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

Colorectal Adenocarcinoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

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 COADREAD-TP. Broad Institute of MIT and Harvard. doi:10.7908/C18914VW

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 COADREAD-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: 191
Number of samples: 623
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 4 :[ clus1 ] 151
pheno.type: 2 - 4 :[ clus2 ] 142
pheno.type: 3 - 4 :[ clus3 ] 131
pheno.type: 4 - 4 :[ clus4 ] 199

For the expression subtypes of 18041 genes in 624 samples, GSEA found enriched gene sets in each cluster using 623 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA RACCYCD PATHWAY, BIOCARTA CHREBP2 PATHWAY, BIOCARTA RHO PATHWAY, BIOCARTA WNT PATHWAY, KEGG CITRATE CYCLE TCA CYCLE, KEGG LYSINE DEGRADATION, KEGG SELENOAMINO ACID METABOLISM, KEGG PYRUVATE METABOLISM, KEGG PROPANOATE METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS

And common core enriched genes are LSM3, LSM5, LSM6, NAA38, AADAT, AASDH, AASDHPPT, AASS, ACAT1, ALDH1B1

clus2

Top enriched gene sets are BIOCARTA FAS PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA DEATH PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA KERATINOCYTE PATHWAY, BIOCARTA PYK2 PATHWAY, BIOCARTA TNFR1 PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG STARCH AND SUCROSE METABOLISM, KEGG O GLYCAN BIOSYNTHESIS

And common core enriched genes are CASP3, CASP8, LMNA, MAPK8, RIPK1, BCL2, CASP7, FAS, MAP2K4, APAF1

clus3

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA ALK PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA BCR PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA CARM ER PATHWAY, BIOCARTA G1 PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA EGF PATHWAY

And common core enriched genes are PIK3CD, PIK3CG, PIK3R5, AKT3, PDGFB, PIK3CA, FIGF, HGF, PAK3, PGF

clus4

Top enriched gene sets are BIOCARTA FMLP PATHWAY, KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG OXIDATIVE PHOSPHORYLATION, KEGG PYRIMIDINE METABOLISM, KEGG ARGININE AND PROLINE METABOLISM, KEGG GLUTATHIONE METABOLISM, KEGG STARCH AND SUCROSE METABOLISM, KEGG ARACHIDONIC ACID METABOLISM

And common core enriched genes are TUBA1A, TUBA3D, TUBA3E, TUBAL3, TUBB2A, TUBB3, TUBB4Q, TUBB8, C1QB, C1QC

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 RACCYCD PATHWAY	25	genes.ES.table	0.26	1.1	0.31	0.6	1	1	0.74	0.26	0.55	0.11
BIOCARTA CHREBP2 PATHWAY	40	genes.ES.table	0.24	0.93	0.56	0.71	1	0.15	0.15	0.13	0.7	0.13
BIOCARTA RHO PATHWAY	30	genes.ES.table	0.19	0.73	0.77	0.92	1	1	0.81	0.19	0.93	0.31
BIOCARTA WNT PATHWAY	25	genes.ES.table	0.26	0.96	0.48	0.74	1	0.04	0.0027	0.04	0.72	0.17
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.36	1.1	0.32	0.59	1	0.45	0.34	0.3	0.53	0.12
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.52	2	0.0043	0.023	0.04	0.42	0.24	0.32	0	0.004
KEGG SELENOAMINO ACID METABOLISM	25	genes.ES.table	0.36	1.2	0.29	0.61	1	0.44	0.28	0.32	0.53	0.13
KEGG PYRUVATE METABOLISM	37	genes.ES.table	0.23	0.78	0.75	0.87	1	0.54	0.32	0.37	0.88	0.24
KEGG PROPANOATE METABOLISM	31	genes.ES.table	0.38	1.2	0.26	0.68	1	0.61	0.34	0.4	0.59	0.2
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.38	1.3	0.2	0.64	0.97	0.65	0.38	0.4	0.5	0.19

genes ES table in pathway: BIOCARTA RACCYCD 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	PIPOX	PIPOX	PIPOX	41	0.4	0.15	YES
2	OGDHL	OGDHL	OGDHL	250	0.26	0.24	YES
3	SETDB2	SETDB2	SETDB2	922	0.16	0.26	YES
4	AASDHPPT	AASDHPPT	AASDHPPT	1741	0.11	0.26	YES
5	AASS	AASS	AASS	2167	0.1	0.28	YES
6	SETMAR	SETMAR	SETMAR	2352	0.094	0.3	YES
7	PLOD2	PLOD2	PLOD2	2725	0.085	0.31	YES
8	ALDH7A1	ALDH7A1	ALDH7A1	2841	0.082	0.34	YES
9	SETD2	SETD2	SETD2	3048	0.078	0.36	YES
10	SUV39H2	SUV39H2	SUV39H2	3205	0.074	0.38	YES
11	WHSC1L1	WHSC1L1	WHSC1L1	3237	0.074	0.4	YES
12	ASH1L	ASH1L	ASH1L	3266	0.073	0.43	YES
13	AADAT	AADAT	AADAT	3290	0.072	0.46	YES
14	SUV420H1	SUV420H1	SUV420H1	3652	0.066	0.46	YES
15	ACAT1	ACAT1	ACAT1	3766	0.064	0.48	YES
16	TMLHE	TMLHE	TMLHE	3841	0.062	0.5	YES
17	AASDH	AASDH	AASDH	4071	0.058	0.51	YES
18	ALDH1B1	ALDH1B1	ALDH1B1	4236	0.055	0.52	YES
19	ACAT2	ACAT2	ACAT2	4660	0.048	0.52	NO
20	ALDH2	ALDH2	ALDH2	5568	0.035	0.48	NO
21	SUV39H1	SUV39H1	SUV39H1	6161	0.027	0.46	NO
22	SETD1A	SETD1A	SETD1A	6303	0.025	0.46	NO
23	SETDB1	SETDB1	SETDB1	6530	0.022	0.46	NO
24	ALDH9A1	ALDH9A1	ALDH9A1	6758	0.019	0.45	NO
25	WHSC1	WHSC1	WHSC1	6839	0.018	0.45	NO
26	PLOD3	PLOD3	PLOD3	7073	0.016	0.45	NO
27	NSD1	NSD1	NSD1	7149	0.015	0.45	NO
28	EHMT2	EHMT2	EHMT2	7160	0.015	0.45	NO
29	HADHA	HADHA	HADHA	7191	0.014	0.46	NO
30	HADH	HADH	HADH	7934	0.0051	0.42	NO
31	GCDH	GCDH	GCDH	8094	0.0032	0.41	NO
32	SETD1B	SETD1B	SETD1B	8689	-0.0046	0.38	NO
33	BBOX1	BBOX1	BBOX1	8700	-0.0048	0.38	NO
34	SUV420H2	SUV420H2	SUV420H2	9182	-0.011	0.36	NO
35	OGDH	OGDH	OGDH	9453	-0.015	0.35	NO
36	SETD8	SETD8	SETD8	9522	-0.016	0.35	NO
37	SETD7	SETD7	SETD7	9758	-0.019	0.34	NO
38	ALDH3A2	ALDH3A2	ALDH3A2	10625	-0.033	0.31	NO
39	ECHS1	ECHS1	ECHS1	10767	-0.035	0.31	NO
40	EHMT1	EHMT1	EHMT1	11017	-0.04	0.32	NO
41	PLOD1	PLOD1	PLOD1	11862	-0.056	0.29	NO
42	DOT1L	DOT1L	DOT1L	12212	-0.064	0.3	NO
43	DLST	DLST	DLST	12532	-0.072	0.3	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 RACCYCD PATHWAY.

Figure S2. 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 CHREBP2 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	NAA38	NAA38	NAA38	955	0.15	-0.029	YES
2	CTNNBL1	CTNNBL1	CTNNBL1	1081	0.15	-0.013	YES
3	THOC2	THOC2	THOC2	1123	0.14	0.0076	YES
4	SR140	SR140	SR140	1125	0.14	0.03	YES
5	CWC15	CWC15	CWC15	1417	0.13	0.034	YES
6	SNRNP27	SNRNP27	SNRNP27	1538	0.12	0.046	YES
7	PRPF40B	PRPF40B	PRPF40B	1686	0.12	0.056	YES
8	PRPF6	PRPF6	PRPF6	1791	0.11	0.068	YES
9	LSM5	LSM5	LSM5	1875	0.11	0.081	YES
10	SNRPB2	SNRPB2	SNRPB2	2014	0.1	0.09	YES
11	SYF2	SYF2	SYF2	2021	0.1	0.11	YES
12	PRPF38B	PRPF38B	PRPF38B	2120	0.1	0.12	YES
13	PRPF40A	PRPF40A	PRPF40A	2326	0.095	0.12	YES
14	SNRPA1	SNRPA1	SNRPA1	2420	0.092	0.13	YES
15	ISY1	ISY1	ISY1	2422	0.092	0.14	YES
16	SNRPE	SNRPE	SNRPE	2512	0.09	0.15	YES
17	LSM6	LSM6	LSM6	2680	0.086	0.16	YES
18	CRNKL1	CRNKL1	CRNKL1	2796	0.084	0.16	YES
19	SF3B14	SF3B14	SF3B14	2874	0.082	0.17	YES
20	TCERG1	TCERG1	TCERG1	2960	0.08	0.18	YES
21	LSM3	LSM3	LSM3	3085	0.077	0.19	YES
22	PRPF3	PRPF3	PRPF3	3153	0.076	0.19	YES
23	PRPF18	PRPF18	PRPF18	3264	0.073	0.2	YES
24	SNRPG	SNRPG	SNRPG	3280	0.073	0.21	YES
25	SLU7	SLU7	SLU7	3330	0.072	0.22	YES
26	BCAS2	BCAS2	BCAS2	3402	0.07	0.23	YES
27	MAGOH	MAGOH	MAGOH	3430	0.07	0.24	YES
28	SFRS6	SFRS6	SFRS6	3479	0.069	0.24	YES
29	CDC40	CDC40	CDC40	3569	0.067	0.25	YES
30	DDX46	DDX46	DDX46	3590	0.067	0.26	YES
31	CDC5L	CDC5L	CDC5L	3636	0.066	0.27	YES
32	SMNDC1	SMNDC1	SMNDC1	3810	0.063	0.27	YES
33	PPIH	PPIH	PPIH	3894	0.061	0.27	YES
34	ZMAT2	ZMAT2	ZMAT2	3920	0.06	0.28	YES
35	SFRS13A	SFRS13A	SFRS13A	4012	0.059	0.28	YES
36	PRPF38A	PRPF38A	PRPF38A	4072	0.058	0.29	YES
37	PQBP1	PQBP1	PQBP1	4075	0.057	0.3	YES
38	RBM25	RBM25	RBM25	4095	0.057	0.31	YES
39	TRA2A	TRA2A	TRA2A	4127	0.057	0.31	YES
40	HNRNPK	HNRNPK	HNRNPK	4379	0.053	0.31	YES
41	MAGOHB	MAGOHB	MAGOHB	4394	0.052	0.32	YES
42	SNRPF	SNRPF	SNRPF	4641	0.049	0.31	YES
43	THOC1	THOC1	THOC1	4666	0.048	0.32	YES
44	HNRNPU	HNRNPU	HNRNPU	4874	0.045	0.31	YES
45	RBMX	RBMX	RBMX	4896	0.045	0.32	YES
46	SFRS1	SFRS1	SFRS1	4928	0.045	0.32	YES
47	NCBP1	NCBP1	NCBP1	5042	0.043	0.32	YES
48	HNRNPA3	HNRNPA3	HNRNPA3	5055	0.043	0.33	YES
49	SFRS3	SFRS3	SFRS3	5057	0.043	0.34	YES
50	DDX42	DDX42	DDX42	5113	0.042	0.34	YES
51	SF3B1	SF3B1	SF3B1	5119	0.042	0.35	YES
52	RBM17	RBM17	RBM17	5128	0.042	0.35	YES
53	SNRNP200	SNRNP200	SNRNP200	5152	0.041	0.36	YES
54	SNRPD3	SNRPD3	SNRPD3	5194	0.04	0.36	YES
55	SNW1	SNW1	SNW1	5262	0.04	0.36	YES
56	SF3B2	SF3B2	SF3B2	5333	0.038	0.37	YES
57	SART1	SART1	SART1	5457	0.037	0.36	YES
58	USP39	USP39	USP39	5551	0.036	0.37	YES
59	SF3B3	SF3B3	SF3B3	5699	0.034	0.36	YES
60	AQR	AQR	AQR	5735	0.033	0.37	YES
61	DHX8	DHX8	DHX8	5747	0.033	0.37	YES
62	SNRPC	SNRPC	SNRPC	5763	0.033	0.38	YES
63	BUD31	BUD31	BUD31	5773	0.032	0.38	YES
64	CHERP	CHERP	CHERP	5975	0.03	0.37	NO
65	PLRG1	PLRG1	PLRG1	6044	0.029	0.37	NO
66	PRPF19	PRPF19	PRPF19	6109	0.028	0.38	NO
67	SFRS5	SFRS5	SFRS5	6320	0.025	0.37	NO
68	SFRS4	SFRS4	SFRS4	6396	0.024	0.37	NO
69	SF3A3	SF3A3	SF3A3	6487	0.023	0.36	NO
70	SNRPD2	SNRPD2	SNRPD2	6507	0.023	0.37	NO
71	DHX15	DHX15	DHX15	6593	0.022	0.37	NO
72	PPIE	PPIE	PPIE	6634	0.021	0.37	NO
73	DDX5	DDX5	DDX5	6667	0.021	0.37	NO
74	RBM22	RBM22	RBM22	6871	0.018	0.36	NO
75	PPIL1	PPIL1	PPIL1	6959	0.017	0.36	NO
76	SNRPA	SNRPA	SNRPA	7064	0.016	0.36	NO
77	EFTUD2	EFTUD2	EFTUD2	7105	0.015	0.36	NO
78	SFRS2B	SFRS2B	SFRS2B	7255	0.013	0.35	NO
79	ACIN1	ACIN1	ACIN1	7286	0.013	0.35	NO
80	THOC4	THOC4	THOC4	7308	0.013	0.35	NO
81	NHP2L1	NHP2L1	NHP2L1	7329	0.012	0.35	NO
82	WBP11	WBP11	WBP11	7349	0.012	0.35	NO
83	U2AF2	U2AF2	U2AF2	7401	0.012	0.35	NO
84	BAT1	BAT1	BAT1	7547	0.0098	0.34	NO
85	DDX23	DDX23	DDX23	7555	0.0097	0.34	NO
86	U2AF1	U2AF1	U2AF1	7596	0.009	0.34	NO
87	HNRNPC	HNRNPC	HNRNPC	7697	0.0078	0.34	NO
88	CCDC12	CCDC12	CCDC12	7775	0.0069	0.34	NO
89	SNRNP70	SNRNP70	SNRNP70	7788	0.0068	0.34	NO
90	TRA2B	TRA2B	TRA2B	7803	0.0066	0.34	NO
91	DHX38	DHX38	DHX38	7936	0.005	0.33	NO
92	PCBP1	PCBP1	PCBP1	7969	0.0046	0.33	NO
93	SF3A2	SF3A2	SF3A2	8065	0.0035	0.32	NO
94	SFRS7	SFRS7	SFRS7	8158	0.0022	0.32	NO
95	RBM8A	RBM8A	RBM8A	8275	0.00084	0.31	NO
96	PRPF4	PRPF4	PRPF4	8423	-0.0012	0.31	NO
97	SNRPB	SNRPB	SNRPB	8452	-0.0016	0.3	NO
98	HNRNPM	HNRNPM	HNRNPM	8471	-0.0018	0.3	NO
99	LSM4	LSM4	LSM4	8603	-0.0034	0.3	NO
100	HSPA1A	HSPA1A	HSPA1A	8605	-0.0035	0.3	NO
101	DHX16	DHX16	DHX16	8836	-0.0063	0.29	NO
102	SFRS2	SFRS2	SFRS2	8964	-0.0082	0.28	NO
103	SF3B4	SF3B4	SF3B4	8972	-0.0083	0.28	NO
104	SNRPD1	SNRPD1	SNRPD1	9010	-0.0089	0.28	NO
105	SFRS9	SFRS9	SFRS9	9157	-0.011	0.27	NO
106	XAB2	XAB2	XAB2	9344	-0.013	0.27	NO
107	PUF60	PUF60	PUF60	9576	-0.016	0.26	NO
108	SF3A1	SF3A1	SF3A1	9829	-0.02	0.24	NO
109	PRPF31	PRPF31	PRPF31	9836	-0.02	0.25	NO
110	HNRNPA1	HNRNPA1	HNRNPA1	9905	-0.022	0.25	NO
111	THOC3	THOC3	THOC3	10006	-0.023	0.24	NO
112	PHF5A	PHF5A	PHF5A	10142	-0.025	0.24	NO
113	EIF4A3	EIF4A3	EIF4A3	10227	-0.026	0.24	NO
114	LSM2	LSM2	LSM2	10282	-0.027	0.24	NO
115	HSPA8	HSPA8	HSPA8	10498	-0.031	0.24	NO
116	LSM7	LSM7	LSM7	10503	-0.031	0.24	NO
117	PRPF8	PRPF8	PRPF8	10648	-0.033	0.24	NO
118	SNRNP40	SNRNP40	SNRNP40	10738	-0.035	0.24	NO
119	SF3B5	SF3B5	SF3B5	11360	-0.046	0.21	NO
120	TXNL4A	TXNL4A	TXNL4A	12886	-0.082	0.14	NO
121	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	13014	-0.086	0.14	NO
122	HSPA1B	HSPA1B	HSPA1B	14584	-0.15	0.08	NO
123	HSPA6	HSPA6	HSPA6	15003	-0.17	0.084	NO
124	HSPA2	HSPA2	HSPA2	15252	-0.18	0.099	NO
125	HSPA1L	HSPA1L	HSPA1L	17122	-0.35	0.05	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 CHREBP2 PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CHREBP2 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 RHO 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	NAA38	NAA38	NAA38	955	0.15	-0.0013	YES
2	C1D	C1D	C1D	1012	0.15	0.046	YES
3	PNPT1	PNPT1	PNPT1	1352	0.13	0.07	YES
4	MPHOSPH6	MPHOSPH6	MPHOSPH6	1382	0.13	0.11	YES
5	LSM5	LSM5	LSM5	1875	0.11	0.12	YES
6	HSPD1	HSPD1	HSPD1	2082	0.1	0.14	YES
7	DIS3	DIS3	DIS3	2441	0.092	0.16	YES
8	LSM6	LSM6	LSM6	2680	0.086	0.17	YES
9	EXOSC8	EXOSC8	EXOSC8	3016	0.079	0.18	YES
10	LSM3	LSM3	LSM3	3085	0.077	0.2	YES
11	TTC37	TTC37	TTC37	3265	0.073	0.22	YES
12	ZCCHC7	ZCCHC7	ZCCHC7	3372	0.071	0.23	YES
13	PAPOLG	PAPOLG	PAPOLG	3437	0.07	0.25	YES
14	SKIV2L2	SKIV2L2	SKIV2L2	3551	0.067	0.27	YES
15	EXOSC9	EXOSC9	EXOSC9	3602	0.066	0.29	YES
16	CNOT4	CNOT4	CNOT4	3661	0.066	0.31	YES
17	EXOSC5	EXOSC5	EXOSC5	4141	0.056	0.3	YES
18	XRN2	XRN2	XRN2	4177	0.056	0.32	YES
19	PAPOLA	PAPOLA	PAPOLA	4417	0.052	0.32	YES
20	PARN	PARN	PARN	4787	0.047	0.32	YES
21	HSPA9	HSPA9	HSPA9	4807	0.046	0.33	YES
22	LSM1	LSM1	LSM1	4812	0.046	0.35	YES
23	DCP2	DCP2	DCP2	4931	0.045	0.35	YES
24	PATL1	PATL1	PATL1	5110	0.042	0.36	YES
25	EXOSC3	EXOSC3	EXOSC3	5389	0.038	0.36	YES
26	XRN1	XRN1	XRN1	5450	0.037	0.36	YES
27	CNOT1	CNOT1	CNOT1	5499	0.036	0.37	YES
28	DDX6	DDX6	DDX6	5637	0.034	0.38	YES
29	CNOT10	CNOT10	CNOT10	5681	0.034	0.39	YES
30	CNOT6L	CNOT6L	CNOT6L	5930	0.03	0.38	YES
31	DCP1A	DCP1A	DCP1A	6031	0.029	0.39	YES
32	EXOSC7	EXOSC7	EXOSC7	6210	0.026	0.39	YES
33	CNOT6	CNOT6	CNOT6	6273	0.026	0.39	YES
34	EXOSC1	EXOSC1	EXOSC1	6278	0.026	0.4	YES
35	DCP1B	DCP1B	DCP1B	6529	0.022	0.39	NO
36	PAPD7	PAPD7	PAPD7	6672	0.021	0.39	NO
37	CNOT2	CNOT2	CNOT2	6711	0.02	0.4	NO
38	EXOSC10	EXOSC10	EXOSC10	7198	0.014	0.38	NO
39	CNOT7	CNOT7	CNOT7	7631	0.0086	0.35	NO
40	EXOSC2	EXOSC2	EXOSC2	7792	0.0068	0.35	NO
41	EDC3	EDC3	EDC3	7823	0.0064	0.35	NO
42	SKIV2L	SKIV2L	SKIV2L	8072	0.0035	0.34	NO
43	EDC4	EDC4	EDC4	8255	0.0011	0.32	NO
44	LSM4	LSM4	LSM4	8603	-0.0034	0.31	NO
45	WDR61	WDR61	WDR61	9636	-0.017	0.26	NO
46	ENO3	ENO3	ENO3	9868	-0.021	0.25	NO
47	CNOT3	CNOT3	CNOT3	10039	-0.024	0.25	NO
48	LSM2	LSM2	LSM2	10282	-0.027	0.24	NO
49	LSM7	LSM7	LSM7	10503	-0.031	0.24	NO
50	ENO1	ENO1	ENO1	10895	-0.038	0.23	NO
51	PAPOLB	PAPOLB	PAPOLB	11173	-0.042	0.23	NO
52	EXOSC4	EXOSC4	EXOSC4	11506	-0.049	0.23	NO
53	DCPS	DCPS	DCPS	11886	-0.056	0.23	NO
54	RQCD1	RQCD1	RQCD1	12418	-0.07	0.22	NO
55	EXOSC6	EXOSC6	EXOSC6	12453	-0.07	0.24	NO
56	ENO2	ENO2	ENO2	15552	-0.2	0.14	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 RHO PATHWAY.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA RHO 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 WNT 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	XRCC2	XRCC2	XRCC2	549	0.2	0.072	YES
2	MRE11A	MRE11A	MRE11A	720	0.18	0.16	YES
3	BRCA2	BRCA2	BRCA2	749	0.18	0.24	YES
4	RPA4	RPA4	RPA4	782	0.17	0.33	YES
5	SHFM1	SHFM1	SHFM1	1333	0.13	0.37	YES
6	RAD54B	RAD54B	RAD54B	1512	0.12	0.42	YES
7	RAD50	RAD50	RAD50	1724	0.11	0.47	YES
8	BLM	BLM	BLM	2686	0.086	0.46	YES
9	RPA3	RPA3	RPA3	3197	0.075	0.47	YES
10	SSBP1	SSBP1	SSBP1	3460	0.069	0.49	YES
11	NBN	NBN	NBN	4200	0.056	0.48	YES
12	EME1	EME1	EME1	4399	0.052	0.49	YES
13	RAD51L3	RAD51L3	RAD51L3	4574	0.05	0.51	YES
14	RAD51L1	RAD51L1	RAD51L1	6027	0.029	0.44	NO
15	POLD2	POLD2	POLD2	6694	0.02	0.42	NO
16	RAD52	RAD52	RAD52	6844	0.018	0.42	NO
17	RAD54L	RAD54L	RAD54L	6970	0.017	0.42	NO
18	POLD3	POLD3	POLD3	8566	-0.0028	0.33	NO
19	MUS81	MUS81	MUS81	9508	-0.016	0.29	NO
20	RPA2	RPA2	RPA2	9734	-0.019	0.29	NO
21	RAD51	RAD51	RAD51	10392	-0.029	0.26	NO
22	RPA1	RPA1	RPA1	10677	-0.034	0.27	NO
23	POLD1	POLD1	POLD1	10804	-0.036	0.28	NO
24	TOP3B	TOP3B	TOP3B	11368	-0.046	0.27	NO
25	POLD4	POLD4	POLD4	11924	-0.057	0.27	NO
26	TOP3A	TOP3A	TOP3A	12271	-0.066	0.28	NO
27	XRCC3	XRCC3	XRCC3	12395	-0.069	0.31	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 WNT PATHWAY.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA WNT 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 CITRATE CYCLE TCA CYCLE

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	DARS	DARS	DARS	1706	0.12	-0.022	YES
2	NARS2	NARS2	NARS2	1746	0.11	0.049	YES
3	DARS2	DARS2	DARS2	2948	0.08	0.033	YES
4	LARS	LARS	LARS	3467	0.069	0.048	YES
5	SEPSECS	SEPSECS	SEPSECS	3556	0.067	0.086	YES
6	GARS	GARS	GARS	3870	0.062	0.11	YES
7	TARS	TARS	TARS	3890	0.061	0.15	YES
8	LARS2	LARS2	LARS2	4226	0.055	0.16	YES
9	MARS2	MARS2	MARS2	4248	0.055	0.2	YES
10	FARSB	FARSB	FARSB	4447	0.052	0.22	YES
11	CARS2	CARS2	CARS2	5241	0.04	0.2	YES
12	RARS2	RARS2	RARS2	5451	0.037	0.21	YES
13	EPRS	EPRS	EPRS	5528	0.036	0.23	YES
14	CARS	CARS	CARS	5533	0.036	0.25	YES
15	KARS	KARS	KARS	5668	0.034	0.27	YES
16	IARS2	IARS2	IARS2	5978	0.03	0.27	YES
17	HARS2	HARS2	HARS2	6000	0.029	0.29	YES
18	EARS2	EARS2	EARS2	6091	0.028	0.3	YES
19	AARS	AARS	AARS	6151	0.027	0.31	YES
20	TARSL2	TARSL2	TARSL2	6225	0.026	0.33	YES
21	VARS2	VARS2	VARS2	6308	0.025	0.34	YES
22	RARS	RARS	RARS	6407	0.024	0.35	YES
23	PSTK	PSTK	PSTK	6423	0.024	0.36	YES
24	YARS	YARS	YARS	6594	0.022	0.37	YES
25	SARS	SARS	SARS	6718	0.02	0.37	YES
26	YARS2	YARS2	YARS2	6881	0.018	0.38	YES
27	IARS	IARS	IARS	7069	0.016	0.38	NO
28	NARS	NARS	NARS	7522	0.01	0.36	NO
29	AARS2	AARS2	AARS2	7627	0.0086	0.36	NO
30	HARS	HARS	HARS	7677	0.008	0.36	NO
31	WARS2	WARS2	WARS2	7757	0.0071	0.36	NO
32	PARS2	PARS2	PARS2	8512	-0.0022	0.32	NO
33	MTFMT	MTFMT	MTFMT	8520	-0.0023	0.32	NO
34	QARS	QARS	QARS	8750	-0.0054	0.31	NO
35	FARSA	FARSA	FARSA	8805	-0.006	0.31	NO
36	VARS	VARS	VARS	8951	-0.0079	0.31	NO
37	MARS	MARS	MARS	9226	-0.012	0.3	NO
38	SARS2	SARS2	SARS2	10145	-0.025	0.26	NO
39	FARS2	FARS2	FARS2	13366	-0.097	0.15	NO
40	WARS	WARS	WARS	15048	-0.17	0.17	NO

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

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

genes ES table in pathway: KEGG LYSINE DEGRADATION

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	ACSL6	ACSL6	ACSL6	35	0.41	0.066	YES
2	PIPOX	PIPOX	PIPOX	41	0.4	0.13	YES
3	AGXT	AGXT	AGXT	259	0.26	0.16	YES
4	AMACR	AMACR	AMACR	323	0.24	0.2	YES
5	MPV17L	MPV17L	MPV17L	888	0.16	0.19	YES
6	PEX12	PEX12	PEX12	952	0.16	0.21	YES
7	PXMP4	PXMP4	PXMP4	1039	0.15	0.23	YES
8	PECR	PECR	PECR	1225	0.14	0.24	YES
9	BAAT	BAAT	BAAT	1266	0.13	0.26	YES
10	PHYH	PHYH	PHYH	1322	0.13	0.28	YES
11	CROT	CROT	CROT	1467	0.12	0.29	YES
12	NUDT12	NUDT12	NUDT12	1564	0.12	0.31	YES
13	PRDX5	PRDX5	PRDX5	1689	0.12	0.32	YES
14	DDO	DDO	DDO	1745	0.11	0.34	YES
15	PEX1	PEX1	PEX1	2051	0.1	0.34	YES
16	ACSL5	ACSL5	ACSL5	2272	0.097	0.34	YES
17	ACOT8	ACOT8	ACOT8	2475	0.091	0.34	YES
18	PEX3	PEX3	PEX3	2599	0.088	0.35	YES
19	PEX13	PEX13	PEX13	2946	0.08	0.34	NO
20	NUDT19	NUDT19	NUDT19	3821	0.063	0.31	NO
21	ACOX1	ACOX1	ACOX1	3929	0.06	0.31	NO
22	FAR1	FAR1	FAR1	3944	0.06	0.32	NO
23	ACSL3	ACSL3	ACSL3	4353	0.053	0.3	NO
24	HSD17B4	HSD17B4	HSD17B4	4482	0.051	0.31	NO
25	PEX7	PEX7	PEX7	4639	0.049	0.3	NO
26	ACSL4	ACSL4	ACSL4	4731	0.048	0.31	NO
27	PEX11A	PEX11A	PEX11A	4752	0.047	0.31	NO
28	FAR2	FAR2	FAR2	4821	0.046	0.32	NO
29	SCP2	SCP2	SCP2	4832	0.046	0.32	NO
30	HAO2	HAO2	HAO2	4933	0.045	0.33	NO
31	EPHX2	EPHX2	EPHX2	5012	0.043	0.33	NO
32	HACL1	HACL1	HACL1	5234	0.04	0.32	NO
33	AGPS	AGPS	AGPS	5255	0.04	0.33	NO
34	PEX5	PEX5	PEX5	5447	0.037	0.32	NO
35	CAT	CAT	CAT	5536	0.036	0.32	NO
36	GNPAT	GNPAT	GNPAT	5667	0.034	0.32	NO
37	PEX16	PEX16	PEX16	5947	0.03	0.31	NO
38	IDH1	IDH1	IDH1	6047	0.029	0.31	NO
39	DECR2	DECR2	DECR2	6510	0.023	0.29	NO
40	PEX11B	PEX11B	PEX11B	6589	0.022	0.29	NO
41	SLC25A17	SLC25A17	SLC25A17	6714	0.02	0.29	NO
42	PEX2	PEX2	PEX2	6738	0.02	0.29	NO
43	EHHADH	EHHADH	EHHADH	7038	0.016	0.27	NO
44	MPV17	MPV17	MPV17	7051	0.016	0.28	NO
45	ABCD3	ABCD3	ABCD3	7078	0.015	0.28	NO
46	PRDX1	PRDX1	PRDX1	7271	0.013	0.27	NO
47	PEX19	PEX19	PEX19	7569	0.0095	0.25	NO
48	PEX10	PEX10	PEX10	7789	0.0068	0.24	NO
49	MLYCD	MLYCD	MLYCD	7903	0.0055	0.24	NO
50	ACOX3	ACOX3	ACOX3	8033	0.004	0.23	NO
51	GSTK1	GSTK1	GSTK1	8266	0.00096	0.22	NO
52	IDH2	IDH2	IDH2	8709	-0.0049	0.19	NO
53	SLC27A2	SLC27A2	SLC27A2	8852	-0.0066	0.19	NO
54	PMVK	PMVK	PMVK	9349	-0.013	0.16	NO
55	MVK	MVK	MVK	9599	-0.017	0.15	NO
56	SOD1	SOD1	SOD1	9625	-0.017	0.15	NO
57	ACAA1	ACAA1	ACAA1	10265	-0.027	0.12	NO
58	HMGCL	HMGCL	HMGCL	10543	-0.032	0.11	NO
59	ABCD1	ABCD1	ABCD1	10555	-0.032	0.11	NO
60	ECH1	ECH1	ECH1	10662	-0.034	0.11	NO
61	PEX6	PEX6	PEX6	10664	-0.034	0.12	NO
62	PEX14	PEX14	PEX14	10734	-0.035	0.12	NO
63	DHRS4	DHRS4	DHRS4	10820	-0.036	0.12	NO
64	PEX26	PEX26	PEX26	10854	-0.037	0.13	NO
65	PXMP2	PXMP2	PXMP2	11987	-0.058	0.073	NO
66	PECI	PECI	PECI	12087	-0.061	0.077	NO
67	ACSL1	ACSL1	ACSL1	12481	-0.071	0.067	NO
68	PEX11G	PEX11G	PEX11G	13074	-0.088	0.048	NO
69	ABCD4	ABCD4	ABCD4	13078	-0.088	0.063	NO
70	SOD2	SOD2	SOD2	13183	-0.091	0.072	NO
71	CRAT	CRAT	CRAT	13543	-0.1	0.068	NO
72	PAOX	PAOX	PAOX	13757	-0.11	0.075	NO
73	XDH	XDH	XDH	14521	-0.15	0.056	NO
74	DAO	DAO	DAO	14786	-0.16	0.068	NO
75	NOS2	NOS2	NOS2	16939	-0.33	0.001	NO
76	ABCD2	ABCD2	ABCD2	17193	-0.36	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: KEGG LYSINE DEGRADATION.

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

genes ES table in pathway: KEGG SELENOAMINO ACID METABOLISM

Table 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	RPA4	RPA4	RPA4	782	0.17	0.035	YES
2	RFC3	RFC3	RFC3	1374	0.13	0.061	YES
3	CUL4B	CUL4B	CUL4B	2024	0.1	0.072	YES
4	CETN2	CETN2	CETN2	2103	0.1	0.11	YES
5	CDK7	CDK7	CDK7	2370	0.094	0.14	YES
6	ERCC5	ERCC5	ERCC5	2568	0.089	0.17	YES
7	GTF2H5	GTF2H5	GTF2H5	2643	0.087	0.21	YES
8	CUL4A	CUL4A	CUL4A	2759	0.084	0.24	YES
9	RFC4	RFC4	RFC4	2918	0.08	0.27	YES
10	CCNH	CCNH	CCNH	2966	0.08	0.3	YES
11	RPA3	RPA3	RPA3	3197	0.075	0.32	YES
12	RFC1	RFC1	RFC1	3611	0.066	0.33	YES
13	GTF2H1	GTF2H1	GTF2H1	3878	0.061	0.34	YES
14	ERCC8	ERCC8	ERCC8	4606	0.049	0.32	YES
15	XPA	XPA	XPA	4701	0.048	0.34	YES
16	ERCC6	ERCC6	ERCC6	4724	0.048	0.36	YES
17	ERCC4	ERCC4	ERCC4	5232	0.04	0.35	YES
18	ERCC3	ERCC3	ERCC3	5620	0.035	0.35	YES
19	RAD23A	RAD23A	RAD23A	5753	0.033	0.35	YES
20	POLE4	POLE4	POLE4	6043	0.029	0.35	YES
21	POLE	POLE	POLE	6262	0.026	0.35	YES
22	RFC2	RFC2	RFC2	6301	0.025	0.36	YES
23	POLD2	POLD2	POLD2	6694	0.02	0.35	YES
24	XPC	XPC	XPC	6724	0.02	0.35	YES
25	MNAT1	MNAT1	MNAT1	6834	0.018	0.36	YES
26	RFC5	RFC5	RFC5	7029	0.016	0.35	YES
27	LIG1	LIG1	LIG1	7147	0.015	0.35	YES
28	GTF2H3	GTF2H3	GTF2H3	7175	0.014	0.36	YES
29	DDB1	DDB1	DDB1	7181	0.014	0.36	YES
30	POLE3	POLE3	POLE3	7483	0.011	0.35	NO
31	RBX1	RBX1	RBX1	8426	-0.0012	0.3	NO
32	POLD3	POLD3	POLD3	8566	-0.0028	0.29	NO
33	POLE2	POLE2	POLE2	8809	-0.0061	0.28	NO
34	PCNA	PCNA	PCNA	8991	-0.0086	0.28	NO
35	ERCC1	ERCC1	ERCC1	9687	-0.018	0.25	NO
36	RPA2	RPA2	RPA2	9734	-0.019	0.25	NO
37	GTF2H4	GTF2H4	GTF2H4	9898	-0.021	0.25	NO
38	RPA1	RPA1	RPA1	10677	-0.034	0.23	NO
39	ERCC2	ERCC2	ERCC2	10688	-0.034	0.24	NO
40	POLD1	POLD1	POLD1	10804	-0.036	0.25	NO
41	POLD4	POLD4	POLD4	11924	-0.057	0.21	NO
42	DDB2	DDB2	DDB2	14052	-0.12	0.15	NO
43	GTF2H2	GTF2H2	GTF2H2	14582	-0.15	0.19	NO

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

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

genes ES table in pathway: KEGG PYRUVATE METABOLISM

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	ABAT	ABAT	ABAT	55	0.38	0.19	YES
2	ACSS1	ACSS1	ACSS1	1901	0.11	0.15	YES
3	ACACB	ACACB	ACACB	2789	0.084	0.14	YES
4	LDHB	LDHB	LDHB	2792	0.084	0.18	YES
5	ALDH7A1	ALDH7A1	ALDH7A1	2841	0.082	0.22	YES
6	SUCLA2	SUCLA2	SUCLA2	3412	0.07	0.23	YES
7	HIBCH	HIBCH	HIBCH	3523	0.068	0.26	YES
8	ACAT1	ACAT1	ACAT1	3766	0.064	0.28	YES
9	ALDH1B1	ALDH1B1	ALDH1B1	4236	0.055	0.28	YES
10	SUCLG1	SUCLG1	SUCLG1	4395	0.052	0.3	YES
11	ACACA	ACACA	ACACA	4654	0.049	0.31	YES
12	ACAT2	ACAT2	ACAT2	4660	0.048	0.33	YES
13	SUCLG2	SUCLG2	SUCLG2	5006	0.043	0.34	YES
14	LDHAL6A	LDHAL6A	LDHAL6A	5298	0.039	0.34	YES
15	ALDH2	ALDH2	ALDH2	5568	0.035	0.34	YES
16	ACADM	ACADM	ACADM	5627	0.035	0.36	YES
17	ACSS2	ACSS2	ACSS2	5709	0.033	0.37	YES
18	MCEE	MCEE	MCEE	5889	0.031	0.38	YES
19	MUT	MUT	MUT	6141	0.027	0.38	YES
20	ALDH9A1	ALDH9A1	ALDH9A1	6758	0.019	0.36	NO
21	EHHADH	EHHADH	EHHADH	7038	0.016	0.35	NO
22	HADHA	HADHA	HADHA	7191	0.014	0.35	NO
23	MLYCD	MLYCD	MLYCD	7903	0.0055	0.31	NO
24	LDHA	LDHA	LDHA	9322	-0.013	0.24	NO
25	ALDH3A2	ALDH3A2	ALDH3A2	10625	-0.033	0.18	NO
26	ECHS1	ECHS1	ECHS1	10767	-0.035	0.19	NO
27	PCCA	PCCA	PCCA	11858	-0.056	0.16	NO
28	PCCB	PCCB	PCCB	11923	-0.057	0.19	NO
29	ALDH6A1	ALDH6A1	ALDH6A1	12915	-0.083	0.18	NO
30	ACSS3	ACSS3	ACSS3	13309	-0.095	0.2	NO
31	LDHAL6B	LDHAL6B	LDHAL6B	13788	-0.11	0.24	NO

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

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

genes ES table in pathway: KEGG PROPANOATE METABOLISM

Table 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	RPA4	RPA4	RPA4	782	0.17	0.075	YES
2	RFC3	RFC3	RFC3	1374	0.13	0.13	YES
3	RNASEH2B	RNASEH2B	RNASEH2B	1599	0.12	0.2	YES
4	DNA2	DNA2	DNA2	1904	0.11	0.26	YES
5	RFC4	RFC4	RFC4	2918	0.08	0.26	YES
6	RPA3	RPA3	RPA3	3197	0.075	0.29	YES
7	SSBP1	SSBP1	SSBP1	3460	0.069	0.32	YES
8	RFC1	RFC1	RFC1	3611	0.066	0.36	YES
9	PRIM1	PRIM1	PRIM1	3779	0.064	0.4	YES
10	RNASEH1	RNASEH1	RNASEH1	4990	0.044	0.36	YES
11	POLE4	POLE4	POLE4	6043	0.029	0.32	YES
12	MCM3	MCM3	MCM3	6048	0.029	0.34	YES
13	POLE	POLE	POLE	6262	0.026	0.35	YES
14	RFC2	RFC2	RFC2	6301	0.025	0.36	YES
15	MCM6	MCM6	MCM6	6425	0.024	0.37	YES
16	POLD2	POLD2	POLD2	6694	0.02	0.37	YES
17	FEN1	FEN1	FEN1	6708	0.02	0.38	YES
18	PRIM2	PRIM2	PRIM2	6819	0.019	0.39	YES
19	RFC5	RFC5	RFC5	7029	0.016	0.39	YES
20	MCM7	MCM7	MCM7	7100	0.015	0.4	YES
21	LIG1	LIG1	LIG1	7147	0.015	0.4	YES
22	POLE3	POLE3	POLE3	7483	0.011	0.39	NO
23	MCM4	MCM4	MCM4	7613	0.0088	0.39	NO
24	RNASEH2C	RNASEH2C	RNASEH2C	7841	0.0062	0.38	NO
25	POLD3	POLD3	POLD3	8566	-0.0028	0.34	NO
26	POLA2	POLA2	POLA2	8660	-0.0042	0.34	NO
27	POLE2	POLE2	POLE2	8809	-0.0061	0.34	NO
28	PCNA	PCNA	PCNA	8991	-0.0086	0.33	NO
29	RNASEH2A	RNASEH2A	RNASEH2A	9052	-0.0094	0.34	NO
30	MCM2	MCM2	MCM2	9710	-0.019	0.31	NO
31	RPA2	RPA2	RPA2	9734	-0.019	0.32	NO
32	RPA1	RPA1	RPA1	10677	-0.034	0.3	NO
33	POLD1	POLD1	POLD1	10804	-0.036	0.31	NO
34	POLD4	POLD4	POLD4	11924	-0.057	0.29	NO
35	MCM5	MCM5	MCM5	12541	-0.072	0.3	NO

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

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

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	GGT7	GGT7	GGT7	290	0.25	0.14	YES
2	MAT1A	MAT1A	MAT1A	1190	0.14	0.17	YES
3	CBS	CBS	CBS	1507	0.12	0.23	YES
4	TRMT11	TRMT11	TRMT11	1790	0.11	0.29	YES
5	METTL6	METTL6	METTL6	1952	0.11	0.34	YES
6	AHCY	AHCY	AHCY	3786	0.064	0.28	YES
7	MARS2	MARS2	MARS2	4248	0.055	0.29	YES
8	LCMT2	LCMT2	LCMT2	4316	0.054	0.32	YES
9	WBSCR22	WBSCR22	WBSCR22	4497	0.051	0.34	YES
10	CTH	CTH	CTH	4936	0.045	0.34	YES
11	SEPHS1	SEPHS1	SEPHS1	5046	0.043	0.36	YES
12	GGT1	GGT1	GGT1	5784	0.032	0.34	NO
13	HEMK1	HEMK1	HEMK1	6051	0.029	0.35	NO
14	LCMT1	LCMT1	LCMT1	6093	0.028	0.36	NO
15	METTL2B	METTL2B	METTL2B	6921	0.017	0.33	NO
16	GGT6	GGT6	GGT6	8212	0.0017	0.26	NO
17	MAT2A	MAT2A	MAT2A	8318	0.00024	0.25	NO
18	SCLY	SCLY	SCLY	8361	-0.00041	0.25	NO
19	MARS	MARS	MARS	9226	-0.012	0.21	NO
20	AHCYL1	AHCYL1	AHCYL1	9583	-0.017	0.2	NO
21	MAT2B	MAT2B	MAT2B	9661	-0.018	0.2	NO
22	PAPSS1	PAPSS1	PAPSS1	9798	-0.02	0.21	NO
23	AHCYL2	AHCYL2	AHCYL2	13408	-0.099	0.069	NO
24	PAPSS2	PAPSS2	PAPSS2	14122	-0.13	0.11	NO
25	GGT5	GGT5	GGT5	15073	-0.17	0.16	NO

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

Figure S20. 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

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
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.5	1.7	0.034	0.43	0.44	0.34	0.21	0.27	0	0.14
BIOCARTA HIVNEF PATHWAY	57	genes.ES.table	0.43	1.9	0.006	0.18	0.12	0.3	0.21	0.24	0	0.058
BIOCARTA DEATH PATHWAY	32	genes.ES.table	0.39	1.5	0.087	0.59	0.8	0.5	0.24	0.38	0.38	0.18
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.28	1.2	0.25	1	1	1	0.72	0.28	0.91	0.43
BIOCARTA KERATINOCYTE PATHWAY	45	genes.ES.table	0.44	1.5	0.067	0.72	0.79	0.31	0.19	0.25	0.45	0.24
BIOCARTA PYK2 PATHWAY	27	genes.ES.table	0.35	1.4	0.13	0.78	0.95	0.37	0.24	0.28	0.62	0.28
BIOCARTA TNFR1 PATHWAY	28	genes.ES.table	0.41	1.7	0.032	0.47	0.6	1	0.59	0.41	0.22	0.15
KEGG FRUCTOSE AND MANNOSE METABOLISM	33	genes.ES.table	0.44	1.4	0.078	0.68	0.91	0.27	0.094	0.25	0.51	0.23
KEGG STARCH AND SUCROSE METABOLISM	42	genes.ES.table	0.47	1.2	0.24	1	1	0.33	0.06	0.31	0.88	0.42
KEGG O GLYCAN BIOSYNTHESIS	28	genes.ES.table	0.52	1.3	0.14	0.8	0.97	0.39	0.075	0.36	0.64	0.28

genes ES table in pathway: BIOCARTA FAS PATHWAY

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	FAS	FAS	FAS	634	0.18	0.036	YES
2	MAP3K5	MAP3K5	MAP3K5	678	0.17	0.1	YES
3	CASP7	CASP7	CASP7	698	0.17	0.17	YES
4	BIRC3	BIRC3	BIRC3	847	0.15	0.22	YES
5	BCL2	BCL2	BCL2	849	0.15	0.28	YES
6	MDM2	MDM2	MDM2	1438	0.11	0.29	YES
7	APAF1	APAF1	APAF1	1488	0.1	0.33	YES
8	CASP3	CASP3	CASP3	2086	0.078	0.33	YES
9	RIPK1	RIPK1	RIPK1	2565	0.063	0.33	YES
10	CYCS	CYCS	CYCS	2703	0.061	0.34	YES
11	LMNA	LMNA	LMNA	2715	0.06	0.37	YES
12	GSN	GSN	GSN	2953	0.056	0.38	YES
13	PSEN1	PSEN1	PSEN1	2969	0.056	0.4	YES
14	BIRC2	BIRC2	BIRC2	3266	0.05	0.4	YES
15	MAPK8	MAPK8	MAPK8	3307	0.05	0.42	YES
16	BAG4	BAG4	BAG4	3450	0.048	0.43	YES
17	CASP8	CASP8	CASP8	3738	0.043	0.43	YES
18	CHUK	CHUK	CHUK	4053	0.038	0.43	NO
19	CASP9	CASP9	CASP9	4303	0.035	0.43	NO
20	PARP1	PARP1	PARP1	4544	0.032	0.43	NO
21	RB1	RB1	RB1	4930	0.027	0.42	NO
22	PAK2	PAK2	PAK2	4994	0.026	0.43	NO
23	LMNB1	LMNB1	LMNB1	5255	0.023	0.42	NO
24	CASP6	CASP6	CASP6	5606	0.019	0.41	NO
25	NFKB1	NFKB1	NFKB1	5749	0.018	0.41	NO
26	MAP2K7	MAP2K7	MAP2K7	5841	0.017	0.41	NO
27	SPTAN1	SPTAN1	SPTAN1	5905	0.016	0.42	NO
28	MAP3K1	MAP3K1	MAP3K1	6095	0.014	0.41	NO
29	RASA1	RASA1	RASA1	6291	0.012	0.4	NO
30	CRADD	CRADD	CRADD	6355	0.011	0.4	NO
31	CDK11B	CDK11B	CDK11B	6582	0.0088	0.4	NO
32	ARHGDIB	ARHGDIB	ARHGDIB	6857	0.006	0.38	NO
33	NFKBIA	NFKBIA	NFKBIA	6936	0.0053	0.38	NO
34	CASP2	CASP2	CASP2	6980	0.0048	0.38	NO
35	PRKCD	PRKCD	PRKCD	6994	0.0046	0.38	NO
36	XIAP	XIAP	XIAP	7079	0.0036	0.38	NO
37	ACTG1	ACTG1	ACTG1	7472	-0.00075	0.36	NO
38	TNFRSF1A	TNFRSF1A	TNFRSF1A	7595	-0.0022	0.35	NO
39	DFFB	DFFB	DFFB	7622	-0.0025	0.35	NO
40	LMNB2	LMNB2	LMNB2	7711	-0.0035	0.35	NO
41	DAXX	DAXX	DAXX	7860	-0.0051	0.34	NO
42	TRADD	TRADD	TRADD	8138	-0.0077	0.33	NO
43	TRAF2	TRAF2	TRAF2	8398	-0.011	0.32	NO
44	PTK2	PTK2	PTK2	8920	-0.016	0.3	NO
45	DFFA	DFFA	DFFA	9368	-0.021	0.28	NO
46	RELA	RELA	RELA	9562	-0.024	0.28	NO
47	CDK11A	CDK11A	CDK11A	9637	-0.025	0.28	NO
48	NUMA1	NUMA1	NUMA1	9748	-0.026	0.29	NO
49	FADD	FADD	FADD	10254	-0.032	0.27	NO
50	PRKDC	PRKDC	PRKDC	10414	-0.035	0.28	NO
51	TNF	TNF	TNF	10587	-0.037	0.28	NO
52	PSEN2	PSEN2	PSEN2	10699	-0.039	0.29	NO
53	MAP3K14	MAP3K14	MAP3K14	10790	-0.04	0.3	NO
54	TNFRSF1B	TNFRSF1B	TNFRSF1B	10826	-0.041	0.32	NO
55	CFLAR	CFLAR	CFLAR	10837	-0.041	0.33	NO
56	BID	BID	BID	11288	-0.048	0.33	NO
57	TRAF1	TRAF1	TRAF1	13834	-0.12	0.23	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: BIOCARTA FAS PATHWAY.

Figure S22. 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 HIVNEF PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PTPN13	PTPN13	PTPN13	595	0.18	0.093	YES
2	FAS	FAS	FAS	634	0.18	0.21	YES
3	CASP7	CASP7	CASP7	698	0.17	0.32	YES
4	CASP10	CASP10	CASP10	1322	0.11	0.36	YES
5	MAP2K4	MAP2K4	MAP2K4	2001	0.081	0.38	YES
6	CASP3	CASP3	CASP3	2086	0.078	0.43	YES
7	FASLG	FASLG	FASLG	2140	0.076	0.48	YES
8	LMNA	LMNA	LMNA	2715	0.06	0.49	YES
9	MAPK8	MAPK8	MAPK8	3307	0.05	0.49	YES
10	CASP8	CASP8	CASP8	3738	0.043	0.5	YES
11	PARP1	PARP1	PARP1	4544	0.032	0.47	NO
12	RB1	RB1	RB1	4930	0.027	0.47	NO
13	PAK2	PAK2	PAK2	4994	0.026	0.48	NO
14	CASP6	CASP6	CASP6	5606	0.019	0.46	NO
15	SPTAN1	SPTAN1	SPTAN1	5905	0.016	0.46	NO
16	PAK1	PAK1	PAK1	5920	0.016	0.47	NO
17	MAP3K1	MAP3K1	MAP3K1	6095	0.014	0.47	NO
18	ARHGDIB	ARHGDIB	ARHGDIB	6857	0.006	0.43	NO
19	DFFB	DFFB	DFFB	7622	-0.0025	0.39	NO
20	LMNB2	LMNB2	LMNB2	7711	-0.0035	0.39	NO
21	DAXX	DAXX	DAXX	7860	-0.0051	0.38	NO
22	MAP3K7	MAP3K7	MAP3K7	9228	-0.02	0.32	NO
23	FAF1	FAF1	FAF1	9316	-0.021	0.33	NO
24	DFFA	DFFA	DFFA	9368	-0.021	0.34	NO
25	JUN	JUN	JUN	10139	-0.031	0.32	NO
26	FADD	FADD	FADD	10254	-0.032	0.34	NO
27	PRKDC	PRKDC	PRKDC	10414	-0.035	0.35	NO
28	CFLAR	CFLAR	CFLAR	10837	-0.041	0.36	NO
29	RIPK2	RIPK2	RIPK2	12106	-0.065	0.33	NO

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

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

genes ES table in pathway: BIOCARTA DEATH PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MAP2K4	MAP2K4	MAP2K4	2001	0.081	-0.01	YES
2	CASP3	CASP3	CASP3	2086	0.078	0.082	YES
3	RIPK1	RIPK1	RIPK1	2565	0.063	0.13	YES
4	LMNA	LMNA	LMNA	2715	0.06	0.2	YES
5	MAPK8	MAPK8	MAPK8	3307	0.05	0.23	YES
6	BAG4	BAG4	BAG4	3450	0.048	0.28	YES
7	CASP8	CASP8	CASP8	3738	0.043	0.32	YES
8	PARP1	PARP1	PARP1	4544	0.032	0.31	YES
9	RB1	RB1	RB1	4930	0.027	0.33	YES
10	PAK2	PAK2	PAK2	4994	0.026	0.36	YES
11	LMNB1	LMNB1	LMNB1	5255	0.023	0.37	YES
12	SPTAN1	SPTAN1	SPTAN1	5905	0.016	0.35	YES
13	PAK1	PAK1	PAK1	5920	0.016	0.37	YES
14	MAP3K1	MAP3K1	MAP3K1	6095	0.014	0.38	YES
15	MADD	MADD	MADD	6147	0.014	0.39	YES
16	CRADD	CRADD	CRADD	6355	0.011	0.4	YES
17	ARHGDIB	ARHGDIB	ARHGDIB	6857	0.006	0.38	YES
18	CASP2	CASP2	CASP2	6980	0.0048	0.38	YES
19	TNFRSF1A	TNFRSF1A	TNFRSF1A	7595	-0.0022	0.34	YES
20	DFFB	DFFB	DFFB	7622	-0.0025	0.34	YES
21	LMNB2	LMNB2	LMNB2	7711	-0.0035	0.34	YES
22	TRADD	TRADD	TRADD	8138	-0.0077	0.33	YES
23	MAP3K7	MAP3K7	MAP3K7	9228	-0.02	0.29	YES
24	DFFA	DFFA	DFFA	9368	-0.021	0.31	YES
25	JUN	JUN	JUN	10139	-0.031	0.31	YES
26	FADD	FADD	FADD	10254	-0.032	0.34	YES
27	PRKDC	PRKDC	PRKDC	10414	-0.035	0.38	YES
28	TNF	TNF	TNF	10587	-0.037	0.41	YES

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: BIOCARTA DEATH PATHWAY.

Figure S26. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA DEATH 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 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	PRKCG	PRKCG	PRKCG	377	0.23	0.07	YES
2	FAS	FAS	FAS	634	0.18	0.12	YES
3	MAP3K5	MAP3K5	MAP3K5	678	0.17	0.19	YES
4	FOS	FOS	FOS	802	0.16	0.24	YES
5	BCL2	BCL2	BCL2	849	0.15	0.3	YES
6	EGF	EGF	EGF	890	0.15	0.36	YES
7	MAP2K6	MAP2K6	MAP2K6	1351	0.11	0.37	YES
8	PRKCA	PRKCA	PRKCA	1922	0.084	0.37	YES
9	MAP2K4	MAP2K4	MAP2K4	2001	0.081	0.4	YES
10	FASLG	FASLG	FASLG	2140	0.076	0.42	YES
11	RIPK1	RIPK1	RIPK1	2565	0.063	0.42	YES
12	MAP2K1	MAP2K1	MAP2K1	3027	0.055	0.42	YES
13	MAPK8	MAPK8	MAPK8	3307	0.05	0.42	YES
14	SP1	SP1	SP1	3385	0.049	0.44	YES
15	MAPK3	MAPK3	MAPK3	4010	0.039	0.42	NO
16	CHUK	CHUK	CHUK	4053	0.038	0.43	NO
17	MAP2K3	MAP2K3	MAP2K3	4413	0.034	0.43	NO
18	ETS1	ETS1	ETS1	5314	0.023	0.38	NO
19	PPP2CA	PPP2CA	PPP2CA	5481	0.021	0.38	NO
20	EGFR	EGFR	EGFR	5683	0.019	0.38	NO
21	NFKB1	NFKB1	NFKB1	5749	0.018	0.38	NO
22	MAP2K7	MAP2K7	MAP2K7	5841	0.017	0.38	NO
23	MAPK1	MAPK1	MAPK1	5957	0.016	0.38	NO
24	MAP3K1	MAP3K1	MAP3K1	6095	0.014	0.38	NO
25	NFKBIA	NFKBIA	NFKBIA	6936	0.0053	0.34	NO
26	PRKCD	PRKCD	PRKCD	6994	0.0046	0.34	NO
27	RAF1	RAF1	RAF1	7006	0.0045	0.34	NO
28	PRKCE	PRKCE	PRKCE	7108	0.0032	0.33	NO
29	TNFRSF1A	TNFRSF1A	TNFRSF1A	7595	-0.0022	0.31	NO
30	ETS2	ETS2	ETS2	7706	-0.0035	0.3	NO
31	DAXX	DAXX	DAXX	7860	-0.0051	0.3	NO
32	HOXA7	HOXA7	HOXA7	8427	-0.011	0.27	NO
33	MAPK13	MAPK13	MAPK13	9485	-0.023	0.22	NO
34	RELA	RELA	RELA	9562	-0.024	0.22	NO
35	IKBKB	IKBKB	IKBKB	9627	-0.024	0.23	NO
36	JUN	JUN	JUN	10139	-0.031	0.21	NO
37	PRKCH	PRKCH	PRKCH	10278	-0.033	0.22	NO
38	TNF	TNF	TNF	10587	-0.037	0.22	NO
39	MAPK14	MAPK14	MAPK14	10705	-0.039	0.22	NO
40	MAP3K14	MAP3K14	MAP3K14	10790	-0.04	0.24	NO
41	TNFRSF1B	TNFRSF1B	TNFRSF1B	10826	-0.041	0.25	NO
42	PRKCB	PRKCB	PRKCB	10974	-0.043	0.26	NO
43	HRAS	HRAS	HRAS	11072	-0.045	0.27	NO
44	CEBPA	CEBPA	CEBPA	12484	-0.073	0.22	NO
45	PRKCQ	PRKCQ	PRKCQ	16136	-0.22	0.1	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: BIOCARTA RACCYCD PATHWAY.

Figure S28. 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 KERATINOCYTE PATHWAY

Table S15. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CASP7	CASP7	CASP7	698	0.17	0.041	YES
2	BIRC3	BIRC3	BIRC3	847	0.15	0.1	YES
3	BCL2	BCL2	BCL2	849	0.15	0.18	YES
4	CASP10	CASP10	CASP10	1322	0.11	0.2	YES
5	TNFSF10	TNFSF10	TNFSF10	1478	0.1	0.24	YES
6	APAF1	APAF1	APAF1	1488	0.1	0.29	YES
7	CASP3	CASP3	CASP3	2086	0.078	0.3	YES
8	RIPK1	RIPK1	RIPK1	2565	0.063	0.3	YES
9	CYCS	CYCS	CYCS	2703	0.061	0.32	YES
10	LMNA	LMNA	LMNA	2715	0.06	0.35	YES
11	TNFRSF10A	TNFRSF10A	TNFRSF10A	3016	0.055	0.36	YES
12	BIRC2	BIRC2	BIRC2	3266	0.05	0.37	YES
13	TNFRSF10B	TNFRSF10B	TNFRSF10B	3581	0.046	0.37	YES
14	CASP8	CASP8	CASP8	3738	0.043	0.38	YES
15	CHUK	CHUK	CHUK	4053	0.038	0.39	YES
16	CASP9	CASP9	CASP9	4303	0.035	0.39	YES
17	CASP6	CASP6	CASP6	5606	0.019	0.33	NO
18	NFKB1	NFKB1	NFKB1	5749	0.018	0.33	NO
19	SPTAN1	SPTAN1	SPTAN1	5905	0.016	0.32	NO
20	NFKBIA	NFKBIA	NFKBIA	6936	0.0053	0.27	NO
21	XIAP	XIAP	XIAP	7079	0.0036	0.26	NO
22	DFFB	DFFB	DFFB	7622	-0.0025	0.24	NO
23	TRADD	TRADD	TRADD	8138	-0.0077	0.21	NO
24	TRAF2	TRAF2	TRAF2	8398	-0.011	0.2	NO
25	DFFA	DFFA	DFFA	9368	-0.021	0.16	NO
26	RELA	RELA	RELA	9562	-0.024	0.16	NO
27	FADD	FADD	FADD	10254	-0.032	0.14	NO
28	MAP3K14	MAP3K14	MAP3K14	10790	-0.04	0.12	NO
29	CFLAR	CFLAR	CFLAR	10837	-0.041	0.14	NO
30	TNFSF12	TNFSF12	TNFSF12	13170	-0.093	0.056	NO
31	TNFRSF25	TNFRSF25	TNFRSF25	15512	-0.19	0.016	NO
32	GAS2	GAS2	GAS2	16650	-0.26	0.076	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: BIOCARTA KERATINOCYTE PATHWAY.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA KERATINOCYTE 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 PYK2 PATHWAY

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	CYP2C18	CYP2C18	CYP2C18	56	0.41	0.056	YES
2	DHRS9	DHRS9	DHRS9	64	0.4	0.11	YES
3	UGT1A10	UGT1A10	UGT1A10	151	0.33	0.16	YES
4	UGT1A1	UGT1A1	UGT1A1	167	0.32	0.2	YES
5	CYP2C9	CYP2C9	CYP2C9	215	0.29	0.24	YES
6	BCMO1	BCMO1	BCMO1	270	0.26	0.27	YES
7	CYP3A5	CYP3A5	CYP3A5	326	0.25	0.31	YES
8	ADH6	ADH6	ADH6	338	0.24	0.34	YES
9	UGT2B15	UGT2B15	UGT2B15	360	0.24	0.37	YES
10	UGT2B7	UGT2B7	UGT2B7	385	0.23	0.4	YES
11	UGT1A8	UGT1A8	UGT1A8	442	0.22	0.43	YES
12	CYP2C19	CYP2C19	CYP2C19	566	0.19	0.45	YES
13	ALDH1A2	ALDH1A2	ALDH1A2	586	0.19	0.48	YES
14	UGT1A9	UGT1A9	UGT1A9	608	0.18	0.5	YES
15	UGT2B4	UGT2B4	UGT2B4	707	0.17	0.52	YES
16	CYP1A1	CYP1A1	CYP1A1	717	0.16	0.55	YES
17	ADH1C	ADH1C	ADH1C	748	0.16	0.57	YES
18	UGT1A6	UGT1A6	UGT1A6	824	0.15	0.58	YES
19	ALDH1A1	ALDH1A1	ALDH1A1	858	0.15	0.6	YES
20	RDH5	RDH5	RDH5	1012	0.14	0.62	YES
21	DHRS4	DHRS4	DHRS4	1728	0.092	0.59	NO
22	RDH11	RDH11	RDH11	2647	0.062	0.55	NO
23	RETSAT	RETSAT	RETSAT	2797	0.059	0.55	NO
24	RPE65	RPE65	RPE65	3229	0.051	0.53	NO
25	CYP2C8	CYP2C8	CYP2C8	3505	0.047	0.52	NO
26	ADH4	ADH4	ADH4	3855	0.042	0.51	NO
27	CYP26B1	CYP26B1	CYP26B1	4038	0.039	0.5	NO
28	RDH16	RDH16	RDH16	4305	0.035	0.49	NO
29	UGT1A3	UGT1A3	UGT1A3	5489	0.021	0.43	NO
30	RDH10	RDH10	RDH10	5862	0.016	0.41	NO
31	ADH5	ADH5	ADH5	6635	0.0082	0.37	NO
32	DHRS4L2	DHRS4L2	DHRS4L2	7304	0.0011	0.33	NO
33	DHRS3	DHRS3	DHRS3	7787	-0.0044	0.31	NO
34	DGAT1	DGAT1	DGAT1	8616	-0.013	0.26	NO
35	RDH8	RDH8	RDH8	9183	-0.019	0.23	NO
36	UGT2B11	UGT2B11	UGT2B11	9518	-0.023	0.22	NO
37	CYP4A11	CYP4A11	CYP4A11	9578	-0.024	0.22	NO
38	ADH1A	ADH1A	ADH1A	11303	-0.049	0.13	NO
39	UGT2A3	UGT2A3	UGT2A3	11490	-0.052	0.13	NO
40	ADH1B	ADH1B	ADH1B	13103	-0.091	0.051	NO
41	PNPLA4	PNPLA4	PNPLA4	13192	-0.093	0.059	NO
42	CYP2A6	CYP2A6	CYP2A6	13351	-0.098	0.064	NO
43	CYP3A43	CYP3A43	CYP3A43	13816	-0.11	0.055	NO
44	RDH12	RDH12	RDH12	13860	-0.12	0.069	NO
45	LRAT	LRAT	LRAT	13883	-0.12	0.085	NO
46	CYP3A7	CYP3A7	CYP3A7	14273	-0.13	0.082	NO
47	UGT2B10	UGT2B10	UGT2B10	14559	-0.14	0.086	NO
48	CYP26A1	CYP26A1	CYP26A1	14674	-0.15	0.1	NO
49	DGAT2	DGAT2	DGAT2	15381	-0.18	0.088	NO
50	CYP2B6	CYP2B6	CYP2B6	15626	-0.2	0.1	NO
51	CYP26C1	CYP26C1	CYP26C1	15906	-0.21	0.12	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: BIOCARTA PYK2 PATHWAY.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA PYK2 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 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	UGT1A10	UGT1A10	UGT1A10	151	0.33	0.1	YES
2	UGT1A1	UGT1A1	UGT1A1	167	0.32	0.21	YES
3	UGT2B15	UGT2B15	UGT2B15	360	0.24	0.28	YES
4	UGT2B7	UGT2B7	UGT2B7	385	0.23	0.35	YES
5	UGT1A8	UGT1A8	UGT1A8	442	0.22	0.42	YES
6	UGT1A9	UGT1A9	UGT1A9	608	0.18	0.47	YES
7	UGT2B4	UGT2B4	UGT2B4	707	0.17	0.52	YES
8	UGT1A6	UGT1A6	UGT1A6	824	0.15	0.57	YES
9	BLVRA	BLVRA	BLVRA	1729	0.092	0.55	YES
10	FECH	FECH	FECH	1888	0.085	0.57	YES
11	ALAS1	ALAS1	ALAS1	2432	0.067	0.56	YES
12	BLVRB	BLVRB	BLVRB	2941	0.056	0.55	YES
13	EPRS	EPRS	EPRS	2951	0.056	0.57	YES
14	COX10	COX10	COX10	3320	0.05	0.57	NO
15	CPOX	CPOX	CPOX	3745	0.043	0.56	NO
16	COX15	COX15	COX15	4808	0.029	0.51	NO
17	UGT1A3	UGT1A3	UGT1A3	5489	0.021	0.48	NO
18	GUSB	GUSB	GUSB	6443	0.01	0.43	NO
19	ALAD	ALAD	ALAD	7944	-0.006	0.34	NO
20	HMOX1	HMOX1	HMOX1	8033	-0.0069	0.34	NO
21	MMAB	MMAB	MMAB	8376	-0.01	0.33	NO
22	EARS2	EARS2	EARS2	8698	-0.014	0.31	NO
23	HMOX2	HMOX2	HMOX2	8883	-0.016	0.31	NO
24	UGT2B11	UGT2B11	UGT2B11	9518	-0.023	0.28	NO
25	HMBS	HMBS	HMBS	9543	-0.023	0.29	NO
26	UROS	UROS	UROS	9942	-0.028	0.28	NO
27	UROD	UROD	UROD	9972	-0.029	0.28	NO
28	UGT2A3	UGT2A3	UGT2A3	11490	-0.052	0.22	NO
29	PPOX	PPOX	PPOX	12024	-0.063	0.21	NO
30	FTH1	FTH1	FTH1	12124	-0.065	0.22	NO
31	CP	CP	CP	12444	-0.072	0.23	NO
32	ALAS2	ALAS2	ALAS2	13280	-0.096	0.22	NO
33	UGT2B10	UGT2B10	UGT2B10	14559	-0.14	0.19	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: BIOCARTA TNFR1 PATHWAY.

Figure S34. 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 FRUCTOSE AND MANNOSE 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	AKR1B10	AKR1B10	AKR1B10	66	0.4	0.14	YES
2	ALDOB	ALDOB	ALDOB	235	0.28	0.24	YES
3	HK2	HK2	HK2	962	0.14	0.24	YES
4	PFKFB4	PFKFB4	PFKFB4	1226	0.12	0.27	YES
5	MTMR7	MTMR7	MTMR7	1227	0.12	0.32	YES
6	GMDS	GMDS	GMDS	1330	0.11	0.35	YES
7	PFKFB2	PFKFB2	PFKFB2	1609	0.097	0.37	YES
8	FPGT	FPGT	FPGT	1697	0.094	0.4	YES
9	PFKP	PFKP	PFKP	1698	0.093	0.44	YES
10	MPI	MPI	MPI	2503	0.065	0.41	NO
11	TSTA3	TSTA3	TSTA3	2631	0.062	0.43	NO
12	GMPPB	GMPPB	GMPPB	3528	0.047	0.4	NO
13	PFKFB3	PFKFB3	PFKFB3	3696	0.044	0.4	NO
14	HK1	HK1	HK1	4502	0.032	0.37	NO
15	PMM2	PMM2	PMM2	4522	0.032	0.38	NO
16	TPI1	TPI1	TPI1	4770	0.029	0.38	NO
17	GMPPA	GMPPA	GMPPA	5126	0.025	0.37	NO
18	PFKL	PFKL	PFKL	6684	0.0077	0.28	NO
19	SORD	SORD	SORD	6858	0.0059	0.28	NO
20	MTMR2	MTMR2	MTMR2	7174	0.0026	0.26	NO
21	MTMR6	MTMR6	MTMR6	7724	-0.0037	0.23	NO
22	FBP1	FBP1	FBP1	8435	-0.011	0.2	NO
23	PMM1	PMM1	PMM1	8495	-0.012	0.2	NO
24	PHPT1	PHPT1	PHPT1	8529	-0.012	0.2	NO
25	ALDOC	ALDOC	ALDOC	9492	-0.023	0.15	NO
26	MTMR1	MTMR1	MTMR1	10432	-0.035	0.11	NO
27	FUK	FUK	FUK	10486	-0.036	0.12	NO
28	FBP2	FBP2	FBP2	11154	-0.046	0.1	NO
29	PFKM	PFKM	PFKM	11293	-0.048	0.11	NO
30	KHK	KHK	KHK	13066	-0.09	0.048	NO
31	PFKFB1	PFKFB1	PFKFB1	15613	-0.2	-0.022	NO
32	AKR1B1	AKR1B1	AKR1B1	15797	-0.21	0.042	NO
33	HK3	HK3	HK3	16104	-0.22	0.11	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 FRUCTOSE AND MANNOSE METABOLISM.

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

genes ES table in pathway: KEGG STARCH AND SUCROSE 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	SGMS2	SGMS2	SGMS2	461	0.21	0.048	YES
2	DEGS2	DEGS2	DEGS2	628	0.18	0.099	YES
3	UGT8	UGT8	UGT8	648	0.18	0.16	YES
4	B4GALT6	B4GALT6	B4GALT6	716	0.16	0.21	YES
5	ACER2	ACER2	ACER2	817	0.15	0.26	YES
6	SGMS1	SGMS1	SGMS1	922	0.14	0.3	YES
7	SGPP1	SGPP1	SGPP1	1108	0.13	0.33	YES
8	SGPP2	SGPP2	SGPP2	1135	0.13	0.38	YES
9	SPTLC2	SPTLC2	SPTLC2	1321	0.11	0.4	YES
10	SMPD3	SMPD3	SMPD3	2101	0.078	0.39	YES
11	ACER3	ACER3	ACER3	2109	0.077	0.41	YES
12	KDSR	KDSR	KDSR	3703	0.044	0.34	NO
13	ARSA	ARSA	ARSA	3720	0.044	0.35	NO
14	NEU4	NEU4	NEU4	4190	0.037	0.34	NO
15	ASAH1	ASAH1	ASAH1	4477	0.033	0.33	NO
16	SPTLC1	SPTLC1	SPTLC1	4661	0.03	0.33	NO
17	DEGS1	DEGS1	DEGS1	5106	0.025	0.32	NO
18	SGPL1	SGPL1	SGPL1	6012	0.015	0.27	NO
19	PPAP2C	PPAP2C	PPAP2C	6847	0.0061	0.23	NO
20	GAL3ST1	GAL3ST1	GAL3ST1	7074	0.0036	0.22	NO
21	UGCG	UGCG	UGCG	7097	0.0034	0.22	NO
22	SMPD2	SMPD2	SMPD2	7390	0.00016	0.2	NO
23	GALC	GALC	GALC	8575	-0.012	0.14	NO
24	GBA	GBA	GBA	8731	-0.014	0.14	NO
25	GLB1	GLB1	GLB1	9203	-0.019	0.12	NO
26	SMPD4	SMPD4	SMPD4	10604	-0.037	0.05	NO
27	SPHK2	SPHK2	SPHK2	10808	-0.04	0.052	NO
28	GLA	GLA	GLA	11823	-0.058	0.016	NO
29	SMPD1	SMPD1	SMPD1	12338	-0.07	0.011	NO
30	NEU3	NEU3	NEU3	13141	-0.092	-0.0021	NO
31	PPAP2A	PPAP2A	PPAP2A	13481	-0.1	0.014	NO
32	PPAP2B	PPAP2B	PPAP2B	13674	-0.11	0.04	NO
33	CERK	CERK	CERK	14164	-0.13	0.056	NO
34	SPHK1	SPHK1	SPHK1	14270	-0.13	0.095	NO
35	NEU1	NEU1	NEU1	14561	-0.14	0.13	NO
36	ASAH2	ASAH2	ASAH2	15511	-0.19	0.14	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 STARCH AND SUCROSE METABOLISM.

Figure S38. 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 O GLYCAN BIOSYNTHESIS

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	GNAQ	GNAQ	GNAQ	1153	0.12	0.058	YES
2	PRKCA	PRKCA	PRKCA	1922	0.084	0.098	YES
3	MAP2K4	MAP2K4	MAP2K4	2001	0.081	0.17	YES
4	MAP2K1	MAP2K1	MAP2K1	3027	0.055	0.17	YES
5	PTK2B	PTK2B	PTK2B	3047	0.054	0.22	YES
6	CALM2	CALM2	CALM2	3194	0.052	0.26	YES
7	MAPK8	MAPK8	MAPK8	3307	0.05	0.31	YES
8	MAPK3	MAPK3	MAPK3	4010	0.039	0.31	YES
9	CALM3	CALM3	CALM3	4325	0.035	0.32	YES
10	MAP2K3	MAP2K3	MAP2K3	4413	0.034	0.35	YES
11	SOS1	SOS1	SOS1	5284	0.023	0.33	NO
12	RAC1	RAC1	RAC1	5456	0.021	0.34	NO
13	PAK1	PAK1	PAK1	5920	0.016	0.33	NO
14	MAPK1	MAPK1	MAPK1	5957	0.016	0.34	NO
15	MAP3K1	MAP3K1	MAP3K1	6095	0.014	0.35	NO
16	CALM1	CALM1	CALM1	6524	0.0092	0.33	NO
17	BCAR1	BCAR1	BCAR1	6688	0.0076	0.33	NO
18	RAF1	RAF1	RAF1	7006	0.0045	0.32	NO
19	GRB2	GRB2	GRB2	7727	-0.0037	0.28	NO
20	MAP2K2	MAP2K2	MAP2K2	7766	-0.0042	0.28	NO
21	CRKL	CRKL	CRKL	7864	-0.0051	0.28	NO
22	SHC1	SHC1	SHC1	8687	-0.014	0.25	NO
23	JUN	JUN	JUN	10139	-0.031	0.2	NO
24	SRC	SRC	SRC	10316	-0.033	0.22	NO
25	MAPK14	MAPK14	MAPK14	10705	-0.039	0.24	NO
26	PRKCB	PRKCB	PRKCB	10974	-0.043	0.27	NO
27	PLCG1	PLCG1	PLCG1	14190	-0.13	0.21	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 O GLYCAN BIOSYNTHESIS.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG O GLYCAN 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

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 NO1 PATHWAY	28	genes.ES.table	0.54	1.4	0.086	0.13	0.91	0.32	0.18	0.26	0.091	0.001
BIOCARTA AGR PATHWAY	34	genes.ES.table	0.46	1.4	0.077	0.15	0.93	0.38	0.29	0.27	0.11	0.001
BIOCARTA ALK PATHWAY	32	genes.ES.table	0.46	1.4	0.094	0.17	0.95	0.44	0.27	0.32	0.13	0.001
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.4	1.6	0.049	0.1	0.74	0.28	0.29	0.2	0.054	0
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.57	1.7	0.034	0.08	0.59	0.3	0.24	0.23	0.034	0.001
BIOCARTA BIOPEPTIDES PATHWAY	40	genes.ES.table	0.43	1.5	0.072	0.13	0.9	0.28	0.2	0.22	0.089	0.001
BIOCARTA CARM ER PATHWAY	34	genes.ES.table	0.36	1.3	0.17	0.21	0.97	0.38	0.32	0.26	0.17	0
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.46	1.5	0.077	0.12	0.88	0.18	0.15	0.16	0.084	0.001
BIOCARTA HDAC PATHWAY	26	genes.ES.table	0.53	1.6	0.045	0.1	0.78	0.42	0.29	0.3	0.061	0
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.46	1.6	0.048	0.092	0.67	0.73	0.44	0.41	0.046	0.001

genes ES table in pathway: BIOCARTA NO1 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	TGFB3	TGFB3	TGFB3	81	0.73	0.076	YES
2	VEGFC	VEGFC	VEGFC	206	0.65	0.14	YES
3	AKT3	AKT3	AKT3	502	0.54	0.18	YES
4	PIK3R5	PIK3R5	PIK3R5	582	0.53	0.24	YES
5	TGFB2	TGFB2	TGFB2	667	0.51	0.29	YES
6	PIK3CG	PIK3CG	PIK3CG	732	0.49	0.34	YES
7	HGF	HGF	HGF	991	0.45	0.38	YES
8	PAK3	PAK3	PAK3	1184	0.41	0.41	YES
9	PIK3CD	PIK3CD	PIK3CD	1205	0.41	0.46	YES
10	ARNT2	ARNT2	ARNT2	1263	0.4	0.5	YES
11	ETS1	ETS1	ETS1	2149	0.3	0.48	YES
12	PDGFB	PDGFB	PDGFB	2314	0.28	0.5	YES
13	FIGF	FIGF	FIGF	2450	0.26	0.52	YES
14	TGFB1	TGFB1	TGFB1	2706	0.24	0.54	YES
15	PGF	PGF	PGF	2997	0.21	0.54	YES
16	PIK3CA	PIK3CA	PIK3CA	3454	0.17	0.54	NO
17	HIF1A	HIF1A	HIF1A	3799	0.15	0.54	NO
18	SOS1	SOS1	SOS1	4868	0.1	0.49	NO
19	EP300	EP300	EP300	5018	0.098	0.49	NO
20	RAPGEF1	RAPGEF1	RAPGEF1	5097	0.095	0.5	NO
21	EPAS1	EPAS1	EPAS1	5330	0.088	0.49	NO
22	PIK3R3	PIK3R3	PIK3R3	5358	0.088	0.5	NO
23	ARNT	ARNT	ARNT	5379	0.087	0.51	NO
24	SOS2	SOS2	SOS2	5506	0.083	0.51	NO
25	PIK3R1	PIK3R1	PIK3R1	5657	0.08	0.51	NO
26	CREBBP	CREBBP	CREBBP	5799	0.076	0.51	NO
27	RAP1A	RAP1A	RAP1A	5811	0.076	0.52	NO
28	PTPN11	PTPN11	PTPN11	5842	0.075	0.53	NO
29	BRAF	BRAF	BRAF	6094	0.069	0.52	NO
30	KRAS	KRAS	KRAS	6619	0.057	0.5	NO
31	PAK2	PAK2	PAK2	6700	0.056	0.5	NO
32	FLCN	FLCN	FLCN	6776	0.054	0.5	NO
33	GRB2	GRB2	GRB2	7110	0.048	0.49	NO
34	MAP2K1	MAP2K1	MAP2K1	7174	0.047	0.49	NO
35	VEGFB	VEGFB	VEGFB	7357	0.044	0.48	NO
36	PIK3CB	PIK3CB	PIK3CB	7407	0.043	0.49	NO
37	TGFA	TGFA	TGFA	7693	0.038	0.48	NO
38	CRK	CRK	CRK	7938	0.034	0.46	NO
39	CDC42	CDC42	CDC42	8049	0.033	0.46	NO
40	MAPK1	MAPK1	MAPK1	8307	0.028	0.45	NO
41	MET	MET	MET	8477	0.026	0.44	NO
42	CRKL	CRKL	CRKL	8516	0.025	0.45	NO
43	GAB1	GAB1	GAB1	8638	0.024	0.44	NO
44	NRAS	NRAS	NRAS	9110	0.017	0.42	NO
45	CUL2	CUL2	CUL2	9776	0.0073	0.38	NO
46	AKT1	AKT1	AKT1	9910	0.0055	0.37	NO
47	EGLN1	EGLN1	EGLN1	9949	0.0049	0.37	NO
48	JUN	JUN	JUN	10056	0.0034	0.37	NO
49	EGLN2	EGLN2	EGLN2	10314	-0.00031	0.35	NO
50	RAF1	RAF1	RAF1	10396	-0.0013	0.35	NO
51	EGLN3	EGLN3	EGLN3	10497	-0.0026	0.34	NO
52	SLC2A1	SLC2A1	SLC2A1	10618	-0.0045	0.34	NO
53	TCEB1	TCEB1	TCEB1	10916	-0.0092	0.32	NO
54	VHL	VHL	VHL	11028	-0.011	0.32	NO
55	VEGFA	VEGFA	VEGFA	11067	-0.011	0.32	NO
56	RAC1	RAC1	RAC1	11370	-0.016	0.3	NO
57	AKT2	AKT2	AKT2	11376	-0.016	0.3	NO
58	PAK1	PAK1	PAK1	11848	-0.024	0.28	NO
59	RAP1B	RAP1B	RAP1B	11952	-0.026	0.28	NO
60	RBX1	RBX1	RBX1	12842	-0.041	0.23	NO
61	PIK3R2	PIK3R2	PIK3R2	12957	-0.043	0.23	NO
62	PAK4	PAK4	PAK4	13282	-0.049	0.22	NO
63	ARAF	ARAF	ARAF	13329	-0.05	0.22	NO
64	PAK6	PAK6	PAK6	14143	-0.066	0.18	NO
65	MAPK3	MAPK3	MAPK3	14185	-0.067	0.19	NO
66	MAP2K2	MAP2K2	MAP2K2	14366	-0.071	0.18	NO
67	FH	FH	FH	14728	-0.081	0.17	NO
68	TCEB2	TCEB2	TCEB2	15230	-0.095	0.16	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 NO1 PATHWAY.

Figure S42. 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 AGR 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	THBS4	THBS4	THBS4	62	0.75	0.017	YES
2	COMP	COMP	COMP	79	0.73	0.036	YES
3	COL11A1	COL11A1	COL11A1	162	0.67	0.05	YES
4	VEGFC	VEGFC	VEGFC	206	0.65	0.066	YES
5	IGF1	IGF1	IGF1	338	0.6	0.075	YES
6	THBS2	THBS2	THBS2	397	0.58	0.087	YES
7	LAMA2	LAMA2	LAMA2	459	0.56	0.099	YES
8	IBSP	IBSP	IBSP	479	0.55	0.11	YES
9	TNXB	TNXB	TNXB	480	0.55	0.13	YES
10	SPP1	SPP1	SPP1	491	0.55	0.14	YES
11	AKT3	AKT3	AKT3	502	0.54	0.16	YES
12	PIK3R5	PIK3R5	PIK3R5	582	0.53	0.17	YES
13	ITGA10	ITGA10	ITGA10	600	0.52	0.18	YES
14	RELN	RELN	RELN	602	0.52	0.2	YES
15	ITGA11	ITGA11	ITGA11	692	0.5	0.2	YES
16	COL6A6	COL6A6	COL6A6	724	0.5	0.22	YES
17	PIK3CG	PIK3CG	PIK3CG	732	0.49	0.23	YES
18	PRKCB	PRKCB	PRKCB	784	0.48	0.24	YES
19	SHC4	SHC4	SHC4	786	0.48	0.25	YES
20	TNC	TNC	TNC	955	0.45	0.26	YES
21	PDGFC	PDGFC	PDGFC	980	0.45	0.27	YES
22	HGF	HGF	HGF	991	0.45	0.28	YES
23	FLT4	FLT4	FLT4	1092	0.43	0.28	YES
24	FLNC	FLNC	FLNC	1169	0.42	0.29	YES
25	FN1	FN1	FN1	1170	0.42	0.3	YES
26	PAK3	PAK3	PAK3	1184	0.41	0.31	YES
27	PIK3CD	PIK3CD	PIK3CD	1205	0.41	0.32	YES
28	ITGB3	ITGB3	ITGB3	1220	0.41	0.33	YES
29	TNN	TNN	TNN	1233	0.41	0.34	YES
30	PARVG	PARVG	PARVG	1254	0.4	0.35	YES
31	COL5A3	COL5A3	COL5A3	1339	0.39	0.36	YES
32	MYLK	MYLK	MYLK	1356	0.39	0.37	YES
33	ITGA7	ITGA7	ITGA7	1404	0.38	0.38	YES
34	COL5A2	COL5A2	COL5A2	1446	0.38	0.39	YES
35	COL4A4	COL4A4	COL4A4	1559	0.36	0.39	YES
36	ITGA5	ITGA5	ITGA5	1582	0.36	0.4	YES
37	COL6A3	COL6A3	COL6A3	1613	0.36	0.41	YES
38	ITGA4	ITGA4	ITGA4	1643	0.35	0.41	YES
39	MAPK10	MAPK10	MAPK10	1766	0.34	0.42	YES
40	COL5A1	COL5A1	COL5A1	1817	0.33	0.42	YES
41	MYL9	MYL9	MYL9	1824	0.33	0.43	YES
42	PDGFRB	PDGFRB	PDGFRB	1855	0.33	0.44	YES
43	COL1A1	COL1A1	COL1A1	1988	0.32	0.44	YES
44	COL1A2	COL1A2	COL1A2	2000	0.31	0.45	YES
45	FYN	FYN	FYN	2017	0.31	0.46	YES
46	COL3A1	COL3A1	COL3A1	2042	0.31	0.46	YES
47	CAV2	CAV2	CAV2	2120	0.3	0.47	YES
48	ACTN2	ACTN2	ACTN2	2195	0.29	0.47	YES
49	TNR	TNR	TNR	2200	0.29	0.48	YES
50	VTN	VTN	VTN	2257	0.28	0.48	YES
51	KDR	KDR	KDR	2275	0.28	0.49	YES
52	PDGFB	PDGFB	PDGFB	2314	0.28	0.5	YES
53	FLNA	FLNA	FLNA	2322	0.28	0.5	YES
54	LAMA4	LAMA4	LAMA4	2329	0.28	0.51	YES
55	FLT1	FLT1	FLT1	2356	0.27	0.52	YES
56	COL6A2	COL6A2	COL6A2	2410	0.27	0.52	YES
57	COL6A1	COL6A1	COL6A1	2412	0.27	0.53	YES
58	CAV1	CAV1	CAV1	2440	0.27	0.53	YES
59	VAV1	VAV1	VAV1	2449	0.26	0.54	YES
60	FIGF	FIGF	FIGF	2450	0.26	0.55	YES
61	ACTN3	ACTN3	ACTN3	2525	0.26	0.55	YES
62	VWF	VWF	VWF	2549	0.26	0.56	YES
63	BCL2	BCL2	BCL2	2812	0.23	0.55	YES
64	THBS1	THBS1	THBS1	2816	0.23	0.55	YES
65	LAMB2	LAMB2	LAMB2	2817	0.23	0.56	YES
66	ITGAV	ITGAV	ITGAV	2852	0.23	0.56	YES
67	ITGA1	ITGA1	ITGA1	2908	0.22	0.57	YES
68	PDGFRA	PDGFRA	PDGFRA	2919	0.22	0.57	YES
69	THBS3	THBS3	THBS3	2963	0.22	0.58	YES
70	COL4A2	COL4A2	COL4A2	2977	0.21	0.58	YES
71	PGF	PGF	PGF	2997	0.21	0.59	YES
72	COL4A1	COL4A1	COL4A1	3032	0.21	0.59	YES
73	PDGFD	PDGFD	PDGFD	3064	0.2	0.59	YES
74	BIRC3	BIRC3	BIRC3	3145	0.2	0.6	YES
75	ITGA9	ITGA9	ITGA9	3181	0.2	0.6	YES
76	ITGB7	ITGB7	ITGB7	3259	0.19	0.6	YES
77	ITGB8	ITGB8	ITGB8	3376	0.18	0.6	YES
78	LAMC1	LAMC1	LAMC1	3391	0.18	0.6	YES
79	PIK3CA	PIK3CA	PIK3CA	3454	0.17	0.6	YES
80	ROCK1	ROCK1	ROCK1	3504	0.17	0.6	YES
81	MYLK3	MYLK3	MYLK3	3749	0.16	0.6	NO
82	LAMB1	LAMB1	LAMB1	3826	0.15	0.6	NO
83	LAMA5	LAMA5	LAMA5	3854	0.15	0.6	NO
84	VCL	VCL	VCL	3930	0.14	0.6	NO
85	TLN1	TLN1	TLN1	3977	0.14	0.6	NO
86	PPP1R12A	PPP1R12A	PPP1R12A	4209	0.13	0.59	NO
87	LAMA1	LAMA1	LAMA1	4376	0.12	0.58	NO
88	ACTN1	ACTN1	ACTN1	4419	0.12	0.58	NO
89	LAMC2	LAMC2	LAMC2	4541	0.12	0.58	NO
90	LAMB4	LAMB4	LAMB4	4548	0.12	0.58	NO
91	EGFR	EGFR	EGFR	4563	0.12	0.59	NO
92	ARHGAP5	ARHGAP5	ARHGAP5	4660	0.11	0.58	NO
93	MYLK2	MYLK2	MYLK2	4681	0.11	0.59	NO
94	SHC2	SHC2	SHC2	4726	0.11	0.59	NO
95	ITGB1	ITGB1	ITGB1	4822	0.1	0.58	NO
96	LAMA3	LAMA3	LAMA3	4840	0.1	0.59	NO
97	SOS1	SOS1	SOS1	4868	0.1	0.59	NO
98	PARVB	PARVB	PARVB	4879	0.1	0.59	NO
99	ITGB5	ITGB5	ITGB5	4936	0.1	0.59	NO
100	DOCK1	DOCK1	DOCK1	4997	0.099	0.59	NO
101	PIP5K1C	PIP5K1C	PIP5K1C	5001	0.098	0.59	NO
102	RAC2	RAC2	RAC2	5080	0.096	0.59	NO
103	RAPGEF1	RAPGEF1	RAPGEF1	5097	0.095	0.59	NO
104	BIRC2	BIRC2	BIRC2	5107	0.095	0.59	NO
105	IGF1R	IGF1R	IGF1R	5158	0.094	0.59	NO
106	PIK3R3	PIK3R3	PIK3R3	5358	0.088	0.58	NO
107	SOS2	SOS2	SOS2	5506	0.083	0.58	NO
108	COL11A2	COL11A2	COL11A2	5607	0.081	0.57	NO
109	PIK3R1	PIK3R1	PIK3R1	5657	0.08	0.57	NO
110	CCND1	CCND1	CCND1	5699	0.079	0.57	NO
111	RAP1A	RAP1A	RAP1A	5811	0.076	0.57	NO
112	PDGFA	PDGFA	PDGFA	6011	0.071	0.56	NO
113	PARVA	PARVA	PARVA	6043	0.07	0.56	NO
114	BRAF	BRAF	BRAF	6094	0.069	0.56	NO
115	VAV2	VAV2	VAV2	6156	0.068	0.56	NO
116	ITGA2	ITGA2	ITGA2	6170	0.067	0.56	NO
117	PTEN	PTEN	PTEN	6399	0.062	0.55	NO
118	SHC1	SHC1	SHC1	6431	0.061	0.55	NO
119	ROCK2	ROCK2	ROCK2	6464	0.06	0.55	NO
120	ZYX	ZYX	ZYX	6622	0.057	0.54	NO
121	PAK2	PAK2	PAK2	6700	0.056	0.54	NO
122	ITGA8	ITGA8	ITGA8	6933	0.051	0.53	NO
123	GRB2	GRB2	GRB2	7110	0.048	0.52	NO
124	GRLF1	GRLF1	GRLF1	7135	0.047	0.52	NO
125	ILK	ILK	ILK	7168	0.047	0.52	NO
126	MAP2K1	MAP2K1	MAP2K1	7174	0.047	0.52	NO
127	PRKCG	PRKCG	PRKCG	7177	0.047	0.52	NO
128	CAPN2	CAPN2	CAPN2	7243	0.045	0.52	NO
129	VEGFB	VEGFB	VEGFB	7357	0.044	0.51	NO
130	PIK3CB	PIK3CB	PIK3CB	7407	0.043	0.51	NO
131	LAMB3	LAMB3	LAMB3	7523	0.041	0.5	NO
132	TLN2	TLN2	TLN2	7865	0.036	0.49	NO
133	XIAP	XIAP	XIAP	7898	0.035	0.49	NO
134	MAPK8	MAPK8	MAPK8	7904	0.035	0.49	NO
135	FLNB	FLNB	FLNB	7921	0.035	0.49	NO
136	CRK	CRK	CRK	7938	0.034	0.49	NO
137	CDC42	CDC42	CDC42	8049	0.033	0.48	NO
138	PTK2	PTK2	PTK2	8241	0.03	0.47	NO
139	MAPK1	MAPK1	MAPK1	8307	0.028	0.47	NO
140	PRKCA	PRKCA	PRKCA	8422	0.027	0.46	NO
141	MYL12A	MYL12A	MYL12A	8465	0.026	0.46	NO
142	MET	MET	MET	8477	0.026	0.46	NO
143	CRKL	CRKL	CRKL	8516	0.025	0.46	NO
144	SHC3	SHC3	SHC3	8582	0.024	0.46	NO
145	ELK1	ELK1	ELK1	8620	0.024	0.46	NO
146	PPP1CB	PPP1CB	PPP1CB	8645	0.023	0.46	NO
147	GSK3B	GSK3B	GSK3B	8734	0.022	0.45	NO
148	DIAPH1	DIAPH1	DIAPH1	8833	0.021	0.45	NO
149	PDPK1	PDPK1	PDPK1	8842	0.021	0.45	NO
150	PXN	PXN	PXN	8843	0.021	0.45	NO
151	RHOA	RHOA	RHOA	8942	0.019	0.44	NO
152	ACTN4	ACTN4	ACTN4	9299	0.014	0.42	NO
153	RASGRF1	RASGRF1	RASGRF1	9324	0.014	0.42	NO
154	RAC3	RAC3	RAC3	9336	0.014	0.42	NO
155	BCAR1	BCAR1	BCAR1	9515	0.011	0.41	NO
156	AKT1	AKT1	AKT1	9910	0.0055	0.39	NO
157	ITGB4	ITGB4	ITGB4	9948	0.0049	0.39	NO
158	ACTB	ACTB	ACTB	10010	0.004	0.38	NO
159	JUN	JUN	JUN	10056	0.0034	0.38	NO
160	ITGA3	ITGA3	ITGA3	10321	-0.00038	0.37	NO
161	VASP	VASP	VASP	10391	-0.0012	0.36	NO
162	RAF1	RAF1	RAF1	10396	-0.0013	0.36	NO
163	LAMC3	LAMC3	LAMC3	10728	-0.0061	0.34	NO
164	CTNNB1	CTNNB1	CTNNB1	10807	-0.0076	0.34	NO
165	VEGFA	VEGFA	VEGFA	11067	-0.011	0.33	NO
166	MAPK9	MAPK9	MAPK9	11110	-0.012	0.32	NO
167	PPP1CC	PPP1CC	PPP1CC	11191	-0.013	0.32	NO
168	ERBB2	ERBB2	ERBB2	11363	-0.016	0.31	NO
169	RAC1	RAC1	RAC1	11370	-0.016	0.31	NO
170	AKT2	AKT2	AKT2	11376	-0.016	0.31	NO
171	ITGA6	ITGA6	ITGA6	11569	-0.019	0.3	NO
172	PAK1	PAK1	PAK1	11848	-0.024	0.28	NO
173	MYL12B	MYL12B	MYL12B	11891	-0.025	0.28	NO
174	RAP1B	RAP1B	RAP1B	11952	-0.026	0.28	NO
175	ACTG1	ACTG1	ACTG1	12176	-0.029	0.27	NO
176	CCND3	CCND3	CCND3	12194	-0.029	0.27	NO
177	SRC	SRC	SRC	12512	-0.035	0.25	NO
178	ITGB6	ITGB6	ITGB6	12701	-0.038	0.24	NO
179	PIK3R2	PIK3R2	PIK3R2	12957	-0.043	0.23	NO
180	PAK4	PAK4	PAK4	13282	-0.049	0.21	NO
181	PPP1CA	PPP1CA	PPP1CA	14011	-0.063	0.17	NO
182	PAK6	PAK6	PAK6	14143	-0.066	0.17	NO
183	MAPK3	MAPK3	MAPK3	14185	-0.067	0.17	NO
184	COL2A1	COL2A1	COL2A1	14245	-0.068	0.17	NO
185	BAD	BAD	BAD	14457	-0.074	0.16	NO
186	ITGA2B	ITGA2B	ITGA2B	14978	-0.088	0.13	NO
187	CCND2	CCND2	CCND2	15055	-0.09	0.13	NO
188	EGF	EGF	EGF	15755	-0.12	0.092	NO
189	CHAD	CHAD	CHAD	16359	-0.15	0.062	NO
190	MYL5	MYL5	MYL5	16739	-0.18	0.046	NO
191	VAV3	VAV3	VAV3	16822	-0.19	0.046	NO
192	COL4A6	COL4A6	COL4A6	17757	-0.38	0.0044	NO
193	MYLPF	MYLPF	MYLPF	17761	-0.39	0.015	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 AGR PATHWAY.

Figure S44. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AGR 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 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	NGFR	NGFR	NGFR	388	0.58	0.021	YES
2	AKT3	AKT3	AKT3	502	0.54	0.054	YES
3	PIK3R5	PIK3R5	PIK3R5	582	0.53	0.088	YES
4	PIK3CG	PIK3CG	PIK3CG	732	0.49	0.12	YES
5	CAMK2A	CAMK2A	CAMK2A	780	0.48	0.15	YES
6	SHC4	SHC4	SHC4	786	0.48	0.18	YES
7	NTRK3	NTRK3	NTRK3	1003	0.44	0.2	YES
8	PIK3CD	PIK3CD	PIK3CD	1205	0.41	0.22	YES
9	MAPK11	MAPK11	MAPK11	1259	0.4	0.25	YES
10	NGF	NGF	NGF	1272	0.4	0.28	YES
11	IRAK3	IRAK3	IRAK3	1371	0.39	0.3	YES
12	PLCG2	PLCG2	PLCG2	1391	0.39	0.33	YES
13	NTRK1	NTRK1	NTRK1	1547	0.36	0.35	YES
14	MAPK10	MAPK10	MAPK10	1766	0.34	0.36	YES
15	CAMK4	CAMK4	CAMK4	2087	0.3	0.36	YES
16	FASLG	FASLG	FASLG	2123	0.3	0.38	YES
17	BDNF	BDNF	BDNF	2358	0.27	0.39	YES
18	CAMK2B	CAMK2B	CAMK2B	2553	0.26	0.4	YES
19	NTRK2	NTRK2	NTRK2	2611	0.25	0.42	YES
20	BCL2	BCL2	BCL2	2812	0.23	0.42	YES
21	MAPK12	MAPK12	MAPK12	2935	0.22	0.43	YES
22	MAP3K3	MAP3K3	MAP3K3	3062	0.2	0.44	YES
23	RPS6KA2	RPS6KA2	RPS6KA2	3104	0.2	0.45	YES
24	IRS1	IRS1	IRS1	3157	0.2	0.46	YES
25	PIK3CA	PIK3CA	PIK3CA	3454	0.17	0.46	YES
26	SH2B3	SH2B3	SH2B3	3627	0.16	0.46	YES
27	NTF4	NTF4	NTF4	4080	0.14	0.44	YES
28	IRAK2	IRAK2	IRAK2	4097	0.14	0.45	YES
29	KIDINS220	KIDINS220	KIDINS220	4230	0.13	0.46	YES
30	MAP3K1	MAP3K1	MAP3K1	4238	0.13	0.46	YES
31	SHC2	SHC2	SHC2	4726	0.11	0.45	NO
32	ARHGDIB	ARHGDIB	ARHGDIB	4789	0.11	0.45	NO
33	SOS1	SOS1	SOS1	4868	0.1	0.45	NO
34	RAPGEF1	RAPGEF1	RAPGEF1	5097	0.095	0.45	NO
35	NGFRAP1	NGFRAP1	NGFRAP1	5140	0.094	0.45	NO
36	PIK3R3	PIK3R3	PIK3R3	5358	0.088	0.45	NO
37	FRS2	FRS2	FRS2	5364	0.087	0.45	NO
38	SOS2	SOS2	SOS2	5506	0.083	0.45	NO
39	MAP3K5	MAP3K5	MAP3K5	5547	0.082	0.45	NO
40	PIK3R1	PIK3R1	PIK3R1	5657	0.08	0.45	NO
41	RAP1A	RAP1A	RAP1A	5811	0.076	0.45	NO
42	PTPN11	PTPN11	PTPN11	5842	0.075	0.46	NO
43	NTF3	NTF3	NTF3	6027	0.071	0.45	NO
44	BRAF	BRAF	BRAF	6094	0.069	0.45	NO
45	NFKBIA	NFKBIA	NFKBIA	6260	0.066	0.45	NO
46	SHC1	SHC1	SHC1	6431	0.061	0.44	NO
47	ABL1	ABL1	ABL1	6547	0.059	0.44	NO
48	KRAS	KRAS	KRAS	6619	0.057	0.44	NO
49	YWHAG	YWHAG	YWHAG	6780	0.054	0.44	NO
50	GRB2	GRB2	GRB2	7110	0.048	0.42	NO
51	MAP2K1	MAP2K1	MAP2K1	7174	0.047	0.42	NO
52	MAPKAPK2	MAPKAPK2	MAPKAPK2	7216	0.046	0.42	NO
53	TRAF6	TRAF6	TRAF6	7235	0.046	0.42	NO
54	ZNF274	ZNF274	ZNF274	7262	0.045	0.42	NO
55	PLCG1	PLCG1	PLCG1	7316	0.044	0.43	NO
56	PIK3CB	PIK3CB	PIK3CB	7407	0.043	0.42	NO
57	RPS6KA5	RPS6KA5	RPS6KA5	7467	0.042	0.42	NO
58	YWHAH	YWHAH	YWHAH	7484	0.042	0.43	NO
59	RIPK2	RIPK2	RIPK2	7534	0.041	0.43	NO
60	MAP2K7	MAP2K7	MAP2K7	7620	0.039	0.42	NO
61	MAPK7	MAPK7	MAPK7	7662	0.039	0.42	NO
62	CAMK2D	CAMK2D	CAMK2D	7753	0.037	0.42	NO
63	NFKB1	NFKB1	NFKB1	7760	0.037	0.42	NO
64	MAPK8	MAPK8	MAPK8	7904	0.035	0.42	NO
65	CRK	CRK	CRK	7938	0.034	0.42	NO
66	NFKBIE	NFKBIE	NFKBIE	7995	0.034	0.42	NO
67	CDC42	CDC42	CDC42	8049	0.033	0.42	NO
68	IKBKB	IKBKB	IKBKB	8295	0.029	0.41	NO
69	MAPK1	MAPK1	MAPK1	8307	0.028	0.41	NO
70	IRS2	IRS2	IRS2	8354	0.028	0.41	NO
71	RELA	RELA	RELA	8473	0.026	0.4	NO
72	CRKL	CRKL	CRKL	8516	0.025	0.4	NO
73	SHC3	SHC3	SHC3	8582	0.024	0.4	NO
74	MAGED1	MAGED1	MAGED1	8622	0.024	0.4	NO
75	GAB1	GAB1	GAB1	8638	0.024	0.4	NO
76	GSK3B	GSK3B	GSK3B	8734	0.022	0.4	NO
77	PSEN1	PSEN1	PSEN1	8749	0.022	0.4	NO
78	RHOA	RHOA	RHOA	8942	0.019	0.39	NO
79	NRAS	NRAS	NRAS	9110	0.017	0.38	NO
80	FOXO3	FOXO3	FOXO3	9181	0.016	0.38	NO
81	CALM1	CALM1	CALM1	9204	0.016	0.38	NO
82	YWHAZ	YWHAZ	YWHAZ	9207	0.016	0.38	NO
83	CAMK2G	CAMK2G	CAMK2G	9507	0.011	0.36	NO
84	TP73	TP73	TP73	9724	0.0082	0.35	NO
85	AKT1	AKT1	AKT1	9910	0.0055	0.34	NO
86	JUN	JUN	JUN	10056	0.0034	0.33	NO
87	PRDM4	PRDM4	PRDM4	10066	0.0032	0.33	NO
88	CALM2	CALM2	CALM2	10075	0.0031	0.33	NO
89	CALM3	CALM3	CALM3	10204	0.0011	0.33	NO
90	SORT1	SORT1	SORT1	10230	0.00085	0.32	NO
91	RAF1	RAF1	RAF1	10396	-0.0013	0.32	NO
92	YWHAB	YWHAB	YWHAB	10418	-0.0016	0.32	NO
93	MAPK14	MAPK14	MAPK14	10727	-0.0061	0.3	NO
94	RPS6KA3	RPS6KA3	RPS6KA3	10804	-0.0074	0.3	NO
95	IRAK4	IRAK4	IRAK4	10871	-0.0085	0.29	NO
96	RPS6KA4	RPS6KA4	RPS6KA4	11029	-0.011	0.28	NO
97	MAPK9	MAPK9	MAPK9	11110	-0.012	0.28	NO
98	CSK	CSK	CSK	11139	-0.012	0.28	NO
99	ATF4	ATF4	ATF4	11155	-0.012	0.28	NO
100	SH2B1	SH2B1	SH2B1	11229	-0.014	0.28	NO
101	IRAK1	IRAK1	IRAK1	11248	-0.014	0.28	NO
102	YWHAE	YWHAE	YWHAE	11300	-0.015	0.28	NO
103	NFKBIB	NFKBIB	NFKBIB	11368	-0.016	0.27	NO
104	RAC1	RAC1	RAC1	11370	-0.016	0.27	NO
105	AKT2	AKT2	AKT2	11376	-0.016	0.27	NO
106	ARHGDIA	ARHGDIA	ARHGDIA	11436	-0.017	0.27	NO
107	YWHAQ	YWHAQ	YWHAQ	11589	-0.019	0.26	NO
108	PRKCD	PRKCD	PRKCD	11631	-0.02	0.26	NO
109	RAP1B	RAP1B	RAP1B	11952	-0.026	0.25	NO
110	PDK1	PDK1	PDK1	12311	-0.032	0.23	NO
111	MAP2K5	MAP2K5	MAP2K5	12651	-0.038	0.21	NO
112	BAX	BAX	BAX	12742	-0.039	0.21	NO
113	PIK3R2	PIK3R2	PIK3R2	12957	-0.043	0.2	NO
114	TP53	TP53	TP53	13277	-0.049	0.19	NO
115	MAPK3	MAPK3	MAPK3	14185	-0.067	0.14	NO
116	MAP2K2	MAP2K2	MAP2K2	14366	-0.071	0.14	NO
117	BAD	BAD	BAD	14457	-0.074	0.14	NO
118	RPS6KA1	RPS6KA1	RPS6KA1	14680	-0.08	0.13	NO
119	MAPK13	MAPK13	MAPK13	15080	-0.091	0.12	NO
120	RPS6KA6	RPS6KA6	RPS6KA6	16141	-0.13	0.067	NO
121	SH2B2	SH2B2	SH2B2	16304	-0.14	0.068	NO
122	CALML3	CALML3	CALML3	16441	-0.15	0.072	NO
123	CALML6	CALML6	CALML6	17115	-0.22	0.051	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 ALK PATHWAY.

Figure S46. 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 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	FGF1	FGF1	FGF1	49	0.76	0.021	YES
2	ITGAM	ITGAM	ITGAM	171	0.67	0.036	YES
3	FGF7	FGF7	FGF7	183	0.66	0.056	YES
4	FGF14	FGF14	FGF14	190	0.66	0.076	YES
5	FGF5	FGF5	FGF5	232	0.64	0.094	YES
6	CHRM2	CHRM2	CHRM2	399	0.58	0.1	YES
7	FGF2	FGF2	FGF2	400	0.58	0.12	YES
8	MRAS	MRAS	MRAS	486	0.55	0.13	YES
9	TIAM1	TIAM1	TIAM1	578	0.53	0.14	YES
10	PIK3R5	PIK3R5	PIK3R5	582	0.53	0.16	YES
11	ITGA10	ITGA10	ITGA10	600	0.52	0.18	YES
12	ITGAX	ITGAX	ITGAX	664	0.51	0.19	YES
13	ITGA11	ITGA11	ITGA11	692	0.5	0.2	YES
14	PIK3CG	PIK3CG	PIK3CG	732	0.49	0.22	YES
15	FGF10	FGF10	FGF10	886	0.46	0.22	YES
16	PDGFC	PDGFC	PDGFC	980	0.45	0.23	YES
17	ITGAL	ITGAL	ITGAL	994	0.44	0.24	YES
18	NCKAP1L	NCKAP1L	NCKAP1L	1021	0.44	0.26	YES
19	WAS	WAS	WAS	1031	0.44	0.27	YES
20	MYH10	MYH10	MYH10	1036	0.44	0.28	YES
21	ARHGEF6	ARHGEF6	ARHGEF6	1156	0.42	0.29	YES
22	FN1	FN1	FN1	1170	0.42	0.3	YES
23	PAK3	PAK3	PAK3	1184	0.41	0.32	YES
24	PIK3CD	PIK3CD	PIK3CD	1205	0.41	0.33	YES
25	ITGB3	ITGB3	ITGB3	1220	0.41	0.34	YES
26	ITGB2	ITGB2	ITGB2	1303	0.4	0.35	YES
27	FGFR1	FGFR1	FGFR1	1309	0.4	0.36	YES
28	MYLK	MYLK	MYLK	1356	0.39	0.37	YES
29	ITGA7	ITGA7	ITGA7	1404	0.38	0.38	YES
30	CFL2	CFL2	CFL2	1570	0.36	0.38	YES
31	ITGA5	ITGA5	ITGA5	1582	0.36	0.39	YES
32	ITGA4	ITGA4	ITGA4	1643	0.35	0.4	YES
33	FGF12	FGF12	FGF12	1649	0.35	0.41	YES
34	RDX	RDX	RDX	1658	0.35	0.42	YES
35	MYL9	MYL9	MYL9	1824	0.33	0.42	YES
36	PDGFRB	PDGFRB	PDGFRB	1855	0.33	0.43	YES
37	FGF11	FGF11	FGF11	1924	0.32	0.44	YES
38	WASF1	WASF1	WASF1	1955	0.32	0.45	YES
39	ACTN2	ACTN2	ACTN2	2195	0.29	0.44	YES
40	CD14	CD14	CD14	2285	0.28	0.44	YES
41	PDGFB	PDGFB	PDGFB	2314	0.28	0.45	YES
42	MSN	MSN	MSN	2385	0.27	0.46	YES
43	CHRM4	CHRM4	CHRM4	2447	0.26	0.46	YES
44	VAV1	VAV1	VAV1	2449	0.26	0.47	YES
45	F2R	F2R	F2R	2459	0.26	0.48	YES
46	ACTN3	ACTN3	ACTN3	2525	0.26	0.48	YES
47	ARHGEF4	ARHGEF4	ARHGEF4	2580	0.25	0.49	YES
48	TIAM2	TIAM2	TIAM2	2684	0.24	0.49	YES
49	ITGAV	ITGAV	ITGAV	2852	0.23	0.49	YES
50	ITGA1	ITGA1	ITGA1	2908	0.22	0.49	YES
51	PDGFRA	PDGFRA	PDGFRA	2919	0.22	0.5	YES
52	FGF9	FGF9	FGF9	2979	0.21	0.5	YES
53	PIP4K2A	PIP4K2A	PIP4K2A	3060	0.2	0.5	YES
54	PDGFD	PDGFD	PDGFD	3064	0.2	0.51	YES
55	FGF13	FGF13	FGF13	3166	0.2	0.51	YES
56	ITGA9	ITGA9	ITGA9	3181	0.2	0.52	YES
57	FGFR2	FGFR2	FGFR2	3225	0.19	0.52	YES
58	ITGB7	ITGB7	ITGB7	3259	0.19	0.52	YES
59	APC	APC	APC	3304	0.19	0.53	YES
60	ITGB8	ITGB8	ITGB8	3376	0.18	0.53	YES
61	SSH1	SSH1	SSH1	3435	0.18	0.53	YES
62	PIK3CA	PIK3CA	PIK3CA	3454	0.17	0.53	YES
63	ROCK1	ROCK1	ROCK1	3504	0.17	0.54	YES
64	CHRM5	CHRM5	CHRM5	3520	0.17	0.54	YES
65	INSRR	INSRR	INSRR	3545	0.17	0.55	YES
66	MYLK3	MYLK3	MYLK3	3749	0.16	0.54	NO
67	BDKRB1	BDKRB1	BDKRB1	3911	0.14	0.53	NO
68	PIKFYVE	PIKFYVE	PIKFYVE	3923	0.14	0.54	NO
69	VCL	VCL	VCL	3930	0.14	0.54	NO
70	ITGAD	ITGAD	ITGAD	3990	0.14	0.54	NO
71	FGF18	FGF18	FGF18	4146	0.13	0.54	NO
72	PPP1R12A	PPP1R12A	PPP1R12A	4209	0.13	0.54	NO
73	FGD1	FGD1	FGD1	4291	0.13	0.54	NO
74	ACTN1	ACTN1	ACTN1	4419	0.12	0.54	NO
75	ENAH	ENAH	ENAH	4515	0.12	0.53	NO
76	ABI2	ABI2	ABI2	4537	0.12	0.54	NO
77	EGFR	EGFR	EGFR	4563	0.12	0.54	NO
78	MYLK2	MYLK2	MYLK2	4681	0.11	0.54	NO
79	GSN	GSN	GSN	4702	0.11	0.54	NO
80	ITGB1	ITGB1	ITGB1	4822	0.1	0.54	NO
81	SOS1	SOS1	SOS1	4868	0.1	0.54	NO
82	ITGB5	ITGB5	ITGB5	4936	0.1	0.54	NO
83	DOCK1	DOCK1	DOCK1	4997	0.099	0.54	NO
84	PIP5K1C	PIP5K1C	PIP5K1C	5001	0.098	0.54	NO
85	RAC2	RAC2	RAC2	5080	0.096	0.54	NO
86	GNA12	GNA12	GNA12	5081	0.096	0.54	NO
87	ARHGEF12	ARHGEF12	ARHGEF12	5231	0.091	0.53	NO
88	MYH9	MYH9	MYH9	5237	0.091	0.54	NO
89	PIK3R3	PIK3R3	PIK3R3	5358	0.088	0.53	NO
90	PIP4K2B	PIP4K2B	PIP4K2B	5476	0.084	0.53	NO
91	SOS2	SOS2	SOS2	5506	0.083	0.53	NO
92	LIMK1	LIMK1	LIMK1	5556	0.082	0.53	NO
93	PIK3R1	PIK3R1	PIK3R1	5657	0.08	0.53	NO
94	SSH2	SSH2	SSH2	5680	0.079	0.53	NO
95	BAIAP2	BAIAP2	BAIAP2	5815	0.076	0.52	NO
96	PDGFA	PDGFA	PDGFA	6011	0.071	0.51	NO
97	BRAF	BRAF	BRAF	6094	0.069	0.51	NO
98	VAV2	VAV2	VAV2	6156	0.068	0.51	NO
99	ITGA2	ITGA2	ITGA2	6170	0.067	0.51	NO
100	FGD3	FGD3	FGD3	6207	0.067	0.51	NO
101	GNA13	GNA13	GNA13	6227	0.066	0.51	NO
102	IQGAP1	IQGAP1	IQGAP1	6258	0.066	0.51	NO
103	WASF2	WASF2	WASF2	6372	0.063	0.51	NO
104	ROCK2	ROCK2	ROCK2	6464	0.06	0.5	NO
105	ARHGEF1	ARHGEF1	ARHGEF1	6488	0.06	0.51	NO
106	KRAS	KRAS	KRAS	6619	0.057	0.5	NO
107	PAK2	PAK2	PAK2	6700	0.056	0.5	NO
108	PFN2	PFN2	PFN2	6918	0.052	0.49	NO
109	ITGA8	ITGA8	ITGA8	6933	0.051	0.49	NO
110	FGF19	FGF19	FGF19	7008	0.05	0.48	NO
111	PIP5K1A	PIP5K1A	PIP5K1A	7132	0.048	0.48	NO
112	GRLF1	GRLF1	GRLF1	7135	0.047	0.48	NO
113	MAP2K1	MAP2K1	MAP2K1	7174	0.047	0.48	NO
114	PIK3CB	PIK3CB	PIK3CB	7407	0.043	0.47	NO
115	NCKAP1	NCKAP1	NCKAP1	7505	0.041	0.46	NO
116	ARPC3	ARPC3	ARPC3	7830	0.036	0.45	NO
117	FGF23	FGF23	FGF23	7879	0.036	0.45	NO
118	CRK	CRK	CRK	7938	0.034	0.44	NO
119	BDKRB2	BDKRB2	BDKRB2	7965	0.034	0.44	NO
120	PIP4K2C	PIP4K2C	PIP4K2C	7997	0.034	0.44	NO
121	CDC42	CDC42	CDC42	8049	0.033	0.44	NO
122	FGF3	FGF3	FGF3	8135	0.031	0.44	NO
123	PTK2	PTK2	PTK2	8241	0.03	0.43	NO
124	SLC9A1	SLC9A1	SLC9A1	8270	0.029	0.43	NO
125	MAPK1	MAPK1	MAPK1	8307	0.028	0.43	NO
126	MYL12A	MYL12A	MYL12A	8465	0.026	0.42	NO
127	WASL	WASL	WASL	8491	0.026	0.42	NO
128	CRKL	CRKL	CRKL	8516	0.025	0.42	NO
129	PPP1CB	PPP1CB	PPP1CB	8645	0.023	0.42	NO
130	RRAS	RRAS	RRAS	8697	0.022	0.41	NO
131	EZR	EZR	EZR	8719	0.022	0.41	NO
132	ITGAE	ITGAE	ITGAE	8831	0.021	0.41	NO
133	DIAPH1	DIAPH1	DIAPH1	8833	0.021	0.41	NO
134	PXN	PXN	PXN	8843	0.021	0.41	NO
135	FGF20	FGF20	FGF20	8885	0.02	0.41	NO
136	RHOA	RHOA	RHOA	8942	0.019	0.4	NO
137	DIAPH2	DIAPH2	DIAPH2	9016	0.018	0.4	NO
138	ARHGEF7	ARHGEF7	ARHGEF7	9038	0.018	0.4	NO
139	NRAS	NRAS	NRAS	9110	0.017	0.4	NO
140	ACTN4	ACTN4	ACTN4	9299	0.014	0.38	NO
141	RAC3	RAC3	RAC3	9336	0.014	0.38	NO
142	RRAS2	RRAS2	RRAS2	9360	0.013	0.38	NO
143	ARPC2	ARPC2	ARPC2	9373	0.013	0.38	NO
144	CYFIP1	CYFIP1	CYFIP1	9476	0.012	0.38	NO
145	GNG12	GNG12	GNG12	9514	0.011	0.38	NO
146	BCAR1	BCAR1	BCAR1	9515	0.011	0.38	NO
147	LIMK2	LIMK2	LIMK2	9528	0.011	0.38	NO
148	ARPC5	ARPC5	ARPC5	9633	0.0093	0.37	NO
149	ARPC1B	ARPC1B	ARPC1B	9702	0.0085	0.37	NO
150	IQGAP2	IQGAP2	IQGAP2	9939	0.0051	0.35	NO
151	ITGB4	ITGB4	ITGB4	9948	0.0049	0.35	NO
152	ACTB	ACTB	ACTB	10010	0.004	0.35	NO
153	ITGA3	ITGA3	ITGA3	10321	-0.00038	0.33	NO
154	RAF1	RAF1	RAF1	10396	-0.0013	0.33	NO
155	CSK	CSK	CSK	11139	-0.012	0.29	NO
156	GIT1	GIT1	GIT1	11159	-0.012	0.29	NO
157	PPP1CC	PPP1CC	PPP1CC	11191	-0.013	0.28	NO
158	CHRM3	CHRM3	CHRM3	11362	-0.016	0.28	NO
159	RAC1	RAC1	RAC1	11370	-0.016	0.28	NO
160	FGF8	FGF8	FGF8	11399	-0.016	0.28	NO
161	CFL1	CFL1	CFL1	11481	-0.018	0.27	NO
162	ITGA6	ITGA6	ITGA6	11569	-0.019	0.27	NO
163	ARPC4	ARPC4	ARPC4	11592	-0.019	0.27	NO
164	MYH14	MYH14	MYH14	11765	-0.022	0.26	NO
165	PAK1	PAK1	PAK1	11848	-0.024	0.25	NO
166	SCIN	SCIN	SCIN	11849	-0.024	0.25	NO
167	MYL12B	MYL12B	MYL12B	11891	-0.025	0.25	NO
168	PFN4	PFN4	PFN4	12064	-0.027	0.24	NO
169	ACTG1	ACTG1	ACTG1	12176	-0.029	0.24	NO
170	PFN1	PFN1	PFN1	12275	-0.031	0.23	NO
171	DIAPH3	DIAPH3	DIAPH3	12280	-0.031	0.24	NO
172	ITGB6	ITGB6	ITGB6	12701	-0.038	0.21	NO
173	SSH3	SSH3	SSH3	12846	-0.041	0.21	NO
174	CYFIP2	CYFIP2	CYFIP2	12921	-0.042	0.2	NO
175	PIK3R2	PIK3R2	PIK3R2	12957	-0.043	0.2	NO
176	CHRM1	CHRM1	CHRM1	13005	-0.044	0.2	NO
177	IQGAP3	IQGAP3	IQGAP3	13074	-0.045	0.2	NO
178	TMSB4Y	TMSB4Y	TMSB4Y	13275	-0.049	0.19	NO
179	PAK4	PAK4	PAK4	13282	-0.049	0.19	NO
180	ARAF	ARAF	ARAF	13329	-0.05	0.19	NO
181	ARPC1A	ARPC1A	ARPC1A	13424	-0.051	0.18	NO
182	APC2	APC2	APC2	13451	-0.052	0.19	NO
183	PPP1CA	PPP1CA	PPP1CA	14011	-0.063	0.16	NO
184	PAK6	PAK6	PAK6	14143	-0.066	0.15	NO
185	MAPK3	MAPK3	MAPK3	14185	-0.067	0.15	NO
186	MAP2K2	MAP2K2	MAP2K2	14366	-0.071	0.14	NO
187	TMSL3	TMSL3	TMSL3	14369	-0.071	0.14	NO
188	ARPC5L	ARPC5L	ARPC5L	14404	-0.072	0.14	NO
189	ITGA2B	ITGA2B	ITGA2B	14978	-0.088	0.12	NO
190	FGF17	FGF17	FGF17	15492	-0.1	0.091	NO
191	EGF	EGF	EGF	15755	-0.12	0.08	NO
192	PIP5K1B	PIP5K1B	PIP5K1B	15888	-0.12	0.076	NO
193	FGFR4	FGFR4	FGFR4	16244	-0.14	0.06	NO
194	MYL5	MYL5	MYL5	16739	-0.18	0.038	NO
195	VAV3	VAV3	VAV3	16822	-0.19	0.04	NO
196	F2	F2	F2	17256	-0.25	0.023	NO
197	FGFR3	FGFR3	FGFR3	17282	-0.25	0.03	NO
198	MYLPF	MYLPF	MYLPF	17761	-0.39	0.015	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 AT1R PATHWAY.

Figure S48. 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 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	FGF1	FGF1	FGF1	49	0.76	0.014	YES
2	GLI3	GLI3	GLI3	55	0.76	0.029	YES
3	TGFB3	TGFB3	TGFB3	81	0.73	0.043	YES
4	FGF7	FGF7	FGF7	183	0.66	0.052	YES
5	FGF14	FGF14	FGF14	190	0.66	0.065	YES
6	VEGFC	VEGFC	VEGFC	206	0.65	0.078	YES
7	RUNX1T1	RUNX1T1	RUNX1T1	209	0.65	0.092	YES
8	MITF	MITF	MITF	211	0.65	0.11	YES
9	FGF5	FGF5	FGF5	232	0.64	0.12	YES
10	IGF1	IGF1	IGF1	338	0.6	0.12	YES
11	GLI2	GLI2	GLI2	352	0.59	0.14	YES
12	FGF2	FGF2	FGF2	400	0.58	0.15	YES
13	LAMA2	LAMA2	LAMA2	459	0.56	0.16	YES
14	AKT3	AKT3	AKT3	502	0.54	0.16	YES
15	PIK3R5	PIK3R5	PIK3R5	582	0.53	0.17	YES
16	AR	AR	AR	622	0.52	0.18	YES
17	RARB	RARB	RARB	660	0.51	0.19	YES
18	TGFB2	TGFB2	TGFB2	667	0.51	0.2	YES
19	PIK3CG	PIK3CG	PIK3CG	732	0.49	0.21	YES
20	PRKCB	PRKCB	PRKCB	784	0.48	0.21	YES
21	GLI1	GLI1	GLI1	787	0.48	0.22	YES
22	FGF10	FGF10	FGF10	886	0.46	0.23	YES
23	ZBTB16	ZBTB16	ZBTB16	943	0.45	0.23	YES
24	HGF	HGF	HGF	991	0.45	0.24	YES
25	CSF3R	CSF3R	CSF3R	1062	0.43	0.25	YES
26	FN1	FN1	FN1	1170	0.42	0.25	YES
27	PIK3CD	PIK3CD	PIK3CD	1205	0.41	0.26	YES
28	CCNA1	CCNA1	CCNA1	1223	0.41	0.26	YES
29	WNT9A	WNT9A	WNT9A	1261	0.4	0.27	YES
30	ARNT2	ARNT2	ARNT2	1263	0.4	0.28	YES
31	FGFR1	FGFR1	FGFR1	1309	0.4	0.28	YES
32	MMP9	MMP9	MMP9	1319	0.4	0.29	YES
33	CSF1R	CSF1R	CSF1R	1389	0.39	0.3	YES
34	PLCG2	PLCG2	PLCG2	1391	0.39	0.3	YES
35	SPI1	SPI1	SPI1	1418	0.38	0.31	YES
36	WNT9B	WNT9B	WNT9B	1546	0.37	0.31	YES
37	NTRK1	NTRK1	NTRK1	1547	0.36	0.32	YES
38	COL4A4	COL4A4	COL4A4	1559	0.36	0.33	YES
39	FGF12	FGF12	FGF12	1649	0.35	0.33	YES
40	WNT2	WNT2	WNT2	1711	0.35	0.33	YES
41	MAPK10	MAPK10	MAPK10	1766	0.34	0.34	YES
42	DAPK1	DAPK1	DAPK1	1776	0.34	0.34	YES
43	PTCH2	PTCH2	PTCH2	1847	0.33	0.35	YES
44	PDGFRB	PDGFRB	PDGFRB	1855	0.33	0.35	YES
45	MMP2	MMP2	MMP2	1856	0.33	0.36	YES
46	FGF11	FGF11	FGF11	1924	0.32	0.36	YES
47	CSF2RA	CSF2RA	CSF2RA	1958	0.32	0.37	YES
48	IL6	IL6	IL6	1960	0.32	0.38	YES
49	RASSF5	RASSF5	RASSF5	2026	0.31	0.38	YES
50	FASLG	FASLG	FASLG	2123	0.3	0.38	YES
51	CDKN2B	CDKN2B	CDKN2B	2125	0.3	0.39	YES
52	FZD4	FZD4	FZD4	2129	0.3	0.39	YES
53	ETS1	ETS1	ETS1	2149	0.3	0.4	YES
54	WNT7B	WNT7B	WNT7B	2243	0.28	0.4	YES
55	PDGFB	PDGFB	PDGFB	2314	0.28	0.4	YES
56	LAMA4	LAMA4	LAMA4	2329	0.28	0.4	YES
57	FIGF	FIGF	FIGF	2450	0.26	0.4	YES
58	NKX3-1	NKX3-1	NKX3-1	2455	0.26	0.41	YES
59	CTNNA3	CTNNA3	CTNNA3	2487	0.26	0.41	YES
60	FLT3	FLT3	FLT3	2501	0.26	0.42	YES
61	FZD2	FZD2	FZD2	2542	0.26	0.42	YES
62	TCF7L1	TCF7L1	TCF7L1	2547	0.26	0.43	YES
63	TGFB1	TGFB1	TGFB1	2706	0.24	0.42	YES
64	SMO	SMO	SMO	2710	0.24	0.43	YES
65	LEF1	LEF1	LEF1	2751	0.24	0.43	YES
66	KIT	KIT	KIT	2762	0.24	0.43	YES
67	BCL2	BCL2	BCL2	2812	0.23	0.44	YES
68	LAMB2	LAMB2	LAMB2	2817	0.23	0.44	YES
69	FZD1	FZD1	FZD1	2828	0.23	0.45	YES
70	ITGAV	ITGAV	ITGAV	2852	0.23	0.45	YES
71	PTGS2	PTGS2	PTGS2	2894	0.22	0.45	YES
72	PDGFRA	PDGFRA	PDGFRA	2919	0.22	0.46	YES
73	COL4A2	COL4A2	COL4A2	2977	0.21	0.46	YES
74	FLT3LG	FLT3LG	FLT3LG	2978	0.21	0.46	YES
75	FGF9	FGF9	FGF9	2979	0.21	0.46	YES
76	PGF	PGF	PGF	2997	0.21	0.47	YES
77	TRAF1	TRAF1	TRAF1	3016	0.21	0.47	YES
78	COL4A1	COL4A1	COL4A1	3032	0.21	0.48	YES
79	RET	RET	RET	3056	0.21	0.48	YES
80	WNT7A	WNT7A	WNT7A	3103	0.2	0.48	YES
81	BIRC3	BIRC3	BIRC3	3145	0.2	0.48	YES
82	FGF13	FGF13	FGF13	3166	0.2	0.48	YES
83	HHIP	HHIP	HHIP	3176	0.2	0.49	YES
84	FZD8	FZD8	FZD8	3186	0.2	0.49	YES
85	DCC	DCC	DCC	3188	0.2	0.5	YES
86	FGFR2	FGFR2	FGFR2	3225	0.19	0.5	YES
87	APC	APC	APC	3304	0.19	0.5	YES
88	IL8	IL8	IL8	3360	0.18	0.5	YES
89	LAMC1	LAMC1	LAMC1	3391	0.18	0.5	YES
90	FZD7	FZD7	FZD7	3449	0.17	0.5	YES
91	MMP1	MMP1	MMP1	3450	0.17	0.5	YES
92	PIK3CA	PIK3CA	PIK3CA	3454	0.17	0.51	YES
93	RUNX1	RUNX1	RUNX1	3499	0.17	0.51	YES
94	FOXO1	FOXO1	FOXO1	3563	0.17	0.51	YES
95	STAT1	STAT1	STAT1	3614	0.16	0.51	YES
96	PIAS3	PIAS3	PIAS3	3662	0.16	0.51	YES
97	WNT10B	WNT10B	WNT10B	3686	0.16	0.51	YES
98	HIF1A	HIF1A	HIF1A	3799	0.15	0.51	YES
99	LAMB1	LAMB1	LAMB1	3826	0.15	0.51	YES
100	TGFBR1	TGFBR1	TGFBR1	3837	0.15	0.52	YES
101	LAMA5	LAMA5	LAMA5	3854	0.15	0.52	YES
102	WNT10A	WNT10A	WNT10A	3861	0.15	0.52	YES
103	CBL	CBL	CBL	3941	0.14	0.52	YES
104	WNT16	WNT16	WNT16	3953	0.14	0.52	YES
105	WNT1	WNT1	WNT1	4134	0.13	0.51	NO
106	FGF18	FGF18	FGF18	4146	0.13	0.52	NO
107	KITLG	KITLG	KITLG	4265	0.13	0.51	NO
108	CBLB	CBLB	CBLB	4349	0.12	0.51	NO
109	LAMA1	LAMA1	LAMA1	4376	0.12	0.51	NO
110	NFKB2	NFKB2	NFKB2	4522	0.12	0.5	NO
111	LAMC2	LAMC2	LAMC2	4541	0.12	0.51	NO
112	LAMB4	LAMB4	LAMB4	4548	0.12	0.51	NO
113	SUFU	SUFU	SUFU	4557	0.12	0.51	NO
114	EGFR	EGFR	EGFR	4563	0.12	0.51	NO
115	FAS	FAS	FAS	4778	0.11	0.5	NO
116	TGFBR2	TGFBR2	TGFBR2	4820	0.1	0.5	NO
117	ITGB1	ITGB1	ITGB1	4822	0.1	0.5	NO
118	LAMA3	LAMA3	LAMA3	4840	0.1	0.51	NO
119	SOS1	SOS1	SOS1	4868	0.1	0.51	NO
120	EP300	EP300	EP300	5018	0.098	0.5	NO
121	RAC2	RAC2	RAC2	5080	0.096	0.5	NO
122	CDK6	CDK6	CDK6	5106	0.095	0.5	NO
123	BIRC2	BIRC2	BIRC2	5107	0.095	0.5	NO
124	IGF1R	IGF1R	IGF1R	5158	0.094	0.5	NO
125	EPAS1	EPAS1	EPAS1	5330	0.088	0.49	NO
126	PIK3R3	PIK3R3	PIK3R3	5358	0.088	0.49	NO
127	ARNT	ARNT	ARNT	5379	0.087	0.49	NO
128	SOS2	SOS2	SOS2	5506	0.083	0.49	NO
129	APPL1	APPL1	APPL1	5535	0.083	0.49	NO
130	PIK3R1	PIK3R1	PIK3R1	5657	0.08	0.48	NO
131	PIAS2	PIAS2	PIAS2	5685	0.079	0.48	NO
132	CCND1	CCND1	CCND1	5699	0.079	0.48	NO
133	CREBBP	CREBBP	CREBBP	5799	0.076	0.48	NO
134	TPR	TPR	TPR	5806	0.076	0.48	NO
135	PML	PML	PML	5854	0.075	0.48	NO
136	JAK1	JAK1	JAK1	5900	0.074	0.48	NO
137	SMAD2	SMAD2	SMAD2	5995	0.072	0.48	NO
138	PDGFA	PDGFA	PDGFA	6011	0.071	0.48	NO
139	WNT5A	WNT5A	WNT5A	6013	0.071	0.48	NO
140	BRAF	BRAF	BRAF	6094	0.069	0.48	NO
141	TRAF3	TRAF3	TRAF3	6149	0.068	0.47	NO
142	MAX	MAX	MAX	6152	0.068	0.48	NO
143	ITGA2	ITGA2	ITGA2	6170	0.067	0.48	NO
144	STAT5B	STAT5B	STAT5B	6172	0.067	0.48	NO
145	NFKBIA	NFKBIA	NFKBIA	6260	0.066	0.47	NO
146	RARA	RARA	RARA	6267	0.065	0.48	NO
147	STK4	STK4	STK4	6365	0.063	0.47	NO
148	PTEN	PTEN	PTEN	6399	0.062	0.47	NO
149	WNT6	WNT6	WNT6	6463	0.06	0.47	NO
150	HSP90B1	HSP90B1	HSP90B1	6521	0.06	0.47	NO
151	STAT5A	STAT5A	STAT5A	6545	0.059	0.47	NO
152	ABL1	ABL1	ABL1	6547	0.059	0.47	NO
153	KRAS	KRAS	KRAS	6619	0.057	0.46	NO
154	MTOR	MTOR	MTOR	6631	0.057	0.46	NO
155	PLD1	PLD1	PLD1	6648	0.057	0.46	NO
156	HSP90AA1	HSP90AA1	HSP90AA1	6689	0.056	0.46	NO
157	RB1	RB1	RB1	6702	0.056	0.46	NO
158	E2F3	E2F3	E2F3	6711	0.056	0.46	NO
159	SMAD3	SMAD3	SMAD3	6877	0.052	0.46	NO
160	PIAS1	PIAS1	PIAS1	6921	0.052	0.46	NO
161	PTCH1	PTCH1	PTCH1	6927	0.051	0.46	NO
162	FZD6	FZD6	FZD6	6976	0.05	0.46	NO
163	FGF19	FGF19	FGF19	7008	0.05	0.45	NO
164	GRB2	GRB2	GRB2	7110	0.048	0.45	NO
165	BMP4	BMP4	BMP4	7143	0.047	0.45	NO
166	MAP2K1	MAP2K1	MAP2K1	7174	0.047	0.45	NO
167	PRKCG	PRKCG	PRKCG	7177	0.047	0.45	NO
168	TRAF6	TRAF6	TRAF6	7235	0.046	0.45	NO
169	SMAD4	SMAD4	SMAD4	7241	0.046	0.45	NO
170	FZD10	FZD10	FZD10	7314	0.044	0.44	NO
171	PLCG1	PLCG1	PLCG1	7316	0.044	0.44	NO
172	VEGFB	VEGFB	VEGFB	7357	0.044	0.44	NO
173	PIK3CB	PIK3CB	PIK3CB	7407	0.043	0.44	NO
174	CTNNA2	CTNNA2	CTNNA2	7444	0.042	0.44	NO
175	FOS	FOS	FOS	7506	0.041	0.44	NO
176	LAMB3	LAMB3	LAMB3	7523	0.041	0.44	NO
177	RALB	RALB	RALB	7578	0.04	0.44	NO
178	STAT3	STAT3	STAT3	7600	0.04	0.44	NO
179	CHUK	CHUK	CHUK	7654	0.039	0.43	NO
180	TGFA	TGFA	TGFA	7693	0.038	0.43	NO
181	RALBP1	RALBP1	RALBP1	7715	0.038	0.43	NO
182	NFKB1	NFKB1	NFKB1	7760	0.037	0.43	NO
183	FGF23	FGF23	FGF23	7879	0.036	0.42	NO
184	CDKN1B	CDKN1B	CDKN1B	7885	0.035	0.42	NO
185	XIAP	XIAP	XIAP	7898	0.035	0.42	NO
186	MAPK8	MAPK8	MAPK8	7904	0.035	0.42	NO
187	CRK	CRK	CRK	7938	0.034	0.42	NO
188	BRCA2	BRCA2	BRCA2	8044	0.033	0.42	NO
189	CDC42	CDC42	CDC42	8049	0.033	0.42	NO
190	RALGDS	RALGDS	RALGDS	8074	0.032	0.42	NO
191	FGF3	FGF3	FGF3	8135	0.031	0.42	NO
192	CASP8	CASP8	CASP8	8187	0.031	0.41	NO
193	PTK2	PTK2	PTK2	8241	0.03	0.41	NO
194	IKBKB	IKBKB	IKBKB	8295	0.029	0.41	NO
195	MAPK1	MAPK1	MAPK1	8307	0.028	0.41	NO
196	WNT8B	WNT8B	WNT8B	8333	0.028	0.41	NO
197	PPARD	PPARD	PPARD	8389	0.027	0.41	NO
198	PRKCA	PRKCA	PRKCA	8422	0.027	0.4	NO
199	RELA	RELA	RELA	8473	0.026	0.4	NO
200	MET	MET	MET	8477	0.026	0.4	NO
201	WNT2B	WNT2B	WNT2B	8494	0.026	0.4	NO
202	CRKL	CRKL	CRKL	8516	0.025	0.4	NO
203	DVL2	DVL2	DVL2	8518	0.025	0.4	NO
204	CDKN2A	CDKN2A	CDKN2A	8555	0.025	0.4	NO
205	MDM2	MDM2	MDM2	8579	0.024	0.4	NO
206	MSH6	MSH6	MSH6	8588	0.024	0.4	NO
207	WNT3A	WNT3A	WNT3A	8628	0.024	0.4	NO
208	HSP90AB1	HSP90AB1	HSP90AB1	8678	0.023	0.4	NO
209	MSH3	MSH3	MSH3	8724	0.022	0.39	NO
210	GSK3B	GSK3B	GSK3B	8734	0.022	0.39	NO
211	NCOA4	NCOA4	NCOA4	8801	0.021	0.39	NO
212	DVL3	DVL3	DVL3	8880	0.02	0.39	NO
213	FGF20	FGF20	FGF20	8885	0.02	0.39	NO
214	BCL2L1	BCL2L1	BCL2L1	8908	0.02	0.39	NO
215	RHOA	RHOA	RHOA	8942	0.019	0.38	NO
216	DAPK3	DAPK3	DAPK3	9007	0.018	0.38	NO
217	NRAS	NRAS	NRAS	9110	0.017	0.38	NO
218	CCNE2	CCNE2	CCNE2	9201	0.016	0.37	NO
219	RAC3	RAC3	RAC3	9336	0.014	0.36	NO
220	TRAF2	TRAF2	TRAF2	9371	0.013	0.36	NO
221	TRAF5	TRAF5	TRAF5	9564	0.01	0.35	NO
222	RALA	RALA	RALA	9568	0.01	0.35	NO
223	CCDC6	CCDC6	CCDC6	9737	0.0079	0.34	NO
224	CUL2	CUL2	CUL2	9776	0.0073	0.34	NO
225	AKT1	AKT1	AKT1	9910	0.0055	0.33	NO
226	RXRG	RXRG	RXRG	9914	0.0055	0.33	NO
227	EGLN1	EGLN1	EGLN1	9949	0.0049	0.33	NO
228	RXRB	RXRB	RXRB	9960	0.0048	0.33	NO
229	MSH2	MSH2	MSH2	9993	0.0043	0.33	NO
230	CDK2	CDK2	CDK2	10035	0.0038	0.33	NO
231	JUN	JUN	JUN	10056	0.0034	0.32	NO
232	TPM3	TPM3	TPM3	10125	0.0022	0.32	NO
233	HDAC2	HDAC2	HDAC2	10157	0.0016	0.32	NO
234	MLH1	MLH1	MLH1	10217	0.00095	0.32	NO
235	EGLN2	EGLN2	EGLN2	10314	-0.00031	0.31	NO
236	ITGA3	ITGA3	ITGA3	10321	-0.00038	0.31	NO
237	RXRA	RXRA	RXRA	10354	-0.00075	0.31	NO
238	RAF1	RAF1	RAF1	10396	-0.0013	0.31	NO
239	EGLN3	EGLN3	EGLN3	10497	-0.0026	0.3	NO
240	WNT11	WNT11	WNT11	10553	-0.0035	0.3	NO
241	SLC2A1	SLC2A1	SLC2A1	10618	-0.0045	0.29	NO
242	CASP3	CASP3	CASP3	10631	-0.0047	0.29	NO
243	CASP9	CASP9	CASP9	10676	-0.0054	0.29	NO
244	LAMC3	LAMC3	LAMC3	10728	-0.0061	0.29	NO
245	BCR	BCR	BCR	10783	-0.0071	0.29	NO
246	CTNNB1	CTNNB1	CTNNB1	10807	-0.0076	0.28	NO
247	CTNNA1	CTNNA1	CTNNA1	10828	-0.0078	0.28	NO
248	TCF7L2	TCF7L2	TCF7L2	10873	-0.0085	0.28	NO
249	TCEB1	TCEB1	TCEB1	10916	-0.0092	0.28	NO
250	VHL	VHL	VHL	11028	-0.011	0.27	NO
251	VEGFA	VEGFA	VEGFA	11067	-0.011	0.27	NO
252	MAPK9	MAPK9	MAPK9	11110	-0.012	0.27	NO
253	STK36	STK36	STK36	11133	-0.012	0.27	NO
254	ERBB2	ERBB2	ERBB2	11363	-0.016	0.26	NO
255	RAC1	RAC1	RAC1	11370	-0.016	0.26	NO
256	AKT2	AKT2	AKT2	11376	-0.016	0.26	NO
257	FGF8	FGF8	FGF8	11399	-0.016	0.26	NO
258	RASSF1	RASSF1	RASSF1	11417	-0.017	0.25	NO
259	CDH1	CDH1	CDH1	11465	-0.018	0.25	NO
260	ITGA6	ITGA6	ITGA6	11569	-0.019	0.25	NO
261	CTBP1	CTBP1	CTBP1	11915	-0.025	0.23	NO
262	CTBP2	CTBP2	CTBP2	11969	-0.026	0.22	NO
263	PIAS4	PIAS4	PIAS4	12148	-0.029	0.22	NO
264	HDAC1	HDAC1	HDAC1	12158	-0.029	0.22	NO
265	IKBKG	IKBKG	IKBKG	12182	-0.029	0.22	NO
266	JUP	JUP	JUP	12289	-0.031	0.21	NO
267	AXIN1	AXIN1	AXIN1	12493	-0.035	0.2	NO
268	FZD3	FZD3	FZD3	12638	-0.038	0.19	NO
269	CYCS	CYCS	CYCS	12715	-0.039	0.19	NO
270	TCF7	TCF7	TCF7	12719	-0.039	0.19	NO
271	BAX	BAX	BAX	12742	-0.039	0.19	NO
272	RBX1	RBX1	RBX1	12842	-0.041	0.18	NO
273	FADD	FADD	FADD	12903	-0.042	0.18	NO
274	CDKN1A	CDKN1A	CDKN1A	12925	-0.042	0.18	NO
275	PIK3R2	PIK3R2	PIK3R2	12957	-0.043	0.18	NO
276	TFG	TFG	TFG	13050	-0.045	0.18	NO
277	TP53	TP53	TP53	13277	-0.049	0.16	NO
278	MECOM	MECOM	MECOM	13283	-0.049	0.16	NO
279	MYC	MYC	MYC	13291	-0.049	0.17	NO
280	DVL1	DVL1	DVL1	13304	-0.049	0.17	NO
281	ARAF	ARAF	ARAF	13329	-0.05	0.17	NO
282	BMP2	BMP2	BMP2	13403	-0.051	0.16	NO
283	APC2	APC2	APC2	13451	-0.052	0.16	NO
284	CDK4	CDK4	CDK4	13782	-0.058	0.14	NO
285	WNT3	WNT3	WNT3	13865	-0.06	0.14	NO
286	FZD5	FZD5	FZD5	13868	-0.06	0.14	NO
287	WNT5B	WNT5B	WNT5B	13932	-0.061	0.14	NO
288	SKP2	SKP2	SKP2	14131	-0.066	0.13	NO
289	MAPK3	MAPK3	MAPK3	14185	-0.067	0.13	NO
290	PAX8	PAX8	PAX8	14331	-0.071	0.12	NO
291	MAP2K2	MAP2K2	MAP2K2	14366	-0.071	0.12	NO
292	BIRC5	BIRC5	BIRC5	14431	-0.073	0.12	NO
293	BAD	BAD	BAD	14457	-0.074	0.12	NO
294	FH	FH	FH	14728	-0.081	0.1	NO
295	RAD51	RAD51	RAD51	14763	-0.082	0.1	NO
296	ITGA2B	ITGA2B	ITGA2B	14978	-0.088	0.095	NO
297	GSTP1	GSTP1	GSTP1	15024	-0.09	0.094	NO
298	TCEB2	TCEB2	TCEB2	15230	-0.095	0.085	NO
299	E2F1	E2F1	E2F1	15383	-0.1	0.078	NO
300	FZD9	FZD9	FZD9	15480	-0.1	0.075	NO
301	FGF17	FGF17	FGF17	15492	-0.1	0.077	NO
302	TRAF4	TRAF4	TRAF4	15749	-0.12	0.065	NO
303	EGF	EGF	EGF	15755	-0.12	0.067	NO
304	CKS1B	CKS1B	CKS1B	15876	-0.12	0.062	NO
305	BID	BID	BID	15877	-0.12	0.065	NO
306	E2F2	E2F2	E2F2	16017	-0.13	0.06	NO
307	CEBPA	CEBPA	CEBPA	16246	-0.14	0.05	NO
308	PPARG	PPARG	PPARG	16260	-0.14	0.052	NO
309	CBLC	CBLC	CBLC	16280	-0.14	0.054	NO
310	CCNE1	CCNE1	CCNE1	16348	-0.14	0.053	NO
311	KLK3	KLK3	KLK3	16354	-0.14	0.056	NO
312	DAPK2	DAPK2	DAPK2	16470	-0.15	0.053	NO
313	AXIN2	AXIN2	AXIN2	16547	-0.16	0.052	NO
314	NOS2	NOS2	NOS2	17070	-0.22	0.027	NO
315	FGFR3	FGFR3	FGFR3	17282	-0.25	0.021	NO
316	SHH	SHH	SHH	17486	-0.29	0.015	NO
317	WNT4	WNT4	WNT4	17575	-0.32	0.017	NO
318	COL4A6	COL4A6	COL4A6	17757	-0.38	0.015	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 BCR PATHWAY.

Figure S50. 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 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	SNAI2	SNAI2	SNAI2	977	0.45	0.0063	YES
2	WAS	WAS	WAS	1031	0.44	0.063	YES
3	FGFR1	FGFR1	FGFR1	1309	0.4	0.1	YES
4	PTPRM	PTPRM	PTPRM	1682	0.35	0.13	YES
5	WASF1	WASF1	WASF1	1955	0.32	0.16	YES
6	FYN	FYN	FYN	2017	0.31	0.2	YES
7	WASF3	WASF3	WASF3	2122	0.3	0.23	YES
8	SORBS1	SORBS1	SORBS1	2157	0.3	0.27	YES
9	ACTN2	ACTN2	ACTN2	2195	0.29	0.3	YES
10	CTNNA3	CTNNA3	CTNNA3	2487	0.26	0.32	YES
11	ACTN3	ACTN3	ACTN3	2525	0.26	0.36	YES
12	TCF7L1	TCF7L1	TCF7L1	2547	0.26	0.39	YES
13	LEF1	LEF1	LEF1	2751	0.24	0.41	YES
14	SNAI1	SNAI1	SNAI1	2854	0.23	0.44	YES
15	FER	FER	FER	3182	0.2	0.44	YES
16	TGFBR1	TGFBR1	TGFBR1	3837	0.15	0.43	YES
17	VCL	VCL	VCL	3930	0.14	0.44	YES
18	ACTN1	ACTN1	ACTN1	4419	0.12	0.43	YES
19	EGFR	EGFR	EGFR	4563	0.12	0.44	YES
20	TGFBR2	TGFBR2	TGFBR2	4820	0.1	0.44	YES
21	EP300	EP300	EP300	5018	0.098	0.44	YES
22	RAC2	RAC2	RAC2	5080	0.096	0.45	YES
23	PTPRJ	PTPRJ	PTPRJ	5122	0.094	0.46	YES
24	IGF1R	IGF1R	IGF1R	5158	0.094	0.47	YES
25	TJP1	TJP1	TJP1	5536	0.083	0.46	NO
26	CREBBP	CREBBP	CREBBP	5799	0.076	0.46	NO
27	BAIAP2	BAIAP2	BAIAP2	5815	0.076	0.47	NO
28	SMAD2	SMAD2	SMAD2	5995	0.072	0.47	NO
29	IQGAP1	IQGAP1	IQGAP1	6258	0.066	0.46	NO
30	WASF2	WASF2	WASF2	6372	0.063	0.46	NO
31	LMO7	LMO7	LMO7	6479	0.06	0.47	NO
32	PTPRB	PTPRB	PTPRB	6589	0.058	0.47	NO
33	MAP3K7	MAP3K7	MAP3K7	6768	0.054	0.46	NO
34	SMAD3	SMAD3	SMAD3	6877	0.052	0.47	NO
35	SMAD4	SMAD4	SMAD4	7241	0.046	0.45	NO
36	INSR	INSR	INSR	7253	0.045	0.46	NO
37	CTNNA2	CTNNA2	CTNNA2	7444	0.042	0.45	NO
38	PTPN6	PTPN6	PTPN6	7908	0.035	0.43	NO
39	CDC42	CDC42	CDC42	8049	0.033	0.43	NO
40	YES1	YES1	YES1	8061	0.032	0.43	NO
41	CTNND1	CTNND1	CTNND1	8174	0.031	0.43	NO
42	MAPK1	MAPK1	MAPK1	8307	0.028	0.43	NO
43	SSX2IP	SSX2IP	SSX2IP	8357	0.028	0.43	NO
44	PARD3	PARD3	PARD3	8358	0.028	0.43	NO
45	MLLT4	MLLT4	MLLT4	8436	0.026	0.43	NO
46	MET	MET	MET	8477	0.026	0.43	NO
47	WASL	WASL	WASL	8491	0.026	0.44	NO
48	RHOA	RHOA	RHOA	8942	0.019	0.41	NO
49	CSNK2A1	CSNK2A1	CSNK2A1	8981	0.019	0.41	NO
50	PTPN1	PTPN1	PTPN1	9095	0.017	0.41	NO
51	ACTN4	ACTN4	ACTN4	9299	0.014	0.4	NO
52	RAC3	RAC3	RAC3	9336	0.014	0.4	NO
53	PVRL2	PVRL2	PVRL2	9797	0.007	0.38	NO
54	ACTB	ACTB	ACTB	10010	0.004	0.36	NO
55	PTPRF	PTPRF	PTPRF	10617	-0.0045	0.33	NO
56	CTNNB1	CTNNB1	CTNNB1	10807	-0.0076	0.32	NO
57	CTNNA1	CTNNA1	CTNNA1	10828	-0.0078	0.32	NO
58	TCF7L2	TCF7L2	TCF7L2	10873	-0.0085	0.32	NO
59	NLK	NLK	NLK	11009	-0.01	0.31	NO
60	ERBB2	ERBB2	ERBB2	11363	-0.016	0.3	NO
61	RAC1	RAC1	RAC1	11370	-0.016	0.3	NO
62	CDH1	CDH1	CDH1	11465	-0.018	0.3	NO
63	PVRL1	PVRL1	PVRL1	11995	-0.026	0.27	NO
64	ACTG1	ACTG1	ACTG1	12176	-0.029	0.26	NO
65	SRC	SRC	SRC	12512	-0.035	0.25	NO
66	ACP1	ACP1	ACP1	12524	-0.035	0.25	NO
67	FARP2	FARP2	FARP2	12567	-0.036	0.26	NO
68	TCF7	TCF7	TCF7	12719	-0.039	0.25	NO
69	CSNK2A2	CSNK2A2	CSNK2A2	13806	-0.058	0.2	NO
70	CSNK2B	CSNK2B	CSNK2B	13828	-0.059	0.21	NO
71	PVRL4	PVRL4	PVRL4	14065	-0.064	0.2	NO
72	MAPK3	MAPK3	MAPK3	14185	-0.067	0.2	NO
73	PVRL3	PVRL3	PVRL3	14238	-0.068	0.21	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 BIOPEPTIDES PATHWAY.

Figure S52. 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 CARM ER 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	NEFH	NEFH	NEFH	42	0.77	0.1	YES
2	NEFM	NEFM	NEFM	143	0.68	0.19	YES
3	PRPH2	PRPH2	PRPH2	496	0.55	0.24	YES
4	GRIN2A	GRIN2A	GRIN2A	620	0.52	0.3	YES
5	NOS1	NOS1	NOS1	1128	0.42	0.33	YES
6	MAPK11	MAPK11	MAPK11	1259	0.4	0.38	YES
7	NEFL	NEFL	NEFL	1485	0.37	0.42	YES
8	PRPH	PRPH	PRPH	1489	0.37	0.47	YES
9	GRIA2	GRIA2	GRIA2	2317	0.28	0.46	YES
10	SLC1A2	SLC1A2	SLC1A2	2541	0.26	0.48	YES
11	TNF	TNF	TNF	2594	0.25	0.51	YES
12	BCL2	BCL2	BCL2	2812	0.23	0.53	YES
13	MAPK12	MAPK12	MAPK12	2935	0.22	0.55	YES
14	GRIA1	GRIA1	GRIA1	2973	0.21	0.58	YES
15	PPP3CC	PPP3CC	PPP3CC	4260	0.13	0.52	NO
16	MAP3K5	MAP3K5	MAP3K5	5547	0.082	0.46	NO
17	TNFRSF1B	TNFRSF1B	TNFRSF1B	5679	0.079	0.47	NO
18	PPP3CA	PPP3CA	PPP3CA	6037	0.07	0.46	NO
19	PPP3CB	PPP3CB	PPP3CB	6483	0.06	0.44	NO
20	RAB5A	RAB5A	RAB5A	6804	0.054	0.43	NO
21	DAXX	DAXX	DAXX	8478	0.026	0.34	NO
22	BCL2L1	BCL2L1	BCL2L1	8908	0.02	0.32	NO
23	PPP3R1	PPP3R1	PPP3R1	9537	0.011	0.28	NO
24	GRIN2C	GRIN2C	GRIN2C	9657	0.0091	0.28	NO
25	DERL1	DERL1	DERL1	9906	0.0056	0.27	NO
26	CCS	CCS	CCS	9969	0.0046	0.26	NO
27	GRIN1	GRIN1	GRIN1	10207	0.0011	0.25	NO
28	TNFRSF1A	TNFRSF1A	TNFRSF1A	10457	-0.0022	0.24	NO
29	MAP2K3	MAP2K3	MAP2K3	10569	-0.0038	0.23	NO
30	CASP3	CASP3	CASP3	10631	-0.0047	0.23	NO
31	CASP9	CASP9	CASP9	10676	-0.0054	0.23	NO
32	MAPK14	MAPK14	MAPK14	10727	-0.0061	0.22	NO
33	APAF1	APAF1	APAF1	10888	-0.0087	0.22	NO
34	RAC1	RAC1	RAC1	11370	-0.016	0.19	NO
35	TOMM40L	TOMM40L	TOMM40L	11419	-0.017	0.19	NO
36	SOD1	SOD1	SOD1	12154	-0.029	0.16	NO
37	CYCS	CYCS	CYCS	12715	-0.039	0.13	NO
38	BAX	BAX	BAX	12742	-0.039	0.13	NO
39	TOMM40	TOMM40	TOMM40	12805	-0.04	0.13	NO
40	CHP	CHP	CHP	13191	-0.047	0.12	NO
41	GRIN2D	GRIN2D	GRIN2D	13244	-0.048	0.12	NO
42	TP53	TP53	TP53	13277	-0.049	0.13	NO
43	CAT	CAT	CAT	13476	-0.052	0.12	NO
44	GPX1	GPX1	GPX1	13540	-0.054	0.13	NO
45	GRIN2B	GRIN2B	GRIN2B	13812	-0.058	0.12	NO
46	BAD	BAD	BAD	14457	-0.074	0.094	NO
47	MAPK13	MAPK13	MAPK13	15080	-0.091	0.072	NO
48	CASP1	CASP1	CASP1	15299	-0.098	0.073	NO
49	BID	BID	BID	15877	-0.12	0.057	NO
50	MAP2K6	MAP2K6	MAP2K6	16394	-0.15	0.048	NO
51	CHP2	CHP2	CHP2	17586	-0.32	0.024	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 CARM ER PATHWAY.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CARM ER 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 G1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	LY96	LY96	LY96	263	0.62	0.18	YES
2	GJA1	GJA1	GJA1	2051	0.31	0.18	YES
3	CD14	CD14	CD14	2285	0.28	0.26	YES
4	LEF1	LEF1	LEF1	2751	0.24	0.31	YES
5	FZD1	FZD1	FZD1	2828	0.23	0.38	YES
6	APC	APC	APC	3304	0.19	0.41	YES
7	TLR4	TLR4	TLR4	3398	0.18	0.46	YES
8	GNAI1	GNAI1	GNAI1	3436	0.18	0.51	YES
9	PIK3CA	PIK3CA	PIK3CA	3454	0.17	0.57	YES
10	EIF2AK2	EIF2AK2	EIF2AK2	3835	0.15	0.59	YES
11	WNT1	WNT1	WNT1	4134	0.13	0.62	YES
12	PIK3R1	PIK3R1	PIK3R1	5657	0.08	0.56	NO
13	CCND1	CCND1	CCND1	5699	0.079	0.58	NO
14	LBP	LBP	LBP	7198	0.046	0.51	NO
15	NFKB1	NFKB1	NFKB1	7760	0.037	0.5	NO
16	RELA	RELA	RELA	8473	0.026	0.46	NO
17	GSK3B	GSK3B	GSK3B	8734	0.022	0.46	NO
18	PDPK1	PDPK1	PDPK1	8842	0.021	0.46	NO
19	TIRAP	TIRAP	TIRAP	8985	0.018	0.46	NO
20	MYD88	MYD88	MYD88	9027	0.018	0.46	NO
21	AKT1	AKT1	AKT1	9910	0.0055	0.41	NO
22	CTNNB1	CTNNB1	CTNNB1	10807	-0.0076	0.36	NO
23	IRAK1	IRAK1	IRAK1	11248	-0.014	0.34	NO
24	PPP2CA	PPP2CA	PPP2CA	11642	-0.02	0.33	NO
25	AXIN1	AXIN1	AXIN1	12493	-0.035	0.29	NO
26	DVL1	DVL1	DVL1	13304	-0.049	0.26	NO

Figure S55. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA G1 PATHWAY.

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

genes ES table in pathway: BIOCARTA HDAC PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AKT3	AKT3	AKT3	502	0.54	0.056	YES
2	PIK3R5	PIK3R5	PIK3R5	582	0.53	0.13	YES
3	TGFB2	TGFB2	TGFB2	667	0.51	0.21	YES
4	PIK3CG	PIK3CG	PIK3CG	732	0.49	0.28	YES
5	PIK3CD	PIK3CD	PIK3CD	1205	0.41	0.32	YES
6	MAPK10	MAPK10	MAPK10	1766	0.34	0.34	YES
7	TCF7L1	TCF7L1	TCF7L1	2547	0.26	0.33	YES
8	TGFB1	TGFB1	TGFB1	2706	0.24	0.36	YES
9	LEF1	LEF1	LEF1	2751	0.24	0.4	YES
10	BCL2	BCL2	BCL2	2812	0.23	0.43	YES
11	DCC	DCC	DCC	3188	0.2	0.44	YES
12	APC	APC	APC	3304	0.19	0.46	YES
13	PIK3CA	PIK3CA	PIK3CA	3454	0.17	0.48	YES
14	TGFBR1	TGFBR1	TGFBR1	3837	0.15	0.48	YES
15	TGFBR2	TGFBR2	TGFBR2	4820	0.1	0.44	NO
16	RAC2	RAC2	RAC2	5080	0.096	0.44	NO
17	PIK3R3	PIK3R3	PIK3R3	5358	0.088	0.44	NO
18	APPL1	APPL1	APPL1	5535	0.083	0.44	NO
19	PIK3R1	PIK3R1	PIK3R1	5657	0.08	0.45	NO
20	CCND1	CCND1	CCND1	5699	0.079	0.46	NO
21	SMAD2	SMAD2	SMAD2	5995	0.072	0.45	NO
22	BRAF	BRAF	BRAF	6094	0.069	0.46	NO
23	KRAS	KRAS	KRAS	6619	0.057	0.44	NO
24	SMAD3	SMAD3	SMAD3	6877	0.052	0.43	NO
25	MAP2K1	MAP2K1	MAP2K1	7174	0.047	0.42	NO
26	SMAD4	SMAD4	SMAD4	7241	0.046	0.42	NO
27	PIK3CB	PIK3CB	PIK3CB	7407	0.043	0.42	NO
28	FOS	FOS	FOS	7506	0.041	0.42	NO
29	MAPK8	MAPK8	MAPK8	7904	0.035	0.41	NO
30	RALGDS	RALGDS	RALGDS	8074	0.032	0.4	NO
31	MAPK1	MAPK1	MAPK1	8307	0.028	0.39	NO
32	MSH6	MSH6	MSH6	8588	0.024	0.38	NO
33	MSH3	MSH3	MSH3	8724	0.022	0.38	NO
34	GSK3B	GSK3B	GSK3B	8734	0.022	0.38	NO
35	RHOA	RHOA	RHOA	8942	0.019	0.37	NO
36	RAC3	RAC3	RAC3	9336	0.014	0.35	NO
37	AKT1	AKT1	AKT1	9910	0.0055	0.32	NO
38	MSH2	MSH2	MSH2	9993	0.0043	0.32	NO
39	JUN	JUN	JUN	10056	0.0034	0.31	NO
40	MLH1	MLH1	MLH1	10217	0.00095	0.3	NO
41	RAF1	RAF1	RAF1	10396	-0.0013	0.3	NO
42	CASP3	CASP3	CASP3	10631	-0.0047	0.28	NO
43	CASP9	CASP9	CASP9	10676	-0.0054	0.28	NO
44	CTNNB1	CTNNB1	CTNNB1	10807	-0.0076	0.28	NO
45	TCF7L2	TCF7L2	TCF7L2	10873	-0.0085	0.27	NO
46	MAPK9	MAPK9	MAPK9	11110	-0.012	0.26	NO
47	RAC1	RAC1	RAC1	11370	-0.016	0.25	NO
48	AKT2	AKT2	AKT2	11376	-0.016	0.25	NO
49	AXIN1	AXIN1	AXIN1	12493	-0.035	0.2	NO
50	CYCS	CYCS	CYCS	12715	-0.039	0.19	NO
51	TCF7	TCF7	TCF7	12719	-0.039	0.19	NO
52	BAX	BAX	BAX	12742	-0.039	0.2	NO
53	PIK3R2	PIK3R2	PIK3R2	12957	-0.043	0.19	NO
54	TP53	TP53	TP53	13277	-0.049	0.18	NO
55	MYC	MYC	MYC	13291	-0.049	0.19	NO
56	ARAF	ARAF	ARAF	13329	-0.05	0.2	NO
57	APC2	APC2	APC2	13451	-0.052	0.2	NO
58	MAPK3	MAPK3	MAPK3	14185	-0.067	0.17	NO
59	BIRC5	BIRC5	BIRC5	14431	-0.073	0.16	NO
60	BAD	BAD	BAD	14457	-0.074	0.17	NO
61	AXIN2	AXIN2	AXIN2	16547	-0.16	0.082	NO

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

Figure S58. 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 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	PGR	PGR	PGR	88	0.72	0.062	YES
2	IGF1	IGF1	IGF1	338	0.6	0.1	YES
3	AKT3	AKT3	AKT3	502	0.54	0.14	YES
4	PIK3R5	PIK3R5	PIK3R5	582	0.53	0.19	YES
5	ADCY2	ADCY2	ADCY2	649	0.51	0.23	YES
6	PIK3CG	PIK3CG	PIK3CG	732	0.49	0.27	YES
7	CPEB1	CPEB1	CPEB1	913	0.46	0.3	YES
8	PIK3CD	PIK3CD	PIK3CD	1205	0.41	0.33	YES
9	CCNA1	CCNA1	CCNA1	1223	0.41	0.36	YES
10	MAPK11	MAPK11	MAPK11	1259	0.4	0.4	YES
11	MAPK10	MAPK10	MAPK10	1766	0.34	0.4	YES
12	ADCY5	ADCY5	ADCY5	2036	0.31	0.42	YES
13	ADCY1	ADCY1	ADCY1	2613	0.25	0.41	YES
14	PDE3A	PDE3A	PDE3A	2635	0.25	0.43	YES
15	ADCY4	ADCY4	ADCY4	2826	0.23	0.44	YES
16	MAPK12	MAPK12	MAPK12	2935	0.22	0.45	YES
17	RPS6KA2	RPS6KA2	RPS6KA2	3104	0.2	0.46	YES
18	ADCY7	ADCY7	ADCY7	3422	0.18	0.46	YES
19	GNAI1	GNAI1	GNAI1	3436	0.18	0.48	YES
20	PIK3CA	PIK3CA	PIK3CA	3454	0.17	0.49	YES
21	GNAI2	GNAI2	GNAI2	4114	0.13	0.47	NO
22	ADCY9	ADCY9	ADCY9	4572	0.11	0.45	NO
23	CCNB3	CCNB3	CCNB3	4946	0.1	0.44	NO
24	IGF1R	IGF1R	IGF1R	5158	0.094	0.44	NO
25	PIK3R3	PIK3R3	PIK3R3	5358	0.088	0.44	NO
26	CDC27	CDC27	CDC27	5643	0.08	0.43	NO
27	PIK3R1	PIK3R1	PIK3R1	5657	0.08	0.43	NO
28	BRAF	BRAF	BRAF	6094	0.069	0.42	NO
29	KRAS	KRAS	KRAS	6619	0.057	0.39	NO
30	HSP90AA1	HSP90AA1	HSP90AA1	6689	0.056	0.39	NO
31	PRKACA	PRKACA	PRKACA	7042	0.049	0.38	NO
32	MAP2K1	MAP2K1	MAP2K1	7174	0.047	0.38	NO
33	PIK3CB	PIK3CB	PIK3CB	7407	0.043	0.37	NO
34	PRKX	PRKX	PRKX	7587	0.04	0.36	NO
35	PDE3B	PDE3B	PDE3B	7766	0.037	0.35	NO
36	MAPK8	MAPK8	MAPK8	7904	0.035	0.35	NO
37	PRKACB	PRKACB	PRKACB	7948	0.034	0.35	NO
38	MAPK1	MAPK1	MAPK1	8307	0.028	0.33	NO
39	ANAPC13	ANAPC13	ANAPC13	9031	0.018	0.29	NO
40	GNAI3	GNAI3	GNAI3	9394	0.012	0.27	NO
41	ANAPC10	ANAPC10	ANAPC10	9596	0.0097	0.26	NO
42	AKT1	AKT1	AKT1	9910	0.0055	0.25	NO
43	CDK2	CDK2	CDK2	10035	0.0038	0.24	NO
44	ADCY3	ADCY3	ADCY3	10145	0.0019	0.24	NO
45	RAF1	RAF1	RAF1	10396	-0.0013	0.22	NO
46	ANAPC4	ANAPC4	ANAPC4	10579	-0.0039	0.21	NO
47	MAPK14	MAPK14	MAPK14	10727	-0.0061	0.2	NO
48	RPS6KA3	RPS6KA3	RPS6KA3	10804	-0.0074	0.2	NO
49	CDC23	CDC23	CDC23	11042	-0.011	0.19	NO
50	BUB1	BUB1	BUB1	11084	-0.012	0.19	NO
51	CDC25B	CDC25B	CDC25B	11085	-0.012	0.19	NO
52	MAPK9	MAPK9	MAPK9	11110	-0.012	0.19	NO
53	AKT2	AKT2	AKT2	11376	-0.016	0.17	NO
54	MAD2L2	MAD2L2	MAD2L2	11622	-0.02	0.16	NO
55	ANAPC2	ANAPC2	ANAPC2	11950	-0.026	0.15	NO
56	ADCY6	ADCY6	ADCY6	12025	-0.027	0.14	NO
57	FZR1	FZR1	FZR1	12075	-0.028	0.14	NO
58	CDK1	CDK1	CDK1	12191	-0.029	0.14	NO
59	CDC16	CDC16	CDC16	12392	-0.033	0.13	NO
60	PIK3R2	PIK3R2	PIK3R2	12957	-0.043	0.1	NO
61	ANAPC7	ANAPC7	ANAPC7	12989	-0.044	0.11	NO
62	ARAF	ARAF	ARAF	13329	-0.05	0.093	NO
63	ANAPC5	ANAPC5	ANAPC5	13526	-0.054	0.087	NO
64	ANAPC1	ANAPC1	ANAPC1	13797	-0.058	0.078	NO
65	MAD2L1	MAD2L1	MAD2L1	14064	-0.064	0.069	NO
66	MAPK3	MAPK3	MAPK3	14185	-0.067	0.068	NO
67	RPS6KA1	RPS6KA1	RPS6KA1	14680	-0.08	0.048	NO
68	CCNA2	CCNA2	CCNA2	14743	-0.082	0.052	NO
69	CDC25A	CDC25A	CDC25A	15028	-0.09	0.045	NO
70	MAPK13	MAPK13	MAPK13	15080	-0.091	0.05	NO
71	CCNB2	CCNB2	CCNB2	15081	-0.091	0.059	NO
72	CCNB1	CCNB1	CCNB1	15138	-0.092	0.064	NO
73	SPDYC	SPDYC	SPDYC	15228	-0.095	0.068	NO
74	PLK1	PLK1	PLK1	15385	-0.1	0.068	NO
75	CDC25C	CDC25C	CDC25C	15895	-0.12	0.051	NO
76	PKMYT1	PKMYT1	PKMYT1	15987	-0.12	0.058	NO
77	RPS6KA6	RPS6KA6	RPS6KA6	16141	-0.13	0.062	NO
78	SPDYA	SPDYA	SPDYA	16379	-0.15	0.062	NO
79	ANAPC11	ANAPC11	ANAPC11	16403	-0.15	0.074	NO
80	CDC26	CDC26	CDC26	16675	-0.17	0.075	NO

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

Figure S60. 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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus4 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA FMLP PATHWAY	34	genes.ES.table	0.49	1.6	0.052	1	0.73	0.088	0.063	0.083	0.63	0.34
KEGG GLYCOLYSIS GLUCONEOGENESIS	57	genes.ES.table	0.44	1.4	0.085	1	0.95	0.35	0.27	0.26	1	0.5
KEGG PENTOSE PHOSPHATE PATHWAY	26	genes.ES.table	0.52	1.6	0.047	0.87	0.8	0.65	0.34	0.43	0.52	0.29
KEGG FRUCTOSE AND MANNOSE METABOLISM	33	genes.ES.table	0.41	1.3	0.14	1	0.97	0.64	0.33	0.43	0.87	0.43
KEGG OXIDATIVE PHOSPHORYLATION	111	genes.ES.table	0.35	1.3	0.22	1	0.96	0.35	0.24	0.27	0.87	0.44
KEGG PYRIMIDINE METABOLISM	96	genes.ES.table	0.28	1.2	0.2	0.95	0.99	0.42	0.33	0.28	0.81	0.38
KEGG ARGININE AND PROLINE METABOLISM	52	genes.ES.table	0.41	1.4	0.096	1	0.96	0.36	0.21	0.29	0.88	0.43
KEGG GLUTATHIONE METABOLISM	45	genes.ES.table	0.43	1.4	0.11	1	0.96	0.58	0.32	0.4	0.96	0.48
KEGG STARCH AND SUCROSE METABOLISM	42	genes.ES.table	0.5	1.3	0.17	1	0.99	0.21	0.13	0.19	0.89	0.43
KEGG ARACHIDONIC ACID METABOLISM	51	genes.ES.table	0.55	1.4	0.041	1	0.92	0.65	0.32	0.44	1	0.52

genes ES table in pathway: BIOCARTA FMLP PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TUBB4Q	TUBB4Q	TUBB4Q	18	1.5	0.18	YES
2	TUBB8	TUBB8	TUBB8	48	1.3	0.32	YES
3	TUBA1A	TUBA1A	TUBA1A	483	0.49	0.36	YES
4	TUBA3D	TUBA3D	TUBA3D	497	0.48	0.41	YES
5	TUBB2A	TUBB2A	TUBB2A	524	0.46	0.46	YES
6	TUBB3	TUBB3	TUBB3	767	0.34	0.49	YES
7	TUBAL3	TUBAL3	TUBAL3	1489	0.21	0.48	YES
8	TUBA3E	TUBA3E	TUBA3E	1563	0.2	0.5	YES
9	TUBA1C	TUBA1C	TUBA1C	2221	0.16	0.48	NO
10	TUBB2B	TUBB2B	TUBB2B	2382	0.15	0.48	NO
11	TUBA8	TUBA8	TUBA8	2737	0.13	0.48	NO
12	CD14	CD14	CD14	2805	0.13	0.49	NO
13	TUBA3C	TUBA3C	TUBA3C	3030	0.12	0.49	NO
14	TUBB6	TUBB6	TUBB6	3659	0.1	0.47	NO
15	TUBB2C	TUBB2C	TUBB2C	3718	0.099	0.48	NO
16	TUBB4	TUBB4	TUBB4	3889	0.094	0.48	NO
17	TUBA4A	TUBA4A	TUBA4A	4195	0.086	0.47	NO
18	ARPC5L	ARPC5L	ARPC5L	5000	0.066	0.44	NO
19	WAS	WAS	WAS	5235	0.061	0.43	NO
20	OCLN	OCLN	OCLN	5318	0.059	0.43	NO
21	TUBA1B	TUBA1B	TUBA1B	5662	0.052	0.42	NO
22	ACTB	ACTB	ACTB	5695	0.052	0.42	NO
23	ACTG1	ACTG1	ACTG1	5876	0.048	0.42	NO
24	ARPC1B	ARPC1B	ARPC1B	6206	0.042	0.41	NO
25	ARPC1A	ARPC1A	ARPC1A	6807	0.032	0.38	NO
26	NCK2	NCK2	NCK2	7265	0.024	0.35	NO
27	TUBB	TUBB	TUBB	7313	0.023	0.35	NO
28	KRT18	KRT18	KRT18	7551	0.019	0.34	NO
29	CTNNB1	CTNNB1	CTNNB1	7559	0.019	0.34	NO
30	YWHAQ	YWHAQ	YWHAQ	7699	0.016	0.34	NO
31	CTTN	CTTN	CTTN	7764	0.015	0.34	NO
32	ARPC2	ARPC2	ARPC2	8100	0.01	0.32	NO
33	ARPC4	ARPC4	ARPC4	8293	0.0071	0.31	NO
34	RHOA	RHOA	RHOA	9472	-0.01	0.24	NO
35	EZR	EZR	EZR	10581	-0.027	0.19	NO
36	ARPC5	ARPC5	ARPC5	10946	-0.033	0.17	NO
37	ABL1	ABL1	ABL1	10965	-0.033	0.17	NO
38	HCLS1	HCLS1	HCLS1	11107	-0.036	0.17	NO
39	CDH1	CDH1	CDH1	12175	-0.053	0.12	NO
40	ITGB1	ITGB1	ITGB1	12215	-0.054	0.12	NO
41	CLDN1	CLDN1	CLDN1	12476	-0.058	0.11	NO
42	YWHAZ	YWHAZ	YWHAZ	12608	-0.06	0.11	NO
43	TUBB1	TUBB1	TUBB1	12760	-0.063	0.11	NO
44	ARHGEF2	ARHGEF2	ARHGEF2	13024	-0.068	0.1	NO
45	NCK1	NCK1	NCK1	13779	-0.082	0.072	NO
46	PRKCA	PRKCA	PRKCA	14082	-0.088	0.066	NO
47	CDC42	CDC42	CDC42	14149	-0.09	0.073	NO
48	WASL	WASL	WASL	14229	-0.091	0.079	NO
49	LY96	LY96	LY96	14316	-0.093	0.085	NO
50	FYN	FYN	FYN	14771	-0.1	0.072	NO
51	NCL	NCL	NCL	15016	-0.11	0.071	NO
52	TLR4	TLR4	TLR4	15430	-0.12	0.062	NO
53	ARPC3	ARPC3	ARPC3	16602	-0.16	0.015	NO
54	ROCK1	ROCK1	ROCK1	16850	-0.17	0.021	NO
55	ROCK2	ROCK2	ROCK2	16884	-0.17	0.038	NO
56	TLR5	TLR5	TLR5	17525	-0.21	0.028	NO

Figure S61. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FMLP PATHWAY.

Figure S62. 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

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HIST1H4K	HIST1H4K	HIST1H4K	4	1.7	0.064	YES
2	HIST2H2AC	HIST2H2AC	HIST2H2AC	58	1.2	0.11	YES
3	HIST1H2BO	HIST1H2BO	HIST1H2BO	78	1.1	0.15	YES
4	HIST2H3C	HIST2H3C	HIST2H3C	173	0.85	0.17	YES
5	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	182	0.83	0.2	YES
6	HIST2H3D	HIST2H3D	HIST2H3D	225	0.76	0.23	YES
7	FCGR2C	FCGR2C	FCGR2C	254	0.72	0.26	YES
8	HIST1H2BN	HIST1H2BN	HIST1H2BN	337	0.61	0.27	YES
9	HIST3H2A	HIST3H2A	HIST3H2A	352	0.6	0.29	YES
10	FCGR3B	FCGR3B	FCGR3B	419	0.55	0.31	YES
11	HIST1H4J	HIST1H4J	HIST1H4J	430	0.54	0.33	YES
12	HIST2H2BF	HIST2H2BF	HIST2H2BF	461	0.51	0.35	YES
13	HIST1H2BE	HIST1H2BE	HIST1H2BE	492	0.49	0.36	YES
14	FCGR1A	FCGR1A	FCGR1A	504	0.47	0.38	YES
15	HIST1H2BL	HIST1H2BL	HIST1H2BL	514	0.47	0.4	YES
16	HLA-DQA2	HLA-DQA2	HLA-DQA2	551	0.44	0.41	YES
17	HIST1H4I	HIST1H4I	HIST1H4I	563	0.44	0.43	YES
18	HIST2H4A	HIST2H4A	HIST2H4A	572	0.43	0.44	YES
19	H3F3C	H3F3C	H3F3C	579	0.43	0.46	YES
20	HLA-DRB5	HLA-DRB5	HLA-DRB5	671	0.38	0.47	YES
21	HIST1H4A	HIST1H4A	HIST1H4A	677	0.38	0.48	YES
22	HIST1H4B	HIST1H4B	HIST1H4B	685	0.38	0.5	YES
23	H2AFB1	H2AFB1	H2AFB1	747	0.35	0.5	YES
24	HIST1H4E	HIST1H4E	HIST1H4E	772	0.34	0.52	YES
25	FCGR2B	FCGR2B	FCGR2B	820	0.32	0.52	YES
26	C8G	C8G	C8G	848	0.31	0.54	YES
27	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	874	0.31	0.55	YES
28	HIST1H3H	HIST1H3H	HIST1H3H	876	0.31	0.56	YES
29	HIST1H2AG	HIST1H2AG	HIST1H2AG	954	0.29	0.56	YES
30	HIST1H3D	HIST1H3D	HIST1H3D	1032	0.27	0.57	YES
31	HIST1H4C	HIST1H4C	HIST1H4C	1068	0.26	0.58	YES
32	HIST3H2BB	HIST3H2BB	HIST3H2BB	1069	0.26	0.59	YES
33	HIST1H3B	HIST1H3B	HIST1H3B	1091	0.26	0.6	YES
34	HIST1H4D	HIST1H4D	HIST1H4D	1100	0.26	0.6	YES
35	HIST1H2AL	HIST1H2AL	HIST1H2AL	1175	0.24	0.61	YES
36	HIST1H2AM	HIST1H2AM	HIST1H2AM	1327	0.23	0.61	YES
37	HIST1H3F	HIST1H3F	HIST1H3F	1405	0.22	0.61	YES
38	HIST1H2AK	HIST1H2AK	HIST1H2AK	1407	0.22	0.62	YES
39	HLA-DRB1	HLA-DRB1	HLA-DRB1	1424	0.22	0.63	YES
40	HIST1H2BI	HIST1H2BI	HIST1H2BI	1436	0.22	0.64	YES
41	HLA-DQA1	HLA-DQA1	HLA-DQA1	1515	0.21	0.64	YES
42	HIST1H2AH	HIST1H2AH	HIST1H2AH	1529	0.21	0.65	YES
43	HIST1H2BH	HIST1H2BH	HIST1H2BH	1541	0.21	0.65	YES
44	HIST2H2AB	HIST2H2AB	HIST2H2AB	1585	0.2	0.66	YES
45	HIST1H2BF	HIST1H2BF	HIST1H2BF	1667	0.2	0.66	YES
46	HIST1H2BG	HIST1H2BG	HIST1H2BG	1685	0.19	0.67	YES
47	HLA-DQB1	HLA-DQB1	HLA-DQB1	1687	0.19	0.67	YES
48	HIST1H4H	HIST1H4H	HIST1H4H	1714	0.19	0.68	YES
49	C1QB	C1QB	C1QB	1803	0.18	0.68	YES
50	HIST1H3G	HIST1H3G	HIST1H3G	1837	0.18	0.69	YES
51	C1QC	C1QC	C1QC	1851	0.18	0.69	YES
52	HIST1H3J	HIST1H3J	HIST1H3J	1879	0.18	0.7	YES
53	HIST1H2BC	HIST1H2BC	HIST1H2BC	1887	0.18	0.7	YES
54	HIST1H3A	HIST1H3A	HIST1H3A	1889	0.18	0.71	YES
55	HIST1H2AB	HIST1H2AB	HIST1H2AB	1902	0.18	0.72	YES
56	ELANE	ELANE	ELANE	1932	0.18	0.72	YES
57	HIST1H3I	HIST1H3I	HIST1H3I	1939	0.17	0.73	YES
58	H2AFX	H2AFX	H2AFX	2083	0.16	0.72	YES
59	HIST3H3	HIST3H3	HIST3H3	2111	0.16	0.73	YES
60	HLA-DPB1	HLA-DPB1	HLA-DPB1	2215	0.16	0.73	YES
61	IL10	IL10	IL10	2376	0.15	0.73	NO
62	HLA-DMB	HLA-DMB	HLA-DMB	2546	0.14	0.72	NO
63	TNF	TNF	TNF	2768	0.13	0.72	NO
64	H3F3A	H3F3A	H3F3A	2876	0.12	0.71	NO
65	CD80	CD80	CD80	3312	0.11	0.69	NO
66	HIST1H2BM	HIST1H2BM	HIST1H2BM	3362	0.11	0.69	NO
67	HLA-DPA1	HLA-DPA1	HLA-DPA1	3435	0.11	0.69	NO
68	C4A	C4A	C4A	3517	0.1	0.69	NO
69	HIST1H2BK	HIST1H2BK	HIST1H2BK	3553	0.1	0.7	NO
70	HIST1H3C	HIST1H3C	HIST1H3C	3560	0.1	0.7	NO
71	HIST1H2AE	HIST1H2AE	HIST1H2AE	3573	0.1	0.7	NO
72	C1QA	C1QA	C1QA	3933	0.092	0.69	NO
73	H2AFJ	H2AFJ	H2AFJ	4105	0.088	0.68	NO
74	HLA-DRA	HLA-DRA	HLA-DRA	4419	0.08	0.66	NO
75	SNRPB	SNRPB	SNRPB	4838	0.07	0.64	NO
76	HLA-DMA	HLA-DMA	HLA-DMA	5035	0.065	0.64	NO
77	FCGR2A	FCGR2A	FCGR2A	5202	0.061	0.63	NO
78	HLA-DOA	HLA-DOA	HLA-DOA	5252	0.06	0.63	NO
79	HIST1H2BD	HIST1H2BD	HIST1H2BD	5525	0.055	0.62	NO
80	CD40LG	CD40LG	CD40LG	5546	0.054	0.62	NO
81	CD40	CD40	CD40	5636	0.053	0.61	NO
82	CTSG	CTSG	CTSG	5762	0.051	0.61	NO
83	C2	C2	C2	6202	0.042	0.58	NO
84	CD86	CD86	CD86	6453	0.038	0.57	NO
85	FCGR3A	FCGR3A	FCGR3A	7246	0.024	0.53	NO
86	IFNG	IFNG	IFNG	7739	0.016	0.5	NO
87	HLA-DOB	HLA-DOB	HLA-DOB	7757	0.015	0.5	NO
88	H2AFY	H2AFY	H2AFY	8201	0.0086	0.48	NO
89	H2AFZ	H2AFZ	H2AFZ	8309	0.0068	0.47	NO
90	HIST1H2AC	HIST1H2AC	HIST1H2AC	8964	-0.0032	0.44	NO
91	TRIM21	TRIM21	TRIM21	9016	-0.0038	0.43	NO
92	C1R	C1R	C1R	9449	-0.01	0.41	NO
93	H2AFV	H2AFV	H2AFV	9546	-0.012	0.4	NO
94	C3	C3	C3	9698	-0.014	0.4	NO
95	H2AFY2	H2AFY2	H2AFY2	9812	-0.016	0.39	NO
96	ACTN4	ACTN4	ACTN4	10363	-0.024	0.36	NO
97	CD28	CD28	CD28	10682	-0.029	0.34	NO
98	ACTN1	ACTN1	ACTN1	10805	-0.031	0.34	NO
99	C9	C9	C9	11329	-0.039	0.31	NO
100	SNRPD3	SNRPD3	SNRPD3	11499	-0.042	0.3	NO
101	C1S	C1S	C1S	11593	-0.044	0.3	NO
102	GRIN2B	GRIN2B	GRIN2B	12100	-0.052	0.27	NO
103	ACTN2	ACTN2	ACTN2	12186	-0.053	0.27	NO
104	SNRPD1	SNRPD1	SNRPD1	12505	-0.059	0.25	NO
105	HIST2H2BE	HIST2H2BE	HIST2H2BE	13081	-0.069	0.22	NO
106	HIST1H3E	HIST1H3E	HIST1H3E	13334	-0.074	0.21	NO
107	H3F3B	H3F3B	H3F3B	13444	-0.076	0.21	NO
108	HIST1H2AD	HIST1H2AD	HIST1H2AD	14201	-0.091	0.17	NO
109	C6	C6	C6	14573	-0.098	0.15	NO
110	HIST4H4	HIST4H4	HIST4H4	14722	-0.1	0.15	NO
111	C5	C5	C5	15213	-0.11	0.13	NO
112	GRIN2A	GRIN2A	GRIN2A	15573	-0.12	0.11	NO
113	ACTN3	ACTN3	ACTN3	15893	-0.13	0.098	NO
114	TROVE2	TROVE2	TROVE2	16387	-0.15	0.076	NO
115	C7	C7	C7	16622	-0.16	0.068	NO
116	SSB	SSB	SSB	17846	-0.26	0.01	NO

Figure S63. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS.

Figure S64. 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 PHOSPHATE PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NCF1C	NCF1C	NCF1C	160	0.88	0.27	YES
2	GNGT1	GNGT1	GNGT1	344	0.6	0.45	YES
3	FPR1	FPR1	FPR1	1130	0.26	0.49	YES
4	CAMK1G	CAMK1G	CAMK1G	2915	0.12	0.43	NO
5	HRAS	HRAS	HRAS	3568	0.1	0.43	NO
6	MAP2K2	MAP2K2	MAP2K2	4597	0.076	0.39	NO
7	MAPK3	MAPK3	MAPK3	4606	0.075	0.42	NO
8	NFATC3	NFATC3	NFATC3	4697	0.073	0.43	NO
9	NCF2	NCF2	NCF2	5645	0.052	0.4	NO
10	CAMK1	CAMK1	CAMK1	5648	0.052	0.42	NO
11	NFATC1	NFATC1	NFATC1	6667	0.034	0.37	NO
12	NFKBIA	NFKBIA	NFKBIA	7722	0.016	0.32	NO
13	GNB1	GNB1	GNB1	7948	0.012	0.31	NO
14	MAP2K6	MAP2K6	MAP2K6	8089	0.01	0.3	NO
15	RELA	RELA	RELA	8431	0.0048	0.28	NO
16	MAP2K3	MAP2K3	MAP2K3	8446	0.0046	0.28	NO
17	RAF1	RAF1	RAF1	8453	0.0045	0.29	NO
18	CALM3	CALM3	CALM3	8465	0.0044	0.29	NO
19	PPP3CC	PPP3CC	PPP3CC	8596	0.0026	0.28	NO
20	MAPK14	MAPK14	MAPK14	8633	0.002	0.28	NO
21	CALM1	CALM1	CALM1	8936	-0.0026	0.26	NO
22	NFKB1	NFKB1	NFKB1	9617	-0.013	0.23	NO
23	ELK1	ELK1	ELK1	9768	-0.015	0.23	NO
24	RAC1	RAC1	RAC1	9893	-0.017	0.22	NO
25	NFATC2	NFATC2	NFATC2	10242	-0.022	0.21	NO
26	PAK1	PAK1	PAK1	10424	-0.025	0.21	NO
27	MAPK1	MAPK1	MAPK1	10507	-0.026	0.21	NO
28	PPP3CB	PPP3CB	PPP3CB	11328	-0.039	0.18	NO
29	NFATC4	NFATC4	NFATC4	11461	-0.042	0.19	NO
30	CALM2	CALM2	CALM2	11874	-0.048	0.18	NO
31	MAP2K1	MAP2K1	MAP2K1	12239	-0.054	0.18	NO
32	PPP3CA	PPP3CA	PPP3CA	14578	-0.098	0.077	NO
33	MAP3K1	MAP3K1	MAP3K1	15989	-0.13	0.041	NO
34	PLCB1	PLCB1	PLCB1	17636	-0.23	0.022	NO

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

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	RPL21	RPL21	RPL21	23	1.5	0.12	YES
2	RPL36A	RPL36A	RPL36A	134	0.96	0.2	YES
3	RPL39	RPL39	RPL39	231	0.76	0.25	YES
4	RPS28	RPS28	RPS28	256	0.72	0.31	YES
5	RPS27	RPS27	RPS27	380	0.58	0.35	YES
6	RPL9	RPL9	RPL9	403	0.56	0.4	YES
7	RPS26	RPS26	RPS26	448	0.52	0.44	YES
8	RPL7	RPL7	RPL7	472	0.5	0.48	YES
9	RPL18A	RPL18A	RPL18A	556	0.44	0.51	YES
10	RPS3A	RPS3A	RPS3A	841	0.32	0.52	YES
11	RPSA	RPSA	RPSA	1262	0.24	0.52	YES
12	RPL23A	RPL23A	RPL23A	1293	0.23	0.54	YES
13	RPS15	RPS15	RPS15	1718	0.19	0.53	YES
14	RPS2	RPS2	RPS2	1860	0.18	0.54	YES
15	RPL10L	RPL10L	RPL10L	2120	0.16	0.53	YES
16	RPL13	RPL13	RPL13	2476	0.14	0.53	YES
17	RPS5	RPS5	RPS5	2661	0.13	0.53	YES
18	RPL41	RPL41	RPL41	2840	0.13	0.53	YES
19	RPLP0	RPLP0	RPLP0	2847	0.13	0.54	YES
20	RPL29	RPL29	RPL29	3056	0.12	0.54	YES
21	RPL28	RPL28	RPL28	3189	0.12	0.54	YES
22	RPL10	RPL10	RPL10	3195	0.11	0.55	YES
23	UBA52	UBA52	UBA52	3713	0.099	0.53	NO
24	RPL15	RPL15	RPL15	4077	0.089	0.51	NO
25	RPLP2	RPLP2	RPLP2	4305	0.083	0.51	NO
26	RPS10	RPS10	RPS10	4613	0.075	0.5	NO
27	RPS3	RPS3	RPS3	4690	0.073	0.5	NO
28	RPL8	RPL8	RPL8	4749	0.072	0.5	NO
29	RPS9	RPS9	RPS9	4864	0.069	0.5	NO
30	RPS4Y1	RPS4Y1	RPS4Y1	5011	0.066	0.5	NO
31	RPS21	RPS21	RPS21	5058	0.065	0.5	NO
32	RPL36	RPL36	RPL36	5257	0.06	0.5	NO
33	RPL27	RPL27	RPL27	5513	0.055	0.48	NO
34	RPS16	RPS16	RPS16	5679	0.052	0.48	NO
35	RPS6	RPS6	RPS6	6029	0.046	0.46	NO
36	RPL26L1	RPL26L1	RPL26L1	6134	0.044	0.46	NO
37	RPL35	RPL35	RPL35	6248	0.042	0.46	NO
38	FAU	FAU	FAU	6426	0.038	0.45	NO
39	RPLP1	RPLP1	RPLP1	6710	0.033	0.44	NO
40	RPS8	RPS8	RPS8	6950	0.029	0.43	NO
41	RPS13	RPS13	RPS13	7169	0.025	0.42	NO
42	RPS11	RPS11	RPS11	7262	0.024	0.42	NO
43	RPL17	RPL17	RPL17	7637	0.017	0.4	NO
44	RPL3	RPL3	RPL3	7641	0.017	0.4	NO
45	RPS19	RPS19	RPS19	7712	0.016	0.4	NO
46	RPL10A	RPL10A	RPL10A	7827	0.014	0.39	NO
47	RPL6	RPL6	RPL6	7889	0.013	0.39	NO
48	RPL7A	RPL7A	RPL7A	7985	0.012	0.38	NO
49	RPS4X	RPS4X	RPS4X	8040	0.011	0.38	NO
50	RPL38	RPL38	RPL38	8176	0.0089	0.38	NO
51	RPS15A	RPS15A	RPS15A	8188	0.0087	0.38	NO
52	RPL37A	RPL37A	RPL37A	8655	0.0017	0.35	NO
53	RPL35A	RPL35A	RPL35A	8663	0.0016	0.35	NO
54	RPL32	RPL32	RPL32	9129	-0.0056	0.32	NO
55	RPS17	RPS17	RPS17	9293	-0.0082	0.32	NO
56	RPL27A	RPL27A	RPL27A	9468	-0.01	0.31	NO
57	RPL37	RPL37	RPL37	9556	-0.012	0.3	NO
58	RPS29	RPS29	RPS29	9557	-0.012	0.3	NO
59	MRPL13	MRPL13	MRPL13	10078	-0.02	0.28	NO
60	RPL31	RPL31	RPL31	10304	-0.023	0.26	NO
61	RPL23	RPL23	RPL23	10479	-0.026	0.26	NO
62	RPS23	RPS23	RPS23	10533	-0.027	0.26	NO
63	RPL5	RPL5	RPL5	10553	-0.027	0.26	NO
64	RPL19	RPL19	RPL19	10574	-0.027	0.26	NO
65	RPL30	RPL30	RPL30	10662	-0.028	0.26	NO
66	RPL34	RPL34	RPL34	10934	-0.033	0.24	NO
67	RPL22	RPL22	RPL22	11104	-0.036	0.24	NO
68	RPL11	RPL11	RPL11	11148	-0.036	0.24	NO
69	RPL13A	RPL13A	RPL13A	11275	-0.038	0.24	NO
70	RPL36AL	RPL36AL	RPL36AL	11387	-0.04	0.23	NO
71	RPL4	RPL4	RPL4	11583	-0.043	0.22	NO
72	RPL14	RPL14	RPL14	11810	-0.047	0.22	NO
73	RPL26	RPL26	RPL26	13093	-0.069	0.15	NO
74	RPS20	RPS20	RPS20	13190	-0.071	0.15	NO
75	RPS7	RPS7	RPS7	13610	-0.079	0.13	NO
76	RSL24D1	RSL24D1	RSL24D1	14640	-0.1	0.085	NO
77	RPS24	RPS24	RPS24	15506	-0.12	0.047	NO
78	RPS18	RPS18	RPS18	15551	-0.12	0.055	NO
79	RPL12	RPL12	RPL12	15681	-0.13	0.058	NO
80	RPL24	RPL24	RPL24	15739	-0.13	0.065	NO
81	RPS25	RPS25	RPS25	15891	-0.13	0.068	NO
82	RPS12	RPS12	RPS12	16107	-0.14	0.067	NO
83	RPS27L	RPS27L	RPS27L	16401	-0.15	0.063	NO
84	RPL22L1	RPL22L1	RPL22L1	16598	-0.16	0.065	NO
85	RPS27A	RPS27A	RPS27A	16906	-0.17	0.062	NO

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

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

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

Table S35. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRPS1L1	PRPS1L1	PRPS1L1	247	0.73	0.23	YES
2	LOC729020	LOC729020	LOC729020	373	0.58	0.42	YES
3	PGLS	PGLS	PGLS	1940	0.17	0.4	YES
4	TKTL1	TKTL1	TKTL1	2193	0.16	0.44	YES
5	FBP2	FBP2	FBP2	3198	0.11	0.42	YES
6	ALDOC	ALDOC	ALDOC	3615	0.1	0.43	YES
7	ALDOB	ALDOB	ALDOB	4144	0.087	0.43	YES
8	PFKL	PFKL	PFKL	4436	0.08	0.44	YES
9	FBP1	FBP1	FBP1	4883	0.069	0.44	YES
10	PGD	PGD	PGD	5084	0.064	0.45	YES
11	RBKS	RBKS	RBKS	5123	0.063	0.47	YES
12	PGM1	PGM1	PGM1	5403	0.057	0.47	YES
13	G6PD	G6PD	G6PD	5515	0.055	0.49	YES
14	PFKP	PFKP	PFKP	5640	0.053	0.5	YES
15	TKT	TKT	TKT	5818	0.05	0.5	YES
16	GPI	GPI	GPI	5905	0.048	0.52	YES
17	TALDO1	TALDO1	TALDO1	6158	0.043	0.52	YES
18	DERA	DERA	DERA	7977	0.012	0.42	NO
19	PRPS2	PRPS2	PRPS2	9224	-0.0071	0.35	NO
20	PFKM	PFKM	PFKM	9338	-0.0089	0.35	NO
21	RPIA	RPIA	RPIA	9542	-0.012	0.34	NO
22	PRPS1	PRPS1	PRPS1	10534	-0.027	0.3	NO
23	TKTL2	TKTL2	TKTL2	12140	-0.053	0.22	NO
24	H6PD	H6PD	H6PD	12886	-0.065	0.2	NO
25	PGM2	PGM2	PGM2	14180	-0.09	0.16	NO
26	RPE	RPE	RPE	16337	-0.14	0.094	NO

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

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

genes ES table in pathway: KEGG PYRIMIDINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	LTC4S	LTC4S	LTC4S	261	0.71	0.11	YES
2	ALOX12	ALOX12	ALOX12	306	0.66	0.23	YES
3	CYP4F2	CYP4F2	CYP4F2	1198	0.24	0.22	YES
4	PLA2G2A	PLA2G2A	PLA2G2A	1823	0.18	0.22	YES
5	CBR3	CBR3	CBR3	2046	0.17	0.24	YES
6	PTGDS	PTGDS	PTGDS	2102	0.16	0.26	YES
7	ALOX15	ALOX15	ALOX15	2149	0.16	0.29	YES
8	PLA2G4E	PLA2G4E	PLA2G4E	2194	0.16	0.32	YES
9	GPX4	GPX4	GPX4	2214	0.16	0.34	YES
10	PLA2G10	PLA2G10	PLA2G10	2237	0.16	0.37	YES
11	GPX1	GPX1	GPX1	2374	0.15	0.39	YES
12	PTGES2	PTGES2	PTGES2	2776	0.13	0.39	YES
13	GGT1	GGT1	GGT1	2815	0.13	0.41	YES
14	PLA2G12B	PLA2G12B	PLA2G12B	2921	0.12	0.43	YES
15	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	3169	0.12	0.43	YES
16	GPX7	GPX7	GPX7	3219	0.11	0.45	YES
17	ALOX12B	ALOX12B	ALOX12B	3350	0.11	0.46	YES
18	CBR1	CBR1	CBR1	3409	0.11	0.48	YES
19	CYP2B6	CYP2B6	CYP2B6	3632	0.1	0.49	YES
20	CYP2C18	CYP2C18	CYP2C18	3795	0.097	0.5	YES
21	PLA2G2D	PLA2G2D	PLA2G2D	3873	0.094	0.51	YES
22	GGT6	GGT6	GGT6	4096	0.088	0.51	YES
23	GPX3	GPX3	GPX3	4178	0.086	0.52	YES
24	PLA2G2F	PLA2G2F	PLA2G2F	4384	0.081	0.52	YES
25	CYP2C9	CYP2C9	CYP2C9	4801	0.07	0.51	YES
26	CYP2E1	CYP2E1	CYP2E1	4820	0.07	0.53	YES
27	CYP4F3	CYP4F3	CYP4F3	4980	0.066	0.53	YES
28	CYP2C19	CYP2C19	CYP2C19	5030	0.065	0.54	YES
29	PLA2G6	PLA2G6	PLA2G6	5158	0.062	0.54	YES
30	EPHX2	EPHX2	EPHX2	5595	0.054	0.53	YES
31	PLA2G3	PLA2G3	PLA2G3	5600	0.054	0.54	YES
32	PLA2G1B	PLA2G1B	PLA2G1B	5691	0.052	0.54	YES
33	GGT7	GGT7	GGT7	5734	0.051	0.55	YES
34	AKR1C3	AKR1C3	AKR1C3	6178	0.043	0.53	NO
35	GPX2	GPX2	GPX2	6654	0.034	0.51	NO
36	CYP4A11	CYP4A11	CYP4A11	7089	0.027	0.49	NO
37	ALOX15B	ALOX15B	ALOX15B	7247	0.024	0.49	NO
38	PTGS1	PTGS1	PTGS1	7378	0.022	0.48	NO
39	ALOX5	ALOX5	ALOX5	7575	0.018	0.48	NO
40	TBXAS1	TBXAS1	TBXAS1	8278	0.0072	0.44	NO
41	PTGES	PTGES	PTGES	9345	-0.009	0.38	NO
42	HPGDS	HPGDS	HPGDS	9937	-0.018	0.35	NO
43	PLA2G12A	PLA2G12A	PLA2G12A	10374	-0.024	0.33	NO
44	CYP2C8	CYP2C8	CYP2C8	10419	-0.025	0.33	NO
45	PTGS2	PTGS2	PTGS2	11011	-0.034	0.31	NO
46	LTA4H	LTA4H	LTA4H	11230	-0.038	0.3	NO
47	PTGIS	PTGIS	PTGIS	11689	-0.045	0.28	NO
48	GGT5	GGT5	GGT5	11868	-0.048	0.28	NO
49	PLA2G4A	PLA2G4A	PLA2G4A	12540	-0.059	0.26	NO
50	PLA2G5	PLA2G5	PLA2G5	15350	-0.12	0.12	NO
51	CYP2U1	CYP2U1	CYP2U1	16688	-0.16	0.074	NO

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

Figure S72. 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 ARGININE AND PROLINE METABOLISM

Table S37. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GSTM1	GSTM1	GSTM1	333	0.62	0.063	YES
2	AKR1C2	AKR1C2	AKR1C2	407	0.55	0.13	YES
3	AKR1C4	AKR1C4	AKR1C4	532	0.46	0.19	YES
4	CYP2F1	CYP2F1	CYP2F1	629	0.4	0.23	YES
5	ADH1A	ADH1A	ADH1A	774	0.34	0.27	YES
6	AKR1C1	AKR1C1	AKR1C1	896	0.3	0.3	YES
7	GSTA2	GSTA2	GSTA2	950	0.29	0.34	YES
8	UGT2B11	UGT2B11	UGT2B11	966	0.28	0.38	YES
9	GSTM2	GSTM2	GSTM2	1149	0.25	0.4	YES
10	DHDH	DHDH	DHDH	1365	0.22	0.42	YES
11	ADH1B	ADH1B	ADH1B	1434	0.22	0.44	YES
12	GSTT2	GSTT2	GSTT2	1440	0.22	0.47	YES
13	UGT1A9	UGT1A9	UGT1A9	1693	0.19	0.48	YES
14	UGT2B15	UGT2B15	UGT2B15	1733	0.19	0.5	YES
15	GSTO2	GSTO2	GSTO2	2274	0.15	0.5	YES
16	UGT1A8	UGT1A8	UGT1A8	2400	0.15	0.51	YES
17	ADH1C	ADH1C	ADH1C	2738	0.13	0.51	YES
18	ALDH3B2	ALDH3B2	ALDH3B2	2750	0.13	0.52	YES
19	GSTM5	GSTM5	GSTM5	2763	0.13	0.54	YES
20	GSTP1	GSTP1	GSTP1	2769	0.13	0.56	YES
21	UGT2B10	UGT2B10	UGT2B10	2874	0.12	0.57	YES
22	CYP2B6	CYP2B6	CYP2B6	3632	0.1	0.54	NO
23	CYP2C18	CYP2C18	CYP2C18	3795	0.097	0.54	NO
24	GSTT1	GSTT1	GSTT1	4423	0.08	0.52	NO
25	ALDH3A1	ALDH3A1	ALDH3A1	4685	0.073	0.51	NO
26	GSTZ1	GSTZ1	GSTZ1	4735	0.072	0.52	NO
27	CYP2C9	CYP2C9	CYP2C9	4801	0.07	0.52	NO
28	CYP2E1	CYP2E1	CYP2E1	4820	0.07	0.53	NO
29	MGST3	MGST3	MGST3	4835	0.07	0.54	NO
30	CYP2C19	CYP2C19	CYP2C19	5030	0.065	0.54	NO
31	GSTA1	GSTA1	GSTA1	5465	0.056	0.52	NO
32	UGT2A3	UGT2A3	UGT2A3	5544	0.055	0.53	NO
33	CYP3A43	CYP3A43	CYP3A43	5554	0.054	0.53	NO
34	CYP2S1	CYP2S1	CYP2S1	5602	0.053	0.54	NO
35	CYP1A1	CYP1A1	CYP1A1	5966	0.047	0.52	NO
36	UGT2B7	UGT2B7	UGT2B7	6107	0.044	0.52	NO
37	AKR1C3	AKR1C3	AKR1C3	6178	0.043	0.52	NO
38	MGST1	MGST1	MGST1	6677	0.034	0.5	NO
39	GSTO1	GSTO1	GSTO1	7105	0.026	0.48	NO
40	GSTK1	GSTK1	GSTK1	7345	0.022	0.47	NO
41	ADH4	ADH4	ADH4	7369	0.022	0.47	NO
42	ADH6	ADH6	ADH6	7553	0.019	0.46	NO
43	GSTM4	GSTM4	GSTM4	7705	0.016	0.46	NO
44	ALDH3B1	ALDH3B1	ALDH3B1	8022	0.011	0.44	NO
45	ADH5	ADH5	ADH5	8133	0.0095	0.44	NO
46	CYP3A7	CYP3A7	CYP3A7	8234	0.0081	0.43	NO
47	UGT1A10	UGT1A10	UGT1A10	8654	0.0017	0.41	NO
48	EPHX1	EPHX1	EPHX1	9869	-0.016	0.34	NO
49	UGT1A1	UGT1A1	UGT1A1	10131	-0.02	0.33	NO
50	CYP2C8	CYP2C8	CYP2C8	10419	-0.025	0.32	NO
51	UGT1A3	UGT1A3	UGT1A3	10671	-0.029	0.31	NO
52	GSTM3	GSTM3	GSTM3	11635	-0.044	0.26	NO
53	UGT1A6	UGT1A6	UGT1A6	12405	-0.057	0.22	NO
54	MGST2	MGST2	MGST2	12427	-0.057	0.23	NO
55	UGT2B4	UGT2B4	UGT2B4	12967	-0.066	0.21	NO
56	CYP3A5	CYP3A5	CYP3A5	14408	-0.095	0.14	NO
57	ALDH1A3	ALDH1A3	ALDH1A3	14652	-0.1	0.14	NO
58	GSTA4	GSTA4	GSTA4	16489	-0.15	0.061	NO
59	CYP1B1	CYP1B1	CYP1B1	17190	-0.19	0.046	NO

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

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

genes ES table in pathway: KEGG GLUTATHIONE METABOLISM

Table S38. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PGAM4	PGAM4	PGAM4	82	1.1	0.21	YES
2	ADH1A	ADH1A	ADH1A	774	0.34	0.23	YES
3	PGAM2	PGAM2	PGAM2	862	0.31	0.29	YES
4	ADH1B	ADH1B	ADH1B	1434	0.22	0.3	YES
5	HK3	HK3	HK3	1730	0.19	0.31	YES
6	ENO3	ENO3	ENO3	1999	0.17	0.33	YES
7	GCK	GCK	GCK	2369	0.15	0.34	YES
8	PKLR	PKLR	PKLR	2694	0.13	0.35	YES
9	ADH1C	ADH1C	ADH1C	2738	0.13	0.37	YES
10	ALDH3B2	ALDH3B2	ALDH3B2	2750	0.13	0.39	YES
11	PGAM1	PGAM1	PGAM1	2997	0.12	0.4	YES
12	FBP2	FBP2	FBP2	3198	0.11	0.41	YES
13	ALDOC	ALDOC	ALDOC	3615	0.1	0.41	YES
14	ALDOB	ALDOB	ALDOB	4144	0.087	0.39	YES
15	PFKL	PFKL	PFKL	4436	0.08	0.39	YES
16	ALDOA	ALDOA	ALDOA	4541	0.077	0.4	YES
17	AKR1A1	AKR1A1	AKR1A1	4632	0.074	0.41	YES
18	ALDH3A1	ALDH3A1	ALDH3A1	4685	0.073	0.42	YES
19	PCK2	PCK2	PCK2	4771	0.071	0.43	YES
20	FBP1	FBP1	FBP1	4883	0.069	0.44	YES
21	TPI1	TPI1	TPI1	5187	0.062	0.43	NO
22	PGM1	PGM1	PGM1	5403	0.057	0.43	NO
23	PFKP	PFKP	PFKP	5640	0.053	0.43	NO
24	GAPDH	GAPDH	GAPDH	5733	0.051	0.43	NO
25	GPI	GPI	GPI	5905	0.048	0.43	NO
26	ACSS2	ACSS2	ACSS2	6262	0.041	0.42	NO
27	PGK1	PGK1	PGK1	6668	0.034	0.4	NO
28	PDHA1	PDHA1	PDHA1	7281	0.023	0.37	NO
29	ADH4	ADH4	ADH4	7369	0.022	0.37	NO
30	ALDH1B1	ALDH1B1	ALDH1B1	7381	0.022	0.38	NO
31	ADH6	ADH6	ADH6	7553	0.019	0.37	NO
32	PKM2	PKM2	PKM2	7689	0.016	0.37	NO
33	ENO1	ENO1	ENO1	7735	0.016	0.37	NO
34	HK1	HK1	HK1	7969	0.012	0.36	NO
35	ALDH3B1	ALDH3B1	ALDH3B1	8022	0.011	0.36	NO
36	PDHB	PDHB	PDHB	8047	0.011	0.36	NO
37	ADH5	ADH5	ADH5	8133	0.0095	0.35	NO
38	LDHA	LDHA	LDHA	8483	0.0042	0.33	NO
39	ACSS1	ACSS1	ACSS1	8499	0.0039	0.33	NO
40	LDHAL6A	LDHAL6A	LDHAL6A	8547	0.0031	0.33	NO
41	ALDH2	ALDH2	ALDH2	8676	0.0014	0.32	NO
42	PFKM	PFKM	PFKM	9338	-0.0089	0.29	NO
43	LDHB	LDHB	LDHB	9854	-0.016	0.26	NO
44	PCK1	PCK1	PCK1	10041	-0.019	0.26	NO
45	G6PC2	G6PC2	G6PC2	10248	-0.022	0.25	NO
46	ALDH3A2	ALDH3A2	ALDH3A2	11520	-0.042	0.19	NO
47	ALDH9A1	ALDH9A1	ALDH9A1	11700	-0.046	0.19	NO
48	HK2	HK2	HK2	12637	-0.061	0.15	NO
49	DLAT	DLAT	DLAT	12726	-0.063	0.15	NO
50	DLD	DLD	DLD	13107	-0.069	0.14	NO
51	GALM	GALM	GALM	13200	-0.071	0.15	NO
52	ENO2	ENO2	ENO2	13267	-0.073	0.16	NO
53	LDHAL6B	LDHAL6B	LDHAL6B	13871	-0.084	0.14	NO
54	PGM2	PGM2	PGM2	14180	-0.09	0.14	NO
55	ALDH7A1	ALDH7A1	ALDH7A1	14496	-0.097	0.15	NO
56	ALDH1A3	ALDH1A3	ALDH1A3	14652	-0.1	0.16	NO
57	BPGM	BPGM	BPGM	16829	-0.17	0.067	NO

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

Figure S76. 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 S39. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	COX4I2	COX4I2	COX4I2	758	0.35	-0.0014	YES
2	SLC18A2	SLC18A2	SLC18A2	1096	0.26	0.01	YES
3	TH	TH	TH	1164	0.25	0.036	YES
4	NDUFS7	NDUFS7	NDUFS7	1428	0.22	0.046	YES
5	ATP5D	ATP5D	ATP5D	1596	0.2	0.061	YES
6	COX6A1	COX6A1	COX6A1	1713	0.19	0.077	YES
7	NDUFS8	NDUFS8	NDUFS8	1793	0.18	0.094	YES
8	CYC1	CYC1	CYC1	1808	0.18	0.12	YES
9	COX5B	COX5B	COX5B	1905	0.18	0.13	YES
10	COX7A1	COX7A1	COX7A1	2015	0.17	0.14	YES
11	UQCR11	UQCR11	UQCR11	2327	0.15	0.14	YES
12	UQCRQ	UQCRQ	UQCRQ	2662	0.13	0.14	YES
13	NDUFB10	NDUFB10	NDUFB10	2712	0.13	0.15	YES
14	NDUFB7	NDUFB7	NDUFB7	2806	0.13	0.16	YES
15	NDUFA3	NDUFA3	NDUFA3	2860	0.13	0.18	YES
16	COX6B2	COX6B2	COX6B2	2943	0.12	0.18	YES
17	COX8A	COX8A	COX8A	3014	0.12	0.2	YES
18	NDUFS6	NDUFS6	NDUFS6	3043	0.12	0.21	YES
19	SLC25A5	SLC25A5	SLC25A5	3057	0.12	0.22	YES
20	UQCRC1	UQCRC1	UQCRC1	3095	0.12	0.23	YES
21	UQCR10	UQCR10	UQCR10	3107	0.12	0.25	YES
22	VDAC2	VDAC2	VDAC2	3214	0.11	0.25	YES
23	NDUFA9	NDUFA9	NDUFA9	3319	0.11	0.26	YES
24	NDUFA4L2	NDUFA4L2	NDUFA4L2	3447	0.11	0.27	YES
25	NDUFS3	NDUFS3	NDUFS3	3665	0.1	0.27	YES
26	COX5A	COX5A	COX5A	3670	0.1	0.28	YES
27	NDUFV1	NDUFV1	NDUFV1	3720	0.099	0.29	YES
28	UBE2J2	UBE2J2	UBE2J2	3790	0.097	0.29	YES
29	NDUFB8	NDUFB8	NDUFB8	4037	0.09	0.29	YES
30	UBE2L6	UBE2L6	UBE2L6	4057	0.089	0.3	YES
31	UQCRFS1	UQCRFS1	UQCRFS1	4172	0.086	0.3	YES
32	COX7B	COX7B	COX7B	4308	0.083	0.31	YES
33	UBB	UBB	UBB	4310	0.083	0.32	YES
34	COX4I1	COX4I1	COX4I1	4329	0.082	0.32	YES
35	NDUFA6	NDUFA6	NDUFA6	4330	0.082	0.33	YES
36	NDUFA7	NDUFA7	NDUFA7	4350	0.082	0.34	YES
37	NDUFA2	NDUFA2	NDUFA2	4351	0.082	0.35	YES
38	SLC25A4	SLC25A4	SLC25A4	4795	0.07	0.34	YES
39	SDHA	SDHA	SDHA	4996	0.066	0.33	YES
40	NDUFAB1	NDUFAB1	NDUFAB1	5022	0.066	0.34	YES
41	ATP5B	ATP5B	ATP5B	5499	0.055	0.32	YES
42	NDUFS5	NDUFS5	NDUFS5	5527	0.055	0.32	YES
43	UQCRHL	UQCRHL	UQCRHL	5547	0.054	0.33	YES
44	SNCA	SNCA	SNCA	5550	0.054	0.34	YES
45	SLC25A6	SLC25A6	SLC25A6	5688	0.052	0.33	YES
46	SLC18A1	SLC18A1	SLC18A1	5833	0.049	0.33	YES
47	ATP5G1	ATP5G1	ATP5G1	5897	0.048	0.33	YES
48	NDUFA8	NDUFA8	NDUFA8	5998	0.046	0.33	YES
49	NDUFS2	NDUFS2	NDUFS2	6022	0.046	0.34	YES
50	HTRA2	HTRA2	HTRA2	6142	0.044	0.34	YES
51	UQCRC2	UQCRC2	UQCRC2	6236	0.042	0.34	YES
52	NDUFB9	NDUFB9	NDUFB9	6244	0.042	0.34	YES
53	SDHB	SDHB	SDHB	6308	0.041	0.34	YES
54	COX6B1	COX6B1	COX6B1	6353	0.04	0.34	YES
55	PINK1	PINK1	PINK1	6483	0.037	0.34	YES
56	COX7A2	COX7A2	COX7A2	6493	0.037	0.34	YES
57	ATP5G3	ATP5G3	ATP5G3	6516	0.037	0.35	YES
58	ATP5C1	ATP5C1	ATP5C1	6519	0.037	0.35	YES
59	UBA7	UBA7	UBA7	6558	0.036	0.35	YES
60	SDHC	SDHC	SDHC	6699	0.034	0.35	NO
61	NDUFA10	NDUFA10	NDUFA10	6702	0.034	0.35	NO
62	ATP5F1	ATP5F1	ATP5F1	6924	0.03	0.34	NO
63	UBA1	UBA1	UBA1	6944	0.029	0.35	NO
64	PARK2	PARK2	PARK2	6988	0.028	0.35	NO
65	ATP5A1	ATP5A1	ATP5A1	7175	0.025	0.34	NO
66	NDUFB2	NDUFB2	NDUFB2	7290	0.023	0.34	NO
67	NDUFS4	NDUFS4	NDUFS4	7478	0.02	0.33	NO
68	NDUFB4	NDUFB4	NDUFB4	7502	0.02	0.33	NO
69	CASP9	CASP9	CASP9	7956	0.012	0.31	NO
70	ATP5O	ATP5O	ATP5O	8054	0.011	0.3	NO
71	UBE2L3	UBE2L3	UBE2L3	8178	0.0088	0.3	NO
72	VDAC3	VDAC3	VDAC3	8296	0.007	0.29	NO
73	SLC6A3	SLC6A3	SLC6A3	8500	0.0038	0.28	NO
74	PARK7	PARK7	PARK7	8724	0.00063	0.27	NO
75	NDUFV3	NDUFV3	NDUFV3	9303	-0.0083	0.24	NO
76	ATP5G2	ATP5G2	ATP5G2	9334	-0.0088	0.24	NO
77	UCHL1	UCHL1	UCHL1	9482	-0.011	0.23	NO
78	NDUFC2	NDUFC2	NDUFC2	9509	-0.011	0.23	NO
79	SNCAIP	SNCAIP	SNCAIP	9578	-0.012	0.23	NO
80	NDUFB1	NDUFB1	NDUFB1	9706	-0.014	0.22	NO
81	COX7A2L	COX7A2L	COX7A2L	9856	-0.016	0.21	NO
82	NDUFC1	NDUFC1	NDUFC1	10151	-0.021	0.2	NO
83	VDAC1	VDAC1	VDAC1	10161	-0.021	0.2	NO
84	NDUFS1	NDUFS1	NDUFS1	10480	-0.026	0.19	NO
85	SDHD	SDHD	SDHD	11269	-0.038	0.15	NO
86	NDUFB6	NDUFB6	NDUFB6	11326	-0.039	0.15	NO
87	ATP5J	ATP5J	ATP5J	11339	-0.04	0.15	NO
88	UBE2G1	UBE2G1	UBE2G1	11418	-0.041	0.15	NO
89	NDUFA1	NDUFA1	NDUFA1	11777	-0.047	0.14	NO
90	COX6C	COX6C	COX6C	11936	-0.049	0.14	NO
91	NDUFB5	NDUFB5	NDUFB5	12168	-0.053	0.13	NO
92	UQCRH	UQCRH	UQCRH	12225	-0.054	0.13	NO
93	COX7C	COX7C	COX7C	12344	-0.056	0.13	NO
94	NDUFB3	NDUFB3	NDUFB3	12510	-0.059	0.13	NO
95	GPR37	GPR37	GPR37	12707	-0.062	0.13	NO
96	UBE2J1	UBE2J1	UBE2J1	12785	-0.064	0.13	NO
97	CASP3	CASP3	CASP3	12855	-0.065	0.13	NO
98	UBE2G2	UBE2G2	UBE2G2	13062	-0.068	0.13	NO
99	PPID	PPID	PPID	13933	-0.085	0.091	NO
100	ATP5E	ATP5E	ATP5E	14432	-0.096	0.075	NO
101	CYCS	CYCS	CYCS	14471	-0.096	0.084	NO
102	LRRK2	LRRK2	LRRK2	14490	-0.097	0.094	NO
103	APAF1	APAF1	APAF1	14980	-0.11	0.08	NO
104	NDUFV2	NDUFV2	NDUFV2	15391	-0.12	0.071	NO
105	ATP5H	ATP5H	ATP5H	15590	-0.12	0.074	NO
106	NDUFA4	NDUFA4	NDUFA4	15615	-0.12	0.088	NO
107	UQCRB	UQCRB	UQCRB	16409	-0.15	0.061	NO
108	NDUFA5	NDUFA5	NDUFA5	17774	-0.25	0.014	NO

Figure S77. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG STARCH AND SUCROSE METABOLISM.

Figure S78. 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 ARACHIDONIC ACID METABOLISM

Table S40. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GSTM1	GSTM1	GSTM1	333	0.62	0.11	YES
2	GSTA2	GSTA2	GSTA2	950	0.29	0.14	YES
3	GSTM2	GSTM2	GSTM2	1149	0.25	0.18	YES
4	GSTT2	GSTT2	GSTT2	1440	0.22	0.21	YES
5	SRM	SRM	SRM	2115	0.16	0.21	YES
6	GPX4	GPX4	GPX4	2214	0.16	0.24	YES
7	GSTO2	GSTO2	GSTO2	2274	0.15	0.26	YES
8	GPX1	GPX1	GPX1	2374	0.15	0.29	YES
9	OPLAH	OPLAH	OPLAH	2751	0.13	0.3	YES
10	GSTM5	GSTM5	GSTM5	2763	0.13	0.32	YES
11	GSTP1	GSTP1	GSTP1	2769	0.13	0.35	YES
12	GGT1	GGT1	GGT1	2815	0.13	0.38	YES
13	GPX7	GPX7	GPX7	3219	0.11	0.38	YES
14	ANPEP	ANPEP	ANPEP	3651	0.1	0.38	YES
15	GGT6	GGT6	GGT6	4096	0.088	0.37	YES
16	GPX3	GPX3	GPX3	4178	0.086	0.38	YES
17	GSTT1	GSTT1	GSTT1	4423	0.08	0.39	YES
18	GSTZ1	GSTZ1	GSTZ1	4735	0.072	0.38	YES
19	MGST3	MGST3	MGST3	4835	0.07	0.39	YES
20	IDH2	IDH2	IDH2	4884	0.069	0.4	YES
21	GSR	GSR	GSR	5350	0.058	0.39	YES
22	GSS	GSS	GSS	5429	0.057	0.4	YES
23	GSTA1	GSTA1	GSTA1	5465	0.056	0.41	YES
24	G6PD	G6PD	G6PD	5515	0.055	0.42	YES
25	ODC1	ODC1	ODC1	5726	0.051	0.42	YES
26	GGT7	GGT7	GGT7	5734	0.051	0.43	YES
27	GPX2	GPX2	GPX2	6654	0.034	0.38	NO
28	MGST1	MGST1	MGST1	6677	0.034	0.39	NO
29	GSTO1	GSTO1	GSTO1	7105	0.026	0.37	NO
30	GSTK1	GSTK1	GSTK1	7345	0.022	0.36	NO
31	GSTM4	GSTM4	GSTM4	7705	0.016	0.35	NO
32	RRM2	RRM2	RRM2	8017	0.011	0.33	NO
33	LAP3	LAP3	LAP3	9822	-0.016	0.24	NO
34	IDH1	IDH1	IDH1	10176	-0.021	0.22	NO
35	TXNDC12	TXNDC12	TXNDC12	10893	-0.032	0.19	NO
36	GSTM3	GSTM3	GSTM3	11635	-0.044	0.16	NO
37	GGT5	GGT5	GGT5	11868	-0.048	0.15	NO
38	MGST2	MGST2	MGST2	12427	-0.057	0.13	NO
39	RRM1	RRM1	RRM1	12779	-0.064	0.13	NO
40	GCLC	GCLC	GCLC	13117	-0.07	0.12	NO
41	GCLM	GCLM	GCLM	13251	-0.072	0.13	NO
42	GGCT	GGCT	GGCT	15298	-0.12	0.042	NO
43	SMS	SMS	SMS	16427	-0.15	0.011	NO
44	GSTA4	GSTA4	GSTA4	16489	-0.15	0.04	NO
45	RRM2B	RRM2B	RRM2B	17553	-0.22	0.026	NO

Figure S79. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG ARACHIDONIC ACID METABOLISM.

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

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 = COADREAD-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = COADREAD-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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