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

Stomach Adenocarcinoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in STAD-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1JW8D1F

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 STAD-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: 195
Number of samples: 274
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 5 :[ clus1 ] 66
pheno.type: 2 - 5 :[ clus2 ] 63
pheno.type: 3 - 5 :[ clus3 ] 46
pheno.type: 4 - 5 :[ clus4 ] 37
pheno.type: 5 - 5 :[ clus5 ] 62

For the expression subtypes of 23365 genes in 275 samples, GSEA found enriched gene sets in each cluster using 274 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA INFLAM PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA IL2RB PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA TNFR1 PATHWAY, KEGG PYRIMIDINE METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RIBOSOME, KEGG RNA DEGRADATION

And common core enriched genes are PSME1, PSME2, LIG1, PCNA, POLD1, POLD2, POLE, POLE2, POLE3, RFC2

clus2

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

And common core enriched genes are AKT3, MAPK10, PIK3CD, PIK3CG, PIK3R1, PIK3R5, RPS6KA2, RPS6KA6, PRKAA2, BCL2

clus3

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG FATTY ACID METABOLISM, KEGG OXIDATIVE PHOSPHORYLATION, KEGG HISTIDINE METABOLISM, KEGG GLUTATHIONE METABOLISM, KEGG O GLYCAN BIOSYNTHESIS, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG ARACHIDONIC ACID METABOLISM

And common core enriched genes are ADH1A, ADH1B, ADH1C, ADH6, ADH7, ALDH2, ALDH3A1, ALDH3B1, ATP4A, ATP4B

clus4

Top enriched gene sets are BIOCARTA DEATH PATHWAY, BIOCARTA PPARA PATHWAY, BIOCARTA TNFR1 PATHWAY, KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG CITRATE CYCLE TCA CYCLE, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG ARGININE AND PROLINE METABOLISM, KEGG GLUTATHIONE METABOLISM

And common core enriched genes are ACAA1, DLD, EHHADH, HMGCL, IDH1, IDH2, ABAT, ACAA2, ACADS, ACADSB

clus5

Top enriched gene sets are BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA G1 PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA MPR PATHWAY, BIOCARTA CHREBP2 PATHWAY, BIOCARTA PAR1 PATHWAY, KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG CYSTEINE AND METHIONINE METABOLISM, KEGG LYSINE DEGRADATION, KEGG SELENOAMINO ACID METABOLISM

And common core enriched genes are BHMT, CBS, TUBA3C, TUBB1, TUBB2A, TUBB2B, TUBB3, DNMT3A, DNMT3B, DNMT3L

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 INFLAM PATHWAY	26	genes.ES.table	0.62	1.4	0.079	0.22	0.88	0.54	0.083	0.49	0.16	0.003
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.48	1.6	0.03	0.088	0.56	0.45	0.23	0.34	0.034	0.002
BIOCARTA HIVNEF PATHWAY	56	genes.ES.table	0.39	1.5	0.1	0.18	0.83	0.39	0.23	0.3	0.12	0.001
BIOCARTA IL2RB PATHWAY	37	genes.ES.table	0.49	1.6	0.093	0.12	0.7	0.38	0.17	0.31	0.067	0.002
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.42	1.4	0.1	0.2	0.86	1	0.58	0.42	0.14	0.003
BIOCARTA TNFR1 PATHWAY	28	genes.ES.table	0.51	1.7	0.015	0.11	0.48	0.43	0.23	0.33	0	0.007
KEGG PYRIMIDINE METABOLISM	94	genes.ES.table	0.31	1.3	0.19	0.25	0.9	0.36	0.16	0.31	0.2	0.003
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.53	1.5	0.072	0.14	0.74	0.62	0.28	0.45	0.08	0.001
KEGG RIBOSOME	81	genes.ES.table	0.68	2	0.01	0.021	0.078	0.88	0.26	0.66	0	0.001
KEGG RNA DEGRADATION	56	genes.ES.table	0.47	1.6	0.032	0.088	0.53	0.43	0.18	0.35	0.032	0.003

genes ES table in pathway: BIOCARTA INFLAM 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	IFNG	IFNG	IFNG	3	0.53	0.22	YES
2	PSMB9	PSMB9	PSMB9	645	0.15	0.26	YES
3	PSME2	PSME2	PSME2	857	0.13	0.31	YES
4	PSMB8	PSMB8	PSMB8	1708	0.088	0.31	YES
5	PSME1	PSME1	PSME1	1738	0.086	0.34	YES
6	PSMA6	PSMA6	PSMA6	1977	0.078	0.36	YES
7	PSMA4	PSMA4	PSMA4	2105	0.073	0.39	YES
8	PSMA5	PSMA5	PSMA5	2193	0.071	0.42	YES
9	PSMC1	PSMC1	PSMC1	2259	0.069	0.44	YES
10	POMP	POMP	POMP	2398	0.065	0.46	YES
11	PSMB6	PSMB6	PSMB6	2569	0.061	0.48	YES
12	PSMD12	PSMD12	PSMD12	2622	0.06	0.5	YES
13	PSMD14	PSMD14	PSMD14	2721	0.058	0.52	YES
14	PSMA3	PSMA3	PSMA3	2860	0.054	0.54	YES
15	PSMB2	PSMB2	PSMB2	2953	0.053	0.56	YES
16	PSMD6	PSMD6	PSMD6	3121	0.05	0.57	YES
17	PSMA1	PSMA1	PSMA1	3142	0.05	0.6	YES
18	PSMA2	PSMA2	PSMA2	3371	0.046	0.6	YES
19	PSMC6	PSMC6	PSMC6	3385	0.046	0.62	YES
20	PSMD2	PSMD2	PSMD2	3683	0.042	0.63	YES
21	PSMD13	PSMD13	PSMD13	3925	0.038	0.63	YES
22	PSMB5	PSMB5	PSMB5	3972	0.038	0.65	YES
23	PSMD11	PSMD11	PSMD11	4003	0.037	0.66	YES
24	PSMB7	PSMB7	PSMB7	4011	0.037	0.68	YES
25	SHFM1	SHFM1	SHFM1	4035	0.037	0.69	YES
26	PSMB1	PSMB1	PSMB1	4097	0.036	0.7	YES
27	PSMC4	PSMC4	PSMC4	4466	0.032	0.7	YES
28	PSMB3	PSMB3	PSMB3	4649	0.029	0.71	YES
29	PSMD1	PSMD1	PSMD1	4886	0.027	0.71	YES
30	PSMD8	PSMD8	PSMD8	4970	0.026	0.71	YES
31	PSMD3	PSMD3	PSMD3	5716	0.018	0.69	NO
32	PSMD7	PSMD7	PSMD7	5735	0.018	0.7	NO
33	PSME3	PSME3	PSME3	5755	0.018	0.7	NO
34	PSMC2	PSMC2	PSMC2	6087	0.014	0.69	NO
35	PSMC5	PSMC5	PSMC5	6321	0.012	0.69	NO
36	PSMC3	PSMC3	PSMC3	6474	0.01	0.69	NO
37	PSME4	PSME4	PSME4	7730	-0.0014	0.63	NO
38	PSMB4	PSMB4	PSMB4	7876	-0.0027	0.63	NO
39	PSMA7	PSMA7	PSMA7	8086	-0.0048	0.62	NO
40	PSMF1	PSMF1	PSMF1	8832	-0.012	0.59	NO
41	PSMD4	PSMD4	PSMD4	8970	-0.013	0.59	NO
42	PSMA8	PSMA8	PSMA8	11058	-0.035	0.51	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 INFLAM PATHWAY.

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

genes ES table in pathway: BIOCARTA FAS PATHWAY

Table 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	MCM2	MCM2	MCM2	890	0.13	0.015	YES
2	POLE2	POLE2	POLE2	1063	0.12	0.056	YES
3	MCM4	MCM4	MCM4	1100	0.12	0.1	YES
4	MCM5	MCM5	MCM5	1168	0.11	0.15	YES
5	PCNA	PCNA	PCNA	1189	0.11	0.19	YES
6	FEN1	FEN1	FEN1	1338	0.1	0.23	YES
7	RFC4	RFC4	RFC4	1386	0.1	0.27	YES
8	POLD1	POLD1	POLD1	1424	0.099	0.31	YES
9	RFC2	RFC2	RFC2	1480	0.097	0.34	YES
10	DNA2	DNA2	DNA2	1507	0.096	0.38	YES
11	RNASEH2A	RNASEH2A	RNASEH2A	1620	0.091	0.41	YES
12	LIG1	LIG1	LIG1	1636	0.09	0.45	YES
13	RFC5	RFC5	RFC5	1741	0.086	0.48	YES
14	PRIM1	PRIM1	PRIM1	1856	0.082	0.51	YES
15	MCM7	MCM7	MCM7	2082	0.074	0.53	YES
16	MCM6	MCM6	MCM6	2118	0.073	0.56	YES
17	MCM3	MCM3	MCM3	2182	0.071	0.59	YES
18	POLA2	POLA2	POLA2	2203	0.071	0.62	YES
19	RFC3	RFC3	RFC3	2225	0.07	0.64	YES
20	SSBP1	SSBP1	SSBP1	2320	0.068	0.67	YES
21	POLD2	POLD2	POLD2	2339	0.067	0.69	YES
22	PRIM2	PRIM2	PRIM2	2362	0.066	0.72	YES
23	POLE	POLE	POLE	2554	0.061	0.74	YES
24	RPA3	RPA3	RPA3	2576	0.061	0.76	YES
25	POLE3	POLE3	POLE3	2776	0.056	0.78	YES
26	RPA2	RPA2	RPA2	4025	0.037	0.74	NO
27	RFC1	RFC1	RFC1	4911	0.027	0.71	NO
28	RPA1	RPA1	RPA1	5301	0.022	0.7	NO
29	POLE4	POLE4	POLE4	5497	0.02	0.7	NO
30	RNASEH2B	RNASEH2B	RNASEH2B	5921	0.016	0.69	NO
31	RNASEH1	RNASEH1	RNASEH1	8064	-0.0046	0.6	NO
32	POLD3	POLD3	POLD3	8456	-0.008	0.58	NO
33	POLD4	POLD4	POLD4	8883	-0.012	0.57	NO
34	RNASEH2C	RNASEH2C	RNASEH2C	10246	-0.026	0.52	NO
35	RPA4	RPA4	RPA4	13851	-0.075	0.39	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 FAS PATHWAY.

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

genes ES table in pathway: BIOCARTA HIVNEF PATHWAY

Table 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	RPL22L1	RPL22L1	RPL22L1	188	0.24	0.058	YES
2	RPL7	RPL7	RPL7	746	0.14	0.072	YES
3	RPL3L	RPL3L	RPL3L	844	0.13	0.1	YES
4	RPL26L1	RPL26L1	RPL26L1	1103	0.12	0.12	YES
5	RPL9	RPL9	RPL9	1244	0.11	0.15	YES
6	RPL18A	RPL18A	RPL18A	1609	0.092	0.16	YES
7	RPL35	RPL35	RPL35	1916	0.08	0.17	YES
8	RPS7	RPS7	RPS7	1925	0.08	0.19	YES
9	RPL29	RPL29	RPL29	2273	0.069	0.19	YES
10	RPL21	RPL21	RPL21	2360	0.066	0.2	YES
11	RPL24	RPL24	RPL24	2445	0.064	0.22	YES
12	RPL36	RPL36	RPL36	2502	0.062	0.23	YES
13	RPS2	RPS2	RPS2	2513	0.062	0.25	YES
14	RPS15	RPS15	RPS15	2625	0.06	0.26	YES
15	MRPL13	MRPL13	MRPL13	2653	0.059	0.28	YES
16	RPL26	RPL26	RPL26	2677	0.059	0.29	YES
17	RPS19	RPS19	RPS19	2712	0.058	0.31	YES
18	RPL7A	RPL7A	RPL7A	2991	0.052	0.31	YES
19	RPL12	RPL12	RPL12	3043	0.052	0.32	YES
20	RPL39	RPL39	RPL39	3085	0.051	0.33	YES
21	RPL41	RPL41	RPL41	3099	0.051	0.35	YES
22	RPS18	RPS18	RPS18	3129	0.05	0.36	YES
23	RPS3A	RPS3A	RPS3A	3168	0.05	0.37	YES
24	RPL13A	RPL13A	RPL13A	3192	0.049	0.38	YES
25	RPL8	RPL8	RPL8	3209	0.049	0.4	YES
26	RSL24D1	RSL24D1	RSL24D1	3241	0.048	0.41	YES
27	RPLP0	RPLP0	RPLP0	3343	0.047	0.42	YES
28	RPL27A	RPL27A	RPL27A	3421	0.046	0.42	YES
29	RPS27L	RPS27L	RPS27L	3463	0.045	0.44	YES
30	RPS29	RPS29	RPS29	3479	0.045	0.45	YES
31	RPL14	RPL14	RPL14	3499	0.044	0.46	YES
32	RPL6	RPL6	RPL6	3508	0.044	0.47	YES
33	RPL35A	RPL35A	RPL35A	3532	0.044	0.48	YES
34	RPL10A	RPL10A	RPL10A	3784	0.04	0.48	YES
35	RPL10	RPL10	RPL10	3861	0.039	0.49	YES
36	RPS27	RPS27	RPS27	3973	0.038	0.49	YES
37	RPS8	RPS8	RPS8	4000	0.037	0.5	YES
38	RPL37A	RPL37A	RPL37A	4046	0.037	0.51	YES
39	RPL34	RPL34	RPL34	4050	0.037	0.52	YES
40	RPL38	RPL38	RPL38	4109	0.036	0.53	YES
41	RPS6	RPS6	RPS6	4191	0.035	0.53	YES
42	RPS9	RPS9	RPS9	4235	0.034	0.54	YES
43	RPL36AL	RPL36AL	RPL36AL	4309	0.033	0.55	YES
44	RPL32	RPL32	RPL32	4383	0.033	0.55	YES
45	RPS27A	RPS27A	RPS27A	4397	0.032	0.56	YES
46	RPS12	RPS12	RPS12	4478	0.031	0.57	YES
47	RPL27	RPL27	RPL27	4564	0.03	0.57	YES
48	RPLP2	RPLP2	RPLP2	4617	0.03	0.58	YES
49	RPS3	RPS3	RPS3	4621	0.03	0.58	YES
50	RPL28	RPL28	RPL28	4650	0.029	0.59	YES
51	RPS5	RPS5	RPS5	4700	0.029	0.6	YES
52	RPL31	RPL31	RPL31	4705	0.029	0.6	YES
53	RPS23	RPS23	RPS23	4719	0.029	0.61	YES
54	RPL4	RPL4	RPL4	4798	0.028	0.62	YES
55	RPS15A	RPS15A	RPS15A	4837	0.027	0.62	YES
56	RPS16	RPS16	RPS16	4843	0.027	0.63	YES
57	RPS28	RPS28	RPS28	4859	0.027	0.64	YES
58	RPL13	RPL13	RPL13	4930	0.026	0.64	YES
59	RPL23A	RPL23A	RPL23A	5015	0.025	0.64	YES
60	RPS4X	RPS4X	RPS4X	5036	0.025	0.65	YES
61	RPS13	RPS13	RPS13	5093	0.025	0.65	YES
62	RPSA	RPSA	RPSA	5167	0.024	0.66	YES
63	RPS25	RPS25	RPS25	5175	0.024	0.66	YES
64	RPL3	RPL3	RPL3	5177	0.024	0.67	YES
65	RPS20	RPS20	RPS20	5338	0.022	0.67	YES
66	RPS11	RPS11	RPS11	5483	0.021	0.67	YES
67	RPLP1	RPLP1	RPLP1	5542	0.02	0.67	YES
68	FAU	FAU	FAU	5553	0.02	0.68	YES
69	RPL22	RPL22	RPL22	5588	0.019	0.68	YES
70	UBA52	UBA52	UBA52	5743	0.018	0.68	YES
71	RPL11	RPL11	RPL11	5784	0.018	0.68	YES
72	RPL37	RPL37	RPL37	5968	0.015	0.68	NO
73	RPS24	RPS24	RPS24	6121	0.014	0.67	NO
74	RPS26	RPS26	RPS26	6279	0.012	0.67	NO
75	RPL15	RPL15	RPL15	6383	0.011	0.67	NO
76	RPL5	RPL5	RPL5	6655	0.0085	0.66	NO
77	RPL30	RPL30	RPL30	6933	0.006	0.65	NO
78	RPS21	RPS21	RPS21	7242	0.0032	0.64	NO
79	RPL19	RPL19	RPL19	7254	0.0031	0.64	NO
80	RPL23	RPL23	RPL23	8480	-0.0082	0.58	NO
81	RPL10L	RPL10L	RPL10L	17248	-0.16	0.24	NO

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

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

genes ES table in pathway: BIOCARTA IL2RB PATHWAY

Table S4. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	POLE2	POLE2	POLE2	1063	0.12	0.016	YES
2	PCNA	PCNA	PCNA	1189	0.11	0.07	YES
3	RFC4	RFC4	RFC4	1386	0.1	0.12	YES
4	POLD1	POLD1	POLD1	1424	0.099	0.17	YES
5	RFC2	RFC2	RFC2	1480	0.097	0.22	YES
6	DDB2	DDB2	DDB2	1550	0.094	0.26	YES
7	LIG1	LIG1	LIG1	1636	0.09	0.31	YES
8	RFC5	RFC5	RFC5	1741	0.086	0.35	YES
9	CDK7	CDK7	CDK7	1766	0.085	0.39	YES
10	GTF2H3	GTF2H3	GTF2H3	2027	0.076	0.42	YES
11	RFC3	RFC3	RFC3	2225	0.07	0.45	YES
12	POLD2	POLD2	POLD2	2339	0.067	0.48	YES
13	POLE	POLE	POLE	2554	0.061	0.5	YES
14	RPA3	RPA3	RPA3	2576	0.061	0.54	YES
15	POLE3	POLE3	POLE3	2776	0.056	0.56	YES
16	RBX1	RBX1	RBX1	3360	0.047	0.56	YES
17	MNAT1	MNAT1	MNAT1	3374	0.046	0.58	YES
18	RPA2	RPA2	RPA2	4025	0.037	0.57	YES
19	GTF2H4	GTF2H4	GTF2H4	4426	0.032	0.57	YES
20	CCNH	CCNH	CCNH	4516	0.031	0.58	YES
21	GTF2H2	GTF2H2	GTF2H2	4534	0.031	0.6	YES
22	RFC1	RFC1	RFC1	4911	0.027	0.6	YES
23	RPA1	RPA1	RPA1	5301	0.022	0.59	YES
24	RAD23A	RAD23A	RAD23A	5337	0.022	0.6	YES
25	POLE4	POLE4	POLE4	5497	0.02	0.6	YES
26	CUL4A	CUL4A	CUL4A	6635	0.0087	0.56	NO
27	GTF2H1	GTF2H1	GTF2H1	7009	0.0053	0.55	NO
28	ERCC3	ERCC3	ERCC3	7023	0.0052	0.55	NO
29	ERCC2	ERCC2	ERCC2	7163	0.004	0.54	NO
30	ERCC1	ERCC1	ERCC1	7682	-0.00089	0.52	NO
31	CETN2	CETN2	CETN2	7821	-0.0023	0.52	NO
32	GTF2H5	GTF2H5	GTF2H5	8198	-0.0056	0.5	NO
33	XPC	XPC	XPC	8265	-0.0062	0.5	NO
34	POLD3	POLD3	POLD3	8456	-0.008	0.5	NO
35	ERCC8	ERCC8	ERCC8	8735	-0.011	0.49	NO
36	POLD4	POLD4	POLD4	8883	-0.012	0.49	NO
37	XPA	XPA	XPA	8995	-0.013	0.49	NO
38	DDB1	DDB1	DDB1	9299	-0.016	0.49	NO
39	ERCC6	ERCC6	ERCC6	10719	-0.031	0.44	NO
40	CUL4B	CUL4B	CUL4B	10826	-0.032	0.46	NO
41	ERCC4	ERCC4	ERCC4	12371	-0.052	0.41	NO
42	RPA4	RPA4	RPA4	13851	-0.075	0.39	NO

Figure S7. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA IL2RB PATHWAY.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL2RB PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA RACCYCD PATHWAY

Table 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	KIR3DL2	KIR3DL2	KIR3DL2	31	0.37	0.061	YES
2	KLRD1	KLRD1	KLRD1	42	0.35	0.12	YES
3	KLRC2	KLRC2	KLRC2	153	0.26	0.16	YES
4	KLRC1	KLRC1	KLRC1	186	0.24	0.2	YES
5	KIR2DL2	KIR2DL2	KIR2DL2	193	0.24	0.24	YES
6	IFNA1	IFNA1	IFNA1	335	0.2	0.26	YES
7	KIR2DL1	KIR2DL1	KIR2DL1	340	0.2	0.3	YES
8	KLRC4	KLRC4	KLRC4	405	0.18	0.32	YES
9	TAP1	TAP1	TAP1	467	0.17	0.35	YES
10	HLA-DQB1	HLA-DQB1	HLA-DQB1	511	0.17	0.38	YES
11	HLA-DQA1	HLA-DQA1	HLA-DQA1	519	0.16	0.4	YES
12	CIITA	CIITA	CIITA	544	0.16	0.43	YES
13	CD8A	CD8A	CD8A	549	0.16	0.46	YES
14	LTA	LTA	LTA	644	0.15	0.48	YES
15	HLA-DOA	HLA-DOA	HLA-DOA	768	0.14	0.5	YES
16	PSME2	PSME2	PSME2	857	0.13	0.51	YES
17	HLA-DMA	HLA-DMA	HLA-DMA	969	0.12	0.53	YES
18	HSPA1B	HSPA1B	HSPA1B	1082	0.12	0.54	YES
19	HLA-DRB5	HLA-DRB5	HLA-DRB5	1117	0.12	0.56	YES
20	HLA-DMB	HLA-DMB	HLA-DMB	1124	0.12	0.58	YES
21	TAP2	TAP2	TAP2	1149	0.11	0.6	YES
22	HLA-DRA	HLA-DRA	HLA-DRA	1248	0.11	0.61	YES
23	HLA-DPA1	HLA-DPA1	HLA-DPA1	1423	0.099	0.62	YES
24	CD74	CD74	CD74	1547	0.094	0.63	YES
25	PSME1	PSME1	PSME1	1738	0.086	0.64	YES
26	IFI30	IFI30	IFI30	1743	0.086	0.65	YES
27	HLA-DPB1	HLA-DPB1	HLA-DPB1	1829	0.083	0.66	YES
28	HLA-F	HLA-F	HLA-F	1922	0.08	0.67	YES
29	HSPA6	HSPA6	HSPA6	1954	0.079	0.68	YES
30	HLA-DQA2	HLA-DQA2	HLA-DQA2	2328	0.067	0.68	YES
31	TAPBP	TAPBP	TAPBP	2614	0.06	0.67	YES
32	B2M	B2M	B2M	2740	0.057	0.68	YES
33	CTSS	CTSS	CTSS	2834	0.055	0.68	YES
34	RFXANK	RFXANK	RFXANK	3006	0.052	0.68	YES
35	HSPA4	HSPA4	HSPA4	3064	0.052	0.69	YES
36	HLA-E	HLA-E	HLA-E	3498	0.044	0.68	YES
37	HLA-G	HLA-G	HLA-G	3538	0.044	0.68	YES
38	CD4	CD4	CD4	3544	0.044	0.69	YES
39	HSP90AA1	HSP90AA1	HSP90AA1	3580	0.043	0.7	YES
40	CTSB	CTSB	CTSB	3763	0.041	0.7	YES
41	CTSL1	CTSL1	CTSL1	3766	0.041	0.7	YES
42	LGMN	LGMN	LGMN	3832	0.04	0.71	YES
43	HSPA5	HSPA5	HSPA5	3955	0.038	0.71	YES
44	HLA-C	HLA-C	HLA-C	4373	0.033	0.69	NO
45	HLA-A	HLA-A	HLA-A	4603	0.03	0.69	NO
46	RFX5	RFX5	RFX5	4724	0.029	0.69	NO
47	HSPA8	HSPA8	HSPA8	5296	0.022	0.67	NO
48	CD8B	CD8B	CD8B	5325	0.022	0.67	NO
49	PDIA3	PDIA3	PDIA3	5460	0.021	0.67	NO
50	CALR	CALR	CALR	5509	0.02	0.67	NO
51	PSME3	PSME3	PSME3	5755	0.018	0.66	NO
52	CANX	CANX	CANX	7547	0.00037	0.58	NO
53	NFYA	NFYA	NFYA	8349	-0.0071	0.55	NO
54	NFYC	NFYC	NFYC	8370	-0.0073	0.55	NO
55	NFYB	NFYB	NFYB	9008	-0.013	0.52	NO
56	CREB1	CREB1	CREB1	10339	-0.027	0.47	NO
57	RFXAP	RFXAP	RFXAP	11532	-0.041	0.42	NO
58	HSPA1L	HSPA1L	HSPA1L	14480	-0.086	0.3	NO
59	HSPA1A	HSPA1A	HSPA1A	14533	-0.088	0.32	NO
60	HSPA2	HSPA2	HSPA2	19608	-0.25	0.13	NO

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

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

genes ES table in pathway: BIOCARTA TNFR1 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	AIM2	AIM2	AIM2	5	0.48	0.12	YES
2	CXCL10	CXCL10	CXCL10	9	0.45	0.24	YES
3	POLR3G	POLR3G	POLR3G	77	0.31	0.31	YES
4	CCL4	CCL4	CCL4	131	0.26	0.38	YES
5	IL18	IL18	IL18	315	0.2	0.42	YES
6	IFNA1	IFNA1	IFNA1	335	0.2	0.47	YES
7	CCL5	CCL5	CCL5	401	0.18	0.52	YES
8	IFNB1	IFNB1	IFNB1	813	0.14	0.53	YES
9	ZBP1	ZBP1	ZBP1	1503	0.096	0.53	YES
10	CASP1	CASP1	CASP1	1599	0.092	0.55	YES
11	IL6	IL6	IL6	1790	0.084	0.56	YES
12	POLR3K	POLR3K	POLR3K	2329	0.067	0.55	YES
13	IKBKE	IKBKE	IKBKE	2469	0.063	0.56	YES
14	IL1B	IL1B	IL1B	3298	0.048	0.54	NO
15	NFKB1	NFKB1	NFKB1	3519	0.044	0.54	NO
16	IRF7	IRF7	IRF7	4087	0.036	0.52	NO
17	PYCARD	PYCARD	PYCARD	4272	0.034	0.53	NO
18	CHUK	CHUK	CHUK	4430	0.032	0.53	NO
19	POLR1C	POLR1C	POLR1C	4547	0.031	0.53	NO
20	IRF3	IRF3	IRF3	4558	0.03	0.54	NO
21	POLR3D	POLR3D	POLR3D	4688	0.029	0.54	NO
22	TREX1	TREX1	TREX1	4847	0.027	0.54	NO
23	POLR3B	POLR3B	POLR3B	5013	0.026	0.54	NO
24	CCL4L2	CCL4L2	CCL4L2	5275	0.023	0.53	NO
25	DDX58	DDX58	DDX58	5395	0.022	0.53	NO
26	POLR1D	POLR1D	POLR1D	5504	0.02	0.53	NO
27	TBK1	TBK1	TBK1	5782	0.018	0.52	NO
28	RELA	RELA	RELA	6159	0.014	0.51	NO
29	IKBKB	IKBKB	IKBKB	6479	0.01	0.5	NO
30	NFKBIA	NFKBIA	NFKBIA	6574	0.0093	0.5	NO
31	POLR3H	POLR3H	POLR3H	7094	0.0047	0.48	NO
32	IKBKG	IKBKG	IKBKG	7628	-0.00049	0.45	NO
33	ADAR	ADAR	ADAR	7770	-0.0018	0.45	NO
34	RIPK1	RIPK1	RIPK1	8432	-0.0078	0.42	NO
35	NFKBIB	NFKBIB	NFKBIB	8451	-0.0079	0.42	NO
36	POLR3A	POLR3A	POLR3A	8503	-0.0084	0.42	NO
37	TMEM173	TMEM173	TMEM173	9274	-0.016	0.39	NO
38	POLR3GL	POLR3GL	POLR3GL	10287	-0.027	0.35	NO
39	POLR3F	POLR3F	POLR3F	11692	-0.043	0.3	NO
40	POLR3C	POLR3C	POLR3C	11789	-0.044	0.31	NO
41	MAVS	MAVS	MAVS	14492	-0.087	0.21	NO
42	RIPK3	RIPK3	RIPK3	16027	-0.12	0.18	NO
43	IL33	IL33	IL33	22126	-0.46	0.023	NO

Figure S11. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA TNFR1 PATHWAY.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PYRIMIDINE METABOLISM

Table 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	IFNG	IFNG	IFNG	3	0.53	0.1	YES
2	GZMB	GZMB	GZMB	14	0.43	0.18	YES
3	KIR3DL2	KIR3DL2	KIR3DL2	31	0.37	0.25	YES
4	KLRD1	KLRD1	KLRD1	42	0.35	0.32	YES
5	FASLG	FASLG	FASLG	47	0.34	0.39	YES
6	CD80	CD80	CD80	169	0.25	0.43	YES
7	KLRC1	KLRC1	KLRC1	186	0.24	0.47	YES
8	KIR2DL2	KIR2DL2	KIR2DL2	193	0.24	0.52	YES
9	PRF1	PRF1	PRF1	228	0.23	0.56	YES
10	KIR2DL1	KIR2DL1	KIR2DL1	340	0.2	0.59	YES
11	FAS	FAS	FAS	504	0.17	0.62	YES
12	HLA-DQA1	HLA-DQA1	HLA-DQA1	519	0.16	0.65	YES
13	IL1A	IL1A	IL1A	715	0.14	0.67	YES
14	HLA-DOA	HLA-DOA	HLA-DOA	768	0.14	0.69	YES
15	HLA-DMA	HLA-DMA	HLA-DMA	969	0.12	0.71	YES
16	HLA-DRB5	HLA-DRB5	HLA-DRB5	1117	0.12	0.72	YES
17	HLA-DMB	HLA-DMB	HLA-DMB	1124	0.12	0.75	YES
18	HLA-DRA	HLA-DRA	HLA-DRA	1248	0.11	0.76	YES
19	CD86	CD86	CD86	1287	0.11	0.78	YES
20	TNF	TNF	TNF	1405	0.1	0.79	YES
21	HLA-DPA1	HLA-DPA1	HLA-DPA1	1423	0.099	0.81	YES
22	IL6	IL6	IL6	1790	0.084	0.81	YES
23	HLA-DPB1	HLA-DPB1	HLA-DPB1	1829	0.083	0.83	YES
24	HLA-F	HLA-F	HLA-F	1922	0.08	0.84	YES
25	HLA-DQA2	HLA-DQA2	HLA-DQA2	2328	0.067	0.83	NO
26	IL1B	IL1B	IL1B	3298	0.048	0.8	NO
27	HLA-E	HLA-E	HLA-E	3498	0.044	0.8	NO
28	HLA-G	HLA-G	HLA-G	3538	0.044	0.8	NO
29	HLA-C	HLA-C	HLA-C	4373	0.033	0.77	NO
30	HLA-A	HLA-A	HLA-A	4603	0.03	0.77	NO
31	IL2	IL2	IL2	12433	-0.053	0.43	NO
32	CD28	CD28	CD28	14795	-0.093	0.35	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 PYRIMIDINE METABOLISM.

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

Table 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	LMNB1	LMNB1	LMNB1	675	0.15	0.11	YES
2	LMNB2	LMNB2	LMNB2	1370	0.1	0.18	YES
3	BAG4	BAG4	BAG4	1392	0.1	0.28	YES
4	TNF	TNF	TNF	1405	0.1	0.37	YES
5	CASP2	CASP2	CASP2	1660	0.09	0.44	YES
6	RB1	RB1	RB1	2949	0.053	0.44	YES
7	CASP8	CASP8	CASP8	3561	0.043	0.45	YES
8	DFFB	DFFB	DFFB	4591	0.03	0.44	YES
9	MAP2K4	MAP2K4	MAP2K4	4646	0.029	0.46	YES
10	CASP3	CASP3	CASP3	4852	0.027	0.48	YES
11	ARHGDIB	ARHGDIB	ARHGDIB	5196	0.024	0.49	YES
12	FADD	FADD	FADD	5235	0.023	0.51	YES
13	DFFA	DFFA	DFFA	5723	0.018	0.5	NO
14	LMNA	LMNA	LMNA	6579	0.0093	0.47	NO
15	SPTAN1	SPTAN1	SPTAN1	6627	0.0088	0.48	NO
16	TRADD	TRADD	TRADD	6765	0.0075	0.48	NO
17	MAP3K1	MAP3K1	MAP3K1	7063	0.0049	0.47	NO
18	PARP1	PARP1	PARP1	7129	0.0044	0.47	NO
19	PRKDC	PRKDC	PRKDC	7995	-0.0039	0.44	NO
20	PAK1	PAK1	PAK1	8236	-0.0059	0.43	NO
21	PAK2	PAK2	PAK2	8297	-0.0065	0.44	NO
22	RIPK1	RIPK1	RIPK1	8432	-0.0078	0.44	NO
23	TNFRSF1A	TNFRSF1A	TNFRSF1A	8563	-0.0089	0.44	NO
24	MAP3K7	MAP3K7	MAP3K7	9309	-0.016	0.42	NO
25	CRADD	CRADD	CRADD	9974	-0.023	0.42	NO
26	MAPK8	MAPK8	MAPK8	11660	-0.043	0.38	NO
27	MADD	MADD	MADD	11719	-0.043	0.42	NO
28	JUN	JUN	JUN	13141	-0.063	0.42	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 AMINOACYL TRNA BIOSYNTHESIS.

Figure S16. 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 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	NEIL3	NEIL3	NEIL3	1016	0.12	0.025	YES
2	POLE2	POLE2	POLE2	1063	0.12	0.091	YES
3	POLB	POLB	POLB	1094	0.12	0.16	YES
4	PCNA	PCNA	PCNA	1189	0.11	0.22	YES
5	FEN1	FEN1	FEN1	1338	0.1	0.27	YES
6	POLD1	POLD1	POLD1	1424	0.099	0.32	YES
7	LIG1	LIG1	LIG1	1636	0.09	0.36	YES
8	PARP3	PARP3	PARP3	1646	0.09	0.42	YES
9	POLD2	POLD2	POLD2	2339	0.067	0.42	YES
10	POLE	POLE	POLE	2554	0.061	0.45	YES
11	UNG	UNG	UNG	2623	0.06	0.48	YES
12	POLE3	POLE3	POLE3	2776	0.056	0.51	YES
13	MPG	MPG	MPG	3230	0.048	0.52	YES
14	APEX2	APEX2	APEX2	3780	0.041	0.51	YES
15	NTHL1	NTHL1	NTHL1	3819	0.04	0.54	YES
16	POLE4	POLE4	POLE4	5497	0.02	0.47	NO
17	PARP2	PARP2	PARP2	5995	0.015	0.46	NO
18	PARP4	PARP4	PARP4	6150	0.014	0.46	NO
19	XRCC1	XRCC1	XRCC1	6331	0.012	0.46	NO
20	PARP1	PARP1	PARP1	7129	0.0044	0.43	NO
21	APEX1	APEX1	APEX1	7162	0.004	0.43	NO
22	NEIL2	NEIL2	NEIL2	7250	0.0031	0.43	NO
23	POLL	POLL	POLL	7299	0.0027	0.42	NO
24	POLD3	POLD3	POLD3	8456	-0.008	0.38	NO
25	POLD4	POLD4	POLD4	8883	-0.012	0.37	NO
26	TDG	TDG	TDG	9138	-0.014	0.36	NO
27	MBD4	MBD4	MBD4	9145	-0.014	0.37	NO
28	SMUG1	SMUG1	SMUG1	10369	-0.028	0.33	NO
29	OGG1	OGG1	OGG1	11733	-0.044	0.3	NO
30	MUTYH	MUTYH	MUTYH	11745	-0.044	0.32	NO
31	LIG3	LIG3	LIG3	12658	-0.056	0.32	NO
32	NEIL1	NEIL1	NEIL1	18904	-0.22	0.16	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 RIBOSOME.

Figure S18. 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 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	POLR3G	POLR3G	POLR3G	77	0.31	0.29	YES
2	POLR3K	POLR3K	POLR3K	2329	0.067	0.25	YES
3	POLR2F	POLR2F	POLR2F	3035	0.052	0.27	YES
4	POLR2L	POLR2L	POLR2L	3322	0.047	0.3	YES
5	ZNRD1	ZNRD1	ZNRD1	3400	0.046	0.34	YES
6	POLR2D	POLR2D	POLR2D	3419	0.046	0.39	YES
7	POLR1B	POLR1B	POLR1B	3545	0.044	0.42	YES
8	POLR1C	POLR1C	POLR1C	4547	0.031	0.41	YES
9	POLR2A	POLR2A	POLR2A	4673	0.029	0.43	YES
10	POLR3D	POLR3D	POLR3D	4688	0.029	0.46	YES
11	POLR2E	POLR2E	POLR2E	4753	0.028	0.48	YES
12	POLR3B	POLR3B	POLR3B	5013	0.026	0.5	YES
13	POLR1E	POLR1E	POLR1E	5204	0.024	0.51	YES
14	POLR1D	POLR1D	POLR1D	5504	0.02	0.52	YES
15	POLR2G	POLR2G	POLR2G	5693	0.018	0.52	YES
16	POLR2I	POLR2I	POLR2I	5831	0.017	0.53	YES
17	POLR1A	POLR1A	POLR1A	5984	0.015	0.54	YES
18	POLR2J	POLR2J	POLR2J	6600	0.0091	0.52	NO
19	POLR3H	POLR3H	POLR3H	7094	0.0047	0.51	NO
20	POLR2J2	POLR2J2	POLR2J2	7257	0.0031	0.5	NO
21	POLR2C	POLR2C	POLR2C	7908	-0.0031	0.48	NO
22	POLR3A	POLR3A	POLR3A	8503	-0.0084	0.46	NO
23	POLR2J3	POLR2J3	POLR2J3	9011	-0.013	0.45	NO
24	POLR2K	POLR2K	POLR2K	9453	-0.018	0.45	NO
25	POLR3GL	POLR3GL	POLR3GL	10287	-0.027	0.43	NO
26	POLR2B	POLR2B	POLR2B	10649	-0.03	0.45	NO
27	POLR3F	POLR3F	POLR3F	11692	-0.043	0.44	NO
28	POLR3C	POLR3C	POLR3C	11789	-0.044	0.48	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 RNA DEGRADATION.

Figure S20. 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 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 NO1 PATHWAY	29	genes.ES.table	0.51	1.5	0.016	0.11	0.74	0.21	0.068	0.19	0.068	0
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.5	1.6	0.027	0.09	0.64	0.29	0.2	0.23	0.044	0
BIOCARTA ALK PATHWAY	35	genes.ES.table	0.47	1.5	0.026	0.11	0.76	0.54	0.35	0.35	0.07	0
BIOCARTA AT1R PATHWAY	31	genes.ES.table	0.46	1.8	0	0.075	0.33	0.064	0.054	0.061	0	0.002
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.49	1.6	0.069	0.093	0.68	0.46	0.38	0.28	0.051	0
BIOCARTA BIOPEPTIDES PATHWAY	41	genes.ES.table	0.51	1.8	0.0079	0.073	0.25	0.29	0.25	0.22	0	0.008
BIOCARTA HDAC PATHWAY	25	genes.ES.table	0.57	1.9	0.006	0.093	0.19	0.68	0.37	0.43	0	0.015
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.43	1.6	0.038	0.094	0.68	0.53	0.4	0.32	0.052	0
BIOCARTA ERK PATHWAY	26	genes.ES.table	0.53	1.7	0.015	0.059	0.4	0.077	0.025	0.075	0	0
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.5	1.7	0.027	0.06	0.43	0.46	0.38	0.28	0	0

genes ES table in pathway: BIOCARTA NO1 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	NEFM	NEFM	NEFM	227	0.79	0.081	YES
2	GRIN2A	GRIN2A	GRIN2A	289	0.75	0.16	YES
3	GRIA1	GRIA1	GRIA1	297	0.74	0.25	YES
4	NOS1	NOS1	NOS1	462	0.67	0.32	YES
5	PRPH	PRPH	PRPH	529	0.64	0.39	YES
6	NEFL	NEFL	NEFL	558	0.63	0.46	YES
7	NEFH	NEFH	NEFH	1014	0.51	0.5	YES
8	PRPH2	PRPH2	PRPH2	1034	0.5	0.56	YES
9	GRIA2	GRIA2	GRIA2	1457	0.43	0.59	YES
10	BCL2	BCL2	BCL2	2473	0.31	0.58	NO
11	SLC1A2	SLC1A2	SLC1A2	3048	0.26	0.58	NO
12	MAPK11	MAPK11	MAPK11	4584	0.18	0.54	NO
13	PPP3CC	PPP3CC	PPP3CC	6172	0.11	0.48	NO
14	PPP3CB	PPP3CB	PPP3CB	6551	0.1	0.48	NO
15	GRIN2C	GRIN2C	GRIN2C	6577	0.1	0.48	NO
16	TNFRSF1A	TNFRSF1A	TNFRSF1A	9663	0.032	0.35	NO
17	PPP3CA	PPP3CA	PPP3CA	9739	0.03	0.35	NO
18	TNFRSF1B	TNFRSF1B	TNFRSF1B	9862	0.028	0.35	NO
19	MAPK14	MAPK14	MAPK14	10104	0.024	0.34	NO
20	CAT	CAT	CAT	10465	0.019	0.33	NO
21	MAP3K5	MAP3K5	MAP3K5	10910	0.013	0.31	NO
22	CCS	CCS	CCS	11094	0.0097	0.3	NO
23	CASP1	CASP1	CASP1	11355	0.0059	0.29	NO
24	TP53	TP53	TP53	11642	0.002	0.28	NO
25	BAD	BAD	BAD	12213	-0.0054	0.26	NO
26	GPX1	GPX1	GPX1	13067	-0.016	0.22	NO
27	CASP9	CASP9	CASP9	13331	-0.02	0.21	NO
28	RAB5A	RAB5A	RAB5A	13399	-0.02	0.21	NO
29	MAPK12	MAPK12	MAPK12	13460	-0.021	0.21	NO
30	PPP3R1	PPP3R1	PPP3R1	13638	-0.023	0.2	NO
31	BAX	BAX	BAX	14188	-0.03	0.18	NO
32	RAC1	RAC1	RAC1	14606	-0.035	0.17	NO
33	APAF1	APAF1	APAF1	14787	-0.037	0.16	NO
34	MAP2K6	MAP2K6	MAP2K6	15268	-0.043	0.15	NO
35	GRIN2B	GRIN2B	GRIN2B	15470	-0.045	0.14	NO
36	DERL1	DERL1	DERL1	15609	-0.047	0.14	NO
37	TOMM40L	TOMM40L	TOMM40L	15979	-0.052	0.13	NO
38	TNF	TNF	TNF	16346	-0.057	0.12	NO
39	DAXX	DAXX	DAXX	16389	-0.057	0.13	NO
40	MAP2K3	MAP2K3	MAP2K3	16531	-0.059	0.13	NO
41	SOD1	SOD1	SOD1	16619	-0.061	0.13	NO
42	PPP3R2	PPP3R2	PPP3R2	17474	-0.073	0.1	NO
43	CHP2	CHP2	CHP2	18080	-0.084	0.086	NO
44	GRIN2D	GRIN2D	GRIN2D	18081	-0.084	0.096	NO
45	BCL2L1	BCL2L1	BCL2L1	18364	-0.089	0.094	NO
46	CYCS	CYCS	CYCS	19638	-0.12	0.051	NO
47	CASP3	CASP3	CASP3	19813	-0.12	0.057	NO
48	BID	BID	BID	19821	-0.12	0.071	NO
49	GRIN1	GRIN1	GRIN1	20528	-0.15	0.057	NO
50	TOMM40	TOMM40	TOMM40	20599	-0.15	0.071	NO
51	MAPK13	MAPK13	MAPK13	21082	-0.17	0.069	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 NO1 PATHWAY.

Figure S22. 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 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	NGFR	NGFR	NGFR	121	0.88	0.054	YES
2	NTRK3	NTRK3	NTRK3	273	0.76	0.099	YES
3	CAMK2A	CAMK2A	CAMK2A	410	0.69	0.14	YES
4	MAPK10	MAPK10	MAPK10	489	0.66	0.18	YES
5	NGF	NGF	NGF	563	0.63	0.22	YES
6	RPS6KA6	RPS6KA6	RPS6KA6	628	0.61	0.26	YES
7	SHC4	SHC4	SHC4	889	0.54	0.28	YES
8	NTRK2	NTRK2	NTRK2	1254	0.46	0.3	YES
9	NTRK1	NTRK1	NTRK1	1494	0.42	0.32	YES
10	AKT3	AKT3	AKT3	2185	0.34	0.31	YES
11	CAMK4	CAMK4	CAMK4	2294	0.32	0.33	YES
12	SHC3	SHC3	SHC3	2370	0.32	0.34	YES
13	BCL2	BCL2	BCL2	2473	0.31	0.36	YES
14	SHC2	SHC2	SHC2	2913	0.27	0.36	YES
15	NGFRAP1	NGFRAP1	NGFRAP1	3400	0.24	0.35	YES
16	PIK3CG	PIK3CG	PIK3CG	3894	0.21	0.35	YES
17	IRS4	IRS4	IRS4	3926	0.21	0.36	YES
18	MAP3K3	MAP3K3	MAP3K3	4130	0.2	0.36	YES
19	GAB1	GAB1	GAB1	4416	0.18	0.36	YES
20	NTF3	NTF3	NTF3	4538	0.18	0.37	YES
21	MAPK11	MAPK11	MAPK11	4584	0.18	0.38	YES
22	CAMK2B	CAMK2B	CAMK2B	4627	0.17	0.39	YES
23	PLCG2	PLCG2	PLCG2	4648	0.17	0.4	YES
24	PIK3CD	PIK3CD	PIK3CD	4905	0.16	0.4	YES
25	RPS6KA2	RPS6KA2	RPS6KA2	4952	0.16	0.41	YES
26	PIK3R1	PIK3R1	PIK3R1	4987	0.16	0.42	YES
27	PIK3R5	PIK3R5	PIK3R5	5008	0.16	0.43	YES
28	IRS1	IRS1	IRS1	5097	0.15	0.43	YES
29	IRS2	IRS2	IRS2	5126	0.15	0.44	YES
30	CAMK2G	CAMK2G	CAMK2G	5332	0.14	0.44	YES
31	ABL1	ABL1	ABL1	5733	0.13	0.44	NO
32	RPS6KA5	RPS6KA5	RPS6KA5	5783	0.13	0.44	NO
33	FASLG	FASLG	FASLG	5946	0.12	0.44	NO
34	RAP1A	RAP1A	RAP1A	6293	0.11	0.44	NO
35	IRAK3	IRAK3	IRAK3	6462	0.1	0.44	NO
36	PIK3CA	PIK3CA	PIK3CA	6915	0.092	0.42	NO
37	ARHGDIB	ARHGDIB	ARHGDIB	7141	0.085	0.42	NO
38	KIDINS220	KIDINS220	KIDINS220	7409	0.078	0.41	NO
39	PIK3R3	PIK3R3	PIK3R3	7420	0.078	0.42	NO
40	SH2B3	SH2B3	SH2B3	7546	0.075	0.41	NO
41	RAPGEF1	RAPGEF1	RAPGEF1	7669	0.072	0.41	NO
42	JUN	JUN	JUN	7855	0.067	0.41	NO
43	SOS2	SOS2	SOS2	7968	0.064	0.41	NO
44	CALM1	CALM1	CALM1	8440	0.054	0.39	NO
45	MAPK7	MAPK7	MAPK7	8479	0.053	0.39	NO
46	PLCG1	PLCG1	PLCG1	8483	0.053	0.4	NO
47	MAP2K5	MAP2K5	MAP2K5	8596	0.051	0.4	NO
48	SOS1	SOS1	SOS1	8673	0.049	0.4	NO
49	TRAF6	TRAF6	TRAF6	8784	0.047	0.39	NO
50	FOXO3	FOXO3	FOXO3	8863	0.046	0.39	NO
51	NFKBIA	NFKBIA	NFKBIA	9006	0.043	0.39	NO
52	SORT1	SORT1	SORT1	9149	0.04	0.39	NO
53	MAP2K7	MAP2K7	MAP2K7	9258	0.038	0.38	NO
54	PTPN11	PTPN11	PTPN11	9338	0.037	0.38	NO
55	IRAK4	IRAK4	IRAK4	9650	0.032	0.37	NO
56	FRS2	FRS2	FRS2	9675	0.032	0.37	NO
57	ZNF274	ZNF274	ZNF274	9949	0.027	0.36	NO
58	RPS6KA3	RPS6KA3	RPS6KA3	9969	0.026	0.36	NO
59	MAPK14	MAPK14	MAPK14	10104	0.024	0.36	NO
60	RAP1B	RAP1B	RAP1B	10190	0.023	0.36	NO
61	BRAF	BRAF	BRAF	10381	0.02	0.35	NO
62	IKBKB	IKBKB	IKBKB	10735	0.015	0.34	NO
63	MAPK1	MAPK1	MAPK1	10793	0.014	0.33	NO
64	MAGED1	MAGED1	MAGED1	10812	0.014	0.33	NO
65	AKT2	AKT2	AKT2	10837	0.014	0.33	NO
66	MAP3K5	MAP3K5	MAP3K5	10910	0.013	0.33	NO
67	NFKB1	NFKB1	NFKB1	11307	0.0066	0.32	NO
68	CAMK2D	CAMK2D	CAMK2D	11366	0.0057	0.31	NO
69	SHC1	SHC1	SHC1	11483	0.0041	0.31	NO
70	CRKL	CRKL	CRKL	11531	0.0036	0.31	NO
71	TP53	TP53	TP53	11642	0.002	0.3	NO
72	AKT1	AKT1	AKT1	11677	0.0016	0.3	NO
73	RAF1	RAF1	RAF1	11688	0.0015	0.3	NO
74	CRK	CRK	CRK	11712	0.0012	0.3	NO
75	MAP3K1	MAP3K1	MAP3K1	11741	0.00073	0.3	NO
76	CALM2	CALM2	CALM2	11803	-7.5e-06	0.29	NO
77	CDC42	CDC42	CDC42	11954	-0.002	0.29	NO
78	SH2B1	SH2B1	SH2B1	12059	-0.0034	0.28	NO
79	RELA	RELA	RELA	12079	-0.0036	0.28	NO
80	BAD	BAD	BAD	12213	-0.0054	0.28	NO
81	SH2B2	SH2B2	SH2B2	12391	-0.0079	0.27	NO
82	RHOA	RHOA	RHOA	12545	-0.0097	0.26	NO
83	YWHAQ	YWHAQ	YWHAQ	12556	-0.0099	0.26	NO
84	MAPKAPK2	MAPKAPK2	MAPKAPK2	12631	-0.011	0.26	NO
85	YWHAH	YWHAH	YWHAH	12936	-0.015	0.25	NO
86	GSK3B	GSK3B	GSK3B	13080	-0.016	0.24	NO
87	MAPK9	MAPK9	MAPK9	13113	-0.017	0.24	NO
88	CALM3	CALM3	CALM3	13287	-0.019	0.24	NO
89	MAP2K2	MAP2K2	MAP2K2	13326	-0.019	0.24	NO
90	ATF4	ATF4	ATF4	13415	-0.02	0.23	NO
91	MAPK12	MAPK12	MAPK12	13460	-0.021	0.23	NO
92	GRB2	GRB2	GRB2	13953	-0.027	0.21	NO
93	ARHGDIA	ARHGDIA	ARHGDIA	14138	-0.029	0.21	NO
94	BAX	BAX	BAX	14188	-0.03	0.21	NO
95	MAPK3	MAPK3	MAPK3	14344	-0.032	0.2	NO
96	KRAS	KRAS	KRAS	14494	-0.033	0.2	NO
97	RAC1	RAC1	RAC1	14606	-0.035	0.2	NO
98	YWHAB	YWHAB	YWHAB	14907	-0.039	0.18	NO
99	PRDM4	PRDM4	PRDM4	14983	-0.04	0.18	NO
100	YWHAG	YWHAG	YWHAG	15193	-0.042	0.18	NO
101	BDNF	BDNF	BDNF	15428	-0.045	0.17	NO
102	PSEN1	PSEN1	PSEN1	15500	-0.046	0.17	NO
103	MAP2K1	MAP2K1	MAP2K1	15554	-0.046	0.17	NO
104	PIK3CB	PIK3CB	PIK3CB	15564	-0.046	0.17	NO
105	MAPK8	MAPK8	MAPK8	15636	-0.047	0.17	NO
106	CALML3	CALML3	CALML3	15813	-0.05	0.17	NO
107	NTF4	NTF4	NTF4	16014	-0.052	0.16	NO
108	CSK	CSK	CSK	16299	-0.056	0.16	NO
109	RPS6KA4	RPS6KA4	RPS6KA4	16328	-0.056	0.16	NO
110	NFKBIB	NFKBIB	NFKBIB	16719	-0.062	0.14	NO
111	IRAK1	IRAK1	IRAK1	16849	-0.064	0.14	NO
112	IRAK2	IRAK2	IRAK2	16852	-0.064	0.15	NO
113	YWHAZ	YWHAZ	YWHAZ	16895	-0.065	0.15	NO
114	YWHAE	YWHAE	YWHAE	17842	-0.079	0.11	NO
115	PIK3R2	PIK3R2	PIK3R2	17998	-0.082	0.11	NO
116	RIPK2	RIPK2	RIPK2	18225	-0.086	0.11	NO
117	NRAS	NRAS	NRAS	18248	-0.086	0.11	NO
118	NFKBIE	NFKBIE	NFKBIE	18794	-0.097	0.095	NO
119	PRKCD	PRKCD	PRKCD	19292	-0.11	0.081	NO
120	PDK1	PDK1	PDK1	19367	-0.11	0.085	NO
121	RPS6KA1	RPS6KA1	RPS6KA1	20053	-0.13	0.063	NO
122	CALML6	CALML6	CALML6	20765	-0.16	0.042	NO
123	CALML5	CALML5	CALML5	20938	-0.16	0.046	NO
124	MAPK13	MAPK13	MAPK13	21082	-0.17	0.051	NO
125	TP73	TP73	TP73	22234	-0.27	0.018	NO

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

Figure S24. 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 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	SLC2A4	SLC2A4	SLC2A4	100	0.9	0.087	YES
2	RXRG	RXRG	RXRG	322	0.72	0.15	YES
3	MAPK10	MAPK10	MAPK10	489	0.66	0.21	YES
4	PRKAA2	PRKAA2	PRKAA2	559	0.63	0.27	YES
5	NPY	NPY	NPY	953	0.52	0.31	YES
6	ADIPOQ	ADIPOQ	ADIPOQ	960	0.52	0.36	YES
7	POMC	POMC	POMC	1386	0.44	0.39	YES
8	LEPR	LEPR	LEPR	1949	0.36	0.4	YES
9	CPT1C	CPT1C	CPT1C	2174	0.34	0.42	YES
10	AKT3	AKT3	AKT3	2185	0.34	0.46	YES
11	ACSL6	ACSL6	ACSL6	2189	0.34	0.49	YES
12	CD36	CD36	CD36	2273	0.33	0.52	YES
13	ACACB	ACACB	ACACB	2525	0.3	0.54	YES
14	IRS4	IRS4	IRS4	3926	0.21	0.5	NO
15	PRKCQ	PRKCQ	PRKCQ	4174	0.2	0.51	NO
16	LEP	LEP	LEP	4679	0.17	0.5	NO
17	IRS1	IRS1	IRS1	5097	0.15	0.5	NO
18	IRS2	IRS2	IRS2	5126	0.15	0.51	NO
19	PPARGC1A	PPARGC1A	PPARGC1A	5664	0.13	0.5	NO
20	PRKAG2	PRKAG2	PRKAG2	5856	0.12	0.51	NO
21	PRKAB2	PRKAB2	PRKAB2	6786	0.096	0.48	NO
22	AGRP	AGRP	AGRP	6959	0.09	0.48	NO
23	CAMKK1	CAMKK1	CAMKK1	8368	0.056	0.42	NO
24	JAK2	JAK2	JAK2	8540	0.052	0.42	NO
25	RXRA	RXRA	RXRA	8708	0.048	0.42	NO
26	NFKBIA	NFKBIA	NFKBIA	9006	0.043	0.41	NO
27	STAT3	STAT3	STAT3	9069	0.042	0.41	NO
28	ACSL1	ACSL1	ACSL1	9190	0.04	0.41	NO
29	SOCS3	SOCS3	SOCS3	9192	0.04	0.41	NO
30	PTPN11	PTPN11	PTPN11	9338	0.037	0.41	NO
31	TNFRSF1A	TNFRSF1A	TNFRSF1A	9663	0.032	0.4	NO
32	TNFRSF1B	TNFRSF1B	TNFRSF1B	9862	0.028	0.39	NO
33	CPT1A	CPT1A	CPT1A	9871	0.028	0.39	NO
34	CAMKK2	CAMKK2	CAMKK2	10235	0.022	0.38	NO
35	PRKAB1	PRKAB1	PRKAB1	10459	0.019	0.37	NO
36	ACSL4	ACSL4	ACSL4	10678	0.016	0.36	NO
37	IKBKB	IKBKB	IKBKB	10735	0.015	0.36	NO
38	AKT2	AKT2	AKT2	10837	0.014	0.36	NO
39	PPARA	PPARA	PPARA	10971	0.012	0.36	NO
40	TRADD	TRADD	TRADD	11132	0.0092	0.35	NO
41	RXRB	RXRB	RXRB	11159	0.0088	0.35	NO
42	NFKB1	NFKB1	NFKB1	11307	0.0066	0.34	NO
43	AKT1	AKT1	AKT1	11677	0.0016	0.33	NO
44	RELA	RELA	RELA	12079	-0.0036	0.31	NO
45	IKBKG	IKBKG	IKBKG	12230	-0.0057	0.3	NO
46	STK11	STK11	STK11	12269	-0.0061	0.3	NO
47	MAPK9	MAPK9	MAPK9	13113	-0.017	0.27	NO
48	MTOR	MTOR	MTOR	13253	-0.018	0.26	NO
49	PRKAG1	PRKAG1	PRKAG1	14227	-0.03	0.22	NO
50	PCK1	PCK1	PCK1	14309	-0.031	0.22	NO
51	PRKAA1	PRKAA1	PRKAA1	14735	-0.037	0.21	NO
52	MAPK8	MAPK8	MAPK8	15636	-0.047	0.17	NO
53	CPT1B	CPT1B	CPT1B	15671	-0.048	0.18	NO
54	ADIPOR2	ADIPOR2	ADIPOR2	16197	-0.055	0.16	NO
55	TNF	TNF	TNF	16346	-0.057	0.16	NO
56	NFKBIB	NFKBIB	NFKBIB	16719	-0.062	0.15	NO
57	CHUK	CHUK	CHUK	17042	-0.067	0.14	NO
58	ADIPOR1	ADIPOR1	ADIPOR1	17213	-0.069	0.14	NO
59	ACSL5	ACSL5	ACSL5	17371	-0.072	0.14	NO
60	TRAF2	TRAF2	TRAF2	18468	-0.09	0.1	NO
61	NFKBIE	NFKBIE	NFKBIE	18794	-0.097	0.095	NO
62	ACSL3	ACSL3	ACSL3	18955	-0.1	0.099	NO
63	G6PC2	G6PC2	G6PC2	19807	-0.12	0.073	NO
64	PCK2	PCK2	PCK2	20561	-0.15	0.055	NO
65	G6PC	G6PC	G6PC	20636	-0.15	0.067	NO
66	SLC2A1	SLC2A1	SLC2A1	21726	-0.22	0.041	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: BIOCARTA ALK PATHWAY.

Figure S26. 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 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	AGTR1	AGTR1	AGTR1	48	1	0.038	YES
2	ACTG2	ACTG2	ACTG2	200	0.81	0.063	YES
3	ADCY5	ADCY5	ADCY5	211	0.8	0.094	YES
4	KCNMA1	KCNMA1	KCNMA1	237	0.78	0.12	YES
5	MYH11	MYH11	MYH11	277	0.76	0.15	YES
6	KCNMB1	KCNMB1	KCNMB1	290	0.75	0.18	YES
7	ADCY2	ADCY2	ADCY2	439	0.68	0.2	YES
8	ADRA1D	ADRA1D	ADRA1D	498	0.65	0.22	YES
9	PLA2G5	PLA2G5	PLA2G5	674	0.6	0.24	YES
10	PLA2G2C	PLA2G2C	PLA2G2C	688	0.59	0.26	YES
11	PPP1R14A	PPP1R14A	PPP1R14A	746	0.57	0.28	YES
12	MYLK	MYLK	MYLK	787	0.56	0.3	YES
13	ADRA1A	ADRA1A	ADRA1A	793	0.56	0.32	YES
14	PPP1R12B	PPP1R12B	PPP1R12B	866	0.54	0.34	YES
15	CACNA1C	CACNA1C	CACNA1C	873	0.54	0.36	YES
16	MYL9	MYL9	MYL9	1089	0.49	0.37	YES
17	AVPR1A	AVPR1A	AVPR1A	1102	0.49	0.39	YES
18	MRVI1	MRVI1	MRVI1	1143	0.48	0.41	YES
19	PRKCB	PRKCB	PRKCB	1229	0.47	0.42	YES
20	NPR1	NPR1	NPR1	1403	0.44	0.43	YES
21	GUCY1A3	GUCY1A3	GUCY1A3	1521	0.42	0.44	YES
22	PRKG1	PRKG1	PRKG1	1534	0.42	0.46	YES
23	ACTA2	ACTA2	ACTA2	1564	0.41	0.48	YES
24	KCNMB2	KCNMB2	KCNMB2	1632	0.4	0.49	YES
25	GUCY1B3	GUCY1B3	GUCY1B3	1868	0.37	0.49	YES
26	CALD1	CALD1	CALD1	1874	0.37	0.51	YES
27	PTGIR	PTGIR	PTGIR	1904	0.37	0.52	YES
28	EDNRA	EDNRA	EDNRA	2015	0.36	0.53	YES
29	RAMP1	RAMP1	RAMP1	2163	0.34	0.54	YES
30	MYLK3	MYLK3	MYLK3	2368	0.32	0.54	YES
31	ITPR1	ITPR1	ITPR1	2451	0.31	0.55	YES
32	NPR2	NPR2	NPR2	2574	0.3	0.56	YES
33	RAMP3	RAMP3	RAMP3	2586	0.3	0.57	YES
34	GUCY1A2	GUCY1A2	GUCY1A2	2673	0.29	0.57	YES
35	ADCY4	ADCY4	ADCY4	2769	0.28	0.58	YES
36	KCNMB4	KCNMB4	KCNMB4	3081	0.26	0.58	YES
37	RAMP2	RAMP2	RAMP2	3316	0.24	0.58	YES
38	CALCRL	CALCRL	CALCRL	3511	0.23	0.58	YES
39	PLA2G2D	PLA2G2D	PLA2G2D	3757	0.22	0.57	YES
40	PRKACB	PRKACB	PRKACB	3875	0.21	0.58	YES
41	PLCB1	PLCB1	PLCB1	4017	0.2	0.58	YES
42	PRKCQ	PRKCQ	PRKCQ	4174	0.2	0.58	YES
43	AVPR1B	AVPR1B	AVPR1B	4182	0.2	0.59	YES
44	ADCY9	ADCY9	ADCY9	4410	0.18	0.58	YES
45	PLCB4	PLCB4	PLCB4	4569	0.18	0.58	YES
46	PPP1R12A	PPP1R12A	PPP1R12A	4705	0.17	0.58	YES
47	CACNA1S	CACNA1S	CACNA1S	4716	0.17	0.59	YES
48	PRKCG	PRKCG	PRKCG	4748	0.17	0.6	YES
49	ADCY8	ADCY8	ADCY8	4764	0.17	0.6	YES
50	ADRA1B	ADRA1B	ADRA1B	4775	0.17	0.61	YES
51	PRKCH	PRKCH	PRKCH	5304	0.15	0.59	NO
52	ADCY1	ADCY1	ADCY1	6046	0.12	0.56	NO
53	PLCB2	PLCB2	PLCB2	6643	0.099	0.54	NO
54	MYL6	MYL6	MYL6	6674	0.098	0.54	NO
55	ADORA2A	ADORA2A	ADORA2A	6711	0.097	0.55	NO
56	PRKCA	PRKCA	PRKCA	6793	0.095	0.55	NO
57	ITPR2	ITPR2	ITPR2	6985	0.09	0.54	NO
58	PRKCE	PRKCE	PRKCE	7033	0.088	0.54	NO
59	ROCK1	ROCK1	ROCK1	7252	0.082	0.54	NO
60	CACNA1D	CACNA1D	CACNA1D	7322	0.08	0.54	NO
61	GNA12	GNA12	GNA12	7863	0.067	0.51	NO
62	GNAQ	GNAQ	GNAQ	7892	0.066	0.52	NO
63	ADCY7	ADCY7	ADCY7	8254	0.058	0.5	NO
64	PRKACA	PRKACA	PRKACA	8279	0.058	0.5	NO
65	PLA2G2A	PLA2G2A	PLA2G2A	8333	0.056	0.5	NO
66	CALM1	CALM1	CALM1	8440	0.054	0.5	NO
67	PLA2G4A	PLA2G4A	PLA2G4A	8490	0.053	0.5	NO
68	PPP1CB	PPP1CB	PPP1CB	8843	0.046	0.49	NO
69	KCNMB3	KCNMB3	KCNMB3	9177	0.04	0.47	NO
70	ARHGEF12	ARHGEF12	ARHGEF12	9384	0.036	0.46	NO
71	PLA2G10	PLA2G10	PLA2G10	9404	0.036	0.46	NO
72	ROCK2	ROCK2	ROCK2	9544	0.034	0.46	NO
73	GNA13	GNA13	GNA13	9591	0.033	0.46	NO
74	PLA2G12A	PLA2G12A	PLA2G12A	10344	0.021	0.43	NO
75	BRAF	BRAF	BRAF	10381	0.02	0.43	NO
76	MYL6B	MYL6B	MYL6B	10658	0.016	0.42	NO
77	MAPK1	MAPK1	MAPK1	10793	0.014	0.41	NO
78	CYP4A11	CYP4A11	CYP4A11	11227	0.0078	0.39	NO
79	ARHGEF1	ARHGEF1	ARHGEF1	11280	0.007	0.39	NO
80	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	11350	0.006	0.39	NO
81	GNA11	GNA11	GNA11	11364	0.0058	0.38	NO
82	RAF1	RAF1	RAF1	11688	0.0015	0.37	NO
83	CALM2	CALM2	CALM2	11803	-7.5e-06	0.37	NO
84	RHOA	RHOA	RHOA	12545	-0.0097	0.33	NO
85	ADCY6	ADCY6	ADCY6	12567	-0.01	0.33	NO
86	ARAF	ARAF	ARAF	12636	-0.011	0.33	NO
87	GNAS	GNAS	GNAS	12911	-0.014	0.32	NO
88	ARHGEF11	ARHGEF11	ARHGEF11	12993	-0.015	0.32	NO
89	CALM3	CALM3	CALM3	13287	-0.019	0.3	NO
90	MAP2K2	MAP2K2	MAP2K2	13326	-0.019	0.3	NO
91	PRKX	PRKX	PRKX	13862	-0.026	0.28	NO
92	MAPK3	MAPK3	MAPK3	14344	-0.032	0.26	NO
93	PPP1CC	PPP1CC	PPP1CC	14816	-0.038	0.24	NO
94	CACNA1F	CACNA1F	CACNA1F	15281	-0.043	0.22	NO
95	MAP2K1	MAP2K1	MAP2K1	15554	-0.046	0.21	NO
96	CALML3	CALML3	CALML3	15813	-0.05	0.2	NO
97	PRKACG	PRKACG	PRKACG	15906	-0.051	0.2	NO
98	PLA2G6	PLA2G6	PLA2G6	16373	-0.057	0.18	NO
99	PLA2G1B	PLA2G1B	PLA2G1B	17850	-0.08	0.12	NO
100	PLA2G2F	PLA2G2F	PLA2G2F	18734	-0.096	0.083	NO
101	PPP1CA	PPP1CA	PPP1CA	19140	-0.1	0.07	NO
102	PRKCD	PRKCD	PRKCD	19292	-0.11	0.067	NO
103	ITPR3	ITPR3	ITPR3	19325	-0.11	0.07	NO
104	CYP4A22	CYP4A22	CYP4A22	19432	-0.11	0.07	NO
105	PLCB3	PLCB3	PLCB3	19465	-0.11	0.073	NO
106	MYLK2	MYLK2	MYLK2	20381	-0.14	0.038	NO
107	CALML6	CALML6	CALML6	20765	-0.16	0.027	NO
108	ADORA2B	ADORA2B	ADORA2B	20907	-0.16	0.027	NO
109	CALML5	CALML5	CALML5	20938	-0.16	0.032	NO
110	PLA2G12B	PLA2G12B	PLA2G12B	21178	-0.18	0.028	NO
111	PLA2G2E	PLA2G2E	PLA2G2E	22002	-0.24	0.0013	NO
112	PLA2G3	PLA2G3	PLA2G3	22448	-0.31	-0.0062	NO
113	PLA2G4E	PLA2G4E	PLA2G4E	22589	-0.38	0.0024	NO

Figure S27. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA AT1R PATHWAY.

Figure S28. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AT1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA BCR PATHWAY

Table 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	IGF1	IGF1	IGF1	533	0.64	0.09	YES
2	PRKAA2	PRKAA2	PRKAA2	559	0.63	0.2	YES
3	RPS6KA6	RPS6KA6	RPS6KA6	628	0.61	0.3	YES
4	CAB39L	CAB39L	CAB39L	2120	0.34	0.3	YES
5	AKT3	AKT3	AKT3	2185	0.34	0.36	YES
6	VEGFC	VEGFC	VEGFC	2964	0.27	0.37	YES
7	ULK2	ULK2	ULK2	3666	0.22	0.38	YES
8	PIK3CG	PIK3CG	PIK3CG	3894	0.21	0.4	YES
9	PIK3CD	PIK3CD	PIK3CD	4905	0.16	0.39	YES
10	RPS6KA2	RPS6KA2	RPS6KA2	4952	0.16	0.41	YES
11	PIK3R1	PIK3R1	PIK3R1	4987	0.16	0.44	YES
12	PIK3R5	PIK3R5	PIK3R5	5008	0.16	0.47	YES
13	VEGFB	VEGFB	VEGFB	5719	0.13	0.46	NO
14	PIK3CA	PIK3CA	PIK3CA	6915	0.092	0.42	NO
15	PIK3R3	PIK3R3	PIK3R3	7420	0.078	0.41	NO
16	ULK1	ULK1	ULK1	7549	0.075	0.42	NO
17	TSC2	TSC2	TSC2	8837	0.046	0.37	NO
18	RICTOR	RICTOR	RICTOR	9434	0.035	0.35	NO
19	RPTOR	RPTOR	RPTOR	9749	0.03	0.34	NO
20	TSC1	TSC1	TSC1	9935	0.027	0.34	NO
21	RPS6KA3	RPS6KA3	RPS6KA3	9969	0.026	0.34	NO
22	FIGF	FIGF	FIGF	9972	0.026	0.35	NO
23	EIF4B	EIF4B	EIF4B	10275	0.022	0.34	NO
24	BRAF	BRAF	BRAF	10381	0.02	0.34	NO
25	PDPK1	PDPK1	PDPK1	10587	0.017	0.33	NO
26	STRADA	STRADA	STRADA	10726	0.015	0.33	NO
27	MAPK1	MAPK1	MAPK1	10793	0.014	0.33	NO
28	AKT2	AKT2	AKT2	10837	0.014	0.33	NO
29	RPS6KB1	RPS6KB1	RPS6KB1	11548	0.0033	0.3	NO
30	RHEB	RHEB	RHEB	11577	0.003	0.3	NO
31	AKT1	AKT1	AKT1	11677	0.0016	0.29	NO
32	STK11	STK11	STK11	12269	-0.0061	0.27	NO
33	CAB39	CAB39	CAB39	12840	-0.014	0.24	NO
34	MTOR	MTOR	MTOR	13253	-0.018	0.23	NO
35	RPS6	RPS6	RPS6	13530	-0.022	0.22	NO
36	HIF1A	HIF1A	HIF1A	13616	-0.023	0.22	NO
37	DDIT4	DDIT4	DDIT4	13629	-0.023	0.22	NO
38	MAPK3	MAPK3	MAPK3	14344	-0.032	0.2	NO
39	PRKAA1	PRKAA1	PRKAA1	14735	-0.037	0.19	NO
40	PIK3CB	PIK3CB	PIK3CB	15564	-0.046	0.16	NO
41	EIF4E2	EIF4E2	EIF4E2	15985	-0.052	0.15	NO
42	MLST8	MLST8	MLST8	16702	-0.062	0.13	NO
43	ULK3	ULK3	ULK3	16756	-0.063	0.14	NO
44	PIK3R2	PIK3R2	PIK3R2	17998	-0.082	0.097	NO
45	EIF4E	EIF4E	EIF4E	18013	-0.082	0.11	NO
46	RPS6KB2	RPS6KB2	RPS6KB2	18933	-0.1	0.088	NO
47	RPS6KA1	RPS6KA1	RPS6KA1	20053	-0.13	0.061	NO
48	EIF4EBP1	EIF4EBP1	EIF4EBP1	20354	-0.14	0.073	NO
49	VEGFA	VEGFA	VEGFA	20920	-0.16	0.076	NO

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

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

genes ES table in pathway: BIOCARTA BIOPEPTIDES PATHWAY

Table 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	IGF1	IGF1	IGF1	533	0.64	0.21	YES
2	PIK3CG	PIK3CG	PIK3CG	3894	0.21	0.14	YES
3	NFATC1	NFATC1	NFATC1	3913	0.21	0.22	YES
4	MEF2A	MEF2A	MEF2A	4932	0.16	0.23	YES
5	PIK3R1	PIK3R1	PIK3R1	4987	0.16	0.29	YES
6	CAMK1G	CAMK1G	CAMK1G	5003	0.16	0.34	YES
7	CAMK1	CAMK1	CAMK1	5534	0.14	0.37	YES
8	IGF1R	IGF1R	IGF1R	5723	0.13	0.41	YES
9	HDAC5	HDAC5	HDAC5	5792	0.13	0.46	YES
10	PPP3CC	PPP3CC	PPP3CC	6172	0.11	0.48	YES
11	PPP3CB	PPP3CB	PPP3CB	6551	0.1	0.5	YES
12	MEF2D	MEF2D	MEF2D	6738	0.097	0.53	YES
13	PIK3CA	PIK3CA	PIK3CA	6915	0.092	0.55	YES
14	INSR	INSR	INSR	7911	0.066	0.53	YES
15	NFATC2	NFATC2	NFATC2	8036	0.063	0.55	YES
16	CALM1	CALM1	CALM1	8440	0.054	0.55	YES
17	MAPK7	MAPK7	MAPK7	8479	0.053	0.57	YES
18	PPP3CA	PPP3CA	PPP3CA	9739	0.03	0.53	NO
19	MAPK14	MAPK14	MAPK14	10104	0.024	0.52	NO
20	CABIN1	CABIN1	CABIN1	10752	0.015	0.5	NO
21	AKT1	AKT1	AKT1	11677	0.0016	0.46	NO
22	CALM2	CALM2	CALM2	11803	-7.5e-06	0.45	NO
23	YWHAH	YWHAH	YWHAH	12936	-0.015	0.41	NO
24	CALM3	CALM3	CALM3	13287	-0.019	0.4	NO
25	MAP2K6	MAP2K6	MAP2K6	15268	-0.043	0.33	NO

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

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

genes ES table in pathway: BIOCARTA HDAC PATHWAY

Table 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	VIPR2	VIPR2	VIPR2	179	0.82	0.27	YES
2	PRKAR2B	PRKAR2B	PRKAR2B	1447	0.43	0.36	YES
3	EGR3	EGR3	EGR3	3337	0.24	0.36	YES
4	PRKACB	PRKACB	PRKACB	3875	0.21	0.41	YES
5	EGR2	EGR2	EGR2	3903	0.21	0.48	YES
6	NFATC1	NFATC1	NFATC1	3913	0.21	0.55	YES
7	PPP3CC	PPP3CC	PPP3CC	6172	0.11	0.49	NO
8	PPP3CB	PPP3CB	PPP3CB	6551	0.1	0.5	NO
9	GNAQ	GNAQ	GNAQ	7892	0.066	0.47	NO
10	NFATC2	NFATC2	NFATC2	8036	0.063	0.48	NO
11	CALM1	CALM1	CALM1	8440	0.054	0.48	NO
12	PLCG1	PLCG1	PLCG1	8483	0.053	0.5	NO
13	PRKAR1A	PRKAR1A	PRKAR1A	8724	0.048	0.5	NO
14	NFKBIA	NFKBIA	NFKBIA	9006	0.043	0.51	NO
15	PPP3CA	PPP3CA	PPP3CA	9739	0.03	0.48	NO
16	PRKAR2A	PRKAR2A	PRKAR2A	9956	0.027	0.48	NO
17	NFKB1	NFKB1	NFKB1	11307	0.0066	0.43	NO
18	MAP3K1	MAP3K1	MAP3K1	11741	0.00073	0.41	NO
19	CALM2	CALM2	CALM2	11803	-7.5e-06	0.4	NO
20	RELA	RELA	RELA	12079	-0.0036	0.39	NO
21	CALM3	CALM3	CALM3	13287	-0.019	0.35	NO
22	MYC	MYC	MYC	13619	-0.023	0.34	NO
23	PRKACG	PRKACG	PRKACG	15906	-0.051	0.26	NO
24	PRKAR1B	PRKAR1B	PRKAR1B	16199	-0.055	0.26	NO
25	CHUK	CHUK	CHUK	17042	-0.067	0.25	NO

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

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

genes ES table in pathway: BIOCARTA EGF PATHWAY

Table 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	CTNNA3	CTNNA3	CTNNA3	22	1.1	0.059	YES
2	DES	DES	DES	85	0.93	0.11	YES
3	SGCA	SGCA	SGCA	125	0.88	0.16	YES
4	ACTN2	ACTN2	ACTN2	173	0.83	0.2	YES
5	CACNB2	CACNB2	CACNB2	499	0.65	0.22	YES
6	SGCG	SGCG	SGCG	540	0.64	0.26	YES
7	RYR2	RYR2	RYR2	601	0.62	0.29	YES
8	CACNA2D3	CACNA2D3	CACNA2D3	692	0.59	0.32	YES
9	ITGA7	ITGA7	ITGA7	766	0.57	0.34	YES
10	DMD	DMD	DMD	795	0.56	0.37	YES
11	CACNA1C	CACNA1C	CACNA1C	873	0.54	0.4	YES
12	CACNA2D1	CACNA2D1	CACNA2D1	931	0.53	0.43	YES
13	SGCD	SGCD	SGCD	1066	0.5	0.45	YES
14	ITGA9	ITGA9	ITGA9	1178	0.48	0.47	YES
15	ITGA8	ITGA8	ITGA8	1202	0.47	0.5	YES
16	LAMA2	LAMA2	LAMA2	1459	0.43	0.51	YES
17	CACNB4	CACNB4	CACNB4	1680	0.4	0.52	YES
18	CTNNA2	CTNNA2	CTNNA2	1692	0.4	0.54	YES
19	ITGA10	ITGA10	ITGA10	1777	0.38	0.56	YES
20	SLC8A1	SLC8A1	SLC8A1	2000	0.36	0.57	YES
21	TCF7L1	TCF7L1	TCF7L1	2084	0.35	0.58	YES
22	CACNG7	CACNG7	CACNG7	2137	0.34	0.6	YES
23	CACNG4	CACNG4	CACNG4	2188	0.34	0.62	YES
24	ITGB3	ITGB3	ITGB3	2326	0.32	0.63	YES
25	CDH2	CDH2	CDH2	2947	0.27	0.62	YES
26	ITGA1	ITGA1	ITGA1	3050	0.26	0.63	YES
27	ACTN3	ACTN3	ACTN3	3386	0.24	0.63	YES
28	ITGA5	ITGA5	ITGA5	3401	0.24	0.64	YES
29	CACNA2D2	CACNA2D2	CACNA2D2	3445	0.24	0.65	YES
30	GJA1	GJA1	GJA1	3622	0.22	0.65	YES
31	ACTN1	ACTN1	ACTN1	3968	0.2	0.65	NO
32	CACNG1	CACNG1	CACNG1	4252	0.19	0.65	NO
33	CACNA1S	CACNA1S	CACNA1S	4716	0.17	0.64	NO
34	LEF1	LEF1	LEF1	5294	0.15	0.62	NO
35	SGCB	SGCB	SGCB	5538	0.14	0.62	NO
36	CACNG8	CACNG8	CACNG8	5780	0.13	0.61	NO
37	ITGA11	ITGA11	ITGA11	6213	0.11	0.6	NO
38	ITGB1	ITGB1	ITGB1	6335	0.11	0.6	NO
39	ITGA4	ITGA4	ITGA4	6434	0.11	0.6	NO
40	ITGAV	ITGAV	ITGAV	6908	0.092	0.59	NO
41	CACNG2	CACNG2	CACNG2	7212	0.083	0.58	NO
42	CACNB3	CACNB3	CACNB3	7320	0.08	0.58	NO
43	CACNA1D	CACNA1D	CACNA1D	7322	0.08	0.58	NO
44	ITGB5	ITGB5	ITGB5	7433	0.078	0.58	NO
45	TCF7	TCF7	TCF7	7748	0.07	0.57	NO
46	ITGB8	ITGB8	ITGB8	7785	0.069	0.57	NO
47	ACTB	ACTB	ACTB	8588	0.051	0.54	NO
48	CACNB1	CACNB1	CACNB1	8669	0.049	0.54	NO
49	ITGB7	ITGB7	ITGB7	8680	0.049	0.54	NO
50	CACNA2D4	CACNA2D4	CACNA2D4	9347	0.037	0.51	NO
51	ITGA2B	ITGA2B	ITGA2B	10457	0.019	0.47	NO
52	LMNA	LMNA	LMNA	10712	0.015	0.46	NO
53	ACTN4	ACTN4	ACTN4	11670	0.0017	0.41	NO
54	CTNNA1	CTNNA1	CTNNA1	12102	-0.0039	0.4	NO
55	EMD	EMD	EMD	12820	-0.013	0.36	NO
56	CACNG3	CACNG3	CACNG3	13091	-0.016	0.35	NO
57	CTNNB1	CTNNB1	CTNNB1	13143	-0.017	0.35	NO
58	DAG1	DAG1	DAG1	13199	-0.018	0.35	NO
59	TCF7L2	TCF7L2	TCF7L2	13228	-0.018	0.35	NO
60	ITGA3	ITGA3	ITGA3	13941	-0.027	0.32	NO
61	CACNG6	CACNG6	CACNG6	14797	-0.038	0.28	NO
62	ACTG1	ACTG1	ACTG1	14946	-0.039	0.28	NO
63	ATP2A2	ATP2A2	ATP2A2	15087	-0.041	0.28	NO
64	CACNA1F	CACNA1F	CACNA1F	15281	-0.043	0.27	NO
65	ITGB4	ITGB4	ITGB4	16130	-0.054	0.24	NO
66	ITGA2	ITGA2	ITGA2	16653	-0.061	0.22	NO
67	ITGB6	ITGB6	ITGB6	17109	-0.068	0.2	NO
68	ITGA6	ITGA6	ITGA6	17196	-0.069	0.2	NO
69	PKP2	PKP2	PKP2	19113	-0.1	0.12	NO
70	DSP	DSP	DSP	19239	-0.11	0.12	NO
71	CACNG5	CACNG5	CACNG5	19667	-0.12	0.11	NO
72	DSG2	DSG2	DSG2	20279	-0.14	0.088	NO
73	JUP	JUP	JUP	20543	-0.15	0.085	NO
74	DSC2	DSC2	DSC2	20609	-0.15	0.09	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: BIOCARTA EGF PATHWAY.

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

genes ES table in pathway: BIOCARTA ERK PATHWAY

Table 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	ACTN2	ACTN2	ACTN2	173	0.83	0.16	YES
2	PPP1R12B	PPP1R12B	PPP1R12B	866	0.54	0.24	YES
3	ACTA1	ACTA1	ACTA1	1196	0.47	0.32	YES
4	TNS1	TNS1	TNS1	1207	0.47	0.41	YES
5	CAV1	CAV1	CAV1	2400	0.32	0.42	YES
6	ITGA1	ITGA1	ITGA1	3050	0.26	0.45	YES
7	ACTN3	ACTN3	ACTN3	3386	0.24	0.48	YES
8	ACTN1	ACTN1	ACTN1	3968	0.2	0.5	YES
9	VCL	VCL	VCL	4565	0.18	0.51	YES
10	FYN	FYN	FYN	5561	0.14	0.49	YES
11	ZYX	ZYX	ZYX	5941	0.12	0.5	YES
12	RAP1A	RAP1A	RAP1A	6293	0.11	0.5	YES
13	ITGB1	ITGB1	ITGB1	6335	0.11	0.52	YES
14	ROCK1	ROCK1	ROCK1	7252	0.082	0.5	NO
15	RAPGEF1	RAPGEF1	RAPGEF1	7669	0.072	0.5	NO
16	JUN	JUN	JUN	7855	0.067	0.5	NO
17	SOS1	SOS1	SOS1	8673	0.049	0.47	NO
18	BCR	BCR	BCR	9134	0.041	0.46	NO
19	MAPK1	MAPK1	MAPK1	10793	0.014	0.39	NO
20	SHC1	SHC1	SHC1	11483	0.0041	0.36	NO
21	CRKL	CRKL	CRKL	11531	0.0036	0.36	NO
22	PXN	PXN	PXN	11649	0.002	0.36	NO
23	RAF1	RAF1	RAF1	11688	0.0015	0.36	NO
24	RHOA	RHOA	RHOA	12545	-0.0097	0.32	NO
25	MAP2K2	MAP2K2	MAP2K2	13326	-0.019	0.29	NO
26	CAPNS1	CAPNS1	CAPNS1	13885	-0.026	0.27	NO
27	GRB2	GRB2	GRB2	13953	-0.027	0.27	NO
28	PTK2	PTK2	PTK2	14320	-0.031	0.26	NO
29	MAPK3	MAPK3	MAPK3	14344	-0.032	0.27	NO
30	MAP2K1	MAP2K1	MAP2K1	15554	-0.046	0.22	NO
31	MAPK8	MAPK8	MAPK8	15636	-0.047	0.23	NO
32	CAPN1	CAPN1	CAPN1	16094	-0.053	0.22	NO
33	CSK	CSK	CSK	16299	-0.056	0.22	NO
34	HRAS	HRAS	HRAS	16737	-0.062	0.21	NO
35	CAPNS2	CAPNS2	CAPNS2	17114	-0.068	0.21	NO
36	BCAR1	BCAR1	BCAR1	17356	-0.072	0.22	NO
37	SRC	SRC	SRC	18613	-0.093	0.18	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: BIOCARTA ERK PATHWAY.

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

genes ES table in pathway: BIOCARTA FCER1 PATHWAY

Table 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	CTNNA3	CTNNA3	CTNNA3	22	1.1	0.11	YES
2	ACTN2	ACTN2	ACTN2	173	0.83	0.19	YES
3	SORBS1	SORBS1	SORBS1	779	0.57	0.22	YES
4	WASF3	WASF3	WASF3	1651	0.4	0.23	YES
5	CTNNA2	CTNNA2	CTNNA2	1692	0.4	0.27	YES
6	TCF7L1	TCF7L1	TCF7L1	2084	0.35	0.29	YES
7	FGFR1	FGFR1	FGFR1	2142	0.34	0.32	YES
8	WASF1	WASF1	WASF1	2950	0.27	0.31	YES
9	PTPRM	PTPRM	PTPRM	3125	0.26	0.33	YES
10	ACTN3	ACTN3	ACTN3	3386	0.24	0.34	YES
11	ACTN1	ACTN1	ACTN1	3968	0.2	0.34	YES
12	FER	FER	FER	4246	0.19	0.35	YES
13	VCL	VCL	VCL	4565	0.18	0.35	YES
14	PTPRB	PTPRB	PTPRB	4797	0.16	0.36	YES
15	TGFBR1	TGFBR1	TGFBR1	5289	0.15	0.35	YES
16	LEF1	LEF1	LEF1	5294	0.15	0.37	YES
17	WAS	WAS	WAS	5306	0.15	0.38	YES
18	TGFBR2	TGFBR2	TGFBR2	5389	0.14	0.39	YES
19	FYN	FYN	FYN	5561	0.14	0.4	YES
20	SNAI2	SNAI2	SNAI2	5587	0.14	0.41	YES
21	IGF1R	IGF1R	IGF1R	5723	0.13	0.42	YES
22	EGFR	EGFR	EGFR	6759	0.096	0.38	NO
23	WASF2	WASF2	WASF2	7133	0.085	0.38	NO
24	TJP1	TJP1	TJP1	7200	0.083	0.38	NO
25	SMAD4	SMAD4	SMAD4	7728	0.07	0.37	NO
26	TCF7	TCF7	TCF7	7748	0.07	0.37	NO
27	CREBBP	CREBBP	CREBBP	7790	0.069	0.38	NO
28	INSR	INSR	INSR	7911	0.066	0.38	NO
29	ACTB	ACTB	ACTB	8588	0.051	0.36	NO
30	RAC2	RAC2	RAC2	8804	0.047	0.35	NO
31	PARD3	PARD3	PARD3	8950	0.044	0.35	NO
32	SNAI1	SNAI1	SNAI1	9658	0.032	0.32	NO
33	SMAD2	SMAD2	SMAD2	9917	0.027	0.31	NO
34	BAIAP2	BAIAP2	BAIAP2	10205	0.023	0.3	NO
35	CSNK2A2	CSNK2A2	CSNK2A2	10523	0.018	0.29	NO
36	MAPK1	MAPK1	MAPK1	10793	0.014	0.28	NO
37	IQGAP1	IQGAP1	IQGAP1	11047	0.01	0.27	NO
38	EP300	EP300	EP300	11091	0.0098	0.27	NO
39	ACTN4	ACTN4	ACTN4	11670	0.0017	0.24	NO
40	PVRL3	PVRL3	PVRL3	11729	0.00092	0.24	NO
41	CDC42	CDC42	CDC42	11954	-0.002	0.23	NO
42	WASL	WASL	WASL	12022	-0.0028	0.23	NO
43	CTNNA1	CTNNA1	CTNNA1	12102	-0.0039	0.22	NO
44	MAP3K7	MAP3K7	MAP3K7	12351	-0.0073	0.22	NO
45	RHOA	RHOA	RHOA	12545	-0.0097	0.21	NO
46	SMAD3	SMAD3	SMAD3	12900	-0.014	0.19	NO
47	PTPN1	PTPN1	PTPN1	12982	-0.015	0.19	NO
48	CTNNB1	CTNNB1	CTNNB1	13143	-0.017	0.18	NO
49	TCF7L2	TCF7L2	TCF7L2	13228	-0.018	0.18	NO
50	PTPRJ	PTPRJ	PTPRJ	13936	-0.026	0.16	NO
51	MAPK3	MAPK3	MAPK3	14344	-0.032	0.14	NO
52	CTNND1	CTNND1	CTNND1	14458	-0.033	0.14	NO
53	RAC1	RAC1	RAC1	14606	-0.035	0.14	NO
54	FARP2	FARP2	FARP2	14746	-0.037	0.13	NO
55	ACTG1	ACTG1	ACTG1	14946	-0.039	0.13	NO
56	PTPN6	PTPN6	PTPN6	15215	-0.042	0.12	NO
57	MLLT4	MLLT4	MLLT4	15350	-0.044	0.12	NO
58	NLK	NLK	NLK	15748	-0.049	0.11	NO
59	SSX2IP	SSX2IP	SSX2IP	16784	-0.063	0.068	NO
60	CSNK2B	CSNK2B	CSNK2B	16891	-0.065	0.07	NO
61	MET	MET	MET	17043	-0.067	0.071	NO
62	YES1	YES1	YES1	17399	-0.072	0.062	NO
63	CSNK2A1	CSNK2A1	CSNK2A1	17749	-0.078	0.055	NO
64	PTPRF	PTPRF	PTPRF	18106	-0.084	0.048	NO
65	PVRL1	PVRL1	PVRL1	18414	-0.09	0.044	NO
66	SRC	SRC	SRC	18613	-0.093	0.045	NO
67	ACP1	ACP1	ACP1	19302	-0.11	0.026	NO
68	PVRL2	PVRL2	PVRL2	19398	-0.11	0.033	NO
69	LMO7	LMO7	LMO7	20034	-0.13	0.018	NO
70	ERBB2	ERBB2	ERBB2	20358	-0.14	0.019	NO
71	CDH1	CDH1	CDH1	22063	-0.25	-0.031	NO
72	PVRL4	PVRL4	PVRL4	22163	-0.26	-0.0081	NO
73	RAC3	RAC3	RAC3	22313	-0.28	0.015	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: BIOCARTA FCER1 PATHWAY.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG GLYCOLYSIS GLUCONEOGENESIS	59	genes.ES.table	0.56	1.9	0	0.11	0.13	0.29	0.12	0.25	0	0.038
KEGG PENTOSE PHOSPHATE PATHWAY	25	genes.ES.table	0.51	1.6	0.032	0.22	0.6	0.24	0.14	0.21	0.086	0.044
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.55	1.7	0.03	0.19	0.42	0.34	0.13	0.3	0	0.043
KEGG FATTY ACID METABOLISM	39	genes.ES.table	0.58	1.8	0.008	0.12	0.24	0.2	0.067	0.19	0	0.035
KEGG OXIDATIVE PHOSPHORYLATION	112	genes.ES.table	0.48	2	0.03	0.13	0.084	0.55	0.26	0.41	0	0.049
KEGG HISTIDINE METABOLISM	28	genes.ES.table	0.59	1.7	0.008	0.17	0.48	0.39	0.15	0.34	0	0.034
KEGG GLUTATHIONE METABOLISM	45	genes.ES.table	0.53	1.7	0.026	0.21	0.41	0.44	0.21	0.35	0	0.058
KEGG O GLYCAN BIOSYNTHESIS	29	genes.ES.table	0.57	1.5	0.03	0.28	0.71	0.41	0.094	0.38	0.14	0.064
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	42	genes.ES.table	0.4	1.5	0.1	0.29	0.77	0.43	0.21	0.34	0.17	0.056
KEGG ARACHIDONIC ACID METABOLISM	53	genes.ES.table	0.57	1.5	0.032	0.26	0.74	0.34	0.088	0.31	0.14	0.052

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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	ATP4B	ATP4B	ATP4B	76	0.48	0.11	YES
2	ATP4A	ATP4A	ATP4A	130	0.41	0.2	YES
3	ATP6V0D2	ATP6V0D2	ATP6V0D2	774	0.2	0.22	YES
4	UQCRHL	UQCRHL	UQCRHL	2561	0.076	0.16	YES
5	COX17	COX17	COX17	2912	0.065	0.16	YES
6	NDUFA1	NDUFA1	NDUFA1	3160	0.058	0.16	YES
7	ATP6V0B	ATP6V0B	ATP6V0B	3184	0.058	0.17	YES
8	NDUFA2	NDUFA2	NDUFA2	3242	0.056	0.18	YES
9	UQCR10	UQCR10	UQCR10	3261	0.056	0.19	YES
10	NDUFB10	NDUFB10	NDUFB10	3488	0.051	0.2	YES
11	UQCRQ	UQCRQ	UQCRQ	3509	0.051	0.21	YES
12	NDUFS7	NDUFS7	NDUFS7	3580	0.049	0.22	YES
13	NDUFA7	NDUFA7	NDUFA7	3599	0.049	0.22	YES
14	COX7B	COX7B	COX7B	3627	0.048	0.24	YES
15	ATP6V0C	ATP6V0C	ATP6V0C	3628	0.048	0.25	YES
16	NDUFV2	NDUFV2	NDUFV2	3634	0.048	0.26	YES
17	UQCRH	UQCRH	UQCRH	3771	0.045	0.26	YES
18	COX7C	COX7C	COX7C	3797	0.045	0.27	YES
19	NDUFA3	NDUFA3	NDUFA3	3825	0.044	0.28	YES
20	COX8A	COX8A	COX8A	3853	0.044	0.29	YES
21	ATP5G3	ATP5G3	ATP5G3	3877	0.043	0.3	YES
22	ATP6V0D1	ATP6V0D1	ATP6V0D1	4005	0.041	0.3	YES
23	NDUFB3	NDUFB3	NDUFB3	4041	0.04	0.31	YES
24	NDUFA4	NDUFA4	NDUFA4	4052	0.04	0.32	YES
25	UQCRC2	UQCRC2	UQCRC2	4054	0.04	0.33	YES
26	ATP5D	ATP5D	ATP5D	4116	0.039	0.34	YES
27	LHPP	LHPP	LHPP	4144	0.038	0.34	YES
28	COX11	COX11	COX11	4176	0.038	0.35	YES
29	ATP6V0E2	ATP6V0E2	ATP6V0E2	4231	0.037	0.36	YES
30	NDUFB7	NDUFB7	NDUFB7	4294	0.036	0.36	YES
31	COX5B	COX5B	COX5B	4348	0.035	0.37	YES
32	COX6A1	COX6A1	COX6A1	4391	0.034	0.37	YES
33	NDUFS2	NDUFS2	NDUFS2	4410	0.034	0.38	YES
34	NDUFS8	NDUFS8	NDUFS8	4415	0.034	0.39	YES
35	COX5A	COX5A	COX5A	4448	0.034	0.4	YES
36	ATP5I	ATP5I	ATP5I	4462	0.034	0.4	YES
37	COX4I1	COX4I1	COX4I1	4467	0.034	0.41	YES
38	UQCR11	UQCR11	UQCR11	4529	0.033	0.42	YES
39	ATP5G2	ATP5G2	ATP5G2	4533	0.033	0.42	YES
40	NDUFB5	NDUFB5	NDUFB5	4535	0.033	0.43	YES
41	NDUFS6	NDUFS6	NDUFS6	4712	0.03	0.43	YES
42	NDUFS4	NDUFS4	NDUFS4	4725	0.03	0.44	YES
43	NDUFC1	NDUFC1	NDUFC1	4761	0.029	0.44	YES
44	NDUFB1	NDUFB1	NDUFB1	4788	0.029	0.45	YES
45	PPA2	PPA2	PPA2	4935	0.027	0.45	YES
46	COX6B1	COX6B1	COX6B1	5045	0.026	0.45	YES
47	ATP6V0E1	ATP6V0E1	ATP6V0E1	5055	0.026	0.45	YES
48	NDUFB9	NDUFB9	NDUFB9	5087	0.025	0.46	YES
49	ATP5F1	ATP5F1	ATP5F1	5112	0.025	0.46	YES
50	NDUFV1	NDUFV1	NDUFV1	5179	0.024	0.46	YES
51	NDUFB6	NDUFB6	NDUFB6	5192	0.024	0.47	YES
52	NDUFB4	NDUFB4	NDUFB4	5216	0.024	0.47	YES
53	UQCRB	UQCRB	UQCRB	5399	0.022	0.47	YES
54	NDUFS3	NDUFS3	NDUFS3	5456	0.021	0.47	YES
55	COX6B2	COX6B2	COX6B2	5499	0.02	0.48	YES
56	NDUFAB1	NDUFAB1	NDUFAB1	5519	0.02	0.48	YES
57	ATP6V0A4	ATP6V0A4	ATP6V0A4	5787	0.017	0.47	YES
58	SDHA	SDHA	SDHA	5830	0.017	0.48	YES
59	ATP5H	ATP5H	ATP5H	5876	0.016	0.48	YES
60	COX7A2L	COX7A2L	COX7A2L	5910	0.016	0.48	YES
61	NDUFA6	NDUFA6	NDUFA6	5956	0.015	0.48	YES
62	COX4I2	COX4I2	COX4I2	5958	0.015	0.48	YES
63	NDUFS5	NDUFS5	NDUFS5	6178	0.013	0.48	NO
64	ATP6V0A2	ATP6V0A2	ATP6V0A2	6249	0.012	0.48	NO
65	ATP6V1G1	ATP6V1G1	ATP6V1G1	6264	0.012	0.48	NO
66	ATP5J	ATP5J	ATP5J	6346	0.012	0.48	NO
67	SDHC	SDHC	SDHC	6403	0.011	0.48	NO
68	NDUFA10	NDUFA10	NDUFA10	6447	0.011	0.48	NO
69	COX7A2	COX7A2	COX7A2	6474	0.011	0.48	NO
70	ATP5E	ATP5E	ATP5E	6488	0.01	0.48	NO
71	ATP5G1	ATP5G1	ATP5G1	6539	0.01	0.48	NO
72	UQCRC1	UQCRC1	UQCRC1	6655	0.009	0.48	NO
73	NDUFB2	NDUFB2	NDUFB2	6661	0.0089	0.48	NO
74	ATP5B	ATP5B	ATP5B	6681	0.0087	0.48	NO
75	CYC1	CYC1	CYC1	6757	0.0081	0.48	NO
76	ATP5A1	ATP5A1	ATP5A1	6790	0.0078	0.48	NO
77	TCIRG1	TCIRG1	TCIRG1	6934	0.0067	0.48	NO
78	ATP6V1D	ATP6V1D	ATP6V1D	6952	0.0066	0.48	NO
79	COX6C	COX6C	COX6C	7039	0.0059	0.48	NO
80	NDUFB8	NDUFB8	NDUFB8	7117	0.0051	0.47	NO
81	SDHB	SDHB	SDHB	7163	0.0047	0.47	NO
82	NDUFA11	NDUFA11	NDUFA11	7200	0.0044	0.47	NO
83	COX15	COX15	COX15	7242	0.0041	0.47	NO
84	ATP6V1A	ATP6V1A	ATP6V1A	7382	0.0029	0.46	NO
85	ATP6V1E1	ATP6V1E1	ATP6V1E1	7452	0.0023	0.46	NO
86	PPA1	PPA1	PPA1	7906	-0.0011	0.44	NO
87	ATP5C1	ATP5C1	ATP5C1	7928	-0.0013	0.44	NO
88	NDUFS1	NDUFS1	NDUFS1	8264	-0.0038	0.43	NO
89	ATP5L	ATP5L	ATP5L	8436	-0.0052	0.42	NO
90	ATP6V0A1	ATP6V0A1	ATP6V0A1	8439	-0.0052	0.42	NO
91	SDHD	SDHD	SDHD	8466	-0.0054	0.42	NO
92	UQCRFS1	UQCRFS1	UQCRFS1	8556	-0.0061	0.42	NO
93	ATP6AP1	ATP6AP1	ATP6AP1	8743	-0.0075	0.41	NO
94	ATP6V1C2	ATP6V1C2	ATP6V1C2	8860	-0.0082	0.41	NO
95	NDUFV3	NDUFV3	NDUFV3	8888	-0.0085	0.41	NO
96	NDUFA5	NDUFA5	NDUFA5	9127	-0.01	0.4	NO
97	NDUFA9	NDUFA9	NDUFA9	9419	-0.012	0.39	NO
98	NDUFA8	NDUFA8	NDUFA8	9827	-0.015	0.38	NO
99	ATP6V1F	ATP6V1F	ATP6V1F	10801	-0.021	0.34	NO
100	ATP6V1C1	ATP6V1C1	ATP6V1C1	10986	-0.022	0.34	NO
101	ATP6V1B2	ATP6V1B2	ATP6V1B2	11171	-0.023	0.33	NO
102	ATP12A	ATP12A	ATP12A	11244	-0.024	0.34	NO
103	ATP6V1E2	ATP6V1E2	ATP6V1E2	11260	-0.024	0.34	NO
104	ATP6V1H	ATP6V1H	ATP6V1H	11815	-0.027	0.32	NO
105	COX10	COX10	COX10	12797	-0.034	0.29	NO
106	COX7B2	COX7B2	COX7B2	14719	-0.05	0.21	NO
107	NDUFA4L2	NDUFA4L2	NDUFA4L2	15400	-0.055	0.2	NO
108	ATP6V1B1	ATP6V1B1	ATP6V1B1	16593	-0.068	0.16	NO
109	COX8C	COX8C	COX8C	17456	-0.08	0.14	NO
110	COX7A1	COX7A1	COX7A1	19170	-0.11	0.089	NO
111	COX6A2	COX6A2	COX6A2	20153	-0.14	0.077	NO
112	ATP6V1G2	ATP6V1G2	ATP6V1G2	20469	-0.14	0.096	NO

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

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

genes ES table in pathway: KEGG PENTOSE PHOSPHATE PATHWAY

Table 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	ADH1C	ADH1C	ADH1C	38	0.58	0.1	YES
2	ADH7	ADH7	ADH7	44	0.55	0.2	YES
3	ALDH3A1	ALDH3A1	ALDH3A1	49	0.53	0.29	YES
4	FBP2	FBP2	FBP2	87	0.46	0.37	YES
5	ALDOB	ALDOB	ALDOB	346	0.3	0.41	YES
6	ADH1B	ADH1B	ADH1B	557	0.24	0.44	YES
7	FBP1	FBP1	FBP1	772	0.2	0.47	YES
8	ADH1A	ADH1A	ADH1A	809	0.19	0.5	YES
9	ALDH3B1	ALDH3B1	ALDH3B1	1131	0.16	0.51	YES
10	ALDH2	ALDH2	ALDH2	1403	0.13	0.52	YES
11	ADH6	ADH6	ADH6	1515	0.12	0.54	YES
12	PCK1	PCK1	PCK1	2307	0.085	0.52	YES
13	G6PC2	G6PC2	G6PC2	2313	0.084	0.54	YES
14	ACSS1	ACSS1	ACSS1	2423	0.08	0.55	YES
15	ACSS2	ACSS2	ACSS2	2642	0.073	0.55	YES
16	ADH4	ADH4	ADH4	2702	0.071	0.56	YES
17	AKR1A1	AKR1A1	AKR1A1	2824	0.068	0.56	YES
18	PGM1	PGM1	PGM1	3131	0.059	0.56	NO
19	HK2	HK2	HK2	3321	0.054	0.56	NO
20	ALDH3B2	ALDH3B2	ALDH3B2	3904	0.043	0.54	NO
21	HK1	HK1	HK1	4006	0.041	0.55	NO
22	GALM	GALM	GALM	4036	0.04	0.55	NO
23	ALDOA	ALDOA	ALDOA	4947	0.027	0.52	NO
24	ALDH9A1	ALDH9A1	ALDH9A1	4987	0.026	0.52	NO
25	BPGM	BPGM	BPGM	5436	0.021	0.5	NO
26	PFKL	PFKL	PFKL	5848	0.016	0.49	NO
27	LDHB	LDHB	LDHB	5997	0.015	0.48	NO
28	ALDH3A2	ALDH3A2	ALDH3A2	6175	0.013	0.48	NO
29	ALDH7A1	ALDH7A1	ALDH7A1	6246	0.012	0.48	NO
30	G6PC	G6PC	G6PC	6318	0.012	0.48	NO
31	PGK1	PGK1	PGK1	6550	0.0099	0.47	NO
32	PDHA1	PDHA1	PDHA1	7015	0.006	0.45	NO
33	TPI1	TPI1	TPI1	7610	0.00098	0.42	NO
34	PFKP	PFKP	PFKP	7843	-0.0006	0.41	NO
35	PCK2	PCK2	PCK2	8064	-0.0022	0.4	NO
36	DLD	DLD	DLD	8609	-0.0066	0.38	NO
37	GPI	GPI	GPI	8925	-0.0087	0.37	NO
38	PDHB	PDHB	PDHB	9374	-0.012	0.35	NO
39	PKLR	PKLR	PKLR	10044	-0.016	0.32	NO
40	GAPDH	GAPDH	GAPDH	10207	-0.017	0.32	NO
41	LDHA	LDHA	LDHA	10670	-0.02	0.3	NO
42	PGM2	PGM2	PGM2	10888	-0.021	0.3	NO
43	ENO1	ENO1	ENO1	11019	-0.022	0.29	NO
44	GCK	GCK	GCK	11051	-0.022	0.3	NO
45	LDHAL6B	LDHAL6B	LDHAL6B	12036	-0.029	0.26	NO
46	ADH5	ADH5	ADH5	12729	-0.034	0.23	NO
47	ALDOC	ALDOC	ALDOC	12983	-0.036	0.23	NO
48	PKM2	PKM2	PKM2	13009	-0.036	0.23	NO
49	ALDH1A3	ALDH1A3	ALDH1A3	13235	-0.038	0.23	NO
50	PGAM2	PGAM2	PGAM2	13963	-0.043	0.21	NO
51	PGAM1	PGAM1	PGAM1	15402	-0.055	0.15	NO
52	DLAT	DLAT	DLAT	16241	-0.064	0.13	NO
53	PFKM	PFKM	PFKM	16937	-0.072	0.11	NO
54	PGAM4	PGAM4	PGAM4	17267	-0.077	0.11	NO
55	LDHAL6A	LDHAL6A	LDHAL6A	19288	-0.11	0.038	NO
56	HK3	HK3	HK3	20087	-0.13	0.026	NO
57	ENO3	ENO3	ENO3	20916	-0.16	0.017	NO
58	ENO2	ENO2	ENO2	21022	-0.17	0.042	NO
59	ALDH1B1	ALDH1B1	ALDH1B1	21138	-0.17	0.067	NO

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

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

Table 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	AQP2	AQP2	AQP2	248	0.34	0.14	YES
2	CREB3L3	CREB3L3	CREB3L3	431	0.27	0.26	YES
3	CREB3L1	CREB3L1	CREB3L1	933	0.18	0.32	YES
4	AQP4	AQP4	AQP4	1130	0.16	0.38	YES
5	CREB3L4	CREB3L4	CREB3L4	1197	0.15	0.45	YES
6	AQP3	AQP3	AQP3	1779	0.11	0.47	YES
7	CREB3	CREB3	CREB3	2798	0.068	0.46	NO
8	DYNC2LI1	DYNC2LI1	DYNC2LI1	4071	0.04	0.42	NO
9	ARHGDIB	ARHGDIB	ARHGDIB	4779	0.029	0.4	NO
10	STX4	STX4	STX4	4819	0.028	0.41	NO
11	RAB11B	RAB11B	RAB11B	4874	0.028	0.42	NO
12	ARHGDIA	ARHGDIA	ARHGDIA	5133	0.025	0.42	NO
13	RAB5A	RAB5A	RAB5A	5361	0.022	0.42	NO
14	NSF	NSF	NSF	6431	0.011	0.38	NO
15	RAB5C	RAB5C	RAB5C	6702	0.0085	0.37	NO
16	RAB11A	RAB11A	RAB11A	6711	0.0084	0.38	NO
17	DCTN6	DCTN6	DCTN6	6975	0.0064	0.37	NO
18	DCTN5	DCTN5	DCTN5	7657	0.00066	0.34	NO
19	RAB5B	RAB5B	RAB5B	7850	-0.00065	0.33	NO
20	DYNC2H1	DYNC2H1	DYNC2H1	8173	-0.0031	0.32	NO
21	DCTN4	DCTN4	DCTN4	8315	-0.0041	0.31	NO
22	CREB3L2	CREB3L2	CREB3L2	8781	-0.0078	0.3	NO
23	DYNC1LI1	DYNC1LI1	DYNC1LI1	8826	-0.008	0.3	NO
24	DCTN1	DCTN1	DCTN1	8845	-0.0082	0.3	NO
25	PRKACA	PRKACA	PRKACA	9373	-0.012	0.28	NO
26	DYNLL1	DYNLL1	DYNLL1	9548	-0.013	0.28	NO
27	ADCY9	ADCY9	ADCY9	9576	-0.013	0.28	NO
28	VAMP2	VAMP2	VAMP2	10086	-0.016	0.27	NO
29	ADCY6	ADCY6	ADCY6	10167	-0.017	0.27	NO
30	DCTN2	DCTN2	DCTN2	10174	-0.017	0.28	NO
31	GNAS	GNAS	GNAS	10357	-0.018	0.28	NO
32	DYNLL2	DYNLL2	DYNLL2	10719	-0.02	0.27	NO
33	DYNC1I2	DYNC1I2	DYNC1I2	11123	-0.023	0.27	NO
34	PRKACG	PRKACG	PRKACG	12784	-0.034	0.21	NO
35	PRKACB	PRKACB	PRKACB	12799	-0.034	0.22	NO
36	DYNC1LI2	DYNC1LI2	DYNC1LI2	12837	-0.035	0.24	NO
37	DYNC1H1	DYNC1H1	DYNC1H1	13169	-0.037	0.24	NO
38	CREB1	CREB1	CREB1	14018	-0.044	0.22	NO
39	PRKX	PRKX	PRKX	17531	-0.081	0.1	NO
40	DYNC1I1	DYNC1I1	DYNC1I1	17665	-0.083	0.14	NO
41	AVPR2	AVPR2	AVPR2	17802	-0.085	0.17	NO
42	CREB5	CREB5	CREB5	18516	-0.097	0.18	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: KEGG FRUCTOSE AND MANNOSE METABOLISM.

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

genes ES table in pathway: KEGG FATTY ACID METABOLISM

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	ADH1C	ADH1C	ADH1C	38	0.58	0.15	YES
2	ADH7	ADH7	ADH7	44	0.55	0.3	YES
3	CYP4A11	CYP4A11	CYP4A11	156	0.39	0.4	YES
4	ADH1B	ADH1B	ADH1B	557	0.24	0.44	YES
5	ACADL	ACADL	ACADL	621	0.22	0.5	YES
6	ADH1A	ADH1A	ADH1A	809	0.19	0.55	YES
7	ALDH2	ALDH2	ALDH2	1403	0.13	0.55	YES
8	ADH6	ADH6	ADH6	1515	0.12	0.58	YES
9	EHHADH	EHHADH	EHHADH	2252	0.087	0.57	NO
10	ADH4	ADH4	ADH4	2702	0.071	0.57	NO
11	CPT2	CPT2	CPT2	3312	0.055	0.56	NO
12	ACAA1	ACAA1	ACAA1	3407	0.053	0.57	NO
13	ACADS	ACADS	ACADS	3723	0.046	0.57	NO
14	ACADM	ACADM	ACADM	3749	0.046	0.58	NO
15	CPT1A	CPT1A	CPT1A	4035	0.04	0.58	NO
16	ACSL5	ACSL5	ACSL5	4187	0.038	0.58	NO
17	ACADVL	ACADVL	ACADVL	4927	0.027	0.56	NO
18	ALDH9A1	ALDH9A1	ALDH9A1	4987	0.026	0.56	NO
19	HADH	HADH	HADH	5057	0.026	0.56	NO
20	CYP4A22	CYP4A22	CYP4A22	5397	0.022	0.56	NO
21	ACSL3	ACSL3	ACSL3	5403	0.022	0.56	NO
22	HADHA	HADHA	HADHA	5658	0.019	0.55	NO
23	ECHS1	ECHS1	ECHS1	6041	0.014	0.54	NO
24	ALDH3A2	ALDH3A2	ALDH3A2	6175	0.013	0.54	NO
25	ALDH7A1	ALDH7A1	ALDH7A1	6246	0.012	0.54	NO
26	GCDH	GCDH	GCDH	6476	0.011	0.53	NO
27	HADHB	HADHB	HADHB	6522	0.01	0.53	NO
28	ACOX3	ACOX3	ACOX3	6528	0.01	0.54	NO
29	ACADSB	ACADSB	ACADSB	6740	0.0082	0.53	NO
30	ACSL1	ACSL1	ACSL1	9689	-0.014	0.4	NO
31	ACAT2	ACAT2	ACAT2	9764	-0.014	0.4	NO
32	ACSL4	ACSL4	ACSL4	10434	-0.018	0.38	NO
33	CPT1B	CPT1B	CPT1B	11717	-0.026	0.33	NO
34	ADH5	ADH5	ADH5	12729	-0.034	0.29	NO
35	ACAT1	ACAT1	ACAT1	14015	-0.044	0.25	NO
36	ACAA2	ACAA2	ACAA2	15419	-0.056	0.2	NO
37	ACSL6	ACSL6	ACSL6	16624	-0.069	0.16	NO
38	ALDH1B1	ALDH1B1	ALDH1B1	21138	-0.17	0.01	NO
39	CPT1C	CPT1C	CPT1C	21808	-0.21	0.037	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: KEGG FATTY ACID METABOLISM.

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

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

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	ADH1C	ADH1C	ADH1C	38	0.58	0.057	YES
2	ADH7	ADH7	ADH7	44	0.55	0.11	YES
3	ALDH3A1	ALDH3A1	ALDH3A1	49	0.53	0.16	YES
4	GSTA1	GSTA1	GSTA1	51	0.53	0.22	YES
5	UGT2B15	UGT2B15	UGT2B15	66	0.5	0.27	YES
6	CYP2C19	CYP2C19	CYP2C19	74	0.48	0.32	YES
7	CYP2C9	CYP2C9	CYP2C9	114	0.42	0.36	YES
8	GSTA2	GSTA2	GSTA2	134	0.4	0.4	YES
9	UGT1A1	UGT1A1	UGT1A1	171	0.38	0.44	YES
10	CYP2C8	CYP2C8	CYP2C8	243	0.34	0.47	YES
11	AKR1C2	AKR1C2	AKR1C2	308	0.31	0.5	YES
12	DHDH	DHDH	DHDH	394	0.28	0.52	YES
13	CYP3A7	CYP3A7	CYP3A7	428	0.27	0.55	YES
14	UGT2A3	UGT2A3	UGT2A3	454	0.26	0.57	YES
15	ADH1B	ADH1B	ADH1B	557	0.24	0.59	YES
16	AKR1C3	AKR1C3	AKR1C3	581	0.23	0.61	YES
17	UGT2B28	UGT2B28	UGT2B28	741	0.2	0.63	YES
18	ADH1A	ADH1A	ADH1A	809	0.19	0.64	YES
19	CYP2E1	CYP2E1	CYP2E1	873	0.19	0.66	YES
20	UGT2B11	UGT2B11	UGT2B11	1083	0.16	0.67	YES
21	ALDH3B1	ALDH3B1	ALDH3B1	1131	0.16	0.68	YES
22	GSTA3	GSTA3	GSTA3	1237	0.15	0.69	YES
23	CYP2S1	CYP2S1	CYP2S1	1274	0.14	0.7	YES
24	ADH6	ADH6	ADH6	1515	0.12	0.7	YES
25	GSTT1	GSTT1	GSTT1	1524	0.12	0.72	YES
26	AKR1C4	AKR1C4	AKR1C4	1629	0.12	0.72	YES
27	UGT2B7	UGT2B7	UGT2B7	2143	0.091	0.71	NO
28	ADH4	ADH4	ADH4	2702	0.071	0.69	NO
29	MGST3	MGST3	MGST3	2723	0.07	0.7	NO
30	GSTM3	GSTM3	GSTM3	2920	0.064	0.7	NO
31	GSTP1	GSTP1	GSTP1	3543	0.05	0.68	NO
32	ALDH3B2	ALDH3B2	ALDH3B2	3904	0.043	0.66	NO
33	GSTO2	GSTO2	GSTO2	3915	0.042	0.67	NO
34	GSTZ1	GSTZ1	GSTZ1	4022	0.04	0.67	NO
35	MGST2	MGST2	MGST2	4554	0.032	0.65	NO
36	MGST1	MGST1	MGST1	4589	0.032	0.65	NO
37	GSTM4	GSTM4	GSTM4	4767	0.029	0.64	NO
38	EPHX1	EPHX1	EPHX1	5054	0.026	0.63	NO
39	GSTK1	GSTK1	GSTK1	5449	0.021	0.62	NO
40	UGT2B17	UGT2B17	UGT2B17	6563	0.0098	0.57	NO
41	GSTO1	GSTO1	GSTO1	9093	-0.01	0.46	NO
42	GSTM5	GSTM5	GSTM5	12133	-0.03	0.33	NO
43	GSTA4	GSTA4	GSTA4	12231	-0.03	0.33	NO
44	ADH5	ADH5	ADH5	12729	-0.034	0.31	NO
45	ALDH1A3	ALDH1A3	ALDH1A3	13235	-0.038	0.29	NO
46	GSTM1	GSTM1	GSTM1	13580	-0.04	0.28	NO
47	CYP1A1	CYP1A1	CYP1A1	14914	-0.051	0.22	NO
48	CYP3A43	CYP3A43	CYP3A43	17242	-0.077	0.13	NO
49	CYP2B6	CYP2B6	CYP2B6	17780	-0.085	0.11	NO
50	CYP1A2	CYP1A2	CYP1A2	18260	-0.092	0.1	NO
51	UGT2A1	UGT2A1	UGT2A1	18475	-0.096	0.1	NO
52	CYP2F1	CYP2F1	CYP2F1	20156	-0.14	0.041	NO
53	UGT2B10	UGT2B10	UGT2B10	20248	-0.14	0.051	NO
54	GSTT2	GSTT2	GSTT2	20319	-0.14	0.062	NO
55	UGT2B4	UGT2B4	UGT2B4	21654	-0.2	0.023	NO
56	CYP1B1	CYP1B1	CYP1B1	21761	-0.21	0.039	NO

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

Figure S50. 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 HISTIDINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GSTA1	GSTA1	GSTA1	51	0.53	0.17	YES
2	GSTA2	GSTA2	GSTA2	134	0.4	0.29	YES
3	ANPEP	ANPEP	ANPEP	1026	0.17	0.31	YES
4	GGT6	GGT6	GGT6	1074	0.16	0.36	YES
5	GSTA3	GSTA3	GSTA3	1237	0.15	0.4	YES
6	GPX2	GPX2	GPX2	1521	0.12	0.42	YES
7	GSTT1	GSTT1	GSTT1	1524	0.12	0.46	YES
8	GGT1	GGT1	GGT1	1788	0.11	0.49	YES
9	MGST3	MGST3	MGST3	2723	0.07	0.47	YES
10	GSTM3	GSTM3	GSTM3	2920	0.064	0.48	YES
11	GGT7	GGT7	GGT7	2931	0.064	0.5	YES
12	GSR	GSR	GSR	3431	0.052	0.49	YES
13	GSTP1	GSTP1	GSTP1	3543	0.05	0.5	YES
14	IDH1	IDH1	IDH1	3761	0.046	0.51	YES
15	GSTO2	GSTO2	GSTO2	3915	0.042	0.52	YES
16	GSTZ1	GSTZ1	GSTZ1	4022	0.04	0.52	YES
17	MGST2	MGST2	MGST2	4554	0.032	0.51	YES
18	MGST1	MGST1	MGST1	4589	0.032	0.52	YES
19	GSTM4	GSTM4	GSTM4	4767	0.029	0.52	YES
20	TXNDC12	TXNDC12	TXNDC12	4840	0.028	0.53	YES
21	GSTK1	GSTK1	GSTK1	5449	0.021	0.51	NO
22	GCLM	GCLM	GCLM	6654	0.009	0.46	NO
23	GSS	GSS	GSS	6851	0.0074	0.45	NO
24	OPLAH	OPLAH	OPLAH	6897	0.007	0.45	NO
25	G6PD	G6PD	G6PD	6968	0.0064	0.45	NO
26	GPX1	GPX1	GPX1	7012	0.0061	0.45	NO
27	GPX4	GPX4	GPX4	7919	-0.0012	0.41	NO
28	GCLC	GCLC	GCLC	8235	-0.0036	0.4	NO
29	GSTO1	GSTO1	GSTO1	9093	-0.01	0.36	NO
30	GPX3	GPX3	GPX3	10523	-0.019	0.31	NO
31	LAP3	LAP3	LAP3	10784	-0.021	0.3	NO
32	RRM1	RRM1	RRM1	10910	-0.021	0.3	NO
33	SRM	SRM	SRM	11543	-0.025	0.28	NO
34	GSTM5	GSTM5	GSTM5	12133	-0.03	0.27	NO
35	GSTA4	GSTA4	GSTA4	12231	-0.03	0.27	NO
36	SMS	SMS	SMS	12499	-0.032	0.27	NO
37	GGCT	GGCT	GGCT	12557	-0.032	0.28	NO
38	RRM2	RRM2	RRM2	13563	-0.04	0.25	NO
39	GSTM1	GSTM1	GSTM1	13580	-0.04	0.26	NO
40	RRM2B	RRM2B	RRM2B	14065	-0.044	0.25	NO
41	IDH2	IDH2	IDH2	14912	-0.051	0.23	NO
42	ODC1	ODC1	ODC1	15480	-0.056	0.22	NO
43	GGT5	GGT5	GGT5	17173	-0.076	0.17	NO
44	GPX7	GPX7	GPX7	17594	-0.082	0.18	NO
45	GSTT2	GSTT2	GSTT2	20319	-0.14	0.1	NO

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

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

genes ES table in pathway: KEGG GLUTATHIONE METABOLISM

Table 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	AKR1B10	AKR1B10	AKR1B10	27	0.61	0.19	YES
2	FBP2	FBP2	FBP2	87	0.46	0.33	YES
3	ALDOB	ALDOB	ALDOB	346	0.3	0.41	YES
4	FBP1	FBP1	FBP1	772	0.2	0.46	YES
5	GMDS	GMDS	GMDS	1263	0.14	0.48	YES
6	TSTA3	TSTA3	TSTA3	2215	0.088	0.46	YES
7	GMPPB	GMPPB	GMPPB	2251	0.087	0.49	YES
8	PMM2	PMM2	PMM2	2353	0.083	0.51	YES
9	PFKFB2	PFKFB2	PFKFB2	2567	0.076	0.52	YES
10	GMPPA	GMPPA	GMPPA	2833	0.067	0.54	YES
11	AKR1B1	AKR1B1	AKR1B1	2866	0.066	0.55	YES
12	HK2	HK2	HK2	3321	0.054	0.55	NO
13	HK1	HK1	HK1	4006	0.041	0.53	NO
14	PFKFB3	PFKFB3	PFKFB3	5033	0.026	0.5	NO
15	PFKL	PFKL	PFKL	5848	0.016	0.46	NO
16	TPI1	TPI1	TPI1	7610	0.00098	0.39	NO
17	PFKP	PFKP	PFKP	7843	-0.0006	0.38	NO
18	MPI	MPI	MPI	8374	-0.0046	0.36	NO
19	PMM1	PMM1	PMM1	9294	-0.011	0.32	NO
20	FUK	FUK	FUK	10113	-0.016	0.29	NO
21	MTMR1	MTMR1	MTMR1	11722	-0.026	0.22	NO
22	MTMR2	MTMR2	MTMR2	12574	-0.033	0.2	NO
23	ALDOC	ALDOC	ALDOC	12983	-0.036	0.19	NO
24	MTMR7	MTMR7	MTMR7	13201	-0.037	0.19	NO
25	MTMR6	MTMR6	MTMR6	13565	-0.04	0.19	NO
26	PHPT1	PHPT1	PHPT1	14217	-0.045	0.17	NO
27	SORD	SORD	SORD	14240	-0.046	0.19	NO
28	PFKM	PFKM	PFKM	16937	-0.072	0.091	NO
29	KHK	KHK	KHK	18234	-0.092	0.062	NO
30	PFKFB1	PFKFB1	PFKFB1	19284	-0.11	0.051	NO
31	HK3	HK3	HK3	20087	-0.13	0.056	NO
32	PFKFB4	PFKFB4	PFKFB4	21339	-0.18	0.058	NO

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

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

genes ES table in pathway: KEGG O GLYCAN BIOSYNTHESIS

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	PSAPL1	PSAPL1	PSAPL1	22	0.64	0.12	YES
2	CTSE	CTSE	CTSE	65	0.5	0.21	YES
3	HYAL1	HYAL1	HYAL1	226	0.35	0.26	YES
4	ATP6V0D2	ATP6V0D2	ATP6V0D2	774	0.2	0.27	YES
5	NAPSA	NAPSA	NAPSA	1447	0.13	0.27	YES
6	CTSH	CTSH	CTSH	1517	0.12	0.29	YES
7	DNASE2B	DNASE2B	DNASE2B	1839	0.11	0.29	YES
8	AP1M2	AP1M2	AP1M2	2293	0.085	0.29	YES
9	AP1S3	AP1S3	AP1S3	2527	0.077	0.29	YES
10	NAGPA	NAGPA	NAGPA	2914	0.065	0.29	YES
11	FUCA1	FUCA1	FUCA1	2932	0.064	0.3	YES
12	ATP6V0B	ATP6V0B	ATP6V0B	3184	0.058	0.3	YES
13	CLTB	CLTB	CLTB	3214	0.057	0.3	YES
14	IDUA	IDUA	IDUA	3273	0.055	0.31	YES
15	GALC	GALC	GALC	3575	0.049	0.31	YES
16	ATP6V0C	ATP6V0C	ATP6V0C	3628	0.048	0.32	YES
17	CD63	CD63	CD63	3642	0.048	0.32	YES
18	GNPTG	GNPTG	GNPTG	3796	0.045	0.32	YES
19	CTSL2	CTSL2	CTSL2	3810	0.045	0.33	YES
20	SLC17A5	SLC17A5	SLC17A5	3836	0.044	0.34	YES
21	CLN3	CLN3	CLN3	3964	0.041	0.34	YES
22	ATP6V0D1	ATP6V0D1	ATP6V0D1	4005	0.041	0.35	YES
23	MAN2B1	MAN2B1	MAN2B1	4008	0.041	0.35	YES
24	SUMF1	SUMF1	SUMF1	4010	0.04	0.36	YES
25	CD68	CD68	CD68	4129	0.039	0.36	YES
26	CTSS	CTSS	CTSS	4250	0.037	0.36	YES
27	AGA	AGA	AGA	4289	0.036	0.37	YES
28	GLB1	GLB1	GLB1	4316	0.036	0.37	YES
29	SGSH	SGSH	SGSH	4381	0.035	0.38	YES
30	LIPA	LIPA	LIPA	4436	0.034	0.38	YES
31	NAGLU	NAGLU	NAGLU	4885	0.028	0.37	NO
32	AP4B1	AP4B1	AP4B1	4892	0.028	0.37	NO
33	DNASE2	DNASE2	DNASE2	4894	0.028	0.38	NO
34	AP1G1	AP1G1	AP1G1	5178	0.024	0.37	NO
35	CTSF	CTSF	CTSF	5207	0.024	0.37	NO
36	ENTPD4	ENTPD4	ENTPD4	5589	0.019	0.36	NO
37	ARSA	ARSA	ARSA	5594	0.019	0.36	NO
38	SMPD1	SMPD1	SMPD1	5595	0.019	0.36	NO
39	CTNS	CTNS	CTNS	5608	0.019	0.37	NO
40	LGMN	LGMN	LGMN	5630	0.019	0.37	NO
41	AP3B1	AP3B1	AP3B1	5738	0.018	0.37	NO
42	CTSD	CTSD	CTSD	5780	0.017	0.37	NO
43	ATP6V0A4	ATP6V0A4	ATP6V0A4	5787	0.017	0.37	NO
44	ACP5	ACP5	ACP5	5936	0.016	0.37	NO
45	GUSB	GUSB	GUSB	5980	0.015	0.37	NO
46	GBA	GBA	GBA	6240	0.012	0.36	NO
47	ATP6V0A2	ATP6V0A2	ATP6V0A2	6249	0.012	0.36	NO
48	CLTA	CLTA	CLTA	6273	0.012	0.36	NO
49	CTSC	CTSC	CTSC	6436	0.011	0.36	NO
50	CTSA	CTSA	CTSA	6443	0.011	0.36	NO
51	AP3D1	AP3D1	AP3D1	6602	0.0095	0.36	NO
52	MCOLN1	MCOLN1	MCOLN1	6676	0.0087	0.35	NO
53	AP1B1	AP1B1	AP1B1	6685	0.0086	0.36	NO
54	AP3B2	AP3B2	AP3B2	6700	0.0085	0.36	NO
55	PSAP	PSAP	PSAP	6845	0.0075	0.35	NO
56	GM2A	GM2A	GM2A	6873	0.0072	0.35	NO
57	ASAH1	ASAH1	ASAH1	6919	0.0068	0.35	NO
58	TCIRG1	TCIRG1	TCIRG1	6934	0.0067	0.35	NO
59	HEXB	HEXB	HEXB	6936	0.0067	0.35	NO
60	GALNS	GALNS	GALNS	7131	0.005	0.34	NO
61	GNPTAB	GNPTAB	GNPTAB	7283	0.0037	0.34	NO
62	ARSG	ARSG	ARSG	7404	0.0026	0.33	NO
63	CTSG	CTSG	CTSG	7424	0.0025	0.33	NO
64	CLTC	CLTC	CLTC	7473	0.0021	0.33	NO
65	MANBA	MANBA	MANBA	7550	0.0015	0.33	NO
66	NPC2	NPC2	NPC2	7687	0.00049	0.32	NO
67	NPC1	NPC1	NPC1	7907	-0.0011	0.31	NO
68	CTSZ	CTSZ	CTSZ	8073	-0.0023	0.3	NO
69	CTSO	CTSO	CTSO	8175	-0.0032	0.3	NO
70	AP1S1	AP1S1	AP1S1	8273	-0.0038	0.3	NO
71	ATP6V0A1	ATP6V0A1	ATP6V0A1	8439	-0.0052	0.29	NO
72	LAPTM5	LAPTM5	LAPTM5	8568	-0.0062	0.29	NO
73	ABCB9	ABCB9	ABCB9	8689	-0.0072	0.28	NO
74	ATP6AP1	ATP6AP1	ATP6AP1	8743	-0.0075	0.28	NO
75	TPP1	TPP1	TPP1	9022	-0.0093	0.27	NO
76	CTSW	CTSW	CTSW	9104	-0.01	0.27	NO
77	CD164	CD164	CD164	9165	-0.01	0.27	NO
78	AP3M1	AP3M1	AP3M1	9247	-0.011	0.27	NO
79	M6PR	M6PR	M6PR	9379	-0.012	0.26	NO
80	CTSB	CTSB	CTSB	9604	-0.013	0.26	NO
81	NAGA	NAGA	NAGA	9608	-0.013	0.26	NO
82	ACP2	ACP2	ACP2	9642	-0.013	0.26	NO
83	AP3S1	AP3S1	AP3S1	9656	-0.014	0.26	NO
84	GGA2	GGA2	GGA2	9665	-0.014	0.26	NO
85	LAPTM4B	LAPTM4B	LAPTM4B	9838	-0.015	0.26	NO
86	GGA1	GGA1	GGA1	9888	-0.015	0.26	NO
87	LAPTM4A	LAPTM4A	LAPTM4A	9961	-0.015	0.26	NO
88	GLA	GLA	GLA	10111	-0.016	0.26	NO
89	MFSD8	MFSD8	MFSD8	10134	-0.016	0.26	NO
90	LAMP2	LAMP2	LAMP2	10384	-0.018	0.25	NO
91	CLN5	CLN5	CLN5	10951	-0.022	0.23	NO
92	PLA2G15	PLA2G15	PLA2G15	10982	-0.022	0.23	NO
93	GGA3	GGA3	GGA3	10985	-0.022	0.23	NO
94	HEXA	HEXA	HEXA	11237	-0.023	0.23	NO
95	LAMP1	LAMP1	LAMP1	11444	-0.025	0.22	NO
96	AP1M1	AP1M1	AP1M1	11715	-0.026	0.22	NO
97	ATP6V1H	ATP6V1H	ATP6V1H	11815	-0.027	0.22	NO
98	GAA	GAA	GAA	12037	-0.029	0.21	NO
99	IDS	IDS	IDS	12935	-0.035	0.18	NO
100	GNS	GNS	GNS	13223	-0.038	0.17	NO
101	IGF2R	IGF2R	IGF2R	13646	-0.041	0.16	NO
102	SCARB2	SCARB2	SCARB2	13710	-0.041	0.17	NO
103	SLC11A2	SLC11A2	SLC11A2	13761	-0.041	0.17	NO
104	PPT1	PPT1	PPT1	13879	-0.042	0.17	NO
105	PPT2	PPT2	PPT2	14400	-0.047	0.16	NO
106	AP4M1	AP4M1	AP4M1	14497	-0.048	0.16	NO
107	AP4E1	AP4E1	AP4E1	14647	-0.049	0.17	NO
108	LAMP3	LAMP3	LAMP3	14790	-0.05	0.17	NO
109	CTSL1	CTSL1	CTSL1	15493	-0.056	0.15	NO
110	SLC11A1	SLC11A1	SLC11A1	15549	-0.057	0.16	NO
111	CTSK	CTSK	CTSK	16168	-0.063	0.14	NO
112	AP1S2	AP1S2	AP1S2	16530	-0.068	0.14	NO
113	NEU1	NEU1	NEU1	16599	-0.069	0.14	NO
114	SORT1	SORT1	SORT1	16654	-0.069	0.16	NO
115	AP3M2	AP3M2	AP3M2	17136	-0.075	0.15	NO
116	ABCA2	ABCA2	ABCA2	17269	-0.077	0.16	NO
117	AP4S1	AP4S1	AP4S1	17812	-0.085	0.15	NO
118	ARSB	ARSB	ARSB	17995	-0.088	0.16	NO
119	CLTCL1	CLTCL1	CLTCL1	22421	-0.28	0.0099	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 O GLYCAN BIOSYNTHESIS.

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

genes ES table in pathway: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AKR1B10	AKR1B10	AKR1B10	27	0.61	0.2	YES
2	ACSM1	ACSM1	ACSM1	151	0.39	0.33	YES
3	HMGCS2	HMGCS2	HMGCS2	260	0.33	0.44	YES
4	ABAT	ABAT	ABAT	1013	0.17	0.46	YES
5	ACSM3	ACSM3	ACSM3	1043	0.17	0.51	YES
6	ALDH2	ALDH2	ALDH2	1403	0.13	0.54	YES
7	GAD2	GAD2	GAD2	2536	0.077	0.52	NO
8	BDH2	BDH2	BDH2	2761	0.069	0.53	NO
9	AACS	AACS	AACS	3267	0.056	0.53	NO
10	ACADS	ACADS	ACADS	3723	0.046	0.52	NO
11	BDH1	BDH1	BDH1	4622	0.031	0.49	NO
12	ALDH9A1	ALDH9A1	ALDH9A1	4987	0.026	0.49	NO
13	HADH	HADH	HADH	5057	0.026	0.49	NO
14	HADHA	HADHA	HADHA	5658	0.019	0.47	NO
15	ECHS1	ECHS1	ECHS1	6041	0.014	0.46	NO
16	ALDH3A2	ALDH3A2	ALDH3A2	6175	0.013	0.46	NO
17	ALDH7A1	ALDH7A1	ALDH7A1	6246	0.012	0.46	NO
18	ACSM5	ACSM5	ACSM5	6781	0.0078	0.44	NO
19	HMGCS1	HMGCS1	HMGCS1	6819	0.0076	0.44	NO
20	PDHA1	PDHA1	PDHA1	7015	0.006	0.43	NO
21	HMGCL	HMGCL	HMGCL	7379	0.0029	0.42	NO
22	ALDH5A1	ALDH5A1	ALDH5A1	7537	0.0016	0.41	NO
23	PDHB	PDHB	PDHB	9374	-0.012	0.33	NO
24	ACAT2	ACAT2	ACAT2	9764	-0.014	0.32	NO
25	L2HGDH	L2HGDH	L2HGDH	13262	-0.038	0.18	NO
26	ACAT1	ACAT1	ACAT1	14015	-0.044	0.16	NO
27	OXCT1	OXCT1	OXCT1	14735	-0.05	0.14	NO
28	ACSM4	ACSM4	ACSM4	15801	-0.059	0.12	NO
29	OXCT2	OXCT2	OXCT2	15845	-0.06	0.14	NO
30	ACSM2A	ACSM2A	ACSM2A	20233	-0.14	-0.013	NO
31	ALDH1B1	ALDH1B1	ALDH1B1	21138	-0.17	0.0048	NO
32	GAD1	GAD1	GAD1	21391	-0.18	0.055	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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

Figure S58. 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 ARACHIDONIC ACID METABOLISM

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	ALDH3A1	ALDH3A1	ALDH3A1	49	0.53	0.21	YES
2	HDC	HDC	HDC	407	0.28	0.3	YES
3	ASPA	ASPA	ASPA	717	0.21	0.37	YES
4	ACY3	ACY3	ACY3	858	0.19	0.44	YES
5	ALDH3B1	ALDH3B1	ALDH3B1	1131	0.16	0.49	YES
6	ALDH2	ALDH2	ALDH2	1403	0.13	0.53	YES
7	ABP1	ABP1	ABP1	1736	0.11	0.56	YES
8	MAOB	MAOB	MAOB	2469	0.079	0.56	YES
9	MAOA	MAOA	MAOA	2626	0.074	0.58	YES
10	FTCD	FTCD	FTCD	3014	0.062	0.58	YES
11	UROC1	UROC1	UROC1	3307	0.055	0.59	YES
12	ALDH3B2	ALDH3B2	ALDH3B2	3904	0.043	0.58	NO
13	DDC	DDC	DDC	4393	0.034	0.58	NO
14	ALDH9A1	ALDH9A1	ALDH9A1	4987	0.026	0.56	NO
15	ALDH3A2	ALDH3A2	ALDH3A2	6175	0.013	0.51	NO
16	LCMT1	LCMT1	LCMT1	6189	0.013	0.52	NO
17	ALDH7A1	ALDH7A1	ALDH7A1	6246	0.012	0.52	NO
18	HEMK1	HEMK1	HEMK1	8640	-0.0068	0.42	NO
19	WBSCR22	WBSCR22	WBSCR22	10017	-0.016	0.36	NO
20	HAL	HAL	HAL	10095	-0.016	0.37	NO
21	METTL6	METTL6	METTL6	10183	-0.017	0.37	NO
22	HNMT	HNMT	HNMT	10892	-0.021	0.35	NO
23	TRMT11	TRMT11	TRMT11	12553	-0.032	0.29	NO
24	ALDH1A3	ALDH1A3	ALDH1A3	13235	-0.038	0.27	NO
25	LCMT2	LCMT2	LCMT2	13944	-0.043	0.26	NO
26	METTL2B	METTL2B	METTL2B	15225	-0.054	0.22	NO
27	AMDHD1	AMDHD1	AMDHD1	18627	-0.099	0.11	NO
28	ALDH1B1	ALDH1B1	ALDH1B1	21138	-0.17	0.066	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 ARACHIDONIC ACID METABOLISM.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus4 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA DEATH PATHWAY	31	genes.ES.table	0.55	1.9	0.0099	0.069	0.2	0.42	0.24	0.32	0	0.008
BIOCARTA PPARA PATHWAY	55	genes.ES.table	0.44	1.6	0.024	0.18	0.58	0.18	0.11	0.16	0.074	0.022
BIOCARTA TNFR1 PATHWAY	28	genes.ES.table	0.47	1.6	0.045	0.23	0.72	0.39	0.25	0.29	0.13	0.03
KEGG GLYCOLYSIS GLUCONEOGENESIS	59	genes.ES.table	0.45	1.5	0.054	0.24	0.77	0.49	0.22	0.38	0.15	0.026
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.69	2.1	0	0.026	0.038	0.79	0.22	0.62	0	0.009
KEGG PENTOSE PHOSPHATE PATHWAY	25	genes.ES.table	0.51	1.6	0.052	0.23	0.68	0.48	0.22	0.37	0.11	0.034
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.63	2	0.006	0.048	0.13	0.62	0.24	0.48	0	0.008
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.61	2.2	0.0043	0.028	0.019	0.65	0.24	0.5	0	0.011
KEGG ARGININE AND PROLINE METABOLISM	53	genes.ES.table	0.49	1.7	0.017	0.17	0.55	0.19	0.04	0.18	0.065	0.025
KEGG GLUTATHIONE METABOLISM	45	genes.ES.table	0.47	1.5	0.057	0.24	0.74	0.49	0.2	0.39	0.14	0.026

genes ES table in pathway: BIOCARTA DEATH PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HMGCS2	HMGCS2	HMGCS2	308	0.32	0.11	YES
2	ACADS	ACADS	ACADS	1147	0.16	0.14	YES
3	ACAA2	ACAA2	ACAA2	1381	0.14	0.18	YES
4	HADH	HADH	HADH	1786	0.12	0.21	YES
5	HIBCH	HIBCH	HIBCH	2122	0.1	0.23	YES
6	BCKDHB	BCKDHB	BCKDHB	2343	0.092	0.26	YES
7	DLD	DLD	DLD	2434	0.09	0.29	YES
8	HMGCL	HMGCL	HMGCL	2588	0.085	0.32	YES
9	AUH	AUH	AUH	2905	0.078	0.33	YES
10	HADHA	HADHA	HADHA	3008	0.075	0.36	YES
11	MCCC1	MCCC1	MCCC1	3084	0.073	0.38	YES
12	PCCA	PCCA	PCCA	3150	0.072	0.41	YES
13	HADHB	HADHB	HADHB	3270	0.069	0.43	YES
14	ECHS1	ECHS1	ECHS1	3332	0.068	0.46	YES
15	MCCC2	MCCC2	MCCC2	3544	0.064	0.47	YES
16	PCCB	PCCB	PCCB	4110	0.054	0.47	YES
17	ACADSB	ACADSB	ACADSB	4403	0.05	0.47	YES
18	MCEE	MCEE	MCEE	4458	0.049	0.49	YES
19	MUT	MUT	MUT	4531	0.048	0.51	YES
20	ALDH2	ALDH2	ALDH2	4581	0.047	0.52	YES
21	ALDH9A1	ALDH9A1	ALDH9A1	4802	0.044	0.53	YES
22	ALDH1B1	ALDH1B1	ALDH1B1	4984	0.042	0.54	YES
23	ABAT	ABAT	ABAT	5080	0.041	0.55	YES
24	EHHADH	EHHADH	EHHADH	5187	0.04	0.56	YES
25	ACAA1	ACAA1	ACAA1	5194	0.039	0.58	YES
26	OXCT2	OXCT2	OXCT2	5267	0.039	0.59	YES
27	ACAT2	ACAT2	ACAT2	5391	0.037	0.6	YES
28	HIBADH	HIBADH	HIBADH	5445	0.037	0.61	YES
29	ACADM	ACADM	ACADM	7558	0.018	0.52	NO
30	HMGCS1	HMGCS1	HMGCS1	7724	0.017	0.52	NO
31	IVD	IVD	IVD	8089	0.014	0.51	NO
32	HSD17B10	HSD17B10	HSD17B10	8826	0.0088	0.48	NO
33	ALDH3A2	ALDH3A2	ALDH3A2	8862	0.0085	0.48	NO
34	ACAD8	ACAD8	ACAD8	9191	0.0062	0.47	NO
35	ALDH6A1	ALDH6A1	ALDH6A1	9203	0.0062	0.48	NO
36	OXCT1	OXCT1	OXCT1	10276	-0.0018	0.43	NO
37	BCAT2	BCAT2	BCAT2	11318	-0.01	0.39	NO
38	ACAT1	ACAT1	ACAT1	11964	-0.016	0.36	NO
39	ALDH7A1	ALDH7A1	ALDH7A1	12197	-0.018	0.36	NO
40	BCKDHA	BCKDHA	BCKDHA	12663	-0.023	0.35	NO
41	DBT	DBT	DBT	12702	-0.024	0.36	NO
42	IL4I1	IL4I1	IL4I1	12952	-0.026	0.36	NO
43	AOX1	AOX1	AOX1	20266	-0.18	0.1	NO

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

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA DEATH PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA PPARA PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PCK1	PCK1	PCK1	102	0.47	0.19	YES
2	PCK2	PCK2	PCK2	822	0.19	0.24	YES
3	IDH2	IDH2	IDH2	1440	0.14	0.27	YES
4	IDH3A	IDH3A	IDH3A	1833	0.11	0.3	YES
5	SUCLG1	SUCLG1	SUCLG1	1913	0.11	0.34	YES
6	SUCLG2	SUCLG2	SUCLG2	2199	0.097	0.37	YES
7	DLD	DLD	DLD	2434	0.09	0.39	YES
8	PDHA1	PDHA1	PDHA1	2460	0.089	0.43	YES
9	SDHB	SDHB	SDHB	2658	0.083	0.46	YES
10	IDH3B	IDH3B	IDH3B	2717	0.082	0.49	YES
11	CS	CS	CS	3076	0.074	0.5	YES
12	DLST	DLST	DLST	3223	0.07	0.52	YES
13	FH	FH	FH	3248	0.07	0.55	YES
14	MDH2	MDH2	MDH2	3662	0.062	0.56	YES
15	IDH3G	IDH3G	IDH3G	3744	0.06	0.58	YES
16	SUCLA2	SUCLA2	SUCLA2	3886	0.058	0.6	YES
17	ACO2	ACO2	ACO2	4193	0.053	0.61	YES
18	SDHD	SDHD	SDHD	4330	0.05	0.62	YES
19	DLAT	DLAT	DLAT	4510	0.048	0.63	YES
20	IDH1	IDH1	IDH1	4605	0.047	0.65	YES
21	ACO1	ACO1	ACO1	4668	0.046	0.67	YES
22	SDHA	SDHA	SDHA	4769	0.044	0.68	YES
23	OGDH	OGDH	OGDH	4962	0.042	0.69	YES
24	MDH1	MDH1	MDH1	5819	0.033	0.66	NO
25	PC	PC	PC	7911	0.016	0.58	NO
26	PDHB	PDHB	PDHB	8745	0.0093	0.55	NO
27	ACLY	ACLY	ACLY	10131	-0.00054	0.48	NO
28	SDHC	SDHC	SDHC	10194	-0.0011	0.48	NO
29	OGDHL	OGDHL	OGDHL	19764	-0.16	0.13	NO

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

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

genes ES table in pathway: BIOCARTA TNFR1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NOS2	NOS2	NOS2	16	0.68	0.11	YES
2	XDH	XDH	XDH	118	0.45	0.18	YES
3	AGXT	AGXT	AGXT	448	0.26	0.21	YES
4	FAR2	FAR2	FAR2	467	0.26	0.25	YES
5	EPHX2	EPHX2	EPHX2	478	0.26	0.29	YES
6	SLC27A2	SLC27A2	SLC27A2	754	0.2	0.32	YES
7	ACSL6	ACSL6	ACSL6	885	0.18	0.34	YES
8	HAO2	HAO2	HAO2	952	0.18	0.36	YES
9	AMACR	AMACR	AMACR	1213	0.15	0.38	YES
10	ACSL5	ACSL5	ACSL5	1270	0.15	0.4	YES
11	IDH2	IDH2	IDH2	1440	0.14	0.42	YES
12	PEX6	PEX6	PEX6	1499	0.13	0.43	YES
13	NUDT12	NUDT12	NUDT12	1641	0.12	0.45	YES
14	PEX11A	PEX11A	PEX11A	1747	0.12	0.46	YES
15	PEX7	PEX7	PEX7	2001	0.1	0.47	YES
16	PXMP2	PXMP2	PXMP2	2165	0.098	0.48	YES
17	MLYCD	MLYCD	MLYCD	2269	0.094	0.49	YES
18	HSD17B4	HSD17B4	HSD17B4	2497	0.088	0.49	YES
19	HMGCL	HMGCL	HMGCL	2588	0.085	0.5	YES
20	DECR2	DECR2	DECR2	2706	0.082	0.51	YES
21	PEX11G	PEX11G	PEX11G	3218	0.07	0.5	YES
22	PEX1	PEX1	PEX1	3289	0.069	0.51	YES
23	GSTK1	GSTK1	GSTK1	3292	0.069	0.52	YES
24	DHRS4	DHRS4	DHRS4	3363	0.067	0.53	YES
25	ABCD3	ABCD3	ABCD3	3803	0.059	0.52	YES
26	ABCD4	ABCD4	ABCD4	3856	0.058	0.52	YES
27	SOD1	SOD1	SOD1	4142	0.054	0.52	YES
28	PAOX	PAOX	PAOX	4257	0.052	0.52	YES
29	PEX11B	PEX11B	PEX11B	4273	0.052	0.53	YES
30	IDH1	IDH1	IDH1	4605	0.047	0.52	YES
31	PEX2	PEX2	PEX2	4766	0.044	0.52	YES
32	SCP2	SCP2	SCP2	5163	0.04	0.51	YES
33	MVK	MVK	MVK	5167	0.04	0.52	YES
34	ABCD1	ABCD1	ABCD1	5175	0.04	0.53	YES
35	EHHADH	EHHADH	EHHADH	5187	0.04	0.53	YES
36	ACAA1	ACAA1	ACAA1	5194	0.039	0.54	YES
37	HACL1	HACL1	HACL1	5543	0.035	0.53	NO
38	CAT	CAT	CAT	5859	0.032	0.52	NO
39	PECR	PECR	PECR	5993	0.031	0.52	NO
40	CRAT	CRAT	CRAT	6125	0.03	0.52	NO
41	PEX14	PEX14	PEX14	6505	0.027	0.51	NO
42	GNPAT	GNPAT	GNPAT	6549	0.026	0.51	NO
43	PEX26	PEX26	PEX26	6865	0.024	0.5	NO
44	AGPS	AGPS	AGPS	7289	0.02	0.48	NO
45	PRDX5	PRDX5	PRDX5	7329	0.02	0.48	NO
46	PEX10	PEX10	PEX10	7387	0.019	0.49	NO
47	PEX16	PEX16	PEX16	7431	0.019	0.49	NO
48	PHYH	PHYH	PHYH	7440	0.019	0.49	NO
49	ACOX3	ACOX3	ACOX3	7717	0.017	0.48	NO
50	PEX5	PEX5	PEX5	7975	0.015	0.47	NO
51	NUDT19	NUDT19	NUDT19	8597	0.01	0.44	NO
52	PEX13	PEX13	PEX13	9045	0.0073	0.43	NO
53	PIPOX	PIPOX	PIPOX	9106	0.0068	0.42	NO
54	PXMP4	PXMP4	PXMP4	9725	0.0026	0.4	NO
55	ACOT8	ACOT8	ACOT8	9901	0.0012	0.39	NO
56	ACOX1	ACOX1	ACOX1	10668	-0.005	0.36	NO
57	SOD2	SOD2	SOD2	10764	-0.0058	0.35	NO
58	PRDX1	PRDX1	PRDX1	10913	-0.007	0.35	NO
59	FAR1	FAR1	FAR1	11263	-0.0099	0.34	NO
60	MPV17	MPV17	MPV17	11641	-0.013	0.32	NO
61	SLC25A17	SLC25A17	SLC25A17	11767	-0.014	0.32	NO
62	PEX3	PEX3	PEX3	12286	-0.019	0.3	NO
63	CROT	CROT	CROT	12585	-0.022	0.29	NO
64	ACSL3	ACSL3	ACSL3	12649	-0.023	0.29	NO
65	PMVK	PMVK	PMVK	13516	-0.032	0.26	NO
66	ACSL4	ACSL4	ACSL4	13530	-0.032	0.26	NO
67	DAO	DAO	DAO	13811	-0.036	0.25	NO
68	PEX12	PEX12	PEX12	14175	-0.04	0.24	NO
69	ACSL1	ACSL1	ACSL1	14856	-0.05	0.22	NO
70	BAAT	BAAT	BAAT	15169	-0.055	0.22	NO
71	MPV17L	MPV17L	MPV17L	17527	-0.1	0.13	NO
72	HAO1	HAO1	HAO1	17858	-0.11	0.13	NO
73	DDO	DDO	DDO	21159	-0.23	0.025	NO
74	ABCD2	ABCD2	ABCD2	21432	-0.25	0.054	NO

Figure S65. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA TNFR1 PATHWAY.

Figure S66. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ALDOB	ALDOB	ALDOB	55	0.56	0.19	YES
2	PFKFB4	PFKFB4	PFKFB4	484	0.26	0.25	YES
3	KHK	KHK	KHK	552	0.24	0.33	YES
4	AKR1B10	AKR1B10	AKR1B10	692	0.21	0.4	YES
5	PFKFB2	PFKFB2	PFKFB2	766	0.2	0.46	YES
6	SORD	SORD	SORD	1062	0.16	0.5	YES
7	FUK	FUK	FUK	1902	0.11	0.5	YES
8	FBP1	FBP1	FBP1	2126	0.1	0.52	YES
9	GMDS	GMDS	GMDS	2314	0.093	0.55	YES
10	PFKFB1	PFKFB1	PFKFB1	2615	0.084	0.56	YES
11	PFKL	PFKL	PFKL	3009	0.075	0.57	YES
12	PMM2	PMM2	PMM2	3043	0.074	0.59	YES
13	TSTA3	TSTA3	TSTA3	3531	0.064	0.59	YES
14	TPI1	TPI1	TPI1	3808	0.059	0.6	YES
15	PMM1	PMM1	PMM1	3888	0.058	0.62	YES
16	ALDOC	ALDOC	ALDOC	4340	0.05	0.61	YES
17	GMPPB	GMPPB	GMPPB	4720	0.045	0.61	YES
18	PFKP	PFKP	PFKP	4783	0.044	0.62	YES
19	GMPPA	GMPPA	GMPPA	5282	0.038	0.62	YES
20	MPI	MPI	MPI	5314	0.038	0.63	YES
21	MTMR6	MTMR6	MTMR6	6666	0.025	0.58	NO
22	MTMR1	MTMR1	MTMR1	6969	0.023	0.57	NO
23	HK3	HK3	HK3	7148	0.021	0.57	NO
24	FBP2	FBP2	FBP2	7297	0.02	0.57	NO
25	PFKFB3	PFKFB3	PFKFB3	7479	0.018	0.57	NO
26	MTMR7	MTMR7	MTMR7	7732	0.017	0.56	NO
27	HK2	HK2	HK2	8647	0.01	0.52	NO
28	PFKM	PFKM	PFKM	10499	-0.0037	0.44	NO
29	PHPT1	PHPT1	PHPT1	11129	-0.0088	0.42	NO
30	MTMR2	MTMR2	MTMR2	13769	-0.035	0.32	NO
31	HK1	HK1	HK1	17458	-0.1	0.18	NO
32	AKR1B1	AKR1B1	AKR1B1	18637	-0.13	0.18	NO

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

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

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TNFRSF25	TNFRSF25	TNFRSF25	965	0.18	0.073	YES
2	CASP6	CASP6	CASP6	1036	0.17	0.18	YES
3	DFFB	DFFB	DFFB	1246	0.15	0.27	YES
4	GAS2	GAS2	GAS2	1319	0.14	0.36	YES
5	CASP10	CASP10	CASP10	1522	0.13	0.44	YES
6	CASP7	CASP7	CASP7	2063	0.1	0.48	YES
7	CASP3	CASP3	CASP3	3418	0.066	0.46	YES
8	APAF1	APAF1	APAF1	3540	0.064	0.5	YES
9	CYCS	CYCS	CYCS	4089	0.054	0.51	YES
10	TNFSF10	TNFSF10	TNFSF10	4964	0.042	0.5	YES
11	CASP9	CASP9	CASP9	5417	0.037	0.51	YES
12	TNFRSF10A	TNFRSF10A	TNFRSF10A	5425	0.037	0.53	YES
13	CASP8	CASP8	CASP8	5506	0.036	0.55	YES
14	CHUK	CHUK	CHUK	6636	0.025	0.52	NO
15	XIAP	XIAP	XIAP	7484	0.018	0.49	NO
16	RIPK1	RIPK1	RIPK1	7690	0.017	0.5	NO
17	SPTAN1	SPTAN1	SPTAN1	8630	0.01	0.46	NO
18	FADD	FADD	FADD	8922	0.0081	0.45	NO
19	TRAF2	TRAF2	TRAF2	9457	0.0044	0.43	NO
20	NFKB1	NFKB1	NFKB1	9637	0.0033	0.43	NO
21	TNFRSF10B	TNFRSF10B	TNFRSF10B	9676	0.003	0.43	NO
22	MAP3K14	MAP3K14	MAP3K14	10991	-0.0076	0.37	NO
23	BIRC2	BIRC2	BIRC2	11831	-0.015	0.35	NO
24	LMNA	LMNA	LMNA	11931	-0.016	0.35	NO
25	RELA	RELA	RELA	12050	-0.017	0.36	NO
26	DFFA	DFFA	DFFA	12225	-0.019	0.36	NO
27	NFKBIA	NFKBIA	NFKBIA	12853	-0.025	0.35	NO
28	CFLAR	CFLAR	CFLAR	12860	-0.025	0.37	NO
29	BIRC3	BIRC3	BIRC3	13232	-0.029	0.37	NO
30	TRADD	TRADD	TRADD	13573	-0.033	0.38	NO
31	BCL2	BCL2	BCL2	13780	-0.035	0.39	NO

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

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

genes ES table in pathway: KEGG PENTOSE PHOSPHATE PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NEU4	NEU4	NEU4	419	0.28	0.083	YES
2	DEGS2	DEGS2	DEGS2	515	0.25	0.17	YES
3	ASAH2	ASAH2	ASAH2	584	0.24	0.25	YES
4	UGT8	UGT8	UGT8	624	0.23	0.34	YES
5	SMPD3	SMPD3	SMPD3	695	0.21	0.41	YES
6	GALC	GALC	GALC	1627	0.12	0.42	YES
7	B4GALT6	B4GALT6	B4GALT6	2295	0.094	0.42	YES
8	PPAP2C	PPAP2C	PPAP2C	2488	0.088	0.44	YES
9	SGPP2	SGPP2	SGPP2	2512	0.088	0.48	YES
10	SMPD2	SMPD2	SMPD2	2836	0.079	0.49	YES
11	SPTLC2	SPTLC2	SPTLC2	2892	0.078	0.52	YES
12	ACER2	ACER2	ACER2	3195	0.071	0.53	YES
13	CERK	CERK	CERK	3242	0.07	0.55	YES
14	SPHK2	SPHK2	SPHK2	3716	0.061	0.55	YES
15	SPTLC1	SPTLC1	SPTLC1	5519	0.036	0.49	NO
16	GLA	GLA	GLA	6090	0.03	0.47	NO
17	SGMS1	SGMS1	SGMS1	6447	0.027	0.47	NO
18	GAL3ST1	GAL3ST1	GAL3ST1	6627	0.026	0.47	NO
19	GLB1	GLB1	GLB1	7587	0.018	0.43	NO
20	NEU3	NEU3	NEU3	7949	0.015	0.42	NO
21	ARSA	ARSA	ARSA	9326	0.0053	0.36	NO
22	SMPD4	SMPD4	SMPD4	9936	0.0011	0.34	NO
23	KDSR	KDSR	KDSR	10496	-0.0036	0.31	NO
24	ASAH1	ASAH1	ASAH1	10883	-0.0067	0.3	NO
25	GBA	GBA	GBA	11108	-0.0087	0.29	NO
26	ACER3	ACER3	ACER3	11271	-0.01	0.29	NO
27	ACER1	ACER1	ACER1	12432	-0.021	0.25	NO
28	NEU1	NEU1	NEU1	13022	-0.027	0.23	NO
29	SGPL1	SGPL1	SGPL1	13323	-0.03	0.23	NO
30	SGMS2	SGMS2	SGMS2	13861	-0.036	0.22	NO
31	DEGS1	DEGS1	DEGS1	14054	-0.039	0.22	NO
32	SMPD1	SMPD1	SMPD1	14907	-0.051	0.2	NO
33	PPAP2A	PPAP2A	PPAP2A	15387	-0.059	0.2	NO
34	UGCG	UGCG	UGCG	15394	-0.059	0.22	NO
35	PPAP2B	PPAP2B	PPAP2B	16636	-0.081	0.2	NO
36	SGPP1	SGPP1	SGPP1	16810	-0.085	0.22	NO
37	SPHK1	SPHK1	SPHK1	17099	-0.092	0.24	NO

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

Figure S72. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PENTOSE PHOSPHATE PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AARS2	AARS2	AARS2	1743	0.12	-0.018	YES
2	SEPSECS	SEPSECS	SEPSECS	2010	0.1	0.022	YES
3	MARS2	MARS2	MARS2	2225	0.096	0.061	YES
4	PARS2	PARS2	PARS2	2340	0.092	0.1	YES
5	FARSB	FARSB	FARSB	2443	0.089	0.14	YES
6	DARS2	DARS2	DARS2	2543	0.087	0.18	YES
7	LARS2	LARS2	LARS2	2663	0.083	0.22	YES
8	WARS2	WARS2	WARS2	2964	0.076	0.24	YES
9	NARS	NARS	NARS	3023	0.075	0.28	YES
10	EPRS	EPRS	EPRS	3103	0.073	0.31	YES
11	QARS	QARS	QARS	3278	0.069	0.34	YES
12	IARS2	IARS2	IARS2	3284	0.069	0.37	YES
13	IARS	IARS	IARS	3607	0.063	0.39	YES
14	HARS2	HARS2	HARS2	4014	0.056	0.4	YES
15	YARS2	YARS2	YARS2	4031	0.055	0.43	YES
16	NARS2	NARS2	NARS2	4043	0.055	0.45	YES
17	SARS	SARS	SARS	4408	0.05	0.46	YES
18	FARSA	FARSA	FARSA	4474	0.048	0.48	YES
19	PSTK	PSTK	PSTK	4499	0.048	0.51	YES
20	LARS	LARS	LARS	4689	0.045	0.52	YES
21	CARS2	CARS2	CARS2	4707	0.045	0.54	YES
22	MTFMT	MTFMT	MTFMT	4930	0.042	0.56	YES
23	VARS	VARS	VARS	5462	0.036	0.55	YES
24	RARS	RARS	RARS	5512	0.036	0.56	YES
25	GARS	GARS	GARS	5541	0.036	0.58	YES
26	EARS2	EARS2	EARS2	5574	0.035	0.6	YES
27	KARS	KARS	KARS	5769	0.033	0.61	YES
28	YARS	YARS	YARS	6247	0.029	0.6	NO
29	CARS	CARS	CARS	6598	0.026	0.6	NO
30	RARS2	RARS2	RARS2	7068	0.022	0.59	NO
31	TARS	TARS	TARS	7155	0.021	0.59	NO
32	VARS2	VARS2	VARS2	7244	0.02	0.6	NO
33	AARS	AARS	AARS	7833	0.016	0.58	NO
34	FARS2	FARS2	FARS2	8609	0.01	0.55	NO
35	HARS	HARS	HARS	9246	0.0058	0.53	NO
36	MARS	MARS	MARS	9285	0.0056	0.53	NO
37	DARS	DARS	DARS	10137	-0.00057	0.49	NO
38	SARS2	SARS2	SARS2	12906	-0.026	0.38	NO
39	TARSL2	TARSL2	TARSL2	13556	-0.033	0.37	NO
40	WARS	WARS	WARS	15745	-0.065	0.3	NO

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

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

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PCK1	PCK1	PCK1	102	0.47	0.16	YES
2	PKLR	PKLR	PKLR	483	0.26	0.24	YES
3	ACSS2	ACSS2	ACSS2	644	0.22	0.31	YES
4	PCK2	PCK2	PCK2	822	0.19	0.37	YES
5	LDHD	LDHD	LDHD	1845	0.11	0.36	YES
6	ACSS1	ACSS1	ACSS1	2022	0.1	0.39	YES
7	DLD	DLD	DLD	2434	0.09	0.41	YES
8	PDHA1	PDHA1	PDHA1	2460	0.089	0.44	YES
9	ME2	ME2	ME2	2494	0.088	0.47	YES
10	ACOT12	ACOT12	ACOT12	3339	0.068	0.45	YES
11	ACYP1	ACYP1	ACYP1	3390	0.067	0.48	YES
12	MDH2	MDH2	MDH2	3662	0.062	0.48	YES
13	ME1	ME1	ME1	4299	0.051	0.48	YES
14	DLAT	DLAT	DLAT	4510	0.048	0.48	YES
15	ALDH2	ALDH2	ALDH2	4581	0.047	0.5	YES
16	ALDH9A1	ALDH9A1	ALDH9A1	4802	0.044	0.5	YES
17	HAGHL	HAGHL	HAGHL	4850	0.044	0.52	YES
18	ALDH1B1	ALDH1B1	ALDH1B1	4984	0.042	0.52	YES
19	ACAT2	ACAT2	ACAT2	5391	0.037	0.52	NO
20	MDH1	MDH1	MDH1	5819	0.033	0.51	NO
21	ACACA	ACACA	ACACA	5916	0.032	0.52	NO
22	ACACB	ACACB	ACACB	6970	0.023	0.48	NO
23	LDHA	LDHA	LDHA	7126	0.021	0.48	NO
24	PC	PC	PC	7911	0.016	0.45	NO
25	PKM2	PKM2	PKM2	8580	0.01	0.43	NO
26	GRHPR	GRHPR	GRHPR	8719	0.0094	0.42	NO
27	PDHB	PDHB	PDHB	8745	0.0093	0.43	NO
28	ALDH3A2	ALDH3A2	ALDH3A2	8862	0.0085	0.42	NO
29	GLO1	GLO1	GLO1	10156	-0.00078	0.37	NO
30	LDHAL6B	LDHAL6B	LDHAL6B	11019	-0.0078	0.33	NO
31	ACAT1	ACAT1	ACAT1	11964	-0.016	0.3	NO
32	ALDH7A1	ALDH7A1	ALDH7A1	12197	-0.018	0.29	NO
33	HAGH	HAGH	HAGH	12751	-0.024	0.28	NO
34	ME3	ME3	ME3	13575	-0.033	0.25	NO
35	ACYP2	ACYP2	ACYP2	15470	-0.06	0.19	NO
36	LDHAL6A	LDHAL6A	LDHAL6A	15878	-0.067	0.2	NO
37	AKR1B1	AKR1B1	AKR1B1	18637	-0.13	0.12	NO
38	LDHB	LDHB	LDHB	19749	-0.16	0.13	NO

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

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

genes ES table in pathway: KEGG ARGININE AND PROLINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MUC2	MUC2	MUC2	130	0.44	0.11	YES
2	CFTR	CFTR	CFTR	299	0.32	0.19	YES
3	ATP6V0D2	ATP6V0D2	ATP6V0D2	312	0.32	0.27	YES
4	KCNQ1	KCNQ1	KCNQ1	520	0.25	0.32	YES
5	PRKACG	PRKACG	PRKACG	665	0.22	0.38	YES
6	SLC12A2	SLC12A2	SLC12A2	788	0.2	0.42	YES
7	ATP6V1E2	ATP6V1E2	ATP6V1E2	2515	0.087	0.37	NO
8	TJP2	TJP2	TJP2	4810	0.044	0.28	NO
9	ATP6V0D1	ATP6V0D1	ATP6V0D1	4836	0.044	0.29	NO
10	ATP6V0A2	ATP6V0A2	ATP6V0A2	5946	0.032	0.25	NO
11	ATP6V0A1	ATP6V0A1	ATP6V0A1	6036	0.031	0.25	NO
12	PDIA4	PDIA4	PDIA4	6238	0.029	0.25	NO
13	ERO1L	ERO1L	ERO1L	6311	0.028	0.25	NO
14	ARF1	ARF1	ARF1	6732	0.025	0.24	NO
15	ATP6V1C2	ATP6V1C2	ATP6V1C2	6800	0.024	0.24	NO
16	ATP6V1B2	ATP6V1B2	ATP6V1B2	7210	0.021	0.23	NO
17	KDELR2	KDELR2	KDELR2	7299	0.02	0.23	NO
18	ATP6V1D	ATP6V1D	ATP6V1D	7608	0.018	0.22	NO
19	KDELR1	KDELR1	KDELR1	7615	0.018	0.23	NO
20	ATP6V1C1	ATP6V1C1	ATP6V1C1	8318	0.012	0.2	NO
21	ACTG1	ACTG1	ACTG1	8322	0.012	0.2	NO
22	SEC61B	SEC61B	SEC61B	8522	0.011	0.2	NO
23	PRKX	PRKX	PRKX	8793	0.009	0.19	NO
24	TCIRG1	TCIRG1	TCIRG1	8911	0.0082	0.18	NO
25	KDELR3	KDELR3	KDELR3	9151	0.0065	0.18	NO
26	SEC61A1	SEC61A1	SEC61A1	9513	0.0041	0.16	NO
27	ATP6V0B	ATP6V0B	ATP6V0B	9594	0.0036	0.16	NO
28	ATP6V1E1	ATP6V1E1	ATP6V1E1	9827	0.0019	0.15	NO
29	ATP6AP1	ATP6AP1	ATP6AP1	10281	-0.0018	0.13	NO
30	ATP6V0C	ATP6V0C	ATP6V0C	10865	-0.0065	0.1	NO
31	ATP6V0E1	ATP6V0E1	ATP6V0E1	11367	-0.011	0.085	NO
32	ATP6V1F	ATP6V1F	ATP6V1F	11450	-0.012	0.084	NO
33	ATP6V1H	ATP6V1H	ATP6V1H	11593	-0.013	0.081	NO
34	SEC61G	SEC61G	SEC61G	11796	-0.015	0.076	NO
35	ATP6V1G1	ATP6V1G1	ATP6V1G1	11910	-0.016	0.075	NO
36	PLCG1	PLCG1	PLCG1	12132	-0.018	0.07	NO
37	SEC61A2	SEC61A2	SEC61A2	12366	-0.02	0.065	NO
38	PRKCA	PRKCA	PRKCA	12383	-0.02	0.069	NO
39	ATP6V1A	ATP6V1A	ATP6V1A	12946	-0.026	0.051	NO
40	PLCG2	PLCG2	PLCG2	13393	-0.031	0.039	NO
41	ACTB	ACTB	ACTB	13443	-0.031	0.045	NO
42	TJP1	TJP1	TJP1	14119	-0.04	0.026	NO
43	PRKACA	PRKACA	PRKACA	14389	-0.043	0.025	NO
44	ADCY9	ADCY9	ADCY9	15027	-0.052	0.01	NO
45	PRKACB	PRKACB	PRKACB	16534	-0.079	-0.036	NO
46	GNAS	GNAS	GNAS	16907	-0.087	-0.029	NO
47	ATP6V0E2	ATP6V0E2	ATP6V0E2	17260	-0.096	-0.02	NO
48	PRKCG	PRKCG	PRKCG	19080	-0.14	-0.063	NO
49	ATP6V0A4	ATP6V0A4	ATP6V0A4	19794	-0.16	-0.052	NO
50	ATP6V1B1	ATP6V1B1	ATP6V1B1	20163	-0.18	-0.021	NO
51	PRKCB	PRKCB	PRKCB	20281	-0.18	0.022	NO
52	ATP6V1G2	ATP6V1G2	ATP6V1G2	22227	-0.32	0.018	NO

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

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ARGININE AND PROLINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG GLUTATHIONE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PLA2G12B	PLA2G12B	PLA2G12B	33	0.6	0.18	YES
2	PLA2G2F	PLA2G2F	PLA2G2F	223	0.37	0.29	YES
3	PLA2G2A	PLA2G2A	PLA2G2A	481	0.26	0.36	YES
4	PLA2G4E	PLA2G4E	PLA2G4E	761	0.2	0.41	YES
5	PLA2G4A	PLA2G4A	PLA2G4A	995	0.17	0.45	YES
6	PLA2G3	PLA2G3	PLA2G3	1378	0.14	0.48	YES
7	PLA2G1B	PLA2G1B	PLA2G1B	2306	0.094	0.46	YES
8	PAFAH2	PAFAH2	PAFAH2	2417	0.09	0.49	YES
9	PPAP2C	PPAP2C	PPAP2C	2488	0.088	0.51	YES
10	PLD1	PLD1	PLD1	2959	0.076	0.51	YES
11	PLA2G7	PLA2G7	PLA2G7	3310	0.068	0.52	YES
12	PLA2G6	PLA2G6	PLA2G6	3493	0.065	0.53	YES
13	LPCAT4	LPCAT4	LPCAT4	3504	0.065	0.55	YES
14	PLA2G2E	PLA2G2E	PLA2G2E	3792	0.059	0.56	YES
15	PLA2G10	PLA2G10	PLA2G10	4103	0.054	0.56	YES
16	LPCAT1	LPCAT1	LPCAT1	6000	0.031	0.48	NO
17	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	6206	0.029	0.48	NO
18	LPCAT2	LPCAT2	LPCAT2	6451	0.027	0.48	NO
19	AGPS	AGPS	AGPS	7289	0.02	0.45	NO
20	CHPT1	CHPT1	CHPT1	7791	0.016	0.43	NO
21	PLD2	PLD2	PLD2	8337	0.012	0.41	NO
22	PAFAH1B1	PAFAH1B1	PAFAH1B1	8959	0.0079	0.39	NO
23	PAFAH1B3	PAFAH1B3	PAFAH1B3	9376	0.0049	0.37	NO
24	PLA2G12A	PLA2G12A	PLA2G12A	9505	0.0041	0.37	NO
25	PAFAH1B2	PAFAH1B2	PAFAH1B2	12547	-0.022	0.24	NO
26	PLA2G2C	PLA2G2C	PLA2G2C	13490	-0.032	0.21	NO
27	PPAP2A	PPAP2A	PPAP2A	15387	-0.059	0.14	NO
28	ENPP2	ENPP2	ENPP2	16541	-0.08	0.12	NO
29	PPAP2B	PPAP2B	PPAP2B	16636	-0.081	0.14	NO
30	PLA2G2D	PLA2G2D	PLA2G2D	20549	-0.2	0.024	NO
31	PLA2G5	PLA2G5	PLA2G5	21063	-0.22	0.07	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus5 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA BIOPEPTIDES PATHWAY	41	genes.ES.table	0.41	1.4	0.1	0.75	0.84	0.098	0.054	0.092	0.47	0.29
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.42	1.4	0.14	0.84	0.89	0.41	0.34	0.27	0.64	0.33
BIOCARTA ERK PATHWAY	26	genes.ES.table	0.37	1.3	0.23	0.88	0.93	0.038	0.0043	0.038	0.74	0.37
BIOCARTA MPR PATHWAY	32	genes.ES.table	0.42	1.5	0.049	0.96	0.76	0.28	0.25	0.21	0.51	0.34
BIOCARTA CHREBP2 PATHWAY	39	genes.ES.table	0.41	1.5	0.048	1	0.71	0.13	0.098	0.12	0.58	0.37
BIOCARTA PAR1 PATHWAY	36	genes.ES.table	0.42	1.4	0.099	0.8	0.83	0.17	0.11	0.15	0.49	0.31
KEGG GLYCINE SERINE AND THREONINE METABOLISM	30	genes.ES.table	0.61	1.6	0.01	1	0.61	0.4	0.17	0.33	0.41	0.34
KEGG CYSTEINE AND METHIONINE METABOLISM	33	genes.ES.table	0.49	1.6	0.006	1	0.57	0.21	0.13	0.18	0.47	0.37
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.33	1.3	0.2	0.85	0.92	0.42	0.43	0.24	0.7	0.35
KEGG SELENOAMINO ACID METABOLISM	25	genes.ES.table	0.41	1.3	0.16	0.8	0.9	0.16	0.098	0.14	0.62	0.31

genes ES table in pathway: BIOCARTA BIOPEPTIDES PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TUBB2B	TUBB2B	TUBB2B	206	0.51	0.12	YES
2	TUBB1	TUBB1	TUBB1	388	0.44	0.22	YES
3	TUBB2A	TUBB2A	TUBB2A	480	0.42	0.32	YES
4	TUBA3C	TUBA3C	TUBA3C	1475	0.28	0.34	YES
5	TUBB3	TUBB3	TUBB3	1710	0.26	0.4	YES
6	TUBA3E	TUBA3E	TUBA3E	3655	0.16	0.35	NO
7	TUBA8	TUBA8	TUBA8	6506	0.091	0.25	NO
8	NCK2	NCK2	NCK2	7741	0.073	0.21	NO
9	FYN	FYN	FYN	7810	0.072	0.22	NO
10	CTNNB1	CTNNB1	CTNNB1	9728	0.051	0.15	NO
11	TUBB8	TUBB8	TUBB8	9768	0.05	0.16	NO
12	NCL	NCL	NCL	10277	0.045	0.15	NO
13	CDH1	CDH1	CDH1	10292	0.045	0.16	NO
14	TUBA1C	TUBA1C	TUBA1C	10873	0.04	0.15	NO
15	ROCK2	ROCK2	ROCK2	11079	0.038	0.15	NO
16	ROCK1	ROCK1	ROCK1	11144	0.037	0.15	NO
17	ARPC5L	ARPC5L	ARPC5L	11469	0.035	0.15	NO
18	TUBB	TUBB	TUBB	11626	0.033	0.15	NO
19	ARHGEF2	ARHGEF2	ARHGEF2	11914	0.031	0.14	NO
20	YWHAQ	YWHAQ	YWHAQ	12463	0.026	0.12	NO
21	YWHAZ	YWHAZ	YWHAZ	13185	0.019	0.098	NO
22	PRKCA	PRKCA	PRKCA	13187	0.019	0.1	NO
23	TUBA3D	TUBA3D	TUBA3D	13387	0.018	0.098	NO
24	ARPC5	ARPC5	ARPC5	14447	0.0074	0.053	NO
25	ABL1	ABL1	ABL1	14817	0.0039	0.038	NO
26	CTTN	CTTN	CTTN	14868	0.0032	0.036	NO
27	ITGB1	ITGB1	ITGB1	14933	0.0025	0.034	NO
28	TUBA1A	TUBA1A	TUBA1A	15063	0.0011	0.029	NO
29	OCLN	OCLN	OCLN	15092	0.00082	0.028	NO
30	TUBA4A	TUBA4A	TUBA4A	15119	0.0005	0.027	NO
31	TUBA1B	TUBA1B	TUBA1B	15640	-0.0049	0.005	NO
32	TLR5	TLR5	TLR5	15940	-0.0079	-0.0063	NO
33	WASL	WASL	WASL	16280	-0.012	-0.018	NO
34	ARPC2	ARPC2	ARPC2	16513	-0.015	-0.025	NO
35	ARPC1A	ARPC1A	ARPC1A	16686	-0.017	-0.028	NO
36	CDC42	CDC42	CDC42	17030	-0.022	-0.038	NO
37	ARPC3	ARPC3	ARPC3	17202	-0.024	-0.04	NO
38	ACTG1	ACTG1	ACTG1	17247	-0.024	-0.036	NO
39	ARPC1B	ARPC1B	ARPC1B	17395	-0.027	-0.036	NO
40	RHOA	RHOA	RHOA	17537	-0.029	-0.035	NO
41	TUBB6	TUBB6	TUBB6	17560	-0.029	-0.029	NO
42	NCK1	NCK1	NCK1	18177	-0.039	-0.046	NO
43	KRT18	KRT18	KRT18	18401	-0.044	-0.046	NO
44	ACTB	ACTB	ACTB	18544	-0.047	-0.04	NO
45	LY96	LY96	LY96	19121	-0.06	-0.051	NO
46	TLR4	TLR4	TLR4	19620	-0.074	-0.055	NO
47	EZR	EZR	EZR	19705	-0.077	-0.039	NO
48	CD14	CD14	CD14	20157	-0.093	-0.036	NO
49	CLDN1	CLDN1	CLDN1	20324	-0.1	-0.019	NO
50	HCLS1	HCLS1	HCLS1	21274	-0.15	-0.024	NO
51	TUBAL3	TUBAL3	TUBAL3	21346	-0.16	0.011	NO
52	WAS	WAS	WAS	21743	-0.19	0.04	NO

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

Figure S82. 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 G1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DNMT3B	DNMT3B	DNMT3B	363	0.45	0.12	YES
2	CBS	CBS	CBS	440	0.43	0.25	YES
3	TAT	TAT	TAT	1242	0.3	0.3	YES
4	DNMT3L	DNMT3L	DNMT3L	1956	0.24	0.34	YES
5	MAT1A	MAT1A	MAT1A	2213	0.23	0.4	YES
6	BHMT	BHMT	BHMT	2564	0.21	0.45	YES
7	DNMT3A	DNMT3A	DNMT3A	2933	0.19	0.49	YES
8	LDHAL6A	LDHAL6A	LDHAL6A	5693	0.11	0.4	NO
9	ENOPH1	ENOPH1	ENOPH1	7910	0.071	0.33	NO
10	APIP	APIP	APIP	8549	0.063	0.32	NO
11	AHCY	AHCY	AHCY	8677	0.062	0.33	NO
12	SRM	SRM	SRM	10641	0.042	0.26	NO
13	TRDMT1	TRDMT1	TRDMT1	11000	0.039	0.25	NO
14	LDHAL6B	LDHAL6B	LDHAL6B	11639	0.033	0.24	NO
15	MAT2A	MAT2A	MAT2A	11741	0.032	0.24	NO
16	DNMT1	DNMT1	DNMT1	12338	0.027	0.22	NO
17	AMD1	AMD1	AMD1	12394	0.026	0.23	NO
18	MPST	MPST	MPST	12942	0.021	0.21	NO
19	CTH	CTH	CTH	13314	0.018	0.2	NO
20	MTR	MTR	MTR	13502	0.016	0.2	NO
21	AHCYL1	AHCYL1	AHCYL1	13579	0.016	0.2	NO
22	LDHB	LDHB	LDHB	13625	0.016	0.2	NO
23	ADI1	ADI1	ADI1	14631	0.0057	0.16	NO
24	SMS	SMS	SMS	14657	0.0054	0.16	NO
25	IL4I1	IL4I1	IL4I1	14840	0.0036	0.15	NO
26	GOT1	GOT1	GOT1	15885	-0.0074	0.11	NO
27	GOT2	GOT2	GOT2	17026	-0.021	0.064	NO
28	LDHA	LDHA	LDHA	17624	-0.03	0.046	NO
29	MTAP	MTAP	MTAP	18484	-0.045	0.022	NO
30	MAT2B	MAT2B	MAT2B	20154	-0.093	-0.024	NO
31	CDO1	CDO1	CDO1	20382	-0.1	-0.0026	NO
32	SDS	SDS	SDS	20616	-0.11	0.021	NO
33	AHCYL2	AHCYL2	AHCYL2	22091	-0.23	0.024	NO

Figure S83. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA G1 PATHWAY.

Figure S84. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA G1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA ERK PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GLDC	GLDC	GLDC	26	0.68	0.14	YES
2	CBS	CBS	CBS	440	0.43	0.21	YES
3	AGXT	AGXT	AGXT	500	0.41	0.29	YES
4	AGXT2	AGXT2	AGXT2	1077	0.32	0.33	YES
5	PIPOX	PIPOX	PIPOX	1087	0.32	0.4	YES
6	PHGDH	PHGDH	PHGDH	1105	0.32	0.46	YES
7	GAMT	GAMT	GAMT	1770	0.26	0.48	YES
8	GNMT	GNMT	GNMT	1830	0.25	0.53	YES
9	DAO	DAO	DAO	1833	0.25	0.59	YES
10	BHMT	BHMT	BHMT	2564	0.21	0.6	YES
11	PSPH	PSPH	PSPH	3259	0.18	0.6	YES
12	ALAS2	ALAS2	ALAS2	3922	0.16	0.61	YES
13	GLYCTK	GLYCTK	GLYCTK	4854	0.13	0.59	NO
14	SARDH	SARDH	SARDH	5687	0.11	0.58	NO
15	CHDH	CHDH	CHDH	7185	0.081	0.53	NO
16	PSAT1	PSAT1	PSAT1	9533	0.052	0.43	NO
17	AOC2	AOC2	AOC2	11232	0.037	0.37	NO
18	GCAT	GCAT	GCAT	11335	0.036	0.37	NO
19	SHMT1	SHMT1	SHMT1	11386	0.035	0.38	NO
20	MAOB	MAOB	MAOB	12544	0.025	0.33	NO
21	SRR	SRR	SRR	13204	0.019	0.3	NO
22	CTH	CTH	CTH	13314	0.018	0.3	NO
23	ALAS1	ALAS1	ALAS1	15108	0.00057	0.22	NO
24	SHMT2	SHMT2	SHMT2	15408	-0.0025	0.21	NO
25	DLD	DLD	DLD	15960	-0.0082	0.19	NO
26	GATM	GATM	GATM	18185	-0.04	0.098	NO
27	MAOA	MAOA	MAOA	20358	-0.1	0.022	NO
28	SDS	SDS	SDS	20616	-0.11	0.034	NO
29	DMGDH	DMGDH	DMGDH	20925	-0.13	0.047	NO
30	AOC3	AOC3	AOC3	21133	-0.14	0.067	NO

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

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

genes ES table in pathway: BIOCARTA MPR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PPP2R2C	PPP2R2C	PPP2R2C	511	0.41	0.1	YES
2	PRKAA2	PRKAA2	PRKAA2	681	0.38	0.21	YES
3	MLXIPL	MLXIPL	MLXIPL	688	0.38	0.32	YES
4	PKLR	PKLR	PKLR	1377	0.29	0.38	YES
5	GCK	GCK	GCK	2219	0.23	0.41	YES
6	PPP2R3B	PPP2R3B	PPP2R3B	5109	0.12	0.32	NO
7	PRKAB2	PRKAB2	PRKAB2	5897	0.1	0.32	NO
8	FASN	FASN	FASN	6128	0.098	0.34	NO
9	ACACA	ACACA	ACACA	6346	0.094	0.36	NO
10	PPP2R1B	PPP2R1B	PPP2R1B	6527	0.091	0.37	NO
11	PRKACG	PRKACG	PRKACG	8690	0.062	0.3	NO
12	YWHAB	YWHAB	YWHAB	8789	0.061	0.31	NO
13	PRKAB1	PRKAB1	PRKAB1	9613	0.052	0.29	NO
14	PRKAA1	PRKAA1	PRKAA1	10100	0.047	0.28	NO
15	PPP2R2D	PPP2R2D	PPP2R2D	10453	0.044	0.28	NO
16	YWHAG	YWHAG	YWHAG	11038	0.038	0.27	NO
17	PRKAR1A	PRKAR1A	PRKAR1A	11367	0.036	0.26	NO
18	PPP2R3A	PPP2R3A	PPP2R3A	11501	0.034	0.27	NO
19	YWHAE	YWHAE	YWHAE	12008	0.03	0.25	NO
20	PPP2R5D	PPP2R5D	PPP2R5D	12138	0.029	0.26	NO
21	PRKAG1	PRKAG1	PRKAG1	12233	0.028	0.26	NO
22	PPP2R1A	PPP2R1A	PPP2R1A	12333	0.027	0.26	NO
23	YWHAQ	YWHAQ	YWHAQ	12463	0.026	0.27	NO
24	PPP2R4	PPP2R4	PPP2R4	12791	0.023	0.26	NO
25	PPP2R5A	PPP2R5A	PPP2R5A	12924	0.022	0.26	NO
26	YWHAZ	YWHAZ	YWHAZ	13185	0.019	0.25	NO
27	PPP2R5B	PPP2R5B	PPP2R5B	13192	0.019	0.26	NO
28	PRKAR2A	PRKAR2A	PRKAR2A	13728	0.014	0.24	NO
29	PRKAR1B	PRKAR1B	PRKAR1B	14044	0.011	0.23	NO
30	MLX	MLX	MLX	14837	0.0036	0.2	NO
31	PRKACA	PRKACA	PRKACA	15047	0.0013	0.19	NO
32	PPP2R5E	PPP2R5E	PPP2R5E	15852	-0.007	0.15	NO
33	PRKAG2	PRKAG2	PRKAG2	15951	-0.0081	0.15	NO
34	PPP2R5C	PPP2R5C	PPP2R5C	16478	-0.014	0.13	NO
35	PRKACB	PRKACB	PRKACB	16679	-0.017	0.13	NO
36	YWHAH	YWHAH	YWHAH	18682	-0.05	0.056	NO
37	PPP2CB	PPP2CB	PPP2CB	18935	-0.056	0.061	NO
38	PRKAR2B	PRKAR2B	PRKAR2B	21399	-0.16	0.00073	NO
39	PPP2R2B	PPP2R2B	PPP2R2B	21657	-0.18	0.044	NO

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

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

genes ES table in pathway: BIOCARTA CHREBP2 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MGAT5B	MGAT5B	MGAT5B	925	0.34	0.076	YES
2	ALG10B	ALG10B	ALG10B	3806	0.16	0.0034	YES
3	TUSC3	TUSC3	TUSC3	4678	0.13	0.01	YES
4	DPM1	DPM1	DPM1	5170	0.12	0.03	YES
5	RPN2	RPN2	RPN2	5304	0.12	0.064	YES
6	ST6GAL1	ST6GAL1	ST6GAL1	5445	0.11	0.097	YES
7	DOLPP1	DOLPP1	DOLPP1	5574	0.11	0.13	YES
8	B4GALT3	B4GALT3	B4GALT3	5633	0.11	0.16	YES
9	MOGS	MOGS	MOGS	6472	0.092	0.16	YES
10	ALG8	ALG8	ALG8	6760	0.087	0.18	YES
11	MAN2A2	MAN2A2	MAN2A2	6859	0.086	0.2	YES
12	MGAT4A	MGAT4A	MGAT4A	7540	0.076	0.2	YES
13	ALG12	ALG12	ALG12	7579	0.075	0.22	YES
14	DPM3	DPM3	DPM3	7775	0.073	0.24	YES
15	MAN1B1	MAN1B1	MAN1B1	7882	0.071	0.26	YES
16	ALG10	ALG10	ALG10	8027	0.069	0.28	YES
17	MAN1A1	MAN1A1	MAN1A1	8040	0.069	0.3	YES
18	ALG6	ALG6	ALG6	8213	0.067	0.32	YES
19	DPM2	DPM2	DPM2	8829	0.06	0.31	YES
20	DDOST	DDOST	DDOST	8977	0.059	0.32	YES
21	ALG3	ALG3	ALG3	9438	0.054	0.32	YES
22	GANAB	GANAB	GANAB	9528	0.053	0.33	YES
23	DPAGT1	DPAGT1	DPAGT1	9564	0.052	0.35	YES
24	ALG14	ALG14	ALG14	10476	0.044	0.33	YES
25	MAN1C1	MAN1C1	MAN1C1	10576	0.043	0.34	YES
26	B4GALT2	B4GALT2	B4GALT2	10623	0.042	0.35	YES
27	ALG5	ALG5	ALG5	10645	0.042	0.36	YES
28	STT3B	STT3B	STT3B	10675	0.042	0.38	YES
29	STT3A	STT3A	STT3A	10745	0.041	0.39	YES
30	RPN1	RPN1	RPN1	11983	0.03	0.34	NO
31	MAN1A2	MAN1A2	MAN1A2	12119	0.029	0.35	NO
32	B4GALT1	B4GALT1	B4GALT1	12486	0.026	0.34	NO
33	MGAT5	MGAT5	MGAT5	12840	0.022	0.33	NO
34	ALG2	ALG2	ALG2	13661	0.015	0.3	NO
35	ALG9	ALG9	ALG9	13966	0.012	0.29	NO
36	DAD1	DAD1	DAD1	15076	0.00098	0.24	NO
37	MGAT2	MGAT2	MGAT2	15106	0.00061	0.24	NO
38	ALG1	ALG1	ALG1	16502	-0.015	0.18	NO
39	MGAT1	MGAT1	MGAT1	16810	-0.018	0.18	NO
40	MGAT4B	MGAT4B	MGAT4B	17119	-0.023	0.17	NO
41	ALG13	ALG13	ALG13	17804	-0.033	0.15	NO
42	MGAT3	MGAT3	MGAT3	18552	-0.047	0.14	NO
43	FUT8	FUT8	FUT8	19346	-0.066	0.12	NO
44	MAN2A1	MAN2A1	MAN2A1	19367	-0.067	0.14	NO

Figure S89. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA CHREBP2 PATHWAY.

Figure S90. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CHREBP2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA PAR1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GNGT1	GNGT1	GNGT1	98	0.58	0.2	YES
2	MYT1	MYT1	MYT1	797	0.36	0.3	YES
3	PAQR5	PAQR5	PAQR5	3340	0.18	0.25	YES
4	ACTA1	ACTA1	ACTA1	3932	0.16	0.28	YES
5	PAQR7	PAQR7	PAQR7	5038	0.12	0.28	YES
6	CDC25C	CDC25C	CDC25C	5072	0.12	0.32	YES
7	GNAI1	GNAI1	GNAI1	5324	0.12	0.35	YES
8	CDK1	CDK1	CDK1	5556	0.11	0.38	YES
9	GNAS	GNAS	GNAS	5684	0.11	0.42	YES
10	SRC	SRC	SRC	8283	0.066	0.32	NO
11	PRKACG	PRKACG	PRKACG	8690	0.062	0.33	NO
12	CCNB1	CCNB1	CCNB1	9446	0.053	0.31	NO
13	HRAS	HRAS	HRAS	10000	0.048	0.31	NO
14	GNB1	GNB1	GNB1	11355	0.036	0.26	NO
15	PRKAR1A	PRKAR1A	PRKAR1A	11367	0.036	0.27	NO
16	PRKAR2A	PRKAR2A	PRKAR2A	13728	0.014	0.17	NO
17	PRKAR1B	PRKAR1B	PRKAR1B	14044	0.011	0.16	NO
18	ARPC5	ARPC5	ARPC5	14447	0.0074	0.15	NO
19	ACTR3	ACTR3	ACTR3	14659	0.0054	0.14	NO
20	ACTR2	ACTR2	ACTR2	14724	0.0047	0.14	NO
21	MAPK1	MAPK1	MAPK1	14862	0.0033	0.14	NO
22	MAPK3	MAPK3	MAPK3	15268	-0.001	0.12	NO
23	ARPC2	ARPC2	ARPC2	16513	-0.015	0.067	NO
24	PRKACB	PRKACB	PRKACB	16679	-0.017	0.066	NO
25	ARPC1A	ARPC1A	ARPC1A	16686	-0.017	0.072	NO
26	CAP1	CAP1	CAP1	16740	-0.018	0.076	NO
27	PIN1	PIN1	PIN1	17198	-0.024	0.064	NO
28	ARPC3	ARPC3	ARPC3	17202	-0.024	0.073	NO
29	ARPC1B	ARPC1B	ARPC1B	17395	-0.027	0.074	NO
30	RPS6KA1	RPS6KA1	RPS6KA1	19341	-0.066	0.012	NO
31	PRKAR2B	PRKAR2B	PRKAR2B	21399	-0.16	-0.022	NO
32	PGR	PGR	PGR	21993	-0.21	0.029	NO

Figure S91. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA PAR1 PATHWAY.

Figure S92. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA PAR1 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 GLYCINE SERINE AND THREONINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HAP1	HAP1	HAP1	162	0.54	0.046	YES
2	DNAI1	DNAI1	DNAI1	226	0.5	0.092	YES
3	COX6A2	COX6A2	COX6A2	608	0.39	0.11	YES
4	PPARGC1A	PPARGC1A	PPARGC1A	1129	0.31	0.12	YES
5	DNALI1	DNALI1	DNALI1	1241	0.3	0.15	YES
6	COX7B2	COX7B2	COX7B2	1255	0.3	0.18	YES
7	GRIN2B	GRIN2B	GRIN2B	1357	0.29	0.2	YES
8	DNAH2	DNAH2	DNAH2	1618	0.27	0.21	YES
9	CLTCL1	CLTCL1	CLTCL1	1640	0.27	0.24	YES
10	UCP1	UCP1	UCP1	1726	0.26	0.26	YES
11	DNAH3	DNAH3	DNAH3	2216	0.23	0.26	YES
12	BDNF	BDNF	BDNF	2240	0.23	0.28	YES
13	PLCB1	PLCB1	PLCB1	2453	0.22	0.29	YES
14	CREB3L4	CREB3L4	CREB3L4	2635	0.21	0.31	YES
15	CREB3L3	CREB3L3	CREB3L3	3209	0.18	0.3	NO
16	TAF4	TAF4	TAF4	3991	0.15	0.28	NO
17	COX6B2	COX6B2	COX6B2	4672	0.13	0.26	NO
18	HIP1	HIP1	HIP1	4995	0.12	0.26	NO
19	GRIN1	GRIN1	GRIN1	5003	0.12	0.27	NO
20	COX8C	COX8C	COX8C	5284	0.12	0.27	NO
21	DNAI2	DNAI2	DNAI2	5508	0.11	0.27	NO
22	UQCRFS1	UQCRFS1	UQCRFS1	6931	0.085	0.22	NO
23	HDAC2	HDAC2	HDAC2	7214	0.08	0.21	NO
24	DNAL4	DNAL4	DNAL4	7471	0.077	0.21	NO
25	POLR2I	POLR2I	POLR2I	7587	0.075	0.21	NO
26	NDUFS6	NDUFS6	NDUFS6	7610	0.075	0.22	NO
27	POLR2D	POLR2D	POLR2D	7646	0.074	0.22	NO
28	POLR2K	POLR2K	POLR2K	7826	0.072	0.22	NO
29	ATP5E	ATP5E	ATP5E	7971	0.07	0.22	NO
30	SDHC	SDHC	SDHC	8267	0.067	0.22	NO
31	CASP9	CASP9	CASP9	8604	0.063	0.21	NO
32	PLCB4	PLCB4	PLCB4	8699	0.062	0.21	NO
33	TBP	TBP	TBP	8875	0.06	0.21	NO
34	POLR2C	POLR2C	POLR2C	8933	0.059	0.21	NO
35	TFAM	TFAM	TFAM	9039	0.058	0.21	NO
36	NDUFB9	NDUFB9	NDUFB9	9204	0.056	0.21	NO
37	TBPL1	TBPL1	TBPL1	9297	0.055	0.21	NO
38	NDUFS1	NDUFS1	NDUFS1	9763	0.05	0.2	NO
39	POLR2G	POLR2G	POLR2G	9912	0.049	0.19	NO
40	SLC25A4	SLC25A4	SLC25A4	10354	0.044	0.18	NO
41	COX4I2	COX4I2	COX4I2	10386	0.044	0.18	NO
42	POLR2J	POLR2J	POLR2J	10547	0.043	0.18	NO
43	CYCS	CYCS	CYCS	10712	0.042	0.18	NO
44	POLR2H	POLR2H	POLR2H	10779	0.041	0.18	NO
45	CASP3	CASP3	CASP3	10845	0.04	0.18	NO
46	POLR2F	POLR2F	POLR2F	10903	0.04	0.18	NO
47	NDUFS2	NDUFS2	NDUFS2	10916	0.04	0.18	NO
48	DNAL1	DNAL1	DNAL1	10918	0.04	0.18	NO
49	TGM2	TGM2	TGM2	10989	0.039	0.19	NO
50	SIN3A	SIN3A	SIN3A	11047	0.038	0.19	NO
51	ATP5G1	ATP5G1	ATP5G1	11056	0.038	0.19	NO
52	NRF1	NRF1	NRF1	11284	0.036	0.18	NO
53	AP2A2	AP2A2	AP2A2	11388	0.035	0.18	NO
54	CREB1	CREB1	CREB1	11800	0.032	0.17	NO
55	COX6C	COX6C	COX6C	12091	0.029	0.16	NO
56	EP300	EP300	EP300	12242	0.028	0.15	NO
57	NDUFA8	NDUFA8	NDUFA8	12380	0.026	0.15	NO
58	CLTC	CLTC	CLTC	12549	0.025	0.14	NO
59	NDUFS3	NDUFS3	NDUFS3	12659	0.024	0.14	NO
60	DCTN1	DCTN1	DCTN1	12812	0.023	0.14	NO
61	ATP5C1	ATP5C1	ATP5C1	12917	0.022	0.14	NO
62	DLG4	DLG4	DLG4	13042	0.02	0.13	NO
63	GRM5	GRM5	GRM5	13058	0.02	0.13	NO
64	COX6B1	COX6B1	COX6B1	13406	0.017	0.12	NO
65	NDUFA4	NDUFA4	NDUFA4	13410	0.017	0.12	NO
66	COX7A2L	COX7A2L	COX7A2L	13533	0.016	0.12	NO
67	NDUFV3	NDUFV3	NDUFV3	13643	0.015	0.11	NO
68	HDAC1	HDAC1	HDAC1	13723	0.014	0.11	NO
69	AP2S1	AP2S1	AP2S1	13765	0.014	0.11	NO
70	CYC1	CYC1	CYC1	13913	0.013	0.11	NO
71	AP2A1	AP2A1	AP2A1	13975	0.012	0.1	NO
72	POLR2A	POLR2A	POLR2A	14032	0.012	0.1	NO
73	NDUFS8	NDUFS8	NDUFS8	14083	0.011	0.1	NO
74	CLTA	CLTA	CLTA	14103	0.011	0.1	NO
75	SDHA	SDHA	SDHA	14130	0.011	0.1	NO
76	COX5B	COX5B	COX5B	14255	0.0094	0.098	NO
77	NDUFB3	NDUFB3	NDUFB3	14312	0.0088	0.096	NO
78	NDUFB1	NDUFB1	NDUFB1	14389	0.008	0.094	NO
79	NDUFA5	NDUFA5	NDUFA5	14430	0.0076	0.093	NO
80	CASP8	CASP8	CASP8	14517	0.0068	0.09	NO
81	NDUFA10	NDUFA10	NDUFA10	14698	0.005	0.082	NO
82	AP2M1	AP2M1	AP2M1	14700	0.005	0.082	NO
83	DCTN2	DCTN2	DCTN2	14801	0.004	0.078	NO
84	PPID	PPID	PPID	14856	0.0034	0.076	NO
85	ATP5G2	ATP5G2	ATP5G2	14869	0.0032	0.076	NO
86	POLR2B	POLR2B	POLR2B	14874	0.0031	0.076	NO
87	CREB3L2	CREB3L2	CREB3L2	14919	0.0026	0.075	NO
88	UQCRHL	UQCRHL	UQCRHL	14976	0.0019	0.072	NO
89	NDUFC1	NDUFC1	NDUFC1	14978	0.0019	0.072	NO
90	DCTN4	DCTN4	DCTN4	15008	0.0016	0.071	NO
91	NDUFA4L2	NDUFA4L2	NDUFA4L2	15162	6.1e-06	0.064	NO
92	UQCRB	UQCRB	UQCRB	15176	-0.00014	0.064	NO
93	NDUFB5	NDUFB5	NDUFB5	15230	-0.00056	0.062	NO
94	NDUFA6	NDUFA6	NDUFA6	15251	-0.00078	0.061	NO
95	COX6A1	COX6A1	COX6A1	15315	-0.0015	0.058	NO
96	REST	REST	REST	15328	-0.0017	0.058	NO
97	CREBBP	CREBBP	CREBBP	15484	-0.0034	0.051	NO
98	ATP5H	ATP5H	ATP5H	15547	-0.004	0.049	NO
99	COX7A2	COX7A2	COX7A2	15551	-0.0041	0.049	NO
100	COX5A	COX5A	COX5A	15630	-0.0048	0.046	NO
101	CREB3	CREB3	CREB3	15649	-0.005	0.046	NO
102	NDUFA3	NDUFA3	NDUFA3	15709	-0.0056	0.044	NO
103	HTT	HTT	HTT	15797	-0.0064	0.04	NO
104	POLR2J2	POLR2J2	POLR2J2	15803	-0.0064	0.041	NO
105	ATP5B	ATP5B	ATP5B	15823	-0.0066	0.041	NO
106	SDHB	SDHB	SDHB	15906	-0.0076	0.038	NO
107	NDUFV1	NDUFV1	NDUFV1	15912	-0.0077	0.038	NO
108	UQCRC1	UQCRC1	UQCRC1	15915	-0.0077	0.039	NO
109	UQCRH	UQCRH	UQCRH	15922	-0.0078	0.04	NO
110	POLR2L	POLR2L	POLR2L	15950	-0.008	0.039	NO
111	AP2B1	AP2B1	AP2B1	16061	-0.0095	0.035	NO
112	DNAH1	DNAH1	DNAH1	16092	-0.0098	0.035	NO
113	NDUFA1	NDUFA1	NDUFA1	16097	-0.0099	0.036	NO
114	CREB5	CREB5	CREB5	16239	-0.012	0.03	NO
115	SLC25A31	SLC25A31	SLC25A31	16532	-0.015	0.019	NO
116	VDAC1	VDAC1	VDAC1	16546	-0.015	0.02	NO
117	SLC25A5	SLC25A5	SLC25A5	16644	-0.016	0.017	NO
118	NDUFB8	NDUFB8	NDUFB8	16722	-0.017	0.016	NO
119	POLR2E	POLR2E	POLR2E	16723	-0.017	0.017	NO
120	ATP5J	ATP5J	ATP5J	16732	-0.018	0.018	NO
121	UQCR10	UQCR10	UQCR10	16747	-0.018	0.02	NO
122	ATP5A1	ATP5A1	ATP5A1	16767	-0.018	0.021	NO
123	ATP5G3	ATP5G3	ATP5G3	16834	-0.019	0.02	NO
124	APAF1	APAF1	APAF1	16849	-0.019	0.021	NO
125	GPX1	GPX1	GPX1	16866	-0.019	0.022	NO
126	NDUFB4	NDUFB4	NDUFB4	16871	-0.019	0.024	NO
127	NDUFV2	NDUFV2	NDUFV2	16919	-0.02	0.024	NO
128	SP1	SP1	SP1	16943	-0.02	0.024	NO
129	VDAC2	VDAC2	VDAC2	16986	-0.021	0.025	NO
130	COX8A	COX8A	COX8A	17058	-0.022	0.024	NO
131	SLC25A6	SLC25A6	SLC25A6	17220	-0.024	0.019	NO
132	NDUFB6	NDUFB6	NDUFB6	17229	-0.024	0.021	NO
133	BAX	BAX	BAX	17268	-0.025	0.022	NO
134	RCOR1	RCOR1	RCOR1	17319	-0.025	0.022	NO
135	SOD1	SOD1	SOD1	17349	-0.026	0.023	NO
136	ATP5F1	ATP5F1	ATP5F1	17431	-0.027	0.022	NO
137	NDUFS5	NDUFS5	NDUFS5	17472	-0.028	0.023	NO
138	NDUFA2	NDUFA2	NDUFA2	17512	-0.028	0.024	NO
139	NDUFB10	NDUFB10	NDUFB10	17562	-0.029	0.025	NO
140	GNAQ	GNAQ	GNAQ	17575	-0.029	0.027	NO
141	COX7B	COX7B	COX7B	17595	-0.03	0.029	NO
142	NDUFA7	NDUFA7	NDUFA7	17739	-0.032	0.026	NO
143	SOD2	SOD2	SOD2	17915	-0.035	0.022	NO
144	NDUFAB1	NDUFAB1	NDUFAB1	17962	-0.036	0.023	NO
145	COX4I1	COX4I1	COX4I1	18091	-0.038	0.021	NO
146	SDHD	SDHD	SDHD	18130	-0.038	0.023	NO
147	NDUFA9	NDUFA9	NDUFA9	18341	-0.043	0.018	NO
148	POLR2J3	POLR2J3	POLR2J3	18370	-0.043	0.021	NO
149	NDUFB7	NDUFB7	NDUFB7	18467	-0.045	0.021	NO
150	VDAC3	VDAC3	VDAC3	18533	-0.047	0.023	NO
151	NDUFB2	NDUFB2	NDUFB2	18553	-0.047	0.027	NO
152	UQCRQ	UQCRQ	UQCRQ	18561	-0.047	0.031	NO
153	UQCRC2	UQCRC2	UQCRC2	18788	-0.052	0.026	NO
154	IFT57	IFT57	IFT57	18898	-0.055	0.027	NO
155	TAF4B	TAF4B	TAF4B	19069	-0.059	0.025	NO
156	UQCR11	UQCR11	UQCR11	19297	-0.065	0.021	NO
157	PPARG	PPARG	PPARG	19371	-0.067	0.024	NO
158	PLCB3	PLCB3	PLCB3	19420	-0.068	0.029	NO
159	NDUFS7	NDUFS7	NDUFS7	19560	-0.072	0.03	NO
160	ITPR1	ITPR1	ITPR1	19564	-0.072	0.037	NO
161	ATP5D	ATP5D	ATP5D	19577	-0.073	0.044	NO
162	PLCB2	PLCB2	PLCB2	19729	-0.078	0.044	NO
163	COX7C	COX7C	COX7C	19839	-0.081	0.048	NO
164	NDUFS4	NDUFS4	NDUFS4	20090	-0.09	0.045	NO
165	TP53	TP53	TP53	20109	-0.091	0.053	NO
166	CLTB	CLTB	CLTB	20188	-0.094	0.059	NO
167	CREB3L1	CREB3L1	CREB3L1	20730	-0.12	0.047	NO
168	COX7A1	COX7A1	COX7A1	20885	-0.13	0.052	NO
169	BBC3	BBC3	BBC3	20949	-0.13	0.062	NO
170	TBPL2	TBPL2	TBPL2	20972	-0.13	0.074	NO

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

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

genes ES table in pathway: KEGG CYSTEINE AND METHIONINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	F7	F7	F7	45	0.64	0.052	YES
2	CPB2	CPB2	CPB2	57	0.62	0.1	YES
3	F2	F2	F2	92	0.59	0.15	YES
4	F10	F10	F10	122	0.56	0.2	YES
5	PROC	PROC	PROC	211	0.5	0.24	YES
6	FGA	FGA	FGA	227	0.5	0.28	YES
7	SERPINF2	SERPINF2	SERPINF2	276	0.48	0.32	YES
8	FGG	FGG	FGG	342	0.46	0.35	YES
9	KNG1	KNG1	KNG1	401	0.44	0.38	YES
10	FGB	FGB	FGB	413	0.44	0.42	YES
11	SERPINA5	SERPINA5	SERPINA5	485	0.42	0.45	YES
12	SERPIND1	SERPIND1	SERPIND1	611	0.39	0.48	YES
13	F13B	F13B	F13B	1193	0.31	0.48	YES
14	F5	F5	F5	1444	0.28	0.49	YES
15	C4BPA	C4BPA	C4BPA	1476	0.28	0.52	YES
16	C9	C9	C9	1761	0.26	0.52	YES
17	SERPINC1	SERPINC1	SERPINC1	1800	0.26	0.54	YES
18	C8B	C8B	C8B	2316	0.22	0.54	NO
19	F11	F11	F11	3105	0.19	0.52	NO
20	C5	C5	C5	3915	0.16	0.5	NO
21	SERPINA1	SERPINA1	SERPINA1	4053	0.15	0.5	NO
22	MASP2	MASP2	MASP2	4717	0.13	0.49	NO
23	C8A	C8A	C8A	5012	0.12	0.48	NO
24	PROS1	PROS1	PROS1	5316	0.12	0.48	NO
25	PLG	PLG	PLG	5887	0.1	0.46	NO
26	CD46	CD46	CD46	7936	0.071	0.38	NO
27	SERPINE1	SERPINE1	SERPINE1	9818	0.05	0.3	NO
28	MASP1	MASP1	MASP1	10909	0.04	0.25	NO
29	CFB	CFB	CFB	11057	0.038	0.25	NO
30	THBD	THBD	THBD	11890	0.031	0.22	NO
31	TFPI	TFPI	TFPI	12173	0.028	0.21	NO
32	C8G	C8G	C8G	13345	0.018	0.16	NO
33	PLAT	PLAT	PLAT	13610	0.016	0.15	NO
34	CFI	CFI	CFI	15205	-0.00037	0.075	NO
35	BDKRB2	BDKRB2	BDKRB2	16228	-0.012	0.031	NO
36	PLAU	PLAU	PLAU	16903	-0.02	0.0027	NO
37	F8	F8	F8	16945	-0.02	0.0026	NO
38	KLKB1	KLKB1	KLKB1	17278	-0.025	-0.01	NO
39	F2R	F2R	F2R	17513	-0.028	-0.018	NO
40	F12	F12	F12	18181	-0.04	-0.044	NO
41	C6	C6	C6	18770	-0.052	-0.066	NO
42	VWF	VWF	VWF	18805	-0.053	-0.063	NO
43	MBL2	MBL2	MBL2	19220	-0.063	-0.076	NO
44	C4B	C4B	C4B	19306	-0.065	-0.074	NO
45	F13A1	F13A1	F13A1	19414	-0.068	-0.073	NO
46	C4BPB	C4BPB	C4BPB	19578	-0.073	-0.074	NO
47	C3	C3	C3	19657	-0.076	-0.072	NO
48	CD59	CD59	CD59	19894	-0.083	-0.075	NO
49	C7	C7	C7	19921	-0.084	-0.069	NO
50	BDKRB1	BDKRB1	BDKRB1	20011	-0.087	-0.066	NO
51	F3	F3	F3	20068	-0.09	-0.061	NO
52	C1S	C1S	C1S	20351	-0.1	-0.065	NO
53	CD55	CD55	CD55	20446	-0.1	-0.06	NO
54	C1R	C1R	C1R	20566	-0.11	-0.056	NO
55	SERPING1	SERPING1	SERPING1	20587	-0.11	-0.048	NO
56	CFH	CFH	CFH	20684	-0.12	-0.042	NO
57	C5AR1	C5AR1	C5AR1	20686	-0.12	-0.033	NO
58	CR2	CR2	CR2	20717	-0.12	-0.024	NO
59	C1QC	C1QC	C1QC	21000	-0.13	-0.026	NO
60	C1QB	C1QB	C1QB	21054	-0.14	-0.016	NO
61	PLAUR	PLAUR	PLAUR	21111	-0.14	-0.0072	NO
62	C1QA	C1QA	C1QA	21324	-0.15	-0.0036	NO
63	C3AR1	C3AR1	C3AR1	21495	-0.17	0.0029	NO
64	CR1	CR1	CR1	22325	-0.27	-0.011	NO
65	CFD	CFD	CFD	22434	-0.3	0.0093	NO

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

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

genes ES table in pathway: KEGG LYSINE DEGRADATION

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NKD2	NKD2	NKD2	93	0.59	0.038	YES
2	FZD9	FZD9	FZD9	164	0.54	0.073	YES
3	WIF1	WIF1	WIF1	243	0.49	0.1	YES
4	VANGL2	VANGL2	VANGL2	308	0.47	0.14	YES
5	CXXC4	CXXC4	CXXC4	333	0.46	0.17	YES
6	WNT11	WNT11	WNT11	454	0.42	0.19	YES
7	WNT7A	WNT7A	WNT7A	685	0.38	0.21	YES
8	WNT3A	WNT3A	WNT3A	726	0.37	0.23	YES
9	RAC3	RAC3	RAC3	807	0.36	0.26	YES
10	NKD1	NKD1	NKD1	964	0.33	0.27	YES
11	WNT3	WNT3	WNT3	1097	0.32	0.29	YES
12	CAMK2B	CAMK2B	CAMK2B	1220	0.3	0.31	YES
13	FZD10	FZD10	FZD10	1513	0.28	0.31	YES
14	CER1	CER1	CER1	1841	0.25	0.32	YES
15	SFRP5	SFRP5	SFRP5	2131	0.23	0.32	YES
16	WNT8B	WNT8B	WNT8B	2251	0.23	0.33	YES
17	PLCB1	PLCB1	PLCB1	2453	0.22	0.34	YES
18	TBL1Y	TBL1Y	TBL1Y	2568	0.21	0.35	YES
19	WNT6	WNT6	WNT6	2589	0.21	0.36	YES
20	AXIN2	AXIN2	AXIN2	3065	0.19	0.36	YES
21	PPP3R2	PPP3R2	PPP3R2	3175	0.18	0.36	YES
22	WNT4	WNT4	WNT4	3308	0.18	0.37	YES
23	DKK1	DKK1	DKK1	3390	0.17	0.38	YES
24	FZD2	FZD2	FZD2	3970	0.15	0.36	NO
25	WNT5B	WNT5B	WNT5B	4370	0.14	0.36	NO
26	TCF7L1	TCF7L1	TCF7L1	4504	0.14	0.36	NO
27	WNT7B	WNT7B	WNT7B	4808	0.13	0.36	NO
28	WNT10B	WNT10B	WNT10B	4856	0.13	0.36	NO
29	FZD3	FZD3	FZD3	4977	0.12	0.37	NO
30	LRP5	LRP5	LRP5	5483	0.11	0.35	NO
31	CSNK2A1	CSNK2A1	CSNK2A1	5691	0.11	0.35	NO
32	NLK	NLK	NLK	5816	0.1	0.35	NO
33	TBL1X	TBL1X	TBL1X	5825	0.1	0.36	NO
34	FZD6	FZD6	FZD6	5947	0.1	0.36	NO
35	FZD7	FZD7	FZD7	6157	0.098	0.36	NO
36	PPP2R1B	PPP2R1B	PPP2R1B	6527	0.091	0.35	NO
37	DKK2	DKK2	DKK2	6613	0.09	0.35	NO
38	MAPK8	MAPK8	MAPK8	6917	0.085	0.34	NO
39	LEF1	LEF1	LEF1	7513	0.076	0.32	NO
40	NFATC2	NFATC2	NFATC2	7655	0.074	0.32	NO
41	LRP6	LRP6	LRP6	7679	0.074	0.33	NO
42	CSNK1E	CSNK1E	CSNK1E	7830	0.072	0.33	NO
43	MAP3K7	MAP3K7	MAP3K7	8031	0.069	0.32	NO
44	DVL2	DVL2	DVL2	8289	0.066	0.32	NO
45	WNT1	WNT1	WNT1	8442	0.064	0.31	NO
46	PRKACG	PRKACG	PRKACG	8690	0.062	0.31	NO
47	PLCB4	PLCB4	PLCB4	8699	0.062	0.31	NO
48	RUVBL1	RUVBL1	RUVBL1	9054	0.058	0.3	NO
49	PORCN	PORCN	PORCN	9389	0.054	0.29	NO
50	DVL3	DVL3	DVL3	9492	0.053	0.29	NO
51	NFATC4	NFATC4	NFATC4	9628	0.052	0.28	NO
52	NFAT5	NFAT5	NFAT5	9639	0.052	0.29	NO
53	CTNNB1	CTNNB1	CTNNB1	9728	0.051	0.29	NO
54	DVL1	DVL1	DVL1	9848	0.05	0.29	NO
55	CSNK2B	CSNK2B	CSNK2B	10018	0.048	0.28	NO
56	WNT16	WNT16	WNT16	10099	0.047	0.28	NO
57	TCF7	TCF7	TCF7	10314	0.045	0.28	NO
58	CTNNBIP1	CTNNBIP1	CTNNBIP1	10433	0.044	0.27	NO
59	SENP2	SENP2	SENP2	10555	0.043	0.27	NO
60	BTRC	BTRC	BTRC	10610	0.042	0.27	NO
61	CHD8	CHD8	CHD8	10617	0.042	0.27	NO
62	ROCK2	ROCK2	ROCK2	11079	0.038	0.26	NO
63	CACYBP	CACYBP	CACYBP	11141	0.038	0.26	NO
64	ROCK1	ROCK1	ROCK1	11144	0.037	0.26	NO
65	SMAD3	SMAD3	SMAD3	11323	0.036	0.25	NO
66	SIAH1	SIAH1	SIAH1	11452	0.035	0.25	NO
67	CTBP1	CTBP1	CTBP1	11664	0.033	0.24	NO
68	TBL1XR1	TBL1XR1	TBL1XR1	11937	0.03	0.23	NO
69	GSK3B	GSK3B	GSK3B	12050	0.03	0.23	NO
70	PPP2R5D	PPP2R5D	PPP2R5D	12138	0.029	0.23	NO
71	EP300	EP300	EP300	12242	0.028	0.23	NO
72	PPP2R1A	PPP2R1A	PPP2R1A	12333	0.027	0.22	NO
73	FRAT1	FRAT1	FRAT1	12872	0.022	0.2	NO
74	CSNK2A2	CSNK2A2	CSNK2A2	12898	0.022	0.2	NO
75	PPP2R5A	PPP2R5A	PPP2R5A	12924	0.022	0.2	NO
76	NFATC3	NFATC3	NFATC3	13105	0.02	0.2	NO
77	VANGL1	VANGL1	VANGL1	13168	0.02	0.2	NO
78	PRKCA	PRKCA	PRKCA	13187	0.019	0.2	NO
79	AXIN1	AXIN1	AXIN1	13193	0.019	0.2	NO
80	PPP3R1	PPP3R1	PPP3R1	13218	0.019	0.2	NO
81	JUN	JUN	JUN	13343	0.018	0.19	NO
82	CTBP2	CTBP2	CTBP2	13489	0.017	0.19	NO
83	PPARD	PPARD	PPARD	13854	0.013	0.17	NO
84	RBX1	RBX1	RBX1	13886	0.013	0.17	NO
85	FZD5	FZD5	FZD5	13906	0.013	0.17	NO
86	PPP3CB	PPP3CB	PPP3CB	14049	0.011	0.17	NO
87	FRAT2	FRAT2	FRAT2	14128	0.011	0.16	NO
88	CCND1	CCND1	CCND1	14143	0.01	0.16	NO
89	MMP7	MMP7	MMP7	14470	0.0072	0.15	NO
90	WNT5A	WNT5A	WNT5A	14589	0.0061	0.14	NO
91	FZD8	FZD8	FZD8	14597	0.006	0.14	NO
92	FZD1	FZD1	FZD1	14633	0.0056	0.14	NO
93	PPP3CA	PPP3CA	PPP3CA	14787	0.0042	0.14	NO
94	PRKACA	PRKACA	PRKACA	15047	0.0013	0.13	NO
95	DKK4	DKK4	DKK4	15111	0.00056	0.12	NO
96	CUL1	CUL1	CUL1	15199	-0.00033	0.12	NO
97	WNT9B	WNT9B	WNT9B	15369	-0.002	0.11	NO
98	PSEN1	PSEN1	PSEN1	15470	-0.0032	0.11	NO
99	CREBBP	CREBBP	CREBBP	15484	-0.0034	0.11	NO
100	SMAD2	SMAD2	SMAD2	15592	-0.0045	0.1	NO
101	RAC1	RAC1	RAC1	15612	-0.0047	0.1	NO
102	DAAM1	DAAM1	DAAM1	15613	-0.0047	0.1	NO
103	TCF7L2	TCF7L2	TCF7L2	15817	-0.0066	0.094	NO
104	PPP2R5E	PPP2R5E	PPP2R5E	15852	-0.007	0.094	NO
105	SFRP4	SFRP4	SFRP4	15879	-0.0073	0.093	NO
106	WNT10A	WNT10A	WNT10A	15883	-0.0074	0.093	NO
107	FBXW11	FBXW11	FBXW11	15894	-0.0075	0.093	NO
108	MAPK9	MAPK9	MAPK9	16163	-0.011	0.082	NO
109	PRICKLE1	PRICKLE1	PRICKLE1	16339	-0.013	0.075	NO
110	CAMK2D	CAMK2D	CAMK2D	16415	-0.014	0.073	NO
111	PPP2R5C	PPP2R5C	PPP2R5C	16478	-0.014	0.071	NO
112	PRKACB	PRKACB	PRKACB	16679	-0.017	0.064	NO
113	PPP3CC	PPP3CC	PPP3CC	16700	-0.017	0.064	NO
114	CAMK2G	CAMK2G	CAMK2G	16955	-0.02	0.054	NO
115	SMAD4	SMAD4	SMAD4	17162	-0.023	0.047	NO
116	CCND3	CCND3	CCND3	17169	-0.023	0.048	NO
117	RHOA	RHOA	RHOA	17537	-0.029	0.034	NO
118	SKP1	SKP1	SKP1	17666	-0.031	0.03	NO
119	PRKX	PRKX	PRKX	17737	-0.032	0.029	NO
120	WNT9A	WNT9A	WNT9A	17756	-0.032	0.031	NO
121	FZD4	FZD4	FZD4	17971	-0.036	0.024	NO
122	CSNK1A1	CSNK1A1	CSNK1A1	18534	-0.047	0.0023	NO
123	FOSL1	FOSL1	FOSL1	18724	-0.051	-0.0025	NO
124	CSNK1A1L	CSNK1A1L	CSNK1A1L	18785	-0.052	-0.0014	NO
125	MYC	MYC	MYC	18878	-0.055	-0.0016	NO
126	PPP2CB	PPP2CB	PPP2CB	18935	-0.056	-0.000075	NO
127	CHP2	CHP2	CHP2	19250	-0.064	-0.0095	NO
128	DAAM2	DAAM2	DAAM2	19253	-0.064	-0.005	NO
129	PRICKLE2	PRICKLE2	PRICKLE2	19303	-0.065	-0.0025	NO
130	PLCB3	PLCB3	PLCB3	19420	-0.068	-0.0028	NO
131	APC	APC	APC	19448	-0.069	0.00096	NO
132	PLCB2	PLCB2	PLCB2	19729	-0.078	-0.0059	NO
133	MAPK10	MAPK10	MAPK10	19815	-0.08	-0.004	NO
134	SOX17	SOX17	SOX17	20029	-0.088	-0.0071	NO
135	PRKCG	PRKCG	PRKCG	20101	-0.091	-0.0038	NO
136	TP53	TP53	TP53	20109	-0.091	0.0024	NO
137	NFATC1	NFATC1	NFATC1	20253	-0.097	0.003	NO
138	SFRP2	SFRP2	SFRP2	20649	-0.11	-0.0065	NO
139	WNT2	WNT2	WNT2	20747	-0.12	-0.0023	NO
140	CAMK2A	CAMK2A	CAMK2A	20811	-0.12	0.0037	NO
141	SFRP1	SFRP1	SFRP1	20880	-0.13	0.0097	NO
142	RAC2	RAC2	RAC2	21044	-0.14	0.012	NO
143	WNT2B	WNT2B	WNT2B	21460	-0.16	0.0056	NO
144	CCND2	CCND2	CCND2	21725	-0.19	0.0072	NO
145	APC2	APC2	APC2	21817	-0.19	0.017	NO
146	PRKCB	PRKCB	PRKCB	22334	-0.27	0.014	NO

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

Figure S98. 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 S50. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	F2	F2	F2	92	0.59	0.14	YES
2	GNGT1	GNGT1	GNGT1	98	0.58	0.27	YES
3	ARHGEF19	ARHGEF19	ARHGEF19	1207	0.3	0.3	YES
4	ADCY1	ADCY1	ADCY1	1393	0.29	0.36	YES
5	ARHGEF4	ARHGEF4	ARHGEF4	1741	0.26	0.4	YES
6	PLCB1	PLCB1	PLCB1	2453	0.22	0.42	YES
7	GNAI1	GNAI1	GNAI1	5324	0.12	0.32	NO
8	ARHGEF10	ARHGEF10	ARHGEF10	6050	0.1	0.32	NO
9	ARHGEF11	ARHGEF11	ARHGEF11	7857	0.072	0.25	NO
10	MAP3K7	MAP3K7	MAP3K7	8031	0.069	0.26	NO
11	ARHGEF16	ARHGEF16	ARHGEF16	8802	0.061	0.24	NO
12	GNA12	GNA12	GNA12	9745	0.05	0.21	NO
13	ARHGEF17	ARHGEF17	ARHGEF17	10311	0.045	0.2	NO
14	ARHGEF7	ARHGEF7	ARHGEF7	10941	0.039	0.18	NO
15	ROCK1	ROCK1	ROCK1	11144	0.037	0.18	NO
16	GNB1	GNB1	GNB1	11355	0.036	0.18	NO
17	ARHGEF2	ARHGEF2	ARHGEF2	11914	0.031	0.16	NO
18	ARHGEF1	ARHGEF1	ARHGEF1	12045	0.03	0.16	NO
19	PRKCA	PRKCA	PRKCA	13187	0.019	0.12	NO
20	ARHGEF12	ARHGEF12	ARHGEF12	14399	0.0078	0.066	NO
21	PIK3CA	PIK3CA	PIK3CA	14535	0.0066	0.062	NO
22	ARHGEF5	ARHGEF5	ARHGEF5	15428	-0.0028	0.023	NO
23	ARHGEF9	ARHGEF9	ARHGEF9	15897	-0.0075	0.0041	NO
24	ARHGEF18	ARHGEF18	ARHGEF18	16238	-0.012	-0.0081	NO
25	F2R	F2R	F2R	17513	-0.028	-0.058	NO
26	RHOA	RHOA	RHOA	17537	-0.029	-0.052	NO
27	GNAQ	GNAQ	GNAQ	17575	-0.029	-0.047	NO
28	ARHGEF3	ARHGEF3	ARHGEF3	17724	-0.032	-0.046	NO
29	PIK3R1	PIK3R1	PIK3R1	18520	-0.046	-0.07	NO
30	ARHGEF15	ARHGEF15	ARHGEF15	19655	-0.075	-0.1	NO
31	F2RL3	F2RL3	F2RL3	19683	-0.076	-0.085	NO
32	PTK2B	PTK2B	PTK2B	19770	-0.079	-0.07	NO
33	ARHGEF6	ARHGEF6	ARHGEF6	21298	-0.15	-0.1	NO
34	PPP1R12B	PPP1R12B	PPP1R12B	21751	-0.19	-0.077	NO
35	PIK3CG	PIK3CG	PIK3CG	21994	-0.21	-0.036	NO
36	PRKCB	PRKCB	PRKCB	22334	-0.27	0.014	NO

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

Figure S100. 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

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 = STAD-TP.mRNAseq_RPKM_log2.txt
Phenotype data file = STAD-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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