17453	-0.26	-0.012	NO
107	SNAPC1	SNAPC1	SNAPC1	17605	-0.28	-0.0091	NO
108	TAF1A	TAF1A	TAF1A	17767	-0.3	-0.0061	NO
109	SSB	SSB	SSB	17771	-0.31	0.0057	NO
110	KAT2B	KAT2B	KAT2B	17773	-0.31	0.018	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 TRANSCRIPTION.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Methods & Data

Input

Gene set database = c2.cp.v4.0.symbols.gmt
Expression data file = READ-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = READ-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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