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

Cholangiocarcinoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in CHOL-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1WH2P0B

Overview

Introduction

This pipeline performs Gene Set Enrichment Analysis (GSEA) using The Broad Institute GSEA tool with MSigDB - Class2: Canonical Pathways gene sets. For a given phenotype subtype, it shows what pathways are significantly enriched in each subtype by comparing gene expression profiles between subtypes. Here, the phenotype is mRNAseq_cNMF subtypes in CHOL-TP. This pipeline has the following features:

For each subtype, calculates enrichment scores (ES) using signal to noise (S2N) that checks similarity between subtypes in expression level then calculates p values through permutation test.
Lists pathways significantly enriched in each phenotype subtype and their enrichment scores (ES).
Lists top 20 core genes enriched in each significant gene set and their enrichment scores (ES).
Checks if the top core genes are up-regulated or down-regulated.
Checks if the top core genes are high expressed or low expressed.
Checks if the top core genes are significantly differently expressed genes.

Summary

Table 1. Get Full Table basic data info

basic data info
Number of Gene Sets: 192
Number of samples: 36
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 3 :[ clus1 ] 12
pheno.type: 2 - 3 :[ clus2 ] 15
pheno.type: 3 - 3 :[ clus3 ] 9

For the expression subtypes of 18131 genes in 37 samples, GSEA found enriched gene sets in each cluster using 36 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA BCR PATHWAY, BIOCARTA G1 PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA FCER1 PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA IL2RB PATHWAY, BIOCARTA GSK3 PATHWAY, BIOCARTA KERATINOCYTE PATHWAY, BIOCARTA MYOSIN PATHWAY

And common core enriched genes are EGF, BIRC3, BCL2, FAS, MAP3K5, PRKCB, PRKCD, PRKCG, TNF, TNFRSF1B

clus2

Top enriched gene sets are BIOCARTA DEATH PATHWAY, KEGG OXIDATIVE PHOSPHORYLATION, KEGG RNA DEGRADATION, KEGG RNA POLYMERASE, KEGG SPLICEOSOME, KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT, KEGG NOTCH SIGNALING PATHWAY, KEGG VASOPRESSIN REGULATED WATER REABSORPTION, KEGG HUNTINGTONS DISEASE

And common core enriched genes are LSM2, LSM3, LSM4, LSM5, LSM6, LSM7, NAA38, ATP5A1, ATP5C1, ATP5D

clus3

Top enriched gene sets are BIOCARTA AT1R PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA PPARA PATHWAY, BIOCARTA CHREBP2 PATHWAY, KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG CITRATE CYCLE TCA CYCLE, KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG FATTY ACID METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS

And common core enriched genes are LDHAL6B, ACAA1, ACOX1, ACSL1, ACSL5, ACSL6, EHHADH, PCK1, PCK2, SCP2

Results

Subtype clus1 enriched pathways

Table 3. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus1. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.54	1.5	0.074	0.23	0.83	0.52	0.32	0.35	0.16	0.024
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.51	1.5	0.083	0.22	0.86	0.52	0.28	0.37	0.15	0.017
BIOCARTA HDAC PATHWAY	27	genes.ES.table	0.5	1.5	0.064	0.22	0.8	0.26	0.2	0.21	0.14	0.023
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.45	1.6	0.06	0.27	0.74	0.59	0.4	0.35	0.16	0.047
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.53	1.5	0.087	0.23	0.85	0.51	0.32	0.35	0.16	0.022
BIOCARTA HIVNEF PATHWAY	57	genes.ES.table	0.43	1.8	0.018	0.23	0.23	0.53	0.4	0.32	0	0.068
BIOCARTA IL2RB PATHWAY	37	genes.ES.table	0.6	1.6	0.053	0.24	0.75	0.4	0.19	0.33	0.15	0.036
BIOCARTA GSK3 PATHWAY	26	genes.ES.table	0.53	1.6	0.04	0.25	0.74	0.23	0.13	0.2	0.15	0.035
BIOCARTA KERATINOCYTE PATHWAY	45	genes.ES.table	0.56	1.8	0.0041	0.34	0.23	0.31	0.19	0.25	0	0.12
BIOCARTA MYOSIN PATHWAY	28	genes.ES.table	0.42	1.4	0.09	0.25	0.95	0.46	0.34	0.31	0.19	0.005

genes ES table in pathway: BIOCARTA BCR PATHWAY

Table S1. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HERC3	HERC3	HERC3	1080	0.39	-0.017	YES
2	SOCS1	SOCS1	SOCS1	1713	0.32	-0.018	YES
3	SOCS3	SOCS3	SOCS3	1728	0.32	0.016	YES
4	UBE2C	UBE2C	UBE2C	2034	0.28	0.03	YES
5	CDC20	CDC20	CDC20	2381	0.26	0.038	YES
6	MID1	MID1	MID1	2629	0.24	0.05	YES
7	UBE2E2	UBE2E2	UBE2E2	2854	0.22	0.062	YES
8	AIRE	AIRE	AIRE	2902	0.22	0.082	YES
9	DET1	DET1	DET1	2955	0.21	0.1	YES
10	PARK2	PARK2	PARK2	3209	0.2	0.11	YES
11	BIRC3	BIRC3	BIRC3	3519	0.18	0.11	YES
12	FBXW7	FBXW7	FBXW7	3899	0.16	0.11	YES
13	CBLB	CBLB	CBLB	3978	0.16	0.12	YES
14	TRAF6	TRAF6	TRAF6	4194	0.15	0.12	YES
15	CDC26	CDC26	CDC26	4226	0.14	0.14	YES
16	UBE2J1	UBE2J1	UBE2J1	4274	0.14	0.15	YES
17	BRCA1	BRCA1	BRCA1	4336	0.14	0.16	YES
18	UBE2S	UBE2S	UBE2S	4358	0.14	0.18	YES
19	PML	PML	PML	4407	0.14	0.19	YES
20	SMURF2	SMURF2	SMURF2	4577	0.13	0.2	YES
21	UBE2O	UBE2O	UBE2O	5080	0.11	0.18	YES
22	UBE4B	UBE4B	UBE4B	5094	0.11	0.19	YES
23	SKP2	SKP2	SKP2	5128	0.11	0.2	YES
24	UBA7	UBA7	UBA7	5274	0.1	0.2	YES
25	ANAPC10	ANAPC10	ANAPC10	5310	0.1	0.21	YES
26	VHL	VHL	VHL	5319	0.1	0.22	YES
27	UBE2U	UBE2U	UBE2U	5333	0.1	0.24	YES
28	NHLRC1	NHLRC1	NHLRC1	5719	0.092	0.22	YES
29	UBA3	UBA3	UBA3	5852	0.088	0.23	YES
30	CUL1	CUL1	CUL1	6039	0.084	0.22	YES
31	UBE2E1	UBE2E1	UBE2E1	6094	0.082	0.23	YES
32	CDC16	CDC16	CDC16	6147	0.081	0.24	YES
33	TRIM32	TRIM32	TRIM32	6375	0.076	0.23	YES
34	FANCL	FANCL	FANCL	6386	0.075	0.24	YES
35	UBA6	UBA6	UBA6	6482	0.073	0.24	YES
36	CBL	CBL	CBL	6627	0.07	0.24	YES
37	UBE2H	UBE2H	UBE2H	6631	0.07	0.25	YES
38	RCHY1	RCHY1	RCHY1	6721	0.068	0.25	YES
39	CDC27	CDC27	CDC27	6962	0.064	0.24	YES
40	CUL4A	CUL4A	CUL4A	7012	0.063	0.25	YES
41	PIAS1	PIAS1	PIAS1	7090	0.061	0.25	YES
42	UBR5	UBR5	UBR5	7139	0.06	0.26	YES
43	BIRC6	BIRC6	BIRC6	7240	0.058	0.26	YES
44	TCEB1	TCEB1	TCEB1	7340	0.056	0.26	YES
45	UBE2J2	UBE2J2	UBE2J2	7453	0.054	0.26	YES
46	KLHL9	KLHL9	KLHL9	7502	0.054	0.26	YES
47	UBE2D1	UBE2D1	UBE2D1	7584	0.052	0.26	YES
48	HERC2	HERC2	HERC2	7620	0.051	0.26	YES
49	ANAPC1	ANAPC1	ANAPC1	7691	0.05	0.27	YES
50	UBE3C	UBE3C	UBE3C	7723	0.05	0.27	YES
51	BIRC2	BIRC2	BIRC2	7866	0.047	0.27	YES
52	UBE2L6	UBE2L6	UBE2L6	7877	0.046	0.27	YES
53	UBE2F	UBE2F	UBE2F	8025	0.044	0.27	YES
54	ITCH	ITCH	ITCH	8044	0.043	0.27	YES
55	UBE2K	UBE2K	UBE2K	8085	0.042	0.27	YES
56	UBE2W	UBE2W	UBE2W	8092	0.042	0.28	YES
57	UBE2D4	UBE2D4	UBE2D4	8184	0.041	0.28	YES
58	RHOBTB2	RHOBTB2	RHOBTB2	8226	0.04	0.28	YES
59	ANAPC4	ANAPC4	ANAPC4	8300	0.039	0.28	YES
60	ANAPC13	ANAPC13	ANAPC13	8320	0.039	0.28	YES
61	TRIM37	TRIM37	TRIM37	8329	0.039	0.29	YES
62	ANAPC2	ANAPC2	ANAPC2	8408	0.037	0.29	YES
63	UBE2D3	UBE2D3	UBE2D3	8415	0.037	0.29	YES
64	MDM2	MDM2	MDM2	8417	0.037	0.29	YES
65	UBE2Q2	UBE2Q2	UBE2Q2	8424	0.037	0.3	YES
66	UBA2	UBA2	UBA2	8440	0.037	0.3	YES
67	STUB1	STUB1	STUB1	8650	0.034	0.29	NO
68	PIAS3	PIAS3	PIAS3	8651	0.034	0.3	NO
69	UBE2N	UBE2N	UBE2N	8729	0.032	0.3	NO
70	HERC4	HERC4	HERC4	8776	0.031	0.3	NO
71	CDC23	CDC23	CDC23	8843	0.03	0.3	NO
72	RNF7	RNF7	RNF7	8923	0.029	0.3	NO
73	UBOX5	UBOX5	UBOX5	8975	0.028	0.3	NO
74	KEAP1	KEAP1	KEAP1	9025	0.028	0.3	NO
75	UBE2I	UBE2I	UBE2I	9069	0.027	0.3	NO
76	UBE3A	UBE3A	UBE3A	9118	0.026	0.3	NO
77	UBA1	UBA1	UBA1	9146	0.026	0.3	NO
78	UBE2Z	UBE2Z	UBE2Z	9319	0.023	0.29	NO
79	PRPF19	PRPF19	PRPF19	9551	0.019	0.28	NO
80	ANAPC11	ANAPC11	ANAPC11	9566	0.019	0.28	NO
81	HERC1	HERC1	HERC1	9572	0.019	0.28	NO
82	WWP2	WWP2	WWP2	9640	0.018	0.28	NO
83	CUL2	CUL2	CUL2	9657	0.018	0.28	NO
84	HUWE1	HUWE1	HUWE1	9723	0.017	0.28	NO
85	UBE2D2	UBE2D2	UBE2D2	9746	0.016	0.28	NO
86	UBE2A	UBE2A	UBE2A	9766	0.016	0.28	NO
87	XIAP	XIAP	XIAP	9958	0.013	0.27	NO
88	TRIP12	TRIP12	TRIP12	10029	0.012	0.27	NO
89	UBE2R2	UBE2R2	UBE2R2	10165	0.01	0.26	NO
90	UBE4A	UBE4A	UBE4A	10245	0.0089	0.26	NO
91	FBXW8	FBXW8	FBXW8	10498	0.0051	0.25	NO
92	TCEB2	TCEB2	TCEB2	10577	0.0039	0.24	NO
93	UBE2B	UBE2B	UBE2B	10630	0.0031	0.24	NO
94	CUL5	CUL5	CUL5	10680	0.0024	0.24	NO
95	CUL3	CUL3	CUL3	10816	0.00021	0.23	NO
96	PIAS2	PIAS2	PIAS2	10839	-0.00019	0.23	NO
97	SMURF1	SMURF1	SMURF1	10884	-0.00082	0.23	NO
98	FBXO4	FBXO4	FBXO4	10896	-0.0011	0.23	NO
99	FZR1	FZR1	FZR1	11229	-0.0066	0.21	NO
100	CUL4B	CUL4B	CUL4B	11300	-0.0078	0.2	NO
101	UBE2G1	UBE2G1	UBE2G1	11460	-0.011	0.2	NO
102	SKP1	SKP1	SKP1	11461	-0.011	0.2	NO
103	UBE2NL	UBE2NL	UBE2NL	11641	-0.013	0.19	NO
104	UBE2L3	UBE2L3	UBE2L3	11678	-0.014	0.19	NO
105	RBX1	RBX1	RBX1	11916	-0.018	0.18	NO
106	FBXO2	FBXO2	FBXO2	11965	-0.018	0.18	NO
107	MGRN1	MGRN1	MGRN1	12002	-0.019	0.18	NO
108	ANAPC7	ANAPC7	ANAPC7	12126	-0.021	0.17	NO
109	UBE2QL1	UBE2QL1	UBE2QL1	12271	-0.023	0.17	NO
110	ANAPC5	ANAPC5	ANAPC5	12294	-0.024	0.17	NO
111	SIAH1	SIAH1	SIAH1	12413	-0.026	0.16	NO
112	WWP1	WWP1	WWP1	12703	-0.031	0.15	NO
113	DDB1	DDB1	DDB1	12747	-0.031	0.15	NO
114	UBE3B	UBE3B	UBE3B	12913	-0.035	0.15	NO
115	UBE2E3	UBE2E3	UBE2E3	12969	-0.036	0.15	NO
116	NEDD4L	NEDD4L	NEDD4L	13002	-0.036	0.15	NO
117	UBE2M	UBE2M	UBE2M	13041	-0.037	0.15	NO
118	UBE2Q1	UBE2Q1	UBE2Q1	13213	-0.04	0.15	NO
119	UBE2G2	UBE2G2	UBE2G2	13256	-0.041	0.15	NO
120	PIAS4	PIAS4	PIAS4	13331	-0.042	0.15	NO
121	PPIL2	PPIL2	PPIL2	13340	-0.042	0.15	NO
122	CUL7	CUL7	CUL7	13472	-0.045	0.15	NO
123	SAE1	SAE1	SAE1	13586	-0.047	0.15	NO
124	MAP3K1	MAP3K1	MAP3K1	13631	-0.048	0.15	NO
125	DDB2	DDB2	DDB2	13700	-0.05	0.16	NO
126	SYVN1	SYVN1	SYVN1	13838	-0.054	0.15	NO
127	ERCC8	ERCC8	ERCC8	13914	-0.056	0.16	NO
128	CDC34	CDC34	CDC34	14698	-0.077	0.12	NO
129	FBXW11	FBXW11	FBXW11	14963	-0.087	0.12	NO
130	RFWD2	RFWD2	RFWD2	15326	-0.1	0.11	NO
131	KLHL13	KLHL13	KLHL13	15817	-0.13	0.093	NO
132	NEDD4	NEDD4	NEDD4	15975	-0.14	0.099	NO
133	CBLC	CBLC	CBLC	16625	-0.18	0.083	NO

Figure S1. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA BCR PATHWAY.

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

genes ES table in pathway: BIOCARTA G1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HOXA7	HOXA7	HOXA7	112	0.68	0.096	YES
2	PRKCB	PRKCB	PRKCB	329	0.56	0.17	YES
3	EGF	EGF	EGF	450	0.52	0.24	YES
4	FASLG	FASLG	FASLG	549	0.49	0.31	YES
5	MAP3K5	MAP3K5	MAP3K5	1246	0.37	0.33	YES
6	PRKCH	PRKCH	PRKCH	1314	0.36	0.38	YES
7	TNFRSF1B	TNFRSF1B	TNFRSF1B	1327	0.36	0.43	YES
8	PRKCQ	PRKCQ	PRKCQ	2301	0.26	0.42	YES
9	ETS1	ETS1	ETS1	2521	0.25	0.44	YES
10	TNF	TNF	TNF	2602	0.24	0.47	YES
11	BCL2	BCL2	BCL2	2609	0.24	0.51	YES
12	PRKCG	PRKCG	PRKCG	2832	0.22	0.53	YES
13	PRKCD	PRKCD	PRKCD	3276	0.19	0.54	YES
14	FAS	FAS	FAS	3413	0.19	0.56	YES
15	MAPK8	MAPK8	MAPK8	4907	0.12	0.49	NO
16	FOS	FOS	FOS	5125	0.11	0.5	NO
17	MAP2K1	MAP2K1	MAP2K1	5241	0.11	0.5	NO
18	MAPK3	MAPK3	MAPK3	5820	0.09	0.49	NO
19	IKBKB	IKBKB	IKBKB	6705	0.069	0.45	NO
20	MAP3K14	MAP3K14	MAP3K14	7079	0.061	0.44	NO
21	HRAS	HRAS	HRAS	7390	0.055	0.43	NO
22	RAF1	RAF1	RAF1	8071	0.043	0.4	NO
23	NFKB1	NFKB1	NFKB1	8321	0.039	0.39	NO
24	PRKCE	PRKCE	PRKCE	8633	0.034	0.38	NO
25	MAPK1	MAPK1	MAPK1	9347	0.023	0.34	NO
26	MAP2K6	MAP2K6	MAP2K6	9409	0.022	0.34	NO
27	CHUK	CHUK	CHUK	9445	0.021	0.34	NO
28	NFKBIA	NFKBIA	NFKBIA	9478	0.02	0.34	NO
29	RELA	RELA	RELA	10068	0.011	0.31	NO
30	PRKCA	PRKCA	PRKCA	10189	0.0097	0.31	NO
31	ETS2	ETS2	ETS2	10656	0.0027	0.28	NO
32	DAXX	DAXX	DAXX	10909	-0.0013	0.27	NO
33	TNFRSF1A	TNFRSF1A	TNFRSF1A	10911	-0.0013	0.27	NO
34	PPP2CA	PPP2CA	PPP2CA	11118	-0.0048	0.26	NO
35	JUN	JUN	JUN	11328	-0.0084	0.25	NO
36	MAPK14	MAPK14	MAPK14	12581	-0.029	0.18	NO
37	MAP2K7	MAP2K7	MAP2K7	12749	-0.031	0.18	NO
38	SP1	SP1	SP1	13188	-0.039	0.16	NO
39	MAP3K1	MAP3K1	MAP3K1	13631	-0.048	0.14	NO
40	MAP2K4	MAP2K4	MAP2K4	13924	-0.056	0.14	NO
41	RIPK1	RIPK1	RIPK1	14375	-0.068	0.12	NO
42	MAP2K3	MAP2K3	MAP2K3	14962	-0.087	0.1	NO
43	EGFR	EGFR	EGFR	15766	-0.12	0.075	NO
44	MAPK13	MAPK13	MAPK13	16126	-0.15	0.077	NO
45	CEBPA	CEBPA	CEBPA	16898	-0.22	0.067	NO

Figure S3. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA G1 PATHWAY.

Figure S4. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA G1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA HDAC PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MAP3K5	MAP3K5	MAP3K5	1246	0.37	-0.00078	YES
2	TNFRSF1B	TNFRSF1B	TNFRSF1B	1327	0.36	0.061	YES
3	ARHGDIB	ARHGDIB	ARHGDIB	2192	0.27	0.064	YES
4	TNF	TNF	TNF	2602	0.24	0.086	YES
5	BCL2	BCL2	BCL2	2609	0.24	0.13	YES
6	CDK11A	CDK11A	CDK11A	2979	0.21	0.15	YES
7	PRKCD	PRKCD	PRKCD	3276	0.19	0.17	YES
8	FAS	FAS	FAS	3413	0.19	0.2	YES
9	TRAF1	TRAF1	TRAF1	3440	0.18	0.23	YES
10	BIRC3	BIRC3	BIRC3	3519	0.18	0.26	YES
11	BID	BID	BID	3604	0.18	0.28	YES
12	DFFB	DFFB	DFFB	3821	0.16	0.3	YES
13	DFFA	DFFA	DFFA	4111	0.15	0.31	YES
14	GSN	GSN	GSN	4275	0.14	0.33	YES
15	LMNB1	LMNB1	LMNB1	4591	0.13	0.34	YES
16	LMNB2	LMNB2	LMNB2	4734	0.12	0.35	YES
17	MAPK8	MAPK8	MAPK8	4907	0.12	0.37	YES
18	RB1	RB1	RB1	4944	0.12	0.38	YES
19	CASP3	CASP3	CASP3	5224	0.11	0.39	YES
20	CDK11B	CDK11B	CDK11B	5613	0.096	0.39	YES
21	TRADD	TRADD	TRADD	5762	0.091	0.4	YES
22	CFLAR	CFLAR	CFLAR	5916	0.087	0.4	YES
23	PAK2	PAK2	PAK2	6231	0.079	0.4	YES
24	PRKDC	PRKDC	PRKDC	6313	0.077	0.41	YES
25	CASP9	CASP9	CASP9	6572	0.072	0.41	YES
26	BAG4	BAG4	BAG4	6739	0.068	0.41	YES
27	FADD	FADD	FADD	6938	0.064	0.41	YES
28	MAP3K14	MAP3K14	MAP3K14	7079	0.061	0.42	YES
29	CASP8	CASP8	CASP8	7108	0.061	0.43	YES
30	CASP7	CASP7	CASP7	7214	0.059	0.43	YES
31	PTK2	PTK2	PTK2	7509	0.053	0.42	NO
32	CASP2	CASP2	CASP2	7593	0.052	0.43	NO
33	BIRC2	BIRC2	BIRC2	7866	0.047	0.42	NO
34	NUMA1	NUMA1	NUMA1	7962	0.045	0.43	NO
35	NFKB1	NFKB1	NFKB1	8321	0.039	0.41	NO
36	MDM2	MDM2	MDM2	8417	0.037	0.42	NO
37	CASP6	CASP6	CASP6	8419	0.037	0.42	NO
38	TRAF2	TRAF2	TRAF2	9424	0.022	0.37	NO
39	CHUK	CHUK	CHUK	9445	0.021	0.37	NO
40	NFKBIA	NFKBIA	NFKBIA	9478	0.02	0.38	NO
41	PSEN1	PSEN1	PSEN1	9677	0.017	0.37	NO
42	PARP1	PARP1	PARP1	9829	0.015	0.36	NO
43	XIAP	XIAP	XIAP	9958	0.013	0.36	NO
44	RELA	RELA	RELA	10068	0.011	0.35	NO
45	CYCS	CYCS	CYCS	10411	0.0064	0.34	NO
46	DAXX	DAXX	DAXX	10909	-0.0013	0.31	NO
47	TNFRSF1A	TNFRSF1A	TNFRSF1A	10911	-0.0013	0.31	NO
48	ACTG1	ACTG1	ACTG1	11169	-0.0055	0.3	NO
49	APAF1	APAF1	APAF1	11881	-0.017	0.26	NO
50	SPTAN1	SPTAN1	SPTAN1	11942	-0.018	0.26	NO
51	RASA1	RASA1	RASA1	12732	-0.031	0.22	NO
52	MAP2K7	MAP2K7	MAP2K7	12749	-0.031	0.23	NO
53	LMNA	LMNA	LMNA	13352	-0.043	0.2	NO
54	MAP3K1	MAP3K1	MAP3K1	13631	-0.048	0.19	NO
55	RIPK1	RIPK1	RIPK1	14375	-0.068	0.17	NO
56	PSEN2	PSEN2	PSEN2	14798	-0.081	0.16	NO
57	CRADD	CRADD	CRADD	16035	-0.14	0.12	NO

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

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

genes ES table in pathway: BIOCARTA FAS PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PIK3CG	PIK3CG	PIK3CG	75	0.72	0.12	YES
2	EGF	EGF	EGF	450	0.52	0.18	YES
3	PIK3R5	PIK3R5	PIK3R5	466	0.51	0.26	YES
4	LEF1	LEF1	LEF1	638	0.47	0.34	YES
5	AXIN2	AXIN2	AXIN2	869	0.43	0.39	YES
6	PIK3CD	PIK3CD	PIK3CD	895	0.42	0.46	YES
7	TCF7	TCF7	TCF7	1115	0.39	0.52	YES
8	MYC	MYC	MYC	3158	0.2	0.44	NO
9	PIK3R3	PIK3R3	PIK3R3	4370	0.14	0.39	NO
10	PIK3CA	PIK3CA	PIK3CA	4897	0.12	0.38	NO
11	AKT3	AKT3	AKT3	5193	0.11	0.38	NO
12	MAP2K1	MAP2K1	MAP2K1	5241	0.11	0.4	NO
13	SOS1	SOS1	SOS1	5817	0.09	0.38	NO
14	MAPK3	MAPK3	MAPK3	5820	0.09	0.4	NO
15	KRAS	KRAS	KRAS	6308	0.077	0.38	NO
16	CASP9	CASP9	CASP9	6572	0.072	0.38	NO
17	CTNNB1	CTNNB1	CTNNB1	6591	0.071	0.39	NO
18	PIK3CB	PIK3CB	PIK3CB	6609	0.071	0.4	NO
19	FOXO3	FOXO3	FOXO3	7114	0.061	0.38	NO
20	CTNNA2	CTNNA2	CTNNA2	8021	0.044	0.34	NO
21	GSK3B	GSK3B	GSK3B	8056	0.043	0.35	NO
22	RAF1	RAF1	RAF1	8071	0.043	0.35	NO
23	MLH1	MLH1	MLH1	8634	0.034	0.33	NO
24	GRB2	GRB2	GRB2	8881	0.03	0.32	NO
25	APC2	APC2	APC2	9296	0.024	0.3	NO
26	MAPK1	MAPK1	MAPK1	9347	0.023	0.3	NO
27	PDPK1	PDPK1	PDPK1	9474	0.02	0.3	NO
28	PTEN	PTEN	PTEN	9549	0.019	0.3	NO
29	AKT1	AKT1	AKT1	9715	0.017	0.29	NO
30	AXIN1	AXIN1	AXIN1	9803	0.015	0.29	NO
31	ERBB2	ERBB2	ERBB2	10041	0.012	0.28	NO
32	ELK1	ELK1	ELK1	10062	0.012	0.28	NO
33	TCF7L1	TCF7L1	TCF7L1	10191	0.0097	0.27	NO
34	BRAF	BRAF	BRAF	10737	0.0016	0.24	NO
35	MAP2K2	MAP2K2	MAP2K2	10978	-0.0024	0.23	NO
36	ILK	ILK	ILK	11240	-0.0067	0.22	NO
37	ARAF	ARAF	ARAF	11378	-0.0092	0.21	NO
38	TP53	TP53	TP53	11484	-0.011	0.21	NO
39	AKT2	AKT2	AKT2	11585	-0.012	0.2	NO
40	CTNNA1	CTNNA1	CTNNA1	11948	-0.018	0.19	NO
41	SOS2	SOS2	SOS2	12019	-0.019	0.18	NO
42	PIK3R2	PIK3R2	PIK3R2	12661	-0.03	0.16	NO
43	TCF7L2	TCF7L2	TCF7L2	13289	-0.041	0.13	NO
44	APC	APC	APC	13644	-0.049	0.12	NO
45	BAD	BAD	BAD	13854	-0.054	0.11	NO
46	NRAS	NRAS	NRAS	14613	-0.074	0.084	NO
47	PIK3R1	PIK3R1	PIK3R1	14733	-0.078	0.09	NO
48	CDH1	CDH1	CDH1	15755	-0.12	0.054	NO
49	EGFR	EGFR	EGFR	15766	-0.12	0.074	NO
50	CTNNA3	CTNNA3	CTNNA3	16274	-0.16	0.073	NO
51	CCND1	CCND1	CCND1	16472	-0.17	0.091	NO

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

Figure S8. 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 FCER1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PIK3CG	PIK3CG	PIK3CG	75	0.72	0.093	YES
2	PRKCB	PRKCB	PRKCB	329	0.56	0.15	YES
3	EGF	EGF	EGF	450	0.52	0.22	YES
4	PIK3R5	PIK3R5	PIK3R5	466	0.51	0.29	YES
5	RARB	RARB	RARB	774	0.44	0.33	YES
6	PIK3CD	PIK3CD	PIK3CD	895	0.42	0.38	YES
7	CDK6	CDK6	CDK6	1092	0.39	0.42	YES
8	RXRG	RXRG	RXRG	1397	0.35	0.45	YES
9	RASSF5	RASSF5	RASSF5	1962	0.29	0.46	YES
10	PRKCG	PRKCG	PRKCG	2832	0.22	0.44	YES
11	E2F2	E2F2	E2F2	3179	0.2	0.45	YES
12	PIK3R3	PIK3R3	PIK3R3	4370	0.14	0.4	YES
13	STK4	STK4	STK4	4371	0.14	0.42	YES
14	CDKN2A	CDKN2A	CDKN2A	4606	0.13	0.43	YES
15	PIK3CA	PIK3CA	PIK3CA	4897	0.12	0.43	YES
16	RB1	RB1	RB1	4944	0.12	0.44	YES
17	RASSF1	RASSF1	RASSF1	5168	0.11	0.44	YES
18	AKT3	AKT3	AKT3	5193	0.11	0.46	YES
19	PLCG1	PLCG1	PLCG1	5209	0.11	0.47	YES
20	MAP2K1	MAP2K1	MAP2K1	5241	0.11	0.48	YES
21	FHIT	FHIT	FHIT	5598	0.096	0.48	YES
22	SOS1	SOS1	SOS1	5817	0.09	0.48	YES
23	MAPK3	MAPK3	MAPK3	5820	0.09	0.49	YES
24	KRAS	KRAS	KRAS	6308	0.077	0.47	NO
25	CASP9	CASP9	CASP9	6572	0.072	0.47	NO
26	PIK3CB	PIK3CB	PIK3CB	6609	0.071	0.47	NO
27	PLCG2	PLCG2	PLCG2	6768	0.067	0.48	NO
28	FOXO3	FOXO3	FOXO3	7114	0.061	0.46	NO
29	HRAS	HRAS	HRAS	7390	0.055	0.46	NO
30	RAF1	RAF1	RAF1	8071	0.043	0.42	NO
31	CDK4	CDK4	CDK4	8334	0.038	0.42	NO
32	GRB2	GRB2	GRB2	8881	0.03	0.39	NO
33	MAPK1	MAPK1	MAPK1	9347	0.023	0.37	NO
34	PDPK1	PDPK1	PDPK1	9474	0.02	0.36	NO
35	AKT1	AKT1	AKT1	9715	0.017	0.35	NO
36	ERBB2	ERBB2	ERBB2	10041	0.012	0.33	NO
37	PRKCA	PRKCA	PRKCA	10189	0.0097	0.33	NO
38	BRAF	BRAF	BRAF	10737	0.0016	0.3	NO
39	MAP2K2	MAP2K2	MAP2K2	10978	-0.0024	0.28	NO
40	ARAF	ARAF	ARAF	11378	-0.0092	0.26	NO
41	TP53	TP53	TP53	11484	-0.011	0.26	NO
42	AKT2	AKT2	AKT2	11585	-0.012	0.26	NO
43	SOS2	SOS2	SOS2	12019	-0.019	0.23	NO
44	RXRA	RXRA	RXRA	12611	-0.029	0.2	NO
45	PIK3R2	PIK3R2	PIK3R2	12661	-0.03	0.21	NO
46	RXRB	RXRB	RXRB	12792	-0.032	0.2	NO
47	BAD	BAD	BAD	13854	-0.054	0.15	NO
48	TGFA	TGFA	TGFA	14453	-0.07	0.13	NO
49	NRAS	NRAS	NRAS	14613	-0.074	0.13	NO
50	PIK3R1	PIK3R1	PIK3R1	14733	-0.078	0.13	NO
51	E2F3	E2F3	E2F3	15088	-0.092	0.13	NO
52	EGFR	EGFR	EGFR	15766	-0.12	0.11	NO
53	CCND1	CCND1	CCND1	16472	-0.17	0.091	NO

Figure S9. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FCER1 PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA HIVNEF 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	PIK3CG	PIK3CG	PIK3CG	75	0.72	0.098	YES
2	PIK3R5	PIK3R5	PIK3R5	466	0.51	0.15	YES
3	LEF1	LEF1	LEF1	638	0.47	0.21	YES
4	AXIN2	AXIN2	AXIN2	869	0.43	0.26	YES
5	PIK3CD	PIK3CD	PIK3CD	895	0.42	0.32	YES
6	TCF7	TCF7	TCF7	1115	0.39	0.36	YES
7	BCL2	BCL2	BCL2	2609	0.24	0.31	YES
8	BIRC5	BIRC5	BIRC5	2763	0.23	0.34	YES
9	DCC	DCC	DCC	2990	0.21	0.35	YES
10	MYC	MYC	MYC	3158	0.2	0.37	YES
11	MAPK10	MAPK10	MAPK10	3646	0.17	0.37	YES
12	PIK3R3	PIK3R3	PIK3R3	4370	0.14	0.35	YES
13	TGFB1	TGFB1	TGFB1	4599	0.13	0.36	YES
14	RAC2	RAC2	RAC2	4610	0.13	0.38	YES
15	PIK3CA	PIK3CA	PIK3CA	4897	0.12	0.38	YES
16	MAPK8	MAPK8	MAPK8	4907	0.12	0.39	YES
17	RALGDS	RALGDS	RALGDS	5052	0.11	0.4	YES
18	FOS	FOS	FOS	5125	0.11	0.41	YES
19	AKT3	AKT3	AKT3	5193	0.11	0.42	YES
20	TGFBR1	TGFBR1	TGFBR1	5216	0.11	0.44	YES
21	CASP3	CASP3	CASP3	5224	0.11	0.45	YES
22	MAP2K1	MAP2K1	MAP2K1	5241	0.11	0.47	YES
23	MAPK3	MAPK3	MAPK3	5820	0.09	0.45	YES
24	APPL1	APPL1	APPL1	5835	0.089	0.46	YES
25	MSH6	MSH6	MSH6	6149	0.081	0.46	YES
26	KRAS	KRAS	KRAS	6308	0.077	0.46	YES
27	CASP9	CASP9	CASP9	6572	0.072	0.45	YES
28	CTNNB1	CTNNB1	CTNNB1	6591	0.071	0.46	YES
29	PIK3CB	PIK3CB	PIK3CB	6609	0.071	0.47	YES
30	RHOA	RHOA	RHOA	6847	0.066	0.47	YES
31	TGFBR2	TGFBR2	TGFBR2	6868	0.065	0.48	YES
32	MSH2	MSH2	MSH2	7273	0.057	0.46	NO
33	GSK3B	GSK3B	GSK3B	8056	0.043	0.42	NO
34	RAF1	RAF1	RAF1	8071	0.043	0.43	NO
35	RAC3	RAC3	RAC3	8258	0.04	0.43	NO
36	MLH1	MLH1	MLH1	8634	0.034	0.41	NO
37	RAC1	RAC1	RAC1	9013	0.028	0.39	NO
38	APC2	APC2	APC2	9296	0.024	0.38	NO
39	MAPK1	MAPK1	MAPK1	9347	0.023	0.38	NO
40	AKT1	AKT1	AKT1	9715	0.017	0.36	NO
41	AXIN1	AXIN1	AXIN1	9803	0.015	0.36	NO
42	TCF7L1	TCF7L1	TCF7L1	10191	0.0097	0.34	NO
43	CYCS	CYCS	CYCS	10411	0.0064	0.33	NO
44	TGFB2	TGFB2	TGFB2	10735	0.0016	0.31	NO
45	BRAF	BRAF	BRAF	10737	0.0016	0.31	NO
46	MAPK9	MAPK9	MAPK9	10743	0.0014	0.31	NO
47	SMAD3	SMAD3	SMAD3	11078	-0.0041	0.29	NO
48	JUN	JUN	JUN	11328	-0.0084	0.28	NO
49	ARAF	ARAF	ARAF	11378	-0.0092	0.28	NO
50	TP53	TP53	TP53	11484	-0.011	0.28	NO
51	AKT2	AKT2	AKT2	11585	-0.012	0.27	NO
52	SMAD2	SMAD2	SMAD2	12081	-0.02	0.25	NO
53	PIK3R2	PIK3R2	PIK3R2	12661	-0.03	0.22	NO
54	TCF7L2	TCF7L2	TCF7L2	13289	-0.041	0.19	NO
55	APC	APC	APC	13644	-0.049	0.18	NO
56	MSH3	MSH3	MSH3	13846	-0.054	0.18	NO
57	BAD	BAD	BAD	13854	-0.054	0.18	NO
58	SMAD4	SMAD4	SMAD4	13935	-0.056	0.19	NO
59	BAX	BAX	BAX	14236	-0.064	0.18	NO
60	PIK3R1	PIK3R1	PIK3R1	14733	-0.078	0.16	NO
61	CCND1	CCND1	CCND1	16472	-0.17	0.091	NO

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

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

genes ES table in pathway: BIOCARTA IL2RB PATHWAY

Table 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	ZBP1	ZBP1	ZBP1	83	0.71	0.094	YES
2	CCL4L2	CCL4L2	CCL4L2	155	0.64	0.18	YES
3	CCL4	CCL4	CCL4	287	0.57	0.25	YES
4	AIM2	AIM2	AIM2	359	0.55	0.32	YES
5	CCL5	CCL5	CCL5	504	0.5	0.39	YES
6	CASP1	CASP1	CASP1	607	0.48	0.45	YES
7	IL6	IL6	IL6	662	0.47	0.51	YES
8	CXCL10	CXCL10	CXCL10	942	0.41	0.55	YES
9	IFNB1	IFNB1	IFNB1	1215	0.37	0.59	YES
10	TMEM173	TMEM173	TMEM173	1366	0.35	0.63	YES
11	RIPK3	RIPK3	RIPK3	1476	0.34	0.67	YES
12	IL1B	IL1B	IL1B	2302	0.26	0.66	NO
13	IL33	IL33	IL33	3464	0.18	0.62	NO
14	POLR3K	POLR3K	POLR3K	4761	0.12	0.57	NO
15	TREX1	TREX1	TREX1	5167	0.11	0.56	NO
16	POLR1D	POLR1D	POLR1D	6426	0.074	0.5	NO
17	TBK1	TBK1	TBK1	6471	0.074	0.51	NO
18	IKBKE	IKBKE	IKBKE	6478	0.073	0.52	NO
19	IKBKB	IKBKB	IKBKB	6705	0.069	0.52	NO
20	POLR3D	POLR3D	POLR3D	7664	0.05	0.47	NO
21	POLR3GL	POLR3GL	POLR3GL	7710	0.05	0.48	NO
22	POLR1C	POLR1C	POLR1C	7727	0.049	0.48	NO
23	NFKB1	NFKB1	NFKB1	8321	0.039	0.45	NO
24	IKBKG	IKBKG	IKBKG	8583	0.035	0.44	NO
25	NFKBIB	NFKBIB	NFKBIB	9379	0.022	0.4	NO
26	CHUK	CHUK	CHUK	9445	0.021	0.4	NO
27	NFKBIA	NFKBIA	NFKBIA	9478	0.02	0.4	NO
28	POLR3H	POLR3H	POLR3H	9776	0.016	0.39	NO
29	POLR3G	POLR3G	POLR3G	10001	0.012	0.38	NO
30	RELA	RELA	RELA	10068	0.011	0.38	NO
31	POLR3A	POLR3A	POLR3A	10491	0.0052	0.36	NO
32	PYCARD	PYCARD	PYCARD	11119	-0.0048	0.32	NO
33	IL18	IL18	IL18	11824	-0.016	0.28	NO
34	POLR3C	POLR3C	POLR3C	12085	-0.02	0.27	NO
35	DDX58	DDX58	DDX58	12317	-0.024	0.26	NO
36	MAVS	MAVS	MAVS	13170	-0.039	0.22	NO
37	ADAR	ADAR	ADAR	13209	-0.04	0.22	NO
38	POLR3F	POLR3F	POLR3F	13400	-0.044	0.22	NO
39	IRF7	IRF7	IRF7	13907	-0.055	0.2	NO
40	IRF3	IRF3	IRF3	13930	-0.056	0.21	NO
41	RIPK1	RIPK1	RIPK1	14375	-0.068	0.19	NO
42	POLR3B	POLR3B	POLR3B	15511	-0.11	0.14	NO

Figure S13. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA IL2RB PATHWAY.

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL2RB PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA GSK3 PATHWAY

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	PIP5K1B	PIP5K1B	PIP5K1B	43	0.77	0.034	YES
2	ACAP1	ACAP1	ACAP1	121	0.67	0.061	YES
3	IL2RA	IL2RA	IL2RA	128	0.66	0.092	YES
4	AGAP2	AGAP2	AGAP2	168	0.63	0.12	YES
5	IQSEC3	IQSEC3	IQSEC3	201	0.62	0.15	YES
6	CCR5	CCR5	CCR5	293	0.57	0.17	YES
7	EGF	EGF	EGF	450	0.52	0.18	YES
8	NTRK1	NTRK1	NTRK1	502	0.5	0.21	YES
9	IL2RB	IL2RB	IL2RB	511	0.5	0.23	YES
10	ADRB2	ADRB2	ADRB2	770	0.44	0.24	YES
11	KIT	KIT	KIT	798	0.44	0.26	YES
12	IQSEC2	IQSEC2	IQSEC2	999	0.41	0.26	YES
13	IL2RG	IL2RG	IL2RG	1089	0.39	0.28	YES
14	ADRB3	ADRB3	ADRB3	1253	0.37	0.28	YES
15	CXCR4	CXCR4	CXCR4	1273	0.36	0.3	YES
16	CXCR2	CXCR2	CXCR2	1388	0.35	0.31	YES
17	ASAP3	ASAP3	ASAP3	1584	0.33	0.32	YES
18	DNM3	DNM3	DNM3	1622	0.33	0.33	YES
19	ADRB1	ADRB1	ADRB1	1889	0.3	0.33	YES
20	IGF1R	IGF1R	IGF1R	2202	0.27	0.32	YES
21	SH3GL2	SH3GL2	SH3GL2	2312	0.26	0.33	YES
22	RAB31	RAB31	RAB31	2465	0.25	0.33	YES
23	GRK5	GRK5	GRK5	2575	0.24	0.34	YES
24	HLA-G	HLA-G	HLA-G	2623	0.24	0.35	YES
25	CSF1R	CSF1R	CSF1R	2802	0.22	0.35	YES
26	SH3GL3	SH3GL3	SH3GL3	3184	0.2	0.34	YES
27	SH3KBP1	SH3KBP1	SH3KBP1	3208	0.2	0.34	YES
28	GRK7	GRK7	GRK7	3294	0.19	0.35	YES
29	ACAP2	ACAP2	ACAP2	3380	0.19	0.35	YES
30	ARRB1	ARRB1	ARRB1	3460	0.18	0.36	YES
31	EHD3	EHD3	EHD3	3466	0.18	0.37	YES
32	PDGFRA	PDGFRA	PDGFRA	3520	0.18	0.37	YES
33	CBLB	CBLB	CBLB	3978	0.16	0.35	YES
34	LDLRAP1	LDLRAP1	LDLRAP1	3998	0.16	0.36	YES
35	CXCR1	CXCR1	CXCR1	4016	0.15	0.37	YES
36	KDR	KDR	KDR	4073	0.15	0.37	YES
37	TRAF6	TRAF6	TRAF6	4194	0.15	0.37	YES
38	HLA-F	HLA-F	HLA-F	4199	0.15	0.38	YES
39	ADRBK1	ADRBK1	ADRBK1	4576	0.13	0.36	YES
40	SMURF2	SMURF2	SMURF2	4577	0.13	0.37	YES
41	RET	RET	RET	4640	0.13	0.37	YES
42	EHD2	EHD2	EHD2	4674	0.13	0.38	YES
43	CHMP2B	CHMP2B	CHMP2B	4697	0.13	0.38	YES
44	GRK6	GRK6	GRK6	4822	0.12	0.38	YES
45	ADRBK2	ADRBK2	ADRBK2	4825	0.12	0.38	YES
46	ASAP1	ASAP1	ASAP1	4831	0.12	0.39	YES
47	HLA-E	HLA-E	HLA-E	4843	0.12	0.4	YES
48	PRKCI	PRKCI	PRKCI	4868	0.12	0.4	YES
49	F2R	F2R	F2R	5153	0.11	0.39	NO
50	SMAP2	SMAP2	SMAP2	5215	0.11	0.39	NO
51	RAB11FIP2	RAB11FIP2	RAB11FIP2	5244	0.11	0.39	NO
52	HSPA6	HSPA6	HSPA6	5322	0.1	0.4	NO
53	VTA1	VTA1	VTA1	5553	0.097	0.39	NO
54	DNM2	DNM2	DNM2	5736	0.092	0.38	NO
55	HLA-B	HLA-B	HLA-B	5861	0.088	0.38	NO
56	GIT1	GIT1	GIT1	6079	0.083	0.37	NO
57	HSPA1L	HSPA1L	HSPA1L	6107	0.082	0.37	NO
58	FLT1	FLT1	FLT1	6154	0.081	0.37	NO
59	HSPA2	HSPA2	HSPA2	6177	0.081	0.38	NO
60	VPS4A	VPS4A	VPS4A	6272	0.078	0.37	NO
61	ARAP3	ARAP3	ARAP3	6322	0.077	0.38	NO
62	IQSEC1	IQSEC1	IQSEC1	6371	0.076	0.38	NO
63	FAM125B	FAM125B	FAM125B	6443	0.074	0.38	NO
64	RAB5A	RAB5A	RAB5A	6520	0.072	0.38	NO
65	EPS15	EPS15	EPS15	6532	0.072	0.38	NO
66	RAB11FIP3	RAB11FIP3	RAB11FIP3	6619	0.07	0.38	NO
67	CBL	CBL	CBL	6627	0.07	0.38	NO
68	PIKFYVE	PIKFYVE	PIKFYVE	6637	0.07	0.38	NO
69	EHD1	EHD1	EHD1	6661	0.07	0.38	NO
70	GRK4	GRK4	GRK4	6728	0.068	0.38	NO
71	TFRC	TFRC	TFRC	6737	0.068	0.39	NO
72	ARAP1	ARAP1	ARAP1	6769	0.067	0.39	NO
73	PSD	PSD	PSD	6932	0.064	0.38	NO
74	SMAP1	SMAP1	SMAP1	6995	0.063	0.38	NO
75	ZFYVE20	ZFYVE20	ZFYVE20	7013	0.063	0.38	NO
76	EHD4	EHD4	EHD4	7047	0.062	0.38	NO
77	HLA-A	HLA-A	HLA-A	7084	0.061	0.38	NO
78	PARD6A	PARD6A	PARD6A	7245	0.058	0.38	NO
79	CHMP5	CHMP5	CHMP5	7392	0.055	0.37	NO
80	VPS36	VPS36	VPS36	7533	0.053	0.37	NO
81	PDCD6IP	PDCD6IP	PDCD6IP	7570	0.052	0.37	NO
82	ERBB4	ERBB4	ERBB4	7726	0.05	0.36	NO
83	RAB11FIP4	RAB11FIP4	RAB11FIP4	7804	0.048	0.36	NO
84	PIP5K1C	PIP5K1C	PIP5K1C	7812	0.048	0.36	NO
85	PIP4K2B	PIP4K2B	PIP4K2B	8033	0.044	0.35	NO
86	ITCH	ITCH	ITCH	8044	0.043	0.35	NO
87	CDC42	CDC42	CDC42	8081	0.043	0.35	NO
88	PRKCZ	PRKCZ	PRKCZ	8210	0.04	0.35	NO
89	DAB2	DAB2	DAB2	8263	0.04	0.35	NO
90	GIT2	GIT2	GIT2	8387	0.038	0.34	NO
91	MDM2	MDM2	MDM2	8417	0.037	0.34	NO
92	CHMP4B	CHMP4B	CHMP4B	8512	0.036	0.34	NO
93	ACAP3	ACAP3	ACAP3	8564	0.035	0.34	NO
94	SH3GL1	SH3GL1	SH3GL1	8740	0.032	0.33	NO
95	ARRB2	ARRB2	ARRB2	8848	0.03	0.32	NO
96	RNF41	RNF41	RNF41	9139	0.026	0.31	NO
97	RAB22A	RAB22A	RAB22A	9210	0.025	0.31	NO
98	ARFGAP1	ARFGAP1	ARFGAP1	9215	0.025	0.31	NO
99	HSPA8	HSPA8	HSPA8	9295	0.024	0.3	NO
100	SH3GLB1	SH3GLB1	SH3GLB1	9333	0.023	0.3	NO
101	VPS37B	VPS37B	VPS37B	9547	0.019	0.29	NO
102	EEA1	EEA1	EEA1	9576	0.019	0.29	NO
103	DNAJC6	DNAJC6	DNAJC6	9771	0.016	0.28	NO
104	USP8	USP8	USP8	9789	0.016	0.28	NO
105	MET	MET	MET	9870	0.014	0.28	NO
106	STAMBP	STAMBP	STAMBP	10003	0.012	0.27	NO
107	RAB11FIP5	RAB11FIP5	RAB11FIP5	10051	0.012	0.27	NO
108	AP2M1	AP2M1	AP2M1	10102	0.011	0.27	NO
109	AP2B1	AP2B1	AP2B1	10213	0.0093	0.26	NO
110	VPS25	VPS25	VPS25	10218	0.0093	0.26	NO
111	HGS	HGS	HGS	10253	0.0087	0.26	NO
112	RABEP1	RABEP1	RABEP1	10297	0.008	0.26	NO
113	PSD2	PSD2	PSD2	10346	0.0072	0.26	NO
114	ARFGAP3	ARFGAP3	ARFGAP3	10361	0.0071	0.26	NO
115	AP2A2	AP2A2	AP2A2	10394	0.0066	0.25	NO
116	HLA-C	HLA-C	HLA-C	10436	0.006	0.25	NO
117	HSPA1B	HSPA1B	HSPA1B	10473	0.0055	0.25	NO
118	CHMP4A	CHMP4A	CHMP4A	10668	0.0026	0.24	NO
119	TSG101	TSG101	TSG101	10739	0.0015	0.24	NO
120	CHMP1B	CHMP1B	CHMP1B	10770	0.001	0.23	NO
121	ARFGAP2	ARFGAP2	ARFGAP2	10781	0.00088	0.23	NO
122	SH3GLB2	SH3GLB2	SH3GLB2	10795	0.00065	0.23	NO
123	VPS37A	VPS37A	VPS37A	10802	0.00046	0.23	NO
124	SMURF1	SMURF1	SMURF1	10884	-0.00082	0.23	NO
125	RAB5C	RAB5C	RAB5C	10927	-0.0016	0.23	NO
126	SRC	SRC	SRC	10938	-0.0018	0.22	NO
127	DNM1	DNM1	DNM1	11003	-0.0028	0.22	NO
128	HSPA1A	HSPA1A	HSPA1A	11061	-0.0037	0.22	NO
129	CHMP6	CHMP6	CHMP6	11192	-0.0059	0.21	NO
130	PSD4	PSD4	PSD4	11289	-0.0076	0.21	NO
131	RUFY1	RUFY1	RUFY1	11463	-0.011	0.2	NO
132	VPS37D	VPS37D	VPS37D	11571	-0.012	0.19	NO
133	VPS4B	VPS4B	VPS4B	11652	-0.013	0.19	NO
134	DNM1L	DNM1L	DNM1L	11661	-0.014	0.19	NO
135	ARF6	ARF6	ARF6	11784	-0.015	0.18	NO
136	VPS37C	VPS37C	VPS37C	11788	-0.015	0.18	NO
137	AP2A1	AP2A1	AP2A1	11792	-0.015	0.18	NO
138	VPS24	VPS24	VPS24	11845	-0.016	0.18	NO
139	RAB5B	RAB5B	RAB5B	11864	-0.017	0.18	NO
140	ASAP2	ASAP2	ASAP2	11929	-0.018	0.18	NO
141	VPS28	VPS28	VPS28	12021	-0.019	0.18	NO
142	CLTC	CLTC	CLTC	12122	-0.021	0.17	NO
143	STAM2	STAM2	STAM2	12182	-0.022	0.17	NO
144	SNF8	SNF8	SNF8	12217	-0.022	0.17	NO
145	STAM	STAM	STAM	12297	-0.024	0.16	NO
146	PLD2	PLD2	PLD2	12364	-0.025	0.16	NO
147	AGAP1	AGAP1	AGAP1	12379	-0.025	0.16	NO
148	PIP5K1A	PIP5K1A	PIP5K1A	12394	-0.025	0.16	NO
149	WWP1	WWP1	WWP1	12703	-0.031	0.15	NO
150	EPN2	EPN2	EPN2	12728	-0.031	0.15	NO
151	AP2S1	AP2S1	AP2S1	12816	-0.033	0.14	NO
152	ARAP2	ARAP2	ARAP2	12847	-0.033	0.14	NO
153	NEDD4L	NEDD4L	NEDD4L	13002	-0.036	0.14	NO
154	CLTB	CLTB	CLTB	13052	-0.037	0.14	NO
155	FAM125A	FAM125A	FAM125A	13250	-0.041	0.13	NO
156	RAB11A	RAB11A	RAB11A	13270	-0.041	0.13	NO
157	EPN3	EPN3	EPN3	13334	-0.042	0.12	NO
158	RAB11B	RAB11B	RAB11B	13448	-0.045	0.12	NO
159	LDLR	LDLR	LDLR	13693	-0.05	0.11	NO
160	PARD6G	PARD6G	PARD6G	13754	-0.052	0.11	NO
161	CLTA	CLTA	CLTA	13994	-0.058	0.098	NO
162	RAB11FIP1	RAB11FIP1	RAB11FIP1	14182	-0.063	0.091	NO
163	CHMP2A	CHMP2A	CHMP2A	14359	-0.067	0.084	NO
164	CLTCL1	CLTCL1	CLTCL1	14410	-0.069	0.085	NO
165	EPN1	EPN1	EPN1	14669	-0.076	0.074	NO
166	PSD3	PSD3	PSD3	14677	-0.076	0.077	NO
167	VPS45	VPS45	VPS45	14725	-0.078	0.078	NO
168	RAB4A	RAB4A	RAB4A	15217	-0.097	0.056	NO
169	CHMP4C	CHMP4C	CHMP4C	15693	-0.12	0.035	NO
170	EGFR	EGFR	EGFR	15766	-0.12	0.036	NO
171	NEDD4	NEDD4	NEDD4	15975	-0.14	0.031	NO
172	PARD6B	PARD6B	PARD6B	16095	-0.14	0.032	NO
173	CBLC	CBLC	CBLC	16625	-0.18	0.011	NO
174	PARD3	PARD3	PARD3	16626	-0.18	0.02	NO
175	PLD1	PLD1	PLD1	16637	-0.19	0.028	NO
176	FGFR2	FGFR2	FGFR2	17228	-0.26	0.0074	NO
177	ERBB3	ERBB3	ERBB3	17276	-0.27	0.017	NO
178	FGFR3	FGFR3	FGFR3	17405	-0.3	0.024	NO
179	FGFR4	FGFR4	FGFR4	17525	-0.32	0.033	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: BIOCARTA GSK3 PATHWAY.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA GSK3 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 KERATINOCYTE PATHWAY

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	CD8B	CD8B	CD8B	8	0.9	0.04	YES
2	CTLA4	CTLA4	CTLA4	28	0.81	0.075	YES
3	CD8A	CD8A	CD8A	63	0.73	0.11	YES
4	PIK3CG	PIK3CG	PIK3CG	75	0.72	0.14	YES
5	ICOS	ICOS	ICOS	111	0.68	0.17	YES
6	IFNG	IFNG	IFNG	118	0.67	0.2	YES
7	IL10	IL10	IL10	129	0.66	0.22	YES
8	LCK	LCK	LCK	140	0.66	0.25	YES
9	ITK	ITK	ITK	211	0.61	0.28	YES
10	PTPRC	PTPRC	PTPRC	304	0.56	0.3	YES
11	CD247	CD247	CD247	321	0.56	0.32	YES
12	CD3E	CD3E	CD3E	326	0.56	0.35	YES
13	CD28	CD28	CD28	328	0.56	0.37	YES
14	RASGRP1	RASGRP1	RASGRP1	366	0.54	0.4	YES
15	PIK3R5	PIK3R5	PIK3R5	466	0.51	0.41	YES
16	GRAP2	GRAP2	GRAP2	565	0.49	0.43	YES
17	ZAP70	ZAP70	ZAP70	647	0.47	0.44	YES
18	CD3D	CD3D	CD3D	807	0.44	0.46	YES
19	PIK3CD	PIK3CD	PIK3CD	895	0.42	0.47	YES
20	IL2	IL2	IL2	926	0.42	0.49	YES
21	CD3G	CD3G	CD3G	980	0.41	0.5	YES
22	CD40LG	CD40LG	CD40LG	1073	0.4	0.52	YES
23	FYN	FYN	FYN	1142	0.38	0.53	YES
24	CARD11	CARD11	CARD11	1458	0.34	0.53	YES
25	LCP2	LCP2	LCP2	1525	0.34	0.54	YES
26	PDCD1	PDCD1	PDCD1	1616	0.33	0.55	YES
27	TEC	TEC	TEC	1732	0.32	0.56	YES
28	PDK1	PDK1	PDK1	1770	0.31	0.57	YES
29	VAV1	VAV1	VAV1	1856	0.3	0.58	YES
30	CSF2	CSF2	CSF2	1900	0.3	0.59	YES
31	CD4	CD4	CD4	2066	0.28	0.59	YES
32	PRKCQ	PRKCQ	PRKCQ	2301	0.26	0.59	YES
33	CHP2	CHP2	CHP2	2408	0.25	0.6	YES
34	LAT	LAT	LAT	2562	0.24	0.6	YES
35	TNF	TNF	TNF	2602	0.24	0.61	YES
36	MAP3K8	MAP3K8	MAP3K8	2838	0.22	0.6	NO
37	PPP3CA	PPP3CA	PPP3CA	3201	0.2	0.59	NO
38	NFATC2	NFATC2	NFATC2	3669	0.17	0.57	NO
39	NFATC4	NFATC4	NFATC4	3671	0.17	0.58	NO
40	CBLB	CBLB	CBLB	3978	0.16	0.57	NO
41	NCK1	NCK1	NCK1	4220	0.14	0.56	NO
42	PIK3R3	PIK3R3	PIK3R3	4370	0.14	0.56	NO
43	MAP3K7	MAP3K7	MAP3K7	4605	0.13	0.56	NO
44	PIK3CA	PIK3CA	PIK3CA	4897	0.12	0.55	NO
45	FOS	FOS	FOS	5125	0.11	0.54	NO
46	AKT3	AKT3	AKT3	5193	0.11	0.54	NO
47	PLCG1	PLCG1	PLCG1	5209	0.11	0.54	NO
48	MAP2K1	MAP2K1	MAP2K1	5241	0.11	0.55	NO
49	PTPN6	PTPN6	PTPN6	5429	0.1	0.54	NO
50	BCL10	BCL10	BCL10	5679	0.094	0.53	NO
51	SOS1	SOS1	SOS1	5817	0.09	0.53	NO
52	MAPK3	MAPK3	MAPK3	5820	0.09	0.53	NO
53	PAK2	PAK2	PAK2	6231	0.079	0.51	NO
54	KRAS	KRAS	KRAS	6308	0.077	0.51	NO
55	VAV2	VAV2	VAV2	6458	0.074	0.5	NO
56	PIK3CB	PIK3CB	PIK3CB	6609	0.071	0.5	NO
57	CBL	CBL	CBL	6627	0.07	0.5	NO
58	IKBKB	IKBKB	IKBKB	6705	0.069	0.5	NO
59	RHOA	RHOA	RHOA	6847	0.066	0.5	NO
60	PPP3CC	PPP3CC	PPP3CC	6948	0.064	0.49	NO
61	MAP3K14	MAP3K14	MAP3K14	7079	0.061	0.49	NO
62	NFAT5	NFAT5	NFAT5	7361	0.056	0.48	NO
63	NFATC3	NFATC3	NFATC3	7632	0.051	0.46	NO
64	PPP3R1	PPP3R1	PPP3R1	7745	0.049	0.46	NO
65	NFKBIE	NFKBIE	NFKBIE	7821	0.048	0.46	NO
66	GSK3B	GSK3B	GSK3B	8056	0.043	0.45	NO
67	RAF1	RAF1	RAF1	8071	0.043	0.45	NO
68	CDC42	CDC42	CDC42	8081	0.043	0.45	NO
69	NFKB1	NFKB1	NFKB1	8321	0.039	0.44	NO
70	CDK4	CDK4	CDK4	8334	0.038	0.44	NO
71	DLG1	DLG1	DLG1	8497	0.036	0.43	NO
72	IKBKG	IKBKG	IKBKG	8583	0.035	0.43	NO
73	PPP3CB	PPP3CB	PPP3CB	8804	0.031	0.42	NO
74	GRB2	GRB2	GRB2	8881	0.03	0.41	NO
75	PAK1	PAK1	PAK1	8904	0.03	0.41	NO
76	MAPK1	MAPK1	MAPK1	9347	0.023	0.39	NO
77	NFKBIB	NFKBIB	NFKBIB	9379	0.022	0.39	NO
78	CHUK	CHUK	CHUK	9445	0.021	0.39	NO
79	NFKBIA	NFKBIA	NFKBIA	9478	0.02	0.39	NO
80	NFATC1	NFATC1	NFATC1	9479	0.02	0.39	NO
81	AKT1	AKT1	AKT1	9715	0.017	0.38	NO
82	RELA	RELA	RELA	10068	0.011	0.36	NO
83	MAPK9	MAPK9	MAPK9	10743	0.0014	0.32	NO
84	MAP2K2	MAP2K2	MAP2K2	10978	-0.0024	0.31	NO
85	MALT1	MALT1	MALT1	11187	-0.0058	0.3	NO
86	JUN	JUN	JUN	11328	-0.0084	0.29	NO
87	PAK3	PAK3	PAK3	11333	-0.0084	0.29	NO
88	AKT2	AKT2	AKT2	11585	-0.012	0.27	NO
89	SOS2	SOS2	SOS2	12019	-0.019	0.25	NO
90	MAPK14	MAPK14	MAPK14	12581	-0.029	0.22	NO
91	PIK3R2	PIK3R2	PIK3R2	12661	-0.03	0.22	NO
92	MAP2K7	MAP2K7	MAP2K7	12749	-0.031	0.21	NO
93	PAK4	PAK4	PAK4	13787	-0.052	0.16	NO
94	CHP	CHP	CHP	14055	-0.059	0.15	NO
95	MAPK11	MAPK11	MAPK11	14282	-0.065	0.14	NO
96	NRAS	NRAS	NRAS	14613	-0.074	0.12	NO
97	PIK3R1	PIK3R1	PIK3R1	14733	-0.078	0.12	NO
98	NCK2	NCK2	NCK2	15315	-0.1	0.092	NO
99	MAPK13	MAPK13	MAPK13	16126	-0.15	0.053	NO
100	VAV3	VAV3	VAV3	16601	-0.18	0.035	NO
101	CBLC	CBLC	CBLC	16625	-0.18	0.042	NO
102	MAPK12	MAPK12	MAPK12	17332	-0.28	0.016	NO
103	PAK6	PAK6	PAK6	17364	-0.28	0.027	NO
104	PAK7	PAK7	PAK7	17562	-0.33	0.031	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: BIOCARTA KERATINOCYTE PATHWAY.

Figure S18. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA KERATINOCYTE 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 MYOSIN PATHWAY

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	PIK3CG	PIK3CG	PIK3CG	75	0.72	0.088	YES
2	EGF	EGF	EGF	450	0.52	0.13	YES
3	PIK3R5	PIK3R5	PIK3R5	466	0.51	0.2	YES
4	PIK3CD	PIK3CD	PIK3CD	895	0.42	0.23	YES
5	CDK6	CDK6	CDK6	1092	0.39	0.27	YES
6	BRCA2	BRCA2	BRCA2	1376	0.35	0.3	YES
7	VEGFC	VEGFC	VEGFC	1453	0.35	0.34	YES
8	ARHGEF6	ARHGEF6	ARHGEF6	1553	0.33	0.38	YES
9	E2F2	E2F2	E2F2	3179	0.2	0.31	YES
10	MAPK10	MAPK10	MAPK10	3646	0.17	0.31	YES
11	FIGF	FIGF	FIGF	3843	0.16	0.32	YES
12	PIK3R3	PIK3R3	PIK3R3	4370	0.14	0.31	YES
13	RAD51	RAD51	RAD51	4559	0.13	0.31	YES
14	TGFB1	TGFB1	TGFB1	4599	0.13	0.33	YES
15	CDKN2A	CDKN2A	CDKN2A	4606	0.13	0.34	YES
16	RAC2	RAC2	RAC2	4610	0.13	0.36	YES
17	PIK3CA	PIK3CA	PIK3CA	4897	0.12	0.36	YES
18	MAPK8	MAPK8	MAPK8	4907	0.12	0.38	YES
19	RB1	RB1	RB1	4944	0.12	0.39	YES
20	RALGDS	RALGDS	RALGDS	5052	0.11	0.4	YES
21	AKT3	AKT3	AKT3	5193	0.11	0.4	YES
22	TGFBR1	TGFBR1	TGFBR1	5216	0.11	0.42	YES
23	MAP2K1	MAP2K1	MAP2K1	5241	0.11	0.43	YES
24	MAPK3	MAPK3	MAPK3	5820	0.09	0.41	NO
25	KRAS	KRAS	KRAS	6308	0.077	0.39	NO
26	CASP9	CASP9	CASP9	6572	0.072	0.38	NO
27	PIK3CB	PIK3CB	PIK3CB	6609	0.071	0.39	NO
28	IKBKB	IKBKB	IKBKB	6705	0.069	0.4	NO
29	RALBP1	RALBP1	RALBP1	6724	0.068	0.4	NO
30	STAT3	STAT3	STAT3	6821	0.066	0.41	NO
31	TGFBR2	TGFBR2	TGFBR2	6868	0.065	0.41	NO
32	RALA	RALA	RALA	7695	0.05	0.37	NO
33	RAF1	RAF1	RAF1	8071	0.043	0.36	NO
34	CDC42	CDC42	CDC42	8081	0.043	0.36	NO
35	RAC3	RAC3	RAC3	8258	0.04	0.36	NO
36	NFKB1	NFKB1	NFKB1	8321	0.039	0.36	NO
37	CDK4	CDK4	CDK4	8334	0.038	0.36	NO
38	IKBKG	IKBKG	IKBKG	8583	0.035	0.35	NO
39	RAC1	RAC1	RAC1	9013	0.028	0.33	NO
40	MAPK1	MAPK1	MAPK1	9347	0.023	0.32	NO
41	CHUK	CHUK	CHUK	9445	0.021	0.32	NO
42	TGFB3	TGFB3	TGFB3	9525	0.02	0.31	NO
43	AKT1	AKT1	AKT1	9715	0.017	0.31	NO
44	PGF	PGF	PGF	10033	0.012	0.29	NO
45	ERBB2	ERBB2	ERBB2	10041	0.012	0.29	NO
46	RELA	RELA	RELA	10068	0.011	0.29	NO
47	TGFB2	TGFB2	TGFB2	10735	0.0016	0.25	NO
48	BRAF	BRAF	BRAF	10737	0.0016	0.25	NO
49	MAPK9	MAPK9	MAPK9	10743	0.0014	0.25	NO
50	JAK1	JAK1	JAK1	10784	0.00084	0.25	NO
51	SMAD3	SMAD3	SMAD3	11078	-0.0041	0.24	NO
52	ARAF	ARAF	ARAF	11378	-0.0092	0.22	NO
53	TP53	TP53	TP53	11484	-0.011	0.22	NO
54	AKT2	AKT2	AKT2	11585	-0.012	0.21	NO
55	RALB	RALB	RALB	12044	-0.02	0.19	NO
56	SMAD2	SMAD2	SMAD2	12081	-0.02	0.19	NO
57	VEGFB	VEGFB	VEGFB	12100	-0.02	0.19	NO
58	PIK3R2	PIK3R2	PIK3R2	12661	-0.03	0.16	NO
59	STAT1	STAT1	STAT1	12770	-0.032	0.16	NO
60	BAD	BAD	BAD	13854	-0.054	0.11	NO
61	SMAD4	SMAD4	SMAD4	13935	-0.056	0.11	NO
62	TGFA	TGFA	TGFA	14453	-0.07	0.093	NO
63	PIK3R1	PIK3R1	PIK3R1	14733	-0.078	0.088	NO
64	VEGFA	VEGFA	VEGFA	14801	-0.081	0.094	NO
65	E2F3	E2F3	E2F3	15088	-0.092	0.09	NO
66	BCL2L1	BCL2L1	BCL2L1	15606	-0.12	0.076	NO
67	EGFR	EGFR	EGFR	15766	-0.12	0.084	NO
68	CCND1	CCND1	CCND1	16472	-0.17	0.067	NO
69	PLD1	PLD1	PLD1	16637	-0.19	0.082	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: BIOCARTA MYOSIN PATHWAY.

Figure S20. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA MYOSIN 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 clus2 enriched pathways

Table 4. Get Full Table This table shows top 9 pathways which are significantly enriched in cluster clus2. It displays only significant gene sets satisfying nom.p.val.threshold (-1), fwer.p.val.threshold (-1) , fdr.q.val.threshold (0.25) and the default table is sorted by Normalized Enrichment Score (NES). Further details on NES statistics, please visit The Broad GSEA website.

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA DEATH PATHWAY	32	genes.ES.table	0.24	0.92	0.54	1	1	1	0.76	0.24	1	0.86
KEGG OXIDATIVE PHOSPHORYLATION	111	genes.ES.table	0.24	0.73	0.65	1	1	0.37	0.3	0.26	1	0.96
KEGG RNA DEGRADATION	55	genes.ES.table	0.23	1.1	0.38	1	1	1	0.77	0.23	1	0.79
KEGG RNA POLYMERASE	28	genes.ES.table	0.17	0.65	0.88	1	1	0.29	0.23	0.22	1	0.89
KEGG SPLICEOSOME	125	genes.ES.table	0.24	1.1	0.37	1	1	0.98	0.67	0.33	1	0.98
KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT	37	genes.ES.table	0.13	0.57	0.96	0.94	1	0.4	0.29	0.29	0.95	0.037
KEGG NOTCH SIGNALING PATHWAY	46	genes.ES.table	0.15	0.57	0.96	1	1	0.17	0.16	0.15	1	0.87
KEGG VASOPRESSIN REGULATED WATER REABSORPTION	41	genes.ES.table	0.19	0.68	0.86	1	1	0.15	0.1	0.13	1	0.96
KEGG HUNTINGTONS DISEASE	166	genes.ES.table	0.17	0.77	0.69	1	1	0.24	0.23	0.19	1	0.98

genes ES table in pathway: BIOCARTA DEATH PATHWAY

Table S11. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRPF40B	PRPF40B	PRPF40B	963	0.19	-0.012	YES
2	SNRPE	SNRPE	SNRPE	2480	0.096	-0.075	YES
3	LSM2	LSM2	LSM2	2887	0.082	-0.079	YES
4	SF3B4	SF3B4	SF3B4	3122	0.075	-0.076	YES
5	PRPF3	PRPF3	PRPF3	3229	0.072	-0.065	YES
6	PRPF18	PRPF18	PRPF18	3561	0.064	-0.07	YES
7	TXNL4A	TXNL4A	TXNL4A	3612	0.062	-0.059	YES
8	BCAS2	BCAS2	BCAS2	3847	0.057	-0.059	YES
9	HSPA1L	HSPA1L	HSPA1L	4169	0.05	-0.066	YES
10	SNRPB	SNRPB	SNRPB	4202	0.049	-0.057	YES
11	PQBP1	PQBP1	PQBP1	4292	0.048	-0.051	YES
12	SNRPB2	SNRPB2	SNRPB2	4337	0.047	-0.043	YES
13	SFRS2B	SFRS2B	SFRS2B	4362	0.046	-0.034	YES
14	PPIH	PPIH	PPIH	4444	0.044	-0.029	YES
15	CRNKL1	CRNKL1	CRNKL1	4540	0.043	-0.025	YES
16	SFRS9	SFRS9	SFRS9	4561	0.042	-0.017	YES
17	SNRPC	SNRPC	SNRPC	4565	0.042	-0.0074	YES
18	PLRG1	PLRG1	PLRG1	4755	0.039	-0.0093	YES
19	XAB2	XAB2	XAB2	4782	0.038	-0.0023	YES
20	PRPF31	PRPF31	PRPF31	4880	0.036	0.00042	YES
21	HNRNPA1	HNRNPA1	HNRNPA1	4885	0.036	0.0083	YES
22	CWC15	CWC15	CWC15	4943	0.035	0.013	YES
23	RBM8A	RBM8A	RBM8A	5020	0.034	0.016	YES
24	BAT1	BAT1	BAT1	5038	0.034	0.023	YES
25	SF3A2	SF3A2	SF3A2	5122	0.032	0.025	YES
26	SNRNP70	SNRNP70	SNRNP70	5137	0.032	0.032	YES
27	HSPA6	HSPA6	HSPA6	5307	0.029	0.029	YES
28	THOC1	THOC1	THOC1	5349	0.028	0.033	YES
29	LSM7	LSM7	LSM7	5393	0.028	0.036	YES
30	SFRS3	SFRS3	SFRS3	5437	0.027	0.04	YES
31	RBM17	RBM17	RBM17	5441	0.027	0.046	YES
32	LSM3	LSM3	LSM3	5461	0.026	0.05	YES
33	U2AF1	U2AF1	U2AF1	5465	0.026	0.056	YES
34	RBM22	RBM22	RBM22	5657	0.023	0.05	YES
35	SNRPD1	SNRPD1	SNRPD1	5702	0.022	0.053	YES
36	HNRNPU	HNRNPU	HNRNPU	5817	0.021	0.051	YES
37	DHX16	DHX16	DHX16	5869	0.02	0.053	YES
38	PRPF6	PRPF6	PRPF6	5999	0.018	0.05	YES
39	CCDC12	CCDC12	CCDC12	6011	0.018	0.053	YES
40	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	6038	0.017	0.056	YES
41	LSM4	LSM4	LSM4	6044	0.017	0.059	YES
42	DDX23	DDX23	DDX23	6217	0.015	0.053	YES
43	PPIE	PPIE	PPIE	6314	0.013	0.05	YES
44	PRPF38A	PRPF38A	PRPF38A	6352	0.013	0.051	YES
45	SNRPD2	SNRPD2	SNRPD2	6355	0.013	0.054	YES
46	SNRPF	SNRPF	SNRPF	6542	0.01	0.046	YES
47	SART1	SART1	SART1	6605	0.0092	0.044	YES
48	HNRNPC	HNRNPC	HNRNPC	6661	0.0085	0.043	YES
49	CDC5L	CDC5L	CDC5L	6684	0.0081	0.044	YES
50	CTNNBL1	CTNNBL1	CTNNBL1	6726	0.0076	0.043	YES
51	HNRNPM	HNRNPM	HNRNPM	6830	0.0062	0.039	YES
52	ACIN1	ACIN1	ACIN1	6920	0.0048	0.035	YES
53	SNRPD3	SNRPD3	SNRPD3	6924	0.0047	0.036	YES
54	NAA38	NAA38	NAA38	6971	0.0041	0.034	YES
55	TRA2A	TRA2A	TRA2A	6993	0.0038	0.034	YES
56	SF3B2	SF3B2	SF3B2	7140	0.0018	0.026	YES
57	PRPF19	PRPF19	PRPF19	7203	0.00073	0.023	YES
58	MAGOHB	MAGOHB	MAGOHB	7302	-0.0005	0.018	YES
59	RBMX	RBMX	RBMX	7463	-0.003	0.0092	YES
60	PUF60	PUF60	PUF60	7464	-0.003	0.0099	YES
61	SFRS6	SFRS6	SFRS6	7477	-0.0031	0.0099	YES
62	PRPF8	PRPF8	PRPF8	7478	-0.0031	0.011	YES
63	ZMAT2	ZMAT2	ZMAT2	7588	-0.0045	0.0055	YES
64	NHP2L1	NHP2L1	NHP2L1	7707	-0.0066	0.00043	YES
65	WBP11	WBP11	WBP11	7795	-0.0078	-0.0027	YES
66	HNRNPA3	HNRNPA3	HNRNPA3	7804	-0.008	-0.0014	YES
67	U2AF2	U2AF2	U2AF2	7891	-0.009	-0.0042	YES
68	SMNDC1	SMNDC1	SMNDC1	7998	-0.011	-0.0077	YES
69	DHX8	DHX8	DHX8	8158	-0.013	-0.014	YES
70	SNW1	SNW1	SNW1	8164	-0.013	-0.011	YES
71	SFRS1	SFRS1	SFRS1	8311	-0.015	-0.016	YES
72	SNRPA	SNRPA	SNRPA	8367	-0.016	-0.015	YES
73	DDX42	DDX42	DDX42	8415	-0.016	-0.014	YES
74	SNRNP200	SNRNP200	SNRNP200	8441	-0.017	-0.012	YES
75	SFRS4	SFRS4	SFRS4	8446	-0.017	-0.0085	YES
76	SF3A3	SF3A3	SF3A3	8458	-0.017	-0.0053	YES
77	DHX15	DHX15	DHX15	8463	-0.017	-0.0017	YES
78	DDX46	DDX46	DDX46	8549	-0.019	-0.0023	YES
79	SLU7	SLU7	SLU7	8567	-0.019	0.00096	YES
80	SNRPG	SNRPG	SNRPG	8596	-0.02	0.0037	YES
81	PRPF4	PRPF4	PRPF4	8675	-0.021	0.0039	YES
82	PCBP1	PCBP1	PCBP1	8765	-0.022	0.0038	YES
83	SF3B3	SF3B3	SF3B3	8810	-0.022	0.0063	YES
84	CHERP	CHERP	CHERP	8886	-0.024	0.0074	YES
85	SF3B14	SF3B14	SF3B14	8927	-0.024	0.01	YES
86	HNRNPK	HNRNPK	HNRNPK	8988	-0.025	0.013	YES
87	SF3A1	SF3A1	SF3A1	9165	-0.028	0.0091	YES
88	PPIL1	PPIL1	PPIL1	9282	-0.03	0.0092	YES
89	SYF2	SYF2	SYF2	9326	-0.03	0.014	YES
90	DDX5	DDX5	DDX5	9457	-0.032	0.013	YES
91	SFRS2	SFRS2	SFRS2	9514	-0.033	0.018	YES
92	MAGOH	MAGOH	MAGOH	9563	-0.034	0.022	YES
93	SNRNP27	SNRNP27	SNRNP27	9639	-0.035	0.026	YES
94	PRPF38B	PRPF38B	PRPF38B	9648	-0.035	0.033	YES
95	AQR	AQR	AQR	9704	-0.036	0.038	YES
96	BUD31	BUD31	BUD31	9824	-0.038	0.04	YES
97	PRPF40A	PRPF40A	PRPF40A	9826	-0.038	0.048	YES
98	EIF4A3	EIF4A3	EIF4A3	9845	-0.038	0.055	YES
99	DHX38	DHX38	DHX38	9886	-0.038	0.062	YES
100	TRA2B	TRA2B	TRA2B	9998	-0.04	0.064	YES
101	THOC3	THOC3	THOC3	10131	-0.042	0.066	YES
102	THOC4	THOC4	THOC4	10181	-0.043	0.073	YES
103	SF3B5	SF3B5	SF3B5	10308	-0.045	0.076	YES
104	LSM6	LSM6	LSM6	10351	-0.046	0.084	YES
105	SNRPA1	SNRPA1	SNRPA1	10398	-0.047	0.092	YES
106	RBM25	RBM25	RBM25	10409	-0.047	0.1	YES
107	SFRS7	SFRS7	SFRS7	10564	-0.049	0.1	YES
108	EFTUD2	EFTUD2	EFTUD2	10578	-0.05	0.11	YES
109	TCERG1	TCERG1	TCERG1	10658	-0.051	0.12	YES
110	SF3B1	SF3B1	SF3B1	10699	-0.052	0.13	YES
111	HSPA1B	HSPA1B	HSPA1B	10786	-0.054	0.14	YES
112	SFRS5	SFRS5	SFRS5	10845	-0.055	0.15	YES
113	USP39	USP39	USP39	11006	-0.058	0.15	YES
114	LSM5	LSM5	LSM5	11021	-0.058	0.16	YES
115	SNRNP40	SNRNP40	SNRNP40	11042	-0.059	0.17	YES
116	HSPA8	HSPA8	HSPA8	11100	-0.06	0.18	YES
117	SFRS13A	SFRS13A	SFRS13A	11165	-0.062	0.19	YES
118	THOC2	THOC2	THOC2	11222	-0.063	0.2	YES
119	PHF5A	PHF5A	PHF5A	11684	-0.073	0.2	YES
120	HSPA1A	HSPA1A	HSPA1A	11697	-0.074	0.21	YES
121	ISY1	ISY1	ISY1	11885	-0.078	0.22	YES
122	SR140	SR140	SR140	12013	-0.081	0.23	YES
123	NCBP1	NCBP1	NCBP1	12110	-0.083	0.24	YES
124	CDC40	CDC40	CDC40	13844	-0.14	0.18	NO
125	HSPA2	HSPA2	HSPA2	15798	-0.27	0.13	NO

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

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

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

Table S12. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ENO3	ENO3	ENO3	223	0.32	0.11	YES
2	LSM2	LSM2	LSM2	2887	0.082	-0.012	YES
3	EXOSC4	EXOSC4	EXOSC4	4302	0.048	-0.073	YES
4	EDC3	EDC3	EDC3	4387	0.046	-0.06	YES
5	CNOT6L	CNOT6L	CNOT6L	4419	0.045	-0.046	YES
6	SKIV2L2	SKIV2L2	SKIV2L2	4608	0.041	-0.041	YES
7	LSM1	LSM1	LSM1	4643	0.041	-0.028	YES
8	SKIV2L	SKIV2L	SKIV2L	4917	0.036	-0.03	YES
9	CNOT7	CNOT7	CNOT7	5021	0.034	-0.023	YES
10	CNOT2	CNOT2	CNOT2	5331	0.029	-0.03	YES
11	LSM7	LSM7	LSM7	5393	0.028	-0.023	YES
12	LSM3	LSM3	LSM3	5461	0.026	-0.017	YES
13	EXOSC9	EXOSC9	EXOSC9	5564	0.025	-0.014	YES
14	EXOSC3	EXOSC3	EXOSC3	5651	0.023	-0.0097	YES
15	DDX6	DDX6	DDX6	5753	0.022	-0.0073	YES
16	LSM4	LSM4	LSM4	6044	0.017	-0.017	YES
17	WDR61	WDR61	WDR61	6361	0.013	-0.03	YES
18	XRN2	XRN2	XRN2	6522	0.01	-0.035	YES
19	CNOT10	CNOT10	CNOT10	6635	0.0088	-0.038	YES
20	CNOT3	CNOT3	CNOT3	6785	0.0068	-0.044	YES
21	NAA38	NAA38	NAA38	6971	0.0041	-0.052	YES
22	EXOSC7	EXOSC7	EXOSC7	7046	0.003	-0.055	YES
23	EXOSC8	EXOSC8	EXOSC8	7375	-0.0015	-0.073	YES
24	DCP1B	DCP1B	DCP1B	7440	-0.0026	-0.076	YES
25	CNOT4	CNOT4	CNOT4	7927	-0.0095	-0.099	YES
26	EXOSC2	EXOSC2	EXOSC2	8630	-0.02	-0.13	YES
27	PAPD7	PAPD7	PAPD7	8725	-0.021	-0.13	YES
28	ENO2	ENO2	ENO2	8815	-0.022	-0.12	YES
29	EDC4	EDC4	EDC4	8890	-0.024	-0.12	YES
30	EXOSC6	EXOSC6	EXOSC6	8922	-0.024	-0.11	YES
31	PATL1	PATL1	PATL1	8939	-0.024	-0.1	YES
32	EXOSC10	EXOSC10	EXOSC10	9006	-0.025	-0.099	YES
33	C1D	C1D	C1D	9010	-0.026	-0.09	YES
34	PARN	PARN	PARN	9039	-0.026	-0.082	YES
35	EXOSC1	EXOSC1	EXOSC1	9147	-0.028	-0.078	YES
36	ZCCHC7	ZCCHC7	ZCCHC7	9262	-0.029	-0.073	YES
37	CNOT6	CNOT6	CNOT6	9646	-0.035	-0.082	YES
38	EXOSC5	EXOSC5	EXOSC5	9682	-0.035	-0.071	YES
39	DCPS	DCPS	DCPS	9724	-0.036	-0.06	YES
40	DCP1A	DCP1A	DCP1A	10344	-0.046	-0.077	YES
41	LSM6	LSM6	LSM6	10351	-0.046	-0.06	YES
42	PAPOLA	PAPOLA	PAPOLA	10583	-0.05	-0.055	YES
43	HSPA9	HSPA9	HSPA9	10901	-0.056	-0.052	YES
44	LSM5	LSM5	LSM5	11021	-0.058	-0.037	YES
45	CNOT1	CNOT1	CNOT1	11320	-0.065	-0.03	YES
46	XRN1	XRN1	XRN1	11463	-0.068	-0.013	YES
47	PNPT1	PNPT1	PNPT1	11486	-0.069	0.011	YES
48	HSPD1	HSPD1	HSPD1	12431	-0.092	-0.0072	YES
49	ENO1	ENO1	ENO1	12845	-0.11	0.0088	YES
50	TTC37	TTC37	TTC37	13124	-0.12	0.036	YES
51	RQCD1	RQCD1	RQCD1	13191	-0.12	0.075	YES
52	DCP2	DCP2	DCP2	13353	-0.12	0.11	YES
53	PAPOLG	PAPOLG	PAPOLG	13494	-0.13	0.15	YES
54	DIS3	DIS3	DIS3	13580	-0.13	0.2	YES
55	MPHOSPH6	MPHOSPH6	MPHOSPH6	14015	-0.15	0.23	YES

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 OXIDATIVE PHOSPHORYLATION.

Figure S24. 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 RNA DEGRADATION

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	CASP6	CASP6	CASP6	2710	0.087	-0.1	YES
2	TNFRSF10B	TNFRSF10B	TNFRSF10B	3243	0.072	-0.092	YES
3	LMNA	LMNA	LMNA	3487	0.066	-0.07	YES
4	TNFSF12	TNFSF12	TNFSF12	3765	0.059	-0.053	YES
5	GAS2	GAS2	GAS2	3974	0.054	-0.035	YES
6	RIPK1	RIPK1	RIPK1	4475	0.044	-0.038	YES
7	TRAF2	TRAF2	TRAF2	4578	0.042	-0.021	YES
8	NFKB1	NFKB1	NFKB1	4989	0.035	-0.025	YES
9	RELA	RELA	RELA	5069	0.033	-0.011	YES
10	SPTAN1	SPTAN1	SPTAN1	5201	0.031	-0.0014	YES
11	XIAP	XIAP	XIAP	7206	0.00068	-0.11	YES
12	CASP10	CASP10	CASP10	8002	-0.011	-0.15	YES
13	CASP3	CASP3	CASP3	8081	-0.012	-0.15	YES
14	APAF1	APAF1	APAF1	8194	-0.014	-0.15	YES
15	TNFSF10	TNFSF10	TNFSF10	8366	-0.016	-0.15	YES
16	BIRC2	BIRC2	BIRC2	8492	-0.018	-0.14	YES
17	NFKBIA	NFKBIA	NFKBIA	9572	-0.034	-0.19	YES
18	CASP8	CASP8	CASP8	9769	-0.037	-0.18	YES
19	CASP9	CASP9	CASP9	9910	-0.039	-0.16	YES
20	MAP3K14	MAP3K14	MAP3K14	10264	-0.044	-0.16	YES
21	TRADD	TRADD	TRADD	10484	-0.048	-0.14	YES
22	CASP7	CASP7	CASP7	10871	-0.055	-0.14	YES
23	CHUK	CHUK	CHUK	11278	-0.064	-0.12	YES
24	FADD	FADD	FADD	11526	-0.069	-0.099	YES
25	TNFRSF25	TNFRSF25	TNFRSF25	11872	-0.078	-0.076	YES
26	CYCS	CYCS	CYCS	12000	-0.081	-0.039	YES
27	DFFA	DFFA	DFFA	12384	-0.091	-0.011	YES
28	DFFB	DFFB	DFFB	12658	-0.099	0.028	YES
29	TNFRSF10A	TNFRSF10A	TNFRSF10A	12815	-0.1	0.077	YES
30	CFLAR	CFLAR	CFLAR	13320	-0.12	0.12	YES
31	BCL2	BCL2	BCL2	13522	-0.13	0.18	YES
32	BIRC3	BIRC3	BIRC3	13827	-0.14	0.24	YES

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 RNA DEGRADATION.

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

genes ES table in pathway: KEGG RNA POLYMERASE

Table 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	GRM5	GRM5	GRM5	322	0.29	0.012	YES
2	CREB5	CREB5	CREB5	481	0.25	0.029	YES
3	CLTCL1	CLTCL1	CLTCL1	796	0.21	0.032	YES
4	DNAI1	DNAI1	DNAI1	933	0.19	0.044	YES
5	ATP5C1	ATP5C1	ATP5C1	1640	0.13	0.019	YES
6	NDUFC1	NDUFC1	NDUFC1	1680	0.13	0.03	YES
7	DNALI1	DNALI1	DNALI1	1686	0.13	0.043	YES
8	BBC3	BBC3	BBC3	1698	0.13	0.055	YES
9	NDUFS4	NDUFS4	NDUFS4	1708	0.13	0.068	YES
10	HAP1	HAP1	HAP1	1771	0.13	0.077	YES
11	CREB3L4	CREB3L4	CREB3L4	1804	0.12	0.088	YES
12	TP53	TP53	TP53	1879	0.12	0.096	YES
13	PPARGC1A	PPARGC1A	PPARGC1A	2151	0.11	0.092	YES
14	NDUFS2	NDUFS2	NDUFS2	2181	0.11	0.1	YES
15	COX6B2	COX6B2	COX6B2	2195	0.11	0.11	YES
16	ATP5G2	ATP5G2	ATP5G2	2352	0.1	0.11	YES
17	DNAL4	DNAL4	DNAL4	2726	0.087	0.1	YES
18	CLTB	CLTB	CLTB	2801	0.085	0.1	YES
19	GRIN1	GRIN1	GRIN1	2888	0.082	0.11	YES
20	NDUFA4L2	NDUFA4L2	NDUFA4L2	2932	0.081	0.11	YES
21	POLR2J3	POLR2J3	POLR2J3	3028	0.078	0.12	YES
22	DNAH2	DNAH2	DNAH2	3065	0.077	0.12	YES
23	ATP5D	ATP5D	ATP5D	3068	0.077	0.13	YES
24	CREB3	CREB3	CREB3	3225	0.072	0.13	YES
25	NDUFS3	NDUFS3	NDUFS3	3255	0.072	0.14	YES
26	SDHC	SDHC	SDHC	3327	0.07	0.14	YES
27	ATP5A1	ATP5A1	ATP5A1	3381	0.068	0.14	YES
28	POLR2I	POLR2I	POLR2I	3589	0.063	0.14	YES
29	CLTA	CLTA	CLTA	3591	0.063	0.14	YES
30	NDUFS5	NDUFS5	NDUFS5	3658	0.062	0.15	YES
31	POLR2A	POLR2A	POLR2A	3744	0.059	0.15	YES
32	NDUFC2	NDUFC2	NDUFC2	3802	0.058	0.15	YES
33	ATP5O	ATP5O	ATP5O	3820	0.058	0.15	YES
34	NDUFA7	NDUFA7	NDUFA7	4018	0.053	0.15	YES
35	SP1	SP1	SP1	4048	0.053	0.15	YES
36	NDUFB7	NDUFB7	NDUFB7	4069	0.052	0.16	YES
37	BAX	BAX	BAX	4086	0.052	0.16	YES
38	POLR2J2	POLR2J2	POLR2J2	4134	0.051	0.16	YES
39	AP2A2	AP2A2	AP2A2	4187	0.05	0.17	YES
40	COX7A1	COX7A1	COX7A1	4204	0.049	0.17	YES
41	ATP5J	ATP5J	ATP5J	4447	0.044	0.16	NO
42	NDUFS6	NDUFS6	NDUFS6	4468	0.044	0.16	NO
43	NDUFV2	NDUFV2	NDUFV2	4795	0.038	0.15	NO
44	NDUFA3	NDUFA3	NDUFA3	4818	0.038	0.15	NO
45	COX7C	COX7C	COX7C	4846	0.037	0.16	NO
46	NDUFB1	NDUFB1	NDUFB1	4993	0.034	0.15	NO
47	DCTN2	DCTN2	DCTN2	5036	0.034	0.15	NO
48	DCTN1	DCTN1	DCTN1	5049	0.034	0.15	NO
49	UQCRB	UQCRB	UQCRB	5095	0.033	0.16	NO
50	NDUFB2	NDUFB2	NDUFB2	5132	0.032	0.16	NO
51	NDUFA9	NDUFA9	NDUFA9	5141	0.032	0.16	NO
52	NDUFV3	NDUFV3	NDUFV3	5204	0.031	0.16	NO
53	POLR2F	POLR2F	POLR2F	5285	0.029	0.16	NO
54	NDUFB9	NDUFB9	NDUFB9	5290	0.029	0.16	NO
55	SLC25A4	SLC25A4	SLC25A4	5319	0.029	0.16	NO
56	NDUFA6	NDUFA6	NDUFA6	5328	0.029	0.16	NO
57	UQCRQ	UQCRQ	UQCRQ	5384	0.028	0.16	NO
58	NDUFS7	NDUFS7	NDUFS7	5432	0.027	0.16	NO
59	COX6A1	COX6A1	COX6A1	5453	0.026	0.16	NO
60	PLCB3	PLCB3	PLCB3	5468	0.026	0.17	NO
61	HIP1	HIP1	HIP1	5575	0.024	0.16	NO
62	POLR2G	POLR2G	POLR2G	5738	0.022	0.16	NO
63	TAF4	TAF4	TAF4	5739	0.022	0.16	NO
64	COX8A	COX8A	COX8A	5743	0.022	0.16	NO
65	NDUFB6	NDUFB6	NDUFB6	5922	0.019	0.15	NO
66	UQCR11	UQCR11	UQCR11	6005	0.018	0.15	NO
67	POLR2K	POLR2K	POLR2K	6077	0.017	0.15	NO
68	SIN3A	SIN3A	SIN3A	6111	0.016	0.15	NO
69	NDUFB3	NDUFB3	NDUFB3	6116	0.016	0.15	NO
70	COX6B1	COX6B1	COX6B1	6290	0.014	0.14	NO
71	PPID	PPID	PPID	6303	0.014	0.14	NO
72	ATP5B	ATP5B	ATP5B	6328	0.013	0.14	NO
73	NDUFA1	NDUFA1	NDUFA1	6347	0.013	0.14	NO
74	HDAC1	HDAC1	HDAC1	6382	0.013	0.14	NO
75	POLR2L	POLR2L	POLR2L	6410	0.012	0.14	NO
76	VDAC3	VDAC3	VDAC3	6433	0.012	0.14	NO
77	NDUFA10	NDUFA10	NDUFA10	6475	0.011	0.14	NO
78	NRF1	NRF1	NRF1	6509	0.011	0.14	NO
79	UQCRHL	UQCRHL	UQCRHL	6520	0.01	0.14	NO
80	UQCRH	UQCRH	UQCRH	6608	0.0092	0.14	NO
81	NDUFV1	NDUFV1	NDUFV1	6632	0.0088	0.14	NO
82	CREBBP	CREBBP	CREBBP	6681	0.0082	0.13	NO
83	AP2S1	AP2S1	AP2S1	6778	0.007	0.13	NO
84	NDUFB10	NDUFB10	NDUFB10	6795	0.0067	0.13	NO
85	COX7A2L	COX7A2L	COX7A2L	6801	0.0066	0.13	NO
86	CYC1	CYC1	CYC1	6834	0.0062	0.13	NO
87	VDAC1	VDAC1	VDAC1	6838	0.006	0.13	NO
88	UQCRC1	UQCRC1	UQCRC1	6960	0.0042	0.12	NO
89	POLR2H	POLR2H	POLR2H	6962	0.0042	0.12	NO
90	SDHA	SDHA	SDHA	7091	0.0024	0.12	NO
91	NDUFB8	NDUFB8	NDUFB8	7216	0.00056	0.11	NO
92	ATP5H	ATP5H	ATP5H	7229	0.00042	0.11	NO
93	DNAL1	DNAL1	DNAL1	7239	0.00026	0.11	NO
94	COX5B	COX5B	COX5B	7273	-0.00016	0.11	NO
95	ATP5G3	ATP5G3	ATP5G3	7329	-0.00087	0.1	NO
96	IFT57	IFT57	IFT57	7462	-0.003	0.096	NO
97	SLC25A6	SLC25A6	SLC25A6	7488	-0.0032	0.095	NO
98	UQCRFS1	UQCRFS1	UQCRFS1	7506	-0.0035	0.094	NO
99	NDUFA2	NDUFA2	NDUFA2	7572	-0.0043	0.091	NO
100	NDUFA4	NDUFA4	NDUFA4	7705	-0.0065	0.084	NO
101	NDUFA8	NDUFA8	NDUFA8	7786	-0.0078	0.081	NO
102	UQCRC2	UQCRC2	UQCRC2	7817	-0.0081	0.08	NO
103	POLR2E	POLR2E	POLR2E	7824	-0.0082	0.08	NO
104	ATP5E	ATP5E	ATP5E	7883	-0.0088	0.078	NO
105	NDUFAB1	NDUFAB1	NDUFAB1	7892	-0.009	0.078	NO
106	NDUFS8	NDUFS8	NDUFS8	8028	-0.011	0.072	NO
107	CASP3	CASP3	CASP3	8081	-0.012	0.07	NO
108	AP2M1	AP2M1	AP2M1	8151	-0.013	0.068	NO
109	POLR2J	POLR2J	POLR2J	8152	-0.013	0.069	NO
110	DCTN4	DCTN4	DCTN4	8163	-0.013	0.07	NO
111	APAF1	APAF1	APAF1	8194	-0.014	0.07	NO
112	NDUFB4	NDUFB4	NDUFB4	8198	-0.014	0.071	NO
113	AP2B1	AP2B1	AP2B1	8330	-0.015	0.065	NO
114	VDAC2	VDAC2	VDAC2	8337	-0.015	0.066	NO
115	POLR2B	POLR2B	POLR2B	8363	-0.016	0.066	NO
116	ATP5F1	ATP5F1	ATP5F1	8444	-0.017	0.064	NO
117	EP300	EP300	EP300	8547	-0.019	0.06	NO
118	COX4I1	COX4I1	COX4I1	8559	-0.019	0.061	NO
119	COX5A	COX5A	COX5A	8566	-0.019	0.063	NO
120	COX7B	COX7B	COX7B	8634	-0.02	0.061	NO
121	COX6C	COX6C	COX6C	8698	-0.021	0.06	NO
122	SDHD	SDHD	SDHD	8729	-0.021	0.06	NO
123	NDUFS1	NDUFS1	NDUFS1	8805	-0.022	0.058	NO
124	UQCR10	UQCR10	UQCR10	9167	-0.028	0.041	NO
125	POLR2D	POLR2D	POLR2D	9361	-0.031	0.033	NO
126	ATP5G1	ATP5G1	ATP5G1	9507	-0.033	0.029	NO
127	NDUFB5	NDUFB5	NDUFB5	9585	-0.034	0.028	NO
128	CASP8	CASP8	CASP8	9769	-0.037	0.021	NO
129	CREB1	CREB1	CREB1	9788	-0.037	0.024	NO
130	RCOR1	RCOR1	RCOR1	9839	-0.038	0.025	NO
131	CASP9	CASP9	CASP9	9910	-0.039	0.025	NO
132	COX7A2	COX7A2	COX7A2	9914	-0.039	0.029	NO
133	CLTC	CLTC	CLTC	9962	-0.04	0.03	NO
134	HDAC2	HDAC2	HDAC2	10018	-0.041	0.031	NO
135	SLC25A5	SLC25A5	SLC25A5	10127	-0.042	0.03	NO
136	SOD1	SOD1	SOD1	10141	-0.042	0.033	NO
137	PLCB1	PLCB1	PLCB1	10147	-0.042	0.037	NO
138	AP2A1	AP2A1	AP2A1	10365	-0.046	0.03	NO
139	HTT	HTT	HTT	10412	-0.047	0.032	NO
140	GPX1	GPX1	GPX1	10429	-0.047	0.036	NO
141	DNAH1	DNAH1	DNAH1	10499	-0.048	0.037	NO
142	COX4I2	COX4I2	COX4I2	10721	-0.052	0.03	NO
143	POLR2C	POLR2C	POLR2C	10763	-0.053	0.033	NO
144	NDUFA5	NDUFA5	NDUFA5	10790	-0.054	0.037	NO
145	TBPL1	TBPL1	TBPL1	11096	-0.06	0.026	NO
146	DLG4	DLG4	DLG4	11256	-0.063	0.024	NO
147	TFAM	TFAM	TFAM	11381	-0.066	0.024	NO
148	DNAI2	DNAI2	DNAI2	11537	-0.07	0.022	NO
149	SDHB	SDHB	SDHB	11859	-0.077	0.012	NO
150	CYCS	CYCS	CYCS	12000	-0.081	0.012	NO
151	SOD2	SOD2	SOD2	12184	-0.085	0.011	NO
152	GNAQ	GNAQ	GNAQ	12350	-0.09	0.011	NO
153	DNAH3	DNAH3	DNAH3	12479	-0.093	0.013	NO
154	COX6A2	COX6A2	COX6A2	12676	-0.1	0.012	NO
155	ITPR1	ITPR1	ITPR1	12688	-0.1	0.022	NO
156	TBP	TBP	TBP	12766	-0.1	0.028	NO
157	CREB3L2	CREB3L2	CREB3L2	13321	-0.12	0.0094	NO
158	PPARG	PPARG	PPARG	13746	-0.14	-0.000025	NO
159	REST	REST	REST	14469	-0.18	-0.022	NO
160	TGM2	TGM2	TGM2	14583	-0.18	-0.0097	NO
161	PLCB4	PLCB4	PLCB4	14848	-0.2	-0.004	NO
162	BDNF	BDNF	BDNF	15966	-0.29	-0.037	NO
163	CREB3L3	CREB3L3	CREB3L3	16062	-0.3	-0.012	NO
164	CREB3L1	CREB3L1	CREB3L1	16471	-0.34	-0.00054	NO
165	PLCB2	PLCB2	PLCB2	17139	-0.45	0.0077	NO
166	TAF4B	TAF4B	TAF4B	17198	-0.46	0.051	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 RNA POLYMERASE.

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

genes ES table in pathway: KEGG SPLICEOSOME

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	ATP12A	ATP12A	ATP12A	132	0.36	0.062	YES
2	ATP5C1	ATP5C1	ATP5C1	1640	0.13	0.0042	YES
3	NDUFC1	NDUFC1	NDUFC1	1680	0.13	0.027	YES
4	NDUFS4	NDUFS4	NDUFS4	1708	0.13	0.051	YES
5	ATP6V0E2	ATP6V0E2	ATP6V0E2	2017	0.11	0.055	YES
6	NDUFS2	NDUFS2	NDUFS2	2181	0.11	0.067	YES
7	COX6B2	COX6B2	COX6B2	2195	0.11	0.087	YES
8	COX10	COX10	COX10	2226	0.1	0.1	YES
9	ATP5G2	ATP5G2	ATP5G2	2352	0.1	0.12	YES
10	NDUFA4L2	NDUFA4L2	NDUFA4L2	2932	0.081	0.1	YES
11	ATP5D	ATP5D	ATP5D	3068	0.077	0.11	YES
12	NDUFS3	NDUFS3	NDUFS3	3255	0.072	0.11	YES
13	PPA2	PPA2	PPA2	3274	0.071	0.12	YES
14	SDHC	SDHC	SDHC	3327	0.07	0.14	YES
15	ATP5A1	ATP5A1	ATP5A1	3381	0.068	0.14	YES
16	NDUFS5	NDUFS5	NDUFS5	3658	0.062	0.14	YES
17	ATP6V0A1	ATP6V0A1	ATP6V0A1	3768	0.059	0.15	YES
18	NDUFC2	NDUFC2	NDUFC2	3802	0.058	0.16	YES
19	ATP5O	ATP5O	ATP5O	3820	0.058	0.17	YES
20	ATP6V1E2	ATP6V1E2	ATP6V1E2	3874	0.056	0.18	YES
21	NDUFA7	NDUFA7	NDUFA7	4018	0.053	0.18	YES
22	NDUFB7	NDUFB7	NDUFB7	4069	0.052	0.18	YES
23	COX7A1	COX7A1	COX7A1	4204	0.049	0.19	YES
24	ATP6AP1	ATP6AP1	ATP6AP1	4266	0.048	0.19	YES
25	ATP5J	ATP5J	ATP5J	4447	0.044	0.19	YES
26	NDUFS6	NDUFS6	NDUFS6	4468	0.044	0.2	YES
27	NDUFA11	NDUFA11	NDUFA11	4779	0.038	0.19	YES
28	NDUFV2	NDUFV2	NDUFV2	4795	0.038	0.2	YES
29	NDUFA3	NDUFA3	NDUFA3	4818	0.038	0.2	YES
30	COX7C	COX7C	COX7C	4846	0.037	0.21	YES
31	NDUFB1	NDUFB1	NDUFB1	4993	0.034	0.2	YES
32	UQCRB	UQCRB	UQCRB	5095	0.033	0.21	YES
33	NDUFB2	NDUFB2	NDUFB2	5132	0.032	0.21	YES
34	NDUFA9	NDUFA9	NDUFA9	5141	0.032	0.22	YES
35	NDUFV3	NDUFV3	NDUFV3	5204	0.031	0.22	YES
36	NDUFB9	NDUFB9	NDUFB9	5290	0.029	0.22	YES
37	NDUFA6	NDUFA6	NDUFA6	5328	0.029	0.22	YES
38	UQCRQ	UQCRQ	UQCRQ	5384	0.028	0.22	YES
39	NDUFS7	NDUFS7	NDUFS7	5432	0.027	0.23	YES
40	COX6A1	COX6A1	COX6A1	5453	0.026	0.23	YES
41	ATP6V1E1	ATP6V1E1	ATP6V1E1	5482	0.026	0.24	YES
42	ATP6V1H	ATP6V1H	ATP6V1H	5570	0.024	0.24	NO
43	COX8A	COX8A	COX8A	5743	0.022	0.23	NO
44	ATP6V1C2	ATP6V1C2	ATP6V1C2	5807	0.021	0.23	NO
45	NDUFB6	NDUFB6	NDUFB6	5922	0.019	0.23	NO
46	ATP6V0C	ATP6V0C	ATP6V0C	5942	0.019	0.23	NO
47	ATP5I	ATP5I	ATP5I	5988	0.018	0.23	NO
48	UQCR11	UQCR11	UQCR11	6005	0.018	0.23	NO
49	NDUFB3	NDUFB3	NDUFB3	6116	0.016	0.23	NO
50	COX6B1	COX6B1	COX6B1	6290	0.014	0.22	NO
51	ATP5B	ATP5B	ATP5B	6328	0.013	0.22	NO
52	NDUFA1	NDUFA1	NDUFA1	6347	0.013	0.23	NO
53	NDUFA10	NDUFA10	NDUFA10	6475	0.011	0.22	NO
54	ATP5L	ATP5L	ATP5L	6513	0.01	0.22	NO
55	UQCRHL	UQCRHL	UQCRHL	6520	0.01	0.22	NO
56	UQCRH	UQCRH	UQCRH	6608	0.0092	0.22	NO
57	NDUFV1	NDUFV1	NDUFV1	6632	0.0088	0.22	NO
58	ATP6V0E1	ATP6V0E1	ATP6V0E1	6642	0.0087	0.22	NO
59	ATP6V1C1	ATP6V1C1	ATP6V1C1	6750	0.0073	0.22	NO
60	ATP6V1B1	ATP6V1B1	ATP6V1B1	6780	0.0069	0.22	NO
61	NDUFB10	NDUFB10	NDUFB10	6795	0.0067	0.22	NO
62	COX7A2L	COX7A2L	COX7A2L	6801	0.0066	0.22	NO
63	CYC1	CYC1	CYC1	6834	0.0062	0.22	NO
64	ATP6V0B	ATP6V0B	ATP6V0B	6890	0.0052	0.22	NO
65	UQCRC1	UQCRC1	UQCRC1	6960	0.0042	0.21	NO
66	SDHA	SDHA	SDHA	7091	0.0024	0.2	NO
67	COX11	COX11	COX11	7185	0.001	0.2	NO
68	NDUFB8	NDUFB8	NDUFB8	7216	0.00056	0.2	NO
69	ATP5H	ATP5H	ATP5H	7229	0.00042	0.2	NO
70	COX5B	COX5B	COX5B	7273	-0.00016	0.2	NO
71	ATP5G3	ATP5G3	ATP5G3	7329	-0.00087	0.19	NO
72	UQCRFS1	UQCRFS1	UQCRFS1	7506	-0.0035	0.18	NO
73	NDUFA2	NDUFA2	NDUFA2	7572	-0.0043	0.18	NO
74	ATP6V1D	ATP6V1D	ATP6V1D	7692	-0.0063	0.18	NO
75	ATP6V1B2	ATP6V1B2	ATP6V1B2	7695	-0.0064	0.18	NO
76	NDUFA4	NDUFA4	NDUFA4	7705	-0.0065	0.18	NO
77	NDUFA8	NDUFA8	NDUFA8	7786	-0.0078	0.18	NO
78	UQCRC2	UQCRC2	UQCRC2	7817	-0.0081	0.18	NO
79	ATP5E	ATP5E	ATP5E	7883	-0.0088	0.17	NO
80	PPA1	PPA1	PPA1	7885	-0.0089	0.17	NO
81	NDUFAB1	NDUFAB1	NDUFAB1	7892	-0.009	0.18	NO
82	NDUFS8	NDUFS8	NDUFS8	8028	-0.011	0.17	NO
83	NDUFB4	NDUFB4	NDUFB4	8198	-0.014	0.16	NO
84	ATP5F1	ATP5F1	ATP5F1	8444	-0.017	0.15	NO
85	COX4I1	COX4I1	COX4I1	8559	-0.019	0.15	NO
86	COX5A	COX5A	COX5A	8566	-0.019	0.15	NO
87	COX7B	COX7B	COX7B	8634	-0.02	0.15	NO
88	COX6C	COX6C	COX6C	8698	-0.021	0.16	NO
89	SDHD	SDHD	SDHD	8729	-0.021	0.16	NO
90	NDUFS1	NDUFS1	NDUFS1	8805	-0.022	0.16	NO
91	UQCR10	UQCR10	UQCR10	9167	-0.028	0.14	NO
92	ATP6V1G2	ATP6V1G2	ATP6V1G2	9329	-0.03	0.14	NO
93	COX15	COX15	COX15	9382	-0.031	0.14	NO
94	ATP6V1G1	ATP6V1G1	ATP6V1G1	9432	-0.032	0.15	NO
95	ATP5G1	ATP5G1	ATP5G1	9507	-0.033	0.15	NO
96	NDUFB5	NDUFB5	NDUFB5	9585	-0.034	0.15	NO
97	ATP6V1F	ATP6V1F	ATP6V1F	9846	-0.038	0.14	NO
98	COX7A2	COX7A2	COX7A2	9914	-0.039	0.15	NO
99	ATP6V0A2	ATP6V0A2	ATP6V0A2	10083	-0.042	0.15	NO
100	COX4I2	COX4I2	COX4I2	10721	-0.052	0.12	NO
101	NDUFA5	NDUFA5	NDUFA5	10790	-0.054	0.13	NO
102	COX17	COX17	COX17	10908	-0.056	0.13	NO
103	ATP6V0D1	ATP6V0D1	ATP6V0D1	11114	-0.06	0.13	NO
104	ATP5J2	ATP5J2	ATP5J2	11204	-0.062	0.14	NO
105	TCIRG1	TCIRG1	TCIRG1	11563	-0.07	0.13	NO
106	SDHB	SDHB	SDHB	11859	-0.077	0.13	NO
107	COX6A2	COX6A2	COX6A2	12676	-0.1	0.1	NO
108	ATP6V1A	ATP6V1A	ATP6V1A	12937	-0.11	0.11	NO
109	LHPP	LHPP	LHPP	14243	-0.16	0.071	NO
110	ATP6V0A4	ATP6V0A4	ATP6V0A4	16248	-0.32	0.021	NO
111	ATP6V0D2	ATP6V0D2	ATP6V0D2	17056	-0.43	0.059	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 SPLICEOSOME.

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

genes ES table in pathway: KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT

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	CREB5	CREB5	CREB5	481	0.25	0.039	YES
2	AQP4	AQP4	AQP4	534	0.24	0.099	YES
3	AQP3	AQP3	AQP3	1137	0.17	0.11	YES
4	DCTN6	DCTN6	DCTN6	1266	0.16	0.14	YES
5	ADCY6	ADCY6	ADCY6	1391	0.15	0.18	YES
6	CREB3L4	CREB3L4	CREB3L4	1804	0.12	0.18	YES
7	PRKX	PRKX	PRKX	3083	0.076	0.13	NO
8	DYNC2LI1	DYNC2LI1	DYNC2LI1	3215	0.072	0.14	NO
9	CREB3	CREB3	CREB3	3225	0.072	0.16	NO
10	VAMP2	VAMP2	VAMP2	3556	0.064	0.16	NO
11	ADCY9	ADCY9	ADCY9	3584	0.063	0.18	NO
12	RAB11B	RAB11B	RAB11B	3807	0.058	0.18	NO
13	RAB11A	RAB11A	RAB11A	4109	0.051	0.18	NO
14	DYNC1I2	DYNC1I2	DYNC1I2	4635	0.041	0.16	NO
15	PRKACA	PRKACA	PRKACA	4657	0.04	0.17	NO
16	RAB5B	RAB5B	RAB5B	4697	0.04	0.17	NO
17	DCTN2	DCTN2	DCTN2	5036	0.034	0.16	NO
18	DCTN1	DCTN1	DCTN1	5049	0.034	0.17	NO
19	STX4	STX4	STX4	5124	0.032	0.18	NO
20	DCTN5	DCTN5	DCTN5	5130	0.032	0.18	NO
21	DYNC1H1	DYNC1H1	DYNC1H1	5606	0.024	0.16	NO
22	DYNLL1	DYNLL1	DYNLL1	5826	0.021	0.16	NO
23	ARHGDIA	ARHGDIA	ARHGDIA	7946	-0.0097	0.043	NO
24	DCTN4	DCTN4	DCTN4	8163	-0.013	0.034	NO
25	DYNC1LI2	DYNC1LI2	DYNC1LI2	9003	-0.025	-0.0057	NO
26	RAB5C	RAB5C	RAB5C	9034	-0.026	-0.00073	NO
27	DYNC2H1	DYNC2H1	DYNC2H1	9451	-0.032	-0.016	NO
28	NSF	NSF	NSF	9782	-0.037	-0.024	NO
29	CREB1	CREB1	CREB1	9788	-0.037	-0.015	NO
30	DYNC1LI1	DYNC1LI1	DYNC1LI1	9957	-0.04	-0.014	NO
31	AVPR2	AVPR2	AVPR2	11387	-0.066	-0.076	NO
32	RAB5A	RAB5A	RAB5A	11758	-0.075	-0.077	NO
33	DYNLL2	DYNLL2	DYNLL2	12651	-0.099	-0.1	NO
34	GNAS	GNAS	GNAS	12907	-0.11	-0.088	NO
35	DYNC1I1	DYNC1I1	DYNC1I1	13093	-0.11	-0.069	NO
36	CREB3L2	CREB3L2	CREB3L2	13321	-0.12	-0.05	NO
37	AQP2	AQP2	AQP2	14254	-0.16	-0.059	NO
38	PRKACB	PRKACB	PRKACB	14771	-0.2	-0.037	NO
39	ARHGDIB	ARHGDIB	ARHGDIB	15233	-0.23	-0.0044	NO
40	CREB3L3	CREB3L3	CREB3L3	16062	-0.3	0.026	NO
41	CREB3L1	CREB3L1	CREB3L1	16471	-0.34	0.091	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 SNARE INTERACTIONS IN VESICULAR TRANSPORT.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG SNARE INTERACTIONS IN VESICULAR 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: KEGG NOTCH SIGNALING PATHWAY

Table S17. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	POLR3B	POLR3B	POLR3B	2408	0.098	-0.059	YES
2	POLR2J3	POLR2J3	POLR2J3	3028	0.078	-0.035	YES
3	POLR3C	POLR3C	POLR3C	3385	0.068	-0.0026	YES
4	POLR2I	POLR2I	POLR2I	3589	0.063	0.034	YES
5	POLR2A	POLR2A	POLR2A	3744	0.059	0.07	YES
6	POLR3F	POLR3F	POLR3F	3924	0.056	0.1	YES
7	ZNRD1	ZNRD1	ZNRD1	4042	0.053	0.14	YES
8	POLR2J2	POLR2J2	POLR2J2	4134	0.051	0.17	YES
9	POLR3D	POLR3D	POLR3D	5100	0.033	0.14	NO
10	POLR2F	POLR2F	POLR2F	5285	0.029	0.15	NO
11	POLR2G	POLR2G	POLR2G	5738	0.022	0.14	NO
12	POLR1C	POLR1C	POLR1C	5797	0.021	0.16	NO
13	POLR2K	POLR2K	POLR2K	6077	0.017	0.15	NO
14	POLR2L	POLR2L	POLR2L	6410	0.012	0.14	NO
15	POLR1D	POLR1D	POLR1D	6648	0.0086	0.14	NO
16	POLR1E	POLR1E	POLR1E	6706	0.0079	0.14	NO
17	POLR2E	POLR2E	POLR2E	7824	-0.0082	0.086	NO
18	POLR2J	POLR2J	POLR2J	8152	-0.013	0.078	NO
19	POLR2B	POLR2B	POLR2B	8363	-0.016	0.078	NO
20	POLR3H	POLR3H	POLR3H	8782	-0.022	0.071	NO
21	POLR3GL	POLR3GL	POLR3GL	9343	-0.031	0.064	NO
22	POLR1B	POLR1B	POLR1B	9355	-0.031	0.086	NO
23	POLR2D	POLR2D	POLR2D	9361	-0.031	0.11	NO
24	POLR3A	POLR3A	POLR3A	10408	-0.047	0.087	NO
25	POLR2C	POLR2C	POLR2C	10763	-0.053	0.11	NO
26	POLR1A	POLR1A	POLR1A	11022	-0.058	0.14	NO
27	POLR3K	POLR3K	POLR3K	12094	-0.083	0.14	NO
28	POLR3G	POLR3G	POLR3G	15594	-0.25	0.14	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 NOTCH SIGNALING PATHWAY.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG NOTCH 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 VASOPRESSIN REGULATED WATER REABSORPTION

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	DTX3	DTX3	DTX3	200	0.33	0.086	YES
2	HES1	HES1	HES1	1395	0.15	0.065	YES
3	JAG1	JAG1	JAG1	1660	0.13	0.089	YES
4	DLL3	DLL3	DLL3	2002	0.11	0.1	YES
5	PSEN2	PSEN2	PSEN2	2490	0.095	0.1	YES
6	MAML3	MAML3	MAML3	2638	0.09	0.12	YES
7	NCSTN	NCSTN	NCSTN	2852	0.083	0.14	YES
8	CTBP2	CTBP2	CTBP2	2989	0.079	0.15	YES
9	APH1A	APH1A	APH1A	3370	0.069	0.15	NO
10	PSENEN	PSENEN	PSENEN	4154	0.05	0.12	NO
11	NCOR2	NCOR2	NCOR2	4948	0.035	0.09	NO
12	KAT2A	KAT2A	KAT2A	5311	0.029	0.079	NO
13	CTBP1	CTBP1	CTBP1	5330	0.029	0.086	NO
14	DVL2	DVL2	DVL2	5347	0.028	0.094	NO
15	NOTCH3	NOTCH3	NOTCH3	6025	0.018	0.061	NO
16	HDAC1	HDAC1	HDAC1	6382	0.013	0.045	NO
17	CREBBP	CREBBP	CREBBP	6681	0.0082	0.031	NO
18	DLL4	DLL4	DLL4	6690	0.0081	0.033	NO
19	JAG2	JAG2	JAG2	6692	0.0081	0.036	NO
20	HES5	HES5	HES5	6868	0.0056	0.028	NO
21	NOTCH2	NOTCH2	NOTCH2	7105	0.0022	0.015	NO
22	CIR1	CIR1	CIR1	7226	0.00043	0.0086	NO
23	RBPJ	RBPJ	RBPJ	7660	-0.0058	-0.014	NO
24	RFNG	RFNG	RFNG	7721	-0.0068	-0.015	NO
25	PSEN1	PSEN1	PSEN1	7756	-0.0073	-0.015	NO
26	DTX1	DTX1	DTX1	7788	-0.0078	-0.014	NO
27	SNW1	SNW1	SNW1	8164	-0.013	-0.031	NO
28	EP300	EP300	EP300	8547	-0.019	-0.047	NO
29	NOTCH4	NOTCH4	NOTCH4	8655	-0.02	-0.046	NO
30	MAML1	MAML1	MAML1	8733	-0.021	-0.044	NO
31	HDAC2	HDAC2	HDAC2	10018	-0.041	-0.1	NO
32	DVL3	DVL3	DVL3	10803	-0.054	-0.13	NO
33	MAML2	MAML2	MAML2	10919	-0.056	-0.12	NO
34	NOTCH1	NOTCH1	NOTCH1	10922	-0.056	-0.1	NO
35	NUMB	NUMB	NUMB	10957	-0.057	-0.089	NO
36	DTX4	DTX4	DTX4	11125	-0.061	-0.08	NO
37	NUMBL	NUMBL	NUMBL	11499	-0.069	-0.081	NO
38	DVL1	DVL1	DVL1	11501	-0.069	-0.06	NO
39	RBPJL	RBPJL	RBPJL	11753	-0.075	-0.052	NO
40	DTX3L	DTX3L	DTX3L	12202	-0.086	-0.051	NO
41	DTX2	DTX2	DTX2	12605	-0.098	-0.045	NO
42	KAT2B	KAT2B	KAT2B	13429	-0.13	-0.053	NO
43	ADAM17	ADAM17	ADAM17	14444	-0.18	-0.056	NO
44	LFNG	LFNG	LFNG	15039	-0.21	-0.026	NO
45	DLL1	DLL1	DLL1	15964	-0.29	0.0075	NO
46	PTCRA	PTCRA	PTCRA	16754	-0.38	0.075	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 VASOPRESSIN REGULATED WATER REABSORPTION.

Figure S36. 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: KEGG HUNTINGTONS DISEASE

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	SNAP25	SNAP25	SNAP25	421	0.27	0.082	YES
2	STX3	STX3	STX3	2197	0.11	0.025	YES
3	STX8	STX8	STX8	2630	0.09	0.037	YES
4	STX18	STX18	STX18	2635	0.09	0.072	YES
5	STX1B	STX1B	STX1B	3455	0.067	0.052	YES
6	USE1	USE1	USE1	3519	0.065	0.074	YES
7	VAMP2	VAMP2	VAMP2	3556	0.064	0.097	YES
8	STX19	STX19	STX19	3940	0.055	0.098	YES
9	VAMP4	VAMP4	VAMP4	4286	0.048	0.097	YES
10	VAMP8	VAMP8	VAMP8	4378	0.046	0.11	YES
11	SNAP47	SNAP47	SNAP47	4881	0.036	0.097	YES
12	STX10	STX10	STX10	4882	0.036	0.11	YES
13	BNIP1	BNIP1	BNIP1	4901	0.036	0.12	YES
14	STX4	STX4	STX4	5124	0.032	0.12	YES
15	STX6	STX6	STX6	5200	0.031	0.13	YES
16	TSNARE1	TSNARE1	TSNARE1	6902	0.005	0.04	NO
17	STX5	STX5	STX5	7037	0.0031	0.034	NO
18	STX1A	STX1A	STX1A	7295	-0.00042	0.02	NO
19	STX16	STX16	STX16	8859	-0.023	-0.057	NO
20	STX17	STX17	STX17	8872	-0.023	-0.049	NO
21	BET1L	BET1L	BET1L	8920	-0.024	-0.042	NO
22	SEC22B	SEC22B	SEC22B	9356	-0.031	-0.054	NO
23	VTI1B	VTI1B	VTI1B	9399	-0.031	-0.044	NO
24	VAMP7	VAMP7	VAMP7	9785	-0.037	-0.051	NO
25	VAMP5	VAMP5	VAMP5	9805	-0.037	-0.037	NO
26	STX2	STX2	STX2	10028	-0.041	-0.034	NO
27	SNAP23	SNAP23	SNAP23	10159	-0.043	-0.024	NO
28	VTI1A	VTI1A	VTI1A	10438	-0.047	-0.021	NO
29	GOSR1	GOSR1	GOSR1	10475	-0.048	-0.0044	NO
30	GOSR2	GOSR2	GOSR2	10652	-0.051	0.0058	NO
31	YKT6	YKT6	YKT6	10720	-0.052	0.023	NO
32	STX7	STX7	STX7	10983	-0.058	0.031	NO
33	STX12	STX12	STX12	11724	-0.074	0.019	NO
34	VAMP3	VAMP3	VAMP3	13036	-0.11	-0.01	NO
35	VAMP1	VAMP1	VAMP1	14101	-0.16	-0.0077	NO
36	BET1	BET1	BET1	14271	-0.17	0.048	NO
37	STX11	STX11	STX11	17012	-0.42	0.061	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 HUNTINGTONS DISEASE.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.38	1.5	0.081	0.18	0.88	0.16	0.15	0.13	0.13	0.004
BIOCARTA BIOPEPTIDES PATHWAY	39	genes.ES.table	0.57	2	0	0.0094	0.076	0.23	0.17	0.19	0	0
BIOCARTA PPARA PATHWAY	54	genes.ES.table	0.62	2.1	0	0.0043	0.015	0.32	0.19	0.26	0	0
BIOCARTA CHREBP2 PATHWAY	40	genes.ES.table	0.38	1.4	0.094	0.24	0.94	0.22	0.18	0.18	0.18	0.012
KEGG GLYCOLYSIS GLUCONEOGENESIS	57	genes.ES.table	0.7	2.1	0	0.0053	0.011	0.3	0.094	0.27	0	0
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.6	1.6	0.12	0.12	0.77	0.48	0.28	0.35	0.073	0.002
KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS	26	genes.ES.table	0.79	1.5	0.04	0.14	0.81	0.54	0.061	0.51	0.089	0.001
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.69	2.1	0	0.0044	0.011	0.16	0.034	0.15	0	0
KEGG FATTY ACID METABOLISM	40	genes.ES.table	0.8	1.9	0	0.01	0.086	0.6	0.14	0.52	0	0
KEGG STEROID HORMONE BIOSYNTHESIS	50	genes.ES.table	0.8	1.8	0	0.03	0.35	0.48	0.061	0.45	0	0

genes ES table in pathway: BIOCARTA AT1R PATHWAY

Table S20. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TAT	TAT	TAT	27	1.9	0.17	YES
2	BHMT	BHMT	BHMT	60	1.7	0.32	YES
3	CDO1	CDO1	CDO1	67	1.6	0.46	YES
4	DNMT3L	DNMT3L	DNMT3L	131	1.2	0.57	YES
5	MAT1A	MAT1A	MAT1A	190	1	0.65	YES
6	SDS	SDS	SDS	284	0.73	0.71	YES
7	CTH	CTH	CTH	318	0.67	0.77	YES
8	CBS	CBS	CBS	739	0.34	0.78	YES
9	LDHAL6B	LDHAL6B	LDHAL6B	795	0.33	0.8	YES
10	GOT1	GOT1	GOT1	1532	0.2	0.78	NO
11	GOT2	GOT2	GOT2	1968	0.16	0.77	NO
12	LDHAL6A	LDHAL6A	LDHAL6A	2287	0.14	0.77	NO
13	MPST	MPST	MPST	3093	0.1	0.73	NO
14	ADI1	ADI1	ADI1	3269	0.098	0.73	NO
15	AHCY	AHCY	AHCY	4629	0.062	0.66	NO
16	MAT2A	MAT2A	MAT2A	5257	0.049	0.63	NO
17	MTAP	MTAP	MTAP	5801	0.038	0.6	NO
18	AHCYL1	AHCYL1	AHCYL1	5893	0.037	0.6	NO
19	MTR	MTR	MTR	7532	0.015	0.51	NO
20	MAT2B	MAT2B	MAT2B	7683	0.013	0.51	NO
21	DNMT1	DNMT1	DNMT1	8359	0.005	0.47	NO
22	AHCYL2	AHCYL2	AHCYL2	8476	0.0037	0.46	NO
23	SRM	SRM	SRM	8631	0.0018	0.46	NO
24	LDHA	LDHA	LDHA	9002	-0.0022	0.44	NO
25	AMD1	AMD1	AMD1	9570	-0.0085	0.4	NO
26	SMS	SMS	SMS	11054	-0.026	0.32	NO
27	LDHB	LDHB	LDHB	13454	-0.062	0.2	NO
28	ENOPH1	ENOPH1	ENOPH1	13723	-0.067	0.19	NO
29	DNMT3B	DNMT3B	DNMT3B	14566	-0.086	0.15	NO
30	APIP	APIP	APIP	14703	-0.089	0.15	NO
31	TRDMT1	TRDMT1	TRDMT1	14721	-0.09	0.16	NO
32	DNMT3A	DNMT3A	DNMT3A	14886	-0.094	0.16	NO
33	IL4I1	IL4I1	IL4I1	17380	-0.25	0.04	NO

Figure S39. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA AT1R PATHWAY.

Figure S40. 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 BIOPEPTIDES 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	DPYS	DPYS	DPYS	44	1.8	0.17	YES
2	UPB1	UPB1	UPB1	72	1.6	0.32	YES
3	UPP2	UPP2	UPP2	270	0.78	0.38	YES
4	DPYD	DPYD	DPYD	844	0.32	0.38	YES
5	DHODH	DHODH	DHODH	866	0.31	0.41	YES
6	POLR3G	POLR3G	POLR3G	900	0.3	0.44	YES
7	CDA	CDA	CDA	918	0.3	0.46	YES
8	ENTPD5	ENTPD5	ENTPD5	968	0.29	0.49	YES
9	POLE2	POLE2	POLE2	1239	0.24	0.5	YES
10	RRM2	RRM2	RRM2	1650	0.19	0.49	NO
11	NT5C1B	NT5C1B	NT5C1B	2090	0.16	0.48	NO
12	ENTPD8	ENTPD8	ENTPD8	2433	0.14	0.48	NO
13	NT5E	NT5E	NT5E	2540	0.13	0.48	NO
14	TK1	TK1	TK1	3001	0.11	0.47	NO
15	NME1-NME2	NME1-NME2	NME1-NME2	3845	0.081	0.43	NO
16	TYMS	TYMS	TYMS	4068	0.075	0.42	NO
17	CMPK1	CMPK1	CMPK1	4399	0.067	0.41	NO
18	PNP	PNP	PNP	4901	0.055	0.39	NO
19	POLR3A	POLR3A	POLR3A	4978	0.054	0.39	NO
20	POLR2C	POLR2C	POLR2C	5361	0.047	0.37	NO
21	NME1	NME1	NME1	5373	0.046	0.38	NO
22	NT5M	NT5M	NT5M	5380	0.046	0.38	NO
23	TXNRD2	TXNRD2	TXNRD2	5436	0.045	0.38	NO
24	AK3	AK3	AK3	5598	0.042	0.38	NO
25	POLD4	POLD4	POLD4	5683	0.04	0.38	NO
26	UPRT	UPRT	UPRT	5916	0.037	0.37	NO
27	POLR2F	POLR2F	POLR2F	5941	0.036	0.37	NO
28	POLD2	POLD2	POLD2	5954	0.036	0.37	NO
29	NME4	NME4	NME4	6064	0.035	0.37	NO
30	NUDT2	NUDT2	NUDT2	6556	0.028	0.34	NO
31	POLR1B	POLR1B	POLR1B	6709	0.026	0.34	NO
32	NT5C2	NT5C2	NT5C2	6956	0.023	0.33	NO
33	CAD	CAD	CAD	7404	0.017	0.3	NO
34	PNPT1	PNPT1	PNPT1	7547	0.015	0.3	NO
35	POLE	POLE	POLE	7602	0.014	0.3	NO
36	POLR1A	POLR1A	POLR1A	7830	0.011	0.28	NO
37	NME2	NME2	NME2	7935	0.01	0.28	NO
38	POLR3H	POLR3H	POLR3H	7955	0.01	0.28	NO
39	POLR2E	POLR2E	POLR2E	8034	0.009	0.28	NO
40	TYMP	TYMP	TYMP	8112	0.0082	0.27	NO
41	POLE4	POLE4	POLE4	8495	0.0035	0.25	NO
42	POLR3B	POLR3B	POLR3B	8543	0.0029	0.25	NO
43	CANT1	CANT1	CANT1	8554	0.0028	0.25	NO
44	UPP1	UPP1	UPP1	8705	0.0011	0.24	NO
45	RRM2B	RRM2B	RRM2B	8994	-0.0021	0.22	NO
46	POLR2G	POLR2G	POLR2G	9127	-0.0035	0.22	NO
47	TK2	TK2	TK2	9179	-0.0042	0.22	NO
48	POLR2D	POLR2D	POLR2D	9584	-0.0087	0.19	NO
49	POLR1E	POLR1E	POLR1E	9690	-0.01	0.19	NO
50	POLD1	POLD1	POLD1	9777	-0.011	0.18	NO
51	POLE3	POLE3	POLE3	9811	-0.011	0.18	NO
52	UCK1	UCK1	UCK1	10073	-0.014	0.17	NO
53	UMPS	UMPS	UMPS	10236	-0.016	0.16	NO
54	POLR2J	POLR2J	POLR2J	10264	-0.017	0.16	NO
55	POLR3GL	POLR3GL	POLR3GL	10516	-0.02	0.15	NO
56	POLR2H	POLR2H	POLR2H	10531	-0.02	0.15	NO
57	POLR3F	POLR3F	POLR3F	10582	-0.02	0.15	NO
58	DTYMK	DTYMK	DTYMK	10618	-0.021	0.15	NO
59	POLR2I	POLR2I	POLR2I	10880	-0.024	0.14	NO
60	POLR2K	POLR2K	POLR2K	11010	-0.026	0.14	NO
61	NME5	NME5	NME5	11013	-0.026	0.14	NO
62	TXNRD1	TXNRD1	TXNRD1	11066	-0.026	0.14	NO
63	ENTPD6	ENTPD6	ENTPD6	11513	-0.032	0.12	NO
64	RRM1	RRM1	RRM1	11628	-0.034	0.11	NO
65	CMPK2	CMPK2	CMPK2	11748	-0.036	0.11	NO
66	POLR3K	POLR3K	POLR3K	12141	-0.041	0.092	NO
67	POLD3	POLD3	POLD3	12143	-0.041	0.096	NO
68	POLA2	POLA2	POLA2	12452	-0.046	0.083	NO
69	NT5C3	NT5C3	NT5C3	12592	-0.048	0.08	NO
70	ENTPD3	ENTPD3	ENTPD3	12887	-0.053	0.068	NO
71	PRIM1	PRIM1	PRIM1	13176	-0.057	0.058	NO
72	POLR2A	POLR2A	POLR2A	13308	-0.059	0.056	NO
73	NME6	NME6	NME6	13412	-0.061	0.056	NO
74	POLR3C	POLR3C	POLR3C	13655	-0.065	0.049	NO
75	DUT	DUT	DUT	13700	-0.066	0.053	NO
76	POLR2J3	POLR2J3	POLR2J3	13780	-0.068	0.055	NO
77	POLR2L	POLR2L	POLR2L	14034	-0.073	0.048	NO
78	ENTPD1	ENTPD1	ENTPD1	14134	-0.075	0.05	NO
79	ITPA	ITPA	ITPA	14266	-0.078	0.05	NO
80	POLR2B	POLR2B	POLR2B	14339	-0.08	0.054	NO
81	ENTPD4	ENTPD4	ENTPD4	14385	-0.081	0.059	NO
82	DCTD	DCTD	DCTD	14520	-0.084	0.06	NO
83	PRIM2	PRIM2	PRIM2	14579	-0.086	0.065	NO
84	POLA1	POLA1	POLA1	14582	-0.086	0.073	NO
85	POLR1C	POLR1C	POLR1C	14605	-0.087	0.08	NO
86	CTPS2	CTPS2	CTPS2	14695	-0.089	0.084	NO
87	NT5C	NT5C	NT5C	14741	-0.09	0.09	NO
88	NME3	NME3	NME3	14925	-0.096	0.089	NO
89	UCK2	UCK2	UCK2	15022	-0.098	0.093	NO
90	NME7	NME7	NME7	15079	-0.1	0.1	NO
91	POLR1D	POLR1D	POLR1D	15115	-0.1	0.11	NO
92	POLR3D	POLR3D	POLR3D	15209	-0.1	0.11	NO
93	ZNRD1	ZNRD1	ZNRD1	15264	-0.11	0.12	NO
94	DCK	DCK	DCK	15419	-0.11	0.12	NO
95	UCKL1	UCKL1	UCKL1	15746	-0.12	0.12	NO
96	POLR2J2	POLR2J2	POLR2J2	16583	-0.17	0.085	NO

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

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

genes ES table in pathway: BIOCARTA PPARA PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CYP8B1	CYP8B1	CYP8B1	28	1.9	0.074	YES
2	APOA5	APOA5	APOA5	29	1.9	0.15	YES
3	CYP4A22	CYP4A22	CYP4A22	31	1.9	0.22	YES
4	APOC3	APOC3	APOC3	61	1.7	0.29	YES
5	APOA1	APOA1	APOA1	83	1.5	0.34	YES
6	FABP1	FABP1	FABP1	121	1.3	0.39	YES
7	PCK1	PCK1	PCK1	140	1.2	0.44	YES
8	CYP7A1	CYP7A1	CYP7A1	144	1.2	0.48	YES
9	APOA2	APOA2	APOA2	155	1.1	0.53	YES
10	SLC27A5	SLC27A5	SLC27A5	156	1.1	0.57	YES
11	HMGCS2	HMGCS2	HMGCS2	175	1	0.61	YES
12	CYP4A11	CYP4A11	CYP4A11	239	0.83	0.64	YES
13	PLIN1	PLIN1	PLIN1	242	0.83	0.67	YES
14	ACADL	ACADL	ACADL	288	0.72	0.7	YES
15	EHHADH	EHHADH	EHHADH	333	0.65	0.72	YES
16	ACSL1	ACSL1	ACSL1	473	0.49	0.73	YES
17	SLC27A2	SLC27A2	SLC27A2	507	0.46	0.75	YES
18	CYP27A1	CYP27A1	CYP27A1	581	0.42	0.76	YES
19	CD36	CD36	CD36	651	0.38	0.77	YES
20	PCK2	PCK2	PCK2	791	0.33	0.78	YES
21	ANGPTL4	ANGPTL4	ANGPTL4	805	0.33	0.79	YES
22	ACSL6	ACSL6	ACSL6	864	0.31	0.8	YES
23	FABP3	FABP3	FABP3	1179	0.25	0.79	YES
24	ACSL5	ACSL5	ACSL5	1246	0.24	0.8	YES
25	SCD	SCD	SCD	1387	0.22	0.8	YES
26	FABP4	FABP4	FABP4	1465	0.21	0.8	YES
27	ACAA1	ACAA1	ACAA1	1754	0.18	0.79	YES
28	SCP2	SCP2	SCP2	1818	0.18	0.79	YES
29	ACADM	ACADM	ACADM	1865	0.17	0.8	YES
30	RXRG	RXRG	RXRG	1917	0.17	0.8	YES
31	CPT2	CPT2	CPT2	1964	0.16	0.81	YES
32	PPARA	PPARA	PPARA	1990	0.16	0.81	YES
33	ACOX1	ACOX1	ACOX1	2024	0.16	0.82	YES
34	SORBS1	SORBS1	SORBS1	2470	0.13	0.8	NO
35	CPT1C	CPT1C	CPT1C	2480	0.13	0.8	NO
36	AQP7	AQP7	AQP7	3697	0.085	0.74	NO
37	ACSL3	ACSL3	ACSL3	4014	0.076	0.72	NO
38	GK	GK	GK	5111	0.052	0.66	NO
39	CPT1A	CPT1A	CPT1A	5540	0.043	0.64	NO
40	ME1	ME1	ME1	6698	0.026	0.58	NO
41	RXRA	RXRA	RXRA	7058	0.021	0.56	NO
42	FABP5	FABP5	FABP5	7106	0.021	0.56	NO
43	PDPK1	PDPK1	PDPK1	7420	0.016	0.54	NO
44	PLTP	PLTP	PLTP	7779	0.012	0.52	NO
45	ACOX3	ACOX3	ACOX3	7887	0.011	0.52	NO
46	PPARG	PPARG	PPARG	8013	0.0092	0.51	NO
47	CPT1B	CPT1B	CPT1B	8122	0.0081	0.5	NO
48	SLC27A4	SLC27A4	SLC27A4	9019	-0.0025	0.45	NO
49	PPARD	PPARD	PPARD	9334	-0.0059	0.44	NO
50	UBC	UBC	UBC	9593	-0.0088	0.42	NO
51	DBI	DBI	DBI	10492	-0.019	0.37	NO
52	RXRB	RXRB	RXRB	10934	-0.025	0.35	NO
53	FADS2	FADS2	FADS2	10935	-0.025	0.35	NO
54	FABP6	FABP6	FABP6	11291	-0.03	0.33	NO
55	SLC27A1	SLC27A1	SLC27A1	12327	-0.044	0.28	NO
56	ILK	ILK	ILK	12767	-0.051	0.25	NO
57	NR1H3	NR1H3	NR1H3	13296	-0.059	0.23	NO
58	ACSL4	ACSL4	ACSL4	13367	-0.06	0.23	NO
59	SCD5	SCD5	SCD5	14093	-0.074	0.19	NO
60	OLR1	OLR1	OLR1	15569	-0.12	0.11	NO
61	LPL	LPL	LPL	15982	-0.13	0.094	NO
62	MMP1	MMP1	MMP1	17642	-0.3	0.014	NO
63	SLC27A6	SLC27A6	SLC27A6	17735	-0.32	0.021	NO

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

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

genes ES table in pathway: BIOCARTA CHREBP2 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HAO1	HAO1	HAO1	5	2.3	0.13	YES
2	HAO2	HAO2	HAO2	55	1.7	0.23	YES
3	DAO	DAO	DAO	58	1.7	0.33	YES
4	AGXT	AGXT	AGXT	59	1.7	0.42	YES
5	PIPOX	PIPOX	PIPOX	158	1.1	0.48	YES
6	EHHADH	EHHADH	EHHADH	333	0.65	0.51	YES
7	ACSL1	ACSL1	ACSL1	473	0.49	0.53	YES
8	SLC27A2	SLC27A2	SLC27A2	507	0.46	0.56	YES
9	BAAT	BAAT	BAAT	568	0.42	0.58	YES
10	XDH	XDH	XDH	630	0.39	0.6	YES
11	PXMP2	PXMP2	PXMP2	717	0.35	0.62	YES
12	EPHX2	EPHX2	EPHX2	853	0.32	0.63	YES
13	ACSL6	ACSL6	ACSL6	864	0.31	0.64	YES
14	PHYH	PHYH	PHYH	1233	0.24	0.64	YES
15	ACSL5	ACSL5	ACSL5	1246	0.24	0.65	YES
16	PECR	PECR	PECR	1358	0.22	0.66	YES
17	DDO	DDO	DDO	1422	0.21	0.67	YES
18	ACAA1	ACAA1	ACAA1	1754	0.18	0.66	YES
19	HMGCL	HMGCL	HMGCL	1756	0.18	0.67	YES
20	MLYCD	MLYCD	MLYCD	1769	0.18	0.68	YES
21	CAT	CAT	CAT	1814	0.18	0.69	YES
22	SCP2	SCP2	SCP2	1818	0.18	0.7	YES
23	NUDT12	NUDT12	NUDT12	1867	0.17	0.7	YES
24	PEX11G	PEX11G	PEX11G	1953	0.16	0.71	YES
25	ACOX1	ACOX1	ACOX1	2024	0.16	0.71	YES
26	PECI	PECI	PECI	2341	0.14	0.7	YES
27	ABCD3	ABCD3	ABCD3	2410	0.14	0.71	YES
28	HSD17B4	HSD17B4	HSD17B4	2509	0.13	0.71	YES
29	MPV17L	MPV17L	MPV17L	2547	0.13	0.72	YES
30	AMACR	AMACR	AMACR	2687	0.12	0.72	YES
31	PEX3	PEX3	PEX3	2722	0.12	0.72	YES
32	PAOX	PAOX	PAOX	3189	0.1	0.7	NO
33	IDH1	IDH1	IDH1	3226	0.099	0.7	NO
34	SOD1	SOD1	SOD1	3239	0.099	0.71	NO
35	DECR2	DECR2	DECR2	3360	0.095	0.71	NO
36	DHRS4	DHRS4	DHRS4	3497	0.091	0.71	NO
37	CROT	CROT	CROT	3645	0.087	0.7	NO
38	ABCD2	ABCD2	ABCD2	3830	0.082	0.7	NO
39	ECH1	ECH1	ECH1	3860	0.08	0.7	NO
40	PEX26	PEX26	PEX26	3907	0.079	0.7	NO
41	ACSL3	ACSL3	ACSL3	4014	0.076	0.7	NO
42	FAR2	FAR2	FAR2	4025	0.076	0.7	NO
43	SLC25A17	SLC25A17	SLC25A17	4076	0.075	0.71	NO
44	PEX13	PEX13	PEX13	4095	0.074	0.71	NO
45	NUDT19	NUDT19	NUDT19	4120	0.074	0.71	NO
46	GSTK1	GSTK1	GSTK1	4273	0.07	0.71	NO
47	CRAT	CRAT	CRAT	4335	0.068	0.71	NO
48	MVK	MVK	MVK	4379	0.067	0.71	NO
49	AGPS	AGPS	AGPS	4524	0.064	0.71	NO
50	PEX1	PEX1	PEX1	4824	0.057	0.69	NO
51	PEX11A	PEX11A	PEX11A	4914	0.055	0.69	NO
52	SOD2	SOD2	SOD2	5679	0.041	0.65	NO
53	PXMP4	PXMP4	PXMP4	5841	0.038	0.64	NO
54	HACL1	HACL1	HACL1	6076	0.035	0.63	NO
55	PEX12	PEX12	PEX12	6314	0.031	0.62	NO
56	PEX10	PEX10	PEX10	6612	0.027	0.61	NO
57	PEX19	PEX19	PEX19	6846	0.024	0.6	NO
58	ABCD4	ABCD4	ABCD4	7452	0.016	0.56	NO
59	PRDX1	PRDX1	PRDX1	7805	0.012	0.55	NO
60	ACOX3	ACOX3	ACOX3	7887	0.011	0.54	NO
61	NOS2	NOS2	NOS2	7890	0.011	0.54	NO
62	PEX6	PEX6	PEX6	8172	0.0075	0.53	NO
63	GNPAT	GNPAT	GNPAT	8305	0.0058	0.52	NO
64	FAR1	FAR1	FAR1	8459	0.0039	0.51	NO
65	PMVK	PMVK	PMVK	8755	0.00058	0.5	NO
66	PEX11B	PEX11B	PEX11B	8783	0.00026	0.49	NO
67	MPV17	MPV17	MPV17	8998	-0.0022	0.48	NO
68	PEX7	PEX7	PEX7	9164	-0.004	0.47	NO
69	IDH2	IDH2	IDH2	9320	-0.0058	0.46	NO
70	PEX5	PEX5	PEX5	9356	-0.0062	0.46	NO
71	PRDX5	PRDX5	PRDX5	10705	-0.022	0.39	NO
72	ABCD1	ABCD1	ABCD1	11742	-0.035	0.33	NO
73	ACOT8	ACOT8	ACOT8	11979	-0.039	0.32	NO
74	PEX16	PEX16	PEX16	12922	-0.053	0.27	NO
75	ACSL4	ACSL4	ACSL4	13367	-0.06	0.25	NO
76	PEX14	PEX14	PEX14	14218	-0.077	0.21	NO
77	PEX2	PEX2	PEX2	14911	-0.095	0.18	NO

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

Figure S46. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA CHREBP2 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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	ADH4	ADH4	ADH4	43	1.8	0.12	YES
2	ALDOB	ALDOB	ALDOB	129	1.2	0.2	YES
3	PCK1	PCK1	PCK1	140	1.2	0.28	YES
4	ADH1A	ADH1A	ADH1A	147	1.2	0.37	YES
5	ADH1B	ADH1B	ADH1B	196	0.99	0.43	YES
6	PKLR	PKLR	PKLR	279	0.74	0.48	YES
7	G6PC	G6PC	G6PC	297	0.69	0.53	YES
8	ADH1C	ADH1C	ADH1C	302	0.69	0.57	YES
9	ADH6	ADH6	ADH6	329	0.66	0.62	YES
10	FBP1	FBP1	FBP1	490	0.48	0.64	YES
11	PCK2	PCK2	PCK2	791	0.33	0.65	YES
12	LDHAL6B	LDHAL6B	LDHAL6B	795	0.33	0.67	YES
13	ALDH2	ALDH2	ALDH2	1082	0.26	0.67	YES
14	ALDH1B1	ALDH1B1	ALDH1B1	1370	0.22	0.67	YES
15	PGAM2	PGAM2	PGAM2	1378	0.22	0.69	YES
16	HK3	HK3	HK3	1599	0.19	0.69	YES
17	ALDH1A3	ALDH1A3	ALDH1A3	1708	0.18	0.7	YES
18	PGM1	PGM1	PGM1	2116	0.15	0.68	NO
19	ENO3	ENO3	ENO3	2164	0.15	0.69	NO
20	LDHAL6A	LDHAL6A	LDHAL6A	2287	0.14	0.7	NO
21	ALDH7A1	ALDH7A1	ALDH7A1	2555	0.13	0.69	NO
22	PGAM4	PGAM4	PGAM4	2702	0.12	0.69	NO
23	ALDH3A1	ALDH3A1	ALDH3A1	2979	0.11	0.68	NO
24	GALM	GALM	GALM	3147	0.1	0.68	NO
25	ALDOC	ALDOC	ALDOC	3400	0.094	0.67	NO
26	PDHB	PDHB	PDHB	4464	0.065	0.62	NO
27	AKR1A1	AKR1A1	AKR1A1	4495	0.064	0.62	NO
28	DLD	DLD	DLD	4899	0.056	0.6	NO
29	PGM2	PGM2	PGM2	6058	0.035	0.54	NO
30	ALDH3A2	ALDH3A2	ALDH3A2	6217	0.033	0.54	NO
31	PGAM1	PGAM1	PGAM1	6294	0.032	0.53	NO
32	PDHA1	PDHA1	PDHA1	6509	0.029	0.52	NO
33	ACSS2	ACSS2	ACSS2	7075	0.021	0.49	NO
34	PFKM	PFKM	PFKM	7898	0.011	0.45	NO
35	GPI	GPI	GPI	8060	0.0088	0.44	NO
36	ALDH9A1	ALDH9A1	ALDH9A1	8254	0.0064	0.43	NO
37	LDHA	LDHA	LDHA	9002	-0.0022	0.39	NO
38	ALDH3B1	ALDH3B1	ALDH3B1	9412	-0.0067	0.37	NO
39	PGK1	PGK1	PGK1	9470	-0.0074	0.36	NO
40	ENO1	ENO1	ENO1	9872	-0.012	0.34	NO
41	PFKL	PFKL	PFKL	9990	-0.013	0.34	NO
42	ADH5	ADH5	ADH5	10368	-0.018	0.32	NO
43	BPGM	BPGM	BPGM	10665	-0.021	0.3	NO
44	GAPDH	GAPDH	GAPDH	10701	-0.022	0.3	NO
45	ACSS1	ACSS1	ACSS1	11074	-0.027	0.28	NO
46	TPI1	TPI1	TPI1	11099	-0.027	0.28	NO
47	DLAT	DLAT	DLAT	12129	-0.041	0.23	NO
48	HK2	HK2	HK2	12234	-0.042	0.23	NO
49	HK1	HK1	HK1	13126	-0.056	0.18	NO
50	LDHB	LDHB	LDHB	13454	-0.062	0.17	NO
51	ALDOA	ALDOA	ALDOA	13590	-0.064	0.16	NO
52	PKM2	PKM2	PKM2	15166	-0.1	0.085	NO
53	PFKP	PFKP	PFKP	15414	-0.11	0.079	NO
54	GCK	GCK	GCK	16688	-0.18	0.021	NO
55	ENO2	ENO2	ENO2	16948	-0.2	0.02	NO
56	ALDH3B2	ALDH3B2	ALDH3B2	17479	-0.27	0.0098	NO
57	G6PC2	G6PC2	G6PC2	17869	-0.36	0.014	NO

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

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

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

Table 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	PFKFB1	PFKFB1	PFKFB1	89	1.5	0.25	YES
2	ALDOB	ALDOB	ALDOB	129	1.2	0.47	YES
3	KHK	KHK	KHK	416	0.54	0.55	YES
4	FBP1	FBP1	FBP1	490	0.48	0.63	YES
5	SORD	SORD	SORD	622	0.39	0.69	YES
6	HK3	HK3	HK3	1599	0.19	0.67	NO
7	AKR1B10	AKR1B10	AKR1B10	2122	0.15	0.67	NO
8	ALDOC	ALDOC	ALDOC	3400	0.094	0.61	NO
9	GMPPA	GMPPA	GMPPA	4305	0.069	0.57	NO
10	PFKFB3	PFKFB3	PFKFB3	4816	0.057	0.56	NO
11	PMM2	PMM2	PMM2	5234	0.049	0.54	NO
12	MPI	MPI	MPI	5293	0.048	0.55	NO
13	GMPPB	GMPPB	GMPPB	6062	0.035	0.51	NO
14	FPGT	FPGT	FPGT	6873	0.024	0.47	NO
15	MTMR7	MTMR7	MTMR7	7005	0.022	0.47	NO
16	AKR1B1	AKR1B1	AKR1B1	7026	0.022	0.47	NO
17	PFKM	PFKM	PFKM	7898	0.011	0.42	NO
18	PFKFB2	PFKFB2	PFKFB2	8089	0.0084	0.41	NO
19	MTMR6	MTMR6	MTMR6	8202	0.007	0.41	NO
20	FUK	FUK	FUK	8528	0.0031	0.39	NO
21	TSTA3	TSTA3	TSTA3	8712	0.001	0.38	NO
22	MTMR1	MTMR1	MTMR1	9600	-0.009	0.33	NO
23	PFKL	PFKL	PFKL	9990	-0.013	0.32	NO
24	PMM1	PMM1	PMM1	10481	-0.019	0.29	NO
25	TPI1	TPI1	TPI1	11099	-0.027	0.26	NO
26	HK2	HK2	HK2	12234	-0.042	0.21	NO
27	HK1	HK1	HK1	13126	-0.056	0.17	NO
28	GMDS	GMDS	GMDS	13241	-0.058	0.17	NO
29	PHPT1	PHPT1	PHPT1	14115	-0.075	0.14	NO
30	PFKP	PFKP	PFKP	15414	-0.11	0.084	NO
31	MTMR2	MTMR2	MTMR2	16253	-0.15	0.064	NO
32	PFKFB4	PFKFB4	PFKFB4	17143	-0.22	0.054	NO

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

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

genes ES table in pathway: KEGG PENTOSE AND GLUCURONATE INTERCONVERSIONS

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	ARG1	ARG1	ARG1	12	2.1	0.13	YES
2	CPS1	CPS1	CPS1	38	1.8	0.25	YES
3	OTC	OTC	OTC	46	1.8	0.36	YES
4	DAO	DAO	DAO	58	1.7	0.47	YES
5	PRODH2	PRODH2	PRODH2	166	1.1	0.53	YES
6	GLS2	GLS2	GLS2	263	0.8	0.57	YES
7	AGMAT	AGMAT	AGMAT	516	0.46	0.59	YES
8	NAGS	NAGS	NAGS	531	0.45	0.62	YES
9	GAMT	GAMT	GAMT	720	0.35	0.63	YES
10	GATM	GATM	GATM	731	0.35	0.65	YES
11	ALDH4A1	ALDH4A1	ALDH4A1	902	0.3	0.66	YES
12	ALDH2	ALDH2	ALDH2	1082	0.26	0.67	YES
13	PRODH	PRODH	PRODH	1258	0.24	0.67	YES
14	ALDH1B1	ALDH1B1	ALDH1B1	1370	0.22	0.68	YES
15	NOS3	NOS3	NOS3	1412	0.22	0.69	YES
16	PYCR1	PYCR1	PYCR1	1510	0.2	0.7	YES
17	GOT1	GOT1	GOT1	1532	0.2	0.71	YES
18	ACY1	ACY1	ACY1	1681	0.19	0.72	YES
19	GLUD2	GLUD2	GLUD2	1783	0.18	0.72	YES
20	CKMT2	CKMT2	CKMT2	1798	0.18	0.73	YES
21	GOT2	GOT2	GOT2	1968	0.16	0.73	YES
22	ASL	ASL	ASL	2040	0.16	0.74	YES
23	MAOA	MAOA	MAOA	2079	0.16	0.75	YES
24	MAOB	MAOB	MAOB	2413	0.14	0.74	NO
25	ALDH7A1	ALDH7A1	ALDH7A1	2555	0.13	0.74	NO
26	CKB	CKB	CKB	3022	0.11	0.72	NO
27	ABP1	ABP1	ABP1	3043	0.11	0.72	NO
28	ASS1	ASS1	ASS1	3145	0.1	0.73	NO
29	GLUD1	GLUD1	GLUD1	3722	0.085	0.7	NO
30	OAT	OAT	OAT	3863	0.08	0.7	NO
31	CKM	CKM	CKM	4130	0.074	0.69	NO
32	P4HA2	P4HA2	P4HA2	4298	0.069	0.68	NO
33	ODC1	ODC1	ODC1	4655	0.061	0.67	NO
34	ALDH18A1	ALDH18A1	ALDH18A1	4798	0.058	0.66	NO
35	SAT2	SAT2	SAT2	5465	0.044	0.63	NO
36	ARG2	ARG2	ARG2	5534	0.043	0.63	NO
37	LAP3	LAP3	LAP3	6142	0.034	0.6	NO
38	ALDH3A2	ALDH3A2	ALDH3A2	6217	0.033	0.59	NO
39	NOS2	NOS2	NOS2	7890	0.011	0.5	NO
40	ALDH9A1	ALDH9A1	ALDH9A1	8254	0.0064	0.48	NO
41	SRM	SRM	SRM	8631	0.0018	0.46	NO
42	PYCRL	PYCRL	PYCRL	9201	-0.0044	0.43	NO
43	AMD1	AMD1	AMD1	9570	-0.0085	0.41	NO
44	GLS	GLS	GLS	9778	-0.011	0.4	NO
45	GLUL	GLUL	GLUL	9813	-0.011	0.4	NO
46	P4HA1	P4HA1	P4HA1	10941	-0.025	0.34	NO
47	PYCR2	PYCR2	PYCR2	11029	-0.026	0.33	NO
48	SMS	SMS	SMS	11054	-0.026	0.34	NO
49	P4HA3	P4HA3	P4HA3	15104	-0.1	0.12	NO
50	NOS1	NOS1	NOS1	16556	-0.17	0.048	NO
51	CKMT1A	CKMT1A	CKMT1A	16620	-0.17	0.055	NO
52	CKMT1B	CKMT1B	CKMT1B	16739	-0.18	0.06	NO
53	ADC	ADC	ADC	17351	-0.25	0.042	NO

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

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

Table 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	APOA1	APOA1	APOA1	83	1.5	0.18	YES
2	FABP1	FABP1	FABP1	121	1.3	0.33	YES
3	APOA2	APOA2	APOA2	155	1.1	0.46	YES
4	EHHADH	EHHADH	EHHADH	333	0.65	0.53	YES
5	CD36	CD36	CD36	651	0.38	0.56	YES
6	NR0B2	NR0B2	NR0B2	799	0.33	0.59	YES
7	PIK3R1	PIK3R1	PIK3R1	1936	0.17	0.55	YES
8	PPARA	PPARA	PPARA	1990	0.16	0.56	YES
9	PTGS2	PTGS2	PTGS2	2163	0.15	0.57	YES
10	DUSP1	DUSP1	DUSP1	2318	0.14	0.58	YES
11	HSD17B4	HSD17B4	HSD17B4	2509	0.13	0.59	YES
12	PRKAR2A	PRKAR2A	PRKAR2A	2604	0.13	0.6	YES
13	PRKCB	PRKCB	PRKCB	2728	0.12	0.6	YES
14	PRKAR1B	PRKAR1B	PRKAR1B	2940	0.11	0.61	YES
15	HSPA1A	HSPA1A	HSPA1A	3244	0.098	0.6	YES
16	PRKACB	PRKACB	PRKACB	3272	0.097	0.61	YES
17	NRIP1	NRIP1	NRIP1	3393	0.094	0.62	YES
18	PRKAR1A	PRKAR1A	PRKAR1A	4229	0.071	0.58	NO
19	MAPK1	MAPK1	MAPK1	4358	0.068	0.58	NO
20	PPARGC1A	PPARGC1A	PPARGC1A	4518	0.064	0.58	NO
21	EP300	EP300	EP300	4615	0.062	0.58	NO
22	SRA1	SRA1	SRA1	5137	0.051	0.56	NO
23	HSP90AA1	HSP90AA1	HSP90AA1	5943	0.036	0.52	NO
24	MYC	MYC	MYC	5947	0.036	0.52	NO
25	JUN	JUN	JUN	5981	0.036	0.52	NO
26	NR2F1	NR2F1	NR2F1	6025	0.035	0.53	NO
27	PIK3CA	PIK3CA	PIK3CA	6229	0.033	0.52	NO
28	PRKCA	PRKCA	PRKCA	6691	0.026	0.5	NO
29	ME1	ME1	ME1	6698	0.026	0.5	NO
30	PRKAR2B	PRKAR2B	PRKAR2B	6799	0.025	0.5	NO
31	RB1	RB1	RB1	7017	0.022	0.49	NO
32	RXRA	RXRA	RXRA	7058	0.021	0.49	NO
33	NFKBIA	NFKBIA	NFKBIA	7171	0.02	0.48	NO
34	PIK3CG	PIK3CG	PIK3CG	7376	0.017	0.47	NO
35	NOS2	NOS2	NOS2	7890	0.011	0.45	NO
36	CPT1B	CPT1B	CPT1B	8122	0.0081	0.44	NO
37	NCOR2	NCOR2	NCOR2	8825	-0.00015	0.4	NO
38	CITED2	CITED2	CITED2	8892	-0.00091	0.39	NO
39	STAT5B	STAT5B	STAT5B	9597	-0.0089	0.36	NO
40	FAT1	FAT1	FAT1	9683	-0.0099	0.35	NO
41	MED1	MED1	MED1	9875	-0.012	0.34	NO
42	NCOR1	NCOR1	NCOR1	10218	-0.016	0.32	NO
43	PDGFA	PDGFA	PDGFA	10400	-0.018	0.32	NO
44	SP1	SP1	SP1	10718	-0.022	0.3	NO
45	CREBBP	CREBBP	CREBBP	11359	-0.03	0.27	NO
46	MRPL11	MRPL11	MRPL11	11530	-0.033	0.26	NO
47	NCOA1	NCOA1	NCOA1	13130	-0.056	0.18	NO
48	RELA	RELA	RELA	13172	-0.057	0.19	NO
49	NR1H3	NR1H3	NR1H3	13296	-0.059	0.19	NO
50	DUT	DUT	DUT	13700	-0.066	0.17	NO
51	MAPK3	MAPK3	MAPK3	14189	-0.076	0.16	NO
52	LPL	LPL	LPL	15982	-0.13	0.073	NO
53	STAT5A	STAT5A	STAT5A	16109	-0.14	0.083	NO
54	TNF	TNF	TNF	17258	-0.24	0.047	NO

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

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

genes ES table in pathway: KEGG FATTY ACID METABOLISM

Table 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	ABCB11	ABCB11	ABCB11	48	1.8	0.14	YES
2	ABCG8	ABCG8	ABCG8	134	1.2	0.24	YES
3	ABCB4	ABCB4	ABCB4	142	1.2	0.34	YES
4	ABCG5	ABCG5	ABCG5	146	1.2	0.44	YES
5	ABCA6	ABCA6	ABCA6	221	0.9	0.5	YES
6	ABCA9	ABCA9	ABCA9	381	0.58	0.54	YES
7	ABCC11	ABCC11	ABCC11	395	0.56	0.59	YES
8	ABCC9	ABCC9	ABCC9	463	0.5	0.63	YES
9	ABCG2	ABCG2	ABCG2	476	0.49	0.67	YES
10	ABCA10	ABCA10	ABCA10	488	0.48	0.71	YES
11	ABCC2	ABCC2	ABCC2	522	0.46	0.74	YES
12	ABCC6	ABCC6	ABCC6	775	0.33	0.76	YES
13	ABCA12	ABCA12	ABCA12	1185	0.25	0.75	YES
14	ABCG4	ABCG4	ABCG4	1340	0.22	0.76	YES
15	ABCA1	ABCA1	ABCA1	1641	0.19	0.76	NO
16	ABCA5	ABCA5	ABCA5	2407	0.14	0.73	NO
17	ABCD3	ABCD3	ABCD3	2410	0.14	0.74	NO
18	ABCB1	ABCB1	ABCB1	2682	0.12	0.74	NO
19	ABCB8	ABCB8	ABCB8	3091	0.1	0.72	NO
20	ABCB10	ABCB10	ABCB10	3417	0.094	0.71	NO
21	ABCC4	ABCC4	ABCC4	3662	0.086	0.71	NO
22	ABCD2	ABCD2	ABCD2	3830	0.082	0.7	NO
23	CFTR	CFTR	CFTR	4113	0.074	0.7	NO
24	ABCA13	ABCA13	ABCA13	4507	0.064	0.68	NO
25	ABCB6	ABCB6	ABCB6	5321	0.047	0.64	NO
26	ABCB9	ABCB9	ABCB9	7023	0.022	0.55	NO
27	ABCA3	ABCA3	ABCA3	7046	0.022	0.55	NO
28	ABCC3	ABCC3	ABCC3	7426	0.016	0.53	NO
29	ABCD4	ABCD4	ABCD4	7452	0.016	0.53	NO
30	ABCA2	ABCA2	ABCA2	9576	-0.0086	0.41	NO
31	ABCB5	ABCB5	ABCB5	9592	-0.0088	0.41	NO
32	ABCA4	ABCA4	ABCA4	11440	-0.032	0.31	NO
33	ABCC5	ABCC5	ABCC5	11598	-0.034	0.3	NO
34	ABCD1	ABCD1	ABCD1	11742	-0.035	0.3	NO
35	ABCC8	ABCC8	ABCC8	11872	-0.037	0.3	NO
36	TAP1	TAP1	TAP1	12355	-0.044	0.27	NO
37	TAP2	TAP2	TAP2	12737	-0.05	0.26	NO
38	ABCB7	ABCB7	ABCB7	12788	-0.051	0.26	NO
39	ABCC10	ABCC10	ABCC10	14206	-0.077	0.18	NO
40	ABCC1	ABCC1	ABCC1	14825	-0.093	0.16	NO
41	ABCA7	ABCA7	ABCA7	15165	-0.1	0.15	NO
42	ABCG1	ABCG1	ABCG1	16790	-0.19	0.073	NO

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

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

genes ES table in pathway: KEGG STEROID HORMONE BIOSYNTHESIS

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	ACOT12	ACOT12	ACOT12	2	2.8	0.31	YES
2	PCK1	PCK1	PCK1	140	1.2	0.43	YES
3	PKLR	PKLR	PKLR	279	0.74	0.51	YES
4	LDHD	LDHD	LDHD	307	0.68	0.58	YES
5	PC	PC	PC	465	0.5	0.63	YES
6	PCK2	PCK2	PCK2	791	0.33	0.64	YES
7	LDHAL6B	LDHAL6B	LDHAL6B	795	0.33	0.68	YES
8	ALDH2	ALDH2	ALDH2	1082	0.26	0.69	YES
9	ACAT1	ACAT1	ACAT1	1163	0.25	0.72	YES
10	ALDH1B1	ALDH1B1	ALDH1B1	1370	0.22	0.73	YES
11	ACACB	ACACB	ACACB	1791	0.18	0.73	NO
12	LDHAL6A	LDHAL6A	LDHAL6A	2287	0.14	0.72	NO
13	GRHPR	GRHPR	GRHPR	2469	0.13	0.72	NO
14	ALDH7A1	ALDH7A1	ALDH7A1	2555	0.13	0.73	NO
15	ACAT2	ACAT2	ACAT2	2902	0.11	0.72	NO
16	HAGH	HAGH	HAGH	3299	0.096	0.71	NO
17	MDH1	MDH1	MDH1	3617	0.088	0.7	NO
18	PDHB	PDHB	PDHB	4464	0.065	0.66	NO
19	DLD	DLD	DLD	4899	0.056	0.65	NO
20	HAGHL	HAGHL	HAGHL	5714	0.04	0.61	NO
21	MDH2	MDH2	MDH2	5897	0.037	0.6	NO
22	ALDH3A2	ALDH3A2	ALDH3A2	6217	0.033	0.59	NO
23	PDHA1	PDHA1	PDHA1	6509	0.029	0.57	NO
24	ME1	ME1	ME1	6698	0.026	0.57	NO
25	ME2	ME2	ME2	6904	0.023	0.56	NO
26	AKR1B1	AKR1B1	AKR1B1	7026	0.022	0.55	NO
27	ACSS2	ACSS2	ACSS2	7075	0.021	0.55	NO
28	ACACA	ACACA	ACACA	7181	0.02	0.55	NO
29	ALDH9A1	ALDH9A1	ALDH9A1	8254	0.0064	0.49	NO
30	LDHA	LDHA	LDHA	9002	-0.0022	0.45	NO
31	GLO1	GLO1	GLO1	9121	-0.0035	0.44	NO
32	ACYP2	ACYP2	ACYP2	9525	-0.008	0.42	NO
33	ACSS1	ACSS1	ACSS1	11074	-0.027	0.34	NO
34	DLAT	DLAT	DLAT	12129	-0.041	0.28	NO
35	LDHB	LDHB	LDHB	13454	-0.062	0.22	NO
36	ACYP1	ACYP1	ACYP1	13595	-0.064	0.22	NO
37	PKM2	PKM2	PKM2	15166	-0.1	0.14	NO
38	ME3	ME3	ME3	16734	-0.18	0.076	NO

Figure S57. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG STEROID HORMONE BIOSYNTHESIS.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG STEROID HORMONE BIOSYNTHESIS, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Methods & Data

Input

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

GSEA analysis

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

Download Results

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

References

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

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