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

Testicular Germ Cell Tumors (Primary solid tumor)

21 August 2015 | analyses__2015_08_21

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in TGCT-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1N8794W

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 TGCT-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: 198
Number of samples: 150
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 3 :[ clus1 ] 70
pheno.type: 2 - 3 :[ clus2 ] 40
pheno.type: 3 - 3 :[ clus3 ] 40

For the expression subtypes of 19071 genes in 151 samples, GSEA found enriched gene sets in each cluster using 150 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA NKT PATHWAY, BIOCARTA TCR PATHWAY, KEGG BASE EXCISION REPAIR, KEGG HOMOLOGOUS RECOMBINATION, KEGG ANTIGEN PROCESSING AND PRESENTATION, KEGG CYTOSOLIC DNA SENSING PATHWAY, KEGG HEMATOPOIETIC CELL LINEAGE, KEGG NATURAL KILLER CELL MEDIATED CYTOTOXICITY, KEGG T CELL RECEPTOR SIGNALING PATHWAY, KEGG B CELL RECEPTOR SIGNALING PATHWAY

And common core enriched genes are CD40LG, CD28, CD40, HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DQA2, IFNG, IL10, TNF

clus2

Top enriched gene sets are BIOCARTA MPR PATHWAY, KEGG CITRATE CYCLE TCA CYCLE, KEGG OXIDATIVE PHOSPHORYLATION, KEGG PYRIMIDINE METABOLISM, KEGG LYSINE DEGRADATION, KEGG SELENOAMINO ACID METABOLISM, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RIBOSOME, KEGG RNA DEGRADATION

And common core enriched genes are SDHB, SDHD, AP2B1, AP2M1, AP2S1, ATP5B, ATP5C1, ATP5D, ATP5F1, ATP5G1

clus3

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA ALK PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA MYOSIN PATHWAY, BIOCARTA CHREBP2 PATHWAY, KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM, KEGG DRUG METABOLISM OTHER ENZYMES, KEGG WNT SIGNALING PATHWAY

And common core enriched genes are PRKCA, AGT, EGFR, JUN, BMP2, BMP4, BMP5, BMP7, CHRD, SMAD1

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 NKT PATHWAY	27	genes.ES.table	0.65	1.3	0.25	1	0.99	0.67	0.17	0.55	1	0.58
BIOCARTA TCR PATHWAY	43	genes.ES.table	0.45	1.1	0.36	1	1	0.26	0.11	0.23	1	0.66
KEGG BASE EXCISION REPAIR	32	genes.ES.table	0.27	1	0.45	1	1	0.22	0.23	0.17	1	0.76
KEGG HOMOLOGOUS RECOMBINATION	27	genes.ES.table	0.44	1.2	0.31	1	0.99	0.44	0.34	0.3	1	0.53
KEGG ANTIGEN PROCESSING AND PRESENTATION	68	genes.ES.table	0.6	1.3	0.22	1	0.97	0.57	0.24	0.44	1	0.6
KEGG CYTOSOLIC DNA SENSING PATHWAY	42	genes.ES.table	0.54	1.3	0.25	1	0.98	0.64	0.33	0.43	1	0.59
KEGG HEMATOPOIETIC CELL LINEAGE	81	genes.ES.table	0.45	1	0.49	1	1	0.4	0.12	0.35	1	0.75
KEGG NATURAL KILLER CELL MEDIATED CYTOTOXICITY	118	genes.ES.table	0.38	1	0.48	1	1	0.33	0.15	0.28	1	0.72
KEGG T CELL RECEPTOR SIGNALING PATHWAY	107	genes.ES.table	0.49	1.4	0.2	1	0.95	0.4	0.18	0.33	1	0.7
KEGG B CELL RECEPTOR SIGNALING PATHWAY	74	genes.ES.table	0.37	1.1	0.42	1	1	0.36	0.24	0.28	1	0.74

genes ES table in pathway: BIOCARTA NKT 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	HIST1H3C	HIST1H3C	HIST1H3C	18	1.6	0.03	YES
2	HIST1H2AJ	HIST1H2AJ	HIST1H2AJ	65	1.3	0.052	YES
3	HIST1H2AL	HIST1H2AL	HIST1H2AL	66	1.3	0.078	YES
4	HIST1H3A	HIST1H3A	HIST1H3A	67	1.3	0.1	YES
5	HIST1H2BA	HIST1H2BA	HIST1H2BA	72	1.2	0.13	YES
6	HIST1H2AB	HIST1H2AB	HIST1H2AB	112	1.1	0.15	YES
7	HIST1H2AA	HIST1H2AA	HIST1H2AA	129	1.1	0.17	YES
8	HIST1H2BL	HIST1H2BL	HIST1H2BL	152	1	0.18	YES
9	HIST1H2BM	HIST1H2BM	HIST1H2BM	153	1	0.2	YES
10	HIST1H2AE	HIST1H2AE	HIST1H2AE	158	1	0.22	YES
11	HIST1H3H	HIST1H3H	HIST1H3H	198	0.92	0.24	YES
12	HIST1H4D	HIST1H4D	HIST1H4D	203	0.92	0.26	YES
13	HIST1H2BE	HIST1H2BE	HIST1H2BE	242	0.87	0.27	YES
14	HIST1H2BB	HIST1H2BB	HIST1H2BB	290	0.83	0.29	YES
15	HIST1H2AM	HIST1H2AM	HIST1H2AM	347	0.79	0.3	YES
16	HIST1H2BG	HIST1H2BG	HIST1H2BG	355	0.78	0.32	YES
17	IFNG	IFNG	IFNG	378	0.77	0.33	YES
18	CD40LG	CD40LG	CD40LG	424	0.73	0.34	YES
19	HIST1H3D	HIST1H3D	HIST1H3D	503	0.7	0.35	YES
20	HIST1H2BO	HIST1H2BO	HIST1H2BO	541	0.67	0.36	YES
21	HIST1H2BF	HIST1H2BF	HIST1H2BF	542	0.67	0.38	YES
22	HIST1H3E	HIST1H3E	HIST1H3E	543	0.67	0.39	YES
23	HIST1H2BC	HIST1H2BC	HIST1H2BC	563	0.67	0.4	YES
24	HIST2H2BF	HIST2H2BF	HIST2H2BF	576	0.66	0.41	YES
25	HIST1H4H	HIST1H4H	HIST1H4H	592	0.66	0.43	YES
26	HIST1H4E	HIST1H4E	HIST1H4E	613	0.64	0.44	YES
27	HIST1H3G	HIST1H3G	HIST1H3G	712	0.61	0.44	YES
28	HIST1H2BJ	HIST1H2BJ	HIST1H2BJ	777	0.59	0.45	YES
29	HIST1H2BK	HIST1H2BK	HIST1H2BK	780	0.59	0.46	YES
30	HIST1H2AC	HIST1H2AC	HIST1H2AC	794	0.58	0.48	YES
31	HLA-DOB	HLA-DOB	HLA-DOB	807	0.58	0.48	YES
32	HIST1H4C	HIST1H4C	HIST1H4C	812	0.58	0.5	YES
33	HIST1H2BD	HIST1H2BD	HIST1H2BD	817	0.58	0.51	YES
34	CD28	CD28	CD28	841	0.57	0.52	YES
35	HIST1H2AG	HIST1H2AG	HIST1H2AG	902	0.55	0.52	YES
36	HIST1H2AD	HIST1H2AD	HIST1H2AD	917	0.55	0.54	YES
37	HIST1H4B	HIST1H4B	HIST1H4B	920	0.55	0.55	YES
38	TNF	TNF	TNF	955	0.54	0.56	YES
39	HIST1H3B	HIST1H3B	HIST1H3B	1013	0.52	0.56	YES
40	HLA-DQA2	HLA-DQA2	HLA-DQA2	1192	0.48	0.56	YES
41	IL10	IL10	IL10	1214	0.48	0.57	YES
42	HIST1H2AK	HIST1H2AK	HIST1H2AK	1237	0.47	0.58	YES
43	CD80	CD80	CD80	1496	0.42	0.57	YES
44	HIST3H2BB	HIST3H2BB	HIST3H2BB	1619	0.4	0.57	YES
45	HIST1H2BI	HIST1H2BI	HIST1H2BI	1793	0.37	0.57	YES
46	HIST3H2A	HIST3H2A	HIST3H2A	1881	0.36	0.57	YES
47	HIST1H4I	HIST1H4I	HIST1H4I	1953	0.35	0.58	YES
48	C8G	C8G	C8G	2054	0.33	0.58	YES
49	HIST1H2BN	HIST1H2BN	HIST1H2BN	2136	0.32	0.58	YES
50	HLA-DMB	HLA-DMB	HLA-DMB	2144	0.32	0.59	YES
51	C1QB	C1QB	C1QB	2233	0.31	0.59	YES
52	CD40	CD40	CD40	2242	0.31	0.59	YES
53	FCGR1A	FCGR1A	FCGR1A	2277	0.3	0.6	YES
54	HLA-DQA1	HLA-DQA1	HLA-DQA1	2280	0.3	0.6	YES
55	HIST1H4J	HIST1H4J	HIST1H4J	2304	0.3	0.61	YES
56	CD86	CD86	CD86	2401	0.29	0.61	YES
57	HLA-DQB1	HLA-DQB1	HLA-DQB1	2425	0.29	0.61	YES
58	HIST1H4F	HIST1H4F	HIST1H4F	2460	0.28	0.62	YES
59	C1QA	C1QA	C1QA	2573	0.27	0.62	NO
60	C2	C2	C2	2922	0.24	0.6	NO
61	C1QC	C1QC	C1QC	2988	0.24	0.6	NO
62	HLA-DMA	HLA-DMA	HLA-DMA	2992	0.24	0.61	NO
63	HLA-DPA1	HLA-DPA1	HLA-DPA1	3117	0.23	0.61	NO
64	HLA-DOA	HLA-DOA	HLA-DOA	3118	0.23	0.61	NO
65	HLA-DRA	HLA-DRA	HLA-DRA	3258	0.22	0.61	NO
66	ACTN3	ACTN3	ACTN3	3403	0.21	0.6	NO
67	HIST2H2BE	HIST2H2BE	HIST2H2BE	3436	0.21	0.61	NO
68	HIST1H4K	HIST1H4K	HIST1H4K	3482	0.2	0.61	NO
69	HIST1H2AH	HIST1H2AH	HIST1H2AH	3919	0.18	0.59	NO
70	HIST1H4A	HIST1H4A	HIST1H4A	3981	0.17	0.59	NO
71	HLA-DRB1	HLA-DRB1	HLA-DRB1	4067	0.17	0.59	NO
72	HIST1H3I	HIST1H3I	HIST1H3I	4105	0.17	0.59	NO
73	HLA-DPB1	HLA-DPB1	HLA-DPB1	4379	0.15	0.58	NO
74	H2AFY2	H2AFY2	H2AFY2	4487	0.15	0.58	NO
75	HLA-DRB5	HLA-DRB5	HLA-DRB5	4626	0.14	0.57	NO
76	C7	C7	C7	5513	0.1	0.53	NO
77	H2BFWT	H2BFWT	H2BFWT	6190	0.08	0.49	NO
78	TRIM21	TRIM21	TRIM21	7182	0.049	0.44	NO
79	SNRPB	SNRPB	SNRPB	7253	0.047	0.44	NO
80	H2AFV	H2AFV	H2AFV	7273	0.047	0.44	NO
81	C4A	C4A	C4A	7338	0.045	0.44	NO
82	SNRPD3	SNRPD3	SNRPD3	7970	0.027	0.4	NO
83	H3F3A	H3F3A	H3F3A	8357	0.015	0.38	NO
84	ACTN1	ACTN1	ACTN1	8818	0.0014	0.36	NO
85	FCGR2C	FCGR2C	FCGR2C	8956	-0.0021	0.35	NO
86	FCGR2B	FCGR2B	FCGR2B	9003	-0.0035	0.35	NO
87	HIST1H3J	HIST1H3J	HIST1H3J	9821	-0.027	0.31	NO
88	SNRPD1	SNRPD1	SNRPD1	10005	-0.032	0.3	NO
89	TROVE2	TROVE2	TROVE2	10102	-0.035	0.29	NO
90	C9	C9	C9	10521	-0.049	0.27	NO
91	FCGR2A	FCGR2A	FCGR2A	10608	-0.052	0.27	NO
92	HIST1H4L	HIST1H4L	HIST1H4L	11012	-0.065	0.25	NO
93	HIST1H2BH	HIST1H2BH	HIST1H2BH	11123	-0.069	0.24	NO
94	FCGR3A	FCGR3A	FCGR3A	11581	-0.085	0.22	NO
95	H3F3B	H3F3B	H3F3B	11954	-0.1	0.2	NO
96	H2AFY	H2AFY	H2AFY	11979	-0.1	0.2	NO
97	SSB	SSB	SSB	12051	-0.1	0.2	NO
98	HIST2H3D	HIST2H3D	HIST2H3D	12362	-0.12	0.19	NO
99	H2AFZ	H2AFZ	H2AFZ	12406	-0.12	0.19	NO
100	H2BFM	H2BFM	H2BFM	12432	-0.12	0.19	NO
101	C3	C3	C3	12762	-0.13	0.18	NO
102	ACTN4	ACTN4	ACTN4	12963	-0.14	0.17	NO
103	HIST1H3F	HIST1H3F	HIST1H3F	12979	-0.14	0.17	NO
104	HIST4H4	HIST4H4	HIST4H4	13132	-0.15	0.16	NO
105	C8B	C8B	C8B	13302	-0.16	0.16	NO
106	HIST2H2AB	HIST2H2AB	HIST2H2AB	13578	-0.18	0.15	NO
107	GRIN2A	GRIN2A	GRIN2A	13775	-0.19	0.14	NO
108	ACTN2	ACTN2	ACTN2	13779	-0.19	0.14	NO
109	C5	C5	C5	13897	-0.2	0.14	NO
110	H3F3C	H3F3C	H3F3C	13948	-0.2	0.14	NO
111	C6	C6	C6	14031	-0.21	0.14	NO
112	H2AFX	H2AFX	H2AFX	14831	-0.27	0.11	NO
113	C1S	C1S	C1S	14876	-0.27	0.11	NO
114	FCGR3B	FCGR3B	FCGR3B	15586	-0.34	0.078	NO
115	H2AFB1	H2AFB1	H2AFB1	15644	-0.35	0.082	NO
116	HIST2H4A	HIST2H4A	HIST2H4A	15865	-0.38	0.078	NO
117	C1R	C1R	C1R	15939	-0.38	0.082	NO
118	H2AFJ	H2AFJ	H2AFJ	16322	-0.43	0.07	NO
119	HIST2H2AC	HIST2H2AC	HIST2H2AC	16370	-0.44	0.076	NO
120	ELANE	ELANE	ELANE	17252	-0.58	0.041	NO
121	GRIN2B	GRIN2B	GRIN2B	17365	-0.6	0.047	NO
122	CTSG	CTSG	CTSG	17553	-0.64	0.05	NO
123	C8A	C8A	C8A	17556	-0.64	0.062	NO
124	HIST2H3C	HIST2H3C	HIST2H3C	18292	-0.84	0.04	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 NKT PATHWAY.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NKT 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 TCR 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	IL12B	IL12B	IL12B	13	1.6	0.14	YES
2	IFNG	IFNG	IFNG	378	0.77	0.18	YES
3	CD40LG	CD40LG	CD40LG	424	0.73	0.24	YES
4	FASLG	FASLG	FASLG	550	0.67	0.3	YES
5	HLA-DOB	HLA-DOB	HLA-DOB	807	0.58	0.33	YES
6	CD28	CD28	CD28	841	0.57	0.38	YES
7	TNF	TNF	TNF	955	0.54	0.42	YES
8	HLA-DQA2	HLA-DQA2	HLA-DQA2	1192	0.48	0.45	YES
9	IL10	IL10	IL10	1214	0.48	0.49	YES
10	CD80	CD80	CD80	1496	0.42	0.51	YES
11	IL2	IL2	IL2	1573	0.4	0.54	YES
12	PRF1	PRF1	PRF1	1727	0.38	0.56	YES
13	GZMB	GZMB	GZMB	1996	0.34	0.58	YES
14	HLA-DMB	HLA-DMB	HLA-DMB	2144	0.32	0.6	YES
15	CD40	CD40	CD40	2242	0.31	0.62	YES
16	HLA-DQA1	HLA-DQA1	HLA-DQA1	2280	0.3	0.64	YES
17	CD86	CD86	CD86	2401	0.29	0.66	YES
18	HLA-DMA	HLA-DMA	HLA-DMA	2992	0.24	0.65	YES
19	HLA-F	HLA-F	HLA-F	3000	0.24	0.67	YES
20	HLA-DPA1	HLA-DPA1	HLA-DPA1	3117	0.23	0.68	YES
21	HLA-DOA	HLA-DOA	HLA-DOA	3118	0.23	0.7	YES
22	IL4	IL4	IL4	3138	0.23	0.72	YES
23	HLA-DRA	HLA-DRA	HLA-DRA	3258	0.22	0.73	YES
24	IL5	IL5	IL5	3291	0.22	0.75	YES
25	HLA-DRB1	HLA-DRB1	HLA-DRB1	4067	0.17	0.72	NO
26	HLA-DPB1	HLA-DPB1	HLA-DPB1	4379	0.15	0.72	NO
27	HLA-DRB5	HLA-DRB5	HLA-DRB5	4626	0.14	0.72	NO
28	HLA-B	HLA-B	HLA-B	6184	0.08	0.64	NO
29	HLA-E	HLA-E	HLA-E	6838	0.06	0.62	NO
30	HLA-A	HLA-A	HLA-A	7367	0.044	0.59	NO
31	IL12A	IL12A	IL12A	7770	0.032	0.57	NO
32	HLA-C	HLA-C	HLA-C	8317	0.016	0.55	NO
33	HLA-G	HLA-G	HLA-G	11663	-0.088	0.38	NO
34	FAS	FAS	FAS	12846	-0.14	0.33	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 TCR PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TCR 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 BASE EXCISION REPAIR

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	PIK3CG	PIK3CG	PIK3CG	318	0.82	0.013	YES
2	IFNG	IFNG	IFNG	378	0.77	0.037	YES
3	CD40LG	CD40LG	CD40LG	424	0.73	0.062	YES
4	PDCD1	PDCD1	PDCD1	580	0.66	0.077	YES
5	CD3G	CD3G	CD3G	605	0.65	0.099	YES
6	ITK	ITK	ITK	722	0.61	0.12	YES
7	CTLA4	CTLA4	CTLA4	751	0.6	0.14	YES
8	MAP3K8	MAP3K8	MAP3K8	796	0.58	0.15	YES
9	TEC	TEC	TEC	834	0.57	0.17	YES
10	CD28	CD28	CD28	841	0.57	0.19	YES
11	CD3E	CD3E	CD3E	845	0.57	0.21	YES
12	CD3D	CD3D	CD3D	877	0.56	0.23	YES
13	TNF	TNF	TNF	955	0.54	0.25	YES
14	CD247	CD247	CD247	975	0.54	0.26	YES
15	CD8A	CD8A	CD8A	988	0.53	0.28	YES
16	ICOS	ICOS	ICOS	1151	0.49	0.29	YES
17	IL10	IL10	IL10	1214	0.48	0.31	YES
18	PTPRC	PTPRC	PTPRC	1228	0.48	0.32	YES
19	PIK3CD	PIK3CD	PIK3CD	1363	0.44	0.33	YES
20	GRAP2	GRAP2	GRAP2	1374	0.44	0.35	YES
21	VAV1	VAV1	VAV1	1379	0.44	0.36	YES
22	CSF2	CSF2	CSF2	1438	0.43	0.38	YES
23	CD8B	CD8B	CD8B	1455	0.43	0.39	YES
24	LAT	LAT	LAT	1554	0.41	0.4	YES
25	IL2	IL2	IL2	1573	0.4	0.41	YES
26	ZAP70	ZAP70	ZAP70	1601	0.4	0.43	YES
27	LCP2	LCP2	LCP2	1623	0.4	0.44	YES
28	PIK3R3	PIK3R3	PIK3R3	1713	0.38	0.45	YES
29	PAK7	PAK7	PAK7	1852	0.36	0.46	YES
30	RASGRP1	RASGRP1	RASGRP1	2025	0.34	0.46	YES
31	PPP3CC	PPP3CC	PPP3CC	2140	0.32	0.46	YES
32	CBLB	CBLB	CBLB	2416	0.29	0.46	YES
33	CBL	CBL	CBL	2618	0.27	0.46	YES
34	PRKCQ	PRKCQ	PRKCQ	2653	0.27	0.47	YES
35	NFKBIB	NFKBIB	NFKBIB	3070	0.23	0.45	YES
36	NCK2	NCK2	NCK2	3095	0.23	0.46	YES
37	PPP3R2	PPP3R2	PPP3R2	3107	0.23	0.47	YES
38	IL4	IL4	IL4	3138	0.23	0.47	YES
39	CD4	CD4	CD4	3228	0.22	0.48	YES
40	MAPK11	MAPK11	MAPK11	3262	0.22	0.48	YES
41	IL5	IL5	IL5	3291	0.22	0.49	YES
42	NFATC2	NFATC2	NFATC2	3500	0.2	0.49	YES
43	MAPK12	MAPK12	MAPK12	3506	0.2	0.49	YES
44	LCK	LCK	LCK	3674	0.19	0.49	NO
45	CHP	CHP	CHP	3948	0.17	0.48	NO
46	MAPK1	MAPK1	MAPK1	4341	0.16	0.47	NO
47	PIK3R2	PIK3R2	PIK3R2	4375	0.15	0.47	NO
48	VAV2	VAV2	VAV2	4435	0.15	0.47	NO
49	MAP3K14	MAP3K14	MAP3K14	4812	0.13	0.46	NO
50	CHUK	CHUK	CHUK	4966	0.13	0.46	NO
51	PIK3R5	PIK3R5	PIK3R5	5083	0.12	0.45	NO
52	MALT1	MALT1	MALT1	5219	0.12	0.45	NO
53	PTPN6	PTPN6	PTPN6	5295	0.11	0.45	NO
54	NCK1	NCK1	NCK1	5334	0.11	0.45	NO
55	MAP2K7	MAP2K7	MAP2K7	5412	0.11	0.45	NO
56	SOS1	SOS1	SOS1	5783	0.094	0.44	NO
57	NFATC3	NFATC3	NFATC3	6063	0.084	0.42	NO
58	PAK3	PAK3	PAK3	6071	0.084	0.43	NO
59	PDK1	PDK1	PDK1	6342	0.075	0.42	NO
60	NFKBIE	NFKBIE	NFKBIE	6436	0.072	0.41	NO
61	IKBKB	IKBKB	IKBKB	6911	0.058	0.39	NO
62	GSK3B	GSK3B	GSK3B	7041	0.053	0.39	NO
63	AKT3	AKT3	AKT3	7116	0.051	0.38	NO
64	MAP3K7	MAP3K7	MAP3K7	7126	0.051	0.38	NO
65	RAF1	RAF1	RAF1	7500	0.04	0.37	NO
66	FYN	FYN	FYN	7774	0.032	0.35	NO
67	PLCG1	PLCG1	PLCG1	7952	0.027	0.34	NO
68	PPP3R1	PPP3R1	PPP3R1	8234	0.019	0.33	NO
69	MAP2K2	MAP2K2	MAP2K2	8279	0.017	0.33	NO
70	MAP2K1	MAP2K1	MAP2K1	8300	0.017	0.33	NO
71	PIK3CA	PIK3CA	PIK3CA	8721	0.0043	0.31	NO
72	PPP3CB	PPP3CB	PPP3CB	8841	0.00059	0.3	NO
73	RELA	RELA	RELA	8884	-0.00072	0.3	NO
74	DLG1	DLG1	DLG1	8955	-0.0021	0.3	NO
75	AKT2	AKT2	AKT2	9207	-0.0094	0.28	NO
76	RHOA	RHOA	RHOA	9748	-0.025	0.25	NO
77	KRAS	KRAS	KRAS	10065	-0.034	0.24	NO
78	NFKBIA	NFKBIA	NFKBIA	10156	-0.037	0.24	NO
79	IKBKG	IKBKG	IKBKG	10595	-0.051	0.21	NO
80	CDK4	CDK4	CDK4	10598	-0.051	0.22	NO
81	PAK4	PAK4	PAK4	10671	-0.054	0.21	NO
82	CDC42	CDC42	CDC42	11087	-0.068	0.19	NO
83	NFAT5	NFAT5	NFAT5	11190	-0.071	0.19	NO
84	BCL10	BCL10	BCL10	11372	-0.077	0.18	NO
85	NFATC1	NFATC1	NFATC1	11441	-0.08	0.18	NO
86	GRB2	GRB2	GRB2	11451	-0.08	0.19	NO
87	AKT1	AKT1	AKT1	11562	-0.084	0.18	NO
88	PAK2	PAK2	PAK2	11907	-0.098	0.17	NO
89	MAPK14	MAPK14	MAPK14	11981	-0.1	0.17	NO
90	PIK3CB	PIK3CB	PIK3CB	12048	-0.1	0.17	NO
91	PIK3R1	PIK3R1	PIK3R1	12478	-0.12	0.15	NO
92	VAV3	VAV3	VAV3	12709	-0.13	0.14	NO
93	MAPK3	MAPK3	MAPK3	12737	-0.13	0.15	NO
94	NRAS	NRAS	NRAS	12752	-0.13	0.15	NO
95	NFKB1	NFKB1	NFKB1	12815	-0.14	0.15	NO
96	MAPK9	MAPK9	MAPK9	13633	-0.18	0.12	NO
97	NFATC4	NFATC4	NFATC4	13691	-0.18	0.12	NO
98	PAK1	PAK1	PAK1	14290	-0.22	0.096	NO
99	CBLC	CBLC	CBLC	15033	-0.28	0.067	NO
100	SOS2	SOS2	SOS2	15400	-0.32	0.06	NO
101	PAK6	PAK6	PAK6	15535	-0.33	0.064	NO
102	CARD11	CARD11	CARD11	15683	-0.35	0.069	NO
103	PPP3CA	PPP3CA	PPP3CA	15775	-0.36	0.078	NO
104	MAPK13	MAPK13	MAPK13	16287	-0.43	0.066	NO
105	FOS	FOS	FOS	16871	-0.52	0.054	NO
106	JUN	JUN	JUN	17379	-0.6	0.049	NO
107	CHP2	CHP2	CHP2	18761	-1.1	0.015	NO

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

Figure S6. 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 HOMOLOGOUS RECOMBINATION

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	CD40LG	CD40LG	CD40LG	424	0.73	0.044	YES
2	CD19	CD19	CD19	452	0.72	0.11	YES
3	AICDA	AICDA	AICDA	587	0.66	0.16	YES
4	CD3E	CD3E	CD3E	845	0.57	0.2	YES
5	CD3D	CD3D	CD3D	877	0.56	0.25	YES
6	CD79A	CD79A	CD79A	931	0.54	0.3	YES
7	IL7R	IL7R	IL7R	1006	0.53	0.34	YES
8	TNFRSF13B	TNFRSF13B	TNFRSF13B	1126	0.5	0.38	YES
9	ICOS	ICOS	ICOS	1151	0.49	0.42	YES
10	PTPRC	PTPRC	PTPRC	1228	0.48	0.46	YES
11	IL2RG	IL2RG	IL2RG	1284	0.46	0.5	YES
12	CD8B	CD8B	CD8B	1455	0.43	0.53	YES
13	ZAP70	ZAP70	ZAP70	1601	0.4	0.56	YES
14	CIITA	CIITA	CIITA	1722	0.38	0.59	YES
15	BTK	BTK	BTK	2035	0.33	0.6	YES
16	CD40	CD40	CD40	2242	0.31	0.62	YES
17	JAK3	JAK3	JAK3	2503	0.28	0.63	YES
18	TNFRSF13C	TNFRSF13C	TNFRSF13C	2606	0.27	0.65	YES
19	BLNK	BLNK	BLNK	2813	0.25	0.66	YES
20	CD4	CD4	CD4	3228	0.22	0.66	YES
21	UNG	UNG	UNG	3235	0.22	0.68	YES
22	RFXAP	RFXAP	RFXAP	3512	0.2	0.68	YES
23	LCK	LCK	LCK	3674	0.19	0.69	YES
24	TAP1	TAP1	TAP1	3914	0.18	0.7	YES
25	RFX5	RFX5	RFX5	4256	0.16	0.69	YES
26	TAP2	TAP2	TAP2	4418	0.15	0.7	YES
27	IGLL1	IGLL1	IGLL1	5662	0.099	0.64	NO
28	AIRE	AIRE	AIRE	9227	-0.01	0.45	NO
29	RFXANK	RFXANK	RFXANK	9837	-0.027	0.42	NO
30	IKBKG	IKBKG	IKBKG	10595	-0.051	0.39	NO
31	ADA	ADA	ADA	10931	-0.062	0.38	NO
32	DCLRE1C	DCLRE1C	DCLRE1C	11000	-0.065	0.38	NO
33	RAG1	RAG1	RAG1	16672	-0.48	0.12	NO

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

Figure S8. 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

genes ES table in pathway: KEGG ANTIGEN PROCESSING AND PRESENTATION

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	HLA-DOB	HLA-DOB	HLA-DOB	807	0.58	-0.0005	YES
2	LTA	LTA	LTA	852	0.57	0.038	YES
3	CD8A	CD8A	CD8A	988	0.53	0.069	YES
4	HLA-DQA2	HLA-DQA2	HLA-DQA2	1192	0.48	0.094	YES
5	KIR2DL3	KIR2DL3	KIR2DL3	1400	0.44	0.11	YES
6	CD8B	CD8B	CD8B	1455	0.43	0.14	YES
7	KIR3DL2	KIR3DL2	KIR3DL2	1536	0.41	0.17	YES
8	KLRC3	KLRC3	KLRC3	1659	0.39	0.19	YES
9	KIR2DL1	KIR2DL1	KIR2DL1	1668	0.39	0.22	YES
10	CIITA	CIITA	CIITA	1722	0.38	0.24	YES
11	CTSS	CTSS	CTSS	1872	0.36	0.26	YES
12	KLRD1	KLRD1	KLRD1	1930	0.35	0.28	YES
13	KIR3DL3	KIR3DL3	KIR3DL3	2076	0.33	0.3	YES
14	KIR2DL4	KIR2DL4	KIR2DL4	2107	0.32	0.32	YES
15	HLA-DMB	HLA-DMB	HLA-DMB	2144	0.32	0.34	YES
16	KLRC2	KLRC2	KLRC2	2167	0.32	0.36	YES
17	KLRC1	KLRC1	KLRC1	2202	0.31	0.38	YES
18	HSPA1L	HSPA1L	HSPA1L	2270	0.3	0.4	YES
19	HLA-DQA1	HLA-DQA1	HLA-DQA1	2280	0.3	0.42	YES
20	HLA-DQB1	HLA-DQB1	HLA-DQB1	2425	0.29	0.44	YES
21	KIR2DS4	KIR2DS4	KIR2DS4	2587	0.27	0.45	YES
22	KIR3DL1	KIR3DL1	KIR3DL1	2797	0.25	0.46	YES
23	HLA-DMA	HLA-DMA	HLA-DMA	2992	0.24	0.46	YES
24	HLA-F	HLA-F	HLA-F	3000	0.24	0.48	YES
25	IFNA21	IFNA21	IFNA21	3054	0.23	0.49	YES
26	HLA-DPA1	HLA-DPA1	HLA-DPA1	3117	0.23	0.51	YES
27	HLA-DOA	HLA-DOA	HLA-DOA	3118	0.23	0.52	YES
28	CD4	CD4	CD4	3228	0.22	0.53	YES
29	HLA-DRA	HLA-DRA	HLA-DRA	3258	0.22	0.55	YES
30	CD74	CD74	CD74	3265	0.22	0.56	YES
31	RFXAP	RFXAP	RFXAP	3512	0.2	0.56	YES
32	TAP1	TAP1	TAP1	3914	0.18	0.56	YES
33	HLA-DRB1	HLA-DRB1	HLA-DRB1	4067	0.17	0.56	YES
34	KLRC4	KLRC4	KLRC4	4120	0.17	0.57	YES
35	RFX5	RFX5	RFX5	4256	0.16	0.57	YES
36	HLA-DPB1	HLA-DPB1	HLA-DPB1	4379	0.15	0.58	YES
37	TAP2	TAP2	TAP2	4418	0.15	0.59	YES
38	IFI30	IFI30	IFI30	4499	0.15	0.59	YES
39	HLA-DRB5	HLA-DRB5	HLA-DRB5	4626	0.14	0.6	YES
40	B2M	B2M	B2M	5799	0.094	0.54	NO
41	CREB1	CREB1	CREB1	6181	0.08	0.53	NO
42	HLA-B	HLA-B	HLA-B	6184	0.08	0.53	NO
43	HSP90AA1	HSP90AA1	HSP90AA1	6191	0.08	0.54	NO
44	CTSL1	CTSL1	CTSL1	6285	0.077	0.54	NO
45	NFYA	NFYA	NFYA	6628	0.066	0.53	NO
46	PSME2	PSME2	PSME2	6677	0.065	0.53	NO
47	HLA-E	HLA-E	HLA-E	6838	0.06	0.52	NO
48	HSPA4	HSPA4	HSPA4	7128	0.051	0.51	NO
49	CTSB	CTSB	CTSB	7325	0.046	0.5	NO
50	HLA-A	HLA-A	HLA-A	7367	0.044	0.51	NO
51	TAPBP	TAPBP	TAPBP	7924	0.028	0.48	NO
52	HLA-C	HLA-C	HLA-C	8317	0.016	0.46	NO
53	PDIA3	PDIA3	PDIA3	8400	0.014	0.46	NO
54	PSME3	PSME3	PSME3	9051	-0.0048	0.42	NO
55	NFYB	NFYB	NFYB	9347	-0.013	0.41	NO
56	RFXANK	RFXANK	RFXANK	9837	-0.027	0.38	NO
57	PSME1	PSME1	PSME1	9943	-0.031	0.38	NO
58	LGMN	LGMN	LGMN	10542	-0.05	0.35	NO
59	HSPA1B	HSPA1B	HSPA1B	10933	-0.063	0.34	NO
60	HSPA8	HSPA8	HSPA8	11045	-0.066	0.34	NO
61	HSPA1A	HSPA1A	HSPA1A	11047	-0.066	0.34	NO
62	NFYC	NFYC	NFYC	11182	-0.071	0.34	NO
63	HSPA5	HSPA5	HSPA5	11632	-0.087	0.32	NO
64	HLA-G	HLA-G	HLA-G	11663	-0.088	0.33	NO
65	CANX	CANX	CANX	11758	-0.092	0.33	NO
66	CALR	CALR	CALR	12685	-0.13	0.29	NO
67	HSPA2	HSPA2	HSPA2	15104	-0.29	0.18	NO
68	HSPA6	HSPA6	HSPA6	15768	-0.36	0.17	NO

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

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

genes ES table in pathway: KEGG CYTOSOLIC DNA SENSING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CD40LG	CD40LG	CD40LG	424	0.73	0.046	YES
2	FASLG	FASLG	FASLG	550	0.67	0.1	YES
3	CTLA4	CTLA4	CTLA4	751	0.6	0.15	YES
4	HLA-DOB	HLA-DOB	HLA-DOB	807	0.58	0.2	YES
5	CD28	CD28	CD28	841	0.57	0.25	YES
6	HLA-DQA2	HLA-DQA2	HLA-DQA2	1192	0.48	0.28	YES
7	IL10	IL10	IL10	1214	0.48	0.32	YES
8	CD80	CD80	CD80	1496	0.42	0.34	YES
9	TSHR	TSHR	TSHR	1551	0.41	0.38	YES
10	IL2	IL2	IL2	1573	0.4	0.42	YES
11	PRF1	PRF1	PRF1	1727	0.38	0.44	YES
12	GZMB	GZMB	GZMB	1996	0.34	0.46	YES
13	HLA-DMB	HLA-DMB	HLA-DMB	2144	0.32	0.48	YES
14	CD40	CD40	CD40	2242	0.31	0.51	YES
15	HLA-DQA1	HLA-DQA1	HLA-DQA1	2280	0.3	0.53	YES
16	CD86	CD86	CD86	2401	0.29	0.55	YES
17	HLA-DQB1	HLA-DQB1	HLA-DQB1	2425	0.29	0.58	YES
18	HLA-DMA	HLA-DMA	HLA-DMA	2992	0.24	0.57	YES
19	HLA-F	HLA-F	HLA-F	3000	0.24	0.59	YES
20	HLA-DPA1	HLA-DPA1	HLA-DPA1	3117	0.23	0.61	YES
21	HLA-DOA	HLA-DOA	HLA-DOA	3118	0.23	0.63	YES
22	IL4	IL4	IL4	3138	0.23	0.65	YES
23	HLA-DRA	HLA-DRA	HLA-DRA	3258	0.22	0.66	YES
24	IL5	IL5	IL5	3291	0.22	0.68	YES
25	HLA-DRB1	HLA-DRB1	HLA-DRB1	4067	0.17	0.66	NO
26	HLA-DPB1	HLA-DPB1	HLA-DPB1	4379	0.15	0.65	NO
27	HLA-DRB5	HLA-DRB5	HLA-DRB5	4626	0.14	0.66	NO
28	TPO	TPO	TPO	5895	0.09	0.6	NO
29	HLA-B	HLA-B	HLA-B	6184	0.08	0.59	NO
30	HLA-E	HLA-E	HLA-E	6838	0.06	0.56	NO
31	HLA-A	HLA-A	HLA-A	7367	0.044	0.54	NO
32	HLA-C	HLA-C	HLA-C	8317	0.016	0.49	NO
33	TG	TG	TG	11102	-0.068	0.35	NO
34	HLA-G	HLA-G	HLA-G	11663	-0.088	0.33	NO
35	FAS	FAS	FAS	12846	-0.14	0.28	NO
36	CGA	CGA	CGA	16942	-0.53	0.11	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 CYTOSOLIC DNA SENSING PATHWAY.

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

genes ES table in pathway: KEGG HEMATOPOIETIC CELL LINEAGE

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	AIM2	AIM2	AIM2	339	0.8	0.086	YES
2	IL18	IL18	IL18	703	0.61	0.15	YES
3	ZBP1	ZBP1	ZBP1	798	0.58	0.22	YES
4	CCL5	CCL5	CCL5	1530	0.41	0.23	YES
5	CCL4	CCL4	CCL4	1741	0.38	0.27	YES
6	CCL4L2	CCL4L2	CCL4L2	1791	0.37	0.32	YES
7	IL6	IL6	IL6	1981	0.34	0.35	YES
8	RIPK3	RIPK3	RIPK3	2075	0.33	0.39	YES
9	POLR1C	POLR1C	POLR1C	2920	0.24	0.38	YES
10	CXCL10	CXCL10	CXCL10	2960	0.24	0.41	YES
11	PYCARD	PYCARD	PYCARD	3028	0.23	0.44	YES
12	NFKBIB	NFKBIB	NFKBIB	3070	0.23	0.46	YES
13	TREX1	TREX1	TREX1	3805	0.18	0.45	YES
14	POLR3C	POLR3C	POLR3C	3806	0.18	0.47	YES
15	IL1B	IL1B	IL1B	3901	0.18	0.49	YES
16	CASP1	CASP1	CASP1	4028	0.17	0.5	YES
17	IRF7	IRF7	IRF7	4623	0.14	0.49	YES
18	POLR3A	POLR3A	POLR3A	4695	0.14	0.51	YES
19	CHUK	CHUK	CHUK	4966	0.13	0.51	YES
20	IKBKE	IKBKE	IKBKE	5022	0.12	0.52	YES
21	ADAR	ADAR	ADAR	5674	0.099	0.5	YES
22	IL33	IL33	IL33	5710	0.097	0.51	YES
23	MAVS	MAVS	MAVS	5781	0.095	0.52	YES
24	TBK1	TBK1	TBK1	5928	0.089	0.52	YES
25	POLR3F	POLR3F	POLR3F	6230	0.079	0.52	YES
26	POLR3D	POLR3D	POLR3D	6250	0.078	0.53	YES
27	POLR3G	POLR3G	POLR3G	6258	0.078	0.54	YES
28	IKBKB	IKBKB	IKBKB	6911	0.058	0.51	NO
29	POLR3B	POLR3B	POLR3B	7107	0.051	0.51	NO
30	RELA	RELA	RELA	8884	-0.00072	0.41	NO
31	POLR1D	POLR1D	POLR1D	9017	-0.0038	0.41	NO
32	IFNB1	IFNB1	IFNB1	9555	-0.02	0.38	NO
33	NFKBIA	NFKBIA	NFKBIA	10156	-0.037	0.36	NO
34	DDX58	DDX58	DDX58	10356	-0.044	0.35	NO
35	IRF3	IRF3	IRF3	10485	-0.048	0.35	NO
36	IKBKG	IKBKG	IKBKG	10595	-0.051	0.35	NO
37	POLR3GL	POLR3GL	POLR3GL	10630	-0.052	0.36	NO
38	RIPK1	RIPK1	RIPK1	11456	-0.08	0.32	NO
39	POLR3H	POLR3H	POLR3H	12105	-0.11	0.3	NO
40	POLR3K	POLR3K	POLR3K	12166	-0.11	0.31	NO
41	NFKB1	NFKB1	NFKB1	12815	-0.14	0.3	NO
42	TMEM173	TMEM173	TMEM173	14441	-0.23	0.24	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 HEMATOPOIETIC CELL LINEAGE.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG HEMATOPOIETIC CELL LINEAGE, 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 NATURAL KILLER CELL MEDIATED CYTOTOXICITY

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	IL12B	IL12B	IL12B	13	1.6	0.16	YES
2	IFNG	IFNG	IFNG	378	0.77	0.21	YES
3	CD40LG	CD40LG	CD40LG	424	0.73	0.28	YES
4	CXCR3	CXCR3	CXCR3	825	0.57	0.31	YES
5	CD28	CD28	CD28	841	0.57	0.37	YES
6	IL12RB1	IL12RB1	IL12RB1	843	0.57	0.42	YES
7	CCR5	CCR5	CCR5	1342	0.45	0.44	YES
8	IL12RB2	IL12RB2	IL12RB2	1568	0.41	0.47	YES
9	IL2	IL2	IL2	1573	0.4	0.51	YES
10	CCL4	CCL4	CCL4	1741	0.38	0.53	YES
11	CCL3	CCL3	CCL3	1770	0.37	0.57	YES
12	CCR7	CCR7	CCR7	2562	0.27	0.55	YES
13	IL4R	IL4R	IL4R	2885	0.24	0.56	YES
14	CCR1	CCR1	CCR1	2912	0.24	0.58	YES
15	CCR4	CCR4	CCR4	3007	0.24	0.6	YES
16	IL4	IL4	IL4	3138	0.23	0.62	YES
17	CD4	CD4	CD4	3228	0.22	0.63	YES
18	IL5	IL5	IL5	3291	0.22	0.65	YES
19	IL18R1	IL18R1	IL18R1	4284	0.16	0.61	NO
20	CXCR4	CXCR4	CXCR4	4919	0.13	0.59	NO
21	IFNGR1	IFNGR1	IFNGR1	6432	0.072	0.52	NO
22	IL12A	IL12A	IL12A	7770	0.032	0.45	NO
23	TGFB1	TGFB1	TGFB1	9280	-0.012	0.37	NO
24	CCR3	CCR3	CCR3	10019	-0.033	0.34	NO
25	IFNGR2	IFNGR2	IFNGR2	11666	-0.088	0.26	NO
26	TGFB3	TGFB3	TGFB3	15855	-0.37	0.076	NO
27	TGFB2	TGFB2	TGFB2	18557	-0.95	0.026	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 NATURAL KILLER CELL MEDIATED CYTOTOXICITY.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG NATURAL KILLER CELL MEDIATED CYTOTOXICITY, 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 T CELL RECEPTOR SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IFNG	IFNG	IFNG	378	0.77	0.048	YES
2	FASLG	FASLG	FASLG	550	0.67	0.098	YES
3	HLA-DOB	HLA-DOB	HLA-DOB	807	0.58	0.14	YES
4	CD28	CD28	CD28	841	0.57	0.18	YES
5	TNF	TNF	TNF	955	0.54	0.23	YES
6	HLA-DQA2	HLA-DQA2	HLA-DQA2	1192	0.48	0.26	YES
7	KIR2DL3	KIR2DL3	KIR2DL3	1400	0.44	0.28	YES
8	CD80	CD80	CD80	1496	0.42	0.32	YES
9	KIR3DL2	KIR3DL2	KIR3DL2	1536	0.41	0.35	YES
10	IL2	IL2	IL2	1573	0.4	0.38	YES
11	KIR2DL1	KIR2DL1	KIR2DL1	1668	0.39	0.41	YES
12	PRF1	PRF1	PRF1	1727	0.38	0.44	YES
13	KLRD1	KLRD1	KLRD1	1930	0.35	0.46	YES
14	IL6	IL6	IL6	1981	0.34	0.49	YES
15	GZMB	GZMB	GZMB	1996	0.34	0.52	YES
16	HLA-DMB	HLA-DMB	HLA-DMB	2144	0.32	0.54	YES
17	KLRC1	KLRC1	KLRC1	2202	0.31	0.57	YES
18	HLA-DQA1	HLA-DQA1	HLA-DQA1	2280	0.3	0.59	YES
19	CD86	CD86	CD86	2401	0.29	0.61	YES
20	KIR3DL1	KIR3DL1	KIR3DL1	2797	0.25	0.61	YES
21	HLA-DMA	HLA-DMA	HLA-DMA	2992	0.24	0.62	YES
22	HLA-F	HLA-F	HLA-F	3000	0.24	0.64	YES
23	HLA-DPA1	HLA-DPA1	HLA-DPA1	3117	0.23	0.66	YES
24	HLA-DOA	HLA-DOA	HLA-DOA	3118	0.23	0.68	YES
25	HLA-DRA	HLA-DRA	HLA-DRA	3258	0.22	0.69	YES
26	IL1B	IL1B	IL1B	3901	0.18	0.67	NO
27	HLA-DRB1	HLA-DRB1	HLA-DRB1	4067	0.17	0.68	NO
28	HLA-DPB1	HLA-DPB1	HLA-DPB1	4379	0.15	0.67	NO
29	HLA-DRB5	HLA-DRB5	HLA-DRB5	4626	0.14	0.67	NO
30	HLA-B	HLA-B	HLA-B	6184	0.08	0.6	NO
31	HLA-E	HLA-E	HLA-E	6838	0.06	0.57	NO
32	HLA-A	HLA-A	HLA-A	7367	0.044	0.55	NO
33	HLA-C	HLA-C	HLA-C	8317	0.016	0.5	NO
34	HLA-G	HLA-G	HLA-G	11663	-0.088	0.33	NO
35	FAS	FAS	FAS	12846	-0.14	0.28	NO
36	IL1A	IL1A	IL1A	17052	-0.55	0.1	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 T CELL RECEPTOR SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG B CELL RECEPTOR SIGNALING PATHWAY

Table S10. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	OR7E24	OR7E24	OR7E24	17	1.6	0.051	YES
2	OR7D4	OR7D4	OR7D4	61	1.3	0.092	YES
3	OR2L2	OR2L2	OR2L2	90	1.2	0.13	YES
4	OR2B6	OR2B6	OR2B6	176	0.96	0.16	YES
5	OR51I1	OR51I1	OR51I1	190	0.94	0.19	YES
6	OR2C3	OR2C3	OR2C3	319	0.82	0.21	YES
7	OR52D1	OR52D1	OR52D1	387	0.77	0.23	YES
8	OR52E6	OR52E6	OR52E6	449	0.72	0.25	YES
9	OR1C1	OR1C1	OR1C1	457	0.72	0.27	YES
10	OR6F1	OR6F1	OR6F1	510	0.69	0.29	YES
11	OR10AD1	OR10AD1	OR10AD1	781	0.59	0.3	YES
12	OR7C1	OR7C1	OR7C1	863	0.56	0.31	YES
13	OR1L8	OR1L8	OR1L8	880	0.56	0.33	YES
14	OR2W3	OR2W3	OR2W3	967	0.54	0.34	YES
15	OR5AU1	OR5AU1	OR5AU1	1075	0.51	0.35	YES
16	OR3A3	OR3A3	OR3A3	1323	0.45	0.36	YES
17	OR51B5	OR51B5	OR51B5	1334	0.45	0.37	YES
18	OR52N4	OR52N4	OR52N4	1349	0.45	0.38	YES
19	OR2B2	OR2B2	OR2B2	1448	0.43	0.39	YES
20	OR8G5	OR8G5	OR8G5	1507	0.42	0.4	YES
21	OR56B1	OR56B1	OR56B1	1680	0.39	0.41	YES
22	OR1J2	OR1J2	OR1J2	1812	0.37	0.41	YES
23	OR4N4	OR4N4	OR4N4	1890	0.36	0.42	YES
24	CAMK2A	CAMK2A	CAMK2A	1957	0.35	0.43	YES
25	OR13G1	OR13G1	OR13G1	1959	0.35	0.44	YES
26	OR1K1	OR1K1	OR1K1	2134	0.32	0.44	YES
27	OR1E2	OR1E2	OR1E2	2344	0.3	0.44	YES
28	OR6C2	OR6C2	OR6C2	2400	0.29	0.45	YES
29	OR2T8	OR2T8	OR2T8	2412	0.29	0.46	YES
30	OR1J1	OR1J1	OR1J1	2733	0.26	0.45	YES
31	OR3A1	OR3A1	OR3A1	2899	0.24	0.45	YES
32	OR2C1	OR2C1	OR2C1	2904	0.24	0.45	YES
33	OR2L13	OR2L13	OR2L13	2994	0.24	0.46	YES
34	OR51B4	OR51B4	OR51B4	3277	0.22	0.45	NO
35	OR1E1	OR1E1	OR1E1	3614	0.19	0.44	NO
36	OR3A2	OR3A2	OR3A2	3875	0.18	0.43	NO
37	OR5K2	OR5K2	OR5K2	3924	0.18	0.43	NO
38	CAMK2G	CAMK2G	CAMK2G	3940	0.17	0.44	NO
39	GNAL	GNAL	GNAL	4381	0.15	0.42	NO
40	OR4C6	OR4C6	OR4C6	4392	0.15	0.42	NO
41	OR6C70	OR6C70	OR6C70	4437	0.15	0.43	NO
42	GUCA1A	GUCA1A	GUCA1A	5514	0.1	0.37	NO
43	OR2AG2	OR2AG2	OR2AG2	5945	0.089	0.35	NO
44	CALM2	CALM2	CALM2	6124	0.082	0.35	NO
45	OR2A1	OR2A1	OR2A1	6176	0.08	0.35	NO
46	ADRBK2	ADRBK2	ADRBK2	6259	0.078	0.35	NO
47	PRKACG	PRKACG	PRKACG	6424	0.072	0.34	NO
48	CNGB1	CNGB1	CNGB1	6531	0.069	0.34	NO
49	ARRB2	ARRB2	ARRB2	6572	0.068	0.34	NO
50	PRKX	PRKX	PRKX	7846	0.03	0.27	NO
51	CAMK2D	CAMK2D	CAMK2D	8475	0.012	0.24	NO
52	CNGA3	CNGA3	CNGA3	8486	0.011	0.24	NO
53	GUCA1B	GUCA1B	GUCA1B	8563	0.0092	0.23	NO
54	OR9A4	OR9A4	OR9A4	8611	0.0079	0.23	NO
55	PRKACB	PRKACB	PRKACB	8669	0.0057	0.23	NO
56	PRKACA	PRKACA	PRKACA	8995	-0.0032	0.21	NO
57	OR7D2	OR7D2	OR7D2	9165	-0.0085	0.2	NO
58	PDE1C	PDE1C	PDE1C	10091	-0.035	0.16	NO
59	OR6B2	OR6B2	OR6B2	10385	-0.044	0.14	NO
60	CALM1	CALM1	CALM1	10430	-0.046	0.14	NO
61	CNGA4	CNGA4	CNGA4	10475	-0.048	0.14	NO
62	ADCY3	ADCY3	ADCY3	10557	-0.05	0.14	NO
63	OR2H2	OR2H2	OR2H2	10565	-0.05	0.14	NO
64	CALM3	CALM3	CALM3	10915	-0.062	0.12	NO
65	OR52N2	OR52N2	OR52N2	11241	-0.073	0.11	NO
66	OR2A25	OR2A25	OR2A25	11536	-0.083	0.095	NO
67	OR56B4	OR56B4	OR56B4	11965	-0.1	0.076	NO
68	OR51Q1	OR51Q1	OR51Q1	12579	-0.12	0.047	NO
69	OR2A4	OR2A4	OR2A4	13028	-0.15	0.028	NO
70	PRKG2	PRKG2	PRKG2	13561	-0.18	0.0063	NO
71	CLCA2	CLCA2	CLCA2	13965	-0.2	-0.0083	NO
72	OR13A1	OR13A1	OR13A1	14121	-0.21	-0.0095	NO
73	OR2A7	OR2A7	OR2A7	14155	-0.21	-0.0042	NO
74	CLCA4	CLCA4	CLCA4	14411	-0.23	-0.01	NO
75	CALML6	CALML6	CALML6	14517	-0.24	-0.0076	NO
76	GUCY2D	GUCY2D	GUCY2D	14787	-0.26	-0.013	NO
77	OR10A3	OR10A3	OR10A3	14937	-0.28	-0.012	NO
78	OR2T4	OR2T4	OR2T4	15686	-0.35	-0.04	NO
79	OR5M11	OR5M11	OR5M11	15833	-0.37	-0.035	NO
80	OR7A5	OR7A5	OR7A5	15955	-0.38	-0.029	NO
81	PRKG1	PRKG1	PRKG1	16021	-0.39	-0.02	NO
82	OR13J1	OR13J1	OR13J1	16713	-0.49	-0.04	NO
83	CALML3	CALML3	CALML3	16989	-0.54	-0.037	NO
84	CAMK2B	CAMK2B	CAMK2B	17191	-0.57	-0.028	NO
85	CLCA1	CLCA1	CLCA1	17591	-0.65	-0.028	NO
86	OR1F1	OR1F1	OR1F1	17795	-0.7	-0.016	NO
87	OR51E1	OR51E1	OR51E1	18051	-0.77	-0.0038	NO
88	CALML5	CALML5	CALML5	18101	-0.78	0.019	NO
89	OR51E2	OR51E2	OR51E2	18509	-0.93	0.029	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 B CELL RECEPTOR SIGNALING PATHWAY.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA MPR PATHWAY	33	genes.ES.table	0.53	1.7	0.0082	0.34	0.34	0.33	0.16	0.28	0	0.11
KEGG CITRATE CYCLE TCA CYCLE	30	genes.ES.table	0.5	1.7	0.037	0.36	0.5	0.5	0.21	0.39	0	0.11
KEGG OXIDATIVE PHOSPHORYLATION	115	genes.ES.table	0.45	1.6	0.12	0.48	0.68	0.66	0.35	0.43	0.23	0.15
KEGG PYRIMIDINE METABOLISM	96	genes.ES.table	0.32	1.5	0.074	0.51	0.87	0.38	0.29	0.28	0.32	0.15
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.32	1.4	0.12	0.63	0.92	0.19	0.18	0.15	0.46	0.22
KEGG SELENOAMINO ACID METABOLISM	25	genes.ES.table	0.51	1.7	0.01	0.39	0.45	0.56	0.3	0.39	0	0.12
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	43	genes.ES.table	0.4	1.4	0.11	0.6	0.91	0.44	0.22	0.34	0.42	0.2
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.45	1.4	0.17	0.6	0.92	0.68	0.38	0.42	0.43	0.2
KEGG RIBOSOME	86	genes.ES.table	0.5	1.4	0.22	0.61	0.92	0.71	0.42	0.42	0.43	0.2
KEGG RNA DEGRADATION	56	genes.ES.table	0.44	1.6	0.1	0.47	0.69	0.68	0.4	0.41	0.24	0.14

genes ES table in pathway: BIOCARTA MPR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	BDNF	BDNF	BDNF	138	1	0.031	YES
2	COX7A1	COX7A1	COX7A1	274	0.8	0.055	YES
3	GRIN1	GRIN1	GRIN1	411	0.68	0.074	YES
4	HAP1	HAP1	HAP1	512	0.62	0.092	YES
5	CREB3L1	CREB3L1	CREB3L1	530	0.61	0.12	YES
6	CREB5	CREB5	CREB5	863	0.48	0.12	YES
7	UCP1	UCP1	UCP1	963	0.46	0.13	YES
8	BBC3	BBC3	BBC3	1056	0.43	0.14	YES
9	UQCRHL	UQCRHL	UQCRHL	1153	0.41	0.15	YES
10	AP2B1	AP2B1	AP2B1	1416	0.35	0.15	YES
11	SLC25A4	SLC25A4	SLC25A4	1417	0.35	0.16	YES
12	PLCB4	PLCB4	PLCB4	1601	0.32	0.17	YES
13	NDUFS5	NDUFS5	NDUFS5	1624	0.32	0.18	YES
14	UQCRH	UQCRH	UQCRH	1626	0.32	0.19	YES
15	COX7B	COX7B	COX7B	1893	0.29	0.19	YES
16	VDAC1	VDAC1	VDAC1	1984	0.28	0.19	YES
17	ATP5H	ATP5H	ATP5H	2086	0.26	0.2	YES
18	ATP5G1	ATP5G1	ATP5G1	2151	0.26	0.2	YES
19	NDUFS6	NDUFS6	NDUFS6	2302	0.25	0.2	YES
20	NDUFC2	NDUFC2	NDUFC2	2371	0.24	0.21	YES
21	VDAC2	VDAC2	VDAC2	2372	0.24	0.22	YES
22	HDAC1	HDAC1	HDAC1	2395	0.24	0.23	YES
23	SLC25A5	SLC25A5	SLC25A5	2441	0.23	0.23	YES
24	POLR2H	POLR2H	POLR2H	2509	0.23	0.24	YES
25	NDUFA9	NDUFA9	NDUFA9	2535	0.23	0.25	YES
26	POLR2G	POLR2G	POLR2G	2616	0.22	0.25	YES
27	DNAH2	DNAH2	DNAH2	2697	0.22	0.26	YES
28	NDUFA4	NDUFA4	NDUFA4	2705	0.22	0.26	YES
29	NDUFA8	NDUFA8	NDUFA8	2804	0.21	0.27	YES
30	COX5A	COX5A	COX5A	2880	0.2	0.27	YES
31	NDUFAB1	NDUFAB1	NDUFAB1	2989	0.2	0.27	YES
32	HIP1	HIP1	HIP1	3063	0.19	0.28	YES
33	COX7A2	COX7A2	COX7A2	3075	0.19	0.28	YES
34	BAX	BAX	BAX	3086	0.19	0.29	YES
35	ATP5G3	ATP5G3	ATP5G3	3130	0.19	0.29	YES
36	NDUFB10	NDUFB10	NDUFB10	3151	0.19	0.3	YES
37	TFAM	TFAM	TFAM	3279	0.18	0.3	YES
38	CYC1	CYC1	CYC1	3332	0.18	0.3	YES
39	CASP3	CASP3	CASP3	3422	0.17	0.31	YES
40	NDUFA6	NDUFA6	NDUFA6	3434	0.17	0.31	YES
41	ATP5B	ATP5B	ATP5B	3473	0.17	0.32	YES
42	COX5B	COX5B	COX5B	3608	0.17	0.32	YES
43	CLTB	CLTB	CLTB	3620	0.17	0.32	YES
44	AP2M1	AP2M1	AP2M1	3680	0.16	0.32	YES
45	SDHB	SDHB	SDHB	3771	0.16	0.33	YES
46	NDUFB9	NDUFB9	NDUFB9	3791	0.16	0.33	YES
47	SDHD	SDHD	SDHD	3841	0.16	0.34	YES
48	COX8A	COX8A	COX8A	3872	0.15	0.34	YES
49	ATP5C1	ATP5C1	ATP5C1	3929	0.15	0.34	YES
50	COX7C	COX7C	COX7C	3965	0.15	0.35	YES
51	NDUFS8	NDUFS8	NDUFS8	3968	0.15	0.35	YES
52	ATP5F1	ATP5F1	ATP5F1	3983	0.15	0.36	YES
53	NDUFA3	NDUFA3	NDUFA3	4046	0.15	0.36	YES
54	NDUFA1	NDUFA1	NDUFA1	4078	0.14	0.36	YES
55	ATP5J	ATP5J	ATP5J	4155	0.14	0.36	YES
56	COX6A1	COX6A1	COX6A1	4168	0.14	0.37	YES
57	ATP5O	ATP5O	ATP5O	4177	0.14	0.37	YES
58	COX4I1	COX4I1	COX4I1	4284	0.14	0.37	YES
59	AP2S1	AP2S1	AP2S1	4288	0.14	0.38	YES
60	NDUFS7	NDUFS7	NDUFS7	4301	0.14	0.38	YES
61	CYCS	CYCS	CYCS	4365	0.13	0.38	YES
62	UQCRFS1	UQCRFS1	UQCRFS1	4384	0.13	0.39	YES
63	CLTA	CLTA	CLTA	4388	0.13	0.39	YES
64	ATP5D	ATP5D	ATP5D	4769	0.12	0.38	YES
65	NDUFB2	NDUFB2	NDUFB2	4806	0.12	0.38	YES
66	NDUFS4	NDUFS4	NDUFS4	4810	0.12	0.38	YES
67	SLC25A6	SLC25A6	SLC25A6	4817	0.12	0.39	YES
68	NDUFB8	NDUFB8	NDUFB8	4855	0.12	0.39	YES
69	HTT	HTT	HTT	4906	0.11	0.39	YES
70	NDUFV2	NDUFV2	NDUFV2	4930	0.11	0.4	YES
71	HDAC2	HDAC2	HDAC2	4976	0.11	0.4	YES
72	UQCRC2	UQCRC2	UQCRC2	4982	0.11	0.4	YES
73	COX6C	COX6C	COX6C	5021	0.11	0.4	YES
74	POLR2E	POLR2E	POLR2E	5109	0.11	0.4	YES
75	POLR2F	POLR2F	POLR2F	5132	0.1	0.41	YES
76	RCOR1	RCOR1	RCOR1	5179	0.1	0.41	YES
77	UQCR11	UQCR11	UQCR11	5247	0.1	0.41	YES
78	TAF4	TAF4	TAF4	5256	0.1	0.41	YES
79	NDUFV1	NDUFV1	NDUFV1	5316	0.099	0.41	YES
80	NDUFS2	NDUFS2	NDUFS2	5321	0.099	0.42	YES
81	POLR2A	POLR2A	POLR2A	5477	0.094	0.41	YES
82	UQCRQ	UQCRQ	UQCRQ	5499	0.093	0.41	YES
83	TAF4B	TAF4B	TAF4B	5532	0.092	0.42	YES
84	NDUFA4L2	NDUFA4L2	NDUFA4L2	5537	0.092	0.42	YES
85	CASP9	CASP9	CASP9	5619	0.09	0.42	YES
86	NDUFB1	NDUFB1	NDUFB1	5640	0.089	0.42	YES
87	COX6B1	COX6B1	COX6B1	5657	0.089	0.42	YES
88	NDUFB6	NDUFB6	NDUFB6	5881	0.083	0.42	YES
89	CREB3	CREB3	CREB3	5989	0.079	0.41	YES
90	TBPL1	TBPL1	TBPL1	6018	0.079	0.41	YES
91	PPARGC1A	PPARGC1A	PPARGC1A	6054	0.078	0.42	YES
92	TP53	TP53	TP53	6112	0.076	0.42	YES
93	POLR2C	POLR2C	POLR2C	6123	0.075	0.42	YES
94	NDUFA2	NDUFA2	NDUFA2	6337	0.069	0.41	YES
95	GPX1	GPX1	GPX1	6347	0.069	0.41	YES
96	NDUFB7	NDUFB7	NDUFB7	6369	0.068	0.41	YES
97	UQCRB	UQCRB	UQCRB	6375	0.068	0.41	YES
98	REST	REST	REST	6382	0.068	0.42	YES
99	TBP	TBP	TBP	6441	0.066	0.42	YES
100	NDUFB3	NDUFB3	NDUFB3	6457	0.066	0.42	YES
101	SDHC	SDHC	SDHC	6518	0.064	0.42	YES
102	NDUFV3	NDUFV3	NDUFV3	6556	0.063	0.42	YES
103	NDUFS1	NDUFS1	NDUFS1	6592	0.063	0.42	YES
104	POLR2L	POLR2L	POLR2L	6600	0.062	0.42	YES
105	NDUFA5	NDUFA5	NDUFA5	6617	0.062	0.42	YES
106	VDAC3	VDAC3	VDAC3	6631	0.062	0.42	YES
107	NDUFA7	NDUFA7	NDUFA7	6690	0.06	0.42	NO
108	UQCRC1	UQCRC1	UQCRC1	6817	0.056	0.42	NO
109	POLR2J	POLR2J	POLR2J	6824	0.056	0.42	NO
110	APAF1	APAF1	APAF1	6843	0.055	0.42	NO
111	POLR2I	POLR2I	POLR2I	7033	0.051	0.41	NO
112	DNAI2	DNAI2	DNAI2	7063	0.05	0.41	NO
113	DCTN2	DCTN2	DCTN2	7235	0.045	0.41	NO
114	SP1	SP1	SP1	7259	0.045	0.41	NO
115	AP2A1	AP2A1	AP2A1	7294	0.044	0.41	NO
116	NDUFA10	NDUFA10	NDUFA10	7367	0.042	0.4	NO
117	UQCR10	UQCR10	UQCR10	7411	0.041	0.4	NO
118	NDUFB5	NDUFB5	NDUFB5	7416	0.04	0.4	NO
119	CLTC	CLTC	CLTC	7431	0.04	0.41	NO
120	NDUFB4	NDUFB4	NDUFB4	7505	0.038	0.4	NO
121	NDUFS3	NDUFS3	NDUFS3	7604	0.036	0.4	NO
122	ATP5A1	ATP5A1	ATP5A1	7613	0.036	0.4	NO
123	NDUFC1	NDUFC1	NDUFC1	7713	0.033	0.4	NO
124	CREB3L4	CREB3L4	CREB3L4	7966	0.026	0.38	NO
125	COX7B2	COX7B2	COX7B2	7986	0.026	0.38	NO
126	PPID	PPID	PPID	8368	0.016	0.36	NO
127	POLR2D	POLR2D	POLR2D	8501	0.013	0.36	NO
128	PLCB3	PLCB3	PLCB3	8512	0.013	0.36	NO
129	DNAH3	DNAH3	DNAH3	8851	0.0045	0.34	NO
130	ATP5G2	ATP5G2	ATP5G2	8925	0.0027	0.34	NO
131	POLR2K	POLR2K	POLR2K	8983	0.00073	0.33	NO
132	ATP5E	ATP5E	ATP5E	9000	8e-05	0.33	NO
133	POLR2B	POLR2B	POLR2B	9081	-0.0021	0.33	NO
134	NRF1	NRF1	NRF1	9114	-0.0029	0.33	NO
135	SIN3A	SIN3A	SIN3A	9143	-0.0036	0.33	NO
136	TBPL2	TBPL2	TBPL2	9189	-0.0051	0.32	NO
137	SDHA	SDHA	SDHA	9242	-0.0067	0.32	NO
138	AP2A2	AP2A2	AP2A2	9807	-0.022	0.29	NO
139	POLR2J2	POLR2J2	POLR2J2	9855	-0.023	0.29	NO
140	TGM2	TGM2	TGM2	9975	-0.027	0.28	NO
141	CASP8	CASP8	CASP8	10218	-0.033	0.27	NO
142	DCTN1	DCTN1	DCTN1	10254	-0.034	0.27	NO
143	EP300	EP300	EP300	10453	-0.039	0.26	NO
144	SOD1	SOD1	SOD1	10456	-0.039	0.26	NO
145	COX7A2L	COX7A2L	COX7A2L	10514	-0.041	0.26	NO
146	IFT57	IFT57	IFT57	10582	-0.043	0.26	NO
147	DCTN4	DCTN4	DCTN4	10776	-0.049	0.25	NO
148	GRM5	GRM5	GRM5	11289	-0.064	0.23	NO
149	POLR2J3	POLR2J3	POLR2J3	11618	-0.073	0.21	NO
150	COX8C	COX8C	COX8C	11890	-0.082	0.2	NO
151	DNAL1	DNAL1	DNAL1	11997	-0.085	0.2	NO
152	CREBBP	CREBBP	CREBBP	12148	-0.09	0.2	NO
153	GNAQ	GNAQ	GNAQ	12321	-0.095	0.19	NO
154	CLTCL1	CLTCL1	CLTCL1	13079	-0.12	0.16	NO
155	SOD2	SOD2	SOD2	13129	-0.12	0.16	NO
156	CREB3L2	CREB3L2	CREB3L2	13154	-0.12	0.16	NO
157	CREB1	CREB1	CREB1	13319	-0.13	0.16	NO
158	COX6A2	COX6A2	COX6A2	13418	-0.13	0.16	NO
159	DLG4	DLG4	DLG4	13656	-0.14	0.15	NO
160	PLCB2	PLCB2	PLCB2	13809	-0.14	0.15	NO
161	COX4I2	COX4I2	COX4I2	13858	-0.15	0.15	NO
162	GRIN2B	GRIN2B	GRIN2B	13924	-0.15	0.15	NO
163	DNALI1	DNALI1	DNALI1	14842	-0.19	0.11	NO
164	PLCB1	PLCB1	PLCB1	14921	-0.19	0.11	NO
165	DNAL4	DNAL4	DNAL4	15489	-0.22	0.093	NO
166	SLC25A31	SLC25A31	SLC25A31	15665	-0.23	0.093	NO
167	COX6B2	COX6B2	COX6B2	16272	-0.27	0.071	NO
168	CREB3L3	CREB3L3	CREB3L3	16527	-0.29	0.068	NO
169	ITPR1	ITPR1	ITPR1	16585	-0.29	0.077	NO
170	DNAI1	DNAI1	DNAI1	17933	-0.44	0.022	NO
171	PPARG	PPARG	PPARG	18097	-0.47	0.032	NO
172	DNAH1	DNAH1	DNAH1	18163	-0.49	0.047	NO

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

Figure S22. 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: 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	HSPA6	HSPA6	HSPA6	840	0.49	-0.0075	YES
2	HSPA2	HSPA2	HSPA2	1147	0.41	0.0072	YES
3	MAGOH	MAGOH	MAGOH	1301	0.38	0.028	YES
4	PPIH	PPIH	PPIH	1638	0.32	0.034	YES
5	MAGOHB	MAGOHB	MAGOHB	1988	0.28	0.036	YES
6	SNRPA1	SNRPA1	SNRPA1	2084	0.26	0.051	YES
7	SNRPF	SNRPF	SNRPF	2400	0.24	0.052	YES
8	THOC3	THOC3	THOC3	2550	0.23	0.062	YES
9	THOC4	THOC4	THOC4	2654	0.22	0.073	YES
10	SNRPC	SNRPC	SNRPC	2784	0.21	0.082	YES
11	TXNL4A	TXNL4A	TXNL4A	2813	0.21	0.096	YES
12	SF3A3	SF3A3	SF3A3	2882	0.2	0.11	YES
13	BCAS2	BCAS2	BCAS2	2915	0.2	0.12	YES
14	SNRNP40	SNRNP40	SNRNP40	3037	0.2	0.13	YES
15	WBP11	WBP11	WBP11	3057	0.19	0.14	YES
16	PRPF38A	PRPF38A	PRPF38A	3068	0.19	0.16	YES
17	PPIL1	PPIL1	PPIL1	3101	0.19	0.17	YES
18	RBM22	RBM22	RBM22	3228	0.18	0.18	YES
19	LSM3	LSM3	LSM3	3236	0.18	0.19	YES
20	SNRPD1	SNRPD1	SNRPD1	3315	0.18	0.2	YES
21	ZMAT2	ZMAT2	ZMAT2	3551	0.17	0.2	YES
22	BUD31	BUD31	BUD31	3579	0.17	0.21	YES
23	SNRNP27	SNRNP27	SNRNP27	3624	0.17	0.22	YES
24	EIF4A3	EIF4A3	EIF4A3	3717	0.16	0.23	YES
25	SNRPG	SNRPG	SNRPG	3840	0.16	0.24	YES
26	RBM8A	RBM8A	RBM8A	3877	0.15	0.24	YES
27	LSM7	LSM7	LSM7	3899	0.15	0.26	YES
28	LSM6	LSM6	LSM6	3909	0.15	0.27	YES
29	HSPA1A	HSPA1A	HSPA1A	3995	0.15	0.27	YES
30	PCBP1	PCBP1	PCBP1	4032	0.15	0.28	YES
31	EFTUD2	EFTUD2	EFTUD2	4264	0.14	0.28	YES
32	PPIE	PPIE	PPIE	4322	0.14	0.29	YES
33	DHX15	DHX15	DHX15	4402	0.13	0.29	YES
34	DHX8	DHX8	DHX8	4414	0.13	0.3	YES
35	HSPA1B	HSPA1B	HSPA1B	4434	0.13	0.31	YES
36	SNRPB2	SNRPB2	SNRPB2	4495	0.13	0.32	YES
37	PRPF4	PRPF4	PRPF4	4533	0.13	0.33	YES
38	SNRPD3	SNRPD3	SNRPD3	4550	0.13	0.33	YES
39	SNRPA	SNRPA	SNRPA	4616	0.12	0.34	YES
40	SFRS4	SFRS4	SFRS4	4715	0.12	0.34	YES
41	RBMX	RBMX	RBMX	4716	0.12	0.35	YES
42	HSPA8	HSPA8	HSPA8	4735	0.12	0.36	YES
43	CWC15	CWC15	CWC15	4745	0.12	0.37	YES
44	SMNDC1	SMNDC1	SMNDC1	4809	0.12	0.38	YES
45	PRPF40A	PRPF40A	PRPF40A	4878	0.12	0.38	YES
46	SFRS9	SFRS9	SFRS9	4931	0.11	0.39	YES
47	HNRNPA3	HNRNPA3	HNRNPA3	4940	0.11	0.39	YES
48	HNRNPM	HNRNPM	HNRNPM	4956	0.11	0.4	YES
49	SNRPB	SNRPB	SNRPB	4983	0.11	0.41	YES
50	PUF60	PUF60	PUF60	5040	0.11	0.41	YES
51	NAA38	NAA38	NAA38	5141	0.1	0.42	YES
52	DDX46	DDX46	DDX46	5374	0.097	0.41	YES
53	NHP2L1	NHP2L1	NHP2L1	5375	0.097	0.42	YES
54	SR140	SR140	SR140	5388	0.097	0.43	YES
55	PRPF8	PRPF8	PRPF8	5411	0.096	0.43	YES
56	SYF2	SYF2	SYF2	5435	0.095	0.44	YES
57	HNRNPC	HNRNPC	HNRNPC	5540	0.092	0.44	YES
58	SFRS1	SFRS1	SFRS1	5554	0.092	0.45	YES
59	U2AF1	U2AF1	U2AF1	5586	0.091	0.45	YES
60	PRPF18	PRPF18	PRPF18	5618	0.09	0.46	YES
61	PRPF3	PRPF3	PRPF3	5632	0.089	0.46	YES
62	THOC2	THOC2	THOC2	5633	0.089	0.47	YES
63	SF3B14	SF3B14	SF3B14	5659	0.088	0.47	YES
64	LSM2	LSM2	LSM2	5703	0.088	0.48	YES
65	LSM5	LSM5	LSM5	5792	0.085	0.48	YES
66	PQBP1	PQBP1	PQBP1	5863	0.083	0.48	YES
67	SART1	SART1	SART1	6032	0.078	0.48	YES
68	SFRS3	SFRS3	SFRS3	6100	0.076	0.48	YES
69	USP39	USP39	USP39	6176	0.074	0.48	YES
70	SF3B2	SF3B2	SF3B2	6253	0.072	0.48	YES
71	SFRS7	SFRS7	SFRS7	6275	0.071	0.49	YES
72	HNRNPK	HNRNPK	HNRNPK	6276	0.071	0.5	YES
73	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	6306	0.07	0.5	YES
74	SNRPE	SNRPE	SNRPE	6380	0.068	0.5	YES
75	CDC40	CDC40	CDC40	6393	0.068	0.5	YES
76	U2AF2	U2AF2	U2AF2	6401	0.067	0.51	YES
77	PHF5A	PHF5A	PHF5A	6419	0.067	0.51	YES
78	BAT1	BAT1	BAT1	6449	0.066	0.52	YES
79	HNRNPA1	HNRNPA1	HNRNPA1	6497	0.065	0.52	YES
80	TRA2B	TRA2B	TRA2B	6513	0.064	0.52	YES
81	CTNNBL1	CTNNBL1	CTNNBL1	6610	0.062	0.52	YES
82	PRPF19	PRPF19	PRPF19	6650	0.061	0.52	YES
83	SNRPD2	SNRPD2	SNRPD2	6656	0.061	0.53	YES
84	TCERG1	TCERG1	TCERG1	6739	0.059	0.53	YES
85	LSM4	LSM4	LSM4	6742	0.059	0.53	YES
86	SF3A2	SF3A2	SF3A2	6769	0.058	0.54	YES
87	RBM17	RBM17	RBM17	6801	0.056	0.54	YES
88	SFRS2	SFRS2	SFRS2	6802	0.056	0.54	YES
89	HNRNPU	HNRNPU	HNRNPU	7000	0.051	0.54	NO
90	SF3A1	SF3A1	SF3A1	7001	0.051	0.54	NO
91	PRPF31	PRPF31	PRPF31	7110	0.048	0.54	NO
92	ISY1	ISY1	ISY1	7137	0.048	0.54	NO
93	NCBP1	NCBP1	NCBP1	7179	0.047	0.54	NO
94	PRPF6	PRPF6	PRPF6	7329	0.043	0.54	NO
95	CDC5L	CDC5L	CDC5L	7396	0.041	0.54	NO
96	SF3B4	SF3B4	SF3B4	7424	0.04	0.54	NO
97	SLU7	SLU7	SLU7	7448	0.04	0.54	NO
98	SF3B3	SF3B3	SF3B3	7466	0.039	0.54	NO
99	DDX42	DDX42	DDX42	7525	0.038	0.54	NO
100	SNW1	SNW1	SNW1	7658	0.034	0.54	NO
101	SNRNP70	SNRNP70	SNRNP70	7757	0.032	0.54	NO
102	DDX23	DDX23	DDX23	7984	0.026	0.53	NO
103	SF3B5	SF3B5	SF3B5	8024	0.025	0.53	NO
104	CCDC12	CCDC12	CCDC12	8382	0.016	0.51	NO
105	DHX16	DHX16	DHX16	8400	0.016	0.51	NO
106	CRNKL1	CRNKL1	CRNKL1	8874	0.004	0.48	NO
107	SFRS13A	SFRS13A	SFRS13A	8887	0.0036	0.48	NO
108	DHX38	DHX38	DHX38	8951	0.0018	0.48	NO
109	AQR	AQR	AQR	9232	-0.0065	0.47	NO
110	DDX5	DDX5	DDX5	9274	-0.0075	0.46	NO
111	ACIN1	ACIN1	ACIN1	9341	-0.0095	0.46	NO
112	SNRNP200	SNRNP200	SNRNP200	9530	-0.015	0.45	NO
113	CHERP	CHERP	CHERP	9576	-0.016	0.45	NO
114	PLRG1	PLRG1	PLRG1	9633	-0.018	0.45	NO
115	SFRS2B	SFRS2B	SFRS2B	9667	-0.018	0.45	NO
116	THOC1	THOC1	THOC1	9757	-0.021	0.45	NO
117	TRA2A	TRA2A	TRA2A	9912	-0.025	0.44	NO
118	SF3B1	SF3B1	SF3B1	9960	-0.026	0.44	NO
119	XAB2	XAB2	XAB2	9997	-0.027	0.44	NO
120	RBM25	RBM25	RBM25	10268	-0.034	0.43	NO
121	PRPF38B	PRPF38B	PRPF38B	10357	-0.037	0.43	NO
122	SFRS6	SFRS6	SFRS6	10494	-0.04	0.42	NO
123	SFRS5	SFRS5	SFRS5	10566	-0.042	0.42	NO
124	PRPF40B	PRPF40B	PRPF40B	13385	-0.13	0.28	NO
125	HSPA1L	HSPA1L	HSPA1L	15479	-0.22	0.19	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 OXIDATIVE PHOSPHORYLATION

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	PRKACG	PRKACG	PRKACG	432	0.67	0.11	YES
2	ACTA1	ACTA1	ACTA1	580	0.58	0.22	YES
3	PAQR5	PAQR5	PAQR5	1635	0.32	0.23	YES
4	PRKAR1B	PRKAR1B	PRKAR1B	1897	0.29	0.28	YES
5	CDC25C	CDC25C	CDC25C	2273	0.25	0.31	YES
6	CCNB1	CCNB1	CCNB1	2468	0.23	0.35	YES
7	GNAI1	GNAI1	GNAI1	2628	0.22	0.38	YES
8	PRKAR2A	PRKAR2A	PRKAR2A	2638	0.22	0.43	YES
9	CDK1	CDK1	CDK1	2642	0.22	0.47	YES
10	GNGT1	GNGT1	GNGT1	2916	0.2	0.5	YES
11	RPS6KA1	RPS6KA1	RPS6KA1	3061	0.19	0.53	YES
12	HRAS	HRAS	HRAS	4611	0.12	0.47	NO
13	ARPC1B	ARPC1B	ARPC1B	4664	0.12	0.5	NO
14	GNAS	GNAS	GNAS	5579	0.091	0.47	NO
15	ARPC2	ARPC2	ARPC2	5878	0.083	0.47	NO
16	ACTR3	ACTR3	ACTR3	5929	0.082	0.48	NO
17	CAP1	CAP1	CAP1	6115	0.076	0.49	NO
18	ARPC4	ARPC4	ARPC4	6167	0.074	0.5	NO
19	MAPK3	MAPK3	MAPK3	6779	0.057	0.48	NO
20	PRKAR2B	PRKAR2B	PRKAR2B	7212	0.046	0.46	NO
21	PIN1	PIN1	PIN1	7582	0.036	0.45	NO
22	GNB1	GNB1	GNB1	7924	0.028	0.44	NO
23	ARPC3	ARPC3	ARPC3	8092	0.023	0.44	NO
24	ARPC5	ARPC5	ARPC5	9322	-0.0088	0.37	NO
25	PRKAR1A	PRKAR1A	PRKAR1A	9518	-0.014	0.37	NO
26	ARPC1A	ARPC1A	ARPC1A	9577	-0.016	0.37	NO
27	ACTR2	ACTR2	ACTR2	10628	-0.044	0.32	NO
28	MAPK1	MAPK1	MAPK1	11102	-0.058	0.31	NO
29	PGR	PGR	PGR	11402	-0.067	0.31	NO
30	PAQR7	PAQR7	PAQR7	11546	-0.071	0.31	NO
31	SRC	SRC	SRC	11612	-0.073	0.32	NO
32	MYT1	MYT1	MYT1	12340	-0.096	0.3	NO
33	PRKACB	PRKACB	PRKACB	15700	-0.23	0.18	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 OXIDATIVE PHOSPHORYLATION.

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

genes ES table in pathway: KEGG PYRIMIDINE METABOLISM

Table 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	CBS	CBS	CBS	182	0.93	0.22	YES
2	CTH	CTH	CTH	766	0.51	0.32	YES
3	SEPHS1	SEPHS1	SEPHS1	1192	0.4	0.4	YES
4	PAPSS2	PAPSS2	PAPSS2	2991	0.2	0.35	YES
5	GGT1	GGT1	GGT1	3312	0.18	0.38	YES
6	AHCYL1	AHCYL1	AHCYL1	3604	0.17	0.41	YES
7	TRMT11	TRMT11	TRMT11	4345	0.13	0.4	YES
8	LCMT1	LCMT1	LCMT1	4377	0.13	0.44	YES
9	MAT2A	MAT2A	MAT2A	4661	0.12	0.45	YES
10	AHCYL2	AHCYL2	AHCYL2	5239	0.1	0.45	YES
11	MAT2B	MAT2B	MAT2B	5384	0.097	0.46	YES
12	AHCY	AHCY	AHCY	5496	0.093	0.48	YES
13	METTL2B	METTL2B	METTL2B	5530	0.092	0.5	YES
14	MARS	MARS	MARS	5774	0.086	0.51	YES
15	MARS2	MARS2	MARS2	6219	0.073	0.51	NO
16	SCLY	SCLY	SCLY	7244	0.045	0.46	NO
17	METTL6	METTL6	METTL6	7733	0.032	0.45	NO
18	WBSCR22	WBSCR22	WBSCR22	7746	0.032	0.45	NO
19	HEMK1	HEMK1	HEMK1	9969	-0.027	0.34	NO
20	MAT1A	MAT1A	MAT1A	10887	-0.052	0.31	NO
21	GGT6	GGT6	GGT6	11107	-0.058	0.31	NO
22	PAPSS1	PAPSS1	PAPSS1	11395	-0.067	0.31	NO
23	GGT7	GGT7	GGT7	11454	-0.069	0.33	NO
24	GGT5	GGT5	GGT5	11834	-0.08	0.33	NO
25	LCMT2	LCMT2	LCMT2	15134	-0.2	0.21	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 PYRIMIDINE METABOLISM.

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

genes ES table in pathway: KEGG LYSINE DEGRADATION

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PDHA1	PDHA1	PDHA1	1221	0.39	0.024	YES
2	DLAT	DLAT	DLAT	1602	0.32	0.076	YES
3	PC	PC	PC	2129	0.26	0.11	YES
4	MDH2	MDH2	MDH2	2217	0.25	0.16	YES
5	IDH1	IDH1	IDH1	2786	0.21	0.18	YES
6	SUCLA2	SUCLA2	SUCLA2	2888	0.2	0.22	YES
7	PDHB	PDHB	PDHB	2902	0.2	0.26	YES
8	IDH3G	IDH3G	IDH3G	2943	0.2	0.3	YES
9	OGDHL	OGDHL	OGDHL	2970	0.2	0.35	YES
10	IDH3B	IDH3B	IDH3B	3443	0.17	0.36	YES
11	SUCLG1	SUCLG1	SUCLG1	3692	0.16	0.39	YES
12	SDHB	SDHB	SDHB	3771	0.16	0.42	YES
13	SDHD	SDHD	SDHD	3841	0.16	0.45	YES
14	IDH3A	IDH3A	IDH3A	3870	0.15	0.48	YES
15	DLD	DLD	DLD	4052	0.15	0.5	YES
16	FH	FH	FH	4643	0.12	0.5	NO
17	PDHA2	PDHA2	PDHA2	5739	0.086	0.46	NO
18	DLST	DLST	DLST	6247	0.072	0.45	NO
19	CS	CS	CS	6325	0.069	0.46	NO
20	SDHC	SDHC	SDHC	6518	0.064	0.47	NO
21	PCK2	PCK2	PCK2	6876	0.054	0.46	NO
22	MDH1	MDH1	MDH1	7052	0.05	0.46	NO
23	ACLY	ACLY	ACLY	8018	0.025	0.42	NO
24	SDHA	SDHA	SDHA	9242	-0.0067	0.36	NO
25	ACO2	ACO2	ACO2	9601	-0.017	0.34	NO
26	ACO1	ACO1	ACO1	10168	-0.032	0.32	NO
27	IDH2	IDH2	IDH2	11443	-0.069	0.27	NO
28	OGDH	OGDH	OGDH	11918	-0.082	0.26	NO
29	PCK1	PCK1	PCK1	15991	-0.25	0.1	NO
30	SUCLG2	SUCLG2	SUCLG2	16081	-0.26	0.16	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 LYSINE DEGRADATION.

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

genes ES table in pathway: KEGG SELENOAMINO ACID METABOLISM

Table 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	PSMB2	PSMB2	PSMB2	1782	0.3	-0.046	YES
2	PSMD11	PSMD11	PSMD11	1905	0.29	-0.0064	YES
3	PSMB6	PSMB6	PSMB6	1935	0.28	0.037	YES
4	PSMA5	PSMA5	PSMA5	2141	0.26	0.068	YES
5	PSMB3	PSMB3	PSMB3	2455	0.23	0.089	YES
6	PSMC4	PSMC4	PSMC4	2574	0.22	0.12	YES
7	PSMA7	PSMA7	PSMA7	2588	0.22	0.15	YES
8	PSMD12	PSMD12	PSMD12	2706	0.22	0.18	YES
9	PSMA2	PSMA2	PSMA2	2885	0.2	0.2	YES
10	PSMD3	PSMD3	PSMD3	3083	0.19	0.22	YES
11	PSMA1	PSMA1	PSMA1	3214	0.18	0.25	YES
12	PSMB5	PSMB5	PSMB5	3308	0.18	0.27	YES
13	PSMD7	PSMD7	PSMD7	3505	0.17	0.29	YES
14	PSMC1	PSMC1	PSMC1	3516	0.17	0.32	YES
15	POMP	POMP	POMP	3655	0.16	0.33	YES
16	PSMC2	PSMC2	PSMC2	3697	0.16	0.36	YES
17	PSMA6	PSMA6	PSMA6	3971	0.15	0.37	YES
18	PSME4	PSME4	PSME4	3998	0.15	0.39	YES
19	PSMB7	PSMB7	PSMB7	4109	0.14	0.41	YES
20	PSMA3	PSMA3	PSMA3	4219	0.14	0.42	YES
21	PSMC3	PSMC3	PSMC3	4292	0.14	0.44	YES
22	PSMD6	PSMD6	PSMD6	4298	0.14	0.46	YES
23	PSMC5	PSMC5	PSMC5	4366	0.13	0.48	YES
24	PSMB1	PSMB1	PSMB1	4448	0.13	0.5	YES
25	SHFM1	SHFM1	SHFM1	4549	0.13	0.51	YES
26	PSME3	PSME3	PSME3	4641	0.12	0.53	YES
27	PSMD2	PSMD2	PSMD2	4650	0.12	0.55	YES
28	PSMB4	PSMB4	PSMB4	4675	0.12	0.56	YES
29	PSMD14	PSMD14	PSMD14	4777	0.12	0.58	YES
30	PSMA4	PSMA4	PSMA4	5075	0.11	0.58	YES
31	PSMD13	PSMD13	PSMD13	5171	0.1	0.59	YES
32	PSMD4	PSMD4	PSMD4	5565	0.091	0.58	NO
33	PSMC6	PSMC6	PSMC6	5986	0.08	0.57	NO
34	PSMD1	PSMD1	PSMD1	6244	0.072	0.57	NO
35	PSMD8	PSMD8	PSMD8	7284	0.044	0.52	NO
36	PSME2	PSME2	PSME2	8622	0.01	0.46	NO
37	PSME1	PSME1	PSME1	10401	-0.038	0.37	NO
38	PSMF1	PSMF1	PSMF1	11071	-0.057	0.34	NO
39	PSMB8	PSMB8	PSMB8	12244	-0.093	0.3	NO
40	PSMA8	PSMA8	PSMA8	12708	-0.11	0.29	NO
41	PSMB9	PSMB9	PSMB9	13196	-0.12	0.28	NO
42	IFNG	IFNG	IFNG	14069	-0.16	0.26	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 SELENOAMINO ACID METABOLISM.

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

genes ES table in pathway: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR 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	ATP12A	ATP12A	ATP12A	229	0.86	0.041	YES
2	COX7A1	COX7A1	COX7A1	274	0.8	0.088	YES
3	UQCRHL	UQCRHL	UQCRHL	1153	0.41	0.066	YES
4	ATP6V1C2	ATP6V1C2	ATP6V1C2	1452	0.35	0.072	YES
5	NDUFS5	NDUFS5	NDUFS5	1624	0.32	0.082	YES
6	UQCRH	UQCRH	UQCRH	1626	0.32	0.1	YES
7	COX7B	COX7B	COX7B	1893	0.29	0.1	YES
8	ATP6V0A4	ATP6V0A4	ATP6V0A4	1934	0.28	0.12	YES
9	ATP5H	ATP5H	ATP5H	2086	0.26	0.13	YES
10	ATP5G1	ATP5G1	ATP5G1	2151	0.26	0.14	YES
11	NDUFS6	NDUFS6	NDUFS6	2302	0.25	0.15	YES
12	NDUFC2	NDUFC2	NDUFC2	2371	0.24	0.16	YES
13	NDUFA9	NDUFA9	NDUFA9	2535	0.23	0.16	YES
14	NDUFA4	NDUFA4	NDUFA4	2705	0.22	0.17	YES
15	NDUFA8	NDUFA8	NDUFA8	2804	0.21	0.18	YES
16	COX5A	COX5A	COX5A	2880	0.2	0.18	YES
17	NDUFAB1	NDUFAB1	NDUFAB1	2989	0.2	0.19	YES
18	COX7A2	COX7A2	COX7A2	3075	0.19	0.2	YES
19	ATP5G3	ATP5G3	ATP5G3	3130	0.19	0.21	YES
20	NDUFB10	NDUFB10	NDUFB10	3151	0.19	0.22	YES
21	COX11	COX11	COX11	3188	0.19	0.23	YES
22	CYC1	CYC1	CYC1	3332	0.18	0.23	YES
23	ATP5I	ATP5I	ATP5I	3367	0.18	0.24	YES
24	ATP5J2	ATP5J2	ATP5J2	3387	0.18	0.25	YES
25	NDUFA6	NDUFA6	NDUFA6	3434	0.17	0.26	YES
26	ATP5B	ATP5B	ATP5B	3473	0.17	0.27	YES
27	COX5B	COX5B	COX5B	3608	0.17	0.27	YES
28	ATP6V0B	ATP6V0B	ATP6V0B	3623	0.17	0.28	YES
29	ATP6V0E1	ATP6V0E1	ATP6V0E1	3752	0.16	0.28	YES
30	SDHB	SDHB	SDHB	3771	0.16	0.29	YES
31	NDUFB9	NDUFB9	NDUFB9	3791	0.16	0.3	YES
32	SDHD	SDHD	SDHD	3841	0.16	0.31	YES
33	COX8A	COX8A	COX8A	3872	0.15	0.32	YES
34	ATP5C1	ATP5C1	ATP5C1	3929	0.15	0.32	YES
35	COX7C	COX7C	COX7C	3965	0.15	0.33	YES
36	NDUFS8	NDUFS8	NDUFS8	3968	0.15	0.34	YES
37	ATP5F1	ATP5F1	ATP5F1	3983	0.15	0.35	YES
38	NDUFA3	NDUFA3	NDUFA3	4046	0.15	0.35	YES
39	NDUFA1	NDUFA1	NDUFA1	4078	0.14	0.36	YES
40	ATP5J	ATP5J	ATP5J	4155	0.14	0.36	YES
41	COX6A1	COX6A1	COX6A1	4168	0.14	0.37	YES
42	ATP5O	ATP5O	ATP5O	4177	0.14	0.38	YES
43	COX4I1	COX4I1	COX4I1	4284	0.14	0.38	YES
44	NDUFS7	NDUFS7	NDUFS7	4301	0.14	0.39	YES
45	UQCRFS1	UQCRFS1	UQCRFS1	4384	0.13	0.39	YES
46	ATP6V1F	ATP6V1F	ATP6V1F	4749	0.12	0.38	YES
47	ATP5L	ATP5L	ATP5L	4754	0.12	0.39	YES
48	ATP5D	ATP5D	ATP5D	4769	0.12	0.4	YES
49	NDUFB2	NDUFB2	NDUFB2	4806	0.12	0.4	YES
50	NDUFS4	NDUFS4	NDUFS4	4810	0.12	0.41	YES
51	COX17	COX17	COX17	4823	0.12	0.41	YES
52	NDUFB8	NDUFB8	NDUFB8	4855	0.12	0.42	YES
53	NDUFV2	NDUFV2	NDUFV2	4930	0.11	0.42	YES
54	UQCRC2	UQCRC2	UQCRC2	4982	0.11	0.43	YES
55	COX6C	COX6C	COX6C	5021	0.11	0.43	YES
56	UQCR11	UQCR11	UQCR11	5247	0.1	0.42	YES
57	NDUFV1	NDUFV1	NDUFV1	5316	0.099	0.43	YES
58	NDUFS2	NDUFS2	NDUFS2	5321	0.099	0.43	YES
59	ATP6V0E2	ATP6V0E2	ATP6V0E2	5390	0.096	0.44	YES
60	UQCRQ	UQCRQ	UQCRQ	5499	0.093	0.44	YES
61	NDUFA4L2	NDUFA4L2	NDUFA4L2	5537	0.092	0.44	YES
62	NDUFB1	NDUFB1	NDUFB1	5640	0.089	0.44	YES
63	COX6B1	COX6B1	COX6B1	5657	0.089	0.44	YES
64	NDUFA11	NDUFA11	NDUFA11	5841	0.084	0.44	YES
65	NDUFB6	NDUFB6	NDUFB6	5881	0.083	0.44	YES
66	PPA1	PPA1	PPA1	5982	0.08	0.44	YES
67	ATP6V1G1	ATP6V1G1	ATP6V1G1	6084	0.077	0.44	YES
68	NDUFA2	NDUFA2	NDUFA2	6337	0.069	0.43	YES
69	NDUFB7	NDUFB7	NDUFB7	6369	0.068	0.44	YES
70	UQCRB	UQCRB	UQCRB	6375	0.068	0.44	YES
71	NDUFB3	NDUFB3	NDUFB3	6457	0.066	0.44	YES
72	ATP6V1A	ATP6V1A	ATP6V1A	6474	0.066	0.44	YES
73	SDHC	SDHC	SDHC	6518	0.064	0.44	YES
74	NDUFV3	NDUFV3	NDUFV3	6556	0.063	0.45	YES
75	NDUFS1	NDUFS1	NDUFS1	6592	0.063	0.45	YES
76	NDUFA5	NDUFA5	NDUFA5	6617	0.062	0.45	YES
77	NDUFA7	NDUFA7	NDUFA7	6690	0.06	0.45	NO
78	UQCRC1	UQCRC1	UQCRC1	6817	0.056	0.45	NO
79	ATP6AP1	ATP6AP1	ATP6AP1	6888	0.054	0.45	NO
80	LHPP	LHPP	LHPP	7237	0.045	0.43	NO
81	ATP6V1D	ATP6V1D	ATP6V1D	7275	0.044	0.43	NO
82	NDUFA10	NDUFA10	NDUFA10	7367	0.042	0.43	NO
83	ATP6V0D1	ATP6V0D1	ATP6V0D1	7401	0.041	0.43	NO
84	UQCR10	UQCR10	UQCR10	7411	0.041	0.43	NO
85	NDUFB5	NDUFB5	NDUFB5	7416	0.04	0.44	NO
86	NDUFB4	NDUFB4	NDUFB4	7505	0.038	0.43	NO
87	NDUFS3	NDUFS3	NDUFS3	7604	0.036	0.43	NO
88	ATP5A1	ATP5A1	ATP5A1	7613	0.036	0.43	NO
89	ATP6V1E1	ATP6V1E1	ATP6V1E1	7653	0.034	0.43	NO
90	NDUFC1	NDUFC1	NDUFC1	7713	0.033	0.43	NO
91	ATP6V0C	ATP6V0C	ATP6V0C	7932	0.027	0.42	NO
92	COX7B2	COX7B2	COX7B2	7986	0.026	0.42	NO
93	COX10	COX10	COX10	8178	0.021	0.41	NO
94	ATP6V1H	ATP6V1H	ATP6V1H	8206	0.02	0.41	NO
95	ATP6V1C1	ATP6V1C1	ATP6V1C1	8562	0.012	0.39	NO
96	ATP6V0D2	ATP6V0D2	ATP6V0D2	8899	0.0034	0.37	NO
97	ATP5G2	ATP5G2	ATP5G2	8925	0.0027	0.37	NO
98	ATP5E	ATP5E	ATP5E	9000	8e-05	0.37	NO
99	ATP6V1B2	ATP6V1B2	ATP6V1B2	9070	-0.0019	0.37	NO
100	SDHA	SDHA	SDHA	9242	-0.0067	0.36	NO
101	ATP6V0A1	ATP6V0A1	ATP6V0A1	10027	-0.028	0.32	NO
102	COX7A2L	COX7A2L	COX7A2L	10514	-0.041	0.29	NO
103	ATP6V0A2	ATP6V0A2	ATP6V0A2	10857	-0.051	0.28	NO
104	COX8C	COX8C	COX8C	11890	-0.082	0.23	NO
105	COX15	COX15	COX15	12038	-0.086	0.23	NO
106	ATP6V1G2	ATP6V1G2	ATP6V1G2	13052	-0.12	0.18	NO
107	TCIRG1	TCIRG1	TCIRG1	13212	-0.12	0.18	NO
108	COX6A2	COX6A2	COX6A2	13418	-0.13	0.18	NO
109	COX4I2	COX4I2	COX4I2	13858	-0.15	0.16	NO
110	ATP6V1E2	ATP6V1E2	ATP6V1E2	14281	-0.16	0.15	NO
111	PPA2	PPA2	PPA2	14540	-0.18	0.15	NO
112	COX6B2	COX6B2	COX6B2	16272	-0.27	0.074	NO
113	ATP4B	ATP4B	ATP4B	16708	-0.3	0.069	NO
114	ATP4A	ATP4A	ATP4A	17924	-0.44	0.032	NO
115	ATP6V1B1	ATP6V1B1	ATP6V1B1	17959	-0.45	0.058	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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

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	PAPOLB	PAPOLB	PAPOLB	450	0.66	0.082	YES
2	ENO1	ENO1	ENO1	1671	0.31	0.067	YES
3	EXOSC3	EXOSC3	EXOSC3	2693	0.22	0.048	YES
4	ENO3	ENO3	ENO3	2738	0.21	0.08	YES
5	C1D	C1D	C1D	2747	0.21	0.11	YES
6	EXOSC4	EXOSC4	EXOSC4	2904	0.2	0.14	YES
7	HSPA9	HSPA9	HSPA9	3139	0.19	0.16	YES
8	EXOSC7	EXOSC7	EXOSC7	3163	0.19	0.18	YES
9	ENO2	ENO2	ENO2	3225	0.18	0.21	YES
10	LSM3	LSM3	LSM3	3236	0.18	0.24	YES
11	EXOSC2	EXOSC2	EXOSC2	3275	0.18	0.27	YES
12	EXOSC8	EXOSC8	EXOSC8	3541	0.17	0.28	YES
13	EXOSC9	EXOSC9	EXOSC9	3577	0.17	0.3	YES
14	LSM7	LSM7	LSM7	3899	0.15	0.31	YES
15	LSM6	LSM6	LSM6	3909	0.15	0.34	YES
16	PATL1	PATL1	PATL1	4447	0.13	0.33	YES
17	EDC4	EDC4	EDC4	4548	0.13	0.34	YES
18	EXOSC1	EXOSC1	EXOSC1	4658	0.12	0.36	YES
19	HSPD1	HSPD1	HSPD1	4761	0.12	0.37	YES
20	PARN	PARN	PARN	4840	0.12	0.39	YES
21	DCPS	DCPS	DCPS	5028	0.11	0.39	YES
22	PAPOLG	PAPOLG	PAPOLG	5083	0.11	0.41	YES
23	NAA38	NAA38	NAA38	5141	0.1	0.42	YES
24	EXOSC10	EXOSC10	EXOSC10	5417	0.096	0.42	YES
25	LSM2	LSM2	LSM2	5703	0.088	0.42	YES
26	LSM5	LSM5	LSM5	5792	0.085	0.43	YES
27	MPHOSPH6	MPHOSPH6	MPHOSPH6	6187	0.073	0.42	YES
28	DCP1A	DCP1A	DCP1A	6197	0.073	0.43	YES
29	RQCD1	RQCD1	RQCD1	6693	0.06	0.42	YES
30	CNOT6	CNOT6	CNOT6	6699	0.06	0.42	YES
31	LSM4	LSM4	LSM4	6742	0.059	0.43	YES
32	SKIV2L2	SKIV2L2	SKIV2L2	6832	0.056	0.44	YES
33	PAPD7	PAPD7	PAPD7	7193	0.046	0.42	YES
34	SKIV2L	SKIV2L	SKIV2L	7341	0.042	0.42	YES
35	CNOT3	CNOT3	CNOT3	7417	0.04	0.43	YES
36	DCP1B	DCP1B	DCP1B	7470	0.039	0.43	YES
37	XRN2	XRN2	XRN2	7497	0.039	0.44	YES
38	LSM1	LSM1	LSM1	7562	0.037	0.44	YES
39	CNOT1	CNOT1	CNOT1	7866	0.029	0.43	NO
40	CNOT10	CNOT10	CNOT10	8219	0.02	0.41	NO
41	EXOSC5	EXOSC5	EXOSC5	8334	0.017	0.41	NO
42	EXOSC6	EXOSC6	EXOSC6	8722	0.0076	0.39	NO
43	PNPT1	PNPT1	PNPT1	8864	0.0043	0.38	NO
44	DIS3	DIS3	DIS3	8940	0.0022	0.38	NO
45	PAPOLA	PAPOLA	PAPOLA	9267	-0.0073	0.36	NO
46	TTC37	TTC37	TTC37	9756	-0.021	0.34	NO
47	WDR61	WDR61	WDR61	10148	-0.031	0.32	NO
48	ZCCHC7	ZCCHC7	ZCCHC7	10234	-0.033	0.32	NO
49	EDC3	EDC3	EDC3	10476	-0.04	0.32	NO
50	CNOT7	CNOT7	CNOT7	10772	-0.049	0.31	NO
51	CNOT2	CNOT2	CNOT2	10893	-0.052	0.31	NO
52	DCP2	DCP2	DCP2	11273	-0.063	0.3	NO
53	CNOT4	CNOT4	CNOT4	12053	-0.087	0.28	NO
54	DDX6	DDX6	DDX6	13961	-0.15	0.2	NO
55	CNOT6L	CNOT6L	CNOT6L	14191	-0.16	0.21	NO
56	XRN1	XRN1	XRN1	16188	-0.26	0.15	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 AMINOACYL TRNA BIOSYNTHESIS.

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

genes ES table in pathway: KEGG RIBOSOME

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	RNASEH2B	RNASEH2B	RNASEH2B	2101	0.26	-0.049	YES
2	RPA3	RPA3	RPA3	2357	0.24	-0.0068	YES
3	RFC2	RFC2	RFC2	2516	0.23	0.038	YES
4	RFC5	RFC5	RFC5	2597	0.22	0.085	YES
5	PRIM1	PRIM1	PRIM1	2825	0.21	0.12	YES
6	MCM4	MCM4	MCM4	2858	0.21	0.17	YES
7	RNASEH1	RNASEH1	RNASEH1	3159	0.19	0.2	YES
8	RFC3	RFC3	RFC3	3377	0.18	0.22	YES
9	RFC4	RFC4	RFC4	3467	0.17	0.26	YES
10	POLE4	POLE4	POLE4	3470	0.17	0.3	YES
11	SSBP1	SSBP1	SSBP1	3499	0.17	0.34	YES
12	MCM2	MCM2	MCM2	3699	0.16	0.36	YES
13	POLA2	POLA2	POLA2	3815	0.16	0.4	YES
14	RNASEH2A	RNASEH2A	RNASEH2A	4572	0.13	0.38	YES
15	PRIM2	PRIM2	PRIM2	4712	0.12	0.4	YES
16	DNA2	DNA2	DNA2	4763	0.12	0.43	YES
17	RPA2	RPA2	RPA2	4829	0.12	0.45	YES
18	PCNA	PCNA	PCNA	4978	0.11	0.47	YES
19	RNASEH2C	RNASEH2C	RNASEH2C	5229	0.1	0.48	YES
20	MCM7	MCM7	MCM7	5319	0.099	0.5	YES
21	MCM6	MCM6	MCM6	5365	0.097	0.52	YES
22	FEN1	FEN1	FEN1	5572	0.091	0.53	YES
23	POLD1	POLD1	POLD1	5855	0.084	0.54	YES
24	POLD2	POLD2	POLD2	6036	0.078	0.54	YES
25	MCM3	MCM3	MCM3	6351	0.069	0.54	YES
26	MCM5	MCM5	MCM5	6494	0.065	0.55	YES
27	POLE2	POLE2	POLE2	9365	-0.01	0.4	NO
28	RFC1	RFC1	RFC1	9649	-0.018	0.39	NO
29	POLE	POLE	POLE	9836	-0.023	0.39	NO
30	POLD3	POLD3	POLD3	10085	-0.03	0.38	NO
31	POLE3	POLE3	POLE3	10110	-0.03	0.39	NO
32	POLD4	POLD4	POLD4	11674	-0.075	0.32	NO
33	RPA4	RPA4	RPA4	11676	-0.075	0.34	NO
34	LIG1	LIG1	LIG1	12310	-0.095	0.33	NO
35	RPA1	RPA1	RPA1	12955	-0.12	0.32	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 RIBOSOME.

Figure S38. 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 RNA 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	CCNA1	CCNA1	CCNA1	70	1.2	0.054	YES
2	GADD45A	GADD45A	GADD45A	543	0.6	0.058	YES
3	MAD2L2	MAD2L2	MAD2L2	651	0.56	0.08	YES
4	ORC1L	ORC1L	ORC1L	772	0.51	0.098	YES
5	CDC20	CDC20	CDC20	1178	0.4	0.096	YES
6	CCNE1	CCNE1	CCNE1	1230	0.39	0.11	YES
7	SFN	SFN	SFN	1263	0.38	0.13	YES
8	CDC6	CDC6	CDC6	1354	0.36	0.14	YES
9	MAD2L1	MAD2L1	MAD2L1	1385	0.36	0.16	YES
10	CDKN1C	CDKN1C	CDKN1C	1394	0.36	0.18	YES
11	PLK1	PLK1	PLK1	1513	0.34	0.19	YES
12	CDK6	CDK6	CDK6	1584	0.32	0.2	YES
13	MYC	MYC	MYC	1721	0.31	0.21	YES
14	CCNA2	CCNA2	CCNA2	1769	0.3	0.22	YES
15	CDKN1A	CDKN1A	CDKN1A	2051	0.27	0.22	YES
16	GADD45B	GADD45B	GADD45B	2061	0.27	0.23	YES
17	CCND1	CCND1	CCND1	2095	0.26	0.24	YES
18	CCND3	CCND3	CCND3	2109	0.26	0.25	YES
19	CDC25C	CDC25C	CDC25C	2273	0.25	0.26	YES
20	E2F5	E2F5	E2F5	2300	0.25	0.27	YES
21	PTTG1	PTTG1	PTTG1	2321	0.24	0.28	YES
22	HDAC1	HDAC1	HDAC1	2395	0.24	0.28	YES
23	CCNB1	CCNB1	CCNB1	2468	0.23	0.29	YES
24	CDK7	CDK7	CDK7	2619	0.22	0.3	YES
25	CDC25A	CDC25A	CDC25A	2620	0.22	0.3	YES
26	CDK1	CDK1	CDK1	2642	0.22	0.32	YES
27	TFDP2	TFDP2	TFDP2	2744	0.21	0.32	YES
28	MCM4	MCM4	MCM4	2858	0.21	0.32	YES
29	CDC26	CDC26	CDC26	3105	0.19	0.32	YES
30	CDC16	CDC16	CDC16	3457	0.17	0.31	YES
31	ANAPC11	ANAPC11	ANAPC11	3576	0.17	0.31	YES
32	ORC6L	ORC6L	ORC6L	3643	0.16	0.32	YES
33	ORC4L	ORC4L	ORC4L	3694	0.16	0.32	YES
34	MCM2	MCM2	MCM2	3699	0.16	0.33	YES
35	PKMYT1	PKMYT1	PKMYT1	3748	0.16	0.34	YES
36	YWHAH	YWHAH	YWHAH	3882	0.15	0.34	YES
37	CHEK2	CHEK2	CHEK2	4058	0.15	0.33	YES
38	CCNB2	CCNB2	CCNB2	4190	0.14	0.33	YES
39	SKP2	SKP2	SKP2	4232	0.14	0.34	YES
40	E2F4	E2F4	E2F4	4318	0.14	0.34	YES
41	CHEK1	CHEK1	CHEK1	4393	0.13	0.34	YES
42	MDM2	MDM2	MDM2	4565	0.13	0.34	YES
43	TFDP1	TFDP1	TFDP1	4614	0.12	0.34	YES
44	BUB1	BUB1	BUB1	4694	0.12	0.34	YES
45	CDC45	CDC45	CDC45	4965	0.11	0.34	YES
46	HDAC2	HDAC2	HDAC2	4976	0.11	0.34	YES
47	PCNA	PCNA	PCNA	4978	0.11	0.35	YES
48	E2F3	E2F3	E2F3	5106	0.11	0.34	YES
49	SMAD4	SMAD4	SMAD4	5210	0.1	0.34	YES
50	YWHAE	YWHAE	YWHAE	5214	0.1	0.35	YES
51	MCM7	MCM7	MCM7	5319	0.099	0.35	YES
52	MCM6	MCM6	MCM6	5365	0.097	0.35	YES
53	ANAPC5	ANAPC5	ANAPC5	5525	0.092	0.35	YES
54	CUL1	CUL1	CUL1	5548	0.092	0.35	YES
55	SKP1	SKP1	SKP1	5584	0.091	0.35	YES
56	ANAPC10	ANAPC10	ANAPC10	5643	0.089	0.35	YES
57	STAG2	STAG2	STAG2	5838	0.084	0.35	NO
58	CCNH	CCNH	CCNH	6016	0.079	0.34	NO
59	PRKDC	PRKDC	PRKDC	6017	0.079	0.35	NO
60	YWHAZ	YWHAZ	YWHAZ	6048	0.078	0.35	NO
61	TP53	TP53	TP53	6112	0.076	0.35	NO
62	MCM3	MCM3	MCM3	6351	0.069	0.34	NO
63	MCM5	MCM5	MCM5	6494	0.065	0.34	NO
64	E2F1	E2F1	E2F1	6586	0.063	0.33	NO
65	MAD1L1	MAD1L1	MAD1L1	6815	0.056	0.32	NO
66	ANAPC1	ANAPC1	ANAPC1	6826	0.056	0.33	NO
67	CDKN1B	CDKN1B	CDKN1B	7161	0.047	0.31	NO
68	CDK4	CDK4	CDK4	7242	0.045	0.31	NO
69	BUB3	BUB3	BUB3	7269	0.044	0.31	NO
70	TTK	TTK	TTK	7451	0.04	0.3	NO
71	ORC2L	ORC2L	ORC2L	7484	0.039	0.3	NO
72	ESPL1	ESPL1	ESPL1	7549	0.037	0.3	NO
73	SMC1A	SMC1A	SMC1A	7572	0.037	0.3	NO
74	YWHAQ	YWHAQ	YWHAQ	7574	0.037	0.3	NO
75	CDKN2D	CDKN2D	CDKN2D	7715	0.033	0.3	NO
76	CDC23	CDC23	CDC23	8034	0.025	0.28	NO
77	CDC7	CDC7	CDC7	8233	0.02	0.27	NO
78	CDC27	CDC27	CDC27	8252	0.019	0.27	NO
79	GADD45G	GADD45G	GADD45G	8595	0.011	0.25	NO
80	FZR1	FZR1	FZR1	9132	-0.0033	0.23	NO
81	SMC3	SMC3	SMC3	9231	-0.0064	0.22	NO
82	YWHAB	YWHAB	YWHAB	9302	-0.0082	0.22	NO
83	YWHAG	YWHAG	YWHAG	9325	-0.0089	0.22	NO
84	ZBTB17	ZBTB17	ZBTB17	9337	-0.0093	0.22	NO
85	RBX1	RBX1	RBX1	9741	-0.02	0.2	NO
86	ORC5L	ORC5L	ORC5L	9990	-0.027	0.18	NO
87	RAD21	RAD21	RAD21	9996	-0.027	0.19	NO
88	EP300	EP300	EP300	10453	-0.039	0.16	NO
89	CDC14B	CDC14B	CDC14B	10833	-0.05	0.15	NO
90	CCNB3	CCNB3	CCNB3	10849	-0.051	0.15	NO
91	ANAPC2	ANAPC2	ANAPC2	11090	-0.058	0.14	NO
92	SMAD2	SMAD2	SMAD2	11119	-0.058	0.14	NO
93	TGFB3	TGFB3	TGFB3	11122	-0.058	0.14	NO
94	TGFB2	TGFB2	TGFB2	11134	-0.059	0.14	NO
95	STAG1	STAG1	STAG1	11161	-0.06	0.15	NO
96	PTTG2	PTTG2	PTTG2	11252	-0.062	0.14	NO
97	BUB1B	BUB1B	BUB1B	11316	-0.065	0.14	NO
98	ORC3L	ORC3L	ORC3L	11470	-0.069	0.14	NO
99	CDC25B	CDC25B	CDC25B	11626	-0.074	0.14	NO
100	ANAPC13	ANAPC13	ANAPC13	12084	-0.088	0.12	NO
101	TGFB1	TGFB1	TGFB1	12113	-0.088	0.12	NO
102	CREBBP	CREBBP	CREBBP	12148	-0.09	0.12	NO
103	WEE1	WEE1	WEE1	12481	-0.1	0.11	NO
104	GSK3B	GSK3B	GSK3B	12628	-0.1	0.1	NO
105	RBL1	RBL1	RBL1	12788	-0.11	0.1	NO
106	E2F2	E2F2	E2F2	12948	-0.12	0.1	NO
107	ANAPC7	ANAPC7	ANAPC7	13017	-0.12	0.1	NO
108	CDK2	CDK2	CDK2	13789	-0.14	0.068	NO
109	ABL1	ABL1	ABL1	14305	-0.17	0.049	NO
110	ANAPC4	ANAPC4	ANAPC4	14408	-0.17	0.052	NO
111	CCND2	CCND2	CCND2	14850	-0.19	0.038	NO
112	ATM	ATM	ATM	15073	-0.2	0.036	NO
113	SMAD3	SMAD3	SMAD3	15632	-0.23	0.017	NO
114	RB1	RB1	RB1	15675	-0.23	0.026	NO
115	WEE2	WEE2	WEE2	16308	-0.27	0.0064	NO
116	ATR	ATR	ATR	16388	-0.28	0.016	NO
117	CDC14A	CDC14A	CDC14A	16550	-0.29	0.022	NO
118	CDKN2A	CDKN2A	CDKN2A	16643	-0.3	0.031	NO
119	RBL2	RBL2	RBL2	17154	-0.34	0.021	NO
120	CCNE2	CCNE2	CCNE2	17204	-0.34	0.035	NO
121	SMC1B	SMC1B	SMC1B	17306	-0.36	0.047	NO
122	CDKN2C	CDKN2C	CDKN2C	17493	-0.38	0.056	NO
123	CDKN2B	CDKN2B	CDKN2B	18388	-0.55	0.035	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 RNA DEGRADATION.

Figure S40. 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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA NO1 PATHWAY	29	genes.ES.table	0.58	1.5	0.046	0.67	0.89	0.41	0.16	0.35	0.45	0.23
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.51	1.4	0.066	0.61	0.89	0.4	0.27	0.29	0.42	0.19
BIOCARTA ALK PATHWAY	36	genes.ES.table	0.65	1.6	0	1	0.54	0.39	0.2	0.31	0.51	0.36
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.55	1.8	0.002	0.78	0.28	0.19	0.15	0.16	0	0.22
BIOCARTA BIOPEPTIDES PATHWAY	41	genes.ES.table	0.48	1.6	0.019	1	0.68	0.29	0.23	0.22	0.78	0.42
BIOCARTA MYOSIN PATHWAY	30	genes.ES.table	0.5	1.5	0.039	0.87	0.8	0.37	0.24	0.28	0.53	0.3
BIOCARTA CHREBP2 PATHWAY	41	genes.ES.table	0.38	1.4	0.091	0.54	0.9	0.12	0.09	0.11	0.38	0.16
KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM	31	genes.ES.table	0.53	1.5	0.084	0.64	0.89	0.36	0.23	0.27	0.43	0.22
KEGG DRUG METABOLISM OTHER ENZYMES	40	genes.ES.table	0.58	1.5	0.042	0.9	0.87	0.42	0.21	0.34	0.6	0.33
KEGG WNT SIGNALING PATHWAY	149	genes.ES.table	0.44	1.4	0.042	0.55	0.89	0.29	0.21	0.23	0.39	0.17

genes ES table in pathway: BIOCARTA NO1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AGT	AGT	AGT	27	1.5	0.23	YES
2	AGTR1	AGTR1	AGTR1	1112	0.78	0.29	YES
3	EGFR	EGFR	EGFR	1637	0.65	0.36	YES
4	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	1892	0.6	0.44	YES
5	JUN	JUN	JUN	1991	0.59	0.52	YES
6	PRKCA	PRKCA	PRKCA	2877	0.45	0.55	YES
7	SRC	SRC	SRC	4643	0.26	0.49	NO
8	SHC1	SHC1	SHC1	6405	0.14	0.42	NO
9	MAPK3	MAPK3	MAPK3	7027	0.11	0.41	NO
10	MAPK8	MAPK8	MAPK8	7093	0.11	0.42	NO
11	MAP2K4	MAP2K4	MAP2K4	7177	0.1	0.43	NO
12	MEF2A	MEF2A	MEF2A	7283	0.098	0.44	NO
13	SOS1	SOS1	SOS1	7574	0.086	0.44	NO
14	CALM3	CALM3	CALM3	7597	0.085	0.45	NO
15	HRAS	HRAS	HRAS	8209	0.061	0.43	NO
16	PTK2B	PTK2B	PTK2B	8650	0.044	0.41	NO
17	ATF2	ATF2	ATF2	9345	0.02	0.38	NO
18	CALM1	CALM1	CALM1	9354	0.019	0.38	NO
19	ELK1	ELK1	ELK1	9533	0.014	0.37	NO
20	PAK1	PAK1	PAK1	9702	0.0083	0.36	NO
21	GNAQ	GNAQ	GNAQ	10375	-0.013	0.33	NO
22	GRB2	GRB2	GRB2	10416	-0.014	0.33	NO
23	MAP3K1	MAP3K1	MAP3K1	10885	-0.028	0.31	NO
24	RAC1	RAC1	RAC1	10891	-0.028	0.32	NO
25	CALM2	CALM2	CALM2	10948	-0.03	0.32	NO
26	RAF1	RAF1	RAF1	11249	-0.039	0.31	NO
27	MEF2D	MEF2D	MEF2D	11280	-0.04	0.31	NO
28	PTK2	PTK2	PTK2	11282	-0.04	0.32	NO
29	MAP2K2	MAP2K2	MAP2K2	11743	-0.053	0.3	NO
30	MAP2K1	MAP2K1	MAP2K1	12422	-0.073	0.28	NO
31	MAPK1	MAPK1	MAPK1	14349	-0.14	0.2	NO
32	PRKCB	PRKCB	PRKCB	17060	-0.33	0.1	NO

Figure S41. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA NO1 PATHWAY.

Figure S42. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NO1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA AGR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	BMP5	BMP5	BMP5	3	1.8	0.14	YES
2	HNF1A	HNF1A	HNF1A	58	1.4	0.24	YES
3	TGFB2	TGFB2	TGFB2	85	1.3	0.34	YES
4	BMP2	BMP2	BMP2	358	1	0.4	YES
5	NOG	NOG	NOG	882	0.84	0.44	YES
6	BMP4	BMP4	BMP4	1144	0.76	0.48	YES
7	FZD1	FZD1	FZD1	1537	0.67	0.51	YES
8	NKX2-5	NKX2-5	NKX2-5	1769	0.62	0.55	YES
9	BMP7	BMP7	BMP7	2087	0.57	0.57	YES
10	TGFB3	TGFB3	TGFB3	2501	0.51	0.59	YES
11	CHRD	CHRD	CHRD	2828	0.46	0.61	YES
12	SMAD6	SMAD6	SMAD6	2966	0.44	0.63	YES
13	SMAD1	SMAD1	SMAD1	3428	0.38	0.64	YES
14	TGFBR2	TGFBR2	TGFBR2	3722	0.35	0.65	YES
15	CTNNB1	CTNNB1	CTNNB1	4402	0.29	0.63	NO
16	SMAD4	SMAD4	SMAD4	5033	0.23	0.62	NO
17	NPPB	NPPB	NPPB	5135	0.22	0.63	NO
18	MYL2	MYL2	MYL2	5994	0.16	0.6	NO
19	TGFBR3	TGFBR3	TGFBR3	6084	0.16	0.6	NO
20	BMPR2	BMPR2	BMPR2	6417	0.14	0.6	NO
21	TGFB1	TGFB1	TGFB1	7215	0.1	0.56	NO
22	SMAD5	SMAD5	SMAD5	7920	0.071	0.53	NO
23	WNT1	WNT1	WNT1	8107	0.065	0.52	NO
24	BMPR1A	BMPR1A	BMPR1A	8198	0.061	0.52	NO
25	APC	APC	APC	8495	0.05	0.51	NO
26	GSK3B	GSK3B	GSK3B	8891	0.036	0.5	NO
27	ATF2	ATF2	ATF2	9345	0.02	0.47	NO
28	TGFBR1	TGFBR1	TGFBR1	9586	0.012	0.46	NO
29	AXIN1	AXIN1	AXIN1	10367	-0.013	0.42	NO
30	RFC1	RFC1	RFC1	10517	-0.017	0.42	NO
31	NPPA	NPPA	NPPA	10867	-0.027	0.4	NO
32	GATA4	GATA4	GATA4	11517	-0.047	0.37	NO
33	ACVR1	ACVR1	ACVR1	12155	-0.065	0.34	NO
34	DVL1	DVL1	DVL1	13235	-0.099	0.29	NO
35	BMP10	BMP10	BMP10	13282	-0.1	0.3	NO
36	MAP3K7	MAP3K7	MAP3K7	13555	-0.11	0.29	NO

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

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

genes ES table in pathway: BIOCARTA ALK PATHWAY

Table S23. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AGT	AGT	AGT	27	1.5	0.15	YES
2	AGTR2	AGTR2	AGTR2	321	1.1	0.25	YES
3	CAMK2B	CAMK2B	CAMK2B	1465	0.68	0.26	YES
4	F2	F2	F2	2387	0.52	0.26	YES
5	MYLK	MYLK	MYLK	2587	0.49	0.3	YES
6	GNAI1	GNAI1	GNAI1	2830	0.46	0.34	YES
7	PRKCA	PRKCA	PRKCA	2877	0.45	0.38	YES
8	MAPT	MAPT	MAPT	3184	0.41	0.41	YES
9	GNGT1	GNGT1	GNGT1	3658	0.36	0.42	YES
10	CAMK2D	CAMK2D	CAMK2D	3803	0.34	0.45	YES
11	CAMK2A	CAMK2A	CAMK2A	3860	0.34	0.48	YES
12	STAT6	STAT6	STAT6	4412	0.29	0.48	YES
13	GNA11	GNA11	GNA11	4903	0.24	0.48	NO
14	MAPK14	MAPK14	MAPK14	6050	0.16	0.44	NO
15	SHC1	SHC1	SHC1	6405	0.14	0.44	NO
16	MAPK3	MAPK3	MAPK3	7027	0.11	0.41	NO
17	MAPK8	MAPK8	MAPK8	7093	0.11	0.42	NO
18	SOS1	SOS1	SOS1	7574	0.086	0.4	NO
19	CALM3	CALM3	CALM3	7597	0.085	0.41	NO
20	PTK2B	PTK2B	PTK2B	8650	0.044	0.36	NO
21	PLCG1	PLCG1	PLCG1	8791	0.04	0.36	NO
22	GNB1	GNB1	GNB1	9029	0.031	0.35	NO
23	STAT3	STAT3	STAT3	9056	0.03	0.35	NO
24	FYN	FYN	FYN	9215	0.025	0.35	NO
25	CALM1	CALM1	CALM1	9354	0.019	0.34	NO
26	STAT2	STAT2	STAT2	10186	-0.0078	0.3	NO
27	STAT5B	STAT5B	STAT5B	10303	-0.011	0.29	NO
28	GRB2	GRB2	GRB2	10416	-0.014	0.29	NO
29	CAMK2G	CAMK2G	CAMK2G	10642	-0.021	0.28	NO
30	CALM2	CALM2	CALM2	10948	-0.03	0.27	NO
31	RAF1	RAF1	RAF1	11249	-0.039	0.25	NO
32	JAK2	JAK2	JAK2	11735	-0.053	0.23	NO
33	MAP2K2	MAP2K2	MAP2K2	11743	-0.053	0.24	NO
34	STAT5A	STAT5A	STAT5A	12206	-0.067	0.22	NO
35	MAP2K1	MAP2K1	MAP2K1	12422	-0.073	0.22	NO
36	STAT1	STAT1	STAT1	13413	-0.11	0.18	NO
37	MAPK1	MAPK1	MAPK1	14349	-0.14	0.14	NO
38	CDK5	CDK5	CDK5	15342	-0.19	0.11	NO
39	STAT4	STAT4	STAT4	15601	-0.2	0.12	NO
40	KNG1	KNG1	KNG1	16699	-0.29	0.089	NO
41	PRKCB	PRKCB	PRKCB	17060	-0.33	0.1	NO

Figure S45. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA ALK PATHWAY.

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

genes ES table in pathway: BIOCARTA AT1R PATHWAY

Table S24. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	BMP5	BMP5	BMP5	3	1.8	0.064	YES
2	PITX2	PITX2	PITX2	73	1.4	0.11	YES
3	TGFB2	TGFB2	TGFB2	85	1.3	0.15	YES
4	BMP2	BMP2	BMP2	358	1	0.18	YES
5	GDF6	GDF6	GDF6	423	1	0.21	YES
6	FST	FST	FST	516	0.98	0.24	YES
7	GDF7	GDF7	GDF7	743	0.88	0.26	YES
8	GDF5	GDF5	GDF5	1115	0.78	0.26	YES
9	BMP4	BMP4	BMP4	1144	0.76	0.29	YES
10	INHBA	INHBA	INHBA	1335	0.71	0.3	YES
11	DCN	DCN	DCN	1416	0.7	0.32	YES
12	ID2	ID2	ID2	1868	0.61	0.32	YES
13	LTBP1	LTBP1	LTBP1	1886	0.6	0.34	YES
14	INHBB	INHBB	INHBB	1919	0.6	0.36	YES
15	ID3	ID3	ID3	1920	0.6	0.38	YES
16	BMP7	BMP7	BMP7	2087	0.57	0.39	YES
17	AMH	AMH	AMH	2209	0.55	0.41	YES
18	BMP8B	BMP8B	BMP8B	2224	0.55	0.42	YES
19	THBS1	THBS1	THBS1	2313	0.53	0.44	YES
20	TGFB3	TGFB3	TGFB3	2501	0.51	0.45	YES
21	CDKN2B	CDKN2B	CDKN2B	2579	0.49	0.46	YES
22	THBS3	THBS3	THBS3	2600	0.49	0.48	YES
23	INHBC	INHBC	INHBC	2717	0.47	0.49	YES
24	ID1	ID1	ID1	2735	0.47	0.5	YES
25	CHRD	CHRD	CHRD	2828	0.46	0.51	YES
26	AMHR2	AMHR2	AMHR2	2945	0.44	0.52	YES
27	SMAD6	SMAD6	SMAD6	2966	0.44	0.54	YES
28	SMAD1	SMAD1	SMAD1	3428	0.38	0.53	YES
29	BMPR1B	BMPR1B	BMPR1B	3577	0.37	0.53	YES
30	TGFBR2	TGFBR2	TGFBR2	3722	0.35	0.54	YES
31	LEFTY2	LEFTY2	LEFTY2	3779	0.34	0.55	YES
32	INHBE	INHBE	INHBE	3933	0.33	0.55	YES
33	ACVR2A	ACVR2A	ACVR2A	4030	0.32	0.55	YES
34	ACVRL1	ACVRL1	ACVRL1	4226	0.3	0.56	YES
35	THBS4	THBS4	THBS4	4351	0.29	0.56	YES
36	THBS2	THBS2	THBS2	4462	0.28	0.56	YES
37	SMAD9	SMAD9	SMAD9	4514	0.28	0.57	YES
38	BMP6	BMP6	BMP6	4543	0.27	0.58	YES
39	SMAD4	SMAD4	SMAD4	5033	0.23	0.56	NO
40	SMAD7	SMAD7	SMAD7	5308	0.21	0.55	NO
41	COMP	COMP	COMP	5369	0.2	0.56	NO
42	ROCK2	ROCK2	ROCK2	5538	0.2	0.56	NO
43	LEFTY1	LEFTY1	LEFTY1	5944	0.17	0.54	NO
44	BMPR2	BMPR2	BMPR2	6417	0.14	0.52	NO
45	E2F5	E2F5	E2F5	6563	0.13	0.52	NO
46	MAPK3	MAPK3	MAPK3	7027	0.11	0.5	NO
47	ZFYVE16	ZFYVE16	ZFYVE16	7194	0.1	0.49	NO
48	TGFB1	TGFB1	TGFB1	7215	0.1	0.49	NO
49	SMAD3	SMAD3	SMAD3	7385	0.094	0.49	NO
50	TFDP1	TFDP1	TFDP1	7565	0.086	0.48	NO
51	MYC	MYC	MYC	7829	0.075	0.47	NO
52	SMAD5	SMAD5	SMAD5	7920	0.071	0.47	NO
53	RBL2	RBL2	RBL2	8048	0.067	0.46	NO
54	BMPR1A	BMPR1A	BMPR1A	8198	0.061	0.46	NO
55	SMURF1	SMURF1	SMURF1	8471	0.051	0.44	NO
56	CREBBP	CREBBP	CREBBP	8684	0.043	0.44	NO
57	ACVR1C	ACVR1C	ACVR1C	8859	0.037	0.43	NO
58	RHOA	RHOA	RHOA	9233	0.024	0.41	NO
59	ROCK1	ROCK1	ROCK1	9425	0.018	0.4	NO
60	TGFBR1	TGFBR1	TGFBR1	9586	0.012	0.39	NO
61	SMAD2	SMAD2	SMAD2	9597	0.012	0.39	NO
62	RPS6KB2	RPS6KB2	RPS6KB2	9598	0.012	0.39	NO
63	PPP2CB	PPP2CB	PPP2CB	9612	0.011	0.39	NO
64	SMURF2	SMURF2	SMURF2	10097	-0.0045	0.37	NO
65	SKP1	SKP1	SKP1	10219	-0.0088	0.36	NO
66	SP1	SP1	SP1	10338	-0.012	0.35	NO
67	BMP8A	BMP8A	BMP8A	10469	-0.016	0.35	NO
68	RPS6KB1	RPS6KB1	RPS6KB1	10584	-0.019	0.34	NO
69	PPP2R1A	PPP2R1A	PPP2R1A	10929	-0.029	0.32	NO
70	PPP2CA	PPP2CA	PPP2CA	11607	-0.049	0.29	NO
71	E2F4	E2F4	E2F4	11841	-0.056	0.28	NO
72	ACVR1	ACVR1	ACVR1	12155	-0.065	0.27	NO
73	ID4	ID4	ID4	13167	-0.097	0.22	NO
74	RBL1	RBL1	RBL1	13928	-0.12	0.18	NO
75	EP300	EP300	EP300	13964	-0.13	0.18	NO
76	PPP2R1B	PPP2R1B	PPP2R1B	13992	-0.13	0.19	NO
77	MAPK1	MAPK1	MAPK1	14349	-0.14	0.17	NO
78	RBX1	RBX1	RBX1	14408	-0.14	0.18	NO
79	CUL1	CUL1	CUL1	14457	-0.15	0.18	NO
80	ACVR2B	ACVR2B	ACVR2B	14633	-0.15	0.17	NO
81	ZFYVE9	ZFYVE9	ZFYVE9	15054	-0.17	0.16	NO
82	NODAL	NODAL	NODAL	16233	-0.25	0.1	NO
83	TNF	TNF	TNF	18113	-0.53	0.023	NO
84	IFNG	IFNG	IFNG	18662	-0.75	0.02	NO

Figure S47. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA AT1R PATHWAY.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AT1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA BIOPEPTIDES PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ITGB6	ITGB6	ITGB6	10	1.6	0.025	YES
2	TNN	TNN	TNN	164	1.2	0.036	YES
3	COL2A1	COL2A1	COL2A1	197	1.2	0.052	YES
4	MAPK10	MAPK10	MAPK10	239	1.1	0.067	YES
5	ITGB8	ITGB8	ITGB8	387	1	0.075	YES
6	MYL7	MYL7	MYL7	444	1	0.088	YES
7	RELN	RELN	RELN	595	0.94	0.095	YES
8	ITGA8	ITGA8	ITGA8	619	0.93	0.11	YES
9	HGF	HGF	HGF	640	0.92	0.12	YES
10	LAMB3	LAMB3	LAMB3	669	0.91	0.13	YES
11	COL4A6	COL4A6	COL4A6	711	0.89	0.14	YES
12	LAMB4	LAMB4	LAMB4	946	0.82	0.15	YES
13	ITGA10	ITGA10	ITGA10	962	0.82	0.16	YES
14	VTN	VTN	VTN	1016	0.8	0.17	YES
15	PDGFC	PDGFC	PDGFC	1031	0.8	0.18	YES
16	PDGFRA	PDGFRA	PDGFRA	1183	0.76	0.18	YES
17	CCND1	CCND1	CCND1	1448	0.69	0.18	YES
18	COL5A2	COL5A2	COL5A2	1464	0.68	0.19	YES
19	COL11A2	COL11A2	COL11A2	1467	0.68	0.2	YES
20	CAV3	CAV3	CAV3	1473	0.68	0.21	YES
21	COL3A1	COL3A1	COL3A1	1483	0.68	0.22	YES
22	FIGF	FIGF	FIGF	1548	0.67	0.23	YES
23	PDGFD	PDGFD	PDGFD	1562	0.66	0.24	YES
24	EGFR	EGFR	EGFR	1637	0.65	0.24	YES
25	COL1A1	COL1A1	COL1A1	1705	0.64	0.25	YES
26	COL11A1	COL11A1	COL11A1	1751	0.63	0.26	YES
27	MYLK2	MYLK2	MYLK2	1765	0.62	0.26	YES
28	IBSP	IBSP	IBSP	1799	0.62	0.27	YES
29	JUN	JUN	JUN	1991	0.59	0.27	YES
30	FN1	FN1	FN1	1999	0.58	0.28	YES
31	ITGA2	ITGA2	ITGA2	2005	0.58	0.29	YES
32	MET	MET	MET	2061	0.58	0.3	YES
33	COL5A1	COL5A1	COL5A1	2064	0.57	0.3	YES
34	EGF	EGF	EGF	2117	0.56	0.31	YES
35	ITGA3	ITGA3	ITGA3	2136	0.56	0.32	YES
36	CAV2	CAV2	CAV2	2157	0.56	0.32	YES
37	PARVA	PARVA	PARVA	2169	0.56	0.33	YES
38	FLNC	FLNC	FLNC	2192	0.55	0.34	YES
39	KDR	KDR	KDR	2289	0.54	0.34	YES
40	THBS1	THBS1	THBS1	2313	0.53	0.35	YES
41	VEGFA	VEGFA	VEGFA	2451	0.51	0.35	YES
42	TNC	TNC	TNC	2523	0.5	0.36	YES
43	ITGA11	ITGA11	ITGA11	2542	0.5	0.36	YES
44	ITGA1	ITGA1	ITGA1	2564	0.5	0.37	YES
45	MYLK	MYLK	MYLK	2587	0.49	0.38	YES
46	THBS3	THBS3	THBS3	2600	0.49	0.38	YES
47	MYL10	MYL10	MYL10	2623	0.48	0.39	YES
48	LAMB2	LAMB2	LAMB2	2647	0.48	0.39	YES
49	COL6A3	COL6A3	COL6A3	2658	0.48	0.4	YES
50	SHC2	SHC2	SHC2	2686	0.48	0.41	YES
51	MYLPF	MYLPF	MYLPF	2741	0.47	0.41	YES
52	COL1A2	COL1A2	COL1A2	2793	0.46	0.42	YES
53	VEGFC	VEGFC	VEGFC	2848	0.46	0.42	YES
54	MYLK3	MYLK3	MYLK3	2872	0.45	0.43	YES
55	PRKCA	PRKCA	PRKCA	2877	0.45	0.43	YES
56	PDGFRB	PDGFRB	PDGFRB	2879	0.45	0.44	YES
57	PGF	PGF	PGF	2961	0.44	0.44	YES
58	FLT1	FLT1	FLT1	3008	0.43	0.45	YES
59	LAMB1	LAMB1	LAMB1	3037	0.43	0.45	YES
60	MYL9	MYL9	MYL9	3230	0.41	0.45	YES
61	COL6A2	COL6A2	COL6A2	3231	0.41	0.45	YES
62	PIK3R1	PIK3R1	PIK3R1	3252	0.4	0.46	YES
63	COL6A1	COL6A1	COL6A1	3298	0.4	0.46	YES
64	COL5A3	COL5A3	COL5A3	3363	0.39	0.47	YES
65	ITGA5	ITGA5	ITGA5	3399	0.38	0.47	YES
66	ITGAV	ITGAV	ITGAV	3414	0.38	0.48	YES
67	ERBB2	ERBB2	ERBB2	3499	0.37	0.48	YES
68	BCL2	BCL2	BCL2	3542	0.37	0.48	YES
69	LAMA2	LAMA2	LAMA2	3685	0.36	0.48	YES
70	CAPN2	CAPN2	CAPN2	3689	0.35	0.48	YES
71	CAV1	CAV1	CAV1	3723	0.35	0.49	YES
72	VWF	VWF	VWF	3727	0.35	0.49	YES
73	ITGA7	ITGA7	ITGA7	3804	0.34	0.49	YES
74	SOS2	SOS2	SOS2	3838	0.34	0.5	YES
75	LAMC3	LAMC3	LAMC3	3924	0.33	0.5	YES
76	LAMA4	LAMA4	LAMA4	3932	0.33	0.5	YES
77	LAMA3	LAMA3	LAMA3	3978	0.33	0.5	YES
78	LAMC2	LAMC2	LAMC2	3997	0.32	0.51	YES
79	BAD	BAD	BAD	4007	0.32	0.51	YES
80	VAV3	VAV3	VAV3	4163	0.31	0.51	YES
81	SHC4	SHC4	SHC4	4184	0.31	0.51	YES
82	COL4A1	COL4A1	COL4A1	4330	0.29	0.51	YES
83	THBS4	THBS4	THBS4	4351	0.29	0.51	YES
84	TNXB	TNXB	TNXB	4369	0.29	0.52	YES
85	CTNNB1	CTNNB1	CTNNB1	4402	0.29	0.52	YES
86	THBS2	THBS2	THBS2	4462	0.28	0.52	YES
87	VEGFB	VEGFB	VEGFB	4489	0.28	0.52	YES
88	COL4A2	COL4A2	COL4A2	4495	0.28	0.53	YES
89	SRC	SRC	SRC	4643	0.26	0.52	YES
90	ITGB4	ITGB4	ITGB4	4744	0.26	0.52	YES
91	PAK3	PAK3	PAK3	4746	0.26	0.53	YES
92	FLT4	FLT4	FLT4	4787	0.25	0.53	YES
93	PDGFB	PDGFB	PDGFB	4842	0.25	0.53	YES
94	DOCK1	DOCK1	DOCK1	4906	0.24	0.53	YES
95	BCAR1	BCAR1	BCAR1	4918	0.24	0.53	YES
96	ITGB3	ITGB3	ITGB3	5007	0.23	0.53	YES
97	CHAD	CHAD	CHAD	5008	0.23	0.54	YES
98	PAK7	PAK7	PAK7	5208	0.22	0.53	NO
99	TNR	TNR	TNR	5356	0.21	0.52	NO
100	COMP	COMP	COMP	5369	0.2	0.53	NO
101	ROCK2	ROCK2	ROCK2	5538	0.2	0.52	NO
102	AKT3	AKT3	AKT3	5541	0.2	0.52	NO
103	GRLF1	GRLF1	GRLF1	5605	0.19	0.52	NO
104	ITGB5	ITGB5	ITGB5	5886	0.17	0.51	NO
105	SPP1	SPP1	SPP1	5888	0.17	0.51	NO
106	MYL5	MYL5	MYL5	5908	0.17	0.52	NO
107	VCL	VCL	VCL	5943	0.17	0.52	NO
108	MYL2	MYL2	MYL2	5994	0.16	0.52	NO
109	AKT1	AKT1	AKT1	6171	0.15	0.51	NO
110	LAMA1	LAMA1	LAMA1	6274	0.15	0.51	NO
111	IGF1	IGF1	IGF1	6294	0.15	0.51	NO
112	ILK	ILK	ILK	6305	0.15	0.51	NO
113	SHC1	SHC1	SHC1	6405	0.14	0.51	NO
114	PDPK1	PDPK1	PDPK1	6451	0.14	0.51	NO
115	COL4A4	COL4A4	COL4A4	6487	0.14	0.51	NO
116	PDGFA	PDGFA	PDGFA	6510	0.14	0.51	NO
117	LAMA5	LAMA5	LAMA5	6536	0.13	0.51	NO
118	FLNA	FLNA	FLNA	6614	0.13	0.51	NO
119	ITGA9	ITGA9	ITGA9	6730	0.12	0.5	NO
120	BIRC2	BIRC2	BIRC2	6740	0.12	0.5	NO
121	ARHGAP5	ARHGAP5	ARHGAP5	6926	0.11	0.5	NO
122	MAPK3	MAPK3	MAPK3	7027	0.11	0.49	NO
123	PAK6	PAK6	PAK6	7046	0.11	0.49	NO
124	MAPK8	MAPK8	MAPK8	7093	0.11	0.49	NO
125	CCND2	CCND2	CCND2	7372	0.094	0.48	NO
126	SOS1	SOS1	SOS1	7574	0.086	0.47	NO
127	MYL12B	MYL12B	MYL12B	7600	0.085	0.47	NO
128	TLN1	TLN1	TLN1	7760	0.078	0.46	NO
129	PARVB	PARVB	PARVB	7771	0.077	0.46	NO
130	PPP1R12A	PPP1R12A	PPP1R12A	7801	0.076	0.46	NO
131	ITGA4	ITGA4	ITGA4	7911	0.072	0.46	NO
132	MAPK9	MAPK9	MAPK9	8238	0.06	0.44	NO
133	ITGB1	ITGB1	ITGB1	8271	0.058	0.44	NO
134	PIK3CA	PIK3CA	PIK3CA	8393	0.054	0.43	NO
135	PPP1CB	PPP1CB	PPP1CB	8397	0.054	0.44	NO
136	AKT2	AKT2	AKT2	8444	0.052	0.43	NO
137	PIP5K1C	PIP5K1C	PIP5K1C	8535	0.049	0.43	NO
138	ACTG1	ACTG1	ACTG1	8889	0.036	0.41	NO
139	GSK3B	GSK3B	GSK3B	8891	0.036	0.41	NO
140	PAK4	PAK4	PAK4	9043	0.031	0.4	NO
141	PTEN	PTEN	PTEN	9141	0.027	0.4	NO
142	FYN	FYN	FYN	9215	0.025	0.4	NO
143	RHOA	RHOA	RHOA	9233	0.024	0.4	NO
144	SHC3	SHC3	SHC3	9369	0.019	0.39	NO
145	ACTN1	ACTN1	ACTN1	9375	0.019	0.39	NO
146	ROCK1	ROCK1	ROCK1	9425	0.018	0.39	NO
147	ELK1	ELK1	ELK1	9533	0.014	0.38	NO
148	RAP1A	RAP1A	RAP1A	9680	0.009	0.37	NO
149	PAK1	PAK1	PAK1	9702	0.0083	0.37	NO
150	LAMC1	LAMC1	LAMC1	9708	0.0082	0.37	NO
151	CDC42	CDC42	CDC42	9744	0.007	0.37	NO
152	PAK2	PAK2	PAK2	9820	0.0045	0.37	NO
153	ACTN4	ACTN4	ACTN4	10030	-0.0021	0.36	NO
154	PIK3R2	PIK3R2	PIK3R2	10039	-0.0024	0.36	NO
155	ACTB	ACTB	ACTB	10142	-0.006	0.35	NO
156	MYL12A	MYL12A	MYL12A	10212	-0.0085	0.35	NO
157	ACTN2	ACTN2	ACTN2	10261	-0.0098	0.34	NO
158	GRB2	GRB2	GRB2	10416	-0.014	0.34	NO
159	XIAP	XIAP	XIAP	10831	-0.026	0.31	NO
160	RAC1	RAC1	RAC1	10891	-0.028	0.31	NO
161	PPP1CC	PPP1CC	PPP1CC	11076	-0.034	0.3	NO
162	FLNB	FLNB	FLNB	11110	-0.034	0.3	NO
163	IGF1R	IGF1R	IGF1R	11150	-0.036	0.3	NO
164	RAF1	RAF1	RAF1	11249	-0.039	0.3	NO
165	CCND3	CCND3	CCND3	11267	-0.039	0.3	NO
166	PTK2	PTK2	PTK2	11282	-0.04	0.29	NO
167	CRK	CRK	CRK	11290	-0.04	0.3	NO
168	CRKL	CRKL	CRKL	11528	-0.047	0.28	NO
169	PPP1CA	PPP1CA	PPP1CA	11900	-0.058	0.26	NO
170	RAP1B	RAP1B	RAP1B	12027	-0.062	0.26	NO
171	PXN	PXN	PXN	12268	-0.068	0.25	NO
172	TLN2	TLN2	TLN2	12361	-0.071	0.24	NO
173	MAP2K1	MAP2K1	MAP2K1	12422	-0.073	0.24	NO
174	PIK3R5	PIK3R5	PIK3R5	12457	-0.074	0.24	NO
175	DIAPH1	DIAPH1	DIAPH1	12706	-0.082	0.23	NO
176	PIK3R3	PIK3R3	PIK3R3	13421	-0.11	0.19	NO
177	ZYX	ZYX	ZYX	13821	-0.12	0.17	NO
178	VASP	VASP	VASP	13929	-0.12	0.17	NO
179	PIK3CB	PIK3CB	PIK3CB	14057	-0.13	0.16	NO
180	MAPK1	MAPK1	MAPK1	14349	-0.14	0.15	NO
181	RAPGEF1	RAPGEF1	RAPGEF1	14738	-0.16	0.13	NO
182	COL6A6	COL6A6	COL6A6	14784	-0.16	0.13	NO
183	ITGA6	ITGA6	ITGA6	15333	-0.19	0.11	NO
184	RAC3	RAC3	RAC3	15794	-0.22	0.086	NO
185	ACTN3	ACTN3	ACTN3	15926	-0.22	0.082	NO
186	BRAF	BRAF	BRAF	16079	-0.23	0.078	NO
187	VAV2	VAV2	VAV2	16156	-0.24	0.078	NO
188	PARVG	PARVG	PARVG	16811	-0.3	0.048	NO
189	PRKCB	PRKCB	PRKCB	17060	-0.33	0.04	NO
190	RAC2	RAC2	RAC2	17111	-0.34	0.042	NO
191	BIRC3	BIRC3	BIRC3	17322	-0.37	0.036	NO
192	ITGB7	ITGB7	ITGB7	17388	-0.38	0.039	NO
193	RASGRF1	RASGRF1	RASGRF1	17398	-0.38	0.044	NO
194	PIK3CG	PIK3CG	PIK3CG	17452	-0.38	0.047	NO
195	PIK3CD	PIK3CD	PIK3CD	17796	-0.45	0.036	NO
196	VAV1	VAV1	VAV1	17982	-0.49	0.034	NO
197	ITGA2B	ITGA2B	ITGA2B	18389	-0.62	0.022	NO
198	PRKCG	PRKCG	PRKCG	18778	-0.84	0.014	NO

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

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

genes ES table in pathway: BIOCARTA MYOSIN PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SEMA3E	SEMA3E	SEMA3E	136	1.2	0.02	YES
2	SEMA3C	SEMA3C	SEMA3C	181	1.2	0.045	YES
3	EPHA3	EPHA3	EPHA3	187	1.2	0.07	YES
4	EFNA5	EFNA5	EFNA5	196	1.2	0.096	YES
5	SEMA3D	SEMA3D	SEMA3D	201	1.2	0.12	YES
6	NTN1	NTN1	NTN1	370	1	0.14	YES
7	SEMA5B	SEMA5B	SEMA5B	427	1	0.16	YES
8	UNC5C	UNC5C	UNC5C	536	0.97	0.17	YES
9	LRRC4C	LRRC4C	LRRC4C	746	0.88	0.18	YES
10	SEMA6D	SEMA6D	SEMA6D	754	0.88	0.2	YES
11	RHOD	RHOD	RHOD	799	0.86	0.22	YES
12	NTN3	NTN3	NTN3	801	0.86	0.24	YES
13	SLIT3	SLIT3	SLIT3	804	0.86	0.26	YES
14	SEMA5A	SEMA5A	SEMA5A	853	0.85	0.27	YES
15	SEMA3B	SEMA3B	SEMA3B	859	0.85	0.29	YES
16	SRGAP3	SRGAP3	SRGAP3	883	0.84	0.31	YES
17	SLIT2	SLIT2	SLIT2	1027	0.8	0.32	YES
18	EPHA4	EPHA4	EPHA4	1320	0.72	0.32	YES
19	EPHA2	EPHA2	EPHA2	1331	0.71	0.33	YES
20	EFNA1	EFNA1	EFNA1	1394	0.7	0.35	YES
21	PLXNB3	PLXNB3	PLXNB3	1456	0.69	0.36	YES
22	ROBO2	ROBO2	ROBO2	1655	0.65	0.36	YES
23	EFNA2	EFNA2	EFNA2	1714	0.64	0.37	YES
24	EFNB1	EFNB1	EFNB1	1755	0.63	0.38	YES
25	EPHB1	EPHB1	EPHB1	1875	0.61	0.39	YES
26	MET	MET	MET	2061	0.58	0.4	YES
27	ROBO3	ROBO3	ROBO3	2114	0.56	0.4	YES
28	EPHA5	EPHA5	EPHA5	2188	0.55	0.41	YES
29	SEMA3F	SEMA3F	SEMA3F	2230	0.55	0.42	YES
30	EFNB2	EFNB2	EFNB2	2259	0.54	0.43	YES
31	PPP3CA	PPP3CA	PPP3CA	2267	0.54	0.45	YES
32	EPHB2	EPHB2	EPHB2	2293	0.53	0.46	YES
33	CHP2	CHP2	CHP2	2434	0.52	0.46	YES
34	SEMA3G	SEMA3G	SEMA3G	2555	0.5	0.46	YES
35	UNC5A	UNC5A	UNC5A	2589	0.49	0.47	YES
36	NTN4	NTN4	NTN4	2643	0.48	0.48	YES
37	CFL2	CFL2	CFL2	2694	0.48	0.49	YES
38	ROBO1	ROBO1	ROBO1	2786	0.46	0.5	YES
39	GNAI1	GNAI1	GNAI1	2830	0.46	0.5	YES
40	UNC5B	UNC5B	UNC5B	2867	0.45	0.51	YES
41	EPHB3	EPHB3	EPHB3	2898	0.45	0.52	YES
42	PLXNA3	PLXNA3	PLXNA3	2977	0.44	0.53	YES
43	NFATC4	NFATC4	NFATC4	3028	0.43	0.53	YES
44	SEMA4G	SEMA4G	SEMA4G	3110	0.42	0.54	YES
45	PLXNB1	PLXNB1	PLXNB1	3139	0.42	0.55	YES
46	NRP1	NRP1	NRP1	3611	0.36	0.53	YES
47	DCC	DCC	DCC	3694	0.35	0.53	YES
48	RND1	RND1	RND1	3791	0.34	0.54	YES
49	EFNB3	EFNB3	EFNB3	3822	0.34	0.54	YES
50	EPHB6	EPHB6	EPHB6	4017	0.32	0.54	YES
51	EPHA7	EPHA7	EPHA7	4058	0.32	0.54	YES
52	PLXNA2	PLXNA2	PLXNA2	4081	0.32	0.55	YES
53	ABLIM1	ABLIM1	ABLIM1	4197	0.3	0.55	YES
54	SEMA3A	SEMA3A	SEMA3A	4277	0.3	0.55	YES
55	SLIT1	SLIT1	SLIT1	4477	0.28	0.55	NO
56	RGS3	RGS3	RGS3	4578	0.27	0.55	NO
57	UNC5D	UNC5D	UNC5D	4741	0.26	0.55	NO
58	PAK3	PAK3	PAK3	4746	0.26	0.55	NO
59	PLXNB2	PLXNB2	PLXNB2	4875	0.24	0.55	NO
60	SEMA6C	SEMA6C	SEMA6C	5018	0.23	0.55	NO
61	ARHGEF12	ARHGEF12	ARHGEF12	5196	0.22	0.54	NO
62	PAK7	PAK7	PAK7	5208	0.22	0.55	NO
63	NFATC2	NFATC2	NFATC2	5512	0.2	0.54	NO
64	ROCK2	ROCK2	ROCK2	5538	0.2	0.54	NO
65	NFAT5	NFAT5	NFAT5	5777	0.18	0.53	NO
66	EPHA6	EPHA6	EPHA6	5789	0.18	0.53	NO
67	PLXNA1	PLXNA1	PLXNA1	5851	0.18	0.53	NO
68	SEMA4F	SEMA4F	SEMA4F	5906	0.17	0.54	NO
69	CXCL12	CXCL12	CXCL12	6462	0.14	0.51	NO
70	SEMA4B	SEMA4B	SEMA4B	6936	0.11	0.49	NO
71	ABL1	ABL1	ABL1	7024	0.11	0.48	NO
72	MAPK3	MAPK3	MAPK3	7027	0.11	0.49	NO
73	PAK6	PAK6	PAK6	7046	0.11	0.49	NO
74	PLXNC1	PLXNC1	PLXNC1	7135	0.1	0.49	NO
75	ABLIM3	ABLIM3	ABLIM3	7193	0.1	0.48	NO
76	NFATC1	NFATC1	NFATC1	7365	0.094	0.48	NO
77	CXCR4	CXCR4	CXCR4	7544	0.087	0.47	NO
78	GNAI2	GNAI2	GNAI2	7926	0.071	0.45	NO
79	NRAS	NRAS	NRAS	7987	0.069	0.45	NO
80	SRGAP2	SRGAP2	SRGAP2	8237	0.06	0.44	NO
81	ITGB1	ITGB1	ITGB1	8271	0.058	0.44	NO
82	RASA1	RASA1	RASA1	8318	0.057	0.44	NO
83	PPP3CB	PPP3CB	PPP3CB	8733	0.042	0.42	NO
84	CFL1	CFL1	CFL1	8792	0.04	0.41	NO
85	GSK3B	GSK3B	GSK3B	8891	0.036	0.41	NO
86	EPHA1	EPHA1	EPHA1	8977	0.033	0.41	NO
87	PAK4	PAK4	PAK4	9043	0.031	0.4	NO
88	GNAI3	GNAI3	GNAI3	9127	0.027	0.4	NO
89	FYN	FYN	FYN	9215	0.025	0.4	NO
90	RHOA	RHOA	RHOA	9233	0.024	0.4	NO
91	ROCK1	ROCK1	ROCK1	9425	0.018	0.38	NO
92	DPYSL2	DPYSL2	DPYSL2	9508	0.015	0.38	NO
93	NFATC3	NFATC3	NFATC3	9602	0.012	0.38	NO
94	PAK1	PAK1	PAK1	9702	0.0083	0.37	NO
95	CDC42	CDC42	CDC42	9744	0.007	0.37	NO
96	PAK2	PAK2	PAK2	9820	0.0045	0.37	NO
97	SEMA6B	SEMA6B	SEMA6B	9940	0.00063	0.36	NO
98	NCK2	NCK2	NCK2	10357	-0.012	0.34	NO
99	SEMA7A	SEMA7A	SEMA7A	10591	-0.019	0.33	NO
100	NCK1	NCK1	NCK1	10851	-0.027	0.31	NO
101	RAC1	RAC1	RAC1	10891	-0.028	0.31	NO
102	KRAS	KRAS	KRAS	11036	-0.032	0.3	NO
103	L1CAM	L1CAM	L1CAM	11270	-0.039	0.29	NO
104	PTK2	PTK2	PTK2	11282	-0.04	0.29	NO
105	EFNA4	EFNA4	EFNA4	11526	-0.047	0.28	NO
106	PPP3R1	PPP3R1	PPP3R1	11682	-0.051	0.27	NO
107	FES	FES	FES	11696	-0.052	0.28	NO
108	ABLIM2	ABLIM2	ABLIM2	11844	-0.056	0.27	NO
109	NTNG1	NTNG1	NTNG1	12309	-0.069	0.24	NO
110	SEMA4C	SEMA4C	SEMA4C	12470	-0.075	0.24	NO
111	PPP3CC	PPP3CC	PPP3CC	13504	-0.11	0.19	NO
112	LIMK1	LIMK1	LIMK1	13857	-0.12	0.17	NO
113	EFNA3	EFNA3	EFNA3	13923	-0.12	0.17	NO
114	SEMA6A	SEMA6A	SEMA6A	14070	-0.13	0.16	NO
115	MAPK1	MAPK1	MAPK1	14349	-0.14	0.15	NO
116	DPYSL5	DPYSL5	DPYSL5	14588	-0.15	0.14	NO
117	LIMK2	LIMK2	LIMK2	15303	-0.19	0.11	NO
118	CDK5	CDK5	CDK5	15342	-0.19	0.11	NO
119	EPHB4	EPHB4	EPHB4	15662	-0.21	0.1	NO
120	RAC3	RAC3	RAC3	15794	-0.22	0.099	NO
121	SEMA4D	SEMA4D	SEMA4D	16400	-0.26	0.072	NO
122	CHP	CHP	CHP	16545	-0.27	0.071	NO
123	SEMA4A	SEMA4A	SEMA4A	16609	-0.28	0.074	NO
124	SRGAP1	SRGAP1	SRGAP1	16765	-0.3	0.072	NO
125	RAC2	RAC2	RAC2	17111	-0.34	0.062	NO
126	PPP3R2	PPP3R2	PPP3R2	17217	-0.35	0.064	NO
127	EPHA8	EPHA8	EPHA8	18391	-0.62	0.016	NO
128	NGEF	NGEF	NGEF	18793	-0.85	0.014	NO

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

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

genes ES table in pathway: BIOCARTA CHREBP2 PATHWAY

Table 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	TGFB2	TGFB2	TGFB2	85	1.3	0.086	YES
2	ARNT2	ARNT2	ARNT2	305	1.1	0.15	YES
3	HGF	HGF	HGF	640	0.92	0.2	YES
4	FIGF	FIGF	FIGF	1548	0.67	0.19	YES
5	JUN	JUN	JUN	1991	0.59	0.21	YES
6	MET	MET	MET	2061	0.58	0.24	YES
7	VEGFA	VEGFA	VEGFA	2451	0.51	0.26	YES
8	TGFB3	TGFB3	TGFB3	2501	0.51	0.29	YES
9	TGFA	TGFA	TGFA	2660	0.48	0.32	YES
10	VEGFC	VEGFC	VEGFC	2848	0.46	0.34	YES
11	PGF	PGF	PGF	2961	0.44	0.36	YES
12	PIK3R1	PIK3R1	PIK3R1	3252	0.4	0.38	YES
13	EPAS1	EPAS1	EPAS1	3307	0.4	0.4	YES
14	SOS2	SOS2	SOS2	3838	0.34	0.39	YES
15	VEGFB	VEGFB	VEGFB	4489	0.28	0.38	YES
16	PAK3	PAK3	PAK3	4746	0.26	0.38	YES
17	PDGFB	PDGFB	PDGFB	4842	0.25	0.4	YES
18	PAK7	PAK7	PAK7	5208	0.22	0.39	YES
19	GAB1	GAB1	GAB1	5219	0.21	0.4	YES
20	AKT3	AKT3	AKT3	5541	0.2	0.4	NO
21	AKT1	AKT1	AKT1	6171	0.15	0.38	NO
22	EGLN3	EGLN3	EGLN3	6380	0.14	0.38	NO
23	ARAF	ARAF	ARAF	6872	0.12	0.36	NO
24	MAPK3	MAPK3	MAPK3	7027	0.11	0.36	NO
25	PAK6	PAK6	PAK6	7046	0.11	0.37	NO
26	VHL	VHL	VHL	7073	0.11	0.37	NO
27	ARNT	ARNT	ARNT	7078	0.11	0.38	NO
28	TGFB1	TGFB1	TGFB1	7215	0.1	0.38	NO
29	SOS1	SOS1	SOS1	7574	0.086	0.37	NO
30	EGLN1	EGLN1	EGLN1	7589	0.085	0.37	NO
31	NRAS	NRAS	NRAS	7987	0.069	0.36	NO
32	FLCN	FLCN	FLCN	8023	0.068	0.36	NO
33	SLC2A1	SLC2A1	SLC2A1	8310	0.057	0.35	NO
34	PIK3CA	PIK3CA	PIK3CA	8393	0.054	0.35	NO
35	ETS1	ETS1	ETS1	8443	0.052	0.35	NO
36	AKT2	AKT2	AKT2	8444	0.052	0.35	NO
37	CREBBP	CREBBP	CREBBP	8684	0.043	0.34	NO
38	HIF1A	HIF1A	HIF1A	9017	0.032	0.33	NO
39	PAK4	PAK4	PAK4	9043	0.031	0.33	NO
40	FH	FH	FH	9422	0.018	0.31	NO
41	RAP1A	RAP1A	RAP1A	9680	0.009	0.3	NO
42	PAK1	PAK1	PAK1	9702	0.0083	0.29	NO
43	CDC42	CDC42	CDC42	9744	0.007	0.29	NO
44	PAK2	PAK2	PAK2	9820	0.0045	0.29	NO
45	PIK3R2	PIK3R2	PIK3R2	10039	-0.0024	0.28	NO
46	GRB2	GRB2	GRB2	10416	-0.014	0.26	NO
47	PTPN11	PTPN11	PTPN11	10590	-0.019	0.25	NO
48	RAC1	RAC1	RAC1	10891	-0.028	0.24	NO
49	KRAS	KRAS	KRAS	11036	-0.032	0.23	NO
50	RAF1	RAF1	RAF1	11249	-0.039	0.22	NO
51	CRK	CRK	CRK	11290	-0.04	0.22	NO
52	EGLN2	EGLN2	EGLN2	11373	-0.042	0.22	NO
53	CRKL	CRKL	CRKL	11528	-0.047	0.22	NO
54	MAP2K2	MAP2K2	MAP2K2	11743	-0.053	0.21	NO
55	TCEB2	TCEB2	TCEB2	11990	-0.06	0.2	NO
56	RAP1B	RAP1B	RAP1B	12027	-0.062	0.2	NO
57	MAP2K1	MAP2K1	MAP2K1	12422	-0.073	0.19	NO
58	PIK3R5	PIK3R5	PIK3R5	12457	-0.074	0.19	NO
59	PIK3R3	PIK3R3	PIK3R3	13421	-0.11	0.15	NO
60	CUL2	CUL2	CUL2	13925	-0.12	0.13	NO
61	EP300	EP300	EP300	13964	-0.13	0.14	NO
62	PIK3CB	PIK3CB	PIK3CB	14057	-0.13	0.14	NO
63	MAPK1	MAPK1	MAPK1	14349	-0.14	0.14	NO
64	RBX1	RBX1	RBX1	14408	-0.14	0.14	NO
65	RAPGEF1	RAPGEF1	RAPGEF1	14738	-0.16	0.14	NO
66	BRAF	BRAF	BRAF	16079	-0.23	0.081	NO
67	TCEB1	TCEB1	TCEB1	16466	-0.27	0.079	NO
68	PIK3CG	PIK3CG	PIK3CG	17452	-0.38	0.053	NO
69	PIK3CD	PIK3CD	PIK3CD	17796	-0.45	0.066	NO

Figure S53. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA CHREBP2 PATHWAY.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CHREBP2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM

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	MYL7	MYL7	MYL7	444	1	0.12	YES
2	ARHGEF17	ARHGEF17	ARHGEF17	2006	0.58	0.13	YES
3	MYLK	MYLK	MYLK	2587	0.49	0.17	YES
4	PLCB1	PLCB1	PLCB1	2770	0.46	0.23	YES
5	ARHGEF19	ARHGEF19	ARHGEF19	2825	0.46	0.29	YES
6	PRKCA	PRKCA	PRKCA	2877	0.45	0.36	YES
7	GNGT1	GNGT1	GNGT1	3658	0.36	0.37	YES
8	PPP1R12B	PPP1R12B	PPP1R12B	3664	0.36	0.42	YES
9	ARHGEF4	ARHGEF4	ARHGEF4	3850	0.34	0.46	YES
10	ARHGEF9	ARHGEF9	ARHGEF9	4398	0.29	0.47	YES
11	ARHGEF15	ARHGEF15	ARHGEF15	4536	0.28	0.5	YES
12	ARHGEF12	ARHGEF12	ARHGEF12	5196	0.22	0.5	NO
13	MYL2	MYL2	MYL2	5994	0.16	0.48	NO
14	ARHGAP5	ARHGAP5	ARHGAP5	6926	0.11	0.45	NO
15	ARHGEF6	ARHGEF6	ARHGEF6	6969	0.11	0.47	NO
16	ARHGEF2	ARHGEF2	ARHGEF2	7464	0.091	0.45	NO
17	ARHGEF3	ARHGEF3	ARHGEF3	8068	0.066	0.43	NO
18	PKN1	PKN1	PKN1	8191	0.062	0.43	NO
19	GNA12	GNA12	GNA12	8552	0.048	0.42	NO
20	GNB1	GNB1	GNB1	9029	0.031	0.4	NO
21	ARHGEF18	ARHGEF18	ARHGEF18	9365	0.019	0.39	NO
22	ROCK1	ROCK1	ROCK1	9425	0.018	0.39	NO
23	ARHGEF5	ARHGEF5	ARHGEF5	9554	0.013	0.38	NO
24	ARHGEF7	ARHGEF7	ARHGEF7	10092	-0.0043	0.35	NO
25	GNAQ	GNAQ	GNAQ	10375	-0.013	0.34	NO
26	ARHGEF11	ARHGEF11	ARHGEF11	11704	-0.052	0.28	NO
27	ARHGEF1	ARHGEF1	ARHGEF1	12174	-0.066	0.26	NO
28	ARHGEF16	ARHGEF16	ARHGEF16	13449	-0.11	0.21	NO
29	ARHGEF10	ARHGEF10	ARHGEF10	16049	-0.23	0.11	NO
30	PRKCB	PRKCB	PRKCB	17060	-0.33	0.1	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 PORPHYRIN AND CHLOROPHYLL METABOLISM.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PORPHYRIN AND CHLOROPHYLL 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 DRUG METABOLISM OTHER ENZYMES

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	TGFB2	TGFB2	TGFB2	85	1.3	0.011	YES
2	HHIP	HHIP	HHIP	124	1.2	0.023	YES
3	WNT4	WNT4	WNT4	132	1.2	0.037	YES
4	MAPK10	MAPK10	MAPK10	239	1.1	0.045	YES
5	MECOM	MECOM	MECOM	293	1.1	0.055	YES
6	ARNT2	ARNT2	ARNT2	305	1.1	0.066	YES
7	KITLG	KITLG	KITLG	307	1.1	0.079	YES
8	FZD2	FZD2	FZD2	308	1.1	0.092	YES
9	BMP2	BMP2	BMP2	358	1	0.1	YES
10	WNT11	WNT11	WNT11	443	1	0.11	YES
11	GLI3	GLI3	GLI3	574	0.95	0.11	YES
12	FZD7	FZD7	FZD7	580	0.95	0.12	YES
13	HGF	HGF	HGF	640	0.92	0.13	YES
14	FGF5	FGF5	FGF5	641	0.92	0.14	YES
15	WNT5A	WNT5A	WNT5A	652	0.92	0.15	YES
16	LAMB3	LAMB3	LAMB3	669	0.91	0.16	YES
17	COL4A6	COL4A6	COL4A6	711	0.89	0.17	YES
18	MMP1	MMP1	MMP1	814	0.86	0.17	YES
19	LAMB4	LAMB4	LAMB4	946	0.82	0.18	YES
20	FGF10	FGF10	FGF10	1009	0.8	0.18	YES
21	FGF20	FGF20	FGF20	1045	0.8	0.19	YES
22	BMP4	BMP4	BMP4	1144	0.76	0.19	YES
23	PDGFRA	PDGFRA	PDGFRA	1183	0.76	0.2	YES
24	RUNX1T1	RUNX1T1	RUNX1T1	1222	0.74	0.21	YES
25	WNT7B	WNT7B	WNT7B	1333	0.71	0.21	YES
26	FGF1	FGF1	FGF1	1443	0.69	0.21	YES
27	CCND1	CCND1	CCND1	1448	0.69	0.22	YES
28	SHH	SHH	SHH	1505	0.68	0.22	YES
29	FZD1	FZD1	FZD1	1537	0.67	0.23	YES
30	ZBTB16	ZBTB16	ZBTB16	1539	0.67	0.24	YES
31	FIGF	FIGF	FIGF	1548	0.67	0.24	YES
32	EGFR	EGFR	EGFR	1637	0.65	0.25	YES
33	FZD4	FZD4	FZD4	1693	0.64	0.25	YES
34	TCF7L1	TCF7L1	TCF7L1	1785	0.62	0.26	YES
35	TCF7L2	TCF7L2	TCF7L2	1865	0.61	0.26	YES
36	NOS2	NOS2	NOS2	1890	0.6	0.26	YES
37	JUN	JUN	JUN	1991	0.59	0.26	YES
38	FN1	FN1	FN1	1999	0.58	0.27	YES
39	ITGA2	ITGA2	ITGA2	2005	0.58	0.28	YES
40	MET	MET	MET	2061	0.58	0.28	YES
41	EGF	EGF	EGF	2117	0.56	0.28	YES
42	ITGA3	ITGA3	ITGA3	2136	0.56	0.29	YES
43	NTRK1	NTRK1	NTRK1	2262	0.54	0.29	YES
44	FGF23	FGF23	FGF23	2345	0.53	0.29	YES
45	VEGFA	VEGFA	VEGFA	2451	0.51	0.29	YES
46	FGF12	FGF12	FGF12	2474	0.51	0.3	YES
47	TGFB3	TGFB3	TGFB3	2501	0.51	0.3	YES
48	WNT16	WNT16	WNT16	2571	0.49	0.3	YES
49	CDKN2B	CDKN2B	CDKN2B	2579	0.49	0.31	YES
50	LAMB2	LAMB2	LAMB2	2647	0.48	0.31	YES
51	TGFA	TGFA	TGFA	2660	0.48	0.32	YES
52	IL8	IL8	IL8	2827	0.46	0.31	YES
53	PTGS2	PTGS2	PTGS2	2835	0.46	0.32	YES
54	VEGFC	VEGFC	VEGFC	2848	0.46	0.32	YES
55	FGF17	FGF17	FGF17	2862	0.45	0.33	YES
56	PRKCA	PRKCA	PRKCA	2877	0.45	0.33	YES
57	PDGFRB	PDGFRB	PDGFRB	2879	0.45	0.34	YES
58	FGF14	FGF14	FGF14	2901	0.45	0.34	YES
59	PGF	PGF	PGF	2961	0.44	0.34	YES
60	FGF7	FGF7	FGF7	2978	0.44	0.35	YES
61	LAMB1	LAMB1	LAMB1	3037	0.43	0.35	YES
62	RARB	RARB	RARB	3088	0.42	0.35	YES
63	CDK6	CDK6	CDK6	3245	0.4	0.35	YES
64	PIK3R1	PIK3R1	PIK3R1	3252	0.4	0.35	YES
65	RXRA	RXRA	RXRA	3265	0.4	0.36	YES
66	EPAS1	EPAS1	EPAS1	3307	0.4	0.36	YES
67	FZD6	FZD6	FZD6	3362	0.39	0.36	YES
68	ITGAV	ITGAV	ITGAV	3414	0.38	0.36	YES
69	RARA	RARA	RARA	3458	0.38	0.36	YES
70	ERBB2	ERBB2	ERBB2	3499	0.37	0.36	YES
71	LEF1	LEF1	LEF1	3529	0.37	0.37	YES
72	BCL2	BCL2	BCL2	3542	0.37	0.37	YES
73	WNT6	WNT6	WNT6	3587	0.37	0.37	YES
74	NKX3-1	NKX3-1	NKX3-1	3625	0.36	0.38	YES
75	CDKN2A	CDKN2A	CDKN2A	3679	0.36	0.38	YES
76	LAMA2	LAMA2	LAMA2	3685	0.36	0.38	YES
77	DCC	DCC	DCC	3694	0.35	0.38	YES
78	TGFBR2	TGFBR2	TGFBR2	3722	0.35	0.39	YES
79	CDKN1A	CDKN1A	CDKN1A	3745	0.35	0.39	YES
80	SOS2	SOS2	SOS2	3838	0.34	0.39	YES
81	LAMC3	LAMC3	LAMC3	3924	0.33	0.39	YES
82	LAMA4	LAMA4	LAMA4	3932	0.33	0.39	YES
83	LAMA3	LAMA3	LAMA3	3978	0.33	0.39	YES
84	WNT10A	WNT10A	WNT10A	3989	0.32	0.4	YES
85	LAMC2	LAMC2	LAMC2	3997	0.32	0.4	YES
86	FOS	FOS	FOS	4004	0.32	0.4	YES
87	BAD	BAD	BAD	4007	0.32	0.41	YES
88	PLD1	PLD1	PLD1	4119	0.31	0.4	YES
89	APC2	APC2	APC2	4281	0.3	0.4	YES
90	COL4A1	COL4A1	COL4A1	4330	0.29	0.4	YES
91	SMO	SMO	SMO	4342	0.29	0.4	YES
92	CTNNB1	CTNNB1	CTNNB1	4402	0.29	0.4	YES
93	FAS	FAS	FAS	4461	0.28	0.4	YES
94	VEGFB	VEGFB	VEGFB	4489	0.28	0.4	YES
95	COL4A2	COL4A2	COL4A2	4495	0.28	0.41	YES
96	WNT2	WNT2	WNT2	4531	0.28	0.41	YES
97	FGF3	FGF3	FGF3	4613	0.27	0.41	NO
98	RB1	RB1	RB1	4790	0.25	0.4	NO
99	PDGFB	PDGFB	PDGFB	4842	0.25	0.4	NO
100	CDH1	CDH1	CDH1	4876	0.24	0.4	NO
101	WNT5B	WNT5B	WNT5B	4882	0.24	0.4	NO
102	FGF8	FGF8	FGF8	4892	0.24	0.41	NO
103	SMAD4	SMAD4	SMAD4	5033	0.23	0.4	NO
104	RUNX1	RUNX1	RUNX1	5206	0.22	0.4	NO
105	SUFU	SUFU	SUFU	5294	0.21	0.39	NO
106	CTNNA1	CTNNA1	CTNNA1	5319	0.21	0.4	NO
107	APPL1	APPL1	APPL1	5326	0.21	0.4	NO
108	CBLC	CBLC	CBLC	5396	0.2	0.4	NO
109	FGF9	FGF9	FGF9	5417	0.2	0.4	NO
110	NFKB1	NFKB1	NFKB1	5439	0.2	0.4	NO
111	MITF	MITF	MITF	5451	0.2	0.4	NO
112	AKT3	AKT3	AKT3	5541	0.2	0.4	NO
113	WNT9B	WNT9B	WNT9B	5578	0.19	0.4	NO
114	TRAF5	TRAF5	TRAF5	5619	0.19	0.4	NO
115	WNT8B	WNT8B	WNT8B	5646	0.19	0.4	NO
116	CCNE2	CCNE2	CCNE2	5650	0.19	0.4	NO
117	RXRB	RXRB	RXRB	5840	0.18	0.39	NO
118	DAPK2	DAPK2	DAPK2	6005	0.16	0.38	NO
119	FZD9	FZD9	FZD9	6095	0.16	0.38	NO
120	AKT1	AKT1	AKT1	6171	0.15	0.38	NO
121	FGF2	FGF2	FGF2	6212	0.15	0.38	NO
122	CTBP1	CTBP1	CTBP1	6271	0.15	0.38	NO
123	LAMA1	LAMA1	LAMA1	6274	0.15	0.38	NO
124	IGF1	IGF1	IGF1	6294	0.15	0.38	NO
125	FGFR2	FGFR2	FGFR2	6334	0.14	0.38	NO
126	FOXO1	FOXO1	FOXO1	6369	0.14	0.38	NO
127	EGLN3	EGLN3	EGLN3	6380	0.14	0.38	NO
128	CDKN1B	CDKN1B	CDKN1B	6476	0.14	0.38	NO
129	AR	AR	AR	6482	0.14	0.38	NO
130	COL4A4	COL4A4	COL4A4	6487	0.14	0.38	NO
131	PDGFA	PDGFA	PDGFA	6510	0.14	0.38	NO
132	LAMA5	LAMA5	LAMA5	6536	0.13	0.38	NO
133	MMP2	MMP2	MMP2	6651	0.13	0.38	NO
134	BIRC2	BIRC2	BIRC2	6740	0.12	0.37	NO
135	FGFR1	FGFR1	FGFR1	6781	0.12	0.37	NO
136	TFG	TFG	TFG	6815	0.12	0.37	NO
137	RXRG	RXRG	RXRG	6862	0.12	0.37	NO
138	ARAF	ARAF	ARAF	6872	0.12	0.37	NO
139	FGF11	FGF11	FGF11	7013	0.11	0.37	NO
140	ABL1	ABL1	ABL1	7024	0.11	0.37	NO
141	MAPK3	MAPK3	MAPK3	7027	0.11	0.37	NO
142	RALGDS	RALGDS	RALGDS	7061	0.11	0.37	NO
143	VHL	VHL	VHL	7073	0.11	0.37	NO
144	ARNT	ARNT	ARNT	7078	0.11	0.37	NO
145	MAPK8	MAPK8	MAPK8	7093	0.11	0.37	NO
146	WNT7A	WNT7A	WNT7A	7175	0.1	0.37	NO
147	BID	BID	BID	7200	0.1	0.37	NO
148	BCL2L1	BCL2L1	BCL2L1	7213	0.1	0.37	NO
149	TGFB1	TGFB1	TGFB1	7215	0.1	0.37	NO
150	PTCH1	PTCH1	PTCH1	7304	0.097	0.36	NO
151	KLK3	KLK3	KLK3	7308	0.097	0.36	NO
152	RELA	RELA	RELA	7358	0.095	0.36	NO
153	SMAD3	SMAD3	SMAD3	7385	0.094	0.36	NO
154	MLH1	MLH1	MLH1	7414	0.093	0.36	NO
155	RALB	RALB	RALB	7500	0.089	0.36	NO
156	SOS1	SOS1	SOS1	7574	0.086	0.36	NO
157	GLI2	GLI2	GLI2	7577	0.086	0.36	NO
158	EGLN1	EGLN1	EGLN1	7589	0.085	0.36	NO
159	FADD	FADD	FADD	7716	0.08	0.35	NO
160	CDK2	CDK2	CDK2	7799	0.076	0.35	NO
161	MYC	MYC	MYC	7829	0.075	0.35	NO
162	JAK1	JAK1	JAK1	7954	0.07	0.34	NO
163	NRAS	NRAS	NRAS	7987	0.069	0.34	NO
164	WNT1	WNT1	WNT1	8107	0.065	0.34	NO
165	MAPK9	MAPK9	MAPK9	8238	0.06	0.33	NO
166	ITGB1	ITGB1	ITGB1	8271	0.058	0.33	NO
167	SLC2A1	SLC2A1	SLC2A1	8310	0.057	0.33	NO
168	CTNNA3	CTNNA3	CTNNA3	8361	0.056	0.32	NO
169	PIK3CA	PIK3CA	PIK3CA	8393	0.054	0.32	NO
170	ETS1	ETS1	ETS1	8443	0.052	0.32	NO
171	AKT2	AKT2	AKT2	8444	0.052	0.32	NO
172	APC	APC	APC	8495	0.05	0.32	NO
173	TP53	TP53	TP53	8515	0.049	0.32	NO
174	CREBBP	CREBBP	CREBBP	8684	0.043	0.31	NO
175	DVL3	DVL3	DVL3	8706	0.042	0.31	NO
176	DAPK3	DAPK3	DAPK3	8739	0.041	0.31	NO
177	PLCG1	PLCG1	PLCG1	8791	0.04	0.31	NO
178	GSK3B	GSK3B	GSK3B	8891	0.036	0.3	NO
179	HIF1A	HIF1A	HIF1A	9017	0.032	0.3	NO
180	MAX	MAX	MAX	9019	0.032	0.3	NO
181	STAT3	STAT3	STAT3	9056	0.03	0.3	NO
182	TRAF3	TRAF3	TRAF3	9073	0.029	0.29	NO
183	RASSF1	RASSF1	RASSF1	9096	0.029	0.29	NO
184	PTEN	PTEN	PTEN	9141	0.027	0.29	NO
185	IKBKB	IKBKB	IKBKB	9204	0.025	0.29	NO
186	RHOA	RHOA	RHOA	9233	0.024	0.29	NO
187	FZD8	FZD8	FZD8	9338	0.02	0.28	NO
188	CDK4	CDK4	CDK4	9343	0.02	0.28	NO
189	CSF1R	CSF1R	CSF1R	9357	0.019	0.28	NO
190	SKP2	SKP2	SKP2	9370	0.019	0.28	NO
191	FZD3	FZD3	FZD3	9376	0.019	0.28	NO
192	FH	FH	FH	9422	0.018	0.28	NO
193	DVL2	DVL2	DVL2	9434	0.017	0.28	NO
194	FGF13	FGF13	FGF13	9483	0.016	0.28	NO
195	RALBP1	RALBP1	RALBP1	9534	0.014	0.27	NO
196	NFKBIA	NFKBIA	NFKBIA	9547	0.013	0.27	NO
197	TGFBR1	TGFBR1	TGFBR1	9586	0.012	0.27	NO
198	CTNNA2	CTNNA2	CTNNA2	9588	0.012	0.27	NO
199	SMAD2	SMAD2	SMAD2	9597	0.012	0.27	NO
200	LAMC1	LAMC1	LAMC1	9708	0.0082	0.26	NO
201	CDC42	CDC42	CDC42	9744	0.007	0.26	NO
202	PML	PML	PML	9786	0.0055	0.26	NO
203	IKBKG	IKBKG	IKBKG	9819	0.0045	0.26	NO
204	HDAC1	HDAC1	HDAC1	9877	0.0025	0.26	NO
205	HSP90B1	HSP90B1	HSP90B1	9886	0.0022	0.26	NO
206	WNT3A	WNT3A	WNT3A	9897	0.0018	0.26	NO
207	JUP	JUP	JUP	9933	0.00086	0.25	NO
208	GSTP1	GSTP1	GSTP1	9994	-0.0008	0.25	NO
209	PIK3R2	PIK3R2	PIK3R2	10039	-0.0024	0.25	NO
210	CCDC6	CCDC6	CCDC6	10106	-0.0048	0.24	NO
211	STAT5B	STAT5B	STAT5B	10303	-0.011	0.24	NO
212	AXIN1	AXIN1	AXIN1	10367	-0.013	0.23	NO
213	GRB2	GRB2	GRB2	10416	-0.014	0.23	NO
214	AXIN2	AXIN2	AXIN2	10486	-0.016	0.23	NO
215	BRCA2	BRCA2	BRCA2	10623	-0.02	0.22	NO
216	NCOA4	NCOA4	NCOA4	10705	-0.023	0.21	NO
217	CEBPA	CEBPA	CEBPA	10726	-0.023	0.21	NO
218	XIAP	XIAP	XIAP	10831	-0.026	0.21	NO
219	RAC1	RAC1	RAC1	10891	-0.028	0.21	NO
220	KRAS	KRAS	KRAS	11036	-0.032	0.2	NO
221	IGF1R	IGF1R	IGF1R	11150	-0.036	0.19	NO
222	GLI1	GLI1	GLI1	11187	-0.036	0.19	NO
223	HDAC2	HDAC2	HDAC2	11245	-0.039	0.19	NO
224	RAF1	RAF1	RAF1	11249	-0.039	0.19	NO
225	PTK2	PTK2	PTK2	11282	-0.04	0.19	NO
226	CRK	CRK	CRK	11290	-0.04	0.19	NO
227	EGLN2	EGLN2	EGLN2	11373	-0.042	0.18	NO
228	CBLB	CBLB	CBLB	11485	-0.046	0.18	NO
229	CRKL	CRKL	CRKL	11528	-0.047	0.18	NO
230	MSH3	MSH3	MSH3	11539	-0.047	0.18	NO
231	CASP9	CASP9	CASP9	11589	-0.049	0.18	NO
232	TRAF6	TRAF6	TRAF6	11692	-0.052	0.17	NO
233	MAP2K2	MAP2K2	MAP2K2	11743	-0.053	0.17	NO
234	TRAF4	TRAF4	TRAF4	11773	-0.054	0.17	NO
235	MMP9	MMP9	MMP9	11784	-0.054	0.17	NO
236	TPR	TPR	TPR	11919	-0.058	0.16	NO
237	TCEB2	TCEB2	TCEB2	11990	-0.06	0.16	NO
238	PLCG2	PLCG2	PLCG2	12098	-0.064	0.15	NO
239	BCR	BCR	BCR	12099	-0.064	0.15	NO
240	STK4	STK4	STK4	12124	-0.064	0.15	NO
241	CASP3	CASP3	CASP3	12139	-0.065	0.15	NO
242	FGF22	FGF22	FGF22	12184	-0.066	0.15	NO
243	STK36	STK36	STK36	12195	-0.066	0.15	NO
244	STAT5A	STAT5A	STAT5A	12206	-0.067	0.15	NO
245	CSF3R	CSF3R	CSF3R	12249	-0.068	0.15	NO
246	MAP2K1	MAP2K1	MAP2K1	12422	-0.073	0.14	NO
247	PIK3R5	PIK3R5	PIK3R5	12457	-0.074	0.14	NO
248	FGF16	FGF16	FGF16	12618	-0.079	0.13	NO
249	FZD5	FZD5	FZD5	12625	-0.079	0.13	NO
250	FGF18	FGF18	FGF18	12664	-0.08	0.13	NO
251	DAPK1	DAPK1	DAPK1	12666	-0.08	0.13	NO
252	TRAF1	TRAF1	TRAF1	12788	-0.085	0.13	NO
253	TRAF2	TRAF2	TRAF2	12789	-0.085	0.13	NO
254	TPM3	TPM3	TPM3	12820	-0.086	0.13	NO
255	BIRC5	BIRC5	BIRC5	12944	-0.09	0.12	NO
256	CTBP2	CTBP2	CTBP2	13092	-0.095	0.12	NO
257	RALA	RALA	RALA	13107	-0.095	0.12	NO
258	FLT3LG	FLT3LG	FLT3LG	13214	-0.098	0.11	NO
259	DVL1	DVL1	DVL1	13235	-0.099	0.11	NO
260	CHUK	CHUK	CHUK	13281	-0.1	0.11	NO
261	WNT2B	WNT2B	WNT2B	13342	-0.1	0.11	NO
262	STAT1	STAT1	STAT1	13413	-0.11	0.11	NO
263	PIK3R3	PIK3R3	PIK3R3	13421	-0.11	0.11	NO
264	FGF21	FGF21	FGF21	13559	-0.11	0.1	NO
265	PIAS3	PIAS3	PIAS3	13607	-0.11	0.1	NO
266	RASSF5	RASSF5	RASSF5	13645	-0.12	0.099	NO
267	CKS1B	CKS1B	CKS1B	13888	-0.12	0.088	NO
268	CUL2	CUL2	CUL2	13925	-0.12	0.087	NO
269	WNT10B	WNT10B	WNT10B	13944	-0.13	0.088	NO
270	EP300	EP300	EP300	13964	-0.13	0.088	NO
271	E2F3	E2F3	E2F3	14052	-0.13	0.085	NO
272	PIK3CB	PIK3CB	PIK3CB	14057	-0.13	0.086	NO
273	PPARG	PPARG	PPARG	14230	-0.14	0.079	NO
274	PIAS1	PIAS1	PIAS1	14249	-0.14	0.08	NO
275	HSP90AB1	HSP90AB1	HSP90AB1	14263	-0.14	0.08	NO
276	MAPK1	MAPK1	MAPK1	14349	-0.14	0.078	NO
277	BAX	BAX	BAX	14370	-0.14	0.078	NO
278	PAX8	PAX8	PAX8	14401	-0.14	0.078	NO
279	PPARD	PPARD	PPARD	14407	-0.14	0.08	NO
280	RBX1	RBX1	RBX1	14408	-0.14	0.081	NO
281	MDM2	MDM2	MDM2	14433	-0.14	0.082	NO
282	E2F1	E2F1	E2F1	14511	-0.15	0.079	NO
283	HSP90AA1	HSP90AA1	HSP90AA1	14724	-0.16	0.07	NO
284	CBL	CBL	CBL	15094	-0.18	0.052	NO
285	CCNA1	CCNA1	CCNA1	15150	-0.18	0.051	NO
286	MSH6	MSH6	MSH6	15195	-0.18	0.051	NO
287	ITGA6	ITGA6	ITGA6	15333	-0.19	0.046	NO
288	FGFR3	FGFR3	FGFR3	15406	-0.19	0.044	NO
289	FZD10	FZD10	FZD10	15605	-0.2	0.036	NO
290	CCNE1	CCNE1	CCNE1	15698	-0.21	0.034	NO
291	RAC3	RAC3	RAC3	15794	-0.22	0.031	NO
292	CSF2RA	CSF2RA	CSF2RA	15838	-0.22	0.031	NO
293	FGF4	FGF4	FGF4	15869	-0.22	0.032	NO
294	WNT9A	WNT9A	WNT9A	15981	-0.23	0.029	NO
295	SPI1	SPI1	SPI1	16012	-0.23	0.03	NO
296	BRAF	BRAF	BRAF	16079	-0.23	0.029	NO
297	PIAS4	PIAS4	PIAS4	16080	-0.23	0.032	NO
298	TCF7	TCF7	TCF7	16237	-0.25	0.026	NO
299	PIAS2	PIAS2	PIAS2	16274	-0.25	0.027	NO
300	FGF19	FGF19	FGF19	16303	-0.25	0.029	NO
301	TCEB1	TCEB1	TCEB1	16466	-0.27	0.023	NO
302	E2F2	E2F2	E2F2	16647	-0.28	0.017	NO
303	CYCS	CYCS	CYCS	16737	-0.29	0.015	NO
304	CASP8	CASP8	CASP8	16825	-0.3	0.014	NO
305	MSH2	MSH2	MSH2	16942	-0.32	0.012	NO
306	MTOR	MTOR	MTOR	17015	-0.32	0.012	NO
307	PRKCB	PRKCB	PRKCB	17060	-0.33	0.013	NO
308	RAC2	RAC2	RAC2	17111	-0.34	0.014	NO
309	KIT	KIT	KIT	17191	-0.35	0.014	NO
310	PTCH2	PTCH2	PTCH2	17224	-0.35	0.017	NO
311	FLT3	FLT3	FLT3	17248	-0.36	0.019	NO
312	BIRC3	BIRC3	BIRC3	17322	-0.37	0.02	NO
313	PIK3CG	PIK3CG	PIK3CG	17452	-0.38	0.017	NO
314	NFKB2	NFKB2	NFKB2	17671	-0.42	0.011	NO
315	PIK3CD	PIK3CD	PIK3CD	17796	-0.45	0.0092	NO
316	WNT3	WNT3	WNT3	17802	-0.45	0.014	NO
317	RAD51	RAD51	RAD51	17911	-0.48	0.014	NO
318	RET	RET	RET	17948	-0.49	0.018	NO
319	ITGA2B	ITGA2B	ITGA2B	18389	-0.62	0.0014	NO
320	FASLG	FASLG	FASLG	18488	-0.66	0.0038	NO
321	WNT8A	WNT8A	WNT8A	18561	-0.7	0.008	NO
322	IL6	IL6	IL6	18617	-0.72	0.013	NO
323	PRKCG	PRKCG	PRKCG	18778	-0.84	0.015	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 DRUG METABOLISM OTHER ENZYMES.

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

genes ES table in pathway: KEGG WNT SIGNALING PATHWAY

Table 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	UGT2B7	UGT2B7	UGT2B7	39	1.4	0.089	YES
2	UGT2A3	UGT2A3	UGT2A3	134	1.2	0.16	YES
3	NAT2	NAT2	NAT2	198	1.2	0.23	YES
4	CYP3A7	CYP3A7	CYP3A7	315	1.1	0.29	YES
5	CYP3A5	CYP3A5	CYP3A5	365	1	0.36	YES
6	UGT2B4	UGT2B4	UGT2B4	722	0.89	0.39	YES
7	UGT2B11	UGT2B11	UGT2B11	802	0.86	0.44	YES
8	CYP2A6	CYP2A6	CYP2A6	927	0.83	0.49	YES
9	UGT2A1	UGT2A1	UGT2A1	1728	0.63	0.49	YES
10	UGT1A6	UGT1A6	UGT1A6	1997	0.58	0.51	YES
11	CES1	CES1	CES1	2288	0.54	0.53	YES
12	UPP2	UPP2	UPP2	2723	0.47	0.54	YES
13	CYP2A13	CYP2A13	CYP2A13	3394	0.39	0.52	YES
14	XDH	XDH	XDH	3396	0.39	0.55	YES
15	CES2	CES2	CES2	3593	0.36	0.56	YES
16	UGT1A9	UGT1A9	UGT1A9	3824	0.34	0.57	YES
17	UPB1	UPB1	UPB1	4003	0.32	0.58	YES
18	UGT2B15	UGT2B15	UGT2B15	4355	0.29	0.58	NO
19	UGT1A10	UGT1A10	UGT1A10	6225	0.15	0.49	NO
20	TK2	TK2	TK2	6386	0.14	0.49	NO
21	DPYD	DPYD	DPYD	6734	0.12	0.48	NO
22	TK1	TK1	TK1	6897	0.12	0.48	NO
23	ITPA	ITPA	ITPA	6916	0.12	0.49	NO
24	IMPDH2	IMPDH2	IMPDH2	7709	0.08	0.45	NO
25	CES7	CES7	CES7	7866	0.074	0.45	NO
26	UCK2	UCK2	UCK2	8080	0.066	0.44	NO
27	TPMT	TPMT	TPMT	8398	0.054	0.43	NO
28	GUSB	GUSB	GUSB	8695	0.043	0.41	NO
29	GMPS	GMPS	GMPS	8929	0.035	0.4	NO
30	HPRT1	HPRT1	HPRT1	9524	0.014	0.37	NO
31	UCK1	UCK1	UCK1	9697	0.0084	0.36	NO
32	UCKL1	UCKL1	UCKL1	11537	-0.047	0.27	NO
33	IMPDH1	IMPDH1	IMPDH1	11934	-0.059	0.25	NO
34	UMPS	UMPS	UMPS	12157	-0.065	0.25	NO
35	NAT1	NAT1	NAT1	12914	-0.089	0.21	NO
36	CYP3A43	CYP3A43	CYP3A43	13522	-0.11	0.19	NO
37	TYMP	TYMP	TYMP	15607	-0.2	0.091	NO
38	CDA	CDA	CDA	16473	-0.27	0.062	NO
39	DPYS	DPYS	DPYS	17177	-0.34	0.047	NO
40	UPP1	UPP1	UPP1	18764	-0.83	0.015	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 WNT SIGNALING PATHWAY.

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

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