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

Thymoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in THYM-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1K35SS3

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 THYM-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: 193
Number of samples: 120
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 ] 46
pheno.type: 2 - 4 :[ clus2 ] 31
pheno.type: 3 - 4 :[ clus3 ] 29
pheno.type: 4 - 4 :[ clus4 ] 14

For the expression subtypes of 18301 genes in 121 samples, GSEA found enriched gene sets in each cluster using 120 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA CARM ER PATHWAY, KEGG CITRATE CYCLE TCA CYCLE, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS, KEGG PYRIMIDINE METABOLISM, KEGG STARCH AND SUCROSE METABOLISM, KEGG GLYCEROLIPID METABOLISM, KEGG BUTANOATE METABOLISM, KEGG DRUG METABOLISM OTHER ENZYMES, KEGG DNA REPLICATION

And common core enriched genes are PDHA1, RPA3, RPA4, ACAT2, ACSM1, ACSM3, AKR1B10, ALDH5A1, ALDH9A1, BDH1

clus2

Top enriched gene sets are BIOCARTA TCR PATHWAY, BIOCARTA WNT PATHWAY, KEGG OXIDATIVE PHOSPHORYLATION, KEGG PYRIMIDINE METABOLISM, KEGG RIBOSOME, KEGG RNA DEGRADATION, KEGG RNA POLYMERASE, KEGG DNA REPLICATION, KEGG SPLICEOSOME, KEGG PROTEASOME

And common core enriched genes are LSM2, LSM3, LSM4, LSM5, LSM7, NAA38, FAU, MRPL13, RPL10, RPL10A

clus3

Top enriched gene sets are BIOCARTA AGR PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA EDG1 PATHWAY, KEGG N GLYCAN BIOSYNTHESIS, KEGG O GLYCAN BIOSYNTHESIS, KEGG WNT SIGNALING PATHWAY, KEGG TGF BETA SIGNALING PATHWAY, KEGG AXON GUIDANCE, KEGG FOCAL ADHESION, KEGG ECM RECEPTOR INTERACTION

And common core enriched genes are ACTN3, ITGA1, ITGA10, ITGA2, ITGA2B, ITGA3, ITGA6, ITGA8, ITGA9, ITGAV

clus4

Top enriched gene sets are BIOCARTA FMLP PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA DEATH PATHWAY, KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG ARGININE AND PROLINE METABOLISM, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG ETHER LIPID METABOLISM, KEGG ARACHIDONIC ACID METABOLISM, KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM

And common core enriched genes are IL1B, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA

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 CARM ER PATHWAY	34	genes.ES.table	0.39	1.4	0.14	0.83	0.95	0.41	0.32	0.28	0.69	0.34
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.53	1.7	0.054	0.54	0.5	0.62	0.31	0.43	0.26	0.19
KEGG FRUCTOSE AND MANNOSE METABOLISM	33	genes.ES.table	0.4	1.3	0.22	0.86	0.99	0.15	0.11	0.14	0.79	0.35
KEGG STEROID HORMONE BIOSYNTHESIS	36	genes.ES.table	0.51	1.2	0.17	0.84	0.99	0.36	0.13	0.31	0.78	0.35
KEGG PYRIMIDINE METABOLISM	97	genes.ES.table	0.32	1.3	0.22	0.91	0.99	0.44	0.34	0.3	0.84	0.39
KEGG STARCH AND SUCROSE METABOLISM	31	genes.ES.table	0.49	1.5	0.047	1	0.9	0.26	0.11	0.23	0.76	0.41
KEGG GLYCEROLIPID METABOLISM	45	genes.ES.table	0.38	1.3	0.12	1	0.99	0.2	0.13	0.17	0.89	0.44
KEGG BUTANOATE METABOLISM	30	genes.ES.table	0.56	1.7	0.02	1	0.48	0.43	0.21	0.34	0	0.35
KEGG DRUG METABOLISM OTHER ENZYMES	34	genes.ES.table	0.45	1.3	0.15	0.97	0.99	0.24	0.098	0.21	0.88	0.42
KEGG DNA REPLICATION	35	genes.ES.table	0.66	1.4	0.14	0.91	0.91	0.77	0.28	0.56	0.69	0.36

genes ES table in pathway: BIOCARTA CARM ER 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	AKR1B10	AKR1B10	AKR1B10	5	1.5	0.24	YES
2	HMGCS2	HMGCS2	HMGCS2	41	1	0.4	YES
3	ACSM1	ACSM1	ACSM1	447	0.46	0.45	YES
4	ACSM3	ACSM3	ACSM3	1255	0.3	0.45	YES
5	BDH1	BDH1	BDH1	1668	0.25	0.47	YES
6	ALDH5A1	ALDH5A1	ALDH5A1	1844	0.24	0.5	YES
7	OXCT1	OXCT1	OXCT1	1984	0.22	0.53	YES
8	ALDH9A1	ALDH9A1	ALDH9A1	2147	0.21	0.55	YES
9	L2HGDH	L2HGDH	L2HGDH	2916	0.16	0.53	YES
10	HADH	HADH	HADH	3284	0.14	0.53	YES
11	OXCT2	OXCT2	OXCT2	3616	0.12	0.54	YES
12	ACAT2	ACAT2	ACAT2	3767	0.12	0.55	YES
13	PDHA1	PDHA1	PDHA1	3834	0.11	0.56	YES
14	ACAT1	ACAT1	ACAT1	4304	0.099	0.55	NO
15	ACADS	ACADS	ACADS	4909	0.082	0.53	NO
16	HMGCL	HMGCL	HMGCL	6258	0.055	0.46	NO
17	ALDH1B1	ALDH1B1	ALDH1B1	6656	0.047	0.45	NO
18	PDHB	PDHB	PDHB	6781	0.045	0.45	NO
19	ECHS1	ECHS1	ECHS1	7364	0.036	0.42	NO
20	HADHA	HADHA	HADHA	7702	0.029	0.41	NO
21	BDH2	BDH2	BDH2	8872	0.01	0.35	NO
22	AACS	AACS	AACS	10511	-0.02	0.26	NO
23	ABAT	ABAT	ABAT	10699	-0.023	0.26	NO
24	HMGCS1	HMGCS1	HMGCS1	11374	-0.039	0.22	NO
25	GAD1	GAD1	GAD1	12393	-0.068	0.18	NO
26	ALDH7A1	ALDH7A1	ALDH7A1	12874	-0.085	0.17	NO
27	ALDH2	ALDH2	ALDH2	14256	-0.15	0.12	NO
28	ACSM5	ACSM5	ACSM5	14867	-0.19	0.11	NO
29	GAD2	GAD2	GAD2	15302	-0.22	0.12	NO
30	ALDH3A2	ALDH3A2	ALDH3A2	15567	-0.25	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 CARM ER PATHWAY.

Figure S2. 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: KEGG CITRATE CYCLE TCA CYCLE

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	OGDHL	OGDHL	OGDHL	319	0.53	0.14	YES
2	PCK1	PCK1	PCK1	587	0.42	0.24	YES
3	ACO1	ACO1	ACO1	2258	0.2	0.21	YES
4	IDH3A	IDH3A	IDH3A	2327	0.19	0.26	YES
5	IDH2	IDH2	IDH2	2537	0.18	0.3	YES
6	FH	FH	FH	3071	0.15	0.31	YES
7	ACO2	ACO2	ACO2	3251	0.14	0.34	YES
8	DLD	DLD	DLD	3275	0.14	0.38	YES
9	SDHC	SDHC	SDHC	3707	0.12	0.39	YES
10	OGDH	OGDH	OGDH	3724	0.12	0.43	YES
11	SDHA	SDHA	SDHA	3821	0.11	0.46	YES
12	PDHA1	PDHA1	PDHA1	3834	0.11	0.49	YES
13	MDH2	MDH2	MDH2	4339	0.098	0.49	YES
14	SDHD	SDHD	SDHD	4736	0.087	0.49	YES
15	MDH1	MDH1	MDH1	4759	0.087	0.52	YES
16	SDHB	SDHB	SDHB	5077	0.079	0.52	YES
17	DLST	DLST	DLST	5514	0.07	0.52	YES
18	SUCLG1	SUCLG1	SUCLG1	5589	0.068	0.53	YES
19	IDH3G	IDH3G	IDH3G	6317	0.054	0.51	NO
20	PDHB	PDHB	PDHB	6781	0.045	0.5	NO
21	CS	CS	CS	7111	0.04	0.49	NO
22	IDH3B	IDH3B	IDH3B	7161	0.039	0.5	NO
23	DLAT	DLAT	DLAT	7929	0.026	0.46	NO
24	ACLY	ACLY	ACLY	8545	0.016	0.43	NO
25	SUCLG2	SUCLG2	SUCLG2	9983	-0.0098	0.36	NO
26	SUCLA2	SUCLA2	SUCLA2	11224	-0.035	0.3	NO
27	PCK2	PCK2	PCK2	11641	-0.045	0.29	NO
28	IDH1	IDH1	IDH1	11881	-0.052	0.29	NO
29	PC	PC	PC	15032	-0.2	0.18	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: KEGG CITRATE CYCLE TCA CYCLE.

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

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	RPA4	RPA4	RPA4	264	0.58	0.14	YES
2	POLE2	POLE2	POLE2	1474	0.27	0.14	YES
3	GTF2H2	GTF2H2	GTF2H2	1639	0.25	0.2	YES
4	CDK7	CDK7	CDK7	2754	0.16	0.19	YES
5	RPA3	RPA3	RPA3	2996	0.15	0.21	YES
6	RFC4	RFC4	RFC4	3076	0.15	0.25	YES
7	PCNA	PCNA	PCNA	3347	0.13	0.27	YES
8	POLE4	POLE4	POLE4	3505	0.13	0.29	YES
9	GTF2H5	GTF2H5	GTF2H5	3645	0.12	0.32	YES
10	RFC5	RFC5	RFC5	4256	0.1	0.31	YES
11	RBX1	RBX1	RBX1	4310	0.098	0.34	YES
12	MNAT1	MNAT1	MNAT1	4418	0.096	0.36	YES
13	POLE3	POLE3	POLE3	4546	0.092	0.37	YES
14	POLE	POLE	POLE	4588	0.091	0.39	YES
15	POLD1	POLD1	POLD1	4774	0.086	0.41	YES
16	RFC3	RFC3	RFC3	4825	0.085	0.43	YES
17	CCNH	CCNH	CCNH	4988	0.081	0.44	YES
18	LIG1	LIG1	LIG1	5010	0.08	0.46	YES
19	ERCC4	ERCC4	ERCC4	5285	0.075	0.46	YES
20	XPA	XPA	XPA	5621	0.067	0.46	YES
21	RFC2	RFC2	RFC2	5757	0.065	0.47	YES
22	POLD4	POLD4	POLD4	6398	0.052	0.45	NO
23	POLD2	POLD2	POLD2	6625	0.048	0.45	NO
24	CUL4B	CUL4B	CUL4B	6971	0.042	0.44	NO
25	DDB2	DDB2	DDB2	7193	0.038	0.44	NO
26	ERCC3	ERCC3	ERCC3	7537	0.032	0.43	NO
27	ERCC5	ERCC5	ERCC5	7622	0.031	0.44	NO
28	POLD3	POLD3	POLD3	7667	0.03	0.44	NO
29	ERCC1	ERCC1	ERCC1	8026	0.024	0.43	NO
30	RPA2	RPA2	RPA2	8068	0.023	0.43	NO
31	GTF2H4	GTF2H4	GTF2H4	8525	0.016	0.41	NO
32	ERCC6	ERCC6	ERCC6	9314	0.0029	0.37	NO
33	RFC1	RFC1	RFC1	9463	0.00036	0.36	NO
34	RAD23A	RAD23A	RAD23A	9622	-0.0028	0.35	NO
35	RPA1	RPA1	RPA1	9892	-0.0079	0.34	NO
36	ERCC2	ERCC2	ERCC2	10091	-0.012	0.33	NO
37	ERCC8	ERCC8	ERCC8	10235	-0.014	0.33	NO
38	CUL4A	CUL4A	CUL4A	10430	-0.018	0.32	NO
39	CETN2	CETN2	CETN2	11359	-0.038	0.28	NO
40	XPC	XPC	XPC	12146	-0.061	0.26	NO
41	GTF2H1	GTF2H1	GTF2H1	12622	-0.075	0.25	NO
42	DDB1	DDB1	DDB1	12666	-0.077	0.27	NO
43	GTF2H3	GTF2H3	GTF2H3	14289	-0.15	0.22	NO

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

Figure S6. 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 STEROID HORMONE BIOSYNTHESIS

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	RPA4	RPA4	RPA4	264	0.58	0.14	YES
2	RAD54B	RAD54B	RAD54B	647	0.4	0.23	YES
3	RAD51L1	RAD51L1	RAD51L1	1538	0.26	0.25	YES
4	RAD54L	RAD54L	RAD54L	1608	0.26	0.31	YES
5	RAD51	RAD51	RAD51	1717	0.25	0.37	YES
6	BLM	BLM	BLM	1807	0.24	0.43	YES
7	XRCC2	XRCC2	XRCC2	2215	0.2	0.46	YES
8	EME1	EME1	EME1	2217	0.2	0.52	YES
9	RPA3	RPA3	RPA3	2996	0.15	0.52	YES
10	SHFM1	SHFM1	SHFM1	3282	0.14	0.54	YES
11	RAD51L3	RAD51L3	RAD51L3	3420	0.13	0.56	YES
12	SSBP1	SSBP1	SSBP1	3473	0.13	0.59	YES
13	XRCC3	XRCC3	XRCC3	3907	0.11	0.6	YES
14	BRCA2	BRCA2	BRCA2	3998	0.11	0.62	YES
15	TOP3B	TOP3B	TOP3B	4205	0.1	0.64	YES
16	POLD1	POLD1	POLD1	4774	0.086	0.63	NO
17	MUS81	MUS81	MUS81	5392	0.073	0.62	NO
18	TOP3A	TOP3A	TOP3A	6040	0.059	0.6	NO
19	POLD4	POLD4	POLD4	6398	0.052	0.59	NO
20	POLD2	POLD2	POLD2	6625	0.048	0.59	NO
21	POLD3	POLD3	POLD3	7667	0.03	0.54	NO
22	RPA2	RPA2	RPA2	8068	0.023	0.53	NO
23	RAD50	RAD50	RAD50	9473	0.00026	0.45	NO
24	MRE11A	MRE11A	MRE11A	9552	-0.0016	0.45	NO
25	RPA1	RPA1	RPA1	9892	-0.0079	0.43	NO
26	NBN	NBN	NBN	10307	-0.016	0.41	NO
27	RAD52	RAD52	RAD52	13085	-0.093	0.28	NO

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

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

genes ES table in pathway: KEGG PYRIMIDINE 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	ENPP3	ENPP3	ENPP3	12	1.3	0.18	YES
2	UGT2B7	UGT2B7	UGT2B7	80	0.86	0.3	YES
3	AMY1A	AMY1A	AMY1A	155	0.72	0.4	YES
4	AMY2A	AMY2A	AMY2A	573	0.42	0.43	YES
5	PYGM	PYGM	PYGM	1459	0.27	0.42	YES
6	UGT1A6	UGT1A6	UGT1A6	1786	0.24	0.44	YES
7	GPI	GPI	GPI	1833	0.24	0.47	YES
8	HK3	HK3	HK3	2015	0.22	0.49	YES
9	GYS1	GYS1	GYS1	3002	0.15	0.46	NO
10	AMY2B	AMY2B	AMY2B	3003	0.15	0.48	NO
11	UGP2	UGP2	UGP2	3294	0.14	0.48	NO
12	PGM2L1	PGM2L1	PGM2L1	4005	0.11	0.46	NO
13	AGL	AGL	AGL	5420	0.072	0.39	NO
14	PGM1	PGM1	PGM1	6474	0.051	0.34	NO
15	HK1	HK1	HK1	7538	0.032	0.28	NO
16	PYGB	PYGB	PYGB	8824	0.011	0.21	NO
17	HK2	HK2	HK2	9632	-0.003	0.17	NO
18	UGT1A9	UGT1A9	UGT1A9	9677	-0.004	0.17	NO
19	GUSB	GUSB	GUSB	9723	-0.0049	0.17	NO
20	GANC	GANC	GANC	9831	-0.0069	0.16	NO
21	GCK	GCK	GCK	10662	-0.022	0.12	NO
22	GAA	GAA	GAA	11072	-0.031	0.1	NO
23	PGM2	PGM2	PGM2	11657	-0.046	0.076	NO
24	ENPP1	ENPP1	ENPP1	13470	-0.11	-0.008	NO
25	GYS2	GYS2	GYS2	13513	-0.11	0.0052	NO
26	GBE1	GBE1	GBE1	14187	-0.15	-0.011	NO
27	UGDH	UGDH	UGDH	14603	-0.17	-0.01	NO
28	PYGL	PYGL	PYGL	15656	-0.26	-0.031	NO
29	UGT2B15	UGT2B15	UGT2B15	16011	-0.3	-0.0084	NO
30	MGAM	MGAM	MGAM	16837	-0.43	0.0062	NO
31	GBA3	GBA3	GBA3	17259	-0.52	0.056	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 PYRIMIDINE METABOLISM.

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

genes ES table in pathway: KEGG STARCH AND SUCROSE METABOLISM

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	RPA4	RPA4	RPA4	264	0.58	0.12	YES
2	DNA2	DNA2	DNA2	1265	0.3	0.13	YES
3	POLE2	POLE2	POLE2	1474	0.27	0.18	YES
4	RNASEH2B	RNASEH2B	RNASEH2B	2050	0.21	0.2	YES
5	MCM6	MCM6	MCM6	2347	0.19	0.23	YES
6	RNASEH2A	RNASEH2A	RNASEH2A	2797	0.16	0.24	YES
7	FEN1	FEN1	FEN1	2948	0.15	0.27	YES
8	RPA3	RPA3	RPA3	2996	0.15	0.3	YES
9	RFC4	RFC4	RFC4	3076	0.15	0.33	YES
10	PRIM1	PRIM1	PRIM1	3241	0.14	0.35	YES
11	RNASEH1	RNASEH1	RNASEH1	3341	0.13	0.38	YES
12	PCNA	PCNA	PCNA	3347	0.13	0.41	YES
13	SSBP1	SSBP1	SSBP1	3473	0.13	0.43	YES
14	POLE4	POLE4	POLE4	3505	0.13	0.46	YES
15	MCM7	MCM7	MCM7	3630	0.12	0.48	YES
16	RNASEH2C	RNASEH2C	RNASEH2C	3831	0.11	0.49	YES
17	PRIM2	PRIM2	PRIM2	4010	0.11	0.51	YES
18	MCM2	MCM2	MCM2	4061	0.11	0.53	YES
19	RFC5	RFC5	RFC5	4256	0.1	0.54	YES
20	POLA2	POLA2	POLA2	4302	0.099	0.56	YES
21	POLE3	POLE3	POLE3	4546	0.092	0.57	YES
22	POLE	POLE	POLE	4588	0.091	0.59	YES
23	MCM5	MCM5	MCM5	4643	0.09	0.6	YES
24	POLD1	POLD1	POLD1	4774	0.086	0.62	YES
25	RFC3	RFC3	RFC3	4825	0.085	0.63	YES
26	LIG1	LIG1	LIG1	5010	0.08	0.64	YES
27	MCM3	MCM3	MCM3	5027	0.08	0.66	YES
28	RFC2	RFC2	RFC2	5757	0.065	0.63	NO
29	MCM4	MCM4	MCM4	5760	0.065	0.65	NO
30	POLD4	POLD4	POLD4	6398	0.052	0.63	NO
31	POLD2	POLD2	POLD2	6625	0.048	0.62	NO
32	POLD3	POLD3	POLD3	7667	0.03	0.57	NO
33	RPA2	RPA2	RPA2	8068	0.023	0.56	NO
34	RFC1	RFC1	RFC1	9463	0.00036	0.48	NO
35	RPA1	RPA1	RPA1	9892	-0.0079	0.46	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 STARCH AND SUCROSE METABOLISM.

Figure S12. 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 GLYCEROLIPID 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	VAV3	VAV3	VAV3	165	0.7	0.038	YES
2	CD40LG	CD40LG	CD40LG	288	0.56	0.069	YES
3	CD28	CD28	CD28	539	0.43	0.084	YES
4	CHP2	CHP2	CHP2	592	0.41	0.11	YES
5	GRAP2	GRAP2	GRAP2	781	0.37	0.12	YES
6	CD3G	CD3G	CD3G	834	0.36	0.14	YES
7	ITK	ITK	ITK	901	0.35	0.16	YES
8	CD3D	CD3D	CD3D	971	0.34	0.18	YES
9	PAK7	PAK7	PAK7	975	0.34	0.21	YES
10	CD3E	CD3E	CD3E	1088	0.32	0.22	YES
11	CD247	CD247	CD247	1093	0.32	0.24	YES
12	RASGRP1	RASGRP1	RASGRP1	1262	0.3	0.25	YES
13	CD8A	CD8A	CD8A	1359	0.28	0.27	YES
14	CD8B	CD8B	CD8B	1435	0.27	0.28	YES
15	LCK	LCK	LCK	1468	0.27	0.3	YES
16	LAT	LAT	LAT	1512	0.27	0.31	YES
17	PIK3R1	PIK3R1	PIK3R1	1516	0.27	0.33	YES
18	PRKCQ	PRKCQ	PRKCQ	1544	0.26	0.35	YES
19	ICOS	ICOS	ICOS	1569	0.26	0.36	YES
20	ZAP70	ZAP70	ZAP70	1964	0.22	0.36	YES
21	PTPRC	PTPRC	PTPRC	2138	0.21	0.36	YES
22	AKT3	AKT3	AKT3	2200	0.2	0.37	YES
23	LCP2	LCP2	LCP2	2338	0.19	0.38	YES
24	PDCD1	PDCD1	PDCD1	2533	0.18	0.38	YES
25	IKBKG	IKBKG	IKBKG	2550	0.18	0.39	YES
26	CD4	CD4	CD4	2573	0.18	0.4	YES
27	IL4	IL4	IL4	2607	0.17	0.41	YES
28	NFATC3	NFATC3	NFATC3	2611	0.17	0.42	YES
29	VAV1	VAV1	VAV1	2816	0.16	0.42	YES
30	JUN	JUN	JUN	2875	0.16	0.43	YES
31	PDK1	PDK1	PDK1	2899	0.16	0.44	YES
32	PIK3R3	PIK3R3	PIK3R3	2935	0.16	0.44	YES
33	PIK3R5	PIK3R5	PIK3R5	3072	0.15	0.45	YES
34	FYN	FYN	FYN	3080	0.15	0.46	YES
35	CTLA4	CTLA4	CTLA4	3360	0.13	0.45	NO
36	PIK3CG	PIK3CG	PIK3CG	3417	0.13	0.46	NO
37	PTPN6	PTPN6	PTPN6	3579	0.12	0.46	NO
38	CARD11	CARD11	CARD11	3898	0.11	0.44	NO
39	PLCG1	PLCG1	PLCG1	4048	0.11	0.44	NO
40	PIK3CD	PIK3CD	PIK3CD	4305	0.099	0.44	NO
41	CBL	CBL	CBL	4751	0.087	0.42	NO
42	NFKBIB	NFKBIB	NFKBIB	4910	0.082	0.41	NO
43	MAP3K14	MAP3K14	MAP3K14	4933	0.082	0.42	NO
44	CHUK	CHUK	CHUK	4971	0.081	0.42	NO
45	AKT1	AKT1	AKT1	5281	0.075	0.41	NO
46	MAPK9	MAPK9	MAPK9	5295	0.075	0.41	NO
47	GSK3B	GSK3B	GSK3B	5604	0.068	0.4	NO
48	PPP3R2	PPP3R2	PPP3R2	5608	0.068	0.41	NO
49	PIK3R2	PIK3R2	PIK3R2	5892	0.062	0.4	NO
50	IL10	IL10	IL10	6344	0.053	0.37	NO
51	IL5	IL5	IL5	6352	0.053	0.38	NO
52	TEC	TEC	TEC	6460	0.051	0.37	NO
53	PPP3CC	PPP3CC	PPP3CC	6490	0.05	0.38	NO
54	NCK1	NCK1	NCK1	6534	0.05	0.38	NO
55	MAP2K1	MAP2K1	MAP2K1	6654	0.048	0.37	NO
56	NRAS	NRAS	NRAS	6801	0.045	0.37	NO
57	FOS	FOS	FOS	6986	0.042	0.36	NO
58	IKBKB	IKBKB	IKBKB	7407	0.035	0.34	NO
59	MAPK12	MAPK12	MAPK12	7573	0.032	0.33	NO
60	PAK2	PAK2	PAK2	7671	0.03	0.33	NO
61	PIK3CB	PIK3CB	PIK3CB	7695	0.03	0.33	NO
62	KRAS	KRAS	KRAS	7905	0.026	0.32	NO
63	PPP3R1	PPP3R1	PPP3R1	8009	0.024	0.32	NO
64	MAP3K7	MAP3K7	MAP3K7	8116	0.022	0.31	NO
65	PPP3CB	PPP3CB	PPP3CB	8385	0.018	0.3	NO
66	CDK4	CDK4	CDK4	8442	0.017	0.3	NO
67	RAF1	RAF1	RAF1	8578	0.015	0.29	NO
68	MAPK14	MAPK14	MAPK14	8934	0.0093	0.27	NO
69	SOS2	SOS2	SOS2	9070	0.0071	0.26	NO
70	AKT2	AKT2	AKT2	9213	0.0044	0.26	NO
71	RELA	RELA	RELA	9317	0.0028	0.25	NO
72	CDC42	CDC42	CDC42	9326	0.0027	0.25	NO
73	PAK1	PAK1	PAK1	9352	0.0023	0.25	NO
74	MAP2K2	MAP2K2	MAP2K2	9429	0.00098	0.25	NO
75	NFKB1	NFKB1	NFKB1	9539	-0.0014	0.24	NO
76	CSF2	CSF2	CSF2	9971	-0.0096	0.22	NO
77	MALT1	MALT1	MALT1	10016	-0.01	0.22	NO
78	GRB2	GRB2	GRB2	10051	-0.011	0.22	NO
79	RHOA	RHOA	RHOA	10619	-0.022	0.18	NO
80	BCL10	BCL10	BCL10	10744	-0.024	0.18	NO
81	MAP2K7	MAP2K7	MAP2K7	10975	-0.029	0.17	NO
82	MAPK11	MAPK11	MAPK11	11120	-0.032	0.16	NO
83	PPP3CA	PPP3CA	PPP3CA	11320	-0.038	0.16	NO
84	DLG1	DLG1	DLG1	11655	-0.046	0.14	NO
85	MAPK13	MAPK13	MAPK13	11721	-0.048	0.14	NO
86	MAPK1	MAPK1	MAPK1	11892	-0.052	0.13	NO
87	CBLC	CBLC	CBLC	12034	-0.057	0.13	NO
88	PIK3CA	PIK3CA	PIK3CA	12318	-0.065	0.12	NO
89	NFKBIA	NFKBIA	NFKBIA	12520	-0.072	0.11	NO
90	CHP	CHP	CHP	12566	-0.074	0.11	NO
91	PAK4	PAK4	PAK4	12775	-0.081	0.11	NO
92	PAK3	PAK3	PAK3	12971	-0.088	0.1	NO
93	TNF	TNF	TNF	13059	-0.092	0.1	NO
94	SOS1	SOS1	SOS1	13324	-0.1	0.097	NO
95	MAPK3	MAPK3	MAPK3	13417	-0.11	0.099	NO
96	VAV2	VAV2	VAV2	13613	-0.12	0.096	NO
97	NFKBIE	NFKBIE	NFKBIE	13659	-0.12	0.1	NO
98	IL2	IL2	IL2	14146	-0.14	0.085	NO
99	IFNG	IFNG	IFNG	14265	-0.15	0.088	NO
100	NCK2	NCK2	NCK2	14332	-0.16	0.095	NO
101	NFATC1	NFATC1	NFATC1	14715	-0.18	0.086	NO
102	NFAT5	NFAT5	NFAT5	15066	-0.2	0.08	NO
103	MAP3K8	MAP3K8	MAP3K8	15155	-0.21	0.09	NO
104	CBLB	CBLB	CBLB	15454	-0.24	0.089	NO
105	PAK6	PAK6	PAK6	15720	-0.27	0.093	NO
106	NFATC2	NFATC2	NFATC2	16310	-0.34	0.083	NO
107	NFATC4	NFATC4	NFATC4	16550	-0.38	0.095	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 GLYCEROLIPID METABOLISM.

Figure S14. 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

genes ES table in pathway: KEGG BUTANOATE 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	CD40LG	CD40LG	CD40LG	288	0.56	0.064	YES
2	RAG2	RAG2	RAG2	681	0.39	0.099	YES
3	IL7R	IL7R	IL7R	844	0.36	0.14	YES
4	CD3D	CD3D	CD3D	971	0.34	0.18	YES
5	IGLL1	IGLL1	IGLL1	979	0.34	0.23	YES
6	CD79A	CD79A	CD79A	1012	0.33	0.28	YES
7	CD19	CD19	CD19	1068	0.32	0.32	YES
8	CD3E	CD3E	CD3E	1088	0.32	0.37	YES
9	TNFRSF13B	TNFRSF13B	TNFRSF13B	1099	0.32	0.41	YES
10	ADA	ADA	ADA	1252	0.3	0.44	YES
11	CD8B	CD8B	CD8B	1435	0.27	0.48	YES
12	LCK	LCK	LCK	1468	0.27	0.51	YES
13	RAG1	RAG1	RAG1	1522	0.27	0.55	YES
14	ICOS	ICOS	ICOS	1569	0.26	0.58	YES
15	IL2RG	IL2RG	IL2RG	1942	0.22	0.59	YES
16	ZAP70	ZAP70	ZAP70	1964	0.22	0.62	YES
17	PTPRC	PTPRC	PTPRC	2138	0.21	0.64	YES
18	AICDA	AICDA	AICDA	2431	0.19	0.66	YES
19	IKBKG	IKBKG	IKBKG	2550	0.18	0.67	YES
20	CD4	CD4	CD4	2573	0.18	0.7	YES
21	AIRE	AIRE	AIRE	3158	0.14	0.69	NO
22	TNFRSF13C	TNFRSF13C	TNFRSF13C	3618	0.12	0.68	NO
23	JAK3	JAK3	JAK3	5247	0.076	0.6	NO
24	RFXANK	RFXANK	RFXANK	6152	0.057	0.56	NO
25	TAP2	TAP2	TAP2	7710	0.029	0.48	NO
26	BTK	BTK	BTK	8051	0.024	0.46	NO
27	CIITA	CIITA	CIITA	8111	0.023	0.46	NO
28	RFXAP	RFXAP	RFXAP	8294	0.02	0.46	NO
29	UNG	UNG	UNG	8593	0.015	0.44	NO
30	RFX5	RFX5	RFX5	9206	0.0045	0.41	NO
31	TAP1	TAP1	TAP1	9345	0.0024	0.4	NO
32	BLNK	BLNK	BLNK	11551	-0.043	0.29	NO
33	DCLRE1C	DCLRE1C	DCLRE1C	13389	-0.1	0.2	NO
34	CD40	CD40	CD40	17033	-0.47	0.068	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 BUTANOATE METABOLISM.

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

genes ES table in pathway: KEGG DRUG METABOLISM OTHER ENZYMES

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	PPARGC1A	PPARGC1A	PPARGC1A	102	0.8	0.2	YES
2	HDAC9	HDAC9	HDAC9	461	0.46	0.3	YES
3	HIST2H3C	HIST2H3C	HIST2H3C	1418	0.28	0.32	YES
4	NR0B1	NR0B1	NR0B1	2631	0.17	0.3	YES
5	HDAC10	HDAC10	HDAC10	2680	0.17	0.34	YES
6	HDAC4	HDAC4	HDAC4	3354	0.13	0.34	YES
7	BRCA1	BRCA1	BRCA1	3430	0.13	0.37	YES
8	GRIP1	GRIP1	GRIP1	4590	0.091	0.33	YES
9	HDAC7	HDAC7	HDAC7	4659	0.089	0.35	YES
10	HDAC8	HDAC8	HDAC8	5132	0.078	0.35	YES
11	HDAC3	HDAC3	HDAC3	5241	0.076	0.36	YES
12	HDAC11	HDAC11	HDAC11	5531	0.069	0.36	YES
13	NRIP1	NRIP1	NRIP1	5636	0.067	0.38	YES
14	HDAC6	HDAC6	HDAC6	5751	0.065	0.39	YES
15	SRA1	SRA1	SRA1	6867	0.044	0.34	NO
16	ESR1	ESR1	ESR1	7154	0.039	0.33	NO
17	PHB2	PHB2	PHB2	7471	0.033	0.32	NO
18	ERCC3	ERCC3	ERCC3	7537	0.032	0.33	NO
19	HDAC1	HDAC1	HDAC1	7610	0.031	0.33	NO
20	HDAC2	HDAC2	HDAC2	7668	0.03	0.34	NO
21	GTF2E1	GTF2E1	GTF2E1	8351	0.019	0.3	NO
22	TBP	TBP	TBP	9257	0.0038	0.26	NO
23	GTF2F1	GTF2F1	GTF2F1	10013	-0.01	0.22	NO
24	PELP1	PELP1	PELP1	10645	-0.022	0.19	NO
25	NCOR2	NCOR2	NCOR2	11029	-0.03	0.18	NO
26	MED1	MED1	MED1	11228	-0.035	0.17	NO
27	CREBBP	CREBBP	CREBBP	11580	-0.044	0.17	NO
28	EP300	EP300	EP300	11775	-0.049	0.17	NO
29	POLR2A	POLR2A	POLR2A	12028	-0.057	0.17	NO
30	SPEN	SPEN	SPEN	12458	-0.07	0.16	NO
31	GTF2A1	GTF2A1	GTF2A1	12560	-0.073	0.18	NO
32	CARM1	CARM1	CARM1	12708	-0.078	0.19	NO
33	HDAC5	HDAC5	HDAC5	13728	-0.12	0.17	NO
34	CCND1	CCND1	CCND1	16076	-0.31	0.12	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 DRUG METABOLISM OTHER ENZYMES.

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

genes ES table in pathway: KEGG DNA REPLICATION

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	VAV3	VAV3	VAV3	165	0.7	0.077	YES
2	PLA2G2D	PLA2G2D	PLA2G2D	816	0.36	0.086	YES
3	MAP2K6	MAP2K6	MAP2K6	843	0.36	0.13	YES
4	IL13	IL13	IL13	1052	0.33	0.16	YES
5	PRKCB	PRKCB	PRKCB	1157	0.31	0.19	YES
6	LAT	LAT	LAT	1512	0.27	0.2	YES
7	PIK3R1	PIK3R1	PIK3R1	1516	0.27	0.24	YES
8	RAC2	RAC2	RAC2	1931	0.22	0.24	YES
9	AKT3	AKT3	AKT3	2200	0.2	0.25	YES
10	LCP2	LCP2	LCP2	2338	0.19	0.26	YES
11	IL4	IL4	IL4	2607	0.17	0.27	YES
12	PLA2G5	PLA2G5	PLA2G5	2615	0.17	0.29	YES
13	PLA2G1B	PLA2G1B	PLA2G1B	2689	0.17	0.31	YES
14	VAV1	VAV1	VAV1	2816	0.16	0.32	YES
15	PDK1	PDK1	PDK1	2899	0.16	0.34	YES
16	PIK3R3	PIK3R3	PIK3R3	2935	0.16	0.35	YES
17	PIK3R5	PIK3R5	PIK3R5	3072	0.15	0.36	YES
18	FYN	FYN	FYN	3080	0.15	0.38	YES
19	GAB2	GAB2	GAB2	3279	0.14	0.39	YES
20	PIK3CG	PIK3CG	PIK3CG	3417	0.13	0.4	YES
21	PLCG1	PLCG1	PLCG1	4048	0.11	0.38	NO
22	PIK3CD	PIK3CD	PIK3CD	4305	0.099	0.37	NO
23	AKT1	AKT1	AKT1	5281	0.075	0.33	NO
24	MAPK9	MAPK9	MAPK9	5295	0.075	0.34	NO
25	PLA2G6	PLA2G6	PLA2G6	5417	0.072	0.34	NO
26	PIK3R2	PIK3R2	PIK3R2	5892	0.062	0.32	NO
27	PLA2G2A	PLA2G2A	PLA2G2A	6189	0.056	0.31	NO
28	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	6218	0.056	0.32	NO
29	IL5	IL5	IL5	6352	0.053	0.32	NO
30	SYK	SYK	SYK	6561	0.049	0.31	NO
31	MAP2K1	MAP2K1	MAP2K1	6654	0.048	0.31	NO
32	NRAS	NRAS	NRAS	6801	0.045	0.31	NO
33	MAP2K3	MAP2K3	MAP2K3	7075	0.04	0.3	NO
34	MAPK12	MAPK12	MAPK12	7573	0.032	0.28	NO
35	PIK3CB	PIK3CB	PIK3CB	7695	0.03	0.27	NO
36	KRAS	KRAS	KRAS	7905	0.026	0.26	NO
37	MAPK10	MAPK10	MAPK10	7980	0.025	0.26	NO
38	BTK	BTK	BTK	8051	0.024	0.26	NO
39	INPP5D	INPP5D	INPP5D	8292	0.02	0.25	NO
40	RAF1	RAF1	RAF1	8578	0.015	0.24	NO
41	MS4A2	MS4A2	MS4A2	8917	0.0097	0.22	NO
42	MAPK14	MAPK14	MAPK14	8934	0.0093	0.22	NO
43	SOS2	SOS2	SOS2	9070	0.0071	0.21	NO
44	AKT2	AKT2	AKT2	9213	0.0044	0.21	NO
45	MAP2K2	MAP2K2	MAP2K2	9429	0.00098	0.2	NO
46	MAP2K4	MAP2K4	MAP2K4	9590	-0.0024	0.19	NO
47	CSF2	CSF2	CSF2	9971	-0.0096	0.17	NO
48	GRB2	GRB2	GRB2	10051	-0.011	0.16	NO
49	PRKCA	PRKCA	PRKCA	10559	-0.021	0.14	NO
50	PLCG2	PLCG2	PLCG2	10613	-0.022	0.14	NO
51	MAPK8	MAPK8	MAPK8	10668	-0.023	0.14	NO
52	MAP2K7	MAP2K7	MAP2K7	10975	-0.029	0.12	NO
53	MAPK11	MAPK11	MAPK11	11120	-0.032	0.12	NO
54	MAPK13	MAPK13	MAPK13	11721	-0.048	0.093	NO
55	MAPK1	MAPK1	MAPK1	11892	-0.052	0.09	NO
56	RAC1	RAC1	RAC1	12183	-0.062	0.082	NO
57	RAC3	RAC3	RAC3	12241	-0.063	0.087	NO
58	PIK3CA	PIK3CA	PIK3CA	12318	-0.065	0.091	NO
59	PLA2G12A	PLA2G12A	PLA2G12A	12689	-0.078	0.08	NO
60	TNF	TNF	TNF	13059	-0.092	0.071	NO
61	SOS1	SOS1	SOS1	13324	-0.1	0.069	NO
62	MAPK3	MAPK3	MAPK3	13417	-0.11	0.077	NO
63	VAV2	VAV2	VAV2	13613	-0.12	0.08	NO
64	FCER1G	FCER1G	FCER1G	13707	-0.12	0.09	NO
65	FCER1A	FCER1A	FCER1A	13999	-0.14	0.091	NO
66	LYN	LYN	LYN	14056	-0.14	0.1	NO
67	PLA2G10	PLA2G10	PLA2G10	14338	-0.16	0.11	NO
68	PLA2G4A	PLA2G4A	PLA2G4A	14465	-0.16	0.12	NO
69	PRKCD	PRKCD	PRKCD	14599	-0.17	0.14	NO
70	PRKCE	PRKCE	PRKCE	15457	-0.24	0.12	NO
71	PLA2G3	PLA2G3	PLA2G3	16062	-0.31	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 DNA REPLICATION.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype 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 TCR PATHWAY	43	genes.ES.table	0.35	0.9	0.6	1	1	0.28	0.12	0.25	1	0.78
BIOCARTA WNT PATHWAY	25	genes.ES.table	0.27	0.95	0.51	1	1	0.12	0.075	0.11	1	0.73
KEGG OXIDATIVE PHOSPHORYLATION	114	genes.ES.table	0.38	1.1	0.44	1	1	0.69	0.38	0.43	1	0.55
KEGG PYRIMIDINE METABOLISM	97	genes.ES.table	0.26	0.98	0.5	1	1	0.39	0.26	0.29	1	0.78
KEGG RIBOSOME	85	genes.ES.table	0.65	1.6	0.064	1	0.76	0.94	0.33	0.63	0.72	0.42
KEGG RNA DEGRADATION	56	genes.ES.table	0.35	1.4	0.18	1	0.96	0.38	0.27	0.27	1	0.67
KEGG RNA POLYMERASE	28	genes.ES.table	0.38	1.3	0.21	1	0.98	0.43	0.26	0.32	1	0.61
KEGG DNA REPLICATION	35	genes.ES.table	0.55	1.2	0.38	1	1	0.66	0.2	0.52	0.98	0.49
KEGG SPLICEOSOME	125	genes.ES.table	0.39	1.4	0.19	1	0.96	0.59	0.36	0.38	1	0.55
KEGG PROTEASOME	43	genes.ES.table	0.41	1.1	0.43	1	1	0.65	0.36	0.42	1	0.57

genes ES table in pathway: BIOCARTA TCR 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	RPL21	RPL21	RPL21	505	0.38	0.021	YES
2	RPL3L	RPL3L	RPL3L	792	0.33	0.047	YES
3	RPS28	RPS28	RPS28	2503	0.15	-0.027	YES
4	RPSA	RPSA	RPSA	2810	0.14	-0.026	YES
5	RPL18A	RPL18A	RPL18A	2835	0.14	-0.01	YES
6	RPLP2	RPLP2	RPLP2	3188	0.12	-0.014	YES
7	RPL39	RPL39	RPL39	3270	0.12	-0.0033	YES
8	RPL14	RPL14	RPL14	3390	0.12	0.0049	YES
9	RPL22L1	RPL22L1	RPL22L1	3413	0.12	0.018	YES
10	RPL24	RPL24	RPL24	3417	0.12	0.033	YES
11	RPS7	RPS7	RPS7	3490	0.11	0.043	YES
12	RPL28	RPL28	RPL28	3531	0.11	0.055	YES
13	RPL34	RPL34	RPL34	3594	0.11	0.066	YES
14	RPL13	RPL13	RPL13	3611	0.11	0.078	YES
15	RPL29	RPL29	RPL29	3615	0.11	0.092	YES
16	RPS8	RPS8	RPS8	3626	0.11	0.1	YES
17	RPS27L	RPS27L	RPS27L	3628	0.11	0.12	YES
18	RPS9	RPS9	RPS9	3633	0.11	0.13	YES
19	RPL32	RPL32	RPL32	3634	0.11	0.15	YES
20	RPS10	RPS10	RPS10	3639	0.11	0.16	YES
21	RPL27A	RPL27A	RPL27A	3739	0.1	0.17	YES
22	RPS24	RPS24	RPS24	3768	0.1	0.18	YES
23	FAU	FAU	FAU	3806	0.1	0.19	YES
24	UBA52	UBA52	UBA52	3827	0.1	0.2	YES
25	RPL36AL	RPL36AL	RPL36AL	3844	0.1	0.21	YES
26	RPL23A	RPL23A	RPL23A	3893	0.1	0.22	YES
27	RPL35A	RPL35A	RPL35A	3894	0.1	0.24	YES
28	RPS21	RPS21	RPS21	3902	0.1	0.25	YES
29	RPS13	RPS13	RPS13	3909	0.1	0.26	YES
30	RPS16	RPS16	RPS16	3931	0.099	0.27	YES
31	RPS23	RPS23	RPS23	3960	0.098	0.28	YES
32	RPL35	RPL35	RPL35	3971	0.098	0.3	YES
33	RPS11	RPS11	RPS11	3986	0.097	0.31	YES
34	RPS19	RPS19	RPS19	4038	0.096	0.32	YES
35	RPS29	RPS29	RPS29	4094	0.094	0.33	YES
36	RPL22	RPL22	RPL22	4182	0.092	0.33	YES
37	RPL26	RPL26	RPL26	4206	0.092	0.34	YES
38	RPS6	RPS6	RPS6	4226	0.091	0.35	YES
39	RPL27	RPL27	RPL27	4239	0.091	0.36	YES
40	RPL37A	RPL37A	RPL37A	4269	0.09	0.38	YES
41	RPL37	RPL37	RPL37	4281	0.09	0.38	YES
42	RPS12	RPS12	RPS12	4304	0.09	0.4	YES
43	RPL31	RPL31	RPL31	4310	0.09	0.41	YES
44	RPS20	RPS20	RPS20	4340	0.088	0.42	YES
45	RPS3A	RPS3A	RPS3A	4344	0.088	0.43	YES
46	RPS3	RPS3	RPS3	4411	0.087	0.44	YES
47	RPS17	RPS17	RPS17	4417	0.086	0.45	YES
48	RPS15	RPS15	RPS15	4433	0.086	0.46	YES
49	RPL11	RPL11	RPL11	4437	0.086	0.47	YES
50	RPL5	RPL5	RPL5	4445	0.086	0.48	YES
51	RPLP1	RPLP1	RPLP1	4507	0.084	0.48	YES
52	RPL26L1	RPL26L1	RPL26L1	4539	0.083	0.49	YES
53	RPS2	RPS2	RPS2	4592	0.082	0.5	YES
54	RPL19	RPL19	RPL19	4593	0.082	0.51	YES
55	RSL24D1	RSL24D1	RSL24D1	4600	0.082	0.52	YES
56	RPL38	RPL38	RPL38	4660	0.08	0.53	YES
57	RPL23	RPL23	RPL23	4687	0.08	0.54	YES
58	RPS5	RPS5	RPS5	4710	0.079	0.55	YES
59	RPL36	RPL36	RPL36	4745	0.078	0.55	YES
60	RPL36A	RPL36A	RPL36A	4757	0.078	0.56	YES
61	RPL15	RPL15	RPL15	4861	0.075	0.57	YES
62	RPL10A	RPL10A	RPL10A	4886	0.074	0.57	YES
63	RPLP0	RPLP0	RPLP0	4908	0.074	0.58	YES
64	RPS27A	RPS27A	RPS27A	5014	0.072	0.59	YES
65	RPS26	RPS26	RPS26	5042	0.071	0.59	YES
66	RPL4	RPL4	RPL4	5117	0.069	0.6	YES
67	RPL6	RPL6	RPL6	5165	0.068	0.6	YES
68	RPL13A	RPL13A	RPL13A	5179	0.068	0.61	YES
69	RPL30	RPL30	RPL30	5190	0.068	0.62	YES
70	RPS25	RPS25	RPS25	5223	0.067	0.63	YES
71	RPL12	RPL12	RPL12	5299	0.065	0.63	YES
72	RPL41	RPL41	RPL41	5400	0.062	0.63	YES
73	RPL7A	RPL7A	RPL7A	5526	0.059	0.64	YES
74	RPS18	RPS18	RPS18	5642	0.056	0.64	YES
75	MRPL13	MRPL13	MRPL13	5691	0.056	0.64	YES
76	RPS15A	RPS15A	RPS15A	5749	0.054	0.64	YES
77	RPL10	RPL10	RPL10	5885	0.051	0.64	YES
78	RPL9	RPL9	RPL9	5921	0.05	0.65	YES
79	RPL7	RPL7	RPL7	6008	0.048	0.65	YES
80	RPS4X	RPS4X	RPS4X	6091	0.047	0.65	YES
81	RPL8	RPL8	RPL8	6287	0.042	0.64	NO
82	RPL17	RPL17	RPL17	6491	0.039	0.64	NO
83	RPL3	RPL3	RPL3	6637	0.036	0.64	NO
84	RPS4Y1	RPS4Y1	RPS4Y1	6986	0.029	0.62	NO
85	RPS27	RPS27	RPS27	8079	0.0064	0.56	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 TCR PATHWAY.

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

genes ES table in pathway: BIOCARTA WNT 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	ENO3	ENO3	ENO3	226	0.48	0.091	YES
2	LSM2	LSM2	LSM2	2036	0.18	0.03	YES
3	EXOSC8	EXOSC8	EXOSC8	2080	0.18	0.066	YES
4	LSM7	LSM7	LSM7	2141	0.17	0.099	YES
5	LSM4	LSM4	LSM4	2581	0.15	0.11	YES
6	LSM5	LSM5	LSM5	2603	0.15	0.14	YES
7	EXOSC5	EXOSC5	EXOSC5	2606	0.15	0.17	YES
8	EXOSC9	EXOSC9	EXOSC9	2824	0.14	0.19	YES
9	LSM3	LSM3	LSM3	2841	0.14	0.22	YES
10	ENO2	ENO2	ENO2	2890	0.14	0.24	YES
11	EXOSC4	EXOSC4	EXOSC4	2908	0.13	0.27	YES
12	EXOSC7	EXOSC7	EXOSC7	3294	0.12	0.27	YES
13	PAPOLB	PAPOLB	PAPOLB	3503	0.11	0.28	YES
14	CNOT10	CNOT10	CNOT10	3616	0.11	0.3	YES
15	EXOSC1	EXOSC1	EXOSC1	3848	0.1	0.31	YES
16	DCP2	DCP2	DCP2	3905	0.1	0.33	YES
17	DCP1B	DCP1B	DCP1B	4579	0.082	0.31	YES
18	NAA38	NAA38	NAA38	4672	0.08	0.32	YES
19	DCPS	DCPS	DCPS	4901	0.074	0.32	YES
20	MPHOSPH6	MPHOSPH6	MPHOSPH6	4913	0.074	0.34	YES
21	EDC4	EDC4	EDC4	4953	0.073	0.35	YES
22	LSM6	LSM6	LSM6	5490	0.06	0.34	NO
23	EXOSC10	EXOSC10	EXOSC10	5995	0.049	0.32	NO
24	EXOSC2	EXOSC2	EXOSC2	6276	0.043	0.31	NO
25	C1D	C1D	C1D	6355	0.041	0.32	NO
26	CNOT2	CNOT2	CNOT2	6372	0.041	0.33	NO
27	LSM1	LSM1	LSM1	6654	0.036	0.32	NO
28	EXOSC3	EXOSC3	EXOSC3	6693	0.035	0.32	NO
29	CNOT3	CNOT3	CNOT3	6741	0.034	0.33	NO
30	WDR61	WDR61	WDR61	6776	0.033	0.33	NO
31	ENO1	ENO1	ENO1	7162	0.025	0.32	NO
32	EXOSC6	EXOSC6	EXOSC6	7271	0.023	0.32	NO
33	EDC3	EDC3	EDC3	7649	0.015	0.3	NO
34	CNOT6	CNOT6	CNOT6	7666	0.015	0.3	NO
35	SKIV2L	SKIV2L	SKIV2L	7907	0.01	0.29	NO
36	PARN	PARN	PARN	8090	0.0061	0.28	NO
37	ZCCHC7	ZCCHC7	ZCCHC7	8484	-0.0021	0.26	NO
38	CNOT6L	CNOT6L	CNOT6L	8527	-0.0029	0.26	NO
39	CNOT7	CNOT7	CNOT7	8682	-0.0063	0.25	NO
40	DDX6	DDX6	DDX6	9027	-0.013	0.24	NO
41	DCP1A	DCP1A	DCP1A	9046	-0.014	0.24	NO
42	PAPD7	PAPD7	PAPD7	9459	-0.022	0.22	NO
43	CNOT1	CNOT1	CNOT1	9666	-0.026	0.21	NO
44	HSPD1	HSPD1	HSPD1	9996	-0.033	0.2	NO
45	PAPOLA	PAPOLA	PAPOLA	10373	-0.041	0.19	NO
46	SKIV2L2	SKIV2L2	SKIV2L2	10526	-0.045	0.19	NO
47	DIS3	DIS3	DIS3	11342	-0.065	0.16	NO
48	XRN2	XRN2	XRN2	11636	-0.072	0.16	NO
49	XRN1	XRN1	XRN1	11963	-0.081	0.16	NO
50	PATL1	PATL1	PATL1	12224	-0.088	0.16	NO
51	CNOT4	CNOT4	CNOT4	12343	-0.092	0.18	NO
52	HSPA9	HSPA9	HSPA9	12370	-0.093	0.2	NO
53	PNPT1	PNPT1	PNPT1	12409	-0.094	0.21	NO
54	PAPOLG	PAPOLG	PAPOLG	13094	-0.12	0.2	NO
55	RQCD1	RQCD1	RQCD1	13594	-0.14	0.2	NO
56	TTC37	TTC37	TTC37	15570	-0.26	0.15	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 WNT PATHWAY.

Figure S24. 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 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	CCDC12	CCDC12	CCDC12	1785	0.2	-0.077	YES
2	SF3B5	SF3B5	SF3B5	1996	0.18	-0.068	YES
3	LSM2	LSM2	LSM2	2036	0.18	-0.051	YES
4	LSM7	LSM7	LSM7	2141	0.17	-0.038	YES
5	THOC4	THOC4	THOC4	2148	0.17	-0.02	YES
6	TXNL4A	TXNL4A	TXNL4A	2211	0.17	-0.0056	YES
7	SNRPF	SNRPF	SNRPF	2285	0.16	0.008	YES
8	SNRPC	SNRPC	SNRPC	2287	0.16	0.026	YES
9	SNRPA	SNRPA	SNRPA	2297	0.16	0.043	YES
10	LSM4	LSM4	LSM4	2581	0.15	0.043	YES
11	LSM5	LSM5	LSM5	2603	0.15	0.058	YES
12	SNRPD1	SNRPD1	SNRPD1	2684	0.14	0.069	YES
13	MAGOHB	MAGOHB	MAGOHB	2700	0.14	0.083	YES
14	PPIH	PPIH	PPIH	2708	0.14	0.098	YES
15	SNRPD2	SNRPD2	SNRPD2	2767	0.14	0.11	YES
16	U2AF1	U2AF1	U2AF1	2783	0.14	0.12	YES
17	LSM3	LSM3	LSM3	2841	0.14	0.14	YES
18	SF3A2	SF3A2	SF3A2	2859	0.14	0.15	YES
19	SNRPG	SNRPG	SNRPG	2898	0.14	0.16	YES
20	MAGOH	MAGOH	MAGOH	2938	0.13	0.17	YES
21	SNRPA1	SNRPA1	SNRPA1	3017	0.13	0.18	YES
22	SNRPB2	SNRPB2	SNRPB2	3194	0.12	0.19	YES
23	SART1	SART1	SART1	3249	0.12	0.2	YES
24	SNRPB	SNRPB	SNRPB	3290	0.12	0.21	YES
25	XAB2	XAB2	XAB2	3341	0.12	0.22	YES
26	HNRNPA1	HNRNPA1	HNRNPA1	3419	0.12	0.22	YES
27	SNRPE	SNRPE	SNRPE	3614	0.11	0.23	YES
28	PHF5A	PHF5A	PHF5A	3789	0.1	0.23	YES
29	THOC3	THOC3	THOC3	4030	0.096	0.22	YES
30	CWC15	CWC15	CWC15	4110	0.094	0.23	YES
31	SNRPD3	SNRPD3	SNRPD3	4170	0.093	0.24	YES
32	SFRS3	SFRS3	SFRS3	4184	0.092	0.25	YES
33	SF3B14	SF3B14	SF3B14	4240	0.091	0.25	YES
34	PRPF31	PRPF31	PRPF31	4295	0.09	0.26	YES
35	PRPF38A	PRPF38A	PRPF38A	4302	0.09	0.27	YES
36	PRPF19	PRPF19	PRPF19	4376	0.088	0.27	YES
37	PPIE	PPIE	PPIE	4457	0.086	0.28	YES
38	CTNNBL1	CTNNBL1	CTNNBL1	4460	0.086	0.29	YES
39	PQBP1	PQBP1	PQBP1	4509	0.084	0.29	YES
40	SYF2	SYF2	SYF2	4649	0.08	0.3	YES
41	NAA38	NAA38	NAA38	4672	0.08	0.3	YES
42	BUD31	BUD31	BUD31	4679	0.08	0.31	YES
43	SFRS9	SFRS9	SFRS9	4774	0.077	0.31	YES
44	NHP2L1	NHP2L1	NHP2L1	4785	0.077	0.32	YES
45	ISY1	ISY1	ISY1	4799	0.077	0.33	YES
46	SNRNP70	SNRNP70	SNRNP70	4838	0.076	0.34	YES
47	RBM17	RBM17	RBM17	4877	0.075	0.34	YES
48	RBM22	RBM22	RBM22	5113	0.069	0.34	YES
49	PRPF6	PRPF6	PRPF6	5169	0.068	0.34	YES
50	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	5276	0.065	0.34	YES
51	TRA2B	TRA2B	TRA2B	5348	0.064	0.34	YES
52	SF3A3	SF3A3	SF3A3	5432	0.061	0.34	YES
53	LSM6	LSM6	LSM6	5490	0.06	0.35	YES
54	SF3B2	SF3B2	SF3B2	5600	0.057	0.35	YES
55	HNRNPM	HNRNPM	HNRNPM	5624	0.057	0.35	YES
56	PRPF18	PRPF18	PRPF18	5673	0.056	0.36	YES
57	PUF60	PUF60	PUF60	5738	0.054	0.36	YES
58	BAT1	BAT1	BAT1	5827	0.052	0.36	YES
59	PCBP1	PCBP1	PCBP1	5880	0.051	0.36	YES
60	USP39	USP39	USP39	6097	0.046	0.36	YES
61	DHX38	DHX38	DHX38	6125	0.046	0.36	YES
62	SFRS7	SFRS7	SFRS7	6127	0.046	0.36	YES
63	PPIL1	PPIL1	PPIL1	6183	0.045	0.37	YES
64	RBMX	RBMX	RBMX	6191	0.044	0.37	YES
65	SNRNP40	SNRNP40	SNRNP40	6231	0.044	0.37	YES
66	HNRNPA3	HNRNPA3	HNRNPA3	6237	0.044	0.38	YES
67	EIF4A3	EIF4A3	EIF4A3	6247	0.043	0.38	YES
68	HNRNPC	HNRNPC	HNRNPC	6383	0.041	0.38	YES
69	DDX23	DDX23	DDX23	6440	0.04	0.38	YES
70	SFRS4	SFRS4	SFRS4	6481	0.039	0.38	YES
71	ZMAT2	ZMAT2	ZMAT2	6501	0.038	0.38	YES
72	SFRS2	SFRS2	SFRS2	6582	0.037	0.38	YES
73	SF3B4	SF3B4	SF3B4	6644	0.036	0.38	YES
74	THOC1	THOC1	THOC1	6666	0.035	0.39	YES
75	U2AF2	U2AF2	U2AF2	6804	0.032	0.38	NO
76	SFRS1	SFRS1	SFRS1	6996	0.029	0.38	NO
77	SLU7	SLU7	SLU7	7222	0.024	0.36	NO
78	SFRS6	SFRS6	SFRS6	7275	0.023	0.36	NO
79	EFTUD2	EFTUD2	EFTUD2	7276	0.023	0.37	NO
80	HNRNPK	HNRNPK	HNRNPK	7286	0.023	0.37	NO
81	DHX16	DHX16	DHX16	7332	0.022	0.37	NO
82	SFRS13A	SFRS13A	SFRS13A	7526	0.018	0.36	NO
83	SNRNP27	SNRNP27	SNRNP27	7704	0.014	0.35	NO
84	PRPF8	PRPF8	PRPF8	7836	0.011	0.35	NO
85	PRPF3	PRPF3	PRPF3	7944	0.0093	0.34	NO
86	SF3B3	SF3B3	SF3B3	7951	0.0092	0.34	NO
87	DHX8	DHX8	DHX8	8019	0.0077	0.34	NO
88	HNRNPU	HNRNPU	HNRNPU	8081	0.0063	0.34	NO
89	SMNDC1	SMNDC1	SMNDC1	8091	0.0061	0.34	NO
90	SNRNP200	SNRNP200	SNRNP200	8120	0.0055	0.34	NO
91	HSPA8	HSPA8	HSPA8	8158	0.0046	0.33	NO
92	CDC5L	CDC5L	CDC5L	8296	0.002	0.33	NO
93	SFRS5	SFRS5	SFRS5	8390	-6.1e-07	0.32	NO
94	ACIN1	ACIN1	ACIN1	8556	-0.0034	0.31	NO
95	WBP11	WBP11	WBP11	8572	-0.004	0.31	NO
96	CRNKL1	CRNKL1	CRNKL1	8602	-0.0045	0.31	NO
97	BCAS2	BCAS2	BCAS2	8714	-0.0069	0.31	NO
98	TRA2A	TRA2A	TRA2A	8903	-0.01	0.3	NO
99	RBM8A	RBM8A	RBM8A	9016	-0.013	0.29	NO
100	PRPF4	PRPF4	PRPF4	9053	-0.014	0.29	NO
101	SNW1	SNW1	SNW1	9200	-0.017	0.28	NO
102	DDX5	DDX5	DDX5	9260	-0.018	0.28	NO
103	CHERP	CHERP	CHERP	9293	-0.019	0.28	NO
104	PLRG1	PLRG1	PLRG1	9426	-0.022	0.28	NO
105	DHX15	DHX15	DHX15	9450	-0.022	0.28	NO
106	CDC40	CDC40	CDC40	9476	-0.023	0.28	NO
107	DDX42	DDX42	DDX42	9560	-0.024	0.28	NO
108	DDX46	DDX46	DDX46	9819	-0.029	0.27	NO
109	SF3A1	SF3A1	SF3A1	9835	-0.029	0.27	NO
110	PRPF38B	PRPF38B	PRPF38B	9879	-0.03	0.27	NO
111	SFRS2B	SFRS2B	SFRS2B	9884	-0.03	0.27	NO
112	TCERG1	TCERG1	TCERG1	9917	-0.031	0.28	NO
113	NCBP1	NCBP1	NCBP1	10116	-0.036	0.27	NO
114	SF3B1	SF3B1	SF3B1	10319	-0.04	0.26	NO
115	PRPF40A	PRPF40A	PRPF40A	10800	-0.051	0.24	NO
116	SR140	SR140	SR140	11245	-0.062	0.22	NO
117	HSPA1L	HSPA1L	HSPA1L	11503	-0.069	0.22	NO
118	THOC2	THOC2	THOC2	12021	-0.083	0.2	NO
119	PRPF40B	PRPF40B	PRPF40B	12105	-0.085	0.2	NO
120	AQR	AQR	AQR	12405	-0.094	0.2	NO
121	RBM25	RBM25	RBM25	12419	-0.094	0.2	NO
122	HSPA1A	HSPA1A	HSPA1A	13138	-0.12	0.18	NO
123	HSPA6	HSPA6	HSPA6	13236	-0.12	0.18	NO
124	HSPA1B	HSPA1B	HSPA1B	14226	-0.17	0.15	NO
125	HSPA2	HSPA2	HSPA2	18120	-0.7	0.009	NO

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

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

genes ES table in pathway: KEGG PYRIMIDINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ZNRD1	ZNRD1	ZNRD1	1782	0.2	-0.0049	YES
2	POLR2I	POLR2I	POLR2I	2798	0.14	0.0033	YES
3	POLR2F	POLR2F	POLR2F	2911	0.13	0.059	YES
4	POLR2L	POLR2L	POLR2L	3159	0.12	0.1	YES
5	POLR3K	POLR3K	POLR3K	3477	0.11	0.14	YES
6	POLR2J2	POLR2J2	POLR2J2	3547	0.11	0.18	YES
7	POLR2J	POLR2J	POLR2J	3643	0.11	0.23	YES
8	POLR2G	POLR2G	POLR2G	3767	0.1	0.27	YES
9	POLR2D	POLR2D	POLR2D	3872	0.1	0.31	YES
10	POLR1C	POLR1C	POLR1C	3963	0.098	0.35	YES
11	POLR2E	POLR2E	POLR2E	4688	0.08	0.35	YES
12	POLR1D	POLR1D	POLR1D	4747	0.078	0.38	YES
13	POLR3GL	POLR3GL	POLR3GL	5781	0.054	0.35	NO
14	POLR1E	POLR1E	POLR1E	6280	0.043	0.34	NO
15	POLR2K	POLR2K	POLR2K	6398	0.04	0.35	NO
16	POLR2C	POLR2C	POLR2C	6487	0.039	0.36	NO
17	POLR3H	POLR3H	POLR3H	7061	0.027	0.34	NO
18	POLR3F	POLR3F	POLR3F	7678	0.015	0.32	NO
19	POLR3C	POLR3C	POLR3C	8008	0.0078	0.3	NO
20	POLR2A	POLR2A	POLR2A	8745	-0.0077	0.27	NO
21	POLR2J3	POLR2J3	POLR2J3	9264	-0.018	0.25	NO
22	POLR2B	POLR2B	POLR2B	10560	-0.045	0.2	NO
23	POLR3B	POLR3B	POLR3B	10950	-0.055	0.2	NO
24	POLR3D	POLR3D	POLR3D	11781	-0.076	0.19	NO
25	POLR1B	POLR1B	POLR1B	11850	-0.078	0.22	NO
26	POLR3G	POLR3G	POLR3G	11980	-0.082	0.25	NO
27	POLR1A	POLR1A	POLR1A	12305	-0.091	0.28	NO
28	POLR3A	POLR3A	POLR3A	12966	-0.11	0.29	NO

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

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

genes ES table in pathway: KEGG RIBOSOME

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	NEIL3	NEIL3	NEIL3	550	0.37	0.076	YES
2	POLE2	POLE2	POLE2	942	0.3	0.14	YES
3	NEIL1	NEIL1	NEIL1	1079	0.28	0.21	YES
4	FEN1	FEN1	FEN1	1668	0.21	0.24	YES
5	POLD1	POLD1	POLD1	2481	0.15	0.24	YES
6	PCNA	PCNA	PCNA	2549	0.15	0.28	YES
7	MUTYH	MUTYH	MUTYH	2712	0.14	0.31	YES
8	POLD2	POLD2	POLD2	2720	0.14	0.35	YES
9	POLE	POLE	POLE	2733	0.14	0.39	YES
10	NTHL1	NTHL1	NTHL1	2935	0.13	0.42	YES
11	LIG1	LIG1	LIG1	2962	0.13	0.46	YES
12	MPG	MPG	MPG	3217	0.12	0.48	YES
13	OGG1	OGG1	OGG1	3818	0.1	0.47	NO
14	XRCC1	XRCC1	XRCC1	4604	0.082	0.45	NO
15	POLD4	POLD4	POLD4	5170	0.068	0.44	NO
16	POLD3	POLD3	POLD3	5722	0.055	0.43	NO
17	POLE4	POLE4	POLE4	5743	0.054	0.44	NO
18	POLB	POLB	POLB	5947	0.05	0.44	NO
19	POLE3	POLE3	POLE3	5991	0.049	0.46	NO
20	NEIL2	NEIL2	NEIL2	6147	0.045	0.46	NO
21	SMUG1	SMUG1	SMUG1	6427	0.04	0.46	NO
22	MBD4	MBD4	MBD4	6697	0.034	0.45	NO
23	UNG	UNG	UNG	6719	0.034	0.46	NO
24	TDG	TDG	TDG	6984	0.029	0.45	NO
25	APEX1	APEX1	APEX1	7876	0.011	0.41	NO
26	POLL	POLL	POLL	8732	-0.0073	0.36	NO
27	PARP2	PARP2	PARP2	9430	-0.022	0.33	NO
28	APEX2	APEX2	APEX2	10543	-0.045	0.28	NO
29	LIG3	LIG3	LIG3	10937	-0.054	0.28	NO
30	PARP1	PARP1	PARP1	11975	-0.082	0.24	NO
31	PARP4	PARP4	PARP4	12146	-0.086	0.26	NO
32	PARP3	PARP3	PARP3	15828	-0.28	0.14	NO

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

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

genes ES table in pathway: KEGG RNA DEGRADATION

Table 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	AQP2	AQP2	AQP2	41	0.68	0.12	YES
2	CREB3L3	CREB3L3	CREB3L3	66	0.62	0.23	YES
3	AVPR2	AVPR2	AVPR2	300	0.45	0.3	YES
4	CREB3L1	CREB3L1	CREB3L1	1042	0.29	0.31	YES
5	ARHGDIB	ARHGDIB	ARHGDIB	1620	0.22	0.32	YES
6	PRKACB	PRKACB	PRKACB	3654	0.11	0.23	NO
7	DYNLL1	DYNLL1	DYNLL1	3866	0.1	0.24	NO
8	AQP3	AQP3	AQP3	4639	0.081	0.21	NO
9	VAMP2	VAMP2	VAMP2	4883	0.074	0.21	NO
10	RAB11B	RAB11B	RAB11B	5060	0.07	0.21	NO
11	DCTN2	DCTN2	DCTN2	5184	0.068	0.22	NO
12	ARHGDIA	ARHGDIA	ARHGDIA	5430	0.062	0.22	NO
13	GNAS	GNAS	GNAS	5462	0.06	0.22	NO
14	DYNC2LI1	DYNC2LI1	DYNC2LI1	5580	0.058	0.23	NO
15	CREB3L4	CREB3L4	CREB3L4	5596	0.057	0.24	NO
16	DCTN1	DCTN1	DCTN1	6866	0.031	0.18	NO
17	DYNC1LI1	DYNC1LI1	DYNC1LI1	6952	0.03	0.18	NO
18	CREB3	CREB3	CREB3	7264	0.023	0.16	NO
19	PRKACA	PRKACA	PRKACA	7747	0.013	0.14	NO
20	STX4	STX4	STX4	8233	0.0032	0.11	NO
21	RAB5A	RAB5A	RAB5A	8890	-0.01	0.079	NO
22	CREB1	CREB1	CREB1	9078	-0.014	0.071	NO
23	DYNC2H1	DYNC2H1	DYNC2H1	9486	-0.023	0.053	NO
24	DCTN5	DCTN5	DCTN5	9534	-0.024	0.055	NO
25	DYNC1H1	DYNC1H1	DYNC1H1	10170	-0.037	0.026	NO
26	RAB5B	RAB5B	RAB5B	10203	-0.037	0.032	NO
27	RAB5C	RAB5C	RAB5C	10251	-0.039	0.036	NO
28	DYNC1I2	DYNC1I2	DYNC1I2	10256	-0.039	0.043	NO
29	RAB11A	RAB11A	RAB11A	10702	-0.049	0.027	NO
30	DCTN4	DCTN4	DCTN4	10934	-0.054	0.025	NO
31	DCTN6	DCTN6	DCTN6	11264	-0.062	0.018	NO
32	CREB3L2	CREB3L2	CREB3L2	11266	-0.062	0.029	NO
33	DYNC1LI2	DYNC1LI2	DYNC1LI2	11379	-0.066	0.035	NO
34	PRKX	PRKX	PRKX	12125	-0.086	0.0099	NO
35	NSF	NSF	NSF	12486	-0.096	0.0077	NO
36	ADCY9	ADCY9	ADCY9	13061	-0.12	-0.0026	NO
37	DYNLL2	DYNLL2	DYNLL2	13636	-0.14	-0.0087	NO
38	ADCY6	ADCY6	ADCY6	14111	-0.16	-0.0053	NO
39	AQP4	AQP4	AQP4	14452	-0.18	0.0087	NO
40	CREB5	CREB5	CREB5	16661	-0.36	-0.047	NO
41	DYNC1I1	DYNC1I1	DYNC1I1	18166	-0.74	0.0064	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	SLC6A3	SLC6A3	SLC6A3	97	0.59	0.049	YES
2	COX4I2	COX4I2	COX4I2	389	0.42	0.072	YES
3	SNCA	SNCA	SNCA	403	0.41	0.11	YES
4	SNCAIP	SNCAIP	SNCAIP	820	0.32	0.12	YES
5	COX6B2	COX6B2	COX6B2	880	0.31	0.14	YES
6	NDUFA4L2	NDUFA4L2	NDUFA4L2	2534	0.15	0.065	YES
7	NDUFS6	NDUFS6	NDUFS6	2562	0.15	0.078	YES
8	ATP5J	ATP5J	ATP5J	2661	0.15	0.086	YES
9	NDUFB7	NDUFB7	NDUFB7	2925	0.13	0.084	YES
10	NDUFA7	NDUFA7	NDUFA7	2929	0.13	0.096	YES
11	COX4I1	COX4I1	COX4I1	2992	0.13	0.1	YES
12	NDUFS8	NDUFS8	NDUFS8	3031	0.13	0.11	YES
13	NDUFA3	NDUFA3	NDUFA3	3137	0.12	0.12	YES
14	NDUFB1	NDUFB1	NDUFB1	3141	0.12	0.13	YES
15	NDUFS5	NDUFS5	NDUFS5	3161	0.12	0.14	YES
16	NDUFA2	NDUFA2	NDUFA2	3211	0.12	0.15	YES
17	COX7A2	COX7A2	COX7A2	3289	0.12	0.16	YES
18	UBE2J2	UBE2J2	UBE2J2	3321	0.12	0.17	YES
19	NDUFB10	NDUFB10	NDUFB10	3337	0.12	0.18	YES
20	NDUFB8	NDUFB8	NDUFB8	3387	0.12	0.18	YES
21	NDUFS3	NDUFS3	NDUFS3	3410	0.12	0.19	YES
22	UQCR10	UQCR10	UQCR10	3428	0.11	0.2	YES
23	ATP5O	ATP5O	ATP5O	3479	0.11	0.21	YES
24	COX6B1	COX6B1	COX6B1	3650	0.11	0.21	YES
25	HTRA2	HTRA2	HTRA2	3651	0.11	0.22	YES
26	NDUFV2	NDUFV2	NDUFV2	3653	0.11	0.23	YES
27	ATP5E	ATP5E	ATP5E	3897	0.1	0.23	YES
28	ATP5D	ATP5D	ATP5D	3958	0.098	0.23	YES
29	NDUFB2	NDUFB2	NDUFB2	3973	0.098	0.24	YES
30	UBB	UBB	UBB	4129	0.094	0.24	YES
31	ATP5G2	ATP5G2	ATP5G2	4135	0.094	0.25	YES
32	UBE2L3	UBE2L3	UBE2L3	4277	0.09	0.25	YES
33	UQCRQ	UQCRQ	UQCRQ	4293	0.09	0.26	YES
34	NDUFS7	NDUFS7	NDUFS7	4394	0.087	0.26	YES
35	UCHL1	UCHL1	UCHL1	4443	0.086	0.27	YES
36	UBE2J1	UBE2J1	UBE2J1	4485	0.085	0.27	YES
37	PARK7	PARK7	PARK7	4521	0.084	0.28	YES
38	ATP5C1	ATP5C1	ATP5C1	4560	0.083	0.28	YES
39	NDUFB9	NDUFB9	NDUFB9	4608	0.081	0.29	YES
40	COX8A	COX8A	COX8A	4678	0.08	0.29	YES
41	COX6C	COX6C	COX6C	4735	0.078	0.3	YES
42	NDUFB6	NDUFB6	NDUFB6	4791	0.077	0.3	YES
43	COX6A1	COX6A1	COX6A1	4829	0.076	0.3	YES
44	NDUFAB1	NDUFAB1	NDUFAB1	4837	0.076	0.31	YES
45	NDUFC2	NDUFC2	NDUFC2	5091	0.07	0.3	YES
46	NDUFA6	NDUFA6	NDUFA6	5128	0.069	0.31	YES
47	NDUFA9	NDUFA9	NDUFA9	5185	0.068	0.31	YES
48	PINK1	PINK1	PINK1	5250	0.066	0.31	YES
49	NDUFB4	NDUFB4	NDUFB4	5306	0.065	0.32	YES
50	NDUFV1	NDUFV1	NDUFV1	5365	0.063	0.32	YES
51	NDUFS4	NDUFS4	NDUFS4	5401	0.062	0.32	YES
52	UQCRH	UQCRH	UQCRH	5428	0.062	0.33	YES
53	NDUFB3	NDUFB3	NDUFB3	5471	0.06	0.33	YES
54	UQCRHL	UQCRHL	UQCRHL	5481	0.06	0.34	YES
55	VDAC3	VDAC3	VDAC3	5536	0.059	0.34	YES
56	CASP3	CASP3	CASP3	5586	0.058	0.34	YES
57	COX5B	COX5B	COX5B	5665	0.056	0.34	YES
58	UQCR11	UQCR11	UQCR11	5701	0.055	0.35	YES
59	COX7C	COX7C	COX7C	5706	0.055	0.35	YES
60	UQCRC1	UQCRC1	UQCRC1	5793	0.053	0.35	YES
61	UQCRB	UQCRB	UQCRB	5814	0.053	0.36	YES
62	ATP5H	ATP5H	ATP5H	5839	0.052	0.36	YES
63	SDHB	SDHB	SDHB	5914	0.05	0.36	YES
64	NDUFA1	NDUFA1	NDUFA1	5954	0.049	0.36	YES
65	COX5A	COX5A	COX5A	6083	0.047	0.36	YES
66	NDUFA4	NDUFA4	NDUFA4	6133	0.046	0.36	YES
67	SLC25A6	SLC25A6	SLC25A6	6135	0.046	0.36	YES
68	ATP5G3	ATP5G3	ATP5G3	6254	0.043	0.36	YES
69	UQCRFS1	UQCRFS1	UQCRFS1	6293	0.042	0.36	YES
70	ATP5A1	ATP5A1	ATP5A1	6328	0.042	0.36	YES
71	SDHA	SDHA	SDHA	6494	0.039	0.36	YES
72	SLC25A5	SLC25A5	SLC25A5	6569	0.037	0.36	YES
73	NDUFC1	NDUFC1	NDUFC1	6579	0.037	0.36	YES
74	UBE2L6	UBE2L6	UBE2L6	6622	0.036	0.36	YES
75	COX7B	COX7B	COX7B	6626	0.036	0.37	YES
76	TH	TH	TH	6635	0.036	0.37	YES
77	ATP5F1	ATP5F1	ATP5F1	6759	0.033	0.37	NO
78	ATP5G1	ATP5G1	ATP5G1	6798	0.032	0.37	NO
79	NDUFA8	NDUFA8	NDUFA8	6950	0.03	0.36	NO
80	COX7A2L	COX7A2L	COX7A2L	6985	0.029	0.36	NO
81	CYC1	CYC1	CYC1	7114	0.026	0.36	NO
82	PPID	PPID	PPID	7174	0.025	0.36	NO
83	COX6A2	COX6A2	COX6A2	7364	0.021	0.35	NO
84	ATP5B	ATP5B	ATP5B	7646	0.015	0.33	NO
85	NDUFA10	NDUFA10	NDUFA10	7725	0.014	0.33	NO
86	PARK2	PARK2	PARK2	7814	0.012	0.33	NO
87	VDAC2	VDAC2	VDAC2	7837	0.011	0.33	NO
88	UBE2G2	UBE2G2	UBE2G2	7929	0.0096	0.32	NO
89	NDUFB5	NDUFB5	NDUFB5	7931	0.0096	0.32	NO
90	NDUFV3	NDUFV3	NDUFV3	7990	0.0084	0.32	NO
91	NDUFA5	NDUFA5	NDUFA5	8137	0.0051	0.31	NO
92	UBA1	UBA1	UBA1	8323	0.0015	0.3	NO
93	COX7A1	COX7A1	COX7A1	8405	-0.00032	0.3	NO
94	VDAC1	VDAC1	VDAC1	8524	-0.0028	0.29	NO
95	UBE2G1	UBE2G1	UBE2G1	8724	-0.0071	0.28	NO
96	UQCRC2	UQCRC2	UQCRC2	9500	-0.023	0.24	NO
97	UBA7	UBA7	UBA7	9658	-0.026	0.24	NO
98	CYCS	CYCS	CYCS	9988	-0.033	0.22	NO
99	CASP9	CASP9	CASP9	10118	-0.036	0.22	NO
100	SDHD	SDHD	SDHD	10694	-0.049	0.19	NO
101	APAF1	APAF1	APAF1	10886	-0.053	0.18	NO
102	SLC25A31	SLC25A31	SLC25A31	10927	-0.054	0.19	NO
103	SDHC	SDHC	SDHC	11394	-0.066	0.17	NO
104	NDUFS2	NDUFS2	NDUFS2	11561	-0.07	0.16	NO
105	COX8C	COX8C	COX8C	12301	-0.091	0.13	NO
106	NDUFS1	NDUFS1	NDUFS1	12596	-0.099	0.13	NO
107	SLC25A4	SLC25A4	SLC25A4	13902	-0.15	0.068	NO
108	SLC18A2	SLC18A2	SLC18A2	14171	-0.16	0.068	NO
109	SLC18A1	SLC18A1	SLC18A1	15805	-0.27	0.0036	NO
110	LRRK2	LRRK2	LRRK2	18051	-0.65	-0.059	NO
111	GPR37	GPR37	GPR37	18206	-0.78	0.0042	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 DNA REPLICATION

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	CREB3L3	CREB3L3	CREB3L3	66	0.62	0.035	YES
2	COX4I2	COX4I2	COX4I2	389	0.42	0.043	YES
3	COX6B2	COX6B2	COX6B2	880	0.31	0.035	YES
4	CREB3L1	CREB3L1	CREB3L1	1042	0.29	0.044	YES
5	GRIN1	GRIN1	GRIN1	1414	0.24	0.038	YES
6	PLCB4	PLCB4	PLCB4	1636	0.22	0.04	YES
7	TGM2	TGM2	TGM2	1740	0.21	0.047	YES
8	HAP1	HAP1	HAP1	1902	0.19	0.05	YES
9	BAX	BAX	BAX	1962	0.19	0.058	YES
10	NDUFA4L2	NDUFA4L2	NDUFA4L2	2534	0.15	0.036	YES
11	NDUFS6	NDUFS6	NDUFS6	2562	0.15	0.044	YES
12	AP2S1	AP2S1	AP2S1	2650	0.15	0.048	YES
13	ATP5J	ATP5J	ATP5J	2661	0.15	0.056	YES
14	POLR2I	POLR2I	POLR2I	2798	0.14	0.058	YES
15	BBC3	BBC3	BBC3	2812	0.14	0.065	YES
16	POLR2F	POLR2F	POLR2F	2911	0.13	0.068	YES
17	NDUFB7	NDUFB7	NDUFB7	2925	0.13	0.076	YES
18	NDUFA7	NDUFA7	NDUFA7	2929	0.13	0.084	YES
19	COX4I1	COX4I1	COX4I1	2992	0.13	0.088	YES
20	NDUFS8	NDUFS8	NDUFS8	3031	0.13	0.094	YES
21	NDUFA3	NDUFA3	NDUFA3	3137	0.12	0.096	YES
22	NDUFB1	NDUFB1	NDUFB1	3141	0.12	0.1	YES
23	POLR2L	POLR2L	POLR2L	3159	0.12	0.11	YES
24	NDUFS5	NDUFS5	NDUFS5	3161	0.12	0.12	YES
25	NDUFA2	NDUFA2	NDUFA2	3211	0.12	0.12	YES
26	COX7A2	COX7A2	COX7A2	3289	0.12	0.13	YES
27	NDUFB10	NDUFB10	NDUFB10	3337	0.12	0.13	YES
28	NDUFB8	NDUFB8	NDUFB8	3387	0.12	0.14	YES
29	NDUFS3	NDUFS3	NDUFS3	3410	0.12	0.14	YES
30	UQCR10	UQCR10	UQCR10	3428	0.11	0.15	YES
31	ATP5O	ATP5O	ATP5O	3479	0.11	0.15	YES
32	POLR2J2	POLR2J2	POLR2J2	3547	0.11	0.16	YES
33	POLR2J	POLR2J	POLR2J	3643	0.11	0.16	YES
34	COX6B1	COX6B1	COX6B1	3650	0.11	0.16	YES
35	NDUFV2	NDUFV2	NDUFV2	3653	0.11	0.17	YES
36	TP53	TP53	TP53	3693	0.11	0.17	YES
37	TBPL1	TBPL1	TBPL1	3758	0.1	0.18	YES
38	POLR2G	POLR2G	POLR2G	3767	0.1	0.18	YES
39	POLR2D	POLR2D	POLR2D	3872	0.1	0.18	YES
40	DLG4	DLG4	DLG4	3896	0.1	0.19	YES
41	ATP5E	ATP5E	ATP5E	3897	0.1	0.19	YES
42	ATP5D	ATP5D	ATP5D	3958	0.098	0.2	YES
43	NDUFB2	NDUFB2	NDUFB2	3973	0.098	0.2	YES
44	POLR2H	POLR2H	POLR2H	3979	0.098	0.21	YES
45	ATP5G2	ATP5G2	ATP5G2	4135	0.094	0.2	YES
46	UQCRQ	UQCRQ	UQCRQ	4293	0.09	0.2	YES
47	NDUFS7	NDUFS7	NDUFS7	4394	0.087	0.2	YES
48	AP2A2	AP2A2	AP2A2	4438	0.086	0.2	YES
49	HDAC2	HDAC2	HDAC2	4456	0.086	0.21	YES
50	HDAC1	HDAC1	HDAC1	4532	0.083	0.21	YES
51	ATP5C1	ATP5C1	ATP5C1	4560	0.083	0.21	YES
52	NDUFB9	NDUFB9	NDUFB9	4608	0.081	0.22	YES
53	CLTB	CLTB	CLTB	4654	0.08	0.22	YES
54	COX8A	COX8A	COX8A	4678	0.08	0.22	YES
55	POLR2E	POLR2E	POLR2E	4688	0.08	0.23	YES
56	COX6C	COX6C	COX6C	4735	0.078	0.23	YES
57	NRF1	NRF1	NRF1	4750	0.078	0.23	YES
58	NDUFB6	NDUFB6	NDUFB6	4791	0.077	0.24	YES
59	COX6A1	COX6A1	COX6A1	4829	0.076	0.24	YES
60	NDUFAB1	NDUFAB1	NDUFAB1	4837	0.076	0.24	YES
61	GPX1	GPX1	GPX1	5031	0.071	0.24	YES
62	NDUFC2	NDUFC2	NDUFC2	5091	0.07	0.24	YES
63	NDUFA6	NDUFA6	NDUFA6	5128	0.069	0.24	YES
64	DCTN2	DCTN2	DCTN2	5184	0.068	0.24	YES
65	NDUFA9	NDUFA9	NDUFA9	5185	0.068	0.24	YES
66	NDUFB4	NDUFB4	NDUFB4	5306	0.065	0.24	YES
67	NDUFV1	NDUFV1	NDUFV1	5365	0.063	0.24	YES
68	NDUFS4	NDUFS4	NDUFS4	5401	0.062	0.24	YES
69	UQCRH	UQCRH	UQCRH	5428	0.062	0.25	YES
70	NDUFB3	NDUFB3	NDUFB3	5471	0.06	0.25	YES
71	UQCRHL	UQCRHL	UQCRHL	5481	0.06	0.25	YES
72	VDAC3	VDAC3	VDAC3	5536	0.059	0.25	YES
73	CASP3	CASP3	CASP3	5586	0.058	0.25	YES
74	CREB3L4	CREB3L4	CREB3L4	5596	0.057	0.26	YES
75	AP2M1	AP2M1	AP2M1	5661	0.056	0.26	YES
76	COX5B	COX5B	COX5B	5665	0.056	0.26	YES
77	UQCR11	UQCR11	UQCR11	5701	0.055	0.26	YES
78	COX7C	COX7C	COX7C	5706	0.055	0.26	YES
79	DNAL4	DNAL4	DNAL4	5778	0.054	0.26	YES
80	UQCRC1	UQCRC1	UQCRC1	5793	0.053	0.27	YES
81	IFT57	IFT57	IFT57	5806	0.053	0.27	YES
82	UQCRB	UQCRB	UQCRB	5814	0.053	0.27	YES
83	ATP5H	ATP5H	ATP5H	5839	0.052	0.27	YES
84	SDHB	SDHB	SDHB	5914	0.05	0.27	YES
85	NDUFA1	NDUFA1	NDUFA1	5954	0.049	0.27	YES
86	SOD1	SOD1	SOD1	6021	0.048	0.27	YES
87	DNAI2	DNAI2	DNAI2	6077	0.047	0.27	YES
88	COX5A	COX5A	COX5A	6083	0.047	0.28	YES
89	NDUFA4	NDUFA4	NDUFA4	6133	0.046	0.28	YES
90	SLC25A6	SLC25A6	SLC25A6	6135	0.046	0.28	YES
91	CLTA	CLTA	CLTA	6165	0.045	0.28	YES
92	ATP5G3	ATP5G3	ATP5G3	6254	0.043	0.28	NO
93	UQCRFS1	UQCRFS1	UQCRFS1	6293	0.042	0.28	NO
94	ATP5A1	ATP5A1	ATP5A1	6328	0.042	0.28	NO
95	POLR2K	POLR2K	POLR2K	6398	0.04	0.28	NO
96	PPARG	PPARG	PPARG	6448	0.04	0.28	NO
97	POLR2C	POLR2C	POLR2C	6487	0.039	0.28	NO
98	SDHA	SDHA	SDHA	6494	0.039	0.28	NO
99	SLC25A5	SLC25A5	SLC25A5	6569	0.037	0.28	NO
100	NDUFC1	NDUFC1	NDUFC1	6579	0.037	0.28	NO
101	COX7B	COX7B	COX7B	6626	0.036	0.28	NO
102	ATP5F1	ATP5F1	ATP5F1	6759	0.033	0.27	NO
103	ATP5G1	ATP5G1	ATP5G1	6798	0.032	0.27	NO
104	CASP8	CASP8	CASP8	6851	0.031	0.27	NO
105	DCTN1	DCTN1	DCTN1	6866	0.031	0.27	NO
106	NDUFA8	NDUFA8	NDUFA8	6950	0.03	0.27	NO
107	COX7A2L	COX7A2L	COX7A2L	6985	0.029	0.27	NO
108	PLCB2	PLCB2	PLCB2	7021	0.028	0.27	NO
109	CYC1	CYC1	CYC1	7114	0.026	0.27	NO
110	PPID	PPID	PPID	7174	0.025	0.26	NO
111	TBP	TBP	TBP	7197	0.024	0.26	NO
112	CREB3	CREB3	CREB3	7264	0.023	0.26	NO
113	COX6A2	COX6A2	COX6A2	7364	0.021	0.26	NO
114	ATP5B	ATP5B	ATP5B	7646	0.015	0.24	NO
115	NDUFA10	NDUFA10	NDUFA10	7725	0.014	0.24	NO
116	DNALI1	DNALI1	DNALI1	7830	0.012	0.24	NO
117	VDAC2	VDAC2	VDAC2	7837	0.011	0.24	NO
118	NDUFB5	NDUFB5	NDUFB5	7931	0.0096	0.23	NO
119	NDUFV3	NDUFV3	NDUFV3	7990	0.0084	0.23	NO
120	NDUFA5	NDUFA5	NDUFA5	8137	0.0051	0.22	NO
121	COX7A1	COX7A1	COX7A1	8405	-0.00032	0.21	NO
122	VDAC1	VDAC1	VDAC1	8524	-0.0028	0.2	NO
123	POLR2A	POLR2A	POLR2A	8745	-0.0077	0.19	NO
124	AP2A1	AP2A1	AP2A1	8868	-0.0098	0.18	NO
125	SIN3A	SIN3A	SIN3A	8940	-0.011	0.18	NO
126	TFAM	TFAM	TFAM	9051	-0.014	0.17	NO
127	CREB1	CREB1	CREB1	9078	-0.014	0.17	NO
128	RCOR1	RCOR1	RCOR1	9190	-0.016	0.17	NO
129	SP1	SP1	SP1	9257	-0.018	0.17	NO
130	POLR2J3	POLR2J3	POLR2J3	9264	-0.018	0.17	NO
131	HTT	HTT	HTT	9305	-0.019	0.16	NO
132	UQCRC2	UQCRC2	UQCRC2	9500	-0.023	0.16	NO
133	CYCS	CYCS	CYCS	9988	-0.033	0.13	NO
134	DNAH2	DNAH2	DNAH2	10052	-0.034	0.13	NO
135	CASP9	CASP9	CASP9	10118	-0.036	0.13	NO
136	GNAQ	GNAQ	GNAQ	10365	-0.041	0.12	NO
137	POLR2B	POLR2B	POLR2B	10560	-0.045	0.11	NO
138	AP2B1	AP2B1	AP2B1	10569	-0.045	0.11	NO
139	TAF4B	TAF4B	TAF4B	10644	-0.048	0.11	NO
140	SDHD	SDHD	SDHD	10694	-0.049	0.11	NO
141	CREBBP	CREBBP	CREBBP	10801	-0.051	0.11	NO
142	APAF1	APAF1	APAF1	10886	-0.053	0.11	NO
143	SLC25A31	SLC25A31	SLC25A31	10927	-0.054	0.11	NO
144	DCTN4	DCTN4	DCTN4	10934	-0.054	0.11	NO
145	CREB3L2	CREB3L2	CREB3L2	11266	-0.062	0.097	NO
146	SDHC	SDHC	SDHC	11394	-0.066	0.094	NO
147	CLTCL1	CLTCL1	CLTCL1	11400	-0.066	0.098	NO
148	CLTC	CLTC	CLTC	11517	-0.069	0.096	NO
149	NDUFS2	NDUFS2	NDUFS2	11561	-0.07	0.098	NO
150	ITPR1	ITPR1	ITPR1	11941	-0.08	0.082	NO
151	TAF4	TAF4	TAF4	12032	-0.083	0.082	NO
152	COX8C	COX8C	COX8C	12301	-0.091	0.072	NO
153	DNAL1	DNAL1	DNAL1	12408	-0.094	0.072	NO
154	NDUFS1	NDUFS1	NDUFS1	12596	-0.099	0.068	NO
155	PLCB1	PLCB1	PLCB1	12686	-0.1	0.07	NO
156	SOD2	SOD2	SOD2	12707	-0.1	0.075	NO
157	DNAH1	DNAH1	DNAH1	13121	-0.12	0.06	NO
158	EP300	EP300	EP300	13277	-0.12	0.059	NO
159	PLCB3	PLCB3	PLCB3	13441	-0.13	0.058	NO
160	SLC25A4	SLC25A4	SLC25A4	13902	-0.15	0.042	NO
161	GRM5	GRM5	GRM5	15590	-0.26	-0.036	NO
162	DNAH3	DNAH3	DNAH3	15889	-0.28	-0.035	NO
163	CREB5	CREB5	CREB5	16661	-0.36	-0.055	NO
164	DNAI1	DNAI1	DNAI1	16760	-0.37	-0.037	NO
165	REST	REST	REST	16986	-0.4	-0.025	NO
166	HIP1	HIP1	HIP1	16990	-0.4	0.000014	NO
167	PPARGC1A	PPARGC1A	PPARGC1A	17240	-0.44	0.014	NO
168	BDNF	BDNF	BDNF	18129	-0.71	0.0085	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 DNA REPLICATION.

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

genes ES table in pathway: KEGG SPLICEOSOME

Table 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	POLE2	POLE2	POLE2	942	0.3	0.012	YES
2	RNASEH2B	RNASEH2B	RNASEH2B	1196	0.27	0.054	YES
3	FEN1	FEN1	FEN1	1668	0.21	0.073	YES
4	RNASEH2A	RNASEH2A	RNASEH2A	1804	0.2	0.11	YES
5	MCM7	MCM7	MCM7	2127	0.18	0.13	YES
6	RNASEH2C	RNASEH2C	RNASEH2C	2138	0.17	0.16	YES
7	MCM5	MCM5	MCM5	2225	0.17	0.19	YES
8	RPA3	RPA3	RPA3	2342	0.16	0.22	YES
9	MCM6	MCM6	MCM6	2416	0.16	0.25	YES
10	POLD1	POLD1	POLD1	2481	0.15	0.28	YES
11	PCNA	PCNA	PCNA	2549	0.15	0.3	YES
12	POLD2	POLD2	POLD2	2720	0.14	0.33	YES
13	POLE	POLE	POLE	2733	0.14	0.36	YES
14	POLA2	POLA2	POLA2	2750	0.14	0.38	YES
15	RFC4	RFC4	RFC4	2897	0.14	0.4	YES
16	LIG1	LIG1	LIG1	2962	0.13	0.43	YES
17	PRIM1	PRIM1	PRIM1	3099	0.13	0.45	YES
18	RFC2	RFC2	RFC2	3207	0.12	0.47	YES
19	MCM3	MCM3	MCM3	3386	0.12	0.48	YES
20	MCM2	MCM2	MCM2	3446	0.11	0.5	YES
21	DNA2	DNA2	DNA2	3621	0.11	0.51	YES
22	RFC5	RFC5	RFC5	3678	0.11	0.53	YES
23	PRIM2	PRIM2	PRIM2	3729	0.1	0.55	YES
24	SSBP1	SSBP1	SSBP1	4462	0.085	0.53	NO
25	POLD4	POLD4	POLD4	5170	0.068	0.51	NO
26	RFC3	RFC3	RFC3	5394	0.063	0.51	NO
27	POLD3	POLD3	POLD3	5722	0.055	0.5	NO
28	POLE4	POLE4	POLE4	5743	0.054	0.51	NO
29	POLE3	POLE3	POLE3	5991	0.049	0.51	NO
30	RPA1	RPA1	RPA1	6211	0.044	0.5	NO
31	RPA2	RPA2	RPA2	6315	0.042	0.51	NO
32	RFC1	RFC1	RFC1	8771	-0.0081	0.37	NO
33	MCM4	MCM4	MCM4	9218	-0.017	0.35	NO
34	RNASEH1	RNASEH1	RNASEH1	12957	-0.11	0.17	NO
35	RPA4	RPA4	RPA4	17843	-0.57	0.024	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	E2F2	E2F2	E2F2	467	0.39	-0.0041	YES
2	CCNA1	CCNA1	CCNA1	540	0.38	0.013	YES
3	CDKN2D	CDKN2D	CDKN2D	563	0.37	0.032	YES
4	CDC25C	CDC25C	CDC25C	626	0.36	0.048	YES
5	CDC20	CDC20	CDC20	646	0.36	0.066	YES
6	PTTG2	PTTG2	PTTG2	667	0.35	0.085	YES
7	CDC45	CDC45	CDC45	718	0.34	0.1	YES
8	TTK	TTK	TTK	796	0.33	0.11	YES
9	TFDP2	TFDP2	TFDP2	813	0.32	0.13	YES
10	CCNB2	CCNB2	CCNB2	859	0.32	0.15	YES
11	CDKN2C	CDKN2C	CDKN2C	860	0.32	0.16	YES
12	CDC25A	CDC25A	CDC25A	871	0.31	0.18	YES
13	PKMYT1	PKMYT1	PKMYT1	901	0.31	0.2	YES
14	PLK1	PLK1	PLK1	962	0.3	0.21	YES
15	E2F1	E2F1	E2F1	1034	0.29	0.22	YES
16	MAD2L2	MAD2L2	MAD2L2	1076	0.28	0.23	YES
17	ORC1L	ORC1L	ORC1L	1101	0.28	0.25	YES
18	PTTG1	PTTG1	PTTG1	1145	0.28	0.26	YES
19	CCNA2	CCNA2	CCNA2	1284	0.26	0.27	YES
20	CDKN1C	CDKN1C	CDKN1C	1294	0.26	0.28	YES
21	BUB1	BUB1	BUB1	1329	0.25	0.29	YES
22	CHEK1	CHEK1	CHEK1	1427	0.24	0.3	YES
23	ESPL1	ESPL1	ESPL1	1451	0.24	0.31	YES
24	CDK6	CDK6	CDK6	1478	0.23	0.32	YES
25	CDC6	CDC6	CDC6	1543	0.22	0.33	YES
26	CCNB1	CCNB1	CCNB1	1653	0.22	0.34	YES
27	BUB1B	BUB1B	BUB1B	1694	0.21	0.35	YES
28	CDK1	CDK1	CDK1	1802	0.2	0.35	YES
29	CCNE2	CCNE2	CCNE2	1856	0.2	0.36	YES
30	CCND3	CCND3	CCND3	1910	0.19	0.37	YES
31	MCM7	MCM7	MCM7	2127	0.18	0.36	YES
32	MCM5	MCM5	MCM5	2225	0.17	0.37	YES
33	CHEK2	CHEK2	CHEK2	2289	0.16	0.38	YES
34	MCM6	MCM6	MCM6	2416	0.16	0.38	YES
35	RBX1	RBX1	RBX1	2499	0.15	0.38	YES
36	PCNA	PCNA	PCNA	2549	0.15	0.39	YES
37	MAD2L1	MAD2L1	MAD2L1	2576	0.15	0.39	YES
38	CDC25B	CDC25B	CDC25B	2692	0.14	0.39	YES
39	MAD1L1	MAD1L1	MAD1L1	2854	0.14	0.39	NO
40	ANAPC11	ANAPC11	ANAPC11	2984	0.13	0.39	NO
41	CCNE1	CCNE1	CCNE1	3148	0.12	0.39	NO
42	MCM3	MCM3	MCM3	3386	0.12	0.38	NO
43	MCM2	MCM2	MCM2	3446	0.11	0.39	NO
44	TP53	TP53	TP53	3693	0.11	0.38	NO
45	CDC7	CDC7	CDC7	3743	0.1	0.38	NO
46	ORC6L	ORC6L	ORC6L	4265	0.09	0.36	NO
47	CCND2	CCND2	CCND2	4315	0.089	0.36	NO
48	HDAC2	HDAC2	HDAC2	4456	0.086	0.36	NO
49	HDAC1	HDAC1	HDAC1	4532	0.083	0.36	NO
50	CDC26	CDC26	CDC26	4582	0.082	0.36	NO
51	CDK2	CDK2	CDK2	4647	0.08	0.36	NO
52	CDC16	CDC16	CDC16	4690	0.079	0.36	NO
53	CDK4	CDK4	CDK4	4884	0.074	0.36	NO
54	ZBTB17	ZBTB17	ZBTB17	5066	0.07	0.35	NO
55	ANAPC2	ANAPC2	ANAPC2	5313	0.065	0.34	NO
56	CCNH	CCNH	CCNH	5335	0.064	0.34	NO
57	CDKN2A	CDKN2A	CDKN2A	5480	0.06	0.34	NO
58	FZR1	FZR1	FZR1	5501	0.059	0.34	NO
59	YWHAE	YWHAE	YWHAE	5566	0.058	0.34	NO
60	E2F4	E2F4	E2F4	5700	0.055	0.34	NO
61	BUB3	BUB3	BUB3	5711	0.055	0.34	NO
62	ANAPC5	ANAPC5	ANAPC5	5818	0.053	0.34	NO
63	SKP1	SKP1	SKP1	6298	0.042	0.31	NO
64	YWHAQ	YWHAQ	YWHAQ	6396	0.04	0.31	NO
65	CDKN1B	CDKN1B	CDKN1B	6443	0.04	0.31	NO
66	YWHAH	YWHAH	YWHAH	6552	0.037	0.3	NO
67	ANAPC4	ANAPC4	ANAPC4	6565	0.037	0.3	NO
68	GADD45B	GADD45B	GADD45B	6940	0.03	0.29	NO
69	MYC	MYC	MYC	7057	0.027	0.28	NO
70	ANAPC7	ANAPC7	ANAPC7	7077	0.027	0.28	NO
71	TFDP1	TFDP1	TFDP1	7288	0.023	0.27	NO
72	SMAD4	SMAD4	SMAD4	7377	0.021	0.27	NO
73	E2F5	E2F5	E2F5	7522	0.018	0.26	NO
74	TGFB1	TGFB1	TGFB1	7600	0.016	0.26	NO
75	WEE1	WEE1	WEE1	7856	0.011	0.24	NO
76	RAD21	RAD21	RAD21	7920	0.0098	0.24	NO
77	ORC3L	ORC3L	ORC3L	7955	0.0091	0.24	NO
78	YWHAB	YWHAB	YWHAB	8103	0.0059	0.23	NO
79	SMAD2	SMAD2	SMAD2	8169	0.0045	0.23	NO
80	ANAPC10	ANAPC10	ANAPC10	8559	-0.0034	0.21	NO
81	ANAPC13	ANAPC13	ANAPC13	8577	-0.004	0.21	NO
82	YWHAZ	YWHAZ	YWHAZ	8744	-0.0077	0.2	NO
83	SFN	SFN	SFN	8866	-0.0098	0.19	NO
84	ORC4L	ORC4L	ORC4L	8947	-0.011	0.19	NO
85	MDM2	MDM2	MDM2	9141	-0.016	0.18	NO
86	ORC5L	ORC5L	ORC5L	9195	-0.017	0.18	NO
87	MCM4	MCM4	MCM4	9218	-0.017	0.18	NO
88	SMAD3	SMAD3	SMAD3	9703	-0.027	0.15	NO
89	SMC1A	SMC1A	SMC1A	9837	-0.029	0.14	NO
90	STAG2	STAG2	STAG2	9964	-0.032	0.14	NO
91	CDK7	CDK7	CDK7	10064	-0.034	0.14	NO
92	SKP2	SKP2	SKP2	10138	-0.036	0.13	NO
93	RB1	RB1	RB1	10279	-0.039	0.13	NO
94	ABL1	ABL1	ABL1	10326	-0.04	0.13	NO
95	E2F3	E2F3	E2F3	10402	-0.042	0.13	NO
96	SMC3	SMC3	SMC3	10454	-0.043	0.13	NO
97	CDC27	CDC27	CDC27	10511	-0.044	0.12	NO
98	GADD45A	GADD45A	GADD45A	10710	-0.049	0.12	NO
99	CREBBP	CREBBP	CREBBP	10801	-0.051	0.12	NO
100	ORC2L	ORC2L	ORC2L	11224	-0.062	0.095	NO
101	CUL1	CUL1	CUL1	11260	-0.062	0.097	NO
102	CDC23	CDC23	CDC23	11458	-0.068	0.09	NO
103	ANAPC1	ANAPC1	ANAPC1	11506	-0.069	0.091	NO
104	CCND1	CCND1	CCND1	12073	-0.084	0.064	NO
105	PRKDC	PRKDC	PRKDC	12167	-0.087	0.064	NO
106	YWHAG	YWHAG	YWHAG	12823	-0.11	0.034	NO
107	TGFB3	TGFB3	TGFB3	12999	-0.11	0.03	NO
108	RBL2	RBL2	RBL2	13043	-0.12	0.034	NO
109	EP300	EP300	EP300	13277	-0.12	0.028	NO
110	ATR	ATR	ATR	13478	-0.13	0.024	NO
111	GSK3B	GSK3B	GSK3B	13497	-0.13	0.031	NO
112	CDC14A	CDC14A	CDC14A	13763	-0.14	0.024	NO
113	TGFB2	TGFB2	TGFB2	14081	-0.16	0.015	NO
114	ATM	ATM	ATM	14294	-0.17	0.013	NO
115	STAG1	STAG1	STAG1	14526	-0.18	0.01	NO
116	RBL1	RBL1	RBL1	15007	-0.21	-0.0045	NO
117	CDKN1A	CDKN1A	CDKN1A	15255	-0.23	-0.0055	NO
118	SMC1B	SMC1B	SMC1B	15282	-0.23	0.0058	NO
119	CDC14B	CDC14B	CDC14B	15436	-0.24	0.011	NO
120	GADD45G	GADD45G	GADD45G	16292	-0.32	-0.019	NO
121	WEE2	WEE2	WEE2	17913	-0.59	-0.076	NO
122	CCNB3	CCNB3	CCNB3	18114	-0.7	-0.048	NO
123	CDKN2B	CDKN2B	CDKN2B	18280	-1	0.00016	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 AGR PATHWAY	35	genes.ES.table	0.52	1.3	0.15	0.78	0.97	0.46	0.23	0.35	0.7	0.3
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.46	1.3	0.12	0.81	0.96	0.44	0.32	0.3	0.71	0.32
BIOCARTA EDG1 PATHWAY	26	genes.ES.table	0.53	1.4	0.052	0.96	0.91	0.5	0.28	0.36	0.77	0.39
KEGG N GLYCAN BIOSYNTHESIS	45	genes.ES.table	0.35	1.3	0.18	0.86	0.97	0.2	0.17	0.17	0.76	0.35
KEGG O GLYCAN BIOSYNTHESIS	27	genes.ES.table	0.58	1.5	0.021	1	0.85	0.44	0.25	0.33	1	0.72
KEGG WNT SIGNALING PATHWAY	145	genes.ES.table	0.39	1.3	0.088	0.85	0.96	0.32	0.24	0.24	0.74	0.34
KEGG TGF BETA SIGNALING PATHWAY	84	genes.ES.table	0.56	1.4	0.036	1	0.88	0.58	0.3	0.41	0.84	0.44
KEGG AXON GUIDANCE	127	genes.ES.table	0.48	1.4	0.033	0.92	0.92	0.4	0.24	0.31	0.73	0.38
KEGG FOCAL ADHESION	195	genes.ES.table	0.52	1.5	0.037	1	0.82	0.46	0.23	0.36	1	0.8
KEGG ECM RECEPTOR INTERACTION	80	genes.ES.table	0.61	1.4	0.057	0.97	0.89	0.61	0.23	0.47	0.75	0.38

genes ES table in pathway: BIOCARTA AGR 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	ITGB8	ITGB8	ITGB8	44	1.1	0.017	YES
2	MYLK3	MYLK3	MYLK3	61	1.1	0.035	YES
3	ITGA9	ITGA9	ITGA9	96	1	0.051	YES
4	IBSP	IBSP	IBSP	155	0.96	0.065	YES
5	ITGA1	ITGA1	ITGA1	172	0.94	0.08	YES
6	LAMA1	LAMA1	LAMA1	219	0.9	0.093	YES
7	ROCK2	ROCK2	ROCK2	287	0.85	0.1	YES
8	LAMB4	LAMB4	LAMB4	293	0.85	0.12	YES
9	ITGB3	ITGB3	ITGB3	366	0.81	0.13	YES
10	ITGA8	ITGA8	ITGA8	472	0.76	0.14	YES
11	MYLK	MYLK	MYLK	488	0.76	0.15	YES
12	COL11A1	COL11A1	COL11A1	497	0.75	0.16	YES
13	ITGA2	ITGA2	ITGA2	536	0.74	0.17	YES
14	EGFR	EGFR	EGFR	689	0.69	0.18	YES
15	FN1	FN1	FN1	887	0.65	0.18	YES
16	LAMA2	LAMA2	LAMA2	921	0.64	0.19	YES
17	HGF	HGF	HGF	967	0.63	0.2	YES
18	VEGFC	VEGFC	VEGFC	985	0.63	0.2	YES
19	ITGA2B	ITGA2B	ITGA2B	1007	0.62	0.21	YES
20	COL2A1	COL2A1	COL2A1	1008	0.62	0.22	YES
21	MYLK2	MYLK2	MYLK2	1029	0.62	0.24	YES
22	FLNC	FLNC	FLNC	1061	0.61	0.24	YES
23	KDR	KDR	KDR	1090	0.6	0.25	YES
24	MET	MET	MET	1244	0.57	0.25	YES
25	CHAD	CHAD	CHAD	1314	0.56	0.26	YES
26	FLT1	FLT1	FLT1	1351	0.56	0.27	YES
27	THBS1	THBS1	THBS1	1432	0.54	0.27	YES
28	LAMA4	LAMA4	LAMA4	1475	0.53	0.28	YES
29	VEGFA	VEGFA	VEGFA	1497	0.53	0.29	YES
30	PDGFC	PDGFC	PDGFC	1536	0.52	0.3	YES
31	ITGA10	ITGA10	ITGA10	1581	0.51	0.3	YES
32	THBS4	THBS4	THBS4	1583	0.51	0.31	YES
33	ERBB2	ERBB2	ERBB2	1659	0.5	0.32	YES
34	ITGA3	ITGA3	ITGA3	1707	0.5	0.32	YES
35	MYL9	MYL9	MYL9	1804	0.48	0.32	YES
36	DOCK1	DOCK1	DOCK1	1887	0.47	0.33	YES
37	PAK6	PAK6	PAK6	1889	0.47	0.34	YES
38	SHC4	SHC4	SHC4	1930	0.47	0.34	YES
39	COL11A2	COL11A2	COL11A2	1942	0.47	0.35	YES
40	PARVA	PARVA	PARVA	1976	0.46	0.36	YES
41	PDGFD	PDGFD	PDGFD	1978	0.46	0.36	YES
42	LAMB2	LAMB2	LAMB2	2096	0.44	0.36	YES
43	MAPK8	MAPK8	MAPK8	2134	0.44	0.37	YES
44	PDGFB	PDGFB	PDGFB	2223	0.43	0.37	YES
45	SPP1	SPP1	SPP1	2297	0.42	0.38	YES
46	PDGFRA	PDGFRA	PDGFRA	2312	0.42	0.38	YES
47	ITGB4	ITGB4	ITGB4	2331	0.41	0.39	YES
48	COL4A6	COL4A6	COL4A6	2469	0.4	0.39	YES
49	COL5A1	COL5A1	COL5A1	2483	0.4	0.4	YES
50	ITGAV	ITGAV	ITGAV	2493	0.39	0.4	YES
51	PDGFA	PDGFA	PDGFA	2548	0.39	0.4	YES
52	CCND2	CCND2	CCND2	2695	0.38	0.4	YES
53	COL4A1	COL4A1	COL4A1	2696	0.37	0.41	YES
54	PDGFRB	PDGFRB	PDGFRB	2703	0.37	0.42	YES
55	PIK3CA	PIK3CA	PIK3CA	2724	0.37	0.42	YES
56	ITGB5	ITGB5	ITGB5	2757	0.37	0.43	YES
57	LAMA5	LAMA5	LAMA5	2801	0.36	0.43	YES
58	ACTN3	ACTN3	ACTN3	2842	0.36	0.43	YES
59	VCL	VCL	VCL	2905	0.36	0.44	YES
60	LAMC1	LAMC1	LAMC1	2909	0.35	0.44	YES
61	ITGA6	ITGA6	ITGA6	2920	0.35	0.45	YES
62	IGF1R	IGF1R	IGF1R	3069	0.34	0.45	YES
63	FLT4	FLT4	FLT4	3090	0.34	0.45	YES
64	TNC	TNC	TNC	3111	0.34	0.46	YES
65	LAMA3	LAMA3	LAMA3	3174	0.33	0.46	YES
66	ARHGAP5	ARHGAP5	ARHGAP5	3313	0.32	0.46	YES
67	CCND1	CCND1	CCND1	3360	0.32	0.46	YES
68	PDPK1	PDPK1	PDPK1	3382	0.31	0.46	YES
69	COL1A2	COL1A2	COL1A2	3411	0.31	0.47	YES
70	COL5A2	COL5A2	COL5A2	3509	0.3	0.47	YES
71	LAMC3	LAMC3	LAMC3	3605	0.29	0.47	YES
72	ITGB1	ITGB1	ITGB1	3611	0.29	0.47	YES
73	CRK	CRK	CRK	3665	0.29	0.47	YES
74	RASGRF1	RASGRF1	RASGRF1	3666	0.29	0.48	YES
75	PRKCA	PRKCA	PRKCA	3742	0.28	0.48	YES
76	PTK2	PTK2	PTK2	3804	0.28	0.48	YES
77	BCAR1	BCAR1	BCAR1	3820	0.28	0.49	YES
78	COL1A1	COL1A1	COL1A1	3852	0.28	0.49	YES
79	BCL2	BCL2	BCL2	3938	0.27	0.49	YES
80	CAPN2	CAPN2	CAPN2	3967	0.27	0.49	YES
81	TLN2	TLN2	TLN2	3970	0.27	0.5	YES
82	CAV2	CAV2	CAV2	3976	0.27	0.5	YES
83	MYL7	MYL7	MYL7	4008	0.27	0.5	YES
84	COL4A2	COL4A2	COL4A2	4045	0.26	0.51	YES
85	CTNNB1	CTNNB1	CTNNB1	4060	0.26	0.51	YES
86	COL5A3	COL5A3	COL5A3	4080	0.26	0.51	YES
87	MAPK10	MAPK10	MAPK10	4086	0.26	0.52	YES
88	COL6A3	COL6A3	COL6A3	4108	0.26	0.52	YES
89	PAK3	PAK3	PAK3	4176	0.25	0.52	YES
90	BRAF	BRAF	BRAF	4238	0.25	0.52	YES
91	SHC2	SHC2	SHC2	4452	0.24	0.52	NO
92	COL3A1	COL3A1	COL3A1	4474	0.24	0.52	NO
93	GRLF1	GRLF1	GRLF1	4617	0.23	0.51	NO
94	LAMB1	LAMB1	LAMB1	4786	0.22	0.51	NO
95	SOS2	SOS2	SOS2	4843	0.21	0.51	NO
96	TNN	TNN	TNN	4924	0.21	0.51	NO
97	ITGA11	ITGA11	ITGA11	4949	0.21	0.51	NO
98	ACTN4	ACTN4	ACTN4	5035	0.2	0.51	NO
99	MAPK1	MAPK1	MAPK1	5082	0.2	0.51	NO
100	IGF1	IGF1	IGF1	5177	0.2	0.51	NO
101	COL6A2	COL6A2	COL6A2	5190	0.2	0.51	NO
102	PXN	PXN	PXN	5456	0.18	0.5	NO
103	ROCK1	ROCK1	ROCK1	5459	0.18	0.5	NO
104	PPP1R12A	PPP1R12A	PPP1R12A	5478	0.18	0.51	NO
105	COL4A4	COL4A4	COL4A4	5765	0.17	0.49	NO
106	SOS1	SOS1	SOS1	5768	0.17	0.5	NO
107	VWF	VWF	VWF	5813	0.16	0.5	NO
108	TNXB	TNXB	TNXB	5827	0.16	0.5	NO
109	XIAP	XIAP	XIAP	5878	0.16	0.5	NO
110	CRKL	CRKL	CRKL	6011	0.16	0.49	NO
111	VAV2	VAV2	VAV2	6098	0.15	0.49	NO
112	FLNA	FLNA	FLNA	6383	0.14	0.48	NO
113	COL6A1	COL6A1	COL6A1	6414	0.14	0.48	NO
114	CAV1	CAV1	CAV1	6718	0.12	0.46	NO
115	THBS2	THBS2	THBS2	6824	0.12	0.46	NO
116	FLNB	FLNB	FLNB	6905	0.12	0.46	NO
117	PAK4	PAK4	PAK4	6939	0.11	0.46	NO
118	ACTN1	ACTN1	ACTN1	6955	0.11	0.46	NO
119	TLN1	TLN1	TLN1	6996	0.11	0.46	NO
120	SHC1	SHC1	SHC1	7132	0.11	0.45	NO
121	GSK3B	GSK3B	GSK3B	7193	0.1	0.45	NO
122	RAPGEF1	RAPGEF1	RAPGEF1	7374	0.097	0.44	NO
123	JUN	JUN	JUN	7411	0.095	0.44	NO
124	MAP2K1	MAP2K1	MAP2K1	7580	0.088	0.44	NO
125	ITGB6	ITGB6	ITGB6	7662	0.085	0.43	NO
126	MAPK3	MAPK3	MAPK3	7931	0.075	0.42	NO
127	BIRC2	BIRC2	BIRC2	8069	0.069	0.41	NO
128	PAK1	PAK1	PAK1	8130	0.067	0.41	NO
129	AKT3	AKT3	AKT3	8375	0.058	0.4	NO
130	AKT2	AKT2	AKT2	8598	0.05	0.39	NO
131	PAK7	PAK7	PAK7	8665	0.048	0.38	NO
132	PIK3R1	PIK3R1	PIK3R1	8731	0.045	0.38	NO
133	VTN	VTN	VTN	8867	0.04	0.38	NO
134	PIP5K1C	PIP5K1C	PIP5K1C	8925	0.038	0.37	NO
135	PIK3CB	PIK3CB	PIK3CB	8934	0.038	0.37	NO
136	SRC	SRC	SRC	9095	0.033	0.36	NO
137	COL6A6	COL6A6	COL6A6	9329	0.026	0.35	NO
138	RAC1	RAC1	RAC1	9377	0.024	0.35	NO
139	ZYX	ZYX	ZYX	9408	0.023	0.35	NO
140	SHC3	SHC3	SHC3	9415	0.022	0.35	NO
141	RAF1	RAF1	RAF1	9537	0.017	0.34	NO
142	ITGA5	ITGA5	ITGA5	9550	0.017	0.34	NO
143	RAP1A	RAP1A	RAP1A	9614	0.015	0.34	NO
144	PIK3R3	PIK3R3	PIK3R3	9687	0.012	0.34	NO
145	PIK3R2	PIK3R2	PIK3R2	9818	0.0067	0.33	NO
146	MAPK9	MAPK9	MAPK9	9983	0.0017	0.32	NO
147	CDC42	CDC42	CDC42	9987	0.0014	0.32	NO
148	PARVB	PARVB	PARVB	10056	-0.0011	0.32	NO
149	PGF	PGF	PGF	10057	-0.0012	0.32	NO
150	RHOA	RHOA	RHOA	10107	-0.0026	0.31	NO
151	ILK	ILK	ILK	10324	-0.011	0.3	NO
152	GRB2	GRB2	GRB2	10467	-0.016	0.29	NO
153	MYL12A	MYL12A	MYL12A	10607	-0.02	0.28	NO
154	PAK2	PAK2	PAK2	10656	-0.022	0.28	NO
155	ELK1	ELK1	ELK1	10689	-0.023	0.28	NO
156	PIK3CG	PIK3CG	PIK3CG	10942	-0.032	0.27	NO
157	PPP1CC	PPP1CC	PPP1CC	11053	-0.036	0.26	NO
158	PPP1CB	PPP1CB	PPP1CB	11117	-0.038	0.26	NO
159	MYL12B	MYL12B	MYL12B	11378	-0.047	0.25	NO
160	RAP1B	RAP1B	RAP1B	11822	-0.063	0.22	NO
161	ACTG1	ACTG1	ACTG1	11878	-0.065	0.22	NO
162	THBS3	THBS3	THBS3	12012	-0.07	0.22	NO
163	ITGA7	ITGA7	ITGA7	12024	-0.071	0.22	NO
164	COMP	COMP	COMP	12251	-0.08	0.2	NO
165	DIAPH1	DIAPH1	DIAPH1	12284	-0.081	0.2	NO
166	RELN	RELN	RELN	12405	-0.086	0.2	NO
167	AKT1	AKT1	AKT1	12631	-0.096	0.19	NO
168	PTEN	PTEN	PTEN	13056	-0.11	0.17	NO
169	ACTB	ACTB	ACTB	13084	-0.12	0.17	NO
170	ITGA4	ITGA4	ITGA4	13123	-0.12	0.17	NO
171	FIGF	FIGF	FIGF	13180	-0.12	0.17	NO
172	PIK3CD	PIK3CD	PIK3CD	13247	-0.12	0.16	NO
173	RAC3	RAC3	RAC3	13515	-0.13	0.15	NO
174	MYL2	MYL2	MYL2	13523	-0.13	0.15	NO
175	BIRC3	BIRC3	BIRC3	13813	-0.14	0.14	NO
176	VASP	VASP	VASP	13858	-0.15	0.14	NO
177	ITGB7	ITGB7	ITGB7	13928	-0.15	0.14	NO
178	VEGFB	VEGFB	VEGFB	13958	-0.15	0.14	NO
179	PPP1CA	PPP1CA	PPP1CA	14636	-0.19	0.11	NO
180	LAMB3	LAMB3	LAMB3	14710	-0.19	0.11	NO
181	FYN	FYN	FYN	14922	-0.2	0.098	NO
182	LAMC2	LAMC2	LAMC2	15035	-0.21	0.095	NO
183	BAD	BAD	BAD	15050	-0.21	0.098	NO
184	PIK3R5	PIK3R5	PIK3R5	15092	-0.21	0.1	NO
185	ACTN2	ACTN2	ACTN2	15558	-0.24	0.078	NO
186	CCND3	CCND3	CCND3	16155	-0.29	0.05	NO
187	MYL5	MYL5	MYL5	16405	-0.31	0.042	NO
188	PARVG	PARVG	PARVG	16650	-0.34	0.034	NO
189	PRKCG	PRKCG	PRKCG	16740	-0.35	0.036	NO
190	MYLPF	MYLPF	MYLPF	17129	-0.42	0.022	NO
191	EGF	EGF	EGF	17176	-0.42	0.026	NO
192	VAV1	VAV1	VAV1	17256	-0.44	0.03	NO
193	PRKCB	PRKCB	PRKCB	17269	-0.44	0.037	NO
194	RAC2	RAC2	RAC2	17501	-0.49	0.032	NO
195	VAV3	VAV3	VAV3	17925	-0.61	0.02	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 AGR PATHWAY.

Figure S42. 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 ERK 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	GALNT13	GALNT13	GALNT13	522	0.74	0.081	YES
2	GCNT1	GCNT1	GCNT1	727	0.69	0.17	YES
3	GALNT5	GALNT5	GALNT5	779	0.68	0.27	YES
4	GALNTL6	GALNTL6	GALNTL6	1093	0.6	0.34	YES
5	WBSCR17	WBSCR17	WBSCR17	1649	0.5	0.38	YES
6	GALNT8	GALNT8	GALNT8	1962	0.46	0.44	YES
7	GALNT4	GALNT4	GALNT4	2123	0.44	0.49	YES
8	GALNTL2	GALNTL2	GALNTL2	2139	0.44	0.56	YES
9	B4GALT5	B4GALT5	B4GALT5	3442	0.31	0.53	YES
10	GALNT9	GALNT9	GALNT9	3526	0.3	0.57	YES
11	GALNT10	GALNT10	GALNT10	4235	0.25	0.57	YES
12	GALNTL4	GALNTL4	GALNTL4	4556	0.23	0.58	YES
13	GALNT11	GALNT11	GALNT11	5327	0.19	0.57	NO
14	GALNTL1	GALNTL1	GALNTL1	6489	0.13	0.52	NO
15	GALNT14	GALNT14	GALNT14	7037	0.11	0.51	NO
16	GALNT1	GALNT1	GALNT1	8145	0.066	0.46	NO
17	C1GALT1	C1GALT1	C1GALT1	9143	0.031	0.41	NO
18	C1GALT1C1	C1GALT1C1	C1GALT1C1	9216	0.029	0.41	NO
19	GCNT3	GCNT3	GCNT3	9235	0.028	0.41	NO
20	ST3GAL2	ST3GAL2	ST3GAL2	9806	0.0072	0.38	NO
21	GCNT4	GCNT4	GCNT4	10260	-0.0084	0.36	NO
22	GALNT2	GALNT2	GALNT2	10516	-0.017	0.35	NO
23	GALNT7	GALNT7	GALNT7	10757	-0.026	0.34	NO
24	ST6GALNAC1	ST6GALNAC1	ST6GALNAC1	11140	-0.039	0.32	NO
25	GALNT12	GALNT12	GALNT12	11370	-0.047	0.32	NO
26	ST3GAL1	ST3GAL1	ST3GAL1	14425	-0.18	0.18	NO
27	GALNT6	GALNT6	GALNT6	15387	-0.23	0.16	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 ERK PATHWAY.

Figure S44. 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 EDG1 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	PVRL3	PVRL3	PVRL3	64	1.1	0.053	YES
2	EGFR	EGFR	EGFR	689	0.69	0.055	YES
3	MET	MET	MET	1244	0.57	0.054	YES
4	FER	FER	FER	1328	0.56	0.079	YES
5	TCF7L1	TCF7L1	TCF7L1	1578	0.52	0.092	YES
6	WASF3	WASF3	WASF3	1582	0.51	0.12	YES
7	ERBB2	ERBB2	ERBB2	1659	0.5	0.14	YES
8	PTPRB	PTPRB	PTPRB	1692	0.5	0.16	YES
9	TCF7L2	TCF7L2	TCF7L2	2109	0.44	0.16	YES
10	TJP1	TJP1	TJP1	2259	0.42	0.18	YES
11	CTNNA2	CTNNA2	CTNNA2	2293	0.42	0.2	YES
12	MLLT4	MLLT4	MLLT4	2395	0.41	0.22	YES
13	PVRL2	PVRL2	PVRL2	2715	0.37	0.22	YES
14	TGFBR2	TGFBR2	TGFBR2	2814	0.36	0.23	YES
15	ACTN3	ACTN3	ACTN3	2842	0.36	0.25	YES
16	VCL	VCL	VCL	2905	0.36	0.26	YES
17	TGFBR1	TGFBR1	TGFBR1	2957	0.35	0.28	YES
18	SNAI2	SNAI2	SNAI2	3021	0.34	0.29	YES
19	INSR	INSR	INSR	3068	0.34	0.31	YES
20	IGF1R	IGF1R	IGF1R	3069	0.34	0.32	YES
21	YES1	YES1	YES1	3117	0.34	0.34	YES
22	FARP2	FARP2	FARP2	3165	0.33	0.36	YES
23	SORBS1	SORBS1	SORBS1	3406	0.31	0.36	YES
24	FGFR1	FGFR1	FGFR1	3550	0.3	0.37	YES
25	CTNND1	CTNND1	CTNND1	3567	0.3	0.38	YES
26	WASL	WASL	WASL	3617	0.29	0.39	YES
27	LMO7	LMO7	LMO7	3623	0.29	0.41	YES
28	PTPRM	PTPRM	PTPRM	3676	0.29	0.42	YES
29	SMAD3	SMAD3	SMAD3	3988	0.27	0.42	YES
30	PVRL1	PVRL1	PVRL1	4044	0.26	0.43	YES
31	CTNNB1	CTNNB1	CTNNB1	4060	0.26	0.44	YES
32	CDH1	CDH1	CDH1	4114	0.26	0.45	YES
33	EP300	EP300	EP300	4220	0.25	0.46	YES
34	CTNNA1	CTNNA1	CTNNA1	4222	0.25	0.47	YES
35	PVRL4	PVRL4	PVRL4	4721	0.22	0.46	NO
36	PTPRF	PTPRF	PTPRF	4747	0.22	0.47	NO
37	ACTN4	ACTN4	ACTN4	5035	0.2	0.46	NO
38	MAPK1	MAPK1	MAPK1	5082	0.2	0.47	NO
39	CREBBP	CREBBP	CREBBP	5660	0.17	0.45	NO
40	MAP3K7	MAP3K7	MAP3K7	5667	0.17	0.46	NO
41	PTPRJ	PTPRJ	PTPRJ	6233	0.15	0.43	NO
42	BAIAP2	BAIAP2	BAIAP2	6315	0.14	0.43	NO
43	PARD3	PARD3	PARD3	6736	0.12	0.42	NO
44	WASF2	WASF2	WASF2	6759	0.12	0.42	NO
45	ACTN1	ACTN1	ACTN1	6955	0.11	0.42	NO
46	SMAD4	SMAD4	SMAD4	7001	0.11	0.42	NO
47	SNAI1	SNAI1	SNAI1	7092	0.11	0.42	NO
48	IQGAP1	IQGAP1	IQGAP1	7331	0.098	0.41	NO
49	MAPK3	MAPK3	MAPK3	7931	0.075	0.38	NO
50	CSNK2A2	CSNK2A2	CSNK2A2	8397	0.057	0.36	NO
51	CSNK2A1	CSNK2A1	CSNK2A1	8499	0.053	0.36	NO
52	CTNNA3	CTNNA3	CTNNA3	8789	0.043	0.35	NO
53	SMAD2	SMAD2	SMAD2	8891	0.039	0.34	NO
54	NLK	NLK	NLK	8989	0.036	0.34	NO
55	SRC	SRC	SRC	9095	0.033	0.34	NO
56	RAC1	RAC1	RAC1	9377	0.024	0.32	NO
57	WASF1	WASF1	WASF1	9775	0.0084	0.3	NO
58	PTPN1	PTPN1	PTPN1	9950	0.0027	0.29	NO
59	CDC42	CDC42	CDC42	9987	0.0014	0.29	NO
60	RHOA	RHOA	RHOA	10107	-0.0026	0.28	NO
61	ACTG1	ACTG1	ACTG1	11878	-0.065	0.19	NO
62	ACP1	ACP1	ACP1	12519	-0.091	0.16	NO
63	SSX2IP	SSX2IP	SSX2IP	12702	-0.099	0.15	NO
64	ACTB	ACTB	ACTB	13084	-0.12	0.14	NO
65	RAC3	RAC3	RAC3	13515	-0.13	0.12	NO
66	CSNK2B	CSNK2B	CSNK2B	13692	-0.14	0.12	NO
67	FYN	FYN	FYN	14922	-0.2	0.062	NO
68	ACTN2	ACTN2	ACTN2	15558	-0.24	0.04	NO
69	PTPN6	PTPN6	PTPN6	15649	-0.25	0.048	NO
70	LEF1	LEF1	LEF1	17294	-0.45	-0.02	NO
71	WAS	WAS	WAS	17347	-0.45	0.0013	NO
72	TCF7	TCF7	TCF7	17418	-0.47	0.022	NO
73	RAC2	RAC2	RAC2	17501	-0.49	0.043	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 EDG1 PATHWAY.

Figure S46. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA EDG1 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 N GLYCAN BIOSYNTHESIS

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	CACNA2D1	CACNA2D1	CACNA2D1	26	1.2	0.041	YES
2	ITGB8	ITGB8	ITGB8	44	1.1	0.08	YES
3	ITGA9	ITGA9	ITGA9	96	1	0.11	YES
4	ITGA1	ITGA1	ITGA1	172	0.94	0.14	YES
5	TGFB2	TGFB2	TGFB2	178	0.92	0.18	YES
6	ITGB3	ITGB3	ITGB3	366	0.81	0.19	YES
7	ITGA8	ITGA8	ITGA8	472	0.76	0.21	YES
8	ITGA2	ITGA2	ITGA2	536	0.74	0.24	YES
9	DMD	DMD	DMD	615	0.71	0.26	YES
10	LAMA2	LAMA2	LAMA2	921	0.64	0.26	YES
11	ADCY2	ADCY2	ADCY2	943	0.64	0.28	YES
12	ITGA2B	ITGA2B	ITGA2B	1007	0.62	0.3	YES
13	ADCY5	ADCY5	ADCY5	1251	0.57	0.31	YES
14	SLC8A1	SLC8A1	SLC8A1	1341	0.56	0.33	YES
15	CACNA1C	CACNA1C	CACNA1C	1375	0.55	0.34	YES
16	ITGA10	ITGA10	ITGA10	1581	0.51	0.35	YES
17	CACNB4	CACNB4	CACNB4	1705	0.5	0.36	YES
18	ITGA3	ITGA3	ITGA3	1707	0.5	0.38	YES
19	TNNT2	TNNT2	TNNT2	1815	0.48	0.39	YES
20	MYH6	MYH6	MYH6	1915	0.47	0.4	YES
21	CACNA1D	CACNA1D	CACNA1D	2056	0.45	0.41	YES
22	SGCB	SGCB	SGCB	2280	0.42	0.41	YES
23	ITGB4	ITGB4	ITGB4	2331	0.41	0.42	YES
24	CACNA2D2	CACNA2D2	CACNA2D2	2338	0.41	0.44	YES
25	CACNB2	CACNB2	CACNB2	2432	0.4	0.45	YES
26	SGCA	SGCA	SGCA	2481	0.4	0.46	YES
27	ITGAV	ITGAV	ITGAV	2493	0.39	0.47	YES
28	ADCY6	ADCY6	ADCY6	2645	0.38	0.48	YES
29	ITGB5	ITGB5	ITGB5	2757	0.37	0.48	YES
30	DAG1	DAG1	DAG1	2818	0.36	0.49	YES
31	MYL3	MYL3	MYL3	2859	0.36	0.5	YES
32	ITGA6	ITGA6	ITGA6	2920	0.35	0.51	YES
33	RYR2	RYR2	RYR2	2970	0.35	0.52	YES
34	SGCG	SGCG	SGCG	3013	0.34	0.53	YES
35	ADCY4	ADCY4	ADCY4	3033	0.34	0.54	YES
36	ATP2A2	ATP2A2	ATP2A2	3179	0.33	0.55	YES
37	ADCY9	ADCY9	ADCY9	3217	0.33	0.56	YES
38	ADCY1	ADCY1	ADCY1	3327	0.32	0.56	YES
39	TPM1	TPM1	TPM1	3475	0.31	0.56	YES
40	ITGB1	ITGB1	ITGB1	3611	0.29	0.57	YES
41	MYH7	MYH7	MYH7	4202	0.25	0.55	NO
42	ACTC1	ACTC1	ACTC1	4673	0.22	0.53	NO
43	ADCY8	ADCY8	ADCY8	4690	0.22	0.53	NO
44	ADRB1	ADRB1	ADRB1	4862	0.21	0.53	NO
45	ITGA11	ITGA11	ITGA11	4949	0.21	0.54	NO
46	IGF1	IGF1	IGF1	5177	0.2	0.53	NO
47	TNNC1	TNNC1	TNNC1	5359	0.19	0.53	NO
48	PLN	PLN	PLN	5366	0.19	0.53	NO
49	TNF	TNF	TNF	5821	0.16	0.51	NO
50	TGFB3	TGFB3	TGFB3	6330	0.14	0.49	NO
51	TPM4	TPM4	TPM4	6957	0.11	0.46	NO
52	TTN	TTN	TTN	6983	0.11	0.46	NO
53	ITGB6	ITGB6	ITGB6	7662	0.085	0.43	NO
54	PRKX	PRKX	PRKX	7705	0.084	0.43	NO
55	ADCY7	ADCY7	ADCY7	7835	0.079	0.42	NO
56	PRKACA	PRKACA	PRKACA	8158	0.066	0.41	NO
57	CACNA2D3	CACNA2D3	CACNA2D3	8248	0.062	0.41	NO
58	TPM2	TPM2	TPM2	8473	0.054	0.4	NO
59	DES	DES	DES	8928	0.038	0.37	NO
60	LMNA	LMNA	LMNA	9067	0.034	0.37	NO
61	ITGA5	ITGA5	ITGA5	9550	0.017	0.34	NO
62	GNAS	GNAS	GNAS	10138	-0.0036	0.31	NO
63	CACNG4	CACNG4	CACNG4	11320	-0.045	0.24	NO
64	TGFB1	TGFB1	TGFB1	11577	-0.054	0.23	NO
65	CACNA2D4	CACNA2D4	CACNA2D4	11647	-0.056	0.23	NO
66	CACNA1S	CACNA1S	CACNA1S	11787	-0.061	0.22	NO
67	ACTG1	ACTG1	ACTG1	11878	-0.065	0.22	NO
68	ITGA7	ITGA7	ITGA7	12024	-0.071	0.22	NO
69	PRKACB	PRKACB	PRKACB	12182	-0.078	0.21	NO
70	ACTB	ACTB	ACTB	13084	-0.12	0.17	NO
71	ITGA4	ITGA4	ITGA4	13123	-0.12	0.17	NO
72	CACNB1	CACNB1	CACNB1	13236	-0.12	0.17	NO
73	TPM3	TPM3	TPM3	13253	-0.12	0.17	NO
74	MYL2	MYL2	MYL2	13523	-0.13	0.16	NO
75	TNNI3	TNNI3	TNNI3	13693	-0.14	0.16	NO
76	MYBPC3	MYBPC3	MYBPC3	13856	-0.15	0.15	NO
77	ITGB7	ITGB7	ITGB7	13928	-0.15	0.15	NO
78	EMD	EMD	EMD	14578	-0.18	0.12	NO
79	SGCD	SGCD	SGCD	15029	-0.21	0.11	NO
80	CACNG2	CACNG2	CACNG2	15390	-0.23	0.095	NO
81	CACNG3	CACNG3	CACNG3	15986	-0.28	0.072	NO
82	CACNB3	CACNB3	CACNB3	16089	-0.28	0.076	NO
83	CACNG1	CACNG1	CACNG1	17166	-0.42	0.032	NO
84	CACNA1F	CACNA1F	CACNA1F	18231	-0.82	0.0029	NO

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

Figure S48. 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 O GLYCAN BIOSYNTHESIS

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	CACNA2D1	CACNA2D1	CACNA2D1	26	1.2	0.045	YES
2	ITGB8	ITGB8	ITGB8	44	1.1	0.088	YES
3	ITGA9	ITGA9	ITGA9	96	1	0.12	YES
4	ITGA1	ITGA1	ITGA1	172	0.94	0.16	YES
5	ITGB3	ITGB3	ITGB3	366	0.81	0.18	YES
6	ITGA8	ITGA8	ITGA8	472	0.76	0.2	YES
7	ITGA2	ITGA2	ITGA2	536	0.74	0.23	YES
8	DMD	DMD	DMD	615	0.71	0.25	YES
9	LAMA2	LAMA2	LAMA2	921	0.64	0.26	YES
10	ITGA2B	ITGA2B	ITGA2B	1007	0.62	0.28	YES
11	SLC8A1	SLC8A1	SLC8A1	1341	0.56	0.28	YES
12	CACNA1C	CACNA1C	CACNA1C	1375	0.55	0.3	YES
13	TCF7L1	TCF7L1	TCF7L1	1578	0.52	0.31	YES
14	ITGA10	ITGA10	ITGA10	1581	0.51	0.33	YES
15	CACNB4	CACNB4	CACNB4	1705	0.5	0.34	YES
16	ITGA3	ITGA3	ITGA3	1707	0.5	0.36	YES
17	CACNA1D	CACNA1D	CACNA1D	2056	0.45	0.36	YES
18	TCF7L2	TCF7L2	TCF7L2	2109	0.44	0.38	YES
19	SGCB	SGCB	SGCB	2280	0.42	0.38	YES
20	CTNNA2	CTNNA2	CTNNA2	2293	0.42	0.4	YES
21	ITGB4	ITGB4	ITGB4	2331	0.41	0.41	YES
22	CACNA2D2	CACNA2D2	CACNA2D2	2338	0.41	0.43	YES
23	CACNB2	CACNB2	CACNB2	2432	0.4	0.44	YES
24	SGCA	SGCA	SGCA	2481	0.4	0.45	YES
25	ITGAV	ITGAV	ITGAV	2493	0.39	0.47	YES
26	ITGB5	ITGB5	ITGB5	2757	0.37	0.47	YES
27	DAG1	DAG1	DAG1	2818	0.36	0.48	YES
28	ACTN3	ACTN3	ACTN3	2842	0.36	0.49	YES
29	ITGA6	ITGA6	ITGA6	2920	0.35	0.5	YES
30	DSG2	DSG2	DSG2	2969	0.35	0.51	YES
31	RYR2	RYR2	RYR2	2970	0.35	0.52	YES
32	SGCG	SGCG	SGCG	3013	0.34	0.54	YES
33	ATP2A2	ATP2A2	ATP2A2	3179	0.33	0.54	YES
34	PKP2	PKP2	PKP2	3376	0.31	0.54	YES
35	ITGB1	ITGB1	ITGB1	3611	0.29	0.54	YES
36	GJA1	GJA1	GJA1	3719	0.28	0.55	YES
37	CTNNB1	CTNNB1	CTNNB1	4060	0.26	0.54	NO
38	CTNNA1	CTNNA1	CTNNA1	4222	0.25	0.54	NO
39	DSP	DSP	DSP	4264	0.25	0.55	NO
40	JUP	JUP	JUP	4628	0.23	0.53	NO
41	ITGA11	ITGA11	ITGA11	4949	0.21	0.52	NO
42	ACTN4	ACTN4	ACTN4	5035	0.2	0.53	NO
43	CDH2	CDH2	CDH2	5213	0.2	0.52	NO
44	DSC2	DSC2	DSC2	6920	0.12	0.44	NO
45	ACTN1	ACTN1	ACTN1	6955	0.11	0.44	NO
46	ITGB6	ITGB6	ITGB6	7662	0.085	0.4	NO
47	CACNA2D3	CACNA2D3	CACNA2D3	8248	0.062	0.37	NO
48	CTNNA3	CTNNA3	CTNNA3	8789	0.043	0.35	NO
49	DES	DES	DES	8928	0.038	0.34	NO
50	LMNA	LMNA	LMNA	9067	0.034	0.33	NO
51	ITGA5	ITGA5	ITGA5	9550	0.017	0.31	NO
52	CACNG4	CACNG4	CACNG4	11320	-0.045	0.21	NO
53	CACNA2D4	CACNA2D4	CACNA2D4	11647	-0.056	0.2	NO
54	CACNA1S	CACNA1S	CACNA1S	11787	-0.061	0.19	NO
55	ACTG1	ACTG1	ACTG1	11878	-0.065	0.19	NO
56	ITGA7	ITGA7	ITGA7	12024	-0.071	0.18	NO
57	ACTB	ACTB	ACTB	13084	-0.12	0.13	NO
58	ITGA4	ITGA4	ITGA4	13123	-0.12	0.13	NO
59	CACNB1	CACNB1	CACNB1	13236	-0.12	0.13	NO
60	ITGB7	ITGB7	ITGB7	13928	-0.15	0.099	NO
61	EMD	EMD	EMD	14578	-0.18	0.07	NO
62	SGCD	SGCD	SGCD	15029	-0.21	0.054	NO
63	CACNG2	CACNG2	CACNG2	15390	-0.23	0.043	NO
64	ACTN2	ACTN2	ACTN2	15558	-0.24	0.043	NO
65	CACNG3	CACNG3	CACNG3	15986	-0.28	0.031	NO
66	CACNB3	CACNB3	CACNB3	16089	-0.28	0.036	NO
67	CACNG1	CACNG1	CACNG1	17166	-0.42	-0.0065	NO
68	LEF1	LEF1	LEF1	17294	-0.45	0.0039	NO
69	TCF7	TCF7	TCF7	17418	-0.47	0.016	NO
70	CACNA1F	CACNA1F	CACNA1F	18231	-0.82	0.0029	NO

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

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

genes ES table in pathway: KEGG WNT SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CACNA2D1	CACNA2D1	CACNA2D1	26	1.2	0.044	YES
2	ITGB8	ITGB8	ITGB8	44	1.1	0.085	YES
3	ITGA9	ITGA9	ITGA9	96	1	0.12	YES
4	ITGA1	ITGA1	ITGA1	172	0.94	0.15	YES
5	TGFB2	TGFB2	TGFB2	178	0.92	0.19	YES
6	ITGB3	ITGB3	ITGB3	366	0.81	0.21	YES
7	ITGA8	ITGA8	ITGA8	472	0.76	0.23	YES
8	ITGA2	ITGA2	ITGA2	536	0.74	0.26	YES
9	DMD	DMD	DMD	615	0.71	0.28	YES
10	LAMA2	LAMA2	LAMA2	921	0.64	0.29	YES
11	ITGA2B	ITGA2B	ITGA2B	1007	0.62	0.3	YES
12	PRKAA2	PRKAA2	PRKAA2	1179	0.58	0.32	YES
13	SLC8A1	SLC8A1	SLC8A1	1341	0.56	0.33	YES
14	CACNA1C	CACNA1C	CACNA1C	1375	0.55	0.35	YES
15	ITGA10	ITGA10	ITGA10	1581	0.51	0.36	YES
16	CACNB4	CACNB4	CACNB4	1705	0.5	0.37	YES
17	ITGA3	ITGA3	ITGA3	1707	0.5	0.39	YES
18	TNNT2	TNNT2	TNNT2	1815	0.48	0.4	YES
19	MYH6	MYH6	MYH6	1915	0.47	0.41	YES
20	CACNA1D	CACNA1D	CACNA1D	2056	0.45	0.42	YES
21	SGCB	SGCB	SGCB	2280	0.42	0.43	YES
22	ITGB4	ITGB4	ITGB4	2331	0.41	0.44	YES
23	CACNA2D2	CACNA2D2	CACNA2D2	2338	0.41	0.45	YES
24	CACNB2	CACNB2	CACNB2	2432	0.4	0.46	YES
25	SGCA	SGCA	SGCA	2481	0.4	0.48	YES
26	ITGAV	ITGAV	ITGAV	2493	0.39	0.49	YES
27	ACE	ACE	ACE	2699	0.37	0.49	YES
28	ITGB5	ITGB5	ITGB5	2757	0.37	0.5	YES
29	DAG1	DAG1	DAG1	2818	0.36	0.52	YES
30	MYL3	MYL3	MYL3	2859	0.36	0.53	YES
31	ITGA6	ITGA6	ITGA6	2920	0.35	0.54	YES
32	RYR2	RYR2	RYR2	2970	0.35	0.55	YES
33	SGCG	SGCG	SGCG	3013	0.34	0.56	YES
34	ATP2A2	ATP2A2	ATP2A2	3179	0.33	0.56	YES
35	TPM1	TPM1	TPM1	3475	0.31	0.56	NO
36	ITGB1	ITGB1	ITGB1	3611	0.29	0.56	NO
37	MYH7	MYH7	MYH7	4202	0.25	0.54	NO
38	ACTC1	ACTC1	ACTC1	4673	0.22	0.52	NO
39	ITGA11	ITGA11	ITGA11	4949	0.21	0.51	NO
40	PRKAG2	PRKAG2	PRKAG2	5061	0.2	0.51	NO
41	IGF1	IGF1	IGF1	5177	0.2	0.52	NO
42	TNNC1	TNNC1	TNNC1	5359	0.19	0.51	NO
43	IL6	IL6	IL6	5609	0.17	0.5	NO
44	TNF	TNF	TNF	5821	0.16	0.5	NO
45	PRKAB2	PRKAB2	PRKAB2	6002	0.16	0.5	NO
46	TGFB3	TGFB3	TGFB3	6330	0.14	0.48	NO
47	TPM4	TPM4	TPM4	6957	0.11	0.45	NO
48	TTN	TTN	TTN	6983	0.11	0.46	NO
49	PRKAA1	PRKAA1	PRKAA1	7489	0.092	0.43	NO
50	ITGB6	ITGB6	ITGB6	7662	0.085	0.43	NO
51	CACNA2D3	CACNA2D3	CACNA2D3	8248	0.062	0.4	NO
52	TPM2	TPM2	TPM2	8473	0.054	0.39	NO
53	PRKAB1	PRKAB1	PRKAB1	8555	0.051	0.38	NO
54	DES	DES	DES	8928	0.038	0.36	NO
55	LMNA	LMNA	LMNA	9067	0.034	0.36	NO
56	ITGA5	ITGA5	ITGA5	9550	0.017	0.33	NO
57	PRKAG1	PRKAG1	PRKAG1	11308	-0.045	0.24	NO
58	CACNG4	CACNG4	CACNG4	11320	-0.045	0.24	NO
59	TGFB1	TGFB1	TGFB1	11577	-0.054	0.23	NO
60	CACNA2D4	CACNA2D4	CACNA2D4	11647	-0.056	0.22	NO
61	CACNA1S	CACNA1S	CACNA1S	11787	-0.061	0.22	NO
62	ACTG1	ACTG1	ACTG1	11878	-0.065	0.22	NO
63	ITGA7	ITGA7	ITGA7	12024	-0.071	0.21	NO
64	ACTB	ACTB	ACTB	13084	-0.12	0.16	NO
65	ITGA4	ITGA4	ITGA4	13123	-0.12	0.16	NO
66	CACNB1	CACNB1	CACNB1	13236	-0.12	0.16	NO
67	TPM3	TPM3	TPM3	13253	-0.12	0.16	NO
68	MYL2	MYL2	MYL2	13523	-0.13	0.15	NO
69	TNNI3	TNNI3	TNNI3	13693	-0.14	0.15	NO
70	MYBPC3	MYBPC3	MYBPC3	13856	-0.15	0.14	NO
71	ITGB7	ITGB7	ITGB7	13928	-0.15	0.15	NO
72	EMD	EMD	EMD	14578	-0.18	0.12	NO
73	SGCD	SGCD	SGCD	15029	-0.21	0.1	NO
74	CACNG2	CACNG2	CACNG2	15390	-0.23	0.09	NO
75	CACNG3	CACNG3	CACNG3	15986	-0.28	0.068	NO
76	CACNB3	CACNB3	CACNB3	16089	-0.28	0.073	NO
77	CACNG1	CACNG1	CACNG1	17166	-0.42	0.03	NO
78	CACNA1F	CACNA1F	CACNA1F	18231	-0.82	0.0029	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 WNT SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG TGF BETA SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SMAD9	SMAD9	SMAD9	10	1.3	0.049	YES
2	TGFB2	TGFB2	TGFB2	178	0.92	0.075	YES
3	ID4	ID4	ID4	209	0.9	0.11	YES
4	ROCK2	ROCK2	ROCK2	287	0.85	0.14	YES
5	BMP8B	BMP8B	BMP8B	341	0.82	0.17	YES
6	GDF6	GDF6	GDF6	475	0.76	0.19	YES
7	BMP2	BMP2	BMP2	577	0.73	0.21	YES
8	LTBP1	LTBP1	LTBP1	636	0.71	0.23	YES
9	SMAD7	SMAD7	SMAD7	767	0.68	0.25	YES
10	LEFTY2	LEFTY2	LEFTY2	830	0.66	0.28	YES
11	BMP4	BMP4	BMP4	941	0.64	0.29	YES
12	FST	FST	FST	1022	0.62	0.31	YES
13	GDF7	GDF7	GDF7	1184	0.58	0.33	YES
14	ACVR1C	ACVR1C	ACVR1C	1196	0.58	0.35	YES
15	INHBB	INHBB	INHBB	1233	0.58	0.37	YES
16	GDF5	GDF5	GDF5	1257	0.57	0.39	YES
17	BMPR1A	BMPR1A	BMPR1A	1393	0.55	0.4	YES
18	THBS1	THBS1	THBS1	1432	0.54	0.42	YES
19	THBS4	THBS4	THBS4	1583	0.51	0.43	YES
20	INHBC	INHBC	INHBC	1653	0.5	0.45	YES
21	BMP6	BMP6	BMP6	1730	0.49	0.46	YES
22	SMAD6	SMAD6	SMAD6	1750	0.49	0.48	YES
23	ACVR1	ACVR1	ACVR1	2514	0.39	0.46	YES
24	TGFBR2	TGFBR2	TGFBR2	2814	0.36	0.45	YES
25	NODAL	NODAL	NODAL	2931	0.35	0.46	YES
26	TGFBR1	TGFBR1	TGFBR1	2957	0.35	0.47	YES
27	BMPR2	BMPR2	BMPR2	2985	0.35	0.48	YES
28	LEFTY1	LEFTY1	LEFTY1	3314	0.32	0.48	YES
29	ZFYVE9	ZFYVE9	ZFYVE9	3336	0.32	0.49	YES
30	SMAD5	SMAD5	SMAD5	3361	0.32	0.5	YES
31	INHBA	INHBA	INHBA	3388	0.31	0.51	YES
32	ACVR2A	ACVR2A	ACVR2A	3517	0.3	0.52	YES
33	SMURF2	SMURF2	SMURF2	3755	0.28	0.51	YES
34	SMURF1	SMURF1	SMURF1	3837	0.28	0.52	YES
35	ID1	ID1	ID1	3838	0.28	0.53	YES
36	SMAD3	SMAD3	SMAD3	3988	0.27	0.53	YES
37	ZFYVE16	ZFYVE16	ZFYVE16	4013	0.27	0.54	YES
38	BMP5	BMP5	BMP5	4087	0.26	0.55	YES
39	DCN	DCN	DCN	4132	0.26	0.56	YES
40	EP300	EP300	EP300	4220	0.25	0.56	YES
41	BMP7	BMP7	BMP7	4390	0.24	0.56	YES
42	ID2	ID2	ID2	4511	0.23	0.56	YES
43	PPP2CB	PPP2CB	PPP2CB	4692	0.22	0.56	YES
44	RBL1	RBL1	RBL1	4975	0.21	0.55	YES
45	MAPK1	MAPK1	MAPK1	5082	0.2	0.56	YES
46	RBL2	RBL2	RBL2	5211	0.2	0.56	YES
47	SMAD1	SMAD1	SMAD1	5339	0.19	0.56	YES
48	ACVR2B	ACVR2B	ACVR2B	5404	0.18	0.56	YES
49	ROCK1	ROCK1	ROCK1	5459	0.18	0.56	YES
50	CREBBP	CREBBP	CREBBP	5660	0.17	0.56	NO
51	TNF	TNF	TNF	5821	0.16	0.56	NO
52	AMH	AMH	AMH	5970	0.16	0.56	NO
53	TGFB3	TGFB3	TGFB3	6330	0.14	0.54	NO
54	AMHR2	AMHR2	AMHR2	6358	0.14	0.55	NO
55	SP1	SP1	SP1	6421	0.14	0.55	NO
56	RPS6KB1	RPS6KB1	RPS6KB1	6803	0.12	0.53	NO
57	THBS2	THBS2	THBS2	6824	0.12	0.53	NO
58	SMAD4	SMAD4	SMAD4	7001	0.11	0.53	NO
59	ID3	ID3	ID3	7102	0.11	0.53	NO
60	CHRD	CHRD	CHRD	7218	0.1	0.52	NO
61	ACVRL1	ACVRL1	ACVRL1	7381	0.097	0.52	NO
62	MAPK3	MAPK3	MAPK3	7931	0.075	0.49	NO
63	BMPR1B	BMPR1B	BMPR1B	8049	0.07	0.49	NO
64	TFDP1	TFDP1	TFDP1	8269	0.062	0.48	NO
65	E2F5	E2F5	E2F5	8576	0.051	0.46	NO
66	BMP8A	BMP8A	BMP8A	8827	0.042	0.45	NO
67	SMAD2	SMAD2	SMAD2	8891	0.039	0.45	NO
68	SKP1	SKP1	SKP1	8970	0.036	0.45	NO
69	CUL1	CUL1	CUL1	9444	0.021	0.42	NO
70	RHOA	RHOA	RHOA	10107	-0.0026	0.38	NO
71	PPP2R1A	PPP2R1A	PPP2R1A	10574	-0.019	0.36	NO
72	CDKN2B	CDKN2B	CDKN2B	10831	-0.028	0.35	NO
73	TGFB1	TGFB1	TGFB1	11577	-0.054	0.31	NO
74	IFNG	IFNG	IFNG	11642	-0.056	0.31	NO
75	PPP2R1B	PPP2R1B	PPP2R1B	11954	-0.068	0.29	NO
76	THBS3	THBS3	THBS3	12012	-0.07	0.29	NO
77	COMP	COMP	COMP	12251	-0.08	0.28	NO
78	PITX2	PITX2	PITX2	12722	-0.099	0.26	NO
79	E2F4	E2F4	E2F4	12726	-0.1	0.26	NO
80	PPP2CA	PPP2CA	PPP2CA	12933	-0.11	0.26	NO
81	INHBE	INHBE	INHBE	14932	-0.2	0.16	NO
82	RPS6KB2	RPS6KB2	RPS6KB2	15285	-0.22	0.14	NO
83	RBX1	RBX1	RBX1	15770	-0.26	0.13	NO
84	MYC	MYC	MYC	15937	-0.27	0.13	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 TGF BETA SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG AXON GUIDANCE

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	ITGB8	ITGB8	ITGB8	44	1.1	0.035	YES
2	ITGA9	ITGA9	ITGA9	96	1	0.067	YES
3	IBSP	IBSP	IBSP	155	0.96	0.096	YES
4	ITGA1	ITGA1	ITGA1	172	0.94	0.13	YES
5	LAMA1	LAMA1	LAMA1	219	0.9	0.15	YES
6	LAMB4	LAMB4	LAMB4	293	0.85	0.18	YES
7	ITGB3	ITGB3	ITGB3	366	0.81	0.2	YES
8	ITGA8	ITGA8	ITGA8	472	0.76	0.22	YES
9	COL11A1	COL11A1	COL11A1	497	0.75	0.24	YES
10	ITGA2	ITGA2	ITGA2	536	0.74	0.27	YES
11	SDC2	SDC2	SDC2	868	0.65	0.27	YES
12	FN1	FN1	FN1	887	0.65	0.29	YES
13	LAMA2	LAMA2	LAMA2	921	0.64	0.31	YES
14	ITGA2B	ITGA2B	ITGA2B	1007	0.62	0.33	YES
15	COL2A1	COL2A1	COL2A1	1008	0.62	0.35	YES
16	SDC4	SDC4	SDC4	1173	0.58	0.36	YES
17	CHAD	CHAD	CHAD	1314	0.56	0.37	YES
18	THBS1	THBS1	THBS1	1432	0.54	0.38	YES
19	LAMA4	LAMA4	LAMA4	1475	0.53	0.4	YES
20	ITGA10	ITGA10	ITGA10	1581	0.51	0.41	YES
21	THBS4	THBS4	THBS4	1583	0.51	0.42	YES
22	ITGA3	ITGA3	ITGA3	1707	0.5	0.44	YES
23	COL11A2	COL11A2	COL11A2	1942	0.47	0.44	YES
24	LAMB2	LAMB2	LAMB2	2096	0.44	0.44	YES
25	SPP1	SPP1	SPP1	2297	0.42	0.45	YES
26	ITGB4	ITGB4	ITGB4	2331	0.41	0.46	YES
27	COL4A6	COL4A6	COL4A6	2469	0.4	0.46	YES
28	COL5A1	COL5A1	COL5A1	2483	0.4	0.48	YES
29	ITGAV	ITGAV	ITGAV	2493	0.39	0.49	YES
30	AGRN	AGRN	AGRN	2604	0.38	0.5	YES
31	COL4A1	COL4A1	COL4A1	2696	0.37	0.5	YES
32	ITGB5	ITGB5	ITGB5	2757	0.37	0.51	YES
33	LAMA5	LAMA5	LAMA5	2801	0.36	0.52	YES
34	DAG1	DAG1	DAG1	2818	0.36	0.53	YES
35	LAMC1	LAMC1	LAMC1	2909	0.35	0.54	YES
36	ITGA6	ITGA6	ITGA6	2920	0.35	0.55	YES
37	TNC	TNC	TNC	3111	0.34	0.55	YES
38	LAMA3	LAMA3	LAMA3	3174	0.33	0.56	YES
39	COL1A2	COL1A2	COL1A2	3411	0.31	0.56	YES
40	COL5A2	COL5A2	COL5A2	3509	0.3	0.56	YES
41	HSPG2	HSPG2	HSPG2	3569	0.3	0.57	YES
42	LAMC3	LAMC3	LAMC3	3605	0.29	0.58	YES
43	ITGB1	ITGB1	ITGB1	3611	0.29	0.59	YES
44	GP1BA	GP1BA	GP1BA	3731	0.28	0.59	YES
45	COL1A1	COL1A1	COL1A1	3852	0.28	0.59	YES
46	COL4A2	COL4A2	COL4A2	4045	0.26	0.59	YES
47	COL5A3	COL5A3	COL5A3	4080	0.26	0.6	YES
48	COL6A3	COL6A3	COL6A3	4108	0.26	0.6	YES
49	SV2C	SV2C	SV2C	4217	0.25	0.61	YES
50	COL3A1	COL3A1	COL3A1	4474	0.24	0.6	NO
51	LAMB1	LAMB1	LAMB1	4786	0.22	0.59	NO
52	TNN	TNN	TNN	4924	0.21	0.59	NO
53	ITGA11	ITGA11	ITGA11	4949	0.21	0.6	NO
54	SDC1	SDC1	SDC1	4951	0.21	0.6	NO
55	CD36	CD36	CD36	5010	0.21	0.61	NO
56	COL6A2	COL6A2	COL6A2	5190	0.2	0.6	NO
57	COL4A4	COL4A4	COL4A4	5765	0.17	0.58	NO
58	VWF	VWF	VWF	5813	0.16	0.58	NO
59	TNXB	TNXB	TNXB	5827	0.16	0.59	NO
60	COL6A1	COL6A1	COL6A1	6414	0.14	0.56	NO
61	THBS2	THBS2	THBS2	6824	0.12	0.54	NO
62	GP6	GP6	GP6	7171	0.1	0.52	NO
63	CD47	CD47	CD47	7330	0.098	0.52	NO
64	SDC3	SDC3	SDC3	7347	0.098	0.52	NO
65	ITGB6	ITGB6	ITGB6	7662	0.085	0.51	NO
66	COL6A6	COL6A6	COL6A6	9329	0.026	0.42	NO
67	ITGA5	ITGA5	ITGA5	9550	0.017	0.4	NO
68	GP5	GP5	GP5	10083	-0.002	0.38	NO
69	THBS3	THBS3	THBS3	12012	-0.07	0.27	NO
70	ITGA7	ITGA7	ITGA7	12024	-0.071	0.27	NO
71	COMP	COMP	COMP	12251	-0.08	0.26	NO
72	RELN	RELN	RELN	12405	-0.086	0.26	NO
73	SV2A	SV2A	SV2A	12900	-0.11	0.24	NO
74	ITGA4	ITGA4	ITGA4	13123	-0.12	0.23	NO
75	ITGB7	ITGB7	ITGB7	13928	-0.15	0.19	NO
76	LAMB3	LAMB3	LAMB3	14710	-0.19	0.15	NO
77	LAMC2	LAMC2	LAMC2	15035	-0.21	0.14	NO
78	CD44	CD44	CD44	15150	-0.22	0.14	NO
79	SV2B	SV2B	SV2B	17338	-0.45	0.036	NO
80	HMMR	HMMR	HMMR	17437	-0.48	0.046	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 AXON GUIDANCE.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG AXON GUIDANCE, 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 FOCAL ADHESION

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	ITGB3	ITGB3	ITGB3	366	0.81	0.11	YES
2	PLCB1	PLCB1	PLCB1	1619	0.51	0.13	YES
3	GNGT1	GNGT1	GNGT1	2010	0.46	0.18	YES
4	PDGFRA	PDGFRA	PDGFRA	2312	0.42	0.23	YES
5	ITGAV	ITGAV	ITGAV	2493	0.39	0.28	YES
6	PDGFA	PDGFA	PDGFA	2548	0.39	0.34	YES
7	PIK3CA	PIK3CA	PIK3CA	2724	0.37	0.4	YES
8	ASAH1	ASAH1	ASAH1	2964	0.35	0.44	YES
9	PRKCA	PRKCA	PRKCA	3742	0.28	0.44	YES
10	PTK2	PTK2	PTK2	3804	0.28	0.48	YES
11	GNAI1	GNAI1	GNAI1	4139	0.26	0.51	YES
12	SPHK1	SPHK1	SPHK1	4609	0.23	0.52	YES
13	MAPK1	MAPK1	MAPK1	5082	0.2	0.53	YES
14	S1PR1	S1PR1	S1PR1	7269	0.1	0.42	NO
15	MAPK3	MAPK3	MAPK3	7931	0.075	0.4	NO
16	PIK3R1	PIK3R1	PIK3R1	8731	0.045	0.36	NO
17	SRC	SRC	SRC	9095	0.033	0.35	NO
18	RAC1	RAC1	RAC1	9377	0.024	0.34	NO
19	GNB1	GNB1	GNB1	9557	0.017	0.33	NO
20	RHOA	RHOA	RHOA	10107	-0.0026	0.3	NO
21	PIK3CG	PIK3CG	PIK3CG	10942	-0.032	0.26	NO
22	SPHKAP	SPHKAP	SPHKAP	11396	-0.048	0.24	NO
23	SMPD1	SMPD1	SMPD1	11958	-0.068	0.22	NO
24	AKT1	AKT1	AKT1	12631	-0.096	0.2	NO
25	SMPD2	SMPD2	SMPD2	15127	-0.22	0.1	NO
26	PRKCB	PRKCB	PRKCB	17269	-0.44	0.056	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 FOCAL ADHESION.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG FOCAL ADHESION, 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 ECM RECEPTOR INTERACTION

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	SEMA3D	SEMA3D	SEMA3D	43	1.1	0.028	YES
2	NFATC2	NFATC2	NFATC2	65	1.1	0.055	YES
3	SLIT2	SLIT2	SLIT2	90	1	0.081	YES
4	SEMA3E	SEMA3E	SEMA3E	98	1	0.11	YES
5	EPHA3	EPHA3	EPHA3	232	0.89	0.12	YES
6	ROCK2	ROCK2	ROCK2	287	0.85	0.14	YES
7	PLXNC1	PLXNC1	PLXNC1	300	0.84	0.16	YES
8	NGEF	NGEF	NGEF	327	0.83	0.19	YES
9	SEMA5B	SEMA5B	SEMA5B	372	0.8	0.2	YES
10	NTN4	NTN4	NTN4	465	0.76	0.22	YES
11	EFNB3	EFNB3	EFNB3	480	0.76	0.24	YES
12	EPHA2	EPHA2	EPHA2	584	0.72	0.25	YES
13	SEMA3C	SEMA3C	SEMA3C	622	0.71	0.27	YES
14	EPHB3	EPHB3	EPHB3	751	0.68	0.28	YES
15	NRP1	NRP1	NRP1	761	0.68	0.3	YES
16	SEMA6D	SEMA6D	SEMA6D	832	0.66	0.31	YES
17	UNC5C	UNC5C	UNC5C	840	0.66	0.33	YES
18	ROBO2	ROBO2	ROBO2	1072	0.61	0.33	YES
19	NTN1	NTN1	NTN1	1117	0.6	0.34	YES
20	SEMA3B	SEMA3B	SEMA3B	1219	0.58	0.36	YES
21	MET	MET	MET	1244	0.57	0.37	YES
22	EPHA4	EPHA4	EPHA4	1270	0.57	0.38	YES
23	UNC5D	UNC5D	UNC5D	1684	0.5	0.37	YES
24	SEMA5A	SEMA5A	SEMA5A	1812	0.48	0.38	YES
25	ROBO1	ROBO1	ROBO1	1852	0.48	0.39	YES
26	PAK6	PAK6	PAK6	1889	0.47	0.4	YES
27	ARHGEF12	ARHGEF12	ARHGEF12	1944	0.47	0.41	YES
28	EFNA5	EFNA5	EFNA5	1977	0.46	0.42	YES
29	UNC5B	UNC5B	UNC5B	2092	0.44	0.42	YES
30	NFAT5	NFAT5	NFAT5	2277	0.42	0.43	YES
31	SEMA4G	SEMA4G	SEMA4G	2335	0.41	0.43	YES
32	SRGAP1	SRGAP1	SRGAP1	2355	0.41	0.44	YES
33	SRGAP3	SRGAP3	SRGAP3	2535	0.39	0.44	YES
34	EFNB2	EFNB2	EFNB2	2608	0.38	0.45	YES
35	SEMA3F	SEMA3F	SEMA3F	2872	0.36	0.44	YES
36	SEMA4C	SEMA4C	SEMA4C	2938	0.35	0.45	YES
37	PLXNA2	PLXNA2	PLXNA2	3023	0.34	0.46	YES
38	PLXNB2	PLXNB2	PLXNB2	3038	0.34	0.46	YES
39	ITGB1	ITGB1	ITGB1	3611	0.29	0.44	YES
40	SEMA3A	SEMA3A	SEMA3A	3654	0.29	0.45	YES
41	NTN3	NTN3	NTN3	3791	0.28	0.44	YES
42	EPHA7	EPHA7	EPHA7	3800	0.28	0.45	YES
43	PTK2	PTK2	PTK2	3804	0.28	0.46	YES
44	EPHB4	EPHB4	EPHB4	3894	0.27	0.46	YES
45	SEMA6B	SEMA6B	SEMA6B	3902	0.27	0.47	YES
46	ABLIM1	ABLIM1	ABLIM1	3971	0.27	0.47	YES
47	EPHB1	EPHB1	EPHB1	4081	0.26	0.47	YES
48	GNAI1	GNAI1	GNAI1	4139	0.26	0.48	YES
49	PAK3	PAK3	PAK3	4176	0.25	0.48	YES
50	ABL1	ABL1	ABL1	4310	0.24	0.48	YES
51	RASA1	RASA1	RASA1	4363	0.24	0.48	YES
52	SEMA6A	SEMA6A	SEMA6A	4520	0.23	0.48	NO
53	NCK2	NCK2	NCK2	4948	0.21	0.46	NO
54	MAPK1	MAPK1	MAPK1	5082	0.2	0.46	NO
55	NTNG1	NTNG1	NTNG1	5218	0.2	0.46	NO
56	EPHA6	EPHA6	EPHA6	5302	0.19	0.46	NO
57	ROCK1	ROCK1	ROCK1	5459	0.18	0.46	NO
58	LIMK2	LIMK2	LIMK2	5567	0.18	0.46	NO
59	SLIT3	SLIT3	SLIT3	5618	0.17	0.46	NO
60	SEMA3G	SEMA3G	SEMA3G	5661	0.17	0.46	NO
61	CFL2	CFL2	CFL2	5665	0.17	0.46	NO
62	CHP	CHP	CHP	5713	0.17	0.46	NO
63	NFATC4	NFATC4	NFATC4	5718	0.17	0.47	NO
64	ABLIM2	ABLIM2	ABLIM2	5903	0.16	0.46	NO
65	PLXNA1	PLXNA1	PLXNA1	5999	0.16	0.46	NO
66	RHOD	RHOD	RHOD	6251	0.14	0.45	NO
67	EPHB2	EPHB2	EPHB2	6260	0.14	0.46	NO
68	PPP3CA	PPP3CA	PPP3CA	6702	0.12	0.44	NO
69	SEMA4F	SEMA4F	SEMA4F	6863	0.12	0.43	NO
70	SEMA4A	SEMA4A	SEMA4A	6913	0.12	0.43	NO
71	PAK4	PAK4	PAK4	6939	0.11	0.43	NO
72	PLXNB1	PLXNB1	PLXNB1	7062	0.11	0.43	NO
73	EFNA1	EFNA1	EFNA1	7101	0.11	0.43	NO
74	GSK3B	GSK3B	GSK3B	7193	0.1	0.43	NO
75	MAPK3	MAPK3	MAPK3	7931	0.075	0.39	NO
76	EPHA1	EPHA1	EPHA1	7988	0.072	0.39	NO
77	PAK1	PAK1	PAK1	8130	0.067	0.38	NO
78	PPP3R2	PPP3R2	PPP3R2	8247	0.062	0.38	NO
79	SRGAP2	SRGAP2	SRGAP2	8303	0.06	0.37	NO
80	FES	FES	FES	8447	0.055	0.37	NO
81	SEMA4B	SEMA4B	SEMA4B	8599	0.05	0.36	NO
82	PAK7	PAK7	PAK7	8665	0.048	0.36	NO
83	EFNB1	EFNB1	EFNB1	8695	0.047	0.36	NO
84	PLXNA3	PLXNA3	PLXNA3	8848	0.041	0.35	NO
85	SEMA6C	SEMA6C	SEMA6C	9010	0.035	0.34	NO
86	NCK1	NCK1	NCK1	9178	0.03	0.33	NO
87	LIMK1	LIMK1	LIMK1	9270	0.028	0.33	NO
88	PPP3CB	PPP3CB	PPP3CB	9336	0.025	0.33	NO
89	RAC1	RAC1	RAC1	9377	0.024	0.33	NO
90	KRAS	KRAS	KRAS	9778	0.0083	0.3	NO
91	PPP3R1	PPP3R1	PPP3R1	9844	0.006	0.3	NO
92	CDC42	CDC42	CDC42	9987	0.0014	0.29	NO
93	EFNA3	EFNA3	EFNA3	9994	0.0012	0.29	NO
94	GNAI3	GNAI3	GNAI3	10011	0.00031	0.29	NO
95	ROBO3	ROBO3	ROBO3	10047	-0.00082	0.29	NO
96	RHOA	RHOA	RHOA	10107	-0.0026	0.29	NO
97	NFATC1	NFATC1	NFATC1	10316	-0.011	0.28	NO
98	RGS3	RGS3	RGS3	10532	-0.018	0.26	NO
99	PAK2	PAK2	PAK2	10656	-0.022	0.26	NO
100	DCC	DCC	DCC	10687	-0.023	0.26	NO
101	CHP2	CHP2	CHP2	10818	-0.028	0.25	NO
102	GNAI2	GNAI2	GNAI2	10834	-0.028	0.25	NO
103	NRAS	NRAS	NRAS	11154	-0.04	0.23	NO
104	UNC5A	UNC5A	UNC5A	11451	-0.05	0.22	NO
105	RND1	RND1	RND1	12280	-0.081	0.18	NO
106	PPP3CC	PPP3CC	PPP3CC	12390	-0.086	0.17	NO
107	DPYSL2	DPYSL2	DPYSL2	12698	-0.099	0.16	NO
108	EFNA4	EFNA4	EFNA4	12780	-0.1	0.16	NO
109	SLIT1	SLIT1	SLIT1	13136	-0.12	0.14	NO
110	RAC3	RAC3	RAC3	13515	-0.13	0.12	NO
111	DPYSL5	DPYSL5	DPYSL5	13641	-0.14	0.12	NO
112	LRRC4C	LRRC4C	LRRC4C	13880	-0.15	0.11	NO
113	L1CAM	L1CAM	L1CAM	13914	-0.15	0.11	NO
114	SEMA4D	SEMA4D	SEMA4D	14630	-0.19	0.077	NO
115	FYN	FYN	FYN	14922	-0.2	0.066	NO
116	CFL1	CFL1	CFL1	15093	-0.21	0.062	NO
117	NFATC3	NFATC3	NFATC3	15345	-0.23	0.055	NO
118	EPHA8	EPHA8	EPHA8	15605	-0.24	0.047	NO
119	SEMA7A	SEMA7A	SEMA7A	16507	-0.32	0.0058	NO
120	ABLIM3	ABLIM3	ABLIM3	16538	-0.33	0.013	NO
121	EPHB6	EPHB6	EPHB6	16926	-0.38	0.0017	NO
122	CXCL12	CXCL12	CXCL12	17034	-0.4	0.0063	NO
123	CXCR4	CXCR4	CXCR4	17050	-0.4	0.016	NO
124	EPHA5	EPHA5	EPHA5	17100	-0.41	0.024	NO
125	CDK5	CDK5	CDK5	17126	-0.42	0.034	NO
126	RAC2	RAC2	RAC2	17501	-0.49	0.026	NO
127	PLXNB3	PLXNB3	PLXNB3	17997	-0.64	0.016	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 ECM RECEPTOR INTERACTION.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus4 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA FMLP PATHWAY	35	genes.ES.table	0.45	1.6	0.033	0.21	0.66	0.29	0.2	0.23	0.14	0.02
BIOCARTA HIVNEF PATHWAY	57	genes.ES.table	0.4	1.6	0.068	0.2	0.66	0.28	0.2	0.22	0.13	0.018
BIOCARTA DEATH PATHWAY	32	genes.ES.table	0.39	1.5	0.07	0.21	0.77	0.38	0.2	0.3	0.16	0.011
KEGG GLYCOLYSIS GLUCONEOGENESIS	56	genes.ES.table	0.53	1.8	0	0.34	0.29	0.43	0.23	0.33	0	0.13
KEGG FRUCTOSE AND MANNOSE METABOLISM	33	genes.ES.table	0.51	1.6	0.043	0.21	0.63	0.48	0.22	0.38	0.14	0.019
KEGG ARGININE AND PROLINE METABOLISM	52	genes.ES.table	0.51	1.5	0.028	0.21	0.8	0.38	0.2	0.31	0.16	0.009
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	43	genes.ES.table	0.41	1.6	0.049	0.21	0.7	0.3	0.22	0.24	0.15	0.016
KEGG ETHER LIPID METABOLISM	26	genes.ES.table	0.6	1.6	0.013	0.24	0.61	0.27	0.066	0.25	0.15	0.033
KEGG ARACHIDONIC ACID METABOLISM	46	genes.ES.table	0.57	1.6	0.019	0.2	0.72	0.33	0.077	0.3	0.14	0.01
KEGG PORPHYRIN AND CHLOROPHYLL METABOLISM	25	genes.ES.table	0.58	1.6	0.04	0.2	0.71	0.52	0.26	0.39	0.14	0.012

genes ES table in pathway: BIOCARTA FMLP PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CCL4	CCL4	CCL4	54	1	0.095	YES
2	ZBP1	ZBP1	ZBP1	60	1	0.19	YES
3	AIM2	AIM2	AIM2	130	0.89	0.28	YES
4	CXCL10	CXCL10	CXCL10	286	0.76	0.34	YES
5	CCL5	CCL5	CCL5	496	0.64	0.39	YES
6	IL6	IL6	IL6	837	0.53	0.42	YES
7	CCL4L2	CCL4L2	CCL4L2	953	0.5	0.46	YES
8	IL1B	IL1B	IL1B	1127	0.46	0.5	YES
9	IRF7	IRF7	IRF7	1284	0.43	0.53	YES
10	IL33	IL33	IL33	2011	0.32	0.52	YES
11	POLR3D	POLR3D	POLR3D	2179	0.3	0.55	YES
12	PYCARD	PYCARD	PYCARD	2494	0.27	0.55	YES
13	IL18	IL18	IL18	2566	0.26	0.57	YES
14	TBK1	TBK1	TBK1	2680	0.25	0.59	YES
15	IFNB1	IFNB1	IFNB1	2743	0.24	0.61	YES
16	CASP1	CASP1	CASP1	3190	0.2	0.61	YES
17	POLR3G	POLR3G	POLR3G	3240	0.2	0.62	YES
18	NFKBIA	NFKBIA	NFKBIA	3366	0.19	0.64	YES
19	RIPK3	RIPK3	RIPK3	3708	0.16	0.63	YES
20	NFKBIB	NFKBIB	NFKBIB	3777	0.16	0.64	YES
21	IKBKE	IKBKE	IKBKE	3915	0.15	0.65	YES
22	POLR1C	POLR1C	POLR1C	4825	0.11	0.61	NO
23	IRF3	IRF3	IRF3	4971	0.1	0.61	NO
24	TREX1	TREX1	TREX1	5447	0.083	0.6	NO
25	RELA	RELA	RELA	5511	0.08	0.6	NO
26	POLR3B	POLR3B	POLR3B	5517	0.08	0.61	NO
27	POLR3C	POLR3C	POLR3C	5693	0.074	0.6	NO
28	POLR3K	POLR3K	POLR3K	5736	0.073	0.61	NO
29	ADAR	ADAR	ADAR	5947	0.066	0.6	NO
30	POLR1D	POLR1D	POLR1D	6121	0.06	0.6	NO
31	TMEM173	TMEM173	TMEM173	6237	0.057	0.6	NO
32	IKBKB	IKBKB	IKBKB	6261	0.056	0.6	NO
33	POLR3H	POLR3H	POLR3H	7215	0.029	0.56	NO
34	IKBKG	IKBKG	IKBKG	7676	0.017	0.53	NO
35	POLR3F	POLR3F	POLR3F	7760	0.015	0.53	NO
36	POLR3A	POLR3A	POLR3A	8169	0.0053	0.51	NO
37	MAVS	MAVS	MAVS	8945	-0.013	0.46	NO
38	CHUK	CHUK	CHUK	10686	-0.053	0.38	NO
39	DDX58	DDX58	DDX58	11490	-0.072	0.34	NO
40	RIPK1	RIPK1	RIPK1	11918	-0.084	0.32	NO
41	POLR3GL	POLR3GL	POLR3GL	13534	-0.13	0.25	NO
42	NFKB1	NFKB1	NFKB1	13614	-0.14	0.26	NO

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

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

genes ES table in pathway: BIOCARTA HIVNEF 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	FBP1	FBP1	FBP1	208	0.82	0.075	YES
2	ALDH3B1	ALDH3B1	ALDH3B1	735	0.56	0.1	YES
3	ALDOC	ALDOC	ALDOC	857	0.53	0.15	YES
4	HK3	HK3	HK3	957	0.5	0.2	YES
5	ALDH3A1	ALDH3A1	ALDH3A1	988	0.49	0.25	YES
6	ALDOB	ALDOB	ALDOB	1672	0.37	0.25	YES
7	ADH6	ADH6	ADH6	2047	0.32	0.26	YES
8	PCK2	PCK2	PCK2	2106	0.31	0.29	YES
9	ADH1A	ADH1A	ADH1A	2233	0.29	0.32	YES
10	FBP2	FBP2	FBP2	2234	0.29	0.35	YES
11	ALDH1B1	ALDH1B1	ALDH1B1	2258	0.29	0.38	YES
12	ADH7	ADH7	ADH7	2335	0.28	0.4	YES
13	PKLR	PKLR	PKLR	2422	0.27	0.42	YES
14	PFKL	PFKL	PFKL	2853	0.23	0.43	YES
15	GALM	GALM	GALM	3117	0.21	0.43	YES
16	ENO2	ENO2	ENO2	3428	0.18	0.44	YES
17	HK2	HK2	HK2	3568	0.17	0.44	YES
18	TPI1	TPI1	TPI1	3613	0.17	0.46	YES
19	PFKP	PFKP	PFKP	3636	0.17	0.48	YES
20	ADH1C	ADH1C	ADH1C	3664	0.17	0.49	YES
21	PKM2	PKM2	PKM2	3721	0.16	0.51	YES
22	ACSS2	ACSS2	ACSS2	3811	0.16	0.52	YES
23	ACSS1	ACSS1	ACSS1	4179	0.14	0.51	YES
24	PCK1	PCK1	PCK1	4222	0.14	0.52	YES
25	HK1	HK1	HK1	4660	0.11	0.51	NO
26	ENO1	ENO1	ENO1	4788	0.11	0.52	NO
27	ALDOA	ALDOA	ALDOA	5607	0.077	0.48	NO
28	PGM2	PGM2	PGM2	5613	0.076	0.49	NO
29	ALDH3B2	ALDH3B2	ALDH3B2	5905	0.067	0.48	NO
30	GPI	GPI	GPI	6266	0.056	0.47	NO
31	GAPDH	GAPDH	GAPDH	6299	0.055	0.47	NO
32	PGAM1	PGAM1	PGAM1	6509	0.048	0.46	NO
33	LDHA	LDHA	LDHA	6943	0.036	0.44	NO
34	PGAM4	PGAM4	PGAM4	7667	0.017	0.4	NO
35	ADH1B	ADH1B	ADH1B	7730	0.016	0.4	NO
36	LDHAL6B	LDHAL6B	LDHAL6B	7943	0.01	0.39	NO
37	DLD	DLD	DLD	8553	-0.0035	0.36	NO
38	ALDH3A2	ALDH3A2	ALDH3A2	8682	-0.0067	0.35	NO
39	PGK1	PGK1	PGK1	8691	-0.0069	0.35	NO
40	AKR1A1	AKR1A1	AKR1A1	8971	-0.014	0.34	NO
41	ENO3	ENO3	ENO3	9194	-0.019	0.33	NO
42	ALDH2	ALDH2	ALDH2	9949	-0.036	0.29	NO
43	PFKM	PFKM	PFKM	10005	-0.037	0.29	NO
44	DLAT	DLAT	DLAT	10125	-0.04	0.29	NO
45	PDHA1	PDHA1	PDHA1	10291	-0.044	0.29	NO
46	PGAM2	PGAM2	PGAM2	10366	-0.046	0.29	NO
47	ALDH1A3	ALDH1A3	ALDH1A3	11145	-0.064	0.25	NO
48	ALDH9A1	ALDH9A1	ALDH9A1	11517	-0.073	0.24	NO
49	GCK	GCK	GCK	12298	-0.094	0.21	NO
50	PDHB	PDHB	PDHB	12311	-0.095	0.22	NO
51	LDHB	LDHB	LDHB	12513	-0.1	0.21	NO
52	BPGM	BPGM	BPGM	13288	-0.12	0.18	NO
53	ADH5	ADH5	ADH5	13320	-0.13	0.2	NO
54	PGM1	PGM1	PGM1	14158	-0.16	0.17	NO
55	ALDH7A1	ALDH7A1	ALDH7A1	15746	-0.25	0.11	NO
56	LDHAL6A	LDHAL6A	LDHAL6A	16511	-0.32	0.097	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 HIVNEF PATHWAY.

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

genes ES table in pathway: BIOCARTA DEATH PATHWAY

Table 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	IFNG	IFNG	IFNG	76	0.98	0.048	YES
2	IL1A	IL1A	IL1A	345	0.72	0.072	YES
3	NCF1	NCF1	NCF1	414	0.67	0.1	YES
4	TNF	TNF	TNF	427	0.67	0.14	YES
5	FCGR1A	FCGR1A	FCGR1A	470	0.65	0.17	YES
6	IL10	IL10	IL10	612	0.6	0.2	YES
7	NOS2	NOS2	NOS2	687	0.57	0.22	YES
8	HLA-DOB	HLA-DOB	HLA-DOB	779	0.54	0.25	YES
9	IL1B	IL1B	IL1B	1127	0.46	0.25	YES
10	ITGAM	ITGAM	ITGAM	1169	0.46	0.28	YES
11	HLA-DOA	HLA-DOA	HLA-DOA	1300	0.43	0.29	YES
12	HLA-DQA2	HLA-DQA2	HLA-DQA2	1306	0.43	0.31	YES
13	NCF2	NCF2	NCF2	1355	0.42	0.33	YES
14	IL12A	IL12A	IL12A	1363	0.42	0.36	YES
15	FCGR3A	FCGR3A	FCGR3A	1368	0.42	0.38	YES
16	FCGR2C	FCGR2C	FCGR2C	1522	0.39	0.39	YES
17	TLR2	TLR2	TLR2	1585	0.38	0.41	YES
18	HLA-DQA1	HLA-DQA1	HLA-DQA1	1837	0.34	0.41	YES
19	MAPK12	MAPK12	MAPK12	1840	0.34	0.43	YES
20	HLA-DRB5	HLA-DRB5	HLA-DRB5	1856	0.34	0.45	YES
21	HLA-DMA	HLA-DMA	HLA-DMA	2031	0.32	0.45	YES
22	CR1	CR1	CR1	2197	0.3	0.46	YES
23	FCGR3B	FCGR3B	FCGR3B	2214	0.3	0.48	YES
24	HLA-DRB1	HLA-DRB1	HLA-DRB1	2470	0.27	0.48	YES
25	NCF4	NCF4	NCF4	2600	0.25	0.48	YES
26	C3	C3	C3	2653	0.25	0.49	YES
27	MAPK13	MAPK13	MAPK13	2715	0.24	0.5	YES
28	HLA-DRA	HLA-DRA	HLA-DRA	2740	0.24	0.52	YES
29	FCGR2A	FCGR2A	FCGR2A	2753	0.24	0.53	YES
30	HLA-DMB	HLA-DMB	HLA-DMB	2795	0.24	0.54	YES
31	FOS	FOS	FOS	2827	0.23	0.55	YES
32	MAPK11	MAPK11	MAPK11	2851	0.23	0.56	YES
33	HLA-DPA1	HLA-DPA1	HLA-DPA1	3060	0.21	0.56	YES
34	TLR4	TLR4	TLR4	3096	0.21	0.57	YES
35	IFNGR2	IFNGR2	IFNGR2	3176	0.2	0.57	YES
36	HLA-DPB1	HLA-DPB1	HLA-DPB1	3191	0.2	0.58	YES
37	STAT1	STAT1	STAT1	3217	0.2	0.6	YES
38	JAK2	JAK2	JAK2	3236	0.2	0.6	YES
39	CYBA	CYBA	CYBA	3365	0.19	0.61	YES
40	NFKBIA	NFKBIA	NFKBIA	3366	0.19	0.62	YES
41	HLA-DQB1	HLA-DQB1	HLA-DQB1	3589	0.17	0.62	YES
42	TGFB2	TGFB2	TGFB2	3648	0.17	0.62	YES
43	JUN	JUN	JUN	3699	0.16	0.63	YES
44	NFKBIB	NFKBIB	NFKBIB	3777	0.16	0.63	YES
45	IRAK1	IRAK1	IRAK1	3865	0.15	0.63	YES
46	IL12B	IL12B	IL12B	4810	0.11	0.59	NO
47	TGFB1	TGFB1	TGFB1	5149	0.094	0.57	NO
48	RELA	RELA	RELA	5511	0.08	0.56	NO
49	PTPN6	PTPN6	PTPN6	5670	0.075	0.56	NO
50	MYD88	MYD88	MYD88	6304	0.054	0.52	NO
51	ITGB1	ITGB1	ITGB1	6866	0.038	0.49	NO
52	ELK1	ELK1	ELK1	8125	0.0062	0.42	NO
53	TAB1	TAB1	TAB1	8911	-0.012	0.38	NO
54	MAPK3	MAPK3	MAPK3	8962	-0.013	0.38	NO
55	ITGB2	ITGB2	ITGB2	10004	-0.037	0.33	NO
56	JAK1	JAK1	JAK1	11112	-0.063	0.27	NO
57	IRAK4	IRAK4	IRAK4	11212	-0.065	0.27	NO
58	MARCKSL1	MARCKSL1	MARCKSL1	11568	-0.074	0.25	NO
59	TGFB3	TGFB3	TGFB3	12523	-0.1	0.2	NO
60	MAPK1	MAPK1	MAPK1	12925	-0.11	0.19	NO
61	NFKB1	NFKB1	NFKB1	13614	-0.14	0.16	NO
62	IFNGR1	IFNGR1	IFNGR1	13741	-0.14	0.16	NO
63	TAB2	TAB2	TAB2	13769	-0.14	0.16	NO
64	MAPK14	MAPK14	MAPK14	14222	-0.16	0.15	NO
65	TRAF6	TRAF6	TRAF6	14631	-0.18	0.14	NO
66	MAP3K7	MAP3K7	MAP3K7	15010	-0.2	0.12	NO
67	IL4	IL4	IL4	15305	-0.22	0.12	NO
68	PRKCB	PRKCB	PRKCB	16738	-0.34	0.06	NO
69	ITGA4	ITGA4	ITGA4	17440	-0.46	0.046	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 DEATH PATHWAY.

Figure S66. 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: KEGG GLYCOLYSIS GLUCONEOGENESIS

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IFNG	IFNG	IFNG	76	0.98	0.06	YES
2	CD80	CD80	CD80	115	0.92	0.12	YES
3	GZMB	GZMB	GZMB	209	0.82	0.17	YES
4	IL1A	IL1A	IL1A	345	0.72	0.21	YES
5	TNF	TNF	TNF	427	0.67	0.25	YES
6	FASLG	FASLG	FASLG	673	0.58	0.27	YES
7	HLA-DOB	HLA-DOB	HLA-DOB	779	0.54	0.3	YES
8	HLA-G	HLA-G	HLA-G	854	0.53	0.33	YES
9	IL1B	IL1B	IL1B	1127	0.46	0.35	YES
10	CD86	CD86	CD86	1141	0.46	0.38	YES
11	GAD1	GAD1	GAD1	1147	0.46	0.41	YES
12	LTA	LTA	LTA	1162	0.46	0.44	YES
13	HLA-DOA	HLA-DOA	HLA-DOA	1300	0.43	0.46	YES
14	HLA-DQA2	HLA-DQA2	HLA-DQA2	1306	0.43	0.48	YES
15	IL12A	IL12A	IL12A	1363	0.42	0.51	YES
16	PTPRN	PTPRN	PTPRN	1398	0.41	0.53	YES
17	HLA-F	HLA-F	HLA-F	1437	0.4	0.56	YES
18	IL2	IL2	IL2	1474	0.4	0.58	YES
19	GAD2	GAD2	GAD2	1821	0.34	0.58	YES
20	HLA-DQA1	HLA-DQA1	HLA-DQA1	1837	0.34	0.61	YES
21	HLA-DRB5	HLA-DRB5	HLA-DRB5	1856	0.34	0.63	YES
22	PRF1	PRF1	PRF1	1980	0.32	0.64	YES
23	ICA1	ICA1	ICA1	1981	0.32	0.66	YES
24	HLA-DMA	HLA-DMA	HLA-DMA	2031	0.32	0.68	YES
25	HLA-DRB1	HLA-DRB1	HLA-DRB1	2470	0.27	0.68	YES
26	HLA-B	HLA-B	HLA-B	2475	0.27	0.69	YES
27	HLA-DRA	HLA-DRA	HLA-DRA	2740	0.24	0.69	YES
28	HLA-DMB	HLA-DMB	HLA-DMB	2795	0.24	0.71	YES
29	HLA-C	HLA-C	HLA-C	2972	0.22	0.71	YES
30	HLA-A	HLA-A	HLA-A	3013	0.22	0.72	YES
31	HLA-DPA1	HLA-DPA1	HLA-DPA1	3060	0.21	0.74	YES
32	HLA-DPB1	HLA-DPB1	HLA-DPB1	3191	0.2	0.74	YES
33	FAS	FAS	FAS	3262	0.2	0.75	YES
34	HLA-E	HLA-E	HLA-E	3421	0.18	0.75	YES
35	HSPD1	HSPD1	HSPD1	4133	0.14	0.72	NO
36	IL12B	IL12B	IL12B	4810	0.11	0.69	NO
37	CD28	CD28	CD28	14800	-0.19	0.16	NO
38	PTPRN2	PTPRN2	PTPRN2	15242	-0.22	0.15	NO
39	CPE	CPE	CPE	16046	-0.27	0.12	NO

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

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

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	IFNG	IFNG	IFNG	76	0.98	0.072	YES
2	CD80	CD80	CD80	115	0.92	0.14	YES
3	GZMB	GZMB	GZMB	209	0.82	0.2	YES
4	TNF	TNF	TNF	427	0.67	0.24	YES
5	IL10	IL10	IL10	612	0.6	0.28	YES
6	FASLG	FASLG	FASLG	673	0.58	0.32	YES
7	HLA-DOB	HLA-DOB	HLA-DOB	779	0.54	0.36	YES
8	HLA-G	HLA-G	HLA-G	854	0.53	0.39	YES
9	CD86	CD86	CD86	1141	0.46	0.41	YES
10	HLA-DOA	HLA-DOA	HLA-DOA	1300	0.43	0.44	YES
11	HLA-DQA2	HLA-DQA2	HLA-DQA2	1306	0.43	0.47	YES
12	IL12A	IL12A	IL12A	1363	0.42	0.5	YES
13	HLA-F	HLA-F	HLA-F	1437	0.4	0.53	YES
14	IL2	IL2	IL2	1474	0.4	0.56	YES
15	HLA-DQA1	HLA-DQA1	HLA-DQA1	1837	0.34	0.56	YES
16	HLA-DRB5	HLA-DRB5	HLA-DRB5	1856	0.34	0.59	YES
17	PRF1	PRF1	PRF1	1980	0.32	0.61	YES
18	HLA-DMA	HLA-DMA	HLA-DMA	2031	0.32	0.63	YES
19	CD40	CD40	CD40	2115	0.31	0.65	YES
20	HLA-DRB1	HLA-DRB1	HLA-DRB1	2470	0.27	0.65	YES
21	HLA-B	HLA-B	HLA-B	2475	0.27	0.67	YES
22	HLA-DRA	HLA-DRA	HLA-DRA	2740	0.24	0.68	YES
23	HLA-DMB	HLA-DMB	HLA-DMB	2795	0.24	0.69	YES
24	HLA-C	HLA-C	HLA-C	2972	0.22	0.7	YES
25	HLA-A	HLA-A	HLA-A	3013	0.22	0.71	YES
26	HLA-DPA1	HLA-DPA1	HLA-DPA1	3060	0.21	0.73	YES
27	HLA-DPB1	HLA-DPB1	HLA-DPB1	3191	0.2	0.74	YES
28	FAS	FAS	FAS	3262	0.2	0.75	YES
29	HLA-E	HLA-E	HLA-E	3421	0.18	0.75	YES
30	IL12B	IL12B	IL12B	4810	0.11	0.69	NO
31	CD40LG	CD40LG	CD40LG	11711	-0.078	0.32	NO
32	IL5	IL5	IL5	14475	-0.17	0.18	NO
33	CD28	CD28	CD28	14800	-0.19	0.17	NO
34	IL4	IL4	IL4	15305	-0.22	0.16	NO

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

Figure S70. 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 ARGININE AND PROLINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IFNG	IFNG	IFNG	76	0.98	0.064	YES
2	CD80	CD80	CD80	115	0.92	0.13	YES
3	GZMB	GZMB	GZMB	209	0.82	0.18	YES
4	IL1A	IL1A	IL1A	345	0.72	0.22	YES
5	TNF	TNF	TNF	427	0.67	0.26	YES
6	KLRC1	KLRC1	KLRC1	437	0.66	0.31	YES
7	FASLG	FASLG	FASLG	673	0.58	0.34	YES
8	HLA-DOB	HLA-DOB	HLA-DOB	779	0.54	0.37	YES
9	IL6	IL6	IL6	837	0.53	0.4	YES
10	HLA-G	HLA-G	HLA-G	854	0.53	0.44	YES
11	IL1B	IL1B	IL1B	1127	0.46	0.46	YES
12	CD86	CD86	CD86	1141	0.46	0.49	YES
13	HLA-DOA	HLA-DOA	HLA-DOA	1300	0.43	0.51	YES
14	HLA-DQA2	HLA-DQA2	HLA-DQA2	1306	0.43	0.54	YES
15	HLA-F	HLA-F	HLA-F	1437	0.4	0.56	YES
16	IL2	IL2	IL2	1474	0.4	0.59	YES
17	HLA-DQA1	HLA-DQA1	HLA-DQA1	1837	0.34	0.59	YES
18	HLA-DRB5	HLA-DRB5	HLA-DRB5	1856	0.34	0.61	YES
19	PRF1	PRF1	PRF1	1980	0.32	0.63	YES
20	KLRD1	KLRD1	KLRD1	1985	0.32	0.65	YES
21	HLA-DMA	HLA-DMA	HLA-DMA	2031	0.32	0.67	YES
22	HLA-DRB1	HLA-DRB1	HLA-DRB1	2470	0.27	0.67	YES
23	HLA-B	HLA-B	HLA-B	2475	0.27	0.68	YES
24	HLA-DRA	HLA-DRA	HLA-DRA	2740	0.24	0.69	YES
25	HLA-DMB	HLA-DMB	HLA-DMB	2795	0.24	0.7	YES
26	HLA-C	HLA-C	HLA-C	2972	0.22	0.71	YES
27	KIR2DL1	KIR2DL1	KIR2DL1	2980	0.22	0.72	YES
28	HLA-A	HLA-A	HLA-A	3013	0.22	0.73	YES
29	HLA-DPA1	HLA-DPA1	HLA-DPA1	3060	0.21	0.75	YES
30	HLA-DPB1	HLA-DPB1	HLA-DPB1	3191	0.2	0.75	YES
31	FAS	FAS	FAS	3262	0.2	0.76	YES
32	HLA-E	HLA-E	HLA-E	3421	0.18	0.77	YES
33	KIR3DL1	KIR3DL1	KIR3DL1	3703	0.16	0.76	NO
34	KIR2DL3	KIR2DL3	KIR2DL3	4665	0.11	0.72	NO
35	CD28	CD28	CD28	14800	-0.19	0.18	NO
36	KIR3DL2	KIR3DL2	KIR3DL2	14983	-0.2	0.18	NO

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

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

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

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PYDC1	PYDC1	PYDC1	68	0.99	0.061	YES
2	CARD9	CARD9	CARD9	232	0.8	0.1	YES
3	NOD2	NOD2	NOD2	324	0.73	0.15	YES
4	CCL8	CCL8	CCL8	390	0.69	0.19	YES
5	TNF	TNF	TNF	427	0.67	0.23	YES
6	CCL5	CCL5	CCL5	496	0.64	0.27	YES
7	CCL13	CCL13	CCL13	538	0.62	0.3	YES
8	CASP5	CASP5	CASP5	632	0.59	0.34	YES
9	CCL11	CCL11	CCL11	649	0.58	0.38	YES
10	MEFV	MEFV	MEFV	800	0.54	0.4	YES
11	BIRC3	BIRC3	BIRC3	825	0.53	0.44	YES
12	IL6	IL6	IL6	837	0.53	0.47	YES
13	IL1B	IL1B	IL1B	1127	0.46	0.48	YES
14	CCL7	CCL7	CCL7	1633	0.37	0.48	YES
15	MAPK12	MAPK12	MAPK12	1840	0.34	0.49	YES
16	CCL2	CCL2	CCL2	1943	0.33	0.51	YES
17	CXCL2	CXCL2	CXCL2	2130	0.31	0.52	YES
18	NLRP3	NLRP3	NLRP3	2259	0.29	0.53	YES
19	RIPK2	RIPK2	RIPK2	2454	0.27	0.54	YES
20	PYCARD	PYCARD	PYCARD	2494	0.27	0.55	YES
21	PSTPIP1	PSTPIP1	PSTPIP1	2499	0.27	0.57	YES
22	IL18	IL18	IL18	2566	0.26	0.58	YES
23	MAPK13	MAPK13	MAPK13	2715	0.24	0.59	YES
24	MAPK11	MAPK11	MAPK11	2851	0.23	0.6	YES
25	CASP1	CASP1	CASP1	3190	0.2	0.59	NO
26	NFKBIA	NFKBIA	NFKBIA	3366	0.19	0.59	NO
27	NLRC4	NLRC4	NLRC4	3536	0.18	0.6	NO
28	NFKBIB	NFKBIB	NFKBIB	3777	0.16	0.59	NO
29	CXCL1	CXCL1	CXCL1	4532	0.12	0.56	NO
30	TNFAIP3	TNFAIP3	TNFAIP3	4675	0.11	0.56	NO
31	NLRP1	NLRP1	NLRP1	5021	0.099	0.55	NO
32	IL8	IL8	IL8	5377	0.086	0.53	NO
33	RELA	RELA	RELA	5511	0.08	0.53	NO
34	IKBKB	IKBKB	IKBKB	6261	0.056	0.49	NO
35	HSP90AA1	HSP90AA1	HSP90AA1	6435	0.05	0.49	NO
36	TRIP6	TRIP6	TRIP6	6704	0.042	0.48	NO
37	HSP90B1	HSP90B1	HSP90B1	6815	0.04	0.47	NO
38	IKBKG	IKBKG	IKBKG	7676	0.017	0.42	NO
39	SUGT1	SUGT1	SUGT1	7686	0.017	0.43	NO
40	MAPK10	MAPK10	MAPK10	8096	0.007	0.4	NO
41	TAB1	TAB1	TAB1	8911	-0.012	0.36	NO
42	MAPK3	MAPK3	MAPK3	8962	-0.013	0.36	NO
43	NOD1	NOD1	NOD1	9318	-0.022	0.34	NO
44	TAB3	TAB3	TAB3	10198	-0.042	0.29	NO
45	CHUK	CHUK	CHUK	10686	-0.053	0.27	NO
46	CASP8	CASP8	CASP8	11319	-0.068	0.24	NO
47	XIAP	XIAP	XIAP	11613	-0.076	0.23	NO
48	BIRC2	BIRC2	BIRC2	11963	-0.085	0.22	NO
49	CARD6	CARD6	CARD6	11981	-0.085	0.22	NO
50	MAPK9	MAPK9	MAPK9	12728	-0.11	0.19	NO
51	MAPK1	MAPK1	MAPK1	12925	-0.11	0.18	NO
52	CARD8	CARD8	CARD8	13272	-0.12	0.17	NO
53	NFKB1	NFKB1	NFKB1	13614	-0.14	0.16	NO
54	TAB2	TAB2	TAB2	13769	-0.14	0.16	NO
55	MAPK14	MAPK14	MAPK14	14222	-0.16	0.15	NO
56	TRAF6	TRAF6	TRAF6	14631	-0.18	0.14	NO
57	MAP3K7	MAP3K7	MAP3K7	15010	-0.2	0.13	NO
58	MAPK8	MAPK8	MAPK8	15463	-0.23	0.12	NO
59	ERBB2IP	ERBB2IP	ERBB2IP	15743	-0.25	0.12	NO
60	NAIP	NAIP	NAIP	16115	-0.28	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: KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

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

genes ES table in pathway: KEGG ETHER LIPID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CTLA4	CTLA4	CTLA4	35	1.1	0.082	YES
2	CD80	CD80	CD80	115	0.92	0.15	YES
3	GZMB	GZMB	GZMB	209	0.82	0.21	YES
4	IL10	IL10	IL10	612	0.6	0.23	YES
5	FASLG	FASLG	FASLG	673	0.58	0.27	YES
6	HLA-DOB	HLA-DOB	HLA-DOB	779	0.54	0.31	YES
7	HLA-G	HLA-G	HLA-G	854	0.53	0.34	YES
8	CD86	CD86	CD86	1141	0.46	0.36	YES
9	HLA-DOA	HLA-DOA	HLA-DOA	1300	0.43	0.39	YES
10	HLA-DQA2	HLA-DQA2	HLA-DQA2	1306	0.43	0.42	YES
11	HLA-F	HLA-F	HLA-F	1437	0.4	0.44	YES
12	IL2	IL2	IL2	1474	0.4	0.47	YES
13	HLA-DQA1	HLA-DQA1	HLA-DQA1	1837	0.34	0.48	YES
14	HLA-DRB5	HLA-DRB5	HLA-DRB5	1856	0.34	0.5	YES
15	PRF1	PRF1	PRF1	1980	0.32	0.52	YES
16	HLA-DMA	HLA-DMA	HLA-DMA	2031	0.32	0.55	YES
17	CD40	CD40	CD40	2115	0.31	0.56	YES
18	HLA-DRB1	HLA-DRB1	HLA-DRB1	2470	0.27	0.57	YES
19	HLA-B	HLA-B	HLA-B	2475	0.27	0.59	YES
20	HLA-DRA	HLA-DRA	HLA-DRA	2740	0.24	0.59	YES
21	HLA-DMB	HLA-DMB	HLA-DMB	2795	0.24	0.6	YES
22	CGA	CGA	CGA	2953	0.22	0.61	YES
23	HLA-C	HLA-C	HLA-C	2972	0.22	0.63	YES
24	HLA-A	HLA-A	HLA-A	3013	0.22	0.64	YES
25	HLA-DPA1	HLA-DPA1	HLA-DPA1	3060	0.21	0.66	YES
26	HLA-DPB1	HLA-DPB1	HLA-DPB1	3191	0.2	0.67	YES
27	FAS	FAS	FAS	3262	0.2	0.68	YES
28	HLA-E	HLA-E	HLA-E	3421	0.18	0.68	YES
29	HLA-DQB1	HLA-DQB1	HLA-DQB1	3589	0.17	0.69	YES
30	TPO	TPO	TPO	8135	0.006	0.44	NO
31	CD40LG	CD40LG	CD40LG	11711	-0.078	0.25	NO
32	TG	TG	TG	13151	-0.12	0.18	NO
33	IL5	IL5	IL5	14475	-0.17	0.12	NO
34	CD28	CD28	CD28	14800	-0.19	0.12	NO
35	IL4	IL4	IL4	15305	-0.22	0.11	NO
36	TSHR	TSHR	TSHR	18120	-0.74	0.0089	NO

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

Figure S76. 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 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	SNAP25	SNAP25	SNAP25	704	0.57	0.1	YES
2	STX1A	STX1A	STX1A	768	0.55	0.24	YES
3	STX19	STX19	STX19	2218	0.3	0.24	YES
4	STX1B	STX1B	STX1B	2464	0.27	0.29	YES
5	STX11	STX11	STX11	2701	0.24	0.34	YES
6	VAMP5	VAMP5	VAMP5	4223	0.14	0.29	YES
7	VAMP8	VAMP8	VAMP8	4378	0.13	0.31	YES
8	STX4	STX4	STX4	4402	0.13	0.34	YES
9	STX3	STX3	STX3	4426	0.12	0.38	YES
10	SNAP47	SNAP47	SNAP47	6619	0.045	0.27	NO
11	BNIP1	BNIP1	BNIP1	6761	0.041	0.27	NO
12	GOSR1	GOSR1	GOSR1	6776	0.041	0.28	NO
13	VAMP3	VAMP3	VAMP3	7014	0.034	0.28	NO
14	TSNARE1	TSNARE1	TSNARE1	7166	0.03	0.27	NO
15	GOSR2	GOSR2	GOSR2	7384	0.025	0.27	NO
16	STX6	STX6	STX6	7570	0.02	0.26	NO
17	STX8	STX8	STX8	7615	0.019	0.27	NO
18	STX5	STX5	STX5	7697	0.017	0.27	NO
19	STX12	STX12	STX12	7791	0.015	0.26	NO
20	YKT6	YKT6	YKT6	8013	0.0089	0.25	NO
21	VTI1B	VTI1B	VTI1B	8406	0.00014	0.23	NO
22	STX18	STX18	STX18	8499	-0.0019	0.23	NO
23	VTI1A	VTI1A	VTI1A	8952	-0.013	0.21	NO
24	VAMP4	VAMP4	VAMP4	9123	-0.017	0.2	NO
25	SNAP23	SNAP23	SNAP23	9413	-0.024	0.19	NO
26	STX7	STX7	STX7	9586	-0.028	0.19	NO
27	BET1L	BET1L	BET1L	9696	-0.03	0.19	NO
28	STX10	STX10	STX10	9793	-0.033	0.2	NO
29	VAMP2	VAMP2	VAMP2	9931	-0.036	0.2	NO
30	USE1	USE1	USE1	9942	-0.036	0.2	NO
31	STX16	STX16	STX16	10152	-0.041	0.2	NO
32	STX17	STX17	STX17	11127	-0.064	0.17	NO
33	SEC22B	SEC22B	SEC22B	13268	-0.12	0.08	NO
34	BET1	BET1	BET1	13306	-0.12	0.11	NO
35	VAMP1	VAMP1	VAMP1	14006	-0.15	0.11	NO
36	VAMP7	VAMP7	VAMP7	15369	-0.22	0.092	NO
37	STX2	STX2	STX2	15984	-0.27	0.13	NO

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

Figure S78. 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 PORPHYRIN AND CHLOROPHYLL METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PLA2G3	PLA2G3	PLA2G3	11	1.2	0.18	YES
2	PLA2G2D	PLA2G2D	PLA2G2D	548	0.62	0.25	YES
3	PLA2G5	PLA2G5	PLA2G5	676	0.57	0.33	YES
4	PLA2G7	PLA2G7	PLA2G7	869	0.52	0.4	YES
5	PPAP2C	PPAP2C	PPAP2C	1008	0.49	0.47	YES
6	PLA2G2A	PLA2G2A	PLA2G2A	1037	0.48	0.54	YES
7	PLA2G10	PLA2G10	PLA2G10	1215	0.45	0.6	YES
8	CHPT1	CHPT1	CHPT1	3192	0.2	0.52	NO
9	PLA2G4A	PLA2G4A	PLA2G4A	3211	0.2	0.55	NO
10	ENPP2	ENPP2	ENPP2	3867	0.15	0.54	NO
11	PAFAH1B2	PAFAH1B2	PAFAH1B2	6049	0.062	0.43	NO
12	LPCAT1	LPCAT1	LPCAT1	7324	0.026	0.36	NO
13	PLA2G6	PLA2G6	PLA2G6	7393	0.024	0.36	NO
14	PPAP2A	PPAP2A	PPAP2A	8195	0.0048	0.32	NO
15	PAFAH1B3	PAFAH1B3	PAFAH1B3	8818	-0.0097	0.29	NO
16	PLD2	PLD2	PLD2	8860	-0.011	0.29	NO
17	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	9235	-0.02	0.27	NO
18	LPCAT4	LPCAT4	LPCAT4	10381	-0.046	0.22	NO
19	PLA2G12A	PLA2G12A	PLA2G12A	10895	-0.058	0.2	NO
20	PAFAH1B1	PAFAH1B1	PAFAH1B1	12240	-0.093	0.14	NO
21	LPCAT2	LPCAT2	LPCAT2	12806	-0.11	0.12	NO
22	PLD1	PLD1	PLD1	13497	-0.13	0.1	NO
23	AGPS	AGPS	AGPS	13815	-0.14	0.11	NO
24	PPAP2B	PPAP2B	PPAP2B	14640	-0.18	0.092	NO
25	PLA2G1B	PLA2G1B	PLA2G1B	15393	-0.22	0.086	NO
26	PAFAH2	PAFAH2	PAFAH2	17507	-0.47	0.042	NO

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

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

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 = THYM-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = THYM-TP.mergedcluster.txt

GSEA analysis

For the Gene Set Enrichment Analysis (GSEA), Broad GSEA-P-R.1.0 version is used with class2: canonical pathways geneses from MSigDB. Further details about statistics are available inThe Broad GSEA website.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References

[1] Subramanian, A. et al, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles., Proc. Natl. Acad. Sci. USA 102(43) (2005)

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