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

Esophageal Carcinoma (Primary solid tumor)

21 August 2015 | analyses__2015_08_21

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in ESCA-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1XK8DR5

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 ESCA-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: 196
Number of samples: 184
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 4 :[ clus1 ] 82
pheno.type: 2 - 4 :[ clus2 ] 69
pheno.type: 3 - 4 :[ clus3 ] 22
pheno.type: 4 - 4 :[ clus4 ] 11

For the expression subtypes of 18768 genes in 185 samples, GSEA found enriched gene sets in each cluster using 184 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA DEATH PATHWAY, BIOCARTA PPARA PATHWAY, BIOCARTA RHO PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG HISTIDINE METABOLISM, KEGG STARCH AND SUCROSE METABOLISM, KEGG N GLYCAN BIOSYNTHESIS, KEGG GLYCEROLIPID METABOLISM

And common core enriched genes are PRKACG, NOS2, PRKCA, ABCD1, ABCD3, ABCD4, ACAA1, ACOT8, ACOX1, ACSL5

clus2

Top enriched gene sets are BIOCARTA CARM ER PATHWAY, BIOCARTA G1 PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA INTEGRIN PATHWAY, KEGG RNA DEGRADATION, KEGG RNA POLYMERASE, KEGG BASAL TRANSCRIPTION FACTORS, KEGG SPLICEOSOME, KEGG PROTEASOME

And common core enriched genes are CCNB1, CCNB2, CCND1, CCNE2, CDK1, CDK2, CDK4, CDK6, CHEK1, CHEK2

clus3

Top enriched gene sets are BIOCARTA RACCYCD PATHWAY, BIOCARTA MAPK PATHWAY, BIOCARTA CHREBP2 PATHWAY, BIOCARTA IL1R PATHWAY, BIOCARTA WNT PATHWAY, KEGG OXIDATIVE PHOSPHORYLATION, KEGG GLYCEROPHOSPHOLIPID METABOLISM, KEGG ETHER LIPID METABOLISM, KEGG ARACHIDONIC ACID METABOLISM, KEGG LINOLEIC ACID METABOLISM

And common core enriched genes are IKBKB, NFKBIA, RAC1, ATP6V0A1, ATP6V0A4, ATP6V0C, ATP6V0D1, ATP6V0E2, ATP6V1A, ATP6V1B1

clus4

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

And common core enriched genes are AKT3, PIK3CG, PIK3R1, PIK3CD, PIK3R5, PRKAA2, PRKCB, RXRG, CAB39L, FIGF

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 DEATH PATHWAY	32	genes.ES.table	0.48	1.6	0.058	0.32	0.75	0.56	0.29	0.4	0.18	0.064
BIOCARTA PPARA PATHWAY	55	genes.ES.table	0.51	1.7	0	0.47	0.46	0.18	0.11	0.16	0	0.13
BIOCARTA RHO PATHWAY	31	genes.ES.table	0.44	1.7	0.013	0.35	0.47	0.064	0.033	0.062	0	0.096
KEGG FRUCTOSE AND MANNOSE METABOLISM	33	genes.ES.table	0.49	1.6	0.059	0.34	0.82	0.33	0.17	0.28	0.21	0.067
KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM	29	genes.ES.table	0.54	1.6	0.027	0.32	0.82	0.28	0.091	0.25	0.2	0.053
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.51	1.7	0.027	0.28	0.52	0.49	0.27	0.36	0.12	0.064
KEGG HISTIDINE METABOLISM	28	genes.ES.table	0.59	1.6	0.03	0.32	0.83	0.18	0.034	0.17	0.2	0.051
KEGG STARCH AND SUCROSE METABOLISM	46	genes.ES.table	0.56	1.4	0.076	0.44	0.95	0.3	0.094	0.28	0.33	0.089
KEGG N GLYCAN BIOSYNTHESIS	45	genes.ES.table	0.44	1.6	0.064	0.35	0.75	0.42	0.26	0.31	0.2	0.075
KEGG GLYCEROLIPID METABOLISM	47	genes.ES.table	0.45	1.5	0.045	0.43	0.93	0.43	0.2	0.34	0.32	0.089

genes ES table in pathway: BIOCARTA DEATH 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	ACSL5	ACSL5	ACSL5	243	0.94	0.06	YES
2	BAAT	BAAT	BAAT	432	0.75	0.11	YES
3	NOS2	NOS2	NOS2	433	0.75	0.17	YES
4	FAR2	FAR2	FAR2	441	0.74	0.22	YES
5	SLC27A2	SLC27A2	SLC27A2	507	0.7	0.28	YES
6	AGXT	AGXT	AGXT	585	0.66	0.32	YES
7	HAO2	HAO2	HAO2	1054	0.46	0.33	YES
8	PECR	PECR	PECR	1521	0.35	0.34	YES
9	PHYH	PHYH	PHYH	1613	0.34	0.36	YES
10	PEX11A	PEX11A	PEX11A	1968	0.28	0.36	YES
11	EPHX2	EPHX2	EPHX2	2122	0.27	0.37	YES
12	PIPOX	PIPOX	PIPOX	2395	0.24	0.38	YES
13	DECR2	DECR2	DECR2	2477	0.23	0.39	YES
14	DDO	DDO	DDO	2536	0.23	0.41	YES
15	PEX11G	PEX11G	PEX11G	2715	0.21	0.41	YES
16	ABCD3	ABCD3	ABCD3	2771	0.21	0.43	YES
17	ABCD1	ABCD1	ABCD1	2787	0.2	0.44	YES
18	AMACR	AMACR	AMACR	2883	0.2	0.45	YES
19	HACL1	HACL1	HACL1	3135	0.18	0.45	YES
20	PEX7	PEX7	PEX7	3250	0.17	0.46	YES
21	CAT	CAT	CAT	3281	0.17	0.47	YES
22	ACAA1	ACAA1	ACAA1	3320	0.17	0.48	YES
23	ACOX1	ACOX1	ACOX1	3361	0.16	0.49	YES
24	NUDT12	NUDT12	NUDT12	3480	0.16	0.5	YES
25	CRAT	CRAT	CRAT	3592	0.15	0.5	YES
26	HMGCL	HMGCL	HMGCL	3682	0.15	0.51	YES
27	IDH1	IDH1	IDH1	3696	0.14	0.52	YES
28	MLYCD	MLYCD	MLYCD	3761	0.14	0.53	YES
29	PXMP4	PXMP4	PXMP4	3958	0.13	0.53	YES
30	PXMP2	PXMP2	PXMP2	3977	0.13	0.54	YES
31	ACOT8	ACOT8	ACOT8	4214	0.12	0.54	YES
32	SCP2	SCP2	SCP2	4282	0.12	0.54	YES
33	ABCD4	ABCD4	ABCD4	4370	0.11	0.55	YES
34	PEX1	PEX1	PEX1	4462	0.11	0.55	YES
35	GSTK1	GSTK1	GSTK1	4464	0.11	0.56	YES
36	IDH2	IDH2	IDH2	4889	0.094	0.54	NO
37	GNPAT	GNPAT	GNPAT	5410	0.077	0.52	NO
38	PECI	PECI	PECI	5753	0.067	0.51	NO
39	ABCD2	ABCD2	ABCD2	5872	0.064	0.5	NO
40	HSD17B4	HSD17B4	HSD17B4	6238	0.055	0.49	NO
41	ECH1	ECH1	ECH1	6355	0.052	0.49	NO
42	ACSL6	ACSL6	ACSL6	6416	0.05	0.49	NO
43	ACSL3	ACSL3	ACSL3	6513	0.048	0.49	NO
44	PEX16	PEX16	PEX16	6567	0.047	0.49	NO
45	ACSL4	ACSL4	ACSL4	6594	0.046	0.49	NO
46	PEX2	PEX2	PEX2	6647	0.045	0.49	NO
47	PEX6	PEX6	PEX6	7041	0.036	0.47	NO
48	PEX11B	PEX11B	PEX11B	7552	0.025	0.45	NO
49	AGPS	AGPS	AGPS	7640	0.023	0.44	NO
50	FAR1	FAR1	FAR1	8298	0.01	0.41	NO
51	ACOX3	ACOX3	ACOX3	8744	0.0018	0.39	NO
52	PEX26	PEX26	PEX26	8850	0.000053	0.38	NO
53	XDH	XDH	XDH	9256	-0.0074	0.36	NO
54	EHHADH	EHHADH	EHHADH	10167	-0.024	0.31	NO
55	PEX19	PEX19	PEX19	10415	-0.028	0.3	NO
56	SOD1	SOD1	SOD1	10486	-0.03	0.3	NO
57	PMVK	PMVK	PMVK	10635	-0.032	0.3	NO
58	PEX12	PEX12	PEX12	10985	-0.039	0.28	NO
59	PEX3	PEX3	PEX3	11315	-0.045	0.26	NO
60	PEX14	PEX14	PEX14	11369	-0.046	0.27	NO
61	PEX13	PEX13	PEX13	11515	-0.049	0.26	NO
62	PRDX5	PRDX5	PRDX5	11816	-0.056	0.25	NO
63	SOD2	SOD2	SOD2	11837	-0.057	0.25	NO
64	PEX5	PEX5	PEX5	11926	-0.058	0.25	NO
65	PEX10	PEX10	PEX10	12572	-0.073	0.22	NO
66	NUDT19	NUDT19	NUDT19	13366	-0.094	0.19	NO
67	PRDX1	PRDX1	PRDX1	13410	-0.096	0.2	NO
68	MPV17	MPV17	MPV17	13731	-0.11	0.19	NO
69	PAOX	PAOX	PAOX	14235	-0.12	0.17	NO
70	SLC25A17	SLC25A17	SLC25A17	14261	-0.12	0.18	NO
71	MPV17L	MPV17L	MPV17L	14313	-0.13	0.18	NO
72	DHRS4	DHRS4	DHRS4	14695	-0.14	0.18	NO
73	ACSL1	ACSL1	ACSL1	14974	-0.16	0.17	NO
74	MVK	MVK	MVK	15013	-0.16	0.18	NO
75	CROT	CROT	CROT	15921	-0.22	0.15	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 DEATH PATHWAY.

Figure S2. 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 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	CFTR	CFTR	CFTR	78	1.4	0.14	YES
2	KCNQ1	KCNQ1	KCNQ1	319	0.85	0.21	YES
3	PRKCG	PRKCG	PRKCG	405	0.77	0.28	YES
4	MUC2	MUC2	MUC2	494	0.71	0.35	YES
5	PRKACG	PRKACG	PRKACG	522	0.69	0.42	YES
6	SLC12A2	SLC12A2	SLC12A2	884	0.53	0.45	YES
7	PRKCA	PRKCA	PRKCA	1373	0.38	0.47	YES
8	KDELR3	KDELR3	KDELR3	1393	0.38	0.5	YES
9	TJP2	TJP2	TJP2	2636	0.22	0.46	NO
10	ATP6V1C2	ATP6V1C2	ATP6V1C2	2955	0.19	0.46	NO
11	TCIRG1	TCIRG1	TCIRG1	3632	0.15	0.44	NO
12	KDELR2	KDELR2	KDELR2	3653	0.15	0.46	NO
13	KDELR1	KDELR1	KDELR1	4665	0.1	0.41	NO
14	ATP6V0A2	ATP6V0A2	ATP6V0A2	4920	0.093	0.41	NO
15	PDIA4	PDIA4	PDIA4	5142	0.086	0.4	NO
16	ATP6V0E2	ATP6V0E2	ATP6V0E2	5865	0.064	0.37	NO
17	PRKCB	PRKCB	PRKCB	5893	0.063	0.38	NO
18	ATP6V0A1	ATP6V0A1	ATP6V0A1	5923	0.063	0.38	NO
19	ATP6V0B	ATP6V0B	ATP6V0B	5938	0.062	0.39	NO
20	SEC61A2	SEC61A2	SEC61A2	6093	0.058	0.39	NO
21	TJP1	TJP1	TJP1	7000	0.037	0.34	NO
22	ARF1	ARF1	ARF1	7198	0.032	0.33	NO
23	ATP6AP1	ATP6AP1	ATP6AP1	8043	0.015	0.29	NO
24	ATP6V1C1	ATP6V1C1	ATP6V1C1	8477	0.0068	0.27	NO
25	SEC61A1	SEC61A1	SEC61A1	8808	0.00066	0.25	NO
26	SEC61B	SEC61B	SEC61B	9203	-0.0065	0.23	NO
27	SEC61G	SEC61G	SEC61G	10012	-0.021	0.19	NO
28	ACTB	ACTB	ACTB	10068	-0.022	0.19	NO
29	ACTG1	ACTG1	ACTG1	10277	-0.026	0.18	NO
30	ATP6V0E1	ATP6V0E1	ATP6V0E1	10671	-0.033	0.16	NO
31	ATP6V1B2	ATP6V1B2	ATP6V1B2	10719	-0.033	0.16	NO
32	ATP6V0D1	ATP6V0D1	ATP6V0D1	10941	-0.038	0.16	NO
33	GNAS	GNAS	GNAS	11481	-0.048	0.13	NO
34	ERO1L	ERO1L	ERO1L	11611	-0.051	0.13	NO
35	ADCY9	ADCY9	ADCY9	12002	-0.06	0.12	NO
36	ATP6V0C	ATP6V0C	ATP6V0C	12366	-0.068	0.1	NO
37	ATP6V1A	ATP6V1A	ATP6V1A	12561	-0.073	0.1	NO
38	PRKACB	PRKACB	PRKACB	12646	-0.075	0.1	NO
39	ATP6V1G1	ATP6V1G1	ATP6V1G1	12655	-0.076	0.11	NO
40	ATP6V1D	ATP6V1D	ATP6V1D	12861	-0.081	0.11	NO
41	ATP6V1H	ATP6V1H	ATP6V1H	12985	-0.084	0.11	NO
42	PLCG1	PLCG1	PLCG1	13129	-0.088	0.11	NO
43	PRKACA	PRKACA	PRKACA	13401	-0.096	0.11	NO
44	ATP6V1G2	ATP6V1G2	ATP6V1G2	13675	-0.1	0.1	NO
45	ATP6V1F	ATP6V1F	ATP6V1F	13708	-0.11	0.11	NO
46	PLCG2	PLCG2	PLCG2	13723	-0.11	0.12	NO
47	ATP6V1E1	ATP6V1E1	ATP6V1E1	13925	-0.11	0.12	NO
48	ATP6V0D2	ATP6V0D2	ATP6V0D2	14950	-0.16	0.083	NO
49	ATP6V0A4	ATP6V0A4	ATP6V0A4	16007	-0.22	0.05	NO
50	PRKX	PRKX	PRKX	16097	-0.23	0.069	NO
51	ATP6V1E2	ATP6V1E2	ATP6V1E2	17116	-0.36	0.051	NO
52	ATP6V1B1	ATP6V1B1	ATP6V1B1	17127	-0.36	0.087	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 PPARA PATHWAY.

Figure S4. 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 RHO PATHWAY

Table S3. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NR0B2	NR0B2	NR0B2	43	1.6	0.15	YES
2	FABP1	FABP1	FABP1	207	0.99	0.23	YES
3	NOS2	NOS2	NOS2	433	0.75	0.29	YES
4	PRKACG	PRKACG	PRKACG	522	0.69	0.36	YES
5	APOA1	APOA1	APOA1	731	0.59	0.4	YES
6	PPARGC1A	PPARGC1A	PPARGC1A	1105	0.45	0.42	YES
7	APOA2	APOA2	APOA2	1270	0.4	0.45	YES
8	PRKCA	PRKCA	PRKCA	1373	0.38	0.48	YES
9	NR1H3	NR1H3	NR1H3	1722	0.32	0.5	YES
10	PIK3CG	PIK3CG	PIK3CG	1991	0.28	0.51	YES
11	STAT5A	STAT5A	STAT5A	2670	0.22	0.49	NO
12	PRKAR2A	PRKAR2A	PRKAR2A	3862	0.14	0.44	NO
13	PDGFA	PDGFA	PDGFA	3931	0.13	0.45	NO
14	MAPK3	MAPK3	MAPK3	4048	0.13	0.46	NO
15	NR2F1	NR2F1	NR2F1	4527	0.11	0.44	NO
16	PPARA	PPARA	PPARA	4618	0.1	0.45	NO
17	NCOR1	NCOR1	NCOR1	5041	0.089	0.43	NO
18	MED1	MED1	MED1	5874	0.064	0.4	NO
19	PRKCB	PRKCB	PRKCB	5893	0.063	0.4	NO
20	HSD17B4	HSD17B4	HSD17B4	6238	0.055	0.39	NO
21	PTGS2	PTGS2	PTGS2	6351	0.052	0.39	NO
22	STAT5B	STAT5B	STAT5B	6745	0.043	0.37	NO
23	CPT1B	CPT1B	CPT1B	6780	0.042	0.37	NO
24	PRKAR1B	PRKAR1B	PRKAR1B	7002	0.037	0.36	NO
25	LPL	LPL	LPL	7485	0.026	0.34	NO
26	FAT1	FAT1	FAT1	7771	0.021	0.33	NO
27	SP1	SP1	SP1	8643	0.0038	0.28	NO
28	NCOA1	NCOA1	NCOA1	8753	0.0017	0.28	NO
29	PIK3R1	PIK3R1	PIK3R1	8780	0.0012	0.27	NO
30	HSP90AA1	HSP90AA1	HSP90AA1	9381	-0.0096	0.24	NO
31	NCOR2	NCOR2	NCOR2	9433	-0.01	0.24	NO
32	SRA1	SRA1	SRA1	9963	-0.02	0.22	NO
33	EHHADH	EHHADH	EHHADH	10167	-0.024	0.21	NO
34	PRKAR1A	PRKAR1A	PRKAR1A	10215	-0.025	0.21	NO
35	RELA	RELA	RELA	10240	-0.025	0.21	NO
36	MRPL11	MRPL11	MRPL11	10275	-0.026	0.21	NO
37	EP300	EP300	EP300	10512	-0.03	0.2	NO
38	RB1	RB1	RB1	11015	-0.039	0.18	NO
39	CREBBP	CREBBP	CREBBP	11877	-0.057	0.14	NO
40	MAPK1	MAPK1	MAPK1	12040	-0.061	0.13	NO
41	PRKACB	PRKACB	PRKACB	12646	-0.075	0.11	NO
42	CITED2	CITED2	CITED2	12974	-0.084	0.098	NO
43	TNF	TNF	TNF	13840	-0.11	0.062	NO
44	HSPA1A	HSPA1A	HSPA1A	13863	-0.11	0.071	NO
45	JUN	JUN	JUN	14035	-0.12	0.073	NO
46	MYC	MYC	MYC	14307	-0.13	0.071	NO
47	NRIP1	NRIP1	NRIP1	14440	-0.13	0.076	NO
48	DUT	DUT	DUT	14989	-0.16	0.062	NO
49	PRKAR2B	PRKAR2B	PRKAR2B	15190	-0.17	0.068	NO
50	NFKBIA	NFKBIA	NFKBIA	15298	-0.18	0.079	NO
51	ME1	ME1	ME1	15612	-0.2	0.081	NO
52	DUSP1	DUSP1	DUSP1	15710	-0.2	0.095	NO
53	RXRA	RXRA	RXRA	15737	-0.2	0.11	NO
54	PIK3CA	PIK3CA	PIK3CA	15746	-0.2	0.13	NO
55	CD36	CD36	CD36	16690	-0.3	0.11	NO

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

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

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	PIP5K1B	PIP5K1B	PIP5K1B	81	1.3	0.32	YES
2	ARHGAP6	ARHGAP6	ARHGAP6	613	0.64	0.44	YES
3	ARHGAP4	ARHGAP4	ARHGAP4	2577	0.22	0.39	NO
4	SRC	SRC	SRC	3388	0.16	0.39	NO
5	ARPC1B	ARPC1B	ARPC1B	5474	0.075	0.29	NO
6	ARPC4	ARPC4	ARPC4	5588	0.071	0.3	NO
7	RHOA	RHOA	RHOA	5953	0.062	0.3	NO
8	ARHGEF11	ARHGEF11	ARHGEF11	6142	0.057	0.3	NO
9	ARHGEF1	ARHGEF1	ARHGEF1	6793	0.042	0.28	NO
10	PPP1R12B	PPP1R12B	PPP1R12B	7029	0.036	0.28	NO
11	ROCK1	ROCK1	ROCK1	7231	0.032	0.27	NO
12	DIAPH1	DIAPH1	DIAPH1	7385	0.029	0.27	NO
13	CFL1	CFL1	CFL1	8429	0.0077	0.22	NO
14	OPHN1	OPHN1	OPHN1	8495	0.0064	0.22	NO
15	ACTR2	ACTR2	ACTR2	8743	0.0018	0.2	NO
16	ARPC5	ARPC5	ARPC5	9078	-0.004	0.18	NO
17	ARHGAP5	ARHGAP5	ARHGAP5	9149	-0.0054	0.18	NO
18	ARPC1A	ARPC1A	ARPC1A	9441	-0.011	0.17	NO
19	PFN1	PFN1	PFN1	10317	-0.026	0.13	NO
20	ARPC3	ARPC3	ARPC3	10559	-0.031	0.12	NO
21	PIP5K1A	PIP5K1A	PIP5K1A	10643	-0.032	0.13	NO
22	MYL2	MYL2	MYL2	11370	-0.046	0.1	NO
23	VCL	VCL	VCL	11595	-0.051	0.1	NO
24	ARHGAP1	ARHGAP1	ARHGAP1	12198	-0.064	0.083	NO
25	GSN	GSN	GSN	12339	-0.068	0.092	NO
26	ACTR3	ACTR3	ACTR3	12504	-0.072	0.1	NO
27	ARPC2	ARPC2	ARPC2	12602	-0.074	0.11	NO
28	ARHGEF5	ARHGEF5	ARHGEF5	15003	-0.16	0.023	NO
29	LIMK1	LIMK1	LIMK1	15162	-0.17	0.055	NO
30	MYLK	MYLK	MYLK	16340	-0.26	0.054	NO
31	BAIAP2	BAIAP2	BAIAP2	16806	-0.31	0.1	NO

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

Figure S8. 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 ALANINE ASPARTATE AND GLUTAMATE METABOLISM

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	CREB3L3	CREB3L3	CREB3L3	115	1.2	0.15	YES
2	CREB3L1	CREB3L1	CREB3L1	408	0.77	0.23	YES
3	AQP2	AQP2	AQP2	419	0.76	0.33	YES
4	PRKACG	PRKACG	PRKACG	522	0.69	0.41	YES
5	ADCY6	ADCY6	ADCY6	1100	0.45	0.44	YES
6	AVPR2	AVPR2	AVPR2	2447	0.23	0.4	NO
7	CREB3L4	CREB3L4	CREB3L4	3116	0.18	0.39	NO
8	NSF	NSF	NSF	4746	0.098	0.31	NO
9	CREB3	CREB3	CREB3	4913	0.094	0.32	NO
10	DYNC2LI1	DYNC2LI1	DYNC2LI1	5238	0.082	0.31	NO
11	RAB5C	RAB5C	RAB5C	6635	0.045	0.24	NO
12	CREB3L2	CREB3L2	CREB3L2	6661	0.045	0.24	NO
13	RAB11A	RAB11A	RAB11A	6692	0.044	0.25	NO
14	RAB5A	RAB5A	RAB5A	6763	0.042	0.25	NO
15	ARHGDIB	ARHGDIB	ARHGDIB	8002	0.016	0.19	NO
16	ARHGDIA	ARHGDIA	ARHGDIA	8345	0.0091	0.17	NO
17	STX4	STX4	STX4	9173	-0.006	0.13	NO
18	DYNC1I2	DYNC1I2	DYNC1I2	9577	-0.013	0.11	NO
19	DYNLL2	DYNLL2	DYNLL2	9689	-0.015	0.1	NO
20	DCTN6	DCTN6	DCTN6	9811	-0.018	0.098	NO
21	DYNC1LI2	DYNC1LI2	DYNC1LI2	9832	-0.018	0.099	NO
22	RAB5B	RAB5B	RAB5B	10364	-0.027	0.074	NO
23	CREB1	CREB1	CREB1	10507	-0.03	0.07	NO
24	DCTN5	DCTN5	DCTN5	11143	-0.041	0.042	NO
25	DCTN4	DCTN4	DCTN4	11373	-0.046	0.035	NO
26	GNAS	GNAS	GNAS	11481	-0.048	0.036	NO
27	RAB11B	RAB11B	RAB11B	11910	-0.058	0.02	NO
28	ADCY9	ADCY9	ADCY9	12002	-0.06	0.023	NO
29	DYNC1LI1	DYNC1LI1	DYNC1LI1	12298	-0.066	0.016	NO
30	DYNC1H1	DYNC1H1	DYNC1H1	12347	-0.068	0.022	NO
31	PRKACB	PRKACB	PRKACB	12646	-0.075	0.016	NO
32	DCTN1	DCTN1	DCTN1	12869	-0.081	0.015	NO
33	DCTN2	DCTN2	DCTN2	12987	-0.084	0.019	NO
34	DYNLL1	DYNLL1	DYNLL1	13084	-0.087	0.025	NO
35	VAMP2	VAMP2	VAMP2	13262	-0.092	0.028	NO
36	PRKACA	PRKACA	PRKACA	13401	-0.096	0.032	NO
37	AQP4	AQP4	AQP4	13647	-0.1	0.033	NO
38	PRKX	PRKX	PRKX	16097	-0.23	-0.068	NO
39	DYNC2H1	DYNC2H1	DYNC2H1	16959	-0.33	-0.072	NO
40	CREB5	CREB5	CREB5	17262	-0.38	-0.039	NO
41	AQP3	AQP3	AQP3	17440	-0.41	0.0047	NO
42	DYNC1I1	DYNC1I1	DYNC1I1	17861	-0.51	0.047	NO

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

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

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HMGCS2	HMGCS2	HMGCS2	130	1.2	0.18	YES
2	ACAA2	ACAA2	ACAA2	761	0.58	0.24	YES
3	BCKDHB	BCKDHB	BCKDHB	2213	0.26	0.2	YES
4	ACADS	ACADS	ACADS	2323	0.25	0.24	YES
5	ALDH2	ALDH2	ALDH2	2370	0.24	0.27	YES
6	IVD	IVD	IVD	2625	0.22	0.3	YES
7	HIBADH	HIBADH	HIBADH	2791	0.2	0.32	YES
8	ABAT	ABAT	ABAT	2969	0.19	0.34	YES
9	ACAD8	ACAD8	ACAD8	3002	0.19	0.37	YES
10	PCCA	PCCA	PCCA	3084	0.18	0.39	YES
11	ACAA1	ACAA1	ACAA1	3320	0.17	0.41	YES
12	ACADSB	ACADSB	ACADSB	3538	0.15	0.42	YES
13	ALDH1B1	ALDH1B1	ALDH1B1	3585	0.15	0.44	YES
14	HMGCL	HMGCL	HMGCL	3682	0.15	0.46	YES
15	ECHS1	ECHS1	ECHS1	4063	0.13	0.46	YES
16	ACAT1	ACAT1	ACAT1	4253	0.12	0.47	YES
17	HADH	HADH	HADH	4299	0.12	0.49	YES
18	HIBCH	HIBCH	HIBCH	4799	0.096	0.47	YES
19	MCCC2	MCCC2	MCCC2	4879	0.094	0.48	YES
20	ALDH6A1	ALDH6A1	ALDH6A1	4983	0.09	0.49	YES
21	AUH	AUH	AUH	4984	0.09	0.51	YES
22	MCEE	MCEE	MCEE	5661	0.07	0.48	NO
23	OXCT2	OXCT2	OXCT2	6464	0.05	0.45	NO
24	ALDH9A1	ALDH9A1	ALDH9A1	7851	0.019	0.38	NO
25	HADHA	HADHA	HADHA	7959	0.017	0.38	NO
26	BCAT2	BCAT2	BCAT2	7971	0.017	0.38	NO
27	ALDH7A1	ALDH7A1	ALDH7A1	8227	0.011	0.36	NO
28	ACADM	ACADM	ACADM	8396	0.0084	0.36	NO
29	MUT	MUT	MUT	8887	-0.00068	0.33	NO
30	HSD17B10	HSD17B10	HSD17B10	8916	-0.0011	0.33	NO
31	DLD	DLD	DLD	9855	-0.018	0.28	NO
32	EHHADH	EHHADH	EHHADH	10167	-0.024	0.27	NO
33	HMGCS1	HMGCS1	HMGCS1	10592	-0.031	0.25	NO
34	PCCB	PCCB	PCCB	11899	-0.058	0.19	NO
35	HADHB	HADHB	HADHB	12164	-0.063	0.19	NO
36	ACAT2	ACAT2	ACAT2	12308	-0.067	0.19	NO
37	AOX1	AOX1	AOX1	12794	-0.079	0.18	NO
38	IL4I1	IL4I1	IL4I1	12798	-0.079	0.19	NO
39	MCCC1	MCCC1	MCCC1	13822	-0.11	0.15	NO
40	ALDH3A2	ALDH3A2	ALDH3A2	14403	-0.13	0.14	NO
41	DBT	DBT	DBT	14448	-0.13	0.16	NO
42	BCKDHA	BCKDHA	BCKDHA	14596	-0.14	0.18	NO
43	OXCT1	OXCT1	OXCT1	16577	-0.28	0.12	NO

Figure S11. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

Figure S12. 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 HISTIDINE 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	GAL3ST1	GAL3ST1	GAL3ST1	41	1.6	0.16	YES
2	SMPD3	SMPD3	SMPD3	182	1	0.26	YES
3	NEU4	NEU4	NEU4	370	0.79	0.33	YES
4	DEGS2	DEGS2	DEGS2	548	0.68	0.39	YES
5	UGT8	UGT8	UGT8	708	0.6	0.44	YES
6	GALC	GALC	GALC	1259	0.41	0.45	YES
7	ACER2	ACER2	ACER2	1335	0.39	0.49	YES
8	GLB1	GLB1	GLB1	2276	0.25	0.46	YES
9	NEU3	NEU3	NEU3	2505	0.23	0.47	YES
10	SMPD2	SMPD2	SMPD2	2633	0.22	0.49	YES
11	ASAH2	ASAH2	ASAH2	2889	0.2	0.5	YES
12	SGMS2	SGMS2	SGMS2	2947	0.19	0.51	YES
13	SPHK2	SPHK2	SPHK2	2948	0.19	0.53	YES
14	B4GALT6	B4GALT6	B4GALT6	3280	0.17	0.53	YES
15	SGPP2	SGPP2	SGPP2	3440	0.16	0.54	YES
16	PPAP2C	PPAP2C	PPAP2C	3672	0.15	0.54	YES
17	ASAH1	ASAH1	ASAH1	3890	0.14	0.54	YES
18	NEU1	NEU1	NEU1	4424	0.11	0.53	NO
19	SPTLC2	SPTLC2	SPTLC2	4449	0.11	0.54	NO
20	CERK	CERK	CERK	5305	0.081	0.5	NO
21	PPAP2A	PPAP2A	PPAP2A	5330	0.08	0.5	NO
22	GBA	GBA	GBA	5648	0.07	0.5	NO
23	PPAP2B	PPAP2B	PPAP2B	6275	0.054	0.47	NO
24	SMPD1	SMPD1	SMPD1	8154	0.013	0.37	NO
25	SGMS1	SGMS1	SGMS1	8470	0.0069	0.35	NO
26	ACER3	ACER3	ACER3	8994	-0.0024	0.32	NO
27	SMPD4	SMPD4	SMPD4	9680	-0.015	0.29	NO
28	SGPL1	SGPL1	SGPL1	10128	-0.024	0.27	NO
29	UGCG	UGCG	UGCG	10261	-0.026	0.26	NO
30	SGPP1	SGPP1	SGPP1	10489	-0.03	0.25	NO
31	GLA	GLA	GLA	10569	-0.031	0.25	NO
32	SPTLC1	SPTLC1	SPTLC1	10669	-0.033	0.25	NO
33	ARSA	ARSA	ARSA	11001	-0.039	0.24	NO
34	KDSR	KDSR	KDSR	14082	-0.12	0.084	NO
35	DEGS1	DEGS1	DEGS1	15774	-0.21	0.015	NO
36	ACER1	ACER1	ACER1	17276	-0.38	-0.026	NO
37	NEU2	NEU2	NEU2	17793	-0.49	-0.004	NO
38	SPHK1	SPHK1	SPHK1	17984	-0.54	0.041	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 HISTIDINE METABOLISM.

Figure S14. 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 STARCH AND SUCROSE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ACACB	ACACB	ACACB	1246	0.41	0.032	YES
2	LDHAL6B	LDHAL6B	LDHAL6B	1325	0.39	0.12	YES
3	SUCLG2	SUCLG2	SUCLG2	1886	0.3	0.16	YES
4	LDHAL6A	LDHAL6A	LDHAL6A	2266	0.25	0.2	YES
5	ACSS1	ACSS1	ACSS1	2321	0.25	0.26	YES
6	ALDH2	ALDH2	ALDH2	2370	0.24	0.32	YES
7	ACSS2	ACSS2	ACSS2	2555	0.22	0.36	YES
8	ABAT	ABAT	ABAT	2969	0.19	0.38	YES
9	PCCA	PCCA	PCCA	3084	0.18	0.42	YES
10	ALDH1B1	ALDH1B1	ALDH1B1	3585	0.15	0.43	YES
11	MLYCD	MLYCD	MLYCD	3761	0.14	0.46	YES
12	ECHS1	ECHS1	ECHS1	4063	0.13	0.47	YES
13	SUCLG1	SUCLG1	SUCLG1	4240	0.12	0.49	YES
14	ACAT1	ACAT1	ACAT1	4253	0.12	0.52	YES
15	HIBCH	HIBCH	HIBCH	4799	0.096	0.51	YES
16	ALDH6A1	ALDH6A1	ALDH6A1	4983	0.09	0.52	YES
17	MCEE	MCEE	MCEE	5661	0.07	0.5	NO
18	ALDH9A1	ALDH9A1	ALDH9A1	7851	0.019	0.39	NO
19	HADHA	HADHA	HADHA	7959	0.017	0.39	NO
20	ALDH7A1	ALDH7A1	ALDH7A1	8227	0.011	0.38	NO
21	ACADM	ACADM	ACADM	8396	0.0084	0.37	NO
22	SUCLA2	SUCLA2	SUCLA2	8670	0.0032	0.36	NO
23	MUT	MUT	MUT	8887	-0.00068	0.35	NO
24	EHHADH	EHHADH	EHHADH	10167	-0.024	0.28	NO
25	ACSS3	ACSS3	ACSS3	10976	-0.039	0.25	NO
26	PCCB	PCCB	PCCB	11899	-0.058	0.22	NO
27	ACAT2	ACAT2	ACAT2	12308	-0.067	0.21	NO
28	ACACA	ACACA	ACACA	13119	-0.088	0.19	NO
29	LDHA	LDHA	LDHA	13156	-0.089	0.21	NO
30	ALDH3A2	ALDH3A2	ALDH3A2	14403	-0.13	0.17	NO
31	LDHB	LDHB	LDHB	16309	-0.25	0.13	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 STARCH AND SUCROSE METABOLISM.

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

genes ES table in pathway: KEGG N GLYCAN BIOSYNTHESIS

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	MGAT3	MGAT3	MGAT3	345	0.82	0.092	YES
2	MGAT4A	MGAT4A	MGAT4A	603	0.64	0.16	YES
3	ALG11	ALG11	ALG11	1026	0.48	0.21	YES
4	ST6GAL1	ST6GAL1	ST6GAL1	1116	0.44	0.26	YES
5	FUT8	FUT8	FUT8	1489	0.36	0.29	YES
6	MAN1A1	MAN1A1	MAN1A1	1974	0.28	0.3	YES
7	MGAT5	MGAT5	MGAT5	2186	0.26	0.33	YES
8	MGAT4B	MGAT4B	MGAT4B	2406	0.24	0.35	YES
9	ALG5	ALG5	ALG5	2407	0.24	0.38	YES
10	MAN2A2	MAN2A2	MAN2A2	2628	0.22	0.4	YES
11	ALG14	ALG14	ALG14	2649	0.22	0.43	YES
12	DPAGT1	DPAGT1	DPAGT1	2940	0.19	0.44	YES
13	ALG1	ALG1	ALG1	3484	0.16	0.43	YES
14	MAN1C1	MAN1C1	MAN1C1	4151	0.12	0.41	YES
15	MAN2A1	MAN2A1	MAN2A1	4366	0.11	0.41	YES
16	STT3A	STT3A	STT3A	4388	0.11	0.43	YES
17	RPN2	RPN2	RPN2	4807	0.096	0.42	YES
18	ALG8	ALG8	ALG8	4878	0.094	0.43	YES
19	STT3B	STT3B	STT3B	4917	0.093	0.44	YES
20	ALG13	ALG13	ALG13	5528	0.073	0.42	NO
21	ALG2	ALG2	ALG2	5643	0.07	0.42	NO
22	DDOST	DDOST	DDOST	5752	0.067	0.42	NO
23	DPM3	DPM3	DPM3	5762	0.067	0.43	NO
24	ALG9	ALG9	ALG9	6473	0.049	0.4	NO
25	B4GALT3	B4GALT3	B4GALT3	6834	0.041	0.38	NO
26	MAN1A2	MAN1A2	MAN1A2	7685	0.022	0.34	NO
27	DOLPP1	DOLPP1	DOLPP1	7734	0.021	0.34	NO
28	DAD1	DAD1	DAD1	8046	0.015	0.33	NO
29	B4GALT1	B4GALT1	B4GALT1	8120	0.014	0.33	NO
30	RPN1	RPN1	RPN1	8252	0.011	0.32	NO
31	MOGS	MOGS	MOGS	8267	0.011	0.32	NO
32	DPM2	DPM2	DPM2	8401	0.0083	0.32	NO
33	ALG6	ALG6	ALG6	8629	0.0042	0.3	NO
34	MGAT2	MGAT2	MGAT2	8995	-0.0024	0.28	NO
35	GANAB	GANAB	GANAB	9031	-0.0031	0.28	NO
36	DPM1	DPM1	DPM1	9703	-0.016	0.25	NO
37	ALG12	ALG12	ALG12	9734	-0.016	0.25	NO
38	MGAT1	MGAT1	MGAT1	10360	-0.027	0.22	NO
39	MAN1B1	MAN1B1	MAN1B1	10578	-0.031	0.21	NO
40	ALG3	ALG3	ALG3	11970	-0.059	0.15	NO
41	ALG10	ALG10	ALG10	12470	-0.07	0.13	NO
42	ALG10B	ALG10B	ALG10B	12799	-0.079	0.12	NO
43	B4GALT2	B4GALT2	B4GALT2	15169	-0.17	0.019	NO
44	MGAT5B	MGAT5B	MGAT5B	17449	-0.41	-0.047	NO
45	TUSC3	TUSC3	TUSC3	18571	-0.86	0.0095	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 N GLYCAN BIOSYNTHESIS.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG N 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 GLYCEROLIPID METABOLISM

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	GAS2	GAS2	GAS2	402	0.78	0.12	YES
2	BIRC3	BIRC3	BIRC3	741	0.59	0.22	YES
3	CASP10	CASP10	CASP10	908	0.52	0.3	YES
4	DFFB	DFFB	DFFB	1407	0.37	0.35	YES
5	APAF1	APAF1	APAF1	1960	0.28	0.37	YES
6	CASP6	CASP6	CASP6	2388	0.24	0.39	YES
7	CASP8	CASP8	CASP8	3191	0.18	0.38	YES
8	CASP7	CASP7	CASP7	3791	0.14	0.38	YES
9	SPTAN1	SPTAN1	SPTAN1	4500	0.11	0.36	YES
10	MAP3K14	MAP3K14	MAP3K14	4553	0.11	0.38	YES
11	TNFRSF10A	TNFRSF10A	TNFRSF10A	4577	0.1	0.4	YES
12	TRAF2	TRAF2	TRAF2	4583	0.1	0.42	YES
13	CASP9	CASP9	CASP9	4589	0.1	0.44	YES
14	TNFRSF10B	TNFRSF10B	TNFRSF10B	4649	0.1	0.45	YES
15	CHUK	CHUK	CHUK	4801	0.096	0.46	YES
16	CFLAR	CFLAR	CFLAR	4968	0.091	0.47	YES
17	CYCS	CYCS	CYCS	5156	0.085	0.48	YES
18	CASP3	CASP3	CASP3	5397	0.077	0.48	YES
19	XIAP	XIAP	XIAP	5646	0.07	0.48	NO
20	RIPK1	RIPK1	RIPK1	6796	0.042	0.42	NO
21	TNFSF12	TNFSF12	TNFSF12	8239	0.011	0.35	NO
22	DFFA	DFFA	DFFA	8336	0.0092	0.34	NO
23	BIRC2	BIRC2	BIRC2	8587	0.0047	0.33	NO
24	TNFRSF25	TNFRSF25	TNFRSF25	10039	-0.022	0.26	NO
25	RELA	RELA	RELA	10240	-0.025	0.25	NO
26	NFKB1	NFKB1	NFKB1	10702	-0.033	0.24	NO
27	LMNA	LMNA	LMNA	11142	-0.041	0.22	NO
28	TRADD	TRADD	TRADD	14116	-0.12	0.083	NO
29	NFKBIA	NFKBIA	NFKBIA	15298	-0.18	0.052	NO
30	BCL2	BCL2	BCL2	15406	-0.18	0.081	NO
31	TNFSF10	TNFSF10	TNFSF10	16333	-0.26	0.079	NO
32	FADD	FADD	FADD	16425	-0.27	0.12	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 GLYCEROLIPID METABOLISM.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCEROLIPID 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 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 CARM ER PATHWAY	34	genes.ES.table	0.34	1.3	0.19	0.68	1	0.44	0.32	0.3	0.59	0.21
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.44	1.4	0.12	0.67	0.98	0.37	0.22	0.29	0.54	0.22
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.47	1.6	0.048	1	0.79	0.18	0.082	0.17	0.86	0.46
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.35	1.3	0.15	0.67	0.98	0.4	0.31	0.28	0.54	0.21
BIOCARTA INTEGRIN PATHWAY	37	genes.ES.table	0.34	1.3	0.17	0.66	0.99	0.49	0.35	0.32	0.54	0.21
KEGG RNA DEGRADATION	56	genes.ES.table	0.35	1.5	0.11	0.69	0.88	0.61	0.46	0.33	0.46	0.23
KEGG RNA POLYMERASE	28	genes.ES.table	0.43	1.4	0.14	0.83	0.95	0.64	0.39	0.39	0.64	0.29
KEGG BASAL TRANSCRIPTION FACTORS	34	genes.ES.table	0.4	1.5	0.061	0.82	0.83	0.44	0.35	0.29	0.51	0.27
KEGG SPLICEOSOME	125	genes.ES.table	0.41	1.6	0.088	1	0.69	0.61	0.43	0.35	1	0.51
KEGG PROTEASOME	42	genes.ES.table	0.44	1.4	0.2	0.68	0.98	0.64	0.43	0.37	0.54	0.22

genes ES table in pathway: BIOCARTA CARM ER 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	HSPA2	HSPA2	HSPA2	672	0.43	0.028	YES
2	HSPA6	HSPA6	HSPA6	1921	0.24	-0.0025	YES
3	PRPF40B	PRPF40B	PRPF40B	2284	0.21	0.0095	YES
4	THOC3	THOC3	THOC3	2933	0.17	-0.00024	YES
5	HSPA1A	HSPA1A	HSPA1A	3309	0.14	0.0015	YES
6	HSPA1B	HSPA1B	HSPA1B	3318	0.14	0.023	YES
7	PHF5A	PHF5A	PHF5A	3524	0.14	0.032	YES
8	SF3A2	SF3A2	SF3A2	3964	0.12	0.027	YES
9	ISY1	ISY1	ISY1	4035	0.12	0.041	YES
10	SNRPD3	SNRPD3	SNRPD3	4236	0.11	0.047	YES
11	SNRPF	SNRPF	SNRPF	4307	0.11	0.059	YES
12	PRPF4	PRPF4	PRPF4	4308	0.11	0.076	YES
13	PPIE	PPIE	PPIE	4389	0.11	0.087	YES
14	MAGOHB	MAGOHB	MAGOHB	4455	0.1	0.1	YES
15	XAB2	XAB2	XAB2	4485	0.1	0.11	YES
16	PUF60	PUF60	PUF60	4719	0.096	0.12	YES
17	SART1	SART1	SART1	4765	0.095	0.13	YES
18	PLRG1	PLRG1	PLRG1	4793	0.094	0.14	YES
19	EIF4A3	EIF4A3	EIF4A3	4876	0.093	0.15	YES
20	TRA2B	TRA2B	TRA2B	5223	0.083	0.14	YES
21	MAGOH	MAGOH	MAGOH	5255	0.082	0.15	YES
22	SNRNP40	SNRNP40	SNRNP40	5270	0.082	0.17	YES
23	SR140	SR140	SR140	5445	0.077	0.17	YES
24	LSM6	LSM6	LSM6	5449	0.077	0.18	YES
25	SNRPG	SNRPG	SNRPG	5565	0.074	0.18	YES
26	LSM4	LSM4	LSM4	5593	0.074	0.19	YES
27	SF3B4	SF3B4	SF3B4	5656	0.072	0.2	YES
28	PRPF19	PRPF19	PRPF19	5738	0.071	0.21	YES
29	SF3B14	SF3B14	SF3B14	5821	0.069	0.21	YES
30	SNRPB	SNRPB	SNRPB	5834	0.069	0.22	YES
31	SNW1	SNW1	SNW1	5914	0.067	0.23	YES
32	NHP2L1	NHP2L1	NHP2L1	5916	0.067	0.24	YES
33	SNRPD2	SNRPD2	SNRPD2	5968	0.066	0.25	YES
34	HNRNPC	HNRNPC	HNRNPC	6056	0.064	0.25	YES
35	THOC4	THOC4	THOC4	6119	0.063	0.26	YES
36	THOC1	THOC1	THOC1	6182	0.062	0.26	YES
37	WBP11	WBP11	WBP11	6186	0.062	0.27	YES
38	SFRS9	SFRS9	SFRS9	6209	0.061	0.28	YES
39	SNRPE	SNRPE	SNRPE	6227	0.061	0.29	YES
40	LSM7	LSM7	LSM7	6229	0.061	0.3	YES
41	SNRPD1	SNRPD1	SNRPD1	6383	0.058	0.3	YES
42	SFRS4	SFRS4	SFRS4	6678	0.052	0.29	YES
43	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	6721	0.051	0.3	YES
44	BUD31	BUD31	BUD31	6788	0.05	0.3	YES
45	SF3A3	SF3A3	SF3A3	6803	0.049	0.31	YES
46	USP39	USP39	USP39	6887	0.048	0.31	YES
47	SNRPA1	SNRPA1	SNRPA1	6941	0.047	0.31	YES
48	U2AF1	U2AF1	U2AF1	6979	0.046	0.32	YES
49	ZMAT2	ZMAT2	ZMAT2	7005	0.045	0.32	YES
50	SNRPA	SNRPA	SNRPA	7064	0.044	0.33	YES
51	PRPF8	PRPF8	PRPF8	7113	0.043	0.33	YES
52	SF3B3	SF3B3	SF3B3	7164	0.042	0.34	YES
53	HNRNPA3	HNRNPA3	HNRNPA3	7186	0.042	0.34	YES
54	EFTUD2	EFTUD2	EFTUD2	7244	0.041	0.34	YES
55	DHX38	DHX38	DHX38	7264	0.041	0.35	YES
56	BCAS2	BCAS2	BCAS2	7284	0.04	0.35	YES
57	PPIL1	PPIL1	PPIL1	7305	0.04	0.36	YES
58	HNRNPM	HNRNPM	HNRNPM	7383	0.038	0.36	YES
59	PPIH	PPIH	PPIH	7416	0.038	0.36	YES
60	HNRNPA1	HNRNPA1	HNRNPA1	7423	0.038	0.37	YES
61	RBM8A	RBM8A	RBM8A	7424	0.038	0.38	YES
62	SF3B2	SF3B2	SF3B2	7425	0.038	0.38	YES
63	SF3A1	SF3A1	SF3A1	7442	0.038	0.39	YES
64	SFRS7	SFRS7	SFRS7	7474	0.037	0.39	YES
65	PRPF31	PRPF31	PRPF31	7487	0.037	0.4	YES
66	SNRNP27	SNRNP27	SNRNP27	7541	0.036	0.4	YES
67	PCBP1	PCBP1	PCBP1	7613	0.035	0.4	YES
68	HNRNPK	HNRNPK	HNRNPK	7756	0.033	0.4	YES
69	SNRPC	SNRPC	SNRPC	7789	0.032	0.4	YES
70	HNRNPU	HNRNPU	HNRNPU	7841	0.031	0.4	YES
71	SFRS2	SFRS2	SFRS2	7865	0.031	0.4	YES
72	U2AF2	U2AF2	U2AF2	7923	0.03	0.41	YES
73	CWC15	CWC15	CWC15	7956	0.029	0.41	YES
74	RBM17	RBM17	RBM17	7981	0.029	0.41	YES
75	CHERP	CHERP	CHERP	8101	0.027	0.41	YES
76	SFRS1	SFRS1	SFRS1	8111	0.027	0.41	YES
77	SFRS3	SFRS3	SFRS3	8293	0.024	0.41	NO
78	ACIN1	ACIN1	ACIN1	8389	0.022	0.41	NO
79	SMNDC1	SMNDC1	SMNDC1	8547	0.019	0.4	NO
80	TCERG1	TCERG1	TCERG1	8680	0.017	0.4	NO
81	RBMX	RBMX	RBMX	8697	0.017	0.4	NO
82	PRPF40A	PRPF40A	PRPF40A	8748	0.016	0.4	NO
83	SNRNP70	SNRNP70	SNRNP70	8781	0.015	0.4	NO
84	LSM5	LSM5	LSM5	8814	0.015	0.4	NO
85	RBM22	RBM22	RBM22	8845	0.014	0.4	NO
86	SFRS13A	SFRS13A	SFRS13A	8922	0.013	0.4	NO
87	NAA38	NAA38	NAA38	9027	0.011	0.39	NO
88	AQR	AQR	AQR	9368	0.0053	0.38	NO
89	DDX5	DDX5	DDX5	9423	0.0044	0.37	NO
90	NCBP1	NCBP1	NCBP1	9545	0.0023	0.37	NO
91	DHX16	DHX16	DHX16	9597	0.0014	0.36	NO
92	TXNL4A	TXNL4A	TXNL4A	9652	0.00067	0.36	NO
93	CTNNBL1	CTNNBL1	CTNNBL1	9695	-0.00015	0.36	NO
94	SNRPB2	SNRPB2	SNRPB2	9745	-0.00099	0.36	NO
95	RBM25	RBM25	RBM25	9807	-0.0018	0.35	NO
96	SLU7	SLU7	SLU7	9812	-0.0019	0.35	NO
97	DHX8	DHX8	DHX8	9918	-0.0037	0.35	NO
98	PRPF38A	PRPF38A	PRPF38A	9942	-0.0042	0.35	NO
99	SFRS5	SFRS5	SFRS5	9953	-0.0043	0.35	NO
100	LSM2	LSM2	LSM2	10188	-0.0087	0.34	NO
101	SNRNP200	SNRNP200	SNRNP200	10208	-0.0091	0.34	NO
102	DDX42	DDX42	DDX42	10236	-0.0096	0.34	NO
103	PQBP1	PQBP1	PQBP1	10245	-0.0098	0.34	NO
104	HSPA8	HSPA8	HSPA8	10309	-0.011	0.34	NO
105	SYF2	SYF2	SYF2	10421	-0.013	0.33	NO
106	SF3B5	SF3B5	SF3B5	10425	-0.013	0.33	NO
107	DDX46	DDX46	DDX46	10464	-0.014	0.33	NO
108	BAT1	BAT1	BAT1	10554	-0.016	0.33	NO
109	CRNKL1	CRNKL1	CRNKL1	10584	-0.016	0.33	NO
110	CDC5L	CDC5L	CDC5L	10692	-0.018	0.33	NO
111	DDX23	DDX23	DDX23	10981	-0.024	0.32	NO
112	PRPF6	PRPF6	PRPF6	11086	-0.026	0.32	NO
113	TRA2A	TRA2A	TRA2A	11118	-0.027	0.32	NO
114	PRPF3	PRPF3	PRPF3	11175	-0.028	0.32	NO
115	SF3B1	SF3B1	SF3B1	11215	-0.028	0.32	NO
116	PRPF18	PRPF18	PRPF18	11326	-0.031	0.32	NO
117	SFRS6	SFRS6	SFRS6	11361	-0.031	0.32	NO
118	DHX15	DHX15	DHX15	11603	-0.036	0.32	NO
119	HSPA1L	HSPA1L	HSPA1L	11674	-0.038	0.32	NO
120	CDC40	CDC40	CDC40	11909	-0.043	0.31	NO
121	LSM3	LSM3	LSM3	12077	-0.048	0.31	NO
122	PRPF38B	PRPF38B	PRPF38B	12125	-0.049	0.32	NO
123	THOC2	THOC2	THOC2	12743	-0.063	0.29	NO
124	SFRS2B	SFRS2B	SFRS2B	13523	-0.086	0.26	NO
125	CCDC12	CCDC12	CCDC12	14347	-0.12	0.24	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 CARM ER PATHWAY.

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

genes ES table in pathway: BIOCARTA G1 PATHWAY

Table 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	GNGT1	GNGT1	GNGT1	214	0.6	0.13	YES
2	NGF	NGF	NGF	287	0.56	0.26	YES
3	NGFR	NGFR	NGFR	373	0.52	0.38	YES
4	EGFR	EGFR	EGFR	1049	0.35	0.42	YES
5	IGF1R	IGF1R	IGF1R	1530	0.28	0.47	YES
6	SHC1	SHC1	SHC1	3880	0.12	0.37	NO
7	MYC	MYC	MYC	4655	0.098	0.35	NO
8	MKNK1	MKNK1	MKNK1	4948	0.091	0.36	NO
9	MKNK2	MKNK2	MKNK2	5913	0.067	0.32	NO
10	MAP2K1	MAP2K1	MAP2K1	6094	0.063	0.33	NO
11	ITGB1	ITGB1	ITGB1	6277	0.06	0.33	NO
12	MAPK1	MAPK1	MAPK1	6549	0.054	0.33	NO
13	GNAS	GNAS	GNAS	6581	0.054	0.34	NO
14	PPP2CA	PPP2CA	PPP2CA	7217	0.042	0.32	NO
15	GNB1	GNB1	GNB1	7303	0.04	0.32	NO
16	RPS6KA5	RPS6KA5	RPS6KA5	7583	0.035	0.32	NO
17	MAP2K2	MAP2K2	MAP2K2	8177	0.025	0.29	NO
18	SOS1	SOS1	SOS1	8948	0.012	0.25	NO
19	ELK1	ELK1	ELK1	10644	-0.017	0.16	NO
20	STAT3	STAT3	STAT3	10982	-0.024	0.15	NO
21	GRB2	GRB2	GRB2	11064	-0.025	0.15	NO
22	RPS6KA1	RPS6KA1	RPS6KA1	11880	-0.043	0.12	NO
23	RAF1	RAF1	RAF1	12305	-0.053	0.11	NO
24	SRC	SRC	SRC	14511	-0.12	0.022	NO
25	MAPK3	MAPK3	MAPK3	14995	-0.15	0.031	NO
26	PDGFRA	PDGFRA	PDGFRA	16167	-0.22	0.021	NO
27	PTPRR	PTPRR	PTPRR	17925	-0.49	0.044	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 G1 PATHWAY.

Figure S24. 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 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	CCNA1	CCNA1	CCNA1	45	0.8	0.054	YES
2	SFN	SFN	SFN	732	0.41	0.046	YES
3	TGFB3	TGFB3	TGFB3	803	0.4	0.07	YES
4	TGFB1	TGFB1	TGFB1	1399	0.29	0.059	YES
5	PKMYT1	PKMYT1	PKMYT1	1598	0.27	0.067	YES
6	ORC6L	ORC6L	ORC6L	1672	0.26	0.082	YES
7	CDC45	CDC45	CDC45	1709	0.26	0.098	YES
8	TGFB2	TGFB2	TGFB2	2160	0.22	0.089	YES
9	MAD2L2	MAD2L2	MAD2L2	2169	0.22	0.1	YES
10	CDKN2D	CDKN2D	CDKN2D	2258	0.21	0.11	YES
11	MCM2	MCM2	MCM2	2357	0.2	0.12	YES
12	ORC1L	ORC1L	ORC1L	2408	0.2	0.13	YES
13	MCM5	MCM5	MCM5	2435	0.2	0.15	YES
14	PTTG1	PTTG1	PTTG1	2443	0.2	0.16	YES
15	CDC7	CDC7	CDC7	2583	0.19	0.16	YES
16	SKP2	SKP2	SKP2	2601	0.18	0.18	YES
17	CCNE2	CCNE2	CCNE2	2773	0.17	0.18	YES
18	CDC20	CDC20	CDC20	2836	0.17	0.19	YES
19	CCNB1	CCNB1	CCNB1	2975	0.16	0.19	YES
20	MCM4	MCM4	MCM4	3036	0.16	0.2	YES
21	ANAPC10	ANAPC10	ANAPC10	3075	0.16	0.21	YES
22	CHEK2	CHEK2	CHEK2	3161	0.15	0.22	YES
23	CCNA2	CCNA2	CCNA2	3189	0.15	0.23	YES
24	CCND1	CCND1	CCND1	3359	0.14	0.23	YES
25	YWHAQ	YWHAQ	YWHAQ	3388	0.14	0.24	YES
26	BUB1B	BUB1B	BUB1B	3423	0.14	0.24	YES
27	RBX1	RBX1	RBX1	3444	0.14	0.25	YES
28	YWHAG	YWHAG	YWHAG	3563	0.14	0.26	YES
29	GADD45A	GADD45A	GADD45A	3590	0.13	0.26	YES
30	CCNB2	CCNB2	CCNB2	3599	0.13	0.27	YES
31	RBL1	RBL1	RBL1	3615	0.13	0.28	YES
32	CHEK1	CHEK1	CHEK1	3699	0.13	0.28	YES
33	TTK	TTK	TTK	3857	0.12	0.29	YES
34	CDK2	CDK2	CDK2	3882	0.12	0.29	YES
35	CDKN2C	CDKN2C	CDKN2C	4034	0.12	0.29	YES
36	CDK1	CDK1	CDK1	4137	0.11	0.3	YES
37	PLK1	PLK1	PLK1	4171	0.11	0.3	YES
38	CDK6	CDK6	CDK6	4172	0.11	0.31	YES
39	MAD2L1	MAD2L1	MAD2L1	4181	0.11	0.32	YES
40	CDK4	CDK4	CDK4	4214	0.11	0.32	YES
41	FZR1	FZR1	FZR1	4452	0.1	0.32	YES
42	SMAD2	SMAD2	SMAD2	4468	0.1	0.32	YES
43	MCM7	MCM7	MCM7	4484	0.1	0.33	YES
44	TFDP2	TFDP2	TFDP2	4563	0.1	0.33	YES
45	YWHAE	YWHAE	YWHAE	4575	0.1	0.34	YES
46	MYC	MYC	MYC	4655	0.098	0.34	YES
47	PCNA	PCNA	PCNA	4665	0.097	0.35	YES
48	ANAPC7	ANAPC7	ANAPC7	4953	0.09	0.34	YES
49	ORC5L	ORC5L	ORC5L	5000	0.089	0.34	YES
50	ZBTB17	ZBTB17	ZBTB17	5100	0.086	0.34	YES
51	PRKDC	PRKDC	PRKDC	5113	0.086	0.35	YES
52	CDC27	CDC27	CDC27	5145	0.085	0.35	YES
53	GSK3B	GSK3B	GSK3B	5154	0.084	0.36	YES
54	WEE1	WEE1	WEE1	5297	0.081	0.36	YES
55	MCM6	MCM6	MCM6	5314	0.08	0.36	YES
56	ORC3L	ORC3L	ORC3L	5420	0.078	0.36	YES
57	SMC1B	SMC1B	SMC1B	5502	0.076	0.36	YES
58	CDC23	CDC23	CDC23	5574	0.074	0.36	YES
59	TFDP1	TFDP1	TFDP1	5577	0.074	0.37	YES
60	CDC6	CDC6	CDC6	5657	0.072	0.37	YES
61	CDKN1A	CDKN1A	CDKN1A	5691	0.072	0.37	YES
62	STAG1	STAG1	STAG1	5873	0.068	0.37	YES
63	RAD21	RAD21	RAD21	5906	0.067	0.37	YES
64	E2F4	E2F4	E2F4	5978	0.066	0.37	YES
65	MAD1L1	MAD1L1	MAD1L1	6001	0.065	0.38	YES
66	CDKN1C	CDKN1C	CDKN1C	6032	0.065	0.38	YES
67	YWHAZ	YWHAZ	YWHAZ	6163	0.062	0.38	YES
68	BUB1	BUB1	BUB1	6175	0.062	0.38	YES
69	SMAD3	SMAD3	SMAD3	6224	0.061	0.38	YES
70	CUL1	CUL1	CUL1	6233	0.06	0.38	YES
71	CDC25B	CDC25B	CDC25B	6239	0.06	0.39	YES
72	ATR	ATR	ATR	6384	0.058	0.38	NO
73	TP53	TP53	TP53	6636	0.053	0.38	NO
74	ANAPC13	ANAPC13	ANAPC13	6719	0.051	0.38	NO
75	CDC25C	CDC25C	CDC25C	6824	0.049	0.37	NO
76	ANAPC11	ANAPC11	ANAPC11	6839	0.049	0.38	NO
77	SKP1	SKP1	SKP1	6907	0.047	0.38	NO
78	CREBBP	CREBBP	CREBBP	6965	0.046	0.38	NO
79	YWHAH	YWHAH	YWHAH	7016	0.045	0.38	NO
80	E2F2	E2F2	E2F2	7109	0.044	0.37	NO
81	E2F1	E2F1	E2F1	7123	0.043	0.38	NO
82	ABL1	ABL1	ABL1	7406	0.038	0.36	NO
83	SMAD4	SMAD4	SMAD4	7461	0.037	0.36	NO
84	SMC3	SMC3	SMC3	7505	0.036	0.36	NO
85	GADD45B	GADD45B	GADD45B	7579	0.035	0.36	NO
86	RBL2	RBL2	RBL2	7673	0.034	0.36	NO
87	ESPL1	ESPL1	ESPL1	7737	0.033	0.36	NO
88	CDK7	CDK7	CDK7	7862	0.031	0.35	NO
89	STAG2	STAG2	STAG2	7969	0.029	0.35	NO
90	MCM3	MCM3	MCM3	8113	0.027	0.34	NO
91	E2F3	E2F3	E2F3	8175	0.025	0.34	NO
92	ANAPC5	ANAPC5	ANAPC5	8260	0.024	0.34	NO
93	HDAC2	HDAC2	HDAC2	8497	0.02	0.33	NO
94	RB1	RB1	RB1	8505	0.02	0.33	NO
95	ANAPC4	ANAPC4	ANAPC4	8789	0.015	0.32	NO
96	EP300	EP300	EP300	8921	0.013	0.31	NO
97	ANAPC2	ANAPC2	ANAPC2	9089	0.0099	0.3	NO
98	BUB3	BUB3	BUB3	9345	0.0057	0.29	NO
99	SMC1A	SMC1A	SMC1A	9676	0.00016	0.27	NO
100	ANAPC1	ANAPC1	ANAPC1	10137	-0.0079	0.25	NO
101	MDM2	MDM2	MDM2	10324	-0.012	0.24	NO
102	CDKN1B	CDKN1B	CDKN1B	10553	-0.016	0.23	NO
103	CDC25A	CDC25A	CDC25A	10642	-0.017	0.22	NO
104	YWHAB	YWHAB	YWHAB	11644	-0.037	0.17	NO
105	CDC16	CDC16	CDC16	11789	-0.041	0.17	NO
106	ORC4L	ORC4L	ORC4L	11813	-0.041	0.17	NO
107	CCNE1	CCNE1	CCNE1	11886	-0.043	0.17	NO
108	ORC2L	ORC2L	ORC2L	11906	-0.043	0.17	NO
109	CCNH	CCNH	CCNH	12105	-0.048	0.16	NO
110	WEE2	WEE2	WEE2	12198	-0.05	0.16	NO
111	HDAC1	HDAC1	HDAC1	12321	-0.053	0.16	NO
112	ATM	ATM	ATM	12579	-0.059	0.15	NO
113	PTTG2	PTTG2	PTTG2	13306	-0.079	0.12	NO
114	CDC14A	CDC14A	CDC14A	13886	-0.098	0.09	NO
115	CCND3	CCND3	CCND3	14296	-0.12	0.077	NO
116	CCND2	CCND2	CCND2	14891	-0.14	0.055	NO
117	CDC26	CDC26	CDC26	16059	-0.21	0.0068	NO
118	CDC14B	CDC14B	CDC14B	16158	-0.22	0.017	NO
119	CDKN2B	CDKN2B	CDKN2B	16359	-0.24	0.023	NO
120	GADD45G	GADD45G	GADD45G	16587	-0.26	0.029	NO
121	CDKN2A	CDKN2A	CDKN2A	17313	-0.35	0.015	NO
122	CCNB3	CCNB3	CCNB3	17697	-0.43	0.024	NO
123	E2F5	E2F5	E2F5	17789	-0.46	0.052	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 ERK PATHWAY.

Figure S26. 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 RACCYCD PATHWAY

Table S14. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GTF2A1L	GTF2A1L	GTF2A1L	899	0.38	0.11	YES
2	STON1	STON1	STON1	1113	0.34	0.24	YES
3	GTF2H3	GTF2H3	GTF2H3	3862	0.12	0.15	YES
4	GTF2E1	GTF2E1	GTF2E1	3936	0.12	0.2	YES
5	TAF4B	TAF4B	TAF4B	4102	0.12	0.24	YES
6	TAF12	TAF12	TAF12	4703	0.096	0.25	YES
7	GTF2A1	GTF2A1	GTF2A1	5143	0.085	0.26	YES
8	GTF2IRD1	GTF2IRD1	GTF2IRD1	5781	0.07	0.25	YES
9	TAF6	TAF6	TAF6	5824	0.069	0.28	YES
10	GTF2H4	GTF2H4	GTF2H4	5874	0.068	0.31	YES
11	TAF6L	TAF6L	TAF6L	5890	0.067	0.34	YES
12	TAF2	TAF2	TAF2	5917	0.067	0.36	YES
13	TAF5	TAF5	TAF5	5950	0.066	0.39	YES
14	GTF2F2	GTF2F2	GTF2F2	6165	0.062	0.4	YES
15	TAF13	TAF13	TAF13	6590	0.054	0.4	YES
16	GTF2F1	GTF2F1	GTF2F1	7851	0.031	0.35	NO
17	TBPL1	TBPL1	TBPL1	7868	0.031	0.36	NO
18	GTF2H2	GTF2H2	GTF2H2	8082	0.027	0.36	NO
19	TAF9B	TAF9B	TAF9B	8364	0.022	0.36	NO
20	GTF2A2	GTF2A2	GTF2A2	8450	0.021	0.36	NO
21	GTF2I	GTF2I	GTF2I	8621	0.018	0.36	NO
22	TBP	TBP	TBP	8747	0.016	0.36	NO
23	TAF5L	TAF5L	TAF5L	8794	0.015	0.36	NO
24	GTF2H1	GTF2H1	GTF2H1	8897	0.013	0.36	NO
25	GTF2E2	GTF2E2	GTF2E2	9013	0.011	0.36	NO
26	TAF7	TAF7	TAF7	9225	0.0077	0.35	NO
27	TAF9	TAF9	TAF9	9351	0.0056	0.35	NO
28	TAF11	TAF11	TAF11	10143	-0.008	0.31	NO
29	TAF10	TAF10	TAF10	10166	-0.0083	0.31	NO
30	TAF7L	TAF7L	TAF7L	10851	-0.021	0.29	NO
31	GTF2B	GTF2B	GTF2B	11423	-0.033	0.27	NO
32	TAF4	TAF4	TAF4	12667	-0.061	0.23	NO
33	TAF1	TAF1	TAF1	13483	-0.085	0.22	NO
34	TAF1L	TAF1L	TAF1L	14904	-0.14	0.2	NO

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

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

genes ES table in pathway: BIOCARTA INTEGRIN 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	TP53AIP1	TP53AIP1	TP53AIP1	136	0.67	0.056	YES
2	TP73	TP73	TP73	240	0.59	0.11	YES
3	SESN3	SESN3	SESN3	460	0.49	0.14	YES
4	BAI1	BAI1	BAI1	574	0.46	0.18	YES
5	SFN	SFN	SFN	732	0.41	0.21	YES
6	RPRM	RPRM	RPRM	1044	0.35	0.22	YES
7	SERPINE1	SERPINE1	SERPINE1	1058	0.34	0.26	YES
8	SERPINB5	SERPINB5	SERPINB5	1235	0.32	0.28	YES
9	PMAIP1	PMAIP1	PMAIP1	1251	0.31	0.3	YES
10	PERP	PERP	PERP	1475	0.28	0.32	YES
11	DDB2	DDB2	DDB2	2365	0.2	0.29	YES
12	SIAH1	SIAH1	SIAH1	2668	0.18	0.29	YES
13	CCNE2	CCNE2	CCNE2	2773	0.17	0.3	YES
14	CCNB1	CCNB1	CCNB1	2975	0.16	0.31	YES
15	CHEK2	CHEK2	CHEK2	3161	0.15	0.31	YES
16	CCND1	CCND1	CCND1	3359	0.14	0.32	YES
17	GADD45A	GADD45A	GADD45A	3590	0.13	0.32	YES
18	CCNB2	CCNB2	CCNB2	3599	0.13	0.33	YES
19	CHEK1	CHEK1	CHEK1	3699	0.13	0.34	YES
20	THBS1	THBS1	THBS1	3796	0.13	0.34	YES
21	CDK2	CDK2	CDK2	3882	0.12	0.35	YES
22	CDK1	CDK1	CDK1	4137	0.11	0.34	YES
23	GTSE1	GTSE1	GTSE1	4151	0.11	0.36	YES
24	CDK6	CDK6	CDK6	4172	0.11	0.36	YES
25	CDK4	CDK4	CDK4	4214	0.11	0.37	YES
26	RRM2	RRM2	RRM2	4328	0.11	0.38	YES
27	IGFBP3	IGFBP3	IGFBP3	4914	0.092	0.36	NO
28	FAS	FAS	FAS	4978	0.09	0.36	NO
29	RRM2B	RRM2B	RRM2B	5563	0.074	0.34	NO
30	ZMAT3	ZMAT3	ZMAT3	5596	0.074	0.34	NO
31	CDKN1A	CDKN1A	CDKN1A	5691	0.072	0.34	NO
32	ATR	ATR	ATR	6384	0.058	0.31	NO
33	TP53	TP53	TP53	6636	0.053	0.3	NO
34	LRDD	LRDD	LRDD	7192	0.042	0.28	NO
35	BID	BID	BID	7350	0.039	0.27	NO
36	GADD45B	GADD45B	GADD45B	7579	0.035	0.26	NO
37	PTEN	PTEN	PTEN	8480	0.02	0.22	NO
38	TSC2	TSC2	TSC2	8488	0.02	0.22	NO
39	RFWD2	RFWD2	RFWD2	9364	0.0054	0.17	NO
40	IGF1	IGF1	IGF1	9882	-0.0031	0.14	NO
41	TNFRSF10B	TNFRSF10B	TNFRSF10B	9916	-0.0037	0.14	NO
42	CD82	CD82	CD82	10133	-0.0078	0.13	NO
43	MDM2	MDM2	MDM2	10324	-0.012	0.12	NO
44	EI24	EI24	EI24	10325	-0.012	0.12	NO
45	SHISA5	SHISA5	SHISA5	10707	-0.018	0.11	NO
46	CCNE1	CCNE1	CCNE1	11886	-0.043	0.047	NO
47	BAX	BAX	BAX	11962	-0.045	0.047	NO
48	CYCS	CYCS	CYCS	12246	-0.051	0.037	NO
49	ATM	ATM	ATM	12579	-0.059	0.024	NO
50	CASP3	CASP3	CASP3	12754	-0.064	0.021	NO
51	MDM4	MDM4	MDM4	13659	-0.09	-0.019	NO
52	RCHY1	RCHY1	RCHY1	13752	-0.093	-0.015	NO
53	CCNG2	CCNG2	CCNG2	13846	-0.097	-0.011	NO
54	CCND3	CCND3	CCND3	14296	-0.12	-0.024	NO
55	PPM1D	PPM1D	PPM1D	14451	-0.12	-0.021	NO
56	SESN2	SESN2	SESN2	14665	-0.13	-0.02	NO
57	CASP9	CASP9	CASP9	14856	-0.14	-0.017	NO
58	CCND2	CCND2	CCND2	14891	-0.14	-0.0055	NO
59	CASP8	CASP8	CASP8	15082	-0.15	-0.0015	NO
60	CCNG1	CCNG1	CCNG1	15131	-0.15	0.01	NO
61	BBC3	BBC3	BBC3	15537	-0.18	0.0054	NO
62	APAF1	APAF1	APAF1	16089	-0.21	-0.0039	NO
63	SESN1	SESN1	SESN1	16215	-0.22	0.011	NO
64	GADD45G	GADD45G	GADD45G	16587	-0.26	0.015	NO
65	TP53I3	TP53I3	TP53I3	16775	-0.28	0.032	NO
66	CDKN2A	CDKN2A	CDKN2A	17313	-0.35	0.036	NO
67	CCNB3	CCNB3	CCNB3	17697	-0.43	0.056	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 INTEGRIN PATHWAY.

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

genes ES table in pathway: KEGG RNA DEGRADATION

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	ENO2	ENO2	ENO2	1264	0.31	0.03	YES
2	MPHOSPH6	MPHOSPH6	MPHOSPH6	2534	0.19	0.021	YES
3	PAPOLB	PAPOLB	PAPOLB	2743	0.18	0.065	YES
4	EXOSC6	EXOSC6	EXOSC6	3018	0.16	0.1	YES
5	ENO1	ENO1	ENO1	3680	0.13	0.11	YES
6	EXOSC4	EXOSC4	EXOSC4	3736	0.13	0.14	YES
7	PAPD7	PAPD7	PAPD7	4313	0.11	0.15	YES
8	EXOSC9	EXOSC9	EXOSC9	4487	0.1	0.17	YES
9	PAPOLG	PAPOLG	PAPOLG	4608	0.099	0.19	YES
10	PARN	PARN	PARN	4626	0.098	0.22	YES
11	EXOSC2	EXOSC2	EXOSC2	4629	0.098	0.26	YES
12	C1D	C1D	C1D	4933	0.091	0.27	YES
13	LSM6	LSM6	LSM6	5449	0.077	0.26	YES
14	LSM4	LSM4	LSM4	5593	0.074	0.28	YES
15	EDC3	EDC3	EDC3	5723	0.071	0.3	YES
16	EXOSC3	EXOSC3	EXOSC3	6105	0.063	0.29	YES
17	LSM7	LSM7	LSM7	6229	0.061	0.31	YES
18	LSM1	LSM1	LSM1	6237	0.06	0.32	YES
19	PATL1	PATL1	PATL1	6980	0.046	0.3	YES
20	CNOT3	CNOT3	CNOT3	7081	0.044	0.31	YES
21	WDR61	WDR61	WDR61	7312	0.04	0.31	YES
22	PNPT1	PNPT1	PNPT1	7346	0.039	0.32	YES
23	CNOT2	CNOT2	CNOT2	7630	0.035	0.32	YES
24	RQCD1	RQCD1	RQCD1	7643	0.034	0.32	YES
25	EXOSC5	EXOSC5	EXOSC5	7749	0.033	0.33	YES
26	XRN2	XRN2	XRN2	7958	0.029	0.33	YES
27	EDC4	EDC4	EDC4	8094	0.027	0.33	YES
28	XRN1	XRN1	XRN1	8237	0.024	0.33	YES
29	CNOT4	CNOT4	CNOT4	8239	0.024	0.34	YES
30	EXOSC1	EXOSC1	EXOSC1	8321	0.023	0.34	YES
31	ZCCHC7	ZCCHC7	ZCCHC7	8445	0.021	0.34	YES
32	DCPS	DCPS	DCPS	8451	0.021	0.34	YES
33	EXOSC8	EXOSC8	EXOSC8	8551	0.019	0.35	YES
34	EXOSC10	EXOSC10	EXOSC10	8555	0.019	0.35	YES
35	LSM5	LSM5	LSM5	8814	0.015	0.34	NO
36	NAA38	NAA38	NAA38	9027	0.011	0.34	NO
37	PAPOLA	PAPOLA	PAPOLA	9190	0.0085	0.33	NO
38	HSPA9	HSPA9	HSPA9	9252	0.0073	0.33	NO
39	CNOT6	CNOT6	CNOT6	9440	0.0042	0.32	NO
40	CNOT7	CNOT7	CNOT7	9594	0.0014	0.31	NO
41	SKIV2L2	SKIV2L2	SKIV2L2	9808	-0.0019	0.3	NO
42	EXOSC7	EXOSC7	EXOSC7	9861	-0.0028	0.3	NO
43	DCP2	DCP2	DCP2	10069	-0.0065	0.29	NO
44	LSM2	LSM2	LSM2	10188	-0.0087	0.29	NO
45	DDX6	DDX6	DDX6	10561	-0.016	0.27	NO
46	TTC37	TTC37	TTC37	10718	-0.019	0.27	NO
47	DIS3	DIS3	DIS3	10759	-0.019	0.27	NO
48	HSPD1	HSPD1	HSPD1	10890	-0.022	0.27	NO
49	SKIV2L	SKIV2L	SKIV2L	11116	-0.027	0.27	NO
50	CNOT1	CNOT1	CNOT1	11187	-0.028	0.27	NO
51	ENO3	ENO3	ENO3	11873	-0.042	0.25	NO
52	LSM3	LSM3	LSM3	12077	-0.048	0.25	NO
53	DCP1B	DCP1B	DCP1B	12657	-0.061	0.24	NO
54	CNOT6L	CNOT6L	CNOT6L	12720	-0.062	0.26	NO
55	CNOT10	CNOT10	CNOT10	12760	-0.064	0.28	NO
56	DCP1A	DCP1A	DCP1A	14869	-0.14	0.21	NO

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

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

genes ES table in pathway: KEGG RNA POLYMERASE

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	PITX2	PITX2	PITX2	118	0.69	0.038	YES
2	WNT9A	WNT9A	WNT9A	143	0.67	0.079	YES
3	WNT7B	WNT7B	WNT7B	191	0.62	0.12	YES
4	WNT7A	WNT7A	WNT7A	211	0.61	0.15	YES
5	FOXN1	FOXN1	FOXN1	410	0.51	0.18	YES
6	TCF7L1	TCF7L1	TCF7L1	841	0.39	0.18	YES
7	WNT2B	WNT2B	WNT2B	968	0.36	0.19	YES
8	FZD6	FZD6	FZD6	999	0.36	0.22	YES
9	WISP1	WISP1	WISP1	1035	0.35	0.24	YES
10	WNT3	WNT3	WNT3	1121	0.34	0.25	YES
11	WNT10A	WNT10A	WNT10A	1150	0.33	0.27	YES
12	PYGO1	PYGO1	PYGO1	1311	0.3	0.28	YES
13	WNT6	WNT6	WNT6	1494	0.28	0.29	YES
14	KREMEN1	KREMEN1	KREMEN1	1542	0.28	0.31	YES
15	FZD1	FZD1	FZD1	1656	0.26	0.32	YES
16	SFRP1	SFRP1	SFRP1	1736	0.26	0.33	YES
17	T	T	T	1812	0.25	0.34	YES
18	WNT2	WNT2	WNT2	1821	0.25	0.36	YES
19	FOSL1	FOSL1	FOSL1	1876	0.24	0.37	YES
20	DVL2	DVL2	DVL2	2085	0.22	0.37	YES
21	WNT4	WNT4	WNT4	2111	0.22	0.38	YES
22	FZD7	FZD7	FZD7	2159	0.22	0.4	YES
23	FZD2	FZD2	FZD2	2217	0.21	0.41	YES
24	WNT5A	WNT5A	WNT5A	2516	0.19	0.4	YES
25	SFRP4	SFRP4	SFRP4	2658	0.18	0.41	YES
26	CTNNBIP1	CTNNBIP1	CTNNBIP1	2760	0.18	0.41	YES
27	DKK1	DKK1	DKK1	3096	0.16	0.4	YES
28	NKD1	NKD1	NKD1	3151	0.15	0.41	YES
29	WNT16	WNT16	WNT16	3341	0.14	0.41	YES
30	CCND1	CCND1	CCND1	3359	0.14	0.42	YES
31	HPRT1	HPRT1	HPRT1	3540	0.14	0.42	YES
32	LEF1	LEF1	LEF1	3583	0.13	0.42	YES
33	GAPDH	GAPDH	GAPDH	3601	0.13	0.43	YES
34	PORCN	PORCN	PORCN	3704	0.13	0.44	YES
35	SENP2	SENP2	SENP2	4076	0.12	0.42	NO
36	CSNK1A1	CSNK1A1	CSNK1A1	4500	0.1	0.41	NO
37	MYC	MYC	MYC	4655	0.098	0.4	NO
38	WNT5B	WNT5B	WNT5B	4671	0.097	0.41	NO
39	JUN	JUN	JUN	4688	0.097	0.42	NO
40	GSK3B	GSK3B	GSK3B	5154	0.084	0.4	NO
41	DAAM1	DAAM1	DAAM1	5244	0.082	0.4	NO
42	CSNK1G1	CSNK1G1	CSNK1G1	5823	0.069	0.37	NO
43	AXIN1	AXIN1	AXIN1	6183	0.062	0.35	NO
44	FBXW4	FBXW4	FBXW4	6379	0.058	0.35	NO
45	DVL1	DVL1	DVL1	7151	0.043	0.31	NO
46	PPP2CA	PPP2CA	PPP2CA	7217	0.042	0.31	NO
47	FZD3	FZD3	FZD3	7411	0.038	0.3	NO
48	WIF1	WIF1	WIF1	7608	0.035	0.29	NO
49	ACTB	ACTB	ACTB	7831	0.031	0.28	NO
50	FBXW2	FBXW2	FBXW2	8192	0.025	0.26	NO
51	EP300	EP300	EP300	8921	0.013	0.23	NO
52	BTRC	BTRC	BTRC	8968	0.012	0.22	NO
53	CSNK2A1	CSNK2A1	CSNK2A1	9016	0.011	0.22	NO
54	AES	AES	AES	9054	0.01	0.22	NO
55	FZD8	FZD8	FZD8	9295	0.0066	0.21	NO
56	WNT11	WNT11	WNT11	9847	-0.0025	0.18	NO
57	FGF4	FGF4	FGF4	10110	-0.0073	0.16	NO
58	GSK3A	GSK3A	GSK3A	10280	-0.011	0.16	NO
59	APC	APC	APC	10693	-0.018	0.14	NO
60	B2M	B2M	B2M	10736	-0.019	0.14	NO
61	PPP2R1A	PPP2R1A	PPP2R1A	10761	-0.019	0.14	NO
62	SLC9A3R1	SLC9A3R1	SLC9A3R1	10908	-0.022	0.13	NO
63	CTBP1	CTBP1	CTBP1	11551	-0.035	0.096	NO
64	FBXW11	FBXW11	FBXW11	12158	-0.05	0.067	NO
65	CTNNB1	CTNNB1	CTNNB1	12186	-0.05	0.069	NO
66	CSNK1D	CSNK1D	CSNK1D	12291	-0.052	0.067	NO
67	DIXDC1	DIXDC1	DIXDC1	12994	-0.07	0.034	NO
68	BCL9	BCL9	BCL9	13005	-0.07	0.037	NO
69	RPL13A	RPL13A	RPL13A	13340	-0.08	0.025	NO
70	TLE1	TLE1	TLE1	13875	-0.098	0.0022	NO
71	LRP6	LRP6	LRP6	14285	-0.11	-0.012	NO
72	CCND3	CCND3	CCND3	14296	-0.12	-0.0056	NO
73	CTBP2	CTBP2	CTBP2	14422	-0.12	-0.0047	NO
74	NLK	NLK	NLK	14426	-0.12	0.0028	NO
75	LRP5	LRP5	LRP5	14616	-0.13	0.00083	NO
76	CCND2	CCND2	CCND2	14891	-0.14	-0.0049	NO
77	CXXC4	CXXC4	CXXC4	15226	-0.16	-0.013	NO
78	TCF7	TCF7	TCF7	15685	-0.19	-0.025	NO
79	TLE2	TLE2	TLE2	16224	-0.22	-0.04	NO
80	FRAT1	FRAT1	FRAT1	16331	-0.24	-0.03	NO
81	WNT1	WNT1	WNT1	16723	-0.27	-0.034	NO
82	SOX17	SOX17	SOX17	16922	-0.3	-0.026	NO
83	FZD4	FZD4	FZD4	16983	-0.3	-0.0095	NO
84	FZD5	FZD5	FZD5	17921	-0.49	-0.028	NO
85	FRZB	FRZB	FRZB	18043	-0.53	-0.00094	NO
86	RHOU	RHOU	RHOU	18214	-0.61	0.029	NO

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

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RNA POLYMERASE, 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 BASAL TRANSCRIPTION FACTORS

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	POLR3G	POLR3G	POLR3G	2618	0.18	-0.037	YES
2	POLR2J3	POLR2J3	POLR2J3	3183	0.15	0.018	YES
3	POLR2J2	POLR2J2	POLR2J2	3242	0.15	0.098	YES
4	POLR2F	POLR2F	POLR2F	3903	0.12	0.13	YES
5	POLR3H	POLR3H	POLR3H	4601	0.099	0.15	YES
6	POLR2A	POLR2A	POLR2A	5151	0.084	0.17	YES
7	POLR2G	POLR2G	POLR2G	5619	0.073	0.18	YES
8	POLR2J	POLR2J	POLR2J	5628	0.073	0.22	YES
9	POLR2E	POLR2E	POLR2E	5800	0.069	0.25	YES
10	POLR3B	POLR3B	POLR3B	5954	0.066	0.28	YES
11	POLR3D	POLR3D	POLR3D	6098	0.063	0.31	YES
12	POLR1E	POLR1E	POLR1E	6180	0.062	0.34	YES
13	POLR3F	POLR3F	POLR3F	6600	0.054	0.35	YES
14	POLR2K	POLR2K	POLR2K	6920	0.047	0.36	YES
15	POLR3K	POLR3K	POLR3K	7189	0.042	0.36	YES
16	POLR2D	POLR2D	POLR2D	7202	0.042	0.39	YES
17	POLR2C	POLR2C	POLR2C	7215	0.042	0.41	YES
18	POLR2L	POLR2L	POLR2L	7308	0.04	0.43	YES
19	POLR1D	POLR1D	POLR1D	7811	0.032	0.42	NO
20	POLR2B	POLR2B	POLR2B	8575	0.019	0.39	NO
21	POLR2I	POLR2I	POLR2I	9363	0.0054	0.35	NO
22	POLR1A	POLR1A	POLR1A	10269	-0.01	0.31	NO
23	POLR3C	POLR3C	POLR3C	10346	-0.012	0.31	NO
24	POLR3A	POLR3A	POLR3A	10824	-0.021	0.3	NO
25	POLR1B	POLR1B	POLR1B	11083	-0.026	0.3	NO
26	ZNRD1	ZNRD1	ZNRD1	12073	-0.048	0.27	NO
27	POLR3GL	POLR3GL	POLR3GL	12699	-0.062	0.27	NO
28	POLR1C	POLR1C	POLR1C	13748	-0.093	0.27	NO

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

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

genes ES table in pathway: KEGG SPLICEOSOME

Table 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	PGF	PGF	PGF	711	0.42	0.018	YES
2	TGFB3	TGFB3	TGFB3	803	0.4	0.067	YES
3	VEGFC	VEGFC	VEGFC	909	0.38	0.11	YES
4	SLC2A1	SLC2A1	SLC2A1	961	0.36	0.16	YES
5	TGFB1	TGFB1	TGFB1	1399	0.29	0.17	YES
6	PIK3CD	PIK3CD	PIK3CD	1527	0.28	0.2	YES
7	PAK6	PAK6	PAK6	1749	0.26	0.23	YES
8	AKT3	AKT3	AKT3	1795	0.25	0.26	YES
9	PAK7	PAK7	PAK7	2061	0.23	0.28	YES
10	TGFB2	TGFB2	TGFB2	2160	0.22	0.3	YES
11	TGFA	TGFA	TGFA	2600	0.18	0.3	YES
12	PIK3CA	PIK3CA	PIK3CA	3016	0.16	0.3	YES
13	CRKL	CRKL	CRKL	3331	0.14	0.3	YES
14	RBX1	RBX1	RBX1	3444	0.14	0.32	YES
15	VEGFB	VEGFB	VEGFB	3721	0.13	0.32	YES
16	EGLN3	EGLN3	EGLN3	3933	0.12	0.32	YES
17	HIF1A	HIF1A	HIF1A	4082	0.12	0.33	YES
18	PAK2	PAK2	PAK2	4187	0.11	0.34	YES
19	JUN	JUN	JUN	4688	0.097	0.32	YES
20	TCEB1	TCEB1	TCEB1	4711	0.096	0.34	YES
21	PIK3R2	PIK3R2	PIK3R2	4804	0.094	0.34	YES
22	MAP2K1	MAP2K1	MAP2K1	6094	0.063	0.28	NO
23	MAPK1	MAPK1	MAPK1	6549	0.054	0.27	NO
24	CREBBP	CREBBP	CREBBP	6965	0.046	0.25	NO
25	AKT1	AKT1	AKT1	7280	0.04	0.24	NO
26	ARNT2	ARNT2	ARNT2	7382	0.039	0.24	NO
27	CRK	CRK	CRK	7638	0.034	0.23	NO
28	RAPGEF1	RAPGEF1	RAPGEF1	7704	0.034	0.23	NO
29	BRAF	BRAF	BRAF	7821	0.031	0.23	NO
30	PDGFB	PDGFB	PDGFB	7829	0.031	0.23	NO
31	AKT2	AKT2	AKT2	7869	0.031	0.24	NO
32	MAP2K2	MAP2K2	MAP2K2	8177	0.025	0.22	NO
33	NRAS	NRAS	NRAS	8179	0.025	0.23	NO
34	SOS2	SOS2	SOS2	8280	0.024	0.22	NO
35	FH	FH	FH	8401	0.022	0.22	NO
36	RAP1B	RAP1B	RAP1B	8456	0.021	0.22	NO
37	FIGF	FIGF	FIGF	8570	0.019	0.22	NO
38	TCEB2	TCEB2	TCEB2	8605	0.018	0.22	NO
39	CDC42	CDC42	CDC42	8836	0.014	0.21	NO
40	PTPN11	PTPN11	PTPN11	8898	0.013	0.2	NO
41	EP300	EP300	EP300	8921	0.013	0.21	NO
42	SOS1	SOS1	SOS1	8948	0.012	0.21	NO
43	ARNT	ARNT	ARNT	9330	0.006	0.19	NO
44	FLCN	FLCN	FLCN	9476	0.0034	0.18	NO
45	CUL2	CUL2	CUL2	9670	0.00029	0.17	NO
46	EGLN1	EGLN1	EGLN1	9698	-0.00025	0.17	NO
47	RAC1	RAC1	RAC1	9827	-0.0021	0.16	NO
48	PAK4	PAK4	PAK4	10097	-0.007	0.15	NO
49	PAK1	PAK1	PAK1	10290	-0.011	0.14	NO
50	MET	MET	MET	10457	-0.014	0.13	NO
51	GRB2	GRB2	GRB2	11064	-0.025	0.1	NO
52	RAP1A	RAP1A	RAP1A	11532	-0.035	0.082	NO
53	GAB1	GAB1	GAB1	11999	-0.046	0.063	NO
54	PIK3R1	PIK3R1	PIK3R1	12151	-0.049	0.062	NO
55	RAF1	RAF1	RAF1	12305	-0.053	0.061	NO
56	VEGFA	VEGFA	VEGFA	12600	-0.059	0.053	NO
57	EPAS1	EPAS1	EPAS1	12774	-0.064	0.052	NO
58	EGLN2	EGLN2	EGLN2	13119	-0.074	0.044	NO
59	PIK3CB	PIK3CB	PIK3CB	13216	-0.077	0.049	NO
60	VHL	VHL	VHL	13530	-0.086	0.044	NO
61	KRAS	KRAS	KRAS	13602	-0.089	0.052	NO
62	ARAF	ARAF	ARAF	13759	-0.093	0.056	NO
63	ETS1	ETS1	ETS1	13880	-0.098	0.063	NO
64	MAPK3	MAPK3	MAPK3	14995	-0.15	0.023	NO
65	PIK3R3	PIK3R3	PIK3R3	15382	-0.17	0.025	NO
66	PIK3R5	PIK3R5	PIK3R5	15386	-0.17	0.047	NO
67	PAK3	PAK3	PAK3	16364	-0.24	0.026	NO
68	HGF	HGF	HGF	17426	-0.37	0.02	NO
69	PIK3CG	PIK3CG	PIK3CG	17485	-0.38	0.068	NO

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

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

genes ES table in pathway: KEGG PROTEASOME

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	NTF4	NTF4	NTF4	12	0.91	0.056	YES
2	CALML3	CALML3	CALML3	71	0.74	0.1	YES
3	TP73	TP73	TP73	240	0.59	0.13	YES
4	MAPK12	MAPK12	MAPK12	278	0.56	0.16	YES
5	NGF	NGF	NGF	287	0.56	0.2	YES
6	NGFR	NGFR	NGFR	373	0.52	0.22	YES
7	NGFRAP1	NGFRAP1	NGFRAP1	487	0.48	0.25	YES
8	CALML5	CALML5	CALML5	704	0.42	0.26	YES
9	NTRK2	NTRK2	NTRK2	746	0.41	0.29	YES
10	MAPK11	MAPK11	MAPK11	756	0.41	0.31	YES
11	CAMK2B	CAMK2B	CAMK2B	1270	0.31	0.3	YES
12	PIK3CD	PIK3CD	PIK3CD	1527	0.28	0.31	YES
13	MAPK10	MAPK10	MAPK10	1597	0.27	0.32	YES
14	CAMK2A	CAMK2A	CAMK2A	1649	0.26	0.33	YES
15	CAMK4	CAMK4	CAMK4	1705	0.26	0.35	YES
16	AKT3	AKT3	AKT3	1795	0.25	0.36	YES
17	IRS4	IRS4	IRS4	2535	0.19	0.33	NO
18	PDK1	PDK1	PDK1	2577	0.19	0.34	NO
19	PIK3CA	PIK3CA	PIK3CA	3016	0.16	0.33	NO
20	SHC4	SHC4	SHC4	3253	0.15	0.32	NO
21	CRKL	CRKL	CRKL	3331	0.14	0.33	NO
22	YWHAQ	YWHAQ	YWHAQ	3388	0.14	0.33	NO
23	YWHAG	YWHAG	YWHAG	3563	0.14	0.33	NO
24	NFKBIA	NFKBIA	NFKBIA	3690	0.13	0.33	NO
25	SHC1	SHC1	SHC1	3880	0.12	0.33	NO
26	IRS2	IRS2	IRS2	4027	0.12	0.33	NO
27	NTRK1	NTRK1	NTRK1	4099	0.12	0.34	NO
28	IRS1	IRS1	IRS1	4179	0.11	0.34	NO
29	RPS6KA6	RPS6KA6	RPS6KA6	4376	0.11	0.33	NO
30	BDNF	BDNF	BDNF	4562	0.1	0.33	NO
31	YWHAE	YWHAE	YWHAE	4575	0.1	0.34	NO
32	SH2B2	SH2B2	SH2B2	4587	0.1	0.34	NO
33	JUN	JUN	JUN	4688	0.097	0.34	NO
34	MAPK7	MAPK7	MAPK7	4791	0.094	0.34	NO
35	PIK3R2	PIK3R2	PIK3R2	4804	0.094	0.35	NO
36	CALML6	CALML6	CALML6	4868	0.093	0.35	NO
37	PLCG1	PLCG1	PLCG1	4981	0.089	0.35	NO
38	KIDINS220	KIDINS220	KIDINS220	5104	0.086	0.35	NO
39	GSK3B	GSK3B	GSK3B	5154	0.084	0.35	NO
40	RPS6KA4	RPS6KA4	RPS6KA4	5580	0.074	0.33	NO
41	MAP2K7	MAP2K7	MAP2K7	5591	0.074	0.34	NO
42	BAD	BAD	BAD	5592	0.074	0.34	NO
43	SHC3	SHC3	SHC3	5670	0.072	0.34	NO
44	MAP2K1	MAP2K1	MAP2K1	6094	0.063	0.32	NO
45	YWHAZ	YWHAZ	YWHAZ	6163	0.062	0.32	NO
46	ZNF274	ZNF274	ZNF274	6211	0.061	0.32	NO
47	MAPK1	MAPK1	MAPK1	6549	0.054	0.31	NO
48	TP53	TP53	TP53	6636	0.053	0.31	NO
49	YWHAH	YWHAH	YWHAH	7016	0.045	0.29	NO
50	FRS2	FRS2	FRS2	7176	0.042	0.29	NO
51	AKT1	AKT1	AKT1	7280	0.04	0.28	NO
52	ABL1	ABL1	ABL1	7406	0.038	0.28	NO
53	RPS6KA5	RPS6KA5	RPS6KA5	7583	0.035	0.27	NO
54	CRK	CRK	CRK	7638	0.034	0.27	NO
55	RAPGEF1	RAPGEF1	RAPGEF1	7704	0.034	0.27	NO
56	BRAF	BRAF	BRAF	7821	0.031	0.26	NO
57	AKT2	AKT2	AKT2	7869	0.031	0.26	NO
58	MAP2K2	MAP2K2	MAP2K2	8177	0.025	0.25	NO
59	NRAS	NRAS	NRAS	8179	0.025	0.25	NO
60	SOS2	SOS2	SOS2	8280	0.024	0.25	NO
61	PRDM4	PRDM4	PRDM4	8319	0.023	0.25	NO
62	RAP1B	RAP1B	RAP1B	8456	0.021	0.24	NO
63	RELA	RELA	RELA	8514	0.02	0.24	NO
64	CDC42	CDC42	CDC42	8836	0.014	0.22	NO
65	PTPN11	PTPN11	PTPN11	8898	0.013	0.22	NO
66	SOS1	SOS1	SOS1	8948	0.012	0.22	NO
67	NFKB1	NFKB1	NFKB1	8992	0.012	0.22	NO
68	MAP2K5	MAP2K5	MAP2K5	9007	0.011	0.22	NO
69	ARHGDIA	ARHGDIA	ARHGDIA	9202	0.0082	0.21	NO
70	CALM1	CALM1	CALM1	9333	0.0059	0.2	NO
71	BCL2	BCL2	BCL2	9573	0.0018	0.19	NO
72	IRAK1	IRAK1	IRAK1	9743	-0.00094	0.18	NO
73	RAC1	RAC1	RAC1	9827	-0.0021	0.17	NO
74	ATF4	ATF4	ATF4	10054	-0.0062	0.16	NO
75	MAP3K3	MAP3K3	MAP3K3	10530	-0.015	0.14	NO
76	CAMK2D	CAMK2D	CAMK2D	10601	-0.017	0.14	NO
77	MAPKAPK2	MAPKAPK2	MAPKAPK2	10636	-0.017	0.13	NO
78	IRAK4	IRAK4	IRAK4	10925	-0.022	0.12	NO
79	MAPK14	MAPK14	MAPK14	10978	-0.024	0.12	NO
80	GRB2	GRB2	GRB2	11064	-0.025	0.12	NO
81	PLCG2	PLCG2	PLCG2	11138	-0.027	0.11	NO
82	CALM2	CALM2	CALM2	11456	-0.033	0.098	NO
83	RAP1A	RAP1A	RAP1A	11532	-0.035	0.096	NO
84	YWHAB	YWHAB	YWHAB	11644	-0.037	0.093	NO
85	MAGED1	MAGED1	MAGED1	11668	-0.038	0.094	NO
86	SH2B1	SH2B1	SH2B1	11705	-0.039	0.094	NO
87	CAMK2G	CAMK2G	CAMK2G	11755	-0.04	0.094	NO
88	MAPK9	MAPK9	MAPK9	11860	-0.042	0.092	NO
89	RPS6KA1	RPS6KA1	RPS6KA1	11880	-0.043	0.093	NO
90	BAX	BAX	BAX	11962	-0.045	0.092	NO
91	IKBKB	IKBKB	IKBKB	11989	-0.045	0.093	NO
92	GAB1	GAB1	GAB1	11999	-0.046	0.095	NO
93	MAP3K1	MAP3K1	MAP3K1	12007	-0.046	0.098	NO
94	PSEN1	PSEN1	PSEN1	12048	-0.047	0.099	NO
95	CSK	CSK	CSK	12144	-0.049	0.097	NO
96	PIK3R1	PIK3R1	PIK3R1	12151	-0.049	0.099	NO
97	RAF1	RAF1	RAF1	12305	-0.053	0.094	NO
98	ARHGDIB	ARHGDIB	ARHGDIB	12336	-0.054	0.096	NO
99	NFKBIB	NFKBIB	NFKBIB	12448	-0.056	0.094	NO
100	TRAF6	TRAF6	TRAF6	12598	-0.059	0.09	NO
101	MAP3K5	MAP3K5	MAP3K5	12643	-0.06	0.091	NO
102	MAPK8	MAPK8	MAPK8	12800	-0.065	0.087	NO
103	RIPK2	RIPK2	RIPK2	12812	-0.065	0.09	NO
104	MAPK13	MAPK13	MAPK13	12865	-0.067	0.092	NO
105	FOXO3	FOXO3	FOXO3	12960	-0.069	0.091	NO
106	RHOA	RHOA	RHOA	13180	-0.076	0.084	NO
107	PIK3CB	PIK3CB	PIK3CB	13216	-0.077	0.087	NO
108	KRAS	KRAS	KRAS	13602	-0.089	0.072	NO
109	SH2B3	SH2B3	SH2B3	13608	-0.089	0.077	NO
110	CALM3	CALM3	CALM3	14407	-0.12	0.042	NO
111	FASLG	FASLG	FASLG	14833	-0.14	0.027	NO
112	NTF3	NTF3	NTF3	14939	-0.14	0.031	NO
113	MAPK3	MAPK3	MAPK3	14995	-0.15	0.037	NO
114	SHC2	SHC2	SHC2	15027	-0.15	0.045	NO
115	IRAK3	IRAK3	IRAK3	15032	-0.15	0.054	NO
116	RPS6KA3	RPS6KA3	RPS6KA3	15057	-0.15	0.062	NO
117	NTRK3	NTRK3	NTRK3	15358	-0.17	0.056	NO
118	PIK3R3	PIK3R3	PIK3R3	15382	-0.17	0.065	NO
119	PIK3R5	PIK3R5	PIK3R5	15386	-0.17	0.076	NO
120	PRKCD	PRKCD	PRKCD	15474	-0.17	0.082	NO
121	NFKBIE	NFKBIE	NFKBIE	15805	-0.19	0.076	NO
122	RPS6KA2	RPS6KA2	RPS6KA2	16614	-0.26	0.049	NO
123	SORT1	SORT1	SORT1	16689	-0.27	0.062	NO
124	PIK3CG	PIK3CG	PIK3CG	17485	-0.38	0.043	NO
125	IRAK2	IRAK2	IRAK2	17514	-0.39	0.066	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.41	1.6	0.049	0.87	0.75	0.4	0.24	0.3	0.52	0.3
BIOCARTA MAPK PATHWAY	86	genes.ES.table	0.38	1.8	0.0063	0.29	0.3	0.44	0.28	0.32	0	0.08
BIOCARTA CHREBP2 PATHWAY	41	genes.ES.table	0.34	1.3	0.18	1	0.99	0.39	0.27	0.28	0.9	0.43
BIOCARTA IL1R PATHWAY	32	genes.ES.table	0.42	1.2	0.25	0.87	1	0.28	0.18	0.23	0.78	0.31
BIOCARTA WNT PATHWAY	25	genes.ES.table	0.4	1.5	0.053	0.75	0.84	0.36	0.23	0.28	0.51	0.25
KEGG OXIDATIVE PHOSPHORYLATION	113	genes.ES.table	0.42	1.6	0.097	0.67	0.75	0.51	0.34	0.34	0.39	0.22
KEGG GLYCEROPHOSPHOLIPID METABOLISM	71	genes.ES.table	0.32	1.2	0.16	0.96	1	0.16	0.09	0.14	0.86	0.39
KEGG ETHER LIPID METABOLISM	29	genes.ES.table	0.41	1.2	0.18	0.93	1	0.21	0.083	0.19	0.83	0.37
KEGG ARACHIDONIC ACID METABOLISM	52	genes.ES.table	0.57	1.5	0.043	0.81	0.93	0.4	0.095	0.37	0.59	0.29
KEGG LINOLEIC ACID METABOLISM	25	genes.ES.table	0.6	1.4	0.1	1	0.97	0.44	0.084	0.4	0.82	0.39

genes ES table in pathway: BIOCARTA RACCYCD PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CXCR2	CXCR2	CXCR2	117	0.82	0.1	YES
2	ATP6V0A4	ATP6V0A4	ATP6V0A4	126	0.8	0.2	YES
3	PTPRZ1	PTPRZ1	PTPRZ1	339	0.57	0.27	YES
4	MAPK10	MAPK10	MAPK10	601	0.43	0.31	YES
5	ATP6V1B1	ATP6V1B1	ATP6V1B1	1466	0.24	0.3	YES
6	HBEGF	HBEGF	HBEGF	1532	0.23	0.32	YES
7	ATP6V1C2	ATP6V1C2	ATP6V1C2	1620	0.22	0.34	YES
8	MAPK13	MAPK13	MAPK13	2213	0.16	0.33	YES
9	MAP2K4	MAP2K4	MAP2K4	2392	0.15	0.34	YES
10	ADAM17	ADAM17	ADAM17	2799	0.12	0.34	YES
11	ATP6V1D	ATP6V1D	ATP6V1D	2807	0.12	0.36	YES
12	TJP1	TJP1	TJP1	2994	0.12	0.36	YES
13	CSK	CSK	CSK	3030	0.11	0.37	YES
14	NFKBIA	NFKBIA	NFKBIA	3125	0.11	0.38	YES
15	PLCG2	PLCG2	PLCG2	3198	0.11	0.39	YES
16	ATP6V1F	ATP6V1F	ATP6V1F	3287	0.1	0.4	YES
17	ATP6V0D1	ATP6V0D1	ATP6V0D1	3579	0.091	0.4	YES
18	ATP6V0C	ATP6V0C	ATP6V0C	3612	0.09	0.41	YES
19	EGFR	EGFR	EGFR	3660	0.088	0.42	YES
20	ATP6V0A1	ATP6V0A1	ATP6V0A1	3783	0.084	0.42	YES
21	ATP6V1E1	ATP6V1E1	ATP6V1E1	3925	0.078	0.42	YES
22	ATP6V1A	ATP6V1A	ATP6V1A	3966	0.077	0.43	YES
23	IKBKB	IKBKB	IKBKB	4012	0.076	0.44	YES
24	F11R	F11R	F11R	4119	0.073	0.44	YES
25	IKBKG	IKBKG	IKBKG	4186	0.071	0.45	YES
26	ATP6V0E2	ATP6V0E2	ATP6V0E2	4227	0.07	0.46	YES
27	MAPK11	MAPK11	MAPK11	4320	0.067	0.46	YES
28	RAC1	RAC1	RAC1	4425	0.065	0.46	YES
29	ATP6V1H	ATP6V1H	ATP6V1H	4429	0.065	0.47	YES
30	MAPK14	MAPK14	MAPK14	5040	0.049	0.44	NO
31	JUN	JUN	JUN	5106	0.048	0.45	NO
32	ATP6V1B2	ATP6V1B2	ATP6V1B2	5368	0.042	0.44	NO
33	ATP6V1G1	ATP6V1G1	ATP6V1G1	5931	0.032	0.41	NO
34	RELA	RELA	RELA	6106	0.028	0.41	NO
35	NFKB1	NFKB1	NFKB1	6475	0.023	0.39	NO
36	ATP6V1E2	ATP6V1E2	ATP6V1E2	7384	0.0095	0.34	NO
37	CXCR1	CXCR1	CXCR1	8053	0.00023	0.31	NO
38	GIT1	GIT1	GIT1	8077	-0.00012	0.31	NO
39	ATP6V0B	ATP6V0B	ATP6V0B	8182	-0.0016	0.3	NO
40	PAK1	PAK1	PAK1	8276	-0.0029	0.3	NO
41	ATP6AP1	ATP6AP1	ATP6AP1	8419	-0.0048	0.29	NO
42	CDC42	CDC42	CDC42	9278	-0.017	0.25	NO
43	NOD1	NOD1	NOD1	9678	-0.024	0.23	NO
44	CASP3	CASP3	CASP3	10039	-0.029	0.21	NO
45	PTPN11	PTPN11	PTPN11	10631	-0.038	0.19	NO
46	CCL5	CCL5	CCL5	10826	-0.041	0.18	NO
47	MAPK8	MAPK8	MAPK8	10848	-0.041	0.18	NO
48	SRC	SRC	SRC	11118	-0.046	0.18	NO
49	MAPK12	MAPK12	MAPK12	11437	-0.052	0.17	NO
50	ADAM10	ADAM10	ADAM10	11652	-0.056	0.16	NO
51	CXCL1	CXCL1	CXCL1	11655	-0.056	0.17	NO
52	PLCG1	PLCG1	PLCG1	11669	-0.056	0.18	NO
53	CHUK	CHUK	CHUK	11796	-0.058	0.18	NO
54	ATP6V0A2	ATP6V0A2	ATP6V0A2	11913	-0.06	0.18	NO
55	ATP6V1C1	ATP6V1C1	ATP6V1C1	12155	-0.064	0.17	NO
56	LYN	LYN	LYN	12233	-0.066	0.18	NO
57	TCIRG1	TCIRG1	TCIRG1	12604	-0.074	0.17	NO
58	MAPK9	MAPK9	MAPK9	12828	-0.078	0.17	NO
59	JAM2	JAM2	JAM2	13163	-0.086	0.16	NO
60	MAP3K14	MAP3K14	MAP3K14	13378	-0.091	0.16	NO
61	ATP6V1G2	ATP6V1G2	ATP6V1G2	14148	-0.11	0.14	NO
62	IGSF5	IGSF5	IGSF5	14277	-0.12	0.14	NO
63	ATP6V0D2	ATP6V0D2	ATP6V0D2	14668	-0.13	0.14	NO
64	IL8	IL8	IL8	15077	-0.14	0.14	NO
65	MET	MET	MET	16303	-0.2	0.096	NO
66	JAM3	JAM3	JAM3	17317	-0.27	0.077	NO

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

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

genes ES table in pathway: BIOCARTA MAPK PATHWAY

Table 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	MAPK10	MAPK10	MAPK10	601	0.43	0.026	YES
2	MAP3K9	MAP3K9	MAP3K9	882	0.34	0.057	YES
3	MAP3K6	MAP3K6	MAP3K6	1152	0.29	0.082	YES
4	CEBPA	CEBPA	CEBPA	1459	0.24	0.097	YES
5	MKNK2	MKNK2	MKNK2	1892	0.19	0.1	YES
6	TGFB1	TGFB1	TGFB1	2077	0.17	0.11	YES
7	RPS6KA5	RPS6KA5	RPS6KA5	2145	0.17	0.13	YES
8	HRAS	HRAS	HRAS	2177	0.16	0.15	YES
9	MAPK13	MAPK13	MAPK13	2213	0.16	0.17	YES
10	RPS6KB2	RPS6KB2	RPS6KB2	2292	0.16	0.19	YES
11	MAPK6	MAPK6	MAPK6	2296	0.16	0.21	YES
12	MAP2K4	MAP2K4	MAP2K4	2392	0.15	0.23	YES
13	MAP3K8	MAP3K8	MAP3K8	2436	0.15	0.24	YES
14	FOS	FOS	FOS	2496	0.14	0.26	YES
15	MAPK7	MAPK7	MAPK7	2517	0.14	0.28	YES
16	MAP3K1	MAP3K1	MAP3K1	2560	0.14	0.29	YES
17	MAP3K4	MAP3K4	MAP3K4	2638	0.13	0.31	YES
18	BRAF	BRAF	BRAF	2719	0.13	0.32	YES
19	MAPKAPK3	MAPKAPK3	MAPKAPK3	3045	0.11	0.32	YES
20	NFKBIA	NFKBIA	NFKBIA	3125	0.11	0.33	YES
21	MAP3K5	MAP3K5	MAP3K5	3182	0.11	0.34	YES
22	MYC	MYC	MYC	3199	0.11	0.36	YES
23	TRADD	TRADD	TRADD	3445	0.097	0.36	YES
24	RAF1	RAF1	RAF1	3808	0.083	0.35	YES
25	IKBKB	IKBKB	IKBKB	4012	0.076	0.35	YES
26	MAPK11	MAPK11	MAPK11	4320	0.067	0.34	YES
27	MAP2K2	MAP2K2	MAP2K2	4335	0.067	0.35	YES
28	RAC1	RAC1	RAC1	4425	0.065	0.35	YES
29	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	4469	0.064	0.36	YES
30	MAPK3	MAPK3	MAPK3	4498	0.063	0.36	YES
31	MAP4K5	MAP4K5	MAP4K5	4757	0.056	0.36	YES
32	RIPK1	RIPK1	RIPK1	4964	0.051	0.35	YES
33	MAX	MAX	MAX	4978	0.05	0.36	YES
34	RPS6KB1	RPS6KB1	RPS6KB1	5035	0.049	0.36	YES
35	MAPK14	MAPK14	MAPK14	5040	0.049	0.37	YES
36	JUN	JUN	JUN	5106	0.048	0.37	YES
37	MKNK1	MKNK1	MKNK1	5192	0.046	0.38	YES
38	MAPK4	MAPK4	MAPK4	5243	0.045	0.38	YES
39	MAP2K1	MAP2K1	MAP2K1	5447	0.041	0.37	NO
40	MEF2A	MEF2A	MEF2A	5763	0.035	0.36	NO
41	MAP2K5	MAP2K5	MAP2K5	5812	0.034	0.36	NO
42	MAP4K1	MAP4K1	MAP4K1	6040	0.03	0.36	NO
43	RELA	RELA	RELA	6106	0.028	0.36	NO
44	MAPK1	MAPK1	MAPK1	6249	0.026	0.35	NO
45	MAP4K4	MAP4K4	MAP4K4	6310	0.025	0.35	NO
46	NFKB1	NFKB1	NFKB1	6475	0.023	0.35	NO
47	MAPKAPK2	MAPKAPK2	MAPKAPK2	6589	0.021	0.34	NO
48	MAP2K7	MAP2K7	MAP2K7	6748	0.018	0.34	NO
49	RPS6KA4	RPS6KA4	RPS6KA4	6783	0.018	0.34	NO
50	SP1	SP1	SP1	6851	0.017	0.34	NO
51	MAP3K3	MAP3K3	MAP3K3	6934	0.016	0.33	NO
52	MAP3K10	MAP3K10	MAP3K10	7121	0.013	0.32	NO
53	MAP2K3	MAP2K3	MAP2K3	7527	0.0076	0.3	NO
54	DAXX	DAXX	DAXX	7976	0.0013	0.28	NO
55	GRB2	GRB2	GRB2	8128	-0.00085	0.27	NO
56	STAT1	STAT1	STAT1	8231	-0.0023	0.27	NO
57	PAK1	PAK1	PAK1	8276	-0.0029	0.27	NO
58	MAP3K7	MAP3K7	MAP3K7	8306	-0.0032	0.26	NO
59	MAP4K2	MAP4K2	MAP4K2	8400	-0.0046	0.26	NO
60	MAP3K11	MAP3K11	MAP3K11	9081	-0.015	0.23	NO
61	SHC1	SHC1	SHC1	9204	-0.016	0.22	NO
62	PAK2	PAK2	PAK2	9585	-0.022	0.2	NO
63	ARAF	ARAF	ARAF	10105	-0.03	0.18	NO
64	CREB1	CREB1	CREB1	10479	-0.035	0.16	NO
65	MAPK8	MAPK8	MAPK8	10848	-0.041	0.15	NO
66	MAP3K2	MAP3K2	MAP3K2	11369	-0.05	0.13	NO
67	MEF2D	MEF2D	MEF2D	11431	-0.052	0.13	NO
68	MAPK12	MAPK12	MAPK12	11437	-0.052	0.14	NO
69	MAP2K6	MAP2K6	MAP2K6	11540	-0.054	0.14	NO
70	RPS6KA3	RPS6KA3	RPS6KA3	11702	-0.056	0.14	NO
71	MAPKAPK5	MAPKAPK5	MAPKAPK5	11764	-0.058	0.15	NO
72	CHUK	CHUK	CHUK	11796	-0.058	0.15	NO
73	MAP4K3	MAP4K3	MAP4K3	12227	-0.066	0.14	NO
74	RPS6KA2	RPS6KA2	RPS6KA2	12480	-0.071	0.13	NO
75	TGFBR1	TGFBR1	TGFBR1	12526	-0.072	0.14	NO
76	MAPK9	MAPK9	MAPK9	12828	-0.078	0.14	NO
77	MAP3K14	MAP3K14	MAP3K14	13378	-0.091	0.12	NO
78	RPS6KA1	RPS6KA1	RPS6KA1	13399	-0.092	0.13	NO
79	ELK1	ELK1	ELK1	13436	-0.093	0.14	NO
80	ATF2	ATF2	ATF2	13712	-0.1	0.14	NO
81	MAP3K12	MAP3K12	MAP3K12	13921	-0.11	0.14	NO
82	TRAF2	TRAF2	TRAF2	13968	-0.11	0.16	NO
83	TGFB3	TGFB3	TGFB3	14792	-0.13	0.13	NO
84	RAPGEF2	RAPGEF2	RAPGEF2	14836	-0.13	0.14	NO
85	MAP3K13	MAP3K13	MAP3K13	16963	-0.24	0.063	NO
86	TGFB2	TGFB2	TGFB2	16989	-0.24	0.094	NO

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

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

genes ES table in pathway: BIOCARTA CHREBP2 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HRAS	HRAS	HRAS	2177	0.16	0.000082	YES
2	CDKN1A	CDKN1A	CDKN1A	2361	0.15	0.097	YES
3	NFKBIA	NFKBIA	NFKBIA	3125	0.11	0.13	YES
4	RAF1	RAF1	RAF1	3808	0.083	0.16	YES
5	CCND1	CCND1	CCND1	4011	0.076	0.2	YES
6	IKBKB	IKBKB	IKBKB	4012	0.076	0.25	YES
7	IKBKG	IKBKG	IKBKG	4186	0.071	0.29	YES
8	PIK3CA	PIK3CA	PIK3CA	4405	0.065	0.33	YES
9	RAC1	RAC1	RAC1	4425	0.065	0.37	YES
10	MAPK3	MAPK3	MAPK3	4498	0.063	0.41	YES
11	RB1	RB1	RB1	5502	0.04	0.39	NO
12	RELA	RELA	RELA	6106	0.028	0.37	NO
13	MAPK1	MAPK1	MAPK1	6249	0.026	0.38	NO
14	TFDP1	TFDP1	TFDP1	6293	0.025	0.4	NO
15	NFKB1	NFKB1	NFKB1	6475	0.023	0.41	NO
16	RHOA	RHOA	RHOA	6760	0.018	0.4	NO
17	CCNE1	CCNE1	CCNE1	7745	0.0044	0.35	NO
18	CDKN1B	CDKN1B	CDKN1B	8265	-0.0027	0.33	NO
19	PAK1	PAK1	PAK1	8276	-0.0029	0.33	NO
20	AKT1	AKT1	AKT1	9857	-0.026	0.26	NO
21	CDK6	CDK6	CDK6	10360	-0.033	0.26	NO
22	CDK4	CDK4	CDK4	11178	-0.047	0.25	NO
23	PIK3R1	PIK3R1	PIK3R1	11749	-0.057	0.26	NO
24	CHUK	CHUK	CHUK	11796	-0.058	0.3	NO
25	CDK2	CDK2	CDK2	13848	-0.1	0.26	NO

Figure S45. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA CHREBP2 PATHWAY.

Figure S46. 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 IL1R PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ATP6V0A4	ATP6V0A4	ATP6V0A4	126	0.8	0.11	YES
2	ATP12A	ATP12A	ATP12A	234	0.65	0.2	YES
3	NDUFA4L2	NDUFA4L2	NDUFA4L2	720	0.39	0.23	YES
4	ATP6V1B1	ATP6V1B1	ATP6V1B1	1466	0.24	0.22	YES
5	ATP6V1C2	ATP6V1C2	ATP6V1C2	1620	0.22	0.25	YES
6	ATP6V1D	ATP6V1D	ATP6V1D	2807	0.12	0.2	YES
7	LHPP	LHPP	LHPP	3088	0.11	0.2	YES
8	ATP6V1F	ATP6V1F	ATP6V1F	3287	0.1	0.21	YES
9	ATP5A1	ATP5A1	ATP5A1	3488	0.094	0.21	YES
10	ATP6V0D1	ATP6V0D1	ATP6V0D1	3579	0.091	0.22	YES
11	NDUFS4	NDUFS4	NDUFS4	3604	0.09	0.23	YES
12	ATP6V0C	ATP6V0C	ATP6V0C	3612	0.09	0.24	YES
13	ATP6V0A1	ATP6V0A1	ATP6V0A1	3783	0.084	0.25	YES
14	NDUFA11	NDUFA11	NDUFA11	3874	0.08	0.25	YES
15	ATP6V1E1	ATP6V1E1	ATP6V1E1	3925	0.078	0.26	YES
16	ATP5H	ATP5H	ATP5H	3956	0.077	0.27	YES
17	ATP6V1A	ATP6V1A	ATP6V1A	3966	0.077	0.28	YES
18	NDUFS8	NDUFS8	NDUFS8	4010	0.076	0.29	YES
19	ATP5J	ATP5J	ATP5J	4217	0.07	0.29	YES
20	NDUFB4	NDUFB4	NDUFB4	4225	0.07	0.3	YES
21	ATP6V0E2	ATP6V0E2	ATP6V0E2	4227	0.07	0.31	YES
22	NDUFS7	NDUFS7	NDUFS7	4258	0.069	0.32	YES
23	ATP6V1H	ATP6V1H	ATP6V1H	4429	0.065	0.32	YES
24	ATP5D	ATP5D	ATP5D	4485	0.063	0.33	YES
25	ATP5I	ATP5I	ATP5I	4500	0.063	0.33	YES
26	ATP4A	ATP4A	ATP4A	4581	0.06	0.34	YES
27	NDUFV1	NDUFV1	NDUFV1	4727	0.057	0.34	YES
28	NDUFS5	NDUFS5	NDUFS5	4894	0.052	0.34	YES
29	NDUFA10	NDUFA10	NDUFA10	4974	0.051	0.34	YES
30	ATP6V0E1	ATP6V0E1	ATP6V0E1	5063	0.048	0.34	YES
31	UQCRC2	UQCRC2	UQCRC2	5112	0.048	0.35	YES
32	NDUFB3	NDUFB3	NDUFB3	5181	0.046	0.35	YES
33	UQCRFS1	UQCRFS1	UQCRFS1	5259	0.044	0.35	YES
34	NDUFB7	NDUFB7	NDUFB7	5358	0.043	0.35	YES
35	ATP6V1B2	ATP6V1B2	ATP6V1B2	5368	0.042	0.36	YES
36	NDUFV3	NDUFV3	NDUFV3	5390	0.042	0.36	YES
37	NDUFA9	NDUFA9	NDUFA9	5487	0.04	0.37	YES
38	UQCR11	UQCR11	UQCR11	5530	0.039	0.37	YES
39	COX6B1	COX6B1	COX6B1	5535	0.039	0.38	YES
40	COX5A	COX5A	COX5A	5559	0.038	0.38	YES
41	NDUFB1	NDUFB1	NDUFB1	5607	0.038	0.38	YES
42	COX7B	COX7B	COX7B	5644	0.037	0.38	YES
43	COX8A	COX8A	COX8A	5647	0.037	0.39	YES
44	UQCRQ	UQCRQ	UQCRQ	5697	0.036	0.39	YES
45	ATP5G3	ATP5G3	ATP5G3	5741	0.035	0.4	YES
46	ATP5O	ATP5O	ATP5O	5787	0.035	0.4	YES
47	PPA2	PPA2	PPA2	5811	0.034	0.4	YES
48	NDUFB5	NDUFB5	NDUFB5	5860	0.033	0.4	YES
49	UQCRHL	UQCRHL	UQCRHL	5929	0.032	0.41	YES
50	ATP6V1G1	ATP6V1G1	ATP6V1G1	5931	0.032	0.41	YES
51	SDHC	SDHC	SDHC	5994	0.031	0.41	YES
52	NDUFB10	NDUFB10	NDUFB10	6034	0.03	0.41	YES
53	ATP5F1	ATP5F1	ATP5F1	6116	0.028	0.41	YES
54	COX10	COX10	COX10	6153	0.028	0.42	YES
55	NDUFS6	NDUFS6	NDUFS6	6182	0.027	0.42	YES
56	NDUFA6	NDUFA6	NDUFA6	6230	0.026	0.42	YES
57	ATP5B	ATP5B	ATP5B	6281	0.026	0.42	YES
58	UQCR10	UQCR10	UQCR10	6306	0.025	0.42	YES
59	NDUFC1	NDUFC1	NDUFC1	6468	0.023	0.42	NO
60	NDUFV2	NDUFV2	NDUFV2	6616	0.02	0.41	NO
61	COX5B	COX5B	COX5B	6650	0.02	0.41	NO
62	COX4I1	COX4I1	COX4I1	6714	0.019	0.41	NO
63	ATP5G2	ATP5G2	ATP5G2	6879	0.017	0.41	NO
64	COX6A1	COX6A1	COX6A1	6890	0.016	0.41	NO
65	UQCRC1	UQCRC1	UQCRC1	6914	0.016	0.41	NO
66	COX6C	COX6C	COX6C	6946	0.016	0.41	NO
67	COX7C	COX7C	COX7C	6956	0.016	0.41	NO
68	ATP5L	ATP5L	ATP5L	6983	0.015	0.41	NO
69	COX7A2	COX7A2	COX7A2	6993	0.015	0.42	NO
70	ATP5C1	ATP5C1	ATP5C1	7277	0.011	0.4	NO
71	ATP5G1	ATP5G1	ATP5G1	7370	0.0097	0.4	NO
72	ATP6V1E2	ATP6V1E2	ATP6V1E2	7384	0.0095	0.4	NO
73	UQCRH	UQCRH	UQCRH	7453	0.0086	0.4	NO
74	SDHD	SDHD	SDHD	7528	0.0076	0.39	NO
75	NDUFA7	NDUFA7	NDUFA7	7615	0.0065	0.39	NO
76	NDUFC2	NDUFC2	NDUFC2	7734	0.0046	0.38	NO
77	NDUFS3	NDUFS3	NDUFS3	7886	0.0025	0.38	NO
78	NDUFB8	NDUFB8	NDUFB8	7893	0.0025	0.38	NO
79	NDUFB6	NDUFB6	NDUFB6	8176	-0.0015	0.36	NO
80	ATP6V0B	ATP6V0B	ATP6V0B	8182	-0.0016	0.36	NO
81	CYC1	CYC1	CYC1	8211	-0.0021	0.36	NO
82	NDUFAB1	NDUFAB1	NDUFAB1	8226	-0.0023	0.36	NO
83	NDUFB9	NDUFB9	NDUFB9	8285	-0.003	0.36	NO
84	ATP5E	ATP5E	ATP5E	8328	-0.0035	0.36	NO
85	ATP6AP1	ATP6AP1	ATP6AP1	8419	-0.0048	0.35	NO
86	NDUFS2	NDUFS2	NDUFS2	8481	-0.0058	0.35	NO
87	NDUFA1	NDUFA1	NDUFA1	8512	-0.0062	0.35	NO
88	NDUFA4	NDUFA4	NDUFA4	8673	-0.0086	0.34	NO
89	NDUFA2	NDUFA2	NDUFA2	8691	-0.0089	0.34	NO
90	NDUFS1	NDUFS1	NDUFS1	8716	-0.0093	0.34	NO
91	UQCRB	UQCRB	UQCRB	8760	-0.0099	0.34	NO
92	ATP5J2	ATP5J2	ATP5J2	8891	-0.012	0.34	NO
93	NDUFA3	NDUFA3	NDUFA3	9112	-0.015	0.33	NO
94	NDUFB2	NDUFB2	NDUFB2	9143	-0.016	0.33	NO
95	SDHB	SDHB	SDHB	9977	-0.028	0.29	NO
96	COX7A2L	COX7A2L	COX7A2L	10390	-0.034	0.27	NO
97	NDUFA8	NDUFA8	NDUFA8	10401	-0.034	0.27	NO
98	COX17	COX17	COX17	10499	-0.036	0.27	NO
99	PPA1	PPA1	PPA1	10535	-0.036	0.28	NO
100	COX15	COX15	COX15	10586	-0.037	0.28	NO
101	COX6B2	COX6B2	COX6B2	10865	-0.042	0.27	NO
102	ATP4B	ATP4B	ATP4B	10892	-0.042	0.28	NO
103	NDUFA5	NDUFA5	NDUFA5	11879	-0.06	0.23	NO
104	ATP6V0A2	ATP6V0A2	ATP6V0A2	11913	-0.06	0.24	NO
105	ATP6V1C1	ATP6V1C1	ATP6V1C1	12155	-0.064	0.23	NO
106	SDHA	SDHA	SDHA	12164	-0.065	0.24	NO
107	COX8C	COX8C	COX8C	12298	-0.067	0.25	NO
108	TCIRG1	TCIRG1	TCIRG1	12604	-0.074	0.24	NO
109	COX11	COX11	COX11	13686	-0.1	0.2	NO
110	ATP6V1G2	ATP6V1G2	ATP6V1G2	14148	-0.11	0.19	NO
111	COX7A1	COX7A1	COX7A1	14303	-0.12	0.2	NO
112	ATP6V0D2	ATP6V0D2	ATP6V0D2	14668	-0.13	0.2	NO
113	COX4I2	COX4I2	COX4I2	15399	-0.15	0.18	NO

Figure S47. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA IL1R PATHWAY.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA WNT PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	WIF1	WIF1	WIF1	1352	0.25	0.082	YES
2	LEF1	LEF1	LEF1	2848	0.12	0.078	YES
3	CSNK1A1	CSNK1A1	CSNK1A1	2903	0.12	0.15	YES
4	BTRC	BTRC	BTRC	3192	0.11	0.2	YES
5	MYC	MYC	MYC	3199	0.11	0.26	YES
6	APC	APC	APC	3487	0.094	0.31	YES
7	FZD1	FZD1	FZD1	3837	0.082	0.34	YES
8	CCND1	CCND1	CCND1	4011	0.076	0.37	YES
9	PPP2CA	PPP2CA	PPP2CA	4243	0.07	0.4	YES
10	GSK3B	GSK3B	GSK3B	5503	0.04	0.36	NO
11	TAB1	TAB1	TAB1	5865	0.033	0.36	NO
12	DVL1	DVL1	DVL1	6706	0.019	0.33	NO
13	CREBBP	CREBBP	CREBBP	7253	0.011	0.31	NO
14	FRAT1	FRAT1	FRAT1	7447	0.0086	0.3	NO
15	SMAD4	SMAD4	SMAD4	7755	0.0041	0.29	NO
16	MAP3K7	MAP3K7	MAP3K7	8306	-0.0032	0.26	NO
17	HDAC1	HDAC1	HDAC1	9007	-0.014	0.23	NO
18	CSNK1D	CSNK1D	CSNK1D	9151	-0.016	0.23	NO
19	CSNK2A1	CSNK2A1	CSNK2A1	9646	-0.023	0.22	NO
20	AXIN1	AXIN1	AXIN1	9872	-0.026	0.22	NO
21	CTNNB1	CTNNB1	CTNNB1	10127	-0.03	0.23	NO
22	CTBP1	CTBP1	CTBP1	11793	-0.058	0.18	NO
23	TLE1	TLE1	TLE1	12832	-0.078	0.17	NO
24	NLK	NLK	NLK	14164	-0.11	0.17	NO
25	WNT1	WNT1	WNT1	14741	-0.13	0.21	NO

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

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

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

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	TP53AIP1	TP53AIP1	TP53AIP1	228	0.66	0.073	YES
2	SESN3	SESN3	SESN3	542	0.45	0.11	YES
3	SFN	SFN	SFN	616	0.42	0.16	YES
4	SERPINB5	SERPINB5	SERPINB5	727	0.38	0.21	YES
5	PERP	PERP	PERP	931	0.33	0.24	YES
6	TP73	TP73	TP73	1175	0.28	0.26	YES
7	TP53I3	TP53I3	TP53I3	1222	0.27	0.3	YES
8	RPRM	RPRM	RPRM	1417	0.24	0.32	YES
9	BAI1	BAI1	BAI1	1609	0.22	0.34	YES
10	DDB2	DDB2	DDB2	1955	0.18	0.34	YES
11	CDKN1A	CDKN1A	CDKN1A	2361	0.15	0.34	YES
12	CCNG2	CCNG2	CCNG2	2382	0.15	0.36	YES
13	PMAIP1	PMAIP1	PMAIP1	2539	0.14	0.37	YES
14	CD82	CD82	CD82	2796	0.12	0.37	YES
15	SESN2	SESN2	SESN2	2955	0.12	0.38	YES
16	MDM2	MDM2	MDM2	3667	0.088	0.35	NO
17	CCND1	CCND1	CCND1	4011	0.076	0.34	NO
18	IGF1	IGF1	IGF1	4373	0.066	0.33	NO
19	TSC2	TSC2	TSC2	4895	0.052	0.31	NO
20	SHISA5	SHISA5	SHISA5	4923	0.052	0.32	NO
21	CASP9	CASP9	CASP9	5492	0.04	0.29	NO
22	RFWD2	RFWD2	RFWD2	6190	0.027	0.26	NO
23	ZMAT3	ZMAT3	ZMAT3	6280	0.026	0.25	NO
24	PPM1D	PPM1D	PPM1D	6311	0.025	0.26	NO
25	PTEN	PTEN	PTEN	7382	0.0096	0.2	NO
26	CCNE1	CCNE1	CCNE1	7745	0.0044	0.18	NO
27	EI24	EI24	EI24	8094	-0.00039	0.16	NO
28	ATR	ATR	ATR	8099	-0.00044	0.16	NO
29	TP53	TP53	TP53	8118	-0.00073	0.16	NO
30	LRDD	LRDD	LRDD	8267	-0.0028	0.15	NO
31	CYCS	CYCS	CYCS	8723	-0.0093	0.13	NO
32	SIAH1	SIAH1	SIAH1	8766	-0.01	0.13	NO
33	RRM2B	RRM2B	RRM2B	9199	-0.016	0.11	NO
34	CCNG1	CCNG1	CCNG1	9587	-0.022	0.091	NO
35	SESN1	SESN1	SESN1	9631	-0.023	0.092	NO
36	GADD45A	GADD45A	GADD45A	9807	-0.026	0.086	NO
37	MDM4	MDM4	MDM4	9836	-0.026	0.088	NO
38	FAS	FAS	FAS	9902	-0.027	0.088	NO
39	CCND3	CCND3	CCND3	10020	-0.028	0.085	NO
40	CASP3	CASP3	CASP3	10039	-0.029	0.088	NO
41	CDK6	CDK6	CDK6	10360	-0.033	0.075	NO
42	GADD45B	GADD45B	GADD45B	10442	-0.035	0.075	NO
43	BAX	BAX	BAX	10501	-0.036	0.077	NO
44	CCND2	CCND2	CCND2	10521	-0.036	0.08	NO
45	RRM2	RRM2	RRM2	11020	-0.044	0.059	NO
46	CDK4	CDK4	CDK4	11178	-0.047	0.057	NO
47	RCHY1	RCHY1	RCHY1	11371	-0.05	0.053	NO
48	CHEK2	CHEK2	CHEK2	11401	-0.051	0.058	NO
49	CCNE2	CCNE2	CCNE2	11744	-0.057	0.047	NO
50	IGFBP3	IGFBP3	IGFBP3	11952	-0.061	0.044	NO
51	CCNB1	CCNB1	CCNB1	12531	-0.072	0.022	NO
52	CCNB2	CCNB2	CCNB2	13126	-0.085	0.0017	NO
53	CDKN2A	CDKN2A	CDKN2A	13198	-0.087	0.0092	NO
54	BID	BID	BID	13361	-0.091	0.012	NO
55	CASP8	CASP8	CASP8	13529	-0.095	0.016	NO
56	CDK2	CDK2	CDK2	13848	-0.1	0.012	NO
57	CHEK1	CHEK1	CHEK1	14730	-0.13	-0.018	NO
58	CDK1	CDK1	CDK1	14884	-0.14	-0.0092	NO
59	ATM	ATM	ATM	15176	-0.14	-0.0061	NO
60	SERPINE1	SERPINE1	SERPINE1	15258	-0.15	0.0088	NO
61	GADD45G	GADD45G	GADD45G	15426	-0.16	0.02	NO
62	GTSE1	GTSE1	GTSE1	15654	-0.16	0.029	NO
63	TNFRSF10B	TNFRSF10B	TNFRSF10B	16043	-0.18	0.032	NO
64	APAF1	APAF1	APAF1	16325	-0.2	0.043	NO
65	THBS1	THBS1	THBS1	16466	-0.21	0.062	NO
66	CCNB3	CCNB3	CCNB3	16566	-0.21	0.085	NO
67	BBC3	BBC3	BBC3	17062	-0.25	0.09	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 OXIDATIVE PHOSPHORYLATION.

Figure S52. 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 GLYCEROPHOSPHOLIPID 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	ALOX12	ALOX12	ALOX12	72	0.93	0.062	YES
2	PLA2G4E	PLA2G4E	PLA2G4E	109	0.84	0.12	YES
3	ALOX12B	ALOX12B	ALOX12B	153	0.75	0.17	YES
4	ALOX15B	ALOX15B	ALOX15B	155	0.75	0.22	YES
5	PLA2G3	PLA2G3	PLA2G3	204	0.69	0.27	YES
6	CBR3	CBR3	CBR3	307	0.59	0.3	YES
7	CYP2C18	CYP2C18	CYP2C18	350	0.56	0.34	YES
8	GGT6	GGT6	GGT6	385	0.54	0.38	YES
9	CYP2C19	CYP2C19	CYP2C19	554	0.44	0.4	YES
10	GPX3	GPX3	GPX3	654	0.41	0.42	YES
11	CYP4F3	CYP4F3	CYP4F3	704	0.39	0.45	YES
12	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	782	0.37	0.47	YES
13	CYP2C9	CYP2C9	CYP2C9	1061	0.3	0.48	YES
14	ALOX15	ALOX15	ALOX15	1253	0.27	0.49	YES
15	CBR1	CBR1	CBR1	1331	0.26	0.5	YES
16	PLA2G2F	PLA2G2F	PLA2G2F	1559	0.22	0.5	YES
17	CYP4A11	CYP4A11	CYP4A11	1560	0.22	0.52	YES
18	CYP2E1	CYP2E1	CYP2E1	1566	0.22	0.54	YES
19	EPHX2	EPHX2	EPHX2	1573	0.22	0.55	YES
20	CYP4A22	CYP4A22	CYP4A22	1634	0.21	0.56	YES
21	PTGS1	PTGS1	PTGS1	1775	0.2	0.57	YES
22	AKR1C3	AKR1C3	AKR1C3	2386	0.15	0.55	NO
23	LTA4H	LTA4H	LTA4H	2523	0.14	0.55	NO
24	PLA2G4A	PLA2G4A	PLA2G4A	3253	0.1	0.52	NO
25	PTGES	PTGES	PTGES	3320	0.1	0.52	NO
26	LTC4S	LTC4S	LTC4S	3873	0.08	0.5	NO
27	PLA2G2D	PLA2G2D	PLA2G2D	4339	0.066	0.48	NO
28	PTGDS	PTGDS	PTGDS	5057	0.048	0.44	NO
29	GPX2	GPX2	GPX2	5721	0.036	0.41	NO
30	PTGIS	PTGIS	PTGIS	6383	0.024	0.38	NO
31	GPX4	GPX4	GPX4	6516	0.022	0.37	NO
32	HPGDS	HPGDS	HPGDS	7218	0.012	0.33	NO
33	PLA2G12A	PLA2G12A	PLA2G12A	7299	0.011	0.33	NO
34	GPX1	GPX1	GPX1	8174	-0.0015	0.28	NO
35	PLA2G6	PLA2G6	PLA2G6	9298	-0.018	0.22	NO
36	GPX7	GPX7	GPX7	10811	-0.041	0.15	NO
37	PLA2G5	PLA2G5	PLA2G5	10869	-0.042	0.15	NO
38	PTGES2	PTGES2	PTGES2	12848	-0.079	0.047	NO
39	CYP2C8	CYP2C8	CYP2C8	13858	-0.1	0.00022	NO
40	PLA2G2A	PLA2G2A	PLA2G2A	14427	-0.12	-0.022	NO
41	GGT7	GGT7	GGT7	15509	-0.16	-0.068	NO
42	PTGS2	PTGS2	PTGS2	16031	-0.18	-0.083	NO
43	GGT1	GGT1	GGT1	17201	-0.26	-0.13	NO
44	CYP2U1	CYP2U1	CYP2U1	17220	-0.26	-0.11	NO
45	PLA2G1B	PLA2G1B	PLA2G1B	17432	-0.28	-0.1	NO
46	ALOX5	ALOX5	ALOX5	17508	-0.29	-0.085	NO
47	CYP4F2	CYP4F2	CYP4F2	17527	-0.29	-0.066	NO
48	GGT5	GGT5	GGT5	17599	-0.29	-0.049	NO
49	PLA2G12B	PLA2G12B	PLA2G12B	17745	-0.31	-0.035	NO
50	TBXAS1	TBXAS1	TBXAS1	18323	-0.4	-0.038	NO
51	PLA2G10	PLA2G10	PLA2G10	18341	-0.4	-0.01	NO
52	CYP2B6	CYP2B6	CYP2B6	18511	-0.45	0.013	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 GLYCEROPHOSPHOLIPID METABOLISM.

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

genes ES table in pathway: KEGG ETHER LIPID METABOLISM

Table 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	HES5	HES5	HES5	87	0.89	0.19	YES
2	NOTCH3	NOTCH3	NOTCH3	1591	0.22	0.16	YES
3	MAML3	MAML3	MAML3	1595	0.22	0.2	YES
4	KAT2B	KAT2B	KAT2B	1606	0.22	0.25	YES
5	DTX2	DTX2	DTX2	2577	0.14	0.23	YES
6	NOTCH2	NOTCH2	NOTCH2	2692	0.13	0.25	YES
7	ADAM17	ADAM17	ADAM17	2799	0.12	0.27	YES
8	JAG1	JAG1	JAG1	2878	0.12	0.29	YES
9	DTX1	DTX1	DTX1	2886	0.12	0.32	YES
10	HES1	HES1	HES1	2972	0.12	0.34	YES
11	JAG2	JAG2	JAG2	3401	0.098	0.34	YES
12	DVL3	DVL3	DVL3	4141	0.072	0.31	YES
13	DVL2	DVL2	DVL2	4180	0.071	0.33	YES
14	NUMBL	NUMBL	NUMBL	4213	0.07	0.34	YES
15	DLL3	DLL3	DLL3	4319	0.067	0.35	YES
16	DLL1	DLL1	DLL1	5651	0.037	0.28	NO
17	EP300	EP300	EP300	5760	0.035	0.29	NO
18	DTX3	DTX3	DTX3	6074	0.029	0.28	NO
19	DVL1	DVL1	DVL1	6706	0.019	0.25	NO
20	RFNG	RFNG	RFNG	6846	0.017	0.24	NO
21	NOTCH1	NOTCH1	NOTCH1	7197	0.012	0.23	NO
22	CREBBP	CREBBP	CREBBP	7253	0.011	0.23	NO
23	SNW1	SNW1	SNW1	7910	0.0023	0.19	NO
24	NUMB	NUMB	NUMB	8019	0.00062	0.19	NO
25	PSEN1	PSEN1	PSEN1	8263	-0.0027	0.17	NO
26	PSENEN	PSENEN	PSENEN	8278	-0.003	0.17	NO
27	APH1A	APH1A	APH1A	8302	-0.0032	0.17	NO
28	HDAC1	HDAC1	HDAC1	9007	-0.014	0.14	NO
29	MAML1	MAML1	MAML1	9178	-0.016	0.13	NO
30	HDAC2	HDAC2	HDAC2	9569	-0.022	0.12	NO
31	NCSTN	NCSTN	NCSTN	9663	-0.024	0.12	NO
32	PTCRA	PTCRA	PTCRA	9949	-0.028	0.11	NO
33	DTX3L	DTX3L	DTX3L	10137	-0.03	0.1	NO
34	PSEN2	PSEN2	PSEN2	10598	-0.037	0.088	NO
35	CIR1	CIR1	CIR1	10906	-0.042	0.081	NO
36	KAT2A	KAT2A	KAT2A	11138	-0.046	0.078	NO
37	CTBP1	CTBP1	CTBP1	11793	-0.058	0.056	NO
38	MAML2	MAML2	MAML2	11884	-0.06	0.064	NO
39	RBPJ	RBPJ	RBPJ	12260	-0.067	0.058	NO
40	NCOR2	NCOR2	NCOR2	12350	-0.069	0.068	NO
41	CTBP2	CTBP2	CTBP2	13115	-0.085	0.046	NO
42	RBPJL	RBPJL	RBPJL	13533	-0.095	0.044	NO
43	NOTCH4	NOTCH4	NOTCH4	14823	-0.13	0.004	NO
44	LFNG	LFNG	LFNG	17607	-0.3	-0.081	NO
45	DLL4	DLL4	DLL4	17811	-0.32	-0.023	NO
46	DTX4	DTX4	DTX4	17964	-0.34	0.042	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 ETHER LIPID METABOLISM.

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

genes ES table in pathway: KEGG ARACHIDONIC ACID 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	PLA2G4E	PLA2G4E	PLA2G4E	109	0.84	0.12	YES
2	PLA2G3	PLA2G3	PLA2G3	204	0.69	0.22	YES
3	CYP2C18	CYP2C18	CYP2C18	350	0.56	0.29	YES
4	AKR1B10	AKR1B10	AKR1B10	481	0.48	0.36	YES
5	CYP2C19	CYP2C19	CYP2C19	554	0.44	0.42	YES
6	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	782	0.37	0.46	YES
7	CYP2C9	CYP2C9	CYP2C9	1061	0.3	0.49	YES
8	ALOX15	ALOX15	ALOX15	1253	0.27	0.52	YES
9	PLA2G2F	PLA2G2F	PLA2G2F	1559	0.22	0.54	YES
10	CYP2E1	CYP2E1	CYP2E1	1566	0.22	0.57	YES
11	CYP1A2	CYP1A2	CYP1A2	1584	0.22	0.6	YES
12	CYP2J2	CYP2J2	CYP2J2	2342	0.15	0.59	NO
13	PLA2G4A	PLA2G4A	PLA2G4A	3253	0.1	0.55	NO
14	CYP3A5	CYP3A5	CYP3A5	3983	0.077	0.53	NO
15	PLA2G2D	PLA2G2D	PLA2G2D	4339	0.066	0.52	NO
16	PLA2G12A	PLA2G12A	PLA2G12A	7299	0.011	0.36	NO
17	PLA2G6	PLA2G6	PLA2G6	9298	-0.018	0.26	NO
18	PLA2G5	PLA2G5	PLA2G5	10869	-0.042	0.18	NO
19	CYP2C8	CYP2C8	CYP2C8	13858	-0.1	0.035	NO
20	PLA2G2A	PLA2G2A	PLA2G2A	14427	-0.12	0.023	NO
21	CYP3A43	CYP3A43	CYP3A43	15701	-0.17	-0.02	NO
22	CYP3A7	CYP3A7	CYP3A7	16881	-0.23	-0.048	NO
23	PLA2G1B	PLA2G1B	PLA2G1B	17432	-0.28	-0.036	NO
24	PLA2G12B	PLA2G12B	PLA2G12B	17745	-0.31	-0.0064	NO
25	PLA2G10	PLA2G10	PLA2G10	18341	-0.4	0.022	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 ARACHIDONIC ACID METABOLISM.

Figure S58. 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

genes ES table in pathway: KEGG LINOLEIC 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	CALML3	CALML3	CALML3	171	0.72	0.046	YES
2	CALML5	CALML5	CALML5	194	0.7	0.099	YES
3	NTF4	NTF4	NTF4	316	0.59	0.14	YES
4	NTRK2	NTRK2	NTRK2	531	0.46	0.16	YES
5	MAPK10	MAPK10	MAPK10	601	0.43	0.19	YES
6	NGFR	NGFR	NGFR	812	0.36	0.21	YES
7	NGFRAP1	NGFRAP1	NGFRAP1	1002	0.32	0.22	YES
8	NTF3	NTF3	NTF3	1067	0.3	0.24	YES
9	TP73	TP73	TP73	1175	0.28	0.26	YES
10	BDNF	BDNF	BDNF	1230	0.27	0.28	YES
11	RPS6KA6	RPS6KA6	RPS6KA6	1531	0.23	0.28	YES
12	IRS4	IRS4	IRS4	1902	0.19	0.27	YES
13	RPS6KA5	RPS6KA5	RPS6KA5	2145	0.17	0.27	YES
14	MAPK13	MAPK13	MAPK13	2213	0.16	0.28	YES
15	MAPK7	MAPK7	MAPK7	2517	0.14	0.28	YES
16	GAB1	GAB1	GAB1	2519	0.14	0.28	YES
17	MAP3K1	MAP3K1	MAP3K1	2560	0.14	0.29	YES
18	SORT1	SORT1	SORT1	2693	0.13	0.3	YES
19	BRAF	BRAF	BRAF	2719	0.13	0.3	YES
20	ZNF274	ZNF274	ZNF274	3013	0.12	0.3	YES
21	CSK	CSK	CSK	3030	0.11	0.31	YES
22	CAMK2B	CAMK2B	CAMK2B	3096	0.11	0.31	YES
23	NFKBIA	NFKBIA	NFKBIA	3125	0.11	0.32	YES
24	MAP3K5	MAP3K5	MAP3K5	3182	0.11	0.32	YES
25	PLCG2	PLCG2	PLCG2	3198	0.11	0.33	YES
26	BCL2	BCL2	BCL2	3292	0.1	0.33	YES
27	CAMK2A	CAMK2A	CAMK2A	3418	0.098	0.34	YES
28	RAF1	RAF1	RAF1	3808	0.083	0.32	YES
29	CRKL	CRKL	CRKL	3890	0.08	0.32	YES
30	IKBKB	IKBKB	IKBKB	4012	0.076	0.32	YES
31	AKT2	AKT2	AKT2	4172	0.071	0.32	YES
32	YWHAQ	YWHAQ	YWHAQ	4189	0.071	0.32	YES
33	MAPK11	MAPK11	MAPK11	4320	0.067	0.32	YES
34	MAP2K2	MAP2K2	MAP2K2	4335	0.067	0.33	YES
35	PIK3CA	PIK3CA	PIK3CA	4405	0.065	0.33	YES
36	RAC1	RAC1	RAC1	4425	0.065	0.33	YES
37	YWHAZ	YWHAZ	YWHAZ	4433	0.064	0.34	YES
38	SOS2	SOS2	SOS2	4471	0.064	0.34	YES
39	MAPK3	MAPK3	MAPK3	4498	0.063	0.34	YES
40	PIK3R2	PIK3R2	PIK3R2	4758	0.056	0.33	NO
41	TRAF6	TRAF6	TRAF6	4764	0.056	0.34	NO
42	CAMK2D	CAMK2D	CAMK2D	4783	0.055	0.34	NO
43	KIDINS220	KIDINS220	KIDINS220	4821	0.054	0.34	NO
44	PIK3CD	PIK3CD	PIK3CD	5038	0.049	0.33	NO
45	MAPK14	MAPK14	MAPK14	5040	0.049	0.34	NO
46	JUN	JUN	JUN	5106	0.048	0.34	NO
47	CALM1	CALM1	CALM1	5422	0.041	0.32	NO
48	MAP2K1	MAP2K1	MAP2K1	5447	0.041	0.33	NO
49	GSK3B	GSK3B	GSK3B	5503	0.04	0.33	NO
50	MAP2K5	MAP2K5	MAP2K5	5812	0.034	0.31	NO
51	PRDM4	PRDM4	PRDM4	6039	0.03	0.3	NO
52	PRKCD	PRKCD	PRKCD	6065	0.029	0.3	NO
53	RELA	RELA	RELA	6106	0.028	0.3	NO
54	BAD	BAD	BAD	6114	0.028	0.3	NO
55	MAPK1	MAPK1	MAPK1	6249	0.026	0.3	NO
56	IRAK4	IRAK4	IRAK4	6290	0.026	0.3	NO
57	SOS1	SOS1	SOS1	6416	0.024	0.3	NO
58	NFKB1	NFKB1	NFKB1	6475	0.023	0.29	NO
59	ATF4	ATF4	ATF4	6576	0.021	0.29	NO
60	MAPKAPK2	MAPKAPK2	MAPKAPK2	6589	0.021	0.29	NO
61	MAP2K7	MAP2K7	MAP2K7	6748	0.018	0.28	NO
62	RHOA	RHOA	RHOA	6760	0.018	0.28	NO
63	RPS6KA4	RPS6KA4	RPS6KA4	6783	0.018	0.28	NO
64	MAP3K3	MAP3K3	MAP3K3	6934	0.016	0.28	NO
65	CAMK2G	CAMK2G	CAMK2G	7154	0.013	0.27	NO
66	NTRK3	NTRK3	NTRK3	7246	0.012	0.26	NO
67	YWHAE	YWHAE	YWHAE	7304	0.011	0.26	NO
68	ARHGDIA	ARHGDIA	ARHGDIA	7599	0.0066	0.25	NO
69	NGF	NGF	NGF	7835	0.0031	0.23	NO
70	FOXO3	FOXO3	FOXO3	8031	0.0005	0.22	NO
71	TP53	TP53	TP53	8118	-0.00073	0.22	NO
72	GRB2	GRB2	GRB2	8128	-0.00085	0.22	NO
73	SH2B1	SH2B1	SH2B1	8156	-0.0012	0.22	NO
74	CRK	CRK	CRK	8222	-0.0022	0.21	NO
75	PSEN1	PSEN1	PSEN1	8263	-0.0027	0.21	NO
76	NFKBIB	NFKBIB	NFKBIB	8465	-0.0055	0.2	NO
77	YWHAG	YWHAG	YWHAG	8615	-0.0078	0.19	NO
78	PDK1	PDK1	PDK1	8811	-0.011	0.18	NO
79	FRS2	FRS2	FRS2	8855	-0.011	0.18	NO
80	SHC3	SHC3	SHC3	8991	-0.013	0.18	NO
81	SHC1	SHC1	SHC1	9204	-0.016	0.17	NO
82	CDC42	CDC42	CDC42	9278	-0.017	0.16	NO
83	NRAS	NRAS	NRAS	9297	-0.018	0.16	NO
84	IRAK1	IRAK1	IRAK1	9368	-0.019	0.16	NO
85	IRS2	IRS2	IRS2	9502	-0.021	0.16	NO
86	PIK3CB	PIK3CB	PIK3CB	9818	-0.026	0.14	NO
87	AKT1	AKT1	AKT1	9857	-0.026	0.14	NO
88	YWHAB	YWHAB	YWHAB	10330	-0.033	0.12	NO
89	BAX	BAX	BAX	10501	-0.036	0.11	NO
90	PTPN11	PTPN11	PTPN11	10631	-0.038	0.11	NO
91	KRAS	KRAS	KRAS	10710	-0.039	0.11	NO
92	RAP1A	RAP1A	RAP1A	10715	-0.039	0.11	NO
93	MAPK8	MAPK8	MAPK8	10848	-0.041	0.11	NO
94	RAP1B	RAP1B	RAP1B	10979	-0.044	0.1	NO
95	PIK3R3	PIK3R3	PIK3R3	11068	-0.045	0.1	NO
96	MAGED1	MAGED1	MAGED1	11315	-0.049	0.091	NO
97	MAPK12	MAPK12	MAPK12	11437	-0.052	0.089	NO
98	PLCG1	PLCG1	PLCG1	11669	-0.056	0.081	NO
99	RPS6KA3	RPS6KA3	RPS6KA3	11702	-0.056	0.083	NO
100	PIK3R1	PIK3R1	PIK3R1	11749	-0.057	0.085	NO
101	IRAK2	IRAK2	IRAK2	11782	-0.058	0.088	NO
102	ABL1	ABL1	ABL1	12402	-0.07	0.06	NO
103	RPS6KA2	RPS6KA2	RPS6KA2	12480	-0.071	0.061	NO
104	MAPK9	MAPK9	MAPK9	12828	-0.078	0.049	NO
105	ARHGDIB	ARHGDIB	ARHGDIB	12926	-0.081	0.05	NO
106	FASLG	FASLG	FASLG	13107	-0.085	0.047	NO
107	YWHAH	YWHAH	YWHAH	13108	-0.085	0.053	NO
108	SH2B2	SH2B2	SH2B2	13222	-0.087	0.054	NO
109	CALM2	CALM2	CALM2	13228	-0.087	0.06	NO
110	NTRK1	NTRK1	NTRK1	13327	-0.09	0.062	NO
111	CALM3	CALM3	CALM3	13394	-0.092	0.066	NO
112	RPS6KA1	RPS6KA1	RPS6KA1	13399	-0.092	0.072	NO
113	RAPGEF1	RAPGEF1	RAPGEF1	13546	-0.096	0.072	NO
114	IRS1	IRS1	IRS1	13610	-0.098	0.076	NO
115	CAMK4	CAMK4	CAMK4	14290	-0.12	0.049	NO
116	RIPK2	RIPK2	RIPK2	14999	-0.14	0.021	NO
117	PIK3CG	PIK3CG	PIK3CG	15902	-0.18	-0.014	NO
118	PIK3R5	PIK3R5	PIK3R5	16452	-0.21	-0.027	NO
119	AKT3	AKT3	AKT3	16541	-0.21	-0.016	NO
120	NFKBIE	NFKBIE	NFKBIE	16833	-0.23	-0.013	NO
121	CALML6	CALML6	CALML6	16883	-0.23	0.0021	NO
122	SHC4	SHC4	SHC4	17679	-0.3	-0.017	NO
123	SHC2	SHC2	SHC2	17697	-0.3	0.0052	NO
124	IRAK3	IRAK3	IRAK3	17905	-0.33	0.02	NO
125	SH2B3	SH2B3	SH2B3	17938	-0.33	0.044	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 LINOLEIC ACID METABOLISM.

Figure S60. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LINOLEIC 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 AGR PATHWAY	35	genes.ES.table	0.43	1.4	0.091	0.22	0.98	0.26	0.2	0.21	0.18	0
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.43	1.8	0.011	0.24	0.41	0.062	0.021	0.061	0	0.068
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.57	1.7	0.039	0.2	0.6	0.21	0.14	0.18	0.091	0.033
BIOCARTA BIOPEPTIDES PATHWAY	41	genes.ES.table	0.4	1.4	0.11	0.23	0.98	0.098	0.062	0.092	0.19	0
BIOCARTA HDAC PATHWAY	26	genes.ES.table	0.57	1.7	0.013	0.25	0.54	0.58	0.34	0.38	0.11	0.058
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.45	1.6	0.053	0.17	0.73	0.37	0.34	0.24	0.095	0.017
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.41	1.3	0.19	0.25	0.99	0.15	0.18	0.12	0.21	0.001
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.58	1.8	0.0038	0.23	0.3	0.24	0.16	0.2	0	0.063
BIOCARTA FMLP PATHWAY	35	genes.ES.table	0.4	1.4	0.13	0.23	0.98	0.31	0.29	0.22	0.19	0
BIOCARTA GH PATHWAY	25	genes.ES.table	0.54	1.6	0.026	0.18	0.73	0.16	0.045	0.15	0.099	0.019

genes ES table in pathway: BIOCARTA AGR 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	IGF1	IGF1	IGF1	161	0.84	0.096	YES
2	RPS6KA6	RPS6KA6	RPS6KA6	369	0.72	0.18	YES
3	FIGF	FIGF	FIGF	647	0.62	0.24	YES
4	PIK3CG	PIK3CG	PIK3CG	840	0.57	0.3	YES
5	PIK3R5	PIK3R5	PIK3R5	893	0.56	0.36	YES
6	PRKAA2	PRKAA2	PRKAA2	1277	0.49	0.4	YES
7	AKT3	AKT3	AKT3	1399	0.47	0.46	YES
8	CAB39L	CAB39L	CAB39L	2561	0.32	0.44	YES
9	VEGFC	VEGFC	VEGFC	2671	0.31	0.47	YES
10	PIK3R1	PIK3R1	PIK3R1	2844	0.29	0.49	YES
11	PIK3CD	PIK3CD	PIK3CD	2972	0.28	0.52	YES
12	ULK2	ULK2	ULK2	4048	0.2	0.49	NO
13	RPS6KA2	RPS6KA2	RPS6KA2	4721	0.16	0.47	NO
14	VEGFB	VEGFB	VEGFB	5350	0.12	0.45	NO
15	PIK3R3	PIK3R3	PIK3R3	5653	0.11	0.45	NO
16	BRAF	BRAF	BRAF	5935	0.1	0.45	NO
17	PIK3CA	PIK3CA	PIK3CA	6353	0.09	0.44	NO
18	RICTOR	RICTOR	RICTOR	7097	0.067	0.41	NO
19	STRADA	STRADA	STRADA	7510	0.056	0.39	NO
20	EIF4B	EIF4B	EIF4B	8133	0.041	0.36	NO
21	AKT2	AKT2	AKT2	8181	0.04	0.37	NO
22	ULK1	ULK1	ULK1	8307	0.037	0.36	NO
23	TSC2	TSC2	TSC2	8449	0.034	0.36	NO
24	RPS6	RPS6	RPS6	8794	0.027	0.35	NO
25	TSC1	TSC1	TSC1	8831	0.027	0.35	NO
26	RPS6KB1	RPS6KB1	RPS6KB1	9371	0.016	0.32	NO
27	RPS6KA3	RPS6KA3	RPS6KA3	9385	0.016	0.32	NO
28	MTOR	MTOR	MTOR	9525	0.013	0.32	NO
29	RPTOR	RPTOR	RPTOR	9654	0.011	0.31	NO
30	PIK3CB	PIK3CB	PIK3CB	9678	0.011	0.31	NO
31	RHEB	RHEB	RHEB	9980	0.0055	0.3	NO
32	PDPK1	PDPK1	PDPK1	10265	-0.00038	0.28	NO
33	MAPK1	MAPK1	MAPK1	10795	-0.0096	0.25	NO
34	PRKAA1	PRKAA1	PRKAA1	10976	-0.013	0.24	NO
35	EIF4E	EIF4E	EIF4E	11306	-0.019	0.23	NO
36	CAB39	CAB39	CAB39	11395	-0.02	0.23	NO
37	STK11	STK11	STK11	12303	-0.037	0.18	NO
38	HIF1A	HIF1A	HIF1A	12605	-0.042	0.17	NO
39	AKT1	AKT1	AKT1	12804	-0.046	0.17	NO
40	RPS6KA1	RPS6KA1	RPS6KA1	12919	-0.049	0.17	NO
41	PIK3R2	PIK3R2	PIK3R2	12942	-0.049	0.17	NO
42	EIF4E2	EIF4E2	EIF4E2	13966	-0.07	0.13	NO
43	ULK3	ULK3	ULK3	14208	-0.076	0.12	NO
44	MAPK3	MAPK3	MAPK3	14344	-0.08	0.13	NO
45	DDIT4	DDIT4	DDIT4	14743	-0.09	0.12	NO
46	MLST8	MLST8	MLST8	15406	-0.11	0.094	NO
47	RPS6KB2	RPS6KB2	RPS6KB2	16389	-0.15	0.061	NO
48	VEGFA	VEGFA	VEGFA	17736	-0.26	0.022	NO
49	EIF4EBP1	EIF4EBP1	EIF4EBP1	17749	-0.26	0.053	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 AGR PATHWAY.

Figure S62. 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 AT1R 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	RXRG	RXRG	RXRG	333	0.74	0.073	YES
2	PRKCB	PRKCB	PRKCB	391	0.71	0.16	YES
3	PIK3CG	PIK3CG	PIK3CG	840	0.57	0.2	YES
4	RARB	RARB	RARB	870	0.57	0.27	YES
5	PIK3R5	PIK3R5	PIK3R5	893	0.56	0.34	YES
6	AKT3	AKT3	AKT3	1399	0.47	0.37	YES
7	FHIT	FHIT	FHIT	1995	0.38	0.39	YES
8	PLCG2	PLCG2	PLCG2	2269	0.35	0.41	YES
9	PIK3R1	PIK3R1	PIK3R1	2844	0.29	0.42	YES
10	PIK3CD	PIK3CD	PIK3CD	2972	0.28	0.45	YES
11	RASSF5	RASSF5	RASSF5	3107	0.27	0.47	YES
12	PLCG1	PLCG1	PLCG1	5651	0.11	0.35	NO
13	PIK3R3	PIK3R3	PIK3R3	5653	0.11	0.36	NO
14	BRAF	BRAF	BRAF	5935	0.1	0.36	NO
15	PRKCG	PRKCG	PRKCG	6126	0.097	0.36	NO
16	PIK3CA	PIK3CA	PIK3CA	6353	0.09	0.36	NO
17	SOS2	SOS2	SOS2	6660	0.079	0.36	NO
18	STK4	STK4	STK4	6672	0.079	0.36	NO
19	PRKCA	PRKCA	PRKCA	7865	0.047	0.31	NO
20	FOXO3	FOXO3	FOXO3	7909	0.046	0.31	NO
21	AKT2	AKT2	AKT2	8181	0.04	0.3	NO
22	CASP9	CASP9	CASP9	8240	0.039	0.3	NO
23	SOS1	SOS1	SOS1	8280	0.038	0.3	NO
24	TP53	TP53	TP53	8629	0.031	0.29	NO
25	RASSF1	RASSF1	RASSF1	8680	0.03	0.29	NO
26	RXRB	RXRB	RXRB	9002	0.023	0.28	NO
27	RB1	RB1	RB1	9467	0.014	0.25	NO
28	RAF1	RAF1	RAF1	9478	0.014	0.26	NO
29	PIK3CB	PIK3CB	PIK3CB	9678	0.011	0.25	NO
30	EGF	EGF	EGF	10119	0.0024	0.22	NO
31	PDPK1	PDPK1	PDPK1	10265	-0.00038	0.22	NO
32	GRB2	GRB2	GRB2	10703	-0.0078	0.19	NO
33	MAPK1	MAPK1	MAPK1	10795	-0.0096	0.19	NO
34	EGFR	EGFR	EGFR	11089	-0.015	0.18	NO
35	KRAS	KRAS	KRAS	11141	-0.016	0.17	NO
36	BAD	BAD	BAD	11441	-0.021	0.16	NO
37	CCND1	CCND1	CCND1	12468	-0.04	0.11	NO
38	E2F3	E2F3	E2F3	12555	-0.041	0.11	NO
39	AKT1	AKT1	AKT1	12804	-0.046	0.1	NO
40	PIK3R2	PIK3R2	PIK3R2	12942	-0.049	0.1	NO
41	RXRA	RXRA	RXRA	13493	-0.059	0.08	NO
42	MAP2K2	MAP2K2	MAP2K2	13520	-0.06	0.086	NO
43	ARAF	ARAF	ARAF	13643	-0.063	0.087	NO
44	MAP2K1	MAP2K1	MAP2K1	13918	-0.069	0.081	NO
45	NRAS	NRAS	NRAS	13950	-0.07	0.088	NO
46	CDK6	CDK6	CDK6	14045	-0.072	0.092	NO
47	MAPK3	MAPK3	MAPK3	14344	-0.08	0.085	NO
48	CDK4	CDK4	CDK4	15176	-0.1	0.054	NO
49	E2F2	E2F2	E2F2	15752	-0.12	0.038	NO
50	HRAS	HRAS	HRAS	16464	-0.16	0.02	NO
51	ERBB2	ERBB2	ERBB2	17534	-0.24	-0.0082	NO
52	TGFA	TGFA	TGFA	17854	-0.28	0.0087	NO
53	CDKN2A	CDKN2A	CDKN2A	18136	-0.32	0.033	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 AT1R PATHWAY.

Figure S64. 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 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	ZBTB16	ZBTB16	ZBTB16	47	0.97	0.098	YES
2	FLT3	FLT3	FLT3	112	0.89	0.19	YES
3	RUNX1T1	RUNX1T1	RUNX1T1	233	0.79	0.26	YES
4	PIK3CG	PIK3CG	PIK3CG	840	0.57	0.29	YES
5	KIT	KIT	KIT	847	0.57	0.35	YES
6	PIK3R5	PIK3R5	PIK3R5	893	0.56	0.4	YES
7	AKT3	AKT3	AKT3	1399	0.47	0.42	YES
8	SPI1	SPI1	SPI1	1789	0.41	0.45	YES
9	LEF1	LEF1	LEF1	2235	0.35	0.46	YES
10	PIK3R1	PIK3R1	PIK3R1	2844	0.29	0.46	YES
11	TCF7L1	TCF7L1	TCF7L1	2886	0.29	0.48	YES
12	PIK3CD	PIK3CD	PIK3CD	2972	0.28	0.51	YES
13	PIM2	PIM2	PIM2	4221	0.18	0.46	NO
14	TCF7	TCF7	TCF7	4925	0.14	0.44	NO
15	STAT5B	STAT5B	STAT5B	4933	0.14	0.45	NO
16	STAT5A	STAT5A	STAT5A	4956	0.14	0.47	NO
17	PIK3R3	PIK3R3	PIK3R3	5653	0.11	0.44	NO
18	IKBKB	IKBKB	IKBKB	5771	0.11	0.45	NO
19	RUNX1	RUNX1	RUNX1	5836	0.11	0.45	NO
20	BRAF	BRAF	BRAF	5935	0.1	0.46	NO
21	PIK3CA	PIK3CA	PIK3CA	6353	0.09	0.45	NO
22	SOS2	SOS2	SOS2	6660	0.079	0.44	NO
23	PIM1	PIM1	PIM1	6965	0.07	0.43	NO
24	NFKB1	NFKB1	NFKB1	7549	0.055	0.4	NO
25	AKT2	AKT2	AKT2	8181	0.04	0.37	NO
26	SOS1	SOS1	SOS1	8280	0.038	0.37	NO
27	RARA	RARA	RARA	8377	0.036	0.37	NO
28	PML	PML	PML	8641	0.031	0.36	NO
29	RPS6KB1	RPS6KB1	RPS6KB1	9371	0.016	0.32	NO
30	RAF1	RAF1	RAF1	9478	0.014	0.32	NO
31	MTOR	MTOR	MTOR	9525	0.013	0.32	NO
32	PIK3CB	PIK3CB	PIK3CB	9678	0.011	0.31	NO
33	STAT3	STAT3	STAT3	9679	0.011	0.31	NO
34	GRB2	GRB2	GRB2	10703	-0.0078	0.26	NO
35	MAPK1	MAPK1	MAPK1	10795	-0.0096	0.25	NO
36	KRAS	KRAS	KRAS	11141	-0.016	0.24	NO
37	BAD	BAD	BAD	11441	-0.021	0.22	NO
38	IKBKG	IKBKG	IKBKG	11619	-0.024	0.22	NO
39	CCNA1	CCNA1	CCNA1	11684	-0.025	0.22	NO
40	RELA	RELA	RELA	11726	-0.026	0.22	NO
41	CCND1	CCND1	CCND1	12468	-0.04	0.18	NO
42	AKT1	AKT1	AKT1	12804	-0.046	0.17	NO
43	PIK3R2	PIK3R2	PIK3R2	12942	-0.049	0.16	NO
44	CHUK	CHUK	CHUK	13284	-0.055	0.15	NO
45	MYC	MYC	MYC	13405	-0.058	0.15	NO
46	TCF7L2	TCF7L2	TCF7L2	13494	-0.059	0.15	NO
47	MAP2K2	MAP2K2	MAP2K2	13520	-0.06	0.16	NO
48	ARAF	ARAF	ARAF	13643	-0.063	0.16	NO
49	MAP2K1	MAP2K1	MAP2K1	13918	-0.069	0.15	NO
50	NRAS	NRAS	NRAS	13950	-0.07	0.16	NO
51	CEBPA	CEBPA	CEBPA	13969	-0.07	0.16	NO
52	MAPK3	MAPK3	MAPK3	14344	-0.08	0.15	NO
53	RPS6KB2	RPS6KB2	RPS6KB2	16389	-0.15	0.057	NO
54	HRAS	HRAS	HRAS	16464	-0.16	0.07	NO
55	JUP	JUP	JUP	17581	-0.24	0.035	NO
56	EIF4EBP1	EIF4EBP1	EIF4EBP1	17749	-0.26	0.053	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 BCR PATHWAY.

Figure S66. 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 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	SLC2A4	SLC2A4	SLC2A4	183	0.82	0.062	YES
2	RXRG	RXRG	RXRG	333	0.74	0.12	YES
3	ACSL6	ACSL6	ACSL6	613	0.62	0.16	YES
4	PRKCQ	PRKCQ	PRKCQ	777	0.59	0.2	YES
5	MAPK10	MAPK10	MAPK10	804	0.58	0.25	YES
6	LEPR	LEPR	LEPR	1267	0.49	0.27	YES
7	PRKAA2	PRKAA2	PRKAA2	1277	0.49	0.31	YES
8	IRS4	IRS4	IRS4	1363	0.48	0.35	YES
9	AKT3	AKT3	AKT3	1399	0.47	0.39	YES
10	POMC	POMC	POMC	1520	0.45	0.42	YES
11	ACACB	ACACB	ACACB	1560	0.44	0.46	YES
12	ADIPOQ	ADIPOQ	ADIPOQ	1823	0.41	0.48	YES
13	CPT1C	CPT1C	CPT1C	2114	0.37	0.49	YES
14	CD36	CD36	CD36	2236	0.35	0.52	YES
15	PPARGC1A	PPARGC1A	PPARGC1A	2733	0.3	0.52	YES
16	AGRP	AGRP	AGRP	3465	0.24	0.5	YES
17	IRS2	IRS2	IRS2	3542	0.23	0.52	YES
18	TNFRSF1B	TNFRSF1B	TNFRSF1B	3601	0.23	0.53	YES
19	PRKAG2	PRKAG2	PRKAG2	4321	0.18	0.51	NO
20	JAK2	JAK2	JAK2	4387	0.17	0.52	NO
21	ACSL1	ACSL1	ACSL1	5262	0.13	0.49	NO
22	SOCS3	SOCS3	SOCS3	5281	0.13	0.5	NO
23	IKBKB	IKBKB	IKBKB	5771	0.11	0.48	NO
24	ACSL4	ACSL4	ACSL4	6239	0.094	0.46	NO
25	NPY	NPY	NPY	6948	0.071	0.43	NO
26	CPT1B	CPT1B	CPT1B	7269	0.062	0.42	NO
27	NFKB1	NFKB1	NFKB1	7549	0.055	0.41	NO
28	PRKAB2	PRKAB2	PRKAB2	8023	0.044	0.39	NO
29	AKT2	AKT2	AKT2	8181	0.04	0.38	NO
30	PPARA	PPARA	PPARA	8524	0.033	0.37	NO
31	RXRB	RXRB	RXRB	9002	0.023	0.34	NO
32	TRADD	TRADD	TRADD	9147	0.02	0.34	NO
33	MAPK9	MAPK9	MAPK9	9152	0.02	0.34	NO
34	MTOR	MTOR	MTOR	9525	0.013	0.32	NO
35	IRS1	IRS1	IRS1	9563	0.013	0.32	NO
36	CAMKK2	CAMKK2	CAMKK2	9661	0.011	0.32	NO
37	STAT3	STAT3	STAT3	9679	0.011	0.32	NO
38	CAMKK1	CAMKK1	CAMKK1	9715	0.01	0.31	NO
39	NFKBIA	NFKBIA	NFKBIA	9733	0.0098	0.31	NO
40	PTPN11	PTPN11	PTPN11	9953	0.0061	0.3	NO
41	ADIPOR1	ADIPOR1	ADIPOR1	10746	-0.0087	0.26	NO
42	CPT1A	CPT1A	CPT1A	10844	-0.01	0.26	NO
43	PRKAA1	PRKAA1	PRKAA1	10976	-0.013	0.25	NO
44	TRAF2	TRAF2	TRAF2	11344	-0.02	0.23	NO
45	IKBKG	IKBKG	IKBKG	11619	-0.024	0.22	NO
46	RELA	RELA	RELA	11726	-0.026	0.22	NO
47	PRKAG1	PRKAG1	PRKAG1	11730	-0.026	0.22	NO
48	ACSL5	ACSL5	ACSL5	12087	-0.033	0.2	NO
49	PRKAB1	PRKAB1	PRKAB1	12172	-0.035	0.2	NO
50	STK11	STK11	STK11	12303	-0.037	0.2	NO
51	PCK2	PCK2	PCK2	12485	-0.04	0.19	NO
52	TNFRSF1A	TNFRSF1A	TNFRSF1A	12548	-0.041	0.19	NO
53	AKT1	AKT1	AKT1	12804	-0.046	0.18	NO
54	ADIPOR2	ADIPOR2	ADIPOR2	12926	-0.049	0.18	NO
55	PCK1	PCK1	PCK1	12959	-0.049	0.18	NO
56	ACSL3	ACSL3	ACSL3	13144	-0.052	0.18	NO
57	CHUK	CHUK	CHUK	13284	-0.055	0.18	NO
58	NFKBIE	NFKBIE	NFKBIE	13285	-0.055	0.18	NO
59	RXRA	RXRA	RXRA	13493	-0.059	0.17	NO
60	TNF	TNF	TNF	13916	-0.069	0.16	NO
61	MAPK8	MAPK8	MAPK8	14183	-0.076	0.15	NO
62	NFKBIB	NFKBIB	NFKBIB	15717	-0.12	0.078	NO
63	LEP	LEP	LEP	17008	-0.19	0.026	NO
64	SLC2A1	SLC2A1	SLC2A1	17069	-0.2	0.04	NO
65	G6PC	G6PC	G6PC	17913	-0.28	0.02	NO
66	G6PC2	G6PC2	G6PC2	17939	-0.29	0.043	NO

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

Figure S68. 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 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	FCER1A	FCER1A	FCER1A	247	0.78	0.12	YES
2	PRKCB	PRKCB	PRKCB	391	0.71	0.23	YES
3	BTK	BTK	BTK	507	0.66	0.33	YES
4	PIK3CG	PIK3CG	PIK3CG	840	0.57	0.41	YES
5	VAV1	VAV1	VAV1	939	0.55	0.49	YES
6	NFATC4	NFATC4	NFATC4	2414	0.34	0.47	YES
7	NFATC2	NFATC2	NFATC2	2693	0.3	0.51	YES
8	PIK3R1	PIK3R1	PIK3R1	2844	0.29	0.55	YES
9	FCER1G	FCER1G	FCER1G	3098	0.27	0.58	YES
10	NFATC1	NFATC1	NFATC1	3959	0.2	0.56	NO
11	MAP3K1	MAP3K1	MAP3K1	5193	0.13	0.52	NO
12	PPP3CC	PPP3CC	PPP3CC	5426	0.12	0.53	NO
13	PLCG1	PLCG1	PLCG1	5651	0.11	0.54	NO
14	PPP3CB	PPP3CB	PPP3CB	6116	0.098	0.53	NO
15	NFATC3	NFATC3	NFATC3	6320	0.091	0.53	NO
16	PIK3CA	PIK3CA	PIK3CA	6353	0.09	0.54	NO
17	SYK	SYK	SYK	8175	0.04	0.45	NO
18	SOS1	SOS1	SOS1	8280	0.038	0.45	NO
19	PPP3CA	PPP3CA	PPP3CA	8430	0.035	0.45	NO
20	FOS	FOS	FOS	8556	0.032	0.45	NO
21	RAF1	RAF1	RAF1	9478	0.014	0.4	NO
22	MAP2K7	MAP2K7	MAP2K7	9501	0.014	0.4	NO
23	JUN	JUN	JUN	9662	0.011	0.4	NO
24	CALM2	CALM2	CALM2	9814	0.0086	0.39	NO
25	CALM1	CALM1	CALM1	10109	0.0025	0.38	NO
26	PAK2	PAK2	PAK2	10216	0.00054	0.37	NO
27	GRB2	GRB2	GRB2	10703	-0.0078	0.34	NO
28	ELK1	ELK1	ELK1	10780	-0.0093	0.34	NO
29	MAPK1	MAPK1	MAPK1	10795	-0.0096	0.34	NO
30	SHC1	SHC1	SHC1	11026	-0.014	0.33	NO
31	LYN	LYN	LYN	11085	-0.015	0.33	NO
32	MAP2K4	MAP2K4	MAP2K4	11334	-0.019	0.32	NO
33	CALM3	CALM3	CALM3	11681	-0.025	0.31	NO
34	MAP2K1	MAP2K1	MAP2K1	13918	-0.069	0.2	NO
35	MAPK8	MAPK8	MAPK8	14183	-0.076	0.2	NO
36	MAPK3	MAPK3	MAPK3	14344	-0.08	0.2	NO
37	PLA2G4A	PLA2G4A	PLA2G4A	17029	-0.19	0.092	NO

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

Figure S70. 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 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	CPEB1	CPEB1	CPEB1	81	0.92	0.054	YES
2	ADCY5	ADCY5	ADCY5	102	0.9	0.11	YES
3	PGR	PGR	PGR	129	0.87	0.16	YES
4	IGF1	IGF1	IGF1	161	0.84	0.22	YES
5	ADCY2	ADCY2	ADCY2	335	0.74	0.25	YES
6	RPS6KA6	RPS6KA6	RPS6KA6	369	0.72	0.3	YES
7	PDE3A	PDE3A	PDE3A	458	0.68	0.33	YES
8	MAPK10	MAPK10	MAPK10	804	0.58	0.35	YES
9	PIK3CG	PIK3CG	PIK3CG	840	0.57	0.39	YES
10	PIK3R5	PIK3R5	PIK3R5	893	0.56	0.42	YES
11	AKT3	AKT3	AKT3	1399	0.47	0.42	YES
12	ADCY4	ADCY4	ADCY4	1935	0.39	0.42	YES
13	ADCY1	ADCY1	ADCY1	2032	0.38	0.44	YES
14	PDE3B	PDE3B	PDE3B	2385	0.34	0.44	YES
15	PRKACB	PRKACB	PRKACB	2601	0.32	0.45	YES
16	PIK3R1	PIK3R1	PIK3R1	2844	0.29	0.45	YES
17	PIK3CD	PIK3CD	PIK3CD	2972	0.28	0.46	YES
18	RPS6KA2	RPS6KA2	RPS6KA2	4721	0.16	0.38	NO
19	PRKX	PRKX	PRKX	5299	0.13	0.36	NO
20	IGF1R	IGF1R	IGF1R	5601	0.12	0.35	NO
21	PIK3R3	PIK3R3	PIK3R3	5653	0.11	0.35	NO
22	GNAI2	GNAI2	GNAI2	5731	0.11	0.36	NO
23	MAPK11	MAPK11	MAPK11	5744	0.11	0.36	NO
24	ADCY9	ADCY9	ADCY9	5846	0.11	0.36	NO
25	BRAF	BRAF	BRAF	5935	0.1	0.36	NO
26	PIK3CA	PIK3CA	PIK3CA	6353	0.09	0.35	NO
27	ANAPC4	ANAPC4	ANAPC4	6854	0.074	0.32	NO
28	SPDYA	SPDYA	SPDYA	7607	0.054	0.29	NO
29	PRKACA	PRKACA	PRKACA	7844	0.048	0.28	NO
30	ADCY7	ADCY7	ADCY7	8126	0.041	0.27	NO
31	AKT2	AKT2	AKT2	8181	0.04	0.27	NO
32	ADCY3	ADCY3	ADCY3	8371	0.036	0.26	NO
33	GNAI1	GNAI1	GNAI1	8484	0.034	0.25	NO
34	ADCY8	ADCY8	ADCY8	8835	0.027	0.24	NO
35	CDC27	CDC27	CDC27	9136	0.02	0.22	NO
36	MAPK9	MAPK9	MAPK9	9152	0.02	0.22	NO
37	ADCY6	ADCY6	ADCY6	9359	0.016	0.21	NO
38	RPS6KA3	RPS6KA3	RPS6KA3	9385	0.016	0.21	NO
39	RAF1	RAF1	RAF1	9478	0.014	0.21	NO
40	PIK3CB	PIK3CB	PIK3CB	9678	0.011	0.2	NO
41	CDC23	CDC23	CDC23	9813	0.0086	0.19	NO
42	ANAPC10	ANAPC10	ANAPC10	10040	0.0042	0.18	NO
43	MAPK12	MAPK12	MAPK12	10411	-0.0029	0.16	NO
44	ANAPC1	ANAPC1	ANAPC1	10418	-0.003	0.16	NO
45	MAPK14	MAPK14	MAPK14	10545	-0.0052	0.15	NO
46	CDC16	CDC16	CDC16	10662	-0.0072	0.15	NO
47	MAPK1	MAPK1	MAPK1	10795	-0.0096	0.14	NO
48	KRAS	KRAS	KRAS	11141	-0.016	0.12	NO
49	FZR1	FZR1	FZR1	11269	-0.018	0.12	NO
50	ANAPC2	ANAPC2	ANAPC2	11627	-0.024	0.1	NO
51	CCNA1	CCNA1	CCNA1	11684	-0.025	0.099	NO
52	ANAPC5	ANAPC5	ANAPC5	12574	-0.042	0.054	NO
53	ANAPC7	ANAPC7	ANAPC7	12670	-0.044	0.052	NO
54	ANAPC13	ANAPC13	ANAPC13	12765	-0.046	0.05	NO
55	GNAI3	GNAI3	GNAI3	12802	-0.046	0.051	NO
56	AKT1	AKT1	AKT1	12804	-0.046	0.054	NO
57	RPS6KA1	RPS6KA1	RPS6KA1	12919	-0.049	0.05	NO
58	PIK3R2	PIK3R2	PIK3R2	12942	-0.049	0.052	NO
59	CCNB3	CCNB3	CCNB3	13481	-0.059	0.027	NO
60	ARAF	ARAF	ARAF	13643	-0.063	0.022	NO
61	MAP2K1	MAP2K1	MAP2K1	13918	-0.069	0.012	NO
62	MAPK8	MAPK8	MAPK8	14183	-0.076	0.0028	NO
63	MAPK3	MAPK3	MAPK3	14344	-0.08	-0.00073	NO
64	MAD2L2	MAD2L2	MAD2L2	14366	-0.08	0.0032	NO
65	ANAPC11	ANAPC11	ANAPC11	14764	-0.091	-0.012	NO
66	BUB1	BUB1	BUB1	14939	-0.097	-0.016	NO
67	MAD2L1	MAD2L1	MAD2L1	14987	-0.098	-0.012	NO
68	HSP90AA1	HSP90AA1	HSP90AA1	15059	-0.1	-0.0095	NO
69	CDK2	CDK2	CDK2	15128	-0.1	-0.0067	NO
70	CCNA2	CCNA2	CCNA2	15904	-0.13	-0.04	NO
71	CDK1	CDK1	CDK1	16249	-0.15	-0.049	NO
72	CCNB1	CCNB1	CCNB1	16847	-0.18	-0.07	NO
73	MAPK13	MAPK13	MAPK13	16866	-0.18	-0.059	NO
74	CDC25B	CDC25B	CDC25B	16883	-0.18	-0.049	NO
75	CCNB2	CCNB2	CCNB2	16911	-0.18	-0.038	NO
76	PLK1	PLK1	PLK1	17236	-0.21	-0.043	NO
77	CDC25C	CDC25C	CDC25C	17452	-0.23	-0.04	NO
78	CDC25A	CDC25A	CDC25A	17601	-0.25	-0.032	NO
79	PKMYT1	PKMYT1	PKMYT1	17640	-0.25	-0.018	NO
80	SPDYC	SPDYC	SPDYC	18024	-0.3	-0.02	NO
81	CDC26	CDC26	CDC26	18301	-0.35	-0.012	NO
82	PRKACG	PRKACG	PRKACG	18721	-0.58	0.0014	NO

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

Figure S72. 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 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	PRKCB	PRKCB	PRKCB	391	0.71	0.2	YES
2	AGTR1	AGTR1	AGTR1	393	0.71	0.43	YES
3	MEF2A	MEF2A	MEF2A	4775	0.15	0.24	NO
4	MAP3K1	MAP3K1	MAP3K1	5193	0.13	0.26	NO
5	ATF2	ATF2	ATF2	5402	0.12	0.29	NO
6	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	5677	0.11	0.31	NO
7	MEF2D	MEF2D	MEF2D	6198	0.095	0.31	NO
8	AGT	AGT	AGT	6867	0.073	0.3	NO
9	GNAQ	GNAQ	GNAQ	7247	0.063	0.3	NO
10	PRKCA	PRKCA	PRKCA	7865	0.047	0.28	NO
11	SOS1	SOS1	SOS1	8280	0.038	0.27	NO
12	PTK2B	PTK2B	PTK2B	9258	0.018	0.22	NO
13	RAF1	RAF1	RAF1	9478	0.014	0.21	NO
14	JUN	JUN	JUN	9662	0.011	0.21	NO
15	CALM2	CALM2	CALM2	9814	0.0086	0.2	NO
16	CALM1	CALM1	CALM1	10109	0.0025	0.19	NO
17	GRB2	GRB2	GRB2	10703	-0.0078	0.16	NO
18	ELK1	ELK1	ELK1	10780	-0.0093	0.16	NO
19	MAPK1	MAPK1	MAPK1	10795	-0.0096	0.16	NO
20	PTK2	PTK2	PTK2	10930	-0.012	0.16	NO
21	SHC1	SHC1	SHC1	11026	-0.014	0.15	NO
22	EGFR	EGFR	EGFR	11089	-0.015	0.16	NO
23	MAP2K4	MAP2K4	MAP2K4	11334	-0.019	0.15	NO
24	CALM3	CALM3	CALM3	11681	-0.025	0.14	NO
25	MAP2K2	MAP2K2	MAP2K2	13520	-0.06	0.059	NO
26	MAP2K1	MAP2K1	MAP2K1	13918	-0.069	0.059	NO
27	MAPK8	MAPK8	MAPK8	14183	-0.076	0.069	NO
28	MAPK3	MAPK3	MAPK3	14344	-0.08	0.086	NO
29	PAK1	PAK1	PAK1	14405	-0.081	0.11	NO
30	RAC1	RAC1	RAC1	15579	-0.12	0.082	NO
31	SRC	SRC	SRC	15621	-0.12	0.12	NO
32	HRAS	HRAS	HRAS	16464	-0.16	0.12	NO

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

Figure S74. 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 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	CADM3	CADM3	CADM3	17	1.1	0.022	YES
2	NRXN1	NRXN1	NRXN1	35	0.99	0.042	YES
3	NRXN3	NRXN3	NRXN3	94	0.91	0.059	YES
4	JAM2	JAM2	JAM2	135	0.87	0.075	YES
5	NEGR1	NEGR1	NEGR1	159	0.84	0.092	YES
6	NRXN2	NRXN2	NRXN2	196	0.81	0.11	YES
7	ITGA8	ITGA8	ITGA8	213	0.8	0.12	YES
8	NCAM1	NCAM1	NCAM1	221	0.8	0.14	YES
9	ITGA9	ITGA9	ITGA9	225	0.8	0.16	YES
10	CLDN11	CLDN11	CLDN11	248	0.78	0.17	YES
11	NLGN3	NLGN3	NLGN3	265	0.77	0.19	YES
12	CNTN2	CNTN2	CNTN2	285	0.76	0.2	YES
13	CD28	CD28	CD28	328	0.74	0.22	YES
14	SELP	SELP	SELP	351	0.73	0.23	YES
15	CDH2	CDH2	CDH2	370	0.72	0.25	YES
16	NLGN1	NLGN1	NLGN1	398	0.71	0.26	YES
17	SELL	SELL	SELL	484	0.67	0.27	YES
18	CD226	CD226	CD226	499	0.67	0.28	YES
19	NFASC	NFASC	NFASC	545	0.65	0.29	YES
20	SPN	SPN	SPN	565	0.64	0.31	YES
21	MPZ	MPZ	MPZ	586	0.63	0.32	YES
22	HLA-DOA	HLA-DOA	HLA-DOA	631	0.62	0.33	YES
23	HLA-DQA2	HLA-DQA2	HLA-DQA2	706	0.6	0.34	YES
24	ITGAL	ITGAL	ITGAL	739	0.59	0.35	YES
25	NCAM2	NCAM2	NCAM2	748	0.59	0.36	YES
26	CD22	CD22	CD22	761	0.59	0.37	YES
27	SIGLEC1	SIGLEC1	SIGLEC1	787	0.58	0.38	YES
28	CD8A	CD8A	CD8A	920	0.56	0.39	YES
29	NLGN4X	NLGN4X	NLGN4X	950	0.55	0.4	YES
30	CD2	CD2	CD2	958	0.55	0.41	YES
31	ITGAM	ITGAM	ITGAM	989	0.54	0.42	YES
32	ICOS	ICOS	ICOS	1006	0.54	0.43	YES
33	JAM3	JAM3	JAM3	1008	0.54	0.44	YES
34	CTLA4	CTLA4	CTLA4	1037	0.53	0.45	YES
35	PTPRC	PTPRC	PTPRC	1041	0.53	0.46	YES
36	HLA-DOB	HLA-DOB	HLA-DOB	1100	0.52	0.47	YES
37	CD80	CD80	CD80	1137	0.52	0.48	YES
38	CD8B	CD8B	CD8B	1148	0.52	0.49	YES
39	CNTN1	CNTN1	CNTN1	1160	0.51	0.5	YES
40	CADM1	CADM1	CADM1	1185	0.51	0.51	YES
41	HLA-DQA1	HLA-DQA1	HLA-DQA1	1225	0.5	0.52	YES
42	PDCD1LG2	PDCD1LG2	PDCD1LG2	1270	0.49	0.53	YES
43	CLDN5	CLDN5	CLDN5	1416	0.47	0.53	YES
44	CD40LG	CD40LG	CD40LG	1506	0.45	0.54	YES
45	CD6	CD6	CD6	1538	0.45	0.54	YES
46	ITGB2	ITGB2	ITGB2	1589	0.44	0.55	YES
47	CDH4	CDH4	CDH4	1593	0.44	0.56	YES
48	CD4	CD4	CD4	1598	0.44	0.57	YES
49	CD86	CD86	CD86	1599	0.44	0.58	YES
50	PDCD1	PDCD1	PDCD1	1643	0.43	0.59	YES
51	SELE	SELE	SELE	1644	0.43	0.6	YES
52	VCAM1	VCAM1	VCAM1	1645	0.43	0.6	YES
53	ITGB7	ITGB7	ITGB7	1669	0.43	0.61	YES
54	ICAM2	ICAM2	ICAM2	1723	0.42	0.62	YES
55	CNTNAP1	CNTNAP1	CNTNAP1	1746	0.42	0.63	YES
56	ITGA4	ITGA4	ITGA4	1803	0.41	0.63	YES
57	HLA-DPB1	HLA-DPB1	HLA-DPB1	1885	0.4	0.64	YES
58	HLA-DMB	HLA-DMB	HLA-DMB	1917	0.39	0.64	YES
59	SELPLG	SELPLG	SELPLG	1999	0.38	0.65	YES
60	CD40	CD40	CD40	2034	0.38	0.65	YES
61	PTPRM	PTPRM	PTPRM	2050	0.38	0.66	YES
62	HLA-DPA1	HLA-DPA1	HLA-DPA1	2241	0.35	0.66	YES
63	HLA-DQB1	HLA-DQB1	HLA-DQB1	2275	0.35	0.66	YES
64	CLDN16	CLDN16	CLDN16	2405	0.34	0.66	YES
65	NLGN2	NLGN2	NLGN2	2421	0.33	0.67	YES
66	CD34	CD34	CD34	2535	0.32	0.67	YES
67	PECAM1	PECAM1	PECAM1	2564	0.32	0.68	YES
68	L1CAM	L1CAM	L1CAM	2790	0.3	0.67	YES
69	CLDN20	CLDN20	CLDN20	2932	0.28	0.67	YES
70	CDH5	CDH5	CDH5	2976	0.28	0.67	YES
71	SDC2	SDC2	SDC2	3045	0.27	0.68	YES
72	HLA-DRA	HLA-DRA	HLA-DRA	3127	0.26	0.68	YES
73	VCAN	VCAN	VCAN	3308	0.25	0.67	YES
74	HLA-DMA	HLA-DMA	HLA-DMA	3311	0.25	0.68	YES
75	CD274	CD274	CD274	3319	0.25	0.68	YES
76	HLA-DRB1	HLA-DRB1	HLA-DRB1	3437	0.24	0.68	YES
77	ICAM3	ICAM3	ICAM3	3494	0.24	0.68	YES
78	HLA-DRB5	HLA-DRB5	HLA-DRB5	3849	0.21	0.67	NO
79	SDC3	SDC3	SDC3	3866	0.21	0.67	NO
80	CLDN8	CLDN8	CLDN8	4513	0.17	0.64	NO
81	ICOSLG	ICOSLG	ICOSLG	4927	0.14	0.62	NO
82	HLA-F	HLA-F	HLA-F	5486	0.12	0.59	NO
83	ITGAV	ITGAV	ITGAV	5491	0.12	0.6	NO
84	ICAM1	ICAM1	ICAM1	5542	0.12	0.6	NO
85	ESAM	ESAM	ESAM	5641	0.11	0.59	NO
86	NEO1	NEO1	NEO1	5693	0.11	0.59	NO
87	CNTNAP2	CNTNAP2	CNTNAP2	5824	0.11	0.59	NO
88	MADCAM1	MADCAM1	MADCAM1	5971	0.1	0.58	NO
89	HLA-G	HLA-G	HLA-G	5996	0.1	0.58	NO
90	ALCAM	ALCAM	ALCAM	6144	0.097	0.58	NO
91	HLA-E	HLA-E	HLA-E	6170	0.096	0.58	NO
92	CD99	CD99	CD99	6396	0.088	0.57	NO
93	NRCAM	NRCAM	NRCAM	6461	0.086	0.57	NO
94	CD58	CD58	CD58	8067	0.043	0.48	NO
95	GLG1	GLG1	GLG1	8113	0.042	0.48	NO
96	HLA-B	HLA-B	HLA-B	8435	0.035	0.46	NO
97	CLDN1	CLDN1	CLDN1	8458	0.034	0.46	NO
98	ITGB8	ITGB8	ITGB8	8825	0.027	0.44	NO
99	ITGB1	ITGB1	ITGB1	8867	0.026	0.44	NO
100	HLA-C	HLA-C	HLA-C	9219	0.019	0.42	NO
101	PVRL3	PVRL3	PVRL3	9537	0.013	0.41	NO
102	HLA-A	HLA-A	HLA-A	10157	0.0017	0.37	NO
103	MPZL1	MPZL1	MPZL1	12061	-0.032	0.27	NO
104	CDH15	CDH15	CDH15	12124	-0.034	0.27	NO
105	CLDN15	CLDN15	CLDN15	12269	-0.036	0.26	NO
106	PTPRF	PTPRF	PTPRF	13240	-0.054	0.21	NO
107	CLDN10	CLDN10	CLDN10	13295	-0.055	0.21	NO
108	SDC4	SDC4	SDC4	13970	-0.07	0.18	NO
109	CLDN14	CLDN14	CLDN14	14142	-0.075	0.17	NO
110	ITGA6	ITGA6	ITGA6	14453	-0.082	0.15	NO
111	CD276	CD276	CD276	14714	-0.089	0.14	NO
112	F11R	F11R	F11R	14828	-0.093	0.14	NO
113	MAG	MAG	MAG	15039	-0.099	0.13	NO
114	CLDN19	CLDN19	CLDN19	15095	-0.1	0.13	NO
115	CLDN9	CLDN9	CLDN9	15518	-0.12	0.11	NO
116	PVRL2	PVRL2	PVRL2	15813	-0.13	0.093	NO
117	CDH1	CDH1	CDH1	15874	-0.13	0.093	NO
118	CLDN18	CLDN18	CLDN18	15876	-0.13	0.096	NO
119	PVRL1	PVRL1	PVRL1	16256	-0.15	0.078	NO
120	CDH3	CDH3	CDH3	16503	-0.16	0.068	NO
121	CLDN23	CLDN23	CLDN23	16524	-0.16	0.071	NO
122	SDC1	SDC1	SDC1	16656	-0.17	0.068	NO
123	CLDN17	CLDN17	CLDN17	16937	-0.19	0.056	NO
124	CLDN2	CLDN2	CLDN2	17378	-0.22	0.038	NO
125	CLDN3	CLDN3	CLDN3	17426	-0.23	0.04	NO
126	OCLN	OCLN	OCLN	17582	-0.24	0.037	NO
127	CLDN4	CLDN4	CLDN4	17823	-0.27	0.03	NO
128	CLDN7	CLDN7	CLDN7	18411	-0.38	0.0063	NO
129	CLDN6	CLDN6	CLDN6	18706	-0.55	0.0023	NO

Figure S75. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FCER1 PATHWAY.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA FMLP PATHWAY

Table 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	NTRK3	NTRK3	NTRK3	231	0.79	0.036	YES
2	RPS6KA6	RPS6KA6	RPS6KA6	369	0.72	0.073	YES
3	NGFR	NGFR	NGFR	541	0.65	0.1	YES
4	MAPK10	MAPK10	MAPK10	804	0.58	0.12	YES
5	CAMK4	CAMK4	CAMK4	828	0.58	0.16	YES
6	PIK3CG	PIK3CG	PIK3CG	840	0.57	0.19	YES
7	PIK3R5	PIK3R5	PIK3R5	893	0.56	0.23	YES
8	BCL2	BCL2	BCL2	1028	0.54	0.25	YES
9	IRS4	IRS4	IRS4	1363	0.48	0.26	YES
10	AKT3	AKT3	AKT3	1399	0.47	0.29	YES
11	SHC4	SHC4	SHC4	2159	0.36	0.27	YES
12	PLCG2	PLCG2	PLCG2	2269	0.35	0.29	YES
13	FASLG	FASLG	FASLG	2484	0.33	0.3	YES
14	NGF	NGF	NGF	2673	0.31	0.3	YES
15	PIK3R1	PIK3R1	PIK3R1	2844	0.29	0.31	YES
16	ARHGDIB	ARHGDIB	ARHGDIB	2910	0.29	0.33	YES
17	PIK3CD	PIK3CD	PIK3CD	2972	0.28	0.34	YES
18	NTRK2	NTRK2	NTRK2	3259	0.25	0.34	YES
19	RPS6KA5	RPS6KA5	RPS6KA5	3280	0.25	0.36	YES
20	IRS2	IRS2	IRS2	3542	0.23	0.36	YES
21	MAP3K3	MAP3K3	MAP3K3	3604	0.23	0.37	YES
22	NTF3	NTF3	NTF3	3882	0.21	0.36	YES
23	GAB1	GAB1	GAB1	3901	0.21	0.38	YES
24	NGFRAP1	NGFRAP1	NGFRAP1	3908	0.21	0.39	YES
25	CALML6	CALML6	CALML6	3942	0.2	0.4	YES
26	SHC2	SHC2	SHC2	3955	0.2	0.41	YES
27	SH2B2	SH2B2	SH2B2	4354	0.18	0.4	YES
28	CAMK2B	CAMK2B	CAMK2B	4501	0.17	0.4	YES
29	RPS6KA2	RPS6KA2	RPS6KA2	4721	0.16	0.4	YES
30	CAMK2A	CAMK2A	CAMK2A	4791	0.15	0.4	YES
31	SH2B3	SH2B3	SH2B3	4867	0.15	0.41	YES
32	RAP1A	RAP1A	RAP1A	5063	0.14	0.41	YES
33	NTRK1	NTRK1	NTRK1	5139	0.13	0.41	YES
34	MAP3K1	MAP3K1	MAP3K1	5193	0.13	0.42	YES
35	TP73	TP73	TP73	5237	0.13	0.42	YES
36	RAPGEF1	RAPGEF1	RAPGEF1	5276	0.13	0.43	YES
37	PLCG1	PLCG1	PLCG1	5651	0.11	0.42	YES
38	PIK3R3	PIK3R3	PIK3R3	5653	0.11	0.42	YES
39	MAPK11	MAPK11	MAPK11	5744	0.11	0.42	YES
40	IKBKB	IKBKB	IKBKB	5771	0.11	0.43	YES
41	IRAK3	IRAK3	IRAK3	5879	0.1	0.43	YES
42	BRAF	BRAF	BRAF	5935	0.1	0.43	YES
43	CALML5	CALML5	CALML5	6070	0.099	0.43	YES
44	SH2B1	SH2B1	SH2B1	6248	0.093	0.43	YES
45	CAMK2G	CAMK2G	CAMK2G	6315	0.091	0.43	YES
46	PIK3CA	PIK3CA	PIK3CA	6353	0.09	0.43	YES
47	ABL1	ABL1	ABL1	6357	0.09	0.44	YES
48	SOS2	SOS2	SOS2	6660	0.079	0.43	NO
49	ZNF274	ZNF274	ZNF274	6711	0.078	0.43	NO
50	NTF4	NTF4	NTF4	6725	0.077	0.43	NO
51	IRAK4	IRAK4	IRAK4	7145	0.066	0.42	NO
52	TRAF6	TRAF6	TRAF6	7337	0.06	0.41	NO
53	CAMK2D	CAMK2D	CAMK2D	7454	0.058	0.41	NO
54	NFKB1	NFKB1	NFKB1	7549	0.055	0.4	NO
55	MAP3K5	MAP3K5	MAP3K5	7585	0.054	0.41	NO
56	FOXO3	FOXO3	FOXO3	7909	0.046	0.39	NO
57	AKT2	AKT2	AKT2	8181	0.04	0.38	NO
58	SOS1	SOS1	SOS1	8280	0.038	0.38	NO
59	TP53	TP53	TP53	8629	0.031	0.36	NO
60	MAP2K5	MAP2K5	MAP2K5	8660	0.03	0.36	NO
61	FRS2	FRS2	FRS2	8752	0.028	0.36	NO
62	KIDINS220	KIDINS220	KIDINS220	8895	0.026	0.35	NO
63	MAGED1	MAGED1	MAGED1	8994	0.024	0.35	NO
64	MAPK9	MAPK9	MAPK9	9152	0.02	0.34	NO
65	PDK1	PDK1	PDK1	9242	0.018	0.34	NO
66	RPS6KA3	RPS6KA3	RPS6KA3	9385	0.016	0.33	NO
67	CALML3	CALML3	CALML3	9435	0.015	0.33	NO
68	RAF1	RAF1	RAF1	9478	0.014	0.33	NO
69	MAP2K7	MAP2K7	MAP2K7	9501	0.014	0.33	NO
70	ATF4	ATF4	ATF4	9543	0.013	0.32	NO
71	IRS1	IRS1	IRS1	9563	0.013	0.32	NO
72	SORT1	SORT1	SORT1	9564	0.013	0.33	NO
73	JUN	JUN	JUN	9662	0.011	0.32	NO
74	PIK3CB	PIK3CB	PIK3CB	9678	0.011	0.32	NO
75	NFKBIA	NFKBIA	NFKBIA	9733	0.0098	0.32	NO
76	CALM2	CALM2	CALM2	9814	0.0086	0.32	NO
77	MAPKAPK2	MAPKAPK2	MAPKAPK2	9853	0.0079	0.31	NO
78	RHOA	RHOA	RHOA	9864	0.0078	0.31	NO
79	PTPN11	PTPN11	PTPN11	9953	0.0061	0.31	NO
80	CALM1	CALM1	CALM1	10109	0.0025	0.3	NO
81	RAP1B	RAP1B	RAP1B	10405	-0.0028	0.28	NO
82	MAPK12	MAPK12	MAPK12	10411	-0.0029	0.28	NO
83	MAPK14	MAPK14	MAPK14	10545	-0.0052	0.28	NO
84	CRK	CRK	CRK	10638	-0.0066	0.27	NO
85	GRB2	GRB2	GRB2	10703	-0.0078	0.27	NO
86	MAPK1	MAPK1	MAPK1	10795	-0.0096	0.27	NO
87	SHC1	SHC1	SHC1	11026	-0.014	0.26	NO
88	KRAS	KRAS	KRAS	11141	-0.016	0.25	NO
89	MAPK7	MAPK7	MAPK7	11202	-0.017	0.25	NO
90	YWHAH	YWHAH	YWHAH	11423	-0.021	0.24	NO
91	BAD	BAD	BAD	11441	-0.021	0.24	NO
92	CDC42	CDC42	CDC42	11541	-0.023	0.23	NO
93	CALM3	CALM3	CALM3	11681	-0.025	0.23	NO
94	RELA	RELA	RELA	11726	-0.026	0.23	NO
95	YWHAB	YWHAB	YWHAB	11767	-0.027	0.23	NO
96	CRKL	CRKL	CRKL	12288	-0.037	0.2	NO
97	GSK3B	GSK3B	GSK3B	12467	-0.04	0.19	NO
98	AKT1	AKT1	AKT1	12804	-0.046	0.18	NO
99	PRDM4	PRDM4	PRDM4	12809	-0.046	0.18	NO
100	RPS6KA1	RPS6KA1	RPS6KA1	12919	-0.049	0.18	NO
101	PIK3R2	PIK3R2	PIK3R2	12942	-0.049	0.18	NO
102	CSK	CSK	CSK	13111	-0.052	0.17	NO
103	YWHAQ	YWHAQ	YWHAQ	13127	-0.052	0.18	NO
104	NFKBIE	NFKBIE	NFKBIE	13285	-0.055	0.17	NO
105	SHC3	SHC3	SHC3	13467	-0.059	0.16	NO
106	MAP2K2	MAP2K2	MAP2K2	13520	-0.06	0.17	NO
107	RIPK2	RIPK2	RIPK2	13672	-0.064	0.16	NO
108	YWHAE	YWHAE	YWHAE	13877	-0.068	0.16	NO
109	MAP2K1	MAP2K1	MAP2K1	13918	-0.069	0.16	NO
110	PSEN1	PSEN1	PSEN1	13937	-0.07	0.16	NO
111	NRAS	NRAS	NRAS	13950	-0.07	0.16	NO
112	BAX	BAX	BAX	14021	-0.072	0.16	NO
113	MAPK8	MAPK8	MAPK8	14183	-0.076	0.16	NO
114	MAPK3	MAPK3	MAPK3	14344	-0.08	0.16	NO
115	PRKCD	PRKCD	PRKCD	14419	-0.081	0.16	NO
116	YWHAG	YWHAG	YWHAG	14592	-0.086	0.15	NO
117	IRAK1	IRAK1	IRAK1	14673	-0.088	0.16	NO
118	ARHGDIA	ARHGDIA	ARHGDIA	14674	-0.088	0.16	NO
119	BDNF	BDNF	BDNF	14967	-0.097	0.15	NO
120	YWHAZ	YWHAZ	YWHAZ	15217	-0.1	0.14	NO
121	RAC1	RAC1	RAC1	15579	-0.12	0.13	NO
122	NFKBIB	NFKBIB	NFKBIB	15717	-0.12	0.13	NO
123	IRAK2	IRAK2	IRAK2	16262	-0.15	0.11	NO
124	RPS6KA4	RPS6KA4	RPS6KA4	16754	-0.18	0.096	NO
125	MAPK13	MAPK13	MAPK13	16866	-0.18	0.1	NO

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

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

genes ES table in pathway: BIOCARTA GH PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IGF1	IGF1	IGF1	161	0.84	0.21	YES
2	PIK3CG	PIK3CG	PIK3CG	840	0.57	0.32	YES
3	NFATC2	NFATC2	NFATC2	2693	0.3	0.3	YES
4	PIK3R1	PIK3R1	PIK3R1	2844	0.29	0.37	YES
5	CAMK1	CAMK1	CAMK1	3455	0.24	0.4	YES
6	CAMK1G	CAMK1G	CAMK1G	3509	0.24	0.45	YES
7	NFATC1	NFATC1	NFATC1	3959	0.2	0.48	YES
8	MEF2A	MEF2A	MEF2A	4775	0.15	0.48	YES
9	PPP3CC	PPP3CC	PPP3CC	5426	0.12	0.47	YES
10	IGF1R	IGF1R	IGF1R	5601	0.12	0.49	YES
11	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	5677	0.11	0.52	YES
12	PPP3CB	PPP3CB	PPP3CB	6116	0.098	0.52	YES
13	MEF2D	MEF2D	MEF2D	6198	0.095	0.54	YES
14	PIK3CA	PIK3CA	PIK3CA	6353	0.09	0.55	YES
15	HDAC5	HDAC5	HDAC5	6440	0.087	0.57	YES
16	INSR	INSR	INSR	7961	0.045	0.5	NO
17	CABIN1	CABIN1	CABIN1	8071	0.043	0.51	NO
18	PPP3CA	PPP3CA	PPP3CA	8430	0.035	0.5	NO
19	CALM2	CALM2	CALM2	9814	0.0086	0.42	NO
20	CALM1	CALM1	CALM1	10109	0.0025	0.41	NO
21	MAPK14	MAPK14	MAPK14	10545	-0.0052	0.39	NO
22	MAPK7	MAPK7	MAPK7	11202	-0.017	0.36	NO
23	YWHAH	YWHAH	YWHAH	11423	-0.021	0.35	NO
24	CALM3	CALM3	CALM3	11681	-0.025	0.34	NO
25	AKT1	AKT1	AKT1	12804	-0.046	0.3	NO
26	MAP2K6	MAP2K6	MAP2K6	14577	-0.086	0.22	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Methods & Data

Input

Gene set database = c2.cp.v3.0-2.symbols.gmt
Expression data file = ESCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = ESCA-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)

Made with Nozzle