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

Liver Hepatocellular Carcinoma (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 LIHC-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1348JFV

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 LIHC-TP. This pipeline has the following features:

For each subtype, calculates enrichment scores (ES) using signal to noise (S2N) that checks similarity between subtypes in expression level then calculates p values through permutation test.
Lists pathways significantly enriched in each phenotype subtype and their enrichment scores (ES).
Lists top 20 core genes enriched in each significant gene set and their enrichment scores (ES).
Checks if the top core genes are up-regulated or down-regulated.
Checks if the top core genes are high expressed or low expressed.
Checks if the top core genes are significantly differently expressed genes.

Summary

Table 1. Get Full Table basic data info

basic data info
Number of Gene Sets: 192
Number of samples: 371
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 5 :[ clus1 ] 62
pheno.type: 2 - 5 :[ clus2 ] 99
pheno.type: 3 - 5 :[ clus3 ] 71
pheno.type: 4 - 5 :[ clus4 ] 69
pheno.type: 5 - 5 :[ clus5 ] 70

For the expression subtypes of 17745 genes in 372 samples, GSEA found enriched gene sets in each cluster using 371 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA G1 PATHWAY, BIOCARTA FMLP PATHWAY, BIOCARTA MPR PATHWAY, BIOCARTA TOLL PATHWAY, KEGG RNA DEGRADATION, KEGG DNA REPLICATION, KEGG SPLICEOSOME, KEGG BASE EXCISION REPAIR, KEGG NUCLEOTIDE EXCISION REPAIR, KEGG HOMOLOGOUS RECOMBINATION

And common core enriched genes are MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, PCNA, POLD1, RPA4, ACIN1

clus2

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG CITRATE CYCLE TCA CYCLE, KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS, KEGG FATTY ACID METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS, KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG CYSTEINE AND METHIONINE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG LYSINE DEGRADATION

And common core enriched genes are ACAT1, ACAT2, ALDH2, ALDH7A1, ALDH9A1, LDHAL6B, PIPOX, ACACB, ACSS2, EHHADH

clus3

Top enriched gene sets are BIOCARTA G1 PATHWAY, BIOCARTA MPR PATHWAY, BIOCARTA INTEGRIN PATHWAY, BIOCARTA WNT PATHWAY, KEGG INOSITOL PHOSPHATE METABOLISM, KEGG ETHER LIPID METABOLISM, KEGG SPHINGOLIPID METABOLISM, KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES, KEGG RIBOSOME, KEGG DNA REPLICATION

And common core enriched genes are ACTA1, CCNB1, CDC25C, CDK1, MYT1, SRC, RPL10A, RPL12, RPL13A, RPL14

clus4

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA ALK PATHWAY, BIOCARTA BCR PATHWAY, BIOCARTA CARM ER PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA FCER1 PATHWAY

And common core enriched genes are PRKX, FZD1, FZD2, FZD7, FZD8, LEF1, WNT1, WNT10A, WNT11, WNT2

clus5

Top enriched gene sets are BIOCARTA WNT PATHWAY, KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS, KEGG FATTY ACID METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG LYSINE DEGRADATION, KEGG TYROSINE METABOLISM, KEGG TRYPTOPHAN METABOLISM, KEGG PROPANOATE METABOLISM, KEGG BUTANOATE METABOLISM

And common core enriched genes are ACAA1, ACSL5, ACSL6, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7

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 G1 PATHWAY	27	genes.ES.table	0.55	1.6	0.028	0.53	0.79	0.41	0.24	0.31	0.31	0.16
BIOCARTA FMLP PATHWAY	35	genes.ES.table	0.5	1.6	0.029	0.42	0.63	0.2	0.16	0.17	0.21	0.11
BIOCARTA MPR PATHWAY	32	genes.ES.table	0.53	1.7	0.012	0.41	0.57	0.31	0.18	0.26	0.18	0.11
BIOCARTA TOLL PATHWAY	36	genes.ES.table	0.48	1.5	0.068	0.5	0.88	0.19	0.11	0.17	0.31	0.14
KEGG RNA DEGRADATION	55	genes.ES.table	0.34	1.6	0.054	0.4	0.69	0.74	0.51	0.37	0.22	0.096
KEGG DNA REPLICATION	35	genes.ES.table	0.63	1.7	0.067	0.42	0.52	0.74	0.3	0.52	0.17	0.12
KEGG SPLICEOSOME	125	genes.ES.table	0.47	1.9	0.016	0.44	0.15	0.74	0.46	0.4	0	0.13
KEGG BASE EXCISION REPAIR	32	genes.ES.table	0.42	1.5	0.12	0.57	0.92	0.56	0.39	0.34	0.39	0.17
KEGG NUCLEOTIDE EXCISION REPAIR	43	genes.ES.table	0.39	1.5	0.11	0.54	0.84	0.51	0.41	0.3	0.33	0.16
KEGG HOMOLOGOUS RECOMBINATION	27	genes.ES.table	0.67	1.7	0.024	0.5	0.51	0.41	0.14	0.35	0.21	0.15

genes ES table in pathway: BIOCARTA G1 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	HSPA6	HSPA6	HSPA6	1121	0.3	-0.027	YES
2	PPIH	PPIH	PPIH	1829	0.24	-0.038	YES
3	SNRPD1	SNRPD1	SNRPD1	2795	0.18	-0.071	YES
4	THOC4	THOC4	THOC4	2991	0.17	-0.062	YES
5	SNRPA1	SNRPA1	SNRPA1	3139	0.16	-0.05	YES
6	HSPA1B	HSPA1B	HSPA1B	3291	0.16	-0.04	YES
7	SNRNP40	SNRNP40	SNRNP40	3482	0.15	-0.032	YES
8	SNRPA	SNRPA	SNRPA	3674	0.14	-0.026	YES
9	SNRPB	SNRPB	SNRPB	3683	0.14	-0.009	YES
10	SNRPD2	SNRPD2	SNRPD2	3857	0.14	-0.0024	YES
11	NAA38	NAA38	NAA38	3975	0.13	0.0069	YES
12	PRPF38A	PRPF38A	PRPF38A	4006	0.13	0.021	YES
13	SF3A3	SF3A3	SF3A3	4146	0.13	0.028	YES
14	SNRPF	SNRPF	SNRPF	4170	0.13	0.042	YES
15	EFTUD2	EFTUD2	EFTUD2	4277	0.12	0.051	YES
16	SF3B4	SF3B4	SF3B4	4292	0.12	0.065	YES
17	LSM2	LSM2	LSM2	4491	0.12	0.068	YES
18	PPIL1	PPIL1	PPIL1	4533	0.12	0.079	YES
19	SF3A2	SF3A2	SF3A2	4622	0.11	0.087	YES
20	TXNL4A	TXNL4A	TXNL4A	4762	0.11	0.092	YES
21	BUD31	BUD31	BUD31	4967	0.1	0.093	YES
22	PRPF4	PRPF4	PRPF4	5093	0.099	0.098	YES
23	SNRPC	SNRPC	SNRPC	5098	0.099	0.11	YES
24	PRPF3	PRPF3	PRPF3	5166	0.097	0.12	YES
25	PPIE	PPIE	PPIE	5167	0.097	0.13	YES
26	THOC1	THOC1	THOC1	5223	0.096	0.14	YES
27	EIF4A3	EIF4A3	EIF4A3	5335	0.093	0.14	YES
28	TCERG1	TCERG1	TCERG1	5379	0.092	0.15	YES
29	MAGOH	MAGOH	MAGOH	5493	0.089	0.16	YES
30	U2AF2	U2AF2	U2AF2	5536	0.088	0.16	YES
31	PRPF31	PRPF31	PRPF31	5562	0.088	0.17	YES
32	SNRPB2	SNRPB2	SNRPB2	5638	0.086	0.18	YES
33	SFRS9	SFRS9	SFRS9	5698	0.084	0.18	YES
34	SNRPG	SNRPG	SNRPG	5787	0.082	0.19	YES
35	RBM17	RBM17	RBM17	5808	0.082	0.2	YES
36	LSM7	LSM7	LSM7	5882	0.08	0.2	YES
37	HNRNPA3	HNRNPA3	HNRNPA3	5924	0.079	0.21	YES
38	SF3B5	SF3B5	SF3B5	5951	0.079	0.22	YES
39	SF3B3	SF3B3	SF3B3	6012	0.078	0.23	YES
40	RBMX	RBMX	RBMX	6033	0.077	0.23	YES
41	SNRPE	SNRPE	SNRPE	6077	0.076	0.24	YES
42	HSPA2	HSPA2	HSPA2	6134	0.075	0.25	YES
43	PRPF38B	PRPF38B	PRPF38B	6164	0.074	0.25	YES
44	THOC2	THOC2	THOC2	6167	0.074	0.26	YES
45	PRPF40B	PRPF40B	PRPF40B	6250	0.073	0.27	YES
46	LSM5	LSM5	LSM5	6274	0.072	0.27	YES
47	DDX23	DDX23	DDX23	6277	0.072	0.28	YES
48	SFRS13A	SFRS13A	SFRS13A	6334	0.071	0.29	YES
49	LSM4	LSM4	LSM4	6445	0.069	0.29	YES
50	SR140	SR140	SR140	6461	0.068	0.3	YES
51	U2AF1	U2AF1	U2AF1	6542	0.067	0.3	YES
52	ISY1	ISY1	ISY1	6551	0.067	0.31	YES
53	SART1	SART1	SART1	6560	0.067	0.32	YES
54	HNRNPM	HNRNPM	HNRNPM	6697	0.064	0.32	YES
55	PRPF19	PRPF19	PRPF19	6755	0.063	0.32	YES
56	BCAS2	BCAS2	BCAS2	6764	0.063	0.33	YES
57	SFRS3	SFRS3	SFRS3	6776	0.063	0.33	YES
58	RBM22	RBM22	RBM22	6786	0.063	0.34	YES
59	HNRNPA1	HNRNPA1	HNRNPA1	6787	0.063	0.35	YES
60	TRA2B	TRA2B	TRA2B	6908	0.06	0.35	YES
61	RBM8A	RBM8A	RBM8A	6925	0.06	0.36	YES
62	NCBP1	NCBP1	NCBP1	7004	0.058	0.36	YES
63	PUF60	PUF60	PUF60	7008	0.058	0.36	YES
64	CCDC12	CCDC12	CCDC12	7035	0.058	0.37	YES
65	THOC3	THOC3	THOC3	7045	0.058	0.38	YES
66	HNRNPU	HNRNPU	HNRNPU	7094	0.057	0.38	YES
67	PQBP1	PQBP1	PQBP1	7101	0.057	0.39	YES
68	SFRS7	SFRS7	SFRS7	7113	0.057	0.39	YES
69	DHX8	DHX8	DHX8	7148	0.056	0.4	YES
70	DHX15	DHX15	DHX15	7251	0.054	0.4	YES
71	SNRNP70	SNRNP70	SNRNP70	7285	0.054	0.4	YES
72	SF3B2	SF3B2	SF3B2	7292	0.054	0.41	YES
73	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	7468	0.051	0.41	YES
74	CRNKL1	CRNKL1	CRNKL1	7481	0.051	0.41	YES
75	BAT1	BAT1	BAT1	7564	0.05	0.41	YES
76	SFRS2	SFRS2	SFRS2	7647	0.048	0.41	YES
77	PHF5A	PHF5A	PHF5A	7682	0.048	0.42	YES
78	DHX38	DHX38	DHX38	7709	0.047	0.42	YES
79	PRPF6	PRPF6	PRPF6	7748	0.047	0.42	YES
80	PRPF40A	PRPF40A	PRPF40A	7765	0.046	0.43	YES
81	TRA2A	TRA2A	TRA2A	7807	0.046	0.43	YES
82	SFRS1	SFRS1	SFRS1	7830	0.045	0.44	YES
83	SNRNP200	SNRNP200	SNRNP200	7907	0.044	0.44	YES
84	PLRG1	PLRG1	PLRG1	7925	0.044	0.44	YES
85	SYF2	SYF2	SYF2	7948	0.043	0.45	YES
86	ACIN1	ACIN1	ACIN1	7973	0.043	0.45	YES
87	USP39	USP39	USP39	7977	0.043	0.46	YES
88	LSM6	LSM6	LSM6	7983	0.042	0.46	YES
89	HSPA1A	HSPA1A	HSPA1A	8075	0.041	0.46	YES
90	SFRS4	SFRS4	SFRS4	8170	0.039	0.46	YES
91	HNRNPC	HNRNPC	HNRNPC	8181	0.039	0.46	YES
92	HSPA8	HSPA8	HSPA8	8186	0.039	0.47	YES
93	SMNDC1	SMNDC1	SMNDC1	8207	0.039	0.47	YES
94	NHP2L1	NHP2L1	NHP2L1	8372	0.036	0.47	NO
95	MAGOHB	MAGOHB	MAGOHB	8510	0.034	0.46	NO
96	LSM3	LSM3	LSM3	8781	0.03	0.45	NO
97	SF3B14	SF3B14	SF3B14	8972	0.027	0.44	NO
98	SNRNP27	SNRNP27	SNRNP27	9139	0.024	0.44	NO
99	PRPF18	PRPF18	PRPF18	9283	0.022	0.43	NO
100	CDC40	CDC40	CDC40	9307	0.022	0.43	NO
101	HNRNPK	HNRNPK	HNRNPK	9311	0.022	0.44	NO
102	RBM25	RBM25	RBM25	9339	0.021	0.44	NO
103	SF3A1	SF3A1	SF3A1	9362	0.021	0.44	NO
104	DHX16	DHX16	DHX16	9553	0.018	0.43	NO
105	SF3B1	SF3B1	SF3B1	9564	0.018	0.43	NO
106	SNRPD3	SNRPD3	SNRPD3	9717	0.016	0.42	NO
107	SLU7	SLU7	SLU7	9741	0.015	0.42	NO
108	DDX46	DDX46	DDX46	9823	0.014	0.42	NO
109	DDX5	DDX5	DDX5	10079	0.01	0.41	NO
110	XAB2	XAB2	XAB2	10112	0.0096	0.41	NO
111	DDX42	DDX42	DDX42	10354	0.006	0.39	NO
112	SFRS6	SFRS6	SFRS6	10410	0.0052	0.39	NO
113	SNW1	SNW1	SNW1	10530	0.0035	0.38	NO
114	PRPF8	PRPF8	PRPF8	10681	0.0011	0.38	NO
115	CWC15	CWC15	CWC15	10695	0.00074	0.38	NO
116	AQR	AQR	AQR	10841	-0.0018	0.37	NO
117	WBP11	WBP11	WBP11	11073	-0.0052	0.36	NO
118	ZMAT2	ZMAT2	ZMAT2	11132	-0.0063	0.35	NO
119	PCBP1	PCBP1	PCBP1	11283	-0.0088	0.35	NO
120	CDC5L	CDC5L	CDC5L	11351	-0.01	0.34	NO
121	SFRS2B	SFRS2B	SFRS2B	11468	-0.012	0.34	NO
122	CHERP	CHERP	CHERP	11887	-0.02	0.32	NO
123	CTNNBL1	CTNNBL1	CTNNBL1	12228	-0.027	0.3	NO
124	HSPA1L	HSPA1L	HSPA1L	13019	-0.044	0.26	NO
125	SFRS5	SFRS5	SFRS5	13484	-0.054	0.24	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 G1 PATHWAY.

Figure S2. 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 FMLP 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	CARD18	CARD18	CARD18	150	0.51	0.048	YES
2	CASP5	CASP5	CASP5	267	0.46	0.092	YES
3	MAPK13	MAPK13	MAPK13	296	0.45	0.14	YES
4	IL1B	IL1B	IL1B	484	0.4	0.17	YES
5	CXCL1	CXCL1	CXCL1	493	0.4	0.22	YES
6	IL18	IL18	IL18	507	0.4	0.26	YES
7	CCL13	CCL13	CCL13	670	0.36	0.29	YES
8	PYCARD	PYCARD	PYCARD	866	0.33	0.32	YES
9	PSTPIP1	PSTPIP1	PSTPIP1	919	0.33	0.35	YES
10	CARD9	CARD9	CARD9	960	0.32	0.38	YES
11	IL8	IL8	IL8	961	0.32	0.42	YES
12	BIRC3	BIRC3	BIRC3	1069	0.31	0.45	YES
13	NLRC4	NLRC4	NLRC4	1118	0.3	0.48	YES
14	NOD2	NOD2	NOD2	1277	0.29	0.5	YES
15	TNF	TNF	TNF	1415	0.28	0.52	YES
16	CASP1	CASP1	CASP1	1440	0.27	0.55	YES
17	CARD6	CARD6	CARD6	1662	0.26	0.57	YES
18	CCL5	CCL5	CCL5	1712	0.25	0.59	YES
19	CCL8	CCL8	CCL8	1912	0.24	0.61	YES
20	RIPK2	RIPK2	RIPK2	1924	0.24	0.63	YES
21	NLRP3	NLRP3	NLRP3	2111	0.22	0.65	YES
22	MEFV	MEFV	MEFV	2200	0.22	0.66	YES
23	NAIP	NAIP	NAIP	3493	0.15	0.61	NO
24	NLRP1	NLRP1	NLRP1	4241	0.12	0.58	NO
25	CASP8	CASP8	CASP8	4782	0.11	0.56	NO
26	MAPK3	MAPK3	MAPK3	5160	0.097	0.55	NO
27	MAP3K7	MAP3K7	MAP3K7	5288	0.094	0.55	NO
28	MAPK12	MAPK12	MAPK12	5299	0.094	0.56	NO
29	NOD1	NOD1	NOD1	5551	0.088	0.56	NO
30	IKBKG	IKBKG	IKBKG	5602	0.086	0.57	NO
31	IL6	IL6	IL6	6099	0.076	0.55	NO
32	NFKBIB	NFKBIB	NFKBIB	6333	0.071	0.54	NO
33	HSP90AA1	HSP90AA1	HSP90AA1	7828	0.045	0.46	NO
34	HSP90B1	HSP90B1	HSP90B1	7979	0.042	0.46	NO
35	TNFAIP3	TNFAIP3	TNFAIP3	8261	0.038	0.44	NO
36	SUGT1	SUGT1	SUGT1	8658	0.032	0.43	NO
37	IKBKB	IKBKB	IKBKB	9388	0.02	0.39	NO
38	RELA	RELA	RELA	9629	0.017	0.38	NO
39	CCL2	CCL2	CCL2	10060	0.01	0.35	NO
40	CXCL2	CXCL2	CXCL2	10125	0.0093	0.35	NO
41	NFKB1	NFKB1	NFKB1	10302	0.0068	0.34	NO
42	XIAP	XIAP	XIAP	10333	0.0065	0.34	NO
43	MAPK14	MAPK14	MAPK14	11276	-0.0086	0.29	NO
44	MAPK9	MAPK9	MAPK9	11388	-0.011	0.28	NO
45	BIRC2	BIRC2	BIRC2	11472	-0.012	0.28	NO
46	MAPK1	MAPK1	MAPK1	11544	-0.014	0.28	NO
47	ERBB2IP	ERBB2IP	ERBB2IP	11785	-0.018	0.26	NO
48	CARD8	CARD8	CARD8	11806	-0.019	0.27	NO
49	TAB2	TAB2	TAB2	12081	-0.024	0.25	NO
50	TAB3	TAB3	TAB3	12197	-0.027	0.25	NO
51	TRIP6	TRIP6	TRIP6	12531	-0.033	0.23	NO
52	TAB1	TAB1	TAB1	12765	-0.038	0.22	NO
53	CHUK	CHUK	CHUK	13711	-0.061	0.18	NO
54	CCL11	CCL11	CCL11	13758	-0.062	0.18	NO
55	MAPK11	MAPK11	MAPK11	13806	-0.064	0.19	NO
56	TRAF6	TRAF6	TRAF6	13929	-0.068	0.19	NO
57	NFKBIA	NFKBIA	NFKBIA	13964	-0.069	0.19	NO
58	MAPK10	MAPK10	MAPK10	14152	-0.075	0.19	NO
59	MAPK8	MAPK8	MAPK8	14946	-0.1	0.16	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 FMLP PATHWAY.

Figure S4. 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: BIOCARTA MPR 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	E2F2	E2F2	E2F2	32	0.61	0.026	YES
2	CDC20	CDC20	CDC20	37	0.61	0.053	YES
3	ORC1L	ORC1L	ORC1L	54	0.59	0.079	YES
4	TTK	TTK	TTK	72	0.56	0.1	YES
5	ORC6L	ORC6L	ORC6L	87	0.55	0.13	YES
6	CDC25A	CDC25A	CDC25A	107	0.54	0.15	YES
7	PLK1	PLK1	PLK1	109	0.53	0.18	YES
8	PKMYT1	PKMYT1	PKMYT1	115	0.53	0.2	YES
9	CDC45	CDC45	CDC45	121	0.52	0.22	YES
10	BUB1B	BUB1B	BUB1B	124	0.52	0.24	YES
11	BUB1	BUB1	BUB1	134	0.52	0.27	YES
12	PTTG1	PTTG1	PTTG1	138	0.51	0.29	YES
13	CDC25C	CDC25C	CDC25C	182	0.49	0.31	YES
14	CCNB2	CCNB2	CCNB2	276	0.45	0.33	YES
15	CDC6	CDC6	CDC6	285	0.45	0.35	YES
16	CDC7	CDC7	CDC7	315	0.44	0.36	YES
17	CDKN2A	CDKN2A	CDKN2A	417	0.42	0.38	YES
18	CDK1	CDK1	CDK1	427	0.41	0.4	YES
19	CCNB1	CCNB1	CCNB1	440	0.41	0.41	YES
20	CCNE1	CCNE1	CCNE1	461	0.41	0.43	YES
21	MAD2L1	MAD2L1	MAD2L1	464	0.41	0.45	YES
22	SFN	SFN	SFN	523	0.39	0.46	YES
23	PTTG2	PTTG2	PTTG2	592	0.38	0.48	YES
24	CCNE2	CCNE2	CCNE2	594	0.38	0.49	YES
25	CCNA2	CCNA2	CCNA2	761	0.35	0.5	YES
26	ESPL1	ESPL1	ESPL1	827	0.34	0.51	YES
27	SMC1B	SMC1B	SMC1B	840	0.34	0.53	YES
28	CHEK1	CHEK1	CHEK1	988	0.32	0.53	YES
29	MCM2	MCM2	MCM2	1208	0.3	0.53	YES
30	E2F5	E2F5	E2F5	1252	0.29	0.54	YES
31	E2F1	E2F1	E2F1	1302	0.29	0.55	YES
32	RBL1	RBL1	RBL1	1350	0.28	0.56	YES
33	CDC25B	CDC25B	CDC25B	1373	0.28	0.58	YES
34	CDC14A	CDC14A	CDC14A	1941	0.24	0.55	YES
35	CDKN2C	CDKN2C	CDKN2C	2020	0.23	0.56	YES
36	MCM4	MCM4	MCM4	2087	0.22	0.57	YES
37	MCM6	MCM6	MCM6	2125	0.22	0.57	YES
38	MCM7	MCM7	MCM7	2363	0.2	0.57	YES
39	CDKN2D	CDKN2D	CDKN2D	2541	0.2	0.57	YES
40	E2F3	E2F3	E2F3	2796	0.18	0.56	YES
41	CDKN2B	CDKN2B	CDKN2B	2900	0.18	0.56	YES
42	MAD2L2	MAD2L2	MAD2L2	2940	0.17	0.57	YES
43	MCM5	MCM5	MCM5	3202	0.16	0.56	YES
44	MCM3	MCM3	MCM3	3252	0.16	0.57	YES
45	CDK4	CDK4	CDK4	3642	0.14	0.55	YES
46	ZBTB17	ZBTB17	ZBTB17	3685	0.14	0.56	YES
47	SKP2	SKP2	SKP2	3712	0.14	0.56	YES
48	CCNA1	CCNA1	CCNA1	3776	0.14	0.56	YES
49	CHEK2	CHEK2	CHEK2	3777	0.14	0.57	YES
50	TGFB1	TGFB1	TGFB1	3846	0.14	0.57	YES
51	HDAC2	HDAC2	HDAC2	3995	0.13	0.57	YES
52	HDAC1	HDAC1	HDAC1	4063	0.13	0.57	YES
53	CDK2	CDK2	CDK2	4189	0.12	0.57	YES
54	YWHAZ	YWHAZ	YWHAZ	4191	0.12	0.58	YES
55	PCNA	PCNA	PCNA	4203	0.12	0.58	YES
56	ANAPC7	ANAPC7	ANAPC7	4525	0.12	0.57	NO
57	PRKDC	PRKDC	PRKDC	4906	0.1	0.55	NO
58	E2F4	E2F4	E2F4	5060	0.1	0.55	NO
59	CCND2	CCND2	CCND2	5106	0.098	0.55	NO
60	TFDP2	TFDP2	TFDP2	5126	0.098	0.55	NO
61	RAD21	RAD21	RAD21	5823	0.082	0.52	NO
62	CDC27	CDC27	CDC27	6213	0.074	0.5	NO
63	ANAPC11	ANAPC11	ANAPC11	6422	0.069	0.49	NO
64	CCND3	CCND3	CCND3	6557	0.067	0.48	NO
65	ANAPC4	ANAPC4	ANAPC4	6645	0.065	0.48	NO
66	BUB3	BUB3	BUB3	6709	0.064	0.48	NO
67	ORC2L	ORC2L	ORC2L	6785	0.063	0.48	NO
68	ATR	ATR	ATR	7043	0.058	0.47	NO
69	YWHAQ	YWHAQ	YWHAQ	7052	0.058	0.47	NO
70	TGFB2	TGFB2	TGFB2	7146	0.056	0.47	NO
71	SMC1A	SMC1A	SMC1A	7338	0.053	0.46	NO
72	ORC4L	ORC4L	ORC4L	7383	0.052	0.46	NO
73	ANAPC1	ANAPC1	ANAPC1	7388	0.052	0.46	NO
74	YWHAB	YWHAB	YWHAB	7528	0.05	0.46	NO
75	ANAPC5	ANAPC5	ANAPC5	7577	0.049	0.46	NO
76	SMAD2	SMAD2	SMAD2	7750	0.047	0.45	NO
77	RBX1	RBX1	RBX1	7795	0.046	0.45	NO
78	MYC	MYC	MYC	7910	0.044	0.44	NO
79	CDC26	CDC26	CDC26	8124	0.04	0.43	NO
80	YWHAH	YWHAH	YWHAH	8161	0.04	0.43	NO
81	ATM	ATM	ATM	8223	0.038	0.43	NO
82	TFDP1	TFDP1	TFDP1	8296	0.037	0.43	NO
83	CDK7	CDK7	CDK7	8447	0.035	0.42	NO
84	CDKN1C	CDKN1C	CDKN1C	8503	0.034	0.42	NO
85	ABL1	ABL1	ABL1	8520	0.034	0.42	NO
86	YWHAG	YWHAG	YWHAG	8613	0.032	0.42	NO
87	WEE1	WEE1	WEE1	8696	0.031	0.41	NO
88	CDC23	CDC23	CDC23	8771	0.03	0.41	NO
89	ORC5L	ORC5L	ORC5L	8875	0.028	0.41	NO
90	CDK6	CDK6	CDK6	9179	0.024	0.39	NO
91	YWHAE	YWHAE	YWHAE	9643	0.017	0.36	NO
92	ORC3L	ORC3L	ORC3L	9681	0.016	0.36	NO
93	MAD1L1	MAD1L1	MAD1L1	9918	0.013	0.35	NO
94	CDC16	CDC16	CDC16	9966	0.012	0.35	NO
95	CCNH	CCNH	CCNH	10134	0.0092	0.34	NO
96	STAG2	STAG2	STAG2	10240	0.0076	0.33	NO
97	SKP1	SKP1	SKP1	10464	0.0046	0.32	NO
98	ANAPC13	ANAPC13	ANAPC13	10774	-0.00071	0.3	NO
99	SMC3	SMC3	SMC3	10862	-0.0021	0.3	NO
100	CUL1	CUL1	CUL1	10916	-0.003	0.3	NO
101	GSK3B	GSK3B	GSK3B	11142	-0.0065	0.28	NO
102	ANAPC2	ANAPC2	ANAPC2	11446	-0.012	0.27	NO
103	SMAD4	SMAD4	SMAD4	11504	-0.013	0.26	NO
104	CREBBP	CREBBP	CREBBP	11627	-0.015	0.26	NO
105	MDM2	MDM2	MDM2	11919	-0.021	0.24	NO
106	WEE2	WEE2	WEE2	12026	-0.023	0.24	NO
107	ANAPC10	ANAPC10	ANAPC10	12098	-0.025	0.23	NO
108	RB1	RB1	RB1	12331	-0.029	0.22	NO
109	SMAD3	SMAD3	SMAD3	12611	-0.034	0.21	NO
110	CDKN1B	CDKN1B	CDKN1B	12914	-0.041	0.19	NO
111	FZR1	FZR1	FZR1	12932	-0.042	0.19	NO
112	STAG1	STAG1	STAG1	13002	-0.043	0.19	NO
113	EP300	EP300	EP300	13199	-0.048	0.18	NO
114	TGFB3	TGFB3	TGFB3	13305	-0.05	0.18	NO
115	TP53	TP53	TP53	13942	-0.068	0.14	NO
116	CDKN1A	CDKN1A	CDKN1A	14166	-0.076	0.14	NO
117	RBL2	RBL2	RBL2	15377	-0.12	0.073	NO
118	CCND1	CCND1	CCND1	15819	-0.14	0.054	NO
119	CCNB3	CCNB3	CCNB3	15847	-0.15	0.06	NO
120	GADD45B	GADD45B	GADD45B	16911	-0.25	0.01	NO
121	GADD45A	GADD45A	GADD45A	16946	-0.26	0.02	NO
122	GADD45G	GADD45G	GADD45G	16977	-0.26	0.03	NO
123	CDC14B	CDC14B	CDC14B	17064	-0.28	0.038	NO

Figure S5. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA MPR PATHWAY.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA MPR 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 TOLL 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	RAD54L	RAD54L	RAD54L	17	0.64	0.13	YES
2	EME1	EME1	EME1	68	0.57	0.24	YES
3	RAD51	RAD51	RAD51	100	0.54	0.35	YES
4	BLM	BLM	BLM	187	0.49	0.44	YES
5	XRCC2	XRCC2	XRCC2	443	0.41	0.51	YES
6	RAD54B	RAD54B	RAD54B	791	0.34	0.56	YES
7	BRCA2	BRCA2	BRCA2	1998	0.23	0.53	YES
8	RAD51L1	RAD51L1	RAD51L1	2148	0.22	0.57	YES
9	XRCC3	XRCC3	XRCC3	2361	0.2	0.6	YES
10	RPA4	RPA4	RPA4	2393	0.2	0.64	YES
11	POLD1	POLD1	POLD1	2456	0.2	0.67	YES
12	POLD3	POLD3	POLD3	3632	0.14	0.64	NO
13	RPA2	RPA2	RPA2	4240	0.12	0.63	NO
14	MRE11A	MRE11A	MRE11A	4254	0.12	0.65	NO
15	RPA3	RPA3	RPA3	5228	0.095	0.62	NO
16	RAD51L3	RAD51L3	RAD51L3	5410	0.091	0.62	NO
17	NBN	NBN	NBN	6172	0.074	0.59	NO
18	SSBP1	SSBP1	SSBP1	6601	0.066	0.58	NO
19	RPA1	RPA1	RPA1	6975	0.059	0.57	NO
20	SHFM1	SHFM1	SHFM1	8539	0.034	0.49	NO
21	MUS81	MUS81	MUS81	8978	0.027	0.47	NO
22	POLD2	POLD2	POLD2	9017	0.026	0.48	NO
23	TOP3A	TOP3A	TOP3A	9301	0.022	0.46	NO
24	TOP3B	TOP3B	TOP3B	10567	0.003	0.39	NO
25	RAD50	RAD50	RAD50	10796	-0.0011	0.38	NO
26	POLD4	POLD4	POLD4	11493	-0.013	0.34	NO
27	RAD52	RAD52	RAD52	12851	-0.04	0.28	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 TOLL PATHWAY.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TOLL 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 RNA DEGRADATION

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	POLE2	POLE2	POLE2	795	0.34	0.02	YES
2	MCM2	MCM2	MCM2	1208	0.3	0.052	YES
3	PRIM1	PRIM1	PRIM1	1446	0.27	0.09	YES
4	RFC4	RFC4	RFC4	1606	0.26	0.13	YES
5	DNA2	DNA2	DNA2	2035	0.23	0.15	YES
6	POLA2	POLA2	POLA2	2068	0.23	0.19	YES
7	MCM4	MCM4	MCM4	2087	0.22	0.23	YES
8	RNASEH2A	RNASEH2A	RNASEH2A	2123	0.22	0.27	YES
9	MCM6	MCM6	MCM6	2125	0.22	0.31	YES
10	PRIM2	PRIM2	PRIM2	2315	0.21	0.34	YES
11	MCM7	MCM7	MCM7	2363	0.2	0.38	YES
12	RPA4	RPA4	RPA4	2393	0.2	0.41	YES
13	FEN1	FEN1	FEN1	2445	0.2	0.45	YES
14	POLD1	POLD1	POLD1	2456	0.2	0.48	YES
15	POLE4	POLE4	POLE4	2998	0.17	0.49	YES
16	MCM5	MCM5	MCM5	3202	0.16	0.51	YES
17	MCM3	MCM3	MCM3	3252	0.16	0.53	YES
18	RFC3	RFC3	RFC3	3562	0.15	0.54	YES
19	POLD3	POLD3	POLD3	3632	0.14	0.57	YES
20	LIG1	LIG1	LIG1	4076	0.13	0.57	YES
21	RFC2	RFC2	RFC2	4126	0.13	0.59	YES
22	PCNA	PCNA	PCNA	4203	0.12	0.61	YES
23	RPA2	RPA2	RPA2	4240	0.12	0.63	YES
24	RFC5	RFC5	RFC5	4800	0.11	0.62	YES
25	POLE3	POLE3	POLE3	5119	0.098	0.62	YES
26	RPA3	RPA3	RPA3	5228	0.095	0.63	YES
27	RNASEH2B	RNASEH2B	RNASEH2B	5972	0.079	0.6	NO
28	RNASEH1	RNASEH1	RNASEH1	6474	0.068	0.59	NO
29	SSBP1	SSBP1	SSBP1	6601	0.066	0.59	NO
30	POLE	POLE	POLE	6647	0.065	0.6	NO
31	RPA1	RPA1	RPA1	6975	0.059	0.59	NO
32	RNASEH2C	RNASEH2C	RNASEH2C	8869	0.028	0.49	NO
33	POLD2	POLD2	POLD2	9017	0.026	0.49	NO
34	RFC1	RFC1	RFC1	10369	0.0057	0.41	NO
35	POLD4	POLD4	POLD4	11493	-0.013	0.35	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 RNA DEGRADATION.

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

genes ES table in pathway: KEGG DNA REPLICATION

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	GNGT1	GNGT1	GNGT1	38	0.61	0.13	YES
2	CDC25C	CDC25C	CDC25C	182	0.49	0.23	YES
3	CDK1	CDK1	CDK1	427	0.41	0.3	YES
4	CCNB1	CCNB1	CCNB1	440	0.41	0.39	YES
5	PAQR5	PAQR5	PAQR5	1029	0.31	0.42	YES
6	PRKAR2B	PRKAR2B	PRKAR2B	1653	0.26	0.44	YES
7	SRC	SRC	SRC	2094	0.22	0.47	YES
8	RPS6KA1	RPS6KA1	RPS6KA1	2222	0.22	0.51	YES
9	HRAS	HRAS	HRAS	2849	0.18	0.51	YES
10	ARPC1B	ARPC1B	ARPC1B	3126	0.17	0.53	YES
11	ACTA1	ACTA1	ACTA1	4308	0.12	0.49	NO
12	PRKACB	PRKACB	PRKACB	4849	0.1	0.48	NO
13	ARPC3	ARPC3	ARPC3	4978	0.1	0.5	NO
14	MAPK3	MAPK3	MAPK3	5160	0.097	0.51	NO
15	CAP1	CAP1	CAP1	5279	0.094	0.52	NO
16	GNB1	GNB1	GNB1	5744	0.083	0.51	NO
17	ARPC4	ARPC4	ARPC4	6007	0.078	0.52	NO
18	ARPC2	ARPC2	ARPC2	6399	0.07	0.51	NO
19	ACTR3	ACTR3	ACTR3	6746	0.063	0.5	NO
20	ARPC1A	ARPC1A	ARPC1A	7816	0.045	0.45	NO
21	ACTR2	ACTR2	ACTR2	8561	0.033	0.42	NO
22	PGR	PGR	PGR	9435	0.02	0.37	NO
23	ARPC5	ARPC5	ARPC5	10158	0.0088	0.33	NO
24	PAQR7	PAQR7	PAQR7	10427	0.005	0.32	NO
25	PIN1	PIN1	PIN1	11221	-0.0077	0.28	NO
26	MAPK1	MAPK1	MAPK1	11544	-0.014	0.26	NO
27	PRKAR1A	PRKAR1A	PRKAR1A	12070	-0.024	0.24	NO
28	PRKAR2A	PRKAR2A	PRKAR2A	12373	-0.03	0.23	NO
29	GNAS	GNAS	GNAS	13197	-0.048	0.19	NO
30	GNAI1	GNAI1	GNAI1	13286	-0.05	0.2	NO
31	PRKAR1B	PRKAR1B	PRKAR1B	14035	-0.071	0.17	NO
32	MYT1	MYT1	MYT1	16310	-0.18	0.08	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 DNA REPLICATION.

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

genes ES table in pathway: KEGG SPLICEOSOME

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	GNGT1	GNGT1	GNGT1	38	0.61	0.17	YES
2	PLCB1	PLCB1	PLCB1	535	0.39	0.26	YES
3	NCF2	NCF2	NCF2	1007	0.32	0.32	YES
4	FPR1	FPR1	FPR1	1246	0.29	0.39	YES
5	NCF1C	NCF1C	NCF1C	1487	0.27	0.46	YES
6	MAP2K6	MAP2K6	MAP2K6	1992	0.23	0.5	YES
7	HRAS	HRAS	HRAS	2849	0.18	0.5	YES
8	PAK1	PAK1	PAK1	4100	0.13	0.46	NO
9	PIK3C2G	PIK3C2G	PIK3C2G	4937	0.1	0.45	NO
10	NFATC4	NFATC4	NFATC4	4963	0.1	0.48	NO
11	MAPK3	MAPK3	MAPK3	5160	0.097	0.49	NO
12	GNB1	GNB1	GNB1	5744	0.083	0.48	NO
13	RAC1	RAC1	RAC1	6226	0.073	0.48	NO
14	MAP3K1	MAP3K1	MAP3K1	6381	0.07	0.49	NO
15	CAMK1G	CAMK1G	CAMK1G	7022	0.058	0.47	NO
16	MAP2K2	MAP2K2	MAP2K2	7689	0.048	0.44	NO
17	CALM3	CALM3	CALM3	8302	0.037	0.42	NO
18	CALM2	CALM2	CALM2	8639	0.032	0.41	NO
19	PPP3CA	PPP3CA	PPP3CA	8849	0.029	0.41	NO
20	NFATC1	NFATC1	NFATC1	8895	0.028	0.41	NO
21	CAMK1	CAMK1	CAMK1	9341	0.021	0.39	NO
22	PPP3CC	PPP3CC	PPP3CC	9383	0.021	0.4	NO
23	RELA	RELA	RELA	9629	0.017	0.39	NO
24	PPP3CB	PPP3CB	PPP3CB	10246	0.0076	0.36	NO
25	NFKB1	NFKB1	NFKB1	10302	0.0068	0.36	NO
26	ELK1	ELK1	ELK1	10634	0.0019	0.34	NO
27	RAF1	RAF1	RAF1	11143	-0.0065	0.31	NO
28	MAP2K1	MAP2K1	MAP2K1	11250	-0.0082	0.31	NO
29	MAPK14	MAPK14	MAPK14	11276	-0.0086	0.31	NO
30	MAPK1	MAPK1	MAPK1	11544	-0.014	0.3	NO
31	MAP2K3	MAP2K3	MAP2K3	11653	-0.016	0.3	NO
32	NFATC3	NFATC3	NFATC3	11672	-0.016	0.3	NO
33	CALM1	CALM1	CALM1	12528	-0.033	0.26	NO
34	NFATC2	NFATC2	NFATC2	13238	-0.049	0.23	NO
35	NFKBIA	NFKBIA	NFKBIA	13964	-0.069	0.21	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 SPLICEOSOME.

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

genes ES table in pathway: KEGG BASE EXCISION REPAIR

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	CDC20	CDC20	CDC20	37	0.61	0.036	YES
2	SGOL1	SGOL1	SGOL1	84	0.55	0.069	YES
3	PLK1	PLK1	PLK1	109	0.53	0.1	YES
4	PKMYT1	PKMYT1	PKMYT1	115	0.53	0.13	YES
5	BUB1	BUB1	BUB1	134	0.52	0.17	YES
6	PTTG1	PTTG1	PTTG1	138	0.51	0.2	YES
7	CDC25C	CDC25C	CDC25C	182	0.49	0.23	YES
8	CCNB2	CCNB2	CCNB2	276	0.45	0.25	YES
9	CDK1	CDK1	CDK1	427	0.41	0.27	YES
10	FBXO43	FBXO43	FBXO43	430	0.41	0.29	YES
11	CCNB1	CCNB1	CCNB1	440	0.41	0.32	YES
12	CCNE1	CCNE1	CCNE1	461	0.41	0.34	YES
13	MAD2L1	MAD2L1	MAD2L1	464	0.41	0.37	YES
14	PTTG2	PTTG2	PTTG2	592	0.38	0.38	YES
15	FBXO5	FBXO5	FBXO5	593	0.38	0.41	YES
16	CCNE2	CCNE2	CCNE2	594	0.38	0.43	YES
17	ESPL1	ESPL1	ESPL1	827	0.34	0.44	YES
18	SMC1B	SMC1B	SMC1B	840	0.34	0.46	YES
19	ITPR3	ITPR3	ITPR3	1274	0.29	0.46	NO
20	AURKA	AURKA	AURKA	1861	0.24	0.44	NO
21	SPDYA	SPDYA	SPDYA	2031	0.23	0.44	NO
22	RPS6KA1	RPS6KA1	RPS6KA1	2222	0.22	0.44	NO
23	REC8	REC8	REC8	2431	0.2	0.45	NO
24	RPS6KA6	RPS6KA6	RPS6KA6	2691	0.19	0.44	NO
25	MAD2L2	MAD2L2	MAD2L2	2940	0.17	0.44	NO
26	CHP2	CHP2	CHP2	3053	0.17	0.44	NO
27	ADCY7	ADCY7	ADCY7	4061	0.13	0.4	NO
28	CDK2	CDK2	CDK2	4189	0.12	0.4	NO
29	YWHAZ	YWHAZ	YWHAZ	4191	0.12	0.4	NO
30	PPP1CC	PPP1CC	PPP1CC	4477	0.12	0.4	NO
31	ANAPC7	ANAPC7	ANAPC7	4525	0.12	0.4	NO
32	PRKACB	PRKACB	PRKACB	4849	0.1	0.39	NO
33	MAPK3	MAPK3	MAPK3	5160	0.097	0.38	NO
34	PRKX	PRKX	PRKX	5275	0.094	0.38	NO
35	MAPK12	MAPK12	MAPK12	5299	0.094	0.38	NO
36	CDC27	CDC27	CDC27	6213	0.074	0.33	NO
37	ITPR1	ITPR1	ITPR1	6264	0.072	0.34	NO
38	RPS6KA3	RPS6KA3	RPS6KA3	6306	0.072	0.34	NO
39	ANAPC11	ANAPC11	ANAPC11	6422	0.069	0.34	NO
40	PPP1CA	PPP1CA	PPP1CA	6492	0.068	0.34	NO
41	ANAPC4	ANAPC4	ANAPC4	6645	0.065	0.33	NO
42	CPEB1	CPEB1	CPEB1	6696	0.064	0.33	NO
43	YWHAQ	YWHAQ	YWHAQ	7052	0.058	0.32	NO
44	PPP2R1A	PPP2R1A	PPP2R1A	7316	0.053	0.3	NO
45	SMC1A	SMC1A	SMC1A	7338	0.053	0.31	NO
46	ANAPC1	ANAPC1	ANAPC1	7388	0.052	0.31	NO
47	YWHAB	YWHAB	YWHAB	7528	0.05	0.3	NO
48	ANAPC5	ANAPC5	ANAPC5	7577	0.049	0.3	NO
49	RBX1	RBX1	RBX1	7795	0.046	0.29	NO
50	CDC26	CDC26	CDC26	8124	0.04	0.28	NO
51	YWHAH	YWHAH	YWHAH	8161	0.04	0.28	NO
52	CALM3	CALM3	CALM3	8302	0.037	0.27	NO
53	PPP2CA	PPP2CA	PPP2CA	8472	0.035	0.26	NO
54	PPP1CB	PPP1CB	PPP1CB	8515	0.034	0.26	NO
55	YWHAG	YWHAG	YWHAG	8613	0.032	0.26	NO
56	CALM2	CALM2	CALM2	8639	0.032	0.26	NO
57	CDC23	CDC23	CDC23	8771	0.03	0.26	NO
58	PPP3CA	PPP3CA	PPP3CA	8849	0.029	0.25	NO
59	PPP2R5E	PPP2R5E	PPP2R5E	8859	0.028	0.25	NO
60	PPP2R5D	PPP2R5D	PPP2R5D	8998	0.026	0.25	NO
61	PPP2R5B	PPP2R5B	PPP2R5B	9309	0.022	0.23	NO
62	PPP3CC	PPP3CC	PPP3CC	9383	0.021	0.23	NO
63	PGR	PGR	PGR	9435	0.02	0.23	NO
64	YWHAE	YWHAE	YWHAE	9643	0.017	0.22	NO
65	CDC16	CDC16	CDC16	9966	0.012	0.2	NO
66	PPP3CB	PPP3CB	PPP3CB	10246	0.0076	0.18	NO
67	SKP1	SKP1	SKP1	10464	0.0046	0.17	NO
68	FBXW11	FBXW11	FBXW11	10468	0.0046	0.17	NO
69	IGF1R	IGF1R	IGF1R	10541	0.0033	0.17	NO
70	ANAPC13	ANAPC13	ANAPC13	10774	-0.00071	0.16	NO
71	ADCY6	ADCY6	ADCY6	10805	-0.0012	0.15	NO
72	SMC3	SMC3	SMC3	10862	-0.0021	0.15	NO
73	CUL1	CUL1	CUL1	10916	-0.003	0.15	NO
74	CALML3	CALML3	CALML3	11111	-0.0059	0.14	NO
75	MAP2K1	MAP2K1	MAP2K1	11250	-0.0082	0.13	NO
76	CAMK2D	CAMK2D	CAMK2D	11305	-0.0091	0.13	NO
77	ANAPC2	ANAPC2	ANAPC2	11446	-0.012	0.12	NO
78	MAPK1	MAPK1	MAPK1	11544	-0.014	0.12	NO
79	PPP3R1	PPP3R1	PPP3R1	11687	-0.016	0.11	NO
80	PPP2CB	PPP2CB	PPP2CB	12034	-0.023	0.09	NO
81	ANAPC10	ANAPC10	ANAPC10	12098	-0.025	0.088	NO
82	CALM1	CALM1	CALM1	12528	-0.033	0.065	NO
83	CAMK2G	CAMK2G	CAMK2G	12892	-0.041	0.047	NO
84	SLK	SLK	SLK	12928	-0.042	0.048	NO
85	BTRC	BTRC	BTRC	13100	-0.046	0.041	NO
86	PPP2R5C	PPP2R5C	PPP2R5C	13147	-0.046	0.042	NO
87	ADCY2	ADCY2	ADCY2	13629	-0.058	0.018	NO
88	PPP2R5A	PPP2R5A	PPP2R5A	14262	-0.078	-0.013	NO
89	PRKACA	PRKACA	PRKACA	14493	-0.086	-0.021	NO
90	ADCY9	ADCY9	ADCY9	14637	-0.09	-0.023	NO
91	ADCY5	ADCY5	ADCY5	15131	-0.11	-0.044	NO
92	CHP	CHP	CHP	15151	-0.11	-0.038	NO
93	PPP2R1B	PPP2R1B	PPP2R1B	15173	-0.11	-0.032	NO
94	CALML6	CALML6	CALML6	15807	-0.14	-0.059	NO
95	CAMK2A	CAMK2A	CAMK2A	15907	-0.15	-0.055	NO
96	ADCY8	ADCY8	ADCY8	15987	-0.16	-0.05	NO
97	STAG3	STAG3	STAG3	16042	-0.16	-0.042	NO
98	IGF1	IGF1	IGF1	16430	-0.2	-0.052	NO
99	ITPR2	ITPR2	ITPR2	16601	-0.21	-0.048	NO
100	ADCY1	ADCY1	ADCY1	16664	-0.22	-0.038	NO
101	RPS6KA2	RPS6KA2	RPS6KA2	16863	-0.24	-0.034	NO
102	SPDYC	SPDYC	SPDYC	16990	-0.26	-0.024	NO
103	AR	AR	AR	17279	-0.31	-0.021	NO
104	CAMK2B	CAMK2B	CAMK2B	17306	-0.32	-0.0022	NO
105	ADCY4	ADCY4	ADCY4	17572	-0.41	0.0088	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 BASE EXCISION REPAIR.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG BASE EXCISION REPAIR, 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 NUCLEOTIDE EXCISION REPAIR

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	ENO2	ENO2	ENO2	129	0.52	0.11	YES
2	ENO1	ENO1	ENO1	2345	0.21	0.036	YES
3	CNOT6	CNOT6	CNOT6	3311	0.16	0.018	YES
4	NAA38	NAA38	NAA38	3975	0.13	0.012	YES
5	MPHOSPH6	MPHOSPH6	MPHOSPH6	4124	0.13	0.033	YES
6	RQCD1	RQCD1	RQCD1	4220	0.12	0.057	YES
7	EXOSC2	EXOSC2	EXOSC2	4264	0.12	0.083	YES
8	LSM2	LSM2	LSM2	4491	0.12	0.097	YES
9	EXOSC3	EXOSC3	EXOSC3	4556	0.11	0.12	YES
10	EXOSC10	EXOSC10	EXOSC10	4567	0.11	0.15	YES
11	EXOSC9	EXOSC9	EXOSC9	5012	0.1	0.14	YES
12	EXOSC8	EXOSC8	EXOSC8	5056	0.1	0.16	YES
13	CNOT3	CNOT3	CNOT3	5186	0.096	0.18	YES
14	EDC4	EDC4	EDC4	5290	0.094	0.2	YES
15	DCP2	DCP2	DCP2	5369	0.092	0.21	YES
16	CNOT10	CNOT10	CNOT10	5383	0.091	0.23	YES
17	EXOSC4	EXOSC4	EXOSC4	5459	0.09	0.25	YES
18	EXOSC5	EXOSC5	EXOSC5	5532	0.088	0.27	YES
19	DCP1A	DCP1A	DCP1A	5743	0.084	0.28	YES
20	LSM7	LSM7	LSM7	5882	0.08	0.29	YES
21	LSM5	LSM5	LSM5	6274	0.072	0.28	YES
22	LSM4	LSM4	LSM4	6445	0.069	0.29	YES
23	EDC3	EDC3	EDC3	6563	0.067	0.3	YES
24	ZCCHC7	ZCCHC7	ZCCHC7	7014	0.058	0.28	YES
25	EXOSC7	EXOSC7	EXOSC7	7091	0.057	0.29	YES
26	CNOT2	CNOT2	CNOT2	7245	0.054	0.3	YES
27	PARN	PARN	PARN	7443	0.051	0.3	YES
28	EXOSC1	EXOSC1	EXOSC1	7487	0.051	0.31	YES
29	SKIV2L	SKIV2L	SKIV2L	7532	0.05	0.32	YES
30	EXOSC6	EXOSC6	EXOSC6	7681	0.048	0.32	YES
31	PNPT1	PNPT1	PNPT1	7732	0.047	0.33	YES
32	LSM6	LSM6	LSM6	7983	0.042	0.32	YES
33	HSPD1	HSPD1	HSPD1	8059	0.041	0.33	YES
34	PAPOLG	PAPOLG	PAPOLG	8106	0.04	0.34	YES
35	LSM1	LSM1	LSM1	8335	0.037	0.33	YES
36	CNOT1	CNOT1	CNOT1	8407	0.036	0.34	YES
37	SKIV2L2	SKIV2L2	SKIV2L2	8650	0.032	0.33	YES
38	CNOT7	CNOT7	CNOT7	8739	0.03	0.33	YES
39	LSM3	LSM3	LSM3	8781	0.03	0.34	YES
40	DCPS	DCPS	DCPS	8949	0.027	0.33	YES
41	PAPOLA	PAPOLA	PAPOLA	8976	0.027	0.34	YES
42	XRN2	XRN2	XRN2	9344	0.021	0.32	NO
43	PATL1	PATL1	PATL1	10432	0.005	0.26	NO
44	CNOT4	CNOT4	CNOT4	10698	0.00066	0.25	NO
45	DIS3	DIS3	DIS3	11265	-0.0085	0.22	NO
46	DDX6	DDX6	DDX6	11338	-0.0098	0.21	NO
47	HSPA9	HSPA9	HSPA9	11706	-0.017	0.2	NO
48	XRN1	XRN1	XRN1	12112	-0.025	0.18	NO
49	DCP1B	DCP1B	DCP1B	12338	-0.029	0.17	NO
50	C1D	C1D	C1D	12406	-0.03	0.18	NO
51	WDR61	WDR61	WDR61	12807	-0.039	0.16	NO
52	PAPD7	PAPD7	PAPD7	13426	-0.053	0.14	NO
53	TTC37	TTC37	TTC37	13831	-0.064	0.13	NO
54	CNOT6L	CNOT6L	CNOT6L	14602	-0.089	0.11	NO
55	ENO3	ENO3	ENO3	17127	-0.29	0.034	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 NUCLEOTIDE EXCISION REPAIR.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG NUCLEOTIDE EXCISION REPAIR, 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 HOMOLOGOUS RECOMBINATION

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	CDC25A	CDC25A	CDC25A	107	0.54	0.15	YES
2	CDKN2A	CDKN2A	CDKN2A	417	0.42	0.25	YES
3	CDK1	CDK1	CDK1	427	0.41	0.37	YES
4	CCNE1	CCNE1	CCNE1	461	0.41	0.48	YES
5	CDKN2B	CDKN2B	CDKN2B	2900	0.18	0.39	YES
6	CDK4	CDK4	CDK4	3642	0.14	0.39	YES
7	SKP2	SKP2	SKP2	3712	0.14	0.43	YES
8	CCNA1	CCNA1	CCNA1	3776	0.14	0.47	YES
9	TGFB1	TGFB1	TGFB1	3846	0.14	0.5	YES
10	HDAC1	HDAC1	HDAC1	4063	0.13	0.53	YES
11	CDK2	CDK2	CDK2	4189	0.12	0.56	YES
12	ATR	ATR	ATR	7043	0.058	0.41	NO
13	TGFB2	TGFB2	TGFB2	7146	0.056	0.42	NO
14	ATM	ATM	ATM	8223	0.038	0.37	NO
15	TFDP1	TFDP1	TFDP1	8296	0.037	0.38	NO
16	ABL1	ABL1	ABL1	8520	0.034	0.37	NO
17	CDK6	CDK6	CDK6	9179	0.024	0.34	NO
18	DHFR	DHFR	DHFR	9211	0.023	0.35	NO
19	GSK3B	GSK3B	GSK3B	11142	-0.0065	0.24	NO
20	SMAD4	SMAD4	SMAD4	11504	-0.013	0.22	NO
21	RB1	RB1	RB1	12331	-0.029	0.19	NO
22	SMAD3	SMAD3	SMAD3	12611	-0.034	0.18	NO
23	CDKN1B	CDKN1B	CDKN1B	12914	-0.041	0.18	NO
24	TGFB3	TGFB3	TGFB3	13305	-0.05	0.17	NO
25	TP53	TP53	TP53	13942	-0.068	0.15	NO
26	CDKN1A	CDKN1A	CDKN1A	14166	-0.076	0.16	NO
27	CCND1	CCND1	CCND1	15819	-0.14	0.11	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 HOMOLOGOUS RECOMBINATION.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG GLYCOLYSIS GLUCONEOGENESIS	59	genes.ES.table	0.5	1.6	0.018	0.11	0.71	0.37	0.094	0.34	0.064	0.002
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.6	1.7	0.057	0.11	0.45	0.59	0.24	0.44	0	0.008
KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS	26	genes.ES.table	0.72	1.5	0.097	0.19	0.9	0.58	0.15	0.49	0.14	0.004
KEGG FATTY ACID METABOLISM	41	genes.ES.table	0.68	1.6	0.055	0.12	0.69	0.71	0.18	0.58	0.064	0.002
KEGG STEROID HORMONE BIOSYNTHESIS	51	genes.ES.table	0.71	1.6	0.033	0.12	0.73	0.55	0.11	0.49	0.069	0.002
KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM	30	genes.ES.table	0.52	1.4	0.084	0.2	0.92	0.53	0.12	0.47	0.15	0.006
KEGG GLYCINE SERINE AND THREONINE METABOLISM	30	genes.ES.table	0.77	1.7	0.0041	0.093	0.51	0.8	0.18	0.66	0.038	0.002
KEGG CYSTEINE AND METHIONINE METABOLISM	33	genes.ES.table	0.57	1.8	0.0065	0.099	0.35	0.36	0.11	0.32	0	0.012
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.64	1.7	0.034	0.098	0.47	0.74	0.19	0.61	0	0.004
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.58	2	0.0062	0.051	0.043	0.3	0.11	0.27	0	0.019

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AADAT	AADAT	AADAT	32	0.62	0.12	YES
2	BBOX1	BBOX1	BBOX1	39	0.59	0.23	YES
3	AASS	AASS	AASS	165	0.44	0.31	YES
4	OGDHL	OGDHL	OGDHL	410	0.33	0.36	YES
5	PIPOX	PIPOX	PIPOX	530	0.3	0.41	YES
6	GCDH	GCDH	GCDH	1015	0.21	0.43	YES
7	ALDH7A1	ALDH7A1	ALDH7A1	1215	0.19	0.45	YES
8	ALDH2	ALDH2	ALDH2	1372	0.18	0.48	YES
9	ACAT1	ACAT1	ACAT1	1623	0.15	0.49	YES
10	SETD7	SETD7	SETD7	1740	0.14	0.52	YES
11	ACAT2	ACAT2	ACAT2	1797	0.14	0.54	YES
12	ALDH9A1	ALDH9A1	ALDH9A1	1944	0.13	0.56	YES
13	HADH	HADH	HADH	2029	0.13	0.58	YES
14	ALDH1B1	ALDH1B1	ALDH1B1	3156	0.08	0.53	NO
15	ECHS1	ECHS1	ECHS1	3249	0.077	0.54	NO
16	OGDH	OGDH	OGDH	3448	0.07	0.54	NO
17	TMLHE	TMLHE	TMLHE	3741	0.062	0.54	NO
18	PLOD1	PLOD1	PLOD1	4294	0.048	0.52	NO
19	HADHA	HADHA	HADHA	4376	0.046	0.52	NO
20	DLST	DLST	DLST	4728	0.039	0.51	NO
21	SETD2	SETD2	SETD2	4919	0.034	0.5	NO
22	AASDH	AASDH	AASDH	5559	0.023	0.47	NO
23	SUV39H1	SUV39H1	SUV39H1	5727	0.02	0.47	NO
24	SUV420H1	SUV420H1	SUV420H1	6009	0.015	0.45	NO
25	AASDHPPT	AASDHPPT	AASDHPPT	6845	0.0028	0.41	NO
26	ALDH3A2	ALDH3A2	ALDH3A2	8173	-0.016	0.34	NO
27	PLOD3	PLOD3	PLOD3	8245	-0.017	0.33	NO
28	EHMT1	EHMT1	EHMT1	8495	-0.02	0.32	NO
29	SETD1A	SETD1A	SETD1A	8557	-0.022	0.32	NO
30	DOT1L	DOT1L	DOT1L	8752	-0.025	0.32	NO
31	WHSC1L1	WHSC1L1	WHSC1L1	9117	-0.03	0.3	NO
32	ASH1L	ASH1L	ASH1L	9815	-0.04	0.27	NO
33	NSD1	NSD1	NSD1	9898	-0.041	0.28	NO
34	PLOD2	PLOD2	PLOD2	10451	-0.049	0.25	NO
35	SETMAR	SETMAR	SETMAR	10797	-0.055	0.25	NO
36	SETD1B	SETD1B	SETD1B	10937	-0.058	0.25	NO
37	SETDB2	SETDB2	SETDB2	11888	-0.075	0.21	NO
38	WHSC1	WHSC1	WHSC1	12125	-0.08	0.21	NO
39	SETD8	SETD8	SETD8	12301	-0.084	0.22	NO
40	SUV420H2	SUV420H2	SUV420H2	12367	-0.085	0.23	NO
41	SUV39H2	SUV39H2	SUV39H2	13582	-0.12	0.18	NO
42	SETDB1	SETDB1	SETDB1	13661	-0.12	0.2	NO
43	EHMT2	EHMT2	EHMT2	14254	-0.14	0.2	NO

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

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

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACACB	ACACB	ACACB	391	0.34	0.054	YES
2	ALDH6A1	ALDH6A1	ALDH6A1	433	0.32	0.12	YES
3	ABAT	ABAT	ABAT	444	0.32	0.2	YES
4	EHHADH	EHHADH	EHHADH	518	0.3	0.26	YES
5	MUT	MUT	MUT	965	0.22	0.28	YES
6	ACADM	ACADM	ACADM	1075	0.2	0.32	YES
7	ALDH7A1	ALDH7A1	ALDH7A1	1215	0.19	0.36	YES
8	ACSS2	ACSS2	ACSS2	1245	0.19	0.4	YES
9	ALDH2	ALDH2	ALDH2	1372	0.18	0.43	YES
10	LDHAL6B	LDHAL6B	LDHAL6B	1489	0.16	0.46	YES
11	MLYCD	MLYCD	MLYCD	1545	0.16	0.49	YES
12	ACAT1	ACAT1	ACAT1	1623	0.15	0.52	YES
13	ACAT2	ACAT2	ACAT2	1797	0.14	0.55	YES
14	MCEE	MCEE	MCEE	1812	0.14	0.58	YES
15	SUCLG2	SUCLG2	SUCLG2	1865	0.14	0.6	YES
16	PCCA	PCCA	PCCA	1939	0.13	0.63	YES
17	ALDH9A1	ALDH9A1	ALDH9A1	1944	0.13	0.66	YES
18	PCCB	PCCB	PCCB	2299	0.12	0.67	YES
19	HIBCH	HIBCH	HIBCH	2444	0.11	0.68	YES
20	SUCLG1	SUCLG1	SUCLG1	2518	0.1	0.7	YES
21	ACSS3	ACSS3	ACSS3	2884	0.09	0.7	YES
22	ALDH1B1	ALDH1B1	ALDH1B1	3156	0.08	0.7	YES
23	ECHS1	ECHS1	ECHS1	3249	0.077	0.72	YES
24	HADHA	HADHA	HADHA	4376	0.046	0.66	NO
25	LDHA	LDHA	LDHA	7802	-0.011	0.47	NO
26	ALDH3A2	ALDH3A2	ALDH3A2	8173	-0.016	0.45	NO
27	SUCLA2	SUCLA2	SUCLA2	8485	-0.02	0.44	NO
28	LDHAL6A	LDHAL6A	LDHAL6A	9550	-0.036	0.39	NO
29	ACACA	ACACA	ACACA	11225	-0.063	0.31	NO
30	LDHB	LDHB	LDHB	13706	-0.12	0.2	NO
31	ACSS1	ACSS1	ACSS1	14462	-0.14	0.18	NO

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

Figure S24. 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 PENTOSE AND GLUCURONATE INTERCONVERSIONS

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	ACOT12	ACOT12	ACOT12	131	0.47	0.08	YES
2	PCK1	PCK1	PCK1	219	0.41	0.15	YES
3	ACACB	ACACB	ACACB	391	0.34	0.2	YES
4	PCK2	PCK2	PCK2	484	0.31	0.26	YES
5	LDHD	LDHD	LDHD	752	0.25	0.29	YES
6	PKLR	PKLR	PKLR	770	0.25	0.34	YES
7	HAGH	HAGH	HAGH	939	0.22	0.37	YES
8	ALDH7A1	ALDH7A1	ALDH7A1	1215	0.19	0.39	YES
9	ACSS2	ACSS2	ACSS2	1245	0.19	0.42	YES
10	ACYP2	ACYP2	ACYP2	1302	0.18	0.45	YES
11	ALDH2	ALDH2	ALDH2	1372	0.18	0.48	YES
12	LDHAL6B	LDHAL6B	LDHAL6B	1489	0.16	0.51	YES
13	GRHPR	GRHPR	GRHPR	1597	0.16	0.53	YES
14	ACAT1	ACAT1	ACAT1	1623	0.15	0.56	YES
15	ACAT2	ACAT2	ACAT2	1797	0.14	0.57	YES
16	ALDH9A1	ALDH9A1	ALDH9A1	1944	0.13	0.59	YES
17	PC	PC	PC	2328	0.11	0.59	NO
18	ALDH1B1	ALDH1B1	ALDH1B1	3156	0.08	0.56	NO
19	MDH1	MDH1	MDH1	4089	0.052	0.52	NO
20	DLD	DLD	DLD	4182	0.05	0.52	NO
21	PDHB	PDHB	PDHB	4843	0.036	0.49	NO
22	ME1	ME1	ME1	5265	0.028	0.47	NO
23	ME3	ME3	ME3	5324	0.027	0.47	NO
24	GLO1	GLO1	GLO1	5726	0.02	0.45	NO
25	PDHA1	PDHA1	PDHA1	5883	0.017	0.45	NO
26	LDHA	LDHA	LDHA	7802	-0.011	0.34	NO
27	DLAT	DLAT	DLAT	8055	-0.015	0.33	NO
28	ALDH3A2	ALDH3A2	ALDH3A2	8173	-0.016	0.33	NO
29	MDH2	MDH2	MDH2	8710	-0.024	0.3	NO
30	ME2	ME2	ME2	9546	-0.036	0.26	NO
31	LDHAL6A	LDHAL6A	LDHAL6A	9550	-0.036	0.27	NO
32	ACACA	ACACA	ACACA	11225	-0.063	0.18	NO
33	ACYP1	ACYP1	ACYP1	12162	-0.081	0.15	NO
34	AKR1B1	AKR1B1	AKR1B1	12989	-0.099	0.12	NO
35	LDHB	LDHB	LDHB	13706	-0.12	0.1	NO
36	ACSS1	ACSS1	ACSS1	14462	-0.14	0.084	NO
37	PKM2	PKM2	PKM2	16041	-0.22	0.036	NO
38	HAGHL	HAGHL	HAGHL	17036	-0.31	0.039	NO

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

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

genes ES table in pathway: KEGG FATTY ACID METABOLISM

Table 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	HAO2	HAO2	HAO2	7	0.79	0.07	YES
2	XDH	XDH	XDH	38	0.6	0.12	YES
3	DAO	DAO	DAO	94	0.51	0.16	YES
4	SLC27A2	SLC27A2	SLC27A2	269	0.38	0.19	YES
5	AGXT	AGXT	AGXT	276	0.38	0.22	YES
6	PEX11G	PEX11G	PEX11G	406	0.33	0.24	YES
7	HAO1	HAO1	HAO1	473	0.31	0.27	YES
8	EHHADH	EHHADH	EHHADH	518	0.3	0.29	YES
9	PIPOX	PIPOX	PIPOX	530	0.3	0.32	YES
10	EPHX2	EPHX2	EPHX2	552	0.29	0.34	YES
11	ACSL1	ACSL1	ACSL1	582	0.29	0.37	YES
12	PXMP2	PXMP2	PXMP2	605	0.28	0.39	YES
13	SCP2	SCP2	SCP2	760	0.25	0.4	YES
14	BAAT	BAAT	BAAT	824	0.24	0.42	YES
15	NUDT12	NUDT12	NUDT12	899	0.23	0.44	YES
16	NOS2	NOS2	NOS2	923	0.23	0.46	YES
17	CAT	CAT	CAT	991	0.22	0.47	YES
18	DHRS4	DHRS4	DHRS4	1275	0.18	0.47	YES
19	PHYH	PHYH	PHYH	1364	0.18	0.48	YES
20	ACOX1	ACOX1	ACOX1	1382	0.17	0.5	YES
21	MLYCD	MLYCD	MLYCD	1545	0.16	0.5	YES
22	HACL1	HACL1	HACL1	1602	0.16	0.52	YES
23	MPV17L	MPV17L	MPV17L	1676	0.15	0.52	YES
24	PECR	PECR	PECR	1816	0.14	0.53	YES
25	HMGCL	HMGCL	HMGCL	1952	0.13	0.53	YES
26	PECI	PECI	PECI	2114	0.12	0.54	YES
27	DDO	DDO	DDO	2115	0.12	0.55	YES
28	ACAA1	ACAA1	ACAA1	2133	0.12	0.56	YES
29	GSTK1	GSTK1	GSTK1	2156	0.12	0.56	YES
30	PEX1	PEX1	PEX1	2174	0.12	0.57	YES
31	PEX14	PEX14	PEX14	2289	0.12	0.58	YES
32	PEX7	PEX7	PEX7	2387	0.11	0.58	YES
33	PAOX	PAOX	PAOX	2392	0.11	0.59	YES
34	PXMP4	PXMP4	PXMP4	2551	0.1	0.59	YES
35	CRAT	CRAT	CRAT	2874	0.09	0.58	YES
36	SOD1	SOD1	SOD1	2920	0.089	0.59	YES
37	PEX3	PEX3	PEX3	2960	0.088	0.59	YES
38	ACOX3	ACOX3	ACOX3	2985	0.087	0.6	YES
39	SLC25A17	SLC25A17	SLC25A17	3041	0.085	0.6	YES
40	HSD17B4	HSD17B4	HSD17B4	3057	0.084	0.61	YES
41	PEX12	PEX12	PEX12	3070	0.083	0.62	YES
42	PEX16	PEX16	PEX16	3115	0.082	0.62	YES
43	CROT	CROT	CROT	3138	0.081	0.63	YES
44	PEX19	PEX19	PEX19	3141	0.08	0.64	YES
45	ACOT8	ACOT8	ACOT8	3717	0.063	0.61	NO
46	IDH1	IDH1	IDH1	3873	0.058	0.6	NO
47	ECH1	ECH1	ECH1	3896	0.057	0.61	NO
48	ABCD4	ABCD4	ABCD4	3977	0.055	0.61	NO
49	DECR2	DECR2	DECR2	4002	0.054	0.61	NO
50	PEX6	PEX6	PEX6	4119	0.052	0.61	NO
51	PEX13	PEX13	PEX13	4237	0.049	0.61	NO
52	ABCD3	ABCD3	ABCD3	4587	0.042	0.59	NO
53	PRDX5	PRDX5	PRDX5	5113	0.031	0.56	NO
54	PEX10	PEX10	PEX10	5182	0.03	0.56	NO
55	SOD2	SOD2	SOD2	5402	0.025	0.55	NO
56	ACSL5	ACSL5	ACSL5	5664	0.021	0.54	NO
57	PEX26	PEX26	PEX26	5688	0.021	0.54	NO
58	IDH2	IDH2	IDH2	5757	0.02	0.54	NO
59	PMVK	PMVK	PMVK	5874	0.018	0.53	NO
60	PRDX1	PRDX1	PRDX1	5970	0.016	0.53	NO
61	AMACR	AMACR	AMACR	6044	0.015	0.53	NO
62	MVK	MVK	MVK	6944	0.0013	0.48	NO
63	PEX5	PEX5	PEX5	7353	-0.0045	0.45	NO
64	PEX11A	PEX11A	PEX11A	7469	-0.0064	0.45	NO
65	NUDT19	NUDT19	NUDT19	7927	-0.013	0.42	NO
66	PEX11B	PEX11B	PEX11B	8755	-0.025	0.38	NO
67	PEX2	PEX2	PEX2	10033	-0.043	0.31	NO
68	AGPS	AGPS	AGPS	11463	-0.067	0.24	NO
69	FAR1	FAR1	FAR1	14034	-0.13	0.1	NO
70	ABCD1	ABCD1	ABCD1	14063	-0.13	0.11	NO
71	ACSL6	ACSL6	ACSL6	14264	-0.14	0.11	NO
72	GNPAT	GNPAT	GNPAT	14323	-0.14	0.12	NO
73	ACSL3	ACSL3	ACSL3	14440	-0.14	0.13	NO
74	MPV17	MPV17	MPV17	14758	-0.16	0.12	NO
75	ABCD2	ABCD2	ABCD2	14781	-0.16	0.14	NO
76	FAR2	FAR2	FAR2	15110	-0.17	0.13	NO
77	ACSL4	ACSL4	ACSL4	15355	-0.18	0.13	NO

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

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

genes ES table in pathway: KEGG STEROID HORMONE BIOSYNTHESIS

Table 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	TAT	TAT	TAT	29	0.62	0.1	YES
2	SDS	SDS	SDS	34	0.62	0.21	YES
3	DNMT3L	DNMT3L	DNMT3L	54	0.57	0.31	YES
4	BHMT	BHMT	BHMT	110	0.49	0.39	YES
5	CTH	CTH	CTH	344	0.36	0.44	YES
6	CBS	CBS	CBS	568	0.29	0.47	YES
7	CDO1	CDO1	CDO1	615	0.28	0.52	YES
8	MAT1A	MAT1A	MAT1A	1070	0.21	0.53	YES
9	LDHAL6B	LDHAL6B	LDHAL6B	1489	0.16	0.53	YES
10	ADI1	ADI1	ADI1	1805	0.14	0.54	YES
11	GOT2	GOT2	GOT2	2004	0.13	0.55	YES
12	GOT1	GOT1	GOT1	2007	0.13	0.57	YES
13	AHCYL2	AHCYL2	AHCYL2	2853	0.091	0.54	NO
14	MAT2B	MAT2B	MAT2B	3838	0.059	0.49	NO
15	MPST	MPST	MPST	4519	0.043	0.46	NO
16	AHCY	AHCY	AHCY	4856	0.036	0.45	NO
17	MAT2A	MAT2A	MAT2A	5097	0.031	0.44	NO
18	MTAP	MTAP	MTAP	5943	0.016	0.4	NO
19	AHCYL1	AHCYL1	AHCYL1	6179	0.013	0.39	NO
20	LDHA	LDHA	LDHA	7802	-0.011	0.3	NO
21	LDHAL6A	LDHAL6A	LDHAL6A	9550	-0.036	0.2	NO
22	DNMT1	DNMT1	DNMT1	9612	-0.037	0.21	NO
23	APIP	APIP	APIP	10459	-0.049	0.17	NO
24	ENOPH1	ENOPH1	ENOPH1	10628	-0.052	0.17	NO
25	TRDMT1	TRDMT1	TRDMT1	11598	-0.07	0.12	NO
26	AMD1	AMD1	AMD1	11675	-0.071	0.13	NO
27	SRM	SRM	SRM	11779	-0.073	0.14	NO
28	SMS	SMS	SMS	12158	-0.081	0.13	NO
29	LDHB	LDHB	LDHB	13706	-0.12	0.064	NO
30	MTR	MTR	MTR	14136	-0.13	0.063	NO
31	DNMT3B	DNMT3B	DNMT3B	15367	-0.18	0.024	NO
32	DNMT3A	DNMT3A	DNMT3A	16547	-0.26	0.0022	NO
33	IL4I1	IL4I1	IL4I1	17380	-0.38	0.02	NO

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

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

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CYP2A7	CYP2A7	CYP2A7	1	1.1	0.095	YES
2	CYP2A13	CYP2A13	CYP2A13	2	0.87	0.17	YES
3	CYP2A6	CYP2A6	CYP2A6	6	0.82	0.24	YES
4	XDH	XDH	XDH	38	0.6	0.3	YES
5	CDA	CDA	CDA	100	0.5	0.34	YES
6	UPP2	UPP2	UPP2	121	0.48	0.38	YES
7	NAT2	NAT2	NAT2	179	0.43	0.41	YES
8	UGT2B10	UGT2B10	UGT2B10	249	0.39	0.44	YES
9	UGT2B7	UGT2B7	UGT2B7	254	0.39	0.48	YES
10	UPB1	UPB1	UPB1	315	0.37	0.51	YES
11	UGT2B15	UGT2B15	UGT2B15	376	0.34	0.54	YES
12	DPYS	DPYS	DPYS	422	0.33	0.56	YES
13	NAT1	NAT1	NAT1	563	0.29	0.58	YES
14	CES7	CES7	CES7	593	0.29	0.6	YES
15	UGT1A3	UGT1A3	UGT1A3	793	0.25	0.61	YES
16	CES2	CES2	CES2	803	0.24	0.64	YES
17	UGT2B28	UGT2B28	UGT2B28	850	0.24	0.65	YES
18	DPYD	DPYD	DPYD	905	0.23	0.67	YES
19	UGT2A1	UGT2A1	UGT2A1	950	0.22	0.69	YES
20	CYP3A43	CYP3A43	CYP3A43	966	0.22	0.71	YES
21	CYP3A5	CYP3A5	CYP3A5	1088	0.2	0.72	YES
22	CYP3A7	CYP3A7	CYP3A7	1165	0.19	0.73	YES
23	UGT1A9	UGT1A9	UGT1A9	1328	0.18	0.74	YES
24	UGT1A4	UGT1A4	UGT1A4	1528	0.16	0.74	YES
25	UGT2B4	UGT2B4	UGT2B4	1628	0.15	0.75	YES
26	CES1	CES1	CES1	1759	0.14	0.76	YES
27	UGT1A5	UGT1A5	UGT1A5	1834	0.14	0.76	YES
28	GUSB	GUSB	GUSB	2652	0.1	0.73	NO
29	TPMT	TPMT	TPMT	3123	0.081	0.71	NO
30	HPRT1	HPRT1	HPRT1	3261	0.076	0.7	NO
31	TYMP	TYMP	TYMP	3379	0.072	0.7	NO
32	UGT1A1	UGT1A1	UGT1A1	3874	0.058	0.68	NO
33	TK2	TK2	TK2	3915	0.057	0.68	NO
34	UGT1A8	UGT1A8	UGT1A8	4805	0.037	0.64	NO
35	UGT1A6	UGT1A6	UGT1A6	5275	0.028	0.61	NO
36	UGT1A7	UGT1A7	UGT1A7	5450	0.024	0.61	NO
37	UCK1	UCK1	UCK1	6471	0.0083	0.55	NO
38	UCKL1	UCKL1	UCKL1	6955	0.0011	0.52	NO
39	UPP1	UPP1	UPP1	7157	-0.0018	0.51	NO
40	UMPS	UMPS	UMPS	7354	-0.0045	0.5	NO
41	UGT2A3	UGT2A3	UGT2A3	7796	-0.011	0.48	NO
42	GMPS	GMPS	GMPS	10669	-0.053	0.32	NO
43	UGT2B11	UGT2B11	UGT2B11	11592	-0.07	0.27	NO
44	TK1	TK1	TK1	11686	-0.072	0.27	NO
45	UGT1A10	UGT1A10	UGT1A10	12920	-0.098	0.21	NO
46	IMPDH2	IMPDH2	IMPDH2	13043	-0.1	0.22	NO
47	ITPA	ITPA	ITPA	13531	-0.11	0.2	NO
48	UCK2	UCK2	UCK2	14192	-0.13	0.17	NO
49	IMPDH1	IMPDH1	IMPDH1	17067	-0.32	0.037	NO

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

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

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PCK1	PCK1	PCK1	219	0.41	0.13	YES
2	OGDHL	OGDHL	OGDHL	410	0.33	0.24	YES
3	PCK2	PCK2	PCK2	484	0.31	0.35	YES
4	ACO1	ACO1	ACO1	1331	0.18	0.37	YES
5	SUCLG2	SUCLG2	SUCLG2	1865	0.14	0.39	YES
6	SDHD	SDHD	SDHD	2056	0.13	0.42	YES
7	PC	PC	PC	2328	0.11	0.45	YES
8	SDHB	SDHB	SDHB	2330	0.11	0.49	YES
9	SUCLG1	SUCLG1	SUCLG1	2518	0.1	0.52	YES
10	FH	FH	FH	2648	0.1	0.54	YES
11	OGDH	OGDH	OGDH	3448	0.07	0.52	YES
12	SDHA	SDHA	SDHA	3489	0.069	0.55	YES
13	IDH1	IDH1	IDH1	3873	0.058	0.55	YES
14	ACO2	ACO2	ACO2	3982	0.055	0.56	YES
15	MDH1	MDH1	MDH1	4089	0.052	0.57	YES
16	DLD	DLD	DLD	4182	0.05	0.59	YES
17	IDH3A	IDH3A	IDH3A	4286	0.048	0.6	YES
18	DLST	DLST	DLST	4728	0.039	0.59	NO
19	PDHB	PDHB	PDHB	4843	0.036	0.59	NO
20	SDHC	SDHC	SDHC	5232	0.029	0.58	NO
21	IDH2	IDH2	IDH2	5757	0.02	0.56	NO
22	PDHA1	PDHA1	PDHA1	5883	0.017	0.56	NO
23	IDH3B	IDH3B	IDH3B	7235	-0.0028	0.48	NO
24	DLAT	DLAT	DLAT	8055	-0.015	0.44	NO
25	SUCLA2	SUCLA2	SUCLA2	8485	-0.02	0.42	NO
26	MDH2	MDH2	MDH2	8710	-0.024	0.42	NO
27	IDH3G	IDH3G	IDH3G	9692	-0.038	0.38	NO
28	ACLY	ACLY	ACLY	11501	-0.068	0.3	NO
29	CS	CS	CS	14366	-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: KEGG GLYCINE SERINE AND THREONINE METABOLISM.

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

genes ES table in pathway: KEGG CYSTEINE AND METHIONINE 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	ALDH6A1	ALDH6A1	ALDH6A1	433	0.32	0.028	YES
2	ABAT	ABAT	ABAT	444	0.32	0.079	YES
3	EHHADH	EHHADH	EHHADH	518	0.3	0.12	YES
4	HMGCS2	HMGCS2	HMGCS2	584	0.29	0.17	YES
5	BCKDHB	BCKDHB	BCKDHB	834	0.24	0.19	YES
6	ACAA2	ACAA2	ACAA2	916	0.23	0.22	YES
7	MUT	MUT	MUT	965	0.22	0.26	YES
8	ACADM	ACADM	ACADM	1075	0.2	0.28	YES
9	ALDH7A1	ALDH7A1	ALDH7A1	1215	0.19	0.3	YES
10	ALDH2	ALDH2	ALDH2	1372	0.18	0.32	YES
11	IVD	IVD	IVD	1434	0.17	0.35	YES
12	DBT	DBT	DBT	1488	0.16	0.37	YES
13	ACAT1	ACAT1	ACAT1	1623	0.15	0.39	YES
14	ACAT2	ACAT2	ACAT2	1797	0.14	0.4	YES
15	MCEE	MCEE	MCEE	1812	0.14	0.42	YES
16	ACADSB	ACADSB	ACADSB	1889	0.14	0.44	YES
17	PCCA	PCCA	PCCA	1939	0.13	0.46	YES
18	ALDH9A1	ALDH9A1	ALDH9A1	1944	0.13	0.48	YES
19	HMGCL	HMGCL	HMGCL	1952	0.13	0.5	YES
20	HADH	HADH	HADH	2029	0.13	0.52	YES
21	ACAA1	ACAA1	ACAA1	2133	0.12	0.53	YES
22	ACADS	ACADS	ACADS	2183	0.12	0.55	YES
23	HMGCS1	HMGCS1	HMGCS1	2251	0.12	0.56	YES
24	PCCB	PCCB	PCCB	2299	0.12	0.58	YES
25	HSD17B10	HSD17B10	HSD17B10	2329	0.11	0.6	YES
26	HIBCH	HIBCH	HIBCH	2444	0.11	0.61	YES
27	MCCC1	MCCC1	MCCC1	2560	0.1	0.62	YES
28	ACAD8	ACAD8	ACAD8	2603	0.1	0.63	YES
29	BCKDHA	BCKDHA	BCKDHA	3035	0.085	0.62	YES
30	ALDH1B1	ALDH1B1	ALDH1B1	3156	0.08	0.63	YES
31	ECHS1	ECHS1	ECHS1	3249	0.077	0.64	YES
32	MCCC2	MCCC2	MCCC2	3336	0.074	0.64	YES
33	BCAT2	BCAT2	BCAT2	3857	0.058	0.62	NO
34	HADHB	HADHB	HADHB	4052	0.053	0.62	NO
35	DLD	DLD	DLD	4182	0.05	0.62	NO
36	HIBADH	HIBADH	HIBADH	4264	0.049	0.62	NO
37	HADHA	HADHA	HADHA	4376	0.046	0.62	NO
38	AUH	AUH	AUH	5003	0.032	0.6	NO
39	ALDH3A2	ALDH3A2	ALDH3A2	8173	-0.016	0.42	NO
40	AOX1	AOX1	AOX1	9394	-0.034	0.36	NO
41	OXCT2	OXCT2	OXCT2	15021	-0.17	0.063	NO
42	OXCT1	OXCT1	OXCT1	15345	-0.18	0.074	NO
43	IL4I1	IL4I1	IL4I1	17380	-0.38	0.02	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 CYSTEINE AND METHIONINE METABOLISM.

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

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

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	GBA3	GBA3	GBA3	13	0.7	0.073	YES
2	GCK	GCK	GCK	14	0.66	0.14	YES
3	GYS2	GYS2	GYS2	21	0.65	0.21	YES
4	AMY2B	AMY2B	AMY2B	217	0.41	0.24	YES
5	AMY1A	AMY1A	AMY1A	237	0.4	0.29	YES
6	AMY2A	AMY2A	AMY2A	245	0.39	0.33	YES
7	UGT2B10	UGT2B10	UGT2B10	249	0.39	0.37	YES
8	UGT2B7	UGT2B7	UGT2B7	254	0.39	0.41	YES
9	UGT2B15	UGT2B15	UGT2B15	376	0.34	0.44	YES
10	G6PC	G6PC	G6PC	494	0.31	0.47	YES
11	AGL	AGL	AGL	643	0.27	0.49	YES
12	UGT1A3	UGT1A3	UGT1A3	793	0.25	0.5	YES
13	UGT2B28	UGT2B28	UGT2B28	850	0.24	0.53	YES
14	TREH	TREH	TREH	880	0.23	0.55	YES
15	UGT2A1	UGT2A1	UGT2A1	950	0.22	0.57	YES
16	PGM2	PGM2	PGM2	1096	0.2	0.58	YES
17	UGP2	UGP2	UGP2	1123	0.2	0.6	YES
18	PYGL	PYGL	PYGL	1158	0.2	0.62	YES
19	UGT1A9	UGT1A9	UGT1A9	1328	0.18	0.63	YES
20	UGT1A4	UGT1A4	UGT1A4	1528	0.16	0.64	YES
21	PGM1	PGM1	PGM1	1605	0.16	0.65	YES
22	UGT2B4	UGT2B4	UGT2B4	1628	0.15	0.66	YES
23	UGT1A5	UGT1A5	UGT1A5	1834	0.14	0.67	YES
24	GBE1	GBE1	GBE1	1852	0.14	0.68	YES
25	GANC	GANC	GANC	1943	0.13	0.69	YES
26	ENPP1	ENPP1	ENPP1	2278	0.12	0.68	NO
27	GUSB	GUSB	GUSB	2652	0.1	0.67	NO
28	G6PC2	G6PC2	G6PC2	2688	0.098	0.68	NO
29	GAA	GAA	GAA	3403	0.072	0.65	NO
30	UGT1A1	UGT1A1	UGT1A1	3874	0.058	0.63	NO
31	UGT1A8	UGT1A8	UGT1A8	4805	0.037	0.58	NO
32	UGT1A6	UGT1A6	UGT1A6	5275	0.028	0.56	NO
33	UGT1A7	UGT1A7	UGT1A7	5450	0.024	0.55	NO
34	GPI	GPI	GPI	6786	0.0036	0.47	NO
35	UGT2A3	UGT2A3	UGT2A3	7796	-0.011	0.42	NO
36	HK1	HK1	HK1	8036	-0.014	0.4	NO
37	UGDH	UGDH	UGDH	8922	-0.028	0.36	NO
38	ENPP3	ENPP3	ENPP3	10124	-0.044	0.3	NO
39	PYGB	PYGB	PYGB	11275	-0.064	0.24	NO
40	UGT2B11	UGT2B11	UGT2B11	11592	-0.07	0.23	NO
41	GYS1	GYS1	GYS1	11891	-0.075	0.22	NO
42	PYGM	PYGM	PYGM	12596	-0.09	0.19	NO
43	UGT1A10	UGT1A10	UGT1A10	12920	-0.098	0.18	NO
44	MGAM	MGAM	MGAM	13833	-0.12	0.14	NO
45	HK3	HK3	HK3	15164	-0.17	0.084	NO
46	PGM2L1	PGM2L1	PGM2L1	15657	-0.2	0.077	NO
47	HK2	HK2	HK2	17388	-0.38	0.019	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 VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

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

genes ES table in pathway: KEGG LYSINE DEGRADATION

Table 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	SDS	SDS	SDS	34	0.62	0.088	YES
2	DAO	DAO	DAO	94	0.51	0.16	YES
3	BHMT	BHMT	BHMT	110	0.49	0.23	YES
4	GNMT	GNMT	GNMT	194	0.42	0.29	YES
5	AGXT	AGXT	AGXT	276	0.38	0.34	YES
6	GLDC	GLDC	GLDC	278	0.38	0.39	YES
7	DMGDH	DMGDH	DMGDH	343	0.36	0.44	YES
8	CTH	CTH	CTH	344	0.36	0.49	YES
9	AGXT2	AGXT2	AGXT2	363	0.35	0.54	YES
10	SARDH	SARDH	SARDH	524	0.3	0.58	YES
11	PIPOX	PIPOX	PIPOX	530	0.3	0.62	YES
12	CBS	CBS	CBS	568	0.29	0.66	YES
13	SHMT1	SHMT1	SHMT1	634	0.28	0.7	YES
14	GLYCTK	GLYCTK	GLYCTK	786	0.25	0.73	YES
15	GATM	GATM	GATM	1301	0.18	0.72	YES
16	AOC2	AOC2	AOC2	1596	0.16	0.73	YES
17	SRR	SRR	SRR	1685	0.15	0.75	YES
18	PHGDH	PHGDH	PHGDH	1828	0.14	0.76	YES
19	GCAT	GCAT	GCAT	2214	0.12	0.76	YES
20	GAMT	GAMT	GAMT	2366	0.11	0.76	YES
21	ALAS2	ALAS2	ALAS2	2716	0.097	0.76	YES
22	MAOB	MAOB	MAOB	2736	0.096	0.77	YES
23	MAOA	MAOA	MAOA	3046	0.084	0.76	YES
24	AOC3	AOC3	AOC3	3118	0.082	0.77	YES
25	ALAS1	ALAS1	ALAS1	3562	0.067	0.76	NO
26	PSAT1	PSAT1	PSAT1	3602	0.066	0.76	NO
27	DLD	DLD	DLD	4182	0.05	0.74	NO
28	SHMT2	SHMT2	SHMT2	4941	0.034	0.7	NO
29	CHDH	CHDH	CHDH	6163	0.013	0.64	NO
30	PSPH	PSPH	PSPH	14022	-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 LYSINE DEGRADATION.

Figure S40. 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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.34	0.96	0.51	1	1	0.22	0.13	0.19	1	0.8
BIOCARTA MPR PATHWAY	32	genes.ES.table	0.46	1.5	0.076	1	0.92	0.19	0.065	0.18	1	0.84
BIOCARTA INTEGRIN PATHWAY	37	genes.ES.table	0.25	0.98	0.46	1	1	0.081	0.083	0.074	1	0.79
BIOCARTA WNT PATHWAY	25	genes.ES.table	0.31	1.1	0.39	1	1	0.4	0.33	0.27	1	0.77
KEGG INOSITOL PHOSPHATE METABOLISM	53	genes.ES.table	0.3	0.99	0.49	1	1	0.19	0.16	0.16	1	0.8
KEGG ETHER LIPID METABOLISM	26	genes.ES.table	0.44	1.2	0.23	1	1	0.35	0.15	0.29	1	0.72
KEGG SPHINGOLIPID METABOLISM	36	genes.ES.table	0.35	1.1	0.36	1	1	0.11	0.04	0.11	1	0.81
KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES	25	genes.ES.table	0.37	0.95	0.52	1	1	0.28	0.13	0.24	1	0.81
KEGG RIBOSOME	85	genes.ES.table	0.57	1.4	0.21	1	0.95	0.73	0.26	0.55	1	0.8
KEGG DNA REPLICATION	35	genes.ES.table	0.52	1.4	0.21	1	0.96	0.6	0.28	0.43	1	0.67

genes ES table in pathway: BIOCARTA G1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MYT1	MYT1	MYT1	87	0.54	0.14	YES
2	ACTA1	ACTA1	ACTA1	327	0.39	0.23	YES
3	CDK1	CDK1	CDK1	597	0.32	0.3	YES
4	CDC25C	CDC25C	CDC25C	878	0.27	0.35	YES
5	SRC	SRC	SRC	1102	0.24	0.4	YES
6	CCNB1	CCNB1	CCNB1	1154	0.23	0.46	YES
7	GNAS	GNAS	GNAS	2731	0.13	0.41	NO
8	PAQR5	PAQR5	PAQR5	4020	0.087	0.36	NO
9	ARPC3	ARPC3	ARPC3	5455	0.057	0.29	NO
10	PAQR7	PAQR7	PAQR7	6123	0.045	0.26	NO
11	MAPK1	MAPK1	MAPK1	6795	0.034	0.24	NO
12	ARPC1A	ARPC1A	ARPC1A	6907	0.032	0.24	NO
13	ARPC4	ARPC4	ARPC4	7143	0.028	0.23	NO
14	PIN1	PIN1	PIN1	7383	0.025	0.22	NO
15	ARPC2	ARPC2	ARPC2	7719	0.02	0.21	NO
16	PRKAR2B	PRKAR2B	PRKAR2B	8848	0.0035	0.15	NO
17	ACTR2	ACTR2	ACTR2	9134	-0.0012	0.13	NO
18	ACTR3	ACTR3	ACTR3	9203	-0.0022	0.13	NO
19	ARPC5	ARPC5	ARPC5	9251	-0.0029	0.13	NO
20	MAPK3	MAPK3	MAPK3	9334	-0.0044	0.12	NO
21	ARPC1B	ARPC1B	ARPC1B	9731	-0.011	0.1	NO
22	HRAS	HRAS	HRAS	9801	-0.012	0.1	NO
23	PRKAR1B	PRKAR1B	PRKAR1B	9997	-0.015	0.097	NO
24	PRKAR1A	PRKAR1A	PRKAR1A	11606	-0.043	0.018	NO
25	GNB1	GNB1	GNB1	12939	-0.071	-0.039	NO
26	CAP1	CAP1	CAP1	13823	-0.094	-0.064	NO
27	GNAI1	GNAI1	GNAI1	14036	-0.1	-0.049	NO
28	PGR	PGR	PGR	14693	-0.12	-0.054	NO
29	PRKACB	PRKACB	PRKACB	15897	-0.18	-0.073	NO
30	PRKAR2A	PRKAR2A	PRKAR2A	15937	-0.19	-0.026	NO
31	GNGT1	GNGT1	GNGT1	16287	-0.21	0.0099	NO
32	RPS6KA1	RPS6KA1	RPS6KA1	16864	-0.27	0.049	NO

Figure S41. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA G1 PATHWAY.

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

genes ES table in pathway: BIOCARTA MPR 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	RPL21	RPL21	RPL21	1135	0.24	-0.036	YES
2	RPL22L1	RPL22L1	RPL22L1	1349	0.21	-0.023	YES
3	RPL36A	RPL36A	RPL36A	1551	0.2	-0.011	YES
4	RPL9	RPL9	RPL9	1974	0.17	-0.015	YES
5	RPS24	RPS24	RPS24	1994	0.16	0.0036	YES
6	RPSA	RPSA	RPSA	2282	0.15	0.005	YES
7	RPS19	RPS19	RPS19	2307	0.15	0.021	YES
8	RPLP0	RPLP0	RPLP0	2528	0.14	0.025	YES
9	RPS21	RPS21	RPS21	2641	0.13	0.034	YES
10	RPS10	RPS10	RPS10	2678	0.13	0.048	YES
11	RPS18	RPS18	RPS18	2743	0.13	0.059	YES
12	RPS12	RPS12	RPS12	2750	0.13	0.074	YES
13	RPS3	RPS3	RPS3	2784	0.13	0.087	YES
14	RPL27A	RPL27A	RPL27A	2805	0.12	0.1	YES
15	RPS7	RPS7	RPS7	2834	0.12	0.11	YES
16	RPL18A	RPL18A	RPL18A	2870	0.12	0.13	YES
17	RPS17	RPS17	RPS17	2892	0.12	0.14	YES
18	RPL39	RPL39	RPL39	2918	0.12	0.15	YES
19	RPS27	RPS27	RPS27	2921	0.12	0.17	YES
20	RPL26	RPL26	RPL26	2930	0.12	0.18	YES
21	RPS15	RPS15	RPS15	2940	0.12	0.2	YES
22	RPS27A	RPS27A	RPS27A	2953	0.12	0.21	YES
23	RPS5	RPS5	RPS5	2973	0.12	0.22	YES
24	RPL7	RPL7	RPL7	3006	0.12	0.23	YES
25	RPL23A	RPL23A	RPL23A	3022	0.12	0.25	YES
26	RPL28	RPL28	RPL28	3061	0.12	0.26	YES
27	RPS29	RPS29	RPS29	3211	0.11	0.26	YES
28	RPL7A	RPL7A	RPL7A	3227	0.11	0.28	YES
29	RPL36	RPL36	RPL36	3262	0.11	0.29	YES
30	RPS4X	RPS4X	RPS4X	3271	0.11	0.3	YES
31	RPL37A	RPL37A	RPL37A	3309	0.11	0.31	YES
32	RPL17	RPL17	RPL17	3321	0.11	0.32	YES
33	RPL31	RPL31	RPL31	3380	0.11	0.33	YES
34	RPL32	RPL32	RPL32	3385	0.1	0.34	YES
35	RPL3	RPL3	RPL3	3446	0.1	0.35	YES
36	RPL6	RPL6	RPL6	3450	0.1	0.36	YES
37	RPLP2	RPLP2	RPLP2	3457	0.1	0.38	YES
38	RPL13A	RPL13A	RPL13A	3476	0.1	0.39	YES
39	RPL27	RPL27	RPL27	3605	0.098	0.39	YES
40	RPL14	RPL14	RPL14	3661	0.097	0.4	YES
41	RPL38	RPL38	RPL38	3691	0.096	0.41	YES
42	RPL10A	RPL10A	RPL10A	3695	0.096	0.42	YES
43	RPS16	RPS16	RPS16	3777	0.094	0.43	YES
44	RPL4	RPL4	RPL4	3786	0.094	0.44	YES
45	RPL35A	RPL35A	RPL35A	3794	0.093	0.45	YES
46	RPS11	RPS11	RPS11	3810	0.093	0.46	YES
47	RPS28	RPS28	RPS28	4052	0.087	0.46	YES
48	RPL35	RPL35	RPL35	4059	0.086	0.47	YES
49	RPS6	RPS6	RPS6	4095	0.086	0.48	YES
50	RPL8	RPL8	RPL8	4118	0.085	0.48	YES
51	RPL23	RPL23	RPL23	4192	0.083	0.49	YES
52	RPS25	RPS25	RPS25	4209	0.083	0.5	YES
53	RPS9	RPS9	RPS9	4287	0.081	0.5	YES
54	RPL37	RPL37	RPL37	4309	0.08	0.51	YES
55	RPS2	RPS2	RPS2	4358	0.079	0.52	YES
56	RPL41	RPL41	RPL41	4375	0.079	0.53	YES
57	RPS23	RPS23	RPS23	4376	0.079	0.54	YES
58	RPL30	RPL30	RPL30	4396	0.078	0.55	YES
59	RPS13	RPS13	RPS13	4480	0.076	0.55	YES
60	RPL24	RPL24	RPL24	4503	0.076	0.56	YES
61	RPL29	RPL29	RPL29	4526	0.075	0.57	YES
62	RPL12	RPL12	RPL12	4528	0.075	0.57	YES
63	RPLP1	RPLP1	RPLP1	4804	0.07	0.57	NO
64	RPL15	RPL15	RPL15	4832	0.069	0.57	NO
65	RPS20	RPS20	RPS20	5006	0.066	0.57	NO
66	RPL10	RPL10	RPL10	5269	0.06	0.56	NO
67	RPS3A	RPS3A	RPS3A	5281	0.06	0.57	NO
68	RPL5	RPL5	RPL5	5438	0.058	0.57	NO
69	UBA52	UBA52	UBA52	5468	0.057	0.57	NO
70	RPL19	RPL19	RPL19	5826	0.05	0.56	NO
71	RPL34	RPL34	RPL34	5869	0.05	0.56	NO
72	RPS8	RPS8	RPS8	6048	0.046	0.56	NO
73	RSL24D1	RSL24D1	RSL24D1	6068	0.046	0.56	NO
74	RPL13	RPL13	RPL13	6101	0.045	0.57	NO
75	RPS15A	RPS15A	RPS15A	6400	0.041	0.56	NO
76	RPS26	RPS26	RPS26	6757	0.035	0.54	NO
77	FAU	FAU	FAU	6788	0.034	0.54	NO
78	RPL11	RPL11	RPL11	7181	0.028	0.52	NO
79	RPL22	RPL22	RPL22	7420	0.025	0.51	NO
80	MRPL13	MRPL13	MRPL13	7818	0.019	0.49	NO
81	RPL36AL	RPL36AL	RPL36AL	8160	0.013	0.47	NO
82	RPS27L	RPS27L	RPS27L	9733	-0.011	0.39	NO
83	RPL26L1	RPL26L1	RPL26L1	13955	-0.098	0.16	NO
84	RPL10L	RPL10L	RPL10L	16136	-0.2	0.059	NO
85	RPS4Y1	RPS4Y1	RPS4Y1	16812	-0.26	0.052	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 MPR PATHWAY.

Figure S44. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA MPR 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 INTEGRIN 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	TUBB8	TUBB8	TUBB8	262	0.42	0.058	YES
2	TUBB4Q	TUBB4Q	TUBB4Q	320	0.39	0.12	YES
3	TUBB1	TUBB1	TUBB1	342	0.39	0.19	YES
4	NCK2	NCK2	NCK2	382	0.38	0.25	YES
5	TUBA8	TUBA8	TUBA8	456	0.35	0.31	YES
6	TLR5	TLR5	TLR5	725	0.29	0.35	YES
7	ARHGEF2	ARHGEF2	ARHGEF2	849	0.27	0.39	YES
8	CLDN1	CLDN1	CLDN1	2273	0.15	0.34	NO
9	TUBB4	TUBB4	TUBB4	2712	0.13	0.33	NO
10	CDH1	CDH1	CDH1	3126	0.11	0.33	NO
11	ARPC5L	ARPC5L	ARPC5L	4304	0.08	0.28	NO
12	TUBB3	TUBB3	TUBB3	4419	0.078	0.28	NO
13	OCLN	OCLN	OCLN	5235	0.061	0.25	NO
14	ARPC3	ARPC3	ARPC3	5455	0.057	0.25	NO
15	YWHAZ	YWHAZ	YWHAZ	5548	0.055	0.25	NO
16	YWHAQ	YWHAQ	YWHAQ	5609	0.054	0.26	NO
17	ABL1	ABL1	ABL1	6388	0.041	0.22	NO
18	TUBB	TUBB	TUBB	6428	0.04	0.22	NO
19	ACTG1	ACTG1	ACTG1	6558	0.038	0.22	NO
20	NCL	NCL	NCL	6639	0.037	0.23	NO
21	ARPC1A	ARPC1A	ARPC1A	6907	0.032	0.22	NO
22	TUBA1B	TUBA1B	TUBA1B	6920	0.032	0.22	NO
23	TUBB6	TUBB6	TUBB6	7047	0.03	0.22	NO
24	ARPC4	ARPC4	ARPC4	7143	0.028	0.22	NO
25	ARPC2	ARPC2	ARPC2	7719	0.02	0.19	NO
26	KRT18	KRT18	KRT18	8199	0.013	0.17	NO
27	TUBB2A	TUBB2A	TUBB2A	8226	0.012	0.17	NO
28	TUBB2C	TUBB2C	TUBB2C	8254	0.012	0.17	NO
29	ITGB1	ITGB1	ITGB1	8319	0.011	0.16	NO
30	TUBA1C	TUBA1C	TUBA1C	8513	0.0084	0.16	NO
31	EZR	EZR	EZR	8549	0.008	0.16	NO
32	TUBA1A	TUBA1A	TUBA1A	9007	0.0013	0.13	NO
33	TUBB2B	TUBB2B	TUBB2B	9045	0.00053	0.13	NO
34	ARPC5	ARPC5	ARPC5	9251	-0.0029	0.12	NO
35	ARPC1B	ARPC1B	ARPC1B	9731	-0.011	0.091	NO
36	CTTN	CTTN	CTTN	9781	-0.012	0.09	NO
37	CTNNB1	CTNNB1	CTNNB1	9917	-0.014	0.085	NO
38	PRKCA	PRKCA	PRKCA	10055	-0.016	0.08	NO
39	ACTB	ACTB	ACTB	10249	-0.02	0.073	NO
40	WASL	WASL	WASL	10408	-0.022	0.068	NO
41	ROCK1	ROCK1	ROCK1	11098	-0.034	0.035	NO
42	RHOA	RHOA	RHOA	11212	-0.036	0.035	NO
43	TUBA4A	TUBA4A	TUBA4A	11915	-0.049	0.0035	NO
44	WAS	WAS	WAS	12319	-0.058	-0.0092	NO
45	HCLS1	HCLS1	HCLS1	12397	-0.059	-0.0032	NO
46	TUBA3E	TUBA3E	TUBA3E	12440	-0.06	0.005	NO
47	TUBA3D	TUBA3D	TUBA3D	12747	-0.067	-0.00053	NO
48	CDC42	CDC42	CDC42	12940	-0.071	0.0011	NO
49	ROCK2	ROCK2	ROCK2	13246	-0.079	-0.0024	NO
50	NCK1	NCK1	NCK1	13809	-0.093	-0.018	NO
51	FYN	FYN	FYN	15153	-0.14	-0.069	NO
52	CD14	CD14	CD14	15680	-0.17	-0.069	NO
53	TUBAL3	TUBAL3	TUBAL3	15882	-0.18	-0.048	NO
54	TLR4	TLR4	TLR4	16615	-0.24	-0.047	NO
55	TUBA3C	TUBA3C	TUBA3C	17016	-0.29	-0.018	NO
56	LY96	LY96	LY96	17249	-0.33	0.027	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 INTEGRIN PATHWAY.

Figure S46. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA INTEGRIN 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 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	POLE2	POLE2	POLE2	596	0.32	0.071	YES
2	DNA2	DNA2	DNA2	784	0.28	0.15	YES
3	LIG1	LIG1	LIG1	2090	0.16	0.13	YES
4	RFC4	RFC4	RFC4	2741	0.13	0.14	YES
5	MCM2	MCM2	MCM2	2863	0.12	0.17	YES
6	PRIM2	PRIM2	PRIM2	3103	0.12	0.2	YES
7	POLD1	POLD1	POLD1	3129	0.11	0.23	YES
8	PRIM1	PRIM1	PRIM1	3192	0.11	0.27	YES
9	FEN1	FEN1	FEN1	3393	0.1	0.29	YES
10	MCM5	MCM5	MCM5	3481	0.1	0.32	YES
11	MCM4	MCM4	MCM4	3628	0.098	0.34	YES
12	RNASEH2C	RNASEH2C	RNASEH2C	3705	0.096	0.37	YES
13	MCM3	MCM3	MCM3	3747	0.095	0.4	YES
14	RNASEH2B	RNASEH2B	RNASEH2B	4322	0.08	0.39	YES
15	MCM6	MCM6	MCM6	4339	0.08	0.42	YES
16	MCM7	MCM7	MCM7	4539	0.075	0.43	YES
17	POLD3	POLD3	POLD3	4817	0.069	0.44	YES
18	RNASEH2A	RNASEH2A	RNASEH2A	4820	0.069	0.46	YES
19	RFC2	RFC2	RFC2	4829	0.069	0.48	YES
20	RFC5	RFC5	RFC5	4913	0.067	0.5	YES
21	RFC1	RFC1	RFC1	5016	0.065	0.52	YES
22	RPA1	RPA1	RPA1	5719	0.052	0.5	NO
23	POLA2	POLA2	POLA2	6402	0.041	0.47	NO
24	POLE	POLE	POLE	6597	0.038	0.47	NO
25	RFC3	RFC3	RFC3	7222	0.027	0.44	NO
26	PCNA	PCNA	PCNA	8450	0.0091	0.38	NO
27	SSBP1	SSBP1	SSBP1	8517	0.0084	0.38	NO
28	POLE3	POLE3	POLE3	8970	0.0018	0.35	NO
29	RNASEH1	RNASEH1	RNASEH1	9847	-0.013	0.31	NO
30	POLD2	POLD2	POLD2	10622	-0.026	0.27	NO
31	POLD4	POLD4	POLD4	12254	-0.056	0.2	NO
32	RPA3	RPA3	RPA3	13092	-0.074	0.18	NO
33	RPA2	RPA2	RPA2	13282	-0.08	0.19	NO
34	RPA4	RPA4	RPA4	13563	-0.086	0.2	NO
35	POLE4	POLE4	POLE4	13834	-0.094	0.22	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 WNT PATHWAY.

Figure S48. 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 INOSITOL PHOSPHATE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ATP1B2	ATP1B2	ATP1B2	34	0.63	0.086	YES
2	TNNT2	TNNT2	TNNT2	51	0.6	0.17	YES
3	CACNA2D2	CACNA2D2	CACNA2D2	59	0.57	0.25	YES
4	FXYD2	FXYD2	FXYD2	91	0.54	0.32	YES
5	TNNC1	TNNC1	TNNC1	190	0.45	0.38	YES
6	CACNG4	CACNG4	CACNG4	304	0.4	0.43	YES
7	CACNA1D	CACNA1D	CACNA1D	576	0.32	0.46	YES
8	TNNI3	TNNI3	TNNI3	1488	0.2	0.43	NO
9	CACNB3	CACNB3	CACNB3	2040	0.16	0.42	NO
10	CACNA1F	CACNA1F	CACNA1F	2285	0.15	0.43	NO
11	CACNB2	CACNB2	CACNB2	2580	0.13	0.43	NO
12	CACNG1	CACNG1	CACNG1	2684	0.13	0.44	NO
13	CACNB1	CACNB1	CACNB1	3374	0.11	0.42	NO
14	MYL3	MYL3	MYL3	3965	0.089	0.4	NO
15	CACNB4	CACNB4	CACNB4	4166	0.084	0.4	NO
16	TPM4	TPM4	TPM4	4359	0.079	0.4	NO
17	COX6B1	COX6B1	COX6B1	5334	0.059	0.35	NO
18	ATP1B1	ATP1B1	ATP1B1	5833	0.05	0.33	NO
19	COX7A2L	COX7A2L	COX7A2L	5839	0.05	0.34	NO
20	TPM3	TPM3	TPM3	5988	0.047	0.34	NO
21	ATP1A1	ATP1A1	ATP1A1	6216	0.044	0.33	NO
22	COX4I2	COX4I2	COX4I2	6493	0.039	0.32	NO
23	TPM1	TPM1	TPM1	6541	0.039	0.32	NO
24	TPM2	TPM2	TPM2	6631	0.037	0.32	NO
25	CACNA1C	CACNA1C	CACNA1C	7509	0.023	0.28	NO
26	UQCR11	UQCR11	UQCR11	7869	0.018	0.26	NO
27	COX5A	COX5A	COX5A	7875	0.018	0.26	NO
28	UQCRB	UQCRB	UQCRB	7940	0.017	0.26	NO
29	UQCRFS1	UQCRFS1	UQCRFS1	8098	0.014	0.25	NO
30	UQCR10	UQCR10	UQCR10	8483	0.0087	0.23	NO
31	ATP2A2	ATP2A2	ATP2A2	8528	0.0082	0.23	NO
32	COX5B	COX5B	COX5B	8929	0.0024	0.21	NO
33	ATP1A4	ATP1A4	ATP1A4	9038	0.00061	0.2	NO
34	COX8A	COX8A	COX8A	9075	-0.000091	0.2	NO
35	COX6A1	COX6A1	COX6A1	9379	-0.0052	0.18	NO
36	COX6C	COX6C	COX6C	9385	-0.0053	0.18	NO
37	UQCRHL	UQCRHL	UQCRHL	9512	-0.0072	0.18	NO
38	COX7A2	COX7A2	COX7A2	9667	-0.0096	0.17	NO
39	CYC1	CYC1	CYC1	9949	-0.014	0.16	NO
40	COX7C	COX7C	COX7C	10084	-0.017	0.15	NO
41	CACNA1S	CACNA1S	CACNA1S	10107	-0.017	0.15	NO
42	UQCRH	UQCRH	UQCRH	10331	-0.021	0.14	NO
43	COX7A1	COX7A1	COX7A1	10986	-0.032	0.11	NO
44	CACNA2D4	CACNA2D4	CACNA2D4	11070	-0.033	0.11	NO
45	COX7B	COX7B	COX7B	11567	-0.042	0.087	NO
46	RYR2	RYR2	RYR2	11872	-0.048	0.077	NO
47	CACNA2D3	CACNA2D3	CACNA2D3	12022	-0.051	0.075	NO
48	CACNA2D1	CACNA2D1	CACNA2D1	12336	-0.058	0.066	NO
49	ATP1B3	ATP1B3	ATP1B3	12369	-0.059	0.072	NO
50	COX4I1	COX4I1	COX4I1	12512	-0.062	0.072	NO
51	SLC9A1	SLC9A1	SLC9A1	12665	-0.065	0.073	NO
52	COX6B2	COX6B2	COX6B2	12749	-0.067	0.078	NO
53	ATP1A2	ATP1A2	ATP1A2	12914	-0.07	0.078	NO
54	UQCRC1	UQCRC1	UQCRC1	13121	-0.075	0.077	NO
55	ATP1A3	ATP1A3	ATP1A3	13272	-0.079	0.079	NO
56	UQCRQ	UQCRQ	UQCRQ	14472	-0.12	0.028	NO
57	ACTC1	ACTC1	ACTC1	14559	-0.12	0.039	NO
58	SLC9A6	SLC9A6	SLC9A6	14882	-0.13	0.039	NO
59	SLC8A1	SLC8A1	SLC8A1	16520	-0.23	-0.021	NO
60	COX6A2	COX6A2	COX6A2	16863	-0.27	-0.0031	NO
61	COX7B2	COX7B2	COX7B2	17385	-0.37	0.019	NO

Figure S49. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG INOSITOL PHOSPHATE METABOLISM.

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

genes ES table in pathway: KEGG ETHER LIPID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SNRPA1	SNRPA1	SNRPA1	2271	0.15	-0.11	YES
2	SNRPE	SNRPE	SNRPE	2438	0.14	-0.093	YES
3	SF3A2	SF3A2	SF3A2	2510	0.14	-0.075	YES
4	THOC1	THOC1	THOC1	2687	0.13	-0.065	YES
5	SNRPD1	SNRPD1	SNRPD1	2749	0.13	-0.048	YES
6	HSPA1L	HSPA1L	HSPA1L	2846	0.12	-0.034	YES
7	LSM7	LSM7	LSM7	2859	0.12	-0.016	YES
8	SNRPF	SNRPF	SNRPF	3002	0.12	-0.0051	YES
9	LSM2	LSM2	LSM2	3379	0.11	-0.0098	YES
10	THOC4	THOC4	THOC4	3422	0.1	0.0042	YES
11	SNRPB	SNRPB	SNRPB	3539	0.1	0.013	YES
12	SR140	SR140	SR140	3633	0.098	0.024	YES
13	HNRNPA1	HNRNPA1	HNRNPA1	3667	0.097	0.037	YES
14	TCERG1	TCERG1	TCERG1	3684	0.096	0.051	YES
15	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	3697	0.096	0.066	YES
16	USP39	USP39	USP39	3962	0.089	0.065	YES
17	NHP2L1	NHP2L1	NHP2L1	4065	0.086	0.073	YES
18	SNRPG	SNRPG	SNRPG	4163	0.084	0.08	YES
19	PRPF3	PRPF3	PRPF3	4417	0.078	0.078	YES
20	U2AF1	U2AF1	U2AF1	4420	0.078	0.09	YES
21	ACIN1	ACIN1	ACIN1	4454	0.077	0.1	YES
22	RBM8A	RBM8A	RBM8A	4458	0.077	0.11	YES
23	PQBP1	PQBP1	PQBP1	4562	0.075	0.12	YES
24	SNRPA	SNRPA	SNRPA	4825	0.069	0.12	YES
25	SNRNP70	SNRNP70	SNRNP70	4872	0.068	0.12	YES
26	SNRPD3	SNRPD3	SNRPD3	4894	0.068	0.13	YES
27	RBMX	RBMX	RBMX	4898	0.068	0.14	YES
28	SFRS9	SFRS9	SFRS9	4899	0.068	0.15	YES
29	SF3B4	SF3B4	SF3B4	4907	0.067	0.16	YES
30	HNRNPA3	HNRNPA3	HNRNPA3	5058	0.064	0.16	YES
31	PHF5A	PHF5A	PHF5A	5253	0.061	0.16	YES
32	PRPF6	PRPF6	PRPF6	5256	0.061	0.17	YES
33	SFRS3	SFRS3	SFRS3	5270	0.06	0.18	YES
34	PPIL1	PPIL1	PPIL1	5274	0.06	0.19	YES
35	RBM17	RBM17	RBM17	5336	0.059	0.2	YES
36	SFRS6	SFRS6	SFRS6	5347	0.059	0.21	YES
37	SNRPD2	SNRPD2	SNRPD2	5373	0.059	0.21	YES
38	HNRNPU	HNRNPU	HNRNPU	5472	0.057	0.22	YES
39	MAGOHB	MAGOHB	MAGOHB	5623	0.054	0.22	YES
40	SFRS7	SFRS7	SFRS7	5701	0.052	0.22	YES
41	CCDC12	CCDC12	CCDC12	5789	0.051	0.22	YES
42	LSM4	LSM4	LSM4	5903	0.049	0.22	YES
43	SNRPB2	SNRPB2	SNRPB2	5910	0.049	0.23	YES
44	SMNDC1	SMNDC1	SMNDC1	6063	0.046	0.23	YES
45	HSPA2	HSPA2	HSPA2	6065	0.046	0.24	YES
46	RBM25	RBM25	RBM25	6147	0.045	0.24	YES
47	U2AF2	U2AF2	U2AF2	6168	0.044	0.25	YES
48	CRNKL1	CRNKL1	CRNKL1	6261	0.043	0.25	YES
49	WBP11	WBP11	WBP11	6338	0.042	0.25	YES
50	SNRPC	SNRPC	SNRPC	6363	0.041	0.26	YES
51	DDX42	DDX42	DDX42	6412	0.041	0.26	YES
52	XAB2	XAB2	XAB2	6419	0.04	0.27	YES
53	HNRNPC	HNRNPC	HNRNPC	6420	0.04	0.27	YES
54	CWC15	CWC15	CWC15	6443	0.04	0.28	YES
55	PRPF40B	PRPF40B	PRPF40B	6508	0.039	0.28	YES
56	TXNL4A	TXNL4A	TXNL4A	6509	0.039	0.29	YES
57	THOC3	THOC3	THOC3	6577	0.038	0.29	YES
58	BAT1	BAT1	BAT1	6589	0.038	0.29	YES
59	TRA2B	TRA2B	TRA2B	6616	0.037	0.3	YES
60	SFRS2	SFRS2	SFRS2	6660	0.036	0.3	YES
61	NAA38	NAA38	NAA38	6670	0.036	0.31	YES
62	TRA2A	TRA2A	TRA2A	6672	0.036	0.31	YES
63	SNW1	SNW1	SNW1	6714	0.035	0.32	YES
64	DDX46	DDX46	DDX46	6746	0.035	0.32	YES
65	HNRNPM	HNRNPM	HNRNPM	6791	0.034	0.32	YES
66	PRPF31	PRPF31	PRPF31	6845	0.033	0.32	YES
67	SF3B14	SF3B14	SF3B14	6918	0.032	0.32	YES
68	SFRS1	SFRS1	SFRS1	7019	0.03	0.32	NO
69	LSM3	LSM3	LSM3	7152	0.028	0.32	NO
70	THOC2	THOC2	THOC2	7419	0.025	0.31	NO
71	ISY1	ISY1	ISY1	7644	0.021	0.3	NO
72	PRPF40A	PRPF40A	PRPF40A	7664	0.021	0.3	NO
73	CHERP	CHERP	CHERP	7739	0.02	0.3	NO
74	SF3B5	SF3B5	SF3B5	7779	0.019	0.3	NO
75	DHX15	DHX15	DHX15	7780	0.019	0.3	NO
76	SF3B1	SF3B1	SF3B1	7817	0.019	0.31	NO
77	SART1	SART1	SART1	8013	0.015	0.3	NO
78	PRPF8	PRPF8	PRPF8	8071	0.015	0.3	NO
79	PUF60	PUF60	PUF60	8167	0.013	0.29	NO
80	EFTUD2	EFTUD2	EFTUD2	8260	0.012	0.29	NO
81	EIF4A3	EIF4A3	EIF4A3	8357	0.01	0.29	NO
82	BUD31	BUD31	BUD31	8378	0.01	0.29	NO
83	RBM22	RBM22	RBM22	8410	0.0096	0.29	NO
84	HSPA6	HSPA6	HSPA6	8449	0.0091	0.29	NO
85	DDX23	DDX23	DDX23	8539	0.0081	0.28	NO
86	PRPF38B	PRPF38B	PRPF38B	8631	0.0067	0.28	NO
87	SFRS5	SFRS5	SFRS5	8641	0.0065	0.28	NO
88	DHX16	DHX16	DHX16	8686	0.0059	0.28	NO
89	PRPF18	PRPF18	PRPF18	8704	0.0057	0.28	NO
90	PRPF4	PRPF4	PRPF4	8835	0.0038	0.27	NO
91	SF3B2	SF3B2	SF3B2	8905	0.0027	0.27	NO
92	PRPF19	PRPF19	PRPF19	8907	0.0027	0.27	NO
93	CTNNBL1	CTNNBL1	CTNNBL1	8915	0.0026	0.27	NO
94	LSM6	LSM6	LSM6	9109	-0.00064	0.26	NO
95	HNRNPK	HNRNPK	HNRNPK	9199	-0.0021	0.25	NO
96	PCBP1	PCBP1	PCBP1	9217	-0.0024	0.25	NO
97	SNRNP200	SNRNP200	SNRNP200	9324	-0.0042	0.24	NO
98	SNRNP40	SNRNP40	SNRNP40	9631	-0.0091	0.23	NO
99	SFRS13A	SFRS13A	SFRS13A	9965	-0.015	0.21	NO
100	HSPA8	HSPA8	HSPA8	10033	-0.016	0.21	NO
101	CDC5L	CDC5L	CDC5L	10046	-0.016	0.21	NO
102	NCBP1	NCBP1	NCBP1	10173	-0.018	0.21	NO
103	SF3A1	SF3A1	SF3A1	10438	-0.023	0.2	NO
104	DHX8	DHX8	DHX8	11174	-0.035	0.16	NO
105	PPIE	PPIE	PPIE	11280	-0.037	0.16	NO
106	DDX5	DDX5	DDX5	11307	-0.037	0.17	NO
107	SNRNP27	SNRNP27	SNRNP27	11400	-0.039	0.17	NO
108	AQR	AQR	AQR	11432	-0.04	0.17	NO
109	PRPF38A	PRPF38A	PRPF38A	11579	-0.042	0.17	NO
110	CDC40	CDC40	CDC40	11731	-0.045	0.17	NO
111	SLU7	SLU7	SLU7	11785	-0.046	0.17	NO
112	SF3B3	SF3B3	SF3B3	11832	-0.047	0.18	NO
113	SFRS4	SFRS4	SFRS4	11877	-0.048	0.18	NO
114	PPIH	PPIH	PPIH	11933	-0.049	0.19	NO
115	HSPA1A	HSPA1A	HSPA1A	11974	-0.05	0.19	NO
116	MAGOH	MAGOH	MAGOH	11985	-0.05	0.2	NO
117	ZMAT2	ZMAT2	ZMAT2	12115	-0.053	0.2	NO
118	LSM5	LSM5	LSM5	12330	-0.058	0.2	NO
119	SF3A3	SF3A3	SF3A3	12354	-0.058	0.2	NO
120	SYF2	SYF2	SYF2	12928	-0.071	0.18	NO
121	DHX38	DHX38	DHX38	13124	-0.076	0.18	NO
122	BCAS2	BCAS2	BCAS2	13626	-0.088	0.17	NO
123	PLRG1	PLRG1	PLRG1	13769	-0.092	0.18	NO
124	HSPA1B	HSPA1B	HSPA1B	15331	-0.15	0.11	NO
125	SFRS2B	SFRS2B	SFRS2B	15405	-0.15	0.13	NO

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

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

genes ES table in pathway: KEGG SPHINGOLIPID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DTX1	DTX1	DTX1	519	0.34	0.06	YES
2	DTX3	DTX3	DTX3	621	0.31	0.14	YES
3	LFNG	LFNG	LFNG	1086	0.24	0.18	YES
4	CTBP2	CTBP2	CTBP2	1420	0.21	0.21	YES
5	DLL3	DLL3	DLL3	1764	0.18	0.24	YES
6	NOTCH1	NOTCH1	NOTCH1	2015	0.16	0.27	YES
7	DTX4	DTX4	DTX4	2126	0.16	0.3	YES
8	DVL2	DVL2	DVL2	2280	0.15	0.33	YES
9	KAT2A	KAT2A	KAT2A	3540	0.1	0.29	YES
10	HDAC2	HDAC2	HDAC2	3891	0.091	0.29	YES
11	HES1	HES1	HES1	4323	0.08	0.29	YES
12	JAG1	JAG1	JAG1	4439	0.078	0.3	YES
13	DVL3	DVL3	DVL3	4452	0.077	0.32	YES
14	MAML1	MAML1	MAML1	4584	0.074	0.34	YES
15	JAG2	JAG2	JAG2	4587	0.074	0.35	YES
16	APH1A	APH1A	APH1A	5197	0.062	0.34	YES
17	DLL4	DLL4	DLL4	5357	0.059	0.34	YES
18	EP300	EP300	EP300	5371	0.059	0.36	YES
19	CTBP1	CTBP1	CTBP1	5610	0.054	0.36	YES
20	HDAC1	HDAC1	HDAC1	5885	0.049	0.36	YES
21	RBPJ	RBPJ	RBPJ	6026	0.047	0.36	YES
22	DTX2	DTX2	DTX2	6035	0.047	0.37	YES
23	NCOR2	NCOR2	NCOR2	6712	0.036	0.34	NO
24	SNW1	SNW1	SNW1	6714	0.035	0.35	NO
25	NOTCH3	NOTCH3	NOTCH3	6741	0.035	0.36	NO
26	NCSTN	NCSTN	NCSTN	6829	0.034	0.36	NO
27	ADAM17	ADAM17	ADAM17	7760	0.02	0.32	NO
28	PSEN1	PSEN1	PSEN1	7893	0.018	0.31	NO
29	HES5	HES5	HES5	8205	0.013	0.3	NO
30	PSEN2	PSEN2	PSEN2	8264	0.012	0.3	NO
31	CIR1	CIR1	CIR1	8353	0.01	0.3	NO
32	NUMB	NUMB	NUMB	8689	0.0059	0.28	NO
33	NOTCH2	NOTCH2	NOTCH2	9369	-0.0051	0.24	NO
34	NOTCH4	NOTCH4	NOTCH4	10274	-0.02	0.2	NO
35	NUMBL	NUMBL	NUMBL	10628	-0.026	0.18	NO
36	DTX3L	DTX3L	DTX3L	10667	-0.026	0.19	NO
37	PSENEN	PSENEN	PSENEN	10729	-0.028	0.19	NO
38	DVL1	DVL1	DVL1	11678	-0.044	0.15	NO
39	PTCRA	PTCRA	PTCRA	12351	-0.058	0.13	NO
40	CREBBP	CREBBP	CREBBP	12617	-0.064	0.13	NO
41	RFNG	RFNG	RFNG	12658	-0.065	0.14	NO
42	DLL1	DLL1	DLL1	13691	-0.09	0.11	NO
43	MAML2	MAML2	MAML2	13804	-0.093	0.13	NO
44	MAML3	MAML3	MAML3	14963	-0.13	0.099	NO
45	KAT2B	KAT2B	KAT2B	16360	-0.22	0.077	NO

Figure S53. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG SPHINGOLIPID METABOLISM.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG SPHINGOLIPID 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 GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES

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	MAPK13	MAPK13	MAPK13	125	0.5	0.052	YES
2	PLA2G1B	PLA2G1B	PLA2G1B	464	0.35	0.074	YES
3	CACNA1D	CACNA1D	CACNA1D	576	0.32	0.1	YES
4	PLA2G12B	PLA2G12B	PLA2G12B	724	0.29	0.13	YES
5	PRKX	PRKX	PRKX	754	0.29	0.16	YES
6	SRC	SRC	SRC	1102	0.24	0.17	YES
7	CALML6	CALML6	CALML6	1590	0.19	0.17	YES
8	PRKCD	PRKCD	PRKCD	1804	0.18	0.18	YES
9	PLD1	PLD1	PLD1	1930	0.17	0.19	YES
10	PLA2G10	PLA2G10	PLA2G10	2008	0.16	0.2	YES
11	ITPR3	ITPR3	ITPR3	2258	0.15	0.21	YES
12	CACNA1F	CACNA1F	CACNA1F	2285	0.15	0.22	YES
13	ADCY5	ADCY5	ADCY5	2286	0.15	0.24	YES
14	PLCB1	PLCB1	PLCB1	2364	0.14	0.25	YES
15	CAMK2B	CAMK2B	CAMK2B	2370	0.14	0.27	YES
16	CGA	CGA	CGA	2420	0.14	0.28	YES
17	PLCB4	PLCB4	PLCB4	2494	0.14	0.29	YES
18	MAP3K4	MAP3K4	MAP3K4	2515	0.14	0.31	YES
19	PLA2G6	PLA2G6	PLA2G6	2682	0.13	0.32	YES
20	GNRH1	GNRH1	GNRH1	2685	0.13	0.33	YES
21	LHB	LHB	LHB	2707	0.13	0.34	YES
22	GNAS	GNAS	GNAS	2731	0.13	0.36	YES
23	ADCY6	ADCY6	ADCY6	2934	0.12	0.36	YES
24	MAPK12	MAPK12	MAPK12	3617	0.098	0.33	NO
25	MAPK7	MAPK7	MAPK7	3749	0.095	0.34	NO
26	ATF4	ATF4	ATF4	3977	0.089	0.33	NO
27	PLCB3	PLCB3	PLCB3	4506	0.076	0.31	NO
28	KRAS	KRAS	KRAS	4510	0.076	0.32	NO
29	MAPK9	MAPK9	MAPK9	4597	0.074	0.33	NO
30	MAP2K7	MAP2K7	MAP2K7	4667	0.072	0.33	NO
31	PRKACA	PRKACA	PRKACA	4903	0.067	0.32	NO
32	MAP2K4	MAP2K4	MAP2K4	5112	0.063	0.32	NO
33	MAP2K2	MAP2K2	MAP2K2	5395	0.058	0.31	NO
34	MAP3K1	MAP3K1	MAP3K1	5458	0.057	0.32	NO
35	PLA2G2D	PLA2G2D	PLA2G2D	5570	0.055	0.32	NO
36	PLD2	PLD2	PLD2	5831	0.05	0.31	NO
37	RAF1	RAF1	RAF1	5999	0.047	0.3	NO
38	CAMK2G	CAMK2G	CAMK2G	6111	0.045	0.3	NO
39	MAPK14	MAPK14	MAPK14	6352	0.042	0.29	NO
40	CAMK2A	CAMK2A	CAMK2A	6682	0.036	0.28	NO
41	MAPK1	MAPK1	MAPK1	6795	0.034	0.28	NO
42	CALM2	CALM2	CALM2	6970	0.031	0.27	NO
43	GNAQ	GNAQ	GNAQ	7273	0.026	0.26	NO
44	PLA2G5	PLA2G5	PLA2G5	7274	0.026	0.26	NO
45	CALM3	CALM3	CALM3	7452	0.024	0.25	NO
46	CACNA1C	CACNA1C	CACNA1C	7509	0.023	0.25	NO
47	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	7564	0.022	0.25	NO
48	MAP2K6	MAP2K6	MAP2K6	7622	0.021	0.25	NO
49	CAMK2D	CAMK2D	CAMK2D	7746	0.02	0.24	NO
50	GRB2	GRB2	GRB2	7803	0.019	0.24	NO
51	MMP2	MMP2	MMP2	8229	0.012	0.22	NO
52	ELK1	ELK1	ELK1	9001	0.0014	0.18	NO
53	MMP14	MMP14	MMP14	9105	-0.00058	0.17	NO
54	CALM1	CALM1	CALM1	9200	-0.0021	0.17	NO
55	MAPK3	MAPK3	MAPK3	9334	-0.0044	0.16	NO
56	MAPK8	MAPK8	MAPK8	9533	-0.0075	0.15	NO
57	SOS2	SOS2	SOS2	9594	-0.0084	0.15	NO
58	HRAS	HRAS	HRAS	9801	-0.012	0.14	NO
59	ADCY7	ADCY7	ADCY7	9888	-0.014	0.13	NO
60	PRKCA	PRKCA	PRKCA	10055	-0.016	0.13	NO
61	GNRHR	GNRHR	GNRHR	10073	-0.016	0.13	NO
62	CACNA1S	CACNA1S	CACNA1S	10107	-0.017	0.13	NO
63	MAPK11	MAPK11	MAPK11	10775	-0.028	0.093	NO
64	SOS1	SOS1	SOS1	10789	-0.028	0.096	NO
65	MAP3K3	MAP3K3	MAP3K3	10819	-0.029	0.097	NO
66	MAP2K3	MAP2K3	MAP2K3	11044	-0.033	0.088	NO
67	NRAS	NRAS	NRAS	11057	-0.033	0.092	NO
68	ADCY2	ADCY2	ADCY2	11135	-0.034	0.091	NO
69	ADCY4	ADCY4	ADCY4	11340	-0.038	0.084	NO
70	PLA2G12A	PLA2G12A	PLA2G12A	11485	-0.041	0.081	NO
71	PLCB2	PLCB2	PLCB2	11530	-0.041	0.083	NO
72	MAP2K1	MAP2K1	MAP2K1	12327	-0.058	0.045	NO
73	ITPR2	ITPR2	ITPR2	12396	-0.059	0.048	NO
74	EGFR	EGFR	EGFR	12438	-0.06	0.053	NO
75	GNA11	GNA11	GNA11	12625	-0.064	0.05	NO
76	CDC42	CDC42	CDC42	12940	-0.071	0.04	NO
77	PRKCB	PRKCB	PRKCB	13209	-0.078	0.034	NO
78	ADCY1	ADCY1	ADCY1	13610	-0.088	0.022	NO
79	ADCY9	ADCY9	ADCY9	13852	-0.094	0.019	NO
80	CALML3	CALML3	CALML3	14040	-0.1	0.02	NO
81	JUN	JUN	JUN	14167	-0.1	0.026	NO
82	MAPK10	MAPK10	MAPK10	14342	-0.11	0.029	NO
83	PLA2G4A	PLA2G4A	PLA2G4A	14689	-0.12	0.023	NO
84	PTK2B	PTK2B	PTK2B	14719	-0.12	0.036	NO
85	HBEGF	HBEGF	HBEGF	14792	-0.13	0.047	NO
86	PLA2G2A	PLA2G2A	PLA2G2A	15814	-0.18	0.01	NO
87	PRKACB	PRKACB	PRKACB	15897	-0.18	0.027	NO
88	MAP3K2	MAP3K2	MAP3K2	16019	-0.19	0.043	NO
89	ITPR1	ITPR1	ITPR1	16035	-0.19	0.064	NO
90	ADCY8	ADCY8	ADCY8	16845	-0.27	0.05	NO

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

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES, 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 RIBOSOME

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	PLA2G1B	PLA2G1B	PLA2G1B	464	0.35	0.07	YES
2	PPAP2C	PPAP2C	PPAP2C	471	0.35	0.16	YES
3	PAFAH1B3	PAFAH1B3	PAFAH1B3	479	0.35	0.26	YES
4	PLA2G12B	PLA2G12B	PLA2G12B	724	0.29	0.32	YES
5	ENPP2	ENPP2	ENPP2	1208	0.23	0.36	YES
6	PLD1	PLD1	PLD1	1930	0.17	0.36	YES
7	PLA2G10	PLA2G10	PLA2G10	2008	0.16	0.4	YES
8	PLA2G7	PLA2G7	PLA2G7	2443	0.14	0.42	YES
9	PLA2G6	PLA2G6	PLA2G6	2682	0.13	0.44	YES
10	PLA2G2D	PLA2G2D	PLA2G2D	5570	0.055	0.29	NO
11	LPCAT1	LPCAT1	LPCAT1	5805	0.051	0.29	NO
12	PLD2	PLD2	PLD2	5831	0.05	0.3	NO
13	AGPS	AGPS	AGPS	6994	0.031	0.25	NO
14	LPCAT4	LPCAT4	LPCAT4	7245	0.027	0.24	NO
15	PLA2G5	PLA2G5	PLA2G5	7274	0.026	0.25	NO
16	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	7564	0.022	0.24	NO
17	PAFAH1B1	PAFAH1B1	PAFAH1B1	9268	-0.0031	0.14	NO
18	PLA2G12A	PLA2G12A	PLA2G12A	11485	-0.041	0.026	NO
19	CHPT1	CHPT1	CHPT1	12707	-0.066	-0.025	NO
20	PPAP2A	PPAP2A	PPAP2A	12959	-0.072	-0.019	NO
21	PAFAH1B2	PAFAH1B2	PAFAH1B2	13901	-0.096	-0.046	NO
22	PLA2G4A	PLA2G4A	PLA2G4A	14689	-0.12	-0.057	NO
23	PPAP2B	PPAP2B	PPAP2B	15325	-0.15	-0.052	NO
24	PLA2G2A	PLA2G2A	PLA2G2A	15814	-0.18	-0.031	NO
25	PAFAH2	PAFAH2	PAFAH2	16351	-0.22	-0.0023	NO
26	LPCAT2	LPCAT2	LPCAT2	17025	-0.29	0.04	NO

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

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RIBOSOME, 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 DNA REPLICATION

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	CDC25A	CDC25A	CDC25A	421	0.37	0.0042	YES
2	TTK	TTK	TTK	450	0.36	0.03	YES
3	CCNB2	CCNB2	CCNB2	523	0.34	0.051	YES
4	CDKN1C	CDKN1C	CDKN1C	552	0.33	0.075	YES
5	CDK1	CDK1	CDK1	597	0.32	0.097	YES
6	BUB1B	BUB1B	BUB1B	766	0.28	0.11	YES
7	ESPL1	ESPL1	ESPL1	797	0.28	0.13	YES
8	CDC25C	CDC25C	CDC25C	878	0.27	0.14	YES
9	PLK1	PLK1	PLK1	941	0.26	0.16	YES
10	BUB1	BUB1	BUB1	982	0.25	0.18	YES
11	PTTG1	PTTG1	PTTG1	1019	0.25	0.2	YES
12	CCNE1	CCNE1	CCNE1	1085	0.24	0.21	YES
13	CCNB1	CCNB1	CCNB1	1154	0.23	0.22	YES
14	CDC6	CDC6	CDC6	1241	0.22	0.24	YES
15	CCNB3	CCNB3	CCNB3	1294	0.22	0.25	YES
16	CCNA2	CCNA2	CCNA2	1331	0.22	0.26	YES
17	CDC20	CDC20	CDC20	1397	0.21	0.28	YES
18	SKP2	SKP2	SKP2	1572	0.19	0.28	YES
19	CDC45	CDC45	CDC45	1694	0.18	0.29	YES
20	CHEK2	CHEK2	CHEK2	1792	0.18	0.3	YES
21	ORC6L	ORC6L	ORC6L	1849	0.17	0.31	YES
22	TP53	TP53	TP53	1986	0.16	0.31	YES
23	TGFB1	TGFB1	TGFB1	2382	0.14	0.3	YES
24	CDK7	CDK7	CDK7	2439	0.14	0.31	YES
25	E2F1	E2F1	E2F1	2533	0.14	0.31	YES
26	SMC3	SMC3	SMC3	2608	0.13	0.32	YES
27	WEE1	WEE1	WEE1	2694	0.13	0.32	YES
28	MAD2L1	MAD2L1	MAD2L1	2771	0.13	0.33	YES
29	MCM2	MCM2	MCM2	2863	0.12	0.33	YES
30	CCNE2	CCNE2	CCNE2	3081	0.12	0.33	YES
31	CDK4	CDK4	CDK4	3164	0.11	0.33	YES
32	CHEK1	CHEK1	CHEK1	3218	0.11	0.34	YES
33	RBL1	RBL1	RBL1	3451	0.1	0.33	YES
34	MCM5	MCM5	MCM5	3481	0.1	0.34	YES
35	WEE2	WEE2	WEE2	3616	0.098	0.34	YES
36	MCM4	MCM4	MCM4	3628	0.098	0.35	YES
37	CDC7	CDC7	CDC7	3645	0.097	0.35	YES
38	PTTG2	PTTG2	PTTG2	3677	0.096	0.36	YES
39	MCM3	MCM3	MCM3	3747	0.095	0.36	YES
40	ANAPC4	ANAPC4	ANAPC4	3879	0.092	0.36	YES
41	HDAC2	HDAC2	HDAC2	3891	0.091	0.37	YES
42	ANAPC7	ANAPC7	ANAPC7	3995	0.088	0.37	YES
43	ORC2L	ORC2L	ORC2L	4056	0.087	0.37	YES
44	E2F3	E2F3	E2F3	4226	0.082	0.37	YES
45	TFDP1	TFDP1	TFDP1	4277	0.081	0.37	YES
46	FZR1	FZR1	FZR1	4289	0.081	0.38	YES
47	MCM6	MCM6	MCM6	4339	0.08	0.38	YES
48	SMC1B	SMC1B	SMC1B	4479	0.076	0.38	YES
49	MCM7	MCM7	MCM7	4539	0.075	0.38	YES
50	E2F2	E2F2	E2F2	4599	0.074	0.38	YES
51	ORC1L	ORC1L	ORC1L	4712	0.071	0.38	NO
52	ANAPC1	ANAPC1	ANAPC1	4917	0.067	0.38	NO
53	CDC16	CDC16	CDC16	4940	0.067	0.38	NO
54	RBX1	RBX1	RBX1	5113	0.063	0.38	NO
55	EP300	EP300	EP300	5371	0.059	0.37	NO
56	YWHAZ	YWHAZ	YWHAZ	5548	0.055	0.36	NO
57	BUB3	BUB3	BUB3	5562	0.055	0.36	NO
58	YWHAQ	YWHAQ	YWHAQ	5609	0.054	0.36	NO
59	HDAC1	HDAC1	HDAC1	5885	0.049	0.35	NO
60	YWHAH	YWHAH	YWHAH	6050	0.046	0.35	NO
61	CDC26	CDC26	CDC26	6106	0.045	0.35	NO
62	ANAPC5	ANAPC5	ANAPC5	6144	0.045	0.35	NO
63	SMAD3	SMAD3	SMAD3	6323	0.042	0.34	NO
64	ABL1	ABL1	ABL1	6388	0.041	0.34	NO
65	MAD1L1	MAD1L1	MAD1L1	6635	0.037	0.33	NO
66	CDC23	CDC23	CDC23	6848	0.033	0.32	NO
67	STAG1	STAG1	STAG1	7106	0.029	0.31	NO
68	CDK2	CDK2	CDK2	7162	0.028	0.31	NO
69	YWHAE	YWHAE	YWHAE	7249	0.027	0.3	NO
70	CDKN2D	CDKN2D	CDKN2D	7306	0.026	0.3	NO
71	RAD21	RAD21	RAD21	7350	0.025	0.3	NO
72	ORC3L	ORC3L	ORC3L	7592	0.022	0.29	NO
73	E2F5	E2F5	E2F5	7743	0.02	0.28	NO
74	ANAPC11	ANAPC11	ANAPC11	7943	0.017	0.27	NO
75	SMAD4	SMAD4	SMAD4	8018	0.015	0.27	NO
76	PRKDC	PRKDC	PRKDC	8262	0.012	0.26	NO
77	CDC27	CDC27	CDC27	8324	0.011	0.26	NO
78	ORC4L	ORC4L	ORC4L	8382	0.01	0.25	NO
79	PCNA	PCNA	PCNA	8450	0.0091	0.25	NO
80	ATM	ATM	ATM	8598	0.0072	0.24	NO
81	TGFB3	TGFB3	TGFB3	8750	0.0051	0.23	NO
82	ORC5L	ORC5L	ORC5L	8840	0.0038	0.23	NO
83	E2F4	E2F4	E2F4	9113	-0.00071	0.21	NO
84	CCND2	CCND2	CCND2	9267	-0.0031	0.2	NO
85	SKP1	SKP1	SKP1	9611	-0.0087	0.19	NO
86	CDC25B	CDC25B	CDC25B	9654	-0.0094	0.18	NO
87	PKMYT1	PKMYT1	PKMYT1	9746	-0.011	0.18	NO
88	YWHAB	YWHAB	YWHAB	9837	-0.013	0.18	NO
89	CCND1	CCND1	CCND1	9861	-0.013	0.18	NO
90	SMAD2	SMAD2	SMAD2	10108	-0.017	0.16	NO
91	ANAPC2	ANAPC2	ANAPC2	10182	-0.018	0.16	NO
92	CDC14A	CDC14A	CDC14A	10321	-0.021	0.15	NO
93	ATR	ATR	ATR	10330	-0.021	0.16	NO
94	ANAPC13	ANAPC13	ANAPC13	10343	-0.021	0.16	NO
95	STAG2	STAG2	STAG2	10756	-0.028	0.14	NO
96	SMC1A	SMC1A	SMC1A	10904	-0.03	0.13	NO
97	GSK3B	GSK3B	GSK3B	11562	-0.042	0.095	NO
98	YWHAG	YWHAG	YWHAG	11626	-0.043	0.095	NO
99	CDKN1B	CDKN1B	CDKN1B	11651	-0.044	0.097	NO
100	MDM2	MDM2	MDM2	11766	-0.046	0.094	NO
101	MYC	MYC	MYC	11947	-0.049	0.087	NO
102	TFDP2	TFDP2	TFDP2	12497	-0.061	0.061	NO
103	ZBTB17	ZBTB17	ZBTB17	12501	-0.062	0.065	NO
104	CUL1	CUL1	CUL1	12539	-0.062	0.068	NO
105	CREBBP	CREBBP	CREBBP	12617	-0.064	0.069	NO
106	RB1	RB1	RB1	13175	-0.077	0.043	NO
107	TGFB2	TGFB2	TGFB2	13288	-0.08	0.043	NO
108	GADD45B	GADD45B	GADD45B	13662	-0.089	0.028	NO
109	CCND3	CCND3	CCND3	13780	-0.092	0.029	NO
110	CDKN2C	CDKN2C	CDKN2C	13940	-0.097	0.027	NO
111	CCNH	CCNH	CCNH	13975	-0.098	0.033	NO
112	ANAPC10	ANAPC10	ANAPC10	14153	-0.1	0.03	NO
113	CCNA1	CCNA1	CCNA1	14508	-0.12	0.019	NO
114	CDKN1A	CDKN1A	CDKN1A	14538	-0.12	0.027	NO
115	CDK6	CDK6	CDK6	14608	-0.12	0.032	NO
116	SFN	SFN	SFN	15778	-0.18	-0.021	NO
117	MAD2L2	MAD2L2	MAD2L2	15825	-0.18	-0.01	NO
118	RBL2	RBL2	RBL2	16131	-0.2	-0.012	NO
119	GADD45A	GADD45A	GADD45A	16704	-0.25	-0.025	NO
120	GADD45G	GADD45G	GADD45G	16716	-0.25	-0.0066	NO
121	CDKN2B	CDKN2B	CDKN2B	16839	-0.27	0.0069	NO
122	CDC14B	CDC14B	CDC14B	16899	-0.28	0.025	NO
123	CDKN2A	CDKN2A	CDKN2A	17017	-0.29	0.04	NO

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

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

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.
BIOCARTA NO1 PATHWAY	28	genes.ES.table	0.59	1.5	0.046	0.093	0.83	0.46	0.23	0.36	0.061
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.45	1.4	0.05	0.13	0.92	0.6	0.42	0.35	0.098
BIOCARTA ALK PATHWAY	33	genes.ES.table	0.5	1.5	0.051	0.1	0.87	0.48	0.3	0.34	0.072
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.51	1.4	0.11	0.13	0.93	0.24	0.14	0.21	0.098
BIOCARTA CARM ER PATHWAY	34	genes.ES.table	0.34	1.3	0.18	0.24	0.99	0.18	0.27	0.13	0.2
BIOCARTA HDAC PATHWAY	26	genes.ES.table	0.46	1.4	0.11	0.14	0.93	0.15	0.1	0.14	0.11
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.38	1.3	0.24	0.24	0.99	0.5	0.41	0.3	0.21
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.53	1.6	0.028	0.06	0.67	0.18	0.11	0.16	0.035
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.42	1.4	0.16	0.15	0.95	0.66	0.48	0.34	0.12
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.61	1.7	0.012	0.053	0.56	0.27	0.12	0.24	0.026

genes ES table in pathway: BIOCARTA NO1 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	PRKAR2B	PRKAR2B	PRKAR2B	475	0.51	0.029	YES
2	ENDOD1	ENDOD1	ENDOD1	512	0.5	0.081	YES
3	IRAK3	IRAK3	IRAK3	536	0.49	0.13	YES
4	AKT3	AKT3	AKT3	748	0.44	0.17	YES
5	PRKX	PRKX	PRKX	766	0.44	0.22	YES
6	BCL2	BCL2	BCL2	912	0.41	0.25	YES
7	CSF2RB	CSF2RB	CSF2RB	1163	0.38	0.28	YES
8	IL1B	IL1B	IL1B	1250	0.37	0.32	YES
9	PIK3R5	PIK3R5	PIK3R5	1370	0.36	0.35	YES
10	NGF	NGF	NGF	1508	0.34	0.38	YES
11	BIRC3	BIRC3	BIRC3	1774	0.31	0.39	YES
12	TNF	TNF	TNF	1799	0.31	0.43	YES
13	PIK3CG	PIK3CG	PIK3CG	1828	0.31	0.46	YES
14	PIK3CD	PIK3CD	PIK3CD	1884	0.3	0.49	YES
15	TNFRSF10C	TNFRSF10C	TNFRSF10C	2157	0.28	0.5	YES
16	NTRK1	NTRK1	NTRK1	2427	0.26	0.52	YES
17	PRKAR1B	PRKAR1B	PRKAR1B	2672	0.24	0.53	YES
18	TNFRSF10A	TNFRSF10A	TNFRSF10A	2873	0.22	0.54	YES
19	IL3RA	IL3RA	IL3RA	3001	0.22	0.56	YES
20	CAPN2	CAPN2	CAPN2	3864	0.16	0.53	NO
21	TP53	TP53	TP53	4408	0.13	0.51	NO
22	PIK3R3	PIK3R3	PIK3R3	4569	0.12	0.51	NO
23	NFKB1	NFKB1	NFKB1	4811	0.11	0.51	NO
24	PPP3CC	PPP3CC	PPP3CC	5721	0.078	0.47	NO
25	PPP3CA	PPP3CA	PPP3CA	5725	0.078	0.48	NO
26	CFLAR	CFLAR	CFLAR	5922	0.072	0.47	NO
27	IL1R1	IL1R1	IL1R1	5938	0.072	0.48	NO
28	IKBKB	IKBKB	IKBKB	5986	0.07	0.49	NO
29	FAS	FAS	FAS	6001	0.07	0.49	NO
30	TRADD	TRADD	TRADD	6045	0.069	0.5	NO
31	CASP6	CASP6	CASP6	6081	0.068	0.5	NO
32	CASP10	CASP10	CASP10	6611	0.056	0.48	NO
33	CASP7	CASP7	CASP7	6615	0.056	0.49	NO
34	TNFRSF1A	TNFRSF1A	TNFRSF1A	6754	0.052	0.48	NO
35	CAPN1	CAPN1	CAPN1	6755	0.052	0.49	NO
36	IL1A	IL1A	IL1A	6924	0.049	0.48	NO
37	BID	BID	BID	7073	0.046	0.48	NO
38	BCL2L1	BCL2L1	BCL2L1	7085	0.045	0.49	NO
39	PRKACA	PRKACA	PRKACA	7142	0.044	0.49	NO
40	NFKBIA	NFKBIA	NFKBIA	7273	0.041	0.48	NO
41	CYCS	CYCS	CYCS	7422	0.038	0.48	NO
42	IRAK1	IRAK1	IRAK1	7500	0.037	0.48	NO
43	TNFRSF10B	TNFRSF10B	TNFRSF10B	7583	0.036	0.48	NO
44	AKT1	AKT1	AKT1	7775	0.032	0.47	NO
45	IRAK4	IRAK4	IRAK4	7924	0.03	0.47	NO
46	BAX	BAX	BAX	7969	0.029	0.47	NO
47	ATM	ATM	ATM	7989	0.029	0.47	NO
48	BAD	BAD	BAD	8004	0.029	0.47	NO
49	PIK3CA	PIK3CA	PIK3CA	8136	0.026	0.47	NO
50	CHP	CHP	CHP	8154	0.026	0.47	NO
51	PPP3CB	PPP3CB	PPP3CB	8192	0.026	0.47	NO
52	FADD	FADD	FADD	8409	0.023	0.46	NO
53	XIAP	XIAP	XIAP	8458	0.022	0.46	NO
54	CASP8	CASP8	CASP8	8991	0.014	0.43	NO
55	IL1RAP	IL1RAP	IL1RAP	9056	0.013	0.43	NO
56	DFFB	DFFB	DFFB	9593	0.0066	0.4	NO
57	AIFM1	AIFM1	AIFM1	9599	0.0066	0.4	NO
58	MAP3K14	MAP3K14	MAP3K14	9628	0.0061	0.4	NO
59	IKBKG	IKBKG	IKBKG	9663	0.0055	0.4	NO
60	PIK3CB	PIK3CB	PIK3CB	9781	0.0041	0.39	NO
61	CHP2	CHP2	CHP2	9981	0.0016	0.38	NO
62	CHUK	CHUK	CHUK	10385	-0.003	0.36	NO
63	CASP3	CASP3	CASP3	10465	-0.0041	0.35	NO
64	TRAF2	TRAF2	TRAF2	10663	-0.0065	0.34	NO
65	APAF1	APAF1	APAF1	10809	-0.0082	0.34	NO
66	PRKACB	PRKACB	PRKACB	10812	-0.0082	0.34	NO
67	PRKAR1A	PRKAR1A	PRKAR1A	10918	-0.0096	0.33	NO
68	RELA	RELA	RELA	11131	-0.012	0.32	NO
69	TNFRSF10D	TNFRSF10D	TNFRSF10D	11488	-0.016	0.3	NO
70	RIPK1	RIPK1	RIPK1	11493	-0.017	0.3	NO
71	DFFA	DFFA	DFFA	11507	-0.017	0.31	NO
72	PIK3R2	PIK3R2	PIK3R2	11746	-0.02	0.29	NO
73	TNFSF10	TNFSF10	TNFSF10	11893	-0.022	0.29	NO
74	EXOG	EXOG	EXOG	12035	-0.024	0.28	NO
75	BIRC2	BIRC2	BIRC2	12209	-0.026	0.28	NO
76	AKT2	AKT2	AKT2	12348	-0.028	0.27	NO
77	IRAK2	IRAK2	IRAK2	12372	-0.028	0.27	NO
78	PPP3R1	PPP3R1	PPP3R1	12388	-0.028	0.28	NO
79	MYD88	MYD88	MYD88	12856	-0.034	0.25	NO
80	CASP9	CASP9	CASP9	13049	-0.037	0.24	NO
81	ENDOG	ENDOG	ENDOG	13227	-0.04	0.24	NO
82	PIK3R1	PIK3R1	PIK3R1	14760	-0.07	0.16	NO
83	PRKAR2A	PRKAR2A	PRKAR2A	14856	-0.072	0.16	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 NO1 PATHWAY.

Figure S62. 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 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	PRICKLE1	PRICKLE1	PRICKLE1	14	0.84	0.033	YES
2	SFRP4	SFRP4	SFRP4	61	0.73	0.059	YES
3	SFRP1	SFRP1	SFRP1	98	0.7	0.085	YES
4	MAPK10	MAPK10	MAPK10	102	0.7	0.11	YES
5	WNT4	WNT4	WNT4	162	0.65	0.14	YES
6	WNT2	WNT2	WNT2	171	0.64	0.16	YES
7	DKK2	DKK2	DKK2	180	0.64	0.18	YES
8	FZD2	FZD2	FZD2	198	0.63	0.21	YES
9	MMP7	MMP7	MMP7	264	0.59	0.23	YES
10	NKD2	NKD2	NKD2	298	0.57	0.25	YES
11	WNT2B	WNT2B	WNT2B	315	0.56	0.27	YES
12	PLCB4	PLCB4	PLCB4	362	0.54	0.29	YES
13	FZD10	FZD10	FZD10	377	0.54	0.31	YES
14	SFRP5	SFRP5	SFRP5	478	0.51	0.32	YES
15	VANGL2	VANGL2	VANGL2	497	0.5	0.34	YES
16	NFATC1	NFATC1	NFATC1	575	0.48	0.36	YES
17	WNT10A	WNT10A	WNT10A	605	0.48	0.38	YES
18	FZD1	FZD1	FZD1	695	0.46	0.39	YES
19	WNT9A	WNT9A	WNT9A	702	0.45	0.41	YES
20	FZD7	FZD7	FZD7	713	0.45	0.42	YES
21	FZD8	FZD8	FZD8	729	0.45	0.44	YES
22	PRKX	PRKX	PRKX	766	0.44	0.46	YES
23	CTBP2	CTBP2	CTBP2	868	0.42	0.47	YES
24	SFRP2	SFRP2	SFRP2	893	0.42	0.48	YES
25	WNT10B	WNT10B	WNT10B	901	0.41	0.5	YES
26	PRICKLE2	PRICKLE2	PRICKLE2	930	0.41	0.51	YES
27	WNT7B	WNT7B	WNT7B	1003	0.4	0.52	YES
28	SOX17	SOX17	SOX17	1102	0.39	0.54	YES
29	NFATC4	NFATC4	NFATC4	1297	0.36	0.54	YES
30	CCND2	CCND2	CCND2	1353	0.36	0.55	YES
31	PRKCB	PRKCB	PRKCB	1538	0.33	0.55	YES
32	PLCB2	PLCB2	PLCB2	1612	0.33	0.56	YES
33	FOSL1	FOSL1	FOSL1	1633	0.32	0.57	YES
34	RAC2	RAC2	RAC2	1875	0.3	0.57	YES
35	WNT7A	WNT7A	WNT7A	1877	0.3	0.58	YES
36	WNT11	WNT11	WNT11	2070	0.28	0.58	YES
37	WNT1	WNT1	WNT1	2139	0.28	0.59	YES
38	LEF1	LEF1	LEF1	2213	0.27	0.6	YES
39	WNT3A	WNT3A	WNT3A	2845	0.23	0.57	NO
40	CAMK2A	CAMK2A	CAMK2A	3350	0.19	0.55	NO
41	FZD6	FZD6	FZD6	3357	0.19	0.56	NO
42	WNT9B	WNT9B	WNT9B	3585	0.18	0.55	NO
43	WNT6	WNT6	WNT6	3803	0.16	0.55	NO
44	FZD3	FZD3	FZD3	3841	0.16	0.55	NO
45	MYC	MYC	MYC	3924	0.16	0.55	NO
46	CAMK2B	CAMK2B	CAMK2B	4018	0.15	0.55	NO
47	APC2	APC2	APC2	4125	0.15	0.55	NO
48	TP53	TP53	TP53	4408	0.13	0.54	NO
49	CCND3	CCND3	CCND3	4612	0.12	0.53	NO
50	CCND1	CCND1	CCND1	4814	0.11	0.53	NO
51	WNT16	WNT16	WNT16	4844	0.11	0.53	NO
52	NFATC2	NFATC2	NFATC2	4845	0.11	0.53	NO
53	VANGL1	VANGL1	VANGL1	5031	0.1	0.53	NO
54	PORCN	PORCN	PORCN	5043	0.1	0.53	NO
55	AXIN1	AXIN1	AXIN1	5274	0.094	0.52	NO
56	PPARD	PPARD	PPARD	5458	0.087	0.52	NO
57	PPP2CB	PPP2CB	PPP2CB	5634	0.081	0.51	NO
58	PPP3CC	PPP3CC	PPP3CC	5721	0.078	0.51	NO
59	PPP3CA	PPP3CA	PPP3CA	5725	0.078	0.51	NO
60	PLCB3	PLCB3	PLCB3	5773	0.077	0.51	NO
61	PPP2R5E	PPP2R5E	PPP2R5E	5912	0.073	0.5	NO
62	FBXW11	FBXW11	FBXW11	6207	0.065	0.49	NO
63	CSNK1E	CSNK1E	CSNK1E	6271	0.063	0.49	NO
64	NFAT5	NFAT5	NFAT5	6319	0.062	0.49	NO
65	DAAM1	DAAM1	DAAM1	6346	0.061	0.49	NO
66	PPP2R1A	PPP2R1A	PPP2R1A	6792	0.051	0.47	NO
67	DAAM2	DAAM2	DAAM2	6813	0.051	0.47	NO
68	SMAD2	SMAD2	SMAD2	6912	0.049	0.46	NO
69	PRKACA	PRKACA	PRKACA	7142	0.044	0.45	NO
70	RAC1	RAC1	RAC1	7148	0.044	0.46	NO
71	FZD4	FZD4	FZD4	7183	0.043	0.46	NO
72	WNT5A	WNT5A	WNT5A	7279	0.041	0.45	NO
73	CAMK2D	CAMK2D	CAMK2D	7283	0.041	0.45	NO
74	WNT5B	WNT5B	WNT5B	7290	0.041	0.45	NO
75	SKP1	SKP1	SKP1	7885	0.03	0.42	NO
76	ROCK1	ROCK1	ROCK1	7930	0.03	0.42	NO
77	CSNK1A1	CSNK1A1	CSNK1A1	7949	0.03	0.42	NO
78	APC	APC	APC	8023	0.028	0.42	NO
79	CHP	CHP	CHP	8154	0.026	0.41	NO
80	PPP3CB	PPP3CB	PPP3CB	8192	0.026	0.41	NO
81	JUN	JUN	JUN	8506	0.021	0.39	NO
82	CSNK2A1	CSNK2A1	CSNK2A1	8629	0.02	0.39	NO
83	SIAH1	SIAH1	SIAH1	8709	0.018	0.38	NO
84	MAPK9	MAPK9	MAPK9	8780	0.017	0.38	NO
85	TBL1XR1	TBL1XR1	TBL1XR1	9048	0.013	0.36	NO
86	PSEN1	PSEN1	PSEN1	9126	0.012	0.36	NO
87	TCF7L2	TCF7L2	TCF7L2	9172	0.012	0.36	NO
88	MAPK8	MAPK8	MAPK8	9184	0.012	0.36	NO
89	RHOA	RHOA	RHOA	9253	0.011	0.36	NO
90	CSNK2A2	CSNK2A2	CSNK2A2	9394	0.009	0.35	NO
91	RBX1	RBX1	RBX1	9482	0.0079	0.34	NO
92	CAMK2G	CAMK2G	CAMK2G	9541	0.0072	0.34	NO
93	CREBBP	CREBBP	CREBBP	9648	0.0058	0.33	NO
94	BTRC	BTRC	BTRC	9979	0.0016	0.32	NO
95	CHP2	CHP2	CHP2	9981	0.0016	0.32	NO
96	RUVBL1	RUVBL1	RUVBL1	10139	0.000041	0.31	NO
97	SMAD3	SMAD3	SMAD3	10237	-0.0012	0.3	NO
98	CTBP1	CTBP1	CTBP1	10395	-0.0031	0.29	NO
99	PPP2R5C	PPP2R5C	PPP2R5C	10424	-0.0035	0.29	NO
100	PPP2CA	PPP2CA	PPP2CA	10592	-0.0057	0.28	NO
101	TCF7L1	TCF7L1	TCF7L1	10620	-0.006	0.28	NO
102	FZD9	FZD9	FZD9	10675	-0.0067	0.28	NO
103	WNT3	WNT3	WNT3	10734	-0.0072	0.27	NO
104	PRKACB	PRKACB	PRKACB	10812	-0.0082	0.27	NO
105	LRP5	LRP5	LRP5	10843	-0.0087	0.27	NO
106	CUL1	CUL1	CUL1	10947	-0.0099	0.26	NO
107	CHD8	CHD8	CHD8	11055	-0.011	0.26	NO
108	SMAD4	SMAD4	SMAD4	11225	-0.013	0.25	NO
109	DVL3	DVL3	DVL3	11435	-0.016	0.24	NO
110	AXIN2	AXIN2	AXIN2	11458	-0.016	0.24	NO
111	EP300	EP300	EP300	11540	-0.017	0.23	NO
112	GSK3B	GSK3B	GSK3B	11610	-0.018	0.23	NO
113	PPP2R1B	PPP2R1B	PPP2R1B	12056	-0.024	0.2	NO
114	PPP3R1	PPP3R1	PPP3R1	12388	-0.028	0.19	NO
115	DVL1	DVL1	DVL1	12659	-0.032	0.17	NO
116	MAP3K7	MAP3K7	MAP3K7	12693	-0.032	0.17	NO
117	PRKCG	PRKCG	PRKCG	12717	-0.032	0.17	NO
118	DVL2	DVL2	DVL2	12767	-0.033	0.17	NO
119	CTNNB1	CTNNB1	CTNNB1	12896	-0.035	0.16	NO
120	FRAT2	FRAT2	FRAT2	13094	-0.038	0.16	NO
121	LRP6	LRP6	LRP6	13144	-0.038	0.15	NO
122	NFATC3	NFATC3	NFATC3	13325	-0.041	0.15	NO
123	CSNK1A1L	CSNK1A1L	CSNK1A1L	13468	-0.043	0.14	NO
124	ROCK2	ROCK2	ROCK2	13528	-0.044	0.14	NO
125	PPP2R5A	PPP2R5A	PPP2R5A	13662	-0.047	0.13	NO
126	NLK	NLK	NLK	13680	-0.047	0.13	NO
127	CACYBP	CACYBP	CACYBP	13906	-0.051	0.12	NO
128	DKK1	DKK1	DKK1	14104	-0.055	0.11	NO
129	TBL1X	TBL1X	TBL1X	14774	-0.07	0.078	NO
130	CSNK2B	CSNK2B	CSNK2B	14910	-0.073	0.073	NO
131	CXXC4	CXXC4	CXXC4	14924	-0.073	0.075	NO
132	SENP2	SENP2	SENP2	15004	-0.076	0.074	NO
133	FZD5	FZD5	FZD5	15131	-0.08	0.07	NO
134	FRAT1	FRAT1	FRAT1	15184	-0.081	0.07	NO
135	PPP2R5D	PPP2R5D	PPP2R5D	15205	-0.082	0.072	NO
136	PRKCA	PRKCA	PRKCA	15772	-0.1	0.044	NO
137	CTNNBIP1	CTNNBIP1	CTNNBIP1	15867	-0.11	0.043	NO
138	PLCB1	PLCB1	PLCB1	16037	-0.12	0.038	NO
139	DKK4	DKK4	DKK4	16334	-0.14	0.027	NO
140	TBL1Y	TBL1Y	TBL1Y	16446	-0.14	0.026	NO
141	NKD1	NKD1	NKD1	16488	-0.15	0.029	NO
142	WNT8B	WNT8B	WNT8B	17064	-0.19	0.0044	NO
143	TCF7	TCF7	TCF7	17245	-0.22	0.0029	NO
144	WIF1	WIF1	WIF1	17569	-0.3	-0.0038	NO
145	RAC3	RAC3	RAC3	17620	-0.32	0.0061	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: BIOCARTA AGR PATHWAY.

Figure S64. 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 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	MAPK10	MAPK10	MAPK10	102	0.7	0.08	YES
2	CXCL1	CXCL1	CXCL1	468	0.51	0.12	YES
3	JAM2	JAM2	JAM2	545	0.49	0.18	YES
4	IL8	IL8	IL8	631	0.47	0.23	YES
5	PTPRZ1	PTPRZ1	PTPRZ1	883	0.42	0.27	YES
6	CXCR2	CXCR2	CXCR2	993	0.4	0.31	YES
7	IGSF5	IGSF5	IGSF5	1754	0.31	0.31	YES
8	JAM3	JAM3	JAM3	1860	0.3	0.34	YES
9	CXCR1	CXCR1	CXCR1	1866	0.3	0.37	YES
10	MAPK12	MAPK12	MAPK12	1899	0.3	0.41	YES
11	MAPK11	MAPK11	MAPK11	2005	0.29	0.44	YES
12	ATP6V1B1	ATP6V1B1	ATP6V1B1	2846	0.23	0.42	YES
13	CCL5	CCL5	CCL5	2848	0.23	0.45	YES
14	HBEGF	HBEGF	HBEGF	2975	0.22	0.47	YES
15	MAPK13	MAPK13	MAPK13	3056	0.21	0.49	YES
16	NOD1	NOD1	NOD1	3460	0.19	0.49	YES
17	LYN	LYN	LYN	3620	0.18	0.5	YES
18	ATP6V0D2	ATP6V0D2	ATP6V0D2	4052	0.15	0.49	YES
19	ADAM17	ADAM17	ADAM17	4316	0.14	0.5	YES
20	PLCG2	PLCG2	PLCG2	4644	0.12	0.49	YES
21	ATP6V1H	ATP6V1H	ATP6V1H	4656	0.12	0.51	YES
22	SRC	SRC	SRC	4700	0.12	0.52	YES
23	NFKB1	NFKB1	NFKB1	4811	0.11	0.53	YES
24	TCIRG1	TCIRG1	TCIRG1	4847	0.11	0.54	YES
25	EGFR	EGFR	EGFR	5445	0.088	0.52	NO
26	ATP6V1E2	ATP6V1E2	ATP6V1E2	5446	0.088	0.53	NO
27	ADAM10	ADAM10	ADAM10	5579	0.083	0.53	NO
28	IKBKB	IKBKB	IKBKB	5986	0.07	0.51	NO
29	GIT1	GIT1	GIT1	6114	0.067	0.52	NO
30	F11R	F11R	F11R	6149	0.066	0.52	NO
31	ATP6V1B2	ATP6V1B2	ATP6V1B2	6174	0.066	0.53	NO
32	ATP6V0D1	ATP6V0D1	ATP6V0D1	6509	0.058	0.52	NO
33	TJP1	TJP1	TJP1	6765	0.052	0.51	NO
34	ATP6V1E1	ATP6V1E1	ATP6V1E1	6944	0.048	0.5	NO
35	ATP6V1F	ATP6V1F	ATP6V1F	7028	0.047	0.5	NO
36	RAC1	RAC1	RAC1	7148	0.044	0.5	NO
37	MAP2K4	MAP2K4	MAP2K4	7250	0.042	0.5	NO
38	NFKBIA	NFKBIA	NFKBIA	7273	0.041	0.51	NO
39	ATP6V0C	ATP6V0C	ATP6V0C	7342	0.04	0.51	NO
40	PAK1	PAK1	PAK1	7355	0.04	0.51	NO
41	ATP6V1C1	ATP6V1C1	ATP6V1C1	7418	0.039	0.51	NO
42	ATP6V0B	ATP6V0B	ATP6V0B	7477	0.037	0.52	NO
43	ATP6V1D	ATP6V1D	ATP6V1D	7803	0.032	0.5	NO
44	CDC42	CDC42	CDC42	8025	0.028	0.49	NO
45	ATP6V1G2	ATP6V1G2	ATP6V1G2	8114	0.027	0.49	NO
46	ATP6V0A4	ATP6V0A4	ATP6V0A4	8263	0.025	0.48	NO
47	JUN	JUN	JUN	8506	0.021	0.47	NO
48	ATP6V1A	ATP6V1A	ATP6V1A	8524	0.021	0.48	NO
49	MAPK9	MAPK9	MAPK9	8780	0.017	0.46	NO
50	ATP6V1G1	ATP6V1G1	ATP6V1G1	9165	0.012	0.44	NO
51	MAPK8	MAPK8	MAPK8	9184	0.012	0.44	NO
52	ATP6V0A1	ATP6V0A1	ATP6V0A1	9203	0.011	0.44	NO
53	MAP3K14	MAP3K14	MAP3K14	9628	0.0061	0.42	NO
54	IKBKG	IKBKG	IKBKG	9663	0.0055	0.42	NO
55	CSK	CSK	CSK	9715	0.0049	0.42	NO
56	CHUK	CHUK	CHUK	10385	-0.003	0.38	NO
57	CASP3	CASP3	CASP3	10465	-0.0041	0.38	NO
58	ATP6AP1	ATP6AP1	ATP6AP1	10715	-0.007	0.36	NO
59	PTPN11	PTPN11	PTPN11	10976	-0.01	0.35	NO
60	RELA	RELA	RELA	11131	-0.012	0.34	NO
61	PLCG1	PLCG1	PLCG1	11593	-0.018	0.32	NO
62	ATP6V1C2	ATP6V1C2	ATP6V1C2	11990	-0.023	0.3	NO
63	MAPK14	MAPK14	MAPK14	12885	-0.035	0.25	NO
64	ATP6V0A2	ATP6V0A2	ATP6V0A2	13112	-0.038	0.24	NO
65	ATP6V0E2	ATP6V0E2	ATP6V0E2	14276	-0.059	0.18	NO
66	MET	MET	MET	15509	-0.093	0.13	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: BIOCARTA ALK PATHWAY.

Figure S66. 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 BCR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SFRP4	SFRP4	SFRP4	61	0.73	0.047	YES
2	SFRP1	SFRP1	SFRP1	98	0.7	0.093	YES
3	WNT4	WNT4	WNT4	162	0.65	0.13	YES
4	WNT2	WNT2	WNT2	171	0.64	0.18	YES
5	FZD2	FZD2	FZD2	198	0.63	0.22	YES
6	WNT2B	WNT2B	WNT2B	315	0.56	0.25	YES
7	WISP1	WISP1	WISP1	327	0.56	0.29	YES
8	WNT10A	WNT10A	WNT10A	605	0.48	0.31	YES
9	FRZB	FRZB	FRZB	609	0.47	0.34	YES
10	FZD1	FZD1	FZD1	695	0.46	0.37	YES
11	WNT9A	WNT9A	WNT9A	702	0.45	0.4	YES
12	FZD7	FZD7	FZD7	713	0.45	0.43	YES
13	FZD8	FZD8	FZD8	729	0.45	0.46	YES
14	CTBP2	CTBP2	CTBP2	868	0.42	0.48	YES
15	PYGO1	PYGO1	PYGO1	990	0.4	0.5	YES
16	WNT7B	WNT7B	WNT7B	1003	0.4	0.53	YES
17	SOX17	SOX17	SOX17	1102	0.39	0.55	YES
18	CCND2	CCND2	CCND2	1353	0.36	0.56	YES
19	FOSL1	FOSL1	FOSL1	1633	0.32	0.56	YES
20	WNT7A	WNT7A	WNT7A	1877	0.3	0.57	YES
21	WNT11	WNT11	WNT11	2070	0.28	0.58	YES
22	WNT1	WNT1	WNT1	2139	0.28	0.6	YES
23	LEF1	LEF1	LEF1	2213	0.27	0.61	YES
24	FZD6	FZD6	FZD6	3357	0.19	0.56	NO
25	WNT6	WNT6	WNT6	3803	0.16	0.55	NO
26	FZD3	FZD3	FZD3	3841	0.16	0.55	NO
27	MYC	MYC	MYC	3924	0.16	0.56	NO
28	CCND3	CCND3	CCND3	4612	0.12	0.53	NO
29	CCND1	CCND1	CCND1	4814	0.11	0.53	NO
30	WNT16	WNT16	WNT16	4844	0.11	0.53	NO
31	TLE2	TLE2	TLE2	4920	0.11	0.54	NO
32	PORCN	PORCN	PORCN	5043	0.1	0.54	NO
33	AXIN1	AXIN1	AXIN1	5274	0.094	0.53	NO
34	B2M	B2M	B2M	5567	0.083	0.52	NO
35	DIXDC1	DIXDC1	DIXDC1	5582	0.083	0.52	NO
36	FBXW11	FBXW11	FBXW11	6207	0.065	0.49	NO
37	DAAM1	DAAM1	DAAM1	6346	0.061	0.49	NO
38	PPP2R1A	PPP2R1A	PPP2R1A	6792	0.051	0.47	NO
39	AES	AES	AES	6951	0.048	0.46	NO
40	FZD4	FZD4	FZD4	7183	0.043	0.45	NO
41	WNT5A	WNT5A	WNT5A	7279	0.041	0.45	NO
42	WNT5B	WNT5B	WNT5B	7290	0.041	0.45	NO
43	KREMEN1	KREMEN1	KREMEN1	7331	0.04	0.45	NO
44	ACTB	ACTB	ACTB	7606	0.035	0.44	NO
45	CSNK1A1	CSNK1A1	CSNK1A1	7949	0.03	0.42	NO
46	APC	APC	APC	8023	0.028	0.42	NO
47	JUN	JUN	JUN	8506	0.021	0.39	NO
48	CSNK2A1	CSNK2A1	CSNK2A1	8629	0.02	0.39	NO
49	GSK3A	GSK3A	GSK3A	8644	0.019	0.39	NO
50	GAPDH	GAPDH	GAPDH	9243	0.011	0.36	NO
51	CSNK1G1	CSNK1G1	CSNK1G1	9355	0.0095	0.35	NO
52	FBXW4	FBXW4	FBXW4	9914	0.0023	0.32	NO
53	BTRC	BTRC	BTRC	9979	0.0016	0.31	NO
54	CTBP1	CTBP1	CTBP1	10395	-0.0031	0.29	NO
55	RPL13A	RPL13A	RPL13A	10437	-0.0037	0.29	NO
56	PPP2CA	PPP2CA	PPP2CA	10592	-0.0057	0.28	NO
57	TCF7L1	TCF7L1	TCF7L1	10620	-0.006	0.28	NO
58	WNT3	WNT3	WNT3	10734	-0.0072	0.27	NO
59	LRP5	LRP5	LRP5	10843	-0.0087	0.27	NO
60	BCL9	BCL9	BCL9	11272	-0.014	0.24	NO
61	EP300	EP300	EP300	11540	-0.017	0.23	NO
62	GSK3B	GSK3B	GSK3B	11610	-0.018	0.23	NO
63	FBXW2	FBXW2	FBXW2	11717	-0.02	0.22	NO
64	DVL1	DVL1	DVL1	12659	-0.032	0.17	NO
65	DVL2	DVL2	DVL2	12767	-0.033	0.17	NO
66	CTNNB1	CTNNB1	CTNNB1	12896	-0.035	0.16	NO
67	CSNK1D	CSNK1D	CSNK1D	13008	-0.036	0.16	NO
68	PITX2	PITX2	PITX2	13031	-0.037	0.16	NO
69	LRP6	LRP6	LRP6	13144	-0.038	0.16	NO
70	RHOU	RHOU	RHOU	13431	-0.043	0.14	NO
71	NLK	NLK	NLK	13680	-0.047	0.13	NO
72	DKK1	DKK1	DKK1	14104	-0.055	0.11	NO
73	CXXC4	CXXC4	CXXC4	14924	-0.073	0.071	NO
74	SENP2	SENP2	SENP2	15004	-0.076	0.072	NO
75	SLC9A3R1	SLC9A3R1	SLC9A3R1	15105	-0.079	0.072	NO
76	FZD5	FZD5	FZD5	15131	-0.08	0.076	NO
77	TLE1	TLE1	TLE1	15137	-0.08	0.081	NO
78	FRAT1	FRAT1	FRAT1	15184	-0.081	0.084	NO
79	HPRT1	HPRT1	HPRT1	15716	-0.1	0.061	NO
80	CTNNBIP1	CTNNBIP1	CTNNBIP1	15867	-0.11	0.06	NO
81	NKD1	NKD1	NKD1	16488	-0.15	0.035	NO
82	TCF7	TCF7	TCF7	17245	-0.22	0.007	NO
83	WIF1	WIF1	WIF1	17569	-0.3	0.009	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: BIOCARTA BCR PATHWAY.

Figure S68. 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 CARM ER PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	WNT4	WNT4	WNT4	162	0.65	0.028	YES
2	WNT2	WNT2	WNT2	171	0.64	0.064	YES
3	ADCY5	ADCY5	ADCY5	196	0.63	0.098	YES
4	FZD2	FZD2	FZD2	198	0.63	0.13	YES
5	CREB3L1	CREB3L1	CREB3L1	206	0.63	0.17	YES
6	WNT2B	WNT2B	WNT2B	315	0.56	0.2	YES
7	PLCB4	PLCB4	PLCB4	362	0.54	0.22	YES
8	FZD10	FZD10	FZD10	377	0.54	0.25	YES
9	WNT10A	WNT10A	WNT10A	605	0.48	0.27	YES
10	FZD1	FZD1	FZD1	695	0.46	0.29	YES
11	WNT9A	WNT9A	WNT9A	702	0.45	0.31	YES
12	FZD7	FZD7	FZD7	713	0.45	0.34	YES
13	FZD8	FZD8	FZD8	729	0.45	0.36	YES
14	PRKX	PRKX	PRKX	766	0.44	0.38	YES
15	MITF	MITF	MITF	768	0.44	0.41	YES
16	ADCY2	ADCY2	ADCY2	778	0.44	0.43	YES
17	EDN1	EDN1	EDN1	780	0.44	0.46	YES
18	WNT10B	WNT10B	WNT10B	901	0.41	0.48	YES
19	WNT7B	WNT7B	WNT7B	1003	0.4	0.49	YES
20	ADCY4	ADCY4	ADCY4	1133	0.38	0.51	YES
21	POMC	POMC	POMC	1179	0.38	0.53	YES
22	PRKCB	PRKCB	PRKCB	1538	0.33	0.52	YES
23	PLCB2	PLCB2	PLCB2	1612	0.33	0.54	YES
24	WNT7A	WNT7A	WNT7A	1877	0.3	0.54	YES
25	KIT	KIT	KIT	1957	0.3	0.55	YES
26	ADCY7	ADCY7	ADCY7	1992	0.29	0.57	YES
27	WNT11	WNT11	WNT11	2070	0.28	0.58	YES
28	WNT1	WNT1	WNT1	2139	0.28	0.59	YES
29	LEF1	LEF1	LEF1	2213	0.27	0.6	YES
30	GNAO1	GNAO1	GNAO1	2369	0.26	0.61	YES
31	WNT3A	WNT3A	WNT3A	2845	0.23	0.6	YES
32	EDNRB	EDNRB	EDNRB	3006	0.22	0.6	YES
33	CAMK2A	CAMK2A	CAMK2A	3350	0.19	0.59	YES
34	FZD6	FZD6	FZD6	3357	0.19	0.6	YES
35	MC1R	MC1R	MC1R	3531	0.18	0.6	YES
36	WNT9B	WNT9B	WNT9B	3585	0.18	0.61	YES
37	WNT6	WNT6	WNT6	3803	0.16	0.6	YES
38	FZD3	FZD3	FZD3	3841	0.16	0.61	YES
39	CAMK2B	CAMK2B	CAMK2B	4018	0.15	0.61	NO
40	WNT16	WNT16	WNT16	4844	0.11	0.57	NO
41	PLCB3	PLCB3	PLCB3	5773	0.077	0.52	NO
42	CREB3	CREB3	CREB3	6068	0.068	0.51	NO
43	KITLG	KITLG	KITLG	6417	0.06	0.49	NO
44	MAPK3	MAPK3	MAPK3	6456	0.059	0.49	NO
45	MAP2K1	MAP2K1	MAP2K1	6763	0.052	0.48	NO
46	KRAS	KRAS	KRAS	7083	0.045	0.46	NO
47	PRKACA	PRKACA	PRKACA	7142	0.044	0.46	NO
48	FZD4	FZD4	FZD4	7183	0.043	0.46	NO
49	CALM2	CALM2	CALM2	7201	0.043	0.46	NO
50	WNT5A	WNT5A	WNT5A	7279	0.041	0.46	NO
51	CAMK2D	CAMK2D	CAMK2D	7283	0.041	0.46	NO
52	WNT5B	WNT5B	WNT5B	7290	0.041	0.47	NO
53	ADCY1	ADCY1	ADCY1	7396	0.039	0.46	NO
54	CALM1	CALM1	CALM1	7491	0.037	0.46	NO
55	ADCY9	ADCY9	ADCY9	7590	0.036	0.46	NO
56	CREB1	CREB1	CREB1	7857	0.031	0.44	NO
57	GNAI3	GNAI3	GNAI3	8086	0.027	0.43	NO
58	GNAS	GNAS	GNAS	8249	0.025	0.42	NO
59	GNAI2	GNAI2	GNAI2	8547	0.021	0.41	NO
60	ADCY6	ADCY6	ADCY6	9127	0.012	0.38	NO
61	TCF7L2	TCF7L2	TCF7L2	9172	0.012	0.37	NO
62	CAMK2G	CAMK2G	CAMK2G	9541	0.0072	0.35	NO
63	CREBBP	CREBBP	CREBBP	9648	0.0058	0.35	NO
64	MAP2K2	MAP2K2	MAP2K2	9712	0.0049	0.34	NO
65	GNAQ	GNAQ	GNAQ	9746	0.0044	0.34	NO
66	TYRP1	TYRP1	TYRP1	10258	-0.0015	0.31	NO
67	TCF7L1	TCF7L1	TCF7L1	10620	-0.006	0.29	NO
68	FZD9	FZD9	FZD9	10675	-0.0067	0.29	NO
69	WNT3	WNT3	WNT3	10734	-0.0072	0.29	NO
70	PRKACB	PRKACB	PRKACB	10812	-0.0082	0.28	NO
71	CALM3	CALM3	CALM3	10832	-0.0086	0.28	NO
72	HRAS	HRAS	HRAS	10983	-0.01	0.28	NO
73	ASIP	ASIP	ASIP	11017	-0.011	0.28	NO
74	MAPK1	MAPK1	MAPK1	11085	-0.012	0.27	NO
75	DVL3	DVL3	DVL3	11435	-0.016	0.25	NO
76	EP300	EP300	EP300	11540	-0.017	0.25	NO
77	GSK3B	GSK3B	GSK3B	11610	-0.018	0.24	NO
78	ADCY8	ADCY8	ADCY8	12247	-0.026	0.21	NO
79	DVL1	DVL1	DVL1	12659	-0.032	0.19	NO
80	PRKCG	PRKCG	PRKCG	12717	-0.032	0.19	NO
81	DVL2	DVL2	DVL2	12767	-0.033	0.19	NO
82	CTNNB1	CTNNB1	CTNNB1	12896	-0.035	0.18	NO
83	NRAS	NRAS	NRAS	13162	-0.039	0.17	NO
84	CREB3L2	CREB3L2	CREB3L2	13508	-0.044	0.15	NO
85	DCT	DCT	DCT	14132	-0.056	0.12	NO
86	RAF1	RAF1	RAF1	14790	-0.07	0.086	NO
87	FZD5	FZD5	FZD5	15131	-0.08	0.071	NO
88	CALML3	CALML3	CALML3	15209	-0.082	0.071	NO
89	CREB3L3	CREB3L3	CREB3L3	15592	-0.096	0.055	NO
90	PRKCA	PRKCA	PRKCA	15772	-0.1	0.051	NO
91	GNAI1	GNAI1	GNAI1	15958	-0.11	0.047	NO
92	PLCB1	PLCB1	PLCB1	16037	-0.12	0.049	NO
93	CREB3L4	CREB3L4	CREB3L4	16484	-0.14	0.032	NO
94	WNT8B	WNT8B	WNT8B	17064	-0.19	0.01	NO
95	TCF7	TCF7	TCF7	17245	-0.22	0.012	NO
96	CALML6	CALML6	CALML6	17488	-0.27	0.014	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: BIOCARTA CARM ER PATHWAY.

Figure S70. 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 HDAC PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PDGFRA	PDGFRA	PDGFRA	146	0.66	0.026	YES
2	IGF1R	IGF1R	IGF1R	511	0.5	0.032	YES
3	EHD3	EHD3	EHD3	719	0.45	0.044	YES
4	IQSEC2	IQSEC2	IQSEC2	813	0.43	0.061	YES
5	RAB31	RAB31	RAB31	907	0.41	0.078	YES
6	F2R	F2R	F2R	973	0.4	0.095	YES
7	CXCR2	CXCR2	CXCR2	993	0.4	0.12	YES
8	DNM3	DNM3	DNM3	1037	0.4	0.13	YES
9	RET	RET	RET	1208	0.37	0.14	YES
10	CCR5	CCR5	CCR5	1251	0.37	0.16	YES
11	ACAP1	ACAP1	ACAP1	1463	0.34	0.17	YES
12	EPN3	EPN3	EPN3	1648	0.32	0.17	YES
13	FGFR2	FGFR2	FGFR2	1727	0.32	0.19	YES
14	EHD2	EHD2	EHD2	1788	0.31	0.2	YES
15	IL2RA	IL2RA	IL2RA	1816	0.31	0.21	YES
16	CXCR1	CXCR1	CXCR1	1866	0.3	0.23	YES
17	ARAP3	ARAP3	ARAP3	1878	0.3	0.24	YES
18	KIT	KIT	KIT	1957	0.3	0.25	YES
19	IL2RG	IL2RG	IL2RG	2106	0.28	0.26	YES
20	ERBB4	ERBB4	ERBB4	2173	0.28	0.27	YES
21	CSF1R	CSF1R	CSF1R	2182	0.28	0.28	YES
22	DNM1	DNM1	DNM1	2201	0.27	0.3	YES
23	DAB2	DAB2	DAB2	2339	0.26	0.3	YES
24	CXCR4	CXCR4	CXCR4	2362	0.26	0.32	YES
25	NTRK1	NTRK1	NTRK1	2427	0.26	0.33	YES
26	ARAP2	ARAP2	ARAP2	2525	0.25	0.33	YES
27	IL2RB	IL2RB	IL2RB	2558	0.25	0.34	YES
28	RAB11FIP5	RAB11FIP5	RAB11FIP5	2570	0.25	0.36	YES
29	PIP5K1B	PIP5K1B	PIP5K1B	2887	0.22	0.35	YES
30	PLD1	PLD1	PLD1	2930	0.22	0.36	YES
31	DNAJC6	DNAJC6	DNAJC6	2939	0.22	0.37	YES
32	HSPA2	HSPA2	HSPA2	3245	0.2	0.36	YES
33	ASAP1	ASAP1	ASAP1	3447	0.19	0.36	YES
34	KDR	KDR	KDR	3540	0.18	0.37	YES
35	GRK5	GRK5	GRK5	3656	0.17	0.37	YES
36	PLD2	PLD2	PLD2	3661	0.17	0.38	YES
37	EGF	EGF	EGF	3750	0.17	0.38	YES
38	ADRB3	ADRB3	ADRB3	3784	0.17	0.39	YES
39	ARRB1	ARRB1	ARRB1	3796	0.16	0.4	YES
40	HSPA6	HSPA6	HSPA6	3855	0.16	0.4	YES
41	CBL	CBL	CBL	3919	0.16	0.41	YES
42	PSD	PSD	PSD	3942	0.16	0.42	YES
43	PIP5K1C	PIP5K1C	PIP5K1C	4092	0.15	0.41	YES
44	RAB11FIP1	RAB11FIP1	RAB11FIP1	4256	0.14	0.41	YES
45	HLA-G	HLA-G	HLA-G	4428	0.13	0.41	YES
46	SH3GL2	SH3GL2	SH3GL2	4565	0.12	0.41	YES
47	SRC	SRC	SRC	4700	0.12	0.41	YES
48	VPS24	VPS24	VPS24	4727	0.12	0.41	YES
49	CBLB	CBLB	CBLB	4807	0.11	0.41	YES
50	HLA-B	HLA-B	HLA-B	4822	0.11	0.42	YES
51	CHMP4C	CHMP4C	CHMP4C	4903	0.11	0.42	YES
52	SH3KBP1	SH3KBP1	SH3KBP1	4957	0.11	0.42	YES
53	CLTB	CLTB	CLTB	4976	0.11	0.43	YES
54	HLA-F	HLA-F	HLA-F	5013	0.1	0.43	YES
55	AGAP2	AGAP2	AGAP2	5134	0.1	0.43	YES
56	AGAP1	AGAP1	AGAP1	5229	0.096	0.43	YES
57	VPS37B	VPS37B	VPS37B	5269	0.095	0.43	YES
58	FLT1	FLT1	FLT1	5322	0.092	0.43	YES
59	ASAP2	ASAP2	ASAP2	5330	0.092	0.44	YES
60	EGFR	EGFR	EGFR	5445	0.088	0.44	NO
61	VPS4A	VPS4A	VPS4A	5598	0.082	0.43	NO
62	SH3GLB1	SH3GLB1	SH3GLB1	5636	0.081	0.43	NO
63	EHD4	EHD4	EHD4	5822	0.075	0.43	NO
64	ARRB2	ARRB2	ARRB2	5899	0.073	0.43	NO
65	VPS4B	VPS4B	VPS4B	6049	0.069	0.42	NO
66	GIT1	GIT1	GIT1	6114	0.067	0.42	NO
67	HLA-C	HLA-C	HLA-C	6197	0.065	0.42	NO
68	GIT2	GIT2	GIT2	6205	0.065	0.42	NO
69	HLA-A	HLA-A	HLA-A	6259	0.064	0.42	NO
70	SMURF1	SMURF1	SMURF1	6348	0.061	0.42	NO
71	HLA-E	HLA-E	HLA-E	6362	0.061	0.42	NO
72	RAB11A	RAB11A	RAB11A	6378	0.061	0.43	NO
73	IQSEC3	IQSEC3	IQSEC3	6423	0.06	0.43	NO
74	FAM125B	FAM125B	FAM125B	6585	0.056	0.42	NO
75	CHMP4B	CHMP4B	CHMP4B	6677	0.054	0.42	NO
76	HSPA8	HSPA8	HSPA8	6814	0.051	0.41	NO
77	PSD2	PSD2	PSD2	6842	0.05	0.42	NO
78	VPS37A	VPS37A	VPS37A	6849	0.05	0.42	NO
79	RABEP1	RABEP1	RABEP1	6899	0.049	0.42	NO
80	PRKCZ	PRKCZ	PRKCZ	6904	0.049	0.42	NO
81	CHMP4A	CHMP4A	CHMP4A	7035	0.046	0.41	NO
82	ARFGAP3	ARFGAP3	ARFGAP3	7067	0.046	0.42	NO
83	TRAF6	TRAF6	TRAF6	7115	0.045	0.41	NO
84	VPS37C	VPS37C	VPS37C	7138	0.044	0.42	NO
85	PARD6B	PARD6B	PARD6B	7158	0.044	0.42	NO
86	ACAP2	ACAP2	ACAP2	7292	0.041	0.41	NO
87	EPN2	EPN2	EPN2	7309	0.041	0.41	NO
88	DNM2	DNM2	DNM2	7310	0.041	0.42	NO
89	DNM1L	DNM1L	DNM1L	7353	0.04	0.41	NO
90	PARD6G	PARD6G	PARD6G	7375	0.04	0.42	NO
91	VPS28	VPS28	VPS28	7403	0.039	0.42	NO
92	CHMP1B	CHMP1B	CHMP1B	7427	0.038	0.42	NO
93	RAB11FIP3	RAB11FIP3	RAB11FIP3	7671	0.034	0.4	NO
94	ARAP1	ARAP1	ARAP1	7678	0.034	0.41	NO
95	RAB5C	RAB5C	RAB5C	7921	0.03	0.39	NO
96	CDC42	CDC42	CDC42	8025	0.028	0.39	NO
97	EPS15	EPS15	EPS15	8036	0.028	0.39	NO
98	SH3GLB2	SH3GLB2	SH3GLB2	8048	0.028	0.39	NO
99	ARF6	ARF6	ARF6	8053	0.028	0.39	NO
100	CHMP5	CHMP5	CHMP5	8166	0.026	0.39	NO
101	ADRBK1	ADRBK1	ADRBK1	8206	0.026	0.39	NO
102	RUFY1	RUFY1	RUFY1	8226	0.025	0.39	NO
103	AP2A2	AP2A2	AP2A2	8244	0.025	0.39	NO
104	RAB22A	RAB22A	RAB22A	8334	0.024	0.38	NO
105	SMURF2	SMURF2	SMURF2	8362	0.023	0.38	NO
106	EHD1	EHD1	EHD1	8407	0.023	0.38	NO
107	FGFR3	FGFR3	FGFR3	8591	0.02	0.37	NO
108	CHMP2B	CHMP2B	CHMP2B	8674	0.019	0.37	NO
109	TFRC	TFRC	TFRC	8682	0.019	0.37	NO
110	CBLC	CBLC	CBLC	8701	0.018	0.37	NO
111	FAM125A	FAM125A	FAM125A	8746	0.018	0.37	NO
112	AP2B1	AP2B1	AP2B1	8749	0.018	0.37	NO
113	STAM	STAM	STAM	8815	0.017	0.36	NO
114	PIP5K1A	PIP5K1A	PIP5K1A	8836	0.016	0.36	NO
115	AP2M1	AP2M1	AP2M1	8849	0.016	0.36	NO
116	LDLR	LDLR	LDLR	8908	0.015	0.36	NO
117	PSD4	PSD4	PSD4	8915	0.015	0.36	NO
118	RNF41	RNF41	RNF41	9023	0.014	0.36	NO
119	STAM2	STAM2	STAM2	9379	0.0092	0.34	NO
120	ADRBK2	ADRBK2	ADRBK2	9428	0.0086	0.34	NO
121	SH3GL1	SH3GL1	SH3GL1	9463	0.0081	0.33	NO
122	VPS36	VPS36	VPS36	9629	0.0061	0.32	NO
123	VPS45	VPS45	VPS45	9771	0.0042	0.32	NO
124	SMAP1	SMAP1	SMAP1	9818	0.0036	0.32	NO
125	PRKCI	PRKCI	PRKCI	9941	0.002	0.31	NO
126	ADRB1	ADRB1	ADRB1	10090	0.00055	0.3	NO
127	RAB11B	RAB11B	RAB11B	10354	-0.0026	0.28	NO
128	PDCD6IP	PDCD6IP	PDCD6IP	10416	-0.0033	0.28	NO
129	RAB5A	RAB5A	RAB5A	10475	-0.0042	0.28	NO
130	USP8	USP8	USP8	10537	-0.005	0.28	NO
131	CHMP2A	CHMP2A	CHMP2A	10764	-0.0077	0.26	NO
132	PIKFYVE	PIKFYVE	PIKFYVE	10778	-0.0078	0.26	NO
133	CLTC	CLTC	CLTC	10783	-0.0079	0.26	NO
134	WWP1	WWP1	WWP1	10788	-0.008	0.26	NO
135	CLTA	CLTA	CLTA	11057	-0.011	0.25	NO
136	EPN1	EPN1	EPN1	11124	-0.012	0.24	NO
137	STAMBP	STAMBP	STAMBP	11141	-0.012	0.24	NO
138	LDLRAP1	LDLRAP1	LDLRAP1	11306	-0.014	0.24	NO
139	AP2A1	AP2A1	AP2A1	11308	-0.014	0.24	NO
140	AP2S1	AP2S1	AP2S1	11330	-0.015	0.24	NO
141	MDM2	MDM2	MDM2	11363	-0.015	0.24	NO
142	RAB5B	RAB5B	RAB5B	11486	-0.016	0.23	NO
143	TSG101	TSG101	TSG101	11868	-0.021	0.21	NO
144	ACAP3	ACAP3	ACAP3	12027	-0.024	0.2	NO
145	EEA1	EEA1	EEA1	12181	-0.025	0.19	NO
146	PIP4K2B	PIP4K2B	PIP4K2B	12331	-0.027	0.19	NO
147	SMAP2	SMAP2	SMAP2	12511	-0.03	0.18	NO
148	GRK4	GRK4	GRK4	12515	-0.03	0.18	NO
149	VTA1	VTA1	VTA1	12878	-0.035	0.16	NO
150	PARD3	PARD3	PARD3	12910	-0.035	0.16	NO
151	GRK6	GRK6	GRK6	13006	-0.036	0.16	NO
152	ARFGAP1	ARFGAP1	ARFGAP1	13117	-0.038	0.15	NO
153	SNF8	SNF8	SNF8	13182	-0.039	0.15	NO
154	RAB11FIP4	RAB11FIP4	RAB11FIP4	13294	-0.041	0.15	NO
155	PSD3	PSD3	PSD3	13425	-0.043	0.14	NO
156	RAB11FIP2	RAB11FIP2	RAB11FIP2	13527	-0.044	0.14	NO
157	VPS25	VPS25	VPS25	13538	-0.045	0.14	NO
158	ARFGAP2	ARFGAP2	ARFGAP2	13607	-0.046	0.14	NO
159	IQSEC1	IQSEC1	IQSEC1	13685	-0.047	0.14	NO
160	ASAP3	ASAP3	ASAP3	13737	-0.048	0.14	NO
161	CHMP6	CHMP6	CHMP6	13944	-0.052	0.13	NO
162	ZFYVE20	ZFYVE20	ZFYVE20	14102	-0.055	0.12	NO
163	ITCH	ITCH	ITCH	14124	-0.056	0.12	NO
164	RAB4A	RAB4A	RAB4A	14158	-0.056	0.12	NO
165	FGFR4	FGFR4	FGFR4	14374	-0.06	0.12	NO
166	PARD6A	PARD6A	PARD6A	14543	-0.064	0.11	NO
167	HSPA1B	HSPA1B	HSPA1B	14685	-0.068	0.1	NO
168	HGS	HGS	HGS	14951	-0.074	0.094	NO
169	CLTCL1	CLTCL1	CLTCL1	14976	-0.075	0.096	NO
170	HSPA1A	HSPA1A	HSPA1A	15039	-0.077	0.097	NO
171	NEDD4L	NEDD4L	NEDD4L	15368	-0.088	0.083	NO
172	MET	MET	MET	15509	-0.093	0.08	NO
173	NEDD4	NEDD4	NEDD4	15543	-0.094	0.083	NO
174	ERBB3	ERBB3	ERBB3	16026	-0.12	0.061	NO
175	HSPA1L	HSPA1L	HSPA1L	16628	-0.16	0.035	NO
176	ADRB2	ADRB2	ADRB2	16642	-0.16	0.043	NO
177	VPS37D	VPS37D	VPS37D	16688	-0.16	0.049	NO
178	SH3GL3	SH3GL3	SH3GL3	17083	-0.2	0.037	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: BIOCARTA HDAC PATHWAY.

Figure S72. 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 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	NTRK2	NTRK2	NTRK2	35	0.79	0.021	YES
2	MAPK10	MAPK10	MAPK10	102	0.7	0.038	YES
3	FGF1	FGF1	FGF1	130	0.67	0.056	YES
4	PDGFRA	PDGFRA	PDGFRA	146	0.66	0.074	YES
5	CACNA1C	CACNA1C	CACNA1C	189	0.64	0.09	YES
6	PLA2G4A	PLA2G4A	PLA2G4A	267	0.59	0.1	YES
7	PLA2G5	PLA2G5	PLA2G5	359	0.55	0.11	YES
8	FGF7	FGF7	FGF7	405	0.53	0.13	YES
9	CACNB3	CACNB3	CACNB3	441	0.52	0.14	YES
10	FGFR1	FGFR1	FGFR1	452	0.52	0.15	YES
11	FGF18	FGF18	FGF18	500	0.5	0.17	YES
12	NTF3	NTF3	NTF3	529	0.49	0.18	YES
13	TGFB3	TGFB3	TGFB3	550	0.49	0.19	YES
14	CACNA1H	CACNA1H	CACNA1H	622	0.47	0.2	YES
15	TGFB2	TGFB2	TGFB2	644	0.47	0.21	YES
16	AKT3	AKT3	AKT3	748	0.44	0.22	YES
17	RASGRP1	RASGRP1	RASGRP1	761	0.44	0.23	YES
18	PRKX	PRKX	PRKX	766	0.44	0.24	YES
19	MAP3K12	MAP3K12	MAP3K12	784	0.44	0.26	YES
20	DUSP4	DUSP4	DUSP4	925	0.41	0.26	YES
21	CACNA2D1	CACNA2D1	CACNA2D1	933	0.41	0.27	YES
22	PLA2G2A	PLA2G2A	PLA2G2A	1099	0.39	0.27	YES
23	CACNB1	CACNB1	CACNB1	1120	0.38	0.28	YES
24	FLNC	FLNC	FLNC	1205	0.37	0.29	YES
25	IL1B	IL1B	IL1B	1250	0.37	0.3	YES
26	NFATC4	NFATC4	NFATC4	1297	0.36	0.31	YES
27	NGF	NGF	NGF	1508	0.34	0.3	YES
28	PRKCB	PRKCB	PRKCB	1538	0.33	0.31	YES
29	MAP3K6	MAP3K6	MAP3K6	1560	0.33	0.32	YES
30	TGFB1	TGFB1	TGFB1	1575	0.33	0.33	YES
31	MAP4K1	MAP4K1	MAP4K1	1579	0.33	0.34	YES
32	DUSP5	DUSP5	DUSP5	1674	0.32	0.34	YES
33	MECOM	MECOM	MECOM	1699	0.32	0.35	YES
34	FGFR2	FGFR2	FGFR2	1727	0.32	0.36	YES
35	PDGFA	PDGFA	PDGFA	1768	0.31	0.36	YES
36	TNF	TNF	TNF	1799	0.31	0.37	YES
37	FLNA	FLNA	FLNA	1801	0.31	0.38	YES
38	MAP3K5	MAP3K5	MAP3K5	1836	0.31	0.39	YES
39	PTPN5	PTPN5	PTPN5	1848	0.3	0.4	YES
40	RASGRP4	RASGRP4	RASGRP4	1863	0.3	0.4	YES
41	RAC2	RAC2	RAC2	1875	0.3	0.41	YES
42	MAPK12	MAPK12	MAPK12	1899	0.3	0.42	YES
43	PTPRR	PTPRR	PTPRR	1918	0.3	0.43	YES
44	FGF14	FGF14	FGF14	1936	0.3	0.44	YES
45	FGF11	FGF11	FGF11	1941	0.3	0.44	YES
46	MAPK11	MAPK11	MAPK11	2005	0.29	0.45	YES
47	CACNA2D3	CACNA2D3	CACNA2D3	2015	0.29	0.46	YES
48	FOS	FOS	FOS	2116	0.28	0.46	YES
49	BDNF	BDNF	BDNF	2120	0.28	0.47	YES
50	RPS6KA2	RPS6KA2	RPS6KA2	2165	0.28	0.47	YES
51	PTPN7	PTPN7	PTPN7	2378	0.26	0.47	YES
52	PDGFRB	PDGFRB	PDGFRB	2413	0.26	0.47	YES
53	NTRK1	NTRK1	NTRK1	2427	0.26	0.48	YES
54	RASGRP2	RASGRP2	RASGRP2	2613	0.24	0.48	YES
55	RASGRP3	RASGRP3	RASGRP3	2718	0.24	0.48	YES
56	CACNA1A	CACNA1A	CACNA1A	2760	0.23	0.48	YES
57	DUSP2	DUSP2	DUSP2	2822	0.23	0.48	YES
58	MRAS	MRAS	MRAS	2891	0.22	0.49	YES
59	MAPK13	MAPK13	MAPK13	3056	0.21	0.48	YES
60	CACNA1F	CACNA1F	CACNA1F	3106	0.21	0.49	YES
61	CACNA1D	CACNA1D	CACNA1D	3219	0.2	0.49	YES
62	NR4A1	NR4A1	NR4A1	3228	0.2	0.49	YES
63	HSPA2	HSPA2	HSPA2	3245	0.2	0.5	YES
64	PLA2G2D	PLA2G2D	PLA2G2D	3456	0.19	0.49	YES
65	PDGFB	PDGFB	PDGFB	3570	0.18	0.49	YES
66	RPS6KA6	RPS6KA6	RPS6KA6	3594	0.18	0.49	YES
67	RRAS	RRAS	RRAS	3630	0.17	0.5	YES
68	RASGRF2	RASGRF2	RASGRF2	3681	0.17	0.5	YES
69	CACNA1G	CACNA1G	CACNA1G	3696	0.17	0.5	YES
70	EGF	EGF	EGF	3750	0.17	0.5	YES
71	FGF13	FGF13	FGF13	3793	0.16	0.51	YES
72	ARRB1	ARRB1	ARRB1	3796	0.16	0.51	YES
73	HSPA6	HSPA6	HSPA6	3855	0.16	0.51	YES
74	FGF12	FGF12	FGF12	3893	0.16	0.52	YES
75	MYC	MYC	MYC	3924	0.16	0.52	YES
76	CACNA2D2	CACNA2D2	CACNA2D2	4057	0.15	0.52	YES
77	CACNA2D4	CACNA2D4	CACNA2D4	4058	0.15	0.52	YES
78	RELB	RELB	RELB	4148	0.14	0.52	YES
79	FASLG	FASLG	FASLG	4193	0.14	0.52	YES
80	CACNA1E	CACNA1E	CACNA1E	4370	0.13	0.51	YES
81	FGF9	FGF9	FGF9	4394	0.13	0.52	YES
82	TP53	TP53	TP53	4408	0.13	0.52	YES
83	FGF19	FGF19	FGF19	4465	0.13	0.52	YES
84	CACNA1S	CACNA1S	CACNA1S	4486	0.13	0.52	YES
85	GADD45B	GADD45B	GADD45B	4591	0.12	0.52	NO
86	NFKB1	NFKB1	NFKB1	4811	0.11	0.51	NO
87	NFATC2	NFATC2	NFATC2	4845	0.11	0.51	NO
88	MAPT	MAPT	MAPT	5012	0.1	0.51	NO
89	DUSP1	DUSP1	DUSP1	5037	0.1	0.51	NO
90	GNG12	GNG12	GNG12	5086	0.1	0.51	NO
91	MAP4K3	MAP4K3	MAP4K3	5161	0.099	0.51	NO
92	ZAK	ZAK	ZAK	5190	0.098	0.51	NO
93	MAP3K8	MAP3K8	MAP3K8	5238	0.096	0.51	NO
94	RPS6KA5	RPS6KA5	RPS6KA5	5255	0.095	0.51	NO
95	MAP3K1	MAP3K1	MAP3K1	5333	0.092	0.51	NO
96	TGFBR1	TGFBR1	TGFBR1	5365	0.09	0.51	NO
97	MAPK7	MAPK7	MAPK7	5399	0.089	0.51	NO
98	EGFR	EGFR	EGFR	5445	0.088	0.51	NO
99	NFKB2	NFKB2	NFKB2	5556	0.084	0.51	NO
100	MAPKAPK2	MAPKAPK2	MAPKAPK2	5585	0.083	0.51	NO
101	PPP3CC	PPP3CC	PPP3CC	5721	0.078	0.5	NO
102	PPP3CA	PPP3CA	PPP3CA	5725	0.078	0.5	NO
103	TGFBR2	TGFBR2	TGFBR2	5799	0.076	0.5	NO
104	DUSP7	DUSP7	DUSP7	5854	0.074	0.5	NO
105	MAX	MAX	MAX	5872	0.074	0.5	NO
106	ARRB2	ARRB2	ARRB2	5899	0.073	0.5	NO
107	CRK	CRK	CRK	5901	0.073	0.5	NO
108	IL1R1	IL1R1	IL1R1	5938	0.072	0.5	NO
109	IKBKB	IKBKB	IKBKB	5986	0.07	0.5	NO
110	FAS	FAS	FAS	6001	0.07	0.5	NO
111	MAP3K2	MAP3K2	MAP3K2	6005	0.07	0.51	NO
112	MAPKSP1	MAPKSP1	MAPKSP1	6014	0.07	0.51	NO
113	RPS6KA4	RPS6KA4	RPS6KA4	6026	0.07	0.51	NO
114	GNA12	GNA12	GNA12	6147	0.066	0.5	NO
115	DUSP8	DUSP8	DUSP8	6163	0.066	0.51	NO
116	RPS6KA1	RPS6KA1	RPS6KA1	6164	0.066	0.51	NO
117	PLA2G12A	PLA2G12A	PLA2G12A	6237	0.064	0.5	NO
118	MAPK3	MAPK3	MAPK3	6456	0.059	0.5	NO
119	MAP2K3	MAP2K3	MAP2K3	6478	0.059	0.5	NO
120	CACNA1I	CACNA1I	CACNA1I	6487	0.059	0.5	NO
121	FGF2	FGF2	FGF2	6703	0.054	0.49	NO
122	DUSP6	DUSP6	DUSP6	6741	0.053	0.48	NO
123	TNFRSF1A	TNFRSF1A	TNFRSF1A	6754	0.052	0.49	NO
124	MAP2K1	MAP2K1	MAP2K1	6763	0.052	0.49	NO
125	HSPA8	HSPA8	HSPA8	6814	0.051	0.48	NO
126	IL1A	IL1A	IL1A	6924	0.049	0.48	NO
127	PLA2G10	PLA2G10	PLA2G10	7033	0.047	0.48	NO
128	KRAS	KRAS	KRAS	7083	0.045	0.47	NO
129	TRAF6	TRAF6	TRAF6	7115	0.045	0.47	NO
130	PPM1B	PPM1B	PPM1B	7133	0.044	0.47	NO
131	PRKACA	PRKACA	PRKACA	7142	0.044	0.48	NO
132	RAP1B	RAP1B	RAP1B	7143	0.044	0.48	NO
133	RAC1	RAC1	RAC1	7148	0.044	0.48	NO
134	MAP2K4	MAP2K4	MAP2K4	7250	0.042	0.47	NO
135	STK3	STK3	STK3	7269	0.041	0.47	NO
136	PAK1	PAK1	PAK1	7355	0.04	0.47	NO
137	CACNA1B	CACNA1B	CACNA1B	7518	0.037	0.46	NO
138	MAPK8IP3	MAPK8IP3	MAPK8IP3	7533	0.036	0.46	NO
139	RASA1	RASA1	RASA1	7550	0.036	0.46	NO
140	MAP3K3	MAP3K3	MAP3K3	7637	0.035	0.46	NO
141	DUSP10	DUSP10	DUSP10	7724	0.033	0.45	NO
142	AKT1	AKT1	AKT1	7775	0.032	0.45	NO
143	PPP5C	PPP5C	PPP5C	7839	0.031	0.45	NO
144	SOS2	SOS2	SOS2	7870	0.031	0.45	NO
145	PAK2	PAK2	PAK2	7916	0.03	0.45	NO
146	RASA2	RASA2	RASA2	7937	0.03	0.45	NO
147	CDC42	CDC42	CDC42	8025	0.028	0.44	NO
148	CHP	CHP	CHP	8154	0.026	0.44	NO
149	PPP3CB	PPP3CB	PPP3CB	8192	0.026	0.43	NO
150	HSPB1	HSPB1	HSPB1	8254	0.025	0.43	NO
151	MAPK8IP1	MAPK8IP1	MAPK8IP1	8405	0.023	0.42	NO
152	RAPGEF2	RAPGEF2	RAPGEF2	8406	0.023	0.42	NO
153	DUSP16	DUSP16	DUSP16	8453	0.022	0.42	NO
154	RAP1A	RAP1A	RAP1A	8484	0.022	0.42	NO
155	JUN	JUN	JUN	8506	0.021	0.42	NO
156	ATF4	ATF4	ATF4	8565	0.02	0.42	NO
157	TAOK1	TAOK1	TAOK1	8575	0.02	0.42	NO
158	FGFR3	FGFR3	FGFR3	8591	0.02	0.42	NO
159	CD14	CD14	CD14	8608	0.02	0.42	NO
160	MAP4K4	MAP4K4	MAP4K4	8645	0.019	0.42	NO
161	RASGRF1	RASGRF1	RASGRF1	8652	0.019	0.42	NO
162	TAOK2	TAOK2	TAOK2	8660	0.019	0.42	NO
163	MAPK9	MAPK9	MAPK9	8780	0.017	0.41	NO
164	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	8820	0.017	0.41	NO
165	MKNK1	MKNK1	MKNK1	9170	0.012	0.39	NO
166	MAPK8	MAPK8	MAPK8	9184	0.012	0.39	NO
167	MAPKAPK3	MAPKAPK3	MAPKAPK3	9251	0.011	0.38	NO
168	RRAS2	RRAS2	RRAS2	9444	0.0084	0.37	NO
169	MAP2K5	MAP2K5	MAP2K5	9604	0.0065	0.36	NO
170	MAP3K14	MAP3K14	MAP3K14	9628	0.0061	0.36	NO
171	IKBKG	IKBKG	IKBKG	9663	0.0055	0.36	NO
172	SRF	SRF	SRF	9699	0.005	0.36	NO
173	MAP2K2	MAP2K2	MAP2K2	9712	0.0049	0.36	NO
174	CHP2	CHP2	CHP2	9981	0.0016	0.34	NO
175	DDIT3	DDIT3	DDIT3	10215	-0.001	0.33	NO
176	CACNG4	CACNG4	CACNG4	10295	-0.002	0.33	NO
177	JUND	JUND	JUND	10312	-0.0022	0.33	NO
178	CHUK	CHUK	CHUK	10385	-0.003	0.32	NO
179	CASP3	CASP3	CASP3	10465	-0.0041	0.32	NO
180	DUSP14	DUSP14	DUSP14	10491	-0.0044	0.32	NO
181	ELK4	ELK4	ELK4	10544	-0.0051	0.31	NO
182	NF1	NF1	NF1	10574	-0.0055	0.31	NO
183	TRAF2	TRAF2	TRAF2	10663	-0.0065	0.31	NO
184	CDC25B	CDC25B	CDC25B	10750	-0.0075	0.3	NO
185	PLA2G6	PLA2G6	PLA2G6	10771	-0.0078	0.3	NO
186	MKNK2	MKNK2	MKNK2	10781	-0.0079	0.3	NO
187	PRKACB	PRKACB	PRKACB	10812	-0.0082	0.3	NO
188	DUSP3	DUSP3	DUSP3	10817	-0.0083	0.3	NO
189	HRAS	HRAS	HRAS	10983	-0.01	0.29	NO
190	STK4	STK4	STK4	11019	-0.011	0.29	NO
191	MAPK1	MAPK1	MAPK1	11085	-0.012	0.28	NO
192	RELA	RELA	RELA	11131	-0.012	0.28	NO
193	TAOK3	TAOK3	TAOK3	11362	-0.015	0.27	NO
194	SOS1	SOS1	SOS1	11408	-0.016	0.27	NO
195	FGF21	FGF21	FGF21	11605	-0.018	0.26	NO
196	ELK1	ELK1	ELK1	11676	-0.019	0.25	NO
197	MAP4K2	MAP4K2	MAP4K2	11830	-0.021	0.25	NO
198	PPM1A	PPM1A	PPM1A	12133	-0.025	0.23	NO
199	GADD45G	GADD45G	GADD45G	12174	-0.025	0.23	NO
200	ATF2	ATF2	ATF2	12223	-0.026	0.23	NO
201	GADD45A	GADD45A	GADD45A	12305	-0.027	0.22	NO
202	AKT2	AKT2	AKT2	12348	-0.028	0.22	NO
203	PPP3R1	PPP3R1	PPP3R1	12388	-0.028	0.22	NO
204	FGF22	FGF22	FGF22	12411	-0.028	0.22	NO
205	CACNB4	CACNB4	CACNB4	12417	-0.028	0.22	NO
206	FLNB	FLNB	FLNB	12471	-0.029	0.22	NO
207	TAB1	TAB1	TAB1	12490	-0.029	0.22	NO
208	IL1R2	IL1R2	IL1R2	12499	-0.029	0.22	NO
209	MAPK8IP2	MAPK8IP2	MAPK8IP2	12646	-0.031	0.21	NO
210	MAP3K7	MAP3K7	MAP3K7	12693	-0.032	0.21	NO
211	GRB2	GRB2	GRB2	12701	-0.032	0.21	NO
212	PRKCG	PRKCG	PRKCG	12717	-0.032	0.21	NO
213	MAP2K7	MAP2K7	MAP2K7	12844	-0.034	0.2	NO
214	MAPK14	MAPK14	MAPK14	12885	-0.035	0.2	NO
215	TAB2	TAB2	TAB2	12988	-0.036	0.2	NO
216	NRAS	NRAS	NRAS	13162	-0.039	0.19	NO
217	MAP3K11	MAP3K11	MAP3K11	13208	-0.04	0.19	NO
218	RPS6KA3	RPS6KA3	RPS6KA3	13269	-0.04	0.18	NO
219	DAXX	DAXX	DAXX	13356	-0.041	0.18	NO
220	MAPKAPK5	MAPKAPK5	MAPKAPK5	13371	-0.042	0.18	NO
221	MAP3K4	MAP3K4	MAP3K4	13419	-0.042	0.18	NO
222	CACNB2	CACNB2	CACNB2	13629	-0.046	0.17	NO
223	NLK	NLK	NLK	13680	-0.047	0.17	NO
224	ECSIT	ECSIT	ECSIT	13683	-0.047	0.17	NO
225	MAP3K13	MAP3K13	MAP3K13	13763	-0.049	0.16	NO
226	CRKL	CRKL	CRKL	14312	-0.059	0.14	NO
227	FGFR4	FGFR4	FGFR4	14374	-0.06	0.13	NO
228	HSPA1B	HSPA1B	HSPA1B	14685	-0.068	0.12	NO
229	RAF1	RAF1	RAF1	14790	-0.07	0.11	NO
230	BRAF	BRAF	BRAF	14793	-0.07	0.12	NO
231	HSPA1A	HSPA1A	HSPA1A	15039	-0.077	0.1	NO
232	STMN1	STMN1	STMN1	15094	-0.079	0.1	NO
233	PLA2G1B	PLA2G1B	PLA2G1B	15146	-0.08	0.1	NO
234	PRKCA	PRKCA	PRKCA	15772	-0.1	0.07	NO
235	CACNG1	CACNG1	CACNG1	15830	-0.11	0.07	NO
236	HSPA1L	HSPA1L	HSPA1L	16628	-0.16	0.029	NO
237	FGF17	FGF17	FGF17	16631	-0.16	0.033	NO
238	DUSP9	DUSP9	DUSP9	17193	-0.21	0.0073	NO
239	PLA2G12B	PLA2G12B	PLA2G12B	17315	-0.23	0.0071	NO
240	MAP2K6	MAP2K6	MAP2K6	17390	-0.24	0.0099	NO
241	RAC3	RAC3	RAC3	17620	-0.32	0.0062	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: BIOCARTA EGF PATHWAY.

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

genes ES table in pathway: BIOCARTA ERK PATHWAY

Table 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	HAND2	HAND2	HAND2	1	1	0.14	YES
2	LIF	LIF	LIF	402	0.53	0.19	YES
3	PRKAR2B	PRKAR2B	PRKAR2B	475	0.51	0.26	YES
4	NFATC1	NFATC1	NFATC1	575	0.48	0.32	YES
5	EDN1	EDN1	EDN1	780	0.44	0.37	YES
6	CAMK4	CAMK4	CAMK4	1016	0.4	0.41	YES
7	NFATC4	NFATC4	NFATC4	1297	0.36	0.44	YES
8	CTF1	CTF1	CTF1	1333	0.36	0.49	YES
9	CAMK1G	CAMK1G	CAMK1G	1392	0.35	0.53	YES
10	PIK3CG	PIK3CG	PIK3CG	1828	0.31	0.55	YES
11	MYH2	MYH2	MYH2	2308	0.27	0.56	YES
12	PRKAR1B	PRKAR1B	PRKAR1B	2672	0.24	0.57	YES
13	HBEGF	HBEGF	HBEGF	2975	0.22	0.59	YES
14	NFATC2	NFATC2	NFATC2	4845	0.11	0.5	NO
15	PPP3CC	PPP3CC	PPP3CC	5721	0.078	0.46	NO
16	PPP3CA	PPP3CA	PPP3CA	5725	0.078	0.47	NO
17	MAPK3	MAPK3	MAPK3	6456	0.059	0.44	NO
18	FGF2	FGF2	FGF2	6703	0.054	0.43	NO
19	FKBP1A	FKBP1A	FKBP1A	6739	0.053	0.43	NO
20	MAP2K1	MAP2K1	MAP2K1	6763	0.052	0.44	NO
21	IGF1	IGF1	IGF1	7046	0.046	0.43	NO
22	CALM2	CALM2	CALM2	7201	0.043	0.43	NO
23	CALM1	CALM1	CALM1	7491	0.037	0.42	NO
24	AKT1	AKT1	AKT1	7775	0.032	0.4	NO
25	CSNK1A1	CSNK1A1	CSNK1A1	7949	0.03	0.4	NO
26	PIK3CA	PIK3CA	PIK3CA	8136	0.026	0.39	NO
27	PPP3CB	PPP3CB	PPP3CB	8192	0.026	0.39	NO
28	MAPK8	MAPK8	MAPK8	9184	0.012	0.34	NO
29	CREBBP	CREBBP	CREBBP	9648	0.0058	0.31	NO
30	CALR	CALR	CALR	10507	-0.0046	0.26	NO
31	PRKACB	PRKACB	PRKACB	10812	-0.0082	0.25	NO
32	CALM3	CALM3	CALM3	10832	-0.0086	0.25	NO
33	PRKAR1A	PRKAR1A	PRKAR1A	10918	-0.0096	0.24	NO
34	HRAS	HRAS	HRAS	10983	-0.01	0.24	NO
35	MAPK1	MAPK1	MAPK1	11085	-0.012	0.24	NO
36	GATA4	GATA4	GATA4	11511	-0.017	0.22	NO
37	GSK3B	GSK3B	GSK3B	11610	-0.018	0.21	NO
38	MAPK14	MAPK14	MAPK14	12885	-0.035	0.15	NO
39	NFATC3	NFATC3	NFATC3	13325	-0.041	0.13	NO
40	CAMK1	CAMK1	CAMK1	14001	-0.053	0.096	NO
41	PIK3R1	PIK3R1	PIK3R1	14760	-0.07	0.063	NO
42	RAF1	RAF1	RAF1	14790	-0.07	0.071	NO
43	PRKAR2A	PRKAR2A	PRKAR2A	14856	-0.072	0.077	NO
44	RPS6KB1	RPS6KB1	RPS6KB1	14869	-0.072	0.087	NO
45	AGT	AGT	AGT	14875	-0.072	0.096	NO
46	ACTA1	ACTA1	ACTA1	15319	-0.086	0.083	NO
47	F2	F2	F2	16930	-0.18	0.017	NO
48	NPPA	NPPA	NPPA	17149	-0.2	0.033	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: BIOCARTA ERK PATHWAY.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA ERK PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA FAS PATHWAY

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	GLI2	GLI2	GLI2	5	0.92	0.018	YES
2	LAMA2	LAMA2	LAMA2	67	0.73	0.028	YES
3	MAPK10	MAPK10	MAPK10	102	0.7	0.039	YES
4	FGF1	FGF1	FGF1	130	0.67	0.051	YES
5	PDGFRA	PDGFRA	PDGFRA	146	0.66	0.063	YES
6	GLI3	GLI3	GLI3	161	0.65	0.074	YES
7	WNT4	WNT4	WNT4	162	0.65	0.087	YES
8	WNT2	WNT2	WNT2	171	0.64	0.099	YES
9	MMP2	MMP2	MMP2	193	0.63	0.11	YES
10	FZD2	FZD2	FZD2	198	0.63	0.12	YES
11	WNT2B	WNT2B	WNT2B	315	0.56	0.13	YES
12	LAMC2	LAMC2	LAMC2	332	0.56	0.14	YES
13	ITGA3	ITGA3	ITGA3	346	0.55	0.15	YES
14	PTGS2	PTGS2	PTGS2	372	0.54	0.16	YES
15	HHIP	HHIP	HHIP	374	0.54	0.16	YES
16	FZD10	FZD10	FZD10	377	0.54	0.18	YES
17	FGF7	FGF7	FGF7	405	0.53	0.18	YES
18	COL4A4	COL4A4	COL4A4	420	0.53	0.19	YES
19	FGFR1	FGFR1	FGFR1	452	0.52	0.2	YES
20	LAMC3	LAMC3	LAMC3	457	0.52	0.21	YES
21	FGF18	FGF18	FGF18	500	0.5	0.22	YES
22	IGF1R	IGF1R	IGF1R	511	0.5	0.23	YES
23	TGFB3	TGFB3	TGFB3	550	0.49	0.23	YES
24	WNT10A	WNT10A	WNT10A	605	0.48	0.24	YES
25	LAMA1	LAMA1	LAMA1	621	0.47	0.25	YES
26	IL8	IL8	IL8	631	0.47	0.26	YES
27	TGFB2	TGFB2	TGFB2	644	0.47	0.26	YES
28	FZD1	FZD1	FZD1	695	0.46	0.27	YES
29	TGFA	TGFA	TGFA	698	0.45	0.28	YES
30	GLI1	GLI1	GLI1	700	0.45	0.29	YES
31	WNT9A	WNT9A	WNT9A	702	0.45	0.3	YES
32	FZD7	FZD7	FZD7	713	0.45	0.3	YES
33	FZD8	FZD8	FZD8	729	0.45	0.31	YES
34	AKT3	AKT3	AKT3	748	0.44	0.32	YES
35	MITF	MITF	MITF	768	0.44	0.33	YES
36	RUNX1T1	RUNX1T1	RUNX1T1	793	0.43	0.34	YES
37	HGF	HGF	HGF	820	0.43	0.34	YES
38	ARNT2	ARNT2	ARNT2	838	0.42	0.35	YES
39	CTBP2	CTBP2	CTBP2	868	0.42	0.36	YES
40	WNT10B	WNT10B	WNT10B	901	0.41	0.36	YES
41	BCL2	BCL2	BCL2	912	0.41	0.37	YES
42	VEGFC	VEGFC	VEGFC	928	0.41	0.38	YES
43	IL6	IL6	IL6	959	0.41	0.38	YES
44	WNT7B	WNT7B	WNT7B	1003	0.4	0.39	YES
45	CSF2RA	CSF2RA	CSF2RA	1010	0.4	0.4	YES
46	GSTP1	GSTP1	GSTP1	1056	0.39	0.4	YES
47	RARB	RARB	RARB	1117	0.38	0.4	YES
48	RET	RET	RET	1208	0.37	0.41	YES
49	PGF	PGF	PGF	1244	0.37	0.41	YES
50	PIK3R5	PIK3R5	PIK3R5	1370	0.36	0.41	YES
51	PRKCB	PRKCB	PRKCB	1538	0.33	0.41	YES
52	TGFB1	TGFB1	TGFB1	1575	0.33	0.41	YES
53	CSF3R	CSF3R	CSF3R	1593	0.33	0.42	YES
54	FLT3	FLT3	FLT3	1603	0.33	0.42	YES
55	MECOM	MECOM	MECOM	1699	0.32	0.42	YES
56	FGFR2	FGFR2	FGFR2	1727	0.32	0.43	YES
57	PDGFA	PDGFA	PDGFA	1768	0.31	0.43	YES
58	BIRC3	BIRC3	BIRC3	1774	0.31	0.44	YES
59	PIK3CG	PIK3CG	PIK3CG	1828	0.31	0.44	YES
60	RAC2	RAC2	RAC2	1875	0.3	0.44	YES
61	WNT7A	WNT7A	WNT7A	1877	0.3	0.45	YES
62	MMP9	MMP9	MMP9	1879	0.3	0.46	YES
63	PIK3CD	PIK3CD	PIK3CD	1884	0.3	0.46	YES
64	FGF14	FGF14	FGF14	1936	0.3	0.46	YES
65	FGF11	FGF11	FGF11	1941	0.3	0.47	YES
66	KIT	KIT	KIT	1957	0.3	0.47	YES
67	WNT11	WNT11	WNT11	2070	0.28	0.47	YES
68	FOS	FOS	FOS	2116	0.28	0.48	YES
69	WNT1	WNT1	WNT1	2139	0.28	0.48	YES
70	CSF1R	CSF1R	CSF1R	2182	0.28	0.48	YES
71	LEF1	LEF1	LEF1	2213	0.27	0.49	YES
72	COL4A2	COL4A2	COL4A2	2289	0.27	0.49	YES
73	SPI1	SPI1	SPI1	2343	0.26	0.49	YES
74	LAMB1	LAMB1	LAMB1	2397	0.26	0.49	YES
75	PDGFRB	PDGFRB	PDGFRB	2413	0.26	0.5	YES
76	ITGA2	ITGA2	ITGA2	2421	0.26	0.5	YES
77	PTCH2	PTCH2	PTCH2	2426	0.26	0.5	YES
78	NTRK1	NTRK1	NTRK1	2427	0.26	0.51	YES
79	PTCH1	PTCH1	PTCH1	2471	0.25	0.51	YES
80	ETS1	ETS1	ETS1	2607	0.24	0.51	YES
81	ITGAV	ITGAV	ITGAV	2640	0.24	0.51	YES
82	COL4A1	COL4A1	COL4A1	2792	0.23	0.51	YES
83	WNT3A	WNT3A	WNT3A	2845	0.23	0.51	YES
84	EGLN3	EGLN3	EGLN3	2910	0.22	0.51	YES
85	PLD1	PLD1	PLD1	2930	0.22	0.51	YES
86	RUNX1	RUNX1	RUNX1	2950	0.22	0.52	YES
87	LAMA5	LAMA5	LAMA5	3030	0.21	0.52	YES
88	TRAF5	TRAF5	TRAF5	3036	0.21	0.52	YES
89	CCNA1	CCNA1	CCNA1	3178	0.2	0.51	YES
90	CDH1	CDH1	CDH1	3179	0.2	0.52	YES
91	FZD6	FZD6	FZD6	3357	0.19	0.51	YES
92	FLT3LG	FLT3LG	FLT3LG	3368	0.19	0.52	YES
93	HIF1A	HIF1A	HIF1A	3473	0.18	0.51	YES
94	BMP2	BMP2	BMP2	3522	0.18	0.51	YES
95	NOS2	NOS2	NOS2	3547	0.18	0.52	YES
96	PDGFB	PDGFB	PDGFB	3570	0.18	0.52	YES
97	WNT9B	WNT9B	WNT9B	3585	0.18	0.52	YES
98	EGF	EGF	EGF	3750	0.17	0.51	YES
99	FGF13	FGF13	FGF13	3793	0.16	0.52	YES
100	WNT6	WNT6	WNT6	3803	0.16	0.52	YES
101	FZD3	FZD3	FZD3	3841	0.16	0.52	YES
102	FGF12	FGF12	FGF12	3893	0.16	0.52	YES
103	CBL	CBL	CBL	3919	0.16	0.52	YES
104	MYC	MYC	MYC	3924	0.16	0.52	YES
105	RALGDS	RALGDS	RALGDS	3987	0.16	0.52	YES
106	LAMA4	LAMA4	LAMA4	4025	0.15	0.52	YES
107	ITGA2B	ITGA2B	ITGA2B	4081	0.15	0.52	YES
108	APC2	APC2	APC2	4125	0.15	0.52	YES
109	FASLG	FASLG	FASLG	4193	0.14	0.52	YES
110	RB1	RB1	RB1	4262	0.14	0.52	YES
111	FGF9	FGF9	FGF9	4394	0.13	0.52	YES
112	VEGFB	VEGFB	VEGFB	4400	0.13	0.52	YES
113	TP53	TP53	TP53	4408	0.13	0.52	YES
114	PML	PML	PML	4459	0.13	0.52	YES
115	FGF19	FGF19	FGF19	4465	0.13	0.52	YES
116	TRAF1	TRAF1	TRAF1	4528	0.13	0.52	YES
117	LAMB4	LAMB4	LAMB4	4544	0.12	0.52	YES
118	PIK3R3	PIK3R3	PIK3R3	4569	0.12	0.52	YES
119	PLCG2	PLCG2	PLCG2	4644	0.12	0.52	YES
120	SLC2A1	SLC2A1	SLC2A1	4664	0.12	0.52	YES
121	RASSF5	RASSF5	RASSF5	4728	0.12	0.52	YES
122	CBLB	CBLB	CBLB	4807	0.11	0.52	YES
123	RALB	RALB	RALB	4810	0.11	0.52	YES
124	NFKB1	NFKB1	NFKB1	4811	0.11	0.52	YES
125	CCND1	CCND1	CCND1	4814	0.11	0.53	YES
126	WNT16	WNT16	WNT16	4844	0.11	0.53	YES
127	DAPK1	DAPK1	DAPK1	4942	0.11	0.52	NO
128	STAT5A	STAT5A	STAT5A	4953	0.11	0.52	NO
129	CDKN1A	CDKN1A	CDKN1A	4955	0.11	0.53	NO
130	NKX3-1	NKX3-1	NKX3-1	5027	0.1	0.52	NO
131	E2F3	E2F3	E2F3	5144	0.1	0.52	NO
132	CDK6	CDK6	CDK6	5178	0.098	0.52	NO
133	AXIN1	AXIN1	AXIN1	5274	0.094	0.52	NO
134	ITGB1	ITGB1	ITGB1	5298	0.093	0.52	NO
135	TGFBR1	TGFBR1	TGFBR1	5365	0.09	0.51	NO
136	EGFR	EGFR	EGFR	5445	0.088	0.51	NO
137	PPARD	PPARD	PPARD	5458	0.087	0.51	NO
138	EPAS1	EPAS1	EPAS1	5477	0.086	0.51	NO
139	STAT3	STAT3	STAT3	5518	0.085	0.51	NO
140	NFKB2	NFKB2	NFKB2	5556	0.084	0.51	NO
141	LAMC1	LAMC1	LAMC1	5770	0.077	0.5	NO
142	TGFBR2	TGFBR2	TGFBR2	5799	0.076	0.5	NO
143	STAT1	STAT1	STAT1	5810	0.075	0.5	NO
144	ERBB2	ERBB2	ERBB2	5826	0.075	0.5	NO
145	MAX	MAX	MAX	5872	0.074	0.5	NO
146	CRK	CRK	CRK	5901	0.073	0.5	NO
147	CDKN2B	CDKN2B	CDKN2B	5927	0.072	0.5	NO
148	ABL1	ABL1	ABL1	5944	0.072	0.5	NO
149	JAK1	JAK1	JAK1	5965	0.071	0.5	NO
150	COL4A6	COL4A6	COL4A6	5968	0.071	0.5	NO
151	IKBKB	IKBKB	IKBKB	5986	0.07	0.5	NO
152	FAS	FAS	FAS	6001	0.07	0.5	NO
153	PAX8	PAX8	PAX8	6245	0.064	0.49	NO
154	KITLG	KITLG	KITLG	6417	0.06	0.48	NO
155	MAPK3	MAPK3	MAPK3	6456	0.059	0.48	NO
156	EGLN1	EGLN1	EGLN1	6650	0.055	0.47	NO
157	SUFU	SUFU	SUFU	6684	0.054	0.47	NO
158	FGF2	FGF2	FGF2	6703	0.054	0.47	NO
159	LAMB3	LAMB3	LAMB3	6740	0.053	0.47	NO
160	CCDC6	CCDC6	CCDC6	6752	0.052	0.47	NO
161	MAP2K1	MAP2K1	MAP2K1	6763	0.052	0.47	NO
162	BCR	BCR	BCR	6766	0.052	0.47	NO
163	PIAS3	PIAS3	PIAS3	6851	0.05	0.47	NO
164	SMAD2	SMAD2	SMAD2	6912	0.049	0.46	NO
165	DAPK3	DAPK3	DAPK3	6931	0.049	0.46	NO
166	TRAF3	TRAF3	TRAF3	6994	0.047	0.46	NO
167	IGF1	IGF1	IGF1	7046	0.046	0.46	NO
168	BID	BID	BID	7073	0.046	0.46	NO
169	KRAS	KRAS	KRAS	7083	0.045	0.46	NO
170	BCL2L1	BCL2L1	BCL2L1	7085	0.045	0.46	NO
171	TRAF6	TRAF6	TRAF6	7115	0.045	0.46	NO
172	RAC1	RAC1	RAC1	7148	0.044	0.46	NO
173	ZBTB16	ZBTB16	ZBTB16	7178	0.043	0.46	NO
174	FZD4	FZD4	FZD4	7183	0.043	0.46	NO
175	NFKBIA	NFKBIA	NFKBIA	7273	0.041	0.45	NO
176	WNT5A	WNT5A	WNT5A	7279	0.041	0.45	NO
177	WNT5B	WNT5B	WNT5B	7290	0.041	0.46	NO
178	LAMA3	LAMA3	LAMA3	7365	0.04	0.45	NO
179	FOXO1	FOXO1	FOXO1	7410	0.039	0.45	NO
180	CYCS	CYCS	CYCS	7422	0.038	0.45	NO
181	JUP	JUP	JUP	7587	0.036	0.44	NO
182	AKT1	AKT1	AKT1	7775	0.032	0.43	NO
183	LAMB2	LAMB2	LAMB2	7799	0.032	0.43	NO
184	PTK2	PTK2	PTK2	7848	0.031	0.43	NO
185	SOS2	SOS2	SOS2	7870	0.031	0.43	NO
186	CTNNA1	CTNNA1	CTNNA1	7942	0.03	0.42	NO
187	BAX	BAX	BAX	7969	0.029	0.42	NO
188	BAD	BAD	BAD	8004	0.029	0.42	NO
189	DAPK2	DAPK2	DAPK2	8009	0.028	0.42	NO
190	APC	APC	APC	8023	0.028	0.42	NO
191	CDC42	CDC42	CDC42	8025	0.028	0.42	NO
192	PIK3CA	PIK3CA	PIK3CA	8136	0.026	0.42	NO
193	FADD	FADD	FADD	8409	0.023	0.4	NO
194	XIAP	XIAP	XIAP	8458	0.022	0.4	NO
195	JUN	JUN	JUN	8506	0.021	0.4	NO
196	TPM3	TPM3	TPM3	8519	0.021	0.4	NO
197	FGFR3	FGFR3	FGFR3	8591	0.02	0.39	NO
198	CBLC	CBLC	CBLC	8701	0.018	0.39	NO
199	MAPK9	MAPK9	MAPK9	8780	0.017	0.38	NO
200	TCEB1	TCEB1	TCEB1	8818	0.017	0.38	NO
201	RALA	RALA	RALA	8891	0.015	0.38	NO
202	ARAF	ARAF	ARAF	8957	0.014	0.37	NO
203	CASP8	CASP8	CASP8	8991	0.014	0.37	NO
204	TCF7L2	TCF7L2	TCF7L2	9172	0.012	0.36	NO
205	MAPK8	MAPK8	MAPK8	9184	0.012	0.36	NO
206	RHOA	RHOA	RHOA	9253	0.011	0.36	NO
207	PTEN	PTEN	PTEN	9257	0.011	0.36	NO
208	MMP1	MMP1	MMP1	9298	0.01	0.36	NO
209	RBX1	RBX1	RBX1	9482	0.0079	0.34	NO
210	CREBBP	CREBBP	CREBBP	9648	0.0058	0.34	NO
211	IKBKG	IKBKG	IKBKG	9663	0.0055	0.34	NO
212	MAP2K2	MAP2K2	MAP2K2	9712	0.0049	0.33	NO
213	PIK3CB	PIK3CB	PIK3CB	9781	0.0041	0.33	NO
214	RASSF1	RASSF1	RASSF1	9809	0.0037	0.33	NO
215	FN1	FN1	FN1	9821	0.0036	0.33	NO
216	TCEB2	TCEB2	TCEB2	9877	0.0028	0.32	NO
217	HSP90AA1	HSP90AA1	HSP90AA1	10025	0.0012	0.32	NO
218	HDAC1	HDAC1	HDAC1	10089	0.00055	0.31	NO
219	SMAD3	SMAD3	SMAD3	10237	-0.0012	0.3	NO
220	APPL1	APPL1	APPL1	10346	-0.0026	0.3	NO
221	RALBP1	RALBP1	RALBP1	10383	-0.0029	0.3	NO
222	CHUK	CHUK	CHUK	10385	-0.003	0.3	NO
223	CTBP1	CTBP1	CTBP1	10395	-0.0031	0.29	NO
224	CASP3	CASP3	CASP3	10465	-0.0041	0.29	NO
225	PIAS2	PIAS2	PIAS2	10575	-0.0055	0.28	NO
226	TCF7L1	TCF7L1	TCF7L1	10620	-0.006	0.28	NO
227	TRAF2	TRAF2	TRAF2	10663	-0.0065	0.28	NO
228	FZD9	FZD9	FZD9	10675	-0.0067	0.28	NO
229	WNT3	WNT3	WNT3	10734	-0.0072	0.28	NO
230	HSP90B1	HSP90B1	HSP90B1	10851	-0.0088	0.27	NO
231	STK4	STK4	STK4	11019	-0.011	0.26	NO
232	HSP90AB1	HSP90AB1	HSP90AB1	11079	-0.012	0.26	NO
233	MAPK1	MAPK1	MAPK1	11085	-0.012	0.26	NO
234	RELA	RELA	RELA	11131	-0.012	0.25	NO
235	PIAS4	PIAS4	PIAS4	11137	-0.012	0.25	NO
236	HDAC2	HDAC2	HDAC2	11195	-0.013	0.25	NO
237	RARA	RARA	RARA	11221	-0.013	0.25	NO
238	SMAD4	SMAD4	SMAD4	11225	-0.013	0.25	NO
239	MLH1	MLH1	MLH1	11232	-0.014	0.25	NO
240	EGLN2	EGLN2	EGLN2	11291	-0.014	0.25	NO
241	MDM2	MDM2	MDM2	11363	-0.015	0.24	NO
242	SOS1	SOS1	SOS1	11408	-0.016	0.24	NO
243	DVL3	DVL3	DVL3	11435	-0.016	0.24	NO
244	AXIN2	AXIN2	AXIN2	11458	-0.016	0.24	NO
245	EP300	EP300	EP300	11540	-0.017	0.24	NO
246	PLCG1	PLCG1	PLCG1	11593	-0.018	0.23	NO
247	FGF21	FGF21	FGF21	11605	-0.018	0.23	NO
248	GSK3B	GSK3B	GSK3B	11610	-0.018	0.23	NO
249	FH	FH	FH	11669	-0.019	0.23	NO
250	PIK3R2	PIK3R2	PIK3R2	11746	-0.02	0.22	NO
251	RXRG	RXRG	RXRG	11870	-0.021	0.22	NO
252	MSH3	MSH3	MSH3	12083	-0.024	0.21	NO
253	BIRC2	BIRC2	BIRC2	12209	-0.026	0.2	NO
254	AKT2	AKT2	AKT2	12348	-0.028	0.19	NO
255	TFG	TFG	TFG	12362	-0.028	0.19	NO
256	FGF22	FGF22	FGF22	12411	-0.028	0.19	NO
257	TPR	TPR	TPR	12508	-0.03	0.18	NO
258	DVL1	DVL1	DVL1	12659	-0.032	0.18	NO
259	GRB2	GRB2	GRB2	12701	-0.032	0.18	NO
260	PRKCG	PRKCG	PRKCG	12717	-0.032	0.18	NO
261	DVL2	DVL2	DVL2	12767	-0.033	0.17	NO
262	CDKN1B	CDKN1B	CDKN1B	12895	-0.035	0.17	NO
263	CTNNB1	CTNNB1	CTNNB1	12896	-0.035	0.17	NO
264	MTOR	MTOR	MTOR	12905	-0.035	0.17	NO
265	CCNE1	CCNE1	CCNE1	12938	-0.036	0.17	NO
266	ITGA6	ITGA6	ITGA6	12983	-0.036	0.16	NO
267	CASP9	CASP9	CASP9	13049	-0.037	0.16	NO
268	STAT5B	STAT5B	STAT5B	13085	-0.038	0.16	NO
269	CDK4	CDK4	CDK4	13105	-0.038	0.16	NO
270	CUL2	CUL2	CUL2	13120	-0.038	0.16	NO
271	NRAS	NRAS	NRAS	13162	-0.039	0.16	NO
272	ARNT	ARNT	ARNT	13197	-0.039	0.16	NO
273	MSH6	MSH6	MSH6	13270	-0.04	0.15	NO
274	VHL	VHL	VHL	13398	-0.042	0.15	NO
275	RXRA	RXRA	RXRA	13551	-0.045	0.14	NO
276	VEGFA	VEGFA	VEGFA	13730	-0.048	0.13	NO
277	NCOA4	NCOA4	NCOA4	14022	-0.054	0.11	NO
278	TRAF4	TRAF4	TRAF4	14052	-0.054	0.11	NO
279	CRKL	CRKL	CRKL	14312	-0.059	0.1	NO
280	CKS1B	CKS1B	CKS1B	14373	-0.06	0.097	NO
281	STK36	STK36	STK36	14462	-0.063	0.093	NO
282	SHH	SHH	SHH	14717	-0.069	0.08	NO
283	PIK3R1	PIK3R1	PIK3R1	14760	-0.07	0.079	NO
284	PIAS1	PIAS1	PIAS1	14761	-0.07	0.08	NO
285	RAF1	RAF1	RAF1	14790	-0.07	0.08	NO
286	BRAF	BRAF	BRAF	14793	-0.07	0.081	NO
287	RXRB	RXRB	RXRB	14964	-0.075	0.073	NO
288	BMP4	BMP4	BMP4	15122	-0.08	0.066	NO
289	FZD5	FZD5	FZD5	15131	-0.08	0.067	NO
290	MSH2	MSH2	MSH2	15214	-0.082	0.064	NO
291	MET	MET	MET	15509	-0.093	0.048	NO
292	CDK2	CDK2	CDK2	15701	-0.1	0.039	NO
293	AR	AR	AR	15756	-0.1	0.038	NO
294	PRKCA	PRKCA	PRKCA	15772	-0.1	0.039	NO
295	E2F2	E2F2	E2F2	16011	-0.12	0.028	NO
296	CEBPA	CEBPA	CEBPA	16184	-0.12	0.02	NO
297	PPARG	PPARG	PPARG	16361	-0.14	0.013	NO
298	RAD51	RAD51	RAD51	16385	-0.14	0.014	NO
299	CCNE2	CCNE2	CCNE2	16531	-0.15	0.0088	NO
300	FGF17	FGF17	FGF17	16631	-0.16	0.0062	NO
301	CTNNA3	CTNNA3	CTNNA3	16715	-0.16	0.0045	NO
302	SMO	SMO	SMO	16853	-0.17	0.000022	NO
303	BRCA2	BRCA2	BRCA2	16871	-0.18	0.0024	NO
304	WNT8B	WNT8B	WNT8B	17064	-0.19	-0.0049	NO
305	FIGF	FIGF	FIGF	17088	-0.2	-0.0024	NO
306	CDKN2A	CDKN2A	CDKN2A	17201	-0.21	-0.0047	NO
307	TCF7	TCF7	TCF7	17245	-0.22	-0.003	NO
308	E2F1	E2F1	E2F1	17261	-0.22	0.00036	NO
309	BIRC5	BIRC5	BIRC5	17368	-0.24	-0.0011	NO
310	DCC	DCC	DCC	17432	-0.25	0.00014	NO
311	CTNNA2	CTNNA2	CTNNA2	17452	-0.26	0.004	NO
312	SKP2	SKP2	SKP2	17533	-0.29	0.0049	NO
313	RAC3	RAC3	RAC3	17620	-0.32	0.0062	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: BIOCARTA FAS PATHWAY.

Figure S78. 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 FCER1 PATHWAY

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	TGFB3	TGFB3	TGFB3	550	0.49	0.027	YES
2	TGFB2	TGFB2	TGFB2	644	0.47	0.078	YES
3	TGFA	TGFA	TGFA	698	0.45	0.13	YES
4	AKT3	AKT3	AKT3	748	0.44	0.18	YES
5	HGF	HGF	HGF	820	0.43	0.23	YES
6	ARNT2	ARNT2	ARNT2	838	0.42	0.28	YES
7	VEGFC	VEGFC	VEGFC	928	0.41	0.32	YES
8	PGF	PGF	PGF	1244	0.37	0.35	YES
9	PIK3R5	PIK3R5	PIK3R5	1370	0.36	0.38	YES
10	TGFB1	TGFB1	TGFB1	1575	0.33	0.41	YES
11	PIK3CG	PIK3CG	PIK3CG	1828	0.31	0.43	YES
12	PIK3CD	PIK3CD	PIK3CD	1884	0.3	0.47	YES
13	PAK7	PAK7	PAK7	2424	0.26	0.47	YES
14	ETS1	ETS1	ETS1	2607	0.24	0.48	YES
15	EGLN3	EGLN3	EGLN3	2910	0.22	0.5	YES
16	PAK3	PAK3	PAK3	3461	0.19	0.49	YES
17	HIF1A	HIF1A	HIF1A	3473	0.18	0.51	YES
18	PDGFB	PDGFB	PDGFB	3570	0.18	0.52	YES
19	PAK6	PAK6	PAK6	4254	0.14	0.5	NO
20	VEGFB	VEGFB	VEGFB	4400	0.13	0.51	NO
21	PIK3R3	PIK3R3	PIK3R3	4569	0.12	0.51	NO
22	SLC2A1	SLC2A1	SLC2A1	4664	0.12	0.52	NO
23	EPAS1	EPAS1	EPAS1	5477	0.086	0.49	NO
24	CRK	CRK	CRK	5901	0.073	0.47	NO
25	MAPK3	MAPK3	MAPK3	6456	0.059	0.45	NO
26	EGLN1	EGLN1	EGLN1	6650	0.055	0.44	NO
27	MAP2K1	MAP2K1	MAP2K1	6763	0.052	0.44	NO
28	KRAS	KRAS	KRAS	7083	0.045	0.43	NO
29	RAP1B	RAP1B	RAP1B	7143	0.044	0.43	NO
30	GAB1	GAB1	GAB1	7147	0.044	0.44	NO
31	RAC1	RAC1	RAC1	7148	0.044	0.44	NO
32	RAPGEF1	RAPGEF1	RAPGEF1	7289	0.041	0.44	NO
33	PAK1	PAK1	PAK1	7355	0.04	0.44	NO
34	AKT1	AKT1	AKT1	7775	0.032	0.42	NO
35	SOS2	SOS2	SOS2	7870	0.031	0.42	NO
36	PAK2	PAK2	PAK2	7916	0.03	0.42	NO
37	CDC42	CDC42	CDC42	8025	0.028	0.42	NO
38	PIK3CA	PIK3CA	PIK3CA	8136	0.026	0.42	NO
39	RAP1A	RAP1A	RAP1A	8484	0.022	0.4	NO
40	JUN	JUN	JUN	8506	0.021	0.4	NO
41	TCEB1	TCEB1	TCEB1	8818	0.017	0.38	NO
42	ARAF	ARAF	ARAF	8957	0.014	0.38	NO
43	RBX1	RBX1	RBX1	9482	0.0079	0.35	NO
44	CREBBP	CREBBP	CREBBP	9648	0.0058	0.34	NO
45	MAP2K2	MAP2K2	MAP2K2	9712	0.0049	0.34	NO
46	FLCN	FLCN	FLCN	9721	0.0048	0.34	NO
47	PIK3CB	PIK3CB	PIK3CB	9781	0.0041	0.34	NO
48	TCEB2	TCEB2	TCEB2	9877	0.0028	0.33	NO
49	PTPN11	PTPN11	PTPN11	10976	-0.01	0.27	NO
50	MAPK1	MAPK1	MAPK1	11085	-0.012	0.26	NO
51	EGLN2	EGLN2	EGLN2	11291	-0.014	0.25	NO
52	SOS1	SOS1	SOS1	11408	-0.016	0.25	NO
53	PAK4	PAK4	PAK4	11444	-0.016	0.25	NO
54	EP300	EP300	EP300	11540	-0.017	0.25	NO
55	FH	FH	FH	11669	-0.019	0.24	NO
56	PIK3R2	PIK3R2	PIK3R2	11746	-0.02	0.24	NO
57	AKT2	AKT2	AKT2	12348	-0.028	0.21	NO
58	GRB2	GRB2	GRB2	12701	-0.032	0.19	NO
59	CUL2	CUL2	CUL2	13120	-0.038	0.17	NO
60	NRAS	NRAS	NRAS	13162	-0.039	0.18	NO
61	ARNT	ARNT	ARNT	13197	-0.039	0.18	NO
62	VHL	VHL	VHL	13398	-0.042	0.17	NO
63	VEGFA	VEGFA	VEGFA	13730	-0.048	0.16	NO
64	CRKL	CRKL	CRKL	14312	-0.059	0.13	NO
65	PIK3R1	PIK3R1	PIK3R1	14760	-0.07	0.12	NO
66	RAF1	RAF1	RAF1	14790	-0.07	0.12	NO
67	BRAF	BRAF	BRAF	14793	-0.07	0.13	NO
68	MET	MET	MET	15509	-0.093	0.1	NO
69	FIGF	FIGF	FIGF	17088	-0.2	0.036	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: BIOCARTA FCER1 PATHWAY.

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus5 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA WNT PATHWAY	25	genes.ES.table	0.35	1.2	0.29	0.6	1	0.28	0.14	0.24	0.54	0.13
KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS	26	genes.ES.table	0.7	1.4	0.13	0.67	0.96	0.54	0.086	0.49	0.53	0.21
KEGG FATTY ACID METABOLISM	41	genes.ES.table	0.68	1.6	0.028	1	0.72	0.56	0.14	0.48	0.84	0.45
KEGG STEROID HORMONE BIOSYNTHESIS	51	genes.ES.table	0.65	1.4	0.086	0.67	0.95	0.53	0.093	0.48	0.52	0.22
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.53	1.4	0.19	0.62	0.97	0.63	0.21	0.5	0.49	0.18
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.38	1.3	0.25	0.62	0.99	0.35	0.19	0.28	0.54	0.16
KEGG TYROSINE METABOLISM	39	genes.ES.table	0.57	1.5	0.047	0.73	0.86	0.41	0.11	0.37	0.5	0.25
KEGG TRYPTOPHAN METABOLISM	38	genes.ES.table	0.48	1.2	0.22	0.61	1	0.34	0.087	0.31	0.53	0.14
KEGG PROPANOATE METABOLISM	31	genes.ES.table	0.43	1.1	0.36	0.69	1	0.48	0.17	0.4	0.64	0.17
KEGG BUTANOATE METABOLISM	30	genes.ES.table	0.55	1.4	0.15	0.58	0.97	0.57	0.17	0.47	0.46	0.15

genes ES table in pathway: BIOCARTA WNT PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACSL6	ACSL6	ACSL6	55	0.77	0.11	YES
2	ACSL5	ACSL5	ACSL5	174	0.48	0.18	YES
3	ADH1B	ADH1B	ADH1B	194	0.47	0.25	YES
4	ADH4	ADH4	ADH4	230	0.43	0.32	YES
5	ADH6	ADH6	ADH6	237	0.43	0.38	YES
6	EHHADH	EHHADH	EHHADH	627	0.26	0.4	YES
7	ADH1C	ADH1C	ADH1C	691	0.25	0.43	YES
8	ALDH3A2	ALDH3A2	ALDH3A2	878	0.22	0.46	YES
9	ACADL	ACADL	ACADL	1071	0.19	0.47	YES
10	ADH7	ADH7	ADH7	1082	0.19	0.5	YES
11	HADH	HADH	HADH	1253	0.17	0.52	YES
12	ALDH2	ALDH2	ALDH2	1357	0.16	0.54	YES
13	ALDH1B1	ALDH1B1	ALDH1B1	1361	0.16	0.56	YES
14	GCDH	GCDH	GCDH	1464	0.15	0.57	YES
15	ACADSB	ACADSB	ACADSB	1529	0.14	0.59	YES
16	ACAA1	ACAA1	ACAA1	1658	0.13	0.61	YES
17	PECI	PECI	PECI	1793	0.12	0.62	YES
18	ADH5	ADH5	ADH5	1876	0.12	0.63	YES
19	ADH1A	ADH1A	ADH1A	1914	0.12	0.64	YES
20	DCI	DCI	DCI	1958	0.11	0.66	YES
21	CPT2	CPT2	CPT2	2064	0.11	0.67	YES
22	ACADM	ACADM	ACADM	2401	0.09	0.66	YES
23	ECHS1	ECHS1	ECHS1	2429	0.088	0.68	YES
24	CYP4A11	CYP4A11	CYP4A11	2821	0.073	0.67	NO
25	ALDH7A1	ALDH7A1	ALDH7A1	2851	0.072	0.68	NO
26	ALDH9A1	ALDH9A1	ALDH9A1	3054	0.065	0.67	NO
27	CPT1C	CPT1C	CPT1C	3308	0.058	0.67	NO
28	CYP4A22	CYP4A22	CYP4A22	3394	0.056	0.67	NO
29	ACAA2	ACAA2	ACAA2	3577	0.051	0.67	NO
30	ACSL1	ACSL1	ACSL1	4345	0.034	0.63	NO
31	ACADVL	ACADVL	ACADVL	4486	0.032	0.63	NO
32	ACAT1	ACAT1	ACAT1	4859	0.024	0.61	NO
33	ACSL3	ACSL3	ACSL3	4948	0.022	0.61	NO
34	HADHB	HADHB	HADHB	5851	0.0068	0.56	NO
35	HADHA	HADHA	HADHA	5855	0.0068	0.56	NO
36	ACAT2	ACAT2	ACAT2	7881	-0.024	0.45	NO
37	ACADS	ACADS	ACADS	8671	-0.037	0.41	NO
38	ACOX3	ACOX3	ACOX3	8819	-0.04	0.41	NO
39	CPT1A	CPT1A	CPT1A	9156	-0.046	0.4	NO
40	CPT1B	CPT1B	CPT1B	12074	-0.13	0.25	NO
41	ACSL4	ACSL4	ACSL4	16983	-0.46	0.042	NO

Figure S81. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA WNT PATHWAY.

Figure S82. 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 PENTOSE AND GLUCURONATE INTERCONVERSIONS

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	UGT1A3	UGT1A3	UGT1A3	49	0.78	0.1	YES
2	UGT1A5	UGT1A5	UGT1A5	56	0.76	0.21	YES
3	UGT1A4	UGT1A4	UGT1A4	74	0.69	0.3	YES
4	UGT1A1	UGT1A1	UGT1A1	181	0.48	0.36	YES
5	UGT1A9	UGT1A9	UGT1A9	302	0.38	0.41	YES
6	UGT1A6	UGT1A6	UGT1A6	469	0.31	0.44	YES
7	UGT2B28	UGT2B28	UGT2B28	496	0.31	0.48	YES
8	ALAS1	ALAS1	ALAS1	514	0.3	0.52	YES
9	UGT2B10	UGT2B10	UGT2B10	607	0.27	0.56	YES
10	UGT2B7	UGT2B7	UGT2B7	937	0.21	0.56	YES
11	ALAD	ALAD	ALAD	1068	0.19	0.58	YES
12	UGT1A8	UGT1A8	UGT1A8	1170	0.18	0.6	YES
13	UGT2B11	UGT2B11	UGT2B11	1269	0.16	0.62	YES
14	MMAB	MMAB	MMAB	1378	0.15	0.64	YES
15	UGT2B4	UGT2B4	UGT2B4	1532	0.14	0.65	YES
16	BLVRB	BLVRB	BLVRB	1820	0.12	0.65	YES
17	UGT2B15	UGT2B15	UGT2B15	2095	0.1	0.64	YES
18	HMOX2	HMOX2	HMOX2	2237	0.098	0.65	YES
19	EARS2	EARS2	EARS2	2398	0.09	0.65	YES
20	PPOX	PPOX	PPOX	2490	0.086	0.66	YES
21	FECH	FECH	FECH	2896	0.07	0.65	NO
22	UROS	UROS	UROS	3307	0.058	0.63	NO
23	COX15	COX15	COX15	3502	0.053	0.63	NO
24	UROD	UROD	UROD	5578	0.012	0.51	NO
25	EPRS	EPRS	EPRS	5931	0.0054	0.49	NO
26	CPOX	CPOX	CPOX	5987	0.0045	0.49	NO
27	COX10	COX10	COX10	6947	-0.01	0.44	NO
28	HMBS	HMBS	HMBS	7220	-0.014	0.42	NO
29	ALAS2	ALAS2	ALAS2	7664	-0.021	0.4	NO
30	UGT1A7	UGT1A7	UGT1A7	7830	-0.024	0.4	NO
31	FTH1	FTH1	FTH1	8529	-0.034	0.36	NO
32	GUSB	GUSB	GUSB	9575	-0.054	0.31	NO
33	HMOX1	HMOX1	HMOX1	11236	-0.097	0.23	NO
34	CP	CP	CP	11957	-0.12	0.21	NO
35	UGT2A1	UGT2A1	UGT2A1	12806	-0.16	0.18	NO
36	UGT1A10	UGT1A10	UGT1A10	13047	-0.17	0.19	NO
37	UGT2A3	UGT2A3	UGT2A3	13587	-0.2	0.19	NO
38	BLVRA	BLVRA	BLVRA	15959	-0.35	0.1	NO

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

Figure S84. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG FATTY ACID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NARS2	NARS2	NARS2	1174	0.18	0.022	YES
2	FARS2	FARS2	FARS2	1363	0.16	0.09	YES
3	EARS2	EARS2	EARS2	2398	0.09	0.076	YES
4	PSTK	PSTK	PSTK	2409	0.089	0.12	YES
5	SEPSECS	SEPSECS	SEPSECS	2648	0.08	0.15	YES
6	PARS2	PARS2	PARS2	2995	0.067	0.16	YES
7	IARS2	IARS2	IARS2	3114	0.063	0.19	YES
8	VARS	VARS	VARS	3510	0.053	0.19	YES
9	KARS	KARS	KARS	3520	0.052	0.22	YES
10	HARS2	HARS2	HARS2	3549	0.052	0.24	YES
11	AARS	AARS	AARS	3580	0.051	0.26	YES
12	HARS	HARS	HARS	3973	0.042	0.26	YES
13	DARS	DARS	DARS	4200	0.037	0.27	YES
14	RARS	RARS	RARS	4283	0.035	0.28	YES
15	MTFMT	MTFMT	MTFMT	4555	0.03	0.28	YES
16	LARS2	LARS2	LARS2	4919	0.023	0.27	YES
17	QARS	QARS	QARS	5376	0.015	0.26	YES
18	AARS2	AARS2	AARS2	5826	0.0073	0.23	YES
19	FARSB	FARSB	FARSB	5870	0.0065	0.24	YES
20	EPRS	EPRS	EPRS	5931	0.0054	0.23	YES
21	VARS2	VARS2	VARS2	6163	0.0016	0.22	YES
22	NARS	NARS	NARS	6268	9.8e-06	0.22	YES
23	FARSA	FARSA	FARSA	6468	-0.003	0.21	YES
24	YARS2	YARS2	YARS2	7227	-0.015	0.17	YES
25	IARS	IARS	IARS	7233	-0.015	0.18	YES
26	DARS2	DARS2	DARS2	7364	-0.017	0.18	YES
27	WARS2	WARS2	WARS2	7956	-0.025	0.16	YES
28	TARSL2	TARSL2	TARSL2	8276	-0.031	0.16	YES
29	LARS	LARS	LARS	8524	-0.034	0.16	YES
30	WARS	WARS	WARS	9386	-0.05	0.14	YES
31	RARS2	RARS2	RARS2	9424	-0.051	0.16	YES
32	CARS2	CARS2	CARS2	9506	-0.052	0.18	YES
33	SARS	SARS	SARS	9863	-0.06	0.19	YES
34	YARS	YARS	YARS	9883	-0.061	0.22	YES
35	MARS	MARS	MARS	10114	-0.066	0.24	YES
36	GARS	GARS	GARS	10156	-0.067	0.27	YES
37	MARS2	MARS2	MARS2	10376	-0.072	0.3	YES
38	SARS2	SARS2	SARS2	10427	-0.073	0.33	YES
39	CARS	CARS	CARS	10774	-0.082	0.35	YES
40	TARS	TARS	TARS	10784	-0.082	0.39	YES

Figure S85. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG FATTY ACID METABOLISM.

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

genes ES table in pathway: KEGG STEROID HORMONE BIOSYNTHESIS

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ALDH3A1	ALDH3A1	ALDH3A1	6	1.2	0.15	YES
2	AOX1	AOX1	AOX1	177	0.48	0.21	YES
3	ADH1B	ADH1B	ADH1B	194	0.47	0.27	YES
4	HPD	HPD	HPD	216	0.44	0.32	YES
5	ADH4	ADH4	ADH4	230	0.43	0.38	YES
6	ADH6	ADH6	ADH6	237	0.43	0.44	YES
7	ADH1C	ADH1C	ADH1C	691	0.25	0.44	YES
8	HGD	HGD	HGD	784	0.23	0.47	YES
9	NAT6	NAT6	NAT6	851	0.22	0.5	YES
10	ADH7	ADH7	ADH7	1082	0.19	0.51	YES
11	DDC	DDC	DDC	1147	0.18	0.53	YES
12	MAOA	MAOA	MAOA	1509	0.14	0.53	YES
13	MAOB	MAOB	MAOB	1541	0.14	0.54	YES
14	AOC2	AOC2	AOC2	1767	0.12	0.55	YES
15	ADH5	ADH5	ADH5	1876	0.12	0.56	YES
16	ADH1A	ADH1A	ADH1A	1914	0.12	0.57	YES
17	GSTZ1	GSTZ1	GSTZ1	2261	0.096	0.56	NO
18	TAT	TAT	TAT	2485	0.086	0.56	NO
19	LCMT2	LCMT2	LCMT2	2658	0.079	0.56	NO
20	HEMK1	HEMK1	HEMK1	3383	0.056	0.53	NO
21	DCT	DCT	DCT	3695	0.048	0.52	NO
22	PNMT	PNMT	PNMT	3746	0.047	0.52	NO
23	WBSCR22	WBSCR22	WBSCR22	4235	0.036	0.5	NO
24	COMT	COMT	COMT	4258	0.036	0.5	NO
25	GOT2	GOT2	GOT2	4496	0.031	0.49	NO
26	FAH	FAH	FAH	5555	0.012	0.43	NO
27	MIF	MIF	MIF	5583	0.012	0.43	NO
28	METTL2B	METTL2B	METTL2B	6408	-0.0021	0.39	NO
29	METTL6	METTL6	METTL6	6516	-0.0038	0.38	NO
30	TRMT11	TRMT11	TRMT11	6987	-0.011	0.36	NO
31	LCMT1	LCMT1	LCMT1	10010	-0.064	0.19	NO
32	AOC3	AOC3	AOC3	10692	-0.08	0.17	NO
33	DBH	DBH	DBH	12789	-0.16	0.069	NO
34	GOT1	GOT1	GOT1	13119	-0.17	0.073	NO
35	TH	TH	TH	13354	-0.19	0.084	NO
36	ALDH1A3	ALDH1A3	ALDH1A3	14455	-0.25	0.055	NO
37	ALDH3B1	ALDH3B1	ALDH3B1	14713	-0.26	0.075	NO
38	ALDH3B2	ALDH3B2	ALDH3B2	16070	-0.36	0.046	NO
39	IL4I1	IL4I1	IL4I1	16146	-0.36	0.089	NO

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

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

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACSL6	ACSL6	ACSL6	55	0.77	0.077	YES
2	AMACR	AMACR	AMACR	130	0.57	0.13	YES
3	ACSL5	ACSL5	ACSL5	174	0.48	0.18	YES
4	HAO1	HAO1	HAO1	589	0.27	0.18	YES
5	EHHADH	EHHADH	EHHADH	627	0.26	0.21	YES
6	PEX11G	PEX11G	PEX11G	703	0.25	0.23	YES
7	PEX12	PEX12	PEX12	773	0.23	0.25	YES
8	BAAT	BAAT	BAAT	877	0.22	0.27	YES
9	HSD17B4	HSD17B4	HSD17B4	897	0.21	0.29	YES
10	PEX11A	PEX11A	PEX11A	967	0.2	0.31	YES
11	PECR	PECR	PECR	1167	0.18	0.31	YES
12	DAO	DAO	DAO	1171	0.18	0.33	YES
13	MLYCD	MLYCD	MLYCD	1379	0.15	0.34	YES
14	GNPAT	GNPAT	GNPAT	1487	0.14	0.34	YES
15	DECR2	DECR2	DECR2	1510	0.14	0.36	YES
16	SOD1	SOD1	SOD1	1548	0.14	0.37	YES
17	PIPOX	PIPOX	PIPOX	1568	0.14	0.38	YES
18	ACAA1	ACAA1	ACAA1	1658	0.13	0.39	YES
19	MVK	MVK	MVK	1690	0.13	0.4	YES
20	PEX5	PEX5	PEX5	1743	0.12	0.41	YES
21	PECI	PECI	PECI	1793	0.12	0.42	YES
22	PAOX	PAOX	PAOX	1881	0.12	0.43	YES
23	PEX6	PEX6	PEX6	2010	0.11	0.44	YES
24	CAT	CAT	CAT	2011	0.11	0.45	YES
25	HMGCL	HMGCL	HMGCL	2058	0.11	0.46	YES
26	SCP2	SCP2	SCP2	2167	0.1	0.46	YES
27	EPHX2	EPHX2	EPHX2	2236	0.098	0.46	YES
28	PEX14	PEX14	PEX14	2287	0.095	0.47	YES
29	IDH1	IDH1	IDH1	2327	0.093	0.48	YES
30	CRAT	CRAT	CRAT	2351	0.092	0.49	YES
31	PMVK	PMVK	PMVK	2692	0.078	0.48	YES
32	ABCD3	ABCD3	ABCD3	2709	0.077	0.48	YES
33	PEX19	PEX19	PEX19	2718	0.077	0.49	YES
34	PEX2	PEX2	PEX2	2824	0.073	0.49	YES
35	ACOX1	ACOX1	ACOX1	2833	0.073	0.5	YES
36	DHRS4	DHRS4	DHRS4	2890	0.071	0.5	YES
37	PEX10	PEX10	PEX10	3002	0.067	0.5	YES
38	GSTK1	GSTK1	GSTK1	3034	0.066	0.51	YES
39	HACL1	HACL1	HACL1	3275	0.059	0.5	NO
40	PEX1	PEX1	PEX1	3538	0.052	0.49	NO
41	PXMP2	PXMP2	PXMP2	3786	0.046	0.48	NO
42	PEX11B	PEX11B	PEX11B	3882	0.044	0.48	NO
43	ECH1	ECH1	ECH1	4190	0.037	0.47	NO
44	ACSL1	ACSL1	ACSL1	4345	0.034	0.46	NO
45	SLC27A2	SLC27A2	SLC27A2	4510	0.031	0.46	NO
46	ABCD2	ABCD2	ABCD2	4591	0.029	0.46	NO
47	PEX13	PEX13	PEX13	4835	0.024	0.45	NO
48	ACSL3	ACSL3	ACSL3	4948	0.022	0.44	NO
49	PRDX1	PRDX1	PRDX1	5005	0.021	0.44	NO
50	AGPS	AGPS	AGPS	5500	0.013	0.41	NO
51	NUDT12	NUDT12	NUDT12	5756	0.0086	0.4	NO
52	DDO	DDO	DDO	5831	0.0072	0.4	NO
53	PEX26	PEX26	PEX26	5899	0.0059	0.39	NO
54	ABCD1	ABCD1	ABCD1	6648	-0.0059	0.35	NO
55	NUDT19	NUDT19	NUDT19	6753	-0.0074	0.35	NO
56	PEX16	PEX16	PEX16	6822	-0.0084	0.34	NO
57	PEX3	PEX3	PEX3	7040	-0.011	0.33	NO
58	PEX7	PEX7	PEX7	7237	-0.015	0.32	NO
59	ABCD4	ABCD4	ABCD4	7389	-0.017	0.32	NO
60	IDH2	IDH2	IDH2	7601	-0.02	0.31	NO
61	ACOT8	ACOT8	ACOT8	7776	-0.023	0.3	NO
62	PXMP4	PXMP4	PXMP4	8488	-0.034	0.26	NO
63	SLC25A17	SLC25A17	SLC25A17	8704	-0.038	0.25	NO
64	ACOX3	ACOX3	ACOX3	8819	-0.04	0.25	NO
65	NOS2	NOS2	NOS2	8954	-0.042	0.25	NO
66	PRDX5	PRDX5	PRDX5	9621	-0.055	0.22	NO
67	AGXT	AGXT	AGXT	9655	-0.056	0.22	NO
68	PHYH	PHYH	PHYH	9780	-0.058	0.22	NO
69	SOD2	SOD2	SOD2	9787	-0.058	0.22	NO
70	MPV17	MPV17	MPV17	10449	-0.074	0.2	NO
71	MPV17L	MPV17L	MPV17L	11824	-0.12	0.13	NO
72	CROT	CROT	CROT	14066	-0.23	0.026	NO
73	XDH	XDH	XDH	14964	-0.28	0.0048	NO
74	HAO2	HAO2	HAO2	15025	-0.28	0.031	NO
75	FAR1	FAR1	FAR1	15562	-0.32	0.034	NO
76	FAR2	FAR2	FAR2	16571	-0.4	0.018	NO
77	ACSL4	ACSL4	ACSL4	16983	-0.46	0.042	NO

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

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

genes ES table in pathway: KEGG LYSINE DEGRADATION

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ALDH3A1	ALDH3A1	ALDH3A1	6	1.2	0.066	YES
2	CYP1A1	CYP1A1	CYP1A1	15	1	0.12	YES
3	UGT1A3	UGT1A3	UGT1A3	49	0.78	0.17	YES
4	UGT1A5	UGT1A5	UGT1A5	56	0.76	0.21	YES
5	CYP1A2	CYP1A2	CYP1A2	64	0.74	0.25	YES
6	UGT1A4	UGT1A4	UGT1A4	74	0.69	0.29	YES
7	CYP2E1	CYP2E1	CYP2E1	92	0.64	0.33	YES
8	UGT1A1	UGT1A1	UGT1A1	181	0.48	0.35	YES
9	ADH1B	ADH1B	ADH1B	194	0.47	0.38	YES
10	ADH4	ADH4	ADH4	230	0.43	0.4	YES
11	ADH6	ADH6	ADH6	237	0.43	0.42	YES
12	UGT1A9	UGT1A9	UGT1A9	302	0.38	0.44	YES
13	CYP2C9	CYP2C9	CYP2C9	386	0.34	0.46	YES
14	AKR1C2	AKR1C2	AKR1C2	455	0.32	0.47	YES
15	UGT1A6	UGT1A6	UGT1A6	469	0.31	0.49	YES
16	CYP3A43	CYP3A43	CYP3A43	485	0.31	0.5	YES
17	UGT2B28	UGT2B28	UGT2B28	496	0.31	0.52	YES
18	AKR1C1	AKR1C1	AKR1C1	602	0.27	0.53	YES
19	UGT2B10	UGT2B10	UGT2B10	607	0.27	0.55	YES
20	ADH1C	ADH1C	ADH1C	691	0.25	0.56	YES
21	AKR1C4	AKR1C4	AKR1C4	707	0.25	0.57	YES
22	CYP2C19	CYP2C19	CYP2C19	723	0.24	0.58	YES
23	UGT2B7	UGT2B7	UGT2B7	937	0.21	0.58	YES
24	ADH7	ADH7	ADH7	1082	0.19	0.58	YES
25	EPHX1	EPHX1	EPHX1	1139	0.18	0.59	YES
26	UGT1A8	UGT1A8	UGT1A8	1170	0.18	0.6	YES
27	MGST1	MGST1	MGST1	1187	0.18	0.61	YES
28	GSTM4	GSTM4	GSTM4	1201	0.17	0.62	YES
29	UGT2B11	UGT2B11	UGT2B11	1269	0.16	0.62	YES
30	UGT2B4	UGT2B4	UGT2B4	1532	0.14	0.62	YES
31	MGST2	MGST2	MGST2	1551	0.14	0.62	YES
32	GSTM3	GSTM3	GSTM3	1586	0.14	0.63	YES
33	CYP2C8	CYP2C8	CYP2C8	1869	0.12	0.62	YES
34	ADH5	ADH5	ADH5	1876	0.12	0.63	YES
35	ADH1A	ADH1A	ADH1A	1914	0.12	0.63	YES
36	UGT2B15	UGT2B15	UGT2B15	2095	0.1	0.63	NO
37	GSTA4	GSTA4	GSTA4	2170	0.1	0.63	NO
38	GSTZ1	GSTZ1	GSTZ1	2261	0.096	0.63	NO
39	GSTM2	GSTM2	GSTM2	2385	0.09	0.63	NO
40	GSTO1	GSTO1	GSTO1	2462	0.087	0.63	NO
41	CYP1B1	CYP1B1	CYP1B1	2793	0.074	0.61	NO
42	GSTK1	GSTK1	GSTK1	3034	0.066	0.6	NO
43	GSTA1	GSTA1	GSTA1	3440	0.055	0.58	NO
44	GSTM1	GSTM1	GSTM1	3617	0.05	0.58	NO
45	CYP3A5	CYP3A5	CYP3A5	3725	0.047	0.57	NO
46	MGST3	MGST3	MGST3	3986	0.042	0.56	NO
47	GSTA2	GSTA2	GSTA2	4017	0.041	0.56	NO
48	GSTT1	GSTT1	GSTT1	4708	0.027	0.52	NO
49	AKR1C3	AKR1C3	AKR1C3	5091	0.02	0.5	NO
50	CYP2B6	CYP2B6	CYP2B6	5237	0.017	0.5	NO
51	GSTO2	GSTO2	GSTO2	6819	-0.0083	0.41	NO
52	UGT1A7	UGT1A7	UGT1A7	7830	-0.024	0.35	NO
53	UGT2A1	UGT2A1	UGT2A1	12806	-0.16	0.08	NO
54	UGT1A10	UGT1A10	UGT1A10	13047	-0.17	0.076	NO
55	UGT2A3	UGT2A3	UGT2A3	13587	-0.2	0.057	NO
56	ALDH1A3	ALDH1A3	ALDH1A3	14455	-0.25	0.022	NO
57	GSTT2	GSTT2	GSTT2	14598	-0.26	0.029	NO
58	CYP2C18	CYP2C18	CYP2C18	14698	-0.26	0.038	NO
59	ALDH3B1	ALDH3B1	ALDH3B1	14713	-0.26	0.053	NO
60	GSTM5	GSTM5	GSTM5	14930	-0.28	0.056	NO
61	CYP2S1	CYP2S1	CYP2S1	15444	-0.31	0.045	NO
62	GSTP1	GSTP1	GSTP1	16041	-0.35	0.032	NO
63	ALDH3B2	ALDH3B2	ALDH3B2	16070	-0.36	0.05	NO
64	DHDH	DHDH	DHDH	16152	-0.36	0.067	NO
65	CYP3A7	CYP3A7	CYP3A7	16474	-0.39	0.071	NO

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

Figure S92. 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 TYROSINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CYP1A1	CYP1A1	CYP1A1	15	1	0.079	YES
2	UGT1A3	UGT1A3	UGT1A3	49	0.78	0.14	YES
3	UGT1A5	UGT1A5	UGT1A5	56	0.76	0.2	YES
4	UGT1A4	UGT1A4	UGT1A4	74	0.69	0.25	YES
5	HSD11B1	HSD11B1	HSD11B1	163	0.5	0.28	YES
6	UGT1A1	UGT1A1	UGT1A1	181	0.48	0.32	YES
7	SRD5A2	SRD5A2	SRD5A2	227	0.44	0.35	YES
8	SULT2B1	SULT2B1	SULT2B1	290	0.39	0.38	YES
9	UGT1A9	UGT1A9	UGT1A9	302	0.38	0.41	YES
10	CYP7B1	CYP7B1	CYP7B1	426	0.33	0.43	YES
11	AKR1C2	AKR1C2	AKR1C2	455	0.32	0.45	YES
12	UGT1A6	UGT1A6	UGT1A6	469	0.31	0.48	YES
13	CYP3A43	CYP3A43	CYP3A43	485	0.31	0.5	YES
14	UGT2B28	UGT2B28	UGT2B28	496	0.31	0.52	YES
15	AKR1C1	AKR1C1	AKR1C1	602	0.27	0.54	YES
16	UGT2B10	UGT2B10	UGT2B10	607	0.27	0.56	YES
17	AKR1C4	AKR1C4	AKR1C4	707	0.25	0.57	YES
18	UGT2B7	UGT2B7	UGT2B7	937	0.21	0.57	YES
19	HSD17B8	HSD17B8	HSD17B8	968	0.2	0.59	YES
20	CYP11A1	CYP11A1	CYP11A1	1017	0.2	0.6	YES
21	HSD17B3	HSD17B3	HSD17B3	1118	0.18	0.61	YES
22	UGT1A8	UGT1A8	UGT1A8	1170	0.18	0.62	YES
23	UGT2B11	UGT2B11	UGT2B11	1269	0.16	0.63	YES
24	CYP17A1	CYP17A1	CYP17A1	1370	0.15	0.64	YES
25	UGT2B4	UGT2B4	UGT2B4	1532	0.14	0.64	YES
26	HSD17B6	HSD17B6	HSD17B6	1550	0.14	0.65	YES
27	HSD17B7	HSD17B7	HSD17B7	1641	0.13	0.65	YES
28	CYP7A1	CYP7A1	CYP7A1	1871	0.12	0.65	NO
29	UGT2B15	UGT2B15	UGT2B15	2095	0.1	0.64	NO
30	SULT1E1	SULT1E1	SULT1E1	2500	0.086	0.63	NO
31	SRD5A1	SRD5A1	SRD5A1	2785	0.074	0.62	NO
32	CYP1B1	CYP1B1	CYP1B1	2793	0.074	0.62	NO
33	CYP3A5	CYP3A5	CYP3A5	3725	0.047	0.57	NO
34	COMT	COMT	COMT	4258	0.036	0.55	NO
35	HSD17B1	HSD17B1	HSD17B1	4284	0.035	0.55	NO
36	AKR1C3	AKR1C3	AKR1C3	5091	0.02	0.5	NO
37	HSD11B2	HSD11B2	HSD11B2	5171	0.018	0.5	NO
38	UGT1A7	UGT1A7	UGT1A7	7830	-0.024	0.35	NO
39	HSD17B12	HSD17B12	HSD17B12	8512	-0.034	0.32	NO
40	SRD5A3	SRD5A3	SRD5A3	9550	-0.054	0.26	NO
41	CYP21A2	CYP21A2	CYP21A2	11646	-0.11	0.15	NO
42	AKR1D1	AKR1D1	AKR1D1	12305	-0.14	0.13	NO
43	UGT2A1	UGT2A1	UGT2A1	12806	-0.16	0.11	NO
44	UGT1A10	UGT1A10	UGT1A10	13047	-0.17	0.11	NO
45	HSD17B2	HSD17B2	HSD17B2	13087	-0.17	0.12	NO
46	UGT2A3	UGT2A3	UGT2A3	13587	-0.2	0.11	NO
47	HSD3B2	HSD3B2	HSD3B2	14779	-0.27	0.062	NO
48	STS	STS	STS	14942	-0.28	0.075	NO
49	HSD3B1	HSD3B1	HSD3B1	15595	-0.32	0.063	NO
50	CYP19A1	CYP19A1	CYP19A1	15869	-0.34	0.074	NO
51	CYP3A7	CYP3A7	CYP3A7	16474	-0.39	0.071	NO

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

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

genes ES table in pathway: KEGG TRYPTOPHAN METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	UGT1A3	UGT1A3	UGT1A3	49	0.78	0.12	YES
2	UGT1A5	UGT1A5	UGT1A5	56	0.76	0.23	YES
3	UGT1A4	UGT1A4	UGT1A4	74	0.69	0.33	YES
4	UGT1A1	UGT1A1	UGT1A1	181	0.48	0.4	YES
5	UGT1A9	UGT1A9	UGT1A9	302	0.38	0.45	YES
6	DCXR	DCXR	DCXR	392	0.34	0.5	YES
7	UGT1A6	UGT1A6	UGT1A6	469	0.31	0.54	YES
8	UGT2B28	UGT2B28	UGT2B28	496	0.31	0.58	YES
9	UGT2B10	UGT2B10	UGT2B10	607	0.27	0.62	YES
10	UGT2B7	UGT2B7	UGT2B7	937	0.21	0.63	YES
11	CRYL1	CRYL1	CRYL1	1141	0.18	0.65	YES
12	UGT1A8	UGT1A8	UGT1A8	1170	0.18	0.67	YES
13	UGT2B11	UGT2B11	UGT2B11	1269	0.16	0.69	YES
14	UGT2B4	UGT2B4	UGT2B4	1532	0.14	0.7	YES
15	UGT2B15	UGT2B15	UGT2B15	2095	0.1	0.68	NO
16	XYLB	XYLB	XYLB	2900	0.07	0.65	NO
17	LOC729020	LOC729020	LOC729020	4657	0.028	0.55	NO
18	RPE	RPE	RPE	6721	-0.0069	0.44	NO
19	UGT1A7	UGT1A7	UGT1A7	7830	-0.024	0.38	NO
20	UGP2	UGP2	UGP2	8856	-0.04	0.32	NO
21	GUSB	GUSB	GUSB	9575	-0.054	0.29	NO
22	UGT2A1	UGT2A1	UGT2A1	12806	-0.16	0.13	NO
23	UGT1A10	UGT1A10	UGT1A10	13047	-0.17	0.15	NO
24	UGT2A3	UGT2A3	UGT2A3	13587	-0.2	0.14	NO
25	AKR1B1	AKR1B1	AKR1B1	14039	-0.22	0.15	NO
26	DHDH	DHDH	DHDH	16152	-0.36	0.089	NO

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

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

genes ES table in pathway: KEGG PROPANOATE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AOX1	AOX1	AOX1	177	0.48	0.085	YES
2	HIBADH	HIBADH	HIBADH	579	0.28	0.12	YES
3	ALDH6A1	ALDH6A1	ALDH6A1	604	0.27	0.17	YES
4	EHHADH	EHHADH	EHHADH	627	0.26	0.22	YES
5	ALDH3A2	ALDH3A2	ALDH3A2	878	0.22	0.25	YES
6	MCEE	MCEE	MCEE	1087	0.19	0.27	YES
7	HADH	HADH	HADH	1253	0.17	0.3	YES
8	ALDH2	ALDH2	ALDH2	1357	0.16	0.32	YES
9	ALDH1B1	ALDH1B1	ALDH1B1	1361	0.16	0.35	YES
10	ACADSB	ACADSB	ACADSB	1529	0.14	0.37	YES
11	ACAA1	ACAA1	ACAA1	1658	0.13	0.39	YES
12	ABAT	ABAT	ABAT	1674	0.13	0.41	YES
13	AUH	AUH	AUH	1874	0.12	0.42	YES
14	HMGCL	HMGCL	HMGCL	2058	0.11	0.44	YES
15	BCKDHB	BCKDHB	BCKDHB	2159	0.1	0.45	YES
16	ACADM	ACADM	ACADM	2401	0.09	0.45	YES
17	ECHS1	ECHS1	ECHS1	2429	0.088	0.47	YES
18	DBT	DBT	DBT	2571	0.083	0.48	YES
19	MCCC2	MCCC2	MCCC2	2586	0.082	0.49	YES
20	HIBCH	HIBCH	HIBCH	2622	0.081	0.51	YES
21	IVD	IVD	IVD	2657	0.079	0.52	YES
22	ALDH7A1	ALDH7A1	ALDH7A1	2851	0.072	0.52	YES
23	ALDH9A1	ALDH9A1	ALDH9A1	3054	0.065	0.52	YES
24	HSD17B10	HSD17B10	HSD17B10	3277	0.059	0.52	YES
25	HMGCS1	HMGCS1	HMGCS1	3561	0.052	0.52	YES
26	ACAA2	ACAA2	ACAA2	3577	0.051	0.53	YES
27	PCCA	PCCA	PCCA	3697	0.048	0.53	YES
28	BCKDHA	BCKDHA	BCKDHA	4220	0.037	0.51	NO
29	ACAT1	ACAT1	ACAT1	4859	0.024	0.48	NO
30	HADHB	HADHB	HADHB	5851	0.0068	0.42	NO
31	HADHA	HADHA	HADHA	5855	0.0068	0.42	NO
32	PCCB	PCCB	PCCB	6156	0.0018	0.41	NO
33	MUT	MUT	MUT	6570	-0.0044	0.38	NO
34	ACAD8	ACAD8	ACAD8	6777	-0.0077	0.37	NO
35	MCCC1	MCCC1	MCCC1	7104	-0.012	0.36	NO
36	DLD	DLD	DLD	7411	-0.018	0.34	NO
37	ACAT2	ACAT2	ACAT2	7881	-0.024	0.32	NO
38	ACADS	ACADS	ACADS	8671	-0.037	0.28	NO
39	HMGCS2	HMGCS2	HMGCS2	10405	-0.073	0.2	NO
40	OXCT1	OXCT1	OXCT1	10868	-0.085	0.19	NO
41	BCAT2	BCAT2	BCAT2	13492	-0.19	0.082	NO
42	IL4I1	IL4I1	IL4I1	16146	-0.36	0.003	NO
43	OXCT2	OXCT2	OXCT2	16868	-0.44	0.049	NO

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

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

genes ES table in pathway: KEGG BUTANOATE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACSM3	ACSM3	ACSM3	344	0.37	0.078	YES
2	ACSM5	ACSM5	ACSM5	367	0.35	0.17	YES
3	ACSM2A	ACSM2A	ACSM2A	488	0.31	0.24	YES
4	ALDH3A2	ALDH3A2	ALDH3A2	878	0.22	0.28	YES
5	HADH	HADH	HADH	1253	0.17	0.3	YES
6	ALDH2	ALDH2	ALDH2	1357	0.16	0.34	YES
7	ALDH1B1	ALDH1B1	ALDH1B1	1361	0.16	0.38	YES
8	ALDH5A1	ALDH5A1	ALDH5A1	1515	0.14	0.41	YES
9	ABAT	ABAT	ABAT	1674	0.13	0.43	YES
10	BDH1	BDH1	BDH1	1865	0.12	0.45	YES
11	L2HGDH	L2HGDH	L2HGDH	1950	0.11	0.48	YES
12	HMGCL	HMGCL	HMGCL	2058	0.11	0.5	YES
13	ACSM1	ACSM1	ACSM1	2283	0.095	0.51	YES
14	ECHS1	ECHS1	ECHS1	2429	0.088	0.53	YES
15	ALDH7A1	ALDH7A1	ALDH7A1	2851	0.072	0.52	YES
16	GAD1	GAD1	GAD1	2970	0.068	0.54	YES
17	ALDH9A1	ALDH9A1	ALDH9A1	3054	0.065	0.55	YES
18	HMGCS1	HMGCS1	HMGCS1	3561	0.052	0.53	NO
19	ACAT1	ACAT1	ACAT1	4859	0.024	0.46	NO
20	HADHA	HADHA	HADHA	5855	0.0068	0.41	NO
21	PDHB	PDHB	PDHB	6150	0.0018	0.4	NO
22	ACAT2	ACAT2	ACAT2	7881	-0.024	0.3	NO
23	ACADS	ACADS	ACADS	8671	-0.037	0.27	NO
24	PDHA1	PDHA1	PDHA1	9009	-0.043	0.26	NO
25	BDH2	BDH2	BDH2	9936	-0.062	0.22	NO
26	AKR1B10	AKR1B10	AKR1B10	10202	-0.068	0.23	NO
27	HMGCS2	HMGCS2	HMGCS2	10405	-0.073	0.24	NO
28	OXCT1	OXCT1	OXCT1	10868	-0.085	0.23	NO
29	AACS	AACS	AACS	12555	-0.15	0.18	NO
30	OXCT2	OXCT2	OXCT2	16868	-0.44	0.049	NO

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

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

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