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

Lung Squamous Cell Carcinoma (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2016): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in LUSC-TP. Broad Institute of MIT and Harvard. doi:10.7908/C14M940K

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 having more than three samples and the input expression file "LUSC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run. 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: 717
Number of samples: 501
Original number of Gene Sets: 1320
Maximum gene set size: 933

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 4 :[ clus1 ] 106
pheno.type: 2 - 4 :[ clus2 ] 151
pheno.type: 3 - 4 :[ clus3 ] 160
pheno.type: 4 - 4 :[ clus4 ] 84

For the expression subtypes of 18514 genes in 502 samples, GSEA found enriched gene sets in each cluster using 501 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA RACCYCD PATHWAY, BIOCARTA IL1R PATHWAY, BIOCARTA TNFR1 PATHWAY, PID P73PATHWAY, PID TRAIL PATHWAY, PID IL1PATHWAY, PID P53DOWNSTREAMPATHWAY, PID P38ALPHABETADOWNSTREAMPATHWAY, PID DELTANP63PATHWAY, PID P53REGULATIONPATHWAY

And common core enriched genes are IL1RAP, CHUK, IL1A, IL1B, IL1R2, IL1RN, MAPK3, CDK6, CDKN1A, RB1

clus2

Top enriched gene sets are KEGG GLUTATHIONE METABOLISM, KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS, BIOCARTA CHREBP2 PATHWAY, PID FANCONI PATHWAY, PID ATR PATHWAY, PID HEDGEHOG GLIPATHWAY, PID BARD1PATHWAY, REACTOME METABOLISM OF NON CODING RNA, REACTOME MITOCHONDRIAL PROTEIN IMPORT, REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM

And common core enriched genes are NUP133, NUP153, NUP188, NUP205, NUP210, NUP214, NUP35, NUP37, NUP50, NUP88

clus3

Top enriched gene sets are KEGG CYSTEINE AND METHIONINE METABOLISM, BIOCARTA MPR PATHWAY, BIOCARTA DEATH PATHWAY, PID SMAD2 3NUCLEARPATHWAY, PID CASPASE PATHWAY, REACTOME SIGNALING BY FGFR1 MUTANTS, REACTOME GENERIC TRANSCRIPTION PATHWAY, REACTOME TRANSMISSION ACROSS CHEMICAL SYNAPSES, REACTOME NEURONAL SYSTEM, REACTOME P75 NTR RECEPTOR MEDIATED SIGNALLING

And common core enriched genes are AR, CDK2, E2F5, ESR1, GATA3, HDAC2, HNF4A, IFNB1, IRF7, RUNX2

clus4

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG FATTY ACID METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG ARGININE AND PROLINE METABOLISM, KEGG HISTIDINE METABOLISM, KEGG TYROSINE METABOLISM, KEGG TRYPTOPHAN METABOLISM, KEGG O GLYCAN BIOSYNTHESIS, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG GLYCEROPHOSPHOLIPID METABOLISM

And common core enriched genes are FOS, AGER, DUSP4, DUSP6, IRAK2, JUN, MEF2C, RPS6KA2, S100B, SAA1

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 RACCYCD PATHWAY	26	genes.ES.table	0.42	1.8	0.018	0.99	0.74	0.42	0.21	0.34	0.35	0.23
BIOCARTA IL1R PATHWAY	32	genes.ES.table	0.56	1.6	0.054	0.86	0.97	0.25	0.1	0.22	0.48	0.26
BIOCARTA TNFR1 PATHWAY	29	genes.ES.table	0.37	1.5	0.062	0.89	0.99	0.38	0.25	0.29	0.55	0.28
PID P73PATHWAY	79	genes.ES.table	0.43	1.8	0.01	0.81	0.74	0.25	0.16	0.22	0.28	0.19
PID TRAIL PATHWAY	28	genes.ES.table	0.55	1.8	0.014	1	0.66	0.57	0.25	0.43	0.31	0.21
PID IL1PATHWAY	34	genes.ES.table	0.61	2	0.0039	0.31	0.23	0.24	0.11	0.21	0	0.063
PID P53DOWNSTREAMPATHWAY	134	genes.ES.table	0.42	1.7	0.01	0.95	0.84	0.26	0.13	0.23	0.41	0.24
PID P38ALPHABETADOWNSTREAMPATHWAY	38	genes.ES.table	0.45	1.7	0.019	0.94	0.88	0.32	0.15	0.27	0.41	0.26
PID DELTANP63PATHWAY	47	genes.ES.table	0.55	1.6	0.019	0.96	0.91	0.21	0.064	0.2	0.46	0.27
PID P53REGULATIONPATHWAY	58	genes.ES.table	0.29	1.5	0.062	0.88	0.99	0.034	0.034	0.033	0.57	0.28

genes ES table in pathway: BIOCARTA RACCYCD 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	IL1RN	IL1RN	IL1RN	47	0.51	0.15	YES
2	IL1A	IL1A	IL1A	58	0.49	0.29	YES
3	IL1R2	IL1R2	IL1R2	408	0.25	0.35	YES
4	IL1B	IL1B	IL1B	450	0.24	0.42	YES
5	IL1RAP	IL1RAP	IL1RAP	489	0.22	0.48	YES
6	NOD2	NOD2	NOD2	571	0.2	0.54	YES
7	IRAK2	IRAK2	IRAK2	645	0.19	0.59	YES
8	TMEM189-UBE2V1	TMEM189-UBE2V1	TMEM189-UBE2V1	719	0.18	0.64	YES
9	MAP3K8	MAP3K8	MAP3K8	1310	0.12	0.64	YES
10	TOLLIP	TOLLIP	TOLLIP	1927	0.086	0.63	NO
11	RBX1	RBX1	RBX1	2601	0.064	0.62	NO
12	BTRC	BTRC	BTRC	3252	0.05	0.6	NO
13	CHUK	CHUK	CHUK	3304	0.049	0.61	NO
14	UBE2N	UBE2N	UBE2N	5431	0.018	0.5	NO
15	IKBKB	IKBKB	IKBKB	5521	0.017	0.5	NO
16	TNIP2	TNIP2	TNIP2	5569	0.017	0.5	NO
17	MAP2K1	MAP2K1	MAP2K1	6139	0.011	0.47	NO
18	TAB1	TAB1	TAB1	7037	0.0026	0.42	NO
19	IRAK3	IRAK3	IRAK3	7064	0.0024	0.42	NO
20	MYD88	MYD88	MYD88	7118	0.002	0.42	NO
21	TAB3	TAB3	TAB3	7426	-0.0007	0.4	NO
22	SKP1	SKP1	SKP1	7632	-0.0029	0.4	NO
23	TAB2	TAB2	TAB2	7782	-0.0041	0.39	NO
24	IKBKG	IKBKG	IKBKG	8023	-0.0062	0.38	NO
25	MAP3K7	MAP3K7	MAP3K7	8503	-0.011	0.35	NO
26	NOD1	NOD1	NOD1	8785	-0.013	0.34	NO
27	IL1R1	IL1R1	IL1R1	8802	-0.014	0.35	NO
28	TRAF6	TRAF6	TRAF6	9052	-0.016	0.34	NO
29	MAP2K4	MAP2K4	MAP2K4	9531	-0.021	0.32	NO
30	IRAK1	IRAK1	IRAK1	9716	-0.022	0.31	NO
31	CUL1	CUL1	CUL1	10185	-0.028	0.3	NO
32	IRAK4	IRAK4	IRAK4	10376	-0.03	0.3	NO
33	PELI1	PELI1	PELI1	10404	-0.03	0.3	NO
34	PELI3	PELI3	PELI3	11101	-0.038	0.28	NO
35	RIPK2	RIPK2	RIPK2	11575	-0.044	0.26	NO
36	MAP3K3	MAP3K3	MAP3K3	12569	-0.058	0.23	NO
37	SQSTM1	SQSTM1	SQSTM1	13406	-0.073	0.2	NO
38	MAP2K6	MAP2K6	MAP2K6	14233	-0.092	0.19	NO
39	PELI2	PELI2	PELI2	16184	-0.15	0.12	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 RACCYCD PATHWAY.

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

genes ES table in pathway: BIOCARTA IL1R PATHWAY

Table S2. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IL1RN	IL1RN	IL1RN	47	0.51	0.18	YES
2	IL1A	IL1A	IL1A	58	0.49	0.36	YES
3	IL1R2	IL1R2	IL1R2	408	0.25	0.44	YES
4	IL1B	IL1B	IL1B	450	0.24	0.52	YES
5	IL1RAP	IL1RAP	IL1RAP	489	0.22	0.6	YES
6	CASP1	CASP1	CASP1	1545	0.1	0.58	YES
7	TOLLIP	TOLLIP	TOLLIP	1927	0.086	0.59	YES
8	PRKCZ	PRKCZ	PRKCZ	2052	0.082	0.62	YES
9	NFKB1	NFKB1	NFKB1	3013	0.054	0.58	NO
10	CHUK	CHUK	CHUK	3304	0.049	0.58	NO
11	MAPK8	MAPK8	MAPK8	3931	0.038	0.56	NO
12	UBE2V1	UBE2V1	UBE2V1	4057	0.036	0.57	NO
13	PIK3R1	PIK3R1	PIK3R1	4571	0.028	0.55	NO
14	UBE2N	UBE2N	UBE2N	5431	0.018	0.51	NO
15	IKBKB	IKBKB	IKBKB	5521	0.017	0.52	NO
16	RELA	RELA	RELA	5667	0.016	0.51	NO
17	JUN	JUN	JUN	6807	0.0046	0.45	NO
18	TAB1	TAB1	TAB1	7037	0.0026	0.44	NO
19	IRAK3	IRAK3	IRAK3	7064	0.0024	0.44	NO
20	MYD88	MYD88	MYD88	7118	0.002	0.44	NO
21	TAB2	TAB2	TAB2	7782	-0.0041	0.4	NO
22	IKBKG	IKBKG	IKBKG	8023	-0.0062	0.39	NO
23	MAP3K7	MAP3K7	MAP3K7	8503	-0.011	0.37	NO
24	IL1R1	IL1R1	IL1R1	8802	-0.014	0.36	NO
25	TRAF6	TRAF6	TRAF6	9052	-0.016	0.35	NO
26	ERC1	ERC1	ERC1	9265	-0.018	0.35	NO
27	IRAK1	IRAK1	IRAK1	9716	-0.022	0.33	NO
28	IRAK4	IRAK4	IRAK4	10376	-0.03	0.31	NO
29	PRKCI	PRKCI	PRKCI	10415	-0.03	0.32	NO
30	PIK3CA	PIK3CA	PIK3CA	12032	-0.05	0.25	NO
31	MAP3K3	MAP3K3	MAP3K3	12569	-0.058	0.24	NO
32	TICAM2	TICAM2	TICAM2	12646	-0.059	0.26	NO
33	SQSTM1	SQSTM1	SQSTM1	13406	-0.073	0.24	NO
34	MAP2K6	MAP2K6	MAP2K6	14233	-0.092	0.23	NO

Figure S3. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA IL1R PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA TNFR1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TNFRSF10D	TNFRSF10D	TNFRSF10D	599	0.2	0.13	YES
2	TNFSF10	TNFSF10	TNFSF10	1202	0.13	0.19	YES
3	CASP10	CASP10	CASP10	1326	0.12	0.28	YES
4	TNFRSF10A	TNFRSF10A	TNFRSF10A	1879	0.088	0.32	YES
5	TNFRSF10B	TNFRSF10B	TNFRSF10B	3008	0.054	0.3	YES
6	FADD	FADD	FADD	3014	0.054	0.35	YES
7	CHUK	CHUK	CHUK	3304	0.049	0.37	YES
8	CASP8	CASP8	CASP8	3704	0.041	0.38	YES
9	MAPK3	MAPK3	MAPK3	3833	0.039	0.4	YES
10	TNFRSF10C	TNFRSF10C	TNFRSF10C	3863	0.038	0.43	YES
11	TRADD	TRADD	TRADD	3906	0.038	0.46	YES
12	MAPK8	MAPK8	MAPK8	3931	0.038	0.49	YES
13	CFLAR	CFLAR	CFLAR	4300	0.032	0.5	YES
14	MAP3K1	MAP3K1	MAP3K1	4501	0.029	0.51	YES
15	RIPK1	RIPK1	RIPK1	4556	0.028	0.53	YES
16	PIK3R1	PIK3R1	PIK3R1	4571	0.028	0.55	YES
17	IKBKB	IKBKB	IKBKB	5521	0.017	0.51	NO
18	PIK3CB	PIK3CB	PIK3CB	5791	0.014	0.51	NO
19	PIK3CD	PIK3CD	PIK3CD	7046	0.0026	0.44	NO
20	PIK3R3	PIK3R3	PIK3R3	7167	0.0016	0.44	NO
21	PIK3R2	PIK3R2	PIK3R2	7284	0.0007	0.43	NO
22	MAPK1	MAPK1	MAPK1	7705	-0.0034	0.41	NO
23	IKBKG	IKBKG	IKBKG	8023	-0.0062	0.4	NO
24	DAP3	DAP3	DAP3	9381	-0.019	0.34	NO
25	MAP2K4	MAP2K4	MAP2K4	9531	-0.021	0.35	NO
26	PIK3CA	PIK3CA	PIK3CA	12032	-0.05	0.26	NO
27	TRAF2	TRAF2	TRAF2	12300	-0.054	0.28	NO
28	SMPD1	SMPD1	SMPD1	13006	-0.066	0.3	NO

Figure S5. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA TNFR1 PATHWAY.

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID P73PATHWAY

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	CDKN1A	CDKN1A	CDKN1A	1569	0.1	0.00068	YES
2	CDK6	CDK6	CDK6	1599	0.1	0.084	YES
3	CCND1	CCND1	CCND1	1873	0.089	0.14	YES
4	RAC1	RAC1	RAC1	2049	0.082	0.2	YES
5	RB1	RB1	RB1	2356	0.071	0.24	YES
6	AKT1	AKT1	AKT1	2637	0.063	0.28	YES
7	NFKBIA	NFKBIA	NFKBIA	2878	0.057	0.32	YES
8	NFKB1	NFKB1	NFKB1	3013	0.054	0.36	YES
9	CHUK	CHUK	CHUK	3304	0.049	0.38	YES
10	HRAS	HRAS	HRAS	3511	0.045	0.41	YES
11	MAPK3	MAPK3	MAPK3	3833	0.039	0.42	YES
12	PIK3R1	PIK3R1	PIK3R1	4571	0.028	0.41	NO
13	TFDP1	TFDP1	TFDP1	5366	0.019	0.38	NO
14	IKBKB	IKBKB	IKBKB	5521	0.017	0.38	NO
15	RELA	RELA	RELA	5667	0.016	0.39	NO
16	PAK1	PAK1	PAK1	6094	0.011	0.38	NO
17	RHOA	RHOA	RHOA	6928	0.0035	0.33	NO
18	RAF1	RAF1	RAF1	7272	0.00079	0.32	NO
19	MAPK1	MAPK1	MAPK1	7705	-0.0034	0.3	NO
20	CCNE1	CCNE1	CCNE1	7904	-0.0052	0.29	NO
21	IKBKG	IKBKG	IKBKG	8023	-0.0062	0.29	NO
22	CDK4	CDK4	CDK4	11555	-0.043	0.13	NO
23	CDK2	CDK2	CDK2	11824	-0.047	0.16	NO
24	PIK3CA	PIK3CA	PIK3CA	12032	-0.05	0.19	NO
25	CDKN1B	CDKN1B	CDKN1B	14005	-0.086	0.15	NO
26	E2F1	E2F1	E2F1	14797	-0.11	0.2	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: PID P73PATHWAY.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: PID P73PATHWAY, 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: PID TRAIL PATHWAY

Table S5. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TP53AIP1	TP53AIP1	TP53AIP1	28	0.58	0.095	YES
2	S100A2	S100A2	S100A2	84	0.45	0.17	YES
3	CLCA2	CLCA2	CLCA2	118	0.41	0.23	YES
4	D4S234E	D4S234E	D4S234E	485	0.23	0.25	YES
5	IL1RAP	IL1RAP	IL1RAP	489	0.22	0.29	YES
6	SFN	SFN	SFN	546	0.21	0.32	YES
7	TP73	TP73	TP73	665	0.19	0.35	YES
8	TP63	TP63	TP63	680	0.19	0.38	YES
9	IL4R	IL4R	IL4R	883	0.16	0.39	YES
10	CDKN1A	CDKN1A	CDKN1A	1569	0.1	0.37	YES
11	BAK1	BAK1	BAK1	1594	0.1	0.39	YES
12	CDK6	CDK6	CDK6	1599	0.1	0.4	YES
13	HEY2	HEY2	HEY2	1957	0.085	0.4	YES
14	PLK3	PLK3	PLK3	1982	0.084	0.41	YES
15	JAG2	JAG2	JAG2	2243	0.075	0.41	YES
16	RB1	RB1	RB1	2356	0.071	0.42	YES
17	FBXO45	FBXO45	FBXO45	2368	0.07	0.43	YES
18	MAPK11	MAPK11	MAPK11	2593	0.064	0.42	YES
19	YAP1	YAP1	YAP1	2701	0.061	0.43	YES
20	MYC	MYC	MYC	2860	0.057	0.43	YES
21	GRAMD4	GRAMD4	GRAMD4	3082	0.053	0.43	NO
22	PPAP2A	PPAP2A	PPAP2A	3248	0.05	0.43	NO
23	HSF1	HSF1	HSF1	3385	0.047	0.43	NO
24	UBE4B	UBE4B	UBE4B	3650	0.042	0.42	NO
25	ITCH	ITCH	ITCH	4217	0.033	0.39	NO
26	CCNE2	CCNE2	CCNE2	4549	0.029	0.38	NO
27	ADA	ADA	ADA	4639	0.027	0.38	NO
28	CCNB1	CCNB1	CCNB1	4677	0.027	0.38	NO
29	KAT5	KAT5	KAT5	5161	0.021	0.36	NO
30	SERPINE1	SERPINE1	SERPINE1	5312	0.02	0.36	NO
31	CDK1	CDK1	CDK1	5634	0.016	0.34	NO
32	RELA	RELA	RELA	5667	0.016	0.34	NO
33	BAX	BAX	BAX	5779	0.014	0.34	NO
34	TP53I3	TP53I3	TP53I3	5849	0.014	0.34	NO
35	PLK1	PLK1	PLK1	5990	0.012	0.33	NO
36	MAPK14	MAPK14	MAPK14	6078	0.011	0.33	NO
37	DEDD	DEDD	DEDD	6178	0.01	0.32	NO
38	PIN1	PIN1	PIN1	6252	0.0098	0.32	NO
39	PML	PML	PML	6460	0.0079	0.31	NO
40	BUB3	BUB3	BUB3	6617	0.0066	0.3	NO
41	RAD51	RAD51	RAD51	6877	0.004	0.29	NO
42	CCNA2	CCNA2	CCNA2	7175	0.0015	0.28	NO
43	AEN	AEN	AEN	7186	0.0014	0.28	NO
44	RCHY1	RCHY1	RCHY1	7215	0.0012	0.27	NO
45	CHEK1	CHEK1	CHEK1	7350	0.000037	0.27	NO
46	JAK1	JAK1	JAK1	7409	-0.00049	0.26	NO
47	EP300	EP300	EP300	7545	-0.002	0.26	NO
48	PEA15	PEA15	PEA15	8242	-0.0083	0.22	NO
49	NDUFS2	NDUFS2	NDUFS2	8267	-0.0086	0.22	NO
50	CASP2	CASP2	CASP2	8449	-0.01	0.21	NO
51	SP1	SP1	SP1	8752	-0.013	0.2	NO
52	GDF15	GDF15	GDF15	8767	-0.013	0.2	NO
53	PFDN5	PFDN5	PFDN5	8820	-0.014	0.2	NO
54	FOXO3	FOXO3	FOXO3	8940	-0.015	0.2	NO
55	MDM2	MDM2	MDM2	9016	-0.016	0.19	NO
56	GNB2L1	GNB2L1	GNB2L1	9839	-0.024	0.15	NO
57	GATA1	GATA1	GATA1	10071	-0.026	0.14	NO
58	FASN	FASN	FASN	10118	-0.027	0.15	NO
59	FAS	FAS	FAS	10187	-0.028	0.15	NO
60	BCL2L11	BCL2L11	BCL2L11	11417	-0.042	0.088	NO
61	HAGH	HAGH	HAGH	11806	-0.047	0.075	NO
62	CDK2	CDK2	CDK2	11824	-0.047	0.082	NO
63	BUB1	BUB1	BUB1	12099	-0.051	0.075	NO
64	FLOT2	FLOT2	FLOT2	12534	-0.057	0.061	NO
65	PRKACB	PRKACB	PRKACB	13045	-0.066	0.044	NO
66	SIRT1	SIRT1	SIRT1	13070	-0.067	0.054	NO
67	RNF43	RNF43	RNF43	13263	-0.07	0.056	NO
68	ABL1	ABL1	ABL1	13533	-0.076	0.054	NO
69	NEDD4L	NEDD4L	NEDD4L	13864	-0.083	0.05	NO
70	DCP1B	DCP1B	DCP1B	13880	-0.084	0.063	NO
71	TUBA1A	TUBA1A	TUBA1A	14292	-0.094	0.056	NO
72	SERPINA1	SERPINA1	SERPINA1	14442	-0.098	0.064	NO
73	WWOX	WWOX	WWOX	14795	-0.11	0.063	NO
74	BBC3	BBC3	BBC3	14837	-0.11	0.078	NO
75	BRCA2	BRCA2	BRCA2	14861	-0.11	0.095	NO
76	AFP	AFP	AFP	14915	-0.11	0.11	NO
77	NTRK1	NTRK1	NTRK1	15242	-0.12	0.11	NO
78	BIN1	BIN1	BIN1	16543	-0.17	0.07	NO
79	WT1	WT1	WT1	17311	-0.22	0.064	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: PID TRAIL PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: PID TRAIL 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: PID IL1PATHWAY

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	S100A2	S100A2	S100A2	84	0.45	0.04	YES
2	BDKRB2	BDKRB2	BDKRB2	113	0.41	0.079	YES
3	SERPINB5	SERPINB5	SERPINB5	262	0.31	0.1	YES
4	EDN2	EDN2	EDN2	297	0.29	0.13	YES
5	PPM1J	PPM1J	PPM1J	305	0.29	0.16	YES
6	EPHA2	EPHA2	EPHA2	334	0.28	0.18	YES
7	SFN	SFN	SFN	546	0.21	0.19	YES
8	TNFRSF10D	TNFRSF10D	TNFRSF10D	599	0.2	0.21	YES
9	TP73	TP73	TP73	665	0.19	0.22	YES
10	TP63	TP63	TP63	680	0.19	0.24	YES
11	TGFA	TGFA	TGFA	717	0.18	0.26	YES
12	NDRG1	NDRG1	NDRG1	812	0.17	0.27	YES
13	FOXA1	FOXA1	FOXA1	830	0.17	0.28	YES
14	FDXR	FDXR	FDXR	887	0.16	0.3	YES
15	PERP	PERP	PERP	966	0.15	0.31	YES
16	SNAI2	SNAI2	SNAI2	1048	0.14	0.32	YES
17	VDR	VDR	VDR	1177	0.13	0.32	YES
18	CD82	CD82	CD82	1187	0.13	0.34	YES
19	CASP10	CASP10	CASP10	1326	0.12	0.34	YES
20	EGFR	EGFR	EGFR	1521	0.1	0.34	YES
21	CASP1	CASP1	CASP1	1545	0.1	0.35	YES
22	CDKN1A	CDKN1A	CDKN1A	1569	0.1	0.36	YES
23	BAK1	BAK1	BAK1	1594	0.1	0.36	YES
24	PPP1R13B	PPP1R13B	PPP1R13B	1662	0.098	0.37	YES
25	ZNF385A	ZNF385A	ZNF385A	1799	0.092	0.37	YES
26	DUSP5	DUSP5	DUSP5	1831	0.09	0.38	YES
27	RNF144B	RNF144B	RNF144B	1842	0.09	0.39	YES
28	TNFRSF10A	TNFRSF10A	TNFRSF10A	1879	0.088	0.4	YES
29	PLK3	PLK3	PLK3	1982	0.084	0.4	YES
30	E2F2	E2F2	E2F2	2012	0.083	0.4	YES
31	PRDM1	PRDM1	PRDM1	2162	0.078	0.4	YES
32	DDB2	DDB2	DDB2	2186	0.077	0.41	YES
33	CCNK	CCNK	CCNK	2349	0.071	0.41	YES
34	BCL2A1	BCL2A1	BCL2A1	2354	0.071	0.42	YES
35	RB1	RB1	RB1	2356	0.071	0.42	YES
36	BID	BID	BID	2531	0.066	0.42	NO
37	DDIT4	DDIT4	DDIT4	2825	0.058	0.41	NO
38	TNFRSF10B	TNFRSF10B	TNFRSF10B	3008	0.054	0.4	NO
39	BCL2L2	BCL2L2	BCL2L2	3085	0.053	0.41	NO
40	CAV1	CAV1	CAV1	3491	0.045	0.39	NO
41	STEAP3	STEAP3	STEAP3	3691	0.041	0.38	NO
42	TNFRSF10C	TNFRSF10C	TNFRSF10C	3863	0.038	0.38	NO
43	TRIAP1	TRIAP1	TRIAP1	3879	0.038	0.38	NO
44	GADD45A	GADD45A	GADD45A	4115	0.035	0.37	NO
45	PTEN	PTEN	PTEN	4171	0.034	0.37	NO
46	SESN1	SESN1	SESN1	4499	0.029	0.36	NO
47	GPX1	GPX1	GPX1	4574	0.028	0.35	NO
48	CCNB1	CCNB1	CCNB1	4677	0.027	0.35	NO
49	CARM1	CARM1	CARM1	4802	0.025	0.35	NO
50	CSE1L	CSE1L	CSE1L	4884	0.024	0.34	NO
51	RRM2B	RRM2B	RRM2B	4991	0.023	0.34	NO
52	SERPINE1	SERPINE1	SERPINE1	5312	0.02	0.33	NO
53	TFDP1	TFDP1	TFDP1	5366	0.019	0.32	NO
54	NFYC	NFYC	NFYC	5432	0.018	0.32	NO
55	PYCARD	PYCARD	PYCARD	5715	0.015	0.31	NO
56	BAX	BAX	BAX	5779	0.014	0.31	NO
57	MMP2	MMP2	MMP2	5804	0.014	0.31	NO
58	TP53I3	TP53I3	TP53I3	5849	0.014	0.31	NO
59	PMS2	PMS2	PMS2	5963	0.012	0.3	NO
60	MCL1	MCL1	MCL1	6099	0.011	0.3	NO
61	SMARCA4	SMARCA4	SMARCA4	6145	0.011	0.29	NO
62	TAF9	TAF9	TAF9	6189	0.01	0.29	NO
63	TADA2B	TADA2B	TADA2B	6332	0.0091	0.28	NO
64	TSC2	TSC2	TSC2	6425	0.0082	0.28	NO
65	PML	PML	PML	6460	0.0079	0.28	NO
66	ARID3A	ARID3A	ARID3A	6499	0.0076	0.28	NO
67	PCBP4	PCBP4	PCBP4	6631	0.0064	0.27	NO
68	JUN	JUN	JUN	6807	0.0046	0.26	NO
69	PCNA	PCNA	PCNA	6909	0.0037	0.26	NO
70	BCL2L1	BCL2L1	BCL2L1	6926	0.0035	0.26	NO
71	BCL6	BCL6	BCL6	7041	0.0026	0.25	NO
72	RCHY1	RCHY1	RCHY1	7215	0.0012	0.24	NO
73	BNIP3L	BNIP3L	BNIP3L	7250	0.00094	0.24	NO
74	PRMT1	PRMT1	PRMT1	7280	0.00074	0.24	NO
75	HTT	HTT	HTT	7351	0.000025	0.24	NO
76	EP300	EP300	EP300	7545	-0.002	0.22	NO
77	PRKAB1	PRKAB1	PRKAB1	7615	-0.0027	0.22	NO
78	DGCR8	DGCR8	DGCR8	8048	-0.0064	0.2	NO
79	KAT2A	KAT2A	KAT2A	8069	-0.0067	0.2	NO
80	C12orf5	C12orf5	C12orf5	8154	-0.0074	0.19	NO
81	TP53INP1	TP53INP1	TP53INP1	8253	-0.0084	0.19	NO
82	HDAC2	HDAC2	HDAC2	8376	-0.0096	0.18	NO
83	CTSD	CTSD	CTSD	8450	-0.01	0.18	NO
84	RPS27L	RPS27L	RPS27L	8620	-0.012	0.17	NO
85	APC	APC	APC	8684	-0.012	0.17	NO
86	MAP4K4	MAP4K4	MAP4K4	8745	-0.013	0.17	NO
87	SP1	SP1	SP1	8752	-0.013	0.17	NO
88	GDF15	GDF15	GDF15	8767	-0.013	0.17	NO
89	MET	MET	MET	8985	-0.015	0.16	NO
90	MDM2	MDM2	MDM2	9016	-0.016	0.16	NO
91	APAF1	APAF1	APAF1	9037	-0.016	0.16	NO
92	BTG2	BTG2	BTG2	9056	-0.016	0.16	NO
93	TAP1	TAP1	TAP1	9672	-0.022	0.13	NO
94	DDX5	DDX5	DDX5	9958	-0.025	0.12	NO
95	DKK1	DKK1	DKK1	10182	-0.028	0.11	NO
96	FAS	FAS	FAS	10187	-0.028	0.11	NO
97	IGFBP3	IGFBP3	IGFBP3	10382	-0.03	0.1	NO
98	MLH1	MLH1	MLH1	10450	-0.031	0.1	NO
99	CREBBP	CREBBP	CREBBP	10580	-0.032	0.098	NO
100	CEBPZ	CEBPZ	CEBPZ	10642	-0.033	0.097	NO
101	RFWD2	RFWD2	RFWD2	10967	-0.036	0.083	NO
102	DUSP1	DUSP1	DUSP1	11030	-0.037	0.084	NO
103	TP53BP2	TP53BP2	TP53BP2	11135	-0.038	0.082	NO
104	NFYA	NFYA	NFYA	11230	-0.039	0.08	NO
105	CCNG1	CCNG1	CCNG1	11670	-0.045	0.061	NO
106	TP53	TP53	TP53	11746	-0.046	0.062	NO
107	PMAIP1	PMAIP1	PMAIP1	11762	-0.046	0.065	NO
108	VCAN	VCAN	VCAN	11782	-0.047	0.069	NO
109	JMY	JMY	JMY	11814	-0.047	0.072	NO
110	NFYB	NFYB	NFYB	11915	-0.048	0.071	NO
111	LIF	LIF	LIF	12155	-0.052	0.063	NO
112	HIC1	HIC1	HIC1	12727	-0.061	0.038	NO
113	COL18A1	COL18A1	COL18A1	13029	-0.066	0.028	NO
114	CASP6	CASP6	CASP6	13052	-0.066	0.034	NO
115	IRF5	IRF5	IRF5	13278	-0.071	0.028	NO
116	MSH2	MSH2	MSH2	13307	-0.071	0.034	NO
117	E2F3	E2F3	E2F3	13554	-0.076	0.028	NO
118	BCL2L14	BCL2L14	BCL2L14	13867	-0.083	0.019	NO
119	TRRAP	TRRAP	TRRAP	14058	-0.088	0.018	NO
120	C13orf15	C13orf15	C13orf15	14225	-0.092	0.018	NO
121	TYRP1	TYRP1	TYRP1	14740	-0.1	-0.00014	NO
122	E2F1	E2F1	E2F1	14797	-0.11	0.0073	NO
123	BBC3	BBC3	BBC3	14837	-0.11	0.016	NO
124	AFP	AFP	AFP	14915	-0.11	0.022	NO
125	CX3CL1	CX3CL1	CX3CL1	15244	-0.12	0.016	NO
126	POU4F1	POU4F1	POU4F1	15714	-0.13	0.0041	NO
127	SH2D1A	SH2D1A	SH2D1A	15861	-0.14	0.0098	NO
128	SPP1	SPP1	SPP1	16251	-0.16	0.0039	NO
129	NLRC4	NLRC4	NLRC4	16361	-0.16	0.014	NO
130	ATF3	ATF3	ATF3	16817	-0.18	0.007	NO
131	AIFM2	AIFM2	AIFM2	16890	-0.19	0.022	NO
132	SCN3B	SCN3B	SCN3B	16949	-0.19	0.037	NO
133	BCL2	BCL2	BCL2	17398	-0.22	0.035	NO
134	HGF	HGF	HGF	17691	-0.25	0.044	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: PID IL1PATHWAY.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: PID IL1PATHWAY, 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: PID P53DOWNSTREAMPATHWAY

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	HSPB1	HSPB1	HSPB1	811	0.17	0.042	YES
2	RPS6KA5	RPS6KA5	RPS6KA5	1134	0.13	0.093	YES
3	SLC9A1	SLC9A1	SLC9A1	1389	0.11	0.14	YES
4	EIF4EBP1	EIF4EBP1	EIF4EBP1	1469	0.11	0.19	YES
5	RPS6KA4	RPS6KA4	RPS6KA4	1559	0.1	0.24	YES
6	PTGS2	PTGS2	PTGS2	1681	0.097	0.28	YES
7	NOS2	NOS2	NOS2	1682	0.097	0.33	YES
8	KRT19	KRT19	KRT19	2027	0.082	0.35	YES
9	PLA2G4A	PLA2G4A	PLA2G4A	2210	0.076	0.38	YES
10	ESR1	ESR1	ESR1	2448	0.068	0.4	YES
11	MAPK11	MAPK11	MAPK11	2593	0.064	0.43	YES
12	EIF4E	EIF4E	EIF4E	2731	0.06	0.45	YES
13	CEBPB	CEBPB	CEBPB	4613	0.028	0.36	NO
14	MKNK1	MKNK1	MKNK1	5146	0.021	0.34	NO
15	CREB1	CREB1	CREB1	5211	0.02	0.35	NO
16	MAPKAPK2	MAPKAPK2	MAPKAPK2	5297	0.02	0.36	NO
17	USF1	USF1	USF1	5336	0.019	0.36	NO
18	CSNK2B	CSNK2B	CSNK2B	5910	0.013	0.34	NO
19	MAPK14	MAPK14	MAPK14	6078	0.011	0.34	NO
20	MAPKAPK3	MAPKAPK3	MAPKAPK3	6194	0.01	0.34	NO
21	JUN	JUN	JUN	6807	0.0046	0.31	NO
22	RAB5A	RAB5A	RAB5A	6821	0.0045	0.31	NO
23	MAPKAPK5	MAPKAPK5	MAPKAPK5	7779	-0.004	0.26	NO
24	CSNK2A1	CSNK2A1	CSNK2A1	7848	-0.0047	0.26	NO
25	ELK4	ELK4	ELK4	7897	-0.0051	0.26	NO
26	MEF2A	MEF2A	MEF2A	9013	-0.016	0.2	NO
27	ATF2	ATF2	ATF2	9896	-0.024	0.17	NO
28	HBP1	HBP1	HBP1	9969	-0.025	0.18	NO
29	CSNK2A2	CSNK2A2	CSNK2A2	10228	-0.028	0.18	NO
30	GDI1	GDI1	GDI1	10311	-0.029	0.19	NO
31	ATF1	ATF1	ATF1	10485	-0.031	0.2	NO
32	ATF6	ATF6	ATF6	10627	-0.033	0.2	NO
33	DDIT3	DDIT3	DDIT3	11428	-0.042	0.18	NO
34	TP53	TP53	TP53	11746	-0.046	0.19	NO
35	MITF	MITF	MITF	12711	-0.06	0.17	NO
36	PPARGC1A	PPARGC1A	PPARGC1A	12744	-0.061	0.2	NO
37	MEF2C	MEF2C	MEF2C	14037	-0.087	0.17	NO
38	KRT8	KRT8	KRT8	15828	-0.14	0.14	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: PID P53DOWNSTREAMPATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: PID P53DOWNSTREAMPATHWAY, 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: PID P38ALPHABETADOWNSTREAMPATHWAY

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	IL1A	IL1A	IL1A	58	0.49	0.1	YES
2	KRT14	KRT14	KRT14	112	0.42	0.19	YES
3	BDKRB2	BDKRB2	BDKRB2	113	0.41	0.28	YES
4	RAB38	RAB38	RAB38	207	0.34	0.35	YES
5	KRT5	KRT5	KRT5	246	0.32	0.42	YES
6	SFN	SFN	SFN	546	0.21	0.45	YES
7	TP63	TP63	TP63	680	0.19	0.48	YES
8	HES1	HES1	HES1	893	0.16	0.51	YES
9	PERP	PERP	PERP	966	0.15	0.54	YES
10	VDR	VDR	VDR	1177	0.13	0.55	YES
11	YAP1	YAP1	YAP1	2701	0.061	0.48	NO
12	SEC14L2	SEC14L2	SEC14L2	3044	0.054	0.48	NO
13	GSK3B	GSK3B	GSK3B	3314	0.048	0.47	NO
14	FOSL2	FOSL2	FOSL2	3708	0.041	0.46	NO
15	ITGA3	ITGA3	ITGA3	3748	0.04	0.47	NO
16	NRG1	NRG1	NRG1	3864	0.038	0.47	NO
17	CEBPD	CEBPD	CEBPD	3930	0.038	0.47	NO
18	ITCH	ITCH	ITCH	4217	0.033	0.46	NO
19	HELLS	HELLS	HELLS	4470	0.03	0.46	NO
20	ADA	ADA	ADA	4639	0.027	0.46	NO
21	ADRM1	ADRM1	ADRM1	4701	0.027	0.46	NO
22	GPX2	GPX2	GPX2	4713	0.026	0.46	NO
23	WWP1	WWP1	WWP1	5193	0.021	0.44	NO
24	RUNX1	RUNX1	RUNX1	6484	0.0077	0.37	NO
25	CDKN2A	CDKN2A	CDKN2A	7210	0.0012	0.33	NO
26	RRAD	RRAD	RRAD	7227	0.0011	0.33	NO
27	PPP2R5A	PPP2R5A	PPP2R5A	7519	-0.0017	0.32	NO
28	FBXW7	FBXW7	FBXW7	7621	-0.0028	0.31	NO
29	COL5A1	COL5A1	COL5A1	8526	-0.011	0.27	NO
30	MDM2	MDM2	MDM2	9016	-0.016	0.24	NO
31	GNB2L1	GNB2L1	GNB2L1	9839	-0.024	0.2	NO
32	HBP1	HBP1	HBP1	9969	-0.025	0.2	NO
33	POU2F2	POU2F2	POU2F2	10068	-0.026	0.2	NO
34	FASN	FASN	FASN	10118	-0.027	0.21	NO
35	IGFBP3	IGFBP3	IGFBP3	10382	-0.03	0.2	NO
36	CCNB2	CCNB2	CCNB2	10660	-0.033	0.19	NO
37	MRE11A	MRE11A	MRE11A	10743	-0.034	0.19	NO
38	NOTCH1	NOTCH1	NOTCH1	11306	-0.04	0.17	NO
39	AXL	AXL	AXL	12606	-0.059	0.11	NO
40	TOP2A	TOP2A	TOP2A	12743	-0.061	0.12	NO
41	TCF7L1	TCF7L1	TCF7L1	12881	-0.064	0.13	NO
42	ATM	ATM	ATM	13365	-0.072	0.12	NO
43	STXBP4	STXBP4	STXBP4	14092	-0.089	0.096	NO
44	DLX5	DLX5	DLX5	14719	-0.1	0.085	NO
45	BRCA2	BRCA2	BRCA2	14861	-0.11	0.1	NO
46	T	T	T	16851	-0.18	0.034	NO
47	DLX6	DLX6	DLX6	17702	-0.25	0.043	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: PID P38ALPHABETADOWNSTREAMPATHWAY.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: PID P38ALPHABETADOWNSTREAMPATHWAY, 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: PID DELTANP63PATHWAY

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	ETFDH	ETFDH	ETFDH	1459	0.11	-0.027	YES
2	UQCRHL	UQCRHL	UQCRHL	1692	0.096	0.0069	YES
3	UQCRH	UQCRH	UQCRH	2142	0.078	0.02	YES
4	NDUFB1	NDUFB1	NDUFB1	2219	0.076	0.053	YES
5	NDUFB3	NDUFB3	NDUFB3	2234	0.075	0.088	YES
6	NDUFS4	NDUFS4	NDUFS4	2396	0.07	0.11	YES
7	NDUFS5	NDUFS5	NDUFS5	2442	0.068	0.14	YES
8	NDUFC1	NDUFC1	NDUFC1	2959	0.055	0.14	YES
9	NDUFA6	NDUFA6	NDUFA6	3059	0.053	0.16	YES
10	CYC1	CYC1	CYC1	3113	0.052	0.18	YES
11	COX6C	COX6C	COX6C	3150	0.051	0.21	YES
12	NDUFB9	NDUFB9	NDUFB9	3189	0.051	0.23	YES
13	COX7B	COX7B	COX7B	3193	0.051	0.26	YES
14	SDHB	SDHB	SDHB	3201	0.051	0.28	YES
15	NDUFS6	NDUFS6	NDUFS6	3220	0.05	0.3	YES
16	CYCS	CYCS	CYCS	3329	0.048	0.32	YES
17	COX8A	COX8A	COX8A	3343	0.048	0.34	YES
18	NDUFV1	NDUFV1	NDUFV1	3425	0.046	0.36	YES
19	NDUFS7	NDUFS7	NDUFS7	3470	0.046	0.38	YES
20	NDUFA10	NDUFA10	NDUFA10	3495	0.045	0.4	YES
21	NDUFB4	NDUFB4	NDUFB4	3591	0.043	0.42	YES
22	NDUFAB1	NDUFAB1	NDUFAB1	3758	0.04	0.43	YES
23	NDUFA12	NDUFA12	NDUFA12	3802	0.039	0.44	YES
24	SDHD	SDHD	SDHD	3830	0.039	0.46	YES
25	SDHA	SDHA	SDHA	3993	0.037	0.47	YES
26	UQCRB	UQCRB	UQCRB	4116	0.035	0.48	YES
27	UQCRC2	UQCRC2	UQCRC2	4153	0.034	0.49	YES
28	NDUFS8	NDUFS8	NDUFS8	4275	0.032	0.5	YES
29	UQCRQ	UQCRQ	UQCRQ	4374	0.031	0.51	YES
30	NDUFB7	NDUFB7	NDUFB7	4408	0.03	0.52	YES
31	SDHC	SDHC	SDHC	4432	0.03	0.54	YES
32	COX6A1	COX6A1	COX6A1	4480	0.03	0.55	YES
33	UQCR11	UQCR11	UQCR11	4648	0.027	0.56	YES
34	NDUFA3	NDUFA3	NDUFA3	4774	0.026	0.56	YES
35	NDUFB8	NDUFB8	NDUFB8	4782	0.026	0.57	YES
36	NDUFV2	NDUFV2	NDUFV2	4830	0.025	0.58	YES
37	NDUFA11	NDUFA11	NDUFA11	4932	0.024	0.59	YES
38	COX4I1	COX4I1	COX4I1	5002	0.023	0.6	YES
39	NDUFA1	NDUFA1	NDUFA1	5160	0.021	0.6	YES
40	NDUFB10	NDUFB10	NDUFB10	5167	0.021	0.61	YES
41	COX7C	COX7C	COX7C	5280	0.02	0.61	YES
42	UQCRC1	UQCRC1	UQCRC1	5338	0.019	0.62	YES
43	NDUFV3	NDUFV3	NDUFV3	5378	0.019	0.62	YES
44	NDUFS1	NDUFS1	NDUFS1	5878	0.013	0.6	NO
45	NDUFB2	NDUFB2	NDUFB2	6067	0.012	0.6	NO
46	NDUFB6	NDUFB6	NDUFB6	6141	0.011	0.6	NO
47	NDUFA7	NDUFA7	NDUFA7	6308	0.0092	0.6	NO
48	NDUFC2	NDUFC2	NDUFC2	6356	0.0088	0.6	NO
49	NDUFA5	NDUFA5	NDUFA5	6370	0.0087	0.6	NO
50	COX6B1	COX6B1	COX6B1	6440	0.0081	0.6	NO
51	NDUFA9	NDUFA9	NDUFA9	6594	0.0068	0.6	NO
52	NDUFA4	NDUFA4	NDUFA4	6902	0.0038	0.58	NO
53	NDUFB5	NDUFB5	NDUFB5	6971	0.0032	0.58	NO
54	ETFA	ETFA	ETFA	7460	-0.001	0.55	NO
55	NDUFA2	NDUFA2	NDUFA2	7724	-0.0036	0.54	NO
56	NDUFS3	NDUFS3	NDUFS3	7807	-0.0043	0.54	NO
57	NDUFA13	NDUFA13	NDUFA13	7899	-0.0051	0.54	NO
58	UQCRFS1	UQCRFS1	UQCRFS1	7917	-0.0053	0.54	NO
59	COX5A	COX5A	COX5A	8096	-0.0068	0.53	NO
60	NDUFS2	NDUFS2	NDUFS2	8267	-0.0086	0.52	NO
61	COX5B	COX5B	COX5B	8379	-0.0096	0.52	NO
62	COX7A2L	COX7A2L	COX7A2L	8604	-0.012	0.52	NO
63	ETFB	ETFB	ETFB	9240	-0.018	0.49	NO
64	NDUFA8	NDUFA8	NDUFA8	9746	-0.023	0.48	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: PID DELTANP63PATHWAY.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: PID DELTANP63PATHWAY, 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: PID P53REGULATIONPATHWAY

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	S100A12	S100A12	S100A12	9	0.68	0.15	YES
2	SAA1	SAA1	SAA1	370	0.27	0.19	YES
3	NOD2	NOD2	NOD2	571	0.2	0.23	YES
4	IRAK2	IRAK2	IRAK2	645	0.19	0.27	YES
5	TMEM189-UBE2V1	TMEM189-UBE2V1	TMEM189-UBE2V1	719	0.18	0.31	YES
6	DUSP7	DUSP7	DUSP7	769	0.17	0.34	YES
7	MAPK10	MAPK10	MAPK10	1041	0.14	0.36	YES
8	RPS6KA5	RPS6KA5	RPS6KA5	1134	0.13	0.39	YES
9	MAPK11	MAPK11	MAPK11	2593	0.064	0.32	NO
10	NFKBIA	NFKBIA	NFKBIA	2878	0.057	0.32	NO
11	CHUK	CHUK	CHUK	3304	0.049	0.31	NO
12	MAPK3	MAPK3	MAPK3	3833	0.039	0.29	NO
13	MAPK8	MAPK8	MAPK8	3931	0.038	0.29	NO
14	APP	APP	APP	3946	0.037	0.3	NO
15	NFKB2	NFKB2	NFKB2	4266	0.032	0.29	NO
16	NFKBIB	NFKBIB	NFKBIB	4457	0.03	0.28	NO
17	MAP3K1	MAP3K1	MAP3K1	4501	0.029	0.29	NO
18	MAP2K3	MAP2K3	MAP2K3	4762	0.026	0.28	NO
19	RPS6KA1	RPS6KA1	RPS6KA1	5168	0.021	0.26	NO
20	ECSIT	ECSIT	ECSIT	5175	0.021	0.27	NO
21	CREB1	CREB1	CREB1	5211	0.02	0.27	NO
22	PPP2CB	PPP2CB	PPP2CB	5260	0.02	0.27	NO
23	MAPKAPK2	MAPKAPK2	MAPKAPK2	5297	0.02	0.28	NO
24	MAPK7	MAPK7	MAPK7	5306	0.02	0.28	NO
25	PPP2CA	PPP2CA	PPP2CA	5337	0.019	0.28	NO
26	UBE2N	UBE2N	UBE2N	5431	0.018	0.28	NO
27	IKBKB	IKBKB	IKBKB	5521	0.017	0.28	NO
28	CDK1	CDK1	CDK1	5634	0.016	0.28	NO
29	RELA	RELA	RELA	5667	0.016	0.28	NO
30	MAPK14	MAPK14	MAPK14	6078	0.011	0.26	NO
31	MAP2K1	MAP2K1	MAP2K1	6139	0.011	0.26	NO
32	MAPKAPK3	MAPKAPK3	MAPKAPK3	6194	0.01	0.26	NO
33	UBA52	UBA52	UBA52	6207	0.01	0.26	NO
34	MAP2K2	MAP2K2	MAP2K2	6461	0.0079	0.25	NO
35	JUN	JUN	JUN	6807	0.0046	0.23	NO
36	PPP2R1A	PPP2R1A	PPP2R1A	6822	0.0045	0.23	NO
37	PPP2R1B	PPP2R1B	PPP2R1B	6898	0.0039	0.23	NO
38	MAP2K7	MAP2K7	MAP2K7	6936	0.0034	0.23	NO
39	TAB1	TAB1	TAB1	7037	0.0026	0.22	NO
40	MYD88	MYD88	MYD88	7118	0.002	0.22	NO
41	TAB3	TAB3	TAB3	7426	-0.0007	0.2	NO
42	MAPK1	MAPK1	MAPK1	7705	-0.0034	0.19	NO
43	TAB2	TAB2	TAB2	7782	-0.0041	0.18	NO
44	IKBKG	IKBKG	IKBKG	8023	-0.0062	0.17	NO
45	RPS27A	RPS27A	RPS27A	8263	-0.0086	0.16	NO
46	HMGB1	HMGB1	HMGB1	8285	-0.0088	0.16	NO
47	MAP3K7	MAP3K7	MAP3K7	8503	-0.011	0.15	NO
48	S100B	S100B	S100B	8614	-0.012	0.15	NO
49	FOS	FOS	FOS	8619	-0.012	0.15	NO
50	NOD1	NOD1	NOD1	8785	-0.013	0.14	NO
51	MEF2A	MEF2A	MEF2A	9013	-0.016	0.14	NO
52	TRAF6	TRAF6	TRAF6	9052	-0.016	0.14	NO
53	MAP2K4	MAP2K4	MAP2K4	9531	-0.021	0.12	NO
54	IRAK1	IRAK1	IRAK1	9716	-0.022	0.11	NO
55	PPP2R5D	PPP2R5D	PPP2R5D	9732	-0.023	0.12	NO
56	ATF2	ATF2	ATF2	9896	-0.024	0.11	NO
57	ELK1	ELK1	ELK1	10291	-0.029	0.098	NO
58	IRAK4	IRAK4	IRAK4	10376	-0.03	0.1	NO
59	PELI1	PELI1	PELI1	10404	-0.03	0.1	NO
60	ATF1	ATF1	ATF1	10485	-0.031	0.11	NO
61	DUSP3	DUSP3	DUSP3	11070	-0.038	0.085	NO
62	PELI3	PELI3	PELI3	11101	-0.038	0.092	NO
63	RIPK2	RIPK2	RIPK2	11575	-0.044	0.076	NO
64	RPS6KA3	RPS6KA3	RPS6KA3	11631	-0.044	0.083	NO
65	MAPK9	MAPK9	MAPK9	12104	-0.051	0.069	NO
66	DUSP6	DUSP6	DUSP6	12493	-0.057	0.061	NO
67	MEF2C	MEF2C	MEF2C	14037	-0.087	-0.0031	NO
68	MAP2K6	MAP2K6	MAP2K6	14233	-0.092	0.0073	NO
69	TLR9	TLR9	TLR9	14588	-0.1	0.011	NO
70	RPS6KA2	RPS6KA2	RPS6KA2	14647	-0.1	0.031	NO
71	TLR8	TLR8	TLR8	15777	-0.14	0.00051	NO
72	TLR7	TLR7	TLR7	15989	-0.14	0.022	NO
73	PELI2	PELI2	PELI2	16184	-0.15	0.046	NO
74	DUSP4	DUSP4	DUSP4	16642	-0.17	0.06	NO
75	AGER	AGER	AGER	16745	-0.18	0.095	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: PID P53REGULATIONPATHWAY.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: PID P53REGULATIONPATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG GLUTATHIONE METABOLISM	47	genes.ES.table	0.64	1.8	0.0041	0.53	0.66	0.4	0.11	0.36	0.14	0.11
KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS	25	genes.ES.table	0.52	1.7	0.019	0.62	0.78	0.44	0.2	0.35	0.21	0.15
BIOCARTA CHREBP2 PATHWAY	41	genes.ES.table	0.58	2	0.0042	0.38	0.16	0.17	0.085	0.16	0	0.057
PID FANCONI PATHWAY	46	genes.ES.table	0.55	1.8	0.042	0.57	0.73	0.48	0.22	0.38	0.17	0.13
PID ATR PATHWAY	39	genes.ES.table	0.54	1.7	0.065	0.54	0.86	0.49	0.22	0.38	0.23	0.13
PID HEDGEHOG GLIPATHWAY	48	genes.ES.table	0.44	1.7	0.026	0.6	0.8	0.12	0.042	0.12	0.22	0.14
PID BARD1PATHWAY	29	genes.ES.table	0.53	1.7	0.059	0.55	0.82	0.55	0.29	0.39	0.23	0.13
REACTOME METABOLISM OF NON CODING RNA	47	genes.ES.table	0.56	1.9	0.014	0.36	0.35	0.66	0.32	0.45	0	0.06
REACTOME MITOCHONDRIAL PROTEIN IMPORT	49	genes.ES.table	0.56	1.8	0.054	0.6	0.66	0.74	0.32	0.5	0.15	0.13
REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM	44	genes.ES.table	0.46	1.7	0.05	0.51	0.86	0.55	0.32	0.37	0.22	0.13

genes ES table in pathway: KEGG GLUTATHIONE METABOLISM

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	NUP210	NUP210	NUP210	1452	0.17	0.029	YES
2	PSIP1	PSIP1	PSIP1	2497	0.11	0.04	YES
3	NUP205	NUP205	NUP205	2529	0.1	0.1	YES
4	NUP88	NUP88	NUP88	2535	0.1	0.17	YES
5	NUP214	NUP214	NUP214	3055	0.087	0.2	YES
6	NUP188	NUP188	NUP188	3118	0.085	0.25	YES
7	POM121	POM121	POM121	3211	0.082	0.29	YES
8	SLC25A5	SLC25A5	SLC25A5	3467	0.075	0.33	YES
9	NUPL2	NUPL2	NUPL2	3556	0.073	0.37	YES
10	NUP37	NUP37	NUP37	3725	0.068	0.4	YES
11	KPNA1	KPNA1	KPNA1	3886	0.064	0.44	YES
12	NUP35	NUP35	NUP35	4096	0.059	0.46	YES
13	NUP50	NUP50	NUP50	4155	0.058	0.49	YES
14	SEH1L	SEH1L	SEH1L	4184	0.057	0.53	YES
15	HMGA1	HMGA1	HMGA1	4507	0.052	0.54	YES
16	SLC25A4	SLC25A4	SLC25A4	4977	0.042	0.55	YES
17	NUP133	NUP133	NUP133	5507	0.033	0.54	YES
18	NUP93	NUP93	NUP93	5672	0.031	0.55	YES
19	NUP153	NUP153	NUP153	5747	0.029	0.56	YES
20	RANBP2	RANBP2	RANBP2	5869	0.028	0.57	YES
21	RAE1	RAE1	RAE1	5889	0.028	0.59	YES
22	NUP107	NUP107	NUP107	6291	0.021	0.58	NO
23	AAAS	AAAS	AAAS	6531	0.018	0.58	NO
24	NUPL1	NUPL1	NUPL1	6734	0.015	0.58	NO
25	NUP155	NUP155	NUP155	7923	-0.0024	0.52	NO
26	NUP54	NUP54	NUP54	7995	-0.0036	0.51	NO
27	TPR	TPR	TPR	7998	-0.0036	0.52	NO
28	NUP43	NUP43	NUP43	8020	-0.0039	0.52	NO
29	NUP85	NUP85	NUP85	8272	-0.0078	0.51	NO
30	BANF1	BANF1	BANF1	9235	-0.022	0.47	NO
31	SLC25A6	SLC25A6	SLC25A6	9239	-0.022	0.48	NO
32	NUP62	NUP62	NUP62	9591	-0.028	0.48	NO

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

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

genes ES table in pathway: KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR BIOSYNTHESIS

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	PPP2R2B	PPP2R2B	PPP2R2B	141	0.54	0.15	YES
2	PPP2R2C	PPP2R2C	PPP2R2C	289	0.41	0.27	YES
3	PRKAA2	PRKAA2	PRKAA2	368	0.38	0.38	YES
4	PRKAG3	PRKAG3	PRKAG3	712	0.28	0.44	YES
5	MLXIPL	MLXIPL	MLXIPL	829	0.26	0.51	YES
6	PPP2R5A	PPP2R5A	PPP2R5A	1221	0.19	0.55	YES
7	PPP2R3A	PPP2R3A	PPP2R3A	1578	0.16	0.58	YES
8	YWHAG	YWHAG	YWHAG	2746	0.098	0.54	NO
9	PRKAB2	PRKAB2	PRKAB2	3801	0.066	0.5	NO
10	GCK	GCK	GCK	3981	0.062	0.51	NO
11	MLX	MLX	MLX	4642	0.049	0.49	NO
12	YWHAQ	YWHAQ	YWHAQ	4935	0.043	0.49	NO
13	ACACA	ACACA	ACACA	5246	0.038	0.48	NO
14	PPP2R4	PPP2R4	PPP2R4	5389	0.035	0.49	NO
15	PPP2R3B	PPP2R3B	PPP2R3B	5454	0.034	0.49	NO
16	PRKAR2A	PRKAR2A	PRKAR2A	5455	0.034	0.5	NO
17	YWHAE	YWHAE	YWHAE	5464	0.034	0.51	NO
18	YWHAZ	YWHAZ	YWHAZ	6107	0.024	0.48	NO
19	PPP2R1B	PPP2R1B	PPP2R1B	6116	0.024	0.49	NO
20	PRKAG1	PRKAG1	PRKAG1	6134	0.024	0.5	NO
21	PRKACA	PRKACA	PRKACA	6736	0.015	0.47	NO
22	PPP2R5D	PPP2R5D	PPP2R5D	7014	0.011	0.46	NO
23	PKLR	PKLR	PKLR	7123	0.0089	0.46	NO
24	PPP2CA	PPP2CA	PPP2CA	7411	0.0048	0.44	NO
25	PPP2R2A	PPP2R2A	PPP2R2A	7528	0.0034	0.44	NO
26	YWHAH	YWHAH	YWHAH	7618	0.0023	0.43	NO
27	PPP2R5E	PPP2R5E	PPP2R5E	8055	-0.0045	0.41	NO
28	PPP2R5C	PPP2R5C	PPP2R5C	8193	-0.0065	0.4	NO
29	FASN	FASN	FASN	8628	-0.013	0.38	NO
30	PRKAR1B	PRKAR1B	PRKAR1B	9352	-0.024	0.35	NO
31	PRKACB	PRKACB	PRKACB	9421	-0.025	0.36	NO
32	PPP2CB	PPP2CB	PPP2CB	9441	-0.025	0.36	NO
33	PRKAB1	PRKAB1	PRKAB1	9449	-0.025	0.37	NO
34	PRKAR1A	PRKAR1A	PRKAR1A	9820	-0.031	0.36	NO
35	PPP2R2D	PPP2R2D	PPP2R2D	9968	-0.034	0.36	NO
36	YWHAB	YWHAB	YWHAB	10126	-0.036	0.36	NO
37	PRKAA1	PRKAA1	PRKAA1	10234	-0.038	0.37	NO
38	PPP2R1A	PPP2R1A	PPP2R1A	11160	-0.054	0.33	NO
39	PPP2R5B	PPP2R5B	PPP2R5B	11199	-0.055	0.35	NO
40	PRKAG2	PRKAG2	PRKAG2	11592	-0.063	0.35	NO
41	PRKAR2B	PRKAR2B	PRKAR2B	12827	-0.093	0.31	NO

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

Figure S24. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCOSYLPHOSPHATIDYLINOSITOL GPI ANCHOR 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: BIOCARTA CHREBP2 PATHWAY

Table S13. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NUP210	NUP210	NUP210	1452	0.17	0.05	YES
2	NUP205	NUP205	NUP205	2529	0.1	0.072	YES
3	NUP88	NUP88	NUP88	2535	0.1	0.15	YES
4	NUP214	NUP214	NUP214	3055	0.087	0.19	YES
5	NUP188	NUP188	NUP188	3118	0.085	0.25	YES
6	POM121	POM121	POM121	3211	0.082	0.31	YES
7	NUPL2	NUPL2	NUPL2	3556	0.073	0.34	YES
8	NUP37	NUP37	NUP37	3725	0.068	0.38	YES
9	KPNA1	KPNA1	KPNA1	3886	0.064	0.42	YES
10	NUP35	NUP35	NUP35	4096	0.059	0.46	YES
11	KPNB1	KPNB1	KPNB1	4116	0.059	0.5	YES
12	NUP50	NUP50	NUP50	4155	0.058	0.54	YES
13	SEH1L	SEH1L	SEH1L	4184	0.057	0.58	YES
14	NUP133	NUP133	NUP133	5507	0.033	0.54	YES
15	NUP93	NUP93	NUP93	5672	0.031	0.55	YES
16	NUP153	NUP153	NUP153	5747	0.029	0.57	YES
17	RANBP2	RANBP2	RANBP2	5869	0.028	0.58	YES
18	RAE1	RAE1	RAE1	5889	0.028	0.6	YES
19	NUP107	NUP107	NUP107	6291	0.021	0.6	NO
20	AAAS	AAAS	AAAS	6531	0.018	0.6	NO
21	NUPL1	NUPL1	NUPL1	6734	0.015	0.6	NO
22	NUP155	NUP155	NUP155	7923	-0.0024	0.54	NO
23	NUP54	NUP54	NUP54	7995	-0.0036	0.54	NO
24	TPR	TPR	TPR	7998	-0.0036	0.54	NO
25	NUP43	NUP43	NUP43	8020	-0.0039	0.54	NO
26	NUP85	NUP85	NUP85	8272	-0.0078	0.53	NO
27	NUP62	NUP62	NUP62	9591	-0.028	0.48	NO

Figure S25. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA CHREBP2 PATHWAY.

Figure S26. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CHREBP2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID FANCONI PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NUP210	NUP210	NUP210	1452	0.17	0.056	YES
2	NUP205	NUP205	NUP205	2529	0.1	0.081	YES
3	NUP88	NUP88	NUP88	2535	0.1	0.16	YES
4	NUP214	NUP214	NUP214	3055	0.087	0.2	YES
5	NUP188	NUP188	NUP188	3118	0.085	0.27	YES
6	POM121	POM121	POM121	3211	0.082	0.33	YES
7	NUPL2	NUPL2	NUPL2	3556	0.073	0.37	YES
8	NUP37	NUP37	NUP37	3725	0.068	0.41	YES
9	XPO1	XPO1	XPO1	3892	0.064	0.45	YES
10	NUP35	NUP35	NUP35	4096	0.059	0.49	YES
11	NUP50	NUP50	NUP50	4155	0.058	0.53	YES
12	SEH1L	SEH1L	SEH1L	4184	0.057	0.58	YES
13	NUP133	NUP133	NUP133	5507	0.033	0.53	YES
14	NUP93	NUP93	NUP93	5672	0.031	0.55	YES
15	NUP153	NUP153	NUP153	5747	0.029	0.56	YES
16	RANBP2	RANBP2	RANBP2	5869	0.028	0.58	YES
17	RAE1	RAE1	RAE1	5889	0.028	0.6	YES
18	NUP107	NUP107	NUP107	6291	0.021	0.6	NO
19	AAAS	AAAS	AAAS	6531	0.018	0.6	NO
20	NUPL1	NUPL1	NUPL1	6734	0.015	0.6	NO
21	RAN	RAN	RAN	7779	-0.0003	0.54	NO
22	NUP155	NUP155	NUP155	7923	-0.0024	0.54	NO
23	NUP54	NUP54	NUP54	7995	-0.0036	0.54	NO
24	TPR	TPR	TPR	7998	-0.0036	0.54	NO
25	NUP43	NUP43	NUP43	8020	-0.0039	0.54	NO
26	NUP85	NUP85	NUP85	8272	-0.0078	0.53	NO
27	NUP62	NUP62	NUP62	9591	-0.028	0.48	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: PID FANCONI PATHWAY.

Figure S28. Get High-res Image For the top 5 core enriched genes in the pathway: PID FANCONI 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: PID ATR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	NUP210	NUP210	NUP210	1452	0.17	-0.0054	YES
2	SMN1	SMN1	SMN1	2149	0.12	0.01	YES
3	NCBP1	NCBP1	NCBP1	2355	0.11	0.048	YES
4	GEMIN4	GEMIN4	GEMIN4	2431	0.11	0.091	YES
5	NUP205	NUP205	NUP205	2529	0.1	0.13	YES
6	NUP88	NUP88	NUP88	2535	0.1	0.18	YES
7	NUP214	NUP214	NUP214	3055	0.087	0.18	YES
8	NCBP2	NCBP2	NCBP2	3077	0.086	0.22	YES
9	NUP188	NUP188	NUP188	3118	0.085	0.25	YES
10	SNRPD1	SNRPD1	SNRPD1	3156	0.084	0.29	YES
11	POM121	POM121	POM121	3211	0.082	0.32	YES
12	SNRPG	SNRPG	SNRPG	3244	0.081	0.35	YES
13	NUPL2	NUPL2	NUPL2	3556	0.073	0.37	YES
14	NUP37	NUP37	NUP37	3725	0.068	0.39	YES
15	NUP35	NUP35	NUP35	4096	0.059	0.39	YES
16	NUP50	NUP50	NUP50	4155	0.058	0.42	YES
17	SEH1L	SEH1L	SEH1L	4184	0.057	0.44	YES
18	GEMIN6	GEMIN6	GEMIN6	4255	0.056	0.46	YES
19	SNRPF	SNRPF	SNRPF	4995	0.042	0.44	YES
20	SNRPB	SNRPB	SNRPB	5022	0.042	0.45	YES
21	PRMT5	PRMT5	PRMT5	5297	0.037	0.45	YES
22	SNRPD3	SNRPD3	SNRPD3	5327	0.036	0.47	YES
23	SNUPN	SNUPN	SNUPN	5481	0.034	0.47	YES
24	NUP133	NUP133	NUP133	5507	0.033	0.49	YES
25	SNRPE	SNRPE	SNRPE	5521	0.033	0.5	YES
26	SMN2	SMN2	SMN2	5663	0.031	0.5	YES
27	NUP93	NUP93	NUP93	5672	0.031	0.52	YES
28	NUP153	NUP153	NUP153	5747	0.029	0.53	YES
29	TGS1	TGS1	TGS1	5758	0.029	0.54	YES
30	RANBP2	RANBP2	RANBP2	5869	0.028	0.55	YES
31	RAE1	RAE1	RAE1	5889	0.028	0.56	YES
32	CLNS1A	CLNS1A	CLNS1A	6094	0.024	0.56	NO
33	NUP107	NUP107	NUP107	6291	0.021	0.55	NO
34	AAAS	AAAS	AAAS	6531	0.018	0.55	NO
35	GEMIN5	GEMIN5	GEMIN5	6622	0.016	0.55	NO
36	NUPL1	NUPL1	NUPL1	6734	0.015	0.55	NO
37	SNRPD2	SNRPD2	SNRPD2	6779	0.014	0.55	NO
38	NUP155	NUP155	NUP155	7923	-0.0024	0.49	NO
39	NUP54	NUP54	NUP54	7995	-0.0036	0.49	NO
40	TPR	TPR	TPR	7998	-0.0036	0.49	NO
41	NUP43	NUP43	NUP43	8020	-0.0039	0.49	NO
42	NUP85	NUP85	NUP85	8272	-0.0078	0.48	NO
43	PHAX	PHAX	PHAX	8506	-0.012	0.48	NO
44	WDR77	WDR77	WDR77	9368	-0.024	0.44	NO
45	NUP62	NUP62	NUP62	9591	-0.028	0.44	NO
46	DDX20	DDX20	DDX20	10977	-0.051	0.38	NO
47	GEMIN7	GEMIN7	GEMIN7	11108	-0.053	0.4	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: PID ATR PATHWAY.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: PID ATR 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: PID HEDGEHOG GLIPATHWAY

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	NUP210	NUP210	NUP210	1452	0.17	0.024	YES
2	NCBP1	NCBP1	NCBP1	2355	0.11	0.043	YES
3	NUP205	NUP205	NUP205	2529	0.1	0.097	YES
4	NUP88	NUP88	NUP88	2535	0.1	0.16	YES
5	THOC4	THOC4	THOC4	3011	0.088	0.19	YES
6	NUP214	NUP214	NUP214	3055	0.087	0.24	YES
7	NCBP2	NCBP2	NCBP2	3077	0.086	0.29	YES
8	NUP188	NUP188	NUP188	3118	0.085	0.34	YES
9	POM121	POM121	POM121	3211	0.082	0.38	YES
10	NUPL2	NUPL2	NUPL2	3556	0.073	0.4	YES
11	NUP37	NUP37	NUP37	3725	0.068	0.44	YES
12	NUP35	NUP35	NUP35	4096	0.059	0.45	YES
13	NUP50	NUP50	NUP50	4155	0.058	0.48	YES
14	SEH1L	SEH1L	SEH1L	4184	0.057	0.52	YES
15	CPSF3	CPSF3	CPSF3	5254	0.037	0.48	YES
16	NUP133	NUP133	NUP133	5507	0.033	0.49	YES
17	NUP93	NUP93	NUP93	5672	0.031	0.5	YES
18	NUP153	NUP153	NUP153	5747	0.029	0.51	YES
19	RANBP2	RANBP2	RANBP2	5869	0.028	0.52	YES
20	RAE1	RAE1	RAE1	5889	0.028	0.54	YES
21	NUP107	NUP107	NUP107	6291	0.021	0.53	NO
22	AAAS	AAAS	AAAS	6531	0.018	0.52	NO
23	NUPL1	NUPL1	NUPL1	6734	0.015	0.52	NO
24	CPSF2	CPSF2	CPSF2	7631	0.0021	0.47	NO
25	NUP155	NUP155	NUP155	7923	-0.0024	0.46	NO
26	NUP54	NUP54	NUP54	7995	-0.0036	0.46	NO
27	TPR	TPR	TPR	7998	-0.0036	0.46	NO
28	NUP43	NUP43	NUP43	8020	-0.0039	0.46	NO
29	NUP85	NUP85	NUP85	8272	-0.0078	0.45	NO
30	EIF4E	EIF4E	EIF4E	8301	-0.0083	0.46	NO
31	NUP62	NUP62	NUP62	9591	-0.028	0.4	NO
32	NXF1	NXF1	NXF1	10465	-0.042	0.38	NO
33	CPSF1	CPSF1	CPSF1	12762	-0.091	0.31	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: PID HEDGEHOG GLIPATHWAY.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: PID HEDGEHOG GLIPATHWAY, 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: PID BARD1PATHWAY

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	DNAJC19	DNAJC19	DNAJC19	859	0.25	0.047	YES
2	FXN	FXN	FXN	1807	0.14	0.05	YES
3	TOMM5	TOMM5	TOMM5	1903	0.14	0.097	YES
4	COQ2	COQ2	COQ2	2284	0.12	0.12	YES
5	ATP5G1	ATP5G1	ATP5G1	2880	0.092	0.12	YES
6	TIMM44	TIMM44	TIMM44	2996	0.088	0.15	YES
7	TOMM22	TOMM22	TOMM22	3329	0.079	0.16	YES
8	TIMM8A	TIMM8A	TIMM8A	3515	0.074	0.18	YES
9	TOMM20	TOMM20	TOMM20	3525	0.073	0.2	YES
10	GRPEL2	GRPEL2	GRPEL2	3553	0.073	0.23	YES
11	PMPCA	PMPCA	PMPCA	3634	0.071	0.25	YES
12	HSPD1	HSPD1	HSPD1	3677	0.07	0.28	YES
13	HSCB	HSCB	HSCB	3861	0.065	0.29	YES
14	TIMM50	TIMM50	TIMM50	3882	0.064	0.32	YES
15	LDHD	LDHD	LDHD	4025	0.061	0.33	YES
16	C18orf55	C18orf55	C18orf55	4137	0.058	0.34	YES
17	ACO2	ACO2	ACO2	4239	0.056	0.36	YES
18	HSPA9	HSPA9	HSPA9	4293	0.056	0.38	YES
19	SAMM50	SAMM50	SAMM50	4406	0.053	0.39	YES
20	TAZ	TAZ	TAZ	4464	0.052	0.41	YES
21	CHCHD4	CHCHD4	CHCHD4	4510	0.051	0.43	YES
22	ATP5B	ATP5B	ATP5B	4709	0.048	0.43	YES
23	PMPCB	PMPCB	PMPCB	4894	0.044	0.44	YES
24	SLC25A4	SLC25A4	SLC25A4	4977	0.042	0.45	YES
25	GRPEL1	GRPEL1	GRPEL1	5049	0.041	0.46	YES
26	TIMM22	TIMM22	TIMM22	5125	0.04	0.47	YES
27	SLC25A13	SLC25A13	SLC25A13	5178	0.039	0.49	YES
28	FXC1	FXC1	FXC1	5241	0.038	0.5	YES
29	TIMM8B	TIMM8B	TIMM8B	5251	0.038	0.51	YES
30	ATP5A1	ATP5A1	ATP5A1	5561	0.032	0.5	YES
31	TIMM17A	TIMM17A	TIMM17A	5602	0.032	0.52	YES
32	TIMM13	TIMM13	TIMM13	5607	0.032	0.53	YES
33	TOMM40	TOMM40	TOMM40	5734	0.03	0.53	YES
34	TIMM10	TIMM10	TIMM10	5792	0.029	0.54	YES
35	TOMM7	TOMM7	TOMM7	5793	0.029	0.55	YES
36	MTX1	MTX1	MTX1	5864	0.028	0.56	YES
37	CS	CS	CS	6165	0.023	0.55	NO
38	TOMM70A	TOMM70A	TOMM70A	6333	0.021	0.55	NO
39	SLC25A12	SLC25A12	SLC25A12	6738	0.015	0.53	NO
40	VDAC1	VDAC1	VDAC1	6751	0.015	0.54	NO
41	MTX2	MTX2	MTX2	6871	0.013	0.53	NO
42	CYC1	CYC1	CYC1	7078	0.0097	0.53	NO
43	TIMM9	TIMM9	TIMM9	7533	0.0033	0.5	NO
44	TIMM17B	TIMM17B	TIMM17B	8056	-0.0045	0.48	NO
45	COX17	COX17	COX17	8131	-0.0054	0.48	NO
46	SLC25A6	SLC25A6	SLC25A6	9239	-0.022	0.42	NO
47	GFER	GFER	GFER	11172	-0.054	0.34	NO
48	IDH3G	IDH3G	IDH3G	11435	-0.06	0.35	NO
49	BCS1L	BCS1L	BCS1L	12919	-0.096	0.3	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: PID BARD1PATHWAY.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: PID BARD1PATHWAY, 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: REACTOME METABOLISM OF NON CODING RNA

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	GPX2	GPX2	GPX2	77	0.64	0.072	YES
2	GSTM2	GSTM2	GSTM2	94	0.6	0.14	YES
3	GSTM3	GSTM3	GSTM3	105	0.58	0.21	YES
4	GSTA1	GSTA1	GSTA1	140	0.54	0.28	YES
5	GSTM4	GSTM4	GSTM4	228	0.46	0.32	YES
6	GCLM	GCLM	GCLM	258	0.43	0.38	YES
7	GCLC	GCLC	GCLC	272	0.42	0.42	YES
8	ODC1	ODC1	ODC1	473	0.33	0.45	YES
9	GSR	GSR	GSR	492	0.33	0.49	YES
10	GSTA4	GSTA4	GSTA4	573	0.31	0.52	YES
11	PGD	PGD	PGD	580	0.3	0.56	YES
12	G6PD	G6PD	G6PD	633	0.29	0.59	YES
13	GSTA2	GSTA2	GSTA2	1215	0.2	0.58	YES
14	GSTM1	GSTM1	GSTM1	1232	0.19	0.6	YES
15	SMS	SMS	SMS	1734	0.15	0.6	YES
16	RRM1	RRM1	RRM1	1824	0.14	0.61	YES
17	GSTT2	GSTT2	GSTT2	2007	0.13	0.61	YES
18	GSTO1	GSTO1	GSTO1	2056	0.13	0.63	YES
19	IDH1	IDH1	IDH1	2111	0.13	0.64	YES
20	GGCT	GGCT	GGCT	2948	0.09	0.6	NO
21	RRM2	RRM2	RRM2	2988	0.089	0.61	NO
22	GSTP1	GSTP1	GSTP1	3430	0.076	0.6	NO
23	MGST2	MGST2	MGST2	4426	0.053	0.55	NO
24	GSTZ1	GSTZ1	GSTZ1	4862	0.044	0.53	NO
25	MGST1	MGST1	MGST1	6060	0.025	0.47	NO
26	GGT6	GGT6	GGT6	6222	0.022	0.46	NO
27	GSS	GSS	GSS	6368	0.02	0.46	NO
28	GSTT1	GSTT1	GSTT1	6575	0.017	0.45	NO
29	GPX4	GPX4	GPX4	6865	0.013	0.44	NO
30	TXNDC12	TXNDC12	TXNDC12	7753	0.0001	0.39	NO
31	MGST3	MGST3	MGST3	8572	-0.012	0.34	NO
32	GGT7	GGT7	GGT7	10178	-0.037	0.26	NO
33	GSTA3	GSTA3	GSTA3	10558	-0.043	0.25	NO
34	RRM2B	RRM2B	RRM2B	10908	-0.05	0.23	NO
35	GSTK1	GSTK1	GSTK1	10962	-0.05	0.24	NO
36	GPX1	GPX1	GPX1	11388	-0.059	0.22	NO
37	LAP3	LAP3	LAP3	12351	-0.081	0.18	NO
38	IDH2	IDH2	IDH2	12454	-0.084	0.18	NO
39	GSTM5	GSTM5	GSTM5	12671	-0.088	0.18	NO
40	SRM	SRM	SRM	12821	-0.093	0.18	NO
41	OPLAH	OPLAH	OPLAH	12915	-0.096	0.19	NO
42	GSTO2	GSTO2	GSTO2	13052	-0.1	0.2	NO
43	GPX3	GPX3	GPX3	13163	-0.1	0.2	NO
44	GGT5	GGT5	GGT5	14335	-0.14	0.16	NO
45	ANPEP	ANPEP	ANPEP	14980	-0.16	0.14	NO
46	GPX7	GPX7	GPX7	15407	-0.18	0.14	NO
47	GGT1	GGT1	GGT1	16576	-0.24	0.1	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: REACTOME METABOLISM OF NON CODING RNA.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME METABOLISM OF NON CODING RNA, 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: REACTOME MITOCHONDRIAL PROTEIN IMPORT

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	RFC4	RFC4	RFC4	1130	0.2	-0.0055	YES
2	BRIP1	BRIP1	BRIP1	1139	0.2	0.05	YES
3	RMI1	RMI1	RMI1	1317	0.18	0.09	YES
4	BRCA2	BRCA2	BRCA2	1344	0.18	0.14	YES
5	BLM	BLM	BLM	1445	0.17	0.18	YES
6	FANCC	FANCC	FANCC	1475	0.17	0.22	YES
7	BRCA1	BRCA1	BRCA1	1558	0.16	0.26	YES
8	FANCE	FANCE	FANCE	1684	0.15	0.3	YES
9	FANCB	FANCB	FANCB	1739	0.15	0.34	YES
10	FANCI	FANCI	FANCI	1786	0.14	0.37	YES
11	FANCG	FANCG	FANCG	1854	0.14	0.41	YES
12	RFC5	RFC5	RFC5	1983	0.13	0.44	YES
13	UBE2T	UBE2T	UBE2T	2395	0.11	0.44	YES
14	RPA1	RPA1	RPA1	2421	0.11	0.47	YES
15	FANCL	FANCL	FANCL	2593	0.1	0.49	YES
16	H2AFX	H2AFX	H2AFX	3210	0.082	0.48	YES
17	TOPBP1	TOPBP1	TOPBP1	3237	0.081	0.5	YES
18	FANCD2	FANCD2	FANCD2	3370	0.077	0.52	YES
19	RFC2	RFC2	RFC2	3535	0.073	0.53	YES
20	RFC3	RFC3	RFC3	3628	0.071	0.54	YES
21	HUS1	HUS1	HUS1	4023	0.061	0.54	YES
22	C19orf40	C19orf40	C19orf40	4044	0.06	0.55	YES
23	ATRIP	ATRIP	ATRIP	4863	0.044	0.52	NO
24	RAD50	RAD50	RAD50	5034	0.042	0.52	NO
25	TOP3A	TOP3A	TOP3A	5097	0.04	0.53	NO
26	ATR	ATR	ATR	5165	0.039	0.54	NO
27	PALB2	PALB2	PALB2	5278	0.037	0.54	NO
28	XRCC3	XRCC3	XRCC3	6046	0.025	0.51	NO
29	FANCM	FANCM	FANCM	6158	0.024	0.51	NO
30	MRE11A	MRE11A	MRE11A	6428	0.019	0.5	NO
31	FANCA	FANCA	FANCA	6462	0.019	0.5	NO
32	CHEK1	CHEK1	CHEK1	6625	0.016	0.5	NO
33	APITD1	APITD1	APITD1	6697	0.015	0.5	NO
34	WDR48	WDR48	WDR48	8296	-0.0082	0.41	NO
35	FBXW11	FBXW11	FBXW11	8665	-0.014	0.4	NO
36	C17orf70	C17orf70	C17orf70	8666	-0.014	0.4	NO
37	RAD1	RAD1	RAD1	9080	-0.02	0.38	NO
38	FANCF	FANCF	FANCF	9229	-0.022	0.38	NO
39	USP1	USP1	USP1	9359	-0.024	0.38	NO
40	ATM	ATM	ATM	9754	-0.03	0.37	NO
41	RAD17	RAD17	RAD17	10079	-0.035	0.36	NO
42	HES1	HES1	HES1	11315	-0.058	0.31	NO
43	SSPO	SSPO	SSPO	11363	-0.058	0.32	NO
44	NBN	NBN	NBN	12190	-0.077	0.3	NO
45	RPA2	RPA2	RPA2	12211	-0.078	0.32	NO
46	RAD9A	RAD9A	RAD9A	12498	-0.084	0.32	NO

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

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME MITOCHONDRIAL PROTEIN IMPORT, 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: REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM

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	GPLD1	GPLD1	GPLD1	221	0.47	0.18	YES
2	PGAP1	PGAP1	PGAP1	1045	0.22	0.23	YES
3	PIGX	PIGX	PIGX	1106	0.21	0.32	YES
4	PIGZ	PIGZ	PIGZ	1617	0.16	0.35	YES
5	PIGW	PIGW	PIGW	1651	0.15	0.42	YES
6	PIGN	PIGN	PIGN	2660	0.1	0.4	YES
7	PIGS	PIGS	PIGS	2731	0.098	0.44	YES
8	PIGF	PIGF	PIGF	3023	0.088	0.46	YES
9	PIGO	PIGO	PIGO	3097	0.086	0.5	YES
10	PIGM	PIGM	PIGM	3544	0.073	0.5	YES
11	DPM2	DPM2	DPM2	3780	0.067	0.52	YES
12	PIGY	PIGY	PIGY	4651	0.049	0.49	NO
13	PIGC	PIGC	PIGC	4653	0.049	0.51	NO
14	PIGB	PIGB	PIGB	5527	0.033	0.48	NO
15	PIGA	PIGA	PIGA	6822	0.013	0.42	NO
16	PIGH	PIGH	PIGH	7062	0.0099	0.41	NO
17	PIGP	PIGP	PIGP	7328	0.006	0.39	NO
18	PIGV	PIGV	PIGV	7495	0.0037	0.39	NO
19	PIGU	PIGU	PIGU	8887	-0.017	0.32	NO
20	GPAA1	GPAA1	GPAA1	10978	-0.051	0.23	NO
21	PIGG	PIGG	PIGG	11370	-0.059	0.23	NO
22	PIGT	PIGT	PIGT	11857	-0.069	0.23	NO
23	PIGL	PIGL	PIGL	12513	-0.085	0.23	NO
24	PIGQ	PIGQ	PIGQ	12881	-0.095	0.25	NO
25	PIGK	PIGK	PIGK	13725	-0.12	0.26	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: REACTOME TRANSPORT OF MATURE TRANSCRIPT TO CYTOPLASM.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG CYSTEINE AND METHIONINE METABOLISM	33	genes.ES.table	0.47	1.5	0.06	1	0.99	0.24	0.15	0.21	1	0.9
BIOCARTA MPR PATHWAY	33	genes.ES.table	0.4	1.4	0.12	1	1	0.21	0.21	0.17	1	0.85
BIOCARTA DEATH PATHWAY	33	genes.ES.table	0.4	1.4	0.16	1	1	0.36	0.33	0.24	1	0.86
PID SMAD2 3NUCLEARPATHWAY	80	genes.ES.table	0.38	1.6	0.032	1	0.96	0.38	0.35	0.25	1	0.95
PID CASPASE PATHWAY	51	genes.ES.table	0.36	1.5	0.096	1	1	0.37	0.33	0.25	1	0.9
REACTOME SIGNALING BY FGFR1 MUTANTS	26	genes.ES.table	0.46	1.3	0.12	1	1	0.46	0.3	0.33	1	0.84
REACTOME GENERIC TRANSCRIPTION PATHWAY	339	genes.ES.table	0.46	1.6	0.078	1	0.98	0.44	0.28	0.32	1	0.93
REACTOME TRANSMISSION ACROSS CHEMICAL SYNAPSES	174	genes.ES.table	0.47	1.4	0.05	1	1	0.4	0.21	0.32	1	0.86
REACTOME NEURONAL SYSTEM	260	genes.ES.table	0.48	1.4	0.036	1	1	0.42	0.21	0.33	1	0.87
REACTOME P75 NTR RECEPTOR MEDIATED SIGNALLING	79	genes.ES.table	0.35	1.4	0.079	1	1	0.37	0.33	0.25	1	0.88

genes ES table in pathway: KEGG CYSTEINE AND METHIONINE METABOLISM

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	GATA3	GATA3	GATA3	38	0.43	0.081	YES
2	E2F5	E2F5	E2F5	195	0.34	0.14	YES
3	IFNB1	IFNB1	IFNB1	536	0.28	0.17	YES
4	GSC	GSC	GSC	667	0.26	0.22	YES
5	RUNX2	RUNX2	RUNX2	897	0.24	0.25	YES
6	FOXG1	FOXG1	FOXG1	1180	0.21	0.27	YES
7	SMAD7	SMAD7	SMAD7	2365	0.15	0.24	YES
8	IRF7	IRF7	IRF7	2382	0.15	0.27	YES
9	ESR1	ESR1	ESR1	2473	0.15	0.29	YES
10	TGIF2	TGIF2	TGIF2	2720	0.14	0.3	YES
11	NKX2-5	NKX2-5	NKX2-5	2869	0.13	0.32	YES
12	ZBTB17	ZBTB17	ZBTB17	4163	0.097	0.27	YES
13	RBBP4	RBBP4	RBBP4	4220	0.095	0.28	YES
14	AR	AR	AR	4345	0.092	0.3	YES
15	SKI	SKI	SKI	4378	0.091	0.31	YES
16	HNF4A	HNF4A	HNF4A	4621	0.085	0.32	YES
17	IL10	IL10	IL10	4712	0.083	0.33	YES
18	CITED1	CITED1	CITED1	4968	0.077	0.33	YES
19	FOXO4	FOXO4	FOXO4	5060	0.076	0.34	YES
20	SAP30	SAP30	SAP30	5465	0.068	0.33	YES
21	COL1A2	COL1A2	COL1A2	5697	0.063	0.33	YES
22	RUNX3	RUNX3	RUNX3	5807	0.062	0.33	YES
23	CEBPB	CEBPB	CEBPB	5936	0.06	0.34	YES
24	DLX1	DLX1	DLX1	6013	0.058	0.34	YES
25	CDK2	CDK2	CDK2	6020	0.058	0.36	YES
26	NCOA2	NCOA2	NCOA2	6055	0.057	0.36	YES
27	HDAC2	HDAC2	HDAC2	6069	0.057	0.38	YES
28	CTBP1	CTBP1	CTBP1	6390	0.052	0.37	YES
29	SKIL	SKIL	SKIL	6413	0.052	0.38	YES
30	SNIP1	SNIP1	SNIP1	6436	0.052	0.38	YES
31	TCF3	TCF3	TCF3	7582	0.038	0.33	NO
32	MEF2C	MEF2C	MEF2C	7616	0.037	0.34	NO
33	RBBP7	RBBP7	RBBP7	8633	0.026	0.28	NO
34	ATF2	ATF2	ATF2	8664	0.026	0.29	NO
35	JUN	JUN	JUN	8678	0.026	0.29	NO
36	FOXH1	FOXH1	FOXH1	8770	0.025	0.29	NO
37	LAMC1	LAMC1	LAMC1	8891	0.024	0.29	NO
38	SIN3B	SIN3B	SIN3B	8915	0.024	0.29	NO
39	VDR	VDR	VDR	8954	0.024	0.3	NO
40	NCOA1	NCOA1	NCOA1	9109	0.022	0.29	NO
41	DCP1A	DCP1A	DCP1A	9237	0.021	0.29	NO
42	CREB1	CREB1	CREB1	9351	0.02	0.29	NO
43	SMAD4	SMAD4	SMAD4	10025	0.014	0.25	NO
44	NCOR1	NCOR1	NCOR1	10065	0.013	0.25	NO
45	SERPINE1	SERPINE1	SERPINE1	10177	0.012	0.25	NO
46	MYOD1	MYOD1	MYOD1	10199	0.012	0.25	NO
47	KAT2B	KAT2B	KAT2B	10228	0.012	0.25	NO
48	CDK4	CDK4	CDK4	10411	0.0098	0.24	NO
49	MED15	MED15	MED15	10480	0.0092	0.24	NO
50	SAP18	SAP18	SAP18	10525	0.0088	0.24	NO
51	PIAS3	PIAS3	PIAS3	10607	0.0081	0.24	NO
52	RBL1	RBL1	RBL1	10701	0.0073	0.24	NO
53	SIN3A	SIN3A	SIN3A	10834	0.0061	0.23	NO
54	PIAS4	PIAS4	PIAS4	11440	0.00045	0.2	NO
55	KAT2A	KAT2A	KAT2A	11490	-0.00016	0.19	NO
56	TFE3	TFE3	TFE3	11508	-0.00034	0.19	NO
57	SP3	SP3	SP3	11672	-0.002	0.18	NO
58	CBFB	CBFB	CBFB	11719	-0.0023	0.18	NO
59	FOXO3	FOXO3	FOXO3	11805	-0.003	0.18	NO
60	CREBBP	CREBBP	CREBBP	11869	-0.0038	0.18	NO
61	HDAC1	HDAC1	HDAC1	12097	-0.0059	0.16	NO
62	SP1	SP1	SP1	12165	-0.0066	0.16	NO
63	EP300	EP300	EP300	12351	-0.0086	0.15	NO
64	TFDP1	TFDP1	TFDP1	12460	-0.01	0.15	NO
65	HSPA8	HSPA8	HSPA8	12868	-0.014	0.13	NO
66	RUNX1	RUNX1	RUNX1	13185	-0.018	0.12	NO
67	E2F4	E2F4	E2F4	13982	-0.028	0.078	NO
68	SMAD2	SMAD2	SMAD2	14118	-0.03	0.077	NO
69	NR3C1	NR3C1	NR3C1	14386	-0.034	0.069	NO
70	TGIF1	TGIF1	TGIF1	14457	-0.035	0.072	NO
71	MAX	MAX	MAX	14514	-0.036	0.076	NO
72	ITGB5	ITGB5	ITGB5	15052	-0.045	0.055	NO
73	CDKN1A	CDKN1A	CDKN1A	15081	-0.046	0.062	NO
74	AKT1	AKT1	AKT1	15415	-0.053	0.054	NO
75	FOXO1	FOXO1	FOXO1	15824	-0.064	0.045	NO
76	ATF3	ATF3	ATF3	16116	-0.074	0.043	NO
77	FOS	FOS	FOS	16505	-0.09	0.039	NO
78	SMAD3	SMAD3	SMAD3	16632	-0.095	0.05	NO
79	CDKN2B	CDKN2B	CDKN2B	16792	-0.1	0.062	NO
80	MYC	MYC	MYC	17464	-0.16	0.056	NO

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

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

genes ES table in pathway: BIOCARTA MPR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ESRRB	ESRRB	ESRRB	122	0.37	0.0059	YES
2	E2F5	E2F5	E2F5	195	0.34	0.014	YES
3	ZNF439	ZNF439	ZNF439	243	0.33	0.022	YES
4	ZNF620	ZNF620	ZNF620	263	0.32	0.032	YES
5	ZNF167	ZNF167	ZNF167	342	0.31	0.038	YES
6	ZNF415	ZNF415	ZNF415	345	0.31	0.048	YES
7	NR5A1	NR5A1	NR5A1	515	0.28	0.048	YES
8	ZNF347	ZNF347	ZNF347	567	0.27	0.054	YES
9	ZNF334	ZNF334	ZNF334	606	0.26	0.061	YES
10	ZNF643	ZNF643	ZNF643	607	0.26	0.07	YES
11	ZNF610	ZNF610	ZNF610	612	0.26	0.079	YES
12	ZNF577	ZNF577	ZNF577	671	0.26	0.084	YES
13	ZNF43	ZNF43	ZNF43	676	0.26	0.093	YES
14	ZNF214	ZNF214	ZNF214	776	0.25	0.096	YES
15	NR1I2	NR1I2	NR1I2	819	0.24	0.1	YES
16	ZNF382	ZNF382	ZNF382	824	0.24	0.11	YES
17	ZNF221	ZNF221	ZNF221	850	0.24	0.12	YES
18	RUNX2	RUNX2	RUNX2	897	0.24	0.12	YES
19	ZNF157	ZNF157	ZNF157	951	0.23	0.13	YES
20	ZNF254	ZNF254	ZNF254	954	0.23	0.13	YES
21	ZNF418	ZNF418	ZNF418	963	0.23	0.14	YES
22	ZNF454	ZNF454	ZNF454	1090	0.22	0.14	YES
23	ZNF625	ZNF625	ZNF625	1121	0.22	0.15	YES
24	ZNF540	ZNF540	ZNF540	1155	0.22	0.15	YES
25	ZFP28	ZFP28	ZFP28	1248	0.21	0.16	YES
26	ZNF320	ZNF320	ZNF320	1284	0.21	0.16	YES
27	ZNF285	ZNF285	ZNF285	1339	0.2	0.16	YES
28	TBX5	TBX5	TBX5	1356	0.2	0.17	YES
29	ZNF583	ZNF583	ZNF583	1380	0.2	0.18	YES
30	ZNF519	ZNF519	ZNF519	1455	0.2	0.18	YES
31	ZNF10	ZNF10	ZNF10	1483	0.2	0.18	YES
32	ZNF471	ZNF471	ZNF471	1496	0.19	0.19	YES
33	ZNF649	ZNF649	ZNF649	1497	0.19	0.2	YES
34	ZNF154	ZNF154	ZNF154	1586	0.19	0.2	YES
35	ZNF98	ZNF98	ZNF98	1593	0.19	0.2	YES
36	ZNF560	ZNF560	ZNF560	1595	0.19	0.21	YES
37	ZFP2	ZFP2	ZFP2	1599	0.19	0.22	YES
38	ZNF607	ZNF607	ZNF607	1652	0.19	0.22	YES
39	ZNF569	ZNF569	ZNF569	1700	0.18	0.22	YES
40	ZNF492	ZNF492	ZNF492	1717	0.18	0.23	YES
41	ZNF432	ZNF432	ZNF432	1829	0.18	0.23	YES
42	ZNF611	ZNF611	ZNF611	2041	0.17	0.22	YES
43	ZNF606	ZNF606	ZNF606	2062	0.17	0.23	YES
44	ZNF354C	ZNF354C	ZNF354C	2091	0.17	0.23	YES
45	ZNF596	ZNF596	ZNF596	2097	0.16	0.24	YES
46	ZNF571	ZNF571	ZNF571	2179	0.16	0.24	YES
47	ZIK1	ZIK1	ZIK1	2242	0.16	0.24	YES
48	ZNF222	ZNF222	ZNF222	2255	0.16	0.24	YES
49	NPPA	NPPA	NPPA	2330	0.15	0.24	YES
50	ZNF613	ZNF613	ZNF613	2341	0.15	0.25	YES
51	SMAD7	SMAD7	SMAD7	2365	0.15	0.25	YES
52	ZNF331	ZNF331	ZNF331	2403	0.15	0.26	YES
53	ZKSCAN3	ZKSCAN3	ZKSCAN3	2442	0.15	0.26	YES
54	ESR1	ESR1	ESR1	2473	0.15	0.26	YES
55	ZNF547	ZNF547	ZNF547	2495	0.15	0.27	YES
56	NR2E1	NR2E1	NR2E1	2524	0.15	0.27	YES
57	ZNF493	ZNF493	ZNF493	2540	0.15	0.27	YES
58	ZNF100	ZNF100	ZNF100	2546	0.15	0.28	YES
59	ZNF615	ZNF615	ZNF615	2590	0.14	0.28	YES
60	ZNF250	ZNF250	ZNF250	2649	0.14	0.28	YES
61	ZNF141	ZNF141	ZNF141	2675	0.14	0.29	YES
62	ZNF420	ZNF420	ZNF420	2714	0.14	0.29	YES
63	TGIF2	TGIF2	TGIF2	2720	0.14	0.29	YES
64	ZNF773	ZNF773	ZNF773	2757	0.14	0.3	YES
65	ZNF585B	ZNF585B	ZNF585B	2764	0.14	0.3	YES
66	TEAD2	TEAD2	TEAD2	2817	0.14	0.3	YES
67	ZNF595	ZNF595	ZNF595	2836	0.14	0.3	YES
68	ZNF215	ZNF215	ZNF215	2898	0.13	0.31	YES
69	ZNF530	ZNF530	ZNF530	2921	0.13	0.31	YES
70	ZNF230	ZNF230	ZNF230	3002	0.13	0.31	YES
71	ZNF223	ZNF223	ZNF223	3050	0.13	0.31	YES
72	ZNF235	ZNF235	ZNF235	3059	0.13	0.32	YES
73	ZNF614	ZNF614	ZNF614	3064	0.13	0.32	YES
74	NR3C2	NR3C2	NR3C2	3094	0.13	0.32	YES
75	ZNF605	ZNF605	ZNF605	3105	0.13	0.33	YES
76	ZNF570	ZNF570	ZNF570	3108	0.13	0.33	YES
77	ZNF192	ZNF192	ZNF192	3158	0.12	0.33	YES
78	ZNF528	ZNF528	ZNF528	3172	0.12	0.34	YES
79	ZNF300	ZNF300	ZNF300	3193	0.12	0.34	YES
80	ZNF529	ZNF529	ZNF529	3200	0.12	0.34	YES
81	ZNF208	ZNF208	ZNF208	3207	0.12	0.34	YES
82	NR2E3	NR2E3	NR2E3	3312	0.12	0.34	YES
83	ZNF350	ZNF350	ZNF350	3335	0.12	0.35	YES
84	ZNF234	ZNF234	ZNF234	3368	0.12	0.35	YES
85	ZNF582	ZNF582	ZNF582	3399	0.12	0.35	YES
86	ZNF184	ZNF184	ZNF184	3408	0.12	0.35	YES
87	ZFP112	ZFP112	ZFP112	3428	0.12	0.36	YES
88	ZNF433	ZNF433	ZNF433	3446	0.12	0.36	YES
89	ZNF225	ZNF225	ZNF225	3484	0.11	0.36	YES
90	ZNF28	ZNF28	ZNF28	3555	0.11	0.36	YES
91	ZNF548	ZNF548	ZNF548	3583	0.11	0.36	YES
92	ZNF517	ZNF517	ZNF517	3630	0.11	0.36	YES
93	ZNF708	ZNF708	ZNF708	3643	0.11	0.37	YES
94	ZNF485	ZNF485	ZNF485	3689	0.11	0.37	YES
95	RORB	RORB	RORB	3755	0.11	0.37	YES
96	ZNF419	ZNF419	ZNF419	3779	0.11	0.37	YES
97	ZNF180	ZNF180	ZNF180	3780	0.11	0.38	YES
98	ZNF585A	ZNF585A	ZNF585A	3804	0.11	0.38	YES
99	ZNF354B	ZNF354B	ZNF354B	3814	0.1	0.38	YES
100	ZNF354A	ZNF354A	ZNF354A	3842	0.1	0.38	YES
101	PRIC285	PRIC285	PRIC285	3862	0.1	0.38	YES
102	ZNF599	ZNF599	ZNF599	3891	0.1	0.39	YES
103	ZNF211	ZNF211	ZNF211	3913	0.1	0.39	YES
104	ZNF33A	ZNF33A	ZNF33A	3919	0.1	0.39	YES
105	ZNF155	ZNF155	ZNF155	3938	0.1	0.4	YES
106	ZNF304	ZNF304	ZNF304	3964	0.1	0.4	YES
107	ZNF256	ZNF256	ZNF256	3974	0.1	0.4	YES
108	ZNF473	ZNF473	ZNF473	4024	0.1	0.4	YES
109	ZNF417	ZNF417	ZNF417	4045	0.1	0.4	YES
110	ZKSCAN4	ZKSCAN4	ZKSCAN4	4156	0.097	0.4	YES
111	ZNF496	ZNF496	ZNF496	4167	0.096	0.4	YES
112	ZNF226	ZNF226	ZNF226	4172	0.096	0.41	YES
113	ZNF45	ZNF45	ZNF45	4229	0.095	0.41	YES
114	ESRRG	ESRRG	ESRRG	4278	0.094	0.41	YES
115	ZNF587	ZNF587	ZNF587	4296	0.093	0.41	YES
116	ZNF286A	ZNF286A	ZNF286A	4304	0.093	0.41	YES
117	ZNF642	ZNF642	ZNF642	4313	0.093	0.41	YES
118	AR	AR	AR	4345	0.092	0.42	YES
119	ZNF468	ZNF468	ZNF468	4358	0.092	0.42	YES
120	SKI	SKI	SKI	4378	0.091	0.42	YES
121	ZNF224	ZNF224	ZNF224	4383	0.091	0.42	YES
122	ZNF227	ZNF227	ZNF227	4421	0.09	0.42	YES
123	ZNF26	ZNF26	ZNF26	4557	0.087	0.42	YES
124	RBPJ	RBPJ	RBPJ	4608	0.085	0.42	YES
125	ZNF30	ZNF30	ZNF30	4615	0.085	0.42	YES
126	CTGF	CTGF	CTGF	4620	0.085	0.42	YES
127	HNF4A	HNF4A	HNF4A	4621	0.085	0.43	YES
128	ZNF274	ZNF274	ZNF274	4630	0.084	0.43	YES
129	ZNF248	ZNF248	ZNF248	4635	0.084	0.43	YES
130	ZNF566	ZNF566	ZNF566	4642	0.084	0.44	YES
131	ZNF33B	ZNF33B	ZNF33B	4645	0.084	0.44	YES
132	ZNF544	ZNF544	ZNF544	4651	0.084	0.44	YES
133	ZNF17	ZNF17	ZNF17	4667	0.084	0.44	YES
134	NOTCH4	NOTCH4	NOTCH4	4731	0.082	0.44	YES
135	ZNF311	ZNF311	ZNF311	4738	0.082	0.44	YES
136	MED25	MED25	MED25	4788	0.081	0.44	YES
137	ZNF446	ZNF446	ZNF446	4822	0.08	0.44	YES
138	ZNF175	ZNF175	ZNF175	4825	0.08	0.45	YES
139	ZNF140	ZNF140	ZNF140	4879	0.079	0.45	YES
140	ZNF546	ZNF546	ZNF546	4891	0.079	0.45	YES
141	ZNF616	ZNF616	ZNF616	4915	0.079	0.45	YES
142	ZNF160	ZNF160	ZNF160	4923	0.078	0.45	YES
143	MED12	MED12	MED12	4969	0.077	0.45	YES
144	ZNF567	ZNF567	ZNF567	4994	0.077	0.46	YES
145	PGR	PGR	PGR	4995	0.077	0.46	YES
146	RARA	RARA	RARA	5026	0.076	0.46	YES
147	ZNF600	ZNF600	ZNF600	5069	0.075	0.46	YES
148	ZNF627	ZNF627	ZNF627	5101	0.075	0.46	YES
149	ZNF287	ZNF287	ZNF287	5132	0.074	0.46	YES
150	RXRB	RXRB	RXRB	5148	0.074	0.46	YES
151	ZNF426	ZNF426	ZNF426	5263	0.072	0.46	NO
152	ZNF514	ZNF514	ZNF514	5405	0.069	0.45	NO
153	ZNF555	ZNF555	ZNF555	5470	0.068	0.45	NO
154	ZNF2	ZNF2	ZNF2	5495	0.067	0.45	NO
155	MAML2	MAML2	MAML2	5560	0.066	0.45	NO
156	ZNF445	ZNF445	ZNF445	5573	0.066	0.45	NO
157	MED23	MED23	MED23	5605	0.065	0.45	NO
158	NCOR2	NCOR2	NCOR2	5638	0.064	0.45	NO
159	ZNF264	ZNF264	ZNF264	5701	0.063	0.45	NO
160	ZNF14	ZNF14	ZNF14	5733	0.063	0.45	NO
161	ZNF333	ZNF333	ZNF333	5802	0.062	0.45	NO
162	ZNF197	ZNF197	ZNF197	5857	0.061	0.45	NO
163	ZNF205	ZNF205	ZNF205	5956	0.059	0.45	NO
164	ZNF383	ZNF383	ZNF383	6024	0.058	0.44	NO
165	ZNF92	ZNF92	ZNF92	6051	0.058	0.44	NO
166	NCOA2	NCOA2	NCOA2	6055	0.057	0.45	NO
167	ZNF543	ZNF543	ZNF543	6121	0.056	0.44	NO
168	ZNF25	ZNF25	ZNF25	6152	0.056	0.44	NO
169	NR0B2	NR0B2	NR0B2	6379	0.052	0.44	NO
170	ZNF559	ZNF559	ZNF559	6396	0.052	0.44	NO
171	SKIL	SKIL	SKIL	6413	0.052	0.44	NO
172	ZNF138	ZNF138	ZNF138	6428	0.052	0.44	NO
173	TEAD1	TEAD1	TEAD1	6466	0.051	0.44	NO
174	ZFP1	ZFP1	ZFP1	6488	0.051	0.44	NO
175	ZFP37	ZFP37	ZFP37	6530	0.05	0.44	NO
176	ZNF558	ZNF558	ZNF558	6598	0.05	0.44	NO
177	TRIM28	TRIM28	TRIM28	6671	0.049	0.43	NO
178	HNF4G	HNF4G	HNF4G	6735	0.048	0.43	NO
179	ZNF483	ZNF483	ZNF483	6756	0.048	0.43	NO
180	ZNF37A	ZNF37A	ZNF37A	6790	0.048	0.43	NO
181	ZNF460	ZNF460	ZNF460	6885	0.046	0.43	NO
182	NOTCH2	NOTCH2	NOTCH2	6944	0.045	0.43	NO
183	ZNF480	ZNF480	ZNF480	6952	0.045	0.43	NO
184	ZNF506	ZNF506	ZNF506	6955	0.045	0.43	NO
185	ZNF416	ZNF416	ZNF416	6983	0.045	0.43	NO
186	NR1H3	NR1H3	NR1H3	7057	0.044	0.43	NO
187	ZNF641	ZNF641	ZNF641	7063	0.044	0.43	NO
188	PARP1	PARP1	PARP1	7069	0.044	0.43	NO
189	MED17	MED17	MED17	7091	0.043	0.43	NO
190	ZNF23	ZNF23	ZNF23	7145	0.043	0.43	NO
191	RORC	RORC	RORC	7240	0.042	0.42	NO
192	ZNF20	ZNF20	ZNF20	7245	0.042	0.42	NO
193	ZNF551	ZNF551	ZNF551	7319	0.041	0.42	NO
194	ZNF19	ZNF19	ZNF19	7321	0.041	0.42	NO
195	UBE2D1	UBE2D1	UBE2D1	7351	0.04	0.42	NO
196	ZNF266	ZNF266	ZNF266	7359	0.04	0.42	NO
197	MEN1	MEN1	MEN1	7401	0.04	0.42	NO
198	NR4A3	NR4A3	NR4A3	7549	0.038	0.42	NO
199	MED14	MED14	MED14	7574	0.038	0.42	NO
200	MED24	MED24	MED24	7695	0.036	0.41	NO
201	ZNF441	ZNF441	ZNF441	7784	0.036	0.41	NO
202	ZNF563	ZNF563	ZNF563	7796	0.035	0.41	NO
203	NR1I3	NR1I3	NR1I3	7910	0.034	0.4	NO
204	ZNF136	ZNF136	ZNF136	8012	0.033	0.4	NO
205	ZNF3	ZNF3	ZNF3	8037	0.033	0.4	NO
206	ZNF443	ZNF443	ZNF443	8072	0.033	0.4	NO
207	USP9X	USP9X	USP9X	8094	0.032	0.4	NO
208	ZNF621	ZNF621	ZNF621	8107	0.032	0.4	NO
209	ZNF500	ZNF500	ZNF500	8195	0.031	0.39	NO
210	MED8	MED8	MED8	8205	0.031	0.4	NO
211	TEAD4	TEAD4	TEAD4	8208	0.031	0.4	NO
212	MAMLD1	MAMLD1	MAMLD1	8264	0.03	0.39	NO
213	ZFP90	ZFP90	ZFP90	8394	0.029	0.39	NO
214	NR4A1	NR4A1	NR4A1	8476	0.028	0.38	NO
215	MAML1	MAML1	MAML1	8556	0.027	0.38	NO
216	NCOA6	NCOA6	NCOA6	8583	0.027	0.38	NO
217	TEAD3	TEAD3	TEAD3	8625	0.027	0.38	NO
218	ZNF510	ZNF510	ZNF510	8660	0.026	0.38	NO
219	SMARCD3	SMARCD3	SMARCD3	8793	0.025	0.37	NO
220	MED16	MED16	MED16	8858	0.024	0.37	NO
221	THRA	THRA	THRA	8919	0.024	0.37	NO
222	VDR	VDR	VDR	8954	0.024	0.36	NO
223	MED7	MED7	MED7	9032	0.023	0.36	NO
224	NCOA1	NCOA1	NCOA1	9109	0.022	0.36	NO
225	NR5A2	NR5A2	NR5A2	9124	0.022	0.36	NO
226	ZNF169	ZNF169	ZNF169	9155	0.022	0.36	NO
227	ZNF584	ZNF584	ZNF584	9249	0.021	0.35	NO
228	TRIM33	TRIM33	TRIM33	9355	0.02	0.35	NO
229	ZNF337	ZNF337	ZNF337	9505	0.018	0.34	NO
230	ZKSCAN5	ZKSCAN5	ZKSCAN5	9526	0.018	0.34	NO
231	ZNF213	ZNF213	ZNF213	9554	0.018	0.34	NO
232	MED10	MED10	MED10	9621	0.017	0.34	NO
233	ZNF324	ZNF324	ZNF324	9868	0.015	0.32	NO
234	ESR2	ESR2	ESR2	9878	0.015	0.32	NO
235	SMAD4	SMAD4	SMAD4	10025	0.014	0.32	NO
236	ZNF624	ZNF624	ZNF624	10056	0.013	0.31	NO
237	NCOR1	NCOR1	NCOR1	10065	0.013	0.31	NO
238	SERPINE1	SERPINE1	SERPINE1	10177	0.012	0.31	NO
239	KAT2B	KAT2B	KAT2B	10228	0.012	0.3	NO
240	TGS1	TGS1	TGS1	10279	0.011	0.3	NO
241	MED20	MED20	MED20	10280	0.011	0.3	NO
242	ZNF212	ZNF212	ZNF212	10398	0.0099	0.3	NO
243	SMURF2	SMURF2	SMURF2	10404	0.0099	0.3	NO
244	ZNF101	ZNF101	ZNF101	10444	0.0096	0.3	NO
245	MED15	MED15	MED15	10480	0.0092	0.29	NO
246	ZNF490	ZNF490	ZNF490	10490	0.0091	0.29	NO
247	ZNF619	ZNF619	ZNF619	10563	0.0084	0.29	NO
248	ZKSCAN1	ZKSCAN1	ZKSCAN1	10617	0.008	0.29	NO
249	ZNF552	ZNF552	ZNF552	10644	0.0078	0.29	NO
250	MED30	MED30	MED30	10649	0.0078	0.29	NO
251	ZNF498	ZNF498	ZNF498	10652	0.0078	0.29	NO
252	RBL1	RBL1	RBL1	10701	0.0073	0.28	NO
253	UBE2D3	UBE2D3	UBE2D3	10800	0.0064	0.28	NO
254	ZNF202	ZNF202	ZNF202	10826	0.0062	0.28	NO
255	ZNF12	ZNF12	ZNF12	10894	0.0055	0.27	NO
256	CCNC	CCNC	CCNC	10941	0.0051	0.27	NO
257	CDK8	CDK8	CDK8	11041	0.0043	0.27	NO
258	ZNF431	ZNF431	ZNF431	11288	0.002	0.25	NO
259	ZNF565	ZNF565	ZNF565	11314	0.0018	0.25	NO
260	KAT2A	KAT2A	KAT2A	11490	-0.00016	0.24	NO
261	RPS27A	RPS27A	RPS27A	11491	-0.00016	0.24	NO
262	RXRG	RXRG	RXRG	11520	-0.00043	0.24	NO
263	ZNF200	ZNF200	ZNF200	11687	-0.0021	0.23	NO
264	CCNT2	CCNT2	CCNT2	11810	-0.0031	0.22	NO
265	ZNF267	ZNF267	ZNF267	11849	-0.0035	0.22	NO
266	CREBBP	CREBBP	CREBBP	11869	-0.0038	0.22	NO
267	MED4	MED4	MED4	12057	-0.0056	0.21	NO
268	NR2F6	NR2F6	NR2F6	12075	-0.0057	0.21	NO
269	HDAC1	HDAC1	HDAC1	12097	-0.0059	0.21	NO
270	SP1	SP1	SP1	12165	-0.0066	0.21	NO
271	ZNF564	ZNF564	ZNF564	12255	-0.0076	0.2	NO
272	MED26	MED26	MED26	12339	-0.0085	0.2	NO
273	MED1	MED1	MED1	12399	-0.0092	0.2	NO
274	ZNF436	ZNF436	ZNF436	12405	-0.0092	0.2	NO
275	TFDP1	TFDP1	TFDP1	12460	-0.01	0.19	NO
276	ZNF655	ZNF655	ZNF655	12497	-0.01	0.19	NO
277	ZNF434	ZNF434	ZNF434	12501	-0.01	0.19	NO
278	NRBF2	NRBF2	NRBF2	12591	-0.011	0.19	NO
279	YAP1	YAP1	YAP1	12676	-0.012	0.18	NO
280	ZNF263	ZNF263	ZNF263	12685	-0.012	0.18	NO
281	SNW1	SNW1	SNW1	12808	-0.014	0.18	NO
282	ZNF317	ZNF317	ZNF317	12916	-0.015	0.17	NO
283	NR2F1	NR2F1	NR2F1	12945	-0.015	0.17	NO
284	PPM1A	PPM1A	PPM1A	12990	-0.016	0.17	NO
285	NR1H2	NR1H2	NR1H2	13012	-0.016	0.17	NO
286	ZNF343	ZNF343	ZNF343	13016	-0.016	0.17	NO
287	ZNF282	ZNF282	ZNF282	13033	-0.016	0.17	NO
288	CDK9	CDK9	CDK9	13063	-0.016	0.17	NO
289	ZNF273	ZNF273	ZNF273	13184	-0.018	0.16	NO
290	MED27	MED27	MED27	13239	-0.018	0.16	NO
291	UBA52	UBA52	UBA52	13251	-0.019	0.16	NO
292	MED6	MED6	MED6	13277	-0.019	0.16	NO
293	ZNF561	ZNF561	ZNF561	13398	-0.021	0.15	NO
294	MED31	MED31	MED31	13403	-0.021	0.15	NO
295	ZNF484	ZNF484	ZNF484	13498	-0.022	0.15	NO
296	NRBP1	NRBP1	NRBP1	13502	-0.022	0.15	NO
297	ZNF440	ZNF440	ZNF440	13702	-0.024	0.14	NO
298	PPARD	PPARD	PPARD	13845	-0.026	0.13	NO
299	ZNF394	ZNF394	ZNF394	13860	-0.026	0.13	NO
300	E2F4	E2F4	E2F4	13982	-0.028	0.12	NO
301	SMAD2	SMAD2	SMAD2	14118	-0.03	0.12	NO
302	ZNF556	ZNF556	ZNF556	14213	-0.032	0.11	NO
303	ZNF597	ZNF597	ZNF597	14245	-0.032	0.11	NO
304	NR3C1	NR3C1	NR3C1	14386	-0.034	0.11	NO
305	TGIF1	TGIF1	TGIF1	14457	-0.035	0.1	NO
306	ZNF189	ZNF189	ZNF189	14548	-0.036	0.1	NO
307	NR2C2AP	NR2C2AP	NR2C2AP	14585	-0.037	0.1	NO
308	CCNT1	CCNT1	CCNT1	14612	-0.037	0.1	NO
309	ZNF557	ZNF557	ZNF557	14806	-0.041	0.09	NO
310	NR1D2	NR1D2	NR1D2	15044	-0.045	0.079	NO
311	ESRRA	ESRRA	ESRRA	15228	-0.048	0.07	NO
312	NCOA3	NCOA3	NCOA3	15293	-0.05	0.069	NO
313	JUNB	JUNB	JUNB	15501	-0.055	0.059	NO
314	ZNF398	ZNF398	ZNF398	15589	-0.057	0.056	NO
315	ZNF18	ZNF18	ZNF18	15686	-0.06	0.053	NO
316	ZNF589	ZNF589	ZNF589	15837	-0.064	0.047	NO
317	MAML3	MAML3	MAML3	15890	-0.066	0.046	NO
318	ZNF425	ZNF425	ZNF425	15915	-0.067	0.047	NO
319	NR4A2	NR4A2	NR4A2	15926	-0.067	0.049	NO
320	RXRA	RXRA	RXRA	15990	-0.07	0.048	NO
321	ZNF114	ZNF114	ZNF114	16177	-0.076	0.04	NO
322	ZNF430	ZNF430	ZNF430	16245	-0.079	0.039	NO
323	RARG	RARG	RARG	16508	-0.09	0.028	NO
324	ZNF442	ZNF442	ZNF442	16571	-0.093	0.027	NO
325	PPARA	PPARA	PPARA	16628	-0.095	0.028	NO
326	SMAD3	SMAD3	SMAD3	16632	-0.095	0.031	NO
327	TBL1XR1	TBL1XR1	TBL1XR1	16749	-0.1	0.028	NO
328	CDKN2B	CDKN2B	CDKN2B	16792	-0.1	0.029	NO
329	WWTR1	WWTR1	WWTR1	16820	-0.11	0.031	NO
330	NR1D1	NR1D1	NR1D1	16885	-0.11	0.031	NO
331	ZNF658	ZNF658	ZNF658	17068	-0.12	0.025	NO
332	NR6A1	NR6A1	NR6A1	17155	-0.13	0.025	NO
333	NOTCH3	NOTCH3	NOTCH3	17211	-0.13	0.026	NO
334	RORA	RORA	RORA	17284	-0.14	0.027	NO
335	MYC	MYC	MYC	17464	-0.16	0.023	NO
336	TBL1X	TBL1X	TBL1X	17477	-0.16	0.028	NO
337	NR0B1	NR0B1	NR0B1	18000	-0.25	0.007	NO
338	THRB	THRB	THRB	18069	-0.27	0.012	NO
339	PPARG	PPARG	PPARG	18247	-0.33	0.014	NO

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

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

genes ES table in pathway: BIOCARTA DEATH 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	BMF	BMF	BMF	829	0.24	0.11	YES
2	BCL2	BCL2	BCL2	2164	0.16	0.15	YES
3	GZMB	GZMB	GZMB	3218	0.12	0.17	YES
4	BBC3	BBC3	BBC3	3332	0.12	0.24	YES
5	MAPK8	MAPK8	MAPK8	3613	0.11	0.3	YES
6	APAF1	APAF1	APAF1	4301	0.093	0.32	YES
7	E2F1	E2F1	E2F1	4403	0.09	0.38	YES
8	CASP9	CASP9	CASP9	5351	0.07	0.37	YES
9	BCL2L11	BCL2L11	BCL2L11	5994	0.059	0.38	YES
10	PMAIP1	PMAIP1	PMAIP1	6129	0.056	0.4	YES
11	DIABLO	DIABLO	DIABLO	8358	0.03	0.3	NO
12	TP53	TP53	TP53	8987	0.023	0.28	NO
13	BAX	BAX	BAX	9706	0.016	0.26	NO
14	BAD	BAD	BAD	9960	0.014	0.25	NO
15	BAK1	BAK1	BAK1	10463	0.0094	0.23	NO
16	BCL2L1	BCL2L1	BCL2L1	10492	0.0091	0.24	NO
17	YWHAB	YWHAB	YWHAB	10738	0.0069	0.23	NO
18	PPP3R1	PPP3R1	PPP3R1	11355	0.0012	0.19	NO
19	DYNLL1	DYNLL1	DYNLL1	12335	-0.0085	0.15	NO
20	TFDP1	TFDP1	TFDP1	12460	-0.01	0.15	NO
21	CASP7	CASP7	CASP7	12561	-0.011	0.15	NO
22	CASP3	CASP3	CASP3	12942	-0.015	0.14	NO
23	NMT1	NMT1	NMT1	13129	-0.017	0.14	NO
24	DYNLL2	DYNLL2	DYNLL2	13686	-0.024	0.12	NO
25	CASP8	CASP8	CASP8	13815	-0.026	0.14	NO
26	XIAP	XIAP	XIAP	14200	-0.031	0.14	NO
27	BID	BID	BID	15163	-0.047	0.11	NO
28	CYCS	CYCS	CYCS	15292	-0.05	0.14	NO
29	AKT1	AKT1	AKT1	15415	-0.053	0.17	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 DEATH PATHWAY.

Figure S46. 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: PID SMAD2 3NUCLEARPATHWAY

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	GATA3	GATA3	GATA3	38	0.43	0.05	YES
2	KIF5A	KIF5A	KIF5A	295	0.32	0.074	YES
3	IFNB1	IFNB1	IFNB1	536	0.28	0.094	YES
4	HIST1H3I	HIST1H3I	HIST1H3I	650	0.26	0.12	YES
5	ZFPM2	ZFPM2	ZFPM2	848	0.24	0.14	YES
6	CABLES1	CABLES1	CABLES1	1172	0.22	0.14	YES
7	SH2B2	SH2B2	SH2B2	1196	0.21	0.17	YES
8	GATA5	GATA5	GATA5	1614	0.19	0.17	YES
9	KIF26A	KIF26A	KIF26A	1679	0.18	0.19	YES
10	HIST1H3J	HIST1H3J	HIST1H3J	2219	0.16	0.18	YES
11	GATA6	GATA6	GATA6	2222	0.16	0.2	YES
12	HIST1H3C	HIST1H3C	HIST1H3C	2350	0.15	0.21	YES
13	IRF7	IRF7	IRF7	2382	0.15	0.22	YES
14	KIF3C	KIF3C	KIF3C	2747	0.14	0.22	YES
15	HIST1H3A	HIST1H3A	HIST1H3A	2842	0.14	0.23	YES
16	PRKAR2B	PRKAR2B	PRKAR2B	3061	0.13	0.24	YES
17	KIF9	KIF9	KIF9	3271	0.12	0.24	YES
18	DOCK10	DOCK10	DOCK10	3341	0.12	0.25	YES
19	KIF4B	KIF4B	KIF4B	3397	0.12	0.26	YES
20	KIF2C	KIF2C	KIF2C	3422	0.12	0.27	YES
21	HIST1H3B	HIST1H3B	HIST1H3B	3758	0.11	0.27	YES
22	SH2B3	SH2B3	SH2B3	3763	0.11	0.28	YES
23	MYB	MYB	MYB	3846	0.1	0.29	YES
24	PRKAR1B	PRKAR1B	PRKAR1B	3895	0.1	0.3	YES
25	HIST2H3D	HIST2H3D	HIST2H3D	4000	0.1	0.3	YES
26	KIFAP3	KIFAP3	KIFAP3	4114	0.098	0.31	YES
27	HIST1H3F	HIST1H3F	HIST1H3F	4305	0.093	0.31	YES
28	JMJD1C	JMJD1C	JMJD1C	4428	0.09	0.32	YES
29	HBD	HBD	HBD	4536	0.087	0.32	YES
30	CABLES2	CABLES2	CABLES2	4627	0.084	0.32	YES
31	KIFC1	KIFC1	KIFC1	4748	0.082	0.33	YES
32	KLC4	KLC4	KLC4	4845	0.08	0.33	YES
33	IRF3	IRF3	IRF3	4955	0.078	0.34	YES
34	CBX5	CBX5	CBX5	5009	0.077	0.34	YES
35	KDM1A	KDM1A	KDM1A	5109	0.074	0.34	YES
36	DOCK1	DOCK1	DOCK1	5140	0.074	0.35	YES
37	EHD1	EHD1	EHD1	5297	0.071	0.35	YES
38	DOCK3	DOCK3	DOCK3	5299	0.071	0.36	YES
39	KIF2A	KIF2A	KIF2A	5382	0.069	0.36	YES
40	GATA4	GATA4	GATA4	5460	0.068	0.37	YES
41	KIF18A	KIF18A	KIF18A	5528	0.067	0.37	YES
42	DOCK2	DOCK2	DOCK2	5743	0.063	0.37	YES
43	DOCK8	DOCK8	DOCK8	5749	0.063	0.38	YES
44	KIF20A	KIF20A	KIF20A	5781	0.062	0.38	YES
45	NFE2	NFE2	NFE2	5836	0.061	0.39	YES
46	HIST1H3H	HIST1H3H	HIST1H3H	5899	0.06	0.39	YES
47	CDK2	CDK2	CDK2	6020	0.058	0.39	YES
48	HDAC2	HDAC2	HDAC2	6069	0.057	0.4	YES
49	KIF15	KIF15	KIF15	6131	0.056	0.4	YES
50	HIST1H3G	HIST1H3G	HIST1H3G	6587	0.05	0.38	NO
51	IRF1	IRF1	IRF1	6591	0.05	0.38	NO
52	PRKACB	PRKACB	PRKACB	6716	0.048	0.38	NO
53	GATA2	GATA2	GATA2	6729	0.048	0.39	NO
54	HBE1	HBE1	HBE1	6826	0.047	0.39	NO
55	DOCK4	DOCK4	DOCK4	6917	0.046	0.39	NO
56	VPS45	VPS45	VPS45	6986	0.045	0.39	NO
57	HIST2H3C	HIST2H3C	HIST2H3C	7043	0.044	0.39	NO
58	HBG2	HBG2	HBG2	7243	0.042	0.39	NO
59	KIF3B	KIF3B	KIF3B	7262	0.041	0.39	NO
60	KIF22	KIF22	KIF22	7281	0.041	0.4	NO
61	SH2B1	SH2B1	SH2B1	7509	0.038	0.39	NO
62	KIF4A	KIF4A	KIF4A	7647	0.037	0.39	NO
63	JAK2	JAK2	JAK2	7915	0.034	0.38	NO
64	H3F3A	H3F3A	H3F3A	7930	0.034	0.38	NO
65	RAD51C	RAD51C	RAD51C	8190	0.031	0.37	NO
66	KIF23	KIF23	KIF23	8238	0.031	0.37	NO
67	ZFPM1	ZFPM1	ZFPM1	8320	0.03	0.37	NO
68	ABL1	ABL1	ABL1	8640	0.026	0.35	NO
69	HIST1H3D	HIST1H3D	HIST1H3D	8719	0.026	0.35	NO
70	TP53	TP53	TP53	8987	0.023	0.34	NO
71	KIF11	KIF11	KIF11	9115	0.022	0.34	NO
72	HBB	HBB	HBB	9180	0.021	0.34	NO
73	H3F3B	H3F3B	H3F3B	9198	0.021	0.34	NO
74	PRKAR1A	PRKAR1A	PRKAR1A	9275	0.02	0.34	NO
75	ZFYVE20	ZFYVE20	ZFYVE20	9824	0.015	0.31	NO
76	RACGAP1	RACGAP1	RACGAP1	9891	0.015	0.31	NO
77	HMG20B	HMG20B	HMG20B	9893	0.015	0.31	NO
78	CDC42	CDC42	CDC42	10253	0.011	0.29	NO
79	KIF5B	KIF5B	KIF5B	10357	0.01	0.28	NO
80	SIN3A	SIN3A	SIN3A	10834	0.0061	0.26	NO
81	DOCK5	DOCK5	DOCK5	11695	-0.0021	0.21	NO
82	CREBBP	CREBBP	CREBBP	11869	-0.0038	0.2	NO
83	IRF2	IRF2	IRF2	12069	-0.0057	0.2	NO
84	WEE1	WEE1	WEE1	12096	-0.0059	0.19	NO
85	HDAC1	HDAC1	HDAC1	12097	-0.0059	0.2	NO
86	EP300	EP300	EP300	12351	-0.0086	0.18	NO
87	MFN2	MFN2	MFN2	12627	-0.012	0.17	NO
88	PRKACA	PRKACA	PRKACA	12628	-0.012	0.17	NO
89	KLC2	KLC2	KLC2	12807	-0.014	0.16	NO
90	RAB5A	RAB5A	RAB5A	13122	-0.017	0.15	NO
91	CAPZA1	CAPZA1	CAPZA1	13305	-0.02	0.14	NO
92	KLC1	KLC1	KLC1	13575	-0.023	0.13	NO
93	RAC1	RAC1	RAC1	13655	-0.024	0.13	NO
94	AKAP10	AKAP10	AKAP10	13734	-0.025	0.12	NO
95	AK3	AK3	AK3	13850	-0.026	0.12	NO
96	CDK5	CDK5	CDK5	13904	-0.027	0.12	NO
97	EHD2	EHD2	EHD2	13942	-0.028	0.12	NO
98	AKAP1	AKAP1	AKAP1	13996	-0.028	0.12	NO
99	MAFK	MAFK	MAFK	14677	-0.038	0.091	NO
100	CAPZA2	CAPZA2	CAPZA2	14699	-0.039	0.095	NO
101	ITPK1	ITPK1	ITPK1	15068	-0.045	0.08	NO
102	DOCK6	DOCK6	DOCK6	15075	-0.046	0.085	NO
103	GATA1	GATA1	GATA1	15663	-0.059	0.06	NO
104	MFN1	MFN1	MFN1	15872	-0.066	0.057	NO
105	DOCK9	DOCK9	DOCK9	15891	-0.066	0.064	NO
106	MAFF	MAFF	MAFF	16044	-0.071	0.064	NO
107	PRKAR2A	PRKAR2A	PRKAR2A	16133	-0.074	0.068	NO
108	HIST1H3E	HIST1H3E	HIST1H3E	16305	-0.081	0.069	NO
109	RCOR1	RCOR1	RCOR1	16494	-0.089	0.069	NO
110	MAFG	MAFG	MAFG	17173	-0.13	0.048	NO
111	KLC3	KLC3	KLC3	17768	-0.2	0.04	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: PID SMAD2 3NUCLEARPATHWAY.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: PID SMAD2 3NUCLEARPATHWAY, 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: PID CASPASE PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TRDMT1	TRDMT1	TRDMT1	1191	0.21	0.031	YES
2	LDHC	LDHC	LDHC	1401	0.2	0.11	YES
3	IL4I1	IL4I1	IL4I1	1430	0.2	0.2	YES
4	TAT	TAT	TAT	1703	0.18	0.26	YES
5	LDHAL6A	LDHAL6A	LDHAL6A	2472	0.15	0.29	YES
6	DNMT3B	DNMT3B	DNMT3B	2526	0.15	0.35	YES
7	DNMT3A	DNMT3A	DNMT3A	2565	0.14	0.42	YES
8	MAT1A	MAT1A	MAT1A	2709	0.14	0.47	YES
9	LDHAL6B	LDHAL6B	LDHAL6B	4429	0.09	0.42	NO
10	DNMT1	DNMT1	DNMT1	7716	0.036	0.26	NO
11	CBS	CBS	CBS	7932	0.034	0.26	NO
12	MAT2B	MAT2B	MAT2B	8102	0.032	0.26	NO
13	SRM	SRM	SRM	8187	0.031	0.27	NO
14	CTH	CTH	CTH	8999	0.023	0.24	NO
15	APIP	APIP	APIP	9255	0.021	0.24	NO
16	ENOPH1	ENOPH1	ENOPH1	10678	0.0075	0.16	NO
17	MTR	MTR	MTR	10688	0.0074	0.16	NO
18	MAT2A	MAT2A	MAT2A	11015	0.0045	0.15	NO
19	AHCY	AHCY	AHCY	11067	0.004	0.15	NO
20	CDO1	CDO1	CDO1	11195	0.0029	0.14	NO
21	AHCYL1	AHCYL1	AHCYL1	12027	-0.0053	0.1	NO
22	ADI1	ADI1	ADI1	12717	-0.013	0.069	NO
23	LDHB	LDHB	LDHB	13651	-0.024	0.029	NO
24	SDS	SDS	SDS	13882	-0.027	0.028	NO
25	LDHA	LDHA	LDHA	13911	-0.027	0.039	NO
26	GOT1	GOT1	GOT1	14329	-0.033	0.032	NO
27	MTAP	MTAP	MTAP	14382	-0.034	0.044	NO
28	AMD1	AMD1	AMD1	14481	-0.036	0.054	NO
29	AHCYL2	AHCYL2	AHCYL2	14996	-0.044	0.046	NO
30	SMS	SMS	SMS	15124	-0.046	0.06	NO
31	MPST	MPST	MPST	15522	-0.055	0.064	NO
32	GOT2	GOT2	GOT2	16054	-0.072	0.067	NO
33	BHMT	BHMT	BHMT	17331	-0.15	0.063	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: PID CASPASE PATHWAY.

Figure S50. Get High-res Image For the top 5 core enriched genes in the pathway: PID CASPASE 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: REACTOME SIGNALING BY FGFR1 MUTANTS

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	KCNJ6	KCNJ6	KCNJ6	71	0.4	0.023	YES
2	PRKCG	PRKCG	PRKCG	87	0.39	0.048	YES
3	GRIK4	GRIK4	GRIK4	184	0.35	0.066	YES
4	GRIA4	GRIA4	GRIA4	257	0.32	0.083	YES
5	CAMK2B	CAMK2B	CAMK2B	305	0.31	0.1	YES
6	CHRNA6	CHRNA6	CHRNA6	439	0.29	0.11	YES
7	ADCY1	ADCY1	ADCY1	542	0.28	0.13	YES
8	CHRNA9	CHRNA9	CHRNA9	546	0.28	0.14	YES
9	GRIK5	GRIK5	GRIK5	574	0.27	0.16	YES
10	ACTN2	ACTN2	ACTN2	636	0.26	0.18	YES
11	CHRNA3	CHRNA3	CHRNA3	715	0.25	0.19	YES
12	GABRB1	GABRB1	GABRB1	766	0.25	0.2	YES
13	KCNJ12	KCNJ12	KCNJ12	791	0.25	0.22	YES
14	GABBR2	GABBR2	GABBR2	802	0.25	0.23	YES
15	GRIA2	GRIA2	GRIA2	870	0.24	0.24	YES
16	GRIN1	GRIN1	GRIN1	912	0.24	0.26	YES
17	CHRNB2	CHRNB2	CHRNB2	935	0.23	0.27	YES
18	CAMK4	CAMK4	CAMK4	977	0.23	0.28	YES
19	GRIN2A	GRIN2A	GRIN2A	1315	0.2	0.28	YES
20	GRIP2	GRIP2	GRIP2	1327	0.2	0.29	YES
21	GRIK1	GRIK1	GRIK1	1353	0.2	0.3	YES
22	KCNJ4	KCNJ4	KCNJ4	1393	0.2	0.32	YES
23	AKAP5	AKAP5	AKAP5	1442	0.2	0.33	YES
24	CHRNA1	CHRNA1	CHRNA1	1469	0.2	0.34	YES
25	GRIN2C	GRIN2C	GRIN2C	1507	0.19	0.35	YES
26	KCNJ9	KCNJ9	KCNJ9	1518	0.19	0.36	YES
27	CHRNA2	CHRNA2	CHRNA2	1782	0.18	0.36	YES
28	RASGRF2	RASGRF2	RASGRF2	1788	0.18	0.37	YES
29	GNG3	GNG3	GNG3	1817	0.18	0.38	YES
30	GNG7	GNG7	GNG7	2083	0.17	0.38	YES
31	GABRR2	GABRR2	GABRR2	2106	0.16	0.39	YES
32	KCNJ5	KCNJ5	KCNJ5	2271	0.16	0.39	YES
33	GNG2	GNG2	GNG2	2354	0.15	0.39	YES
34	GABRG2	GABRG2	GABRG2	2381	0.15	0.4	YES
35	KCNJ3	KCNJ3	KCNJ3	2393	0.15	0.41	YES
36	CHRNE	CHRNE	CHRNE	2453	0.15	0.42	YES
37	GNG4	GNG4	GNG4	2490	0.15	0.43	YES
38	KCNJ10	KCNJ10	KCNJ10	2520	0.15	0.43	YES
39	GRIA3	GRIA3	GRIA3	2548	0.15	0.44	YES
40	CHRNG	CHRNG	CHRNG	2696	0.14	0.44	YES
41	ARHGEF9	ARHGEF9	ARHGEF9	2923	0.13	0.44	YES
42	GRIN2D	GRIN2D	GRIN2D	2935	0.13	0.45	YES
43	ADCY6	ADCY6	ADCY6	2994	0.13	0.45	YES
44	GABBR1	GABBR1	GABBR1	3163	0.12	0.45	YES
45	RASGRF1	RASGRF1	RASGRF1	3232	0.12	0.46	YES
46	ADCY2	ADCY2	ADCY2	3333	0.12	0.46	YES
47	GNGT1	GNGT1	GNGT1	3439	0.12	0.46	YES
48	CHRNA4	CHRNA4	CHRNA4	3520	0.11	0.46	YES
49	GNG11	GNG11	GNG11	3543	0.11	0.47	YES
50	CAMK2A	CAMK2A	CAMK2A	3558	0.11	0.48	YES
51	CACNG4	CACNG4	CACNG4	3639	0.11	0.48	YES
52	CHRNA5	CHRNA5	CHRNA5	3791	0.11	0.48	YES
53	GRIK3	GRIK3	GRIK3	3867	0.1	0.48	YES
54	PLCB1	PLCB1	PLCB1	3870	0.1	0.49	YES
55	GABRB3	GABRB3	GABRB3	3944	0.1	0.49	YES
56	NCALD	NCALD	NCALD	4041	0.1	0.49	YES
57	PRKCA	PRKCA	PRKCA	4330	0.092	0.48	NO
58	GRIA1	GRIA1	GRIA1	4579	0.086	0.48	NO
59	GRIN2B	GRIN2B	GRIN2B	4740	0.082	0.47	NO
60	RRAS	RRAS	RRAS	5011	0.076	0.46	NO
61	GABRA1	GABRA1	GABRA1	5044	0.076	0.47	NO
62	GNG13	GNG13	GNG13	5076	0.075	0.47	NO
63	GNGT2	GNGT2	GNGT2	5320	0.07	0.46	NO
64	MYO6	MYO6	MYO6	5322	0.07	0.46	NO
65	GRIK2	GRIK2	GRIK2	5416	0.069	0.46	NO
66	CALM3	CALM3	CALM3	5971	0.059	0.44	NO
67	AKAP9	AKAP9	AKAP9	6218	0.055	0.43	NO
68	GABRG3	GABRG3	GABRG3	6238	0.055	0.43	NO
69	GNB1	GNB1	GNB1	6630	0.049	0.41	NO
70	PRKACB	PRKACB	PRKACB	6716	0.048	0.41	NO
71	PRKCB	PRKCB	PRKCB	7006	0.045	0.4	NO
72	DLG3	DLG3	DLG3	7422	0.04	0.38	NO
73	ADCY5	ADCY5	ADCY5	7440	0.039	0.38	NO
74	GNG5	GNG5	GNG5	7452	0.039	0.38	NO
75	RPS6KA1	RPS6KA1	RPS6KA1	7685	0.037	0.37	NO
76	PLCB2	PLCB2	PLCB2	7734	0.036	0.37	NO
77	GNAI2	GNAI2	GNAI2	7859	0.035	0.37	NO
78	RPS6KA2	RPS6KA2	RPS6KA2	7961	0.034	0.36	NO
79	AP2A1	AP2A1	AP2A1	8025	0.033	0.36	NO
80	GNB3	GNB3	GNB3	8164	0.032	0.36	NO
81	AP2B1	AP2B1	AP2B1	8270	0.03	0.35	NO
82	GNB4	GNB4	GNB4	8547	0.027	0.34	NO
83	PICK1	PICK1	PICK1	8766	0.025	0.33	NO
84	CHRFAM7A	CHRFAM7A	CHRFAM7A	9264	0.021	0.3	NO
85	CREB1	CREB1	CREB1	9351	0.02	0.3	NO
86	ADCY4	ADCY4	ADCY4	9495	0.018	0.3	NO
87	AP2A2	AP2A2	AP2A2	9519	0.018	0.3	NO
88	CALM2	CALM2	CALM2	9669	0.017	0.29	NO
89	GABRA2	GABRA2	GABRA2	10037	0.014	0.27	NO
90	PDPK1	PDPK1	PDPK1	11048	0.0042	0.21	NO
91	RAF1	RAF1	RAF1	11095	0.0037	0.21	NO
92	RPS6KA6	RPS6KA6	RPS6KA6	11464	0.0002	0.19	NO
93	AP2S1	AP2S1	AP2S1	11784	-0.0029	0.18	NO
94	GABRA5	GABRA5	GABRA5	11848	-0.0035	0.17	NO
95	ADCY7	ADCY7	ADCY7	11868	-0.0037	0.17	NO
96	PLCB3	PLCB3	PLCB3	12213	-0.0071	0.15	NO
97	GNAI3	GNAI3	GNAI3	12296	-0.008	0.15	NO
98	CAMK2D	CAMK2D	CAMK2D	13645	-0.024	0.077	NO
99	GABRB2	GABRB2	GABRB2	14173	-0.031	0.05	NO
100	GNB2	GNB2	GNB2	14287	-0.033	0.046	NO
101	MAPK1	MAPK1	MAPK1	14307	-0.033	0.047	NO
102	GNB5	GNB5	GNB5	14340	-0.034	0.048	NO
103	MDM2	MDM2	MDM2	14466	-0.035	0.043	NO
104	GNG12	GNG12	GNG12	14780	-0.04	0.029	NO
105	CHRNA7	CHRNA7	CHRNA7	15203	-0.048	0.0089	NO
106	CAMKK1	CAMKK1	CAMKK1	15214	-0.048	0.012	NO
107	HRAS	HRAS	HRAS	15441	-0.053	0.0028	NO
108	GNG10	GNG10	GNG10	15495	-0.055	0.0035	NO
109	BRAF	BRAF	BRAF	15615	-0.058	0.00083	NO
110	RPS6KA3	RPS6KA3	RPS6KA3	15688	-0.06	0.00088	NO
111	AP2M1	AP2M1	AP2M1	15950	-0.068	-0.0088	NO
112	NSF	NSF	NSF	16015	-0.07	-0.0077	NO
113	ADCY9	ADCY9	ADCY9	16046	-0.071	-0.0046	NO
114	DLG1	DLG1	DLG1	16055	-0.072	-0.00031	NO
115	ADCY3	ADCY3	ADCY3	16421	-0.086	-0.014	NO
116	GABRA3	GABRA3	GABRA3	16472	-0.088	-0.011	NO
117	CALM1	CALM1	CALM1	16528	-0.091	-0.0084	NO
118	GNAI1	GNAI1	GNAI1	16995	-0.12	-0.026	NO
119	KCNJ15	KCNJ15	KCNJ15	17128	-0.13	-0.025	NO
120	EPB41L1	EPB41L1	EPB41L1	17304	-0.14	-0.025	NO
121	KCNJ2	KCNJ2	KCNJ2	17385	-0.15	-0.019	NO
122	NEFL	NEFL	NEFL	17533	-0.17	-0.016	NO
123	GNAL	GNAL	GNAL	17551	-0.17	-0.0059	NO
124	GABRR1	GABRR1	GABRR1	17562	-0.17	0.0047	NO
125	CHRNB4	CHRNB4	CHRNB4	17591	-0.17	0.015	NO
126	KCNJ16	KCNJ16	KCNJ16	17758	-0.2	0.019	NO
127	ADCY8	ADCY8	ADCY8	18226	-0.32	0.015	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: REACTOME SIGNALING BY FGFR1 MUTANTS.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME SIGNALING BY FGFR1 MUTANTS, 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: REACTOME GENERIC TRANSCRIPTION 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	GAS2	GAS2	GAS2	31	0.44	0.12	YES
2	TNF	TNF	TNF	710	0.25	0.16	YES
3	ACTA1	ACTA1	ACTA1	875	0.24	0.22	YES
4	BIRC3	BIRC3	BIRC3	1682	0.18	0.23	YES
5	BCL2	BCL2	BCL2	2164	0.16	0.25	YES
6	DFFB	DFFB	DFFB	2367	0.15	0.28	YES
7	GZMB	GZMB	GZMB	3218	0.12	0.27	YES
8	APAF1	APAF1	APAF1	4301	0.093	0.24	YES
9	VIM	VIM	VIM	4595	0.085	0.24	YES
10	TRAF2	TRAF2	TRAF2	4683	0.083	0.26	YES
11	CASP6	CASP6	CASP6	4777	0.081	0.28	YES
12	PRF1	PRF1	PRF1	4990	0.077	0.29	YES
13	CASP9	CASP9	CASP9	5351	0.07	0.29	YES
14	BIRC2	BIRC2	BIRC2	5716	0.063	0.29	YES
15	ARHGDIB	ARHGDIB	ARHGDIB	5895	0.06	0.3	YES
16	TFAP2A	TFAP2A	TFAP2A	5950	0.059	0.31	YES
17	NUMA1	NUMA1	NUMA1	5992	0.059	0.33	YES
18	SATB1	SATB1	SATB1	6000	0.058	0.34	YES
19	DFFA	DFFA	DFFA	6057	0.057	0.36	YES
20	LMNB1	LMNB1	LMNB1	6988	0.045	0.32	NO
21	PARP1	PARP1	PARP1	7069	0.044	0.33	NO
22	MADD	MADD	MADD	7296	0.041	0.33	NO
23	DIABLO	DIABLO	DIABLO	8358	0.03	0.28	NO
24	APP	APP	APP	8990	0.023	0.25	NO
25	RIPK1	RIPK1	RIPK1	9039	0.023	0.25	NO
26	PTK2	PTK2	PTK2	9163	0.022	0.25	NO
27	TOP1	TOP1	TOP1	9508	0.018	0.24	NO
28	KRT18	KRT18	KRT18	9647	0.017	0.24	NO
29	BAX	BAX	BAX	9706	0.016	0.24	NO
30	SPTAN1	SPTAN1	SPTAN1	10399	0.0099	0.2	NO
31	LMNB2	LMNB2	LMNB2	11689	-0.0021	0.13	NO
32	CFL2	CFL2	CFL2	12129	-0.0062	0.11	NO
33	CASP7	CASP7	CASP7	12561	-0.011	0.092	NO
34	CASP2	CASP2	CASP2	12659	-0.012	0.09	NO
35	CASP4	CASP4	CASP4	12845	-0.014	0.084	NO
36	CASP3	CASP3	CASP3	12942	-0.015	0.083	NO
37	MAP3K1	MAP3K1	MAP3K1	13564	-0.023	0.056	NO
38	CASP8	CASP8	CASP8	13815	-0.026	0.05	NO
39	LMNA	LMNA	LMNA	13936	-0.028	0.051	NO
40	XIAP	XIAP	XIAP	14200	-0.031	0.046	NO
41	TNFRSF1A	TNFRSF1A	TNFRSF1A	14651	-0.038	0.032	NO
42	SLK	SLK	SLK	14688	-0.038	0.041	NO
43	CASP1	CASP1	CASP1	15028	-0.045	0.035	NO
44	CASP10	CASP10	CASP10	15034	-0.045	0.048	NO
45	BID	BID	BID	15163	-0.047	0.054	NO
46	TRADD	TRADD	TRADD	15286	-0.05	0.062	NO
47	CYCS	CYCS	CYCS	15292	-0.05	0.076	NO
48	LIMK1	LIMK1	LIMK1	15570	-0.056	0.076	NO
49	SREBF1	SREBF1	SREBF1	16515	-0.09	0.051	NO
50	GSN	GSN	GSN	16538	-0.092	0.076	NO
51	CRADD	CRADD	CRADD	16800	-0.11	0.092	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: REACTOME GENERIC TRANSCRIPTION PATHWAY.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME GENERIC TRANSCRIPTION 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: REACTOME TRANSMISSION ACROSS CHEMICAL SYNAPSES

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	TUBB3	TUBB3	TUBB3	851	0.24	0.094	YES
2	TUBB2B	TUBB2B	TUBB2B	994	0.23	0.22	YES
3	TUBA3C	TUBA3C	TUBA3C	1563	0.19	0.3	YES
4	TUBB1	TUBB1	TUBB1	2076	0.17	0.37	YES
5	TUBA1A	TUBA1A	TUBA1A	2702	0.14	0.41	YES
6	TUBA3D	TUBA3D	TUBA3D	2837	0.14	0.48	YES
7	PFDN4	PFDN4	PFDN4	5547	0.066	0.38	NO
8	PFDN6	PFDN6	PFDN6	6341	0.053	0.36	NO
9	CCT5	CCT5	CCT5	8342	0.03	0.27	NO
10	CCT2	CCT2	CCT2	8463	0.028	0.28	NO
11	PFDN5	PFDN5	PFDN5	8833	0.025	0.28	NO
12	CCT3	CCT3	CCT3	9491	0.018	0.25	NO
13	CCT8	CCT8	CCT8	9670	0.017	0.25	NO
14	PFDN1	PFDN1	PFDN1	9707	0.016	0.26	NO
15	TCP1	TCP1	TCP1	9826	0.015	0.26	NO
16	PFDN2	PFDN2	PFDN2	10088	0.013	0.26	NO
17	CCT7	CCT7	CCT7	10566	0.0084	0.24	NO
18	CCT4	CCT4	CCT4	10692	0.0074	0.23	NO
19	ACTB	ACTB	ACTB	10724	0.0071	0.24	NO
20	TUBB2A	TUBB2A	TUBB2A	10801	0.0064	0.23	NO
21	VBP1	VBP1	VBP1	11279	0.002	0.21	NO
22	CCT6A	CCT6A	CCT6A	12044	-0.0055	0.17	NO
23	TUBA1C	TUBA1C	TUBA1C	15948	-0.068	-0.00051	NO
24	TUBB6	TUBB6	TUBB6	16732	-0.1	0.016	NO
25	TUBA4A	TUBA4A	TUBA4A	17243	-0.14	0.068	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: REACTOME TRANSMISSION ACROSS CHEMICAL SYNAPSES.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME TRANSMISSION ACROSS CHEMICAL SYNAPSES, 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: REACTOME NEURONAL SYSTEM

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	KCNJ6	KCNJ6	KCNJ6	71	0.4	0.024	YES
2	KCNMB4	KCNMB4	KCNMB4	119	0.38	0.048	YES
3	KCNH3	KCNH3	KCNH3	131	0.37	0.074	YES
4	HCN4	HCN4	HCN4	148	0.36	0.098	YES
5	KCNN1	KCNN1	KCNN1	251	0.33	0.12	YES
6	KCNB2	KCNB2	KCNB2	274	0.32	0.14	YES
7	KCND1	KCND1	KCND1	388	0.3	0.15	YES
8	KCNF1	KCNF1	KCNF1	395	0.3	0.17	YES
9	KCNA6	KCNA6	KCNA6	419	0.3	0.19	YES
10	KCNH2	KCNH2	KCNH2	425	0.29	0.21	YES
11	KCNK4	KCNK4	KCNK4	467	0.29	0.23	YES
12	KCNA1	KCNA1	KCNA1	489	0.28	0.25	YES
13	KCNA2	KCNA2	KCNA2	706	0.25	0.25	YES
14	KCNH5	KCNH5	KCNH5	725	0.25	0.27	YES
15	KCNC1	KCNC1	KCNC1	787	0.25	0.28	YES
16	KCNJ12	KCNJ12	KCNJ12	791	0.25	0.3	YES
17	KCNH6	KCNH6	KCNH6	794	0.25	0.32	YES
18	GABBR2	GABBR2	GABBR2	802	0.25	0.34	YES
19	KCNQ2	KCNQ2	KCNQ2	913	0.24	0.35	YES
20	HCN2	HCN2	HCN2	967	0.23	0.36	YES
21	KCNJ1	KCNJ1	KCNJ1	1007	0.23	0.37	YES
22	KCNK9	KCNK9	KCNK9	1008	0.23	0.39	YES
23	KCNAB3	KCNAB3	KCNAB3	1082	0.22	0.4	YES
24	KCNJ4	KCNJ4	KCNJ4	1393	0.2	0.4	YES
25	KCNJ9	KCNJ9	KCNJ9	1518	0.19	0.4	YES
26	KCNG2	KCNG2	KCNG2	1522	0.19	0.42	YES
27	KCNH7	KCNH7	KCNH7	1526	0.19	0.43	YES
28	GNG3	GNG3	GNG3	1817	0.18	0.43	YES
29	KCNMB1	KCNMB1	KCNMB1	1870	0.18	0.44	YES
30	KCNK3	KCNK3	KCNK3	1874	0.18	0.45	YES
31	KCNN4	KCNN4	KCNN4	1970	0.17	0.46	YES
32	KCNB1	KCNB1	KCNB1	2023	0.17	0.47	YES
33	GNG7	GNG7	GNG7	2083	0.17	0.48	YES
34	HCN3	HCN3	HCN3	2132	0.16	0.48	YES
35	KCNK13	KCNK13	KCNK13	2147	0.16	0.49	YES
36	KCNJ5	KCNJ5	KCNJ5	2271	0.16	0.5	YES
37	GNG2	GNG2	GNG2	2354	0.15	0.5	YES
38	KCNJ3	KCNJ3	KCNJ3	2393	0.15	0.51	YES
39	GNG4	GNG4	GNG4	2490	0.15	0.52	YES
40	KCNJ10	KCNJ10	KCNJ10	2520	0.15	0.53	YES
41	KCNS1	KCNS1	KCNS1	2581	0.14	0.53	YES
42	KCNQ4	KCNQ4	KCNQ4	2843	0.14	0.53	YES
43	KCNA7	KCNA7	KCNA7	2906	0.13	0.54	YES
44	GABBR1	GABBR1	GABBR1	3163	0.12	0.53	YES
45	KCNN2	KCNN2	KCNN2	3322	0.12	0.53	YES
46	KCNJ8	KCNJ8	KCNJ8	3416	0.12	0.53	YES
47	GNGT1	GNGT1	GNGT1	3439	0.12	0.54	YES
48	KCNC4	KCNC4	KCNC4	3521	0.11	0.54	YES
49	HCN1	HCN1	HCN1	3586	0.11	0.55	YES
50	KCNH4	KCNH4	KCNH4	3603	0.11	0.56	YES
51	KCNV2	KCNV2	KCNV2	3644	0.11	0.56	YES
52	ABCC9	ABCC9	ABCC9	4367	0.091	0.53	NO
53	KCNA3	KCNA3	KCNA3	4552	0.087	0.52	NO
54	KCNQ3	KCNQ3	KCNQ3	4688	0.083	0.52	NO
55	KCNA5	KCNA5	KCNA5	4864	0.08	0.52	NO
56	KCND2	KCND2	KCND2	5095	0.075	0.51	NO
57	KCNN3	KCNN3	KCNN3	5149	0.074	0.51	NO
58	GNGT2	GNGT2	GNGT2	5320	0.07	0.51	NO
59	KCNJ14	KCNJ14	KCNJ14	5599	0.065	0.5	NO
60	KCND3	KCND3	KCND3	6566	0.05	0.45	NO
61	KCNAB2	KCNAB2	KCNAB2	6602	0.05	0.45	NO
62	GNB1	GNB1	GNB1	6630	0.049	0.45	NO
63	KCNV1	KCNV1	KCNV1	6773	0.048	0.45	NO
64	GNG5	GNG5	GNG5	7452	0.039	0.41	NO
65	GNB3	GNB3	GNB3	8164	0.032	0.38	NO
66	KCNK17	KCNK17	KCNK17	8429	0.029	0.37	NO
67	ABCC8	ABCC8	ABCC8	8904	0.024	0.34	NO
68	KCNA10	KCNA10	KCNA10	9029	0.023	0.34	NO
69	KCNAB1	KCNAB1	KCNAB1	9494	0.018	0.31	NO
70	KCNG1	KCNG1	KCNG1	9749	0.016	0.3	NO
71	KCNQ1	KCNQ1	KCNQ1	10196	0.012	0.28	NO
72	KCNJ11	KCNJ11	KCNJ11	10588	0.0082	0.26	NO
73	KCNC3	KCNC3	KCNC3	11322	0.0016	0.22	NO
74	KCNMB3	KCNMB3	KCNMB3	11542	-0.00066	0.2	NO
75	KCNH8	KCNH8	KCNH8	11833	-0.0033	0.19	NO
76	KCNS2	KCNS2	KCNS2	12146	-0.0065	0.17	NO
77	GNB2	GNB2	GNB2	14287	-0.033	0.058	NO
78	GNG12	GNG12	GNG12	14780	-0.04	0.034	NO
79	GNG10	GNG10	GNG10	15495	-0.055	-0.00075	NO
80	KCNQ5	KCNQ5	KCNQ5	15878	-0.066	-0.017	NO
81	KCNK10	KCNK10	KCNK10	16027	-0.071	-0.02	NO
82	KCNMB2	KCNMB2	KCNMB2	17082	-0.12	-0.068	NO
83	KCNJ15	KCNJ15	KCNJ15	17128	-0.13	-0.062	NO
84	KCNA4	KCNA4	KCNA4	17183	-0.13	-0.056	NO
85	KCNK6	KCNK6	KCNK6	17281	-0.14	-0.051	NO
86	KCNJ2	KCNJ2	KCNJ2	17385	-0.15	-0.046	NO
87	KCNS3	KCNS3	KCNS3	17474	-0.16	-0.04	NO
88	KCNK2	KCNK2	KCNK2	17485	-0.16	-0.029	NO
89	KCNG3	KCNG3	KCNG3	17664	-0.18	-0.026	NO
90	KCNJ16	KCNJ16	KCNJ16	17758	-0.2	-0.017	NO
91	KCNH1	KCNH1	KCNH1	18025	-0.25	-0.014	NO
92	KCNK7	KCNK7	KCNK7	18036	-0.26	0.0036	NO
93	KCNK1	KCNK1	KCNK1	18182	-0.3	0.017	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: REACTOME NEURONAL SYSTEM.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME NEURONAL SYSTEM, 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: REACTOME P75 NTR RECEPTOR MEDIATED SIGNALLING

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	LINGO1	LINGO1	LINGO1	102	0.38	0.066	YES
2	TIAM2	TIAM2	TIAM2	858	0.24	0.07	YES
3	MCF2	MCF2	MCF2	1062	0.22	0.1	YES
4	VAV3	VAV3	VAV3	1783	0.18	0.096	YES
5	RASGRF2	RASGRF2	RASGRF2	1788	0.18	0.13	YES
6	ARHGAP4	ARHGAP4	ARHGAP4	2034	0.17	0.15	YES
7	PLEKHG2	PLEKHG2	PLEKHG2	2328	0.16	0.16	YES
8	NGFR	NGFR	NGFR	2755	0.14	0.16	YES
9	ARHGEF17	ARHGEF17	ARHGEF17	2870	0.13	0.18	YES
10	ARHGEF9	ARHGEF9	ARHGEF9	2923	0.13	0.2	YES
11	OMG	OMG	OMG	3024	0.13	0.22	YES
12	ITGB3BP	ITGB3BP	ITGB3BP	3101	0.13	0.24	YES
13	RASGRF1	RASGRF1	RASGRF1	3232	0.12	0.26	YES
14	APH1B	APH1B	APH1B	3527	0.11	0.26	YES
15	MAPK8	MAPK8	MAPK8	3613	0.11	0.28	YES
16	RIPK2	RIPK2	RIPK2	4241	0.095	0.26	YES
17	PREX1	PREX1	PREX1	4247	0.095	0.28	YES
18	MAG	MAG	MAG	4303	0.093	0.3	YES
19	TIAM1	TIAM1	TIAM1	4375	0.091	0.31	YES
20	PSEN2	PSEN2	PSEN2	5022	0.076	0.29	YES
21	ARHGEF2	ARHGEF2	ARHGEF2	5055	0.076	0.3	YES
22	VAV1	VAV1	VAV1	5063	0.075	0.31	YES
23	ITSN1	ITSN1	ITSN1	5091	0.075	0.33	YES
24	ARHGEF6	ARHGEF6	ARHGEF6	5134	0.074	0.34	YES
25	TRIO	TRIO	TRIO	5429	0.068	0.34	YES
26	OBSCN	OBSCN	OBSCN	5502	0.067	0.34	YES
27	MAGED1	MAGED1	MAGED1	5816	0.062	0.34	YES
28	BCL2L11	BCL2L11	BCL2L11	5994	0.059	0.34	YES
29	HDAC2	HDAC2	HDAC2	6069	0.057	0.35	YES
30	FGD4	FGD4	FGD4	6569	0.05	0.33	NO
31	ARHGEF16	ARHGEF16	ARHGEF16	6967	0.045	0.32	NO
32	PRDM4	PRDM4	PRDM4	7087	0.043	0.32	NO
33	ABR	ABR	ABR	7323	0.041	0.31	NO
34	FGD1	FGD1	FGD1	8030	0.033	0.28	NO
35	SORCS3	SORCS3	SORCS3	8276	0.03	0.27	NO
36	PSENEN	PSENEN	PSENEN	8282	0.03	0.28	NO
37	SMPD2	SMPD2	SMPD2	8514	0.028	0.27	NO
38	SOS1	SOS1	SOS1	8903	0.024	0.25	NO
39	IKBKB	IKBKB	IKBKB	9069	0.022	0.25	NO
40	ARHGEF18	ARHGEF18	ARHGEF18	9446	0.019	0.23	NO
41	ARHGEF11	ARHGEF11	ARHGEF11	9459	0.019	0.24	NO
42	RELA	RELA	RELA	9916	0.014	0.21	NO
43	BAD	BAD	BAD	9960	0.014	0.21	NO
44	FGD3	FGD3	FGD3	10133	0.013	0.21	NO
45	HDAC3	HDAC3	HDAC3	10157	0.012	0.21	NO
46	NCSTN	NCSTN	NCSTN	10267	0.011	0.2	NO
47	ARHGEF1	ARHGEF1	ARHGEF1	10329	0.011	0.2	NO
48	ARHGEF3	ARHGEF3	ARHGEF3	10351	0.01	0.2	NO
49	YWHAE	YWHAE	YWHAE	10506	0.009	0.2	NO
50	NGFRAP1	NGFRAP1	NGFRAP1	10679	0.0075	0.19	NO
51	RHOA	RHOA	RHOA	11467	0.0001	0.15	NO
52	RPS27A	RPS27A	RPS27A	11491	-0.00016	0.14	NO
53	NFKBIA	NFKBIA	NFKBIA	11680	-0.002	0.14	NO
54	KALRN	KALRN	KALRN	11766	-0.0027	0.13	NO
55	FGD2	FGD2	FGD2	11774	-0.0027	0.13	NO
56	RTN4	RTN4	RTN4	11817	-0.0032	0.13	NO
57	APH1A	APH1A	APH1A	12012	-0.0051	0.12	NO
58	HDAC1	HDAC1	HDAC1	12097	-0.0059	0.12	NO
59	ARHGDIA	ARHGDIA	ARHGDIA	12107	-0.006	0.12	NO
60	CASP2	CASP2	CASP2	12659	-0.012	0.089	NO
61	SOS2	SOS2	SOS2	12908	-0.015	0.079	NO
62	CASP3	CASP3	CASP3	12942	-0.015	0.08	NO
63	UBA52	UBA52	UBA52	13251	-0.019	0.066	NO
64	IRAK1	IRAK1	IRAK1	13328	-0.02	0.066	NO
65	ARHGEF12	ARHGEF12	ARHGEF12	13370	-0.02	0.068	NO
66	NET1	NET1	NET1	13568	-0.023	0.061	NO
67	RAC1	RAC1	RAC1	13655	-0.024	0.061	NO
68	MYD88	MYD88	MYD88	13752	-0.025	0.061	NO
69	AATF	AATF	AATF	13767	-0.025	0.064	NO
70	AKAP13	AKAP13	AKAP13	14007	-0.029	0.057	NO
71	ECT2	ECT2	ECT2	14956	-0.043	0.014	NO
72	PSEN1	PSEN1	PSEN1	15086	-0.046	0.015	NO
73	TRAF6	TRAF6	TRAF6	15353	-0.051	0.01	NO
74	PRKCI	PRKCI	PRKCI	15747	-0.062	0.00047	NO
75	SQSTM1	SQSTM1	SQSTM1	16221	-0.078	-0.011	NO
76	ADAM17	ADAM17	ADAM17	16466	-0.088	-0.0073	NO
77	NGF	NGF	NGF	16726	-0.1	-0.0024	NO
78	NGEF	NGEF	NGEF	17998	-0.25	-0.025	NO
79	ARHGEF4	ARHGEF4	ARHGEF4	18111	-0.28	0.021	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: REACTOME P75 NTR RECEPTOR MEDIATED SIGNALLING.

Figure S60. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME P75 NTR RECEPTOR MEDIATED SIGNALLING, 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
KEGG GLYCOLYSIS GLUCONEOGENESIS	59	genes.ES.table	0.43	1.5	0.048	0.22	0.99	0.2	0.15	0.17	0.15	0.006
KEGG FATTY ACID METABOLISM	39	genes.ES.table	0.55	1.7	0.018	0.18	0.81	0.41	0.26	0.3	0.069	0.032
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	44	genes.ES.table	0.37	1.4	0.12	0.25	1	0.41	0.34	0.27	0.19	0.004
KEGG ARGININE AND PROLINE METABOLISM	53	genes.ES.table	0.42	1.4	0.082	0.25	1	0.34	0.24	0.26	0.19	0.004
KEGG HISTIDINE METABOLISM	29	genes.ES.table	0.64	1.7	0	0.18	0.76	0.38	0.15	0.32	0.07	0.034
KEGG TYROSINE METABOLISM	41	genes.ES.table	0.58	1.6	0.013	0.17	0.9	0.32	0.15	0.27	0.081	0.022
KEGG TRYPTOPHAN METABOLISM	39	genes.ES.table	0.61	1.7	0.0042	0.18	0.86	0.51	0.22	0.4	0.076	0.028
KEGG O GLYCAN BIOSYNTHESIS	29	genes.ES.table	0.53	1.5	0.051	0.21	0.99	0.52	0.25	0.39	0.15	0.006
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	44	genes.ES.table	0.38	1.4	0.099	0.22	1	0.39	0.32	0.26	0.15	0.006
KEGG GLYCEROPHOSPHOLIPID METABOLISM	74	genes.ES.table	0.39	1.5	0.045	0.2	0.99	0.32	0.28	0.24	0.13	0.006

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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	NAPSA	NAPSA	NAPSA	32	0.74	0.064	YES
2	CTSE	CTSE	CTSE	63	0.69	0.12	YES
3	CTSG	CTSG	CTSG	339	0.48	0.15	YES
4	HYAL1	HYAL1	HYAL1	1042	0.34	0.14	YES
5	DNASE2B	DNASE2B	DNASE2B	1117	0.33	0.17	YES
6	ATP6V0D2	ATP6V0D2	ATP6V0D2	1426	0.29	0.18	YES
7	CTSW	CTSW	CTSW	1539	0.28	0.2	YES
8	SLC11A1	SLC11A1	SLC11A1	1640	0.27	0.21	YES
9	LAMP3	LAMP3	LAMP3	1705	0.27	0.23	YES
10	ATP6V0A4	ATP6V0A4	ATP6V0A4	1707	0.27	0.26	YES
11	CTSH	CTSH	CTSH	1834	0.26	0.27	YES
12	CTSS	CTSS	CTSS	2337	0.21	0.26	YES
13	LAPTM5	LAPTM5	LAPTM5	2405	0.21	0.28	YES
14	NPC2	NPC2	NPC2	2794	0.18	0.27	YES
15	CTSO	CTSO	CTSO	2799	0.18	0.29	YES
16	ASAH1	ASAH1	ASAH1	3047	0.16	0.29	YES
17	CD68	CD68	CD68	3076	0.16	0.3	YES
18	FUCA1	FUCA1	FUCA1	3077	0.16	0.32	YES
19	ACP5	ACP5	ACP5	3310	0.15	0.32	YES
20	TCIRG1	TCIRG1	TCIRG1	3352	0.14	0.33	YES
21	GALC	GALC	GALC	3353	0.14	0.34	YES
22	IDUA	IDUA	IDUA	3408	0.14	0.35	YES
23	LIPA	LIPA	LIPA	3693	0.13	0.35	YES
24	CTSD	CTSD	CTSD	3700	0.13	0.36	YES
25	CTSL1	CTSL1	CTSL1	3703	0.13	0.37	YES
26	LGMN	LGMN	LGMN	3789	0.12	0.37	YES
27	AP1S3	AP1S3	AP1S3	3811	0.12	0.38	YES
28	SORT1	SORT1	SORT1	3812	0.12	0.4	YES
29	PSAPL1	PSAPL1	PSAPL1	3851	0.12	0.4	YES
30	PLA2G15	PLA2G15	PLA2G15	3995	0.11	0.4	YES
31	ARSA	ARSA	ARSA	4010	0.11	0.41	YES
32	CTSZ	CTSZ	CTSZ	4164	0.1	0.42	YES
33	AP1S2	AP1S2	AP1S2	4184	0.1	0.42	YES
34	ATP6V0D1	ATP6V0D1	ATP6V0D1	4272	0.1	0.43	YES
35	CTSA	CTSA	CTSA	4364	0.097	0.43	YES
36	SMPD1	SMPD1	SMPD1	4406	0.095	0.44	YES
37	CTNS	CTNS	CTNS	4417	0.095	0.44	YES
38	TPP1	TPP1	TPP1	4504	0.092	0.45	YES
39	CTSB	CTSB	CTSB	4531	0.091	0.46	YES
40	CD63	CD63	CD63	4541	0.091	0.46	YES
41	GNS	GNS	GNS	4591	0.089	0.47	YES
42	GNPTG	GNPTG	GNPTG	4617	0.088	0.48	YES
43	ACP2	ACP2	ACP2	4665	0.086	0.48	YES
44	AP4S1	AP4S1	AP4S1	4738	0.084	0.48	YES
45	CTSC	CTSC	CTSC	4877	0.08	0.48	YES
46	SGSH	SGSH	SGSH	4958	0.076	0.48	YES
47	ARSB	ARSB	ARSB	5003	0.075	0.49	YES
48	PSAP	PSAP	PSAP	5120	0.072	0.49	YES
49	CTSK	CTSK	CTSK	5139	0.071	0.5	YES
50	MAN2B1	MAN2B1	MAN2B1	5267	0.067	0.49	YES
51	MCOLN1	MCOLN1	MCOLN1	5348	0.065	0.5	YES
52	SUMF1	SUMF1	SUMF1	5350	0.065	0.5	YES
53	SLC17A5	SLC17A5	SLC17A5	5405	0.063	0.5	YES
54	HEXA	HEXA	HEXA	5568	0.059	0.5	NO
55	IDS	IDS	IDS	5606	0.058	0.5	NO
56	NAGPA	NAGPA	NAGPA	5693	0.056	0.5	NO
57	CLN3	CLN3	CLN3	5798	0.054	0.5	NO
58	GLB1	GLB1	GLB1	5973	0.05	0.5	NO
59	HEXB	HEXB	HEXB	6016	0.049	0.5	NO
60	SLC11A2	SLC11A2	SLC11A2	6131	0.046	0.5	NO
61	MANBA	MANBA	MANBA	6293	0.043	0.49	NO
62	GUSB	GUSB	GUSB	6419	0.04	0.49	NO
63	ATP6V0C	ATP6V0C	ATP6V0C	6575	0.037	0.48	NO
64	LAMP1	LAMP1	LAMP1	6660	0.036	0.48	NO
65	AP1M2	AP1M2	AP1M2	6674	0.036	0.48	NO
66	AP4B1	AP4B1	AP4B1	6695	0.035	0.49	NO
67	AGA	AGA	AGA	6834	0.033	0.48	NO
68	NAGLU	NAGLU	NAGLU	6837	0.032	0.48	NO
69	GBA	GBA	GBA	7023	0.029	0.48	NO
70	ATP6V0B	ATP6V0B	ATP6V0B	7100	0.028	0.48	NO
71	GM2A	GM2A	GM2A	7133	0.027	0.48	NO
72	NEU1	NEU1	NEU1	7181	0.027	0.48	NO
73	SCARB2	SCARB2	SCARB2	7270	0.025	0.47	NO
74	CTSF	CTSF	CTSF	7372	0.024	0.47	NO
75	NAGA	NAGA	NAGA	7413	0.023	0.47	NO
76	AP1G1	AP1G1	AP1G1	7415	0.023	0.47	NO
77	ARSG	ARSG	ARSG	7620	0.02	0.46	NO
78	ABCA2	ABCA2	ABCA2	7645	0.02	0.46	NO
79	CLN5	CLN5	CLN5	7693	0.019	0.46	NO
80	CD164	CD164	CD164	7710	0.019	0.46	NO
81	ATP6AP1	ATP6AP1	ATP6AP1	7714	0.019	0.46	NO
82	ATP6V0A1	ATP6V0A1	ATP6V0A1	7834	0.017	0.46	NO
83	AP1B1	AP1B1	AP1B1	7848	0.017	0.46	NO
84	ATP6V1H	ATP6V1H	ATP6V1H	7945	0.016	0.46	NO
85	IGF2R	IGF2R	IGF2R	8065	0.014	0.45	NO
86	GNPTAB	GNPTAB	GNPTAB	8090	0.014	0.45	NO
87	HGSNAT	HGSNAT	HGSNAT	8151	0.013	0.45	NO
88	ENTPD4	ENTPD4	ENTPD4	8153	0.013	0.45	NO
89	GAA	GAA	GAA	8159	0.013	0.45	NO
90	LAPTM4A	LAPTM4A	LAPTM4A	8447	0.0094	0.44	NO
91	GALNS	GALNS	GALNS	8460	0.0092	0.44	NO
92	MFSD8	MFSD8	MFSD8	8675	0.0063	0.43	NO
93	AP3D1	AP3D1	AP3D1	8678	0.0063	0.43	NO
94	CLTC	CLTC	CLTC	8714	0.0056	0.42	NO
95	AP3S2	AP3S2	AP3S2	8717	0.0056	0.42	NO
96	GGA3	GGA3	GGA3	8916	0.0032	0.42	NO
97	AP3M1	AP3M1	AP3M1	9348	-0.0018	0.39	NO
98	GGA2	GGA2	GGA2	9380	-0.0022	0.39	NO
99	AP3B1	AP3B1	AP3B1	9497	-0.0033	0.38	NO
100	ATP6V0A2	ATP6V0A2	ATP6V0A2	9608	-0.0045	0.38	NO
101	GGA1	GGA1	GGA1	9620	-0.0046	0.38	NO
102	CLTB	CLTB	CLTB	9975	-0.0089	0.36	NO
103	AP4E1	AP4E1	AP4E1	10119	-0.01	0.35	NO
104	AP1M1	AP1M1	AP1M1	10141	-0.011	0.35	NO
105	M6PR	M6PR	M6PR	10407	-0.014	0.34	NO
106	PPT1	PPT1	PPT1	10414	-0.014	0.34	NO
107	AP4M1	AP4M1	AP4M1	10692	-0.017	0.33	NO
108	AP3S1	AP3S1	AP3S1	10761	-0.018	0.32	NO
109	ABCB9	ABCB9	ABCB9	11166	-0.022	0.3	NO
110	LAPTM4B	LAPTM4B	LAPTM4B	11216	-0.023	0.3	NO
111	LAMP2	LAMP2	LAMP2	11577	-0.027	0.29	NO
112	GLA	GLA	GLA	11719	-0.028	0.28	NO
113	CLTA	CLTA	CLTA	12285	-0.035	0.25	NO
114	DNASE2	DNASE2	DNASE2	12533	-0.038	0.24	NO
115	NPC1	NPC1	NPC1	13003	-0.044	0.22	NO
116	AP1S1	AP1S1	AP1S1	13013	-0.044	0.22	NO
117	PPT2	PPT2	PPT2	15162	-0.081	0.12	NO
118	AP3M2	AP3M2	AP3M2	15738	-0.095	0.093	NO
119	CTSL2	CTSL2	CTSL2	17573	-0.2	0.01	NO
120	AP3B2	AP3B2	AP3B2	17799	-0.22	0.017	NO
121	CLTCL1	CLTCL1	CLTCL1	17962	-0.24	0.029	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: KEGG GLYCOLYSIS GLUCONEOGENESIS.

Figure S62. 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 FATTY ACID METABOLISM

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	AGER	AGER	AGER	67	0.68	0.11	YES
2	DUSP4	DUSP4	DUSP4	607	0.4	0.15	YES
3	S100B	S100B	S100B	853	0.36	0.2	YES
4	TLR3	TLR3	TLR3	856	0.36	0.26	YES
5	ZBP1	ZBP1	ZBP1	1151	0.32	0.29	YES
6	RPS6KA2	RPS6KA2	RPS6KA2	1263	0.31	0.34	YES
7	MEF2C	MEF2C	MEF2C	1297	0.31	0.39	YES
8	SAA1	SAA1	SAA1	1922	0.25	0.4	YES
9	RIPK3	RIPK3	RIPK3	2419	0.2	0.4	YES
10	IRAK2	IRAK2	IRAK2	2554	0.2	0.43	YES
11	DUSP6	DUSP6	DUSP6	2613	0.19	0.46	YES
12	IRF7	IRF7	IRF7	2938	0.17	0.47	YES
13	FOS	FOS	FOS	2967	0.17	0.5	YES
14	NOD1	NOD1	NOD1	4253	0.1	0.44	NO
15	RPS6KA1	RPS6KA1	RPS6KA1	4569	0.09	0.44	NO
16	JUN	JUN	JUN	4607	0.088	0.45	NO
17	MAPKAPK3	MAPKAPK3	MAPKAPK3	4983	0.076	0.44	NO
18	MAP2K3	MAP2K3	MAP2K3	5054	0.074	0.45	NO
19	RIPK2	RIPK2	RIPK2	5663	0.057	0.43	NO
20	PPP2CB	PPP2CB	PPP2CB	5869	0.052	0.43	NO
21	NOD2	NOD2	NOD2	6037	0.049	0.43	NO
22	NFKBIA	NFKBIA	NFKBIA	6188	0.045	0.43	NO
23	MAPK3	MAPK3	MAPK3	6354	0.042	0.42	NO
24	TAB2	TAB2	TAB2	6374	0.041	0.43	NO
25	MAPK11	MAPK11	MAPK11	6390	0.041	0.44	NO
26	RIPK1	RIPK1	RIPK1	6413	0.041	0.44	NO
27	DUSP3	DUSP3	DUSP3	6686	0.035	0.43	NO
28	MEF2A	MEF2A	MEF2A	7006	0.03	0.42	NO
29	RPS6KA3	RPS6KA3	RPS6KA3	7011	0.029	0.42	NO
30	MAPK10	MAPK10	MAPK10	7037	0.029	0.43	NO
31	NFKB2	NFKB2	NFKB2	7208	0.026	0.42	NO
32	S100A12	S100A12	S100A12	7282	0.025	0.42	NO
33	MAPKAPK2	MAPKAPK2	MAPKAPK2	7876	0.017	0.4	NO
34	MAPK9	MAPK9	MAPK9	7887	0.016	0.4	NO
35	CHUK	CHUK	CHUK	7902	0.016	0.4	NO
36	IKBKB	IKBKB	IKBKB	7946	0.016	0.4	NO
37	MAPK7	MAPK7	MAPK7	8006	0.015	0.4	NO
38	RELA	RELA	RELA	8166	0.013	0.39	NO
39	IRAK1	IRAK1	IRAK1	8286	0.011	0.39	NO
40	MAPK14	MAPK14	MAPK14	8330	0.011	0.39	NO
41	TBK1	TBK1	TBK1	8517	0.0085	0.38	NO
42	ATF2	ATF2	ATF2	8541	0.0081	0.38	NO
43	IRF3	IRF3	IRF3	8684	0.0061	0.37	NO
44	APP	APP	APP	9082	0.0012	0.35	NO
45	PPP2R1A	PPP2R1A	PPP2R1A	9279	-0.001	0.34	NO
46	MAP2K1	MAP2K1	MAP2K1	9339	-0.0017	0.34	NO
47	MAP2K4	MAP2K4	MAP2K4	9354	-0.0019	0.34	NO
48	CREB1	CREB1	CREB1	9536	-0.0038	0.33	NO
49	MAPK8	MAPK8	MAPK8	9650	-0.005	0.32	NO
50	TICAM1	TICAM1	TICAM1	9887	-0.0079	0.31	NO
51	IKBKG	IKBKG	IKBKG	10022	-0.0094	0.3	NO
52	DUSP7	DUSP7	DUSP7	10374	-0.013	0.29	NO
53	MAP2K2	MAP2K2	MAP2K2	10479	-0.014	0.28	NO
54	PPP2CA	PPP2CA	PPP2CA	10523	-0.015	0.28	NO
55	ATF1	ATF1	ATF1	10763	-0.018	0.28	NO
56	ELK1	ELK1	ELK1	11334	-0.024	0.25	NO
57	NFKBIB	NFKBIB	NFKBIB	11683	-0.028	0.23	NO
58	MAPK1	MAPK1	MAPK1	11849	-0.03	0.23	NO
59	TAB1	TAB1	TAB1	11870	-0.03	0.23	NO
60	PPP2R1B	PPP2R1B	PPP2R1B	12145	-0.033	0.22	NO
61	MAP2K7	MAP2K7	MAP2K7	12313	-0.035	0.22	NO
62	TAB3	TAB3	TAB3	12423	-0.036	0.22	NO
63	UBA52	UBA52	UBA52	12593	-0.038	0.22	NO
64	PPP2R5D	PPP2R5D	PPP2R5D	12715	-0.04	0.22	NO
65	MAP3K7	MAP3K7	MAP3K7	12720	-0.04	0.22	NO
66	TRAF6	TRAF6	TRAF6	12812	-0.041	0.23	NO
67	RPS27A	RPS27A	RPS27A	13068	-0.044	0.22	NO
68	HMGB1	HMGB1	HMGB1	13948	-0.057	0.18	NO
69	RPS6KA5	RPS6KA5	RPS6KA5	14085	-0.059	0.18	NO
70	IKBKE	IKBKE	IKBKE	14437	-0.066	0.18	NO
71	MAP2K6	MAP2K6	MAP2K6	16082	-0.11	0.11	NO
72	CDK1	CDK1	CDK1	16953	-0.15	0.084	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: KEGG FATTY ACID METABOLISM.

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

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

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	MYOCD	MYOCD	MYOCD	214	0.53	0.039	YES
2	PIK3R6	PIK3R6	PIK3R6	438	0.44	0.07	YES
3	S1PR1	S1PR1	S1PR1	569	0.41	0.1	YES
4	PIK3CG	PIK3CG	PIK3CG	693	0.39	0.13	YES
5	BLK	BLK	BLK	746	0.38	0.17	YES
6	ITGB3	ITGB3	ITGB3	830	0.37	0.2	YES
7	PIK3R5	PIK3R5	PIK3R5	969	0.35	0.22	YES
8	FGR	FGR	FGR	1213	0.32	0.24	YES
9	SLA	SLA	SLA	1227	0.32	0.27	YES
10	CYFIP2	CYFIP2	CYFIP2	2006	0.24	0.25	YES
11	LCK	LCK	LCK	2040	0.24	0.27	YES
12	SLC9A3R2	SLC9A3R2	SLC9A3R2	2270	0.22	0.28	YES
13	PAG1	PAG1	PAG1	2351	0.21	0.3	YES
14	DOCK4	DOCK4	DOCK4	2381	0.21	0.32	YES
15	FOS	FOS	FOS	2967	0.17	0.3	YES
16	ACTA2	ACTA2	ACTA2	3037	0.16	0.31	YES
17	LYN	LYN	LYN	3237	0.15	0.32	YES
18	SIPA1	SIPA1	SIPA1	3267	0.15	0.33	YES
19	TAGLN	TAGLN	TAGLN	3300	0.15	0.34	YES
20	PRKCE	PRKCE	PRKCE	3351	0.14	0.35	YES
21	PLA2G4A	PLA2G4A	PLA2G4A	3524	0.14	0.36	YES
22	EPS8	EPS8	EPS8	3526	0.14	0.37	YES
23	PDGFB	PDGFB	PDGFB	3581	0.13	0.38	YES
24	PIK3CD	PIK3CD	PIK3CD	3649	0.13	0.39	YES
25	STAT5A	STAT5A	STAT5A	3730	0.12	0.39	YES
26	DOK1	DOK1	DOK1	3741	0.12	0.4	YES
27	PDGFRB	PDGFRB	PDGFRB	3758	0.12	0.42	YES
28	HCK	HCK	HCK	3819	0.12	0.42	YES
29	ARPC1B	ARPC1B	ARPC1B	3953	0.12	0.43	YES
30	PIK3R3	PIK3R3	PIK3R3	4110	0.11	0.43	YES
31	PTPRJ	PTPRJ	PTPRJ	4302	0.099	0.43	YES
32	PRKCD	PRKCD	PRKCD	4339	0.097	0.44	YES
33	JAK2	JAK2	JAK2	4465	0.093	0.44	YES
34	PRKCA	PRKCA	PRKCA	4472	0.093	0.45	YES
35	JUN	JUN	JUN	4607	0.088	0.45	YES
36	FYN	FYN	FYN	4696	0.085	0.45	YES
37	RAP1A	RAP1A	RAP1A	4708	0.085	0.46	YES
38	BCAR1	BCAR1	BCAR1	4831	0.082	0.46	YES
39	LRP1	LRP1	LRP1	5069	0.073	0.46	YES
40	JUND	JUND	JUND	5079	0.073	0.46	YES
41	VAV2	VAV2	VAV2	5250	0.068	0.46	NO
42	ARAP1	ARAP1	ARAP1	5381	0.064	0.46	NO
43	PTEN	PTEN	PTEN	5443	0.062	0.46	NO
44	RHOA	RHOA	RHOA	5760	0.055	0.45	NO
45	PTPN1	PTPN1	PTPN1	5772	0.054	0.45	NO
46	MLLT4	MLLT4	MLLT4	5959	0.05	0.45	NO
47	GAB1	GAB1	GAB1	6222	0.045	0.44	NO
48	STAT3	STAT3	STAT3	6338	0.042	0.44	NO
49	MAPK3	MAPK3	MAPK3	6354	0.042	0.44	NO
50	WASL	WASL	WASL	6499	0.039	0.44	NO
51	GRB10	GRB10	GRB10	6742	0.034	0.42	NO
52	STAT1	STAT1	STAT1	6935	0.031	0.42	NO
53	RAPGEF1	RAPGEF1	RAPGEF1	6959	0.03	0.42	NO
54	RPS6KA3	RPS6KA3	RPS6KA3	7011	0.029	0.42	NO
55	RAB5A	RAB5A	RAB5A	7028	0.029	0.42	NO
56	MAPK10	MAPK10	MAPK10	7037	0.029	0.42	NO
57	ARPC4	ARPC4	ARPC4	7063	0.029	0.42	NO
58	CRK	CRK	CRK	7173	0.027	0.42	NO
59	CTTN	CTTN	CTTN	7221	0.026	0.42	NO
60	SHC1	SHC1	SHC1	7315	0.024	0.42	NO
61	CBL	CBL	CBL	7359	0.024	0.42	NO
62	PIK3R1	PIK3R1	PIK3R1	7425	0.023	0.42	NO
63	DNM2	DNM2	DNM2	7428	0.023	0.42	NO
64	IQGAP1	IQGAP1	IQGAP1	7626	0.02	0.41	NO
65	ACTN4	ACTN4	ACTN4	7652	0.02	0.41	NO
66	ARPC2	ARPC2	ARPC2	7755	0.018	0.41	NO
67	YWHAH	YWHAH	YWHAH	7825	0.017	0.41	NO
68	MAPK9	MAPK9	MAPK9	7887	0.016	0.4	NO
69	RASA1	RASA1	RASA1	7898	0.016	0.4	NO
70	ARPC3	ARPC3	ARPC3	8026	0.015	0.4	NO
71	GRB2	GRB2	GRB2	8077	0.014	0.4	NO
72	ITGAV	ITGAV	ITGAV	8132	0.013	0.4	NO
73	BAIAP2	BAIAP2	BAIAP2	8177	0.013	0.4	NO
74	ABL1	ABL1	ABL1	8240	0.012	0.39	NO
75	RAF1	RAF1	RAF1	8290	0.011	0.39	NO
76	YWHAB	YWHAB	YWHAB	8292	0.011	0.39	NO
77	ARHGDIA	ARHGDIA	ARHGDIA	8651	0.0066	0.37	NO
78	NRAS	NRAS	NRAS	8751	0.0051	0.37	NO
79	SRC	SRC	SRC	8789	0.0046	0.37	NO
80	STAT5B	STAT5B	STAT5B	8893	0.0035	0.36	NO
81	ARPC5	ARPC5	ARPC5	8897	0.0035	0.36	NO
82	RAP1B	RAP1B	RAP1B	8930	0.0031	0.36	NO
83	CSK	CSK	CSK	8934	0.003	0.36	NO
84	PPP2R1A	PPP2R1A	PPP2R1A	9279	-0.001	0.34	NO
85	MAP2K1	MAP2K1	MAP2K1	9339	-0.0017	0.34	NO
86	MAP2K4	MAP2K4	MAP2K4	9354	-0.0019	0.34	NO
87	SRF	SRF	SRF	9384	-0.0023	0.34	NO
88	MAPK8	MAPK8	MAPK8	9650	-0.005	0.32	NO
89	PTPN11	PTPN11	PTPN11	9785	-0.0066	0.32	NO
90	MAP2K2	MAP2K2	MAP2K2	10479	-0.014	0.28	NO
91	PIK3CB	PIK3CB	PIK3CB	10492	-0.014	0.28	NO
92	PPP2CA	PPP2CA	PPP2CA	10523	-0.015	0.28	NO
93	RAC1	RAC1	RAC1	10562	-0.015	0.28	NO
94	USP6NL	USP6NL	USP6NL	10693	-0.017	0.28	NO
95	KSR1	KSR1	KSR1	10719	-0.017	0.28	NO
96	MYC	MYC	MYC	10727	-0.017	0.28	NO
97	ACTR2	ACTR2	ACTR2	10749	-0.017	0.28	NO
98	PTPN2	PTPN2	PTPN2	10833	-0.018	0.27	NO
99	YES1	YES1	YES1	11047	-0.021	0.26	NO
100	NCKAP1	NCKAP1	NCKAP1	11096	-0.021	0.26	NO
101	WASF2	WASF2	WASF2	11164	-0.022	0.26	NO
102	ELK1	ELK1	ELK1	11334	-0.024	0.26	NO
103	PLCG1	PLCG1	PLCG1	11356	-0.024	0.26	NO
104	RAB4A	RAB4A	RAB4A	11384	-0.025	0.26	NO
105	SOS1	SOS1	SOS1	11526	-0.026	0.25	NO
106	YWHAZ	YWHAZ	YWHAZ	11695	-0.028	0.25	NO
107	ABI1	ABI1	ABI1	11698	-0.028	0.25	NO
108	NCK2	NCK2	NCK2	11824	-0.03	0.24	NO
109	MAPK1	MAPK1	MAPK1	11849	-0.03	0.25	NO
110	ACTR3	ACTR3	ACTR3	11881	-0.03	0.25	NO
111	MAP2K7	MAP2K7	MAP2K7	12313	-0.035	0.23	NO
112	YWHAE	YWHAE	YWHAE	12314	-0.035	0.23	NO
113	YWHAG	YWHAG	YWHAG	12384	-0.036	0.23	NO
114	YWHAQ	YWHAQ	YWHAQ	12899	-0.042	0.21	NO
115	PIN1	PIN1	PIN1	13033	-0.044	0.2	NO
116	NCK1	NCK1	NCK1	13106	-0.045	0.2	NO
117	BRAF	BRAF	BRAF	13771	-0.054	0.17	NO
118	SPHK1	SPHK1	SPHK1	13843	-0.055	0.18	NO
119	SFN	SFN	SFN	13872	-0.055	0.18	NO
120	KRAS	KRAS	KRAS	14153	-0.061	0.17	NO
121	SLC9A3R1	SLC9A3R1	SLC9A3R1	14551	-0.068	0.15	NO
122	HRAS	HRAS	HRAS	14790	-0.072	0.15	NO
123	PIK3R2	PIK3R2	PIK3R2	14899	-0.075	0.15	NO
124	PAK1	PAK1	PAK1	14935	-0.075	0.16	NO
125	EIF2AK2	EIF2AK2	EIF2AK2	14947	-0.076	0.16	NO
126	PIK3CA	PIK3CA	PIK3CA	16580	-0.13	0.085	NO
127	PPP2R2B	PPP2R2B	PPP2R2B	17610	-0.2	0.048	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: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

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

genes ES table in pathway: KEGG ARGININE AND PROLINE METABOLISM

Table 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	FGG	FGG	FGG	45	0.71	0.13	YES
2	LBP	LBP	LBP	691	0.39	0.17	YES
3	A2M	A2M	A2M	1503	0.28	0.17	YES
4	IL6	IL6	IL6	1739	0.27	0.21	YES
5	VAV1	VAV1	VAV1	1864	0.25	0.25	YES
6	MITF	MITF	MITF	2075	0.24	0.28	YES
7	GAB2	GAB2	GAB2	2195	0.22	0.32	YES
8	IL6ST	IL6ST	IL6ST	2383	0.21	0.35	YES
9	IL6R	IL6R	IL6R	2413	0.21	0.38	YES
10	PTPRE	PTPRE	PTPRE	2802	0.18	0.4	YES
11	TIMP1	TIMP1	TIMP1	2953	0.17	0.42	YES
12	FOS	FOS	FOS	2967	0.17	0.45	YES
13	SOCS3	SOCS3	SOCS3	3274	0.15	0.46	YES
14	CEBPB	CEBPB	CEBPB	3393	0.14	0.48	YES
15	HCK	HCK	HCK	3819	0.12	0.48	YES
16	CEBPD	CEBPD	CEBPD	3971	0.11	0.49	YES
17	IRF1	IRF1	IRF1	4080	0.11	0.5	YES
18	TNFSF11	TNFSF11	TNFSF11	4111	0.11	0.52	YES
19	PRKCD	PRKCD	PRKCD	4339	0.097	0.53	YES
20	JAK1	JAK1	JAK1	4352	0.097	0.55	YES
21	JAK2	JAK2	JAK2	4465	0.093	0.56	YES
22	BCL2L1	BCL2L1	BCL2L1	4560	0.09	0.57	YES
23	CRP	CRP	CRP	4600	0.089	0.58	YES
24	JUN	JUN	JUN	4607	0.088	0.6	YES
25	JUNB	JUNB	JUNB	5394	0.064	0.57	NO
26	MCL1	MCL1	MCL1	5435	0.063	0.58	NO
27	GAB1	GAB1	GAB1	6222	0.045	0.54	NO
28	STAT3	STAT3	STAT3	6338	0.042	0.55	NO
29	MAPK11	MAPK11	MAPK11	6390	0.041	0.55	NO
30	STAT1	STAT1	STAT1	6935	0.031	0.53	NO
31	PIK3R1	PIK3R1	PIK3R1	7425	0.023	0.5	NO
32	AKT1	AKT1	AKT1	7477	0.022	0.5	NO
33	GRB2	GRB2	GRB2	8077	0.014	0.48	NO
34	PIAS1	PIAS1	PIAS1	8099	0.014	0.48	NO
35	MAPK14	MAPK14	MAPK14	8330	0.011	0.47	NO
36	FOXO1	FOXO1	FOXO1	8513	0.0086	0.46	NO
37	MAP2K4	MAP2K4	MAP2K4	9354	-0.0019	0.41	NO
38	PTPN11	PTPN11	PTPN11	9785	-0.0066	0.39	NO
39	TYK2	TYK2	TYK2	10217	-0.012	0.37	NO
40	HSP90B1	HSP90B1	HSP90B1	10248	-0.012	0.37	NO
41	RAC1	RAC1	RAC1	10562	-0.015	0.36	NO
42	MYC	MYC	MYC	10727	-0.017	0.35	NO
43	PIAS3	PIAS3	PIAS3	11253	-0.023	0.33	NO
44	SOS1	SOS1	SOS1	11526	-0.026	0.32	NO
45	LMO4	LMO4	LMO4	15693	-0.094	0.11	NO
46	MAP2K6	MAP2K6	MAP2K6	16082	-0.11	0.11	NO
47	PIK3CA	PIK3CA	PIK3CA	16580	-0.13	0.1	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 ARGININE AND PROLINE METABOLISM.

Figure S68. 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 HISTIDINE 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	AGER	AGER	AGER	67	0.68	0.1	YES
2	TLR7	TLR7	TLR7	517	0.42	0.14	YES
3	DUSP4	DUSP4	DUSP4	607	0.4	0.2	YES
4	TLR8	TLR8	TLR8	844	0.36	0.25	YES
5	S100B	S100B	S100B	853	0.36	0.3	YES
6	TLR9	TLR9	TLR9	1048	0.34	0.35	YES
7	RPS6KA2	RPS6KA2	RPS6KA2	1263	0.31	0.38	YES
8	MEF2C	MEF2C	MEF2C	1297	0.31	0.43	YES
9	SAA1	SAA1	SAA1	1922	0.25	0.44	YES
10	IRAK2	IRAK2	IRAK2	2554	0.2	0.43	YES
11	DUSP6	DUSP6	DUSP6	2613	0.19	0.46	YES
12	FOS	FOS	FOS	2967	0.17	0.47	YES
13	NOD1	NOD1	NOD1	4253	0.1	0.41	NO
14	RPS6KA1	RPS6KA1	RPS6KA1	4569	0.09	0.41	NO
15	JUN	JUN	JUN	4607	0.088	0.42	NO
16	MAPKAPK3	MAPKAPK3	MAPKAPK3	4983	0.076	0.41	NO
17	MAP2K3	MAP2K3	MAP2K3	5054	0.074	0.42	NO
18	MYD88	MYD88	MYD88	5609	0.058	0.4	NO
19	RIPK2	RIPK2	RIPK2	5663	0.057	0.4	NO
20	PPP2CB	PPP2CB	PPP2CB	5869	0.052	0.4	NO
21	NOD2	NOD2	NOD2	6037	0.049	0.4	NO
22	NFKBIA	NFKBIA	NFKBIA	6188	0.045	0.4	NO
23	MAPK3	MAPK3	MAPK3	6354	0.042	0.4	NO
24	TAB2	TAB2	TAB2	6374	0.041	0.4	NO
25	MAPK11	MAPK11	MAPK11	6390	0.041	0.41	NO
26	DUSP3	DUSP3	DUSP3	6686	0.035	0.4	NO
27	MEF2A	MEF2A	MEF2A	7006	0.03	0.38	NO
28	RPS6KA3	RPS6KA3	RPS6KA3	7011	0.029	0.39	NO
29	MAPK10	MAPK10	MAPK10	7037	0.029	0.39	NO
30	NFKB2	NFKB2	NFKB2	7208	0.026	0.39	NO
31	S100A12	S100A12	S100A12	7282	0.025	0.39	NO
32	MAP3K1	MAP3K1	MAP3K1	7394	0.023	0.38	NO
33	MAPKAPK2	MAPKAPK2	MAPKAPK2	7876	0.017	0.36	NO
34	MAPK9	MAPK9	MAPK9	7887	0.016	0.36	NO
35	CHUK	CHUK	CHUK	7902	0.016	0.37	NO
36	IKBKB	IKBKB	IKBKB	7946	0.016	0.37	NO
37	MAPK7	MAPK7	MAPK7	8006	0.015	0.36	NO
38	RELA	RELA	RELA	8166	0.013	0.36	NO
39	IRAK1	IRAK1	IRAK1	8286	0.011	0.35	NO
40	MAPK14	MAPK14	MAPK14	8330	0.011	0.35	NO
41	ATF2	ATF2	ATF2	8541	0.0081	0.34	NO
42	APP	APP	APP	9082	0.0012	0.31	NO
43	PPP2R1A	PPP2R1A	PPP2R1A	9279	-0.001	0.3	NO
44	MAP2K1	MAP2K1	MAP2K1	9339	-0.0017	0.3	NO
45	MAP2K4	MAP2K4	MAP2K4	9354	-0.0019	0.3	NO
46	CREB1	CREB1	CREB1	9536	-0.0038	0.29	NO
47	MAPK8	MAPK8	MAPK8	9650	-0.005	0.28	NO
48	IKBKG	IKBKG	IKBKG	10022	-0.0094	0.27	NO
49	DUSP7	DUSP7	DUSP7	10374	-0.013	0.25	NO
50	MAP2K2	MAP2K2	MAP2K2	10479	-0.014	0.25	NO
51	PPP2CA	PPP2CA	PPP2CA	10523	-0.015	0.25	NO
52	ATF1	ATF1	ATF1	10763	-0.018	0.24	NO
53	TMEM189-UBE2V1	TMEM189-UBE2V1	TMEM189-UBE2V1	10988	-0.02	0.23	NO
54	ELK1	ELK1	ELK1	11334	-0.024	0.21	NO
55	NFKBIB	NFKBIB	NFKBIB	11683	-0.028	0.2	NO
56	MAPK1	MAPK1	MAPK1	11849	-0.03	0.19	NO
57	TAB1	TAB1	TAB1	11870	-0.03	0.2	NO
58	UBE2N	UBE2N	UBE2N	11978	-0.032	0.2	NO
59	PPP2R1B	PPP2R1B	PPP2R1B	12145	-0.033	0.19	NO
60	MAP2K7	MAP2K7	MAP2K7	12313	-0.035	0.19	NO
61	TAB3	TAB3	TAB3	12423	-0.036	0.19	NO
62	IRAK4	IRAK4	IRAK4	12565	-0.038	0.19	NO
63	UBA52	UBA52	UBA52	12593	-0.038	0.19	NO
64	PPP2R5D	PPP2R5D	PPP2R5D	12715	-0.04	0.19	NO
65	MAP3K7	MAP3K7	MAP3K7	12720	-0.04	0.2	NO
66	TRAF6	TRAF6	TRAF6	12812	-0.041	0.2	NO
67	RPS27A	RPS27A	RPS27A	13068	-0.044	0.19	NO
68	HMGB1	HMGB1	HMGB1	13948	-0.057	0.15	NO
69	PELI1	PELI1	PELI1	13993	-0.058	0.16	NO
70	RPS6KA5	RPS6KA5	RPS6KA5	14085	-0.059	0.16	NO
71	PELI2	PELI2	PELI2	14221	-0.062	0.17	NO
72	PELI3	PELI3	PELI3	14374	-0.064	0.17	NO
73	ECSIT	ECSIT	ECSIT	15613	-0.092	0.12	NO
74	MAP2K6	MAP2K6	MAP2K6	16082	-0.11	0.11	NO
75	CDK1	CDK1	CDK1	16953	-0.15	0.084	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 HISTIDINE METABOLISM.

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

genes ES table in pathway: KEGG TYROSINE 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	AQP4	AQP4	AQP4	16	0.78	0.2	YES
2	CREB3L1	CREB3L1	CREB3L1	1061	0.33	0.23	YES
3	AVPR2	AVPR2	AVPR2	1113	0.33	0.32	YES
4	AQP3	AQP3	AQP3	1516	0.28	0.37	YES
5	CREB3L3	CREB3L3	CREB3L3	2501	0.2	0.37	YES
6	AQP2	AQP2	AQP2	2674	0.19	0.41	YES
7	ARHGDIB	ARHGDIB	ARHGDIB	2820	0.18	0.44	YES
8	DYNC2H1	DYNC2H1	DYNC2H1	3599	0.13	0.44	YES
9	ADCY6	ADCY6	ADCY6	3961	0.12	0.45	YES
10	CREB3L2	CREB3L2	CREB3L2	4033	0.11	0.47	YES
11	ADCY9	ADCY9	ADCY9	4174	0.1	0.49	YES
12	VAMP2	VAMP2	VAMP2	5695	0.056	0.42	NO
13	PRKACB	PRKACB	PRKACB	6435	0.04	0.4	NO
14	RAB5A	RAB5A	RAB5A	7028	0.029	0.37	NO
15	DYNC1LI2	DYNC1LI2	DYNC1LI2	7084	0.028	0.38	NO
16	DCTN6	DCTN6	DCTN6	7680	0.019	0.35	NO
17	NSF	NSF	NSF	7837	0.017	0.34	NO
18	CREB3	CREB3	CREB3	7909	0.016	0.34	NO
19	STX4	STX4	STX4	7910	0.016	0.35	NO
20	RAB5C	RAB5C	RAB5C	8229	0.012	0.34	NO
21	RAB5B	RAB5B	RAB5B	8385	0.01	0.33	NO
22	ARHGDIA	ARHGDIA	ARHGDIA	8651	0.0066	0.32	NO
23	RAB11A	RAB11A	RAB11A	9066	0.0014	0.29	NO
24	RAB11B	RAB11B	RAB11B	9141	0.00048	0.29	NO
25	DYNC1H1	DYNC1H1	DYNC1H1	9184	7.7e-06	0.29	NO
26	CREB1	CREB1	CREB1	9536	-0.0038	0.27	NO
27	DYNLL2	DYNLL2	DYNLL2	9601	-0.0044	0.27	NO
28	CREB5	CREB5	CREB5	9666	-0.0052	0.27	NO
29	GNAS	GNAS	GNAS	9760	-0.0062	0.26	NO
30	DCTN1	DCTN1	DCTN1	10093	-0.01	0.25	NO
31	DYNC1LI1	DYNC1LI1	DYNC1LI1	10219	-0.012	0.24	NO
32	PRKACA	PRKACA	PRKACA	10602	-0.016	0.23	NO
33	DCTN4	DCTN4	DCTN4	11238	-0.023	0.2	NO
34	DCTN2	DCTN2	DCTN2	11270	-0.023	0.2	NO
35	DYNC1I2	DYNC1I2	DYNC1I2	12029	-0.032	0.17	NO
36	DYNC2LI1	DYNC2LI1	DYNC2LI1	12631	-0.039	0.15	NO
37	DCTN5	DCTN5	DCTN5	12674	-0.039	0.16	NO
38	DYNLL1	DYNLL1	DYNLL1	12791	-0.041	0.16	NO
39	CREB3L4	CREB3L4	CREB3L4	12845	-0.042	0.17	NO
40	ADCY3	ADCY3	ADCY3	14844	-0.074	0.079	NO
41	PRKX	PRKX	PRKX	15611	-0.092	0.061	NO
42	DYNC1I1	DYNC1I1	DYNC1I1	18435	-0.36	0.0033	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 TYROSINE METABOLISM.

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

genes ES table in pathway: KEGG TRYPTOPHAN METABOLISM

Table 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	AGTR1	AGTR1	AGTR1	502	0.43	0.15	YES
2	AGT	AGT	AGT	851	0.36	0.28	YES
3	PRKCB	PRKCB	PRKCB	917	0.35	0.42	YES
4	MEF2C	MEF2C	MEF2C	1297	0.31	0.52	YES
5	PTK2B	PTK2B	PTK2B	3959	0.12	0.43	NO
6	PRKCA	PRKCA	PRKCA	4472	0.093	0.44	NO
7	JUN	JUN	JUN	4607	0.088	0.47	NO
8	GNAQ	GNAQ	GNAQ	5134	0.071	0.47	NO
9	MEF2D	MEF2D	MEF2D	5837	0.053	0.45	NO
10	MAPK3	MAPK3	MAPK3	6354	0.042	0.44	NO
11	CALM1	CALM1	CALM1	6950	0.03	0.42	NO
12	MEF2A	MEF2A	MEF2A	7006	0.03	0.43	NO
13	CALM3	CALM3	CALM3	7053	0.029	0.44	NO
14	SHC1	SHC1	SHC1	7315	0.024	0.43	NO
15	MAP3K1	MAP3K1	MAP3K1	7394	0.023	0.44	NO
16	GRB2	GRB2	GRB2	8077	0.014	0.41	NO
17	RAF1	RAF1	RAF1	8290	0.011	0.4	NO
18	ATF2	ATF2	ATF2	8541	0.0081	0.39	NO
19	CALM2	CALM2	CALM2	8774	0.0048	0.38	NO
20	SRC	SRC	SRC	8789	0.0046	0.38	NO
21	MAP2K1	MAP2K1	MAP2K1	9339	-0.0017	0.35	NO
22	MAP2K4	MAP2K4	MAP2K4	9354	-0.0019	0.35	NO
23	MAPK8	MAPK8	MAPK8	9650	-0.005	0.34	NO
24	MAP2K2	MAP2K2	MAP2K2	10479	-0.014	0.3	NO
25	RAC1	RAC1	RAC1	10562	-0.015	0.3	NO
26	PTK2	PTK2	PTK2	11189	-0.022	0.28	NO
27	ELK1	ELK1	ELK1	11334	-0.024	0.28	NO
28	SOS1	SOS1	SOS1	11526	-0.026	0.28	NO
29	MAPK1	MAPK1	MAPK1	11849	-0.03	0.27	NO
30	EGFR	EGFR	EGFR	14210	-0.062	0.17	NO
31	HRAS	HRAS	HRAS	14790	-0.072	0.17	NO
32	PAK1	PAK1	PAK1	14935	-0.075	0.19	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 TRYPTOPHAN METABOLISM.

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

genes ES table in pathway: KEGG O GLYCAN BIOSYNTHESIS

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	AGER	AGER	AGER	67	0.68	0.11	YES
2	DUSP4	DUSP4	DUSP4	607	0.4	0.14	YES
3	S100B	S100B	S100B	853	0.36	0.19	YES
4	TLR3	TLR3	TLR3	856	0.36	0.25	YES
5	RPS6KA2	RPS6KA2	RPS6KA2	1263	0.31	0.28	YES
6	MEF2C	MEF2C	MEF2C	1297	0.31	0.33	YES
7	TLR4	TLR4	TLR4	1362	0.3	0.37	YES
8	LY96	LY96	LY96	1726	0.27	0.4	YES
9	SAA1	SAA1	SAA1	1922	0.25	0.43	YES
10	IRAK2	IRAK2	IRAK2	2554	0.2	0.43	YES
11	DUSP6	DUSP6	DUSP6	2613	0.19	0.45	YES
12	CD14	CD14	CD14	2694	0.19	0.48	YES
13	FOS	FOS	FOS	2967	0.17	0.49	YES
14	TICAM2	TICAM2	TICAM2	3642	0.13	0.48	NO
15	NOD1	NOD1	NOD1	4253	0.1	0.46	NO
16	RPS6KA1	RPS6KA1	RPS6KA1	4569	0.09	0.46	NO
17	JUN	JUN	JUN	4607	0.088	0.47	NO
18	MAPKAPK3	MAPKAPK3	MAPKAPK3	4983	0.076	0.46	NO
19	MAP2K3	MAP2K3	MAP2K3	5054	0.074	0.47	NO
20	RIPK2	RIPK2	RIPK2	5663	0.057	0.45	NO
21	PPP2CB	PPP2CB	PPP2CB	5869	0.052	0.44	NO
22	NOD2	NOD2	NOD2	6037	0.049	0.44	NO
23	NFKBIA	NFKBIA	NFKBIA	6188	0.045	0.44	NO
24	MAPK3	MAPK3	MAPK3	6354	0.042	0.44	NO
25	TAB2	TAB2	TAB2	6374	0.041	0.45	NO
26	MAPK11	MAPK11	MAPK11	6390	0.041	0.45	NO
27	RIPK1	RIPK1	RIPK1	6413	0.041	0.46	NO
28	DUSP3	DUSP3	DUSP3	6686	0.035	0.45	NO
29	MEF2A	MEF2A	MEF2A	7006	0.03	0.44	NO
30	RPS6KA3	RPS6KA3	RPS6KA3	7011	0.029	0.44	NO
31	MAPK10	MAPK10	MAPK10	7037	0.029	0.44	NO
32	NFKB2	NFKB2	NFKB2	7208	0.026	0.44	NO
33	S100A12	S100A12	S100A12	7282	0.025	0.44	NO
34	MAPKAPK2	MAPKAPK2	MAPKAPK2	7876	0.017	0.41	NO
35	MAPK9	MAPK9	MAPK9	7887	0.016	0.41	NO
36	CHUK	CHUK	CHUK	7902	0.016	0.42	NO
37	IKBKB	IKBKB	IKBKB	7946	0.016	0.42	NO
38	MAPK7	MAPK7	MAPK7	8006	0.015	0.42	NO
39	RELA	RELA	RELA	8166	0.013	0.41	NO
40	IRAK1	IRAK1	IRAK1	8286	0.011	0.4	NO
41	MAPK14	MAPK14	MAPK14	8330	0.011	0.4	NO
42	ATF2	ATF2	ATF2	8541	0.0081	0.39	NO
43	APP	APP	APP	9082	0.0012	0.36	NO
44	PPP2R1A	PPP2R1A	PPP2R1A	9279	-0.001	0.35	NO
45	MAP2K1	MAP2K1	MAP2K1	9339	-0.0017	0.35	NO
46	MAP2K4	MAP2K4	MAP2K4	9354	-0.0019	0.35	NO
47	CREB1	CREB1	CREB1	9536	-0.0038	0.34	NO
48	MAPK8	MAPK8	MAPK8	9650	-0.005	0.34	NO
49	TICAM1	TICAM1	TICAM1	9887	-0.0079	0.32	NO
50	IKBKG	IKBKG	IKBKG	10022	-0.0094	0.32	NO
51	DUSP7	DUSP7	DUSP7	10374	-0.013	0.3	NO
52	MAP2K2	MAP2K2	MAP2K2	10479	-0.014	0.3	NO
53	PPP2CA	PPP2CA	PPP2CA	10523	-0.015	0.3	NO
54	ATF1	ATF1	ATF1	10763	-0.018	0.29	NO
55	ELK1	ELK1	ELK1	11334	-0.024	0.26	NO
56	NFKBIB	NFKBIB	NFKBIB	11683	-0.028	0.25	NO
57	MAPK1	MAPK1	MAPK1	11849	-0.03	0.24	NO
58	TAB1	TAB1	TAB1	11870	-0.03	0.25	NO
59	PPP2R1B	PPP2R1B	PPP2R1B	12145	-0.033	0.24	NO
60	MAP2K7	MAP2K7	MAP2K7	12313	-0.035	0.23	NO
61	TAB3	TAB3	TAB3	12423	-0.036	0.23	NO
62	UBA52	UBA52	UBA52	12593	-0.038	0.23	NO
63	PPP2R5D	PPP2R5D	PPP2R5D	12715	-0.04	0.23	NO
64	MAP3K7	MAP3K7	MAP3K7	12720	-0.04	0.24	NO
65	TRAF6	TRAF6	TRAF6	12812	-0.041	0.24	NO
66	RPS27A	RPS27A	RPS27A	13068	-0.044	0.23	NO
67	HMGB1	HMGB1	HMGB1	13948	-0.057	0.2	NO
68	RPS6KA5	RPS6KA5	RPS6KA5	14085	-0.059	0.2	NO
69	MAP2K6	MAP2K6	MAP2K6	16082	-0.11	0.11	NO
70	CDK1	CDK1	CDK1	16953	-0.15	0.084	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 O GLYCAN BIOSYNTHESIS.

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

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

Table 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	C4BPA	C4BPA	C4BPA	9	0.8	0.028	YES
2	AGER	AGER	AGER	67	0.68	0.049	YES
3	C7	C7	C7	133	0.59	0.066	YES
4	C6	C6	C6	167	0.56	0.084	YES
5	C8B	C8B	C8B	172	0.56	0.1	YES
6	C4BPB	C4BPB	C4BPB	192	0.54	0.12	YES
7	CR1	CR1	CR1	270	0.5	0.14	YES
8	NLRP3	NLRP3	NLRP3	351	0.47	0.15	YES
9	NLRC4	NLRC4	NLRC4	389	0.46	0.16	YES
10	C8A	C8A	C8A	435	0.44	0.17	YES
11	CCR6	CCR6	CCR6	441	0.44	0.19	YES
12	CCR2	CCR2	CCR2	468	0.43	0.2	YES
13	CARD9	CARD9	CARD9	511	0.42	0.22	YES
14	TLR7	TLR7	TLR7	517	0.42	0.23	YES
15	LY86	LY86	LY86	575	0.41	0.24	YES
16	DUSP4	DUSP4	DUSP4	607	0.4	0.25	YES
17	C5	C5	C5	628	0.4	0.27	YES
18	CD180	CD180	CD180	677	0.39	0.28	YES
19	BTK	BTK	BTK	688	0.39	0.29	YES
20	C4A	C4A	C4A	689	0.39	0.3	YES
21	LBP	LBP	LBP	691	0.39	0.32	YES
22	CFI	CFI	CFI	777	0.37	0.33	YES
23	TLR8	TLR8	TLR8	844	0.36	0.34	YES
24	S100B	S100B	S100B	853	0.36	0.35	YES
25	TLR3	TLR3	TLR3	856	0.36	0.36	YES
26	MEFV	MEFV	MEFV	956	0.35	0.37	YES
27	CFB	CFB	CFB	1005	0.34	0.38	YES
28	CFD	CFD	CFD	1029	0.34	0.39	YES
29	TLR9	TLR9	TLR9	1048	0.34	0.4	YES
30	TLR10	TLR10	TLR10	1059	0.34	0.41	YES
31	C3	C3	C3	1137	0.33	0.42	YES
32	ZBP1	ZBP1	ZBP1	1151	0.32	0.43	YES
33	C2	C2	C2	1203	0.32	0.44	YES
34	DEFA1B	DEFA1B	DEFA1B	1230	0.32	0.45	YES
35	RPS6KA2	RPS6KA2	RPS6KA2	1263	0.31	0.46	YES
36	MEF2C	MEF2C	MEF2C	1297	0.31	0.46	YES
37	IRAK3	IRAK3	IRAK3	1317	0.3	0.47	YES
38	TLR4	TLR4	TLR4	1362	0.3	0.48	YES
39	P2RX7	P2RX7	P2RX7	1605	0.28	0.48	YES
40	LY96	LY96	LY96	1726	0.27	0.48	YES
41	BIRC3	BIRC3	BIRC3	1797	0.26	0.49	YES
42	SAA1	SAA1	SAA1	1922	0.25	0.49	YES
43	CD4	CD4	CD4	1928	0.25	0.5	YES
44	RNF125	RNF125	RNF125	1969	0.24	0.5	YES
45	C1QB	C1QB	C1QB	2099	0.23	0.5	YES
46	MASP1	MASP1	MASP1	2169	0.23	0.51	YES
47	C1QC	C1QC	C1QC	2172	0.23	0.52	YES
48	C1QA	C1QA	C1QA	2217	0.22	0.52	YES
49	UBA7	UBA7	UBA7	2329	0.21	0.52	YES
50	CTSS	CTSS	CTSS	2337	0.21	0.53	YES
51	RIPK3	RIPK3	RIPK3	2419	0.2	0.53	YES
52	IRAK2	IRAK2	IRAK2	2554	0.2	0.53	YES
53	CFH	CFH	CFH	2559	0.2	0.54	YES
54	CD55	CD55	CD55	2596	0.19	0.54	YES
55	CASP10	CASP10	CASP10	2606	0.19	0.55	YES
56	DUSP6	DUSP6	DUSP6	2613	0.19	0.56	YES
57	CD14	CD14	CD14	2694	0.19	0.56	YES
58	IRF7	IRF7	IRF7	2938	0.17	0.55	YES
59	FOS	FOS	FOS	2967	0.17	0.56	YES
60	DEFB4A	DEFB4A	DEFB4A	3042	0.16	0.56	YES
61	SIGIRR	SIGIRR	SIGIRR	3134	0.16	0.56	YES
62	TLR2	TLR2	TLR2	3152	0.16	0.56	YES
63	UNC93B1	UNC93B1	UNC93B1	3420	0.14	0.55	YES
64	TICAM2	TICAM2	TICAM2	3642	0.13	0.55	YES
65	LGALS3	LGALS3	LGALS3	3662	0.13	0.55	YES
66	CTSL1	CTSL1	CTSL1	3703	0.13	0.55	YES
67	PSTPIP1	PSTPIP1	PSTPIP1	3706	0.13	0.56	YES
68	DEFB1	DEFB1	DEFB1	3767	0.12	0.56	YES
69	LGMN	LGMN	LGMN	3789	0.12	0.56	YES
70	TXNIP	TXNIP	TXNIP	3827	0.12	0.56	YES
71	PLCG2	PLCG2	PLCG2	3927	0.12	0.56	YES
72	NLRC5	NLRC5	NLRC5	3952	0.12	0.56	YES
73	CASP4	CASP4	CASP4	4046	0.11	0.56	YES
74	IRF1	IRF1	IRF1	4080	0.11	0.56	YES
75	AIM2	AIM2	AIM2	4190	0.1	0.56	YES
76	PROS1	PROS1	PROS1	4239	0.1	0.56	YES
77	NOD1	NOD1	NOD1	4253	0.1	0.56	YES
78	TLR5	TLR5	TLR5	4357	0.097	0.56	YES
79	CTSB	CTSB	CTSB	4531	0.091	0.56	YES
80	BCL2L1	BCL2L1	BCL2L1	4560	0.09	0.56	YES
81	TLR6	TLR6	TLR6	4565	0.09	0.56	YES
82	RPS6KA1	RPS6KA1	RPS6KA1	4569	0.09	0.56	YES
83	CRP	CRP	CRP	4600	0.089	0.57	YES
84	JUN	JUN	JUN	4607	0.088	0.57	YES
85	C1S	C1S	C1S	4678	0.086	0.57	YES
86	CYLD	CYLD	CYLD	4686	0.086	0.57	YES
87	DHX58	DHX58	DHX58	4716	0.085	0.57	YES
88	TLR1	TLR1	TLR1	4886	0.079	0.57	NO
89	MAPKAPK3	MAPKAPK3	MAPKAPK3	4983	0.076	0.56	NO
90	UBE2L6	UBE2L6	UBE2L6	4989	0.076	0.56	NO
91	MAP2K3	MAP2K3	MAP2K3	5054	0.074	0.56	NO
92	TNFAIP3	TNFAIP3	TNFAIP3	5132	0.071	0.56	NO
93	CTSK	CTSK	CTSK	5139	0.071	0.56	NO
94	ZFYVE20	ZFYVE20	ZFYVE20	5440	0.062	0.55	NO
95	MYD88	MYD88	MYD88	5609	0.058	0.54	NO
96	RIPK2	RIPK2	RIPK2	5663	0.057	0.54	NO
97	CAPZA2	CAPZA2	CAPZA2	5699	0.056	0.54	NO
98	NLRP1	NLRP1	NLRP1	5728	0.055	0.54	NO
99	TIRAP	TIRAP	TIRAP	5778	0.054	0.54	NO
100	MASP2	MASP2	MASP2	5828	0.053	0.54	NO
101	PPP2CB	PPP2CB	PPP2CB	5869	0.052	0.54	NO
102	DDX58	DDX58	DDX58	6036	0.049	0.53	NO
103	NOD2	NOD2	NOD2	6037	0.049	0.54	NO
104	CASP9	CASP9	CASP9	6058	0.048	0.54	NO
105	ISG15	ISG15	ISG15	6094	0.047	0.54	NO
106	IFIH1	IFIH1	IFIH1	6139	0.046	0.54	NO
107	NFKBIA	NFKBIA	NFKBIA	6188	0.045	0.53	NO
108	MAPK3	MAPK3	MAPK3	6354	0.042	0.53	NO
109	TAB2	TAB2	TAB2	6374	0.041	0.53	NO
110	MAPK11	MAPK11	MAPK11	6390	0.041	0.53	NO
111	RIPK1	RIPK1	RIPK1	6413	0.041	0.53	NO
112	CASP1	CASP1	CASP1	6464	0.04	0.53	NO
113	IRF2	IRF2	IRF2	6506	0.039	0.52	NO
114	CASP8	CASP8	CASP8	6592	0.037	0.52	NO
115	HERC5	HERC5	HERC5	6629	0.036	0.52	NO
116	TANK	TANK	TANK	6670	0.036	0.52	NO
117	DUSP3	DUSP3	DUSP3	6686	0.035	0.52	NO
118	UBE2D1	UBE2D1	UBE2D1	7004	0.03	0.5	NO
119	MEF2A	MEF2A	MEF2A	7006	0.03	0.51	NO
120	RPS6KA3	RPS6KA3	RPS6KA3	7011	0.029	0.51	NO
121	MAPK10	MAPK10	MAPK10	7037	0.029	0.51	NO
122	NFKB2	NFKB2	NFKB2	7208	0.026	0.5	NO
123	S100A12	S100A12	S100A12	7282	0.025	0.5	NO
124	MAP3K1	MAP3K1	MAP3K1	7394	0.023	0.49	NO
125	DNM2	DNM2	DNM2	7428	0.023	0.49	NO
126	PYCARD	PYCARD	PYCARD	7429	0.023	0.49	NO
127	CAPZA1	CAPZA1	CAPZA1	7525	0.022	0.48	NO
128	UBE2D3	UBE2D3	UBE2D3	7615	0.02	0.48	NO
129	CD46	CD46	CD46	7635	0.02	0.48	NO
130	DDOST	DDOST	DDOST	7810	0.018	0.47	NO
131	MAPKAPK2	MAPKAPK2	MAPKAPK2	7876	0.017	0.47	NO
132	MAPK9	MAPK9	MAPK9	7887	0.016	0.47	NO
133	CHUK	CHUK	CHUK	7902	0.016	0.47	NO
134	IKBKB	IKBKB	IKBKB	7946	0.016	0.47	NO
135	MAPK7	MAPK7	MAPK7	8006	0.015	0.46	NO
136	MAPK13	MAPK13	MAPK13	8164	0.013	0.46	NO
137	RELA	RELA	RELA	8166	0.013	0.46	NO
138	IRAK1	IRAK1	IRAK1	8286	0.011	0.45	NO
139	MAPK14	MAPK14	MAPK14	8330	0.011	0.45	NO
140	TBK1	TBK1	TBK1	8517	0.0085	0.44	NO
141	ATF2	ATF2	ATF2	8541	0.0081	0.44	NO
142	TAX1BP1	TAX1BP1	TAX1BP1	8591	0.0074	0.44	NO
143	IRF3	IRF3	IRF3	8684	0.0061	0.43	NO
144	PANX1	PANX1	PANX1	8750	0.0051	0.43	NO
145	CREBBP	CREBBP	CREBBP	8767	0.005	0.43	NO
146	RNF135	RNF135	RNF135	8954	0.0028	0.42	NO
147	APP	APP	APP	9082	0.0012	0.41	NO
148	BIRC2	BIRC2	BIRC2	9109	0.00086	0.41	NO
149	PPP2R1A	PPP2R1A	PPP2R1A	9279	-0.001	0.4	NO
150	MAP2K1	MAP2K1	MAP2K1	9339	-0.0017	0.4	NO
151	MAP2K4	MAP2K4	MAP2K4	9354	-0.0019	0.39	NO
152	TRAF3	TRAF3	TRAF3	9441	-0.0029	0.39	NO
153	NLRX1	NLRX1	NLRX1	9508	-0.0034	0.39	NO
154	CREB1	CREB1	CREB1	9536	-0.0038	0.38	NO
155	EEA1	EEA1	EEA1	9643	-0.0049	0.38	NO
156	MAPK8	MAPK8	MAPK8	9650	-0.005	0.38	NO
157	OTUD5	OTUD5	OTUD5	9699	-0.0055	0.38	NO
158	C9	C9	C9	9743	-0.006	0.37	NO
159	TICAM1	TICAM1	TICAM1	9887	-0.0079	0.37	NO
160	IKBKG	IKBKG	IKBKG	10022	-0.0094	0.36	NO
161	UBE2D2	UBE2D2	UBE2D2	10130	-0.01	0.35	NO
162	EP300	EP300	EP300	10163	-0.011	0.35	NO
163	HSP90B1	HSP90B1	HSP90B1	10248	-0.012	0.35	NO
164	PCBP2	PCBP2	PCBP2	10324	-0.013	0.34	NO
165	DUSP7	DUSP7	DUSP7	10374	-0.013	0.34	NO
166	MAP2K2	MAP2K2	MAP2K2	10479	-0.014	0.34	NO
167	PPP2CA	PPP2CA	PPP2CA	10523	-0.015	0.34	NO
168	MAVS	MAVS	MAVS	10634	-0.016	0.33	NO
169	ATF1	ATF1	ATF1	10763	-0.018	0.32	NO
170	CASP2	CASP2	CASP2	10801	-0.018	0.32	NO
171	TMEM189-UBE2V1	TMEM189-UBE2V1	TMEM189-UBE2V1	10988	-0.02	0.31	NO
172	UBE2K	UBE2K	UBE2K	11250	-0.023	0.3	NO
173	SIKE1	SIKE1	SIKE1	11283	-0.024	0.3	NO
174	ATG12	ATG12	ATG12	11316	-0.024	0.3	NO
175	ELK1	ELK1	ELK1	11334	-0.024	0.3	NO
176	DAK	DAK	DAK	11352	-0.024	0.3	NO
177	NFKBIB	NFKBIB	NFKBIB	11683	-0.028	0.28	NO
178	MAPK1	MAPK1	MAPK1	11849	-0.03	0.27	NO
179	TAB1	TAB1	TAB1	11870	-0.03	0.27	NO
180	FADD	FADD	FADD	11930	-0.031	0.27	NO
181	PRKCSH	PRKCSH	PRKCSH	11971	-0.031	0.27	NO
182	UBE2N	UBE2N	UBE2N	11978	-0.032	0.27	NO
183	CNPY3	CNPY3	CNPY3	12053	-0.032	0.27	NO
184	PPP2R1B	PPP2R1B	PPP2R1B	12145	-0.033	0.26	NO
185	MAP2K7	MAP2K7	MAP2K7	12313	-0.035	0.26	NO
186	HSP90AB1	HSP90AB1	HSP90AB1	12396	-0.036	0.25	NO
187	TRAF2	TRAF2	TRAF2	12403	-0.036	0.25	NO
188	TAB3	TAB3	TAB3	12423	-0.036	0.25	NO
189	IRAK4	IRAK4	IRAK4	12565	-0.038	0.25	NO
190	UBA52	UBA52	UBA52	12593	-0.038	0.25	NO
191	PIK3R4	PIK3R4	PIK3R4	12706	-0.04	0.24	NO
192	PPP2R5D	PPP2R5D	PPP2R5D	12715	-0.04	0.24	NO
193	MAP3K7	MAP3K7	MAP3K7	12720	-0.04	0.24	NO
194	TRAF6	TRAF6	TRAF6	12812	-0.041	0.24	NO
195	ATG5	ATG5	ATG5	12860	-0.042	0.24	NO
196	TRIM25	TRIM25	TRIM25	12884	-0.042	0.24	NO
197	PIN1	PIN1	PIN1	13033	-0.044	0.23	NO
198	RPS27A	RPS27A	RPS27A	13068	-0.044	0.23	NO
199	MAPK12	MAPK12	MAPK12	13690	-0.053	0.2	NO
200	PIK3C3	PIK3C3	PIK3C3	13816	-0.054	0.2	NO
201	HMGB1	HMGB1	HMGB1	13948	-0.057	0.19	NO
202	PELI1	PELI1	PELI1	13993	-0.058	0.19	NO
203	RPS6KA5	RPS6KA5	RPS6KA5	14085	-0.059	0.19	NO
204	PELI2	PELI2	PELI2	14221	-0.062	0.18	NO
205	PELI3	PELI3	PELI3	14374	-0.064	0.18	NO
206	IKBKE	IKBKE	IKBKE	14437	-0.066	0.18	NO
207	TXN	TXN	TXN	14677	-0.07	0.16	NO
208	DNM1	DNM1	DNM1	14831	-0.073	0.16	NO
209	DEFB103B	DEFB103B	DEFB103B	14978	-0.076	0.15	NO
210	IFNB1	IFNB1	IFNB1	15372	-0.086	0.14	NO
211	BCL2	BCL2	BCL2	15440	-0.087	0.14	NO
212	ECSIT	ECSIT	ECSIT	15613	-0.092	0.13	NO
213	MAP2K6	MAP2K6	MAP2K6	16082	-0.11	0.11	NO
214	CFHR3	CFHR3	CFHR3	16186	-0.11	0.1	NO
215	CDK1	CDK1	CDK1	16953	-0.15	0.068	NO
216	C8G	C8G	C8G	17303	-0.17	0.055	NO
217	DEFB126	DEFB126	DEFB126	18222	-0.28	0.015	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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM.

Figure S78. 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 GLYCEROPHOSPHOLIPID 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	PLA2G1B	PLA2G1B	PLA2G1B	8	0.82	0.15	YES
2	PLA2G10	PLA2G10	PLA2G10	104	0.63	0.26	YES
3	PLA2G12B	PLA2G12B	PLA2G12B	251	0.51	0.35	YES
4	PLA2G2A	PLA2G2A	PLA2G2A	343	0.47	0.43	YES
5	PLA2G4E	PLA2G4E	PLA2G4E	847	0.36	0.47	YES
6	PLA2G5	PLA2G5	PLA2G5	848	0.36	0.54	YES
7	ENPP2	ENPP2	ENPP2	1449	0.29	0.56	YES
8	PLA2G7	PLA2G7	PLA2G7	1620	0.28	0.6	YES
9	LPCAT1	LPCAT1	LPCAT1	1647	0.27	0.65	YES
10	PLA2G2D	PLA2G2D	PLA2G2D	1700	0.27	0.7	YES
11	PLA2G4A	PLA2G4A	PLA2G4A	3524	0.14	0.62	NO
12	PAFAH2	PAFAH2	PAFAH2	3791	0.12	0.63	NO
13	PPAP2B	PPAP2B	PPAP2B	4127	0.11	0.63	NO
14	PPAP2A	PPAP2A	PPAP2A	5078	0.073	0.6	NO
15	PLA2G12A	PLA2G12A	PLA2G12A	6377	0.041	0.53	NO
16	PLD2	PLD2	PLD2	6978	0.03	0.51	NO
17	CHPT1	CHPT1	CHPT1	7072	0.028	0.51	NO
18	PAFAH1B2	PAFAH1B2	PAFAH1B2	7204	0.026	0.5	NO
19	PLA2G2F	PLA2G2F	PLA2G2F	7628	0.02	0.48	NO
20	PAFAH1B1	PAFAH1B1	PAFAH1B1	8225	0.012	0.46	NO
21	PPAP2C	PPAP2C	PPAP2C	8449	0.0094	0.44	NO
22	AGPS	AGPS	AGPS	8581	0.0076	0.44	NO
23	ENPP6	ENPP6	ENPP6	8658	0.0065	0.44	NO
24	LPCAT2	LPCAT2	LPCAT2	10768	-0.018	0.32	NO
25	LPCAT4	LPCAT4	LPCAT4	11104	-0.021	0.31	NO
26	PLA2G3	PLA2G3	PLA2G3	12031	-0.032	0.27	NO
27	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	14658	-0.07	0.14	NO
28	PAFAH1B3	PAFAH1B3	PAFAH1B3	15464	-0.088	0.11	NO
29	PLA2G6	PLA2G6	PLA2G6	16575	-0.13	0.074	NO
30	PLD1	PLD1	PLD1	17122	-0.16	0.074	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 GLYCEROPHOSPHOLIPID METABOLISM.

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

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.v4.0.symbols.gmt
Expression data file = LUSC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = LUSC-TP.mergedcluster.txt

GSEA analysis

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

Download Results

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

References

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

Made with Nozzle