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

Pan-kidney cohort (KICH+KIRC+KIRP) (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 KIPAN-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1542N0M

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 "KIPAN-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: 715
Number of samples: 889
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 :[ clus4 ] 276
pheno.type: 2 - 4 :[ clus1 ] 125
pheno.type: 3 - 4 :[ clus2 ] 200
pheno.type: 4 - 4 :[ clus3 ] 288

For the expression subtypes of 18216 genes in 890 samples, GSEA found enriched gene sets in each cluster using 889 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are KEGG OXIDATIVE PHOSPHORYLATION, KEGG PARKINSONS DISEASE, KEGG VIBRIO CHOLERAE INFECTION, KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION, PID MTOR 4PATHWAY, PID IGF1 PATHWAY, PID PI3KCIAKTPATHWAY, REACTOME PYRUVATE METABOLISM AND CITRIC ACID TCA CYCLE, REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT, REACTOME SIGNALING BY ERBB4

And common core enriched genes are ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D2, ATP6V1A, ATP6V1B1, ATP6V1C2, ATP6V1D, ATP6V1H, FOXO1

clus2

Top enriched gene sets are KEGG ETHER LIPID METABOLISM, KEGG RIBOSOME, KEGG DNA REPLICATION, KEGG HOMOLOGOUS RECOMBINATION, KEGG MAPK SIGNALING PATHWAY, KEGG CALCIUM SIGNALING PATHWAY, KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION, KEGG CHEMOKINE SIGNALING PATHWAY, KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION, KEGG CELL CYCLE

And common core enriched genes are CASP1, IL1B, IL6, AIM2, CCL4, CCL4L2, CCL5, CXCL10, IFNB1, IKBKE

clus3

Top enriched gene sets are KEGG PPAR SIGNALING PATHWAY, KEGG VASCULAR SMOOTH MUSCLE CONTRACTION, KEGG VASOPRESSIN REGULATED WATER REABSORPTION, BIOCARTA AT1R PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA VEGF PATHWAY, PID HIF2PATHWAY, PID ARF6 TRAFFICKINGPATHWAY, PID ANGIOPOIETINRECEPTOR PATHWAY, PID SHP2 PATHWAY

And common core enriched genes are AVPR2, ITGA5, ITGAV, JUN, MAPK1, MAPK8, ADCY3, AQP3, AQP4, ARHGDIB

clus4

Top enriched gene sets are KEGG CITRATE CYCLE TCA CYCLE, KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG HISTIDINE METABOLISM, KEGG SELENOAMINO ACID METABOLISM, KEGG PYRUVATE METABOLISM, KEGG BUTANOATE METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG BASE EXCISION REPAIR, KEGG LYSOSOME, KEGG TIGHT JUNCTION

And common core enriched genes are HEMK1, LCMT1, TRMT11, WBSCR22, ALDH1B1, ALDH2, APEX2, LIG1, MPG, MUTYH

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
KEGG OXIDATIVE PHOSPHORYLATION	113	genes.ES.table	0.63	1.6	0.061	0.77	0.87	0.68	0.21	0.54	0.41	0.25
KEGG PARKINSONS DISEASE	111	genes.ES.table	0.5	1.5	0.12	0.87	0.96	0.69	0.26	0.52	0.57	0.31
KEGG VIBRIO CHOLERAE INFECTION	52	genes.ES.table	0.56	1.9	0.0021	1	0.38	0.27	0.089	0.25	0	0.23
KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION	67	genes.ES.table	0.37	1.4	0.07	1	0.99	0.21	0.13	0.18	0.77	0.38
PID MTOR 4PATHWAY	67	genes.ES.table	0.27	1.5	0.09	1	0.99	0.43	0.26	0.32	0.78	0.39
PID IGF1 PATHWAY	30	genes.ES.table	0.37	1.4	0.11	0.97	0.99	0.13	0.048	0.13	0.76	0.37
PID PI3KCIAKTPATHWAY	35	genes.ES.table	0.41	1.7	0.059	1	0.77	0.51	0.3	0.36	0.62	0.38
REACTOME PYRUVATE METABOLISM AND CITRIC ACID TCA CYCLE	40	genes.ES.table	0.55	1.6	0.066	0.76	0.84	0.6	0.19	0.49	0.39	0.24
REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT	115	genes.ES.table	0.63	1.7	0.048	1	0.76	0.7	0.21	0.56	0.91	0.47
REACTOME SIGNALING BY ERBB4	83	genes.ES.table	0.35	1.4	0.077	1	0.99	0.13	0.076	0.12	0.79	0.4

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

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	ATP6V0A4	ATP6V0A4	ATP6V0A4	18	1.4	0.09	YES
2	ATP6V1B1	ATP6V1B1	ATP6V1B1	27	1.3	0.18	YES
3	CFTR	CFTR	CFTR	46	1.2	0.25	YES
4	ATP6V0D2	ATP6V0D2	ATP6V0D2	64	1.1	0.32	YES
5	PLCG2	PLCG2	PLCG2	169	0.88	0.38	YES
6	KCNQ1	KCNQ1	KCNQ1	187	0.84	0.43	YES
7	ATP6V1C2	ATP6V1C2	ATP6V1C2	214	0.8	0.48	YES
8	ATP6V1A	ATP6V1A	ATP6V1A	908	0.41	0.47	YES
9	ATP6V1H	ATP6V1H	ATP6V1H	1253	0.33	0.48	YES
10	SLC12A2	SLC12A2	SLC12A2	1323	0.32	0.49	YES
11	ATP6V0B	ATP6V0B	ATP6V0B	1370	0.31	0.51	YES
12	ATP6V0E2	ATP6V0E2	ATP6V0E2	1477	0.3	0.53	YES
13	ATP6V1D	ATP6V1D	ATP6V1D	1530	0.29	0.54	YES
14	ATP6V0C	ATP6V0C	ATP6V0C	1618	0.28	0.56	YES
15	ATP6AP1	ATP6AP1	ATP6AP1	2128	0.22	0.54	NO
16	ATP6V1E1	ATP6V1E1	ATP6V1E1	2314	0.2	0.55	NO
17	ATP6V1F	ATP6V1F	ATP6V1F	2895	0.16	0.52	NO
18	GNAS	GNAS	GNAS	3151	0.15	0.52	NO
19	ATP6V0D1	ATP6V0D1	ATP6V0D1	3335	0.14	0.52	NO
20	ATP6V1G1	ATP6V1G1	ATP6V1G1	3749	0.12	0.5	NO
21	ATP6V0A2	ATP6V0A2	ATP6V0A2	4140	0.1	0.49	NO
22	ATP6V0E1	ATP6V0E1	ATP6V0E1	4172	0.1	0.5	NO
23	ERO1L	ERO1L	ERO1L	4325	0.096	0.49	NO
24	PRKACA	PRKACA	PRKACA	4796	0.08	0.47	NO
25	MUC2	MUC2	MUC2	5043	0.072	0.46	NO
26	PRKCA	PRKCA	PRKCA	5170	0.068	0.46	NO
27	TJP2	TJP2	TJP2	5334	0.063	0.46	NO
28	KDELR1	KDELR1	KDELR1	5562	0.056	0.45	NO
29	PRKACB	PRKACB	PRKACB	5758	0.05	0.44	NO
30	SEC61B	SEC61B	SEC61B	6052	0.042	0.43	NO
31	SEC61A1	SEC61A1	SEC61A1	6251	0.036	0.42	NO
32	ATP6V1C1	ATP6V1C1	ATP6V1C1	6393	0.033	0.41	NO
33	ATP6V1E2	ATP6V1E2	ATP6V1E2	6746	0.023	0.4	NO
34	TJP1	TJP1	TJP1	7307	0.0082	0.36	NO
35	ARF1	ARF1	ARF1	7812	-0.0048	0.34	NO
36	ACTB	ACTB	ACTB	8524	-0.023	0.3	NO
37	ACTG1	ACTG1	ACTG1	8873	-0.032	0.28	NO
38	TCIRG1	TCIRG1	TCIRG1	9703	-0.055	0.24	NO
39	SEC61G	SEC61G	SEC61G	10258	-0.071	0.22	NO
40	KDELR2	KDELR2	KDELR2	10312	-0.072	0.22	NO
41	PLCG1	PLCG1	PLCG1	11746	-0.12	0.15	NO
42	ADCY3	ADCY3	ADCY3	12299	-0.14	0.12	NO
43	ATP6V1B2	ATP6V1B2	ATP6V1B2	12631	-0.16	0.12	NO
44	PDIA4	PDIA4	PDIA4	13107	-0.18	0.1	NO
45	ADCY9	ADCY9	ADCY9	13215	-0.18	0.11	NO
46	SEC61A2	SEC61A2	SEC61A2	14401	-0.26	0.061	NO
47	PRKCG	PRKCG	PRKCG	14519	-0.26	0.072	NO
48	ATP6V1G2	ATP6V1G2	ATP6V1G2	14628	-0.27	0.084	NO
49	ATP6V0A1	ATP6V0A1	ATP6V0A1	14716	-0.28	0.098	NO
50	PRKX	PRKX	PRKX	14923	-0.3	0.11	NO
51	KDELR3	KDELR3	KDELR3	16814	-0.51	0.036	NO
52	PRKCB	PRKCB	PRKCB	17319	-0.6	0.048	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: KEGG OXIDATIVE PHOSPHORYLATION.

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

genes ES table in pathway: KEGG PARKINSONS DISEASE

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	PDP2	PDP2	PDP2	574	0.53	-0.0056	YES
2	NNT	NNT	NNT	1032	0.38	-0.012	YES
3	PDP1	PDP1	PDP1	1133	0.35	0.000082	YES
4	IDH3A	IDH3A	IDH3A	1167	0.35	0.016	YES
5	CYCS	CYCS	CYCS	1216	0.34	0.03	YES
6	IDH2	IDH2	IDH2	1218	0.34	0.046	YES
7	COX5A	COX5A	COX5A	1275	0.33	0.06	YES
8	UQCRFS1	UQCRFS1	UQCRFS1	1389	0.31	0.069	YES
9	NDUFA4	NDUFA4	NDUFA4	1463	0.3	0.08	YES
10	NDUFA6	NDUFA6	NDUFA6	1485	0.29	0.093	YES
11	COX7B	COX7B	COX7B	1568	0.28	0.1	YES
12	COX8A	COX8A	COX8A	1580	0.28	0.12	YES
13	COX6C	COX6C	COX6C	1590	0.28	0.13	YES
14	L2HGDH	L2HGDH	L2HGDH	1664	0.27	0.14	YES
15	UQCRC1	UQCRC1	UQCRC1	1668	0.27	0.15	YES
16	PDHX	PDHX	PDHX	1756	0.26	0.16	YES
17	NDUFS7	NDUFS7	NDUFS7	1835	0.25	0.17	YES
18	ATP5A1	ATP5A1	ATP5A1	1838	0.25	0.18	YES
19	NDUFS8	NDUFS8	NDUFS8	1917	0.24	0.19	YES
20	ETFDH	ETFDH	ETFDH	1936	0.24	0.2	YES
21	NDUFA3	NDUFA3	NDUFA3	1955	0.24	0.21	YES
22	SDHD	SDHD	SDHD	1969	0.24	0.22	YES
23	DLAT	DLAT	DLAT	1983	0.23	0.23	YES
24	NDUFA8	NDUFA8	NDUFA8	1994	0.23	0.24	YES
25	UQCR11	UQCR11	UQCR11	1998	0.23	0.25	YES
26	COX6A1	COX6A1	COX6A1	2068	0.22	0.26	YES
27	NDUFB1	NDUFB1	NDUFB1	2101	0.22	0.27	YES
28	PDHA1	PDHA1	PDHA1	2107	0.22	0.28	YES
29	CYC1	CYC1	CYC1	2114	0.22	0.29	YES
30	PDHB	PDHB	PDHB	2176	0.22	0.3	YES
31	NDUFV1	NDUFV1	NDUFV1	2252	0.21	0.31	YES
32	NDUFC2	NDUFC2	NDUFC2	2260	0.21	0.32	YES
33	ATP5L	ATP5L	ATP5L	2261	0.21	0.33	YES
34	ATP5B	ATP5B	ATP5B	2268	0.21	0.34	YES
35	OGDH	OGDH	OGDH	2293	0.2	0.34	YES
36	ATP5D	ATP5D	ATP5D	2316	0.2	0.35	YES
37	NDUFA12	NDUFA12	NDUFA12	2363	0.2	0.36	YES
38	BSG	BSG	BSG	2384	0.2	0.37	YES
39	SLC16A8	SLC16A8	SLC16A8	2394	0.2	0.38	YES
40	DLD	DLD	DLD	2415	0.2	0.39	YES
41	NDUFB7	NDUFB7	NDUFB7	2432	0.19	0.4	YES
42	SDHA	SDHA	SDHA	2468	0.19	0.4	YES
43	FH	FH	FH	2496	0.19	0.41	YES
44	DLST	DLST	DLST	2525	0.19	0.42	YES
45	UQCRHL	UQCRHL	UQCRHL	2536	0.19	0.43	YES
46	CS	CS	CS	2598	0.18	0.43	YES
47	SUCLG2	SUCLG2	SUCLG2	2609	0.18	0.44	YES
48	NDUFA9	NDUFA9	NDUFA9	2614	0.18	0.45	YES
49	UQCRH	UQCRH	UQCRH	2621	0.18	0.46	YES
50	ACO2	ACO2	ACO2	2675	0.18	0.46	YES
51	NDUFB2	NDUFB2	NDUFB2	2681	0.18	0.47	YES
52	NDUFB9	NDUFB9	NDUFB9	2721	0.17	0.48	YES
53	UQCRQ	UQCRQ	UQCRQ	2765	0.17	0.49	YES
54	NDUFA7	NDUFA7	NDUFA7	2789	0.17	0.49	YES
55	NDUFS3	NDUFS3	NDUFS3	2821	0.17	0.5	YES
56	NDUFB6	NDUFB6	NDUFB6	2858	0.16	0.51	YES
57	COX6B1	COX6B1	COX6B1	2859	0.16	0.51	YES
58	COX7C	COX7C	COX7C	2871	0.16	0.52	YES
59	ATP5I	ATP5I	ATP5I	2928	0.16	0.53	YES
60	NDUFA5	NDUFA5	NDUFA5	2948	0.16	0.53	YES
61	COX4I1	COX4I1	COX4I1	2983	0.16	0.54	YES
62	UQCRC2	UQCRC2	UQCRC2	3015	0.16	0.55	YES
63	NDUFA13	NDUFA13	NDUFA13	3073	0.15	0.55	YES
64	NDUFA1	NDUFA1	NDUFA1	3099	0.15	0.56	YES
65	NDUFS6	NDUFS6	NDUFS6	3118	0.15	0.56	YES
66	SUCLG1	SUCLG1	SUCLG1	3222	0.14	0.56	YES
67	ATP5E	ATP5E	ATP5E	3263	0.14	0.57	YES
68	MDH2	MDH2	MDH2	3271	0.14	0.57	YES
69	ATP5J	ATP5J	ATP5J	3281	0.14	0.58	YES
70	COX5B	COX5B	COX5B	3298	0.14	0.59	YES
71	NDUFS1	NDUFS1	NDUFS1	3302	0.14	0.59	YES
72	NDUFAB1	NDUFAB1	NDUFAB1	3337	0.14	0.6	YES
73	NDUFA11	NDUFA11	NDUFA11	3382	0.14	0.6	YES
74	LDHB	LDHB	LDHB	3436	0.13	0.61	YES
75	UQCRB	UQCRB	UQCRB	3445	0.13	0.61	YES
76	ETFA	ETFA	ETFA	3474	0.13	0.62	YES
77	NDUFV2	NDUFV2	NDUFV2	3483	0.13	0.62	YES
78	NDUFB5	NDUFB5	NDUFB5	3525	0.13	0.63	YES
79	ATP5J2	ATP5J2	ATP5J2	3753	0.12	0.62	YES
80	ATP5G1	ATP5G1	ATP5G1	3820	0.12	0.62	YES
81	ATP5O	ATP5O	ATP5O	3822	0.12	0.63	YES
82	NDUFS2	NDUFS2	NDUFS2	3993	0.11	0.63	NO
83	NDUFB8	NDUFB8	NDUFB8	4141	0.1	0.62	NO
84	COX7A2L	COX7A2L	COX7A2L	4254	0.098	0.62	NO
85	NDUFS4	NDUFS4	NDUFS4	4371	0.094	0.62	NO
86	NDUFB10	NDUFB10	NDUFB10	4377	0.094	0.62	NO
87	NDUFA10	NDUFA10	NDUFA10	4452	0.091	0.62	NO
88	SUCLA2	SUCLA2	SUCLA2	4630	0.085	0.62	NO
89	NDUFB4	NDUFB4	NDUFB4	4664	0.084	0.62	NO
90	SDHB	SDHB	SDHB	4870	0.077	0.61	NO
91	NDUFA2	NDUFA2	NDUFA2	5009	0.073	0.61	NO
92	IDH3G	IDH3G	IDH3G	5081	0.07	0.61	NO
93	NDUFC1	NDUFC1	NDUFC1	5187	0.067	0.61	NO
94	ATP5F1	ATP5F1	ATP5F1	5291	0.064	0.6	NO
95	ATP5H	ATP5H	ATP5H	5384	0.061	0.6	NO
96	ATP5C1	ATP5C1	ATP5C1	5387	0.061	0.61	NO
97	ADHFE1	ADHFE1	ADHFE1	5408	0.061	0.61	NO
98	NDUFV3	NDUFV3	NDUFV3	5492	0.058	0.61	NO
99	ETFB	ETFB	ETFB	5504	0.058	0.61	NO
100	UCP2	UCP2	UCP2	5801	0.049	0.59	NO
101	IDH3B	IDH3B	IDH3B	5847	0.047	0.59	NO
102	NDUFB3	NDUFB3	NDUFB3	6023	0.043	0.59	NO
103	SDHC	SDHC	SDHC	6336	0.034	0.57	NO
104	PDK3	PDK3	PDK3	6717	0.024	0.55	NO
105	NDUFS5	NDUFS5	NDUFS5	6865	0.02	0.54	NO
106	PDPR	PDPR	PDPR	7828	-0.0052	0.49	NO
107	UCP3	UCP3	UCP3	8369	-0.02	0.46	NO
108	PDK2	PDK2	PDK2	10936	-0.092	0.32	NO
109	D2HGDH	D2HGDH	D2HGDH	11174	-0.1	0.32	NO
110	IDH1	IDH1	IDH1	11788	-0.12	0.29	NO
111	SLC16A1	SLC16A1	SLC16A1	11818	-0.12	0.29	NO
112	PDK4	PDK4	PDK4	13474	-0.2	0.21	NO
113	LDHA	LDHA	LDHA	13586	-0.2	0.22	NO
114	PDK1	PDK1	PDK1	14794	-0.29	0.16	NO
115	SLC16A3	SLC16A3	SLC16A3	16776	-0.5	0.079	NO

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

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PARKINSONS DISEASE, 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 VIBRIO CHOLERAE INFECTION

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	SLC2A4	SLC2A4	SLC2A4	318	0.7	0.16	YES
2	FOXO1	FOXO1	FOXO1	1339	0.32	0.19	YES
3	TBC1D4	TBC1D4	TBC1D4	2020	0.23	0.21	YES
4	HSP90AA1	HSP90AA1	HSP90AA1	2813	0.17	0.21	YES
5	AKT1	AKT1	AKT1	3207	0.14	0.23	YES
6	RAF1	RAF1	RAF1	3209	0.14	0.27	YES
7	AKT2	AKT2	AKT2	3383	0.14	0.29	YES
8	RICTOR	RICTOR	RICTOR	3581	0.13	0.31	YES
9	PDPK1	PDPK1	PDPK1	4080	0.1	0.31	YES
10	MAPKAP1	MAPKAP1	MAPKAP1	4374	0.094	0.32	YES
11	MLST8	MLST8	MLST8	4591	0.086	0.33	YES
12	MTOR	MTOR	MTOR	4740	0.081	0.35	YES
13	PRKACA	PRKACA	PRKACA	4796	0.08	0.36	YES
14	GSK3A	GSK3A	GSK3A	4985	0.074	0.37	YES
15	GSK3B	GSK3B	GSK3B	5008	0.073	0.39	YES
16	MAP3K5	MAP3K5	MAP3K5	5235	0.066	0.4	YES
17	BCL2L1	BCL2L1	BCL2L1	5429	0.06	0.4	YES
18	YWHAB	YWHAB	YWHAB	5440	0.06	0.42	YES
19	BAD	BAD	BAD	6190	0.038	0.38	NO
20	CHUK	CHUK	CHUK	6454	0.031	0.38	NO
21	PRKDC	PRKDC	PRKDC	6842	0.02	0.36	NO
22	FOXO4	FOXO4	FOXO4	6847	0.02	0.37	NO
23	KPNA1	KPNA1	KPNA1	7058	0.014	0.36	NO
24	YWHAH	YWHAH	YWHAH	8120	-0.013	0.3	NO
25	YWHAZ	YWHAZ	YWHAZ	8782	-0.03	0.28	NO
26	YWHAE	YWHAE	YWHAE	9412	-0.047	0.25	NO
27	SRC	SRC	SRC	9654	-0.054	0.25	NO
28	YWHAG	YWHAG	YWHAG	9831	-0.059	0.26	NO
29	CASP9	CASP9	CASP9	10428	-0.076	0.25	NO
30	CDKN1B	CDKN1B	CDKN1B	10906	-0.091	0.24	NO
31	AKT3	AKT3	AKT3	11294	-0.1	0.25	NO
32	FOXO3	FOXO3	FOXO3	11315	-0.1	0.28	NO
33	YWHAQ	YWHAQ	YWHAQ	11537	-0.11	0.29	NO
34	CDKN1A	CDKN1A	CDKN1A	11645	-0.12	0.32	NO
35	SFN	SFN	SFN	12889	-0.17	0.29	NO

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

Figure S6. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VIBRIO CHOLERAE INFECTION, 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 EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION

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	FGF9	FGF9	FGF9	12	1.4	0.063	YES
2	ATP6V0A4	ATP6V0A4	ATP6V0A4	18	1.4	0.12	YES
3	ATP6V1B1	ATP6V1B1	ATP6V1B1	27	1.3	0.18	YES
4	ATP6V0D2	ATP6V0D2	ATP6V0D2	64	1.1	0.23	YES
5	ATP6V1C2	ATP6V1C2	ATP6V1C2	214	0.8	0.26	YES
6	FGF7	FGF7	FGF7	305	0.71	0.28	YES
7	IRS2	IRS2	IRS2	815	0.44	0.28	YES
8	PRKAG2	PRKAG2	PRKAG2	851	0.43	0.29	YES
9	IRS1	IRS1	IRS1	860	0.43	0.31	YES
10	ATP6V1A	ATP6V1A	ATP6V1A	908	0.41	0.33	YES
11	CAB39L	CAB39L	CAB39L	1159	0.35	0.33	YES
12	ATP6V1H	ATP6V1H	ATP6V1H	1253	0.33	0.34	YES
13	ATP6V0B	ATP6V0B	ATP6V0B	1370	0.31	0.35	YES
14	ATP6V1D	ATP6V1D	ATP6V1D	1530	0.29	0.35	YES
15	ATP6V0C	ATP6V0C	ATP6V0C	1618	0.28	0.36	YES
16	EIF4E	EIF4E	EIF4E	1628	0.28	0.37	YES
17	FGF1	FGF1	FGF1	2182	0.21	0.35	YES
18	PRKAB2	PRKAB2	PRKAB2	2193	0.21	0.36	YES
19	PPM1A	PPM1A	PPM1A	2197	0.21	0.37	YES
20	PDE3B	PDE3B	PDE3B	2220	0.21	0.38	YES
21	ATP6V1E1	ATP6V1E1	ATP6V1E1	2314	0.2	0.38	YES
22	THEM4	THEM4	THEM4	2835	0.17	0.36	NO
23	ATP6V1F	ATP6V1F	ATP6V1F	2895	0.16	0.36	NO
24	SHC3	SHC3	SHC3	2990	0.16	0.37	NO
25	RAF1	RAF1	RAF1	3209	0.14	0.36	NO
26	MAP2K1	MAP2K1	MAP2K1	3247	0.14	0.37	NO
27	ATP6V0D1	ATP6V0D1	ATP6V0D1	3335	0.14	0.37	NO
28	AKT2	AKT2	AKT2	3383	0.14	0.37	NO
29	STK11	STK11	STK11	3513	0.13	0.37	NO
30	PRKAB1	PRKAB1	PRKAB1	3600	0.13	0.37	NO
31	ATP6V1G1	ATP6V1G1	ATP6V1G1	3749	0.12	0.37	NO
32	RHEB	RHEB	RHEB	3971	0.11	0.36	NO
33	MAP2K2	MAP2K2	MAP2K2	4006	0.11	0.36	NO
34	PRKAG1	PRKAG1	PRKAG1	4065	0.11	0.36	NO
35	PDPK1	PDPK1	PDPK1	4080	0.1	0.37	NO
36	ATP6V0A2	ATP6V0A2	ATP6V0A2	4140	0.1	0.37	NO
37	ATP6V0E1	ATP6V0E1	ATP6V0E1	4172	0.1	0.37	NO
38	KLB	KLB	KLB	4292	0.097	0.37	NO
39	TSC1	TSC1	TSC1	4494	0.09	0.36	NO
40	MLST8	MLST8	MLST8	4591	0.086	0.36	NO
41	PIK3R4	PIK3R4	PIK3R4	4684	0.083	0.36	NO
42	MTOR	MTOR	MTOR	4740	0.081	0.36	NO
43	KRAS	KRAS	KRAS	4784	0.08	0.36	NO
44	CAB39	CAB39	CAB39	4989	0.073	0.36	NO
45	FGFR1	FGFR1	FGFR1	5047	0.072	0.36	NO
46	YWHAB	YWHAB	YWHAB	5440	0.06	0.34	NO
47	PRKAA1	PRKAA1	PRKAA1	5570	0.056	0.33	NO
48	PIK3C3	PIK3C3	PIK3C3	5848	0.047	0.32	NO
49	PIK3CA	PIK3CA	PIK3CA	5945	0.045	0.32	NO
50	HRAS	HRAS	HRAS	6087	0.041	0.31	NO
51	EIF4G1	EIF4G1	EIF4G1	6300	0.036	0.3	NO
52	PIK3R2	PIK3R2	PIK3R2	6348	0.034	0.3	NO
53	ATP6V1C1	ATP6V1C1	ATP6V1C1	6393	0.033	0.3	NO
54	ATP6V1E2	ATP6V1E2	ATP6V1E2	6746	0.023	0.28	NO
55	TSC2	TSC2	TSC2	6789	0.022	0.28	NO
56	RPTOR	RPTOR	RPTOR	6932	0.018	0.27	NO
57	RPS6	RPS6	RPS6	7184	0.011	0.26	NO
58	EIF4B	EIF4B	EIF4B	7368	0.0068	0.25	NO
59	FRS2	FRS2	FRS2	7713	-0.002	0.23	NO
60	PRKAA2	PRKAA2	PRKAA2	7968	-0.0093	0.22	NO
61	INSR	INSR	INSR	7977	-0.0095	0.22	NO
62	MAPK1	MAPK1	MAPK1	8032	-0.011	0.21	NO
63	FGF23	FGF23	FGF23	8056	-0.011	0.21	NO
64	TRIB3	TRIB3	TRIB3	8148	-0.014	0.21	NO
65	FGFR2	FGFR2	FGFR2	8352	-0.019	0.2	NO
66	GRB10	GRB10	GRB10	8548	-0.024	0.19	NO
67	FGF18	FGF18	FGF18	8669	-0.027	0.18	NO
68	SOS1	SOS1	SOS1	9385	-0.046	0.14	NO
69	MAPK3	MAPK3	MAPK3	9619	-0.053	0.13	NO
70	TCIRG1	TCIRG1	TCIRG1	9703	-0.055	0.13	NO
71	CRK	CRK	CRK	11264	-0.1	0.05	NO
72	STRADA	STRADA	STRADA	11588	-0.11	0.038	NO
73	PIK3CB	PIK3CB	PIK3CB	11734	-0.12	0.035	NO
74	GRB2	GRB2	GRB2	11942	-0.13	0.03	NO
75	RPS6KB1	RPS6KB1	RPS6KB1	12048	-0.13	0.03	NO
76	CDK1	CDK1	CDK1	12280	-0.14	0.023	NO
77	SHC1	SHC1	SHC1	12366	-0.14	0.025	NO
78	ATP6V1B2	ATP6V1B2	ATP6V1B2	12631	-0.16	0.018	NO
79	GAB1	GAB1	GAB1	12662	-0.16	0.023	NO
80	NRAS	NRAS	NRAS	13190	-0.18	0.0022	NO
81	STRADB	STRADB	STRADB	13363	-0.19	0.0014	NO
82	FGF17	FGF17	FGF17	14210	-0.24	-0.034	NO
83	EEF2K	EEF2K	EEF2K	14347	-0.25	-0.031	NO
84	ATP6V1G2	ATP6V1G2	ATP6V1G2	14628	-0.27	-0.034	NO
85	FGF5	FGF5	FGF5	14688	-0.28	-0.024	NO
86	PIK3R1	PIK3R1	PIK3R1	14710	-0.28	-0.013	NO
87	SHC2	SHC2	SHC2	14721	-0.28	-0.00075	NO
88	FGF2	FGF2	FGF2	15610	-0.36	-0.034	NO
89	FGF20	FGF20	FGF20	15710	-0.37	-0.023	NO
90	DOK1	DOK1	DOK1	16426	-0.45	-0.042	NO
91	EIF4EBP1	EIF4EBP1	EIF4EBP1	16585	-0.48	-0.029	NO
92	TLR9	TLR9	TLR9	16750	-0.5	-0.016	NO
93	KL	KL	KL	17193	-0.57	-0.014	NO
94	FGFR3	FGFR3	FGFR3	17579	-0.66	-0.0055	NO
95	FGFR4	FGFR4	FGFR4	17971	-0.87	0.012	NO

Figure S7. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG EPITHELIAL CELL SIGNALING IN HELICOBACTER PYLORI INFECTION, 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 MTOR 4PATHWAY

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	ERBB4	ERBB4	ERBB4	79	1.1	0.13	YES
2	NRG4	NRG4	NRG4	147	0.91	0.25	YES
3	NRG2	NRG2	NRG2	208	0.8	0.34	YES
4	BTC	BTC	BTC	529	0.56	0.4	YES
5	NR4A1	NR4A1	NR4A1	1046	0.38	0.42	YES
6	FOXO1	FOXO1	FOXO1	1339	0.32	0.44	YES
7	PHLPP1	PHLPP1	PHLPP1	1375	0.31	0.48	YES
8	THEM4	THEM4	THEM4	2835	0.17	0.42	NO
9	AKT1	AKT1	AKT1	3207	0.14	0.42	NO
10	AKT2	AKT2	AKT2	3383	0.14	0.43	NO
11	RICTOR	RICTOR	RICTOR	3581	0.13	0.43	NO
12	PDPK1	PDPK1	PDPK1	4080	0.1	0.42	NO
13	MAPKAP1	MAPKAP1	MAPKAP1	4374	0.094	0.42	NO
14	MLST8	MLST8	MLST8	4591	0.086	0.41	NO
15	MTOR	MTOR	MTOR	4740	0.081	0.42	NO
16	GSK3A	GSK3A	GSK3A	4985	0.074	0.41	NO
17	RPS6KB2	RPS6KB2	RPS6KB2	5663	0.054	0.38	NO
18	PIK3CA	PIK3CA	PIK3CA	5945	0.045	0.37	NO
19	BAD	BAD	BAD	6190	0.038	0.36	NO
20	CHUK	CHUK	CHUK	6454	0.031	0.35	NO
21	TSC2	TSC2	TSC2	6789	0.022	0.34	NO
22	FOXO4	FOXO4	FOXO4	6847	0.02	0.34	NO
23	TRIB3	TRIB3	TRIB3	8148	-0.014	0.27	NO
24	AKT1S1	AKT1S1	AKT1S1	8654	-0.027	0.24	NO
25	CASP9	CASP9	CASP9	10428	-0.076	0.16	NO
26	CDKN1B	CDKN1B	CDKN1B	10906	-0.091	0.14	NO
27	PTEN	PTEN	PTEN	11267	-0.1	0.13	NO
28	AKT3	AKT3	AKT3	11294	-0.1	0.15	NO
29	FOXO3	FOXO3	FOXO3	11315	-0.1	0.16	NO
30	CREB1	CREB1	CREB1	11558	-0.11	0.16	NO
31	CDKN1A	CDKN1A	CDKN1A	11645	-0.12	0.17	NO
32	HBEGF	HBEGF	HBEGF	12340	-0.14	0.15	NO
33	MDM2	MDM2	MDM2	12599	-0.16	0.16	NO
34	PIK3R1	PIK3R1	PIK3R1	14710	-0.28	0.075	NO
35	EREG	EREG	EREG	16184	-0.42	0.047	NO
36	NRG1	NRG1	NRG1	16739	-0.5	0.08	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 MTOR 4PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: PID MTOR 4PATHWAY, 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 IGF1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	LDHD	LDHD	LDHD	588	0.52	0.039	YES
2	COQ2	COQ2	COQ2	854	0.43	0.084	YES
3	SLC25A4	SLC25A4	SLC25A4	983	0.39	0.13	YES
4	TIMM8A	TIMM8A	TIMM8A	1492	0.29	0.14	YES
5	FXC1	FXC1	FXC1	1686	0.27	0.17	YES
6	ATP5A1	ATP5A1	ATP5A1	1838	0.25	0.2	YES
7	CHCHD4	CHCHD4	CHCHD4	2021	0.23	0.22	YES
8	CYC1	CYC1	CYC1	2114	0.22	0.24	YES
9	FXN	FXN	FXN	2134	0.22	0.27	YES
10	ATP5B	ATP5B	ATP5B	2268	0.21	0.29	YES
11	COX17	COX17	COX17	2328	0.2	0.32	YES
12	GRPEL2	GRPEL2	GRPEL2	2333	0.2	0.35	YES
13	TIMM13	TIMM13	TIMM13	2475	0.19	0.36	YES
14	SLC25A12	SLC25A12	SLC25A12	2557	0.18	0.38	YES
15	CS	CS	CS	2598	0.18	0.41	YES
16	PMPCB	PMPCB	PMPCB	2607	0.18	0.43	YES
17	ACO2	ACO2	ACO2	2675	0.18	0.45	YES
18	DNAJC19	DNAJC19	DNAJC19	2882	0.16	0.46	YES
19	TOMM40	TOMM40	TOMM40	2919	0.16	0.48	YES
20	TIMM10	TIMM10	TIMM10	3037	0.15	0.5	YES
21	HSPA9	HSPA9	HSPA9	3141	0.15	0.51	YES
22	C18orf55	C18orf55	C18orf55	3144	0.15	0.54	YES
23	TIMM44	TIMM44	TIMM44	3146	0.15	0.56	YES
24	GFER	GFER	GFER	3347	0.14	0.56	YES
25	SLC25A6	SLC25A6	SLC25A6	3401	0.14	0.58	YES
26	MTX2	MTX2	MTX2	3413	0.13	0.6	YES
27	TIMM17B	TIMM17B	TIMM17B	3585	0.13	0.6	YES
28	TIMM50	TIMM50	TIMM50	3734	0.12	0.61	YES
29	ATP5G1	ATP5G1	ATP5G1	3820	0.12	0.62	YES
30	PMPCA	PMPCA	PMPCA	3920	0.11	0.64	YES
31	GRPEL1	GRPEL1	GRPEL1	4286	0.097	0.63	YES
32	VDAC1	VDAC1	VDAC1	4451	0.091	0.63	YES
33	TOMM22	TOMM22	TOMM22	4606	0.085	0.64	YES
34	IDH3G	IDH3G	IDH3G	5081	0.07	0.62	NO
35	SAMM50	SAMM50	SAMM50	5158	0.068	0.62	NO
36	TIMM9	TIMM9	TIMM9	6621	0.026	0.55	NO
37	TIMM8B	TIMM8B	TIMM8B	6678	0.025	0.55	NO
38	TIMM17A	TIMM17A	TIMM17A	7229	0.01	0.52	NO
39	TOMM7	TOMM7	TOMM7	7438	0.005	0.51	NO
40	HSPD1	HSPD1	HSPD1	7527	0.0028	0.5	NO
41	TOMM5	TOMM5	TOMM5	7907	-0.0075	0.48	NO
42	TIMM22	TIMM22	TIMM22	8331	-0.019	0.46	NO
43	SLC25A13	SLC25A13	SLC25A13	9743	-0.056	0.39	NO
44	HSCB	HSCB	HSCB	9857	-0.06	0.4	NO
45	TOMM20	TOMM20	TOMM20	10176	-0.068	0.39	NO
46	TAZ	TAZ	TAZ	10198	-0.069	0.4	NO
47	BCS1L	BCS1L	BCS1L	11063	-0.096	0.36	NO
48	MTX1	MTX1	MTX1	11500	-0.11	0.35	NO
49	TOMM70A	TOMM70A	TOMM70A	11720	-0.12	0.36	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 IGF1 PATHWAY.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: PID IGF1 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 PI3KCIAKTPATHWAY

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	PDP2	PDP2	PDP2	574	0.53	0.036	YES
2	NNT	NNT	NNT	1032	0.38	0.06	YES
3	PDP1	PDP1	PDP1	1133	0.35	0.1	YES
4	IDH3A	IDH3A	IDH3A	1167	0.35	0.14	YES
5	IDH2	IDH2	IDH2	1218	0.34	0.18	YES
6	L2HGDH	L2HGDH	L2HGDH	1664	0.27	0.2	YES
7	PDHX	PDHX	PDHX	1756	0.26	0.22	YES
8	SDHD	SDHD	SDHD	1969	0.24	0.24	YES
9	DLAT	DLAT	DLAT	1983	0.23	0.27	YES
10	PDHA1	PDHA1	PDHA1	2107	0.22	0.29	YES
11	PDHB	PDHB	PDHB	2176	0.22	0.32	YES
12	OGDH	OGDH	OGDH	2293	0.2	0.34	YES
13	BSG	BSG	BSG	2384	0.2	0.36	YES
14	SLC16A8	SLC16A8	SLC16A8	2394	0.2	0.38	YES
15	DLD	DLD	DLD	2415	0.2	0.41	YES
16	SDHA	SDHA	SDHA	2468	0.19	0.43	YES
17	FH	FH	FH	2496	0.19	0.45	YES
18	DLST	DLST	DLST	2525	0.19	0.48	YES
19	CS	CS	CS	2598	0.18	0.5	YES
20	SUCLG2	SUCLG2	SUCLG2	2609	0.18	0.52	YES
21	ACO2	ACO2	ACO2	2675	0.18	0.54	YES
22	SUCLG1	SUCLG1	SUCLG1	3222	0.14	0.52	YES
23	MDH2	MDH2	MDH2	3271	0.14	0.54	YES
24	LDHB	LDHB	LDHB	3436	0.13	0.55	YES
25	SUCLA2	SUCLA2	SUCLA2	4630	0.085	0.49	NO
26	SDHB	SDHB	SDHB	4870	0.077	0.49	NO
27	IDH3G	IDH3G	IDH3G	5081	0.07	0.49	NO
28	ADHFE1	ADHFE1	ADHFE1	5408	0.061	0.48	NO
29	IDH3B	IDH3B	IDH3B	5847	0.047	0.46	NO
30	SDHC	SDHC	SDHC	6336	0.034	0.44	NO
31	PDK3	PDK3	PDK3	6717	0.024	0.42	NO
32	PDPR	PDPR	PDPR	7828	-0.0052	0.36	NO
33	PDK2	PDK2	PDK2	10936	-0.092	0.2	NO
34	D2HGDH	D2HGDH	D2HGDH	11174	-0.1	0.2	NO
35	IDH1	IDH1	IDH1	11788	-0.12	0.18	NO
36	SLC16A1	SLC16A1	SLC16A1	11818	-0.12	0.2	NO
37	PDK4	PDK4	PDK4	13474	-0.2	0.13	NO
38	LDHA	LDHA	LDHA	13586	-0.2	0.15	NO
39	PDK1	PDK1	PDK1	14794	-0.29	0.12	NO
40	SLC16A3	SLC16A3	SLC16A3	16776	-0.5	0.078	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 PI3KCIAKTPATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: PID PI3KCIAKTPATHWAY, 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 PYRUVATE METABOLISM AND CITRIC ACID TCA CYCLE

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	ATP6V0A4	ATP6V0A4	ATP6V0A4	18	1.4	0.056	YES
2	ATP6V1B1	ATP6V1B1	ATP6V1B1	27	1.3	0.11	YES
3	ATP6V0D2	ATP6V0D2	ATP6V0D2	64	1.1	0.15	YES
4	ATP6V1C2	ATP6V1C2	ATP6V1C2	214	0.8	0.18	YES
5	ATP4B	ATP4B	ATP4B	700	0.47	0.17	YES
6	COX7A1	COX7A1	COX7A1	736	0.46	0.19	YES
7	ATP6V1A	ATP6V1A	ATP6V1A	908	0.41	0.2	YES
8	ATP6V1H	ATP6V1H	ATP6V1H	1253	0.33	0.19	YES
9	COX5A	COX5A	COX5A	1275	0.33	0.2	YES
10	ATP12A	ATP12A	ATP12A	1287	0.33	0.22	YES
11	ATP6V0B	ATP6V0B	ATP6V0B	1370	0.31	0.22	YES
12	UQCRFS1	UQCRFS1	UQCRFS1	1389	0.31	0.24	YES
13	NDUFA4	NDUFA4	NDUFA4	1463	0.3	0.24	YES
14	ATP6V0E2	ATP6V0E2	ATP6V0E2	1477	0.3	0.26	YES
15	NDUFA6	NDUFA6	NDUFA6	1485	0.29	0.27	YES
16	ATP6V1D	ATP6V1D	ATP6V1D	1530	0.29	0.28	YES
17	COX7B	COX7B	COX7B	1568	0.28	0.29	YES
18	COX8A	COX8A	COX8A	1580	0.28	0.3	YES
19	COX6C	COX6C	COX6C	1590	0.28	0.31	YES
20	ATP6V0C	ATP6V0C	ATP6V0C	1618	0.28	0.32	YES
21	UQCRC1	UQCRC1	UQCRC1	1668	0.27	0.33	YES
22	NDUFS7	NDUFS7	NDUFS7	1835	0.25	0.33	YES
23	ATP5A1	ATP5A1	ATP5A1	1838	0.25	0.34	YES
24	NDUFS8	NDUFS8	NDUFS8	1917	0.24	0.34	YES
25	UQCR10	UQCR10	UQCR10	1946	0.24	0.35	YES
26	NDUFA3	NDUFA3	NDUFA3	1955	0.24	0.36	YES
27	SDHD	SDHD	SDHD	1969	0.24	0.37	YES
28	NDUFA8	NDUFA8	NDUFA8	1994	0.23	0.38	YES
29	UQCR11	UQCR11	UQCR11	1998	0.23	0.39	YES
30	PPA2	PPA2	PPA2	2013	0.23	0.4	YES
31	COX6A1	COX6A1	COX6A1	2068	0.22	0.4	YES
32	NDUFB1	NDUFB1	NDUFB1	2101	0.22	0.41	YES
33	CYC1	CYC1	CYC1	2114	0.22	0.42	YES
34	ATP6AP1	ATP6AP1	ATP6AP1	2128	0.22	0.43	YES
35	NDUFV1	NDUFV1	NDUFV1	2252	0.21	0.43	YES
36	NDUFC2	NDUFC2	NDUFC2	2260	0.21	0.44	YES
37	ATP5L	ATP5L	ATP5L	2261	0.21	0.45	YES
38	ATP5B	ATP5B	ATP5B	2268	0.21	0.46	YES
39	ATP6V1E1	ATP6V1E1	ATP6V1E1	2314	0.2	0.46	YES
40	ATP5D	ATP5D	ATP5D	2316	0.2	0.47	YES
41	COX17	COX17	COX17	2328	0.2	0.48	YES
42	NDUFB7	NDUFB7	NDUFB7	2432	0.19	0.48	YES
43	SDHA	SDHA	SDHA	2468	0.19	0.49	YES
44	COX7A2	COX7A2	COX7A2	2476	0.19	0.49	YES
45	UQCRHL	UQCRHL	UQCRHL	2536	0.19	0.5	YES
46	NDUFA9	NDUFA9	NDUFA9	2614	0.18	0.5	YES
47	UQCRH	UQCRH	UQCRH	2621	0.18	0.51	YES
48	NDUFB2	NDUFB2	NDUFB2	2681	0.18	0.51	YES
49	NDUFB9	NDUFB9	NDUFB9	2721	0.17	0.52	YES
50	UQCRQ	UQCRQ	UQCRQ	2765	0.17	0.52	YES
51	NDUFA7	NDUFA7	NDUFA7	2789	0.17	0.53	YES
52	NDUFS3	NDUFS3	NDUFS3	2821	0.17	0.53	YES
53	NDUFB6	NDUFB6	NDUFB6	2858	0.16	0.54	YES
54	COX6B1	COX6B1	COX6B1	2859	0.16	0.55	YES
55	COX7C	COX7C	COX7C	2871	0.16	0.55	YES
56	ATP6V1F	ATP6V1F	ATP6V1F	2895	0.16	0.56	YES
57	ATP5I	ATP5I	ATP5I	2928	0.16	0.56	YES
58	NDUFA5	NDUFA5	NDUFA5	2948	0.16	0.57	YES
59	COX4I1	COX4I1	COX4I1	2983	0.16	0.57	YES
60	UQCRC2	UQCRC2	UQCRC2	3015	0.16	0.58	YES
61	NDUFA1	NDUFA1	NDUFA1	3099	0.15	0.58	YES
62	NDUFS6	NDUFS6	NDUFS6	3118	0.15	0.58	YES
63	ATP5E	ATP5E	ATP5E	3263	0.14	0.58	YES
64	ATP5J	ATP5J	ATP5J	3281	0.14	0.59	YES
65	COX5B	COX5B	COX5B	3298	0.14	0.59	YES
66	NDUFS1	NDUFS1	NDUFS1	3302	0.14	0.6	YES
67	ATP6V0D1	ATP6V0D1	ATP6V0D1	3335	0.14	0.6	YES
68	NDUFAB1	NDUFAB1	NDUFAB1	3337	0.14	0.61	YES
69	NDUFA11	NDUFA11	NDUFA11	3382	0.14	0.61	YES
70	UQCRB	UQCRB	UQCRB	3445	0.13	0.61	YES
71	NDUFV2	NDUFV2	NDUFV2	3483	0.13	0.62	YES
72	NDUFB5	NDUFB5	NDUFB5	3525	0.13	0.62	YES
73	ATP5G3	ATP5G3	ATP5G3	3612	0.13	0.62	YES
74	ATP6V1G1	ATP6V1G1	ATP6V1G1	3749	0.12	0.62	YES
75	ATP5J2	ATP5J2	ATP5J2	3753	0.12	0.62	YES
76	ATP5G1	ATP5G1	ATP5G1	3820	0.12	0.62	YES
77	ATP5O	ATP5O	ATP5O	3822	0.12	0.63	YES
78	NDUFS2	NDUFS2	NDUFS2	3993	0.11	0.62	NO
79	ATP6V0A2	ATP6V0A2	ATP6V0A2	4140	0.1	0.62	NO
80	NDUFB8	NDUFB8	NDUFB8	4141	0.1	0.62	NO
81	ATP6V0E1	ATP6V0E1	ATP6V0E1	4172	0.1	0.63	NO
82	COX7A2L	COX7A2L	COX7A2L	4254	0.098	0.63	NO
83	NDUFS4	NDUFS4	NDUFS4	4371	0.094	0.62	NO
84	NDUFB10	NDUFB10	NDUFB10	4377	0.094	0.63	NO
85	NDUFA10	NDUFA10	NDUFA10	4452	0.091	0.63	NO
86	NDUFB4	NDUFB4	NDUFB4	4664	0.084	0.62	NO
87	SDHB	SDHB	SDHB	4870	0.077	0.61	NO
88	NDUFA2	NDUFA2	NDUFA2	5009	0.073	0.6	NO
89	NDUFC1	NDUFC1	NDUFC1	5187	0.067	0.6	NO
90	ATP5F1	ATP5F1	ATP5F1	5291	0.064	0.6	NO
91	ATP5H	ATP5H	ATP5H	5384	0.061	0.59	NO
92	ATP5C1	ATP5C1	ATP5C1	5387	0.061	0.6	NO
93	NDUFV3	NDUFV3	NDUFV3	5492	0.058	0.59	NO
94	COX10	COX10	COX10	5998	0.043	0.57	NO
95	NDUFB3	NDUFB3	NDUFB3	6023	0.043	0.57	NO
96	COX4I2	COX4I2	COX4I2	6222	0.037	0.56	NO
97	SDHC	SDHC	SDHC	6336	0.034	0.55	NO
98	ATP6V1C1	ATP6V1C1	ATP6V1C1	6393	0.033	0.55	NO
99	ATP6V1E2	ATP6V1E2	ATP6V1E2	6746	0.023	0.53	NO
100	NDUFS5	NDUFS5	NDUFS5	6865	0.02	0.53	NO
101	ATP5G2	ATP5G2	ATP5G2	7295	0.0086	0.5	NO
102	PPA1	PPA1	PPA1	9674	-0.054	0.37	NO
103	TCIRG1	TCIRG1	TCIRG1	9703	-0.055	0.37	NO
104	COX11	COX11	COX11	9730	-0.055	0.38	NO
105	COX15	COX15	COX15	10430	-0.077	0.34	NO
106	COX6B2	COX6B2	COX6B2	11082	-0.097	0.31	NO
107	ATP6V1B2	ATP6V1B2	ATP6V1B2	12631	-0.16	0.23	NO
108	ATP6V1G2	ATP6V1G2	ATP6V1G2	14628	-0.27	0.13	NO
109	ATP6V0A1	ATP6V0A1	ATP6V0A1	14716	-0.28	0.14	NO
110	NDUFA4L2	NDUFA4L2	NDUFA4L2	15125	-0.31	0.13	NO
111	LHPP	LHPP	LHPP	15201	-0.32	0.14	NO
112	COX6A2	COX6A2	COX6A2	15416	-0.34	0.14	NO
113	COX8C	COX8C	COX8C	15716	-0.37	0.14	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: REACTOME PYRUVATE METABOLISM AND CITRIC ACID TCA CYCLE.

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

genes ES table in pathway: REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT

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	ERBB4	ERBB4	ERBB4	79	1.1	0.11	YES
2	NRG4	NRG4	NRG4	147	0.91	0.2	YES
3	NRG2	NRG2	NRG2	208	0.8	0.28	YES
4	EGF	EGF	EGF	320	0.7	0.35	YES
5	BTC	BTC	BTC	529	0.56	0.4	YES
6	NR4A1	NR4A1	NR4A1	1046	0.38	0.41	YES
7	FOXO1	FOXO1	FOXO1	1339	0.32	0.42	YES
8	PHLPP1	PHLPP1	PHLPP1	1375	0.31	0.46	YES
9	THEM4	THEM4	THEM4	2835	0.17	0.39	NO
10	AKT1	AKT1	AKT1	3207	0.14	0.39	NO
11	AKT2	AKT2	AKT2	3383	0.14	0.39	NO
12	RICTOR	RICTOR	RICTOR	3581	0.13	0.39	NO
13	PDPK1	PDPK1	PDPK1	4080	0.1	0.38	NO
14	ERBB2	ERBB2	ERBB2	4143	0.1	0.38	NO
15	MAPKAP1	MAPKAP1	MAPKAP1	4374	0.094	0.38	NO
16	MLST8	MLST8	MLST8	4591	0.086	0.38	NO
17	MTOR	MTOR	MTOR	4740	0.081	0.38	NO
18	GSK3A	GSK3A	GSK3A	4985	0.074	0.37	NO
19	RPS6KB2	RPS6KB2	RPS6KB2	5663	0.054	0.34	NO
20	PIK3CA	PIK3CA	PIK3CA	5945	0.045	0.33	NO
21	BAD	BAD	BAD	6190	0.038	0.32	NO
22	CHUK	CHUK	CHUK	6454	0.031	0.31	NO
23	TSC2	TSC2	TSC2	6789	0.022	0.3	NO
24	FOXO4	FOXO4	FOXO4	6847	0.02	0.29	NO
25	TRIB3	TRIB3	TRIB3	8148	-0.014	0.22	NO
26	AKT1S1	AKT1S1	AKT1S1	8654	-0.027	0.2	NO
27	CASP9	CASP9	CASP9	10428	-0.076	0.11	NO
28	CDKN1B	CDKN1B	CDKN1B	10906	-0.091	0.092	NO
29	PTEN	PTEN	PTEN	11267	-0.1	0.084	NO
30	AKT3	AKT3	AKT3	11294	-0.1	0.093	NO
31	FOXO3	FOXO3	FOXO3	11315	-0.1	0.1	NO
32	CREB1	CREB1	CREB1	11558	-0.11	0.1	NO
33	CDKN1A	CDKN1A	CDKN1A	11645	-0.12	0.11	NO
34	GRB2	GRB2	GRB2	11942	-0.13	0.11	NO
35	HBEGF	HBEGF	HBEGF	12340	-0.14	0.099	NO
36	MDM2	MDM2	MDM2	12599	-0.16	0.1	NO
37	GAB1	GAB1	GAB1	12662	-0.16	0.12	NO
38	EGFR	EGFR	EGFR	13398	-0.19	0.095	NO
39	PIK3R1	PIK3R1	PIK3R1	14710	-0.28	0.052	NO
40	ERBB3	ERBB3	ERBB3	16163	-0.42	0.016	NO
41	EREG	EREG	EREG	16184	-0.42	0.058	NO
42	NRG1	NRG1	NRG1	16739	-0.5	0.08	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: REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME TCA CYCLE AND RESPIRATORY ELECTRON TRANSPORT, 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 ERBB4

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	ERBB4	ERBB4	ERBB4	79	1.1	0.12	YES
2	NRG4	NRG4	NRG4	147	0.91	0.22	YES
3	NRG2	NRG2	NRG2	208	0.8	0.3	YES
4	PGR	PGR	PGR	492	0.58	0.35	YES
5	PRLR	PRLR	PRLR	524	0.56	0.42	YES
6	BTC	BTC	BTC	529	0.56	0.48	YES
7	GFAP	GFAP	GFAP	613	0.5	0.53	YES
8	APH1B	APH1B	APH1B	1872	0.24	0.49	NO
9	SH2B1	SH2B1	SH2B1	2848	0.16	0.45	NO
10	PSEN2	PSEN2	PSEN2	3121	0.15	0.46	NO
11	GHR	GHR	GHR	4216	0.1	0.41	NO
12	PSEN1	PSEN1	PSEN1	4891	0.076	0.38	NO
13	SKP1	SKP1	SKP1	5298	0.064	0.36	NO
14	CUL1	CUL1	CUL1	5932	0.045	0.33	NO
15	YAP1	YAP1	YAP1	6114	0.04	0.33	NO
16	TAB2	TAB2	TAB2	6201	0.038	0.33	NO
17	RBX1	RBX1	RBX1	6529	0.029	0.31	NO
18	APH1A	APH1A	APH1A	7856	-0.0059	0.24	NO
19	JAK2	JAK2	JAK2	8340	-0.019	0.22	NO
20	PSENEN	PSENEN	PSENEN	8853	-0.031	0.19	NO
21	NCOR1	NCOR1	NCOR1	9460	-0.048	0.16	NO
22	STAT5B	STAT5B	STAT5B	9815	-0.059	0.15	NO
23	NCSTN	NCSTN	NCSTN	10320	-0.073	0.13	NO
24	WWOX	WWOX	WWOX	10668	-0.083	0.12	NO
25	BTRC	BTRC	BTRC	10972	-0.093	0.12	NO
26	ADAM17	ADAM17	ADAM17	11945	-0.13	0.076	NO
27	HBEGF	HBEGF	HBEGF	12340	-0.14	0.07	NO
28	STAT5A	STAT5A	STAT5A	12373	-0.14	0.085	NO
29	GH1	GH1	GH1	13191	-0.18	0.06	NO
30	S100B	S100B	S100B	14963	-0.3	-0.0031	NO
31	CXCL12	CXCL12	CXCL12	15389	-0.34	0.012	NO
32	ESR1	ESR1	ESR1	15513	-0.35	0.044	NO
33	EREG	EREG	EREG	16184	-0.42	0.054	NO
34	NRG1	NRG1	NRG1	16739	-0.5	0.08	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: REACTOME SIGNALING BY ERBB4.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: REACTOME SIGNALING BY ERBB4, 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 ETHER LIPID METABOLISM	27	genes.ES.table	0.48	1.4	0.071	0.2	1	0.26	0.17	0.22	0.15	0
KEGG RIBOSOME	85	genes.ES.table	0.48	1.3	0.26	0.23	1	0.86	0.48	0.45	0.18	0
KEGG DNA REPLICATION	36	genes.ES.table	0.47	1.5	0.13	0.15	0.97	0.69	0.46	0.37	0.11	0.001
KEGG HOMOLOGOUS RECOMBINATION	26	genes.ES.table	0.72	1.8	0.0021	0.93	0.5	0.31	0.1	0.28	0.25	0.23
KEGG MAPK SIGNALING PATHWAY	245	genes.ES.table	0.43	1.6	0.011	0.16	0.91	0.44	0.31	0.31	0.1	0.002
KEGG CALCIUM SIGNALING PATHWAY	168	genes.ES.table	0.54	1.6	0.0081	0.16	0.92	0.48	0.23	0.38	0.1	0.002
KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION	238	genes.ES.table	0.64	1.6	0.0042	0.18	0.89	0.54	0.18	0.44	0.11	0.009
KEGG CHEMOKINE SIGNALING PATHWAY	183	genes.ES.table	0.6	1.6	0.013	0.18	0.86	0.44	0.21	0.35	0.11	0.018
KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION	224	genes.ES.table	0.57	1.5	0.0021	0.16	0.95	0.5	0.2	0.4	0.1	0.002
KEGG CELL CYCLE	118	genes.ES.table	0.5	1.6	0.055	0.18	0.88	0.3	0.22	0.23	0.11	0.012

genes ES table in pathway: KEGG ETHER LIPID 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	AIM2	AIM2	AIM2	25	0.78	0.095	YES
2	IL6	IL6	IL6	39	0.74	0.18	YES
3	ZBP1	ZBP1	ZBP1	456	0.51	0.22	YES
4	CCL5	CCL5	CCL5	875	0.43	0.25	YES
5	CCL4	CCL4	CCL4	925	0.42	0.3	YES
6	CXCL10	CXCL10	CXCL10	1080	0.4	0.34	YES
7	TMEM173	TMEM173	TMEM173	1133	0.39	0.39	YES
8	IL33	IL33	IL33	1436	0.36	0.42	YES
9	IL1B	IL1B	IL1B	1465	0.36	0.46	YES
10	RIPK3	RIPK3	RIPK3	1802	0.32	0.48	YES
11	CASP1	CASP1	CASP1	2147	0.29	0.5	YES
12	POLR3G	POLR3G	POLR3G	2198	0.28	0.53	YES
13	CCL4L2	CCL4L2	CCL4L2	2216	0.28	0.56	YES
14	IFNB1	IFNB1	IFNB1	2494	0.26	0.58	YES
15	PYCARD	PYCARD	PYCARD	2639	0.25	0.6	YES
16	IKBKE	IKBKE	IKBKE	2673	0.24	0.63	YES
17	IRF7	IRF7	IRF7	2719	0.24	0.66	YES
18	DDX58	DDX58	DDX58	4694	0.13	0.56	NO
19	POLR3C	POLR3C	POLR3C	5626	0.093	0.52	NO
20	TBK1	TBK1	TBK1	6493	0.071	0.48	NO
21	POLR3D	POLR3D	POLR3D	6694	0.066	0.48	NO
22	POLR3GL	POLR3GL	POLR3GL	6710	0.066	0.49	NO
23	ADAR	ADAR	ADAR	6934	0.061	0.48	NO
24	POLR3A	POLR3A	POLR3A	7447	0.05	0.46	NO
25	POLR3H	POLR3H	POLR3H	7626	0.047	0.46	NO
26	RIPK1	RIPK1	RIPK1	7629	0.047	0.46	NO
27	NFKBIA	NFKBIA	NFKBIA	8275	0.036	0.43	NO
28	RELA	RELA	RELA	8385	0.034	0.43	NO
29	POLR1D	POLR1D	POLR1D	9017	0.024	0.4	NO
30	IRF3	IRF3	IRF3	9378	0.018	0.38	NO
31	IKBKG	IKBKG	IKBKG	9977	0.0086	0.35	NO
32	NFKB1	NFKB1	NFKB1	10698	-0.0022	0.31	NO
33	IL18	IL18	IL18	11272	-0.011	0.28	NO
34	POLR3F	POLR3F	POLR3F	11540	-0.015	0.27	NO
35	IKBKB	IKBKB	IKBKB	11716	-0.018	0.26	NO
36	POLR1C	POLR1C	POLR1C	12381	-0.029	0.23	NO
37	MAVS	MAVS	MAVS	13274	-0.047	0.18	NO
38	TREX1	TREX1	TREX1	13848	-0.059	0.16	NO
39	POLR3K	POLR3K	POLR3K	13985	-0.061	0.16	NO
40	CHUK	CHUK	CHUK	14184	-0.066	0.16	NO
41	NFKBIB	NFKBIB	NFKBIB	14833	-0.084	0.13	NO
42	POLR3B	POLR3B	POLR3B	15130	-0.093	0.13	NO
43	IFNA13	IFNA13	IFNA13	16309	-0.14	0.079	NO
44	IFNA1	IFNA1	IFNA1	17098	-0.21	0.06	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 ETHER LIPID METABOLISM.

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

genes ES table in pathway: KEGG RIBOSOME

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	ACAN	ACAN	ACAN	156	0.6	0.088	YES
2	LUM	LUM	LUM	195	0.59	0.18	YES
3	B3GNT4	B3GNT4	B3GNT4	255	0.56	0.27	YES
4	CHST1	CHST1	CHST1	259	0.56	0.36	YES
5	FMOD	FMOD	FMOD	323	0.55	0.44	YES
6	PRELP	PRELP	PRELP	458	0.51	0.51	YES
7	OMD	OMD	OMD	1157	0.39	0.54	YES
8	OGN	OGN	OGN	1410	0.36	0.58	YES
9	KERA	KERA	KERA	1550	0.35	0.63	YES
10	CHST2	CHST2	CHST2	1867	0.31	0.66	YES
11	CHST6	CHST6	CHST6	2177	0.28	0.69	YES
12	ST3GAL2	ST3GAL2	ST3GAL2	4076	0.16	0.61	NO
13	B3GNT7	B3GNT7	B3GNT7	4198	0.15	0.63	NO
14	B4GALT1	B4GALT1	B4GALT1	6308	0.075	0.52	NO
15	ST3GAL3	ST3GAL3	ST3GAL3	6728	0.065	0.51	NO
16	B4GALT3	B4GALT3	B4GALT3	6955	0.06	0.51	NO
17	B4GALT2	B4GALT2	B4GALT2	7198	0.055	0.5	NO
18	B3GNT2	B3GNT2	B3GNT2	7261	0.054	0.51	NO
19	HEXB	HEXB	HEXB	9106	0.022	0.41	NO
20	HEXA	HEXA	HEXA	9385	0.018	0.4	NO
21	ST3GAL1	ST3GAL1	ST3GAL1	9408	0.018	0.4	NO
22	B4GALT4	B4GALT4	B4GALT4	9820	0.011	0.38	NO
23	GNS	GNS	GNS	10285	0.0041	0.35	NO
24	B3GNT1	B3GNT1	B3GNT1	11060	-0.0077	0.31	NO
25	ST3GAL6	ST3GAL6	ST3GAL6	11672	-0.017	0.28	NO
26	B4GALT5	B4GALT5	B4GALT5	12627	-0.034	0.23	NO
27	B3GNT3	B3GNT3	B3GNT3	14365	-0.07	0.15	NO
28	CHST5	CHST5	CHST5	15153	-0.094	0.12	NO
29	GLB1	GLB1	GLB1	15256	-0.098	0.13	NO
30	B4GALT6	B4GALT6	B4GALT6	16991	-0.2	0.066	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 RIBOSOME.

Figure S24. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RIBOSOME, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG DNA REPLICATION

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	SNAI1	SNAI1	SNAI1	272	0.56	0.099	YES
2	PPP1R14A	PPP1R14A	PPP1R14A	1077	0.4	0.14	YES
3	PARVG	PARVG	PARVG	1891	0.31	0.16	YES
4	ACTN1	ACTN1	ACTN1	2652	0.25	0.16	YES
5	MYL9	MYL9	MYL9	2732	0.24	0.21	YES
6	ARHGEF6	ARHGEF6	ARHGEF6	2810	0.24	0.25	YES
7	TACC3	TACC3	TACC3	2936	0.23	0.29	YES
8	ZEB1	ZEB1	ZEB1	3120	0.21	0.32	YES
9	LIMS1	LIMS1	LIMS1	3203	0.21	0.36	YES
10	AURKA	AURKA	AURKA	3760	0.17	0.37	YES
11	PARVB	PARVB	PARVB	4210	0.15	0.37	YES
12	CCND1	CCND1	CCND1	4707	0.13	0.37	YES
13	JUN	JUN	JUN	4804	0.12	0.39	YES
14	RHOG	RHOG	RHOG	4949	0.12	0.41	YES
15	PARVA	PARVA	PARVA	5201	0.11	0.42	YES
16	GIT2	GIT2	GIT2	5242	0.1	0.43	YES
17	PXN	PXN	PXN	5350	0.1	0.45	YES
18	TNS1	TNS1	TNS1	5494	0.097	0.46	YES
19	PPP1R12A	PPP1R12A	PPP1R12A	6019	0.083	0.45	YES
20	PARP1	PARP1	PARP1	6073	0.082	0.46	YES
21	CREB1	CREB1	CREB1	6311	0.075	0.46	YES
22	IQGAP1	IQGAP1	IQGAP1	6422	0.072	0.47	YES
23	LIMS2	LIMS2	LIMS2	6490	0.071	0.48	YES
24	NACA	NACA	NACA	7269	0.054	0.45	NO
25	NCK2	NCK2	NCK2	7304	0.053	0.46	NO
26	ZYX	ZYX	ZYX	7359	0.052	0.47	NO
27	CKAP5	CKAP5	CKAP5	7366	0.052	0.48	NO
28	PPP1R14B	PPP1R14B	PPP1R14B	8256	0.036	0.44	NO
29	XPO1	XPO1	XPO1	8321	0.035	0.44	NO
30	CDC42	CDC42	CDC42	8943	0.025	0.41	NO
31	ARHGEF7	ARHGEF7	ARHGEF7	8948	0.025	0.42	NO
32	ILK	ILK	ILK	9077	0.023	0.42	NO
33	RAC1	RAC1	RAC1	9290	0.02	0.41	NO
34	ELMO2	ELMO2	ELMO2	9567	0.015	0.4	NO
35	CTNNB1	CTNNB1	CTNNB1	9644	0.014	0.39	NO
36	RICTOR	RICTOR	RICTOR	10230	0.0048	0.36	NO
37	RUVBL2	RUVBL2	RUVBL2	10480	0.00092	0.35	NO
38	CDC37	CDC37	CDC37	11186	-0.0093	0.31	NO
39	AKT1	AKT1	AKT1	11800	-0.02	0.28	NO
40	DIAPH1	DIAPH1	DIAPH1	11864	-0.021	0.28	NO
41	ILKAP	ILKAP	ILKAP	13282	-0.047	0.22	NO
42	GSK3B	GSK3B	GSK3B	13818	-0.058	0.2	NO
43	PPP1R14C	PPP1R14C	PPP1R14C	14072	-0.063	0.2	NO
44	RUVBL1	RUVBL1	RUVBL1	14571	-0.076	0.18	NO
45	HSP90AA1	HSP90AA1	HSP90AA1	14586	-0.077	0.2	NO

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

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

genes ES table in pathway: KEGG HOMOLOGOUS RECOMBINATION

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	BLM	BLM	BLM	446	0.51	0.11	YES
2	RAD54B	RAD54B	RAD54B	966	0.42	0.19	YES
3	RAD51	RAD51	RAD51	1058	0.4	0.29	YES
4	RAD54L	RAD54L	RAD54L	1100	0.4	0.39	YES
5	BRCA2	BRCA2	BRCA2	1199	0.39	0.49	YES
6	EME1	EME1	EME1	1232	0.38	0.59	YES
7	RPA4	RPA4	RPA4	1823	0.32	0.64	YES
8	XRCC2	XRCC2	XRCC2	1895	0.31	0.72	YES
9	POLD3	POLD3	POLD3	4689	0.13	0.6	NO
10	MRE11A	MRE11A	MRE11A	5601	0.094	0.57	NO
11	NBN	NBN	NBN	5609	0.093	0.6	NO
12	POLD4	POLD4	POLD4	6553	0.069	0.56	NO
13	RPA2	RPA2	RPA2	8111	0.038	0.49	NO
14	SHFM1	SHFM1	SHFM1	9047	0.023	0.44	NO
15	RAD51C	RAD51C	RAD51C	9174	0.021	0.44	NO
16	SSBP1	SSBP1	SSBP1	9684	0.013	0.41	NO
17	RPA1	RPA1	RPA1	9811	0.011	0.41	NO
18	RAD50	RAD50	RAD50	10165	0.0059	0.39	NO
19	RAD52	RAD52	RAD52	10393	0.0024	0.38	NO
20	TOP3A	TOP3A	TOP3A	10648	-0.0015	0.37	NO
21	POLD1	POLD1	POLD1	11171	-0.0091	0.34	NO
22	POLD2	POLD2	POLD2	11686	-0.018	0.32	NO
23	MUS81	MUS81	MUS81	12090	-0.024	0.3	NO
24	XRCC3	XRCC3	XRCC3	12325	-0.029	0.3	NO
25	RPA3	RPA3	RPA3	12623	-0.034	0.29	NO
26	TOP3B	TOP3B	TOP3B	14332	-0.069	0.21	NO

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

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

genes ES table in pathway: KEGG MAPK SIGNALING 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	IL1R2	IL1R2	IL1R2	5	0.89	0.055	YES
2	IL6	IL6	IL6	39	0.74	0.099	YES
3	IL2RA	IL2RA	IL2RA	54	0.69	0.14	YES
4	HGF	HGF	HGF	409	0.52	0.15	YES
5	NOD2	NOD2	NOD2	426	0.52	0.18	YES
6	IL2RB	IL2RB	IL2RB	541	0.49	0.21	YES
7	LCK	LCK	LCK	580	0.48	0.24	YES
8	JAK3	JAK3	JAK3	733	0.45	0.26	YES
9	IL2RG	IL2RG	IL2RG	786	0.45	0.28	YES
10	IL1RAP	IL1RAP	IL1RAP	862	0.43	0.3	YES
11	IL7R	IL7R	IL7R	878	0.43	0.33	YES
12	IL2	IL2	IL2	1027	0.41	0.35	YES
13	CDK1	CDK1	CDK1	1064	0.4	0.37	YES
14	CSF2RB	CSF2RB	CSF2RB	1089	0.4	0.39	YES
15	IL3RA	IL3RA	IL3RA	1118	0.4	0.42	YES
16	VAV1	VAV1	VAV1	1268	0.38	0.43	YES
17	IL1RN	IL1RN	IL1RN	1303	0.37	0.45	YES
18	IL1B	IL1B	IL1B	1465	0.36	0.47	YES
19	IL7	IL7	IL7	1680	0.33	0.48	YES
20	CSF2	CSF2	CSF2	1699	0.33	0.49	YES
21	IRAK3	IRAK3	IRAK3	2043	0.3	0.49	YES
22	CSF2RA	CSF2RA	CSF2RA	2093	0.29	0.51	YES
23	CASP1	CASP1	CASP1	2147	0.29	0.52	YES
24	HCK	HCK	HCK	2167	0.29	0.54	YES
25	SOCS3	SOCS3	SOCS3	2188	0.28	0.56	YES
26	MAP3K8	MAP3K8	MAP3K8	2496	0.26	0.56	YES
27	RIPK2	RIPK2	RIPK2	2853	0.23	0.55	YES
28	LYN	LYN	LYN	3020	0.22	0.56	YES
29	IL1R1	IL1R1	IL1R1	3078	0.22	0.57	YES
30	SHC1	SHC1	SHC1	3096	0.22	0.58	YES
31	IL6ST	IL6ST	IL6ST	3331	0.2	0.58	YES
32	PELI1	PELI1	PELI1	3508	0.19	0.58	YES
33	FYN	FYN	FYN	3583	0.18	0.59	YES
34	IL1A	IL1A	IL1A	4051	0.16	0.57	NO
35	TMEM189-UBE2V1	TMEM189-UBE2V1	TMEM189-UBE2V1	4522	0.13	0.55	NO
36	PIK3CD	PIK3CD	PIK3CD	4559	0.13	0.56	NO
37	STAT1	STAT1	STAT1	4591	0.13	0.57	NO
38	JAK2	JAK2	JAK2	4729	0.12	0.57	NO
39	MYD88	MYD88	MYD88	4748	0.12	0.57	NO
40	PIK3R1	PIK3R1	PIK3R1	4819	0.12	0.58	NO
41	NFKB2	NFKB2	NFKB2	5574	0.094	0.54	NO
42	CRKL	CRKL	CRKL	5585	0.094	0.55	NO
43	NRAS	NRAS	NRAS	5632	0.092	0.55	NO
44	NOD1	NOD1	NOD1	5682	0.091	0.55	NO
45	IL5RA	IL5RA	IL5RA	5767	0.089	0.55	NO
46	IRAK2	IRAK2	IRAK2	5886	0.086	0.55	NO
47	CBL	CBL	CBL	6082	0.081	0.55	NO
48	MAP2K1	MAP2K1	MAP2K1	6443	0.072	0.53	NO
49	SOS1	SOS1	SOS1	6632	0.068	0.52	NO
50	PTPN6	PTPN6	PTPN6	6659	0.067	0.53	NO
51	STAT5A	STAT5A	STAT5A	6673	0.067	0.53	NO
52	YWHAZ	YWHAZ	YWHAZ	6733	0.065	0.53	NO
53	STAT3	STAT3	STAT3	6793	0.064	0.53	NO
54	SYK	SYK	SYK	6805	0.064	0.54	NO
55	PIK3CA	PIK3CA	PIK3CA	6830	0.063	0.54	NO
56	PIK3R3	PIK3R3	PIK3R3	7200	0.055	0.52	NO
57	CUL1	CUL1	CUL1	7436	0.05	0.51	NO
58	TAB2	TAB2	TAB2	7699	0.046	0.5	NO
59	MAP2K6	MAP2K6	MAP2K6	7719	0.045	0.5	NO
60	MAPK1	MAPK1	MAPK1	8062	0.039	0.48	NO
61	RBX1	RBX1	RBX1	8235	0.036	0.48	NO
62	RELA	RELA	RELA	8385	0.034	0.47	NO
63	IRAK1	IRAK1	IRAK1	8437	0.033	0.47	NO
64	TNIP2	TNIP2	TNIP2	8679	0.029	0.46	NO
65	PTK2B	PTK2B	PTK2B	8891	0.026	0.45	NO
66	IRAK4	IRAK4	IRAK4	8945	0.025	0.45	NO
67	IL5	IL5	IL5	9048	0.023	0.44	NO
68	MAPK3	MAPK3	MAPK3	9142	0.022	0.44	NO
69	UBE2N	UBE2N	UBE2N	9359	0.018	0.43	NO
70	TYK2	TYK2	TYK2	9540	0.016	0.42	NO
71	JAK1	JAK1	JAK1	9605	0.014	0.42	NO
72	RAPGEF1	RAPGEF1	RAPGEF1	9666	0.013	0.42	NO
73	CRK	CRK	CRK	9824	0.011	0.41	NO
74	MAP3K7	MAP3K7	MAP3K7	9835	0.011	0.41	NO
75	IKBKG	IKBKG	IKBKG	9977	0.0086	0.4	NO
76	YWHAB	YWHAB	YWHAB	10047	0.0076	0.4	NO
77	GRB2	GRB2	GRB2	10108	0.0067	0.39	NO
78	PIK3CB	PIK3CB	PIK3CB	10152	0.006	0.39	NO
79	BLNK	BLNK	BLNK	10198	0.0054	0.39	NO
80	GAB2	GAB2	GAB2	10254	0.0045	0.39	NO
81	IL6R	IL6R	IL6R	10469	0.0011	0.38	NO
82	MAP3K3	MAP3K3	MAP3K3	10797	-0.0038	0.36	NO
83	YES1	YES1	YES1	10870	-0.0048	0.35	NO
84	MAP2K2	MAP2K2	MAP2K2	10960	-0.0062	0.35	NO
85	SKP1	SKP1	SKP1	11074	-0.0079	0.34	NO
86	IL18	IL18	IL18	11272	-0.011	0.33	NO
87	MAP2K4	MAP2K4	MAP2K4	11518	-0.015	0.32	NO
88	SQSTM1	SQSTM1	SQSTM1	11521	-0.015	0.32	NO
89	STAT5B	STAT5B	STAT5B	11568	-0.016	0.32	NO
90	PRKACB	PRKACB	PRKACB	11569	-0.016	0.32	NO
91	TRAF6	TRAF6	TRAF6	11607	-0.016	0.32	NO
92	IKBKB	IKBKB	IKBKB	11716	-0.018	0.32	NO
93	INPPL1	INPPL1	INPPL1	12149	-0.026	0.29	NO
94	RAF1	RAF1	RAF1	12262	-0.027	0.29	NO
95	HRAS	HRAS	HRAS	12430	-0.03	0.28	NO
96	TAB1	TAB1	TAB1	12859	-0.038	0.26	NO
97	TAB3	TAB3	TAB3	13096	-0.043	0.25	NO
98	PIK3R2	PIK3R2	PIK3R2	13129	-0.044	0.25	NO
99	PELI2	PELI2	PELI2	13223	-0.046	0.25	NO
100	BTRC	BTRC	BTRC	13309	-0.047	0.25	NO
101	KRAS	KRAS	KRAS	13554	-0.052	0.24	NO
102	PELI3	PELI3	PELI3	13792	-0.058	0.23	NO
103	CHUK	CHUK	CHUK	14184	-0.066	0.21	NO
104	TEC	TEC	TEC	14827	-0.084	0.18	NO
105	TOLLIP	TOLLIP	TOLLIP	16067	-0.13	0.12	NO

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

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

genes ES table in pathway: KEGG CALCIUM SIGNALING PATHWAY

Table S16. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GZMB	GZMB	GZMB	341	0.54	0.076	YES
2	BIRC3	BIRC3	BIRC3	1081	0.4	0.1	YES
3	PRF1	PRF1	PRF1	1359	0.37	0.16	YES
4	LMNB1	LMNB1	LMNB1	1480	0.35	0.21	YES
5	TFAP2A	TFAP2A	TFAP2A	1744	0.32	0.25	YES
6	CASP1	CASP1	CASP1	2147	0.29	0.28	YES
7	ARHGDIB	ARHGDIB	ARHGDIB	2950	0.22	0.28	YES
8	BID	BID	BID	2955	0.22	0.32	YES
9	VIM	VIM	VIM	3207	0.21	0.34	YES
10	CASP4	CASP4	CASP4	3309	0.2	0.37	YES
11	CASP10	CASP10	CASP10	3569	0.18	0.38	YES
12	ACTA1	ACTA1	ACTA1	4298	0.14	0.37	YES
13	LIMK1	LIMK1	LIMK1	4633	0.13	0.37	YES
14	CASP3	CASP3	CASP3	4877	0.12	0.38	YES
15	CASP8	CASP8	CASP8	5005	0.11	0.4	YES
16	TNF	TNF	TNF	5070	0.11	0.41	YES
17	CASP7	CASP7	CASP7	5287	0.1	0.42	YES
18	TNFRSF1A	TNFRSF1A	TNFRSF1A	5388	0.1	0.43	YES
19	APAF1	APAF1	APAF1	5417	0.099	0.44	YES
20	PARP1	PARP1	PARP1	6073	0.082	0.42	NO
21	BIRC2	BIRC2	BIRC2	6415	0.072	0.42	NO
22	RIPK1	RIPK1	RIPK1	7629	0.047	0.36	NO
23	TOP1	TOP1	TOP1	7665	0.046	0.36	NO
24	PTK2	PTK2	PTK2	8165	0.038	0.34	NO
25	CASP2	CASP2	CASP2	8175	0.037	0.35	NO
26	GSN	GSN	GSN	8354	0.034	0.35	NO
27	DFFB	DFFB	DFFB	8594	0.03	0.34	NO
28	TRADD	TRADD	TRADD	9398	0.018	0.3	NO
29	MADD	MADD	MADD	9523	0.016	0.29	NO
30	XIAP	XIAP	XIAP	9576	0.015	0.29	NO
31	CFL2	CFL2	CFL2	9689	0.013	0.29	NO
32	BAX	BAX	BAX	9825	0.011	0.28	NO
33	LMNA	LMNA	LMNA	10086	0.007	0.27	NO
34	LMNB2	LMNB2	LMNB2	10325	0.0035	0.26	NO
35	CASP6	CASP6	CASP6	10438	0.0015	0.25	NO
36	NUMA1	NUMA1	NUMA1	11529	-0.015	0.19	NO
37	DIABLO	DIABLO	DIABLO	11857	-0.021	0.18	NO
38	CASP9	CASP9	CASP9	11983	-0.023	0.18	NO
39	APP	APP	APP	12088	-0.024	0.18	NO
40	CRADD	CRADD	CRADD	12673	-0.035	0.15	NO
41	SLK	SLK	SLK	12921	-0.04	0.14	NO
42	DFFA	DFFA	DFFA	13073	-0.043	0.14	NO
43	TRAF2	TRAF2	TRAF2	13448	-0.05	0.13	NO
44	SPTAN1	SPTAN1	SPTAN1	14012	-0.062	0.11	NO
45	KRT18	KRT18	KRT18	14174	-0.066	0.11	NO
46	SREBF1	SREBF1	SREBF1	14333	-0.069	0.12	NO
47	SATB1	SATB1	SATB1	14613	-0.078	0.11	NO
48	MAP3K1	MAP3K1	MAP3K1	14903	-0.086	0.11	NO
49	GAS2	GAS2	GAS2	15757	-0.12	0.086	NO
50	BCL2	BCL2	BCL2	16136	-0.14	0.089	NO
51	CYCS	CYCS	CYCS	16249	-0.14	0.11	NO

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

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

genes ES table in pathway: KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION

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	ACAN	ACAN	ACAN	156	0.6	0.09	YES
2	LUM	LUM	LUM	195	0.59	0.18	YES
3	B3GNT4	B3GNT4	B3GNT4	255	0.56	0.27	YES
4	CHST1	CHST1	CHST1	259	0.56	0.36	YES
5	FMOD	FMOD	FMOD	323	0.55	0.45	YES
6	PRELP	PRELP	PRELP	458	0.51	0.52	YES
7	OMD	OMD	OMD	1157	0.39	0.55	YES
8	OGN	OGN	OGN	1410	0.36	0.6	YES
9	KERA	KERA	KERA	1550	0.35	0.64	YES
10	CHST2	CHST2	CHST2	1867	0.31	0.68	YES
11	CHST6	CHST6	CHST6	2177	0.28	0.71	YES
12	ST3GAL2	ST3GAL2	ST3GAL2	4076	0.16	0.63	NO
13	B3GNT7	B3GNT7	B3GNT7	4198	0.15	0.65	NO
14	B4GALT1	B4GALT1	B4GALT1	6308	0.075	0.54	NO
15	ST3GAL3	ST3GAL3	ST3GAL3	6728	0.065	0.53	NO
16	B4GALT3	B4GALT3	B4GALT3	6955	0.06	0.53	NO
17	B4GALT2	B4GALT2	B4GALT2	7198	0.055	0.52	NO
18	B3GNT2	B3GNT2	B3GNT2	7261	0.054	0.53	NO
19	ST3GAL1	ST3GAL1	ST3GAL1	9408	0.018	0.41	NO
20	B4GALT4	B4GALT4	B4GALT4	9820	0.011	0.39	NO
21	B3GNT1	B3GNT1	B3GNT1	11060	-0.0077	0.32	NO
22	ST3GAL6	ST3GAL6	ST3GAL6	11672	-0.017	0.3	NO
23	B4GALT5	B4GALT5	B4GALT5	12627	-0.034	0.25	NO
24	B3GNT3	B3GNT3	B3GNT3	14365	-0.07	0.16	NO
25	CHST5	CHST5	CHST5	15153	-0.094	0.14	NO
26	B4GALT6	B4GALT6	B4GALT6	16991	-0.2	0.066	NO

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

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CYTOKINE CYTOKINE RECEPTOR INTERACTION, 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 CHEMOKINE SIGNALING PATHWAY

Table S18. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	IL2RA	IL2RA	IL2RA	54	0.69	0.11	YES
2	IL2RB	IL2RB	IL2RB	541	0.49	0.16	YES
3	LCK	LCK	LCK	580	0.48	0.23	YES
4	JAK3	JAK3	JAK3	733	0.45	0.29	YES
5	IL2RG	IL2RG	IL2RG	786	0.45	0.36	YES
6	IL2	IL2	IL2	1027	0.41	0.41	YES
7	CDK1	CDK1	CDK1	1064	0.4	0.47	YES
8	CSF2RB	CSF2RB	CSF2RB	1089	0.4	0.53	YES
9	IL3RA	IL3RA	IL3RA	1118	0.4	0.59	YES
10	CSF2	CSF2	CSF2	1699	0.33	0.61	YES
11	CSF2RA	CSF2RA	CSF2RA	2093	0.29	0.64	YES
12	SHC1	SHC1	SHC1	3096	0.22	0.62	NO
13	PIK3CD	PIK3CD	PIK3CD	4559	0.13	0.56	NO
14	JAK2	JAK2	JAK2	4729	0.12	0.57	NO
15	PIK3R1	PIK3R1	PIK3R1	4819	0.12	0.58	NO
16	NRAS	NRAS	NRAS	5632	0.092	0.55	NO
17	IL5RA	IL5RA	IL5RA	5767	0.089	0.56	NO
18	MAP2K1	MAP2K1	MAP2K1	6443	0.072	0.53	NO
19	SOS1	SOS1	SOS1	6632	0.068	0.53	NO
20	PTPN6	PTPN6	PTPN6	6659	0.067	0.54	NO
21	STAT5A	STAT5A	STAT5A	6673	0.067	0.55	NO
22	SYK	SYK	SYK	6805	0.064	0.55	NO
23	PIK3CA	PIK3CA	PIK3CA	6830	0.063	0.56	NO
24	PIK3R3	PIK3R3	PIK3R3	7200	0.055	0.55	NO
25	MAPK1	MAPK1	MAPK1	8062	0.039	0.51	NO
26	PTK2B	PTK2B	PTK2B	8891	0.026	0.47	NO
27	IL5	IL5	IL5	9048	0.023	0.46	NO
28	MAPK3	MAPK3	MAPK3	9142	0.022	0.46	NO
29	JAK1	JAK1	JAK1	9605	0.014	0.44	NO
30	YWHAB	YWHAB	YWHAB	10047	0.0076	0.41	NO
31	GRB2	GRB2	GRB2	10108	0.0067	0.41	NO
32	PIK3CB	PIK3CB	PIK3CB	10152	0.006	0.41	NO
33	GAB2	GAB2	GAB2	10254	0.0045	0.41	NO
34	MAP2K2	MAP2K2	MAP2K2	10960	-0.0062	0.37	NO
35	STAT5B	STAT5B	STAT5B	11568	-0.016	0.34	NO
36	INPPL1	INPPL1	INPPL1	12149	-0.026	0.31	NO
37	RAF1	RAF1	RAF1	12262	-0.027	0.31	NO
38	HRAS	HRAS	HRAS	12430	-0.03	0.3	NO
39	PIK3R2	PIK3R2	PIK3R2	13129	-0.044	0.27	NO
40	KRAS	KRAS	KRAS	13554	-0.052	0.26	NO

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

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

genes ES table in pathway: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION

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	SERPINE1	SERPINE1	SERPINE1	63	0.68	0.062	YES
2	RUNX2	RUNX2	RUNX2	361	0.54	0.098	YES
3	IL10	IL10	IL10	463	0.51	0.14	YES
4	RUNX1	RUNX1	RUNX1	597	0.48	0.18	YES
5	COL1A2	COL1A2	COL1A2	702	0.46	0.22	YES
6	DLX1	DLX1	DLX1	710	0.46	0.26	YES
7	GSC	GSC	GSC	808	0.44	0.3	YES
8	SAP30	SAP30	SAP30	978	0.42	0.33	YES
9	RUNX3	RUNX3	RUNX3	1122	0.4	0.36	YES
10	CEBPB	CEBPB	CEBPB	1930	0.31	0.35	YES
11	MEF2C	MEF2C	MEF2C	2164	0.29	0.36	YES
12	CDKN2B	CDKN2B	CDKN2B	2175	0.28	0.39	YES
13	IFNB1	IFNB1	IFNB1	2494	0.26	0.4	YES
14	NKX2-5	NKX2-5	NKX2-5	2506	0.26	0.42	YES
15	IRF7	IRF7	IRF7	2719	0.24	0.44	YES
16	SKIL	SKIL	SKIL	2781	0.24	0.46	YES
17	FOXG1	FOXG1	FOXG1	2857	0.23	0.47	YES
18	RBL1	RBL1	RBL1	2945	0.22	0.49	YES
19	GATA3	GATA3	GATA3	3052	0.22	0.51	YES
20	NR3C1	NR3C1	NR3C1	3177	0.21	0.52	YES
21	FOS	FOS	FOS	3629	0.18	0.51	YES
22	MYC	MYC	MYC	3777	0.17	0.52	YES
23	ESR1	ESR1	ESR1	4005	0.16	0.52	YES
24	PIAS3	PIAS3	PIAS3	4184	0.15	0.53	YES
25	JUN	JUN	JUN	4804	0.12	0.51	NO
26	ITGB5	ITGB5	ITGB5	4952	0.12	0.51	NO
27	CBFB	CBFB	CBFB	4961	0.12	0.52	NO
28	ATF3	ATF3	ATF3	5103	0.11	0.52	NO
29	SKI	SKI	SKI	5311	0.1	0.52	NO
30	SP3	SP3	SP3	5397	0.1	0.53	NO
31	CDK2	CDK2	CDK2	5726	0.09	0.52	NO
32	KAT2B	KAT2B	KAT2B	5969	0.084	0.51	NO
33	HDAC1	HDAC1	HDAC1	5994	0.083	0.52	NO
34	LAMC1	LAMC1	LAMC1	6119	0.08	0.52	NO
35	CREB1	CREB1	CREB1	6311	0.075	0.52	NO
36	ATF2	ATF2	ATF2	6507	0.07	0.51	NO
37	TFE3	TFE3	TFE3	6963	0.06	0.49	NO
38	HNF4A	HNF4A	HNF4A	7410	0.051	0.47	NO
39	FOXH1	FOXH1	FOXH1	7910	0.042	0.45	NO
40	CDK4	CDK4	CDK4	8070	0.039	0.44	NO
41	TGIF2	TGIF2	TGIF2	8184	0.037	0.44	NO
42	MED15	MED15	MED15	8213	0.037	0.44	NO
43	RBBP4	RBBP4	RBBP4	8251	0.036	0.45	NO
44	TCF3	TCF3	TCF3	8542	0.031	0.43	NO
45	NCOA2	NCOA2	NCOA2	8606	0.03	0.43	NO
46	MAX	MAX	MAX	8667	0.029	0.43	NO
47	FOXO1	FOXO1	FOXO1	8958	0.025	0.42	NO
48	FOXO3	FOXO3	FOXO3	8967	0.025	0.42	NO
49	IL5	IL5	IL5	9048	0.023	0.42	NO
50	EP300	EP300	EP300	9266	0.02	0.41	NO
51	HDAC2	HDAC2	HDAC2	9538	0.016	0.39	NO
52	SMAD7	SMAD7	SMAD7	9550	0.016	0.4	NO
53	SNIP1	SNIP1	SNIP1	9555	0.015	0.4	NO
54	SMAD2	SMAD2	SMAD2	9662	0.014	0.39	NO
55	SP1	SP1	SP1	9700	0.013	0.39	NO
56	NCOA1	NCOA1	NCOA1	9799	0.011	0.39	NO
57	SIN3A	SIN3A	SIN3A	10179	0.0056	0.37	NO
58	ZBTB17	ZBTB17	ZBTB17	10210	0.0052	0.36	NO
59	RBBP7	RBBP7	RBBP7	10350	0.0032	0.36	NO
60	HSPA8	HSPA8	HSPA8	10501	0.00064	0.35	NO
61	CREBBP	CREBBP	CREBBP	10880	-0.005	0.33	NO
62	E2F4	E2F4	E2F4	11009	-0.0069	0.32	NO
63	SIN3B	SIN3B	SIN3B	11175	-0.0091	0.32	NO
64	DCP1A	DCP1A	DCP1A	11201	-0.0097	0.31	NO
65	TFDP1	TFDP1	TFDP1	11292	-0.011	0.31	NO
66	PIAS4	PIAS4	PIAS4	11714	-0.018	0.29	NO
67	AKT1	AKT1	AKT1	11800	-0.02	0.29	NO
68	NCOR1	NCOR1	NCOR1	11847	-0.02	0.29	NO
69	CTBP1	CTBP1	CTBP1	11936	-0.022	0.28	NO
70	SAP18	SAP18	SAP18	12057	-0.024	0.28	NO
71	CDKN1A	CDKN1A	CDKN1A	12156	-0.026	0.28	NO
72	CITED1	CITED1	CITED1	12167	-0.026	0.28	NO
73	KAT2A	KAT2A	KAT2A	12930	-0.04	0.24	NO
74	TGIF1	TGIF1	TGIF1	13229	-0.046	0.23	NO
75	FOXO4	FOXO4	FOXO4	13270	-0.047	0.23	NO
76	SMAD4	SMAD4	SMAD4	13443	-0.05	0.22	NO
77	E2F5	E2F5	E2F5	13820	-0.058	0.21	NO
78	SMAD3	SMAD3	SMAD3	14319	-0.069	0.19	NO
79	VDR	VDR	VDR	15146	-0.094	0.15	NO
80	AR	AR	AR	16541	-0.16	0.091	NO

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

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION, 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 CELL CYCLE

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	SERPINE1	SERPINE1	SERPINE1	63	0.68	0.041	YES
2	FGA	FGA	FGA	142	0.61	0.077	YES
3	F13A1	F13A1	F13A1	276	0.56	0.11	YES
4	HGF	HGF	HGF	409	0.52	0.13	YES
5	FGG	FGG	FGG	430	0.52	0.17	YES
6	TF	TF	TF	586	0.48	0.19	YES
7	MMRN1	MMRN1	MMRN1	588	0.48	0.22	YES
8	FGB	FGB	FGB	688	0.46	0.25	YES
9	ACTN2	ACTN2	ACTN2	769	0.45	0.27	YES
10	FN1	FN1	FN1	1098	0.4	0.28	YES
11	TGFB3	TGFB3	TGFB3	1155	0.39	0.3	YES
12	PRKCB	PRKCB	PRKCB	1166	0.39	0.33	YES
13	PLEK	PLEK	PLEK	1198	0.39	0.35	YES
14	VEGFA	VEGFA	VEGFA	1691	0.33	0.35	YES
15	SELP	SELP	SELP	1713	0.33	0.37	YES
16	TGFB1	TGFB1	TGFB1	1916	0.31	0.38	YES
17	VEGFC	VEGFC	VEGFC	1925	0.31	0.4	YES
18	TIMP1	TIMP1	TIMP1	1964	0.3	0.42	YES
19	TGFB2	TGFB2	TGFB2	2046	0.3	0.43	YES
20	SERPINF2	SERPINF2	SERPINF2	2197	0.28	0.44	YES
21	SRGN	SRGN	SRGN	2334	0.27	0.45	YES
22	SERPINA1	SERPINA1	SERPINA1	2404	0.26	0.46	YES
23	CD36	CD36	CD36	2439	0.26	0.48	YES
24	PECAM1	PECAM1	PECAM1	2480	0.26	0.5	YES
25	SERPING1	SERPING1	SERPING1	2571	0.25	0.51	YES
26	ACTN1	ACTN1	ACTN1	2652	0.25	0.52	YES
27	PPBP	PPBP	PPBP	3017	0.22	0.51	YES
28	CFD	CFD	CFD	3041	0.22	0.53	YES
29	ITGA2B	ITGA2B	ITGA2B	3058	0.22	0.54	YES
30	PROS1	PROS1	PROS1	3114	0.22	0.55	YES
31	SPARC	SPARC	SPARC	3161	0.21	0.56	YES
32	LEFTY2	LEFTY2	LEFTY2	3186	0.21	0.57	YES
33	THBS1	THBS1	THBS1	3283	0.2	0.58	YES
34	VWF	VWF	VWF	3294	0.2	0.6	YES
35	F8	F8	F8	3318	0.2	0.61	YES
36	PDGFB	PDGFB	PDGFB	3526	0.19	0.61	YES
37	A2M	A2M	A2M	3622	0.18	0.62	YES
38	ITGB3	ITGB3	ITGB3	3757	0.17	0.62	YES
39	F5	F5	F5	3843	0.17	0.63	YES
40	CALU	CALU	CALU	3867	0.17	0.64	YES
41	APOA1	APOA1	APOA1	4403	0.14	0.62	NO
42	PF4	PF4	PF4	4734	0.12	0.61	NO
43	VCL	VCL	VCL	5746	0.09	0.56	NO
44	CAP1	CAP1	CAP1	6362	0.074	0.53	NO
45	HSPA5	HSPA5	HSPA5	6822	0.063	0.51	NO
46	STX4	STX4	STX4	7095	0.057	0.49	NO
47	TLN1	TLN1	TLN1	7504	0.049	0.48	NO
48	PFN1	PFN1	PFN1	7672	0.046	0.47	NO
49	ALB	ALB	ALB	8035	0.04	0.45	NO
50	CFL1	CFL1	CFL1	8442	0.033	0.43	NO
51	TUBA4A	TUBA4A	TUBA4A	8664	0.029	0.42	NO
52	CALM3	CALM3	CALM3	9018	0.024	0.4	NO
53	PSAP	PSAP	PSAP	9347	0.019	0.39	NO
54	LAMP2	LAMP2	LAMP2	9376	0.018	0.39	NO
55	PDGFA	PDGFA	PDGFA	9781	0.012	0.36	NO
56	CALM1	CALM1	CALM1	9936	0.0092	0.36	NO
57	CD63	CD63	CD63	10256	0.0045	0.34	NO
58	PRKCG	PRKCG	PRKCG	10424	0.0018	0.33	NO
59	ACTN4	ACTN4	ACTN4	10431	0.0017	0.33	NO
60	ALDOA	ALDOA	ALDOA	10509	0.00056	0.33	NO
61	PPIA	PPIA	PPIA	10639	-0.0013	0.32	NO
62	CALM2	CALM2	CALM2	10653	-0.0015	0.32	NO
63	SOD1	SOD1	SOD1	11047	-0.0074	0.3	NO
64	WDR1	WDR1	WDR1	11898	-0.022	0.25	NO
65	STXBP3	STXBP3	STXBP3	11928	-0.022	0.25	NO
66	BRPF3	BRPF3	BRPF3	11938	-0.022	0.25	NO
67	APP	APP	APP	12088	-0.024	0.25	NO
68	HRG	HRG	HRG	12515	-0.032	0.22	NO
69	VEGFB	VEGFB	VEGFB	12593	-0.034	0.22	NO
70	FIGF	FIGF	FIGF	13272	-0.047	0.19	NO
71	KNG1	KNG1	KNG1	13668	-0.054	0.17	NO
72	PRKCA	PRKCA	PRKCA	14487	-0.074	0.13	NO
73	CLU	CLU	CLU	14701	-0.08	0.12	NO
74	CD9	CD9	CD9	14947	-0.087	0.12	NO
75	SCG3	SCG3	SCG3	15985	-0.13	0.066	NO
76	PLG	PLG	PLG	16768	-0.18	0.035	NO
77	HABP4	HABP4	HABP4	17075	-0.2	0.031	NO
78	ABCC4	ABCC4	ABCC4	17090	-0.2	0.044	NO
79	EGF	EGF	EGF	17456	-0.25	0.041	NO

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

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CELL CYCLE, 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 PPAR SIGNALING PATHWAY	65	genes.ES.table	0.6	1.6	0.018	1	0.93	0.35	0.13	0.31	1	0.58
KEGG VASCULAR SMOOTH MUSCLE CONTRACTION	107	genes.ES.table	0.58	1.6	0.0096	1	0.93	0.36	0.15	0.31	1	0.62
KEGG VASOPRESSIN REGULATED WATER REABSORPTION	42	genes.ES.table	0.47	1.8	0.0098	1	0.62	0.19	0.13	0.16	1	0.57
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.42	1.5	0.055	1	0.97	0.38	0.26	0.28	0.97	0.48
BIOCARTA FAS PATHWAY	30	genes.ES.table	0.46	1.5	0.099	1	0.97	0.33	0.25	0.25	1	0.5
BIOCARTA VEGF PATHWAY	29	genes.ES.table	0.62	1.7	0.016	1	0.85	0.21	0.046	0.2	1	0.58
PID HIF2PATHWAY	34	genes.ES.table	0.63	1.6	0.02	1	0.93	0.41	0.16	0.35	1	0.67
PID ARF6 TRAFFICKINGPATHWAY	48	genes.ES.table	0.58	1.7	0.0077	1	0.82	0.42	0.23	0.32	1	0.62
PID ANGIOPOIETINRECEPTOR PATHWAY	50	genes.ES.table	0.53	1.5	0.033	1	0.97	0.24	0.11	0.22	1	0.5
PID SHP2 PATHWAY	57	genes.ES.table	0.6	1.5	0.023	1	0.97	0.35	0.13	0.31	1	0.56

genes ES table in pathway: KEGG PPAR SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CREB3L3	CREB3L3	CREB3L3	25	0.87	0.16	YES
2	AQP4	AQP4	AQP4	606	0.48	0.22	YES
3	DYNC1I1	DYNC1I1	DYNC1I1	774	0.44	0.28	YES
4	AQP3	AQP3	AQP3	996	0.39	0.34	YES
5	AVPR2	AVPR2	AVPR2	1104	0.37	0.41	YES
6	ADCY3	ADCY3	ADCY3	1861	0.27	0.42	YES
7	DYNC2H1	DYNC2H1	DYNC2H1	2250	0.24	0.44	YES
8	ARHGDIB	ARHGDIB	ARHGDIB	2438	0.23	0.47	YES
9	DCTN6	DCTN6	DCTN6	3316	0.17	0.45	NO
10	CREB1	CREB1	CREB1	4149	0.13	0.43	NO
11	CREB3L4	CREB3L4	CREB3L4	4924	0.1	0.41	NO
12	ADCY9	ADCY9	ADCY9	5196	0.097	0.41	NO
13	DCTN4	DCTN4	DCTN4	5652	0.086	0.4	NO
14	DYNC1I2	DYNC1I2	DYNC1I2	5848	0.081	0.41	NO
15	VAMP2	VAMP2	VAMP2	6140	0.073	0.4	NO
16	CREB5	CREB5	CREB5	7293	0.047	0.35	NO
17	DCTN1	DCTN1	DCTN1	7515	0.042	0.34	NO
18	CREB3L2	CREB3L2	CREB3L2	7663	0.039	0.34	NO
19	CREB3	CREB3	CREB3	7921	0.033	0.34	NO
20	PRKACB	PRKACB	PRKACB	8528	0.02	0.31	NO
21	DYNC1LI2	DYNC1LI2	DYNC1LI2	8619	0.018	0.3	NO
22	RAB11A	RAB11A	RAB11A	8965	0.011	0.29	NO
23	STX4	STX4	STX4	9517	0.00019	0.26	NO
24	RAB5B	RAB5B	RAB5B	10070	-0.012	0.23	NO
25	DYNLL1	DYNLL1	DYNLL1	10207	-0.014	0.22	NO
26	DYNC1H1	DYNC1H1	DYNC1H1	10701	-0.025	0.2	NO
27	DYNLL2	DYNLL2	DYNLL2	10802	-0.027	0.2	NO
28	PRKACA	PRKACA	PRKACA	11069	-0.033	0.19	NO
29	RAB5C	RAB5C	RAB5C	11298	-0.038	0.19	NO
30	DYNC1LI1	DYNC1LI1	DYNC1LI1	11316	-0.038	0.19	NO
31	DCTN5	DCTN5	DCTN5	11460	-0.042	0.19	NO
32	AQP2	AQP2	AQP2	12089	-0.056	0.17	NO
33	NSF	NSF	NSF	12094	-0.056	0.18	NO
34	ARHGDIA	ARHGDIA	ARHGDIA	12159	-0.058	0.19	NO
35	ADCY6	ADCY6	ADCY6	12230	-0.059	0.19	NO
36	RAB5A	RAB5A	RAB5A	12468	-0.065	0.19	NO
37	PRKX	PRKX	PRKX	12570	-0.067	0.2	NO
38	DCTN2	DCTN2	DCTN2	13298	-0.088	0.17	NO
39	DYNC2LI1	DYNC2LI1	DYNC2LI1	13350	-0.089	0.19	NO
40	RAB11B	RAB11B	RAB11B	13545	-0.095	0.2	NO
41	GNAS	GNAS	GNAS	14050	-0.11	0.19	NO
42	CREB3L1	CREB3L1	CREB3L1	16160	-0.22	0.11	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 PPAR SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG VASCULAR SMOOTH MUSCLE CONTRACTION

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	BMX	BMX	BMX	269	0.6	0.065	YES
2	ELMO1	ELMO1	ELMO1	689	0.46	0.1	YES
3	ETS1	ETS1	ETS1	827	0.42	0.15	YES
4	CCND1	CCND1	CCND1	934	0.4	0.2	YES
5	FYN	FYN	FYN	1309	0.34	0.22	YES
6	ITGA5	ITGA5	ITGA5	1956	0.26	0.22	YES
7	ROCK2	ROCK2	ROCK2	2140	0.25	0.25	YES
8	ASAP1	ASAP1	ASAP1	2350	0.23	0.27	YES
9	GIT2	GIT2	GIT2	2507	0.22	0.29	YES
10	ARHGAP26	ARHGAP26	ARHGAP26	2539	0.22	0.32	YES
11	KLF8	KLF8	KLF8	2656	0.21	0.34	YES
12	MAPK8	MAPK8	MAPK8	2968	0.19	0.34	YES
13	MAPK1	MAPK1	MAPK1	3599	0.16	0.33	YES
14	NCK1	NCK1	NCK1	3643	0.15	0.35	YES
15	PIK3CA	PIK3CA	PIK3CA	3863	0.14	0.36	YES
16	ARHGEF7	ARHGEF7	ARHGEF7	4107	0.13	0.36	YES
17	ITGAV	ITGAV	ITGAV	4189	0.13	0.37	YES
18	JUN	JUN	JUN	4537	0.12	0.37	YES
19	CRK	CRK	CRK	4564	0.12	0.38	YES
20	SOS1	SOS1	SOS1	4688	0.11	0.39	YES
21	NCK2	NCK2	NCK2	4751	0.11	0.4	YES
22	PIK3R1	PIK3R1	PIK3R1	4885	0.11	0.41	YES
23	RAPGEF1	RAPGEF1	RAPGEF1	4900	0.11	0.42	YES
24	YES1	YES1	YES1	4983	0.1	0.43	YES
25	RGNEF	RGNEF	RGNEF	5185	0.098	0.44	YES
26	BRAF	BRAF	BRAF	5208	0.097	0.45	YES
27	ITGB1	ITGB1	ITGB1	5253	0.096	0.46	YES
28	DOCK1	DOCK1	DOCK1	5271	0.095	0.47	YES
29	RAP1A	RAP1A	RAP1A	5552	0.088	0.47	NO
30	PTK2	PTK2	PTK2	5727	0.084	0.47	NO
31	TLN1	TLN1	TLN1	6637	0.061	0.42	NO
32	MAPK9	MAPK9	MAPK9	7035	0.052	0.41	NO
33	ACTN1	ACTN1	ACTN1	7080	0.051	0.42	NO
34	RAP1B	RAP1B	RAP1B	7122	0.05	0.42	NO
35	VCL	VCL	VCL	7166	0.049	0.42	NO
36	MAP2K1	MAP2K1	MAP2K1	7286	0.047	0.42	NO
37	RASA1	RASA1	RASA1	7315	0.046	0.43	NO
38	ITGB5	ITGB5	ITGB5	7806	0.035	0.4	NO
39	PAK1	PAK1	PAK1	8467	0.022	0.37	NO
40	SH3GL1	SH3GL1	SH3GL1	8555	0.02	0.37	NO
41	MAP2K4	MAP2K4	MAP2K4	8919	0.012	0.35	NO
42	PLCG1	PLCG1	PLCG1	9566	-0.00095	0.32	NO
43	PXN	PXN	PXN	9618	-0.002	0.31	NO
44	RRAS	RRAS	RRAS	10119	-0.012	0.29	NO
45	WASL	WASL	WASL	10900	-0.029	0.25	NO
46	RHOA	RHOA	RHOA	10930	-0.03	0.25	NO
47	MMP14	MMP14	MMP14	11277	-0.038	0.24	NO
48	RAC1	RAC1	RAC1	11421	-0.041	0.23	NO
49	PTPN21	PTPN21	PTPN21	11422	-0.041	0.24	NO
50	ACTA1	ACTA1	ACTA1	12187	-0.058	0.2	NO
51	CAPN2	CAPN2	CAPN2	12507	-0.066	0.2	NO
52	ARHGEF11	ARHGEF11	ARHGEF11	12697	-0.071	0.2	NO
53	GRB2	GRB2	GRB2	12787	-0.073	0.2	NO
54	RAF1	RAF1	RAF1	13261	-0.087	0.19	NO
55	MAPK8IP3	MAPK8IP3	MAPK8IP3	13328	-0.088	0.19	NO
56	SRC	SRC	SRC	14707	-0.14	0.14	NO
57	BCAR1	BCAR1	BCAR1	15214	-0.16	0.13	NO
58	GRB7	GRB7	GRB7	16640	-0.26	0.086	NO

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

Figure S44. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VASCULAR SMOOTH MUSCLE CONTRACTION, 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 VASOPRESSIN REGULATED WATER REABSORPTION

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	AGTR1	AGTR1	AGTR1	8	0.96	0.1	YES
2	ITGA8	ITGA8	ITGA8	94	0.71	0.18	YES
3	ITGA10	ITGA10	ITGA10	120	0.68	0.25	YES
4	TSHR	TSHR	TSHR	127	0.68	0.33	YES
5	ITGA9	ITGA9	ITGA9	426	0.53	0.37	YES
6	ITGA4	ITGA4	ITGA4	544	0.5	0.42	YES
7	ITGA1	ITGA1	ITGA1	659	0.46	0.46	YES
8	EDNRB	EDNRB	EDNRB	682	0.46	0.51	YES
9	AVPR2	AVPR2	AVPR2	1104	0.37	0.53	YES
10	ITGA5	ITGA5	ITGA5	1956	0.26	0.51	YES
11	ITGA11	ITGA11	ITGA11	2404	0.23	0.51	YES
12	CPE	CPE	CPE	2409	0.23	0.54	YES
13	PLD1	PLD1	PLD1	2929	0.19	0.53	YES
14	ACAP1	ACAP1	ACAP1	3017	0.19	0.55	YES
15	ITGA2	ITGA2	ITGA2	3411	0.17	0.54	YES
16	ITGA6	ITGA6	ITGA6	3586	0.16	0.55	YES
17	EXOC3	EXOC3	EXOC3	3694	0.15	0.56	YES
18	ITGA7	ITGA7	ITGA7	3800	0.15	0.57	YES
19	CTNND1	CTNND1	CTNND1	4122	0.13	0.57	YES
20	ITGAV	ITGAV	ITGAV	4189	0.13	0.58	YES
21	EXOC5	EXOC5	EXOC5	4929	0.1	0.55	NO
22	SPAG9	SPAG9	SPAG9	5109	0.1	0.55	NO
23	CTNNB1	CTNNB1	CTNNB1	5136	0.099	0.56	NO
24	ASAP2	ASAP2	ASAP2	5200	0.097	0.57	NO
25	ITGB1	ITGB1	ITGB1	5253	0.096	0.57	NO
26	VAMP3	VAMP3	VAMP3	5473	0.09	0.57	NO
27	EXOC6	EXOC6	EXOC6	5726	0.084	0.57	NO
28	IL2RA	IL2RA	IL2RA	6503	0.064	0.53	NO
29	EXOC1	EXOC1	EXOC1	7294	0.046	0.49	NO
30	CTNNA1	CTNNA1	CTNNA1	8284	0.025	0.44	NO
31	CDH1	CDH1	CDH1	8901	0.012	0.41	NO
32	KLC1	KLC1	KLC1	9032	0.01	0.4	NO
33	EXOC2	EXOC2	EXOC2	9141	0.0078	0.4	NO
34	SLC2A4	SLC2A4	SLC2A4	9216	0.0062	0.4	NO
35	CLTC	CLTC	CLTC	9711	-0.0041	0.37	NO
36	SCAMP2	SCAMP2	SCAMP2	10121	-0.012	0.35	NO
37	DNM2	DNM2	DNM2	10259	-0.015	0.34	NO
38	PLD2	PLD2	PLD2	10407	-0.018	0.34	NO
39	EXOC4	EXOC4	EXOC4	10596	-0.023	0.33	NO
40	EXOC7	EXOC7	EXOC7	10657	-0.024	0.33	NO
41	RALA	RALA	RALA	10931	-0.03	0.31	NO
42	ARF6	ARF6	ARF6	11724	-0.048	0.28	NO
43	PIP5K1C	PIP5K1C	PIP5K1C	12417	-0.064	0.24	NO
44	ADRB2	ADRB2	ADRB2	12525	-0.066	0.25	NO
45	MAPK8IP3	MAPK8IP3	MAPK8IP3	13328	-0.088	0.21	NO
46	BIN1	BIN1	BIN1	14923	-0.15	0.14	NO
47	ITGA3	ITGA3	ITGA3	14950	-0.15	0.16	NO
48	NME1	NME1	NME1	16124	-0.22	0.11	NO

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

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

genes ES table in pathway: BIOCARTA AT1R PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	KDR	KDR	KDR	108	0.69	0.13	YES
2	FLT1	FLT1	FLT1	163	0.66	0.25	YES
3	FLT4	FLT4	FLT4	284	0.59	0.36	YES
4	VEGFA	VEGFA	VEGFA	335	0.57	0.47	YES
5	NOS3	NOS3	NOS3	529	0.5	0.56	YES
6	PIK3CG	PIK3CG	PIK3CG	844	0.42	0.62	YES
7	PRKCB	PRKCB	PRKCB	2132	0.25	0.6	NO
8	PIK3CA	PIK3CA	PIK3CA	3863	0.14	0.53	NO
9	PIK3R1	PIK3R1	PIK3R1	4885	0.11	0.5	NO
10	ARNT	ARNT	ARNT	5017	0.1	0.51	NO
11	EIF1AX	EIF1AX	EIF1AX	5566	0.088	0.5	NO
12	PTK2	PTK2	PTK2	5727	0.084	0.5	NO
13	EIF2S3	EIF2S3	EIF2S3	5972	0.077	0.51	NO
14	EIF2S1	EIF2S1	EIF2S1	6281	0.07	0.5	NO
15	SHC1	SHC1	SHC1	6401	0.067	0.51	NO
16	EIF1	EIF1	EIF1	8474	0.021	0.4	NO
17	EIF2B4	EIF2B4	EIF2B4	8845	0.014	0.38	NO
18	PLCG1	PLCG1	PLCG1	9566	-0.00095	0.34	NO
19	PXN	PXN	PXN	9618	-0.002	0.34	NO
20	EIF2B2	EIF2B2	EIF2B2	9720	-0.0042	0.34	NO
21	EIF2B3	EIF2B3	EIF2B3	9793	-0.0058	0.33	NO
22	EIF2B5	EIF2B5	EIF2B5	10519	-0.021	0.3	NO
23	EIF2B1	EIF2B1	EIF2B1	10836	-0.028	0.28	NO
24	EIF2S2	EIF2S2	EIF2S2	11234	-0.037	0.27	NO
25	ELAVL1	ELAVL1	ELAVL1	11968	-0.053	0.24	NO
26	HRAS	HRAS	HRAS	12189	-0.058	0.24	NO
27	HIF1A	HIF1A	HIF1A	13880	-0.11	0.17	NO
28	VHL	VHL	VHL	14595	-0.13	0.15	NO
29	PRKCA	PRKCA	PRKCA	16255	-0.23	0.11	NO

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

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

genes ES table in pathway: BIOCARTA FAS 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	RPS6KA5	RPS6KA5	RPS6KA5	643	0.47	0.076	YES
2	MEF2C	MEF2C	MEF2C	756	0.44	0.18	YES
3	DUSP7	DUSP7	DUSP7	1749	0.28	0.19	YES
4	FOS	FOS	FOS	1979	0.26	0.24	YES
5	DUSP4	DUSP4	DUSP4	2407	0.23	0.27	YES
6	MAPK11	MAPK11	MAPK11	2531	0.22	0.32	YES
7	DUSP6	DUSP6	DUSP6	2563	0.22	0.37	YES
8	MAPK8	MAPK8	MAPK8	2968	0.19	0.39	YES
9	RPS6KA2	RPS6KA2	RPS6KA2	3261	0.17	0.42	YES
10	ATF2	ATF2	ATF2	3414	0.17	0.45	YES
11	MAPK1	MAPK1	MAPK1	3599	0.16	0.47	YES
12	MEF2A	MEF2A	MEF2A	3926	0.14	0.49	YES
13	CREB1	CREB1	CREB1	4149	0.13	0.51	YES
14	MAPK10	MAPK10	MAPK10	4324	0.13	0.53	YES
15	JUN	JUN	JUN	4537	0.12	0.55	YES
16	MAPK3	MAPK3	MAPK3	5501	0.09	0.51	NO
17	PPP2R1B	PPP2R1B	PPP2R1B	5671	0.085	0.52	NO
18	ATF1	ATF1	ATF1	6127	0.073	0.52	NO
19	MAPK9	MAPK9	MAPK9	7035	0.052	0.48	NO
20	MAPK14	MAPK14	MAPK14	7231	0.048	0.48	NO
21	RPS6KA3	RPS6KA3	RPS6KA3	7236	0.048	0.49	NO
22	PPP2CA	PPP2CA	PPP2CA	8207	0.027	0.44	NO
23	PPP2R5D	PPP2R5D	PPP2R5D	8288	0.025	0.45	NO
24	PPP2CB	PPP2CB	PPP2CB	8353	0.024	0.45	NO
25	MAPKAPK2	MAPKAPK2	MAPKAPK2	8466	0.022	0.45	NO
26	DUSP3	DUSP3	DUSP3	10885	-0.029	0.32	NO
27	ELK1	ELK1	ELK1	12050	-0.055	0.27	NO
28	MAPK7	MAPK7	MAPK7	12257	-0.06	0.27	NO
29	PPP2R1A	PPP2R1A	PPP2R1A	12314	-0.061	0.28	NO
30	RPS6KA1	RPS6KA1	RPS6KA1	15251	-0.16	0.16	NO

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

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

genes ES table in pathway: BIOCARTA VEGF PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ABCG2	ABCG2	ABCG2	71	0.74	0.091	YES
2	KDR	KDR	KDR	108	0.69	0.18	YES
3	FLT1	FLT1	FLT1	163	0.66	0.26	YES
4	EGLN3	EGLN3	EGLN3	308	0.58	0.33	YES
5	VEGFA	VEGFA	VEGFA	335	0.57	0.4	YES
6	ADORA2A	ADORA2A	ADORA2A	568	0.49	0.45	YES
7	ETS1	ETS1	ETS1	827	0.42	0.49	YES
8	EPAS1	EPAS1	EPAS1	993	0.39	0.53	YES
9	SERPINE1	SERPINE1	SERPINE1	1693	0.29	0.53	YES
10	POU5F1	POU5F1	POU5F1	1729	0.29	0.57	YES
11	SLC2A1	SLC2A1	SLC2A1	1838	0.28	0.6	YES
12	TWIST1	TWIST1	TWIST1	1869	0.27	0.63	YES
13	EPO	EPO	EPO	2435	0.23	0.63	YES
14	SIRT1	SIRT1	SIRT1	2833	0.2	0.63	YES
15	EFNA1	EFNA1	EFNA1	3461	0.16	0.62	NO
16	EGLN1	EGLN1	EGLN1	3721	0.15	0.63	NO
17	PGK1	PGK1	PGK1	4496	0.12	0.6	NO
18	ARNT	ARNT	ARNT	5017	0.1	0.58	NO
19	EP300	EP300	EP300	5555	0.088	0.56	NO
20	EIF3E	EIF3E	EIF3E	6425	0.066	0.53	NO
21	CREBBP	CREBBP	CREBBP	7601	0.04	0.47	NO
22	BHLHE40	BHLHE40	BHLHE40	7687	0.038	0.47	NO
23	APEX1	APEX1	APEX1	7801	0.036	0.46	NO
24	SP1	SP1	SP1	8395	0.023	0.44	NO
25	CITED2	CITED2	CITED2	9462	0.0013	0.38	NO
26	HIF1AN	HIF1AN	HIF1AN	10112	-0.012	0.34	NO
27	MMP14	MMP14	MMP14	11277	-0.038	0.28	NO
28	ELK1	ELK1	ELK1	12050	-0.055	0.25	NO
29	TCEB1	TCEB1	TCEB1	12768	-0.073	0.22	NO
30	EGLN2	EGLN2	EGLN2	13060	-0.08	0.21	NO
31	SLC11A2	SLC11A2	SLC11A2	13209	-0.086	0.22	NO
32	VHL	VHL	VHL	14595	-0.13	0.16	NO
33	FXN	FXN	FXN	14671	-0.14	0.17	NO
34	TCEB2	TCEB2	TCEB2	15728	-0.19	0.14	NO

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

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA VEGF 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 HIF2PATHWAY

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	CYP4A11	CYP4A11	CYP4A11	2	1.2	0.048	YES
2	AGTR1	AGTR1	AGTR1	8	0.96	0.087	YES
3	AVPR1B	AVPR1B	AVPR1B	11	0.95	0.13	YES
4	CYP4A22	CYP4A22	CYP4A22	153	0.66	0.15	YES
5	RAMP3	RAMP3	RAMP3	261	0.6	0.17	YES
6	ADCY4	ADCY4	ADCY4	266	0.6	0.19	YES
7	CALCRL	CALCRL	CALCRL	324	0.58	0.21	YES
8	PLCB1	PLCB1	PLCB1	340	0.57	0.24	YES
9	EDNRA	EDNRA	EDNRA	368	0.56	0.26	YES
10	CACNA1C	CACNA1C	CACNA1C	388	0.55	0.28	YES
11	ADRA1B	ADRA1B	ADRA1B	414	0.54	0.3	YES
12	PLA2G12B	PLA2G12B	PLA2G12B	433	0.53	0.32	YES
13	PRKG1	PRKG1	PRKG1	518	0.5	0.34	YES
14	KCNMA1	KCNMA1	KCNMA1	522	0.5	0.36	YES
15	ADCY5	ADCY5	ADCY5	523	0.5	0.38	YES
16	RAMP2	RAMP2	RAMP2	524	0.5	0.4	YES
17	ADORA2A	ADORA2A	ADORA2A	568	0.49	0.42	YES
18	GUCY1A2	GUCY1A2	GUCY1A2	647	0.47	0.43	YES
19	ACTG2	ACTG2	ACTG2	783	0.43	0.44	YES
20	PRKCH	PRKCH	PRKCH	821	0.42	0.46	YES
21	ADRA1A	ADRA1A	ADRA1A	941	0.4	0.47	YES
22	MYH11	MYH11	MYH11	945	0.4	0.48	YES
23	MRVI1	MRVI1	MRVI1	1095	0.38	0.49	YES
24	PTGIR	PTGIR	PTGIR	1190	0.36	0.5	YES
25	AVPR1A	AVPR1A	AVPR1A	1281	0.34	0.51	YES
26	ADORA2B	ADORA2B	ADORA2B	1523	0.31	0.51	YES
27	KCNMB1	KCNMB1	KCNMB1	1595	0.3	0.52	YES
28	GUCY1A3	GUCY1A3	GUCY1A3	1601	0.3	0.53	YES
29	MYLK	MYLK	MYLK	1725	0.29	0.54	YES
30	ADCY1	ADCY1	ADCY1	1743	0.29	0.55	YES
31	ADCY3	ADCY3	ADCY3	1861	0.27	0.55	YES
32	ACTA2	ACTA2	ACTA2	1944	0.27	0.56	YES
33	PRKCB	PRKCB	PRKCB	2132	0.25	0.56	YES
34	ROCK2	ROCK2	ROCK2	2140	0.25	0.57	YES
35	PRKCE	PRKCE	PRKCE	2260	0.24	0.57	YES
36	GUCY1B3	GUCY1B3	GUCY1B3	2442	0.23	0.57	YES
37	CALD1	CALD1	CALD1	2610	0.21	0.57	YES
38	CACNA1F	CACNA1F	CACNA1F	2702	0.21	0.58	YES
39	PLA2G5	PLA2G5	PLA2G5	2770	0.2	0.58	YES
40	ADCY8	ADCY8	ADCY8	3135	0.18	0.57	NO
41	CACNA1S	CACNA1S	CACNA1S	3248	0.18	0.57	NO
42	PPP1R14A	PPP1R14A	PPP1R14A	3507	0.16	0.56	NO
43	MAPK1	MAPK1	MAPK1	3599	0.16	0.56	NO
44	ROCK1	ROCK1	ROCK1	3743	0.15	0.56	NO
45	PPP1R12B	PPP1R12B	PPP1R12B	4217	0.13	0.54	NO
46	GNA13	GNA13	GNA13	5041	0.1	0.5	NO
47	ITPR1	ITPR1	ITPR1	5047	0.1	0.5	NO
48	ADCY9	ADCY9	ADCY9	5196	0.097	0.5	NO
49	BRAF	BRAF	BRAF	5208	0.097	0.5	NO
50	KCNMB2	KCNMB2	KCNMB2	5471	0.09	0.49	NO
51	MAPK3	MAPK3	MAPK3	5501	0.09	0.49	NO
52	ARHGEF12	ARHGEF12	ARHGEF12	5518	0.089	0.5	NO
53	MYL9	MYL9	MYL9	5661	0.085	0.49	NO
54	PLCB2	PLCB2	PLCB2	5766	0.083	0.49	NO
55	PPP1R12A	PPP1R12A	PPP1R12A	5774	0.083	0.49	NO
56	CALM1	CALM1	CALM1	6035	0.075	0.48	NO
57	PLCB4	PLCB4	PLCB4	6125	0.073	0.48	NO
58	CALM3	CALM3	CALM3	6536	0.064	0.46	NO
59	NPR1	NPR1	NPR1	6653	0.061	0.46	NO
60	GNAQ	GNAQ	GNAQ	6770	0.058	0.45	NO
61	GNA11	GNA11	GNA11	7116	0.05	0.44	NO
62	PLA2G1B	PLA2G1B	PLA2G1B	7253	0.047	0.43	NO
63	MAP2K1	MAP2K1	MAP2K1	7286	0.047	0.43	NO
64	MYL6B	MYL6B	MYL6B	7587	0.04	0.42	NO
65	PPP1CC	PPP1CC	PPP1CC	7642	0.039	0.41	NO
66	PPP1CB	PPP1CB	PPP1CB	7816	0.035	0.41	NO
67	ARHGEF1	ARHGEF1	ARHGEF1	7935	0.032	0.4	NO
68	PRKACB	PRKACB	PRKACB	8528	0.02	0.37	NO
69	ADCY7	ADCY7	ADCY7	9982	-0.0097	0.29	NO
70	GNA12	GNA12	GNA12	10067	-0.011	0.28	NO
71	CALML6	CALML6	CALML6	10837	-0.028	0.24	NO
72	ADCY2	ADCY2	ADCY2	10848	-0.028	0.24	NO
73	RHOA	RHOA	RHOA	10930	-0.03	0.24	NO
74	PRKACA	PRKACA	PRKACA	11069	-0.033	0.23	NO
75	ITPR3	ITPR3	ITPR3	11297	-0.038	0.22	NO
76	MYL6	MYL6	MYL6	11313	-0.038	0.22	NO
77	PLA2G12A	PLA2G12A	PLA2G12A	11325	-0.038	0.22	NO
78	MYLK2	MYLK2	MYLK2	11528	-0.043	0.22	NO
79	ARAF	ARAF	ARAF	11857	-0.051	0.2	NO
80	ADRA1D	ADRA1D	ADRA1D	11961	-0.053	0.2	NO
81	PLCB3	PLCB3	PLCB3	11971	-0.053	0.2	NO
82	ADCY6	ADCY6	ADCY6	12230	-0.059	0.19	NO
83	MYLK3	MYLK3	MYLK3	12535	-0.066	0.17	NO
84	PRKX	PRKX	PRKX	12570	-0.067	0.17	NO
85	ARHGEF11	ARHGEF11	ARHGEF11	12697	-0.071	0.17	NO
86	CALML3	CALML3	CALML3	12714	-0.072	0.17	NO
87	CALM2	CALM2	CALM2	12773	-0.073	0.17	NO
88	PLA2G4A	PLA2G4A	PLA2G4A	12836	-0.074	0.17	NO
89	PPP1CA	PPP1CA	PPP1CA	12898	-0.076	0.17	NO
90	KCNMB3	KCNMB3	KCNMB3	13069	-0.081	0.16	NO
91	RAMP1	RAMP1	RAMP1	13146	-0.083	0.16	NO
92	RAF1	RAF1	RAF1	13261	-0.087	0.16	NO
93	PRKCQ	PRKCQ	PRKCQ	13308	-0.088	0.16	NO
94	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	13376	-0.09	0.16	NO
95	ITPR2	ITPR2	ITPR2	13832	-0.11	0.14	NO
96	GNAS	GNAS	GNAS	14050	-0.11	0.13	NO
97	MAP2K2	MAP2K2	MAP2K2	14176	-0.12	0.13	NO
98	PLA2G10	PLA2G10	PLA2G10	14194	-0.12	0.14	NO
99	PLA2G6	PLA2G6	PLA2G6	15426	-0.17	0.075	NO
100	PLA2G2A	PLA2G2A	PLA2G2A	15528	-0.18	0.077	NO
101	PRKCD	PRKCD	PRKCD	15666	-0.18	0.077	NO
102	NPR2	NPR2	NPR2	15742	-0.19	0.081	NO
103	CACNA1D	CACNA1D	CACNA1D	15744	-0.19	0.089	NO
104	KCNMB4	KCNMB4	KCNMB4	15745	-0.19	0.097	NO
105	PRKCA	PRKCA	PRKCA	16255	-0.23	0.078	NO
106	PLA2G2D	PLA2G2D	PLA2G2D	16841	-0.28	0.058	NO
107	PRKCG	PRKCG	PRKCG	17558	-0.42	0.035	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: PID HIF2PATHWAY.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: PID HIF2PATHWAY, 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 ARF6 TRAFFICKINGPATHWAY

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	CYP4A11	CYP4A11	CYP4A11	2	1.2	0.077	YES
2	CD36	CD36	CD36	68	0.74	0.12	YES
3	FABP7	FABP7	FABP7	117	0.68	0.17	YES
4	CYP4A22	CYP4A22	CYP4A22	153	0.66	0.21	YES
5	ANGPTL4	ANGPTL4	ANGPTL4	158	0.66	0.25	YES
6	HMGCS2	HMGCS2	HMGCS2	225	0.62	0.29	YES
7	FABP4	FABP4	FABP4	248	0.61	0.33	YES
8	PCK1	PCK1	PCK1	454	0.52	0.35	YES
9	CPT1C	CPT1C	CPT1C	581	0.48	0.38	YES
10	FABP6	FABP6	FABP6	597	0.48	0.41	YES
11	SLC27A2	SLC27A2	SLC27A2	628	0.47	0.44	YES
12	LPL	LPL	LPL	631	0.47	0.47	YES
13	PLIN1	PLIN1	PLIN1	718	0.45	0.5	YES
14	ACADL	ACADL	ACADL	869	0.42	0.52	YES
15	RXRG	RXRG	RXRG	1437	0.32	0.51	YES
16	EHHADH	EHHADH	EHHADH	1446	0.32	0.53	YES
17	FABP1	FABP1	FABP1	1471	0.32	0.55	YES
18	AQP7	AQP7	AQP7	1679	0.29	0.56	YES
19	FADS2	FADS2	FADS2	1809	0.28	0.57	YES
20	ACSL5	ACSL5	ACSL5	2230	0.24	0.56	YES
21	MMP1	MMP1	MMP1	2253	0.24	0.58	YES
22	SCD	SCD	SCD	2256	0.24	0.59	YES
23	FABP5	FABP5	FABP5	2428	0.23	0.6	YES
24	SORBS1	SORBS1	SORBS1	2891	0.2	0.59	NO
25	CYP7A1	CYP7A1	CYP7A1	3464	0.16	0.56	NO
26	CYP27A1	CYP27A1	CYP27A1	3548	0.16	0.57	NO
27	CYP8B1	CYP8B1	CYP8B1	3802	0.15	0.57	NO
28	ACADM	ACADM	ACADM	3922	0.14	0.57	NO
29	ACSL1	ACSL1	ACSL1	4154	0.13	0.57	NO
30	RXRA	RXRA	RXRA	4402	0.12	0.56	NO
31	ACOX2	ACOX2	ACOX2	5101	0.1	0.53	NO
32	CPT1A	CPT1A	CPT1A	5118	0.1	0.54	NO
33	GK	GK	GK	5462	0.091	0.52	NO
34	CPT2	CPT2	CPT2	5540	0.089	0.52	NO
35	PCK2	PCK2	PCK2	6212	0.071	0.49	NO
36	NR1H3	NR1H3	NR1H3	6470	0.065	0.48	NO
37	UBC	UBC	UBC	6821	0.056	0.47	NO
38	ILK	ILK	ILK	6926	0.054	0.46	NO
39	SCP2	SCP2	SCP2	7060	0.051	0.46	NO
40	ACSL6	ACSL6	ACSL6	7162	0.049	0.46	NO
41	OLR1	OLR1	OLR1	7498	0.042	0.44	NO
42	PPARA	PPARA	PPARA	7598	0.04	0.44	NO
43	FABP2	FABP2	FABP2	7666	0.038	0.44	NO
44	ADIPOQ	ADIPOQ	ADIPOQ	7679	0.038	0.44	NO
45	SCD5	SCD5	SCD5	8063	0.03	0.42	NO
46	RXRB	RXRB	RXRB	8556	0.02	0.4	NO
47	PDPK1	PDPK1	PDPK1	9014	0.01	0.37	NO
48	ME1	ME1	ME1	9202	0.0064	0.36	NO
49	PPARG	PPARG	PPARG	9274	0.005	0.36	NO
50	PPARD	PPARD	PPARD	9454	0.0014	0.35	NO
51	ACOX1	ACOX1	ACOX1	9855	-0.0072	0.33	NO
52	FABP3	FABP3	FABP3	10141	-0.013	0.31	NO
53	ACSL3	ACSL3	ACSL3	10174	-0.013	0.31	NO
54	ACSL4	ACSL4	ACSL4	11488	-0.042	0.24	NO
55	APOC3	APOC3	APOC3	12010	-0.054	0.22	NO
56	APOA2	APOA2	APOA2	12407	-0.063	0.2	NO
57	SLC27A1	SLC27A1	SLC27A1	12969	-0.078	0.17	NO
58	APOA1	APOA1	APOA1	13286	-0.087	0.16	NO
59	ACAA1	ACAA1	ACAA1	13870	-0.11	0.14	NO
60	ACOX3	ACOX3	ACOX3	14034	-0.11	0.13	NO
61	DBI	DBI	DBI	14180	-0.12	0.13	NO
62	SLC27A4	SLC27A4	SLC27A4	16569	-0.25	0.019	NO
63	CPT1B	CPT1B	CPT1B	16807	-0.28	0.025	NO
64	PLTP	PLTP	PLTP	17416	-0.38	0.017	NO
65	SLC27A5	SLC27A5	SLC27A5	17437	-0.39	0.042	NO

Figure S55. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID ARF6 TRAFFICKINGPATHWAY.

Figure S56. Get High-res Image For the top 5 core enriched genes in the pathway: PID ARF6 TRAFFICKINGPATHWAY, 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 ANGIOPOIETINRECEPTOR PATHWAY

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	ABCG2	ABCG2	ABCG2	71	0.74	0.05	YES
2	CA9	CA9	CA9	74	0.73	0.1	YES
3	EDN1	EDN1	EDN1	184	0.65	0.14	YES
4	NOS2	NOS2	NOS2	274	0.59	0.18	YES
5	EGLN3	EGLN3	EGLN3	308	0.58	0.22	YES
6	PLIN2	PLIN2	PLIN2	322	0.58	0.26	YES
7	VEGFA	VEGFA	VEGFA	335	0.57	0.3	YES
8	CP	CP	CP	497	0.51	0.33	YES
9	ADM	ADM	ADM	775	0.44	0.35	YES
10	ETS1	ETS1	ETS1	827	0.42	0.38	YES
11	TFF3	TFF3	TFF3	949	0.4	0.4	YES
12	HNF4A	HNF4A	HNF4A	1195	0.36	0.41	YES
13	ENG	ENG	ENG	1423	0.32	0.42	YES
14	BNIP3	BNIP3	BNIP3	1666	0.29	0.43	YES
15	SERPINE1	SERPINE1	SERPINE1	1693	0.29	0.45	YES
16	RORA	RORA	RORA	1760	0.28	0.47	YES
17	SLC2A1	SLC2A1	SLC2A1	1838	0.28	0.48	YES
18	CXCR4	CXCR4	CXCR4	1947	0.26	0.5	YES
19	FOS	FOS	FOS	1979	0.26	0.51	YES
20	CXCL12	CXCL12	CXCL12	1996	0.26	0.53	YES
21	NDRG1	NDRG1	NDRG1	2066	0.26	0.55	YES
22	HMOX1	HMOX1	HMOX1	2170	0.25	0.56	YES
23	BHLHE41	BHLHE41	BHLHE41	2235	0.24	0.57	YES
24	PFKFB3	PFKFB3	PFKFB3	2354	0.23	0.58	YES
25	EPO	EPO	EPO	2435	0.23	0.6	YES
26	HK2	HK2	HK2	2705	0.21	0.6	YES
27	GATA2	GATA2	GATA2	2719	0.21	0.61	YES
28	LDHA	LDHA	LDHA	2997	0.19	0.61	YES
29	NCOA2	NCOA2	NCOA2	3685	0.15	0.58	YES
30	EGLN1	EGLN1	EGLN1	3721	0.15	0.59	YES
31	NT5E	NT5E	NT5E	3949	0.14	0.59	YES
32	CREB1	CREB1	CREB1	4149	0.13	0.59	YES
33	NPM1	NPM1	NPM1	4211	0.13	0.59	YES
34	ID2	ID2	ID2	4439	0.12	0.59	YES
35	ITGB2	ITGB2	ITGB2	4441	0.12	0.6	YES
36	PGK1	PGK1	PGK1	4496	0.12	0.6	YES
37	JUN	JUN	JUN	4537	0.12	0.61	YES
38	TFRC	TFRC	TFRC	4921	0.1	0.6	NO
39	ARNT	ARNT	ARNT	5017	0.1	0.6	NO
40	ENO1	ENO1	ENO1	5295	0.095	0.59	NO
41	EP300	EP300	EP300	5555	0.088	0.58	NO
42	NCOA1	NCOA1	NCOA1	5657	0.085	0.58	NO
43	MCL1	MCL1	MCL1	5747	0.083	0.59	NO
44	PFKL	PFKL	PFKL	5862	0.08	0.58	NO
45	HK1	HK1	HK1	5941	0.078	0.59	NO
46	SMAD4	SMAD4	SMAD4	6294	0.069	0.57	NO
47	ABCB1	ABCB1	ABCB1	7408	0.044	0.51	NO
48	CREBBP	CREBBP	CREBBP	7601	0.04	0.51	NO
49	BHLHE40	BHLHE40	BHLHE40	7687	0.038	0.5	NO
50	SP1	SP1	SP1	8395	0.023	0.47	NO
51	FECH	FECH	FECH	9204	0.0064	0.42	NO
52	HDAC7	HDAC7	HDAC7	9277	0.0049	0.42	NO
53	CITED2	CITED2	CITED2	9462	0.0013	0.41	NO
54	COPS5	COPS5	COPS5	9522	0.00012	0.41	NO
55	PKM2	PKM2	PKM2	9595	-0.0016	0.4	NO
56	PGM1	PGM1	PGM1	9816	-0.0063	0.39	NO
57	ALDOA	ALDOA	ALDOA	10156	-0.013	0.37	NO
58	SMAD3	SMAD3	SMAD3	10634	-0.024	0.35	NO
59	TERT	TERT	TERT	10705	-0.025	0.35	NO
60	TF	TF	TF	11251	-0.037	0.32	NO
61	FURIN	FURIN	FURIN	11597	-0.045	0.3	NO
62	AKT1	AKT1	AKT1	11992	-0.054	0.28	NO
63	HIF1A	HIF1A	HIF1A	13880	-0.11	0.19	NO
64	IGFBP1	IGFBP1	IGFBP1	14955	-0.15	0.14	NO
65	LEP	LEP	LEP	16156	-0.22	0.09	NO
66	GCK	GCK	GCK	17013	-0.31	0.065	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: PID ANGIOPOIETINRECEPTOR PATHWAY.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: PID ANGIOPOIETINRECEPTOR 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 SHP2 PATHWAY

Table S30. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	P2RX7	P2RX7	P2RX7	665	0.46	0.045	YES
2	NLRP1	NLRP1	NLRP1	1005	0.39	0.096	YES
3	MEFV	MEFV	MEFV	1147	0.37	0.15	YES
4	NLRC4	NLRC4	NLRC4	1235	0.35	0.21	YES
5	MAPK12	MAPK12	MAPK12	1310	0.34	0.27	YES
6	BIRC3	BIRC3	BIRC3	2009	0.26	0.27	YES
7	CASP1	CASP1	CASP1	2092	0.25	0.31	YES
8	TNFAIP3	TNFAIP3	TNFAIP3	2232	0.24	0.35	YES
9	MAPK11	MAPK11	MAPK11	2531	0.22	0.37	YES
10	NOD2	NOD2	NOD2	2545	0.22	0.41	YES
11	NLRP3	NLRP3	NLRP3	2594	0.22	0.44	YES
12	PSTPIP1	PSTPIP1	PSTPIP1	2664	0.21	0.48	YES
13	IRAK2	IRAK2	IRAK2	2751	0.2	0.51	YES
14	BCL2	BCL2	BCL2	3012	0.19	0.53	YES
15	TRAF6	TRAF6	TRAF6	3071	0.19	0.56	YES
16	AIM2	AIM2	AIM2	3204	0.18	0.58	YES
17	BIRC2	BIRC2	BIRC2	5532	0.089	0.47	NO
18	TXNIP	TXNIP	TXNIP	5757	0.083	0.47	NO
19	CYLD	CYLD	CYLD	6066	0.075	0.47	NO
20	PANX1	PANX1	PANX1	6200	0.071	0.48	NO
21	NOD1	NOD1	NOD1	6746	0.058	0.46	NO
22	CASP8	CASP8	CASP8	6868	0.055	0.46	NO
23	MAPK14	MAPK14	MAPK14	7231	0.048	0.45	NO
24	TAB2	TAB2	TAB2	7571	0.041	0.44	NO
25	APP	APP	APP	8487	0.021	0.39	NO
26	CARD9	CARD9	CARD9	8660	0.018	0.38	NO
27	TMEM189-UBE2V1	TMEM189-UBE2V1	TMEM189-UBE2V1	8802	0.014	0.38	NO
28	HSP90AB1	HSP90AB1	HSP90AB1	8928	0.012	0.37	NO
29	MAP2K6	MAP2K6	MAP2K6	9043	0.0097	0.37	NO
30	UBE2N	UBE2N	UBE2N	9107	0.0086	0.37	NO
31	CASP4	CASP4	CASP4	9225	0.0061	0.36	NO
32	CHUK	CHUK	CHUK	9335	0.0037	0.36	NO
33	MAP3K7	MAP3K7	MAP3K7	9723	-0.0043	0.34	NO
34	RIPK2	RIPK2	RIPK2	9967	-0.0095	0.32	NO
35	TXN	TXN	TXN	9974	-0.0096	0.32	NO
36	TAB1	TAB1	TAB1	10455	-0.019	0.3	NO
37	CASP2	CASP2	CASP2	10542	-0.021	0.3	NO
38	IKBKB	IKBKB	IKBKB	10769	-0.027	0.29	NO
39	TAB3	TAB3	TAB3	11107	-0.034	0.28	NO
40	MAPK13	MAPK13	MAPK13	12683	-0.071	0.21	NO
41	CASP9	CASP9	CASP9	13484	-0.093	0.18	NO
42	IRAK1	IRAK1	IRAK1	13931	-0.11	0.17	NO
43	PYCARD	PYCARD	PYCARD	14015	-0.11	0.19	NO
44	IKBKG	IKBKG	IKBKG	14132	-0.12	0.2	NO
45	BCL2L1	BCL2L1	BCL2L1	14224	-0.12	0.22	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: PID SHP2 PATHWAY.

Figure S60. Get High-res Image For the top 5 core enriched genes in the pathway: PID SHP2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype 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 CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.48	1.2	0.37	1	1	0.69	0.39	0.42	1	0.83
KEGG GLYCINE SERINE AND THREONINE METABOLISM	31	genes.ES.table	0.52	1.2	0.25	1	1	0.48	0.16	0.41	1	0.84
KEGG HISTIDINE METABOLISM	29	genes.ES.table	0.55	1.3	0.2	1	1	0.52	0.22	0.4	1	0.97
KEGG SELENOAMINO ACID METABOLISM	26	genes.ES.table	0.44	1.4	0.1	1	1	0.65	0.35	0.43	1	0.9
KEGG PYRUVATE METABOLISM	39	genes.ES.table	0.45	1.3	0.23	1	1	0.41	0.24	0.31	1	0.92
KEGG BUTANOATE METABOLISM	31	genes.ES.table	0.5	1.3	0.21	1	1	0.55	0.24	0.42	1	0.96
KEGG AMINOACYL TRNA BIOSYNTHESIS	41	genes.ES.table	0.36	1.2	0.27	1	1	0.49	0.35	0.32	1	0.81
KEGG BASE EXCISION REPAIR	33	genes.ES.table	0.48	1.6	0.065	1	0.94	0.55	0.35	0.36	1	0.8
KEGG LYSOSOME	120	genes.ES.table	0.36	1.4	0.14	1	0.99	0.5	0.33	0.34	1	0.92
KEGG TIGHT JUNCTION	125	genes.ES.table	0.3	1.2	0.21	1	1	0.2	0.12	0.18	1	0.85

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

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	NEIL1	NEIL1	NEIL1	981	0.39	0.051	YES
2	NTHL1	NTHL1	NTHL1	1300	0.33	0.12	YES
3	PARP3	PARP3	PARP3	1329	0.33	0.21	YES
4	OGG1	OGG1	OGG1	1353	0.33	0.3	YES
5	MUTYH	MUTYH	MUTYH	1848	0.27	0.34	YES
6	POLD1	POLD1	POLD1	2513	0.22	0.36	YES
7	MPG	MPG	MPG	2954	0.19	0.39	YES
8	POLD2	POLD2	POLD2	3346	0.16	0.41	YES
9	LIG1	LIG1	LIG1	4451	0.12	0.38	YES
10	NEIL2	NEIL2	NEIL2	4662	0.11	0.4	YES
11	UNG	UNG	UNG	4829	0.1	0.42	YES
12	PARP4	PARP4	PARP4	4950	0.099	0.44	YES
13	POLE	POLE	POLE	5167	0.091	0.45	YES
14	SMUG1	SMUG1	SMUG1	5348	0.085	0.46	YES
15	APEX2	APEX2	APEX2	5572	0.078	0.47	YES
16	POLD4	POLD4	POLD4	6049	0.064	0.46	YES
17	POLL	POLL	POLL	6199	0.06	0.47	YES
18	XRCC1	XRCC1	XRCC1	6328	0.056	0.48	YES
19	LIG3	LIG3	LIG3	7089	0.035	0.45	NO
20	PCNA	PCNA	PCNA	7702	0.018	0.42	NO
21	PARP2	PARP2	PARP2	8694	-0.0069	0.36	NO
22	POLE3	POLE3	POLE3	8697	-0.007	0.37	NO
23	POLB	POLB	POLB	9039	-0.016	0.35	NO
24	APEX1	APEX1	APEX1	9063	-0.016	0.36	NO
25	MBD4	MBD4	MBD4	9266	-0.022	0.35	NO
26	FEN1	FEN1	FEN1	9605	-0.03	0.34	NO
27	POLE4	POLE4	POLE4	9733	-0.033	0.34	NO
28	PARP1	PARP1	PARP1	9736	-0.033	0.35	NO
29	TDG	TDG	TDG	10852	-0.062	0.31	NO
30	POLE2	POLE2	POLE2	11059	-0.068	0.31	NO
31	HMGB1	HMGB1	HMGB1	11100	-0.069	0.33	NO
32	POLD3	POLD3	POLD3	12109	-0.1	0.3	NO
33	NEIL3	NEIL3	NEIL3	12882	-0.13	0.29	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 CITRATE CYCLE TCA CYCLE.

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

genes ES table in pathway: KEGG GLYCINE SERINE AND THREONINE 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	NAPSA	NAPSA	NAPSA	188	0.7	0.033	YES
2	CTSL2	CTSL2	CTSL2	267	0.64	0.069	YES
3	AP3B2	AP3B2	AP3B2	434	0.55	0.094	YES
4	AP1M2	AP1M2	AP1M2	940	0.4	0.091	YES
5	CTSC	CTSC	CTSC	975	0.39	0.11	YES
6	IDUA	IDUA	IDUA	1155	0.36	0.13	YES
7	DNASE2B	DNASE2B	DNASE2B	1551	0.3	0.12	YES
8	NAGLU	NAGLU	NAGLU	1704	0.28	0.13	YES
9	GLB1	GLB1	GLB1	1709	0.28	0.15	YES
10	AP1S3	AP1S3	AP1S3	1715	0.28	0.17	YES
11	NEU1	NEU1	NEU1	1743	0.28	0.18	YES
12	ACP5	ACP5	ACP5	1819	0.27	0.2	YES
13	ATP6V0A1	ATP6V0A1	ATP6V0A1	1996	0.26	0.2	YES
14	SMPD1	SMPD1	SMPD1	2229	0.24	0.2	YES
15	NAGPA	NAGPA	NAGPA	2314	0.23	0.21	YES
16	SUMF1	SUMF1	SUMF1	2342	0.23	0.23	YES
17	ABCB9	ABCB9	ABCB9	2398	0.22	0.24	YES
18	PPT2	PPT2	PPT2	2426	0.22	0.25	YES
19	LAPTM4B	LAPTM4B	LAPTM4B	2482	0.22	0.26	YES
20	GALNS	GALNS	GALNS	2646	0.21	0.26	YES
21	PLA2G15	PLA2G15	PLA2G15	2718	0.2	0.27	YES
22	GAA	GAA	GAA	2878	0.19	0.28	YES
23	GNPTG	GNPTG	GNPTG	2985	0.18	0.28	YES
24	SGSH	SGSH	SGSH	3217	0.17	0.28	YES
25	CTSH	CTSH	CTSH	3221	0.17	0.29	YES
26	ATP6V0C	ATP6V0C	ATP6V0C	3229	0.17	0.3	YES
27	AP1S1	AP1S1	AP1S1	3304	0.17	0.31	YES
28	AP4M1	AP4M1	AP4M1	3447	0.16	0.31	YES
29	CTSA	CTSA	CTSA	3822	0.14	0.3	YES
30	CTNS	CTNS	CTNS	3901	0.14	0.3	YES
31	ACP2	ACP2	ACP2	3991	0.14	0.3	YES
32	GGA3	GGA3	GGA3	4003	0.13	0.31	YES
33	GGA1	GGA1	GGA1	4065	0.13	0.32	YES
34	GLA	GLA	GLA	4140	0.13	0.32	YES
35	CTSF	CTSF	CTSF	4154	0.13	0.33	YES
36	ARSA	ARSA	ARSA	4223	0.12	0.33	YES
37	ATP6V0D1	ATP6V0D1	ATP6V0D1	4289	0.12	0.34	YES
38	CTSG	CTSG	CTSG	4324	0.12	0.34	YES
39	CLN3	CLN3	CLN3	4387	0.12	0.34	YES
40	ATP6V0A4	ATP6V0A4	ATP6V0A4	4799	0.1	0.33	YES
41	CTSK	CTSK	CTSK	4896	0.1	0.33	YES
42	CTSB	CTSB	CTSB	5053	0.095	0.33	YES
43	CLTA	CLTA	CLTA	5119	0.093	0.33	YES
44	CTSZ	CTSZ	CTSZ	5127	0.092	0.33	YES
45	CTSD	CTSD	CTSD	5128	0.092	0.34	YES
46	MCOLN1	MCOLN1	MCOLN1	5229	0.089	0.34	YES
47	ARSG	ARSG	ARSG	5333	0.085	0.34	YES
48	AGA	AGA	AGA	5418	0.083	0.34	YES
49	GUSB	GUSB	GUSB	5421	0.083	0.34	YES
50	CD63	CD63	CD63	5443	0.082	0.35	YES
51	CD68	CD68	CD68	5455	0.082	0.35	YES
52	GNS	GNS	GNS	5468	0.081	0.36	YES
53	CTSL1	CTSL1	CTSL1	5624	0.077	0.35	YES
54	LAPTM4A	LAPTM4A	LAPTM4A	5671	0.075	0.36	YES
55	PSAP	PSAP	PSAP	5814	0.071	0.35	YES
56	LAMP1	LAMP1	LAMP1	5831	0.07	0.36	YES
57	SORT1	SORT1	SORT1	5833	0.07	0.36	YES
58	SLC11A1	SLC11A1	SLC11A1	5952	0.067	0.36	YES
59	ATP6V1H	ATP6V1H	ATP6V1H	6000	0.066	0.36	YES
60	NPC2	NPC2	NPC2	6005	0.066	0.36	YES
61	AP1M1	AP1M1	AP1M1	6153	0.061	0.36	NO
62	MAN2B1	MAN2B1	MAN2B1	6532	0.05	0.34	NO
63	ATP6V0B	ATP6V0B	ATP6V0B	6634	0.048	0.34	NO
64	AP3S2	AP3S2	AP3S2	6718	0.046	0.34	NO
65	AP3D1	AP3D1	AP3D1	6726	0.045	0.34	NO
66	AP1G1	AP1G1	AP1G1	6742	0.045	0.34	NO
67	CLTB	CLTB	CLTB	6766	0.044	0.34	NO
68	HGSNAT	HGSNAT	HGSNAT	6804	0.043	0.34	NO
69	SLC11A2	SLC11A2	SLC11A2	6882	0.041	0.34	NO
70	FUCA1	FUCA1	FUCA1	6943	0.039	0.34	NO
71	ATP6V0A2	ATP6V0A2	ATP6V0A2	6978	0.038	0.34	NO
72	CLTC	CLTC	CLTC	7217	0.032	0.33	NO
73	ENTPD4	ENTPD4	ENTPD4	7273	0.03	0.33	NO
74	GBA	GBA	GBA	7332	0.029	0.33	NO
75	HEXA	HEXA	HEXA	7462	0.025	0.32	NO
76	AP1B1	AP1B1	AP1B1	7561	0.022	0.32	NO
77	GM2A	GM2A	GM2A	7563	0.022	0.32	NO
78	HEXB	HEXB	HEXB	7597	0.021	0.32	NO
79	HYAL1	HYAL1	HYAL1	7611	0.021	0.32	NO
80	ARSB	ARSB	ARSB	7617	0.02	0.32	NO
81	NPC1	NPC1	NPC1	7783	0.016	0.31	NO
82	GGA2	GGA2	GGA2	7924	0.013	0.31	NO
83	AP4S1	AP4S1	AP4S1	8267	0.0038	0.29	NO
84	SLC17A5	SLC17A5	SLC17A5	8361	0.0016	0.28	NO
85	ATP6AP1	ATP6AP1	ATP6AP1	8737	-0.0081	0.26	NO
86	NAGA	NAGA	NAGA	8819	-0.01	0.26	NO
87	M6PR	M6PR	M6PR	9257	-0.022	0.24	NO
88	CLTCL1	CLTCL1	CLTCL1	9276	-0.022	0.24	NO
89	ASAH1	ASAH1	ASAH1	9315	-0.023	0.24	NO
90	CLN5	CLN5	CLN5	9441	-0.026	0.23	NO
91	DNASE2	DNASE2	DNASE2	9503	-0.028	0.23	NO
92	AP3B1	AP3B1	AP3B1	9545	-0.029	0.23	NO
93	IGF2R	IGF2R	IGF2R	9612	-0.03	0.23	NO
94	ABCA2	ABCA2	ABCA2	9645	-0.031	0.23	NO
95	CD164	CD164	CD164	9824	-0.036	0.22	NO
96	LIPA	LIPA	LIPA	9856	-0.036	0.22	NO
97	AP3M1	AP3M1	AP3M1	10035	-0.041	0.21	NO
98	TPP1	TPP1	TPP1	10114	-0.043	0.21	NO
99	TCIRG1	TCIRG1	TCIRG1	10361	-0.05	0.2	NO
100	LAMP2	LAMP2	LAMP2	10521	-0.054	0.19	NO
101	AP3M2	AP3M2	AP3M2	10604	-0.056	0.19	NO
102	AP4B1	AP4B1	AP4B1	10760	-0.06	0.19	NO
103	PPT1	PPT1	PPT1	10793	-0.061	0.19	NO
104	SCARB2	SCARB2	SCARB2	11836	-0.091	0.14	NO
105	AP4E1	AP4E1	AP4E1	11848	-0.092	0.14	NO
106	LGMN	LGMN	LGMN	11942	-0.094	0.14	NO
107	MFSD8	MFSD8	MFSD8	11967	-0.095	0.15	NO
108	MANBA	MANBA	MANBA	12182	-0.1	0.14	NO
109	LAPTM5	LAPTM5	LAPTM5	12539	-0.12	0.13	NO
110	GNPTAB	GNPTAB	GNPTAB	12673	-0.12	0.13	NO
111	ATP6V0D2	ATP6V0D2	ATP6V0D2	12674	-0.12	0.14	NO
112	CTSS	CTSS	CTSS	13125	-0.14	0.12	NO
113	CTSE	CTSE	CTSE	13561	-0.16	0.11	NO
114	CTSO	CTSO	CTSO	13831	-0.17	0.1	NO
115	AP3S1	AP3S1	AP3S1	14118	-0.18	0.099	NO
116	GALC	GALC	GALC	14300	-0.19	0.1	NO
117	IDS	IDS	IDS	15162	-0.25	0.069	NO
118	AP1S2	AP1S2	AP1S2	16520	-0.39	0.019	NO
119	CTSW	CTSW	CTSW	17080	-0.5	0.019	NO
120	LAMP3	LAMP3	LAMP3	17603	-0.69	0.033	NO

Figure S63. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM.

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

genes ES table in pathway: KEGG HISTIDINE METABOLISM

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	CBS	CBS	CBS	207	0.68	0.17	YES
2	GGT1	GGT1	GGT1	1156	0.36	0.21	YES
3	HEMK1	HEMK1	HEMK1	1935	0.26	0.24	YES
4	SCLY	SCLY	SCLY	2206	0.24	0.29	YES
5	PAPSS2	PAPSS2	PAPSS2	2893	0.19	0.3	YES
6	WBSCR22	WBSCR22	WBSCR22	3164	0.18	0.33	YES
7	LCMT1	LCMT1	LCMT1	3349	0.16	0.37	YES
8	TRMT11	TRMT11	TRMT11	3508	0.16	0.4	YES
9	SEPHS2	SEPHS2	SEPHS2	3762	0.14	0.42	YES
10	LCMT2	LCMT2	LCMT2	4968	0.098	0.38	YES
11	METTL6	METTL6	METTL6	5065	0.095	0.4	YES
12	SEPHS1	SEPHS1	SEPHS1	5088	0.094	0.43	YES
13	AHCY	AHCY	AHCY	5808	0.071	0.41	YES
14	MARS	MARS	MARS	5975	0.066	0.42	YES
15	CTH	CTH	CTH	6015	0.065	0.43	YES
16	MARS2	MARS2	MARS2	6317	0.056	0.43	YES
17	PAPSS1	PAPSS1	PAPSS1	6347	0.055	0.44	YES
18	METTL2B	METTL2B	METTL2B	6707	0.046	0.44	NO
19	MAT2A	MAT2A	MAT2A	7486	0.024	0.4	NO
20	GGT7	GGT7	GGT7	7737	0.018	0.39	NO
21	GGT6	GGT6	GGT6	8017	0.01	0.38	NO
22	AHCYL1	AHCYL1	AHCYL1	8373	0.0012	0.36	NO
23	AHCYL2	AHCYL2	AHCYL2	8874	-0.011	0.34	NO
24	MAT2B	MAT2B	MAT2B	10450	-0.052	0.26	NO
25	MAT1A	MAT1A	MAT1A	14059	-0.18	0.11	NO
26	GGT5	GGT5	GGT5	16768	-0.43	0.079	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 HISTIDINE METABOLISM.

Figure S66. 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 SELENOAMINO ACID 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	ALDH3A1	ALDH3A1	ALDH3A1	565	0.5	0.073	YES
2	ALDH3B1	ALDH3B1	ALDH3B1	1244	0.34	0.11	YES
3	ALDH2	ALDH2	ALDH2	1463	0.31	0.16	YES
4	FTCD	FTCD	FTCD	1569	0.3	0.21	YES
5	UROC1	UROC1	UROC1	1722	0.28	0.26	YES
6	ACY3	ACY3	ACY3	1837	0.27	0.31	YES
7	CNDP1	CNDP1	CNDP1	1909	0.26	0.36	YES
8	HEMK1	HEMK1	HEMK1	1935	0.26	0.42	YES
9	DDC	DDC	DDC	2271	0.23	0.44	YES
10	AMDHD1	AMDHD1	AMDHD1	3018	0.18	0.44	YES
11	WBSCR22	WBSCR22	WBSCR22	3164	0.18	0.47	YES
12	LCMT1	LCMT1	LCMT1	3349	0.16	0.49	YES
13	TRMT11	TRMT11	TRMT11	3508	0.16	0.52	YES
14	ALDH1A3	ALDH1A3	ALDH1A3	3764	0.14	0.53	YES
15	ALDH1B1	ALDH1B1	ALDH1B1	3958	0.14	0.55	YES
16	LCMT2	LCMT2	LCMT2	4968	0.098	0.51	NO
17	METTL6	METTL6	METTL6	5065	0.095	0.53	NO
18	MAOA	MAOA	MAOA	5508	0.08	0.52	NO
19	ALDH3A2	ALDH3A2	ALDH3A2	5884	0.069	0.51	NO
20	MAOB	MAOB	MAOB	6543	0.05	0.49	NO
21	METTL2B	METTL2B	METTL2B	6707	0.046	0.49	NO
22	HDC	HDC	HDC	6888	0.04	0.49	NO
23	HAL	HAL	HAL	8280	0.0033	0.41	NO
24	ALDH7A1	ALDH7A1	ALDH7A1	9596	-0.03	0.34	NO
25	ALDH9A1	ALDH9A1	ALDH9A1	9937	-0.038	0.33	NO
26	ABP1	ABP1	ABP1	10919	-0.064	0.29	NO
27	ALDH3B2	ALDH3B2	ALDH3B2	11152	-0.071	0.3	NO
28	ASPA	ASPA	ASPA	13520	-0.16	0.2	NO
29	HNMT	HNMT	HNMT	15705	-0.3	0.14	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 SELENOAMINO ACID METABOLISM.

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

genes ES table in pathway: KEGG PYRUVATE 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	ACSM1	ACSM1	ACSM1	23	1	0.14	YES
2	BDH1	BDH1	BDH1	325	0.6	0.2	YES
3	OXCT2	OXCT2	OXCT2	364	0.59	0.28	YES
4	AKR1B10	AKR1B10	AKR1B10	479	0.53	0.35	YES
5	ABAT	ABAT	ABAT	803	0.44	0.39	YES
6	ACSM2A	ACSM2A	ACSM2A	859	0.42	0.44	YES
7	ALDH2	ALDH2	ALDH2	1463	0.31	0.45	YES
8	PDHA1	PDHA1	PDHA1	2568	0.21	0.42	YES
9	ACSM5	ACSM5	ACSM5	2616	0.21	0.44	YES
10	ACSM3	ACSM3	ACSM3	3041	0.18	0.44	YES
11	AACS	AACS	AACS	3226	0.17	0.46	YES
12	HMGCL	HMGCL	HMGCL	3412	0.16	0.47	YES
13	ALDH1B1	ALDH1B1	ALDH1B1	3958	0.14	0.46	YES
14	PDHB	PDHB	PDHB	3965	0.14	0.47	YES
15	ECHS1	ECHS1	ECHS1	4183	0.13	0.48	YES
16	BDH2	BDH2	BDH2	4247	0.12	0.49	YES
17	OXCT1	OXCT1	OXCT1	4356	0.12	0.5	YES
18	ALDH5A1	ALDH5A1	ALDH5A1	4750	0.1	0.5	NO
19	ACAT1	ACAT1	ACAT1	5107	0.093	0.49	NO
20	L2HGDH	L2HGDH	L2HGDH	5650	0.076	0.47	NO
21	ALDH3A2	ALDH3A2	ALDH3A2	5884	0.069	0.46	NO
22	HADH	HADH	HADH	6580	0.049	0.43	NO
23	HMGCS1	HMGCS1	HMGCS1	6764	0.044	0.43	NO
24	ACADS	ACADS	ACADS	6773	0.044	0.43	NO
25	HADHA	HADHA	HADHA	7479	0.024	0.4	NO
26	ACAT2	ACAT2	ACAT2	7910	0.013	0.38	NO
27	EHHADH	EHHADH	EHHADH	9238	-0.021	0.31	NO
28	ALDH7A1	ALDH7A1	ALDH7A1	9596	-0.03	0.29	NO
29	ALDH9A1	ALDH9A1	ALDH9A1	9937	-0.038	0.28	NO
30	GAD1	GAD1	GAD1	17147	-0.52	-0.049	NO
31	HMGCS2	HMGCS2	HMGCS2	17776	-0.8	0.023	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 PYRUVATE METABOLISM.

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

genes ES table in pathway: KEGG BUTANOATE METABOLISM

Table 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	GTF2H4	GTF2H4	GTF2H4	2723	0.2	-0.068	YES
2	POLR2J	POLR2J	POLR2J	2998	0.18	-0.0079	YES
3	ERCC2	ERCC2	ERCC2	3032	0.18	0.065	YES
4	POLR2L	POLR2L	POLR2L	3394	0.16	0.11	YES
5	GTF2F2	GTF2F2	GTF2F2	3972	0.14	0.13	YES
6	WHSC2	WHSC2	WHSC2	4660	0.11	0.14	YES
7	GTF2H2B	GTF2H2B	GTF2H2B	4708	0.11	0.18	YES
8	POLR2E	POLR2E	POLR2E	5383	0.084	0.18	YES
9	POLR2I	POLR2I	POLR2I	5394	0.084	0.21	YES
10	RDBP	RDBP	RDBP	5417	0.083	0.24	YES
11	POLR2G	POLR2G	POLR2G	5481	0.081	0.27	YES
12	TH1L	TH1L	TH1L	5936	0.068	0.28	YES
13	COBRA1	COBRA1	COBRA1	5946	0.067	0.3	YES
14	NCBP2	NCBP2	NCBP2	6081	0.063	0.32	YES
15	SUPT4H1	SUPT4H1	SUPT4H1	6177	0.06	0.34	YES
16	CTDP1	CTDP1	CTDP1	6488	0.051	0.34	YES
17	POLR2H	POLR2H	POLR2H	7104	0.035	0.32	NO
18	POLR2F	POLR2F	POLR2F	7252	0.031	0.33	NO
19	GTF2F1	GTF2F1	GTF2F1	7365	0.028	0.34	NO
20	ERCC3	ERCC3	ERCC3	7738	0.018	0.32	NO
21	POLR2C	POLR2C	POLR2C	8264	0.004	0.3	NO
22	CDK7	CDK7	CDK7	8957	-0.014	0.26	NO
23	CCNH	CCNH	CCNH	9458	-0.026	0.24	NO
24	SUPT5H	SUPT5H	SUPT5H	9463	-0.027	0.26	NO
25	GTF2H2	GTF2H2	GTF2H2	9789	-0.035	0.25	NO
26	POLR2K	POLR2K	POLR2K	9851	-0.036	0.26	NO
27	NCBP1	NCBP1	NCBP1	9875	-0.037	0.28	NO
28	MNAT1	MNAT1	MNAT1	10038	-0.041	0.28	NO
29	POLR2A	POLR2A	POLR2A	10354	-0.05	0.29	NO
30	POLR2B	POLR2B	POLR2B	10391	-0.051	0.31	NO
31	GTF2H1	GTF2H1	GTF2H1	11375	-0.077	0.28	NO
32	POLR2D	POLR2D	POLR2D	12131	-0.1	0.28	NO
33	GTF2H3	GTF2H3	GTF2H3	12726	-0.12	0.3	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 BUTANOATE METABOLISM.

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

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	LDHD	LDHD	LDHD	356	0.59	0.09	YES
2	HAGHL	HAGHL	HAGHL	464	0.54	0.18	YES
3	ACSS2	ACSS2	ACSS2	1232	0.34	0.2	YES
4	ALDH2	ALDH2	ALDH2	1463	0.31	0.25	YES
5	ACYP1	ACYP1	ACYP1	2556	0.21	0.23	YES
6	PDHA1	PDHA1	PDHA1	2568	0.21	0.27	YES
7	PC	PC	PC	2580	0.21	0.3	YES
8	HAGH	HAGH	HAGH	2993	0.18	0.32	YES
9	LDHB	LDHB	LDHB	3055	0.18	0.35	YES
10	ACACA	ACACA	ACACA	3586	0.15	0.34	YES
11	DLD	DLD	DLD	3753	0.14	0.36	YES
12	ALDH1B1	ALDH1B1	ALDH1B1	3958	0.14	0.38	YES
13	PDHB	PDHB	PDHB	3965	0.14	0.4	YES
14	AKR1B1	AKR1B1	AKR1B1	4136	0.13	0.42	YES
15	MDH1	MDH1	MDH1	4311	0.12	0.43	YES
16	MDH2	MDH2	MDH2	4373	0.12	0.45	YES
17	ACAT1	ACAT1	ACAT1	5107	0.093	0.42	NO
18	ALDH3A2	ALDH3A2	ALDH3A2	5884	0.069	0.39	NO
19	PKLR	PKLR	PKLR	6108	0.062	0.39	NO
20	GRHPR	GRHPR	GRHPR	6181	0.06	0.4	NO
21	PCK2	PCK2	PCK2	6237	0.058	0.41	NO
22	ACOT12	ACOT12	ACOT12	6280	0.057	0.42	NO
23	ACAT2	ACAT2	ACAT2	7910	0.013	0.33	NO
24	PKM2	PKM2	PKM2	8573	-0.0037	0.29	NO
25	DLAT	DLAT	DLAT	8822	-0.01	0.28	NO
26	ACSS1	ACSS1	ACSS1	8871	-0.011	0.28	NO
27	PCK1	PCK1	PCK1	9059	-0.016	0.27	NO
28	LDHAL6A	LDHAL6A	LDHAL6A	9422	-0.025	0.26	NO
29	ACACB	ACACB	ACACB	9440	-0.026	0.26	NO
30	ALDH7A1	ALDH7A1	ALDH7A1	9596	-0.03	0.26	NO
31	ACYP2	ACYP2	ACYP2	9806	-0.035	0.25	NO
32	ALDH9A1	ALDH9A1	ALDH9A1	9937	-0.038	0.25	NO
33	GLO1	GLO1	GLO1	10941	-0.065	0.21	NO
34	LDHC	LDHC	LDHC	12101	-0.1	0.16	NO
35	ME2	ME2	ME2	12507	-0.12	0.16	NO
36	ME3	ME3	ME3	13274	-0.14	0.15	NO
37	ME1	ME1	ME1	14580	-0.21	0.12	NO
38	LDHAL6B	LDHAL6B	LDHAL6B	14878	-0.23	0.14	NO
39	LDHA	LDHA	LDHA	14907	-0.23	0.18	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 AMINOACYL TRNA BIOSYNTHESIS.

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

genes ES table in pathway: KEGG BASE EXCISION REPAIR

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	NDUFS8	NDUFS8	NDUFS8	1448	0.31	-0.045	YES
2	ATP5G1	ATP5G1	ATP5G1	1481	0.31	-0.012	YES
3	NDUFB2	NDUFB2	NDUFB2	2004	0.25	-0.012	YES
4	UQCRC1	UQCRC1	UQCRC1	2112	0.24	0.0091	YES
5	UQCRHL	UQCRHL	UQCRHL	2393	0.22	0.019	YES
6	NDUFS7	NDUFS7	NDUFS7	2435	0.22	0.041	YES
7	NDUFA4	NDUFA4	NDUFA4	2612	0.21	0.054	YES
8	ATP5J2	ATP5J2	ATP5J2	2662	0.2	0.075	YES
9	UQCRH	UQCRH	UQCRH	2757	0.2	0.092	YES
10	ATP5D	ATP5D	ATP5D	2809	0.2	0.11	YES
11	COX6A1	COX6A1	COX6A1	2819	0.2	0.13	YES
12	NDUFS6	NDUFS6	NDUFS6	3048	0.18	0.14	YES
13	NDUFA3	NDUFA3	NDUFA3	3190	0.17	0.15	YES
14	COX4I1	COX4I1	COX4I1	3233	0.17	0.17	YES
15	NDUFB9	NDUFB9	NDUFB9	3262	0.17	0.19	YES
16	NDUFA7	NDUFA7	NDUFA7	3281	0.17	0.2	YES
17	ATP5H	ATP5H	ATP5H	3340	0.16	0.22	YES
18	NDUFB10	NDUFB10	NDUFB10	3422	0.16	0.23	YES
19	NDUFA11	NDUFA11	NDUFA11	3485	0.16	0.25	YES
20	NDUFA9	NDUFA9	NDUFA9	3631	0.15	0.26	YES
21	NDUFV1	NDUFV1	NDUFV1	3813	0.14	0.26	YES
22	NDUFB8	NDUFB8	NDUFB8	3889	0.14	0.27	YES
23	NDUFB3	NDUFB3	NDUFB3	4013	0.13	0.28	YES
24	NDUFB7	NDUFB7	NDUFB7	4050	0.13	0.29	YES
25	UQCRC2	UQCRC2	UQCRC2	4084	0.13	0.31	YES
26	CYCS	CYCS	CYCS	4147	0.13	0.32	YES
27	COX5A	COX5A	COX5A	4174	0.13	0.33	YES
28	ATP5I	ATP5I	ATP5I	4185	0.12	0.34	YES
29	NDUFA13	NDUFA13	NDUFA13	4210	0.12	0.36	YES
30	UQCR11	UQCR11	UQCR11	4220	0.12	0.37	YES
31	COX5B	COX5B	COX5B	4288	0.12	0.38	YES
32	ETFB	ETFB	ETFB	4294	0.12	0.39	YES
33	NDUFS5	NDUFS5	NDUFS5	4395	0.12	0.4	YES
34	NDUFB1	NDUFB1	NDUFB1	4481	0.11	0.41	YES
35	NDUFAB1	NDUFAB1	NDUFAB1	4607	0.11	0.41	YES
36	NDUFA8	NDUFA8	NDUFA8	4875	0.1	0.41	YES
37	ATP5B	ATP5B	ATP5B	4879	0.1	0.42	YES
38	NDUFA2	NDUFA2	NDUFA2	4881	0.1	0.43	YES
39	COX6B1	COX6B1	COX6B1	5000	0.097	0.44	YES
40	NDUFA10	NDUFA10	NDUFA10	5052	0.095	0.44	YES
41	ATP5E	ATP5E	ATP5E	5138	0.092	0.45	YES
42	NDUFB5	NDUFB5	NDUFB5	5147	0.092	0.46	YES
43	NDUFS1	NDUFS1	NDUFS1	5155	0.091	0.47	YES
44	UQCRFS1	UQCRFS1	UQCRFS1	5198	0.09	0.48	YES
45	NDUFA5	NDUFA5	NDUFA5	5281	0.087	0.48	YES
46	NDUFS2	NDUFS2	NDUFS2	5294	0.087	0.49	YES
47	CYC1	CYC1	CYC1	5296	0.087	0.5	YES
48	NDUFS3	NDUFS3	NDUFS3	5302	0.087	0.51	YES
49	COX8A	COX8A	COX8A	5334	0.085	0.52	YES
50	NDUFA1	NDUFA1	NDUFA1	5370	0.084	0.52	YES
51	ATP5A1	ATP5A1	ATP5A1	5441	0.082	0.53	YES
52	COX7B	COX7B	COX7B	5465	0.081	0.54	YES
53	ATP5C1	ATP5C1	ATP5C1	5548	0.079	0.54	YES
54	NDUFB4	NDUFB4	NDUFB4	5598	0.077	0.55	YES
55	UQCRQ	UQCRQ	UQCRQ	5738	0.073	0.55	YES
56	NDUFA6	NDUFA6	NDUFA6	5818	0.071	0.55	YES
57	ATP5F1	ATP5F1	ATP5F1	5917	0.068	0.56	YES
58	COX6C	COX6C	COX6C	5957	0.067	0.56	YES
59	COX7C	COX7C	COX7C	6164	0.061	0.56	NO
60	NDUFC2	NDUFC2	NDUFC2	6398	0.054	0.55	NO
61	ATP5J	ATP5J	ATP5J	6407	0.054	0.55	NO
62	ATP5L	ATP5L	ATP5L	6746	0.045	0.54	NO
63	UQCRB	UQCRB	UQCRB	6827	0.042	0.54	NO
64	ATP5O	ATP5O	ATP5O	6851	0.042	0.54	NO
65	NDUFB6	NDUFB6	NDUFB6	6870	0.041	0.55	NO
66	SDHC	SDHC	SDHC	6909	0.04	0.55	NO
67	SDHA	SDHA	SDHA	7116	0.034	0.54	NO
68	SDHB	SDHB	SDHB	7153	0.033	0.55	NO
69	NDUFS4	NDUFS4	NDUFS4	7302	0.029	0.54	NO
70	NDUFA12	NDUFA12	NDUFA12	7692	0.018	0.52	NO
71	ETFA	ETFA	ETFA	7857	0.014	0.51	NO
72	NDUFV3	NDUFV3	NDUFV3	8015	0.01	0.5	NO
73	NDUFV2	NDUFV2	NDUFV2	8699	-0.0071	0.47	NO
74	COX7A2L	COX7A2L	COX7A2L	8967	-0.014	0.46	NO
75	NDUFC1	NDUFC1	NDUFC1	8985	-0.014	0.46	NO
76	SDHD	SDHD	SDHD	9775	-0.034	0.42	NO
77	UCP3	UCP3	UCP3	11900	-0.093	0.31	NO
78	ETFDH	ETFDH	ETFDH	12860	-0.13	0.27	NO
79	UCP2	UCP2	UCP2	14651	-0.21	0.2	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 BASE EXCISION REPAIR.

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

genes ES table in pathway: KEGG LYSOSOME

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	NDUFS8	NDUFS8	NDUFS8	1448	0.31	-0.036	YES
2	NDUFB2	NDUFB2	NDUFB2	2004	0.25	-0.03	YES
3	UQCRC1	UQCRC1	UQCRC1	2112	0.24	-0.0014	YES
4	UQCRHL	UQCRHL	UQCRHL	2393	0.22	0.015	YES
5	NDUFS7	NDUFS7	NDUFS7	2435	0.22	0.044	YES
6	NDUFA4	NDUFA4	NDUFA4	2612	0.21	0.063	YES
7	UQCRH	UQCRH	UQCRH	2757	0.2	0.083	YES
8	COX6A1	COX6A1	COX6A1	2819	0.2	0.11	YES
9	NDUFS6	NDUFS6	NDUFS6	3048	0.18	0.12	YES
10	NDUFA3	NDUFA3	NDUFA3	3190	0.17	0.14	YES
11	COX4I1	COX4I1	COX4I1	3233	0.17	0.16	YES
12	NDUFB9	NDUFB9	NDUFB9	3262	0.17	0.18	YES
13	NDUFA7	NDUFA7	NDUFA7	3281	0.17	0.2	YES
14	NDUFB10	NDUFB10	NDUFB10	3422	0.16	0.22	YES
15	NDUFA11	NDUFA11	NDUFA11	3485	0.16	0.24	YES
16	NDUFA9	NDUFA9	NDUFA9	3631	0.15	0.25	YES
17	NDUFV1	NDUFV1	NDUFV1	3813	0.14	0.26	YES
18	NDUFB8	NDUFB8	NDUFB8	3889	0.14	0.28	YES
19	NDUFB3	NDUFB3	NDUFB3	4013	0.13	0.29	YES
20	NDUFB7	NDUFB7	NDUFB7	4050	0.13	0.3	YES
21	UQCRC2	UQCRC2	UQCRC2	4084	0.13	0.32	YES
22	CYCS	CYCS	CYCS	4147	0.13	0.34	YES
23	COX5A	COX5A	COX5A	4174	0.13	0.35	YES
24	NDUFA13	NDUFA13	NDUFA13	4210	0.12	0.37	YES
25	UQCR11	UQCR11	UQCR11	4220	0.12	0.38	YES
26	COX5B	COX5B	COX5B	4288	0.12	0.4	YES
27	ETFB	ETFB	ETFB	4294	0.12	0.42	YES
28	NDUFS5	NDUFS5	NDUFS5	4395	0.12	0.43	YES
29	NDUFB1	NDUFB1	NDUFB1	4481	0.11	0.44	YES
30	NDUFAB1	NDUFAB1	NDUFAB1	4607	0.11	0.45	YES
31	NDUFA8	NDUFA8	NDUFA8	4875	0.1	0.45	YES
32	NDUFA2	NDUFA2	NDUFA2	4881	0.1	0.46	YES
33	COX6B1	COX6B1	COX6B1	5000	0.097	0.47	YES
34	NDUFA10	NDUFA10	NDUFA10	5052	0.095	0.48	YES
35	NDUFB5	NDUFB5	NDUFB5	5147	0.092	0.49	YES
36	NDUFS1	NDUFS1	NDUFS1	5155	0.091	0.5	YES
37	UQCRFS1	UQCRFS1	UQCRFS1	5198	0.09	0.51	YES
38	NDUFA5	NDUFA5	NDUFA5	5281	0.087	0.52	YES
39	NDUFS2	NDUFS2	NDUFS2	5294	0.087	0.53	YES
40	CYC1	CYC1	CYC1	5296	0.087	0.54	YES
41	NDUFS3	NDUFS3	NDUFS3	5302	0.087	0.55	YES
42	COX8A	COX8A	COX8A	5334	0.085	0.56	YES
43	NDUFA1	NDUFA1	NDUFA1	5370	0.084	0.57	YES
44	COX7B	COX7B	COX7B	5465	0.081	0.58	YES
45	NDUFB4	NDUFB4	NDUFB4	5598	0.077	0.58	YES
46	UQCRQ	UQCRQ	UQCRQ	5738	0.073	0.59	YES
47	NDUFA6	NDUFA6	NDUFA6	5818	0.071	0.59	YES
48	COX6C	COX6C	COX6C	5957	0.067	0.59	YES
49	COX7C	COX7C	COX7C	6164	0.061	0.59	NO
50	NDUFC2	NDUFC2	NDUFC2	6398	0.054	0.58	NO
51	UQCRB	UQCRB	UQCRB	6827	0.042	0.57	NO
52	NDUFB6	NDUFB6	NDUFB6	6870	0.041	0.57	NO
53	SDHC	SDHC	SDHC	6909	0.04	0.57	NO
54	SDHA	SDHA	SDHA	7116	0.034	0.57	NO
55	SDHB	SDHB	SDHB	7153	0.033	0.57	NO
56	NDUFS4	NDUFS4	NDUFS4	7302	0.029	0.57	NO
57	NDUFA12	NDUFA12	NDUFA12	7692	0.018	0.55	NO
58	ETFA	ETFA	ETFA	7857	0.014	0.54	NO
59	NDUFV3	NDUFV3	NDUFV3	8015	0.01	0.53	NO
60	NDUFV2	NDUFV2	NDUFV2	8699	-0.0071	0.5	NO
61	COX7A2L	COX7A2L	COX7A2L	8967	-0.014	0.48	NO
62	NDUFC1	NDUFC1	NDUFC1	8985	-0.014	0.48	NO
63	SDHD	SDHD	SDHD	9775	-0.034	0.45	NO
64	ETFDH	ETFDH	ETFDH	12860	-0.13	0.29	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 LYSOSOME.

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LYSOSOME, 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 TIGHT JUNCTION

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	POLR2J	POLR2J	POLR2J	2998	0.18	-0.13	YES
2	POLR2L	POLR2L	POLR2L	3394	0.16	-0.12	YES
3	SF3B5	SF3B5	SF3B5	3675	0.15	-0.11	YES
4	SNRPB	SNRPB	SNRPB	3802	0.14	-0.088	YES
5	CPSF1	CPSF1	CPSF1	3970	0.14	-0.071	YES
6	GTF2F2	GTF2F2	GTF2F2	3972	0.14	-0.045	YES
7	SNRNP70	SNRNP70	SNRNP70	4413	0.12	-0.047	YES
8	SNRPF	SNRPF	SNRPF	4736	0.11	-0.044	YES
9	CD2BP2	CD2BP2	CD2BP2	4752	0.1	-0.025	YES
10	RBM5	RBM5	RBM5	4768	0.1	-0.0055	YES
11	RNPS1	RNPS1	RNPS1	4857	0.1	0.0093	YES
12	THOC4	THOC4	THOC4	5048	0.095	0.017	YES
13	SF3B4	SF3B4	SF3B4	5257	0.088	0.023	YES
14	POLR2E	POLR2E	POLR2E	5383	0.084	0.032	YES
15	POLR2I	POLR2I	POLR2I	5394	0.084	0.048	YES
16	EFTUD2	EFTUD2	EFTUD2	5408	0.083	0.063	YES
17	POLR2G	POLR2G	POLR2G	5481	0.081	0.074	YES
18	PABPN1	PABPN1	PABPN1	5830	0.07	0.069	YES
19	NCBP2	NCBP2	NCBP2	6081	0.063	0.067	YES
20	SNRPG	SNRPG	SNRPG	6114	0.062	0.077	YES
21	SNRPA	SNRPA	SNRPA	6118	0.062	0.089	YES
22	CSTF3	CSTF3	CSTF3	6600	0.048	0.072	YES
23	U2AF2	U2AF2	U2AF2	6838	0.042	0.067	YES
24	SF3A2	SF3A2	SF3A2	6945	0.039	0.068	YES
25	TXNL4A	TXNL4A	TXNL4A	6987	0.038	0.073	YES
26	HNRNPA2B1	HNRNPA2B1	HNRNPA2B1	7023	0.037	0.078	YES
27	CPSF3	CPSF3	CPSF3	7027	0.037	0.085	YES
28	POLR2H	POLR2H	POLR2H	7104	0.035	0.088	YES
29	DHX38	DHX38	DHX38	7128	0.034	0.093	YES
30	POLR2F	POLR2F	POLR2F	7252	0.031	0.092	YES
31	MAGOH	MAGOH	MAGOH	7298	0.029	0.095	YES
32	U2AF1	U2AF1	U2AF1	7347	0.029	0.098	YES
33	NHP2L1	NHP2L1	NHP2L1	7355	0.028	0.1	YES
34	GTF2F1	GTF2F1	GTF2F1	7365	0.028	0.11	YES
35	PTBP1	PTBP1	PTBP1	7429	0.026	0.11	YES
36	PRPF6	PRPF6	PRPF6	7475	0.025	0.11	YES
37	SNRPD2	SNRPD2	SNRPD2	7588	0.021	0.11	YES
38	SF3B2	SF3B2	SF3B2	7620	0.02	0.11	YES
39	DNAJC8	DNAJC8	DNAJC8	7729	0.018	0.11	YES
40	LSM2	LSM2	LSM2	7939	0.012	0.1	YES
41	PRPF8	PRPF8	PRPF8	8004	0.011	0.099	YES
42	SF3B14	SF3B14	SF3B14	8026	0.01	0.1	YES
43	DDX23	DDX23	DDX23	8133	0.0074	0.095	YES
44	YBX1	YBX1	YBX1	8202	0.0054	0.093	YES
45	HNRNPL	HNRNPL	HNRNPL	8223	0.005	0.093	YES
46	POLR2C	POLR2C	POLR2C	8264	0.004	0.091	YES
47	HNRNPC	HNRNPC	HNRNPC	8287	0.0032	0.09	YES
48	SNRNP200	SNRNP200	SNRNP200	8375	0.0011	0.086	YES
49	FUS	FUS	FUS	8572	-0.0037	0.076	YES
50	SF3B1	SF3B1	SF3B1	8653	-0.0059	0.072	YES
51	HNRNPM	HNRNPM	HNRNPM	8684	-0.0066	0.072	YES
52	HNRNPU	HNRNPU	HNRNPU	8686	-0.0066	0.073	YES
53	SRRM1	SRRM1	SRRM1	8721	-0.0076	0.073	YES
54	SF3B3	SF3B3	SF3B3	8741	-0.0083	0.074	YES
55	PRPF4	PRPF4	PRPF4	8783	-0.009	0.073	YES
56	SNRPD3	SNRPD3	SNRPD3	8789	-0.0091	0.074	YES
57	SNRPA1	SNRPA1	SNRPA1	9094	-0.017	0.061	YES
58	CCAR1	CCAR1	CCAR1	9176	-0.02	0.06	YES
59	SNRPE	SNRPE	SNRPE	9227	-0.021	0.062	YES
60	HNRNPH1	HNRNPH1	HNRNPH1	9373	-0.024	0.058	YES
61	CPSF2	CPSF2	CPSF2	9609	-0.03	0.051	YES
62	UPF3B	UPF3B	UPF3B	9643	-0.031	0.055	YES
63	HNRNPF	HNRNPF	HNRNPF	9644	-0.031	0.061	YES
64	DHX9	DHX9	DHX9	9667	-0.032	0.066	YES
65	SNRPB2	SNRPB2	SNRPB2	9685	-0.032	0.071	YES
66	PCBP1	PCBP1	PCBP1	9724	-0.033	0.076	YES
67	CSTF2	CSTF2	CSTF2	9730	-0.033	0.082	YES
68	HNRNPA0	HNRNPA0	HNRNPA0	9796	-0.035	0.085	YES
69	POLR2K	POLR2K	POLR2K	9851	-0.036	0.089	YES
70	NCBP1	NCBP1	NCBP1	9875	-0.037	0.095	YES
71	SF3A3	SF3A3	SF3A3	10102	-0.043	0.09	YES
72	CDC40	CDC40	CDC40	10219	-0.046	0.093	YES
73	HNRNPA1	HNRNPA1	HNRNPA1	10237	-0.046	0.1	YES
74	HNRNPK	HNRNPK	HNRNPK	10310	-0.048	0.11	YES
75	POLR2A	POLR2A	POLR2A	10354	-0.05	0.11	YES
76	POLR2B	POLR2B	POLR2B	10391	-0.051	0.12	YES
77	CSTF1	CSTF1	CSTF1	10427	-0.052	0.13	YES
78	SF3A1	SF3A1	SF3A1	10456	-0.052	0.14	YES
79	SNRNP40	SNRNP40	SNRNP40	10477	-0.053	0.15	YES
80	SNRPD1	SNRPD1	SNRPD1	10548	-0.055	0.15	YES
81	HNRNPH2	HNRNPH2	HNRNPH2	10552	-0.055	0.16	YES
82	PCBP2	PCBP2	PCBP2	10714	-0.059	0.17	YES
83	HNRNPA3	HNRNPA3	HNRNPA3	10958	-0.065	0.16	YES
84	HNRNPUL1	HNRNPUL1	HNRNPUL1	11052	-0.068	0.17	YES
85	HNRNPR	HNRNPR	HNRNPR	11248	-0.074	0.18	YES
86	HNRNPD	HNRNPD	HNRNPD	11388	-0.077	0.18	YES
87	CLP1	CLP1	CLP1	11431	-0.079	0.2	YES
88	PAPOLA	PAPOLA	PAPOLA	11488	-0.081	0.21	YES
89	NFX1	NFX1	NFX1	11579	-0.083	0.22	YES
90	PHF5A	PHF5A	PHF5A	11606	-0.084	0.24	YES
91	SMC1A	SMC1A	SMC1A	11650	-0.086	0.25	YES
92	RBM8A	RBM8A	RBM8A	11665	-0.086	0.26	YES
93	RBMX	RBMX	RBMX	11675	-0.087	0.28	YES
94	CPSF7	CPSF7	CPSF7	11689	-0.087	0.3	YES
95	NUDT21	NUDT21	NUDT21	12064	-0.099	0.3	YES
96	POLR2D	POLR2D	POLR2D	12131	-0.1	0.31	YES
97	PCF11	PCF11	PCF11	12778	-0.12	0.3	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 TIGHT JUNCTION.

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG TIGHT JUNCTION, 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 = KIPAN-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = KIPAN-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