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

Bladder Urothelial Carcinoma (Primary solid tumor)

21 August 2015 | analyses__2015_08_21

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in BLCA-TP. Broad Institute of MIT and Harvard. doi:10.7908/C18C9VC1

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 in BLCA-TP. 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: 192
Number of samples: 408
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 3 :[ clus1 ] 116
pheno.type: 2 - 3 :[ clus2 ] 182
pheno.type: 3 - 3 :[ clus3 ] 110

For the expression subtypes of 18215 genes in 409 samples, GSEA found enriched gene sets in each cluster using 408 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA ALK PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA BCR PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA FCER1 PATHWAY, BIOCARTA FMLP PATHWAY

And common core enriched genes are PIK3CG, AKT3, IGF1, PIK3CD, PIK3R5, FGFR1, LEF1, PDGFC, PDGFRA, PDGFRB

clus2

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS, KEGG FATTY ACID METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG TYROSINE METABOLISM, KEGG GLUTATHIONE METABOLISM, KEGG STARCH AND SUCROSE METABOLISM, KEGG GLYCEROPHOSPHOLIPID METABOLISM, KEGG ETHER LIPID METABOLISM

And common core enriched genes are UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A8, UGT1A9, UGT2A3, UGT2B10

clus3

Top enriched gene sets are BIOCARTA G1 PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA MAPK PATHWAY, BIOCARTA P38MAPK PATHWAY, BIOCARTA IL1R PATHWAY, BIOCARTA TNFR1 PATHWAY, KEGG PYRIMIDINE METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS

And common core enriched genes are CDK6, CDKN1A, TFDP1, CDK7, PCNA, POLD1, POLD2, POLE2, POLE3, CHUK

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
BIOCARTA NO1 PATHWAY	27	genes.ES.table	0.52	1.3	0.17	0.19	0.97	0.41	0.2	0.33	0.16	0
BIOCARTA ALK PATHWAY	33	genes.ES.table	0.48	1.4	0.09	0.16	0.96	0.33	0.22	0.26	0.13	0
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.39	1.4	0.13	0.18	0.97	0.5	0.38	0.31	0.15	0
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.61	1.7	0.01	0.067	0.49	0.3	0.2	0.24	0	0.003
BIOCARTA BIOPEPTIDES PATHWAY	39	genes.ES.table	0.45	1.5	0.051	0.11	0.86	0.56	0.38	0.35	0.079	0
BIOCARTA HDAC PATHWAY	26	genes.ES.table	0.6	1.7	0.01	0.065	0.47	0.5	0.3	0.35	0	0.003
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.42	1.3	0.23	0.23	0.99	0.5	0.39	0.31	0.2	0
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.43	1.4	0.12	0.16	0.95	0.11	0.074	0.1	0.13	0
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.59	1.7	0.018	0.068	0.57	0.27	0.2	0.22	0.034	0.002
BIOCARTA FMLP PATHWAY	35	genes.ES.table	0.59	1.9	0	0.098	0.17	0.23	0.14	0.2	0	0.022

genes ES table in pathway: BIOCARTA NO1 PATHWAY

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	IGF1	IGF1	IGF1	4	0.88	0.077	YES
2	FGFR1	FGFR1	FGFR1	249	0.64	0.12	YES
3	PIK3R5	PIK3R5	PIK3R5	353	0.61	0.17	YES
4	PDGFRA	PDGFRA	PDGFRA	691	0.53	0.19	YES
5	AKT3	AKT3	AKT3	775	0.51	0.23	YES
6	CREB3L1	CREB3L1	CREB3L1	837	0.5	0.27	YES
7	PDGFC	PDGFC	PDGFC	862	0.5	0.32	YES
8	LEF1	LEF1	LEF1	1081	0.46	0.34	YES
9	PDGFRB	PDGFRB	PDGFRB	1207	0.44	0.38	YES
10	PIK3CG	PIK3CG	PIK3CG	1254	0.44	0.41	YES
11	INSRR	INSRR	INSRR	1284	0.43	0.45	YES
12	CREB5	CREB5	CREB5	1367	0.42	0.48	YES
13	PIK3CD	PIK3CD	PIK3CD	1387	0.42	0.51	YES
14	TCF7L1	TCF7L1	TCF7L1	1770	0.37	0.52	YES
15	BCL2	BCL2	BCL2	2173	0.31	0.53	YES
16	TCF7	TCF7	TCF7	2429	0.28	0.54	YES
17	PDGFB	PDGFB	PDGFB	2464	0.28	0.56	YES
18	PDGFD	PDGFD	PDGFD	2879	0.24	0.56	NO
19	CREB3L3	CREB3L3	CREB3L3	4556	0.12	0.48	NO
20	NKX3-1	NKX3-1	NKX3-1	4583	0.12	0.49	NO
21	PDGFA	PDGFA	PDGFA	4589	0.12	0.5	NO
22	CREB3	CREB3	CREB3	5046	0.095	0.48	NO
23	E2F1	E2F1	E2F1	5449	0.079	0.46	NO
24	CREB3L2	CREB3L2	CREB3L2	5463	0.079	0.47	NO
25	MAPK3	MAPK3	MAPK3	5782	0.068	0.46	NO
26	E2F2	E2F2	E2F2	5902	0.064	0.46	NO
27	GRB2	GRB2	GRB2	6063	0.06	0.46	NO
28	FOXO1	FOXO1	FOXO1	6166	0.057	0.45	NO
29	ARAF	ARAF	ARAF	6619	0.047	0.43	NO
30	CDKN1B	CDKN1B	CDKN1B	6754	0.044	0.43	NO
31	PTEN	PTEN	PTEN	6762	0.044	0.43	NO
32	BAD	BAD	BAD	7053	0.038	0.42	NO
33	TP53	TP53	TP53	7102	0.037	0.42	NO
34	CTNNB1	CTNNB1	CTNNB1	7197	0.035	0.42	NO
35	HSP90B1	HSP90B1	HSP90B1	7562	0.029	0.4	NO
36	IKBKG	IKBKG	IKBKG	7640	0.028	0.4	NO
37	EGF	EGF	EGF	7701	0.026	0.4	NO
38	PIK3R1	PIK3R1	PIK3R1	7820	0.024	0.39	NO
39	CDK2	CDK2	CDK2	7831	0.024	0.4	NO
40	ATF4	ATF4	ATF4	8126	0.02	0.38	NO
41	CHUK	CHUK	CHUK	8167	0.019	0.38	NO
42	NFKB1	NFKB1	NFKB1	8209	0.018	0.38	NO
43	MAP2K2	MAP2K2	MAP2K2	8259	0.018	0.38	NO
44	CCNE1	CCNE1	CCNE1	8536	0.014	0.36	NO
45	PIK3R3	PIK3R3	PIK3R3	8553	0.014	0.36	NO
46	AKT2	AKT2	AKT2	8686	0.012	0.36	NO
47	PIK3CA	PIK3CA	PIK3CA	8689	0.012	0.36	NO
48	MAP2K1	MAP2K1	MAP2K1	9023	0.0074	0.34	NO
49	AR	AR	AR	9054	0.007	0.34	NO
50	PIK3CB	PIK3CB	PIK3CB	9188	0.0054	0.33	NO
51	RELA	RELA	RELA	9209	0.0052	0.33	NO
52	MAPK1	MAPK1	MAPK1	9367	0.0035	0.32	NO
53	NFKBIA	NFKBIA	NFKBIA	9532	0.0019	0.32	NO
54	KLK3	KLK3	KLK3	9970	-0.003	0.29	NO
55	NRAS	NRAS	NRAS	10018	-0.0035	0.29	NO
56	AKT1	AKT1	AKT1	10046	-0.0038	0.29	NO
57	CREBBP	CREBBP	CREBBP	10060	-0.004	0.29	NO
58	RAF1	RAF1	RAF1	10280	-0.0068	0.28	NO
59	CREB1	CREB1	CREB1	10647	-0.011	0.26	NO
60	MTOR	MTOR	MTOR	10706	-0.012	0.26	NO
61	IGF1R	IGF1R	IGF1R	11044	-0.016	0.24	NO
62	HSP90AA1	HSP90AA1	HSP90AA1	11170	-0.017	0.23	NO
63	SOS2	SOS2	SOS2	11197	-0.018	0.23	NO
64	CCNE2	CCNE2	CCNE2	11323	-0.019	0.23	NO
65	SOS1	SOS1	SOS1	12020	-0.027	0.19	NO
66	RB1	RB1	RB1	12198	-0.029	0.18	NO
67	KRAS	KRAS	KRAS	12296	-0.03	0.18	NO
68	GSK3B	GSK3B	GSK3B	12321	-0.031	0.18	NO
69	CDKN1A	CDKN1A	CDKN1A	12459	-0.032	0.18	NO
70	PDPK1	PDPK1	PDPK1	13384	-0.045	0.13	NO
71	MDM2	MDM2	MDM2	13524	-0.047	0.13	NO
72	EGFR	EGFR	EGFR	13569	-0.048	0.13	NO
73	TCF7L2	TCF7L2	TCF7L2	13803	-0.051	0.12	NO
74	EP300	EP300	EP300	13957	-0.053	0.12	NO
75	PIK3R2	PIK3R2	PIK3R2	14062	-0.055	0.12	NO
76	CASP9	CASP9	CASP9	14345	-0.061	0.11	NO
77	FGFR2	FGFR2	FGFR2	14470	-0.064	0.1	NO
78	CREB3L4	CREB3L4	CREB3L4	14908	-0.072	0.086	NO
79	IKBKB	IKBKB	IKBKB	14924	-0.073	0.092	NO
80	CCND1	CCND1	CCND1	15241	-0.08	0.082	NO
81	E2F3	E2F3	E2F3	15555	-0.09	0.072	NO
82	HRAS	HRAS	HRAS	15575	-0.09	0.079	NO
83	ERBB2	ERBB2	ERBB2	16020	-0.11	0.064	NO
84	GSTP1	GSTP1	GSTP1	16147	-0.11	0.067	NO
85	TGFA	TGFA	TGFA	16792	-0.15	0.044	NO
86	BRAF	BRAF	BRAF	17100	-0.18	0.043	NO
87	SRD5A2	SRD5A2	SRD5A2	17343	-0.2	0.047	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: BIOCARTA NO1 PATHWAY.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NO1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA ALK 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	RUNX1T1	RUNX1T1	RUNX1T1	107	0.71	0.085	YES
2	PIK3R5	PIK3R5	PIK3R5	353	0.61	0.15	YES
3	SPI1	SPI1	SPI1	570	0.55	0.21	YES
4	AKT3	AKT3	AKT3	775	0.51	0.26	YES
5	FLT3	FLT3	FLT3	855	0.5	0.32	YES
6	LEF1	LEF1	LEF1	1081	0.46	0.37	YES
7	ZBTB16	ZBTB16	ZBTB16	1198	0.44	0.42	YES
8	PIK3CG	PIK3CG	PIK3CG	1254	0.44	0.47	YES
9	PIK3CD	PIK3CD	PIK3CD	1387	0.42	0.52	YES
10	TCF7L1	TCF7L1	TCF7L1	1770	0.37	0.55	YES
11	TCF7	TCF7	TCF7	2429	0.28	0.55	YES
12	PIM2	PIM2	PIM2	2515	0.27	0.58	YES
13	STAT5A	STAT5A	STAT5A	3869	0.16	0.52	NO
14	KIT	KIT	KIT	3976	0.15	0.54	NO
15	CCNA1	CCNA1	CCNA1	4945	0.099	0.5	NO
16	RARA	RARA	RARA	5561	0.076	0.47	NO
17	MAPK3	MAPK3	MAPK3	5782	0.068	0.47	NO
18	GRB2	GRB2	GRB2	6063	0.06	0.46	NO
19	STAT5B	STAT5B	STAT5B	6262	0.055	0.46	NO
20	ARAF	ARAF	ARAF	6619	0.047	0.44	NO
21	STAT3	STAT3	STAT3	6830	0.043	0.44	NO
22	BAD	BAD	BAD	7053	0.038	0.43	NO
23	RUNX1	RUNX1	RUNX1	7148	0.036	0.43	NO
24	PML	PML	PML	7627	0.028	0.41	NO
25	IKBKG	IKBKG	IKBKG	7640	0.028	0.41	NO
26	PIK3R1	PIK3R1	PIK3R1	7820	0.024	0.4	NO
27	CHUK	CHUK	CHUK	8167	0.019	0.39	NO
28	NFKB1	NFKB1	NFKB1	8209	0.018	0.39	NO
29	MYC	MYC	MYC	8243	0.018	0.39	NO
30	MAP2K2	MAP2K2	MAP2K2	8259	0.018	0.39	NO
31	PIK3R3	PIK3R3	PIK3R3	8553	0.014	0.37	NO
32	AKT2	AKT2	AKT2	8686	0.012	0.37	NO
33	PIK3CA	PIK3CA	PIK3CA	8689	0.012	0.37	NO
34	MAP2K1	MAP2K1	MAP2K1	9023	0.0074	0.35	NO
35	PIK3CB	PIK3CB	PIK3CB	9188	0.0054	0.34	NO
36	RELA	RELA	RELA	9209	0.0052	0.34	NO
37	MAPK1	MAPK1	MAPK1	9367	0.0035	0.34	NO
38	NRAS	NRAS	NRAS	10018	-0.0035	0.3	NO
39	AKT1	AKT1	AKT1	10046	-0.0038	0.3	NO
40	RAF1	RAF1	RAF1	10280	-0.0068	0.29	NO
41	MTOR	MTOR	MTOR	10706	-0.012	0.26	NO
42	SOS2	SOS2	SOS2	11197	-0.018	0.24	NO
43	RPS6KB2	RPS6KB2	RPS6KB2	11579	-0.022	0.22	NO
44	EIF4EBP1	EIF4EBP1	EIF4EBP1	11811	-0.025	0.21	NO
45	SOS1	SOS1	SOS1	12020	-0.027	0.2	NO
46	PIM1	PIM1	PIM1	12144	-0.028	0.2	NO
47	KRAS	KRAS	KRAS	12296	-0.03	0.2	NO
48	RPS6KB1	RPS6KB1	RPS6KB1	13625	-0.048	0.13	NO
49	TCF7L2	TCF7L2	TCF7L2	13803	-0.051	0.13	NO
50	PIK3R2	PIK3R2	PIK3R2	14062	-0.055	0.12	NO
51	IKBKB	IKBKB	IKBKB	14924	-0.073	0.082	NO
52	CCND1	CCND1	CCND1	15241	-0.08	0.075	NO
53	HRAS	HRAS	HRAS	15575	-0.09	0.068	NO
54	BRAF	BRAF	BRAF	17100	-0.18	0.0072	NO
55	JUP	JUP	JUP	17334	-0.2	0.02	NO
56	CEBPA	CEBPA	CEBPA	17464	-0.21	0.04	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: BIOCARTA ALK PATHWAY.

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

genes ES table in pathway: BIOCARTA AT1R PATHWAY

Table 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	IGF1	IGF1	IGF1	4	0.88	0.066	YES
2	FGF7	FGF7	FGF7	37	0.77	0.12	YES
3	FGF2	FGF2	FGF2	161	0.67	0.17	YES
4	HGF	HGF	HGF	186	0.66	0.22	YES
5	FGFR1	FGFR1	FGFR1	249	0.64	0.26	YES
6	FGF14	FGF14	FGF14	328	0.61	0.3	YES
7	PIK3R5	PIK3R5	PIK3R5	353	0.61	0.35	YES
8	FGF1	FGF1	FGF1	580	0.55	0.38	YES
9	PDGFRA	PDGFRA	PDGFRA	691	0.53	0.41	YES
10	AKT3	AKT3	AKT3	775	0.51	0.44	YES
11	PDGFC	PDGFC	PDGFC	862	0.5	0.48	YES
12	MITF	MITF	MITF	1021	0.47	0.5	YES
13	FGF10	FGF10	FGF10	1125	0.46	0.53	YES
14	PDGFRB	PDGFRB	PDGFRB	1207	0.44	0.56	YES
15	PIK3CG	PIK3CG	PIK3CG	1254	0.44	0.59	YES
16	FGF18	FGF18	FGF18	1296	0.43	0.62	YES
17	PIK3CD	PIK3CD	PIK3CD	1387	0.42	0.65	YES
18	FGF13	FGF13	FGF13	1829	0.36	0.65	YES
19	FGF5	FGF5	FGF5	1848	0.36	0.68	YES
20	FGF9	FGF9	FGF9	2071	0.33	0.69	YES
21	PDGFB	PDGFB	PDGFB	2464	0.28	0.69	NO
22	PDGFD	PDGFD	PDGFD	2879	0.24	0.68	NO
23	CDK6	CDK6	CDK6	4112	0.14	0.62	NO
24	CDKN2A	CDKN2A	CDKN2A	4248	0.14	0.63	NO
25	PDGFA	PDGFA	PDGFA	4589	0.12	0.62	NO
26	MAPK3	MAPK3	MAPK3	5782	0.068	0.56	NO
27	E2F2	E2F2	E2F2	5902	0.064	0.56	NO
28	FGF22	FGF22	FGF22	6456	0.05	0.53	NO
29	ARAF	ARAF	ARAF	6619	0.047	0.52	NO
30	PTEN	PTEN	PTEN	6762	0.044	0.52	NO
31	BAD	BAD	BAD	7053	0.038	0.51	NO
32	TP53	TP53	TP53	7102	0.037	0.51	NO
33	CDK4	CDK4	CDK4	7258	0.034	0.5	NO
34	FGF8	FGF8	FGF8	7343	0.033	0.5	NO
35	MET	MET	MET	7535	0.029	0.49	NO
36	EGF	EGF	EGF	7701	0.026	0.48	NO
37	PIK3R1	PIK3R1	PIK3R1	7820	0.024	0.48	NO
38	MAP2K2	MAP2K2	MAP2K2	8259	0.018	0.46	NO
39	PIK3R3	PIK3R3	PIK3R3	8553	0.014	0.44	NO
40	AKT2	AKT2	AKT2	8686	0.012	0.43	NO
41	PIK3CA	PIK3CA	PIK3CA	8689	0.012	0.43	NO
42	MAP2K1	MAP2K1	MAP2K1	9023	0.0074	0.42	NO
43	PIK3CB	PIK3CB	PIK3CB	9188	0.0054	0.41	NO
44	MAPK1	MAPK1	MAPK1	9367	0.0035	0.4	NO
45	NRAS	NRAS	NRAS	10018	-0.0035	0.36	NO
46	AKT1	AKT1	AKT1	10046	-0.0038	0.36	NO
47	FGF19	FGF19	FGF19	10087	-0.0042	0.36	NO
48	RAF1	RAF1	RAF1	10280	-0.0068	0.35	NO
49	FGF12	FGF12	FGF12	10961	-0.015	0.31	NO
50	IGF1R	IGF1R	IGF1R	11044	-0.016	0.31	NO
51	RB1	RB1	RB1	12198	-0.029	0.25	NO
52	KRAS	KRAS	KRAS	12296	-0.03	0.24	NO
53	CDKN1A	CDKN1A	CDKN1A	12459	-0.032	0.24	NO
54	FGF17	FGF17	FGF17	13442	-0.046	0.19	NO
55	MDM2	MDM2	MDM2	13524	-0.047	0.19	NO
56	EGFR	EGFR	EGFR	13569	-0.048	0.19	NO
57	PIK3R2	PIK3R2	PIK3R2	14062	-0.055	0.16	NO
58	CCND1	CCND1	CCND1	15241	-0.08	0.11	NO
59	E2F3	E2F3	E2F3	15555	-0.09	0.096	NO
60	HRAS	HRAS	HRAS	15575	-0.09	0.1	NO
61	FGF11	FGF11	FGF11	16996	-0.17	0.036	NO
62	BRAF	BRAF	BRAF	17100	-0.18	0.044	NO
63	CDH1	CDH1	CDH1	17510	-0.22	0.038	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: BIOCARTA AT1R PATHWAY.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AT1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA BCR 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	IGF1	IGF1	IGF1	4	0.88	0.16	YES
2	PIK3R5	PIK3R5	PIK3R5	353	0.61	0.25	YES
3	AKT3	AKT3	AKT3	775	0.51	0.31	YES
4	PIK3CG	PIK3CG	PIK3CG	1254	0.44	0.36	YES
5	PIK3CD	PIK3CD	PIK3CD	1387	0.42	0.43	YES
6	VEGFC	VEGFC	VEGFC	2409	0.28	0.43	YES
7	PRKAA2	PRKAA2	PRKAA2	2710	0.25	0.46	YES
8	RPS6KA2	RPS6KA2	RPS6KA2	3562	0.18	0.44	YES
9	VEGFB	VEGFB	VEGFB	3781	0.17	0.46	YES
10	FIGF	FIGF	FIGF	4016	0.15	0.47	YES
11	ULK2	ULK2	ULK2	4838	0.1	0.44	NO
12	MAPK3	MAPK3	MAPK3	5782	0.068	0.41	NO
13	EIF4E2	EIF4E2	EIF4E2	6733	0.044	0.36	NO
14	RHEB	RHEB	RHEB	7311	0.033	0.34	NO
15	HIF1A	HIF1A	HIF1A	7589	0.029	0.32	NO
16	PIK3R1	PIK3R1	PIK3R1	7820	0.024	0.32	NO
17	CAB39	CAB39	CAB39	8406	0.016	0.29	NO
18	PIK3R3	PIK3R3	PIK3R3	8553	0.014	0.28	NO
19	AKT2	AKT2	AKT2	8686	0.012	0.28	NO
20	PIK3CA	PIK3CA	PIK3CA	8689	0.012	0.28	NO
21	RPTOR	RPTOR	RPTOR	8696	0.012	0.28	NO
22	PIK3CB	PIK3CB	PIK3CB	9188	0.0054	0.25	NO
23	MAPK1	MAPK1	MAPK1	9367	0.0035	0.24	NO
24	MLST8	MLST8	MLST8	9877	-0.002	0.22	NO
25	AKT1	AKT1	AKT1	10046	-0.0038	0.21	NO
26	RPS6KA3	RPS6KA3	RPS6KA3	10062	-0.004	0.21	NO
27	STRADA	STRADA	STRADA	10503	-0.0095	0.19	NO
28	EIF4B	EIF4B	EIF4B	10578	-0.01	0.18	NO
29	MTOR	MTOR	MTOR	10706	-0.012	0.18	NO
30	TSC2	TSC2	TSC2	10790	-0.013	0.18	NO
31	ULK1	ULK1	ULK1	10841	-0.014	0.18	NO
32	STK11	STK11	STK11	10987	-0.015	0.17	NO
33	DDIT4	DDIT4	DDIT4	11160	-0.017	0.16	NO
34	RPS6KB2	RPS6KB2	RPS6KB2	11579	-0.022	0.15	NO
35	EIF4EBP1	EIF4EBP1	EIF4EBP1	11811	-0.025	0.14	NO
36	TSC1	TSC1	TSC1	12363	-0.031	0.11	NO
37	PDPK1	PDPK1	PDPK1	13384	-0.045	0.064	NO
38	RPS6KB1	RPS6KB1	RPS6KB1	13625	-0.048	0.06	NO
39	EIF4E	EIF4E	EIF4E	13898	-0.052	0.054	NO
40	PIK3R2	PIK3R2	PIK3R2	14062	-0.055	0.055	NO
41	RPS6	RPS6	RPS6	14206	-0.058	0.058	NO
42	RPS6KA1	RPS6KA1	RPS6KA1	14514	-0.064	0.052	NO
43	PRKAA1	PRKAA1	PRKAA1	14529	-0.065	0.063	NO
44	RICTOR	RICTOR	RICTOR	14547	-0.065	0.074	NO
45	ULK3	ULK3	ULK3	14919	-0.073	0.066	NO
46	RPS6KA6	RPS6KA6	RPS6KA6	16129	-0.11	0.02	NO
47	CAB39L	CAB39L	CAB39L	16420	-0.13	0.026	NO
48	BRAF	BRAF	BRAF	17100	-0.18	0.021	NO
49	VEGFA	VEGFA	VEGFA	17530	-0.22	0.037	NO

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

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

genes ES table in pathway: BIOCARTA BIOPEPTIDES PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IGF1	IGF1	IGF1	4	0.88	0.11	YES
2	FGF2	FGF2	FGF2	161	0.67	0.18	YES
3	HAND2	HAND2	HAND2	303	0.62	0.25	YES
4	HAND1	HAND1	HAND1	571	0.55	0.31	YES
5	NFATC1	NFATC1	NFATC1	1043	0.47	0.34	YES
6	PIK3CG	PIK3CG	PIK3CG	1254	0.44	0.38	YES
7	CAMK1G	CAMK1G	CAMK1G	1377	0.42	0.43	YES
8	PRKAR2B	PRKAR2B	PRKAR2B	1959	0.34	0.44	YES
9	CAMK4	CAMK4	CAMK4	1981	0.34	0.48	YES
10	CAMK1	CAMK1	CAMK1	2299	0.3	0.5	YES
11	NFATC4	NFATC4	NFATC4	2389	0.29	0.53	YES
12	NFATC2	NFATC2	NFATC2	2457	0.28	0.56	YES
13	LIF	LIF	LIF	2467	0.28	0.6	YES
14	AGT	AGT	AGT	2569	0.27	0.62	YES
15	ACTA1	ACTA1	ACTA1	3401	0.2	0.6	YES
16	GATA4	GATA4	GATA4	3672	0.18	0.61	YES
17	PPP3CC	PPP3CC	PPP3CC	3721	0.17	0.63	YES
18	EDN1	EDN1	EDN1	3823	0.16	0.64	YES
19	NKX2-5	NKX2-5	NKX2-5	4777	0.11	0.6	NO
20	PRKAR2A	PRKAR2A	PRKAR2A	5121	0.091	0.59	NO
21	PPP3CB	PPP3CB	PPP3CB	5203	0.088	0.6	NO
22	CALM2	CALM2	CALM2	5414	0.08	0.6	NO
23	MAPK3	MAPK3	MAPK3	5782	0.068	0.59	NO
24	PRKACB	PRKACB	PRKACB	6671	0.046	0.54	NO
25	MAPK14	MAPK14	MAPK14	6794	0.043	0.54	NO
26	NFATC3	NFATC3	NFATC3	6862	0.042	0.54	NO
27	PPP3CA	PPP3CA	PPP3CA	6911	0.041	0.55	NO
28	CALM3	CALM3	CALM3	6917	0.041	0.55	NO
29	FKBP1A	FKBP1A	FKBP1A	7093	0.037	0.55	NO
30	CALR	CALR	CALR	7481	0.03	0.53	NO
31	CALM1	CALM1	CALM1	7534	0.03	0.53	NO
32	PIK3R1	PIK3R1	PIK3R1	7820	0.024	0.52	NO
33	PRKAR1A	PRKAR1A	PRKAR1A	8430	0.015	0.49	NO
34	PIK3CA	PIK3CA	PIK3CA	8689	0.012	0.47	NO
35	PRKAR1B	PRKAR1B	PRKAR1B	8843	0.0099	0.47	NO
36	MAP2K1	MAP2K1	MAP2K1	9023	0.0074	0.46	NO
37	MAPK1	MAPK1	MAPK1	9367	0.0035	0.44	NO
38	HBEGF	HBEGF	HBEGF	9502	0.0021	0.43	NO
39	AKT1	AKT1	AKT1	10046	-0.0038	0.4	NO
40	CREBBP	CREBBP	CREBBP	10060	-0.004	0.4	NO
41	CTF1	CTF1	CTF1	10162	-0.0053	0.4	NO
42	RAF1	RAF1	RAF1	10280	-0.0068	0.39	NO
43	MAPK8	MAPK8	MAPK8	11676	-0.023	0.32	NO
44	GSK3B	GSK3B	GSK3B	12321	-0.031	0.28	NO
45	F2	F2	F2	13010	-0.04	0.25	NO
46	RPS6KB1	RPS6KB1	RPS6KB1	13625	-0.048	0.22	NO
47	NPPA	NPPA	NPPA	14243	-0.059	0.2	NO
48	CSNK1A1	CSNK1A1	CSNK1A1	14779	-0.07	0.18	NO
49	HRAS	HRAS	HRAS	15575	-0.09	0.14	NO

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

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA BIOPEPTIDES PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA HDAC 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	FPR1	FPR1	FPR1	141	0.68	0.14	YES
2	NCF1C	NCF1C	NCF1C	382	0.6	0.25	YES
3	NFATC1	NFATC1	NFATC1	1043	0.47	0.31	YES
4	NCF2	NCF2	NCF2	1154	0.45	0.4	YES
5	CAMK1G	CAMK1G	CAMK1G	1377	0.42	0.47	YES
6	CAMK1	CAMK1	CAMK1	2299	0.3	0.48	YES
7	NFATC4	NFATC4	NFATC4	2389	0.29	0.54	YES
8	NFATC2	NFATC2	NFATC2	2457	0.28	0.59	YES
9	PPP3CC	PPP3CC	PPP3CC	3721	0.17	0.56	NO
10	PPP3CB	PPP3CB	PPP3CB	5203	0.088	0.5	NO
11	CALM2	CALM2	CALM2	5414	0.08	0.5	NO
12	MAPK3	MAPK3	MAPK3	5782	0.068	0.5	NO
13	MAPK14	MAPK14	MAPK14	6794	0.043	0.45	NO
14	NFATC3	NFATC3	NFATC3	6862	0.042	0.46	NO
15	ELK1	ELK1	ELK1	6879	0.042	0.46	NO
16	PPP3CA	PPP3CA	PPP3CA	6911	0.041	0.47	NO
17	CALM3	CALM3	CALM3	6917	0.041	0.48	NO
18	CALM1	CALM1	CALM1	7534	0.03	0.45	NO
19	GNB1	GNB1	GNB1	7543	0.029	0.46	NO
20	NFKB1	NFKB1	NFKB1	8209	0.018	0.42	NO
21	MAP2K2	MAP2K2	MAP2K2	8259	0.018	0.42	NO
22	MAP2K3	MAP2K3	MAP2K3	8324	0.017	0.42	NO
23	MAP3K1	MAP3K1	MAP3K1	8370	0.016	0.42	NO
24	MAP2K1	MAP2K1	MAP2K1	9023	0.0074	0.39	NO
25	RELA	RELA	RELA	9209	0.0052	0.38	NO
26	MAPK1	MAPK1	MAPK1	9367	0.0035	0.37	NO
27	NFKBIA	NFKBIA	NFKBIA	9532	0.0019	0.36	NO
28	RAF1	RAF1	RAF1	10280	-0.0068	0.32	NO
29	RAC1	RAC1	RAC1	11993	-0.027	0.24	NO
30	PLCB1	PLCB1	PLCB1	12386	-0.032	0.22	NO
31	MAP2K6	MAP2K6	MAP2K6	12653	-0.035	0.21	NO
32	PIK3C2G	PIK3C2G	PIK3C2G	14757	-0.069	0.11	NO
33	PAK1	PAK1	PAK1	14825	-0.071	0.12	NO
34	HRAS	HRAS	HRAS	15575	-0.09	0.1	NO
35	GNGT1	GNGT1	GNGT1	17369	-0.2	0.046	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: BIOCARTA HDAC PATHWAY.

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

genes ES table in pathway: BIOCARTA EGF PATHWAY

Table S7. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ENPP1	ENPP1	ENPP1	43	0.76	0.038	YES
2	PDE1A	PDE1A	PDE1A	103	0.71	0.072	YES
3	PDE4B	PDE4B	PDE4B	434	0.59	0.084	YES
4	NPR1	NPR1	NPR1	615	0.54	0.1	YES
5	ADCY5	ADCY5	ADCY5	695	0.53	0.13	YES
6	PDE1B	PDE1B	PDE1B	728	0.52	0.15	YES
7	PDE2A	PDE2A	PDE2A	987	0.47	0.16	YES
8	ADCY2	ADCY2	ADCY2	1009	0.47	0.19	YES
9	ENPP3	ENPP3	ENPP3	1055	0.46	0.21	YES
10	PAPSS2	PAPSS2	PAPSS2	1268	0.44	0.22	YES
11	PDE6G	PDE6G	PDE6G	1313	0.43	0.24	YES
12	GUCY1B3	GUCY1B3	GUCY1B3	1372	0.42	0.26	YES
13	GUCY1A3	GUCY1A3	GUCY1A3	1382	0.42	0.28	YES
14	ADCY4	ADCY4	ADCY4	1678	0.38	0.28	YES
15	NT5M	NT5M	NT5M	1710	0.38	0.3	YES
16	PDE5A	PDE5A	PDE5A	1760	0.37	0.32	YES
17	PDE3A	PDE3A	PDE3A	1784	0.37	0.34	YES
18	AMPD1	AMPD1	AMPD1	1809	0.36	0.35	YES
19	NPR2	NPR2	NPR2	1827	0.36	0.37	YES
20	GMPR	GMPR	GMPR	2046	0.33	0.38	YES
21	NT5E	NT5E	NT5E	2060	0.33	0.39	YES
22	PDE1C	PDE1C	PDE1C	2137	0.32	0.4	YES
23	PDE6B	PDE6B	PDE6B	2169	0.31	0.42	YES
24	AK5	AK5	AK5	2428	0.28	0.42	YES
25	GUCY1A2	GUCY1A2	GUCY1A2	2530	0.27	0.43	YES
26	ADCY7	ADCY7	ADCY7	2761	0.25	0.43	YES
27	ENTPD1	ENTPD1	ENTPD1	2782	0.25	0.44	YES
28	PDE11A	PDE11A	PDE11A	2833	0.24	0.45	YES
29	ADCY9	ADCY9	ADCY9	3050	0.22	0.45	YES
30	NME5	NME5	NME5	3229	0.21	0.45	YES
31	PDE3B	PDE3B	PDE3B	3391	0.2	0.45	YES
32	PDE4A	PDE4A	PDE4A	3486	0.19	0.46	YES
33	ADA	ADA	ADA	3637	0.18	0.46	YES
34	AK1	AK1	AK1	4001	0.15	0.45	NO
35	POLR3GL	POLR3GL	POLR3GL	4069	0.15	0.45	NO
36	PDE4D	PDE4D	PDE4D	4652	0.11	0.42	NO
37	PDE9A	PDE9A	PDE9A	4698	0.11	0.43	NO
38	NME7	NME7	NME7	4725	0.11	0.43	NO
39	IMPDH1	IMPDH1	IMPDH1	4742	0.11	0.44	NO
40	AK7	AK7	AK7	4831	0.1	0.44	NO
41	PRIM1	PRIM1	PRIM1	5018	0.096	0.43	NO
42	AK3L1	AK3L1	AK3L1	5553	0.076	0.41	NO
43	POLR1E	POLR1E	POLR1E	5595	0.075	0.41	NO
44	ENTPD8	ENTPD8	ENTPD8	5624	0.074	0.41	NO
45	PDE7B	PDE7B	PDE7B	5645	0.073	0.41	NO
46	PRPS1	PRPS1	PRPS1	5646	0.073	0.42	NO
47	AMPD3	AMPD3	AMPD3	5696	0.071	0.42	NO
48	POLR3C	POLR3C	POLR3C	5901	0.064	0.41	NO
49	POLR3D	POLR3D	POLR3D	5909	0.064	0.41	NO
50	PRPS1L1	PRPS1L1	PRPS1L1	6037	0.061	0.41	NO
51	POLD4	POLD4	POLD4	6553	0.048	0.38	NO
52	POLA2	POLA2	POLA2	6555	0.048	0.39	NO
53	AMPD2	AMPD2	AMPD2	6605	0.047	0.39	NO
54	POLE4	POLE4	POLE4	7013	0.039	0.37	NO
55	GUK1	GUK1	GUK1	7066	0.038	0.36	NO
56	PDE6D	PDE6D	PDE6D	7069	0.038	0.37	NO
57	CANT1	CANT1	CANT1	7126	0.036	0.37	NO
58	GUCY2C	GUCY2C	GUCY2C	7147	0.036	0.37	NO
59	POLR3G	POLR3G	POLR3G	7209	0.035	0.36	NO
60	POLR2L	POLR2L	POLR2L	7286	0.034	0.36	NO
61	ADSL	ADSL	ADSL	7291	0.034	0.36	NO
62	ATIC	ATIC	ATIC	7626	0.028	0.35	NO
63	POLD1	POLD1	POLD1	7733	0.026	0.34	NO
64	POLD3	POLD3	POLD3	7851	0.024	0.34	NO
65	DCK	DCK	DCK	7877	0.023	0.34	NO
66	GUCY2D	GUCY2D	GUCY2D	7997	0.022	0.33	NO
67	PRIM2	PRIM2	PRIM2	8011	0.021	0.33	NO
68	PAPSS1	PAPSS1	PAPSS1	8022	0.021	0.33	NO
69	ADCY6	ADCY6	ADCY6	8046	0.021	0.33	NO
70	POLR2I	POLR2I	POLR2I	8072	0.02	0.33	NO
71	NME4	NME4	NME4	8188	0.019	0.33	NO
72	PDE6A	PDE6A	PDE6A	8207	0.018	0.33	NO
73	NME6	NME6	NME6	8237	0.018	0.33	NO
74	RRM1	RRM1	RRM1	8293	0.017	0.32	NO
75	POLR2D	POLR2D	POLR2D	8305	0.017	0.32	NO
76	POLA1	POLA1	POLA1	8312	0.017	0.32	NO
77	POLR2E	POLR2E	POLR2E	8321	0.017	0.32	NO
78	PDE8B	PDE8B	PDE8B	8322	0.017	0.33	NO
79	PNP	PNP	PNP	8393	0.016	0.32	NO
80	NUDT5	NUDT5	NUDT5	8521	0.014	0.32	NO
81	GMPS	GMPS	GMPS	8579	0.013	0.31	NO
82	POLR2G	POLR2G	POLR2G	8932	0.0085	0.3	NO
83	POLE3	POLE3	POLE3	8937	0.0085	0.3	NO
84	POLR3F	POLR3F	POLR3F	9095	0.0064	0.29	NO
85	NME3	NME3	NME3	9319	0.004	0.28	NO
86	POLR2C	POLR2C	POLR2C	9430	0.0029	0.27	NO
87	NUDT2	NUDT2	NUDT2	9639	0.00063	0.26	NO
88	ITPA	ITPA	ITPA	9778	-0.00096	0.25	NO
89	ADCY1	ADCY1	ADCY1	9854	-0.0018	0.25	NO
90	RRM2	RRM2	RRM2	9915	-0.0024	0.24	NO
91	RRM2B	RRM2B	RRM2B	10032	-0.0036	0.24	NO
92	POLD2	POLD2	POLD2	10141	-0.0051	0.23	NO
93	ADCY10	ADCY10	ADCY10	10344	-0.0076	0.22	NO
94	POLR3A	POLR3A	POLR3A	10468	-0.0092	0.21	NO
95	PKM2	PKM2	PKM2	10677	-0.011	0.2	NO
96	IMPDH2	IMPDH2	IMPDH2	10725	-0.012	0.2	NO
97	POLR1A	POLR1A	POLR1A	10772	-0.012	0.2	NO
98	GMPR2	GMPR2	GMPR2	10958	-0.015	0.19	NO
99	POLR2J2	POLR2J2	POLR2J2	10978	-0.015	0.19	NO
100	PFAS	PFAS	PFAS	11141	-0.017	0.18	NO
101	NME1-NME2	NME1-NME2	NME1-NME2	11161	-0.017	0.18	NO
102	GART	GART	GART	11193	-0.018	0.18	NO
103	AK2	AK2	AK2	11218	-0.018	0.18	NO
104	ADK	ADK	ADK	11240	-0.018	0.18	NO
105	POLE2	POLE2	POLE2	11422	-0.02	0.17	NO
106	POLR2F	POLR2F	POLR2F	11531	-0.021	0.16	NO
107	ENTPD2	ENTPD2	ENTPD2	12019	-0.027	0.14	NO
108	DGUOK	DGUOK	DGUOK	12063	-0.028	0.14	NO
109	POLR2A	POLR2A	POLR2A	12172	-0.029	0.13	NO
110	POLR3H	POLR3H	POLR3H	12180	-0.029	0.14	NO
111	POLE	POLE	POLE	12219	-0.03	0.14	NO
112	PRUNE	PRUNE	PRUNE	12234	-0.03	0.14	NO
113	POLR2B	POLR2B	POLR2B	12346	-0.031	0.13	NO
114	FHIT	FHIT	FHIT	12375	-0.031	0.13	NO
115	POLR3K	POLR3K	POLR3K	12449	-0.032	0.13	NO
116	APRT	APRT	APRT	12729	-0.036	0.12	NO
117	POLR2J	POLR2J	POLR2J	12987	-0.04	0.1	NO
118	PNPT1	PNPT1	PNPT1	13154	-0.042	0.096	NO
119	ENTPD6	ENTPD6	ENTPD6	13316	-0.044	0.09	NO
120	HPRT1	HPRT1	HPRT1	13544	-0.047	0.08	NO
121	ADSS	ADSS	ADSS	13554	-0.048	0.082	NO
122	PDE7A	PDE7A	PDE7A	13584	-0.048	0.082	NO
123	PKLR	PKLR	PKLR	13620	-0.048	0.083	NO
124	NUDT9	NUDT9	NUDT9	13749	-0.05	0.079	NO
125	PRPS2	PRPS2	PRPS2	13785	-0.051	0.079	NO
126	PPAT	PPAT	PPAT	13875	-0.052	0.077	NO
127	POLR2K	POLR2K	POLR2K	14014	-0.054	0.072	NO
128	POLR1D	POLR1D	POLR1D	14024	-0.055	0.075	NO
129	POLR2H	POLR2H	POLR2H	14026	-0.055	0.078	NO
130	NME2	NME2	NME2	14047	-0.055	0.079	NO
131	ENTPD4	ENTPD4	ENTPD4	14130	-0.057	0.078	NO
132	NME1	NME1	NME1	14191	-0.058	0.078	NO
133	POLR3B	POLR3B	POLR3B	14204	-0.058	0.08	NO
134	ZNRD1	ZNRD1	ZNRD1	14394	-0.062	0.073	NO
135	PDE4C	PDE4C	PDE4C	14554	-0.065	0.067	NO
136	PAICS	PAICS	PAICS	14699	-0.068	0.063	NO
137	NT5C3	NT5C3	NT5C3	14743	-0.069	0.064	NO
138	NT5C	NT5C	NT5C	14928	-0.073	0.058	NO
139	PDE8A	PDE8A	PDE8A	15449	-0.086	0.034	NO
140	NT5C2	NT5C2	NT5C2	15469	-0.087	0.037	NO
141	POLR1B	POLR1B	POLR1B	15512	-0.088	0.039	NO
142	POLR1C	POLR1C	POLR1C	15740	-0.096	0.032	NO
143	POLR2J3	POLR2J3	POLR2J3	16501	-0.13	-0.0032	NO
144	ENTPD5	ENTPD5	ENTPD5	16647	-0.14	-0.0038	NO
145	PDE10A	PDE10A	PDE10A	17355	-0.2	-0.032	NO
146	ADSSL1	ADSSL1	ADSSL1	17536	-0.22	-0.031	NO
147	GDA	GDA	GDA	17826	-0.27	-0.032	NO
148	XDH	XDH	XDH	17988	-0.32	-0.024	NO
149	ENTPD3	ENTPD3	ENTPD3	18016	-0.32	-0.009	NO
150	NT5C1B	NT5C1B	NT5C1B	18087	-0.36	0.0061	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: BIOCARTA EGF PATHWAY.

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

genes ES table in pathway: BIOCARTA ERK PATHWAY

Table S8. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	FGF7	FGF7	FGF7	37	0.77	0.02	YES
2	FGF2	FGF2	FGF2	161	0.67	0.032	YES
3	ITGAM	ITGAM	ITGAM	171	0.67	0.05	YES
4	ITGA11	ITGA11	ITGA11	188	0.66	0.068	YES
5	NCKAP1L	NCKAP1L	NCKAP1L	210	0.65	0.085	YES
6	FGFR1	FGFR1	FGFR1	249	0.64	0.1	YES
7	ITGA7	ITGA7	ITGA7	267	0.63	0.12	YES
8	FGF14	FGF14	FGF14	328	0.61	0.13	YES
9	PIK3R5	PIK3R5	PIK3R5	353	0.61	0.15	YES
10	WAS	WAS	WAS	449	0.58	0.16	YES
11	IQGAP2	IQGAP2	IQGAP2	462	0.58	0.18	YES
12	ITGB2	ITGB2	ITGB2	551	0.56	0.19	YES
13	FGF1	FGF1	FGF1	580	0.55	0.2	YES
14	ITGB3	ITGB3	ITGB3	600	0.54	0.21	YES
15	MYLK	MYLK	MYLK	612	0.54	0.23	YES
16	PDGFRA	PDGFRA	PDGFRA	691	0.53	0.24	YES
17	ITGAX	ITGAX	ITGAX	756	0.52	0.25	YES
18	CD14	CD14	CD14	763	0.51	0.26	YES
19	ACTN2	ACTN2	ACTN2	805	0.51	0.28	YES
20	PDGFC	PDGFC	PDGFC	862	0.5	0.29	YES
21	ITGAL	ITGAL	ITGAL	884	0.49	0.3	YES
22	FN1	FN1	FN1	965	0.48	0.31	YES
23	MYL9	MYL9	MYL9	989	0.47	0.32	YES
24	ITGA4	ITGA4	ITGA4	994	0.47	0.33	YES
25	TIAM2	TIAM2	TIAM2	1007	0.47	0.35	YES
26	VAV1	VAV1	VAV1	1049	0.47	0.36	YES
27	MRAS	MRAS	MRAS	1116	0.46	0.37	YES
28	FGF10	FGF10	FGF10	1125	0.46	0.38	YES
29	CHRM2	CHRM2	CHRM2	1143	0.45	0.39	YES
30	PDGFRB	PDGFRB	PDGFRB	1207	0.44	0.4	YES
31	ITGA9	ITGA9	ITGA9	1237	0.44	0.41	YES
32	PIK3CG	PIK3CG	PIK3CG	1254	0.44	0.42	YES
33	INSRR	INSRR	INSRR	1284	0.43	0.43	YES
34	ITGAD	ITGAD	ITGAD	1286	0.43	0.44	YES
35	FGF18	FGF18	FGF18	1296	0.43	0.46	YES
36	PIK3CD	PIK3CD	PIK3CD	1387	0.42	0.46	YES
37	CFL2	CFL2	CFL2	1413	0.41	0.47	YES
38	CHRM4	CHRM4	CHRM4	1591	0.39	0.48	YES
39	ITGA5	ITGA5	ITGA5	1780	0.37	0.48	YES
40	FGF13	FGF13	FGF13	1829	0.36	0.48	YES
41	FGF5	FGF5	FGF5	1848	0.36	0.49	YES
42	ACTN3	ACTN3	ACTN3	1928	0.34	0.5	YES
43	ITGA10	ITGA10	ITGA10	1961	0.34	0.5	YES
44	FGF9	FGF9	FGF9	2071	0.33	0.51	YES
45	ITGA1	ITGA1	ITGA1	2136	0.32	0.51	YES
46	PIP4K2A	PIP4K2A	PIP4K2A	2327	0.3	0.51	YES
47	F2R	F2R	F2R	2412	0.28	0.52	YES
48	PDGFB	PDGFB	PDGFB	2464	0.28	0.52	YES
49	PIP5K1B	PIP5K1B	PIP5K1B	2480	0.28	0.53	YES
50	PAK3	PAK3	PAK3	2503	0.27	0.53	YES
51	BDKRB1	BDKRB1	BDKRB1	2845	0.24	0.52	YES
52	PDGFD	PDGFD	PDGFD	2879	0.24	0.53	YES
53	ARHGEF6	ARHGEF6	ARHGEF6	3020	0.22	0.52	YES
54	ACTN1	ACTN1	ACTN1	3152	0.21	0.52	YES
55	ITGA8	ITGA8	ITGA8	3241	0.21	0.52	YES
56	RRAS	RRAS	RRAS	3256	0.21	0.53	YES
57	MYH10	MYH10	MYH10	3377	0.2	0.53	YES
58	MSN	MSN	MSN	3431	0.19	0.53	YES
59	GSN	GSN	GSN	3441	0.19	0.54	YES
60	CHRM5	CHRM5	CHRM5	3485	0.19	0.54	YES
61	ITGB5	ITGB5	ITGB5	3553	0.18	0.54	YES
62	BDKRB2	BDKRB2	BDKRB2	3647	0.18	0.54	NO
63	RAC2	RAC2	RAC2	3743	0.17	0.54	NO
64	GNA12	GNA12	GNA12	3883	0.16	0.54	NO
65	DIAPH3	DIAPH3	DIAPH3	3967	0.15	0.54	NO
66	PFN4	PFN4	PFN4	4042	0.15	0.54	NO
67	RDX	RDX	RDX	4229	0.14	0.53	NO
68	FGD1	FGD1	FGD1	4232	0.14	0.53	NO
69	ITGB7	ITGB7	ITGB7	4298	0.13	0.53	NO
70	RAC3	RAC3	RAC3	4332	0.13	0.54	NO
71	TMSB4Y	TMSB4Y	TMSB4Y	4426	0.12	0.53	NO
72	CHRM3	CHRM3	CHRM3	4481	0.12	0.53	NO
73	CYFIP2	CYFIP2	CYFIP2	4567	0.12	0.53	NO
74	ITGAV	ITGAV	ITGAV	4587	0.12	0.54	NO
75	PDGFA	PDGFA	PDGFA	4589	0.12	0.54	NO
76	ARPC1B	ARPC1B	ARPC1B	4712	0.11	0.54	NO
77	CHRM1	CHRM1	CHRM1	4781	0.11	0.53	NO
78	VCL	VCL	VCL	4999	0.097	0.52	NO
79	ITGB1	ITGB1	ITGB1	5148	0.09	0.52	NO
80	ENAH	ENAH	ENAH	5185	0.088	0.52	NO
81	LIMK1	LIMK1	LIMK1	5280	0.085	0.52	NO
82	ACTB	ACTB	ACTB	5294	0.084	0.52	NO
83	ITGAE	ITGAE	ITGAE	5363	0.082	0.52	NO
84	ITGA2B	ITGA2B	ITGA2B	5389	0.081	0.52	NO
85	RHOA	RHOA	RHOA	5572	0.075	0.51	NO
86	MYLK3	MYLK3	MYLK3	5619	0.074	0.51	NO
87	MAPK3	MAPK3	MAPK3	5782	0.068	0.5	NO
88	PIP5K1C	PIP5K1C	PIP5K1C	5798	0.068	0.5	NO
89	MYL12A	MYL12A	MYL12A	5923	0.064	0.5	NO
90	ARHGEF1	ARHGEF1	ARHGEF1	5972	0.063	0.5	NO
91	BCAR1	BCAR1	BCAR1	5984	0.062	0.5	NO
92	ABI2	ABI2	ABI2	5998	0.062	0.5	NO
93	TMSL3	TMSL3	TMSL3	6074	0.06	0.5	NO
94	FGD3	FGD3	FGD3	6115	0.059	0.5	NO
95	PFN1	PFN1	PFN1	6212	0.056	0.49	NO
96	ROCK1	ROCK1	ROCK1	6236	0.055	0.49	NO
97	MYH9	MYH9	MYH9	6251	0.055	0.49	NO
98	ROCK2	ROCK2	ROCK2	6446	0.05	0.48	NO
99	FGF22	FGF22	FGF22	6456	0.05	0.48	NO
100	PPP1R12A	PPP1R12A	PPP1R12A	6469	0.05	0.49	NO
101	GNG12	GNG12	GNG12	6571	0.048	0.48	NO
102	ARAF	ARAF	ARAF	6619	0.047	0.48	NO
103	ARPC4	ARPC4	ARPC4	6687	0.045	0.48	NO
104	DIAPH2	DIAPH2	DIAPH2	7022	0.039	0.46	NO
105	SSH1	SSH1	SSH1	7076	0.037	0.46	NO
106	RRAS2	RRAS2	RRAS2	7290	0.034	0.45	NO
107	FGF8	FGF8	FGF8	7343	0.033	0.45	NO
108	DOCK1	DOCK1	DOCK1	7376	0.032	0.44	NO
109	GNA13	GNA13	GNA13	7397	0.032	0.44	NO
110	SSH2	SSH2	SSH2	7412	0.032	0.44	NO
111	IQGAP1	IQGAP1	IQGAP1	7438	0.031	0.44	NO
112	VAV2	VAV2	VAV2	7477	0.031	0.44	NO
113	WASF1	WASF1	WASF1	7499	0.03	0.44	NO
114	CSK	CSK	CSK	7561	0.029	0.44	NO
115	ARPC5	ARPC5	ARPC5	7572	0.029	0.44	NO
116	CFL1	CFL1	CFL1	7694	0.027	0.44	NO
117	EGF	EGF	EGF	7701	0.026	0.44	NO
118	PIK3R1	PIK3R1	PIK3R1	7820	0.024	0.43	NO
119	ACTN4	ACTN4	ACTN4	7857	0.024	0.43	NO
120	PIP5K1A	PIP5K1A	PIP5K1A	8073	0.02	0.42	NO
121	PIP4K2B	PIP4K2B	PIP4K2B	8186	0.019	0.41	NO
122	MAP2K2	MAP2K2	MAP2K2	8259	0.018	0.41	NO
123	ARPC5L	ARPC5L	ARPC5L	8288	0.017	0.41	NO
124	PIK3R3	PIK3R3	PIK3R3	8553	0.014	0.39	NO
125	PIK3CA	PIK3CA	PIK3CA	8689	0.012	0.38	NO
126	MAP2K1	MAP2K1	MAP2K1	9023	0.0074	0.37	NO
127	BAIAP2	BAIAP2	BAIAP2	9089	0.0065	0.36	NO
128	CYFIP1	CYFIP1	CYFIP1	9145	0.0058	0.36	NO
129	PIK3CB	PIK3CB	PIK3CB	9188	0.0054	0.36	NO
130	ARPC2	ARPC2	ARPC2	9212	0.0052	0.36	NO
131	MAPK1	MAPK1	MAPK1	9367	0.0035	0.35	NO
132	APC2	APC2	APC2	9412	0.0031	0.35	NO
133	WASF2	WASF2	WASF2	9413	0.003	0.35	NO
134	PAK2	PAK2	PAK2	9472	0.0025	0.34	NO
135	PPP1CB	PPP1CB	PPP1CB	9500	0.0021	0.34	NO
136	GRLF1	GRLF1	GRLF1	9636	0.00072	0.33	NO
137	NRAS	NRAS	NRAS	10018	-0.0035	0.31	NO
138	ACTG1	ACTG1	ACTG1	10082	-0.0042	0.31	NO
139	FGF19	FGF19	FGF19	10087	-0.0042	0.31	NO
140	CRK	CRK	CRK	10227	-0.0061	0.3	NO
141	PPP1CC	PPP1CC	PPP1CC	10256	-0.0066	0.3	NO
142	RAF1	RAF1	RAF1	10280	-0.0068	0.3	NO
143	PXN	PXN	PXN	10763	-0.012	0.27	NO
144	PPP1CA	PPP1CA	PPP1CA	10765	-0.012	0.27	NO
145	CDC42	CDC42	CDC42	10923	-0.015	0.26	NO
146	FGF12	FGF12	FGF12	10961	-0.015	0.26	NO
147	GIT1	GIT1	GIT1	10967	-0.015	0.26	NO
148	DIAPH1	DIAPH1	DIAPH1	10988	-0.015	0.26	NO
149	ARHGEF7	ARHGEF7	ARHGEF7	11142	-0.017	0.26	NO
150	PIKFYVE	PIKFYVE	PIKFYVE	11172	-0.017	0.25	NO
151	SOS2	SOS2	SOS2	11197	-0.018	0.25	NO
152	MYL12B	MYL12B	MYL12B	11621	-0.022	0.23	NO
153	APC	APC	APC	11907	-0.026	0.22	NO
154	RAC1	RAC1	RAC1	11993	-0.027	0.21	NO
155	SOS1	SOS1	SOS1	12020	-0.027	0.21	NO
156	KRAS	KRAS	KRAS	12296	-0.03	0.2	NO
157	LIMK2	LIMK2	LIMK2	12585	-0.034	0.18	NO
158	ARPC3	ARPC3	ARPC3	12616	-0.034	0.18	NO
159	F2	F2	F2	13010	-0.04	0.16	NO
160	NCKAP1	NCKAP1	NCKAP1	13096	-0.041	0.16	NO
161	ITGA2	ITGA2	ITGA2	13114	-0.041	0.16	NO
162	FGF17	FGF17	FGF17	13442	-0.046	0.14	NO
163	PAK4	PAK4	PAK4	13464	-0.046	0.14	NO
164	EGFR	EGFR	EGFR	13569	-0.048	0.14	NO
165	ARHGEF12	ARHGEF12	ARHGEF12	13672	-0.049	0.13	NO
166	EZR	EZR	EZR	13769	-0.05	0.13	NO
167	ARPC1A	ARPC1A	ARPC1A	13784	-0.051	0.13	NO
168	MYLPF	MYLPF	MYLPF	13867	-0.052	0.12	NO
169	PIP4K2C	PIP4K2C	PIP4K2C	13873	-0.052	0.12	NO
170	PIK3R2	PIK3R2	PIK3R2	14062	-0.055	0.12	NO
171	ARHGEF4	ARHGEF4	ARHGEF4	14121	-0.057	0.12	NO
172	CRKL	CRKL	CRKL	14128	-0.057	0.12	NO
173	FGFR2	FGFR2	FGFR2	14470	-0.064	0.099	NO
174	IQGAP3	IQGAP3	IQGAP3	14478	-0.064	0.1	NO
175	FGFR4	FGFR4	FGFR4	14602	-0.066	0.096	NO
176	ITGB8	ITGB8	ITGB8	14759	-0.069	0.089	NO
177	PAK1	PAK1	PAK1	14825	-0.071	0.087	NO
178	PFN2	PFN2	PFN2	14932	-0.073	0.083	NO
179	WASL	WASL	WASL	15303	-0.082	0.065	NO
180	PTK2	PTK2	PTK2	15586	-0.091	0.052	NO
181	SLC9A1	SLC9A1	SLC9A1	15777	-0.098	0.044	NO
182	MYLK2	MYLK2	MYLK2	16024	-0.11	0.034	NO
183	MYL5	MYL5	MYL5	16071	-0.11	0.034	NO
184	TIAM1	TIAM1	TIAM1	16257	-0.12	0.027	NO
185	ITGA3	ITGA3	ITGA3	16325	-0.12	0.027	NO
186	ITGA6	ITGA6	ITGA6	16326	-0.12	0.03	NO
187	PAK7	PAK7	PAK7	16857	-0.16	0.0056	NO
188	ITGB4	ITGB4	ITGB4	16978	-0.17	0.0036	NO
189	FGF11	FGF11	FGF11	16996	-0.17	0.0074	NO
190	SCIN	SCIN	SCIN	17015	-0.17	0.011	NO
191	BRAF	BRAF	BRAF	17100	-0.18	0.012	NO
192	MYH14	MYH14	MYH14	17159	-0.18	0.014	NO
193	ITGB6	ITGB6	ITGB6	17349	-0.2	0.0088	NO
194	SSH3	SSH3	SSH3	17700	-0.25	-0.0036	NO
195	PAK6	PAK6	PAK6	17935	-0.3	-0.0082	NO
196	VAV3	VAV3	VAV3	18026	-0.33	-0.0039	NO
197	FGFR3	FGFR3	FGFR3	18190	-0.47	0.00039	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: BIOCARTA ERK PATHWAY.

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

genes ES table in pathway: BIOCARTA FCER1 PATHWAY

Table S9. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	LY96	LY96	LY96	158	0.67	0.18	YES
2	CD14	CD14	CD14	763	0.51	0.3	YES
3	LEF1	LEF1	LEF1	1081	0.46	0.41	YES
4	LBP	LBP	LBP	1791	0.37	0.48	YES
5	TLR4	TLR4	TLR4	2272	0.3	0.54	YES
6	WNT1	WNT1	WNT1	2623	0.26	0.59	YES
7	FZD1	FZD1	FZD1	2980	0.23	0.64	YES
8	GJA1	GJA1	GJA1	7024	0.038	0.43	NO
9	IRAK1	IRAK1	IRAK1	7058	0.038	0.44	NO
10	CTNNB1	CTNNB1	CTNNB1	7197	0.035	0.44	NO
11	PIK3R1	PIK3R1	PIK3R1	7820	0.024	0.41	NO
12	EIF2AK2	EIF2AK2	EIF2AK2	8017	0.021	0.41	NO
13	NFKB1	NFKB1	NFKB1	8209	0.018	0.4	NO
14	PIK3CA	PIK3CA	PIK3CA	8689	0.012	0.38	NO
15	RELA	RELA	RELA	9209	0.0052	0.35	NO
16	AKT1	AKT1	AKT1	10046	-0.0038	0.31	NO
17	TIRAP	TIRAP	TIRAP	10495	-0.0095	0.28	NO
18	MYD88	MYD88	MYD88	11236	-0.018	0.25	NO
19	APC	APC	APC	11907	-0.026	0.22	NO
20	PPP2CA	PPP2CA	PPP2CA	12290	-0.03	0.21	NO
21	GSK3B	GSK3B	GSK3B	12321	-0.031	0.21	NO
22	AXIN1	AXIN1	AXIN1	12813	-0.037	0.2	NO
23	PDPK1	PDPK1	PDPK1	13384	-0.045	0.18	NO
24	DVL1	DVL1	DVL1	14040	-0.055	0.16	NO
25	CCND1	CCND1	CCND1	15241	-0.08	0.12	NO
26	GNAI1	GNAI1	GNAI1	16917	-0.16	0.07	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: BIOCARTA FCER1 PATHWAY.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA FMLP PATHWAY

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	PTPN7	PTPN7	PTPN7	752	0.52	0.03	YES
2	ZAP70	ZAP70	ZAP70	1001	0.47	0.081	YES
3	NFATC1	NFATC1	NFATC1	1043	0.47	0.14	YES
4	VAV1	VAV1	VAV1	1049	0.47	0.21	YES
5	CD3E	CD3E	CD3E	1118	0.46	0.26	YES
6	PIK3CG	PIK3CG	PIK3CG	1254	0.44	0.32	YES
7	CD247	CD247	CD247	1275	0.43	0.38	YES
8	LCK	LCK	LCK	1304	0.43	0.43	YES
9	PRKCB	PRKCB	PRKCB	1308	0.43	0.49	YES
10	CD3D	CD3D	CD3D	1487	0.4	0.54	YES
11	CD3G	CD3G	CD3G	1630	0.39	0.58	YES
12	FYN	FYN	FYN	1685	0.38	0.63	YES
13	LAT	LAT	LAT	2375	0.29	0.63	YES
14	NFATC4	NFATC4	NFATC4	2389	0.29	0.67	YES
15	NFATC2	NFATC2	NFATC2	2457	0.28	0.71	YES
16	PPP3CC	PPP3CC	PPP3CC	3721	0.17	0.66	NO
17	PPP3CB	PPP3CB	PPP3CB	5203	0.088	0.59	NO
18	CALM2	CALM2	CALM2	5414	0.08	0.59	NO
19	JUN	JUN	JUN	5425	0.08	0.6	NO
20	MAPK3	MAPK3	MAPK3	5782	0.068	0.59	NO
21	PRKCA	PRKCA	PRKCA	5833	0.067	0.6	NO
22	GRB2	GRB2	GRB2	6063	0.06	0.59	NO
23	SHC1	SHC1	SHC1	6708	0.045	0.56	NO
24	NFATC3	NFATC3	NFATC3	6862	0.042	0.56	NO
25	ELK1	ELK1	ELK1	6879	0.042	0.57	NO
26	PPP3CA	PPP3CA	PPP3CA	6911	0.041	0.57	NO
27	CALM3	CALM3	CALM3	6917	0.041	0.58	NO
28	RASA1	RASA1	RASA1	7028	0.038	0.57	NO
29	CALM1	CALM1	CALM1	7534	0.03	0.55	NO
30	PIK3R1	PIK3R1	PIK3R1	7820	0.024	0.54	NO
31	NFKB1	NFKB1	NFKB1	8209	0.018	0.52	NO
32	PLCG1	PLCG1	PLCG1	8217	0.018	0.52	NO
33	MAP3K1	MAP3K1	MAP3K1	8370	0.016	0.52	NO
34	PIK3CA	PIK3CA	PIK3CA	8689	0.012	0.5	NO
35	MAP2K1	MAP2K1	MAP2K1	9023	0.0074	0.48	NO
36	RELA	RELA	RELA	9209	0.0052	0.47	NO
37	NFKBIA	NFKBIA	NFKBIA	9532	0.0019	0.46	NO
38	RAF1	RAF1	RAF1	10280	-0.0068	0.42	NO
39	MAPK8	MAPK8	MAPK8	11676	-0.023	0.34	NO
40	RAC1	RAC1	RAC1	11993	-0.027	0.33	NO
41	SOS1	SOS1	SOS1	12020	-0.027	0.33	NO
42	FOS	FOS	FOS	12182	-0.029	0.32	NO
43	MAP2K4	MAP2K4	MAP2K4	13229	-0.043	0.27	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: BIOCARTA FMLP PATHWAY.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FMLP 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 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 GLYCOLYSIS GLUCONEOGENESIS	59	genes.ES.table	0.3	1	0.46	0.82	1	0.22	0.13	0.19	0.8	0.24
KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS	26	genes.ES.table	0.79	1.7	0.015	0.29	0.54	0.62	0.12	0.55	0.14	0.068
KEGG FATTY ACID METABOLISM	41	genes.ES.table	0.42	1.3	0.19	0.69	0.99	0.46	0.24	0.35	0.59	0.19
KEGG STEROID HORMONE BIOSYNTHESIS	51	genes.ES.table	0.63	1.5	0.047	0.29	0.85	0.57	0.12	0.5	0.2	0.041
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.36	1.2	0.23	0.68	0.99	0.42	0.23	0.32	0.59	0.18
KEGG TYROSINE METABOLISM	39	genes.ES.table	0.4	1.1	0.34	0.69	1	0.23	0.11	0.2	0.64	0.16
KEGG GLUTATHIONE METABOLISM	45	genes.ES.table	0.38	1.1	0.32	0.73	1	0.33	0.17	0.28	0.67	0.2
KEGG STARCH AND SUCROSE METABOLISM	46	genes.ES.table	0.55	1.4	0.061	0.42	0.93	0.44	0.13	0.38	0.32	0.086
KEGG GLYCEROPHOSPHOLIPID METABOLISM	70	genes.ES.table	0.27	1	0.41	0.8	1	0.51	0.3	0.36	0.77	0.24
KEGG ETHER LIPID METABOLISM	28	genes.ES.table	0.4	1.2	0.23	0.67	1	0.39	0.15	0.33	0.6	0.17

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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	UGT1A1	UGT1A1	UGT1A1	63	0.69	0.086	YES
2	UGT2B28	UGT2B28	UGT2B28	101	0.62	0.16	YES
3	UGT1A9	UGT1A9	UGT1A9	228	0.53	0.23	YES
4	UGT2B15	UGT2B15	UGT2B15	292	0.49	0.29	YES
5	UGT1A6	UGT1A6	UGT1A6	328	0.47	0.34	YES
6	UGT2B11	UGT2B11	UGT2B11	386	0.45	0.4	YES
7	UGT1A3	UGT1A3	UGT1A3	484	0.42	0.45	YES
8	UGT2B7	UGT2B7	UGT2B7	650	0.38	0.49	YES
9	UGT1A4	UGT1A4	UGT1A4	871	0.34	0.52	YES
10	UGT2A3	UGT2A3	UGT2A3	899	0.33	0.56	YES
11	UGT2B10	UGT2B10	UGT2B10	923	0.33	0.6	YES
12	UGT1A5	UGT1A5	UGT1A5	1105	0.3	0.63	YES
13	UGT1A10	UGT1A10	UGT1A10	1438	0.26	0.65	YES
14	UGT2B4	UGT2B4	UGT2B4	1597	0.24	0.67	YES
15	ALAS1	ALAS1	ALAS1	1634	0.24	0.7	YES
16	UGT1A8	UGT1A8	UGT1A8	1917	0.21	0.71	YES
17	PPOX	PPOX	PPOX	2828	0.15	0.68	NO
18	MMAB	MMAB	MMAB	6242	0.045	0.5	NO
19	EARS2	EARS2	EARS2	6533	0.04	0.49	NO
20	UGT1A7	UGT1A7	UGT1A7	6763	0.035	0.48	NO
21	UGT2A1	UGT2A1	UGT2A1	7310	0.025	0.45	NO
22	COX15	COX15	COX15	8174	0.0087	0.41	NO
23	GUSB	GUSB	GUSB	8231	0.0079	0.4	NO
24	HMOX2	HMOX2	HMOX2	8492	0.0031	0.39	NO
25	ALAD	ALAD	ALAD	8684	-0.00044	0.38	NO
26	COX10	COX10	COX10	9744	-0.018	0.32	NO
27	ALAS2	ALAS2	ALAS2	9880	-0.021	0.32	NO
28	FTH1	FTH1	FTH1	10848	-0.04	0.27	NO
29	HMBS	HMBS	HMBS	11034	-0.045	0.27	NO
30	UROD	UROD	UROD	11281	-0.05	0.26	NO
31	CP	CP	CP	11534	-0.055	0.25	NO
32	CPOX	CPOX	CPOX	11837	-0.063	0.24	NO
33	EPRS	EPRS	EPRS	12718	-0.087	0.21	NO
34	BLVRB	BLVRB	BLVRB	12739	-0.088	0.22	NO
35	FECH	FECH	FECH	12936	-0.095	0.22	NO
36	HMOX1	HMOX1	HMOX1	13858	-0.13	0.19	NO
37	UROS	UROS	UROS	13937	-0.14	0.2	NO
38	BLVRA	BLVRA	BLVRA	15856	-0.27	0.13	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 GLYCOLYSIS GLUCONEOGENESIS.

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

genes ES table in pathway: KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS

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	UGT1A1	UGT1A1	UGT1A1	63	0.69	0.096	YES
2	UGT2B28	UGT2B28	UGT2B28	101	0.62	0.18	YES
3	UGT1A9	UGT1A9	UGT1A9	228	0.53	0.25	YES
4	UGT2B15	UGT2B15	UGT2B15	292	0.49	0.32	YES
5	UGT1A6	UGT1A6	UGT1A6	328	0.47	0.38	YES
6	UGT2B11	UGT2B11	UGT2B11	386	0.45	0.45	YES
7	UGT1A3	UGT1A3	UGT1A3	484	0.42	0.5	YES
8	UGT2B7	UGT2B7	UGT2B7	650	0.38	0.55	YES
9	UGT1A4	UGT1A4	UGT1A4	871	0.34	0.58	YES
10	UGT2A3	UGT2A3	UGT2A3	899	0.33	0.63	YES
11	UGT2B10	UGT2B10	UGT2B10	923	0.33	0.68	YES
12	UGT1A5	UGT1A5	UGT1A5	1105	0.3	0.71	YES
13	UGT1A10	UGT1A10	UGT1A10	1438	0.26	0.73	YES
14	UGT2B4	UGT2B4	UGT2B4	1597	0.24	0.75	YES
15	UGT1A8	UGT1A8	UGT1A8	1917	0.21	0.77	YES
16	XYLB	XYLB	XYLB	2104	0.2	0.79	YES
17	DCXR	DCXR	DCXR	3334	0.13	0.74	NO
18	CRYL1	CRYL1	CRYL1	3353	0.13	0.75	NO
19	UGT1A7	UGT1A7	UGT1A7	6763	0.035	0.57	NO
20	UGT2A1	UGT2A1	UGT2A1	7310	0.025	0.55	NO
21	GUSB	GUSB	GUSB	8231	0.0079	0.5	NO
22	DHDH	DHDH	DHDH	8241	0.0078	0.5	NO
23	AKR1B1	AKR1B1	AKR1B1	9340	-0.012	0.44	NO
24	RPE	RPE	RPE	11689	-0.059	0.32	NO
25	UGP2	UGP2	UGP2	12190	-0.072	0.3	NO
26	LOC729020	LOC729020	LOC729020	15183	-0.22	0.17	NO

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

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

genes ES table in pathway: KEGG FATTY ACID METABOLISM

Table 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	UGT1A1	UGT1A1	UGT1A1	63	0.69	0.04	YES
2	UGT2B28	UGT2B28	UGT2B28	101	0.62	0.077	YES
3	CYP3A5	CYP3A5	CYP3A5	103	0.62	0.12	YES
4	CYP2C8	CYP2C8	CYP2C8	215	0.54	0.14	YES
5	ADH6	ADH6	ADH6	216	0.54	0.18	YES
6	UGT1A9	UGT1A9	UGT1A9	228	0.53	0.21	YES
7	UGT2B15	UGT2B15	UGT2B15	292	0.49	0.24	YES
8	UGT1A6	UGT1A6	UGT1A6	328	0.47	0.26	YES
9	UGT2B11	UGT2B11	UGT2B11	386	0.45	0.29	YES
10	UGT1A3	UGT1A3	UGT1A3	484	0.42	0.31	YES
11	CYP2C9	CYP2C9	CYP2C9	485	0.42	0.34	YES
12	AKR1C2	AKR1C2	AKR1C2	514	0.41	0.36	YES
13	UGT2B7	UGT2B7	UGT2B7	650	0.38	0.38	YES
14	CYP3A7	CYP3A7	CYP3A7	732	0.36	0.4	YES
15	GSTM4	GSTM4	GSTM4	767	0.36	0.42	YES
16	AKR1C3	AKR1C3	AKR1C3	780	0.35	0.44	YES
17	CYP1A1	CYP1A1	CYP1A1	844	0.34	0.45	YES
18	UGT1A4	UGT1A4	UGT1A4	871	0.34	0.47	YES
19	GSTM2	GSTM2	GSTM2	894	0.33	0.49	YES
20	UGT2A3	UGT2A3	UGT2A3	899	0.33	0.51	YES
21	UGT2B10	UGT2B10	UGT2B10	923	0.33	0.53	YES
22	UGT1A5	UGT1A5	UGT1A5	1105	0.3	0.54	YES
23	GSTA1	GSTA1	GSTA1	1108	0.3	0.56	YES
24	CYP3A43	CYP3A43	CYP3A43	1123	0.3	0.58	YES
25	ADH1C	ADH1C	ADH1C	1174	0.29	0.59	YES
26	CYP2C19	CYP2C19	CYP2C19	1245	0.28	0.61	YES
27	CYP1A2	CYP1A2	CYP1A2	1252	0.28	0.62	YES
28	GSTM3	GSTM3	GSTM3	1268	0.28	0.64	YES
29	UGT1A10	UGT1A10	UGT1A10	1438	0.26	0.65	YES
30	AKR1C1	AKR1C1	AKR1C1	1475	0.26	0.66	YES
31	MGST2	MGST2	MGST2	1549	0.25	0.67	YES
32	CYP2C18	CYP2C18	CYP2C18	1564	0.25	0.69	YES
33	GSTA2	GSTA2	GSTA2	1592	0.24	0.7	YES
34	UGT2B4	UGT2B4	UGT2B4	1597	0.24	0.72	YES
35	ADH4	ADH4	ADH4	1713	0.23	0.72	YES
36	UGT1A8	UGT1A8	UGT1A8	1917	0.21	0.73	YES
37	ALDH3B2	ALDH3B2	ALDH3B2	1995	0.21	0.74	YES
38	MGST1	MGST1	MGST1	2409	0.18	0.72	NO
39	AKR1C4	AKR1C4	AKR1C4	2512	0.17	0.73	NO
40	GSTM1	GSTM1	GSTM1	2894	0.15	0.72	NO
41	GSTO2	GSTO2	GSTO2	3026	0.14	0.72	NO
42	ADH1A	ADH1A	ADH1A	3706	0.11	0.69	NO
43	CYP2B6	CYP2B6	CYP2B6	4695	0.082	0.64	NO
44	GSTK1	GSTK1	GSTK1	5580	0.06	0.59	NO
45	GSTZ1	GSTZ1	GSTZ1	5772	0.056	0.59	NO
46	GSTT1	GSTT1	GSTT1	6385	0.043	0.56	NO
47	ADH7	ADH7	ADH7	6742	0.036	0.54	NO
48	UGT1A7	UGT1A7	UGT1A7	6763	0.035	0.54	NO
49	MGST3	MGST3	MGST3	6837	0.034	0.54	NO
50	UGT2A1	UGT2A1	UGT2A1	7310	0.025	0.51	NO
51	CYP2E1	CYP2E1	CYP2E1	7502	0.021	0.5	NO
52	ADH5	ADH5	ADH5	7534	0.021	0.5	NO
53	DHDH	DHDH	DHDH	8241	0.0078	0.46	NO
54	ADH1B	ADH1B	ADH1B	8596	0.0015	0.44	NO
55	GSTT2	GSTT2	GSTT2	9094	-0.0074	0.42	NO
56	CYP2F1	CYP2F1	CYP2F1	9228	-0.0098	0.41	NO
57	GSTP1	GSTP1	GSTP1	9623	-0.017	0.39	NO
58	ALDH3A1	ALDH3A1	ALDH3A1	10050	-0.024	0.37	NO
59	EPHX1	EPHX1	EPHX1	11774	-0.061	0.28	NO
60	GSTO1	GSTO1	GSTO1	12133	-0.071	0.26	NO
61	ALDH3B1	ALDH3B1	ALDH3B1	12363	-0.077	0.26	NO
62	GSTA4	GSTA4	GSTA4	13952	-0.14	0.18	NO
63	ALDH1A3	ALDH1A3	ALDH1A3	14609	-0.17	0.15	NO
64	GSTM5	GSTM5	GSTM5	14772	-0.18	0.15	NO
65	CYP2S1	CYP2S1	CYP2S1	15434	-0.24	0.13	NO
66	CYP1B1	CYP1B1	CYP1B1	16545	-0.34	0.091	NO

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

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

genes ES table in pathway: KEGG STEROID HORMONE BIOSYNTHESIS

Table 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	UGT1A1	UGT1A1	UGT1A1	63	0.69	0.042	YES
2	UGT2B28	UGT2B28	UGT2B28	101	0.62	0.081	YES
3	CYP3A5	CYP3A5	CYP3A5	103	0.62	0.12	YES
4	CYP2C8	CYP2C8	CYP2C8	215	0.54	0.15	YES
5	ADH6	ADH6	ADH6	216	0.54	0.19	YES
6	UGT1A9	UGT1A9	UGT1A9	228	0.53	0.22	YES
7	UGT2B15	UGT2B15	UGT2B15	292	0.49	0.25	YES
8	UGT1A6	UGT1A6	UGT1A6	328	0.47	0.28	YES
9	UGT2B11	UGT2B11	UGT2B11	386	0.45	0.3	YES
10	DGAT2	DGAT2	DGAT2	461	0.43	0.33	YES
11	UGT1A3	UGT1A3	UGT1A3	484	0.42	0.36	YES
12	CYP2C9	CYP2C9	CYP2C9	485	0.42	0.38	YES
13	UGT2B7	UGT2B7	UGT2B7	650	0.38	0.4	YES
14	CYP3A7	CYP3A7	CYP3A7	732	0.36	0.42	YES
15	CYP4A11	CYP4A11	CYP4A11	816	0.35	0.44	YES
16	CYP1A1	CYP1A1	CYP1A1	844	0.34	0.46	YES
17	UGT1A4	UGT1A4	UGT1A4	871	0.34	0.48	YES
18	UGT2A3	UGT2A3	UGT2A3	899	0.33	0.5	YES
19	UGT2B10	UGT2B10	UGT2B10	923	0.33	0.52	YES
20	ALDH1A2	ALDH1A2	ALDH1A2	937	0.33	0.54	YES
21	UGT1A5	UGT1A5	UGT1A5	1105	0.3	0.55	YES
22	CYP3A43	CYP3A43	CYP3A43	1123	0.3	0.57	YES
23	ADH1C	ADH1C	ADH1C	1174	0.29	0.58	YES
24	CYP2C19	CYP2C19	CYP2C19	1245	0.28	0.6	YES
25	CYP1A2	CYP1A2	CYP1A2	1252	0.28	0.62	YES
26	UGT1A10	UGT1A10	UGT1A10	1438	0.26	0.62	YES
27	BCMO1	BCMO1	BCMO1	1546	0.25	0.64	YES
28	CYP2C18	CYP2C18	CYP2C18	1564	0.25	0.65	YES
29	UGT2B4	UGT2B4	UGT2B4	1597	0.24	0.66	YES
30	CYP4A22	CYP4A22	CYP4A22	1602	0.24	0.68	YES
31	ADH4	ADH4	ADH4	1713	0.23	0.69	YES
32	UGT1A8	UGT1A8	UGT1A8	1917	0.21	0.69	YES
33	DHRS3	DHRS3	DHRS3	2931	0.15	0.65	NO
34	DGAT1	DGAT1	DGAT1	3007	0.14	0.65	NO
35	ADH1A	ADH1A	ADH1A	3706	0.11	0.62	NO
36	CYP2B6	CYP2B6	CYP2B6	4695	0.082	0.57	NO
37	LRAT	LRAT	LRAT	5094	0.072	0.55	NO
38	RDH16	RDH16	RDH16	5929	0.052	0.51	NO
39	RDH10	RDH10	RDH10	6057	0.049	0.51	NO
40	RDH12	RDH12	RDH12	6532	0.04	0.48	NO
41	ADH7	ADH7	ADH7	6742	0.036	0.48	NO
42	UGT1A7	UGT1A7	UGT1A7	6763	0.035	0.48	NO
43	RDH11	RDH11	RDH11	6767	0.035	0.48	NO
44	UGT2A1	UGT2A1	UGT2A1	7310	0.025	0.45	NO
45	ADH5	ADH5	ADH5	7534	0.021	0.44	NO
46	ADH1B	ADH1B	ADH1B	8596	0.0015	0.38	NO
47	CYP2A6	CYP2A6	CYP2A6	8619	0.00096	0.38	NO
48	CYP26A1	CYP26A1	CYP26A1	8698	-0.0006	0.38	NO
49	PNPLA4	PNPLA4	PNPLA4	9793	-0.019	0.32	NO
50	RDH5	RDH5	RDH5	10060	-0.024	0.3	NO
51	DHRS4	DHRS4	DHRS4	10413	-0.031	0.29	NO
52	DHRS4L2	DHRS4L2	DHRS4L2	10705	-0.037	0.27	NO
53	RETSAT	RETSAT	RETSAT	10816	-0.039	0.27	NO
54	CYP26C1	CYP26C1	CYP26C1	10985	-0.044	0.26	NO
55	AWAT2	AWAT2	AWAT2	12807	-0.09	0.17	NO
56	RPE65	RPE65	RPE65	15256	-0.22	0.048	NO
57	RDH8	RDH8	RDH8	15595	-0.25	0.046	NO
58	ALDH1A1	ALDH1A1	ALDH1A1	16757	-0.37	0.0063	NO
59	DHRS9	DHRS9	DHRS9	17382	-0.47	0.0027	NO
60	CYP26B1	CYP26B1	CYP26B1	17962	-0.64	0.013	NO

Figure S27. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG STEROID HORMONE BIOSYNTHESIS.

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

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

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	UGT1A1	UGT1A1	UGT1A1	63	0.69	0.036	YES
2	UGT2B28	UGT2B28	UGT2B28	101	0.62	0.068	YES
3	CYP3A5	CYP3A5	CYP3A5	103	0.62	0.1	YES
4	FMO5	FMO5	FMO5	188	0.55	0.13	YES
5	CYP2C8	CYP2C8	CYP2C8	215	0.54	0.16	YES
6	ADH6	ADH6	ADH6	216	0.54	0.19	YES
7	UGT1A9	UGT1A9	UGT1A9	228	0.53	0.22	YES
8	UGT2B15	UGT2B15	UGT2B15	292	0.49	0.24	YES
9	MAOA	MAOA	MAOA	311	0.48	0.27	YES
10	UGT1A6	UGT1A6	UGT1A6	328	0.47	0.29	YES
11	UGT2B11	UGT2B11	UGT2B11	386	0.45	0.32	YES
12	UGT1A3	UGT1A3	UGT1A3	484	0.42	0.33	YES
13	CYP2C9	CYP2C9	CYP2C9	485	0.42	0.36	YES
14	UGT2B7	UGT2B7	UGT2B7	650	0.38	0.37	YES
15	CYP3A7	CYP3A7	CYP3A7	732	0.36	0.39	YES
16	GSTM4	GSTM4	GSTM4	767	0.36	0.4	YES
17	CYP2D6	CYP2D6	CYP2D6	788	0.35	0.42	YES
18	UGT1A4	UGT1A4	UGT1A4	871	0.34	0.44	YES
19	GSTM2	GSTM2	GSTM2	894	0.33	0.46	YES
20	UGT2A3	UGT2A3	UGT2A3	899	0.33	0.47	YES
21	UGT2B10	UGT2B10	UGT2B10	923	0.33	0.49	YES
22	UGT1A5	UGT1A5	UGT1A5	1105	0.3	0.5	YES
23	GSTA1	GSTA1	GSTA1	1108	0.3	0.51	YES
24	CYP3A43	CYP3A43	CYP3A43	1123	0.3	0.53	YES
25	ADH1C	ADH1C	ADH1C	1174	0.29	0.54	YES
26	CYP2C19	CYP2C19	CYP2C19	1245	0.28	0.56	YES
27	CYP1A2	CYP1A2	CYP1A2	1252	0.28	0.57	YES
28	GSTM3	GSTM3	GSTM3	1268	0.28	0.58	YES
29	UGT1A10	UGT1A10	UGT1A10	1438	0.26	0.59	YES
30	MGST2	MGST2	MGST2	1549	0.25	0.6	YES
31	CYP2C18	CYP2C18	CYP2C18	1564	0.25	0.61	YES
32	GSTA2	GSTA2	GSTA2	1592	0.24	0.62	YES
33	UGT2B4	UGT2B4	UGT2B4	1597	0.24	0.64	YES
34	ADH4	ADH4	ADH4	1713	0.23	0.64	YES
35	UGT1A8	UGT1A8	UGT1A8	1917	0.21	0.64	YES
36	ALDH3B2	ALDH3B2	ALDH3B2	1995	0.21	0.65	YES
37	MGST1	MGST1	MGST1	2409	0.18	0.64	NO
38	GSTM1	GSTM1	GSTM1	2894	0.15	0.62	NO
39	GSTO2	GSTO2	GSTO2	3026	0.14	0.62	NO
40	ADH1A	ADH1A	ADH1A	3706	0.11	0.59	NO
41	CYP2B6	CYP2B6	CYP2B6	4695	0.082	0.54	NO
42	GSTK1	GSTK1	GSTK1	5580	0.06	0.5	NO
43	GSTZ1	GSTZ1	GSTZ1	5772	0.056	0.49	NO
44	GSTT1	GSTT1	GSTT1	6385	0.043	0.46	NO
45	ADH7	ADH7	ADH7	6742	0.036	0.44	NO
46	UGT1A7	UGT1A7	UGT1A7	6763	0.035	0.44	NO
47	MGST3	MGST3	MGST3	6837	0.034	0.44	NO
48	UGT2A1	UGT2A1	UGT2A1	7310	0.025	0.41	NO
49	CYP2E1	CYP2E1	CYP2E1	7502	0.021	0.4	NO
50	ADH5	ADH5	ADH5	7534	0.021	0.4	NO
51	FMO4	FMO4	FMO4	8578	0.0018	0.34	NO
52	ADH1B	ADH1B	ADH1B	8596	0.0015	0.34	NO
53	CYP2A6	CYP2A6	CYP2A6	8619	0.00096	0.34	NO
54	GSTT2	GSTT2	GSTT2	9094	-0.0074	0.32	NO
55	GSTP1	GSTP1	GSTP1	9623	-0.017	0.29	NO
56	ALDH3A1	ALDH3A1	ALDH3A1	10050	-0.024	0.27	NO
57	GSTO1	GSTO1	GSTO1	12133	-0.071	0.16	NO
58	ALDH3B1	ALDH3B1	ALDH3B1	12363	-0.077	0.15	NO
59	GSTA4	GSTA4	GSTA4	13952	-0.14	0.068	NO
60	ALDH1A3	ALDH1A3	ALDH1A3	14609	-0.17	0.042	NO
61	GSTM5	GSTM5	GSTM5	14772	-0.18	0.043	NO
62	FMO3	FMO3	FMO3	15097	-0.21	0.037	NO
63	AOX1	AOX1	AOX1	17492	-0.49	-0.067	NO
64	MAOB	MAOB	MAOB	17604	-0.52	-0.044	NO
65	FMO2	FMO2	FMO2	17868	-0.6	-0.025	NO
66	FMO1	FMO1	FMO1	18153	-0.77	0.0024	NO

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

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

genes ES table in pathway: KEGG TYROSINE METABOLISM

Table S16. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HSD17B2	HSD17B2	HSD17B2	47	0.74	0.048	YES
2	UGT1A1	UGT1A1	UGT1A1	63	0.69	0.095	YES
3	UGT2B28	UGT2B28	UGT2B28	101	0.62	0.14	YES
4	CYP3A5	CYP3A5	CYP3A5	103	0.62	0.18	YES
5	UGT1A9	UGT1A9	UGT1A9	228	0.53	0.21	YES
6	UGT2B15	UGT2B15	UGT2B15	292	0.49	0.24	YES
7	UGT1A6	UGT1A6	UGT1A6	328	0.47	0.27	YES
8	UGT2B11	UGT2B11	UGT2B11	386	0.45	0.3	YES
9	UGT1A3	UGT1A3	UGT1A3	484	0.42	0.32	YES
10	AKR1C2	AKR1C2	AKR1C2	514	0.41	0.35	YES
11	UGT2B7	UGT2B7	UGT2B7	650	0.38	0.37	YES
12	CYP3A7	CYP3A7	CYP3A7	732	0.36	0.39	YES
13	AKR1C3	AKR1C3	AKR1C3	780	0.35	0.41	YES
14	CYP1A1	CYP1A1	CYP1A1	844	0.34	0.43	YES
15	UGT1A4	UGT1A4	UGT1A4	871	0.34	0.45	YES
16	UGT2A3	UGT2A3	UGT2A3	899	0.33	0.48	YES
17	UGT2B10	UGT2B10	UGT2B10	923	0.33	0.5	YES
18	UGT1A5	UGT1A5	UGT1A5	1105	0.3	0.51	YES
19	CYP3A43	CYP3A43	CYP3A43	1123	0.3	0.53	YES
20	HSD11B2	HSD11B2	HSD11B2	1159	0.29	0.54	YES
21	SULT1E1	SULT1E1	SULT1E1	1191	0.29	0.56	YES
22	UGT1A10	UGT1A10	UGT1A10	1438	0.26	0.57	YES
23	AKR1C1	AKR1C1	AKR1C1	1475	0.26	0.58	YES
24	SRD5A2	SRD5A2	SRD5A2	1499	0.25	0.6	YES
25	UGT2B4	UGT2B4	UGT2B4	1597	0.24	0.61	YES
26	UGT1A8	UGT1A8	UGT1A8	1917	0.21	0.61	YES
27	COMT	COMT	COMT	2052	0.2	0.61	YES
28	HSD3B1	HSD3B1	HSD3B1	2163	0.2	0.62	YES
29	AKR1D1	AKR1D1	AKR1D1	2249	0.19	0.63	YES
30	AKR1C4	AKR1C4	AKR1C4	2512	0.17	0.63	NO
31	HSD17B7	HSD17B7	HSD17B7	2801	0.16	0.62	NO
32	STS	STS	STS	3160	0.14	0.61	NO
33	HSD3B2	HSD3B2	HSD3B2	4411	0.091	0.55	NO
34	SRD5A3	SRD5A3	SRD5A3	5544	0.061	0.49	NO
35	HSD17B8	HSD17B8	HSD17B8	6153	0.047	0.46	NO
36	UGT1A7	UGT1A7	UGT1A7	6763	0.035	0.43	NO
37	UGT2A1	UGT2A1	UGT2A1	7310	0.025	0.4	NO
38	HSD17B1	HSD17B1	HSD17B1	7396	0.023	0.4	NO
39	CYP11A1	CYP11A1	CYP11A1	8956	-0.0049	0.31	NO
40	CYP7A1	CYP7A1	CYP7A1	9287	-0.011	0.3	NO
41	CYP17A1	CYP17A1	CYP17A1	12075	-0.069	0.15	NO
42	HSD17B12	HSD17B12	HSD17B12	12735	-0.088	0.12	NO
43	HSD17B3	HSD17B3	HSD17B3	14109	-0.15	0.051	NO
44	CYP21A2	CYP21A2	CYP21A2	15696	-0.26	-0.019	NO
45	SRD5A1	SRD5A1	SRD5A1	15753	-0.26	-0.0039	NO
46	SULT2B1	SULT2B1	SULT2B1	15873	-0.27	0.0085	NO
47	CYP7B1	CYP7B1	CYP7B1	16154	-0.3	0.014	NO
48	CYP19A1	CYP19A1	CYP19A1	16281	-0.31	0.029	NO
49	CYP1B1	CYP1B1	CYP1B1	16545	-0.34	0.038	NO
50	HSD11B1	HSD11B1	HSD11B1	16812	-0.38	0.05	NO
51	HSD17B6	HSD17B6	HSD17B6	16847	-0.38	0.074	NO

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

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

genes ES table in pathway: KEGG GLUTATHIONE METABOLISM

Table 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	UGT1A1	UGT1A1	UGT1A1	63	0.69	0.061	YES
2	UGT2B28	UGT2B28	UGT2B28	101	0.62	0.12	YES
3	UGT1A9	UGT1A9	UGT1A9	228	0.53	0.16	YES
4	UGT2B15	UGT2B15	UGT2B15	292	0.49	0.2	YES
5	UGT1A6	UGT1A6	UGT1A6	328	0.47	0.24	YES
6	UGT2B11	UGT2B11	UGT2B11	386	0.45	0.28	YES
7	UGT1A3	UGT1A3	UGT1A3	484	0.42	0.32	YES
8	UGT2B7	UGT2B7	UGT2B7	650	0.38	0.34	YES
9	AMY2B	AMY2B	AMY2B	832	0.34	0.36	YES
10	UGT1A4	UGT1A4	UGT1A4	871	0.34	0.39	YES
11	UGT2A3	UGT2A3	UGT2A3	899	0.33	0.42	YES
12	UGT2B10	UGT2B10	UGT2B10	923	0.33	0.45	YES
13	UGT1A5	UGT1A5	UGT1A5	1105	0.3	0.47	YES
14	G6PC	G6PC	G6PC	1218	0.28	0.49	YES
15	TREH	TREH	TREH	1226	0.28	0.52	YES
16	UGT1A10	UGT1A10	UGT1A10	1438	0.26	0.53	YES
17	UGT2B4	UGT2B4	UGT2B4	1597	0.24	0.54	YES
18	UGT1A8	UGT1A8	UGT1A8	1917	0.21	0.54	YES
19	AMY2A	AMY2A	AMY2A	2327	0.18	0.54	YES
20	GYS2	GYS2	GYS2	2400	0.18	0.55	YES
21	AGL	AGL	AGL	5292	0.067	0.4	NO
22	PGM2	PGM2	PGM2	6183	0.046	0.35	NO
23	GYS1	GYS1	GYS1	6347	0.043	0.35	NO
24	UGT1A7	UGT1A7	UGT1A7	6763	0.035	0.33	NO
25	HK2	HK2	HK2	6836	0.034	0.33	NO
26	GBA3	GBA3	GBA3	6838	0.034	0.33	NO
27	UGT2A1	UGT2A1	UGT2A1	7310	0.025	0.31	NO
28	UGDH	UGDH	UGDH	8023	0.012	0.27	NO
29	GUSB	GUSB	GUSB	8231	0.0079	0.26	NO
30	GAA	GAA	GAA	9685	-0.018	0.18	NO
31	GPI	GPI	GPI	10095	-0.025	0.16	NO
32	GCK	GCK	GCK	10971	-0.043	0.12	NO
33	AMY1A	AMY1A	AMY1A	11269	-0.05	0.1	NO
34	HK1	HK1	HK1	11431	-0.053	0.1	NO
35	UGP2	UGP2	UGP2	12190	-0.072	0.065	NO
36	GANC	GANC	GANC	12690	-0.086	0.046	NO
37	MGAM	MGAM	MGAM	13566	-0.12	0.0084	NO
38	PYGL	PYGL	PYGL	13898	-0.13	0.0026	NO
39	PYGM	PYGM	PYGM	14055	-0.14	0.0072	NO
40	GBE1	GBE1	GBE1	14131	-0.15	0.017	NO
41	PYGB	PYGB	PYGB	14462	-0.16	0.014	NO
42	PGM1	PGM1	PGM1	15840	-0.27	-0.037	NO
43	ENPP3	ENPP3	ENPP3	16187	-0.3	-0.028	NO
44	PGM2L1	PGM2L1	PGM2L1	16333	-0.32	-0.006	NO
45	ENPP1	ENPP1	ENPP1	16945	-0.4	-0.0028	NO
46	HK3	HK3	HK3	18159	-0.77	0.0021	NO

Figure S33. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLUTATHIONE METABOLISM.

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

genes ES table in pathway: KEGG STARCH AND SUCROSE METABOLISM

Table 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	UGT1A1	UGT1A1	UGT1A1	63	0.69	0.057	YES
2	UGT2B28	UGT2B28	UGT2B28	101	0.62	0.11	YES
3	CYP3A5	CYP3A5	CYP3A5	103	0.62	0.16	YES
4	UGT1A9	UGT1A9	UGT1A9	228	0.53	0.2	YES
5	UGT2B15	UGT2B15	UGT2B15	292	0.49	0.24	YES
6	UGT1A6	UGT1A6	UGT1A6	328	0.47	0.28	YES
7	UGT2B11	UGT2B11	UGT2B11	386	0.45	0.32	YES
8	UGT1A3	UGT1A3	UGT1A3	484	0.42	0.35	YES
9	UGT2B7	UGT2B7	UGT2B7	650	0.38	0.38	YES
10	CYP3A7	CYP3A7	CYP3A7	732	0.36	0.4	YES
11	UGT1A4	UGT1A4	UGT1A4	871	0.34	0.42	YES
12	UGT2A3	UGT2A3	UGT2A3	899	0.33	0.45	YES
13	UGT2B10	UGT2B10	UGT2B10	923	0.33	0.48	YES
14	UGT1A5	UGT1A5	UGT1A5	1105	0.3	0.5	YES
15	CYP3A43	CYP3A43	CYP3A43	1123	0.3	0.52	YES
16	UGT1A10	UGT1A10	UGT1A10	1438	0.26	0.53	YES
17	UGT2B4	UGT2B4	UGT2B4	1597	0.24	0.54	YES
18	UGT1A8	UGT1A8	UGT1A8	1917	0.21	0.54	YES
19	NAT1	NAT1	NAT1	2347	0.18	0.53	NO
20	UPP2	UPP2	UPP2	4408	0.091	0.43	NO
21	UCKL1	UCKL1	UCKL1	5095	0.072	0.39	NO
22	NAT2	NAT2	NAT2	6093	0.048	0.34	NO
23	UGT1A7	UGT1A7	UGT1A7	6763	0.035	0.31	NO
24	UGT2A1	UGT2A1	UGT2A1	7310	0.025	0.28	NO
25	IMPDH2	IMPDH2	IMPDH2	7598	0.02	0.27	NO
26	ITPA	ITPA	ITPA	8157	0.0092	0.24	NO
27	GUSB	GUSB	GUSB	8231	0.0079	0.24	NO
28	CYP2A6	CYP2A6	CYP2A6	8619	0.00096	0.21	NO
29	TK2	TK2	TK2	9381	-0.012	0.17	NO
30	UMPS	UMPS	UMPS	9409	-0.013	0.17	NO
31	TPMT	TPMT	TPMT	10558	-0.034	0.11	NO
32	UCK1	UCK1	UCK1	11295	-0.05	0.076	NO
33	UPB1	UPB1	UPB1	11850	-0.063	0.051	NO
34	CES2	CES2	CES2	11870	-0.064	0.055	NO
35	HPRT1	HPRT1	HPRT1	12298	-0.075	0.038	NO
36	UCK2	UCK2	UCK2	12446	-0.079	0.037	NO
37	XDH	XDH	XDH	13344	-0.11	-0.0026	NO
38	UPP1	UPP1	UPP1	13809	-0.13	-0.017	NO
39	GMPS	GMPS	GMPS	13959	-0.14	-0.013	NO
40	TK1	TK1	TK1	14077	-0.14	-0.0068	NO
41	IMPDH1	IMPDH1	IMPDH1	15010	-0.2	-0.041	NO
42	DPYS	DPYS	DPYS	15760	-0.26	-0.059	NO
43	CES1	CES1	CES1	16818	-0.38	-0.084	NO
44	TYMP	TYMP	TYMP	17638	-0.53	-0.083	NO
45	CDA	CDA	CDA	17903	-0.61	-0.043	NO
46	DPYD	DPYD	DPYD	18053	-0.68	0.0079	NO

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

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

genes ES table in pathway: KEGG GLYCEROPHOSPHOLIPID METABOLISM

Table 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	SLC27A2	SLC27A2	SLC27A2	419	0.44	0.023	YES
2	ACSL5	ACSL5	ACSL5	682	0.37	0.047	YES
3	CROT	CROT	CROT	783	0.35	0.078	YES
4	PEX11G	PEX11G	PEX11G	946	0.32	0.1	YES
5	AMACR	AMACR	AMACR	1101	0.3	0.13	YES
6	IDH1	IDH1	IDH1	1156	0.29	0.15	YES
7	PEX11A	PEX11A	PEX11A	1310	0.27	0.17	YES
8	ACOX1	ACOX1	ACOX1	1316	0.27	0.2	YES
9	ABCD3	ABCD3	ABCD3	1588	0.24	0.21	YES
10	BAAT	BAAT	BAAT	1614	0.24	0.24	YES
11	ACAA1	ACAA1	ACAA1	1659	0.24	0.26	YES
12	NUDT12	NUDT12	NUDT12	2068	0.2	0.26	YES
13	DECR2	DECR2	DECR2	2641	0.16	0.24	YES
14	FAR2	FAR2	FAR2	2689	0.16	0.26	YES
15	PHYH	PHYH	PHYH	2854	0.15	0.26	YES
16	ACOX3	ACOX3	ACOX3	2917	0.15	0.27	YES
17	AGXT	AGXT	AGXT	3008	0.14	0.28	YES
18	MVK	MVK	MVK	3014	0.14	0.3	YES
19	ACSL1	ACSL1	ACSL1	3278	0.13	0.3	YES
20	HSD17B4	HSD17B4	HSD17B4	3424	0.12	0.3	YES
21	HMGCL	HMGCL	HMGCL	3475	0.12	0.31	YES
22	PEX7	PEX7	PEX7	3559	0.12	0.32	YES
23	CAT	CAT	CAT	3959	0.11	0.31	YES
24	PEX13	PEX13	PEX13	4175	0.098	0.31	YES
25	PEX19	PEX19	PEX19	4266	0.096	0.31	YES
26	SCP2	SCP2	SCP2	4355	0.092	0.32	YES
27	NUDT19	NUDT19	NUDT19	4416	0.091	0.32	YES
28	PXMP4	PXMP4	PXMP4	4418	0.09	0.33	YES
29	EPHX2	EPHX2	EPHX2	4528	0.087	0.34	YES
30	PEX1	PEX1	PEX1	4599	0.084	0.34	YES
31	PEX2	PEX2	PEX2	4630	0.083	0.35	YES
32	HAO2	HAO2	HAO2	4775	0.08	0.35	YES
33	MLYCD	MLYCD	MLYCD	4813	0.078	0.35	YES
34	MPV17L	MPV17L	MPV17L	4874	0.077	0.36	YES
35	PEX14	PEX14	PEX14	4902	0.076	0.36	YES
36	PAOX	PAOX	PAOX	5031	0.073	0.37	YES
37	PEX10	PEX10	PEX10	5097	0.071	0.37	YES
38	GSTK1	GSTK1	GSTK1	5580	0.06	0.35	NO
39	PEX12	PEX12	PEX12	5615	0.059	0.35	NO
40	ECH1	ECH1	ECH1	5632	0.059	0.36	NO
41	CRAT	CRAT	CRAT	5727	0.056	0.36	NO
42	FAR1	FAR1	FAR1	5732	0.056	0.36	NO
43	ACOT8	ACOT8	ACOT8	5862	0.053	0.36	NO
44	PRDX5	PRDX5	PRDX5	6018	0.05	0.36	NO
45	PMVK	PMVK	PMVK	6265	0.045	0.35	NO
46	PEX6	PEX6	PEX6	6295	0.044	0.35	NO
47	MPV17	MPV17	MPV17	6508	0.04	0.35	NO
48	ABCD4	ABCD4	ABCD4	6692	0.037	0.34	NO
49	SOD1	SOD1	SOD1	6786	0.035	0.34	NO
50	EHHADH	EHHADH	EHHADH	6951	0.032	0.33	NO
51	PEX11B	PEX11B	PEX11B	7442	0.022	0.31	NO
52	SLC25A17	SLC25A17	SLC25A17	7602	0.019	0.3	NO
53	HACL1	HACL1	HACL1	7957	0.013	0.28	NO
54	PEX16	PEX16	PEX16	8184	0.0086	0.27	NO
55	ABCD1	ABCD1	ABCD1	8405	0.0048	0.26	NO
56	ACSL3	ACSL3	ACSL3	8878	-0.0038	0.24	NO
57	IDH2	IDH2	IDH2	9441	-0.013	0.2	NO
58	GNPAT	GNPAT	GNPAT	9911	-0.022	0.18	NO
59	ACSL4	ACSL4	ACSL4	10149	-0.026	0.17	NO
60	DHRS4	DHRS4	DHRS4	10413	-0.031	0.16	NO
61	PEX5	PEX5	PEX5	10483	-0.032	0.16	NO
62	PRDX1	PRDX1	PRDX1	10614	-0.035	0.16	NO
63	PEX26	PEX26	PEX26	11622	-0.057	0.11	NO
64	DAO	DAO	DAO	12330	-0.076	0.075	NO
65	PEX3	PEX3	PEX3	12596	-0.084	0.069	NO
66	DDO	DDO	DDO	12774	-0.089	0.069	NO
67	NOS2	NOS2	NOS2	12880	-0.093	0.072	NO
68	AGPS	AGPS	AGPS	13268	-0.11	0.062	NO
69	XDH	XDH	XDH	13344	-0.11	0.069	NO
70	PXMP2	PXMP2	PXMP2	14636	-0.18	0.016	NO
71	PECI	PECI	PECI	14986	-0.2	0.018	NO
72	PECR	PECR	PECR	15278	-0.22	0.025	NO
73	ACSL6	ACSL6	ACSL6	15437	-0.24	0.041	NO
74	SOD2	SOD2	SOD2	15714	-0.26	0.052	NO
75	PIPOX	PIPOX	PIPOX	16654	-0.36	0.038	NO
76	ABCD2	ABCD2	ABCD2	17292	-0.46	0.05	NO

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

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

genes ES table in pathway: KEGG ETHER LIPID METABOLISM

Table 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	ADH6	ADH6	ADH6	216	0.54	0.077	YES
2	ACSL5	ACSL5	ACSL5	682	0.37	0.11	YES
3	CYP4A11	CYP4A11	CYP4A11	816	0.35	0.16	YES
4	ACADSB	ACADSB	ACADSB	1086	0.3	0.2	YES
5	ADH1C	ADH1C	ADH1C	1174	0.29	0.24	YES
6	CYP4A22	CYP4A22	CYP4A22	1602	0.24	0.26	YES
7	ACAA1	ACAA1	ACAA1	1659	0.24	0.29	YES
8	CPT1B	CPT1B	CPT1B	1712	0.23	0.33	YES
9	ADH4	ADH4	ADH4	1713	0.23	0.37	YES
10	ACADL	ACADL	ACADL	2376	0.18	0.36	YES
11	ACOX3	ACOX3	ACOX3	2917	0.15	0.36	YES
12	HADH	HADH	HADH	2978	0.15	0.38	YES
13	ACSL1	ACSL1	ACSL1	3278	0.13	0.38	YES
14	DCI	DCI	DCI	3641	0.12	0.38	YES
15	ADH1A	ADH1A	ADH1A	3706	0.11	0.4	YES
16	ACADVL	ACADVL	ACADVL	3850	0.11	0.41	YES
17	ACADS	ACADS	ACADS	3968	0.1	0.42	YES
18	ECHS1	ECHS1	ECHS1	4174	0.098	0.42	YES
19	HADHB	HADHB	HADHB	4409	0.091	0.42	YES
20	GCDH	GCDH	GCDH	5406	0.064	0.38	NO
21	CPT2	CPT2	CPT2	5657	0.058	0.38	NO
22	ACADM	ACADM	ACADM	6011	0.05	0.36	NO
23	ADH7	ADH7	ADH7	6742	0.036	0.33	NO
24	EHHADH	EHHADH	EHHADH	6951	0.032	0.32	NO
25	ADH5	ADH5	ADH5	7534	0.021	0.3	NO
26	ACAT2	ACAT2	ACAT2	7612	0.019	0.3	NO
27	HADHA	HADHA	HADHA	8445	0.0041	0.25	NO
28	ALDH9A1	ALDH9A1	ALDH9A1	8452	0.0038	0.25	NO
29	ADH1B	ADH1B	ADH1B	8596	0.0015	0.24	NO
30	ACSL3	ACSL3	ACSL3	8878	-0.0038	0.23	NO
31	CPT1A	CPT1A	CPT1A	9865	-0.02	0.18	NO
32	ACSL4	ACSL4	ACSL4	10149	-0.026	0.16	NO
33	ACAA2	ACAA2	ACAA2	12662	-0.086	0.041	NO
34	ALDH7A1	ALDH7A1	ALDH7A1	13256	-0.11	0.026	NO
35	ALDH3A2	ALDH3A2	ALDH3A2	13591	-0.12	0.027	NO
36	CPT1C	CPT1C	CPT1C	14087	-0.14	0.024	NO
37	PECI	PECI	PECI	14986	-0.2	0.0075	NO
38	ALDH1B1	ALDH1B1	ALDH1B1	15220	-0.22	0.031	NO
39	ACAT1	ACAT1	ACAT1	15414	-0.23	0.059	NO
40	ACSL6	ACSL6	ACSL6	15437	-0.24	0.097	NO
41	ALDH2	ALDH2	ALDH2	16477	-0.34	0.095	NO

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

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

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
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.58	1.7	0.0096	0.17	0.44	0.41	0.19	0.33	0	0.031
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.49	1.5	0.084	0.29	0.85	0.3	0.16	0.25	0.19	0.037
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.49	1.6	0.062	0.23	0.68	0.45	0.21	0.36	0.13	0.035
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.49	1.8	0.019	0.52	0.25	0.32	0.2	0.26	0	0.17
BIOCARTA MAPK PATHWAY	86	genes.ES.table	0.35	1.6	0.046	0.23	0.76	0.37	0.23	0.29	0.14	0.029
BIOCARTA P38MAPK PATHWAY	39	genes.ES.table	0.47	1.6	0.029	0.22	0.69	0.64	0.33	0.43	0.13	0.029
BIOCARTA IL1R PATHWAY	32	genes.ES.table	0.57	1.6	0.045	0.24	0.76	0.53	0.2	0.43	0.15	0.034
BIOCARTA TNFR1 PATHWAY	28	genes.ES.table	0.47	1.7	0.026	0.15	0.46	0.43	0.21	0.34	0	0.022
KEGG PYRIMIDINE METABOLISM	96	genes.ES.table	0.4	1.8	0.0057	0.17	0.35	0.3	0.2	0.24	0	0.036
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.45	1.8	0.039	0.15	0.36	0.57	0.35	0.38	0	0.032

genes ES table in pathway: BIOCARTA G1 PATHWAY

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	CDK6	CDK6	CDK6	104	0.59	0.3	YES
2	TFDP1	TFDP1	TFDP1	2831	0.11	0.21	YES
3	HRAS	HRAS	HRAS	2833	0.11	0.27	YES
4	PIK3CA	PIK3CA	PIK3CA	2896	0.11	0.32	YES
5	PAK1	PAK1	PAK1	3075	0.1	0.36	YES
6	CDKN1A	CDKN1A	CDKN1A	3142	0.1	0.41	YES
7	NFKB1	NFKB1	NFKB1	3262	0.096	0.46	YES
8	CHUK	CHUK	CHUK	3546	0.087	0.49	YES
9	MAPK1	MAPK1	MAPK1	4964	0.053	0.44	NO
10	IKBKG	IKBKG	IKBKG	5015	0.052	0.46	NO
11	RAC1	RAC1	RAC1	5759	0.038	0.44	NO
12	RB1	RB1	RB1	6335	0.027	0.42	NO
13	CDK4	CDK4	CDK4	6378	0.026	0.43	NO
14	CCND1	CCND1	CCND1	7008	0.016	0.41	NO
15	AKT1	AKT1	AKT1	7737	0.0045	0.37	NO
16	CDK2	CDK2	CDK2	8228	-0.0032	0.34	NO
17	RHOA	RHOA	RHOA	8234	-0.0033	0.35	NO
18	NFKBIA	NFKBIA	NFKBIA	8271	-0.004	0.35	NO
19	RELA	RELA	RELA	8584	-0.009	0.33	NO
20	MAPK3	MAPK3	MAPK3	8962	-0.015	0.32	NO
21	CDKN1B	CDKN1B	CDKN1B	10608	-0.044	0.25	NO
22	CCNE1	CCNE1	CCNE1	10902	-0.05	0.26	NO
23	PIK3R1	PIK3R1	PIK3R1	11962	-0.073	0.24	NO
24	RAF1	RAF1	RAF1	11996	-0.074	0.28	NO
25	IKBKB	IKBKB	IKBKB	13436	-0.12	0.26	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: BIOCARTA G1 PATHWAY.

Figure S42. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA G1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA EGF PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CDK6	CDK6	CDK6	104	0.59	0.041	YES
2	MYC	MYC	MYC	327	0.4	0.061	YES
3	SFN	SFN	SFN	377	0.38	0.088	YES
4	ORC1L	ORC1L	ORC1L	539	0.33	0.11	YES
5	CCNA1	CCNA1	CCNA1	558	0.32	0.13	YES
6	CDC25B	CDC25B	CDC25B	674	0.3	0.15	YES
7	CCNE2	CCNE2	CCNE2	713	0.29	0.17	YES
8	PTTG1	PTTG1	PTTG1	927	0.25	0.18	YES
9	TGFB2	TGFB2	TGFB2	931	0.25	0.2	YES
10	PKMYT1	PKMYT1	PKMYT1	945	0.25	0.22	YES
11	CCNA2	CCNA2	CCNA2	995	0.24	0.23	YES
12	PLK1	PLK1	PLK1	1041	0.24	0.25	YES
13	E2F2	E2F2	E2F2	1139	0.23	0.26	YES
14	CCNB1	CCNB1	CCNB1	1216	0.22	0.28	YES
15	MAD2L1	MAD2L1	MAD2L1	1231	0.22	0.29	YES
16	CDC20	CDC20	CDC20	1260	0.21	0.31	YES
17	TTK	TTK	TTK	1379	0.2	0.32	YES
18	CCNB2	CCNB2	CCNB2	1393	0.2	0.33	YES
19	BUB1B	BUB1B	BUB1B	1482	0.19	0.34	YES
20	RBL1	RBL1	RBL1	1556	0.18	0.35	YES
21	CDC45	CDC45	CDC45	1775	0.17	0.35	YES
22	MCM4	MCM4	MCM4	1997	0.15	0.35	YES
23	CDK1	CDK1	CDK1	2000	0.15	0.37	YES
24	BUB1	BUB1	BUB1	2134	0.15	0.37	YES
25	CHEK1	CHEK1	CHEK1	2170	0.14	0.38	YES
26	MCM2	MCM2	MCM2	2295	0.14	0.38	YES
27	CDC25C	CDC25C	CDC25C	2297	0.14	0.4	YES
28	YWHAQ	YWHAQ	YWHAQ	2538	0.12	0.39	YES
29	PRKDC	PRKDC	PRKDC	2587	0.12	0.4	YES
30	TGFB1	TGFB1	TGFB1	2610	0.12	0.41	YES
31	STAG1	STAG1	STAG1	2740	0.12	0.41	YES
32	MCM6	MCM6	MCM6	2777	0.12	0.42	YES
33	TFDP1	TFDP1	TFDP1	2831	0.11	0.42	YES
34	ESPL1	ESPL1	ESPL1	3005	0.11	0.42	YES
35	CDC7	CDC7	CDC7	3054	0.1	0.43	YES
36	YWHAG	YWHAG	YWHAG	3140	0.1	0.43	YES
37	CDKN1A	CDKN1A	CDKN1A	3142	0.1	0.44	YES
38	TGFB3	TGFB3	TGFB3	3207	0.098	0.44	YES
39	SMC3	SMC3	SMC3	3208	0.098	0.45	YES
40	CDC25A	CDC25A	CDC25A	3216	0.098	0.46	YES
41	SMC1A	SMC1A	SMC1A	3275	0.096	0.46	YES
42	CDKN2B	CDKN2B	CDKN2B	3341	0.093	0.47	YES
43	GADD45A	GADD45A	GADD45A	3364	0.092	0.47	YES
44	SKP2	SKP2	SKP2	3391	0.092	0.48	YES
45	ANAPC10	ANAPC10	ANAPC10	3575	0.086	0.48	YES
46	CDK7	CDK7	CDK7	3585	0.086	0.48	YES
47	CDC6	CDC6	CDC6	3604	0.085	0.49	YES
48	ORC5L	ORC5L	ORC5L	3636	0.084	0.49	YES
49	MAD2L2	MAD2L2	MAD2L2	3670	0.083	0.5	YES
50	ORC6L	ORC6L	ORC6L	3732	0.082	0.5	YES
51	ANAPC1	ANAPC1	ANAPC1	3980	0.075	0.49	YES
52	PCNA	PCNA	PCNA	4013	0.074	0.5	YES
53	CDC27	CDC27	CDC27	4091	0.072	0.5	YES
54	YWHAH	YWHAH	YWHAH	4152	0.071	0.5	YES
55	STAG2	STAG2	STAG2	4272	0.068	0.5	YES
56	CDKN2A	CDKN2A	CDKN2A	4414	0.064	0.5	YES
57	ORC2L	ORC2L	ORC2L	4497	0.062	0.5	YES
58	CDC23	CDC23	CDC23	4606	0.06	0.5	YES
59	MCM5	MCM5	MCM5	4627	0.059	0.5	YES
60	TFDP2	TFDP2	TFDP2	4650	0.059	0.5	YES
61	YWHAZ	YWHAZ	YWHAZ	4990	0.052	0.49	NO
62	RAD21	RAD21	RAD21	5239	0.047	0.48	NO
63	MCM7	MCM7	MCM7	5264	0.046	0.48	NO
64	ATR	ATR	ATR	5524	0.042	0.47	NO
65	ORC3L	ORC3L	ORC3L	5796	0.037	0.46	NO
66	BUB3	BUB3	BUB3	5843	0.036	0.46	NO
67	CDKN2D	CDKN2D	CDKN2D	5861	0.035	0.46	NO
68	GSK3B	GSK3B	GSK3B	5885	0.035	0.46	NO
69	E2F1	E2F1	E2F1	5923	0.034	0.46	NO
70	CUL1	CUL1	CUL1	5958	0.034	0.46	NO
71	CDC26	CDC26	CDC26	6044	0.032	0.46	NO
72	CDKN2C	CDKN2C	CDKN2C	6086	0.032	0.46	NO
73	CCND3	CCND3	CCND3	6179	0.03	0.46	NO
74	RB1	RB1	RB1	6335	0.027	0.45	NO
75	CDK4	CDK4	CDK4	6378	0.026	0.45	NO
76	ORC4L	ORC4L	ORC4L	6380	0.026	0.45	NO
77	SMAD2	SMAD2	SMAD2	6912	0.018	0.42	NO
78	ABL1	ABL1	ABL1	6917	0.017	0.43	NO
79	CCND1	CCND1	CCND1	7008	0.016	0.42	NO
80	E2F4	E2F4	E2F4	7080	0.015	0.42	NO
81	YWHAE	YWHAE	YWHAE	7193	0.013	0.42	NO
82	FZR1	FZR1	FZR1	7236	0.012	0.41	NO
83	CCNH	CCNH	CCNH	7412	0.0094	0.4	NO
84	HDAC2	HDAC2	HDAC2	7480	0.0084	0.4	NO
85	SMAD3	SMAD3	SMAD3	7593	0.0067	0.4	NO
86	HDAC1	HDAC1	HDAC1	7625	0.0063	0.4	NO
87	WEE2	WEE2	WEE2	7657	0.0058	0.39	NO
88	ANAPC5	ANAPC5	ANAPC5	7684	0.0054	0.39	NO
89	CCND2	CCND2	CCND2	7792	0.0038	0.39	NO
90	SKP1	SKP1	SKP1	7803	0.0036	0.39	NO
91	MAD1L1	MAD1L1	MAD1L1	7827	0.0032	0.39	NO
92	YWHAB	YWHAB	YWHAB	7858	0.0027	0.38	NO
93	WEE1	WEE1	WEE1	8036	-0.000071	0.37	NO
94	ANAPC7	ANAPC7	ANAPC7	8077	-0.001	0.37	NO
95	CREBBP	CREBBP	CREBBP	8147	-0.002	0.37	NO
96	CDK2	CDK2	CDK2	8228	-0.0032	0.36	NO
97	MCM3	MCM3	MCM3	8246	-0.0035	0.36	NO
98	E2F3	E2F3	E2F3	8638	-0.0097	0.34	NO
99	CHEK2	CHEK2	CHEK2	8658	-0.01	0.34	NO
100	ANAPC2	ANAPC2	ANAPC2	8802	-0.012	0.34	NO
101	ANAPC13	ANAPC13	ANAPC13	8869	-0.013	0.33	NO
102	RBX1	RBX1	RBX1	9083	-0.017	0.32	NO
103	SMAD4	SMAD4	SMAD4	9756	-0.028	0.29	NO
104	SMC1B	SMC1B	SMC1B	10153	-0.035	0.27	NO
105	ANAPC11	ANAPC11	ANAPC11	10240	-0.037	0.27	NO
106	CDKN1B	CDKN1B	CDKN1B	10608	-0.044	0.25	NO
107	ZBTB17	ZBTB17	ZBTB17	10612	-0.044	0.25	NO
108	RBL2	RBL2	RBL2	10760	-0.048	0.25	NO
109	MDM2	MDM2	MDM2	10836	-0.049	0.25	NO
110	CCNE1	CCNE1	CCNE1	10902	-0.05	0.25	NO
111	CDC16	CDC16	CDC16	11061	-0.054	0.24	NO
112	EP300	EP300	EP300	11112	-0.055	0.25	NO
113	GADD45B	GADD45B	GADD45B	11725	-0.068	0.22	NO
114	ATM	ATM	ATM	12614	-0.09	0.18	NO
115	TP53	TP53	TP53	12743	-0.094	0.18	NO
116	ANAPC4	ANAPC4	ANAPC4	12977	-0.1	0.17	NO
117	CDC14B	CDC14B	CDC14B	13469	-0.12	0.15	NO
118	CCNB3	CCNB3	CCNB3	14531	-0.16	0.11	NO
119	GADD45G	GADD45G	GADD45G	14920	-0.17	0.1	NO
120	CDKN1C	CDKN1C	CDKN1C	16085	-0.24	0.055	NO
121	PTTG2	PTTG2	PTTG2	16244	-0.25	0.066	NO
122	E2F5	E2F5	E2F5	16284	-0.26	0.084	NO
123	CDC14A	CDC14A	CDC14A	16413	-0.27	0.099	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: BIOCARTA EGF PATHWAY.

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

genes ES table in pathway: BIOCARTA 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	POLE2	POLE2	POLE2	723	0.28	0.055	YES
2	GTF2H3	GTF2H3	GTF2H3	1050	0.24	0.12	YES
3	RFC4	RFC4	RFC4	1942	0.16	0.12	YES
4	POLE3	POLE3	POLE3	2195	0.14	0.15	YES
5	MNAT1	MNAT1	MNAT1	2300	0.14	0.19	YES
6	POLD2	POLD2	POLD2	2305	0.14	0.24	YES
7	RFC3	RFC3	RFC3	2496	0.13	0.27	YES
8	GTF2H1	GTF2H1	GTF2H1	2876	0.11	0.29	YES
9	POLD1	POLD1	POLD1	3007	0.1	0.32	YES
10	ERCC6	ERCC6	ERCC6	3012	0.1	0.35	YES
11	RPA3	RPA3	RPA3	3167	0.1	0.37	YES
12	ERCC8	ERCC8	ERCC8	3393	0.092	0.39	YES
13	CDK7	CDK7	CDK7	3585	0.086	0.41	YES
14	ERCC4	ERCC4	ERCC4	3852	0.079	0.42	YES
15	PCNA	PCNA	PCNA	4013	0.074	0.44	YES
16	POLD3	POLD3	POLD3	4025	0.074	0.46	YES
17	RFC2	RFC2	RFC2	4193	0.07	0.48	YES
18	RPA1	RPA1	RPA1	4567	0.061	0.48	YES
19	RFC1	RFC1	RFC1	4659	0.058	0.49	YES
20	ERCC1	ERCC1	ERCC1	4705	0.058	0.51	YES
21	CUL4A	CUL4A	CUL4A	5666	0.039	0.47	NO
22	GTF2H4	GTF2H4	GTF2H4	5751	0.038	0.48	NO
23	RPA4	RPA4	RPA4	5752	0.038	0.49	NO
24	RFC5	RFC5	RFC5	5777	0.037	0.5	NO
25	POLE	POLE	POLE	6313	0.028	0.48	NO
26	DDB2	DDB2	DDB2	6336	0.027	0.49	NO
27	ERCC3	ERCC3	ERCC3	6564	0.023	0.48	NO
28	CUL4B	CUL4B	CUL4B	6595	0.023	0.49	NO
29	XPA	XPA	XPA	6671	0.021	0.49	NO
30	RAD23A	RAD23A	RAD23A	6691	0.021	0.5	NO
31	POLE4	POLE4	POLE4	6828	0.019	0.5	NO
32	CETN2	CETN2	CETN2	7315	0.011	0.47	NO
33	CCNH	CCNH	CCNH	7412	0.0094	0.47	NO
34	DDB1	DDB1	DDB1	7536	0.0075	0.46	NO
35	POLD4	POLD4	POLD4	8245	-0.0035	0.43	NO
36	LIG1	LIG1	LIG1	8452	-0.0066	0.42	NO
37	RPA2	RPA2	RPA2	8468	-0.0069	0.42	NO
38	RBX1	RBX1	RBX1	9083	-0.017	0.39	NO
39	GTF2H2	GTF2H2	GTF2H2	9190	-0.019	0.39	NO
40	GTF2H5	GTF2H5	GTF2H5	10761	-0.048	0.32	NO
41	ERCC2	ERCC2	ERCC2	11033	-0.053	0.32	NO
42	ERCC5	ERCC5	ERCC5	11783	-0.069	0.3	NO
43	XPC	XPC	XPC	14215	-0.14	0.22	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: BIOCARTA RACCYCD 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	PSMB9	PSMB9	PSMB9	535	0.33	0.085	YES
2	IFNG	IFNG	IFNG	751	0.28	0.17	YES
3	PSMB8	PSMB8	PSMB8	2401	0.13	0.13	YES
4	PSMD1	PSMD1	PSMD1	2955	0.11	0.13	YES
5	PSMD2	PSMD2	PSMD2	2958	0.11	0.17	YES
6	PSMD12	PSMD12	PSMD12	3076	0.1	0.2	YES
7	PSMD14	PSMD14	PSMD14	3096	0.1	0.24	YES
8	PSMB7	PSMB7	PSMB7	3231	0.097	0.26	YES
9	PSMD11	PSMD11	PSMD11	3233	0.097	0.3	YES
10	PSMA6	PSMA6	PSMA6	3302	0.094	0.32	YES
11	PSMB2	PSMB2	PSMB2	3428	0.09	0.35	YES
12	PSME2	PSME2	PSME2	3542	0.087	0.37	YES
13	PSMA1	PSMA1	PSMA1	3826	0.079	0.38	YES
14	PSMA2	PSMA2	PSMA2	3941	0.076	0.41	YES
15	PSMC3	PSMC3	PSMC3	4129	0.071	0.42	YES
16	PSMA3	PSMA3	PSMA3	4212	0.07	0.44	YES
17	PSMA5	PSMA5	PSMA5	4283	0.068	0.46	YES
18	PSMB5	PSMB5	PSMB5	4416	0.064	0.48	YES
19	PSMC2	PSMC2	PSMC2	4454	0.063	0.5	YES
20	PSME3	PSME3	PSME3	4613	0.059	0.51	YES
21	POMP	POMP	POMP	4667	0.058	0.52	YES
22	PSMB1	PSMB1	PSMB1	4744	0.057	0.54	YES
23	PSMC1	PSMC1	PSMC1	4883	0.054	0.55	YES
24	PSMA7	PSMA7	PSMA7	4918	0.054	0.57	YES
25	PSMD13	PSMD13	PSMD13	5023	0.052	0.58	YES
26	PSMA4	PSMA4	PSMA4	5256	0.047	0.58	YES
27	PSMB6	PSMB6	PSMB6	5494	0.042	0.59	YES
28	PSME4	PSME4	PSME4	5546	0.041	0.6	YES
29	PSME1	PSME1	PSME1	5862	0.035	0.59	YES
30	PSMC6	PSMC6	PSMC6	5913	0.034	0.6	YES
31	PSMD7	PSMD7	PSMD7	6374	0.026	0.59	NO
32	PSMF1	PSMF1	PSMF1	6402	0.026	0.59	NO
33	PSMD8	PSMD8	PSMD8	6478	0.025	0.6	NO
34	PSMB3	PSMB3	PSMB3	6867	0.018	0.58	NO
35	PSMD3	PSMD3	PSMD3	7045	0.015	0.58	NO
36	PSMC5	PSMC5	PSMC5	7178	0.013	0.57	NO
37	PSMD6	PSMD6	PSMD6	8058	-0.00049	0.53	NO
38	PSMB4	PSMB4	PSMB4	8470	-0.0069	0.51	NO
39	SHFM1	SHFM1	SHFM1	8770	-0.012	0.5	NO
40	PSMD4	PSMD4	PSMD4	8857	-0.013	0.49	NO
41	PSMC4	PSMC4	PSMC4	9693	-0.027	0.46	NO
42	PSMA8	PSMA8	PSMA8	9903	-0.03	0.46	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: BIOCARTA RACCYCD PATHWAY.

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

genes ES table in pathway: BIOCARTA MAPK PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	POLR3G	POLR3G	POLR3G	88	0.61	0.062	YES
2	DPYD	DPYD	DPYD	145	0.52	0.12	YES
3	TYMP	TYMP	TYMP	298	0.41	0.15	YES
4	CDA	CDA	CDA	372	0.38	0.19	YES
5	POLE2	POLE2	POLE2	723	0.28	0.2	YES
6	NT5E	NT5E	NT5E	872	0.26	0.22	YES
7	RRM2	RRM2	RRM2	1037	0.24	0.24	YES
8	PNP	PNP	PNP	1622	0.18	0.23	YES
9	RRM1	RRM1	RRM1	1626	0.18	0.25	YES
10	CMPK2	CMPK2	CMPK2	1845	0.16	0.25	YES
11	TXNRD1	TXNRD1	TXNRD1	1881	0.16	0.27	YES
12	TK1	TK1	TK1	2077	0.15	0.27	YES
13	PRIM1	PRIM1	PRIM1	2140	0.15	0.28	YES
14	POLE3	POLE3	POLE3	2195	0.14	0.3	YES
15	POLD2	POLD2	POLD2	2305	0.14	0.31	YES
16	POLR1A	POLR1A	POLR1A	2386	0.13	0.32	YES
17	NT5M	NT5M	NT5M	2444	0.13	0.33	YES
18	TYMS	TYMS	TYMS	2493	0.13	0.34	YES
19	UPP1	UPP1	UPP1	2564	0.12	0.35	YES
20	NT5C1B	NT5C1B	NT5C1B	2727	0.12	0.35	YES
21	PRIM2	PRIM2	PRIM2	2868	0.11	0.36	YES
22	POLA1	POLA1	POLA1	2889	0.11	0.37	YES
23	POLD1	POLD1	POLD1	3007	0.1	0.37	YES
24	POLR1E	POLR1E	POLR1E	3238	0.097	0.37	YES
25	CAD	CAD	CAD	3261	0.096	0.38	YES
26	UCK2	UCK2	UCK2	3264	0.096	0.39	YES
27	POLR2D	POLR2D	POLR2D	3285	0.095	0.4	YES
28	POLR1B	POLR1B	POLR1B	3440	0.09	0.4	YES
29	POLR3D	POLR3D	POLR3D	3582	0.086	0.4	YES
30	POLA2	POLA2	POLA2	3829	0.079	0.4	NO
31	POLD3	POLD3	POLD3	4025	0.074	0.4	NO
32	PNPT1	PNPT1	PNPT1	4228	0.069	0.39	NO
33	UMPS	UMPS	UMPS	4255	0.068	0.4	NO
34	POLR3A	POLR3A	POLR3A	4317	0.066	0.4	NO
35	DTYMK	DTYMK	DTYMK	4769	0.056	0.38	NO
36	POLR3F	POLR3F	POLR3F	4813	0.056	0.39	NO
37	CANT1	CANT1	CANT1	4856	0.055	0.39	NO
38	DCK	DCK	DCK	4959	0.053	0.39	NO
39	NT5C3	NT5C3	NT5C3	5190	0.048	0.38	NO
40	CMPK1	CMPK1	CMPK1	5356	0.045	0.38	NO
41	DUT	DUT	DUT	5534	0.042	0.37	NO
42	NME1	NME1	NME1	5972	0.034	0.35	NO
43	POLR3B	POLR3B	POLR3B	6032	0.032	0.35	NO
44	NME2	NME2	NME2	6068	0.032	0.35	NO
45	POLE	POLE	POLE	6313	0.028	0.34	NO
46	POLR2L	POLR2L	POLR2L	6323	0.027	0.35	NO
47	DCTD	DCTD	DCTD	6428	0.025	0.34	NO
48	UCK1	UCK1	UCK1	6676	0.021	0.33	NO
49	NME1-NME2	NME1-NME2	NME1-NME2	6755	0.02	0.33	NO
50	POLE4	POLE4	POLE4	6828	0.019	0.33	NO
51	POLR3H	POLR3H	POLR3H	6872	0.018	0.33	NO
52	POLR2A	POLR2A	POLR2A	6973	0.016	0.32	NO
53	POLR2B	POLR2B	POLR2B	7752	0.0043	0.28	NO
54	DHODH	DHODH	DHODH	7794	0.0037	0.28	NO
55	POLR3C	POLR3C	POLR3C	7915	0.0016	0.27	NO
56	POLR2C	POLR2C	POLR2C	7953	0.0011	0.27	NO
57	POLR2G	POLR2G	POLR2G	7958	0.00099	0.27	NO
58	POLR2H	POLR2H	POLR2H	8207	-0.0029	0.26	NO
59	POLD4	POLD4	POLD4	8245	-0.0035	0.26	NO
60	AK3	AK3	AK3	8300	-0.0045	0.25	NO
61	NT5C	NT5C	NT5C	8383	-0.0057	0.25	NO
62	RRM2B	RRM2B	RRM2B	8429	-0.0063	0.25	NO
63	POLR1D	POLR1D	POLR1D	8481	-0.0071	0.24	NO
64	ITPA	ITPA	ITPA	8688	-0.01	0.24	NO
65	POLR3K	POLR3K	POLR3K	9185	-0.019	0.21	NO
66	POLR2F	POLR2F	POLR2F	9196	-0.019	0.21	NO
67	POLR2E	POLR2E	POLR2E	9284	-0.02	0.21	NO
68	NUDT2	NUDT2	NUDT2	9299	-0.021	0.21	NO
69	NME6	NME6	NME6	9430	-0.023	0.2	NO
70	POLR2K	POLR2K	POLR2K	9559	-0.025	0.2	NO
71	NME7	NME7	NME7	9564	-0.025	0.2	NO
72	TXNRD2	TXNRD2	TXNRD2	9621	-0.026	0.2	NO
73	ENTPD6	ENTPD6	ENTPD6	9860	-0.03	0.19	NO
74	POLR1C	POLR1C	POLR1C	9956	-0.031	0.19	NO
75	ZNRD1	ZNRD1	ZNRD1	10057	-0.033	0.19	NO
76	POLR3GL	POLR3GL	POLR3GL	10339	-0.039	0.18	NO
77	UCKL1	UCKL1	UCKL1	10458	-0.041	0.18	NO
78	POLR2I	POLR2I	POLR2I	10617	-0.045	0.17	NO
79	UPRT	UPRT	UPRT	10691	-0.046	0.17	NO
80	ENTPD4	ENTPD4	ENTPD4	10966	-0.052	0.16	NO
81	ENTPD1	ENTPD1	ENTPD1	11636	-0.066	0.13	NO
82	POLR2J	POLR2J	POLR2J	11666	-0.066	0.14	NO
83	ENTPD8	ENTPD8	ENTPD8	11874	-0.071	0.14	NO
84	TK2	TK2	TK2	12382	-0.084	0.12	NO
85	UPP2	UPP2	UPP2	12813	-0.096	0.1	NO
86	UPB1	UPB1	UPB1	13055	-0.1	0.1	NO
87	NME3	NME3	NME3	13189	-0.11	0.11	NO
88	POLR2J3	POLR2J3	POLR2J3	13447	-0.12	0.1	NO
89	CTPS2	CTPS2	CTPS2	13508	-0.12	0.11	NO
90	DPYS	DPYS	DPYS	13609	-0.12	0.12	NO
91	ENTPD5	ENTPD5	ENTPD5	13970	-0.13	0.12	NO
92	POLR2J2	POLR2J2	POLR2J2	14124	-0.14	0.12	NO
93	NME4	NME4	NME4	14694	-0.16	0.11	NO
94	NT5C2	NT5C2	NT5C2	14713	-0.16	0.13	NO
95	ENTPD3	ENTPD3	ENTPD3	16316	-0.26	0.066	NO
96	NME5	NME5	NME5	17139	-0.34	0.058	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: BIOCARTA MAPK PATHWAY.

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

genes ES table in pathway: BIOCARTA P38MAPK PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	WARS	WARS	WARS	565	0.32	0.11	YES
2	TARS	TARS	TARS	1850	0.16	0.11	YES
3	IARS	IARS	IARS	2457	0.13	0.13	YES
4	YARS	YARS	YARS	2850	0.11	0.16	YES
5	FARSB	FARSB	FARSB	3146	0.1	0.19	YES
6	IARS2	IARS2	IARS2	3306	0.094	0.22	YES
7	DARS	DARS	DARS	3632	0.084	0.24	YES
8	MARS2	MARS2	MARS2	3864	0.078	0.26	YES
9	EPRS	EPRS	EPRS	3993	0.075	0.29	YES
10	RARS	RARS	RARS	4104	0.072	0.31	YES
11	YARS2	YARS2	YARS2	4153	0.071	0.34	YES
12	GARS	GARS	GARS	4190	0.07	0.37	YES
13	SARS	SARS	SARS	4354	0.066	0.39	YES
14	TARSL2	TARSL2	TARSL2	4480	0.063	0.41	YES
15	FARS2	FARS2	FARS2	5075	0.051	0.4	YES
16	DARS2	DARS2	DARS2	5285	0.046	0.41	YES
17	KARS	KARS	KARS	5365	0.045	0.42	YES
18	AARS	AARS	AARS	5693	0.039	0.42	YES
19	MARS	MARS	MARS	5886	0.035	0.43	YES
20	CARS	CARS	CARS	5929	0.034	0.44	YES
21	HARS	HARS	HARS	6163	0.03	0.44	YES
22	FARSA	FARSA	FARSA	6209	0.029	0.45	YES
23	VARS	VARS	VARS	6348	0.027	0.45	YES
24	LARS	LARS	LARS	7012	0.016	0.42	NO
25	PSTK	PSTK	PSTK	7148	0.014	0.42	NO
26	WARS2	WARS2	WARS2	7523	0.0076	0.41	NO
27	RARS2	RARS2	RARS2	7621	0.0063	0.4	NO
28	PARS2	PARS2	PARS2	7835	0.0031	0.39	NO
29	HARS2	HARS2	HARS2	8134	-0.0018	0.38	NO
30	LARS2	LARS2	LARS2	8186	-0.0026	0.38	NO
31	EARS2	EARS2	EARS2	8219	-0.0031	0.38	NO
32	NARS	NARS	NARS	8396	-0.0058	0.37	NO
33	CARS2	CARS2	CARS2	9493	-0.024	0.32	NO
34	MTFMT	MTFMT	MTFMT	9639	-0.026	0.32	NO
35	NARS2	NARS2	NARS2	9655	-0.026	0.33	NO
36	AARS2	AARS2	AARS2	9947	-0.031	0.33	NO
37	VARS2	VARS2	VARS2	11003	-0.052	0.29	NO
38	SARS2	SARS2	SARS2	11706	-0.067	0.28	NO
39	SEPSECS	SEPSECS	SEPSECS	12129	-0.077	0.3	NO
40	QARS	QARS	QARS	12534	-0.088	0.31	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: BIOCARTA P38MAPK PATHWAY.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA P38MAPK PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA IL1R PATHWAY

Table 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	CDK6	CDK6	CDK6	104	0.59	0.22	YES
2	CCNA1	CCNA1	CCNA1	558	0.32	0.31	YES
3	TGFB2	TGFB2	TGFB2	931	0.25	0.39	YES
4	CDK1	CDK1	CDK1	2000	0.15	0.39	YES
5	TGFB1	TGFB1	TGFB1	2610	0.12	0.4	YES
6	TFDP1	TFDP1	TFDP1	2831	0.11	0.43	YES
7	CDKN1A	CDKN1A	CDKN1A	3142	0.1	0.45	YES
8	TGFB3	TGFB3	TGFB3	3207	0.098	0.49	YES
9	CDC25A	CDC25A	CDC25A	3216	0.098	0.52	YES
10	CDKN2B	CDKN2B	CDKN2B	3341	0.093	0.55	YES
11	SKP2	SKP2	SKP2	3391	0.092	0.58	YES
12	CDKN2A	CDKN2A	CDKN2A	4414	0.064	0.55	NO
13	DHFR	DHFR	DHFR	4584	0.06	0.56	NO
14	ATR	ATR	ATR	5524	0.042	0.53	NO
15	GSK3B	GSK3B	GSK3B	5885	0.035	0.52	NO
16	RB1	RB1	RB1	6335	0.027	0.51	NO
17	CDK4	CDK4	CDK4	6378	0.026	0.52	NO
18	ABL1	ABL1	ABL1	6917	0.017	0.49	NO
19	CCND1	CCND1	CCND1	7008	0.016	0.49	NO
20	SMAD3	SMAD3	SMAD3	7593	0.0067	0.46	NO
21	HDAC1	HDAC1	HDAC1	7625	0.0063	0.46	NO
22	CDK2	CDK2	CDK2	8228	-0.0032	0.43	NO
23	SMAD4	SMAD4	SMAD4	9756	-0.028	0.36	NO
24	CDKN1B	CDKN1B	CDKN1B	10608	-0.044	0.33	NO
25	CCNE1	CCNE1	CCNE1	10902	-0.05	0.33	NO
26	ATM	ATM	ATM	12614	-0.09	0.27	NO
27	TP53	TP53	TP53	12743	-0.094	0.3	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: BIOCARTA IL1R PATHWAY.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA TNFR1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TNF	TNF	TNF	1145	0.23	0.038	YES
2	BAG4	BAG4	BAG4	2015	0.15	0.058	YES
3	MAPK8	MAPK8	MAPK8	2016	0.15	0.13	YES
4	MAP3K1	MAP3K1	MAP3K1	2186	0.14	0.18	YES
5	LMNB2	LMNB2	LMNB2	2267	0.14	0.24	YES
6	PRKDC	PRKDC	PRKDC	2587	0.12	0.28	YES
7	LMNB1	LMNB1	LMNB1	2780	0.11	0.32	YES
8	JUN	JUN	JUN	2824	0.11	0.37	YES
9	PAK1	PAK1	PAK1	3075	0.1	0.4	YES
10	MAP3K7	MAP3K7	MAP3K7	3423	0.09	0.42	YES
11	TNFRSF1A	TNFRSF1A	TNFRSF1A	3711	0.082	0.44	YES
12	FADD	FADD	FADD	3781	0.08	0.47	YES
13	PAK2	PAK2	PAK2	5268	0.046	0.41	NO
14	DFFA	DFFA	DFFA	5953	0.034	0.39	NO
15	LMNA	LMNA	LMNA	6093	0.031	0.4	NO
16	PARP1	PARP1	PARP1	6118	0.031	0.41	NO
17	CASP8	CASP8	CASP8	6195	0.03	0.42	NO
18	MAP2K4	MAP2K4	MAP2K4	6217	0.029	0.43	NO
19	RB1	RB1	RB1	6335	0.027	0.43	NO
20	SPTAN1	SPTAN1	SPTAN1	6798	0.019	0.42	NO
21	RIPK1	RIPK1	RIPK1	6958	0.017	0.42	NO
22	TRADD	TRADD	TRADD	7329	0.011	0.4	NO
23	CRADD	CRADD	CRADD	7790	0.0038	0.38	NO
24	CASP2	CASP2	CASP2	7849	0.0029	0.38	NO
25	CASP3	CASP3	CASP3	10019	-0.033	0.27	NO
26	MADD	MADD	MADD	12769	-0.094	0.16	NO
27	DFFB	DFFB	DFFB	14139	-0.14	0.15	NO
28	ARHGDIB	ARHGDIB	ARHGDIB	14788	-0.17	0.19	NO

Figure S55. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA TNFR1 PATHWAY.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 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 PYRIMIDINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	POLR3G	POLR3G	POLR3G	88	0.61	0.097	YES
2	AIM2	AIM2	AIM2	92	0.61	0.2	YES
3	CASP1	CASP1	CASP1	185	0.48	0.27	YES
4	CXCL10	CXCL10	CXCL10	337	0.4	0.33	YES
5	CCL4	CCL4	CCL4	510	0.34	0.38	YES
6	IL18	IL18	IL18	700	0.29	0.42	YES
7	CCL4L2	CCL4L2	CCL4L2	715	0.29	0.46	YES
8	DDX58	DDX58	DDX58	970	0.25	0.49	YES
9	IL1B	IL1B	IL1B	1086	0.23	0.52	YES
10	IFNA13	IFNA13	IFNA13	1572	0.18	0.53	YES
11	IFNA1	IFNA1	IFNA1	1587	0.18	0.56	YES
12	TMEM173	TMEM173	TMEM173	1671	0.18	0.58	YES
13	ZBP1	ZBP1	ZBP1	2003	0.15	0.59	YES
14	CCL5	CCL5	CCL5	2159	0.14	0.6	YES
15	IRF7	IRF7	IRF7	2318	0.14	0.62	YES
16	IL6	IL6	IL6	2372	0.13	0.64	YES
17	NFKB1	NFKB1	NFKB1	3262	0.096	0.6	NO
18	CHUK	CHUK	CHUK	3546	0.087	0.6	NO
19	POLR3D	POLR3D	POLR3D	3582	0.086	0.62	NO
20	PYCARD	PYCARD	PYCARD	4171	0.07	0.6	NO
21	POLR3A	POLR3A	POLR3A	4317	0.066	0.6	NO
22	ADAR	ADAR	ADAR	4510	0.062	0.6	NO
23	IFNB1	IFNB1	IFNB1	4760	0.057	0.6	NO
24	POLR3F	POLR3F	POLR3F	4813	0.056	0.6	NO
25	IKBKG	IKBKG	IKBKG	5015	0.052	0.6	NO
26	IL33	IL33	IL33	5064	0.051	0.6	NO
27	POLR3B	POLR3B	POLR3B	6032	0.032	0.56	NO
28	POLR3H	POLR3H	POLR3H	6872	0.018	0.51	NO
29	RIPK1	RIPK1	RIPK1	6958	0.017	0.51	NO
30	POLR3C	POLR3C	POLR3C	7915	0.0016	0.46	NO
31	IKBKE	IKBKE	IKBKE	7990	0.00064	0.46	NO
32	NFKBIA	NFKBIA	NFKBIA	8271	-0.004	0.44	NO
33	POLR1D	POLR1D	POLR1D	8481	-0.0071	0.43	NO
34	RELA	RELA	RELA	8584	-0.009	0.43	NO
35	TBK1	TBK1	TBK1	8758	-0.012	0.42	NO
36	MAVS	MAVS	MAVS	9165	-0.018	0.4	NO
37	POLR3K	POLR3K	POLR3K	9185	-0.019	0.4	NO
38	POLR1C	POLR1C	POLR1C	9956	-0.031	0.36	NO
39	IRF3	IRF3	IRF3	10095	-0.034	0.36	NO
40	NFKBIB	NFKBIB	NFKBIB	10286	-0.038	0.36	NO
41	POLR3GL	POLR3GL	POLR3GL	10339	-0.039	0.36	NO
42	IKBKB	IKBKB	IKBKB	13436	-0.12	0.21	NO
43	RIPK3	RIPK3	RIPK3	14284	-0.15	0.19	NO
44	TREX1	TREX1	TREX1	14702	-0.16	0.19	NO

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

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

Table 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	POLE2	POLE2	POLE2	723	0.28	0.059	YES
2	RFC4	RFC4	RFC4	1942	0.16	0.046	YES
3	MCM4	MCM4	MCM4	1997	0.15	0.097	YES
4	PRIM1	PRIM1	PRIM1	2140	0.15	0.14	YES
5	POLE3	POLE3	POLE3	2195	0.14	0.19	YES
6	MCM2	MCM2	MCM2	2295	0.14	0.23	YES
7	POLD2	POLD2	POLD2	2305	0.14	0.28	YES
8	RFC3	RFC3	RFC3	2496	0.13	0.31	YES
9	FEN1	FEN1	FEN1	2688	0.12	0.34	YES
10	RNASEH1	RNASEH1	RNASEH1	2693	0.12	0.38	YES
11	MCM6	MCM6	MCM6	2777	0.12	0.42	YES
12	PRIM2	PRIM2	PRIM2	2868	0.11	0.45	YES
13	POLD1	POLD1	POLD1	3007	0.1	0.48	YES
14	RPA3	RPA3	RPA3	3167	0.1	0.5	YES
15	POLA2	POLA2	POLA2	3829	0.079	0.5	YES
16	DNA2	DNA2	DNA2	3975	0.075	0.51	YES
17	PCNA	PCNA	PCNA	4013	0.074	0.54	YES
18	POLD3	POLD3	POLD3	4025	0.074	0.56	YES
19	RFC2	RFC2	RFC2	4193	0.07	0.58	YES
20	RPA1	RPA1	RPA1	4567	0.061	0.58	YES
21	MCM5	MCM5	MCM5	4627	0.059	0.6	YES
22	RFC1	RFC1	RFC1	4659	0.058	0.61	YES
23	RNASEH2A	RNASEH2A	RNASEH2A	5096	0.05	0.61	YES
24	MCM7	MCM7	MCM7	5264	0.046	0.61	YES
25	SSBP1	SSBP1	SSBP1	5501	0.042	0.62	YES
26	RPA4	RPA4	RPA4	5752	0.038	0.62	YES
27	RFC5	RFC5	RFC5	5777	0.037	0.63	YES
28	POLE	POLE	POLE	6313	0.028	0.61	NO
29	POLE4	POLE4	POLE4	6828	0.019	0.58	NO
30	RNASEH2B	RNASEH2B	RNASEH2B	8216	-0.0031	0.51	NO
31	POLD4	POLD4	POLD4	8245	-0.0035	0.51	NO
32	MCM3	MCM3	MCM3	8246	-0.0035	0.51	NO
33	LIG1	LIG1	LIG1	8452	-0.0066	0.5	NO
34	RPA2	RPA2	RPA2	8468	-0.0069	0.5	NO
35	RNASEH2C	RNASEH2C	RNASEH2C	12717	-0.093	0.3	NO

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

Figure S60. 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

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.v3.0-2.symbols.gmt
Expression data file = BLCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = BLCA-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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