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

Brain Lower Grade Glioma (Primary solid tumor)

21 August 2015 | analyses__2015_08_21

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in LGG-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1FN15GC

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 LGG-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: 191
Number of samples: 516
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 5 :[ clus1 ] 134
pheno.type: 2 - 5 :[ clus2 ] 109
pheno.type: 3 - 5 :[ clus3 ] 109
pheno.type: 4 - 5 :[ clus4 ] 134
pheno.type: 5 - 5 :[ clus5 ] 30

For the expression subtypes of 18334 genes in 517 samples, GSEA found enriched gene sets in each cluster using 516 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA BCR PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA FCER1 PATHWAY, BIOCARTA GH PATHWAY, BIOCARTA VIP PATHWAY, BIOCARTA TOLL PATHWAY, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG RIBOSOME, KEGG RNA POLYMERASE, KEGG BASAL TRANSCRIPTION FACTORS

And common core enriched genes are RXRG, ACIN1, AQR, BAT1, BCAS2, CDC5L, CWC15, DDX42, DDX46, DDX5

clus2

Top enriched gene sets are BIOCARTA G1 PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA IL2RB PATHWAY, BIOCARTA DEATH PATHWAY, BIOCARTA P38MAPK PATHWAY, BIOCARTA TCR PATHWAY, BIOCARTA TNFR1 PATHWAY, KEGG N GLYCAN BIOSYNTHESIS, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

And common core enriched genes are CASP3, CASP6, CASP7, CASP8, CFLAR, FADD, FAS, LMNA, MAP3K1, BIRC3

clus3

Top enriched gene sets are BIOCARTA CARM ER PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA RACCYCD PATHWAY, KEGG GALACTOSE METABOLISM, KEGG OXIDATIVE PHOSPHORYLATION, KEGG LYSINE DEGRADATION, KEGG SPHINGOLIPID METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RIBOSOME, KEGG RNA DEGRADATION

And common core enriched genes are CCND1, CREBBP, EP300, ERCC3, GRIP1, GTF2F1, HDAC10, HDAC4, HDAC6, HDAC8

clus4

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA PYK2 PATHWAY, BIOCARTA NFAT PATHWAY, BIOCARTA PDGF PATHWAY

And common core enriched genes are CALM1, CALM3, CALM2, MAP2K1, MAPK1, MAPK3, MAPK8, PRKCB, PTK2B, GNAQ

clus5

Top enriched gene sets are BIOCARTA MYOSIN PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG FATTY ACID METABOLISM, KEGG OXIDATIVE PHOSPHORYLATION, KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG HISTIDINE METABOLISM, KEGG GLUTATHIONE METABOLISM, KEGG ETHER LIPID METABOLISM, KEGG PROPANOATE METABOLISM

And common core enriched genes are ACAA1, ALDH2, ALDH7A1, ALDH9A1, HMGCL, ACAA2, ACADS, AUH, BCAT2, BCKDHA

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	0.55	1.4	0.12	0.77	0.95	0.21	0.042	0.2	0.61	0.27
BIOCARTA HDAC PATHWAY	27	genes.ES.table	0.42	1.2	0.23	0.81	0.99	0.18	0.044	0.18	0.7	0.28
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.54	1.4	0.15	0.7	0.97	0.24	0.07	0.23	0.58	0.21
BIOCARTA GH PATHWAY	25	genes.ES.table	0.53	1.5	0.077	0.74	0.88	0.24	0.087	0.22	0.56	0.25
BIOCARTA VIP PATHWAY	25	genes.ES.table	0.46	1.3	0.2	0.76	0.99	0.24	0.068	0.22	0.66	0.25
BIOCARTA TOLL PATHWAY	36	genes.ES.table	0.55	1.4	0.13	0.7	0.97	0.56	0.26	0.41	0.57	0.23
KEGG PENTOSE PHOSPHATE PATHWAY	25	genes.ES.table	0.47	1.4	0.11	0.73	0.97	0.28	0.16	0.24	0.58	0.24
KEGG RIBOSOME	85	genes.ES.table	0.66	1.6	0.055	0.6	0.65	0.88	0.28	0.64	0.37	0.2
KEGG RNA POLYMERASE	28	genes.ES.table	0.36	1.3	0.22	0.75	0.99	0.5	0.32	0.34	0.65	0.24
KEGG BASAL TRANSCRIPTION FACTORS	34	genes.ES.table	0.39	1.3	0.19	0.8	0.98	0.53	0.38	0.33	0.68	0.27

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	PRPF38A	PRPF38A	PRPF38A	1655	0.14	-0.057	YES
2	PPIH	PPIH	PPIH	1972	0.12	-0.045	YES
3	SFRS4	SFRS4	SFRS4	1975	0.12	-0.016	YES
4	PRPF38B	PRPF38B	PRPF38B	2016	0.12	0.011	YES
5	SYF2	SYF2	SYF2	2307	0.11	0.021	YES
6	SNRNP40	SNRNP40	SNRNP40	2324	0.11	0.046	YES
7	RBM17	RBM17	RBM17	2489	0.1	0.061	YES
8	SF3A3	SF3A3	SF3A3	2775	0.094	0.068	YES
9	PPIE	PPIE	PPIE	3128	0.082	0.068	YES
10	SNRPA	SNRPA	SNRPA	3136	0.082	0.087	YES
11	SNRNP70	SNRNP70	SNRNP70	3254	0.079	0.099	YES
12	MAGOH	MAGOH	MAGOH	3279	0.078	0.12	YES
13	PRPF31	PRPF31	PRPF31	3362	0.076	0.13	YES
14	SMNDC1	SMNDC1	SMNDC1	3606	0.07	0.13	YES
15	THOC2	THOC2	THOC2	3840	0.065	0.14	YES
16	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	3909	0.064	0.15	YES
17	HSPA1L	HSPA1L	HSPA1L	4073	0.06	0.15	YES
18	LSM2	LSM2	LSM2	4074	0.06	0.17	YES
19	HNRNPA1	HNRNPA1	HNRNPA1	4098	0.06	0.18	YES
20	PRPF18	PRPF18	PRPF18	4221	0.058	0.19	YES
21	HNRNPC	HNRNPC	HNRNPC	4246	0.057	0.2	YES
22	SNRPD2	SNRPD2	SNRPD2	4341	0.056	0.21	YES
23	U2AF2	U2AF2	U2AF2	4347	0.056	0.22	YES
24	PUF60	PUF60	PUF60	4368	0.055	0.23	YES
25	PLRG1	PLRG1	PLRG1	4379	0.055	0.24	YES
26	SFRS13A	SFRS13A	SFRS13A	4394	0.055	0.26	YES
27	HSPA1A	HSPA1A	HSPA1A	4713	0.049	0.25	YES
28	PHF5A	PHF5A	PHF5A	4751	0.048	0.26	YES
29	HSPA6	HSPA6	HSPA6	4904	0.046	0.26	YES
30	EIF4A3	EIF4A3	EIF4A3	4989	0.045	0.27	YES
31	LSM6	LSM6	LSM6	5057	0.044	0.27	YES
32	ACIN1	ACIN1	ACIN1	5073	0.044	0.28	YES
33	PPIL1	PPIL1	PPIL1	5097	0.044	0.29	YES
34	HSPA1B	HSPA1B	HSPA1B	5255	0.041	0.29	YES
35	SFRS9	SFRS9	SFRS9	5259	0.041	0.3	YES
36	TRA2A	TRA2A	TRA2A	5342	0.04	0.31	YES
37	THOC1	THOC1	THOC1	5564	0.037	0.3	YES
38	PRPF40A	PRPF40A	PRPF40A	5608	0.036	0.31	YES
39	SNRPC	SNRPC	SNRPC	5610	0.036	0.32	YES
40	SF3B14	SF3B14	SF3B14	5684	0.036	0.32	YES
41	HNRNPM	HNRNPM	HNRNPM	5692	0.035	0.33	YES
42	RBM8A	RBM8A	RBM8A	5724	0.035	0.34	YES
43	BCAS2	BCAS2	BCAS2	5728	0.035	0.35	YES
44	SF3B3	SF3B3	SF3B3	5817	0.034	0.35	YES
45	DHX38	DHX38	DHX38	5958	0.032	0.35	YES
46	SF3B2	SF3B2	SF3B2	5960	0.032	0.36	YES
47	BAT1	BAT1	BAT1	5965	0.032	0.36	YES
48	SR140	SR140	SR140	5977	0.032	0.37	YES
49	SF3B1	SF3B1	SF3B1	6013	0.031	0.38	YES
50	LSM7	LSM7	LSM7	6355	0.027	0.36	YES
51	HNRNPU	HNRNPU	HNRNPU	6409	0.027	0.37	YES
52	DDX5	DDX5	DDX5	6440	0.026	0.37	YES
53	CDC5L	CDC5L	CDC5L	6471	0.026	0.38	YES
54	PQBP1	PQBP1	PQBP1	6598	0.025	0.38	YES
55	SNRPG	SNRPG	SNRPG	6607	0.024	0.38	YES
56	AQR	AQR	AQR	6626	0.024	0.39	YES
57	USP39	USP39	USP39	6631	0.024	0.39	YES
58	DDX42	DDX42	DDX42	6664	0.024	0.4	YES
59	SF3A1	SF3A1	SF3A1	6673	0.024	0.4	YES
60	RBMX	RBMX	RBMX	6750	0.023	0.4	YES
61	SNRPF	SNRPF	SNRPF	6791	0.022	0.4	YES
62	EFTUD2	EFTUD2	EFTUD2	6826	0.022	0.41	YES
63	SNW1	SNW1	SNW1	6861	0.022	0.41	YES
64	TCERG1	TCERG1	TCERG1	6929	0.021	0.41	YES
65	SNRPB	SNRPB	SNRPB	6965	0.02	0.42	YES
66	CWC15	CWC15	CWC15	6967	0.02	0.42	YES
67	NCBP1	NCBP1	NCBP1	7193	0.018	0.41	YES
68	DHX16	DHX16	DHX16	7230	0.018	0.42	YES
69	SNRPD3	SNRPD3	SNRPD3	7250	0.017	0.42	YES
70	SART1	SART1	SART1	7296	0.017	0.42	YES
71	SNRNP27	SNRNP27	SNRNP27	7319	0.017	0.42	YES
72	RBM25	RBM25	RBM25	7405	0.016	0.42	YES
73	DDX46	DDX46	DDX46	7441	0.015	0.42	YES
74	HNRNPK	HNRNPK	HNRNPK	7464	0.015	0.42	YES
75	DHX15	DHX15	DHX15	7615	0.014	0.42	NO
76	BUD31	BUD31	BUD31	7670	0.013	0.42	NO
77	THOC4	THOC4	THOC4	7754	0.012	0.42	NO
78	U2AF1	U2AF1	U2AF1	7771	0.012	0.42	NO
79	XAB2	XAB2	XAB2	7807	0.012	0.42	NO
80	SNRNP200	SNRNP200	SNRNP200	7824	0.011	0.42	NO
81	ISY1	ISY1	ISY1	7869	0.011	0.42	NO
82	CHERP	CHERP	CHERP	7959	0.01	0.42	NO
83	RBM22	RBM22	RBM22	7997	0.0096	0.42	NO
84	SFRS3	SFRS3	SFRS3	8224	0.0075	0.41	NO
85	SF3B4	SF3B4	SF3B4	8300	0.0067	0.41	NO
86	CCDC12	CCDC12	CCDC12	8321	0.0064	0.41	NO
87	SNRPA1	SNRPA1	SNRPA1	8351	0.0061	0.41	NO
88	HSPA2	HSPA2	HSPA2	8357	0.006	0.41	NO
89	SFRS5	SFRS5	SFRS5	8457	0.005	0.4	NO
90	HNRNPA3	HNRNPA3	HNRNPA3	8611	0.0034	0.4	NO
91	LSM3	LSM3	LSM3	8637	0.0031	0.4	NO
92	NAA38	NAA38	NAA38	8677	0.0026	0.4	NO
93	CRNKL1	CRNKL1	CRNKL1	8862	0.00092	0.38	NO
94	SF3A2	SF3A2	SF3A2	8877	0.00078	0.38	NO
95	ZMAT2	ZMAT2	ZMAT2	8890	0.00064	0.38	NO
96	SFRS2B	SFRS2B	SFRS2B	8979	-0.00026	0.38	NO
97	PRPF19	PRPF19	PRPF19	9013	-0.00055	0.38	NO
98	WBP11	WBP11	WBP11	9026	-0.00063	0.38	NO
99	TRA2B	TRA2B	TRA2B	9101	-0.0014	0.37	NO
100	SNRPE	SNRPE	SNRPE	9199	-0.0024	0.37	NO
101	NHP2L1	NHP2L1	NHP2L1	9321	-0.0036	0.36	NO
102	LSM5	LSM5	LSM5	9323	-0.0037	0.36	NO
103	SFRS2	SFRS2	SFRS2	9419	-0.0046	0.36	NO
104	SFRS1	SFRS1	SFRS1	9570	-0.0062	0.35	NO
105	CTNNBL1	CTNNBL1	CTNNBL1	9704	-0.008	0.35	NO
106	SF3B5	SF3B5	SF3B5	9765	-0.0086	0.35	NO
107	PCBP1	PCBP1	PCBP1	9787	-0.0089	0.35	NO
108	PRPF4	PRPF4	PRPF4	10159	-0.013	0.33	NO
109	SLU7	SLU7	SLU7	10202	-0.014	0.33	NO
110	PRPF8	PRPF8	PRPF8	10228	-0.014	0.33	NO
111	SFRS7	SFRS7	SFRS7	10270	-0.014	0.33	NO
112	PRPF6	PRPF6	PRPF6	10317	-0.015	0.34	NO
113	DDX23	DDX23	DDX23	10411	-0.016	0.33	NO
114	PRPF40B	PRPF40B	PRPF40B	10413	-0.016	0.34	NO
115	CDC40	CDC40	CDC40	10540	-0.018	0.33	NO
116	SNRPB2	SNRPB2	SNRPB2	10763	-0.021	0.33	NO
117	DHX8	DHX8	DHX8	11133	-0.026	0.31	NO
118	SNRPD1	SNRPD1	SNRPD1	11134	-0.026	0.32	NO
119	SFRS6	SFRS6	SFRS6	11288	-0.028	0.32	NO
120	HSPA8	HSPA8	HSPA8	11480	-0.031	0.31	NO
121	PRPF3	PRPF3	PRPF3	11599	-0.032	0.32	NO
122	LSM4	LSM4	LSM4	12253	-0.043	0.29	NO
123	TXNL4A	TXNL4A	TXNL4A	12395	-0.046	0.29	NO
124	THOC3	THOC3	THOC3	12778	-0.055	0.28	NO
125	MAGOHB	MAGOHB	MAGOHB	13781	-0.084	0.25	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 HDAC 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	DLL3	DLL3	DLL3	356	0.31	0.079	YES
2	HES5	HES5	HES5	400	0.3	0.17	YES
3	DLL1	DLL1	DLL1	995	0.2	0.2	YES
4	NOTCH2	NOTCH2	NOTCH2	1125	0.19	0.26	YES
5	MAML2	MAML2	MAML2	1242	0.18	0.3	YES
6	HDAC1	HDAC1	HDAC1	1401	0.16	0.35	YES
7	DTX4	DTX4	DTX4	1976	0.12	0.36	YES
8	DVL1	DVL1	DVL1	3023	0.086	0.33	YES
9	CTBP2	CTBP2	CTBP2	3026	0.086	0.35	YES
10	RBPJ	RBPJ	RBPJ	3084	0.084	0.38	YES
11	PSENEN	PSENEN	PSENEN	3246	0.079	0.39	YES
12	NCOR2	NCOR2	NCOR2	3370	0.076	0.41	YES
13	NOTCH1	NOTCH1	NOTCH1	3685	0.068	0.42	YES
14	NOTCH3	NOTCH3	NOTCH3	3974	0.062	0.42	YES
15	MAML3	MAML3	MAML3	4683	0.05	0.4	YES
16	DTX2	DTX2	DTX2	4722	0.049	0.41	YES
17	MAML1	MAML1	MAML1	4918	0.046	0.41	YES
18	LFNG	LFNG	LFNG	5028	0.045	0.42	YES
19	DVL2	DVL2	DVL2	5044	0.044	0.44	YES
20	NUMB	NUMB	NUMB	5100	0.044	0.45	YES
21	HES1	HES1	HES1	5143	0.043	0.46	YES
22	EP300	EP300	EP300	5162	0.043	0.47	YES
23	RFNG	RFNG	RFNG	5829	0.034	0.44	NO
24	DVL3	DVL3	DVL3	5850	0.034	0.46	NO
25	CREBBP	CREBBP	CREBBP	6202	0.029	0.44	NO
26	ADAM17	ADAM17	ADAM17	6542	0.025	0.43	NO
27	APH1A	APH1A	APH1A	6696	0.024	0.43	NO
28	SNW1	SNW1	SNW1	6861	0.022	0.43	NO
29	KAT2B	KAT2B	KAT2B	7047	0.02	0.43	NO
30	NUMBL	NUMBL	NUMBL	7329	0.016	0.42	NO
31	HDAC2	HDAC2	HDAC2	7423	0.016	0.42	NO
32	CIR1	CIR1	CIR1	7549	0.014	0.42	NO
33	DTX3L	DTX3L	DTX3L	8109	0.0084	0.39	NO
34	KAT2A	KAT2A	KAT2A	8679	0.0026	0.36	NO
35	CTBP1	CTBP1	CTBP1	8767	0.0018	0.35	NO
36	NCSTN	NCSTN	NCSTN	8777	0.0017	0.35	NO
37	PSEN1	PSEN1	PSEN1	9048	-0.00086	0.34	NO
38	DTX3	DTX3	DTX3	9052	-0.00087	0.34	NO
39	JAG1	JAG1	JAG1	10829	-0.022	0.25	NO
40	DTX1	DTX1	DTX1	11151	-0.026	0.24	NO
41	DLL4	DLL4	DLL4	12092	-0.04	0.2	NO
42	PTCRA	PTCRA	PTCRA	12313	-0.044	0.2	NO
43	NOTCH4	NOTCH4	NOTCH4	13120	-0.063	0.18	NO
44	JAG2	JAG2	JAG2	13951	-0.09	0.16	NO
45	PSEN2	PSEN2	PSEN2	14235	-0.1	0.18	NO
46	RBPJL	RBPJL	RBPJL	15097	-0.14	0.18	NO

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

Figure S4. 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 FCER1 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	RPL21	RPL21	RPL21	708	0.24	-0.0034	YES
2	RPS8	RPS8	RPS8	1543	0.15	-0.027	YES
3	RPS16	RPS16	RPS16	1568	0.15	-0.0069	YES
4	RPL11	RPL11	RPL11	1578	0.15	0.014	YES
5	RPL9	RPL9	RPL9	1625	0.14	0.033	YES
6	RPL22	RPL22	RPL22	1626	0.14	0.054	YES
7	RPL13A	RPL13A	RPL13A	1688	0.14	0.071	YES
8	RPL5	RPL5	RPL5	1723	0.14	0.09	YES
9	RPS19	RPS19	RPS19	2167	0.12	0.082	YES
10	RPLP0	RPLP0	RPLP0	2214	0.11	0.097	YES
11	RPS5	RPS5	RPS5	2241	0.11	0.11	YES
12	RPS11	RPS11	RPS11	2308	0.11	0.12	YES
13	RPL7	RPL7	RPL7	2315	0.11	0.14	YES
14	RPS3	RPS3	RPS3	2341	0.11	0.16	YES
15	RPL17	RPL17	RPL17	2433	0.11	0.17	YES
16	RPS2	RPS2	RPS2	2499	0.1	0.18	YES
17	RPS10	RPS10	RPS10	2535	0.1	0.19	YES
18	RPL18A	RPL18A	RPL18A	2573	0.1	0.2	YES
19	RPL28	RPL28	RPL28	2681	0.097	0.21	YES
20	RPL7A	RPL7A	RPL7A	2686	0.097	0.23	YES
21	RPL30	RPL30	RPL30	2704	0.096	0.24	YES
22	RPS4Y1	RPS4Y1	RPS4Y1	2737	0.096	0.25	YES
23	RPL23	RPL23	RPL23	2738	0.096	0.26	YES
24	RPLP1	RPLP1	RPLP1	2754	0.095	0.28	YES
25	RPS17	RPS17	RPS17	2762	0.095	0.29	YES
26	RPS15A	RPS15A	RPS15A	2812	0.092	0.3	YES
27	RPS9	RPS9	RPS9	2822	0.092	0.32	YES
28	RPL39	RPL39	RPL39	2824	0.092	0.33	YES
29	RPL12	RPL12	RPL12	2950	0.088	0.34	YES
30	RPS27	RPS27	RPS27	2957	0.088	0.35	YES
31	RPS3A	RPS3A	RPS3A	2979	0.087	0.36	YES
32	RPS25	RPS25	RPS25	3067	0.084	0.37	YES
33	RPS29	RPS29	RPS29	3121	0.082	0.38	YES
34	RPL3	RPL3	RPL3	3162	0.081	0.39	YES
35	RPS24	RPS24	RPS24	3198	0.08	0.4	YES
36	RPS6	RPS6	RPS6	3281	0.078	0.4	YES
37	RPL27	RPL27	RPL27	3300	0.078	0.41	YES
38	RPSA	RPSA	RPSA	3331	0.077	0.42	YES
39	RPL4	RPL4	RPL4	3407	0.075	0.43	YES
40	RPL27A	RPL27A	RPL27A	3434	0.074	0.44	YES
41	RPL34	RPL34	RPL34	3505	0.073	0.45	YES
42	RPL26	RPL26	RPL26	3508	0.072	0.46	YES
43	RPL8	RPL8	RPL8	3510	0.072	0.47	YES
44	RPL19	RPL19	RPL19	3536	0.072	0.48	YES
45	RPL38	RPL38	RPL38	3560	0.071	0.48	YES
46	FAU	FAU	FAU	3621	0.07	0.49	YES
47	RPL32	RPL32	RPL32	3627	0.07	0.5	YES
48	RPL35A	RPL35A	RPL35A	3648	0.069	0.51	YES
49	RPL37A	RPL37A	RPL37A	3654	0.069	0.52	YES
50	RPL29	RPL29	RPL29	3665	0.068	0.53	YES
51	RPL10	RPL10	RPL10	3723	0.067	0.54	YES
52	RPS18	RPS18	RPS18	3727	0.067	0.55	YES
53	RPS15	RPS15	RPS15	3729	0.067	0.56	YES
54	RPLP2	RPLP2	RPLP2	3735	0.067	0.57	YES
55	RPS23	RPS23	RPS23	3784	0.066	0.57	YES
56	RPS27A	RPS27A	RPS27A	3945	0.063	0.57	YES
57	RPL15	RPL15	RPL15	3949	0.063	0.58	YES
58	RPS21	RPS21	RPS21	3953	0.063	0.59	YES
59	RPL6	RPL6	RPL6	4011	0.061	0.6	YES
60	RPS13	RPS13	RPS13	4095	0.06	0.6	YES
61	RPL13	RPL13	RPL13	4129	0.059	0.61	YES
62	RPL36	RPL36	RPL36	4229	0.058	0.61	YES
63	RPL35	RPL35	RPL35	4257	0.057	0.62	YES
64	RPS4X	RPS4X	RPS4X	4260	0.057	0.63	YES
65	RPL37	RPL37	RPL37	4325	0.056	0.63	YES
66	RPL14	RPL14	RPL14	4392	0.055	0.64	YES
67	RPL41	RPL41	RPL41	4455	0.054	0.64	YES
68	RPS12	RPS12	RPS12	4479	0.053	0.65	YES
69	RPL24	RPL24	RPL24	4766	0.048	0.64	YES
70	RPS20	RPS20	RPS20	4784	0.048	0.64	YES
71	RPL36A	RPL36A	RPL36A	4789	0.048	0.65	YES
72	RPL23A	RPL23A	RPL23A	4916	0.046	0.65	YES
73	RPL10A	RPL10A	RPL10A	4971	0.045	0.66	YES
74	UBA52	UBA52	UBA52	5078	0.044	0.66	YES
75	RPS7	RPS7	RPS7	5092	0.044	0.66	YES
76	RSL24D1	RSL24D1	RSL24D1	5501	0.038	0.64	NO
77	RPS26	RPS26	RPS26	5525	0.038	0.65	NO
78	RPL31	RPL31	RPL31	5681	0.036	0.64	NO
79	MRPL13	MRPL13	MRPL13	6173	0.029	0.62	NO
80	RPL10L	RPL10L	RPL10L	6593	0.025	0.6	NO
81	RPS28	RPS28	RPS28	7068	0.02	0.58	NO
82	RPL36AL	RPL36AL	RPL36AL	7403	0.016	0.56	NO
83	RPL26L1	RPL26L1	RPL26L1	10971	-0.024	0.37	NO
84	RPS27L	RPS27L	RPS27L	12194	-0.042	0.31	NO
85	RPL22L1	RPL22L1	RPL22L1	15490	-0.17	0.16	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 FCER1 PATHWAY.

Figure S6. 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 GH 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	426	0.29	0.045	YES
2	RXRG	RXRG	RXRG	435	0.29	0.11	YES
3	PIK3R5	PIK3R5	PIK3R5	453	0.28	0.18	YES
4	EGF	EGF	EGF	456	0.28	0.25	YES
5	PLCG2	PLCG2	PLCG2	656	0.25	0.3	YES
6	CASP9	CASP9	CASP9	722	0.24	0.35	YES
7	E2F2	E2F2	E2F2	834	0.22	0.39	YES
8	CDKN2A	CDKN2A	CDKN2A	899	0.21	0.44	YES
9	NRAS	NRAS	NRAS	2981	0.087	0.35	NO
10	PIK3CD	PIK3CD	PIK3CD	4084	0.06	0.3	NO
11	CCND1	CCND1	CCND1	4137	0.059	0.31	NO
12	AKT2	AKT2	AKT2	4154	0.059	0.33	NO
13	RAF1	RAF1	RAF1	4620	0.051	0.31	NO
14	PIK3R1	PIK3R1	PIK3R1	4856	0.047	0.31	NO
15	BAD	BAD	BAD	4876	0.047	0.32	NO
16	RB1	RB1	RB1	5199	0.042	0.31	NO
17	E2F3	E2F3	E2F3	5397	0.039	0.31	NO
18	SOS2	SOS2	SOS2	5632	0.036	0.31	NO
19	RXRA	RXRA	RXRA	6046	0.031	0.29	NO
20	STK4	STK4	STK4	6116	0.03	0.3	NO
21	SOS1	SOS1	SOS1	6183	0.029	0.3	NO
22	PIK3CA	PIK3CA	PIK3CA	6318	0.028	0.3	NO
23	RASSF1	RASSF1	RASSF1	6364	0.027	0.3	NO
24	CDK6	CDK6	CDK6	6419	0.026	0.3	NO
25	RXRB	RXRB	RXRB	6760	0.023	0.29	NO
26	RASSF5	RASSF5	RASSF5	6783	0.022	0.3	NO
27	PRKCA	PRKCA	PRKCA	6867	0.022	0.3	NO
28	PIK3CB	PIK3CB	PIK3CB	6964	0.021	0.3	NO
29	GRB2	GRB2	GRB2	7015	0.02	0.3	NO
30	ARAF	ARAF	ARAF	7034	0.02	0.3	NO
31	AKT1	AKT1	AKT1	7096	0.019	0.3	NO
32	CDK4	CDK4	CDK4	7165	0.018	0.3	NO
33	AKT3	AKT3	AKT3	7745	0.012	0.27	NO
34	EGFR	EGFR	EGFR	7826	0.011	0.27	NO
35	MAPK1	MAPK1	MAPK1	7941	0.01	0.27	NO
36	FOXO3	FOXO3	FOXO3	8124	0.0084	0.26	NO
37	PLCG1	PLCG1	PLCG1	8558	0.004	0.24	NO
38	MAP2K2	MAP2K2	MAP2K2	8959	-0.000042	0.22	NO
39	MAPK3	MAPK3	MAPK3	9063	-0.0011	0.21	NO
40	PIK3R3	PIK3R3	PIK3R3	10236	-0.014	0.15	NO
41	KRAS	KRAS	KRAS	11016	-0.024	0.11	NO
42	PIK3R2	PIK3R2	PIK3R2	11445	-0.03	0.097	NO
43	PDPK1	PDPK1	PDPK1	12128	-0.041	0.069	NO
44	MAP2K1	MAP2K1	MAP2K1	12456	-0.047	0.062	NO
45	HRAS	HRAS	HRAS	12489	-0.048	0.072	NO
46	TP53	TP53	TP53	12715	-0.053	0.072	NO
47	BRAF	BRAF	BRAF	12726	-0.053	0.084	NO
48	RARB	RARB	RARB	13118	-0.063	0.078	NO
49	ERBB2	ERBB2	ERBB2	13687	-0.081	0.066	NO
50	FHIT	FHIT	FHIT	14576	-0.12	0.045	NO
51	PRKCB	PRKCB	PRKCB	15931	-0.2	0.018	NO
52	TGFA	TGFA	TGFA	16128	-0.22	0.058	NO
53	PRKCG	PRKCG	PRKCG	16581	-0.26	0.095	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 GH PATHWAY.

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

genes ES table in pathway: BIOCARTA VIP 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	RET	RET	RET	39	0.53	0.22	YES
2	RXRG	RXRG	RXRG	435	0.29	0.33	YES
3	TCF7L1	TCF7L1	TCF7L1	1132	0.19	0.37	YES
4	MYC	MYC	MYC	1238	0.18	0.44	YES
5	NTRK1	NTRK1	NTRK1	2472	0.1	0.42	YES
6	CDH1	CDH1	CDH1	2541	0.1	0.46	YES
7	TCF7L2	TCF7L2	TCF7L2	2685	0.097	0.49	YES
8	NRAS	NRAS	NRAS	2981	0.087	0.51	YES
9	TCF7	TCF7	TCF7	3342	0.076	0.52	YES
10	CCND1	CCND1	CCND1	4137	0.059	0.51	NO
11	NCOA4	NCOA4	NCOA4	5244	0.042	0.46	NO
12	RXRA	RXRA	RXRA	6046	0.031	0.43	NO
13	RXRB	RXRB	RXRB	6760	0.023	0.4	NO
14	TPR	TPR	TPR	6825	0.022	0.41	NO
15	MAPK1	MAPK1	MAPK1	7941	0.01	0.35	NO
16	MAP2K2	MAP2K2	MAP2K2	8959	-0.000042	0.3	NO
17	MAPK3	MAPK3	MAPK3	9063	-0.0011	0.29	NO
18	CTNNB1	CTNNB1	CTNNB1	9388	-0.0042	0.28	NO
19	TPM3	TPM3	TPM3	10078	-0.012	0.24	NO
20	CCDC6	CCDC6	CCDC6	10314	-0.015	0.24	NO
21	TFG	TFG	TFG	10352	-0.016	0.24	NO
22	KRAS	KRAS	KRAS	11016	-0.024	0.22	NO
23	MAP2K1	MAP2K1	MAP2K1	12456	-0.047	0.16	NO
24	TP53	TP53	TP53	12715	-0.053	0.17	NO
25	BRAF	BRAF	BRAF	12726	-0.053	0.19	NO
26	PPARG	PPARG	PPARG	13211	-0.065	0.19	NO
27	LEF1	LEF1	LEF1	13542	-0.076	0.21	NO
28	PAX8	PAX8	PAX8	14828	-0.13	0.19	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 VIP PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA VIP 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 TOLL 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	SLC2A4	SLC2A4	SLC2A4	88	0.45	0.18	YES
2	PIK3CG	PIK3CG	PIK3CG	426	0.29	0.28	YES
3	PTPN6	PTPN6	PTPN6	729	0.24	0.37	YES
4	GHR	GHR	GHR	1040	0.2	0.43	YES
5	STAT5A	STAT5A	STAT5A	1372	0.16	0.48	YES
6	RPS6KA1	RPS6KA1	RPS6KA1	1593	0.15	0.53	YES
7	JAK2	JAK2	JAK2	3951	0.063	0.43	NO
8	RAF1	RAF1	RAF1	4620	0.051	0.41	NO
9	STAT5B	STAT5B	STAT5B	4767	0.048	0.42	NO
10	PIK3R1	PIK3R1	PIK3R1	4856	0.047	0.44	NO
11	SOS1	SOS1	SOS1	6183	0.029	0.38	NO
12	PIK3CA	PIK3CA	PIK3CA	6318	0.028	0.38	NO
13	PRKCA	PRKCA	PRKCA	6867	0.022	0.36	NO
14	GRB2	GRB2	GRB2	7015	0.02	0.36	NO
15	MAPK1	MAPK1	MAPK1	7941	0.01	0.32	NO
16	PLCG1	PLCG1	PLCG1	8558	0.004	0.28	NO
17	IRS1	IRS1	IRS1	8605	0.0034	0.28	NO
18	MAPK3	MAPK3	MAPK3	9063	-0.0011	0.26	NO
19	INSR	INSR	INSR	9168	-0.0021	0.25	NO
20	SRF	SRF	SRF	9701	-0.008	0.23	NO
21	HNF1A	HNF1A	HNF1A	11446	-0.03	0.14	NO
22	MAP2K1	MAP2K1	MAP2K1	12456	-0.047	0.11	NO
23	SHC1	SHC1	SHC1	12597	-0.05	0.12	NO
24	PRKCB	PRKCB	PRKCB	15931	-0.2	0.022	NO
25	SOCS1	SOCS1	SOCS1	16560	-0.26	0.096	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 TOLL PATHWAY.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TOLL 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 PENTOSE PHOSPHATE 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	PIK3CG	PIK3CG	PIK3CG	426	0.29	0.061	YES
2	PIK3R5	PIK3R5	PIK3R5	453	0.28	0.14	YES
3	EGF	EGF	EGF	456	0.28	0.22	YES
4	CASP9	CASP9	CASP9	722	0.24	0.28	YES
5	TCF7L1	TCF7L1	TCF7L1	1132	0.19	0.31	YES
6	MYC	MYC	MYC	1238	0.18	0.36	YES
7	CTNNA3	CTNNA3	CTNNA3	2353	0.11	0.33	YES
8	CDH1	CDH1	CDH1	2541	0.1	0.35	YES
9	TCF7L2	TCF7L2	TCF7L2	2685	0.097	0.37	YES
10	NRAS	NRAS	NRAS	2981	0.087	0.38	YES
11	TCF7	TCF7	TCF7	3342	0.076	0.38	YES
12	PIK3CD	PIK3CD	PIK3CD	4084	0.06	0.36	YES
13	CCND1	CCND1	CCND1	4137	0.059	0.37	YES
14	AKT2	AKT2	AKT2	4154	0.059	0.38	YES
15	AXIN2	AXIN2	AXIN2	4570	0.052	0.38	YES
16	RAF1	RAF1	RAF1	4620	0.051	0.39	YES
17	PIK3R1	PIK3R1	PIK3R1	4856	0.047	0.39	YES
18	BAD	BAD	BAD	4876	0.047	0.4	YES
19	AXIN1	AXIN1	AXIN1	5227	0.042	0.4	NO
20	SOS2	SOS2	SOS2	5632	0.036	0.38	NO
21	APC2	APC2	APC2	5795	0.034	0.38	NO
22	SOS1	SOS1	SOS1	6183	0.029	0.37	NO
23	PIK3CA	PIK3CA	PIK3CA	6318	0.028	0.37	NO
24	PIK3CB	PIK3CB	PIK3CB	6964	0.021	0.34	NO
25	GRB2	GRB2	GRB2	7015	0.02	0.35	NO
26	ARAF	ARAF	ARAF	7034	0.02	0.35	NO
27	AKT1	AKT1	AKT1	7096	0.019	0.35	NO
28	AKT3	AKT3	AKT3	7745	0.012	0.32	NO
29	EGFR	EGFR	EGFR	7826	0.011	0.32	NO
30	MAPK1	MAPK1	MAPK1	7941	0.01	0.32	NO
31	FOXO3	FOXO3	FOXO3	8124	0.0084	0.31	NO
32	PTEN	PTEN	PTEN	8349	0.0061	0.3	NO
33	MAP2K2	MAP2K2	MAP2K2	8959	-0.000042	0.27	NO
34	MAPK3	MAPK3	MAPK3	9063	-0.0011	0.26	NO
35	CTNNB1	CTNNB1	CTNNB1	9388	-0.0042	0.24	NO
36	ILK	ILK	ILK	9688	-0.0078	0.23	NO
37	PIK3R3	PIK3R3	PIK3R3	10236	-0.014	0.2	NO
38	CTNNA1	CTNNA1	CTNNA1	10812	-0.022	0.18	NO
39	KRAS	KRAS	KRAS	11016	-0.024	0.18	NO
40	PIK3R2	PIK3R2	PIK3R2	11445	-0.03	0.16	NO
41	APC	APC	APC	11937	-0.038	0.14	NO
42	GSK3B	GSK3B	GSK3B	12041	-0.04	0.15	NO
43	PDPK1	PDPK1	PDPK1	12128	-0.041	0.16	NO
44	MAP2K1	MAP2K1	MAP2K1	12456	-0.047	0.15	NO
45	MLH1	MLH1	MLH1	12554	-0.05	0.16	NO
46	TP53	TP53	TP53	12715	-0.053	0.17	NO
47	BRAF	BRAF	BRAF	12726	-0.053	0.18	NO
48	LEF1	LEF1	LEF1	13542	-0.076	0.16	NO
49	ERBB2	ERBB2	ERBB2	13687	-0.081	0.18	NO
50	CTNNA2	CTNNA2	CTNNA2	14580	-0.12	0.16	NO
51	ELK1	ELK1	ELK1	15187	-0.15	0.17	NO

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

Figure S14. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PENTOSE PHOSPHATE 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 RIBOSOME

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	PIK3CG	PIK3CG	PIK3CG	426	0.29	0.046	YES
2	PIK3R5	PIK3R5	PIK3R5	453	0.28	0.11	YES
3	CASP9	CASP9	CASP9	722	0.24	0.16	YES
4	TGFB1	TGFB1	TGFB1	1051	0.2	0.18	YES
5	TCF7L1	TCF7L1	TCF7L1	1132	0.19	0.22	YES
6	RAC2	RAC2	RAC2	1168	0.18	0.27	YES
7	MYC	MYC	MYC	1238	0.18	0.3	YES
8	RAC3	RAC3	RAC3	1635	0.14	0.32	YES
9	SMAD3	SMAD3	SMAD3	2183	0.12	0.31	YES
10	TCF7L2	TCF7L2	TCF7L2	2685	0.097	0.31	YES
11	FOS	FOS	FOS	2730	0.096	0.33	YES
12	JUN	JUN	JUN	3161	0.081	0.33	YES
13	TCF7	TCF7	TCF7	3342	0.076	0.33	YES
14	TGFBR2	TGFBR2	TGFBR2	3391	0.075	0.35	YES
15	SMAD4	SMAD4	SMAD4	3596	0.07	0.36	YES
16	PIK3CD	PIK3CD	PIK3CD	4084	0.06	0.34	YES
17	CCND1	CCND1	CCND1	4137	0.059	0.36	YES
18	AKT2	AKT2	AKT2	4154	0.059	0.37	YES
19	TGFBR1	TGFBR1	TGFBR1	4409	0.054	0.37	YES
20	AXIN2	AXIN2	AXIN2	4570	0.052	0.37	YES
21	RAF1	RAF1	RAF1	4620	0.051	0.38	YES
22	MAPK8	MAPK8	MAPK8	4679	0.05	0.39	YES
23	PIK3R1	PIK3R1	PIK3R1	4856	0.047	0.39	YES
24	BAD	BAD	BAD	4876	0.047	0.4	YES
25	RHOA	RHOA	RHOA	5039	0.044	0.4	YES
26	BCL2	BCL2	BCL2	5094	0.044	0.41	YES
27	AXIN1	AXIN1	AXIN1	5227	0.042	0.41	YES
28	SMAD2	SMAD2	SMAD2	5438	0.039	0.41	NO
29	DCC	DCC	DCC	5690	0.036	0.4	NO
30	APC2	APC2	APC2	5795	0.034	0.41	NO
31	PIK3CA	PIK3CA	PIK3CA	6318	0.028	0.38	NO
32	APPL1	APPL1	APPL1	6527	0.026	0.38	NO
33	RALGDS	RALGDS	RALGDS	6843	0.022	0.37	NO
34	PIK3CB	PIK3CB	PIK3CB	6964	0.021	0.37	NO
35	ARAF	ARAF	ARAF	7034	0.02	0.37	NO
36	AKT1	AKT1	AKT1	7096	0.019	0.37	NO
37	BAX	BAX	BAX	7157	0.018	0.37	NO
38	AKT3	AKT3	AKT3	7745	0.012	0.34	NO
39	MAPK1	MAPK1	MAPK1	7941	0.01	0.33	NO
40	MSH6	MSH6	MSH6	8303	0.0066	0.31	NO
41	RAC1	RAC1	RAC1	8507	0.0045	0.3	NO
42	MAPK3	MAPK3	MAPK3	9063	-0.0011	0.27	NO
43	CTNNB1	CTNNB1	CTNNB1	9388	-0.0042	0.26	NO
44	MAPK10	MAPK10	MAPK10	9562	-0.0062	0.25	NO
45	PIK3R3	PIK3R3	PIK3R3	10236	-0.014	0.22	NO
46	KRAS	KRAS	KRAS	11016	-0.024	0.18	NO
47	MSH3	MSH3	MSH3	11255	-0.028	0.17	NO
48	PIK3R2	PIK3R2	PIK3R2	11445	-0.03	0.17	NO
49	APC	APC	APC	11937	-0.038	0.15	NO
50	GSK3B	GSK3B	GSK3B	12041	-0.04	0.16	NO
51	MSH2	MSH2	MSH2	12337	-0.045	0.15	NO
52	MAP2K1	MAP2K1	MAP2K1	12456	-0.047	0.15	NO
53	MLH1	MLH1	MLH1	12554	-0.05	0.16	NO
54	TP53	TP53	TP53	12715	-0.053	0.16	NO
55	BRAF	BRAF	BRAF	12726	-0.053	0.18	NO
56	BIRC5	BIRC5	BIRC5	13008	-0.06	0.18	NO
57	MAPK9	MAPK9	MAPK9	13259	-0.067	0.18	NO
58	CASP3	CASP3	CASP3	13521	-0.076	0.18	NO
59	LEF1	LEF1	LEF1	13542	-0.076	0.2	NO
60	CYCS	CYCS	CYCS	14696	-0.12	0.16	NO
61	TGFB2	TGFB2	TGFB2	15081	-0.14	0.18	NO

Figure S15. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RIBOSOME.

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

genes ES table in pathway: KEGG RNA POLYMERASE

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	BLNK	BLNK	BLNK	195	0.37	0.097	YES
2	VAV1	VAV1	VAV1	353	0.31	0.18	YES
3	CD79A	CD79A	CD79A	361	0.31	0.26	YES
4	SYK	SYK	SYK	445	0.29	0.34	YES
5	BTK	BTK	BTK	511	0.27	0.42	YES
6	NFATC1	NFATC1	NFATC1	587	0.26	0.49	YES
7	NFATC2	NFATC2	NFATC2	776	0.23	0.55	YES
8	FOS	FOS	FOS	2730	0.096	0.47	NO
9	LYN	LYN	LYN	2988	0.087	0.48	NO
10	JUN	JUN	JUN	3161	0.081	0.49	NO
11	NFATC3	NFATC3	NFATC3	4551	0.052	0.43	NO
12	RAF1	RAF1	RAF1	4620	0.051	0.44	NO
13	MAPK8	MAPK8	MAPK8	4679	0.05	0.45	NO
14	PPP3CC	PPP3CC	PPP3CC	5677	0.036	0.41	NO
15	SOS1	SOS1	SOS1	6183	0.029	0.39	NO
16	PRKCA	PRKCA	PRKCA	6867	0.022	0.36	NO
17	GRB2	GRB2	GRB2	7015	0.02	0.36	NO
18	NFATC4	NFATC4	NFATC4	7599	0.014	0.33	NO
19	MAP3K1	MAP3K1	MAP3K1	8365	0.006	0.29	NO
20	RAC1	RAC1	RAC1	8507	0.0045	0.28	NO
21	PLCG1	PLCG1	PLCG1	8558	0.004	0.28	NO
22	MAPK14	MAPK14	MAPK14	8668	0.0028	0.27	NO
23	MAPK3	MAPK3	MAPK3	9063	-0.0011	0.25	NO
24	PPP3CB	PPP3CB	PPP3CB	12044	-0.04	0.1	NO
25	MAP2K1	MAP2K1	MAP2K1	12456	-0.047	0.092	NO
26	CALM2	CALM2	CALM2	12591	-0.05	0.1	NO
27	SHC1	SHC1	SHC1	12597	-0.05	0.11	NO
28	CALM3	CALM3	CALM3	12752	-0.054	0.12	NO
29	PPP3CA	PPP3CA	PPP3CA	12992	-0.06	0.12	NO
30	CALM1	CALM1	CALM1	13728	-0.082	0.11	NO
31	ELK1	ELK1	ELK1	15187	-0.15	0.071	NO
32	CD79B	CD79B	CD79B	15247	-0.15	0.11	NO
33	PRKCB	PRKCB	PRKCB	15931	-0.2	0.13	NO

Figure S17. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RNA POLYMERASE.

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

genes ES table in pathway: KEGG BASAL TRANSCRIPTION FACTORS

Table 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	LEFTY2	LEFTY2	LEFTY2	25	0.56	0.06	YES
2	BMP8B	BMP8B	BMP8B	124	0.41	0.099	YES
3	CDKN2B	CDKN2B	CDKN2B	219	0.36	0.13	YES
4	LEFTY1	LEFTY1	LEFTY1	269	0.34	0.17	YES
5	TNF	TNF	TNF	282	0.33	0.2	YES
6	ID3	ID3	ID3	300	0.32	0.24	YES
7	GDF7	GDF7	GDF7	533	0.27	0.25	YES
8	ID4	ID4	ID4	701	0.24	0.27	YES
9	BMP4	BMP4	BMP4	888	0.21	0.28	YES
10	TGFB1	TGFB1	TGFB1	1051	0.2	0.3	YES
11	SMAD6	SMAD6	SMAD6	1076	0.19	0.32	YES
12	BMPR1B	BMPR1B	BMPR1B	1109	0.19	0.33	YES
13	BMP2	BMP2	BMP2	1147	0.18	0.35	YES
14	INHBC	INHBC	INHBC	1187	0.18	0.37	YES
15	ID1	ID1	ID1	1225	0.18	0.39	YES
16	MYC	MYC	MYC	1238	0.18	0.4	YES
17	SMAD9	SMAD9	SMAD9	1472	0.16	0.41	YES
18	ROCK1	ROCK1	ROCK1	1777	0.14	0.41	YES
19	AMH	AMH	AMH	1953	0.13	0.41	YES
20	ACVR2B	ACVR2B	ACVR2B	2071	0.12	0.42	YES
21	SMAD3	SMAD3	SMAD3	2183	0.12	0.42	YES
22	BMPR1A	BMPR1A	BMPR1A	2570	0.1	0.41	NO
23	E2F5	E2F5	E2F5	2715	0.096	0.42	NO
24	SMAD7	SMAD7	SMAD7	3164	0.081	0.4	NO
25	TGFBR2	TGFBR2	TGFBR2	3391	0.075	0.4	NO
26	SMAD4	SMAD4	SMAD4	3596	0.07	0.39	NO
27	SMAD1	SMAD1	SMAD1	3943	0.063	0.38	NO
28	SP1	SP1	SP1	4039	0.061	0.38	NO
29	ZFYVE16	ZFYVE16	ZFYVE16	4369	0.055	0.37	NO
30	TGFBR1	TGFBR1	TGFBR1	4409	0.054	0.37	NO
31	RBL2	RBL2	RBL2	4521	0.052	0.37	NO
32	ID2	ID2	ID2	4861	0.047	0.36	NO
33	SMAD5	SMAD5	SMAD5	4864	0.047	0.36	NO
34	RHOA	RHOA	RHOA	5039	0.044	0.36	NO
35	LTBP1	LTBP1	LTBP1	5043	0.044	0.36	NO
36	EP300	EP300	EP300	5162	0.043	0.36	NO
37	SMAD2	SMAD2	SMAD2	5438	0.039	0.35	NO
38	TFDP1	TFDP1	TFDP1	5869	0.033	0.33	NO
39	CREBBP	CREBBP	CREBBP	6202	0.029	0.32	NO
40	SMURF2	SMURF2	SMURF2	6373	0.027	0.31	NO
41	INHBA	INHBA	INHBA	6623	0.024	0.3	NO
42	RPS6KB2	RPS6KB2	RPS6KB2	6858	0.022	0.29	NO
43	RPS6KB1	RPS6KB1	RPS6KB1	6990	0.02	0.28	NO
44	ZFYVE9	ZFYVE9	ZFYVE9	7062	0.02	0.28	NO
45	INHBB	INHBB	INHBB	7492	0.015	0.26	NO
46	INHBE	INHBE	INHBE	7610	0.014	0.26	NO
47	PPP2R1A	PPP2R1A	PPP2R1A	7729	0.012	0.25	NO
48	E2F4	E2F4	E2F4	7898	0.011	0.24	NO
49	MAPK1	MAPK1	MAPK1	7941	0.01	0.24	NO
50	PPP2CB	PPP2CB	PPP2CB	8482	0.0047	0.21	NO
51	BMPR2	BMPR2	BMPR2	8592	0.0036	0.21	NO
52	RBX1	RBX1	RBX1	8712	0.0023	0.2	NO
53	SMURF1	SMURF1	SMURF1	8715	0.0022	0.2	NO
54	MAPK3	MAPK3	MAPK3	9063	-0.0011	0.18	NO
55	SKP1	SKP1	SKP1	9374	-0.0042	0.16	NO
56	CUL1	CUL1	CUL1	9563	-0.0062	0.16	NO
57	PPP2R1B	PPP2R1B	PPP2R1B	10119	-0.013	0.13	NO
58	THBS3	THBS3	THBS3	10196	-0.014	0.12	NO
59	PPP2CA	PPP2CA	PPP2CA	11008	-0.024	0.082	NO
60	ACVR1	ACVR1	ACVR1	11795	-0.035	0.042	NO
61	ROCK2	ROCK2	ROCK2	12090	-0.04	0.03	NO
62	ACVR2A	ACVR2A	ACVR2A	12159	-0.042	0.031	NO
63	RBL1	RBL1	RBL1	12294	-0.044	0.029	NO
64	CHRD	CHRD	CHRD	12326	-0.044	0.032	NO
65	ACVRL1	ACVRL1	ACVRL1	12606	-0.051	0.022	NO
66	BMP6	BMP6	BMP6	12812	-0.055	0.017	NO
67	BMP8A	BMP8A	BMP8A	12867	-0.057	0.02	NO
68	BMP7	BMP7	BMP7	12995	-0.06	0.019	NO
69	COMP	COMP	COMP	13376	-0.071	0.0063	NO
70	TGFB3	TGFB3	TGFB3	13630	-0.079	0.00097	NO
71	NODAL	NODAL	NODAL	13886	-0.087	-0.0036	NO
72	PITX2	PITX2	PITX2	14361	-0.11	-0.018	NO
73	DCN	DCN	DCN	14972	-0.13	-0.037	NO
74	THBS4	THBS4	THBS4	15039	-0.14	-0.026	NO
75	TGFB2	TGFB2	TGFB2	15081	-0.14	-0.012	NO
76	THBS2	THBS2	THBS2	15422	-0.16	-0.014	NO
77	GDF6	GDF6	GDF6	15751	-0.18	-0.012	NO
78	BMP5	BMP5	BMP5	15863	-0.19	0.003	NO
79	THBS1	THBS1	THBS1	15990	-0.2	0.018	NO
80	GDF5	GDF5	GDF5	16024	-0.21	0.039	NO
81	FST	FST	FST	16462	-0.25	0.042	NO
82	ACVR1C	ACVR1C	ACVR1C	18095	-0.55	0.012	NO

Figure S19. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG BASAL TRANSCRIPTION FACTORS.

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.58	1.6	0.033	0.41	0.79	0.48	0.22	0.38	0.28	0.097
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.61	1.7	0.0039	1	0.46	0.52	0.21	0.41	0	0.39
BIOCARTA HIVNEF PATHWAY	57	genes.ES.table	0.48	1.6	0.025	0.46	0.63	0.47	0.29	0.34	0.28	0.12
BIOCARTA IL2RB PATHWAY	37	genes.ES.table	0.72	1.7	0.0078	0.76	0.5	0.43	0.16	0.37	0.37	0.27
BIOCARTA DEATH PATHWAY	32	genes.ES.table	0.59	1.6	0.019	0.5	0.59	0.5	0.23	0.38	0.28	0.14
BIOCARTA P38MAPK PATHWAY	39	genes.ES.table	0.41	1.5	0.064	0.34	0.88	0.38	0.25	0.29	0.24	0.05
BIOCARTA TCR PATHWAY	43	genes.ES.table	0.57	1.5	0.075	0.36	0.9	0.37	0.18	0.3	0.27	0.057
BIOCARTA TNFR1 PATHWAY	28	genes.ES.table	0.5	1.6	0.042	0.45	0.72	0.46	0.22	0.36	0.28	0.11
KEGG N GLYCAN BIOSYNTHESIS	45	genes.ES.table	0.41	1.6	0.066	0.35	0.8	0.64	0.35	0.42	0.24	0.072
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	43	genes.ES.table	0.49	1.5	0.068	0.35	0.84	0.65	0.37	0.41	0.25	0.065

genes ES table in pathway: BIOCARTA G1 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	CASP8	CASP8	CASP8	416	0.59	0.09	YES
2	FASLG	FASLG	FASLG	446	0.57	0.2	YES
3	CASP6	CASP6	CASP6	781	0.49	0.27	YES
4	FAS	FAS	FAS	1444	0.37	0.31	YES
5	CASP7	CASP7	CASP7	2103	0.29	0.33	YES
6	ARHGDIB	ARHGDIB	ARHGDIB	2769	0.23	0.34	YES
7	CASP10	CASP10	CASP10	2776	0.23	0.38	YES
8	MAP3K1	MAP3K1	MAP3K1	2822	0.23	0.42	YES
9	JUN	JUN	JUN	3096	0.2	0.44	YES
10	LMNA	LMNA	LMNA	3114	0.2	0.48	YES
11	CASP3	CASP3	CASP3	3210	0.2	0.52	YES
12	CFLAR	CFLAR	CFLAR	3435	0.18	0.54	YES
13	PTPN13	PTPN13	PTPN13	3506	0.18	0.57	YES
14	LMNB2	LMNB2	LMNB2	3735	0.16	0.59	YES
15	FADD	FADD	FADD	3888	0.16	0.61	YES
16	RB1	RB1	RB1	4840	0.11	0.58	NO
17	FAF1	FAF1	FAF1	5650	0.082	0.55	NO
18	DFFB	DFFB	DFFB	6140	0.069	0.54	NO
19	DFFA	DFFA	DFFA	7070	0.046	0.49	NO
20	PRKDC	PRKDC	PRKDC	7490	0.037	0.48	NO
21	DAXX	DAXX	DAXX	8345	0.022	0.44	NO
22	MAP3K7	MAP3K7	MAP3K7	8356	0.022	0.44	NO
23	PAK2	PAK2	PAK2	8810	0.014	0.42	NO
24	PARP1	PARP1	PARP1	8820	0.014	0.42	NO
25	PAK1	PAK1	PAK1	9938	-0.0062	0.36	NO
26	SPTAN1	SPTAN1	SPTAN1	12566	-0.054	0.22	NO
27	RIPK2	RIPK2	RIPK2	14059	-0.091	0.16	NO
28	MAP2K4	MAP2K4	MAP2K4	14740	-0.12	0.15	NO
29	MAPK8	MAPK8	MAPK8	16711	-0.26	0.088	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 G1 PATHWAY.

Figure S22. 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 FAS PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SOCS3	SOCS3	SOCS3	106	0.75	0.082	YES
2	IL2RG	IL2RG	IL2RG	163	0.71	0.16	YES
3	IL2RB	IL2RB	IL2RB	181	0.69	0.24	YES
4	SOCS1	SOCS1	SOCS1	190	0.69	0.32	YES
5	FASLG	FASLG	FASLG	446	0.57	0.38	YES
6	JAK3	JAK3	JAK3	628	0.52	0.43	YES
7	IKZF3	IKZF3	IKZF3	729	0.5	0.48	YES
8	PIK3CG	PIK3CG	PIK3CG	812	0.48	0.53	YES
9	NMI	NMI	NMI	958	0.45	0.58	YES
10	IL2RA	IL2RA	IL2RA	1335	0.39	0.6	YES
11	FAS	FAS	FAS	1444	0.37	0.64	YES
12	STAT5A	STAT5A	STAT5A	1833	0.32	0.66	YES
13	PTPN6	PTPN6	PTPN6	2047	0.29	0.68	YES
14	SYK	SYK	SYK	2460	0.26	0.69	YES
15	SHC1	SHC1	SHC1	2731	0.23	0.7	YES
16	FOS	FOS	FOS	2844	0.22	0.72	YES
17	CFLAR	CFLAR	CFLAR	3435	0.18	0.71	NO
18	BCL2L1	BCL2L1	BCL2L1	7668	0.034	0.48	NO
19	AKT1	AKT1	AKT1	7750	0.032	0.48	NO
20	PPIA	PPIA	PPIA	7946	0.029	0.47	NO
21	GRB2	GRB2	GRB2	8816	0.014	0.43	NO
22	BAD	BAD	BAD	8879	0.013	0.43	NO
23	JAK1	JAK1	JAK1	8974	0.011	0.42	NO
24	CBL	CBL	CBL	9423	0.0034	0.4	NO
25	RPS6KB1	RPS6KB1	RPS6KB1	10036	-0.008	0.36	NO
26	BCL2	BCL2	BCL2	10077	-0.0086	0.36	NO
27	RAF1	RAF1	RAF1	10575	-0.017	0.34	NO
28	PIK3CA	PIK3CA	PIK3CA	10748	-0.02	0.33	NO
29	SOS1	SOS1	SOS1	10917	-0.023	0.32	NO
30	STAT5B	STAT5B	STAT5B	11367	-0.03	0.3	NO
31	HRAS	HRAS	HRAS	11935	-0.041	0.28	NO
32	CRKL	CRKL	CRKL	12454	-0.051	0.26	NO
33	MAPK1	MAPK1	MAPK1	12544	-0.053	0.26	NO
34	IRS1	IRS1	IRS1	13583	-0.077	0.21	NO
35	MAPK3	MAPK3	MAPK3	13812	-0.084	0.21	NO
36	PIK3R1	PIK3R1	PIK3R1	15698	-0.17	0.12	NO
37	MYC	MYC	MYC	15730	-0.17	0.14	NO

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

Figure S24. 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 HIVNEF PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	SOCS3	SOCS3	SOCS3	106	0.75	0.064	YES
2	SOCS1	SOCS1	SOCS1	190	0.69	0.12	YES
3	CDC20	CDC20	CDC20	228	0.66	0.18	YES
4	UBE2C	UBE2C	UBE2C	981	0.44	0.18	YES
5	DDB2	DDB2	DDB2	1204	0.41	0.21	YES
6	BIRC3	BIRC3	BIRC3	1765	0.33	0.21	YES
7	BRCA1	BRCA1	BRCA1	2030	0.3	0.22	YES
8	CUL7	CUL7	CUL7	2511	0.25	0.22	YES
9	MAP3K1	MAP3K1	MAP3K1	2822	0.23	0.22	YES
10	UBE2S	UBE2S	UBE2S	2960	0.22	0.24	YES
11	FBXO4	FBXO4	FBXO4	3044	0.21	0.25	YES
12	UBA7	UBA7	UBA7	3045	0.21	0.27	YES
13	SKP2	SKP2	SKP2	3100	0.2	0.29	YES
14	MID1	MID1	MID1	4040	0.15	0.25	NO
15	UBE2J2	UBE2J2	UBE2J2	4882	0.11	0.21	NO
16	CDC26	CDC26	CDC26	4998	0.1	0.22	NO
17	MDM2	MDM2	MDM2	5153	0.099	0.22	NO
18	NEDD4	NEDD4	NEDD4	5465	0.088	0.21	NO
19	UBA6	UBA6	UBA6	5859	0.076	0.19	NO
20	UBE2F	UBE2F	UBE2F	6134	0.069	0.18	NO
21	CUL4A	CUL4A	CUL4A	6135	0.069	0.19	NO
22	ANAPC10	ANAPC10	ANAPC10	6190	0.067	0.2	NO
23	UBE3C	UBE3C	UBE3C	6334	0.064	0.19	NO
24	PML	PML	PML	6454	0.06	0.19	NO
25	UBE2A	UBE2A	UBE2A	6510	0.059	0.19	NO
26	PIAS3	PIAS3	PIAS3	6518	0.058	0.2	NO
27	CUL1	CUL1	CUL1	6540	0.058	0.2	NO
28	UBE2NL	UBE2NL	UBE2NL	6570	0.057	0.21	NO
29	UBE2D4	UBE2D4	UBE2D4	6614	0.056	0.21	NO
30	SAE1	SAE1	SAE1	6694	0.055	0.21	NO
31	TRIP12	TRIP12	TRIP12	6836	0.052	0.21	NO
32	ANAPC4	ANAPC4	ANAPC4	6843	0.051	0.21	NO
33	UBE2L6	UBE2L6	UBE2L6	6916	0.05	0.21	NO
34	UBE2H	UBE2H	UBE2H	7101	0.045	0.21	NO
35	UBE2I	UBE2I	UBE2I	7145	0.044	0.21	NO
36	SMURF1	SMURF1	SMURF1	7333	0.04	0.2	NO
37	ANAPC7	ANAPC7	ANAPC7	7421	0.039	0.2	NO
38	BIRC2	BIRC2	BIRC2	7455	0.038	0.2	NO
39	RNF7	RNF7	RNF7	7465	0.038	0.21	NO
40	UBE2E3	UBE2E3	UBE2E3	7508	0.037	0.21	NO
41	CDC34	CDC34	CDC34	7587	0.036	0.21	NO
42	UBE2Z	UBE2Z	UBE2Z	7780	0.032	0.2	NO
43	ERCC8	ERCC8	ERCC8	7787	0.032	0.2	NO
44	UBE2M	UBE2M	UBE2M	7911	0.029	0.2	NO
45	CDC23	CDC23	CDC23	7924	0.029	0.2	NO
46	ANAPC11	ANAPC11	ANAPC11	7933	0.029	0.2	NO
47	CDC16	CDC16	CDC16	7967	0.028	0.2	NO
48	ITCH	ITCH	ITCH	8168	0.025	0.19	NO
49	UBA3	UBA3	UBA3	8238	0.023	0.19	NO
50	PIAS2	PIAS2	PIAS2	8398	0.021	0.18	NO
51	TRAF6	TRAF6	TRAF6	8458	0.02	0.18	NO
52	UBE2D3	UBE2D3	UBE2D3	8525	0.019	0.18	NO
53	FANCL	FANCL	FANCL	8573	0.018	0.18	NO
54	RFWD2	RFWD2	RFWD2	8581	0.018	0.18	NO
55	UBA2	UBA2	UBA2	8615	0.017	0.18	NO
56	ANAPC1	ANAPC1	ANAPC1	8678	0.016	0.18	NO
57	WWP1	WWP1	WWP1	8944	0.012	0.17	NO
58	PIAS4	PIAS4	PIAS4	9005	0.011	0.16	NO
59	FZR1	FZR1	FZR1	9090	0.0093	0.16	NO
60	SYVN1	SYVN1	SYVN1	9197	0.0076	0.16	NO
61	UBE2J1	UBE2J1	UBE2J1	9359	0.0046	0.15	NO
62	UBE2N	UBE2N	UBE2N	9361	0.0045	0.15	NO
63	CBL	CBL	CBL	9423	0.0034	0.14	NO
64	CDC27	CDC27	CDC27	9438	0.0031	0.14	NO
65	UBE2B	UBE2B	UBE2B	9581	0.00036	0.14	NO
66	FBXW8	FBXW8	FBXW8	9595	0.000032	0.14	NO
67	UBE2D2	UBE2D2	UBE2D2	9623	-0.00037	0.13	NO
68	UBA1	UBA1	UBA1	9701	-0.0016	0.13	NO
69	CUL4B	CUL4B	CUL4B	9789	-0.0034	0.13	NO
70	TCEB2	TCEB2	TCEB2	9837	-0.0044	0.12	NO
71	PPIL2	PPIL2	PPIL2	9851	-0.0047	0.12	NO
72	VHL	VHL	VHL	9943	-0.0062	0.12	NO
73	UBE2L3	UBE2L3	UBE2L3	9988	-0.0072	0.12	NO
74	UBE3A	UBE3A	UBE3A	10042	-0.0081	0.12	NO
75	UBE4B	UBE4B	UBE4B	10143	-0.0098	0.11	NO
76	UBE2K	UBE2K	UBE2K	10237	-0.012	0.11	NO
77	TCEB1	TCEB1	TCEB1	10256	-0.012	0.11	NO
78	UBE3B	UBE3B	UBE3B	10364	-0.014	0.1	NO
79	NEDD4L	NEDD4L	NEDD4L	10391	-0.014	0.1	NO
80	KEAP1	KEAP1	KEAP1	10407	-0.014	0.1	NO
81	SMURF2	SMURF2	SMURF2	10427	-0.015	0.1	NO
82	UBE2E1	UBE2E1	UBE2E1	10473	-0.015	0.1	NO
83	AIRE	AIRE	AIRE	10502	-0.016	0.1	NO
84	UBOX5	UBOX5	UBOX5	10561	-0.017	0.1	NO
85	CUL5	CUL5	CUL5	10587	-0.017	0.1	NO
86	CUL3	CUL3	CUL3	10595	-0.017	0.1	NO
87	ANAPC5	ANAPC5	ANAPC5	10611	-0.018	0.1	NO
88	UBE2Q1	UBE2Q1	UBE2Q1	10824	-0.021	0.092	NO
89	PIAS1	PIAS1	PIAS1	10849	-0.022	0.093	NO
90	UBE2G1	UBE2G1	UBE2G1	10850	-0.022	0.095	NO
91	UBE4A	UBE4A	UBE4A	10989	-0.024	0.09	NO
92	UBE2G2	UBE2G2	UBE2G2	11118	-0.026	0.085	NO
93	RBX1	RBX1	RBX1	11264	-0.028	0.08	NO
94	XIAP	XIAP	XIAP	11277	-0.028	0.082	NO
95	SKP1	SKP1	SKP1	11432	-0.031	0.076	NO
96	MGRN1	MGRN1	MGRN1	11448	-0.032	0.078	NO
97	UBR5	UBR5	UBR5	11548	-0.033	0.076	NO
98	UBE2D1	UBE2D1	UBE2D1	11560	-0.034	0.079	NO
99	ANAPC2	ANAPC2	ANAPC2	11563	-0.034	0.082	NO
100	DDB1	DDB1	DDB1	11603	-0.034	0.083	NO
101	UBE2Q2	UBE2Q2	UBE2Q2	11692	-0.036	0.081	NO
102	ANAPC13	ANAPC13	ANAPC13	11920	-0.041	0.072	NO
103	UBE2W	UBE2W	UBE2W	12010	-0.042	0.072	NO
104	SIAH1	SIAH1	SIAH1	12114	-0.044	0.07	NO
105	UBE2R2	UBE2R2	UBE2R2	12139	-0.045	0.073	NO
106	KLHL13	KLHL13	KLHL13	12205	-0.046	0.074	NO
107	RHOBTB2	RHOBTB2	RHOBTB2	12370	-0.049	0.069	NO
108	RCHY1	RCHY1	RCHY1	12554	-0.054	0.064	NO
109	HUWE1	HUWE1	HUWE1	12735	-0.057	0.06	NO
110	HERC4	HERC4	HERC4	12793	-0.058	0.062	NO
111	PRPF19	PRPF19	PRPF19	12801	-0.058	0.067	NO
112	HERC2	HERC2	HERC2	12944	-0.061	0.065	NO
113	TRIM32	TRIM32	TRIM32	13040	-0.064	0.066	NO
114	BIRC6	BIRC6	BIRC6	13225	-0.068	0.062	NO
115	STUB1	STUB1	STUB1	13395	-0.072	0.059	NO
116	TRIM37	TRIM37	TRIM37	13717	-0.08	0.049	NO
117	HERC3	HERC3	HERC3	13937	-0.087	0.045	NO
118	FBXW11	FBXW11	FBXW11	13957	-0.087	0.052	NO
119	FBXW7	FBXW7	FBXW7	13991	-0.088	0.059	NO
120	NHLRC1	NHLRC1	NHLRC1	14023	-0.09	0.066	NO
121	WWP2	WWP2	WWP2	14108	-0.092	0.069	NO
122	CUL2	CUL2	CUL2	14141	-0.093	0.076	NO
123	UBE2O	UBE2O	UBE2O	14355	-0.1	0.074	NO
124	DET1	DET1	DET1	14514	-0.11	0.075	NO
125	CBLB	CBLB	CBLB	14834	-0.12	0.069	NO
126	HERC1	HERC1	HERC1	15117	-0.13	0.066	NO
127	KLHL9	KLHL9	KLHL9	15126	-0.13	0.078	NO
128	FBXO2	FBXO2	FBXO2	15278	-0.14	0.083	NO
129	UBE2E2	UBE2E2	UBE2E2	15641	-0.16	0.078	NO
130	PARK2	PARK2	PARK2	16479	-0.23	0.054	NO
131	UBE2QL1	UBE2QL1	UBE2QL1	17948	-0.5	0.02	NO

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

Figure S26. 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 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	CASP8	CASP8	CASP8	416	0.59	0.094	YES
2	CASP6	CASP6	CASP6	781	0.49	0.17	YES
3	BIRC3	BIRC3	BIRC3	1765	0.33	0.18	YES
4	TNFRSF10A	TNFRSF10A	TNFRSF10A	1774	0.33	0.25	YES
5	CASP7	CASP7	CASP7	2103	0.29	0.29	YES
6	TRADD	TRADD	TRADD	2301	0.27	0.33	YES
7	TNFSF10	TNFSF10	TNFSF10	2357	0.26	0.38	YES
8	CASP10	CASP10	CASP10	2776	0.23	0.4	YES
9	LMNA	LMNA	LMNA	3114	0.2	0.42	YES
10	CASP3	CASP3	CASP3	3210	0.2	0.46	YES
11	RIPK1	RIPK1	RIPK1	3344	0.19	0.49	YES
12	CFLAR	CFLAR	CFLAR	3435	0.18	0.52	YES
13	MAP3K14	MAP3K14	MAP3K14	3490	0.18	0.55	YES
14	FADD	FADD	FADD	3888	0.16	0.56	YES
15	TNFRSF10B	TNFRSF10B	TNFRSF10B	3986	0.15	0.58	YES
16	NFKB1	NFKB1	NFKB1	4288	0.14	0.59	YES
17	TNFRSF25	TNFRSF25	TNFRSF25	5536	0.086	0.54	NO
18	TNFSF12	TNFSF12	TNFSF12	5616	0.083	0.56	NO
19	TRAF2	TRAF2	TRAF2	5787	0.078	0.56	NO
20	DFFB	DFFB	DFFB	6140	0.069	0.56	NO
21	DFFA	DFFA	DFFA	7070	0.046	0.51	NO
22	BIRC2	BIRC2	BIRC2	7455	0.038	0.5	NO
23	CYCS	CYCS	CYCS	7462	0.038	0.51	NO
24	APAF1	APAF1	APAF1	8866	0.013	0.43	NO
25	RELA	RELA	RELA	9589	0.00021	0.39	NO
26	BCL2	BCL2	BCL2	10077	-0.0086	0.37	NO
27	XIAP	XIAP	XIAP	11277	-0.028	0.31	NO
28	CHUK	CHUK	CHUK	11912	-0.041	0.28	NO
29	SPTAN1	SPTAN1	SPTAN1	12566	-0.054	0.26	NO
30	NFKBIA	NFKBIA	NFKBIA	12695	-0.056	0.26	NO
31	GAS2	GAS2	GAS2	12764	-0.058	0.27	NO
32	CASP9	CASP9	CASP9	15770	-0.17	0.14	NO

Figure S27. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA IL2RB PATHWAY.

Figure S28. 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 DEATH PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CASP8	CASP8	CASP8	416	0.59	0.05	YES
2	CASP6	CASP6	CASP6	781	0.49	0.091	YES
3	FAS	FAS	FAS	1444	0.37	0.1	YES
4	BIRC3	BIRC3	BIRC3	1765	0.33	0.12	YES
5	TNFRSF1A	TNFRSF1A	TNFRSF1A	1846	0.32	0.16	YES
6	CASP7	CASP7	CASP7	2103	0.29	0.18	YES
7	LMNB1	LMNB1	LMNB1	2219	0.28	0.21	YES
8	TRADD	TRADD	TRADD	2301	0.27	0.24	YES
9	TRAF1	TRAF1	TRAF1	2449	0.26	0.26	YES
10	TNFRSF1B	TNFRSF1B	TNFRSF1B	2732	0.23	0.28	YES
11	ARHGDIB	ARHGDIB	ARHGDIB	2769	0.23	0.3	YES
12	MAP3K1	MAP3K1	MAP3K1	2822	0.23	0.33	YES
13	LMNA	LMNA	LMNA	3114	0.2	0.34	YES
14	CASP3	CASP3	CASP3	3210	0.2	0.36	YES
15	PRKCD	PRKCD	PRKCD	3270	0.19	0.38	YES
16	RIPK1	RIPK1	RIPK1	3344	0.19	0.4	YES
17	CFLAR	CFLAR	CFLAR	3435	0.18	0.41	YES
18	MAP3K14	MAP3K14	MAP3K14	3490	0.18	0.43	YES
19	LMNB2	LMNB2	LMNB2	3735	0.16	0.44	YES
20	FADD	FADD	FADD	3888	0.16	0.45	YES
21	CASP2	CASP2	CASP2	4039	0.15	0.46	YES
22	NFKB1	NFKB1	NFKB1	4288	0.14	0.46	YES
23	PSEN2	PSEN2	PSEN2	4489	0.12	0.47	YES
24	RB1	RB1	RB1	4840	0.11	0.46	YES
25	GSN	GSN	GSN	4884	0.11	0.47	YES
26	MDM2	MDM2	MDM2	5153	0.099	0.47	YES
27	CDK11A	CDK11A	CDK11A	5258	0.095	0.48	YES
28	TRAF2	TRAF2	TRAF2	5787	0.078	0.46	NO
29	DFFB	DFFB	DFFB	6140	0.069	0.45	NO
30	CDK11B	CDK11B	CDK11B	6480	0.059	0.44	NO
31	TNF	TNF	TNF	6515	0.058	0.44	NO
32	DFFA	DFFA	DFFA	7070	0.046	0.42	NO
33	ACTG1	ACTG1	ACTG1	7236	0.042	0.41	NO
34	BIRC2	BIRC2	BIRC2	7455	0.038	0.41	NO
35	CYCS	CYCS	CYCS	7462	0.038	0.41	NO
36	PRKDC	PRKDC	PRKDC	7490	0.037	0.41	NO
37	DAXX	DAXX	DAXX	8345	0.022	0.37	NO
38	PAK2	PAK2	PAK2	8810	0.014	0.35	NO
39	PARP1	PARP1	PARP1	8820	0.014	0.35	NO
40	APAF1	APAF1	APAF1	8866	0.013	0.35	NO
41	RASA1	RASA1	RASA1	9355	0.0047	0.32	NO
42	RELA	RELA	RELA	9589	0.00021	0.31	NO
43	PSEN1	PSEN1	PSEN1	9637	-0.00064	0.31	NO
44	MAP2K7	MAP2K7	MAP2K7	9917	-0.0058	0.29	NO
45	BCL2	BCL2	BCL2	10077	-0.0086	0.28	NO
46	XIAP	XIAP	XIAP	11277	-0.028	0.22	NO
47	CHUK	CHUK	CHUK	11912	-0.041	0.19	NO
48	PTK2	PTK2	PTK2	12229	-0.047	0.18	NO
49	SPTAN1	SPTAN1	SPTAN1	12566	-0.054	0.17	NO
50	NFKBIA	NFKBIA	NFKBIA	12695	-0.056	0.17	NO
51	CRADD	CRADD	CRADD	13043	-0.064	0.16	NO
52	NUMA1	NUMA1	NUMA1	14596	-0.11	0.086	NO
53	BAG4	BAG4	BAG4	15269	-0.14	0.067	NO
54	MAP3K5	MAP3K5	MAP3K5	15390	-0.15	0.079	NO
55	CASP9	CASP9	CASP9	15770	-0.17	0.079	NO
56	BID	BID	BID	16446	-0.23	0.07	NO
57	MAPK8	MAPK8	MAPK8	16711	-0.26	0.088	NO

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

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

genes ES table in pathway: BIOCARTA P38MAPK PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CLCF1	CLCF1	CLCF1	11	0.97	0.036	YES
2	LIF	LIF	LIF	33	0.87	0.069	YES
3	CISH	CISH	CISH	39	0.86	0.1	YES
4	SOCS3	SOCS3	SOCS3	106	0.75	0.13	YES
5	IL2RG	IL2RG	IL2RG	163	0.71	0.15	YES
6	IL2RB	IL2RB	IL2RB	181	0.69	0.18	YES
7	SOCS1	SOCS1	SOCS1	190	0.69	0.2	YES
8	IL15	IL15	IL15	200	0.68	0.23	YES
9	IL7	IL7	IL7	252	0.65	0.25	YES
10	CTF1	CTF1	CTF1	372	0.6	0.27	YES
11	IL13RA2	IL13RA2	IL13RA2	388	0.6	0.29	YES
12	OSMR	OSMR	OSMR	395	0.6	0.31	YES
13	SPRY1	SPRY1	SPRY1	519	0.55	0.32	YES
14	SPRY4	SPRY4	SPRY4	593	0.53	0.34	YES
15	JAK3	JAK3	JAK3	628	0.52	0.36	YES
16	SOCS2	SOCS2	SOCS2	656	0.51	0.38	YES
17	CSF2RB	CSF2RB	CSF2RB	717	0.5	0.39	YES
18	PIK3CG	PIK3CG	PIK3CG	812	0.48	0.41	YES
19	IL28RA	IL28RA	IL28RA	870	0.47	0.42	YES
20	IL6	IL6	IL6	899	0.46	0.44	YES
21	IL7R	IL7R	IL7R	979	0.44	0.45	YES
22	IL10	IL10	IL10	1162	0.42	0.46	YES
23	IL12RB1	IL12RB1	IL12RB1	1247	0.4	0.47	YES
24	IL2RA	IL2RA	IL2RA	1335	0.39	0.48	YES
25	PIK3R5	PIK3R5	PIK3R5	1681	0.34	0.47	YES
26	IL22RA1	IL22RA1	IL22RA1	1787	0.32	0.48	YES
27	STAT5A	STAT5A	STAT5A	1833	0.32	0.49	YES
28	OSM	OSM	OSM	1965	0.3	0.49	YES
29	CSF3R	CSF3R	CSF3R	1971	0.3	0.5	YES
30	IL15RA	IL15RA	IL15RA	2003	0.3	0.51	YES
31	PTPN6	PTPN6	PTPN6	2047	0.29	0.52	YES
32	IL10RA	IL10RA	IL10RA	2270	0.27	0.52	YES
33	IL13RA1	IL13RA1	IL13RA1	2461	0.26	0.52	YES
34	PIM1	PIM1	PIM1	2480	0.25	0.53	YES
35	SPRY2	SPRY2	SPRY2	2639	0.24	0.53	YES
36	IL5RA	IL5RA	IL5RA	2707	0.24	0.54	YES
37	PIK3CD	PIK3CD	PIK3CD	2709	0.24	0.54	YES
38	IL4R	IL4R	IL4R	2713	0.24	0.55	YES
39	SPRED2	SPRED2	SPRED2	2786	0.23	0.56	YES
40	IFNGR2	IFNGR2	IFNGR2	2803	0.23	0.56	YES
41	IL24	IL24	IL24	2804	0.23	0.57	YES
42	STAT1	STAT1	STAT1	2869	0.22	0.58	YES
43	CNTF	CNTF	CNTF	2878	0.22	0.59	YES
44	IL21R	IL21R	IL21R	2938	0.22	0.59	YES
45	CSF2RA	CSF2RA	CSF2RA	3001	0.21	0.6	YES
46	IL10RB	IL10RB	IL10RB	3417	0.18	0.58	NO
47	PRLR	PRLR	PRLR	3806	0.16	0.57	NO
48	SPRED1	SPRED1	SPRED1	3868	0.16	0.57	NO
49	IL6R	IL6R	IL6R	3905	0.15	0.57	NO
50	EPO	EPO	EPO	3983	0.15	0.57	NO
51	LEP	LEP	LEP	4000	0.15	0.58	NO
52	STAT6	STAT6	STAT6	4091	0.14	0.58	NO
53	MPL	MPL	MPL	4286	0.14	0.57	NO
54	IL20RA	IL20RA	IL20RA	4488	0.12	0.57	NO
55	AKT2	AKT2	AKT2	4573	0.12	0.57	NO
56	STAT3	STAT3	STAT3	4582	0.12	0.57	NO
57	PIK3R3	PIK3R3	PIK3R3	4859	0.11	0.56	NO
58	IL23A	IL23A	IL23A	5243	0.096	0.54	NO
59	STAT2	STAT2	STAT2	5323	0.093	0.54	NO
60	IFNAR2	IFNAR2	IFNAR2	5367	0.092	0.54	NO
61	JAK2	JAK2	JAK2	5414	0.09	0.55	NO
62	IRF9	IRF9	IRF9	5718	0.08	0.53	NO
63	CCND2	CCND2	CCND2	5739	0.08	0.53	NO
64	IFNE	IFNE	IFNE	5945	0.074	0.52	NO
65	TYK2	TYK2	TYK2	6176	0.067	0.52	NO
66	PIAS3	PIAS3	PIAS3	6518	0.058	0.5	NO
67	IL11	IL11	IL11	6696	0.055	0.49	NO
68	IFNAR1	IFNAR1	IFNAR1	6884	0.05	0.48	NO
69	SOCS4	SOCS4	SOCS4	6969	0.048	0.48	NO
70	IFNGR1	IFNGR1	IFNGR1	6986	0.048	0.48	NO
71	TPO	TPO	TPO	7380	0.04	0.46	NO
72	CCND1	CCND1	CCND1	7386	0.039	0.46	NO
73	BCL2L1	BCL2L1	BCL2L1	7668	0.034	0.45	NO
74	AKT1	AKT1	AKT1	7750	0.032	0.44	NO
75	PIAS2	PIAS2	PIAS2	8398	0.021	0.41	NO
76	IL6ST	IL6ST	IL6ST	8688	0.016	0.39	NO
77	IL3RA	IL3RA	IL3RA	8729	0.015	0.39	NO
78	STAM2	STAM2	STAM2	8762	0.015	0.39	NO
79	GRB2	GRB2	GRB2	8816	0.014	0.39	NO
80	JAK1	JAK1	JAK1	8974	0.011	0.38	NO
81	PIAS4	PIAS4	PIAS4	9005	0.011	0.38	NO
82	IFNA13	IFNA13	IFNA13	9011	0.011	0.38	NO
83	TSLP	TSLP	TSLP	9074	0.0096	0.38	NO
84	CBL	CBL	CBL	9423	0.0034	0.36	NO
85	GHR	GHR	GHR	9802	-0.0038	0.34	NO
86	IL13	IL13	IL13	10157	-0.01	0.32	NO
87	PIK3CA	PIK3CA	PIK3CA	10748	-0.02	0.29	NO
88	EPOR	EPOR	EPOR	10815	-0.021	0.28	NO
89	SOCS5	SOCS5	SOCS5	10820	-0.021	0.28	NO
90	PIAS1	PIAS1	PIAS1	10849	-0.022	0.28	NO
91	SOS1	SOS1	SOS1	10917	-0.023	0.28	NO
92	CSF3	CSF3	CSF3	11007	-0.024	0.28	NO
93	CCND3	CCND3	CCND3	11343	-0.03	0.26	NO
94	STAT5B	STAT5B	STAT5B	11367	-0.03	0.26	NO
95	PTPN11	PTPN11	PTPN11	11698	-0.036	0.24	NO
96	IL20RB	IL20RB	IL20RB	11848	-0.039	0.24	NO
97	LEPR	LEPR	LEPR	12126	-0.044	0.22	NO
98	STAT4	STAT4	STAT4	12306	-0.048	0.21	NO
99	PIK3R2	PIK3R2	PIK3R2	12448	-0.051	0.21	NO
100	IFNW1	IFNW1	IFNW1	12697	-0.056	0.2	NO
101	SPRY3	SPRY3	SPRY3	13030	-0.063	0.18	NO
102	IL5	IL5	IL5	13085	-0.065	0.18	NO
103	CREBBP	CREBBP	CREBBP	13179	-0.066	0.18	NO
104	SOS2	SOS2	SOS2	13664	-0.079	0.15	NO
105	EP300	EP300	EP300	13750	-0.082	0.15	NO
106	LIFR	LIFR	LIFR	14123	-0.092	0.14	NO
107	PIK3CB	PIK3CB	PIK3CB	14310	-0.099	0.13	NO
108	IFNA21	IFNA21	IFNA21	14371	-0.1	0.13	NO
109	IL11RA	IL11RA	IL11RA	14595	-0.11	0.12	NO
110	STAM	STAM	STAM	14736	-0.12	0.12	NO
111	CBLB	CBLB	CBLB	14834	-0.12	0.12	NO
112	PIK3R1	PIK3R1	PIK3R1	15698	-0.17	0.077	NO
113	MYC	MYC	MYC	15730	-0.17	0.082	NO
114	AKT3	AKT3	AKT3	15834	-0.18	0.083	NO
115	IL12RB2	IL12RB2	IL12RB2	16158	-0.2	0.073	NO
116	SOCS7	SOCS7	SOCS7	16213	-0.2	0.078	NO
117	IL12A	IL12A	IL12A	16663	-0.25	0.063	NO
118	CNTFR	CNTFR	CNTFR	16686	-0.25	0.071	NO
119	IL9	IL9	IL9	17853	-0.47	0.025	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: BIOCARTA P38MAPK PATHWAY.

Figure S32. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA P38MAPK 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 TCR 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	CASP8	CASP8	CASP8	416	0.59	0.11	YES
2	TNFRSF1A	TNFRSF1A	TNFRSF1A	1846	0.32	0.11	YES
3	LMNB1	LMNB1	LMNB1	2219	0.28	0.15	YES
4	TRADD	TRADD	TRADD	2301	0.27	0.21	YES
5	ARHGDIB	ARHGDIB	ARHGDIB	2769	0.23	0.23	YES
6	MAP3K1	MAP3K1	MAP3K1	2822	0.23	0.28	YES
7	JUN	JUN	JUN	3096	0.2	0.31	YES
8	LMNA	LMNA	LMNA	3114	0.2	0.36	YES
9	CASP3	CASP3	CASP3	3210	0.2	0.4	YES
10	RIPK1	RIPK1	RIPK1	3344	0.19	0.44	YES
11	LMNB2	LMNB2	LMNB2	3735	0.16	0.45	YES
12	FADD	FADD	FADD	3888	0.16	0.48	YES
13	CASP2	CASP2	CASP2	4039	0.15	0.5	YES
14	RB1	RB1	RB1	4840	0.11	0.48	NO
15	DFFB	DFFB	DFFB	6140	0.069	0.43	NO
16	TNF	TNF	TNF	6515	0.058	0.42	NO
17	DFFA	DFFA	DFFA	7070	0.046	0.4	NO
18	PRKDC	PRKDC	PRKDC	7490	0.037	0.39	NO
19	MAP3K7	MAP3K7	MAP3K7	8356	0.022	0.35	NO
20	PAK2	PAK2	PAK2	8810	0.014	0.32	NO
21	PARP1	PARP1	PARP1	8820	0.014	0.33	NO
22	PAK1	PAK1	PAK1	9938	-0.0062	0.27	NO
23	SPTAN1	SPTAN1	SPTAN1	12566	-0.054	0.14	NO
24	CRADD	CRADD	CRADD	13043	-0.064	0.12	NO
25	MAP2K4	MAP2K4	MAP2K4	14740	-0.12	0.059	NO
26	BAG4	BAG4	BAG4	15269	-0.14	0.063	NO
27	MADD	MADD	MADD	16129	-0.2	0.061	NO
28	MAPK8	MAPK8	MAPK8	16711	-0.26	0.088	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: BIOCARTA TCR PATHWAY.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TCR PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA TNFR1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	COL4A1	COL4A1	COL4A1	267	0.64	0.033	YES
2	LAMB4	LAMB4	LAMB4	312	0.62	0.076	YES
3	COL4A2	COL4A2	COL4A2	530	0.55	0.1	YES
4	PIK3CG	PIK3CG	PIK3CG	812	0.48	0.12	YES
5	LAMB1	LAMB1	LAMB1	877	0.46	0.16	YES
6	CDK2	CDK2	CDK2	1226	0.4	0.16	YES
7	ITGA2	ITGA2	ITGA2	1232	0.4	0.2	YES
8	TRAF5	TRAF5	TRAF5	1297	0.39	0.22	YES
9	LAMA2	LAMA2	LAMA2	1430	0.37	0.24	YES
10	E2F2	E2F2	E2F2	1447	0.37	0.27	YES
11	LAMC1	LAMC1	LAMC1	1484	0.36	0.29	YES
12	PIK3R5	PIK3R5	PIK3R5	1681	0.34	0.3	YES
13	BIRC3	BIRC3	BIRC3	1765	0.33	0.32	YES
14	LAMC3	LAMC3	LAMC3	1828	0.32	0.34	YES
15	ITGA3	ITGA3	ITGA3	1980	0.3	0.36	YES
16	LAMC2	LAMC2	LAMC2	2191	0.28	0.37	YES
17	COL4A6	COL4A6	COL4A6	2279	0.27	0.38	YES
18	FN1	FN1	FN1	2423	0.26	0.39	YES
19	CDK6	CDK6	CDK6	2434	0.26	0.41	YES
20	TRAF1	TRAF1	TRAF1	2449	0.26	0.43	YES
21	CKS1B	CKS1B	CKS1B	2524	0.25	0.44	YES
22	PIK3CD	PIK3CD	PIK3CD	2709	0.24	0.45	YES
23	LAMA4	LAMA4	LAMA4	2743	0.23	0.47	YES
24	SKP2	SKP2	SKP2	3100	0.2	0.46	YES
25	LAMB2	LAMB2	LAMB2	3142	0.2	0.48	YES
26	ITGB1	ITGB1	ITGB1	3285	0.19	0.48	YES
27	CCNE1	CCNE1	CCNE1	3347	0.19	0.49	YES
28	CDK4	CDK4	CDK4	3984	0.15	0.47	NO
29	PTGS2	PTGS2	PTGS2	4151	0.14	0.47	NO
30	NFKB1	NFKB1	NFKB1	4288	0.14	0.47	NO
31	AKT2	AKT2	AKT2	4573	0.12	0.46	NO
32	RB1	RB1	RB1	4840	0.11	0.46	NO
33	PIK3R3	PIK3R3	PIK3R3	4859	0.11	0.47	NO
34	ITGAV	ITGAV	ITGAV	5485	0.088	0.44	NO
35	TP53	TP53	TP53	5518	0.086	0.44	NO
36	IKBKB	IKBKB	IKBKB	5599	0.084	0.44	NO
37	TRAF2	TRAF2	TRAF2	5787	0.078	0.44	NO
38	ITGA6	ITGA6	ITGA6	5870	0.076	0.44	NO
39	CCNE2	CCNE2	CCNE2	6043	0.071	0.44	NO
40	RARB	RARB	RARB	6132	0.069	0.44	NO
41	PIAS3	PIAS3	PIAS3	6518	0.058	0.42	NO
42	LAMA5	LAMA5	LAMA5	6612	0.056	0.42	NO
43	TRAF4	TRAF4	TRAF4	7133	0.045	0.39	NO
44	CCND1	CCND1	CCND1	7386	0.039	0.38	NO
45	E2F3	E2F3	E2F3	7411	0.039	0.38	NO
46	BIRC2	BIRC2	BIRC2	7455	0.038	0.38	NO
47	CYCS	CYCS	CYCS	7462	0.038	0.39	NO
48	BCL2L1	BCL2L1	BCL2L1	7668	0.034	0.38	NO
49	NOS2	NOS2	NOS2	7741	0.032	0.38	NO
50	AKT1	AKT1	AKT1	7750	0.032	0.38	NO
51	PIAS2	PIAS2	PIAS2	8398	0.021	0.34	NO
52	TRAF6	TRAF6	TRAF6	8458	0.02	0.34	NO
53	APAF1	APAF1	APAF1	8866	0.013	0.32	NO
54	PIAS4	PIAS4	PIAS4	9005	0.011	0.32	NO
55	RELA	RELA	RELA	9589	0.00021	0.28	NO
56	FHIT	FHIT	FHIT	9880	-0.0051	0.27	NO
57	IKBKG	IKBKG	IKBKG	10070	-0.0085	0.26	NO
58	BCL2	BCL2	BCL2	10077	-0.0086	0.26	NO
59	LAMA1	LAMA1	LAMA1	10273	-0.012	0.25	NO
60	LAMB3	LAMB3	LAMB3	10309	-0.013	0.25	NO
61	PIK3CA	PIK3CA	PIK3CA	10748	-0.02	0.22	NO
62	PIAS1	PIAS1	PIAS1	10849	-0.022	0.22	NO
63	RXRA	RXRA	RXRA	11052	-0.025	0.21	NO
64	MAX	MAX	MAX	11108	-0.026	0.21	NO
65	XIAP	XIAP	XIAP	11277	-0.028	0.2	NO
66	CHUK	CHUK	CHUK	11912	-0.041	0.17	NO
67	PTK2	PTK2	PTK2	12229	-0.047	0.16	NO
68	TRAF3	TRAF3	TRAF3	12388	-0.05	0.15	NO
69	PIK3R2	PIK3R2	PIK3R2	12448	-0.051	0.15	NO
70	NFKBIA	NFKBIA	NFKBIA	12695	-0.056	0.14	NO
71	CDKN1B	CDKN1B	CDKN1B	13146	-0.066	0.12	NO
72	PTEN	PTEN	PTEN	13570	-0.077	0.11	NO
73	RXRB	RXRB	RXRB	14223	-0.096	0.078	NO
74	PIK3CB	PIK3CB	PIK3CB	14310	-0.099	0.081	NO
75	CDKN2B	CDKN2B	CDKN2B	14752	-0.12	0.065	NO
76	COL4A4	COL4A4	COL4A4	15481	-0.15	0.036	NO
77	PIK3R1	PIK3R1	PIK3R1	15698	-0.17	0.037	NO
78	MYC	MYC	MYC	15730	-0.17	0.047	NO
79	CASP9	CASP9	CASP9	15770	-0.17	0.058	NO
80	AKT3	AKT3	AKT3	15834	-0.18	0.067	NO
81	LAMA3	LAMA3	LAMA3	16335	-0.22	0.056	NO
82	ITGA2B	ITGA2B	ITGA2B	16920	-0.28	0.044	NO
83	RXRG	RXRG	RXRG	17744	-0.43	0.031	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: BIOCARTA TNFR1 PATHWAY.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG N GLYCAN BIOSYNTHESIS

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	SLC11A1	SLC11A1	SLC11A1	248	0.65	0.034	YES
2	AP1S3	AP1S3	AP1S3	314	0.62	0.074	YES
3	CTSW	CTSW	CTSW	345	0.61	0.12	YES
4	LAMP3	LAMP3	LAMP3	850	0.47	0.12	YES
5	TCIRG1	TCIRG1	TCIRG1	1453	0.37	0.12	YES
6	ACP5	ACP5	ACP5	1503	0.36	0.14	YES
7	CTSC	CTSC	CTSC	1563	0.35	0.16	YES
8	CTSS	CTSS	CTSS	1807	0.32	0.17	YES
9	CTSK	CTSK	CTSK	1964	0.3	0.18	YES
10	GLA	GLA	GLA	2278	0.27	0.19	YES
11	CTSZ	CTSZ	CTSZ	2363	0.26	0.2	YES
12	CD68	CD68	CD68	2583	0.24	0.21	YES
13	HEXB	HEXB	HEXB	2682	0.24	0.22	YES
14	FUCA1	FUCA1	FUCA1	2846	0.22	0.23	YES
15	NPC2	NPC2	NPC2	2867	0.22	0.24	YES
16	LAPTM5	LAPTM5	LAPTM5	2873	0.22	0.26	YES
17	GUSB	GUSB	GUSB	2874	0.22	0.27	YES
18	DNASE2B	DNASE2B	DNASE2B	2894	0.22	0.29	YES
19	NAGA	NAGA	NAGA	2935	0.22	0.3	YES
20	SUMF1	SUMF1	SUMF1	3349	0.19	0.29	YES
21	MAN2B1	MAN2B1	MAN2B1	3362	0.18	0.3	YES
22	CD63	CD63	CD63	3505	0.18	0.31	YES
23	GALNS	GALNS	GALNS	3525	0.18	0.32	YES
24	GNS	GNS	GNS	3530	0.17	0.33	YES
25	ARSA	ARSA	ARSA	3535	0.17	0.34	YES
26	CD164	CD164	CD164	3593	0.17	0.35	YES
27	AGA	AGA	AGA	3632	0.17	0.36	YES
28	CTSA	CTSA	CTSA	3714	0.16	0.37	YES
29	GLB1	GLB1	GLB1	4003	0.15	0.37	YES
30	SGSH	SGSH	SGSH	4278	0.14	0.36	YES
31	AP1S2	AP1S2	AP1S2	4402	0.13	0.36	YES
32	CTSB	CTSB	CTSB	4563	0.12	0.36	YES
33	CTSL2	CTSL2	CTSL2	4570	0.12	0.37	YES
34	CTSL1	CTSL1	CTSL1	4638	0.12	0.38	YES
35	GALC	GALC	GALC	4713	0.12	0.38	YES
36	CLN5	CLN5	CLN5	4805	0.11	0.38	YES
37	AP4M1	AP4M1	AP4M1	4874	0.11	0.39	YES
38	PLA2G15	PLA2G15	PLA2G15	4967	0.11	0.39	YES
39	IDUA	IDUA	IDUA	5056	0.1	0.39	YES
40	DNASE2	DNASE2	DNASE2	5064	0.1	0.4	YES
41	NAGLU	NAGLU	NAGLU	5136	0.1	0.4	YES
42	HEXA	HEXA	HEXA	5161	0.099	0.41	YES
43	CTNS	CTNS	CTNS	5378	0.091	0.4	YES
44	AP4B1	AP4B1	AP4B1	5431	0.09	0.41	YES
45	AP3B1	AP3B1	AP3B1	5645	0.083	0.4	YES
46	LAPTM4A	LAPTM4A	LAPTM4A	5706	0.081	0.4	YES
47	ATP6V0B	ATP6V0B	ATP6V0B	5770	0.079	0.41	YES
48	ATP6V0D2	ATP6V0D2	ATP6V0D2	5827	0.077	0.41	YES
49	MANBA	MANBA	MANBA	5830	0.077	0.42	YES
50	CTSD	CTSD	CTSD	5920	0.075	0.42	YES
51	LAMP1	LAMP1	LAMP1	5939	0.074	0.42	YES
52	ABCB9	ABCB9	ABCB9	5997	0.072	0.42	YES
53	GAA	GAA	GAA	6003	0.072	0.43	YES
54	CTSH	CTSH	CTSH	6037	0.071	0.43	YES
55	GGA2	GGA2	GGA2	6082	0.07	0.43	YES
56	CLN3	CLN3	CLN3	6343	0.063	0.42	NO
57	ATP6V0A2	ATP6V0A2	ATP6V0A2	6374	0.062	0.42	NO
58	GBA	GBA	GBA	6415	0.061	0.43	NO
59	LGMN	LGMN	LGMN	6660	0.056	0.42	NO
60	AP1M1	AP1M1	AP1M1	6710	0.054	0.42	NO
61	SMPD1	SMPD1	SMPD1	6782	0.052	0.42	NO
62	M6PR	M6PR	M6PR	6925	0.049	0.42	NO
63	LAMP2	LAMP2	LAMP2	6932	0.049	0.42	NO
64	PPT1	PPT1	PPT1	6963	0.049	0.42	NO
65	MCOLN1	MCOLN1	MCOLN1	7055	0.046	0.42	NO
66	SORT1	SORT1	SORT1	7092	0.046	0.42	NO
67	NEU1	NEU1	NEU1	7238	0.042	0.42	NO
68	SLC17A5	SLC17A5	SLC17A5	7276	0.042	0.42	NO
69	MFSD8	MFSD8	MFSD8	7342	0.04	0.42	NO
70	AP3S1	AP3S1	AP3S1	7399	0.039	0.42	NO
71	ACP2	ACP2	ACP2	7477	0.038	0.41	NO
72	ASAH1	ASAH1	ASAH1	7599	0.035	0.41	NO
73	IGF2R	IGF2R	IGF2R	7956	0.028	0.39	NO
74	AP4E1	AP4E1	AP4E1	8018	0.028	0.39	NO
75	NAGPA	NAGPA	NAGPA	8232	0.024	0.38	NO
76	ARSB	ARSB	ARSB	8433	0.02	0.37	NO
77	TPP1	TPP1	TPP1	8479	0.02	0.37	NO
78	LIPA	LIPA	LIPA	8700	0.016	0.36	NO
79	NAPSA	NAPSA	NAPSA	8731	0.015	0.36	NO
80	ATP6AP1	ATP6AP1	ATP6AP1	8787	0.014	0.36	NO
81	AP1B1	AP1B1	AP1B1	8922	0.012	0.35	NO
82	AP1G1	AP1G1	AP1G1	9434	0.0031	0.32	NO
83	CLTC	CLTC	CLTC	9537	0.0012	0.32	NO
84	LAPTM4B	LAPTM4B	LAPTM4B	9571	0.00056	0.32	NO
85	GM2A	GM2A	GM2A	9678	-0.0013	0.31	NO
86	PSAP	PSAP	PSAP	9796	-0.0036	0.3	NO
87	AP3D1	AP3D1	AP3D1	9878	-0.0051	0.3	NO
88	ATP6V0A4	ATP6V0A4	ATP6V0A4	10097	-0.009	0.29	NO
89	ENTPD4	ENTPD4	ENTPD4	10188	-0.01	0.28	NO
90	AP1S1	AP1S1	AP1S1	10193	-0.011	0.28	NO
91	GNPTAB	GNPTAB	GNPTAB	10862	-0.022	0.25	NO
92	SCARB2	SCARB2	SCARB2	10866	-0.022	0.25	NO
93	GGA3	GGA3	GGA3	11069	-0.025	0.24	NO
94	GNPTG	GNPTG	GNPTG	11083	-0.026	0.24	NO
95	NPC1	NPC1	NPC1	11365	-0.03	0.23	NO
96	CLTA	CLTA	CLTA	11897	-0.04	0.2	NO
97	CTSO	CTSO	CTSO	11917	-0.041	0.2	NO
98	AP3S2	AP3S2	AP3S2	12024	-0.043	0.2	NO
99	ATP6V0C	ATP6V0C	ATP6V0C	12124	-0.044	0.2	NO
100	AP3M1	AP3M1	AP3M1	12183	-0.046	0.2	NO
101	PPT2	PPT2	PPT2	12507	-0.052	0.18	NO
102	ATP6V0D1	ATP6V0D1	ATP6V0D1	12667	-0.056	0.18	NO
103	ABCA2	ABCA2	ABCA2	13201	-0.067	0.16	NO
104	CLTB	CLTB	CLTB	13436	-0.073	0.15	NO
105	GGA1	GGA1	GGA1	13454	-0.074	0.15	NO
106	SLC11A2	SLC11A2	SLC11A2	13536	-0.076	0.15	NO
107	AP3M2	AP3M2	AP3M2	13592	-0.077	0.16	NO
108	HYAL1	HYAL1	HYAL1	13784	-0.083	0.15	NO
109	ATP6V1H	ATP6V1H	ATP6V1H	14134	-0.093	0.14	NO
110	CTSF	CTSF	CTSF	14154	-0.093	0.14	NO
111	ARSG	ARSG	ARSG	14534	-0.11	0.13	NO
112	IDS	IDS	IDS	14856	-0.12	0.12	NO
113	ATP6V0A1	ATP6V0A1	ATP6V0A1	15141	-0.14	0.12	NO
114	AP1M2	AP1M2	AP1M2	15322	-0.14	0.12	NO
115	AP4S1	AP4S1	AP4S1	15569	-0.16	0.12	NO
116	CLTCL1	CLTCL1	CLTCL1	16084	-0.19	0.1	NO
117	AP3B2	AP3B2	AP3B2	17024	-0.3	0.071	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 N GLYCAN BIOSYNTHESIS.

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

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

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	TGFB2	TGFB2	TGFB2	198	0.68	0.15	YES
2	CDK1	CDK1	CDK1	1183	0.41	0.19	YES
3	CDK2	CDK2	CDK2	1226	0.4	0.28	YES
4	CDK6	CDK6	CDK6	2434	0.26	0.28	YES
5	CDC25A	CDC25A	CDC25A	2754	0.23	0.32	YES
6	TGFB1	TGFB1	TGFB1	3031	0.21	0.35	YES
7	HDAC1	HDAC1	HDAC1	3043	0.21	0.4	YES
8	SKP2	SKP2	SKP2	3100	0.2	0.44	YES
9	CCNE1	CCNE1	CCNE1	3347	0.19	0.48	YES
10	CCNA1	CCNA1	CCNA1	3395	0.18	0.52	YES
11	CDK4	CDK4	CDK4	3984	0.15	0.52	YES
12	CDKN1A	CDKN1A	CDKN1A	4030	0.15	0.55	YES
13	TGFB3	TGFB3	TGFB3	4053	0.15	0.58	YES
14	RB1	RB1	RB1	4840	0.11	0.57	NO
15	TP53	TP53	TP53	5518	0.086	0.55	NO
16	ATR	ATR	ATR	5676	0.082	0.56	NO
17	DHFR	DHFR	DHFR	5796	0.078	0.57	NO
18	CCND1	CCND1	CCND1	7386	0.039	0.5	NO
19	SMAD3	SMAD3	SMAD3	10159	-0.01	0.35	NO
20	ATM	ATM	ATM	11382	-0.03	0.29	NO
21	ABL1	ABL1	ABL1	11477	-0.032	0.29	NO
22	SMAD4	SMAD4	SMAD4	11948	-0.041	0.27	NO
23	CDKN2A	CDKN2A	CDKN2A	11960	-0.042	0.28	NO
24	TFDP1	TFDP1	TFDP1	12007	-0.042	0.29	NO
25	GSK3B	GSK3B	GSK3B	12398	-0.05	0.28	NO
26	CDKN1B	CDKN1B	CDKN1B	13146	-0.066	0.26	NO
27	CDKN2B	CDKN2B	CDKN2B	14752	-0.12	0.2	NO

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

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

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 CARM ER PATHWAY	34	genes.ES.table	0.45	1.5	0.057	0.75	0.82	0.47	0.24	0.36	0.52	0.25
BIOCARTA ERK PATHWAY	26	genes.ES.table	0.19	0.64	0.92	1	1	0.19	0.14	0.17	1	0.95
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.19	0.71	0.82	1	1	1	0.81	0.19	1	0.95
KEGG GALACTOSE METABOLISM	25	genes.ES.table	0.34	1.1	0.38	1	1	0.08	0.0026	0.08	1	0.94
KEGG OXIDATIVE PHOSPHORYLATION	114	genes.ES.table	0.13	0.47	0.93	0.99	1	0.035	0.049	0.034	0.99	0.44
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.16	0.72	0.81	1	1	0.28	0.26	0.21	1	0.97
KEGG SPHINGOLIPID METABOLISM	37	genes.ES.table	0.28	0.85	0.67	1	1	0.27	0.18	0.22	1	0.65
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.14	0.57	0.97	1	1	1	0.86	0.14	1	0.99
KEGG RIBOSOME	85	genes.ES.table	0.49	1.2	0.35	1	1	0.69	0.34	0.46	1	0.84
KEGG RNA DEGRADATION	56	genes.ES.table	0.25	1	0.4	1	1	0.41	0.32	0.28	1	0.88

genes ES table in pathway: BIOCARTA CARM ER 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	GRIP1	GRIP1	GRIP1	204	0.46	0.14	YES
2	NR0B1	NR0B1	NR0B1	622	0.3	0.21	YES
3	HDAC9	HDAC9	HDAC9	1131	0.21	0.25	YES
4	HDAC4	HDAC4	HDAC4	1158	0.2	0.31	YES
5	CCND1	CCND1	CCND1	2100	0.13	0.3	YES
6	HDAC10	HDAC10	HDAC10	2586	0.11	0.31	YES
7	GTF2F1	GTF2F1	GTF2F1	2888	0.098	0.32	YES
8	TBP	TBP	TBP	3053	0.094	0.35	YES
9	CREBBP	CREBBP	CREBBP	3465	0.083	0.35	YES
10	HDAC6	HDAC6	HDAC6	3839	0.075	0.35	YES
11	PHB2	PHB2	PHB2	4040	0.071	0.37	YES
12	PELP1	PELP1	PELP1	4220	0.067	0.38	YES
13	ERCC3	ERCC3	ERCC3	4295	0.066	0.4	YES
14	HDAC8	HDAC8	HDAC8	4352	0.064	0.41	YES
15	NCOR2	NCOR2	NCOR2	4361	0.064	0.43	YES
16	EP300	EP300	EP300	4410	0.063	0.45	YES
17	MED1	MED1	MED1	5554	0.045	0.4	NO
18	HDAC2	HDAC2	HDAC2	5670	0.043	0.41	NO
19	POLR2A	POLR2A	POLR2A	6011	0.038	0.4	NO
20	HDAC5	HDAC5	HDAC5	6255	0.035	0.4	NO
21	GTF2E1	GTF2E1	GTF2E1	6527	0.03	0.4	NO
22	PPARGC1A	PPARGC1A	PPARGC1A	8041	0.0082	0.32	NO
23	GTF2A1	GTF2A1	GTF2A1	8172	0.0063	0.31	NO
24	ESR1	ESR1	ESR1	9142	-0.0082	0.26	NO
25	SRA1	SRA1	SRA1	9177	-0.0088	0.26	NO
26	NRIP1	NRIP1	NRIP1	9584	-0.015	0.24	NO
27	HDAC11	HDAC11	HDAC11	10125	-0.026	0.22	NO
28	HDAC7	HDAC7	HDAC7	10142	-0.027	0.23	NO
29	HDAC3	HDAC3	HDAC3	10512	-0.035	0.22	NO
30	HIST2H3C	HIST2H3C	HIST2H3C	12130	-0.08	0.16	NO
31	BRCA1	BRCA1	BRCA1	12340	-0.087	0.18	NO
32	SPEN	SPEN	SPEN	12359	-0.088	0.2	NO
33	CARM1	CARM1	CARM1	12363	-0.088	0.23	NO
34	HDAC1	HDAC1	HDAC1	16417	-0.29	0.1	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 CARM ER PATHWAY.

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

genes ES table in pathway: BIOCARTA ERK PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	RPL21	RPL21	RPL21	89	0.55	0.092	YES
2	RPL22L1	RPL22L1	RPL22L1	472	0.34	0.13	YES
3	RPL36A	RPL36A	RPL36A	1787	0.15	0.083	YES
4	RPS28	RPS28	RPS28	1895	0.14	0.1	YES
5	RPL10L	RPL10L	RPL10L	2297	0.12	0.1	YES
6	RPS13	RPS13	RPS13	2581	0.11	0.1	YES
7	RPL36AL	RPL36AL	RPL36AL	2756	0.1	0.11	YES
8	RPS12	RPS12	RPS12	2792	0.1	0.13	YES
9	RPL26L1	RPL26L1	RPL26L1	2903	0.098	0.14	YES
10	RPS27	RPS27	RPS27	2904	0.098	0.16	YES
11	RPL6	RPL6	RPL6	3050	0.094	0.17	YES
12	RPL7	RPL7	RPL7	3083	0.093	0.18	YES
13	RPS26	RPS26	RPS26	3239	0.089	0.19	YES
14	RPL39	RPL39	RPL39	3305	0.087	0.2	YES
15	RPL13	RPL13	RPL13	3462	0.083	0.2	YES
16	RPL4	RPL4	RPL4	3476	0.082	0.22	YES
17	RPS24	RPS24	RPS24	3616	0.079	0.22	YES
18	RPL3	RPL3	RPL3	3685	0.078	0.24	YES
19	RPL24	RPL24	RPL24	3733	0.077	0.25	YES
20	RPS23	RPS23	RPS23	3746	0.077	0.26	YES
21	RPS25	RPS25	RPS25	3815	0.076	0.27	YES
22	RPS6	RPS6	RPS6	3903	0.074	0.28	YES
23	RPS20	RPS20	RPS20	3971	0.072	0.28	YES
24	RPL10A	RPL10A	RPL10A	4013	0.071	0.3	YES
25	RSL24D1	RSL24D1	RSL24D1	4113	0.069	0.3	YES
26	RPL10	RPL10	RPL10	4117	0.069	0.31	YES
27	RPL18A	RPL18A	RPL18A	4119	0.069	0.33	YES
28	RPL34	RPL34	RPL34	4166	0.068	0.34	YES
29	RPLP2	RPLP2	RPLP2	4224	0.067	0.34	YES
30	RPS4X	RPS4X	RPS4X	4324	0.065	0.35	YES
31	RPL29	RPL29	RPL29	4332	0.065	0.36	YES
32	RPS3	RPS3	RPS3	4342	0.065	0.37	YES
33	RPSA	RPSA	RPSA	4600	0.06	0.37	YES
34	RPL37	RPL37	RPL37	4624	0.06	0.38	YES
35	RPS3A	RPS3A	RPS3A	4629	0.06	0.39	YES
36	RPL23	RPL23	RPL23	4718	0.058	0.39	YES
37	RPS29	RPS29	RPS29	4725	0.058	0.4	YES
38	RPL23A	RPL23A	RPL23A	4778	0.057	0.41	YES
39	RPL31	RPL31	RPL31	4894	0.055	0.41	YES
40	RPL15	RPL15	RPL15	4959	0.054	0.42	YES
41	RPL17	RPL17	RPL17	5111	0.052	0.42	YES
42	RPS15A	RPS15A	RPS15A	5137	0.051	0.43	YES
43	RPL9	RPL9	RPL9	5143	0.051	0.44	YES
44	RPS21	RPS21	RPS21	5257	0.049	0.44	YES
45	RPL37A	RPL37A	RPL37A	5326	0.048	0.44	YES
46	RPL27A	RPL27A	RPL27A	5332	0.048	0.45	YES
47	RPL32	RPL32	RPL32	5347	0.048	0.46	YES
48	RPS27L	RPS27L	RPS27L	5356	0.048	0.47	YES
49	RPS27A	RPS27A	RPS27A	5361	0.048	0.48	YES
50	FAU	FAU	FAU	5474	0.046	0.48	YES
51	RPLP0	RPLP0	RPLP0	5495	0.046	0.48	YES
52	RPL7A	RPL7A	RPL7A	5732	0.042	0.48	YES
53	RPS18	RPS18	RPS18	5788	0.041	0.48	YES
54	RPL30	RPL30	RPL30	5821	0.041	0.49	YES
55	RPL19	RPL19	RPL19	5890	0.04	0.49	YES
56	RPL14	RPL14	RPL14	5992	0.038	0.49	YES
57	RPL8	RPL8	RPL8	6198	0.036	0.49	YES
58	RPL35A	RPL35A	RPL35A	6227	0.035	0.49	YES
59	RPS7	RPS7	RPS7	6322	0.034	0.49	YES
60	RPL36	RPL36	RPL36	6452	0.032	0.49	NO
61	RPL41	RPL41	RPL41	6658	0.028	0.48	NO
62	RPL12	RPL12	RPL12	6915	0.025	0.48	NO
63	RPS15	RPS15	RPS15	7010	0.023	0.47	NO
64	RPL38	RPL38	RPL38	7047	0.023	0.48	NO
65	RPL26	RPL26	RPL26	7108	0.022	0.48	NO
66	RPL27	RPL27	RPL27	7445	0.017	0.46	NO
67	RPS10	RPS10	RPS10	8349	0.0035	0.41	NO
68	RPL35	RPL35	RPL35	8767	-0.0022	0.39	NO
69	RPS17	RPS17	RPS17	8771	-0.0022	0.39	NO
70	RPS9	RPS9	RPS9	8848	-0.0035	0.39	NO
71	UBA52	UBA52	UBA52	8913	-0.0046	0.38	NO
72	RPLP1	RPLP1	RPLP1	9068	-0.007	0.38	NO
73	RPS2	RPS2	RPS2	9110	-0.0077	0.38	NO
74	RPS5	RPS5	RPS5	10862	-0.043	0.29	NO
75	RPL5	RPL5	RPL5	10881	-0.043	0.29	NO
76	RPS4Y1	RPS4Y1	RPS4Y1	10992	-0.046	0.3	NO
77	RPL22	RPL22	RPL22	11093	-0.049	0.3	NO
78	RPS11	RPS11	RPS11	11317	-0.055	0.3	NO
79	RPL13A	RPL13A	RPL13A	11388	-0.057	0.3	NO
80	RPL28	RPL28	RPL28	11558	-0.061	0.3	NO
81	RPS8	RPS8	RPS8	11577	-0.062	0.31	NO
82	RPS16	RPS16	RPS16	11916	-0.072	0.31	NO
83	RPS19	RPS19	RPS19	11935	-0.073	0.32	NO
84	MRPL13	MRPL13	MRPL13	12184	-0.081	0.32	NO
85	RPL11	RPL11	RPL11	12482	-0.093	0.32	NO

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

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

genes ES table in pathway: BIOCARTA RACCYCD 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	G6PC2	G6PC2	G6PC2	2	0.91	0.2	YES
2	G6PC	G6PC	G6PC	48	0.62	0.34	YES
3	PFKM	PFKM	PFKM	3572	0.08	0.17	NO
4	GANC	GANC	GANC	4341	0.065	0.14	NO
5	GALK1	GALK1	GALK1	5651	0.044	0.078	NO
6	GALT	GALT	GALT	6275	0.034	0.051	NO
7	GALK2	GALK2	GALK2	8194	0.0059	-0.052	NO
8	GAA	GAA	GAA	8403	0.0028	-0.063	NO
9	PFKL	PFKL	PFKL	9832	-0.02	-0.14	NO
10	PGM2	PGM2	PGM2	9876	-0.021	-0.13	NO
11	AKR1B1	AKR1B1	AKR1B1	9948	-0.022	-0.13	NO
12	PFKP	PFKP	PFKP	10344	-0.031	-0.15	NO
13	HK1	HK1	HK1	10382	-0.032	-0.14	NO
14	GLB1	GLB1	GLB1	10564	-0.036	-0.14	NO
15	GLA	GLA	GLA	11460	-0.058	-0.18	NO
16	LCT	LCT	LCT	11685	-0.065	-0.18	NO
17	PGM1	PGM1	PGM1	12350	-0.088	-0.2	NO
18	B4GALT2	B4GALT2	B4GALT2	13773	-0.14	-0.24	NO
19	UGP2	UGP2	UGP2	13857	-0.15	-0.21	NO
20	HK3	HK3	HK3	14221	-0.16	-0.19	NO
21	GALE	GALE	GALE	14978	-0.2	-0.19	NO
22	B4GALT1	B4GALT1	B4GALT1	15183	-0.21	-0.16	NO
23	MGAM	MGAM	MGAM	16531	-0.3	-0.16	NO
24	HK2	HK2	HK2	17329	-0.4	-0.12	NO
25	GCK	GCK	GCK	18277	-0.75	0.0021	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 RACCYCD PATHWAY.

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

genes ES table in pathway: KEGG GALACTOSE METABOLISM

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	ZCCHC7	ZCCHC7	ZCCHC7	2071	0.13	-0.07	YES
2	CNOT6	CNOT6	CNOT6	2397	0.12	-0.05	YES
3	DIS3	DIS3	DIS3	2423	0.12	-0.013	YES
4	EXOSC4	EXOSC4	EXOSC4	2434	0.11	0.024	YES
5	DCPS	DCPS	DCPS	2585	0.11	0.052	YES
6	EDC3	EDC3	EDC3	2862	0.099	0.07	YES
7	SKIV2L	SKIV2L	SKIV2L	2867	0.099	0.1	YES
8	EXOSC2	EXOSC2	EXOSC2	3276	0.088	0.11	YES
9	EXOSC6	EXOSC6	EXOSC6	3656	0.079	0.11	YES
10	NAA38	NAA38	NAA38	3864	0.074	0.13	YES
11	LSM7	LSM7	LSM7	4302	0.066	0.13	YES
12	CNOT2	CNOT2	CNOT2	4415	0.063	0.14	YES
13	EXOSC8	EXOSC8	EXOSC8	4453	0.063	0.16	YES
14	PAPD7	PAPD7	PAPD7	4858	0.056	0.16	YES
15	LSM2	LSM2	LSM2	4948	0.054	0.17	YES
16	MPHOSPH6	MPHOSPH6	MPHOSPH6	5093	0.052	0.18	YES
17	XRN1	XRN1	XRN1	5216	0.05	0.19	YES
18	SKIV2L2	SKIV2L2	SKIV2L2	5225	0.05	0.2	YES
19	WDR61	WDR61	WDR61	5524	0.045	0.2	YES
20	LSM3	LSM3	LSM3	5572	0.044	0.22	YES
21	HSPA9	HSPA9	HSPA9	5702	0.043	0.22	YES
22	EXOSC9	EXOSC9	EXOSC9	5742	0.042	0.23	YES
23	CNOT10	CNOT10	CNOT10	5779	0.042	0.25	YES
24	EDC4	EDC4	EDC4	6269	0.034	0.23	NO
25	EXOSC7	EXOSC7	EXOSC7	6396	0.032	0.23	NO
26	ENO3	ENO3	ENO3	6478	0.031	0.24	NO
27	PNPT1	PNPT1	PNPT1	6781	0.027	0.23	NO
28	PATL1	PATL1	PATL1	6938	0.024	0.23	NO
29	EXOSC3	EXOSC3	EXOSC3	6941	0.024	0.24	NO
30	HSPD1	HSPD1	HSPD1	7098	0.022	0.24	NO
31	PAPOLG	PAPOLG	PAPOLG	7385	0.018	0.23	NO
32	CNOT6L	CNOT6L	CNOT6L	7425	0.018	0.23	NO
33	C1D	C1D	C1D	7468	0.017	0.24	NO
34	RQCD1	RQCD1	RQCD1	7515	0.016	0.24	NO
35	LSM5	LSM5	LSM5	7526	0.016	0.24	NO
36	DDX6	DDX6	DDX6	7656	0.014	0.24	NO
37	DCP1A	DCP1A	DCP1A	7817	0.012	0.24	NO
38	CNOT1	CNOT1	CNOT1	7934	0.0098	0.23	NO
39	XRN2	XRN2	XRN2	8122	0.0071	0.22	NO
40	ENO2	ENO2	ENO2	8288	0.0045	0.22	NO
41	LSM6	LSM6	LSM6	8779	-0.0024	0.19	NO
42	EXOSC1	EXOSC1	EXOSC1	8792	-0.0026	0.19	NO
43	CNOT7	CNOT7	CNOT7	8976	-0.0056	0.18	NO
44	LSM4	LSM4	LSM4	9568	-0.015	0.16	NO
45	PAPOLA	PAPOLA	PAPOLA	9709	-0.018	0.15	NO
46	CNOT4	CNOT4	CNOT4	9790	-0.019	0.16	NO
47	TTC37	TTC37	TTC37	9826	-0.02	0.16	NO
48	LSM1	LSM1	LSM1	9932	-0.022	0.16	NO
49	PARN	PARN	PARN	10302	-0.03	0.15	NO
50	DCP2	DCP2	DCP2	10838	-0.042	0.14	NO
51	DCP1B	DCP1B	DCP1B	11714	-0.065	0.11	NO
52	CNOT3	CNOT3	CNOT3	12819	-0.1	0.085	NO
53	ENO1	ENO1	ENO1	13381	-0.13	0.096	NO
54	EXOSC5	EXOSC5	EXOSC5	13434	-0.13	0.14	NO
55	EXOSC10	EXOSC10	EXOSC10	14543	-0.18	0.14	NO
56	PAPOLB	PAPOLB	PAPOLB	15308	-0.22	0.16	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 GALACTOSE METABOLISM.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GALACTOSE 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 OXIDATIVE PHOSPHORYLATION

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	MYH6	MYH6	MYH6	8	0.81	0.072	YES
2	CACNG2	CACNG2	CACNG2	15	0.76	0.14	YES
3	CACNG1	CACNG1	CACNG1	67	0.59	0.19	YES
4	MYH7	MYH7	MYH7	102	0.54	0.24	YES
5	FXYD2	FXYD2	FXYD2	235	0.44	0.27	YES
6	CACNG4	CACNG4	CACNG4	314	0.39	0.3	YES
7	TNNI3	TNNI3	TNNI3	393	0.36	0.33	YES
8	CACNA2D2	CACNA2D2	CACNA2D2	830	0.25	0.32	YES
9	COX4I2	COX4I2	COX4I2	893	0.24	0.34	YES
10	CACNG8	CACNG8	CACNG8	1172	0.2	0.34	YES
11	CACNA2D1	CACNA2D1	CACNA2D1	1783	0.15	0.32	NO
12	CACNG6	CACNG6	CACNG6	1788	0.15	0.34	NO
13	TPM2	TPM2	TPM2	1975	0.14	0.34	NO
14	CACNA1D	CACNA1D	CACNA1D	2234	0.12	0.34	NO
15	CACNA2D3	CACNA2D3	CACNA2D3	2702	0.1	0.32	NO
16	CACNA1C	CACNA1C	CACNA1C	3237	0.089	0.3	NO
17	SLC8A1	SLC8A1	SLC8A1	4493	0.062	0.24	NO
18	CACNB4	CACNB4	CACNB4	4660	0.059	0.23	NO
19	COX7A2	COX7A2	COX7A2	5125	0.051	0.21	NO
20	ATP2A2	ATP2A2	ATP2A2	5127	0.051	0.22	NO
21	COX8A	COX8A	COX8A	5567	0.045	0.2	NO
22	UQCRC1	UQCRC1	UQCRC1	5616	0.044	0.2	NO
23	UQCRB	UQCRB	UQCRB	5677	0.043	0.2	NO
24	CYC1	CYC1	CYC1	5911	0.04	0.19	NO
25	COX7B	COX7B	COX7B	6012	0.038	0.18	NO
26	COX4I1	COX4I1	COX4I1	6538	0.03	0.16	NO
27	ATP1B3	ATP1B3	ATP1B3	6607	0.029	0.16	NO
28	COX7C	COX7C	COX7C	7088	0.022	0.13	NO
29	COX5B	COX5B	COX5B	7284	0.019	0.12	NO
30	ATP1A3	ATP1A3	ATP1A3	7465	0.017	0.12	NO
31	MYL3	MYL3	MYL3	8427	0.0025	0.064	NO
32	CACNG7	CACNG7	CACNG7	8607	-0.00022	0.054	NO
33	UQCR10	UQCR10	UQCR10	8851	-0.0035	0.041	NO
34	ATP1B2	ATP1B2	ATP1B2	9189	-0.0089	0.024	NO
35	UQCRQ	UQCRQ	UQCRQ	9515	-0.014	0.007	NO
36	COX5A	COX5A	COX5A	9641	-0.016	0.0016	NO
37	COX6A1	COX6A1	COX6A1	9648	-0.016	0.0027	NO
38	COX7A2L	COX7A2L	COX7A2L	9859	-0.02	-0.007	NO
39	UQCR11	UQCR11	UQCR11	9962	-0.023	-0.01	NO
40	SLC9A6	SLC9A6	SLC9A6	10007	-0.024	-0.011	NO
41	COX6C	COX6C	COX6C	10473	-0.034	-0.033	NO
42	TPM4	TPM4	TPM4	10571	-0.036	-0.035	NO
43	CACNB1	CACNB1	CACNB1	10748	-0.04	-0.041	NO
44	TPM1	TPM1	TPM1	11140	-0.05	-0.058	NO
45	CACNG3	CACNG3	CACNG3	11625	-0.063	-0.079	NO
46	ACTC1	ACTC1	ACTC1	11961	-0.074	-0.091	NO
47	TPM3	TPM3	TPM3	12026	-0.076	-0.088	NO
48	TNNC1	TNNC1	TNNC1	12701	-0.1	-0.12	NO
49	COX8C	COX8C	COX8C	12737	-0.1	-0.11	NO
50	UQCRH	UQCRH	UQCRH	12919	-0.11	-0.11	NO
51	UQCRFS1	UQCRFS1	UQCRFS1	13007	-0.11	-0.1	NO
52	UQCRHL	UQCRHL	UQCRHL	13093	-0.12	-0.098	NO
53	COX6B2	COX6B2	COX6B2	13410	-0.13	-0.1	NO
54	CACNB3	CACNB3	CACNB3	13595	-0.14	-0.1	NO
55	COX6B1	COX6B1	COX6B1	13639	-0.14	-0.092	NO
56	ATP1B4	ATP1B4	ATP1B4	13729	-0.14	-0.084	NO
57	ATP1A1	ATP1A1	ATP1A1	13769	-0.14	-0.073	NO
58	ATP1A2	ATP1A2	ATP1A2	13801	-0.15	-0.062	NO
59	TNNT2	TNNT2	TNNT2	14693	-0.19	-0.094	NO
60	ATP1B1	ATP1B1	ATP1B1	14923	-0.2	-0.089	NO
61	SLC9A1	SLC9A1	SLC9A1	15209	-0.21	-0.086	NO
62	RYR2	RYR2	RYR2	15445	-0.22	-0.078	NO
63	COX7A1	COX7A1	COX7A1	15745	-0.24	-0.073	NO
64	CACNA1S	CACNA1S	CACNA1S	15924	-0.26	-0.06	NO
65	CACNG5	CACNG5	CACNG5	16210	-0.28	-0.051	NO
66	ATP1A4	ATP1A4	ATP1A4	16237	-0.28	-0.028	NO
67	COX6A2	COX6A2	COX6A2	16366	-0.29	-0.0088	NO
68	CACNB2	CACNB2	CACNB2	16487	-0.3	0.011	NO
69	CACNA2D4	CACNA2D4	CACNA2D4	17810	-0.49	-0.017	NO
70	CACNA1F	CACNA1F	CACNA1F	17858	-0.5	0.025	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 OXIDATIVE PHOSPHORYLATION.

Figure S50. 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 LYSINE DEGRADATION

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	CREB3L1	CREB3L1	CREB3L1	114	0.53	0.14	YES
2	CREB3L4	CREB3L4	CREB3L4	245	0.43	0.25	YES
3	AVPR2	AVPR2	AVPR2	1399	0.18	0.23	NO
4	DCTN4	DCTN4	DCTN4	3352	0.086	0.15	NO
5	ADCY6	ADCY6	ADCY6	3506	0.082	0.16	NO
6	DCTN6	DCTN6	DCTN6	4184	0.068	0.14	NO
7	DCTN5	DCTN5	DCTN5	4565	0.061	0.14	NO
8	RAB11B	RAB11B	RAB11B	4970	0.054	0.13	NO
9	PRKX	PRKX	PRKX	5537	0.045	0.12	NO
10	STX4	STX4	STX4	6792	0.026	0.053	NO
11	CREB3	CREB3	CREB3	7011	0.023	0.048	NO
12	DYNC1LI1	DYNC1LI1	DYNC1LI1	7213	0.02	0.042	NO
13	RAB5C	RAB5C	RAB5C	7271	0.019	0.044	NO
14	RAB5B	RAB5B	RAB5B	7289	0.019	0.049	NO
15	RAB5A	RAB5A	RAB5A	7430	0.018	0.046	NO
16	DCTN1	DCTN1	DCTN1	8081	0.0076	0.012	NO
17	DYNC1I2	DYNC1I2	DYNC1I2	8373	0.0032	-0.0029	NO
18	GNAS	GNAS	GNAS	8414	0.0026	-0.0043	NO
19	DYNC1H1	DYNC1H1	DYNC1H1	8457	0.002	-0.0061	NO
20	ARHGDIA	ARHGDIA	ARHGDIA	8791	-0.0026	-0.024	NO
21	VAMP2	VAMP2	VAMP2	8829	-0.0032	-0.025	NO
22	CREB1	CREB1	CREB1	9459	-0.013	-0.056	NO
23	DCTN2	DCTN2	DCTN2	9466	-0.013	-0.052	NO
24	NSF	NSF	NSF	9616	-0.016	-0.056	NO
25	DYNLL2	DYNLL2	DYNLL2	9719	-0.018	-0.057	NO
26	DYNC1I1	DYNC1I1	DYNC1I1	10438	-0.033	-0.087	NO
27	RAB11A	RAB11A	RAB11A	10959	-0.045	-0.1	NO
28	DYNC1LI2	DYNC1LI2	DYNC1LI2	11220	-0.052	-0.1	NO
29	DYNC2LI1	DYNC2LI1	DYNC2LI1	11466	-0.059	-0.1	NO
30	DYNLL1	DYNLL1	DYNLL1	11803	-0.068	-0.1	NO
31	DYNC2H1	DYNC2H1	DYNC2H1	11845	-0.07	-0.084	NO
32	CREB3L2	CREB3L2	CREB3L2	11949	-0.073	-0.069	NO
33	PRKACB	PRKACB	PRKACB	12043	-0.076	-0.054	NO
34	ADCY9	ADCY9	ADCY9	12215	-0.083	-0.04	NO
35	AQP2	AQP2	AQP2	12234	-0.083	-0.019	NO
36	PRKACA	PRKACA	PRKACA	12441	-0.091	-0.0051	NO
37	CREB3L3	CREB3L3	CREB3L3	12573	-0.096	0.014	NO
38	CREB5	CREB5	CREB5	13178	-0.12	0.013	NO
39	AQP3	AQP3	AQP3	14514	-0.18	-0.011	NO
40	AQP4	AQP4	AQP4	14886	-0.2	0.022	NO
41	ARHGDIB	ARHGDIB	ARHGDIB	15351	-0.22	0.056	NO
42	PRKACG	PRKACG	PRKACG	17241	-0.39	0.059	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 LYSINE DEGRADATION.

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG LYSINE 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 SPHINGOLIPID 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	POLE2	POLE2	POLE2	818	0.25	0.08	YES
2	POLL	POLL	POLL	2079	0.13	0.074	YES
3	PARP3	PARP3	PARP3	2111	0.13	0.14	YES
4	SMUG1	SMUG1	SMUG1	2955	0.097	0.14	YES
5	PARP2	PARP2	PARP2	3108	0.092	0.17	YES
6	FEN1	FEN1	FEN1	3203	0.089	0.21	YES
7	NEIL2	NEIL2	NEIL2	3531	0.081	0.23	YES
8	APEX1	APEX1	APEX1	3869	0.074	0.25	YES
9	NEIL1	NEIL1	NEIL1	4287	0.066	0.26	YES
10	NTHL1	NTHL1	NTHL1	4582	0.06	0.28	YES
11	POLE	POLE	POLE	4591	0.06	0.3	YES
12	OGG1	OGG1	OGG1	5135	0.051	0.3	YES
13	TDG	TDG	TDG	5389	0.047	0.31	YES
14	POLD2	POLD2	POLD2	6358	0.033	0.27	NO
15	POLB	POLB	POLB	6504	0.03	0.28	NO
16	PARP4	PARP4	PARP4	7491	0.017	0.23	NO
17	APEX2	APEX2	APEX2	7980	0.0091	0.21	NO
18	NEIL3	NEIL3	NEIL3	8389	0.003	0.19	NO
19	MPG	MPG	MPG	8546	0.00068	0.18	NO
20	PCNA	PCNA	PCNA	8772	-0.0022	0.17	NO
21	PARP1	PARP1	PARP1	8941	-0.0051	0.16	NO
22	POLD3	POLD3	POLD3	9289	-0.01	0.15	NO
23	LIG3	LIG3	LIG3	9573	-0.015	0.14	NO
24	POLE3	POLE3	POLE3	9730	-0.018	0.14	NO
25	POLD4	POLD4	POLD4	9919	-0.022	0.14	NO
26	MBD4	MBD4	MBD4	10844	-0.042	0.11	NO
27	LIG1	LIG1	LIG1	11165	-0.051	0.12	NO
28	UNG	UNG	UNG	12101	-0.078	0.11	NO
29	XRCC1	XRCC1	XRCC1	12284	-0.085	0.14	NO
30	POLD1	POLD1	POLD1	12395	-0.089	0.18	NO
31	MUTYH	MUTYH	MUTYH	13395	-0.13	0.18	NO
32	POLE4	POLE4	POLE4	14426	-0.17	0.21	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 SPHINGOLIPID METABOLISM.

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

Table 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	POLR2F	POLR2F	POLR2F	1235	0.19	0.05	YES
2	POLR3D	POLR3D	POLR3D	1455	0.17	0.14	YES
3	POLR1B	POLR1B	POLR1B	2541	0.11	0.15	YES
4	POLR3G	POLR3G	POLR3G	3889	0.074	0.12	YES
5	POLR3F	POLR3F	POLR3F	3967	0.072	0.16	YES
6	POLR3GL	POLR3GL	POLR3GL	4202	0.067	0.19	YES
7	POLR1A	POLR1A	POLR1A	4584	0.06	0.21	YES
8	ZNRD1	ZNRD1	ZNRD1	4844	0.056	0.23	YES
9	POLR3K	POLR3K	POLR3K	5617	0.044	0.21	YES
10	POLR1E	POLR1E	POLR1E	5837	0.041	0.22	YES
11	POLR2D	POLR2D	POLR2D	5979	0.039	0.24	YES
12	POLR2A	POLR2A	POLR2A	6011	0.038	0.26	YES
13	POLR1C	POLR1C	POLR1C	6996	0.023	0.22	NO
14	POLR3C	POLR3C	POLR3C	7965	0.0093	0.17	NO
15	POLR3B	POLR3B	POLR3B	7969	0.0093	0.18	NO
16	POLR2G	POLR2G	POLR2G	8148	0.0066	0.17	NO
17	POLR2C	POLR2C	POLR2C	8237	0.0053	0.17	NO
18	POLR2E	POLR2E	POLR2E	8525	0.0011	0.16	NO
19	POLR2B	POLR2B	POLR2B	9472	-0.013	0.11	NO
20	POLR2J3	POLR2J3	POLR2J3	9523	-0.014	0.12	NO
21	POLR3A	POLR3A	POLR3A	9883	-0.021	0.11	NO
22	POLR3H	POLR3H	POLR3H	10199	-0.028	0.11	NO
23	POLR2K	POLR2K	POLR2K	10470	-0.034	0.12	NO
24	POLR2L	POLR2L	POLR2L	10777	-0.041	0.13	NO
25	POLR2J	POLR2J	POLR2J	11816	-0.069	0.11	NO
26	POLR1D	POLR1D	POLR1D	12238	-0.083	0.14	NO
27	POLR2J2	POLR2J2	POLR2J2	13881	-0.15	0.14	NO
28	POLR2I	POLR2I	POLR2I	14254	-0.17	0.22	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 AMINOACYL TRNA BIOSYNTHESIS.

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

genes ES table in pathway: KEGG RIBOSOME

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	POLE2	POLE2	POLE2	818	0.25	0.063	YES
2	PRIM1	PRIM1	PRIM1	1157	0.2	0.13	YES
3	RNASEH2C	RNASEH2C	RNASEH2C	1966	0.14	0.14	YES
4	DNA2	DNA2	DNA2	2092	0.13	0.19	YES
5	MCM4	MCM4	MCM4	2703	0.1	0.2	YES
6	MCM6	MCM6	MCM6	2900	0.098	0.23	YES
7	RPA4	RPA4	RPA4	3062	0.093	0.26	YES
8	FEN1	FEN1	FEN1	3203	0.089	0.29	YES
9	RFC4	RFC4	RFC4	3444	0.083	0.32	YES
10	RNASEH2A	RNASEH2A	RNASEH2A	3493	0.082	0.35	YES
11	POLE	POLE	POLE	4591	0.06	0.31	YES
12	RNASEH2B	RNASEH2B	RNASEH2B	4757	0.058	0.33	YES
13	MCM7	MCM7	MCM7	4794	0.057	0.35	YES
14	POLD2	POLD2	POLD2	6358	0.033	0.28	NO
15	POLA2	POLA2	POLA2	6380	0.033	0.29	NO
16	PRIM2	PRIM2	PRIM2	7041	0.023	0.27	NO
17	RFC3	RFC3	RFC3	7156	0.021	0.27	NO
18	MCM2	MCM2	MCM2	7444	0.017	0.26	NO
19	MCM5	MCM5	MCM5	7588	0.015	0.26	NO
20	SSBP1	SSBP1	SSBP1	8002	0.0088	0.24	NO
21	PCNA	PCNA	PCNA	8772	-0.0022	0.2	NO
22	RNASEH1	RNASEH1	RNASEH1	9098	-0.0075	0.18	NO
23	POLD3	POLD3	POLD3	9289	-0.01	0.18	NO
24	POLE3	POLE3	POLE3	9730	-0.018	0.16	NO
25	POLD4	POLD4	POLD4	9919	-0.022	0.16	NO
26	RFC1	RFC1	RFC1	10088	-0.026	0.16	NO
27	RFC2	RFC2	RFC2	10350	-0.031	0.16	NO
28	RPA1	RPA1	RPA1	10843	-0.042	0.15	NO
29	MCM3	MCM3	MCM3	10861	-0.043	0.17	NO
30	RFC5	RFC5	RFC5	11155	-0.05	0.18	NO
31	LIG1	LIG1	LIG1	11165	-0.051	0.2	NO
32	RPA3	RPA3	RPA3	12246	-0.084	0.17	NO
33	POLD1	POLD1	POLD1	12395	-0.089	0.2	NO
34	RPA2	RPA2	RPA2	13077	-0.11	0.21	NO
35	POLE4	POLE4	POLE4	14426	-0.17	0.21	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 RIBOSOME.

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

genes ES table in pathway: KEGG RNA DEGRADATION

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GAL3ST1	GAL3ST1	GAL3ST1	404	0.36	0.061	YES
2	SMPD3	SMPD3	SMPD3	504	0.33	0.13	YES
3	NEU4	NEU4	NEU4	512	0.32	0.21	YES
4	ACER2	ACER2	ACER2	1106	0.21	0.22	YES
5	NEU3	NEU3	NEU3	1506	0.17	0.24	YES
6	UGT8	UGT8	UGT8	1532	0.16	0.28	YES
7	ASAH2	ASAH2	ASAH2	2175	0.13	0.27	YES
8	B4GALT6	B4GALT6	B4GALT6	2801	0.1	0.26	YES
9	SGMS1	SGMS1	SGMS1	2839	0.1	0.28	YES
10	GBA	GBA	GBA	3214	0.089	0.28	YES
11	SGPP1	SGPP1	SGPP1	5157	0.051	0.19	NO
12	NEU1	NEU1	NEU1	5448	0.047	0.19	NO
13	ACER3	ACER3	ACER3	5540	0.045	0.19	NO
14	SGPL1	SGPL1	SGPL1	6056	0.038	0.17	NO
15	SMPD2	SMPD2	SMPD2	6486	0.031	0.16	NO
16	SPTLC1	SPTLC1	SPTLC1	7581	0.015	0.099	NO
17	SMPD1	SMPD1	SMPD1	7866	0.011	0.086	NO
18	DEGS1	DEGS1	DEGS1	8357	0.0034	0.06	NO
19	SMPD4	SMPD4	SMPD4	9326	-0.011	0.0098	NO
20	KDSR	KDSR	KDSR	10220	-0.028	-0.032	NO
21	PPAP2A	PPAP2A	PPAP2A	10464	-0.034	-0.038	NO
22	SPHK1	SPHK1	SPHK1	10496	-0.034	-0.031	NO
23	GLB1	GLB1	GLB1	10564	-0.036	-0.027	NO
24	CERK	CERK	CERK	10589	-0.037	-0.019	NO
25	DEGS2	DEGS2	DEGS2	10848	-0.042	-0.024	NO
26	ASAH1	ASAH1	ASAH1	11077	-0.048	-0.025	NO
27	SGPP2	SGPP2	SGPP2	11413	-0.057	-0.03	NO
28	GLA	GLA	GLA	11460	-0.058	-0.018	NO
29	PPAP2C	PPAP2C	PPAP2C	12165	-0.081	-0.038	NO
30	SPTLC2	SPTLC2	SPTLC2	12625	-0.098	-0.04	NO
31	SPHK2	SPHK2	SPHK2	13062	-0.11	-0.037	NO
32	ACER1	ACER1	ACER1	13186	-0.12	-0.016	NO
33	GALC	GALC	GALC	14515	-0.18	-0.047	NO
34	ARSA	ARSA	ARSA	14661	-0.18	-0.012	NO
35	UGCG	UGCG	UGCG	14943	-0.2	0.019	NO
36	PPAP2B	PPAP2B	PPAP2B	16603	-0.31	0.00086	NO
37	SGMS2	SGMS2	SGMS2	17308	-0.4	0.055	NO

Figure S59. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG RNA DEGRADATION.

Figure S60. 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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus4 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA NO1 PATHWAY	29	genes.ES.table	0.66	1.6	0.0084	0.088	0.65	0.41	0.16	0.35	0.049	0.001
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.63	1.7	0.0041	0.076	0.54	0.2	0.058	0.19	0.039	0.001
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.56	1.9	0.0041	0.078	0.075	0.5	0.24	0.38	0	0.026
BIOCARTA BIOPEPTIDES PATHWAY	39	genes.ES.table	0.62	1.9	0.0021	0.059	0.12	0.49	0.24	0.37	0	0.011
BIOCARTA HDAC PATHWAY	27	genes.ES.table	0.51	1.6	0.038	0.1	0.79	0.41	0.22	0.32	0.069	0
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.46	1.4	0.11	0.18	0.94	0.2	0.17	0.17	0.14	0.001
BIOCARTA ERK PATHWAY	26	genes.ES.table	0.42	1.4	0.073	0.18	0.94	0.15	0.13	0.13	0.14	0.001
BIOCARTA PYK2 PATHWAY	27	genes.ES.table	0.57	1.9	0	0.15	0.068	0.44	0.24	0.34	0	0.051
BIOCARTA NFAT PATHWAY	50	genes.ES.table	0.43	1.3	0.082	0.23	0.98	0.26	0.17	0.22	0.19	0.001
BIOCARTA PDGF PATHWAY	31	genes.ES.table	0.45	1.4	0.12	0.18	0.94	0.19	0.17	0.16	0.14	0.001

genes ES table in pathway: BIOCARTA NO1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRKCB	PRKCB	PRKCB	781	0.57	0.12	YES
2	PAK1	PAK1	PAK1	802	0.56	0.27	YES
3	PTK2B	PTK2B	PTK2B	1419	0.37	0.34	YES
4	MAP2K4	MAP2K4	MAP2K4	2131	0.24	0.37	YES
5	CALM3	CALM3	CALM3	2141	0.24	0.44	YES
6	MAP2K1	MAP2K1	MAP2K1	2401	0.21	0.49	YES
7	CALM1	CALM1	CALM1	2694	0.18	0.52	YES
8	MAPK8	MAPK8	MAPK8	3036	0.16	0.55	YES
9	MAPK3	MAPK3	MAPK3	4086	0.096	0.52	YES
10	GNAQ	GNAQ	GNAQ	4192	0.091	0.54	YES
11	MAPK1	MAPK1	MAPK1	4299	0.087	0.56	YES
12	CALM2	CALM2	CALM2	4375	0.084	0.57	YES
13	PRKCA	PRKCA	PRKCA	5887	0.038	0.5	NO
14	MAPK14	MAPK14	MAPK14	7452	0.0069	0.42	NO
15	GRB2	GRB2	GRB2	7504	0.0061	0.42	NO
16	CRKL	CRKL	CRKL	7550	0.0054	0.42	NO
17	SRC	SRC	SRC	7925	-0.00081	0.4	NO
18	MAP2K2	MAP2K2	MAP2K2	8550	-0.01	0.36	NO
19	RAC1	RAC1	RAC1	9393	-0.021	0.32	NO
20	SOS1	SOS1	SOS1	9666	-0.025	0.32	NO
21	PLCG1	PLCG1	PLCG1	10537	-0.036	0.28	NO
22	BCAR1	BCAR1	BCAR1	10746	-0.039	0.28	NO
23	RAF1	RAF1	RAF1	12395	-0.061	0.21	NO
24	MAP2K3	MAP2K3	MAP2K3	13842	-0.084	0.15	NO
25	JUN	JUN	JUN	13895	-0.085	0.17	NO
26	SHC1	SHC1	SHC1	15124	-0.12	0.14	NO
27	MAP3K1	MAP3K1	MAP3K1	15752	-0.14	0.14	NO

Figure S61. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA NO1 PATHWAY.

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NO1 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 AGR PATHWAY

Table S32. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRKCB	PRKCB	PRKCB	781	0.57	0.088	YES
2	PAK1	PAK1	PAK1	802	0.56	0.22	YES
3	PTK2B	PTK2B	PTK2B	1419	0.37	0.27	YES
4	MAP2K4	MAP2K4	MAP2K4	2131	0.24	0.28	YES
5	CALM3	CALM3	CALM3	2141	0.24	0.34	YES
6	MAP2K1	MAP2K1	MAP2K1	2401	0.21	0.37	YES
7	ELK1	ELK1	ELK1	2457	0.21	0.42	YES
8	CALM1	CALM1	CALM1	2694	0.18	0.45	YES
9	MEF2D	MEF2D	MEF2D	2704	0.18	0.49	YES
10	MAPK8	MAPK8	MAPK8	3036	0.16	0.51	YES
11	MEF2A	MEF2A	MEF2A	3947	0.1	0.48	YES
12	ATF2	ATF2	ATF2	4044	0.098	0.5	YES
13	MAPK3	MAPK3	MAPK3	4086	0.096	0.52	YES
14	GNAQ	GNAQ	GNAQ	4192	0.091	0.53	YES
15	MAPK1	MAPK1	MAPK1	4299	0.087	0.55	YES
16	CALM2	CALM2	CALM2	4375	0.084	0.56	YES
17	HRAS	HRAS	HRAS	5557	0.046	0.51	NO
18	AGTR1	AGTR1	AGTR1	5637	0.044	0.52	NO
19	PRKCA	PRKCA	PRKCA	5887	0.038	0.51	NO
20	AGT	AGT	AGT	6425	0.026	0.49	NO
21	PTK2	PTK2	PTK2	7257	0.01	0.44	NO
22	GRB2	GRB2	GRB2	7504	0.0061	0.43	NO
23	SRC	SRC	SRC	7925	-0.00081	0.41	NO
24	MAP2K2	MAP2K2	MAP2K2	8550	-0.01	0.38	NO
25	RAC1	RAC1	RAC1	9393	-0.021	0.34	NO
26	SOS1	SOS1	SOS1	9666	-0.025	0.33	NO
27	RAF1	RAF1	RAF1	12395	-0.061	0.19	NO
28	EGFR	EGFR	EGFR	12590	-0.064	0.2	NO
29	JUN	JUN	JUN	13895	-0.085	0.14	NO
30	SHC1	SHC1	SHC1	15124	-0.12	0.1	NO
31	MAP3K1	MAP3K1	MAP3K1	15752	-0.14	0.099	NO
32	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	16650	-0.18	0.091	NO

Figure S63. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA AGR PATHWAY.

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

genes ES table in pathway: BIOCARTA AT1R PATHWAY

Table S33. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CACNA1F	CACNA1F	CACNA1F	268	0.92	0.041	YES
2	GRIN2A	GRIN2A	GRIN2A	411	0.78	0.081	YES
3	GRIN1	GRIN1	GRIN1	442	0.76	0.13	YES
4	GRIN2B	GRIN2B	GRIN2B	500	0.73	0.17	YES
5	SNCA	SNCA	SNCA	569	0.68	0.2	YES
6	ITPR1	ITPR1	ITPR1	645	0.64	0.24	YES
7	COX7A1	COX7A1	COX7A1	730	0.6	0.27	YES
8	CACNA1S	CACNA1S	CACNA1S	731	0.6	0.31	YES
9	CALML3	CALML3	CALML3	1004	0.48	0.32	YES
10	NOS1	NOS1	NOS1	1085	0.46	0.34	YES
11	CHP2	CHP2	CHP2	1900	0.28	0.32	YES
12	PPP3R2	PPP3R2	PPP3R2	1924	0.28	0.33	YES
13	CDK5R1	CDK5R1	CDK5R1	1967	0.27	0.35	YES
14	PPP3R1	PPP3R1	PPP3R1	1995	0.26	0.36	YES
15	CACNA1C	CACNA1C	CACNA1C	2002	0.26	0.38	YES
16	GRIN2C	GRIN2C	GRIN2C	2068	0.25	0.39	YES
17	PPP3CB	PPP3CB	PPP3CB	2076	0.25	0.4	YES
18	CALM3	CALM3	CALM3	2141	0.24	0.42	YES
19	PPP3CA	PPP3CA	PPP3CA	2184	0.24	0.43	YES
20	RYR3	RYR3	RYR3	2242	0.23	0.44	YES
21	CACNA1D	CACNA1D	CACNA1D	2369	0.22	0.44	YES
22	PLCB1	PLCB1	PLCB1	2526	0.2	0.45	YES
23	PLCB4	PLCB4	PLCB4	2545	0.2	0.46	YES
24	MME	MME	MME	2566	0.2	0.47	YES
25	CALM1	CALM1	CALM1	2694	0.18	0.47	YES
26	CDK5	CDK5	CDK5	3038	0.15	0.46	NO
27	APBB1	APBB1	APBB1	3589	0.12	0.44	NO
28	NDUFB8	NDUFB8	NDUFB8	3631	0.12	0.45	NO
29	GRIN2D	GRIN2D	GRIN2D	3915	0.1	0.44	NO
30	MAPK3	MAPK3	MAPK3	4086	0.096	0.43	NO
31	GNAQ	GNAQ	GNAQ	4192	0.091	0.43	NO
32	NDUFA4	NDUFA4	NDUFA4	4256	0.088	0.44	NO
33	MAPK1	MAPK1	MAPK1	4299	0.087	0.44	NO
34	MAPT	MAPT	MAPT	4359	0.085	0.44	NO
35	CALM2	CALM2	CALM2	4375	0.084	0.44	NO
36	ATP2A2	ATP2A2	ATP2A2	4462	0.08	0.44	NO
37	NDUFA5	NDUFA5	NDUFA5	4484	0.079	0.45	NO
38	CYCS	CYCS	CYCS	4626	0.075	0.44	NO
39	NDUFS1	NDUFS1	NDUFS1	4715	0.072	0.44	NO
40	COX7A2L	COX7A2L	COX7A2L	4831	0.068	0.44	NO
41	ATP5G3	ATP5G3	ATP5G3	4952	0.064	0.44	NO
42	PSEN2	PSEN2	PSEN2	5050	0.061	0.44	NO
43	NDUFA8	NDUFA8	NDUFA8	5073	0.06	0.44	NO
44	GSK3B	GSK3B	GSK3B	5176	0.057	0.44	NO
45	UQCRFS1	UQCRFS1	UQCRFS1	5289	0.053	0.44	NO
46	CHP	CHP	CHP	5305	0.052	0.44	NO
47	SDHA	SDHA	SDHA	5541	0.046	0.43	NO
48	COX5A	COX5A	COX5A	5556	0.046	0.43	NO
49	UQCRC2	UQCRC2	UQCRC2	5579	0.045	0.43	NO
50	COX6A1	COX6A1	COX6A1	5600	0.045	0.43	NO
51	IL1B	IL1B	IL1B	5606	0.044	0.44	NO
52	ATP5B	ATP5B	ATP5B	5611	0.044	0.44	NO
53	UQCRH	UQCRH	UQCRH	5695	0.043	0.44	NO
54	ATP5A1	ATP5A1	ATP5A1	5848	0.038	0.43	NO
55	APP	APP	APP	5910	0.037	0.43	NO
56	NDUFB9	NDUFB9	NDUFB9	5973	0.036	0.43	NO
57	COX4I1	COX4I1	COX4I1	6204	0.031	0.42	NO
58	UQCRC1	UQCRC1	UQCRC1	6214	0.031	0.42	NO
59	NDUFS5	NDUFS5	NDUFS5	6357	0.028	0.41	NO
60	NDUFA10	NDUFA10	NDUFA10	6467	0.026	0.41	NO
61	UQCR10	UQCR10	UQCR10	6592	0.023	0.4	NO
62	ATP5G1	ATP5G1	ATP5G1	6608	0.023	0.4	NO
63	NDUFS2	NDUFS2	NDUFS2	6615	0.023	0.4	NO
64	NDUFAB1	NDUFAB1	NDUFAB1	6658	0.022	0.4	NO
65	NDUFA3	NDUFA3	NDUFA3	6685	0.021	0.4	NO
66	ATP5C1	ATP5C1	ATP5C1	6737	0.02	0.4	NO
67	COX7A2	COX7A2	COX7A2	6773	0.02	0.4	NO
68	SDHB	SDHB	SDHB	6792	0.019	0.4	NO
69	ATP5H	ATP5H	ATP5H	6810	0.019	0.4	NO
70	BACE1	BACE1	BACE1	6830	0.018	0.4	NO
71	ATP2A3	ATP2A3	ATP2A3	6849	0.018	0.4	NO
72	NDUFV1	NDUFV1	NDUFV1	6922	0.017	0.4	NO
73	ATP5O	ATP5O	ATP5O	6940	0.016	0.4	NO
74	COX7C	COX7C	COX7C	6999	0.015	0.4	NO
75	UQCRHL	UQCRHL	UQCRHL	7040	0.014	0.39	NO
76	APAF1	APAF1	APAF1	7063	0.014	0.39	NO
77	COX6C	COX6C	COX6C	7079	0.014	0.39	NO
78	COX6A2	COX6A2	COX6A2	7084	0.013	0.39	NO
79	NDUFS3	NDUFS3	NDUFS3	7094	0.013	0.39	NO
80	NDUFB1	NDUFB1	NDUFB1	7119	0.013	0.39	NO
81	COX6B1	COX6B1	COX6B1	7135	0.012	0.39	NO
82	NDUFA1	NDUFA1	NDUFA1	7153	0.012	0.39	NO
83	UQCRB	UQCRB	UQCRB	7215	0.011	0.39	NO
84	COX7B	COX7B	COX7B	7357	0.0086	0.38	NO
85	ATP5J	ATP5J	ATP5J	7360	0.0085	0.38	NO
86	COX5B	COX5B	COX5B	7361	0.0085	0.38	NO
87	NDUFC2	NDUFC2	NDUFC2	7375	0.0083	0.38	NO
88	NDUFB6	NDUFB6	NDUFB6	7399	0.0079	0.38	NO
89	NDUFV2	NDUFV2	NDUFV2	7407	0.0077	0.38	NO
90	NDUFA6	NDUFA6	NDUFA6	7646	0.0038	0.37	NO
91	NDUFB5	NDUFB5	NDUFB5	7725	0.0027	0.37	NO
92	ADAM10	ADAM10	ADAM10	7776	0.002	0.36	NO
93	CYC1	CYC1	CYC1	7795	0.0016	0.36	NO
94	ATP5F1	ATP5F1	ATP5F1	7844	0.00085	0.36	NO
95	ITPR2	ITPR2	ITPR2	7851	0.00068	0.36	NO
96	IDE	IDE	IDE	7909	-0.00057	0.36	NO
97	NDUFB3	NDUFB3	NDUFB3	7949	-0.0012	0.36	NO
98	ATF6	ATF6	ATF6	8068	-0.003	0.35	NO
99	NDUFB4	NDUFB4	NDUFB4	8093	-0.0034	0.35	NO
100	CAPN1	CAPN1	CAPN1	8114	-0.0037	0.35	NO
101	GAPDH	GAPDH	GAPDH	8127	-0.0039	0.35	NO
102	ERN1	ERN1	ERN1	8238	-0.0054	0.34	NO
103	BID	BID	BID	8317	-0.0067	0.34	NO
104	PPP3CC	PPP3CC	PPP3CC	8524	-0.0098	0.33	NO
105	SDHC	SDHC	SDHC	8686	-0.012	0.32	NO
106	NDUFS4	NDUFS4	NDUFS4	8760	-0.013	0.31	NO
107	NDUFV3	NDUFV3	NDUFV3	8978	-0.015	0.3	NO
108	UQCR11	UQCR11	UQCR11	9005	-0.016	0.3	NO
109	PSEN1	PSEN1	PSEN1	9025	-0.016	0.3	NO
110	NDUFB2	NDUFB2	NDUFB2	9350	-0.021	0.29	NO
111	BAD	BAD	BAD	9351	-0.021	0.29	NO
112	NDUFS8	NDUFS8	NDUFS8	9448	-0.022	0.28	NO
113	NDUFS7	NDUFS7	NDUFS7	9450	-0.022	0.28	NO
114	NDUFB10	NDUFB10	NDUFB10	9477	-0.022	0.28	NO
115	ITPR3	ITPR3	ITPR3	9480	-0.022	0.29	NO
116	COX8A	COX8A	COX8A	9537	-0.023	0.28	NO
117	NDUFA2	NDUFA2	NDUFA2	9539	-0.023	0.29	NO
118	NDUFC1	NDUFC1	NDUFC1	9570	-0.024	0.28	NO
119	NDUFA9	NDUFA9	NDUFA9	9607	-0.024	0.28	NO
120	ATP5D	ATP5D	ATP5D	9679	-0.025	0.28	NO
121	UQCRQ	UQCRQ	UQCRQ	9688	-0.025	0.28	NO
122	SDHD	SDHD	SDHD	9718	-0.025	0.28	NO
123	LPL	LPL	LPL	9886	-0.028	0.28	NO
124	NDUFB7	NDUFB7	NDUFB7	10300	-0.033	0.26	NO
125	LRP1	LRP1	LRP1	10311	-0.033	0.26	NO
126	FAS	FAS	FAS	10354	-0.034	0.26	NO
127	NAE1	NAE1	NAE1	10428	-0.034	0.26	NO
128	NDUFA7	NDUFA7	NDUFA7	11003	-0.042	0.22	NO
129	ATP5G2	ATP5G2	ATP5G2	11224	-0.045	0.22	NO
130	ATP5E	ATP5E	ATP5E	11649	-0.051	0.2	NO
131	APOE	APOE	APOE	11734	-0.052	0.19	NO
132	NCSTN	NCSTN	NCSTN	11893	-0.054	0.19	NO
133	CASP9	CASP9	CASP9	12069	-0.056	0.18	NO
134	NDUFS6	NDUFS6	NDUFS6	12186	-0.058	0.18	NO
135	EIF2AK3	EIF2AK3	EIF2AK3	12194	-0.058	0.18	NO
136	CAPN2	CAPN2	CAPN2	12310	-0.06	0.18	NO
137	PSENEN	PSENEN	PSENEN	12368	-0.06	0.18	NO
138	CALML6	CALML6	CALML6	12642	-0.064	0.17	NO
139	ADAM17	ADAM17	ADAM17	12698	-0.065	0.17	NO
140	NDUFA4L2	NDUFA4L2	NDUFA4L2	12971	-0.069	0.16	NO
141	COX4I2	COX4I2	COX4I2	13232	-0.073	0.15	NO
142	APH1A	APH1A	APH1A	13402	-0.076	0.14	NO
143	CASP3	CASP3	CASP3	13478	-0.077	0.15	NO
144	CASP7	CASP7	CASP7	14082	-0.089	0.12	NO
145	HSD17B10	HSD17B10	HSD17B10	14821	-0.11	0.084	NO
146	COX8C	COX8C	COX8C	15333	-0.12	0.063	NO
147	TNF	TNF	TNF	15416	-0.12	0.066	NO
148	PLCB3	PLCB3	PLCB3	15474	-0.12	0.07	NO
149	FADD	FADD	FADD	15732	-0.14	0.065	NO
150	TNFRSF1A	TNFRSF1A	TNFRSF1A	16057	-0.15	0.056	NO
151	PLCB2	PLCB2	PLCB2	16296	-0.16	0.052	NO
152	BACE2	BACE2	BACE2	16679	-0.18	0.042	NO
153	COX6B2	COX6B2	COX6B2	16798	-0.19	0.047	NO
154	ATP2A1	ATP2A1	ATP2A1	17847	-0.29	0.0071	NO
155	CASP8	CASP8	CASP8	17940	-0.31	0.021	NO

Figure S65. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA AT1R PATHWAY.

Figure S66. 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 S34. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	STAT4	STAT4	STAT4	84	1.1	0.16	YES
2	CAMK2A	CAMK2A	CAMK2A	181	1	0.3	YES
3	CAMK2B	CAMK2B	CAMK2B	753	0.58	0.35	YES
4	PRKCB	PRKCB	PRKCB	781	0.57	0.43	YES
5	KNG1	KNG1	KNG1	888	0.52	0.5	YES
6	PTK2B	PTK2B	PTK2B	1419	0.37	0.52	YES
7	CALM3	CALM3	CALM3	2141	0.24	0.52	YES
8	MAP2K1	MAP2K1	MAP2K1	2401	0.21	0.53	YES
9	CAMK2G	CAMK2G	CAMK2G	2593	0.19	0.55	YES
10	CALM1	CALM1	CALM1	2694	0.18	0.57	YES
11	MAPK8	MAPK8	MAPK8	3036	0.16	0.57	YES
12	CDK5	CDK5	CDK5	3038	0.15	0.6	YES
13	GNAI1	GNAI1	GNAI1	3618	0.12	0.58	YES
14	MAPK3	MAPK3	MAPK3	4086	0.096	0.57	YES
15	STAT6	STAT6	STAT6	4117	0.094	0.58	YES
16	MAPK1	MAPK1	MAPK1	4299	0.087	0.58	YES
17	MYLK	MYLK	MYLK	4327	0.086	0.6	YES
18	MAPT	MAPT	MAPT	4359	0.085	0.6	YES
19	CALM2	CALM2	CALM2	4375	0.084	0.62	YES
20	GNB1	GNB1	GNB1	4975	0.063	0.59	NO
21	GNA11	GNA11	GNA11	5295	0.053	0.58	NO
22	PRKCA	PRKCA	PRKCA	5887	0.038	0.56	NO
23	CAMK2D	CAMK2D	CAMK2D	5940	0.036	0.56	NO
24	F2	F2	F2	5941	0.036	0.56	NO
25	AGT	AGT	AGT	6425	0.026	0.54	NO
26	MAPK14	MAPK14	MAPK14	7452	0.0069	0.48	NO
27	GRB2	GRB2	GRB2	7504	0.0061	0.48	NO
28	MAP2K2	MAP2K2	MAP2K2	8550	-0.01	0.43	NO
29	SOS1	SOS1	SOS1	9666	-0.025	0.37	NO
30	STAT5B	STAT5B	STAT5B	10114	-0.03	0.35	NO
31	PLCG1	PLCG1	PLCG1	10537	-0.036	0.33	NO
32	FYN	FYN	FYN	10672	-0.038	0.33	NO
33	JAK2	JAK2	JAK2	10752	-0.039	0.33	NO
34	STAT1	STAT1	STAT1	12055	-0.056	0.27	NO
35	RAF1	RAF1	RAF1	12395	-0.061	0.26	NO
36	STAT2	STAT2	STAT2	12891	-0.068	0.24	NO
37	STAT3	STAT3	STAT3	13765	-0.082	0.2	NO
38	SHC1	SHC1	SHC1	15124	-0.12	0.15	NO
39	STAT5A	STAT5A	STAT5A	16854	-0.19	0.08	NO

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

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

genes ES table in pathway: BIOCARTA HDAC PATHWAY

Table S35. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRPH2	PRPH2	PRPH2	95	1.1	0.085	YES
2	NEFM	NEFM	NEFM	117	1.1	0.17	YES
3	NEFL	NEFL	NEFL	182	1	0.25	YES
4	NEFH	NEFH	NEFH	255	0.93	0.32	YES
5	GRIN2A	GRIN2A	GRIN2A	411	0.78	0.38	YES
6	GRIN1	GRIN1	GRIN1	442	0.76	0.44	YES
7	GRIN2B	GRIN2B	GRIN2B	500	0.73	0.49	YES
8	MAPK13	MAPK13	MAPK13	879	0.53	0.52	YES
9	NOS1	NOS1	NOS1	1085	0.46	0.54	YES
10	SLC1A2	SLC1A2	SLC1A2	1841	0.29	0.52	YES
11	CHP2	CHP2	CHP2	1900	0.28	0.54	YES
12	PPP3R2	PPP3R2	PPP3R2	1924	0.28	0.56	YES
13	PPP3R1	PPP3R1	PPP3R1	1995	0.26	0.58	YES
14	GRIN2C	GRIN2C	GRIN2C	2068	0.25	0.6	YES
15	PPP3CB	PPP3CB	PPP3CB	2076	0.25	0.62	YES
16	PPP3CA	PPP3CA	PPP3CA	2184	0.24	0.63	YES
17	GRIA1	GRIA1	GRIA1	2518	0.2	0.63	NO
18	MAPK11	MAPK11	MAPK11	2793	0.18	0.63	NO
19	GRIA2	GRIA2	GRIA2	3258	0.14	0.61	NO
20	GRIN2D	GRIN2D	GRIN2D	3915	0.1	0.59	NO
21	TOMM40L	TOMM40L	TOMM40L	4282	0.088	0.57	NO
22	CYCS	CYCS	CYCS	4626	0.075	0.56	NO
23	CHP	CHP	CHP	5305	0.052	0.53	NO
24	SOD1	SOD1	SOD1	5806	0.039	0.5	NO
25	MAP3K5	MAP3K5	MAP3K5	6201	0.031	0.48	NO
26	APAF1	APAF1	APAF1	7063	0.014	0.44	NO
27	BCL2	BCL2	BCL2	7292	0.0097	0.43	NO
28	MAPK14	MAPK14	MAPK14	7452	0.0069	0.42	NO
29	MAPK12	MAPK12	MAPK12	7800	0.0015	0.4	NO
30	BID	BID	BID	8317	-0.0067	0.37	NO
31	PPP3CC	PPP3CC	PPP3CC	8524	-0.0098	0.36	NO
32	RAB5A	RAB5A	RAB5A	8674	-0.012	0.35	NO
33	BCL2L1	BCL2L1	BCL2L1	8688	-0.012	0.36	NO
34	BAD	BAD	BAD	9351	-0.021	0.32	NO
35	RAC1	RAC1	RAC1	9393	-0.021	0.32	NO
36	DERL1	DERL1	DERL1	9780	-0.026	0.3	NO
37	TOMM40	TOMM40	TOMM40	9796	-0.026	0.3	NO
38	MAP2K6	MAP2K6	MAP2K6	11608	-0.05	0.21	NO
39	CASP9	CASP9	CASP9	12069	-0.056	0.19	NO
40	CAT	CAT	CAT	12545	-0.063	0.16	NO
41	DAXX	DAXX	DAXX	12573	-0.063	0.17	NO
42	CASP3	CASP3	CASP3	13478	-0.077	0.13	NO
43	CCS	CCS	CCS	13537	-0.078	0.13	NO
44	MAP2K3	MAP2K3	MAP2K3	13842	-0.084	0.12	NO
45	TNF	TNF	TNF	15416	-0.12	0.043	NO
46	GPX1	GPX1	GPX1	15472	-0.12	0.05	NO
47	TP53	TP53	TP53	15831	-0.14	0.042	NO
48	TNFRSF1A	TNFRSF1A	TNFRSF1A	16057	-0.15	0.041	NO
49	BAX	BAX	BAX	16579	-0.17	0.027	NO
50	TNFRSF1B	TNFRSF1B	TNFRSF1B	17309	-0.23	0.0056	NO
51	PRPH	PRPH	PRPH	17568	-0.26	0.012	NO
52	CASP1	CASP1	CASP1	18124	-0.35	0.01	NO

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

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

genes ES table in pathway: BIOCARTA EGF PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRKCG	PRKCG	PRKCG	118	1.1	0.065	YES
2	CAMK2A	CAMK2A	CAMK2A	181	1	0.13	YES
3	GRIN2A	GRIN2A	GRIN2A	411	0.78	0.17	YES
4	GRIN1	GRIN1	GRIN1	442	0.76	0.22	YES
5	GRIN2B	GRIN2B	GRIN2B	500	0.73	0.26	YES
6	GRM1	GRM1	GRM1	514	0.72	0.3	YES
7	CAMK4	CAMK4	CAMK4	608	0.66	0.34	YES
8	ITPR1	ITPR1	ITPR1	645	0.64	0.38	YES
9	GRM5	GRM5	GRM5	674	0.62	0.42	YES
10	CAMK2B	CAMK2B	CAMK2B	753	0.58	0.46	YES
11	PRKCB	PRKCB	PRKCB	781	0.57	0.49	YES
12	CALML3	CALML3	CALML3	1004	0.48	0.51	YES
13	RPS6KA6	RPS6KA6	RPS6KA6	1600	0.33	0.5	YES
14	PPP1R1A	PPP1R1A	PPP1R1A	1871	0.28	0.5	YES
15	CHP2	CHP2	CHP2	1900	0.28	0.52	YES
16	PPP3R2	PPP3R2	PPP3R2	1924	0.28	0.54	YES
17	PPP3R1	PPP3R1	PPP3R1	1995	0.26	0.55	YES
18	CACNA1C	CACNA1C	CACNA1C	2002	0.26	0.57	YES
19	GRIN2C	GRIN2C	GRIN2C	2068	0.25	0.58	YES
20	PPP3CB	PPP3CB	PPP3CB	2076	0.25	0.6	YES
21	CALM3	CALM3	CALM3	2141	0.24	0.61	YES
22	PPP3CA	PPP3CA	PPP3CA	2184	0.24	0.62	YES
23	MAP2K1	MAP2K1	MAP2K1	2401	0.21	0.63	YES
24	GRIA1	GRIA1	GRIA1	2518	0.2	0.63	YES
25	PLCB1	PLCB1	PLCB1	2526	0.2	0.65	YES
26	PLCB4	PLCB4	PLCB4	2545	0.2	0.66	YES
27	CAMK2G	CAMK2G	CAMK2G	2593	0.19	0.67	YES
28	CALM1	CALM1	CALM1	2694	0.18	0.68	YES
29	GRIA2	GRIA2	GRIA2	3258	0.14	0.65	NO
30	BRAF	BRAF	BRAF	3338	0.13	0.66	NO
31	PRKACB	PRKACB	PRKACB	3371	0.13	0.66	NO
32	RPS6KA2	RPS6KA2	RPS6KA2	3741	0.11	0.65	NO
33	GRIN2D	GRIN2D	GRIN2D	3915	0.1	0.65	NO
34	RAPGEF3	RAPGEF3	RAPGEF3	4038	0.098	0.65	NO
35	MAPK3	MAPK3	MAPK3	4086	0.096	0.65	NO
36	GNAQ	GNAQ	GNAQ	4192	0.091	0.65	NO
37	MAPK1	MAPK1	MAPK1	4299	0.087	0.65	NO
38	CALM2	CALM2	CALM2	4375	0.084	0.65	NO
39	ADCY8	ADCY8	ADCY8	4433	0.081	0.66	NO
40	KRAS	KRAS	KRAS	4741	0.071	0.64	NO
41	PRKACA	PRKACA	PRKACA	4889	0.066	0.64	NO
42	CHP	CHP	CHP	5305	0.052	0.62	NO
43	HRAS	HRAS	HRAS	5557	0.046	0.61	NO
44	PRKCA	PRKCA	PRKCA	5887	0.038	0.59	NO
45	CAMK2D	CAMK2D	CAMK2D	5940	0.036	0.59	NO
46	RPS6KA3	RPS6KA3	RPS6KA3	6120	0.032	0.59	NO
47	PRKACG	PRKACG	PRKACG	6800	0.019	0.55	NO
48	PPP1R12A	PPP1R12A	PPP1R12A	7768	0.002	0.5	NO
49	EP300	EP300	EP300	7789	0.0017	0.5	NO
50	ITPR2	ITPR2	ITPR2	7851	0.00068	0.49	NO
51	PPP3CC	PPP3CC	PPP3CC	8524	-0.0098	0.46	NO
52	MAP2K2	MAP2K2	MAP2K2	8550	-0.01	0.46	NO
53	CREBBP	CREBBP	CREBBP	9199	-0.019	0.42	NO
54	PPP1CB	PPP1CB	PPP1CB	9467	-0.022	0.41	NO
55	ITPR3	ITPR3	ITPR3	9480	-0.022	0.41	NO
56	ATF4	ATF4	ATF4	11554	-0.049	0.3	NO
57	PPP1CC	PPP1CC	PPP1CC	11564	-0.05	0.3	NO
58	PPP1CA	PPP1CA	PPP1CA	12283	-0.059	0.27	NO
59	NRAS	NRAS	NRAS	12318	-0.06	0.27	NO
60	RAF1	RAF1	RAF1	12395	-0.061	0.27	NO
61	CALML6	CALML6	CALML6	12642	-0.064	0.26	NO
62	RAP1A	RAP1A	RAP1A	13165	-0.072	0.24	NO
63	RAP1B	RAP1B	RAP1B	13404	-0.076	0.23	NO
64	PRKX	PRKX	PRKX	14049	-0.088	0.2	NO
65	ARAF	ARAF	ARAF	15104	-0.11	0.15	NO
66	PLCB3	PLCB3	PLCB3	15474	-0.12	0.14	NO
67	RPS6KA1	RPS6KA1	RPS6KA1	16154	-0.15	0.11	NO
68	PLCB2	PLCB2	PLCB2	16296	-0.16	0.11	NO

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

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

genes ES table in pathway: BIOCARTA ERK PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PPP2R2C	PPP2R2C	PPP2R2C	694	0.62	0.087	YES
2	PKLR	PKLR	PKLR	856	0.54	0.19	YES
3	PRKAR1B	PRKAR1B	PRKAR1B	1181	0.43	0.26	YES
4	YWHAH	YWHAH	YWHAH	1564	0.34	0.3	YES
5	PRKAR2B	PRKAR2B	PRKAR2B	1587	0.33	0.37	YES
6	YWHAG	YWHAG	YWHAG	2126	0.24	0.39	YES
7	GCK	GCK	GCK	2430	0.21	0.42	YES
8	PRKAA2	PRKAA2	PRKAA2	2449	0.21	0.46	YES
9	MLXIPL	MLXIPL	MLXIPL	2742	0.18	0.48	YES
10	PRKACB	PRKACB	PRKACB	3371	0.13	0.47	YES
11	YWHAB	YWHAB	YWHAB	3761	0.11	0.47	YES
12	PRKAG2	PRKAG2	PRKAG2	3850	0.11	0.49	YES
13	PPP2R5B	PPP2R5B	PPP2R5B	3907	0.1	0.5	YES
14	YWHAZ	YWHAZ	YWHAZ	3943	0.1	0.52	YES
15	PPP2R2B	PPP2R2B	PPP2R2B	4305	0.087	0.52	YES
16	PPP2R2D	PPP2R2D	PPP2R2D	4418	0.082	0.53	YES
17	PPP2R5D	PPP2R5D	PPP2R5D	4551	0.077	0.54	YES
18	PRKACA	PRKACA	PRKACA	4889	0.066	0.54	YES
19	ACACA	ACACA	ACACA	5177	0.057	0.53	YES
20	PRKAR1A	PRKAR1A	PRKAR1A	5184	0.056	0.54	YES
21	PPP2R4	PPP2R4	PPP2R4	5268	0.054	0.55	YES
22	PPP2R1A	PPP2R1A	PPP2R1A	5285	0.053	0.56	YES
23	PPP2CA	PPP2CA	PPP2CA	5459	0.048	0.56	YES
24	FASN	FASN	FASN	5652	0.044	0.56	YES
25	PPP2R5C	PPP2R5C	PPP2R5C	5653	0.044	0.56	YES
26	PPP2R3A	PPP2R3A	PPP2R3A	5825	0.039	0.56	NO
27	PRKAR2A	PRKAR2A	PRKAR2A	6177	0.031	0.55	NO
28	PPP2R5A	PPP2R5A	PPP2R5A	6194	0.031	0.56	NO
29	PPP2R5E	PPP2R5E	PPP2R5E	6291	0.029	0.56	NO
30	PRKAB2	PRKAB2	PRKAB2	6481	0.025	0.55	NO
31	PRKACG	PRKACG	PRKACG	6800	0.019	0.54	NO
32	YWHAQ	YWHAQ	YWHAQ	7118	0.013	0.52	NO
33	PPP2R2A	PPP2R2A	PPP2R2A	7387	0.0081	0.51	NO
34	PPP2CB	PPP2CB	PPP2CB	7775	0.002	0.49	NO
35	YWHAE	YWHAE	YWHAE	7972	-0.0015	0.48	NO
36	PRKAG1	PRKAG1	PRKAG1	9742	-0.026	0.39	NO
37	PRKAA1	PRKAA1	PRKAA1	11379	-0.047	0.31	NO
38	PPP2R1B	PPP2R1B	PPP2R1B	11968	-0.055	0.29	NO
39	PRKAB1	PRKAB1	PRKAB1	12399	-0.061	0.28	NO
40	MLX	MLX	MLX	13001	-0.07	0.26	NO
41	PPP2R3B	PPP2R3B	PPP2R3B	16544	-0.17	0.097	NO

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

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

genes ES table in pathway: BIOCARTA PYK2 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DRD5	DRD5	DRD5	29	1.3	0.022	YES
2	HTR5A	HTR5A	HTR5A	31	1.3	0.046	YES
3	CCKBR	CCKBR	CCKBR	55	1.2	0.068	YES
4	RYR2	RYR2	RYR2	103	1.1	0.086	YES
5	DRD1	DRD1	DRD1	111	1.1	0.11	YES
6	PRKCG	PRKCG	PRKCG	118	1.1	0.12	YES
7	CHRM3	CHRM3	CHRM3	139	1.1	0.14	YES
8	CHRM2	CHRM2	CHRM2	162	1	0.16	YES
9	CAMK2A	CAMK2A	CAMK2A	181	1	0.18	YES
10	CACNA1F	CACNA1F	CACNA1F	268	0.92	0.19	YES
11	ATP2B3	ATP2B3	ATP2B3	292	0.89	0.21	YES
12	ADRB3	ADRB3	ADRB3	310	0.88	0.22	YES
13	NTSR1	NTSR1	NTSR1	319	0.87	0.24	YES
14	CACNA1B	CACNA1B	CACNA1B	362	0.83	0.25	YES
15	HRH2	HRH2	HRH2	369	0.83	0.27	YES
16	CHRM1	CHRM1	CHRM1	370	0.83	0.28	YES
17	HTR2A	HTR2A	HTR2A	399	0.79	0.3	YES
18	HTR4	HTR4	HTR4	402	0.79	0.31	YES
19	CACNA1I	CACNA1I	CACNA1I	405	0.79	0.32	YES
20	GRIN2A	GRIN2A	GRIN2A	411	0.78	0.34	YES
21	PTGER3	PTGER3	PTGER3	439	0.77	0.35	YES
22	GRIN1	GRIN1	GRIN1	442	0.76	0.36	YES
23	ADRA1B	ADRA1B	ADRA1B	445	0.76	0.38	YES
24	HTR2C	HTR2C	HTR2C	456	0.75	0.39	YES
25	HTR6	HTR6	HTR6	458	0.75	0.41	YES
26	TACR2	TACR2	TACR2	476	0.74	0.42	YES
27	ITPKA	ITPKA	ITPKA	494	0.73	0.43	YES
28	SLC8A2	SLC8A2	SLC8A2	501	0.73	0.44	YES
29	GRM1	GRM1	GRM1	514	0.72	0.46	YES
30	PDE1A	PDE1A	PDE1A	597	0.67	0.47	YES
31	CAMK4	CAMK4	CAMK4	608	0.66	0.48	YES
32	HTR7	HTR7	HTR7	611	0.66	0.49	YES
33	PDE1B	PDE1B	PDE1B	613	0.66	0.5	YES
34	ADCY1	ADCY1	ADCY1	634	0.65	0.51	YES
35	ITPR1	ITPR1	ITPR1	645	0.64	0.52	YES
36	GRM5	GRM5	GRM5	674	0.62	0.53	YES
37	ADRB1	ADRB1	ADRB1	721	0.6	0.54	YES
38	CACNA1S	CACNA1S	CACNA1S	731	0.6	0.55	YES
39	CAMK2B	CAMK2B	CAMK2B	753	0.58	0.56	YES
40	PRKCB	PRKCB	PRKCB	781	0.57	0.57	YES
41	CACNA1G	CACNA1G	CACNA1G	805	0.56	0.58	YES
42	TACR3	TACR3	TACR3	928	0.51	0.58	YES
43	GNA14	GNA14	GNA14	995	0.49	0.59	YES
44	CALML3	CALML3	CALML3	1004	0.48	0.6	YES
45	CHRNA7	CHRNA7	CHRNA7	1020	0.47	0.61	YES
46	CACNA1E	CACNA1E	CACNA1E	1084	0.46	0.61	YES
47	NOS1	NOS1	NOS1	1085	0.46	0.62	YES
48	ADORA2B	ADORA2B	ADORA2B	1131	0.45	0.62	YES
49	TNNC2	TNNC2	TNNC2	1263	0.41	0.63	YES
50	ATP2B2	ATP2B2	ATP2B2	1349	0.39	0.63	YES
51	P2RX2	P2RX2	P2RX2	1355	0.38	0.64	YES
52	GNAL	GNAL	GNAL	1363	0.38	0.64	YES
53	PTK2B	PTK2B	PTK2B	1419	0.37	0.65	YES
54	NOS2	NOS2	NOS2	1486	0.36	0.65	YES
55	ATP2B1	ATP2B1	ATP2B1	1490	0.35	0.66	YES
56	GRPR	GRPR	GRPR	1763	0.3	0.65	YES
57	PTGFR	PTGFR	PTGFR	1767	0.3	0.65	YES
58	P2RX5	P2RX5	P2RX5	1786	0.3	0.66	YES
59	ADRA1D	ADRA1D	ADRA1D	1791	0.3	0.66	YES
60	CCKAR	CCKAR	CCKAR	1823	0.29	0.66	YES
61	CHP2	CHP2	CHP2	1900	0.28	0.67	YES
62	PPP3R2	PPP3R2	PPP3R2	1924	0.28	0.67	YES
63	PDE1C	PDE1C	PDE1C	1978	0.27	0.67	YES
64	PPP3R1	PPP3R1	PPP3R1	1995	0.26	0.68	YES
65	CACNA1C	CACNA1C	CACNA1C	2002	0.26	0.68	YES
66	AVPR1B	AVPR1B	AVPR1B	2030	0.26	0.68	YES
67	GRIN2C	GRIN2C	GRIN2C	2068	0.25	0.69	YES
68	PPP3CB	PPP3CB	PPP3CB	2076	0.25	0.69	YES
69	ADRA1A	ADRA1A	ADRA1A	2127	0.24	0.69	YES
70	CALM3	CALM3	CALM3	2141	0.24	0.7	YES
71	AVPR1A	AVPR1A	AVPR1A	2160	0.24	0.7	YES
72	PPP3CA	PPP3CA	PPP3CA	2184	0.24	0.7	YES
73	CHRM5	CHRM5	CHRM5	2195	0.24	0.71	YES
74	RYR3	RYR3	RYR3	2242	0.23	0.71	YES
75	CACNA1D	CACNA1D	CACNA1D	2369	0.22	0.7	YES
76	ERBB4	ERBB4	ERBB4	2478	0.21	0.7	YES
77	PLCB1	PLCB1	PLCB1	2526	0.2	0.7	YES
78	PLCB4	PLCB4	PLCB4	2545	0.2	0.71	YES
79	BDKRB1	BDKRB1	BDKRB1	2583	0.2	0.71	YES
80	CAMK2G	CAMK2G	CAMK2G	2593	0.19	0.71	YES
81	OXTR	OXTR	OXTR	2630	0.19	0.71	YES
82	CACNA1H	CACNA1H	CACNA1H	2645	0.19	0.72	YES
83	CACNA1A	CACNA1A	CACNA1A	2646	0.19	0.72	YES
84	CALM1	CALM1	CALM1	2694	0.18	0.72	YES
85	MYLK3	MYLK3	MYLK3	2787	0.18	0.72	NO
86	TRHR	TRHR	TRHR	2858	0.17	0.72	NO
87	TACR1	TACR1	TACR1	2877	0.17	0.72	NO
88	BDKRB2	BDKRB2	BDKRB2	2971	0.16	0.72	NO
89	TNNC1	TNNC1	TNNC1	3231	0.14	0.71	NO
90	PRKACB	PRKACB	PRKACB	3371	0.13	0.7	NO
91	SLC25A31	SLC25A31	SLC25A31	3523	0.12	0.7	NO
92	SLC25A4	SLC25A4	SLC25A4	3847	0.11	0.68	NO
93	GRIN2D	GRIN2D	GRIN2D	3915	0.1	0.68	NO
94	CYSLTR2	CYSLTR2	CYSLTR2	3930	0.1	0.68	NO
95	ADCY2	ADCY2	ADCY2	4187	0.092	0.67	NO
96	GNAQ	GNAQ	GNAQ	4192	0.091	0.67	NO
97	MYLK	MYLK	MYLK	4327	0.086	0.66	NO
98	HRH1	HRH1	HRH1	4331	0.086	0.66	NO
99	RYR1	RYR1	RYR1	4336	0.086	0.66	NO
100	CALM2	CALM2	CALM2	4375	0.084	0.66	NO
101	ADCY3	ADCY3	ADCY3	4425	0.081	0.66	NO
102	ADCY8	ADCY8	ADCY8	4433	0.081	0.66	NO
103	ATP2A2	ATP2A2	ATP2A2	4462	0.08	0.66	NO
104	ADCY9	ADCY9	ADCY9	4724	0.072	0.65	NO
105	PRKACA	PRKACA	PRKACA	4889	0.066	0.64	NO
106	PPID	PPID	PPID	4890	0.066	0.64	NO
107	VDAC3	VDAC3	VDAC3	4999	0.062	0.64	NO
108	TRPC1	TRPC1	TRPC1	5003	0.062	0.64	NO
109	ATP2B4	ATP2B4	ATP2B4	5282	0.053	0.63	NO
110	GNA11	GNA11	GNA11	5295	0.053	0.63	NO
111	CHP	CHP	CHP	5305	0.052	0.63	NO
112	P2RX6	P2RX6	P2RX6	5335	0.051	0.63	NO
113	VDAC1	VDAC1	VDAC1	5343	0.051	0.63	NO
114	CD38	CD38	CD38	5468	0.048	0.62	NO
115	AGTR1	AGTR1	AGTR1	5637	0.044	0.61	NO
116	PRKCA	PRKCA	PRKCA	5887	0.038	0.6	NO
117	CAMK2D	CAMK2D	CAMK2D	5940	0.036	0.6	NO
118	EDNRB	EDNRB	EDNRB	5971	0.036	0.6	NO
119	P2RX1	P2RX1	P2RX1	6172	0.031	0.58	NO
120	SPHK2	SPHK2	SPHK2	6421	0.026	0.57	NO
121	PLN	PLN	PLN	6602	0.023	0.56	NO
122	SLC8A1	SLC8A1	SLC8A1	6636	0.022	0.56	NO
123	GNAS	GNAS	GNAS	6730	0.02	0.56	NO
124	PRKACG	PRKACG	PRKACG	6800	0.019	0.55	NO
125	ATP2A3	ATP2A3	ATP2A3	6849	0.018	0.55	NO
126	ERBB3	ERBB3	ERBB3	6889	0.017	0.55	NO
127	VDAC2	VDAC2	VDAC2	7213	0.011	0.53	NO
128	NOS3	NOS3	NOS3	7524	0.0058	0.51	NO
129	LHCGR	LHCGR	LHCGR	7735	0.0025	0.5	NO
130	ADRB2	ADRB2	ADRB2	7818	0.0013	0.5	NO
131	ITPR2	ITPR2	ITPR2	7851	0.00068	0.5	NO
132	ITPKB	ITPKB	ITPKB	7916	-0.00065	0.49	NO
133	PHKA1	PHKA1	PHKA1	8265	-0.0058	0.47	NO
134	SLC25A5	SLC25A5	SLC25A5	8419	-0.0082	0.47	NO
135	SLC25A6	SLC25A6	SLC25A6	8422	-0.0082	0.47	NO
136	PHKG2	PHKG2	PHKG2	8500	-0.0095	0.46	NO
137	PPP3CC	PPP3CC	PPP3CC	8524	-0.0098	0.46	NO
138	PDGFRB	PDGFRB	PDGFRB	8678	-0.012	0.45	NO
139	ITPR3	ITPR3	ITPR3	9480	-0.022	0.41	NO
140	PHKB	PHKB	PHKB	9614	-0.024	0.4	NO
141	ADORA2A	ADORA2A	ADORA2A	9644	-0.024	0.4	NO
142	PLCD4	PLCD4	PLCD4	10052	-0.03	0.38	NO
143	PHKA2	PHKA2	PHKA2	10426	-0.034	0.36	NO
144	PLCG1	PLCG1	PLCG1	10537	-0.036	0.35	NO
145	GNA15	GNA15	GNA15	10844	-0.04	0.34	NO
146	P2RX7	P2RX7	P2RX7	10889	-0.041	0.34	NO
147	HTR2B	HTR2B	HTR2B	11514	-0.049	0.3	NO
148	PDGFRA	PDGFRA	PDGFRA	11559	-0.049	0.3	NO
149	P2RX3	P2RX3	P2RX3	11651	-0.051	0.3	NO
150	PLCD3	PLCD3	PLCD3	12495	-0.062	0.25	NO
151	EGFR	EGFR	EGFR	12590	-0.064	0.25	NO
152	CALML6	CALML6	CALML6	12642	-0.064	0.25	NO
153	PHKG1	PHKG1	PHKG1	13246	-0.074	0.21	NO
154	ERBB2	ERBB2	ERBB2	13285	-0.074	0.21	NO
155	ADCY4	ADCY4	ADCY4	13343	-0.075	0.21	NO
156	PLCD1	PLCD1	PLCD1	13784	-0.083	0.19	NO
157	PRKX	PRKX	PRKX	14049	-0.088	0.18	NO
158	MYLK2	MYLK2	MYLK2	14318	-0.093	0.16	NO
159	PLCE1	PLCE1	PLCE1	14703	-0.1	0.14	NO
160	CYSLTR1	CYSLTR1	CYSLTR1	14711	-0.1	0.14	NO
161	ADCY7	ADCY7	ADCY7	14853	-0.11	0.14	NO
162	PLCB3	PLCB3	PLCB3	15474	-0.12	0.11	NO
163	P2RX4	P2RX4	P2RX4	16028	-0.15	0.08	NO
164	SPHK1	SPHK1	SPHK1	16162	-0.15	0.075	NO
165	PLCB2	PLCB2	PLCB2	16296	-0.16	0.071	NO
166	F2R	F2R	F2R	16715	-0.18	0.051	NO
167	PTGER1	PTGER1	PTGER1	16793	-0.19	0.05	NO
168	LTB4R2	LTB4R2	LTB4R2	16927	-0.2	0.047	NO
169	PLCG2	PLCG2	PLCG2	16943	-0.2	0.05	NO
170	PTAFR	PTAFR	PTAFR	17209	-0.22	0.039	NO
171	EDNRA	EDNRA	EDNRA	17358	-0.24	0.035	NO
172	TBXA2R	TBXA2R	TBXA2R	17778	-0.28	0.017	NO
173	ATP2A1	ATP2A1	ATP2A1	17847	-0.29	0.019	NO
174	BST1	BST1	BST1	18151	-0.36	0.009	NO

Figure S75. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA PYK2 PATHWAY.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA PYK2 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 NFAT PATHWAY

Table S39. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRKCG	PRKCG	PRKCG	118	1.1	0.076	YES
2	ITPKA	ITPKA	ITPKA	494	0.73	0.11	YES
3	CDS1	CDS1	CDS1	530	0.7	0.16	YES
4	DGKE	DGKE	DGKE	556	0.69	0.21	YES
5	PIP5K1B	PIP5K1B	PIP5K1B	587	0.67	0.26	YES
6	ITPR1	ITPR1	ITPR1	645	0.64	0.31	YES
7	PRKCB	PRKCB	PRKCB	781	0.57	0.34	YES
8	INPP4B	INPP4B	INPP4B	880	0.53	0.38	YES
9	INPP5J	INPP5J	INPP5J	944	0.5	0.42	YES
10	CALML3	CALML3	CALML3	1004	0.48	0.45	YES
11	SYNJ2	SYNJ2	SYNJ2	1548	0.34	0.44	YES
12	DGKZ	DGKZ	DGKZ	1552	0.34	0.47	YES
13	DGKB	DGKB	DGKB	1897	0.28	0.47	YES
14	PI4KA	PI4KA	PI4KA	1921	0.28	0.49	YES
15	SYNJ1	SYNJ1	SYNJ1	2012	0.26	0.51	YES
16	CALM3	CALM3	CALM3	2141	0.24	0.52	YES
17	PLCB1	PLCB1	PLCB1	2526	0.2	0.51	YES
18	PLCB4	PLCB4	PLCB4	2545	0.2	0.53	YES
19	DGKH	DGKH	DGKH	2599	0.19	0.54	YES
20	DGKI	DGKI	DGKI	2612	0.19	0.55	YES
21	CALM1	CALM1	CALM1	2694	0.18	0.56	YES
22	INPP4A	INPP4A	INPP4A	2880	0.17	0.56	YES
23	INPP5A	INPP5A	INPP5A	2891	0.16	0.58	YES
24	PIP5K1C	PIP5K1C	PIP5K1C	2913	0.16	0.59	YES
25	DGKG	DGKG	DGKG	3029	0.16	0.59	YES
26	PIP4K2C	PIP4K2C	PIP4K2C	3271	0.14	0.59	NO
27	DGKQ	DGKQ	DGKQ	3590	0.12	0.58	NO
28	PIK3CB	PIK3CB	PIK3CB	3602	0.12	0.59	NO
29	CALM2	CALM2	CALM2	4375	0.084	0.56	NO
30	OCRL	OCRL	OCRL	4497	0.079	0.55	NO
31	PIP4K2B	PIP4K2B	PIP4K2B	4498	0.079	0.56	NO
32	PIK3CD	PIK3CD	PIK3CD	4599	0.075	0.56	NO
33	ITPK1	ITPK1	ITPK1	4888	0.066	0.55	NO
34	PIP4K2A	PIP4K2A	PIP4K2A	4953	0.064	0.55	NO
35	PTEN	PTEN	PTEN	5068	0.06	0.55	NO
36	IMPA2	IMPA2	IMPA2	5088	0.06	0.55	NO
37	PIK3C2G	PIK3C2G	PIK3C2G	5328	0.052	0.54	NO
38	PIK3R3	PIK3R3	PIK3R3	5526	0.046	0.54	NO
39	PIK3R1	PIK3R1	PIK3R1	5787	0.04	0.52	NO
40	IMPA1	IMPA1	IMPA1	5796	0.04	0.53	NO
41	PRKCA	PRKCA	PRKCA	5887	0.038	0.52	NO
42	PIKFYVE	PIKFYVE	PIKFYVE	6366	0.028	0.5	NO
43	PIK3C2B	PIK3C2B	PIK3C2B	6444	0.026	0.5	NO
44	IPPK	IPPK	IPPK	6529	0.024	0.5	NO
45	CDIPT	CDIPT	CDIPT	6853	0.018	0.48	NO
46	INPP1	INPP1	INPP1	6863	0.018	0.48	NO
47	CDS2	CDS2	CDS2	6949	0.016	0.48	NO
48	DGKA	DGKA	DGKA	7521	0.0059	0.45	NO
49	ITPR2	ITPR2	ITPR2	7851	0.00068	0.43	NO
50	ITPKB	ITPKB	ITPKB	7916	-0.00065	0.42	NO
51	PIK3R2	PIK3R2	PIK3R2	7920	-0.00074	0.42	NO
52	INPP5K	INPP5K	INPP5K	8439	-0.0085	0.4	NO
53	PIK3C2A	PIK3C2A	PIK3C2A	8631	-0.011	0.39	NO
54	PIK3CA	PIK3CA	PIK3CA	8703	-0.012	0.38	NO
55	INPP5E	INPP5E	INPP5E	9037	-0.016	0.37	NO
56	ITPR3	ITPR3	ITPR3	9480	-0.022	0.34	NO
57	PIK3C3	PIK3C3	PIK3C3	9753	-0.026	0.33	NO
58	PI4KB	PI4KB	PI4KB	9789	-0.026	0.33	NO
59	PIP5K1A	PIP5K1A	PIP5K1A	9943	-0.028	0.33	NO
60	PLCD4	PLCD4	PLCD4	10052	-0.03	0.32	NO
61	PLCG1	PLCG1	PLCG1	10537	-0.036	0.3	NO
62	PLCD3	PLCD3	PLCD3	12495	-0.062	0.2	NO
63	CALML6	CALML6	CALML6	12642	-0.064	0.19	NO
64	DGKD	DGKD	DGKD	12852	-0.068	0.19	NO
65	INPP5B	INPP5B	INPP5B	13186	-0.072	0.17	NO
66	PLCD1	PLCD1	PLCD1	13784	-0.083	0.15	NO
67	INPPL1	INPPL1	INPPL1	14637	-0.1	0.11	NO
68	PLCE1	PLCE1	PLCE1	14703	-0.1	0.11	NO
69	PLCB3	PLCB3	PLCB3	15474	-0.12	0.08	NO
70	PLCB2	PLCB2	PLCB2	16296	-0.16	0.047	NO
71	INPP5D	INPP5D	INPP5D	16330	-0.16	0.057	NO
72	PIK3CG	PIK3CG	PIK3CG	16674	-0.18	0.052	NO
73	PLCG2	PLCG2	PLCG2	16943	-0.2	0.053	NO
74	PIK3R5	PIK3R5	PIK3R5	17884	-0.3	0.024	NO

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

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NFAT 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 PDGF PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	EPHA8	EPHA8	EPHA8	210	0.97	0.027	YES
2	PAK6	PAK6	PAK6	241	0.94	0.062	YES
3	EPHB6	EPHB6	EPHB6	297	0.89	0.094	YES
4	EPHA6	EPHA6	EPHA6	311	0.87	0.13	YES
5	UNC5D	UNC5D	UNC5D	394	0.79	0.15	YES
6	NGEF	NGEF	NGEF	453	0.76	0.18	YES
7	SLIT2	SLIT2	SLIT2	481	0.74	0.21	YES
8	EPHA5	EPHA5	EPHA5	537	0.7	0.23	YES
9	EFNA5	EFNA5	EFNA5	547	0.7	0.26	YES
10	EPHA7	EPHA7	EPHA7	582	0.67	0.28	YES
11	ABLIM2	ABLIM2	ABLIM2	787	0.57	0.3	YES
12	MET	MET	MET	793	0.57	0.32	YES
13	SLIT3	SLIT3	SLIT3	799	0.56	0.34	YES
14	PAK1	PAK1	PAK1	802	0.56	0.36	YES
15	PAK3	PAK3	PAK3	825	0.55	0.38	YES
16	L1CAM	L1CAM	L1CAM	960	0.5	0.39	YES
17	PAK7	PAK7	PAK7	1071	0.46	0.4	YES
18	UNC5A	UNC5A	UNC5A	1123	0.45	0.42	YES
19	SEMA4A	SEMA4A	SEMA4A	1135	0.44	0.44	YES
20	UNC5C	UNC5C	UNC5C	1161	0.44	0.45	YES
21	EPHA4	EPHA4	EPHA4	1278	0.4	0.46	YES
22	NTNG1	NTNG1	NTNG1	1297	0.4	0.48	YES
23	SEMA3E	SEMA3E	SEMA3E	1470	0.36	0.48	YES
24	SEMA3A	SEMA3A	SEMA3A	1627	0.33	0.48	YES
25	EFNA3	EFNA3	EFNA3	1818	0.29	0.49	YES
26	SEMA4F	SEMA4F	SEMA4F	1829	0.29	0.5	YES
27	CHP2	CHP2	CHP2	1900	0.28	0.5	YES
28	PPP3R2	PPP3R2	PPP3R2	1924	0.28	0.51	YES
29	PPP3R1	PPP3R1	PPP3R1	1995	0.26	0.52	YES
30	PPP3CB	PPP3CB	PPP3CB	2076	0.25	0.52	YES
31	RND1	RND1	RND1	2112	0.25	0.53	YES
32	DCC	DCC	DCC	2143	0.24	0.54	YES
33	SEMA3C	SEMA3C	SEMA3C	2153	0.24	0.55	YES
34	PPP3CA	PPP3CA	PPP3CA	2184	0.24	0.56	YES
35	EFNB2	EFNB2	EFNB2	2327	0.22	0.56	YES
36	SEMA6B	SEMA6B	SEMA6B	2461	0.21	0.56	YES
37	ROBO2	ROBO2	ROBO2	2462	0.21	0.57	YES
38	EFNB3	EFNB3	EFNB3	2689	0.18	0.56	YES
39	PLXNA2	PLXNA2	PLXNA2	2753	0.18	0.57	YES
40	RHOD	RHOD	RHOD	2766	0.18	0.57	YES
41	SEMA7A	SEMA7A	SEMA7A	3011	0.16	0.56	YES
42	CDK5	CDK5	CDK5	3038	0.15	0.57	YES
43	PLXNC1	PLXNC1	PLXNC1	3074	0.15	0.57	YES
44	LIMK1	LIMK1	LIMK1	3154	0.15	0.57	YES
45	SEMA3G	SEMA3G	SEMA3G	3188	0.14	0.58	YES
46	NTN4	NTN4	NTN4	3221	0.14	0.58	YES
47	ROCK2	ROCK2	ROCK2	3274	0.14	0.58	YES
48	SLIT1	SLIT1	SLIT1	3539	0.12	0.57	NO
49	GNAI1	GNAI1	GNAI1	3618	0.12	0.58	NO
50	SRGAP3	SRGAP3	SRGAP3	3687	0.11	0.58	NO
51	SEMA6D	SEMA6D	SEMA6D	3833	0.11	0.57	NO
52	SEMA4D	SEMA4D	SEMA4D	3986	0.1	0.57	NO
53	LRRC4C	LRRC4C	LRRC4C	4075	0.097	0.57	NO
54	MAPK3	MAPK3	MAPK3	4086	0.096	0.57	NO
55	EPHA3	EPHA3	EPHA3	4095	0.096	0.57	NO
56	MAPK1	MAPK1	MAPK1	4299	0.087	0.57	NO
57	PLXNA1	PLXNA1	PLXNA1	4545	0.077	0.56	NO
58	KRAS	KRAS	KRAS	4741	0.071	0.55	NO
59	ARHGEF12	ARHGEF12	ARHGEF12	4851	0.067	0.54	NO
60	SEMA3F	SEMA3F	SEMA3F	4932	0.065	0.54	NO
61	GSK3B	GSK3B	GSK3B	5176	0.057	0.53	NO
62	RASA1	RASA1	RASA1	5204	0.056	0.53	NO
63	CHP	CHP	CHP	5305	0.052	0.53	NO
64	SEMA3D	SEMA3D	SEMA3D	5629	0.044	0.51	NO
65	ABLIM3	ABLIM3	ABLIM3	5710	0.042	0.51	NO
66	ABLIM1	ABLIM1	ABLIM1	5744	0.041	0.51	NO
67	NFAT5	NFAT5	NFAT5	5755	0.041	0.51	NO
68	DPYSL2	DPYSL2	DPYSL2	5845	0.038	0.51	NO
69	NFATC4	NFATC4	NFATC4	5997	0.035	0.5	NO
70	SEMA4G	SEMA4G	SEMA4G	6269	0.029	0.49	NO
71	EPHB1	EPHB1	EPHB1	6492	0.025	0.48	NO
72	SEMA4B	SEMA4B	SEMA4B	7004	0.015	0.45	NO
73	RAC3	RAC3	RAC3	7218	0.011	0.44	NO
74	PTK2	PTK2	PTK2	7257	0.01	0.44	NO
75	SEMA4C	SEMA4C	SEMA4C	7376	0.0083	0.43	NO
76	ROBO1	ROBO1	ROBO1	7826	0.0012	0.4	NO
77	CFL2	CFL2	CFL2	8433	-0.0084	0.37	NO
78	PPP3CC	PPP3CC	PPP3CC	8524	-0.0098	0.37	NO
79	SEMA6C	SEMA6C	SEMA6C	8651	-0.011	0.36	NO
80	SEMA6A	SEMA6A	SEMA6A	8669	-0.012	0.36	NO
81	CDC42	CDC42	CDC42	8802	-0.013	0.35	NO
82	CFL1	CFL1	CFL1	9179	-0.018	0.33	NO
83	RAC1	RAC1	RAC1	9393	-0.021	0.32	NO
84	EPHB2	EPHB2	EPHB2	9446	-0.022	0.32	NO
85	NCK2	NCK2	NCK2	9452	-0.022	0.32	NO
86	SEMA3B	SEMA3B	SEMA3B	9495	-0.023	0.32	NO
87	SRGAP2	SRGAP2	SRGAP2	9660	-0.025	0.31	NO
88	UNC5B	UNC5B	UNC5B	9661	-0.025	0.31	NO
89	DPYSL5	DPYSL5	DPYSL5	9874	-0.027	0.3	NO
90	EPHA1	EPHA1	EPHA1	9904	-0.028	0.3	NO
91	PLXNB1	PLXNB1	PLXNB1	10605	-0.037	0.26	NO
92	FYN	FYN	FYN	10672	-0.038	0.26	NO
93	SEMA5A	SEMA5A	SEMA5A	11348	-0.046	0.23	NO
94	NTN3	NTN3	NTN3	11402	-0.047	0.22	NO
95	RHOA	RHOA	RHOA	11530	-0.049	0.22	NO
96	RGS3	RGS3	RGS3	11609	-0.05	0.22	NO
97	ROBO3	ROBO3	ROBO3	11717	-0.052	0.21	NO
98	EPHB3	EPHB3	EPHB3	11740	-0.052	0.22	NO
99	PLXNB3	PLXNB3	PLXNB3	12271	-0.059	0.19	NO
100	NRAS	NRAS	NRAS	12318	-0.06	0.19	NO
101	PAK2	PAK2	PAK2	12616	-0.064	0.17	NO
102	NCK1	NCK1	NCK1	12647	-0.065	0.18	NO
103	ABL1	ABL1	ABL1	12750	-0.066	0.17	NO
104	CXCL12	CXCL12	CXCL12	12954	-0.069	0.16	NO
105	GNAI2	GNAI2	GNAI2	12983	-0.07	0.16	NO
106	SEMA5B	SEMA5B	SEMA5B	13269	-0.074	0.15	NO
107	PAK4	PAK4	PAK4	13367	-0.075	0.15	NO
108	LIMK2	LIMK2	LIMK2	13387	-0.076	0.15	NO
109	ROCK1	ROCK1	ROCK1	13754	-0.082	0.14	NO
110	FES	FES	FES	14110	-0.089	0.12	NO
111	EFNB1	EFNB1	EFNB1	14316	-0.093	0.11	NO
112	PLXNB2	PLXNB2	PLXNB2	14384	-0.095	0.11	NO
113	NRP1	NRP1	NRP1	14766	-0.1	0.094	NO
114	EFNA1	EFNA1	EFNA1	14920	-0.11	0.09	NO
115	NFATC3	NFATC3	NFATC3	15032	-0.11	0.088	NO
116	GNAI3	GNAI3	GNAI3	15047	-0.11	0.092	NO
117	ITGB1	ITGB1	ITGB1	15212	-0.12	0.087	NO
118	SRGAP1	SRGAP1	SRGAP1	15221	-0.12	0.092	NO
119	PLXNA3	PLXNA3	PLXNA3	15613	-0.13	0.075	NO
120	EPHB4	EPHB4	EPHB4	15919	-0.14	0.064	NO
121	NFATC2	NFATC2	NFATC2	16168	-0.15	0.056	NO
122	NTN1	NTN1	NTN1	16493	-0.17	0.045	NO
123	EPHA2	EPHA2	EPHA2	16633	-0.18	0.044	NO
124	EFNA2	EFNA2	EFNA2	16756	-0.18	0.045	NO
125	NFATC1	NFATC1	NFATC1	16845	-0.19	0.048	NO
126	CXCR4	CXCR4	CXCR4	17133	-0.22	0.04	NO
127	EFNA4	EFNA4	EFNA4	17295	-0.23	0.04	NO
128	RAC2	RAC2	RAC2	18217	-0.4	0.0054	NO

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

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA PDGF 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 clus5 enriched pathways

Table 7. Get Full Table This table shows top 10 pathways which are significantly enriched in cluster clus5. 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 MYOSIN PATHWAY	28	genes.ES.table	0.46	1.4	0.095	0.55	0.94	0.11	0.043	0.1	0.42	0.14
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.43	1.4	0.062	0.67	0.92	0.38	0.26	0.28	0.52	0.2
KEGG FATTY ACID METABOLISM	39	genes.ES.table	0.38	1.3	0.2	0.65	1	0.38	0.27	0.28	0.56	0.18
KEGG OXIDATIVE PHOSPHORYLATION	114	genes.ES.table	0.37	1.3	0.26	0.72	0.99	0.63	0.41	0.38	0.63	0.22
KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM	29	genes.ES.table	0.48	1.3	0.21	0.74	0.99	0.21	0.12	0.18	0.64	0.24
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.47	1.7	0.019	0.57	0.39	0.4	0.26	0.29	0	0.2
KEGG HISTIDINE METABOLISM	28	genes.ES.table	0.57	1.5	0.026	1	0.88	0.68	0.31	0.47	0.81	0.41
KEGG GLUTATHIONE METABOLISM	43	genes.ES.table	0.4	1.3	0.15	0.7	0.99	0.44	0.26	0.33	0.58	0.21
KEGG ETHER LIPID METABOLISM	27	genes.ES.table	0.53	1.4	0.054	0.55	0.95	0.3	0.13	0.26	0.42	0.14
KEGG PROPANOATE METABOLISM	31	genes.ES.table	0.37	1.3	0.23	0.71	0.99	0.36	0.26	0.26	0.61	0.21

genes ES table in pathway: BIOCARTA MYOSIN PATHWAY

Table S41. 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	ACADS	ACADS	ACADS	681	0.31	0.079	YES
2	ACAA2	ACAA2	ACAA2	2003	0.16	0.068	YES
3	ALDH7A1	ALDH7A1	ALDH7A1	2111	0.15	0.12	YES
4	IL4I1	IL4I1	IL4I1	2153	0.15	0.18	YES
5	ALDH2	ALDH2	ALDH2	2693	0.12	0.19	YES
6	BCAT2	BCAT2	BCAT2	2718	0.12	0.24	YES
7	ACAA1	ACAA1	ACAA1	2737	0.12	0.28	YES
8	MCEE	MCEE	MCEE	2887	0.12	0.32	YES
9	HMGCL	HMGCL	HMGCL	3427	0.097	0.33	YES
10	BCKDHB	BCKDHB	BCKDHB	3830	0.085	0.34	YES
11	AUH	AUH	AUH	3928	0.082	0.36	YES
12	HIBCH	HIBCH	HIBCH	4055	0.079	0.38	YES
13	HADHB	HADHB	HADHB	4228	0.074	0.4	YES
14	ECHS1	ECHS1	ECHS1	4265	0.074	0.43	YES
15	HSD17B10	HSD17B10	HSD17B10	4638	0.065	0.43	YES
16	ALDH9A1	ALDH9A1	ALDH9A1	4692	0.064	0.46	YES
17	BCKDHA	BCKDHA	BCKDHA	4776	0.062	0.47	YES
18	ALDH6A1	ALDH6A1	ALDH6A1	5873	0.042	0.43	NO
19	ACAT1	ACAT1	ACAT1	5909	0.042	0.44	NO
20	OXCT2	OXCT2	OXCT2	6178	0.038	0.44	NO
21	ACADM	ACADM	ACADM	6729	0.03	0.42	NO
22	ACADSB	ACADSB	ACADSB	6845	0.029	0.43	NO
23	PCCA	PCCA	PCCA	7190	0.024	0.42	NO
24	HADHA	HADHA	HADHA	7207	0.024	0.43	NO
25	HIBADH	HIBADH	HIBADH	7209	0.024	0.44	NO
26	EHHADH	EHHADH	EHHADH	7258	0.023	0.44	NO
27	AOX1	AOX1	AOX1	7385	0.022	0.44	NO
28	IVD	IVD	IVD	8005	0.013	0.42	NO
29	ALDH3A2	ALDH3A2	ALDH3A2	8338	0.0094	0.4	NO
30	MCCC1	MCCC1	MCCC1	8615	0.0059	0.39	NO
31	ACAT2	ACAT2	ACAT2	8788	0.0041	0.38	NO
32	HADH	HADH	HADH	9209	-0.0014	0.36	NO
33	PCCB	PCCB	PCCB	9753	-0.0078	0.33	NO
34	ACAD8	ACAD8	ACAD8	9898	-0.0095	0.33	NO
35	OXCT1	OXCT1	OXCT1	10583	-0.018	0.3	NO
36	MCCC2	MCCC2	MCCC2	10691	-0.02	0.3	NO
37	DBT	DBT	DBT	10749	-0.02	0.3	NO
38	ABAT	ABAT	ABAT	11273	-0.027	0.28	NO
39	MUT	MUT	MUT	11427	-0.029	0.29	NO
40	DLD	DLD	DLD	12630	-0.046	0.24	NO
41	HMGCS1	HMGCS1	HMGCS1	12815	-0.049	0.25	NO
42	HMGCS2	HMGCS2	HMGCS2	13191	-0.055	0.25	NO
43	ALDH1B1	ALDH1B1	ALDH1B1	14786	-0.09	0.19	NO

Figure S81. 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 S82. 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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

Table S42. 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	GPR37	GPR37	GPR37	221	0.48	0.075	YES
2	COX8C	COX8C	COX8C	1061	0.25	0.073	YES
3	COX4I2	COX4I2	COX4I2	1910	0.17	0.057	YES
4	NDUFA3	NDUFA3	NDUFA3	2407	0.14	0.054	YES
5	SNCA	SNCA	SNCA	2754	0.12	0.057	YES
6	COX6B2	COX6B2	COX6B2	3039	0.11	0.062	YES
7	UBA7	UBA7	UBA7	3110	0.11	0.077	YES
8	NDUFS7	NDUFS7	NDUFS7	3115	0.11	0.096	YES
9	COX6A2	COX6A2	COX6A2	3230	0.1	0.11	YES
10	COX7A1	COX7A1	COX7A1	3398	0.098	0.12	YES
11	TH	TH	TH	3619	0.091	0.12	YES
12	NDUFC1	NDUFC1	NDUFC1	3707	0.088	0.13	YES
13	SLC25A31	SLC25A31	SLC25A31	3833	0.085	0.14	YES
14	NDUFB1	NDUFB1	NDUFB1	3966	0.081	0.15	YES
15	COX5B	COX5B	COX5B	3980	0.081	0.16	YES
16	UBB	UBB	UBB	4073	0.079	0.17	YES
17	NDUFA1	NDUFA1	NDUFA1	4120	0.077	0.18	YES
18	NDUFS6	NDUFS6	NDUFS6	4173	0.076	0.19	YES
19	NDUFA2	NDUFA2	NDUFA2	4235	0.074	0.2	YES
20	NDUFB4	NDUFB4	NDUFB4	4245	0.074	0.22	YES
21	NDUFB6	NDUFB6	NDUFB6	4461	0.069	0.22	YES
22	NDUFB3	NDUFB3	NDUFB3	4512	0.068	0.23	YES
23	UQCRQ	UQCRQ	UQCRQ	4567	0.067	0.24	YES
24	NDUFB8	NDUFB8	NDUFB8	4594	0.066	0.25	YES
25	PINK1	PINK1	PINK1	4619	0.065	0.26	YES
26	NDUFB7	NDUFB7	NDUFB7	4681	0.064	0.26	YES
27	ATP5E	ATP5E	ATP5E	4878	0.06	0.26	YES
28	NDUFC2	NDUFC2	NDUFC2	4913	0.059	0.27	YES
29	COX7B	COX7B	COX7B	4914	0.059	0.28	YES
30	COX6B1	COX6B1	COX6B1	4946	0.059	0.29	YES
31	NDUFB10	NDUFB10	NDUFB10	5200	0.054	0.29	YES
32	ATP5D	ATP5D	ATP5D	5217	0.054	0.3	YES
33	COX6C	COX6C	COX6C	5230	0.054	0.31	YES
34	UQCR10	UQCR10	UQCR10	5236	0.053	0.32	YES
35	ATP5J	ATP5J	ATP5J	5244	0.053	0.32	YES
36	UQCR11	UQCR11	UQCR11	5281	0.052	0.33	YES
37	COX4I1	COX4I1	COX4I1	5374	0.051	0.34	YES
38	UQCRB	UQCRB	UQCRB	5453	0.05	0.34	YES
39	NDUFS8	NDUFS8	NDUFS8	5585	0.047	0.34	YES
40	NDUFB9	NDUFB9	NDUFB9	5638	0.046	0.35	YES
41	NDUFB2	NDUFB2	NDUFB2	5826	0.043	0.34	YES
42	NDUFA7	NDUFA7	NDUFA7	5908	0.042	0.35	YES
43	COX6A1	COX6A1	COX6A1	6110	0.039	0.34	YES
44	COX7A2	COX7A2	COX7A2	6244	0.037	0.34	YES
45	NDUFV2	NDUFV2	NDUFV2	6249	0.037	0.35	YES
46	NDUFV1	NDUFV1	NDUFV1	6333	0.036	0.35	YES
47	UBE2G1	UBE2G1	UBE2G1	6377	0.035	0.36	YES
48	PARK7	PARK7	PARK7	6454	0.034	0.36	YES
49	ATP5F1	ATP5F1	ATP5F1	6459	0.034	0.36	YES
50	NDUFS3	NDUFS3	NDUFS3	6463	0.034	0.37	YES
51	COX8A	COX8A	COX8A	6538	0.033	0.37	YES
52	UBE2L3	UBE2L3	UBE2L3	6542	0.032	0.38	YES
53	NDUFA10	NDUFA10	NDUFA10	6601	0.032	0.38	YES
54	COX7C	COX7C	COX7C	6612	0.032	0.38	YES
55	SDHA	SDHA	SDHA	6671	0.031	0.39	YES
56	ATP5G1	ATP5G1	ATP5G1	6744	0.03	0.39	YES
57	UBE2J2	UBE2J2	UBE2J2	6801	0.029	0.39	YES
58	SDHB	SDHB	SDHB	6871	0.028	0.39	YES
59	HTRA2	HTRA2	HTRA2	6884	0.028	0.4	YES
60	NDUFA8	NDUFA8	NDUFA8	6908	0.028	0.4	YES
61	COX5A	COX5A	COX5A	6915	0.028	0.4	YES
62	NDUFB5	NDUFB5	NDUFB5	6996	0.027	0.4	YES
63	NDUFAB1	NDUFAB1	NDUFAB1	7221	0.024	0.4	YES
64	ATP5H	ATP5H	ATP5H	7259	0.023	0.4	YES
65	SDHD	SDHD	SDHD	7276	0.023	0.4	YES
66	ATP5O	ATP5O	ATP5O	7303	0.023	0.4	YES
67	NDUFA5	NDUFA5	NDUFA5	7350	0.022	0.41	YES
68	SDHC	SDHC	SDHC	7363	0.022	0.41	YES
69	CASP9	CASP9	CASP9	7371	0.022	0.41	YES
70	COX7A2L	COX7A2L	COX7A2L	7449	0.02	0.41	YES
71	ATP5G2	ATP5G2	ATP5G2	7494	0.02	0.41	YES
72	UQCRFS1	UQCRFS1	UQCRFS1	7669	0.017	0.41	NO
73	NDUFA6	NDUFA6	NDUFA6	7792	0.016	0.4	NO
74	NDUFV3	NDUFV3	NDUFV3	7872	0.015	0.4	NO
75	UQCRC1	UQCRC1	UQCRC1	7921	0.014	0.4	NO
76	SLC25A4	SLC25A4	SLC25A4	8137	0.012	0.39	NO
77	NDUFS5	NDUFS5	NDUFS5	8180	0.011	0.39	NO
78	NDUFA4	NDUFA4	NDUFA4	8219	0.011	0.39	NO
79	NDUFS4	NDUFS4	NDUFS4	8274	0.01	0.39	NO
80	CYC1	CYC1	CYC1	8341	0.0094	0.39	NO
81	VDAC2	VDAC2	VDAC2	8484	0.0078	0.38	NO
82	NDUFA4L2	NDUFA4L2	NDUFA4L2	8730	0.0047	0.37	NO
83	NDUFS2	NDUFS2	NDUFS2	8923	0.0025	0.36	NO
84	ATP5G3	ATP5G3	ATP5G3	9025	0.00096	0.35	NO
85	VDAC3	VDAC3	VDAC3	9069	0.0003	0.35	NO
86	SLC6A3	SLC6A3	SLC6A3	9247	-0.0018	0.34	NO
87	PPID	PPID	PPID	9455	-0.0043	0.33	NO
88	NDUFA9	NDUFA9	NDUFA9	9457	-0.0043	0.33	NO
89	CASP3	CASP3	CASP3	9584	-0.0058	0.33	NO
90	UBE2G2	UBE2G2	UBE2G2	10198	-0.013	0.3	NO
91	SLC18A1	SLC18A1	SLC18A1	10258	-0.014	0.3	NO
92	ATP5C1	ATP5C1	ATP5C1	10292	-0.014	0.3	NO
93	CYCS	CYCS	CYCS	10355	-0.015	0.3	NO
94	UBE2L6	UBE2L6	UBE2L6	10619	-0.019	0.28	NO
95	UBE2J1	UBE2J1	UBE2J1	10658	-0.019	0.28	NO
96	UQCRH	UQCRH	UQCRH	10660	-0.019	0.29	NO
97	SLC25A6	SLC25A6	SLC25A6	10808	-0.021	0.28	NO
98	ATP5A1	ATP5A1	ATP5A1	10889	-0.022	0.28	NO
99	VDAC1	VDAC1	VDAC1	11494	-0.03	0.26	NO
100	UBA1	UBA1	UBA1	11703	-0.033	0.25	NO
101	UCHL1	UCHL1	UCHL1	11740	-0.033	0.25	NO
102	UQCRHL	UQCRHL	UQCRHL	11962	-0.036	0.25	NO
103	APAF1	APAF1	APAF1	12697	-0.047	0.22	NO
104	UQCRC2	UQCRC2	UQCRC2	12712	-0.047	0.22	NO
105	ATP5B	ATP5B	ATP5B	13024	-0.053	0.22	NO
106	SLC18A2	SLC18A2	SLC18A2	13180	-0.055	0.22	NO
107	SLC25A5	SLC25A5	SLC25A5	13238	-0.056	0.22	NO
108	NDUFS1	NDUFS1	NDUFS1	13306	-0.057	0.23	NO
109	LRRK2	LRRK2	LRRK2	13554	-0.062	0.23	NO
110	PARK2	PARK2	PARK2	14408	-0.081	0.2	NO
111	SNCAIP	SNCAIP	SNCAIP	15012	-0.097	0.18	NO

Figure S83. 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 S84. 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 S43. 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	ASPA	ASPA	ASPA	115	0.62	0.18	YES
2	ACY3	ACY3	ACY3	252	0.46	0.32	YES
3	MAOB	MAOB	MAOB	852	0.28	0.37	YES
4	ALDH3A1	ALDH3A1	ALDH3A1	1292	0.22	0.41	YES
5	AMDHD1	AMDHD1	AMDHD1	2046	0.16	0.42	YES
6	ALDH7A1	ALDH7A1	ALDH7A1	2111	0.15	0.46	YES
7	ALDH3B1	ALDH3B1	ALDH3B1	2259	0.15	0.5	YES
8	ALDH2	ALDH2	ALDH2	2693	0.12	0.51	YES
9	ALDH3B2	ALDH3B2	ALDH3B2	3378	0.099	0.51	YES
10	HAL	HAL	HAL	3641	0.09	0.52	YES
11	HEMK1	HEMK1	HEMK1	4092	0.078	0.52	YES
12	MAOA	MAOA	MAOA	4587	0.066	0.51	YES
13	ALDH9A1	ALDH9A1	ALDH9A1	4692	0.064	0.53	YES
14	HNMT	HNMT	HNMT	4710	0.064	0.55	YES
15	TRMT11	TRMT11	TRMT11	5286	0.052	0.53	YES
16	FTCD	FTCD	FTCD	5505	0.049	0.53	YES
17	ALDH1A3	ALDH1A3	ALDH1A3	5510	0.049	0.55	YES
18	UROC1	UROC1	UROC1	5666	0.046	0.55	YES
19	ABP1	ABP1	ABP1	5689	0.045	0.57	YES
20	WBSCR22	WBSCR22	WBSCR22	6756	0.03	0.52	NO
21	ALDH3A2	ALDH3A2	ALDH3A2	8338	0.0094	0.43	NO
22	LCMT1	LCMT1	LCMT1	9268	-0.002	0.38	NO
23	METTL6	METTL6	METTL6	9693	-0.0072	0.36	NO
24	LCMT2	LCMT2	LCMT2	10723	-0.02	0.31	NO
25	HDC	HDC	HDC	13941	-0.069	0.16	NO
26	DDC	DDC	DDC	14322	-0.079	0.16	NO
27	ALDH1B1	ALDH1B1	ALDH1B1	14786	-0.09	0.16	NO
28	METTL2B	METTL2B	METTL2B	14985	-0.096	0.18	NO

Figure S85. 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 S86. 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 OXIDATIVE PHOSPHORYLATION

Table S44. 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	DAO	DAO	DAO	245	0.47	0.061	YES
2	PAOX	PAOX	PAOX	357	0.4	0.12	YES
3	PEX11G	PEX11G	PEX11G	687	0.31	0.15	YES
4	EPHX2	EPHX2	EPHX2	714	0.3	0.2	YES
5	ACSL1	ACSL1	ACSL1	1085	0.25	0.22	YES
6	BAAT	BAAT	BAAT	1374	0.21	0.23	YES
7	MPV17L	MPV17L	MPV17L	1831	0.17	0.24	YES
8	DDO	DDO	DDO	1929	0.17	0.26	YES
9	HAO1	HAO1	HAO1	2090	0.16	0.27	YES
10	PRDX1	PRDX1	PRDX1	2094	0.16	0.3	YES
11	ACAA1	ACAA1	ACAA1	2737	0.12	0.28	YES
12	PEX16	PEX16	PEX16	2984	0.11	0.29	YES
13	DHRS4	DHRS4	DHRS4	3032	0.11	0.3	YES
14	MVK	MVK	MVK	3166	0.11	0.31	YES
15	PEX7	PEX7	PEX7	3282	0.1	0.32	YES
16	FAR1	FAR1	FAR1	3323	0.1	0.34	YES
17	PMVK	PMVK	PMVK	3373	0.099	0.35	YES
18	HMGCL	HMGCL	HMGCL	3427	0.097	0.36	YES
19	PHYH	PHYH	PHYH	3482	0.095	0.37	YES
20	PIPOX	PIPOX	PIPOX	3667	0.09	0.38	YES
21	ABCD4	ABCD4	ABCD4	4114	0.078	0.36	NO
22	SOD1	SOD1	SOD1	4706	0.064	0.34	NO
23	HSD17B4	HSD17B4	HSD17B4	4738	0.063	0.35	NO
24	PEX10	PEX10	PEX10	4839	0.061	0.36	NO
25	PXMP4	PXMP4	PXMP4	5423	0.05	0.33	NO
26	XDH	XDH	XDH	5431	0.05	0.34	NO
27	DECR2	DECR2	DECR2	5598	0.047	0.34	NO
28	CAT	CAT	CAT	5602	0.047	0.34	NO
29	ACOT8	ACOT8	ACOT8	5657	0.046	0.35	NO
30	NUDT12	NUDT12	NUDT12	5696	0.045	0.35	NO
31	IDH2	IDH2	IDH2	5800	0.043	0.36	NO
32	ECH1	ECH1	ECH1	5974	0.041	0.35	NO
33	NUDT19	NUDT19	NUDT19	6046	0.04	0.36	NO
34	PEX2	PEX2	PEX2	6063	0.04	0.36	NO
35	PECI	PECI	PECI	6217	0.037	0.36	NO
36	GSTK1	GSTK1	GSTK1	6611	0.032	0.34	NO
37	PRDX5	PRDX5	PRDX5	6618	0.032	0.35	NO
38	MPV17	MPV17	MPV17	6914	0.028	0.33	NO
39	PEX11A	PEX11A	PEX11A	6985	0.027	0.34	NO
40	EHHADH	EHHADH	EHHADH	7258	0.023	0.32	NO
41	SCP2	SCP2	SCP2	7386	0.022	0.32	NO
42	HACL1	HACL1	HACL1	7546	0.019	0.31	NO
43	PEX1	PEX1	PEX1	7695	0.017	0.31	NO
44	PEX6	PEX6	PEX6	7769	0.016	0.31	NO
45	SOD2	SOD2	SOD2	7869	0.015	0.3	NO
46	PEX14	PEX14	PEX14	7889	0.015	0.31	NO
47	PEX12	PEX12	PEX12	7957	0.014	0.3	NO
48	ABCD3	ABCD3	ABCD3	8201	0.011	0.29	NO
49	GNPAT	GNPAT	GNPAT	8398	0.0087	0.28	NO
50	PEX5	PEX5	PEX5	8565	0.0066	0.28	NO
51	PEX3	PEX3	PEX3	8991	0.0016	0.25	NO
52	PXMP2	PXMP2	PXMP2	9048	0.00057	0.25	NO
53	ACOX3	ACOX3	ACOX3	9063	0.00038	0.25	NO
54	ACSL3	ACSL3	ACSL3	9112	-0.0002	0.25	NO
55	PEX19	PEX19	PEX19	9565	-0.0056	0.22	NO
56	PEX13	PEX13	PEX13	9812	-0.0085	0.21	NO
57	AGPS	AGPS	AGPS	9972	-0.01	0.2	NO
58	PECR	PECR	PECR	10170	-0.013	0.19	NO
59	CRAT	CRAT	CRAT	10191	-0.013	0.2	NO
60	ACSL5	ACSL5	ACSL5	10248	-0.014	0.19	NO
61	ACOX1	ACOX1	ACOX1	10613	-0.019	0.18	NO
62	ABCD1	ABCD1	ABCD1	10775	-0.021	0.17	NO
63	SLC25A17	SLC25A17	SLC25A17	11197	-0.026	0.15	NO
64	ACSL6	ACSL6	ACSL6	11376	-0.028	0.15	NO
65	MLYCD	MLYCD	MLYCD	11576	-0.031	0.14	NO
66	PEX11B	PEX11B	PEX11B	11885	-0.035	0.13	NO
67	CROT	CROT	CROT	13457	-0.06	0.054	NO
68	HAO2	HAO2	HAO2	14669	-0.087	0.00095	NO
69	AMACR	AMACR	AMACR	14670	-0.087	0.015	NO
70	IDH1	IDH1	IDH1	15125	-0.1	0.0059	NO
71	ACSL4	ACSL4	ACSL4	15259	-0.1	0.015	NO
72	PEX26	PEX26	PEX26	15462	-0.11	0.022	NO
73	NOS2	NOS2	NOS2	16532	-0.16	-0.011	NO
74	ABCD2	ABCD2	ABCD2	17104	-0.2	-0.0097	NO
75	FAR2	FAR2	FAR2	17294	-0.22	0.016	NO
76	SLC27A2	SLC27A2	SLC27A2	17567	-0.25	0.041	NO

Figure S87. 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 S88. 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 ALANINE ASPARTATE AND GLUTAMATE METABOLISM

Table S45. 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	CLDN11	CLDN11	CLDN11	118	0.61	0.042	YES
2	LLGL2	LLGL2	LLGL2	268	0.45	0.069	YES
3	CLDN20	CLDN20	CLDN20	336	0.41	0.098	YES
4	MYH7B	MYH7B	MYH7B	378	0.39	0.13	YES
5	MYH15	MYH15	MYH15	472	0.36	0.15	YES
6	PRKCQ	PRKCQ	PRKCQ	497	0.35	0.18	YES
7	CLDN23	CLDN23	CLDN23	630	0.32	0.2	YES
8	CRB3	CRB3	CRB3	739	0.3	0.21	YES
9	CLDN14	CLDN14	CLDN14	1117	0.24	0.21	YES
10	CTNNA3	CTNNA3	CTNNA3	1199	0.23	0.22	YES
11	PPP2R2C	PPP2R2C	PPP2R2C	1202	0.23	0.24	YES
12	CLDN10	CLDN10	CLDN10	1226	0.23	0.26	YES
13	CLDN7	CLDN7	CLDN7	1439	0.2	0.26	YES
14	MYH3	MYH3	MYH3	1453	0.2	0.28	YES
15	CLDN3	CLDN3	CLDN3	1468	0.2	0.3	YES
16	CLDN9	CLDN9	CLDN9	1481	0.2	0.31	YES
17	MYL5	MYL5	MYL5	1588	0.19	0.32	YES
18	TJAP1	TJAP1	TJAP1	1624	0.19	0.33	YES
19	TJP2	TJP2	TJP2	1913	0.17	0.33	YES
20	EPB41L3	EPB41L3	EPB41L3	1999	0.16	0.34	YES
21	JAM3	JAM3	JAM3	2024	0.16	0.35	YES
22	GNAI1	GNAI1	GNAI1	2047	0.16	0.36	YES
23	ACTN2	ACTN2	ACTN2	2066	0.16	0.37	YES
24	MYH14	MYH14	MYH14	2198	0.15	0.38	YES
25	MYLPF	MYLPF	MYLPF	2321	0.14	0.38	YES
26	LLGL1	LLGL1	LLGL1	2351	0.14	0.39	YES
27	INADL	INADL	INADL	2449	0.14	0.4	YES
28	RRAS	RRAS	RRAS	2721	0.12	0.39	NO
29	PPP2R1B	PPP2R1B	PPP2R1B	2834	0.12	0.4	NO
30	PRKCZ	PRKCZ	PRKCZ	3372	0.099	0.37	NO
31	PARD6B	PARD6B	PARD6B	3489	0.095	0.37	NO
32	PRKCD	PRKCD	PRKCD	3610	0.091	0.38	NO
33	IGSF5	IGSF5	IGSF5	3660	0.09	0.38	NO
34	CGN	CGN	CGN	3780	0.087	0.38	NO
35	RAB13	RAB13	RAB13	3864	0.084	0.38	NO
36	PPP2R2B	PPP2R2B	PPP2R2B	3887	0.083	0.39	NO
37	HCLS1	HCLS1	HCLS1	3962	0.081	0.39	NO
38	PPP2CB	PPP2CB	PPP2CB	4222	0.074	0.38	NO
39	EPB41L2	EPB41L2	EPB41L2	4270	0.074	0.38	NO
40	CLDN2	CLDN2	CLDN2	4414	0.07	0.38	NO
41	CTNNA1	CTNNA1	CTNNA1	4504	0.068	0.38	NO
42	MYL12A	MYL12A	MYL12A	4523	0.068	0.39	NO
43	MYL7	MYL7	MYL7	4647	0.065	0.38	NO
44	CTTN	CTTN	CTTN	4780	0.062	0.38	NO
45	MYH6	MYH6	MYH6	4827	0.061	0.38	NO
46	CLDN5	CLDN5	CLDN5	5048	0.057	0.38	NO
47	CLDN19	CLDN19	CLDN19	5346	0.052	0.36	NO
48	PRKCG	PRKCG	PRKCG	5527	0.048	0.36	NO
49	MRAS	MRAS	MRAS	5713	0.045	0.35	NO
50	TJP1	TJP1	TJP1	5783	0.044	0.35	NO
51	CLDN15	CLDN15	CLDN15	5849	0.043	0.35	NO
52	GNAI2	GNAI2	GNAI2	5946	0.041	0.35	NO
53	MPP5	MPP5	MPP5	6088	0.04	0.35	NO
54	CSNK2B	CSNK2B	CSNK2B	6547	0.032	0.32	NO
55	MYH7	MYH7	MYH7	6548	0.032	0.33	NO
56	RHOA	RHOA	RHOA	6634	0.031	0.32	NO
57	EXOC3	EXOC3	EXOC3	6660	0.031	0.32	NO
58	CSDA	CSDA	CSDA	7214	0.024	0.3	NO
59	ACTB	ACTB	ACTB	7434	0.021	0.29	NO
60	CDC42	CDC42	CDC42	7435	0.021	0.29	NO
61	MAGI2	MAGI2	MAGI2	7518	0.02	0.28	NO
62	EPB41L1	EPB41L1	EPB41L1	7548	0.019	0.28	NO
63	PPP2R2A	PPP2R2A	PPP2R2A	7579	0.018	0.28	NO
64	VAPA	VAPA	VAPA	7639	0.018	0.28	NO
65	YES1	YES1	YES1	7759	0.016	0.28	NO
66	AKT2	AKT2	AKT2	8073	0.013	0.26	NO
67	MPDZ	MPDZ	MPDZ	8199	0.011	0.26	NO
68	ACTG1	ACTG1	ACTG1	8212	0.011	0.26	NO
69	ACTN4	ACTN4	ACTN4	8812	0.0038	0.22	NO
70	SYMPK	SYMPK	SYMPK	8933	0.0023	0.22	NO
71	MYL12B	MYL12B	MYL12B	9289	-0.0022	0.2	NO
72	RRAS2	RRAS2	RRAS2	9568	-0.0056	0.18	NO
73	PRKCH	PRKCH	PRKCH	10288	-0.014	0.14	NO
74	GNAI3	GNAI3	GNAI3	10379	-0.016	0.14	NO
75	PARD6A	PARD6A	PARD6A	10410	-0.016	0.14	NO
76	MLLT4	MLLT4	MLLT4	10422	-0.016	0.14	NO
77	PPP2R1A	PPP2R1A	PPP2R1A	10771	-0.021	0.12	NO
78	PPP2CA	PPP2CA	PPP2CA	10851	-0.022	0.12	NO
79	ZAK	ZAK	ZAK	11033	-0.024	0.11	NO
80	CTNNB1	CTNNB1	CTNNB1	11044	-0.024	0.11	NO
81	PPP2R2D	PPP2R2D	PPP2R2D	11052	-0.024	0.12	NO
82	NRAS	NRAS	NRAS	11147	-0.025	0.11	NO
83	AMOTL1	AMOTL1	AMOTL1	11211	-0.026	0.11	NO
84	AKT1	AKT1	AKT1	11357	-0.028	0.1	NO
85	SPTAN1	SPTAN1	SPTAN1	11358	-0.028	0.11	NO
86	MYL9	MYL9	MYL9	11457	-0.029	0.1	NO
87	PRKCA	PRKCA	PRKCA	11783	-0.034	0.088	NO
88	PARD6G	PARD6G	PARD6G	11791	-0.034	0.09	NO
89	F11R	F11R	F11R	11993	-0.037	0.082	NO
90	EXOC4	EXOC4	EXOC4	12388	-0.042	0.064	NO
91	MYH9	MYH9	MYH9	12542	-0.044	0.059	NO
92	CLDN1	CLDN1	CLDN1	12555	-0.044	0.062	NO
93	PARD3	PARD3	PARD3	12695	-0.047	0.058	NO
94	CLDN4	CLDN4	CLDN4	12946	-0.051	0.048	NO
95	JAM2	JAM2	JAM2	12960	-0.052	0.052	NO
96	CSNK2A2	CSNK2A2	CSNK2A2	13355	-0.058	0.035	NO
97	ASH1L	ASH1L	ASH1L	13508	-0.061	0.031	NO
98	MAGI3	MAGI3	MAGI3	13534	-0.061	0.035	NO
99	MYH13	MYH13	MYH13	13537	-0.061	0.039	NO
100	PTEN	PTEN	PTEN	13625	-0.063	0.04	NO
101	CASK	CASK	CASK	13679	-0.064	0.042	NO
102	CTNNA2	CTNNA2	CTNNA2	14143	-0.075	0.022	NO
103	CSNK2A1	CSNK2A1	CSNK2A1	14185	-0.076	0.026	NO
104	CDK4	CDK4	CDK4	14219	-0.077	0.03	NO
105	TJP3	TJP3	TJP3	14292	-0.078	0.032	NO
106	MAGI1	MAGI1	MAGI1	14390	-0.08	0.034	NO
107	KRAS	KRAS	KRAS	14465	-0.082	0.036	NO
108	SRC	SRC	SRC	14785	-0.09	0.026	NO
109	PRKCI	PRKCI	PRKCI	14964	-0.095	0.023	NO
110	MYH11	MYH11	MYH11	15018	-0.097	0.028	NO
111	EPB41	EPB41	EPB41	15078	-0.099	0.033	NO
112	MYH10	MYH10	MYH10	15584	-0.12	0.014	NO
113	RAB3B	RAB3B	RAB3B	15681	-0.12	0.018	NO
114	CLDN6	CLDN6	CLDN6	15742	-0.12	0.025	NO
115	OCLN	OCLN	OCLN	15846	-0.13	0.029	NO
116	PRKCB	PRKCB	PRKCB	15885	-0.13	0.037	NO
117	ACTN3	ACTN3	ACTN3	15931	-0.13	0.045	NO
118	AKT3	AKT3	AKT3	16084	-0.14	0.047	NO
119	MYH4	MYH4	MYH4	16585	-0.16	0.033	NO
120	ACTN1	ACTN1	ACTN1	16619	-0.17	0.044	NO
121	CLDN18	CLDN18	CLDN18	16722	-0.17	0.052	NO
122	PRKCE	PRKCE	PRKCE	16750	-0.18	0.065	NO
123	CLDN16	CLDN16	CLDN16	17681	-0.27	0.035	NO

Figure S89. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM.

Figure S90. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

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

Table S46. 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	SLC27A6	SLC27A6	SLC27A6	79	0.69	0.085	YES
2	PLIN1	PLIN1	PLIN1	271	0.45	0.13	YES
3	RXRG	RXRG	RXRG	340	0.41	0.18	YES
4	CYP27A1	CYP27A1	CYP27A1	366	0.4	0.23	YES
5	CYP8B1	CYP8B1	CYP8B1	628	0.32	0.26	YES
6	ACSL1	ACSL1	ACSL1	1085	0.25	0.27	YES
7	FABP5	FABP5	FABP5	1220	0.23	0.29	YES
8	OLR1	OLR1	OLR1	1276	0.22	0.31	YES
9	ANGPTL4	ANGPTL4	ANGPTL4	1278	0.22	0.34	YES
10	APOA1	APOA1	APOA1	1357	0.21	0.37	YES
11	FABP6	FABP6	FABP6	1558	0.2	0.38	YES
12	CPT1B	CPT1B	CPT1B	1780	0.18	0.39	YES
13	FABP1	FABP1	FABP1	1807	0.18	0.41	YES
14	ME1	ME1	ME1	1855	0.17	0.43	YES
15	SLC27A5	SLC27A5	SLC27A5	1863	0.17	0.46	YES
16	SCD	SCD	SCD	1932	0.17	0.47	YES
17	SLC27A1	SLC27A1	SLC27A1	2042	0.16	0.49	YES
18	PPARG	PPARG	PPARG	2592	0.13	0.47	YES
19	ACAA1	ACAA1	ACAA1	2737	0.12	0.48	YES
20	FABP4	FABP4	FABP4	2764	0.12	0.5	YES
21	ACADL	ACADL	ACADL	3558	0.093	0.46	NO
22	DBI	DBI	DBI	3674	0.089	0.47	NO
23	FADS2	FADS2	FADS2	3828	0.085	0.47	NO
24	AQP7	AQP7	AQP7	3834	0.085	0.48	NO
25	NR1H3	NR1H3	NR1H3	4641	0.065	0.45	NO
26	PLTP	PLTP	PLTP	4683	0.064	0.45	NO
27	ADIPOQ	ADIPOQ	ADIPOQ	4957	0.059	0.45	NO
28	PCK2	PCK2	PCK2	4993	0.058	0.45	NO
29	GK2	GK2	GK2	5119	0.056	0.45	NO
30	SLC27A4	SLC27A4	SLC27A4	5215	0.054	0.46	NO
31	CPT2	CPT2	CPT2	5630	0.046	0.44	NO
32	SORBS1	SORBS1	SORBS1	5951	0.041	0.43	NO
33	FABP7	FABP7	FABP7	6485	0.033	0.4	NO
34	ACADM	ACADM	ACADM	6729	0.03	0.39	NO
35	PPARA	PPARA	PPARA	6878	0.028	0.39	NO
36	SCD5	SCD5	SCD5	7054	0.026	0.38	NO
37	UBC	UBC	UBC	7069	0.026	0.38	NO
38	EHHADH	EHHADH	EHHADH	7258	0.023	0.38	NO
39	SCP2	SCP2	SCP2	7386	0.022	0.37	NO
40	RXRA	RXRA	RXRA	7540	0.019	0.37	NO
41	ILK	ILK	ILK	7818	0.015	0.35	NO
42	LPL	LPL	LPL	8442	0.0081	0.32	NO
43	ACOX3	ACOX3	ACOX3	9063	0.00038	0.29	NO
44	ACSL3	ACSL3	ACSL3	9112	-0.0002	0.28	NO
45	RXRB	RXRB	RXRB	9458	-0.0043	0.26	NO
46	PCK1	PCK1	PCK1	9588	-0.0058	0.26	NO
47	ACSL5	ACSL5	ACSL5	10248	-0.014	0.22	NO
48	PPARD	PPARD	PPARD	10409	-0.016	0.22	NO
49	ACOX1	ACOX1	ACOX1	10613	-0.019	0.21	NO
50	ACSL6	ACSL6	ACSL6	11376	-0.028	0.17	NO
51	FABP3	FABP3	FABP3	11691	-0.033	0.16	NO
52	CPT1C	CPT1C	CPT1C	13150	-0.055	0.085	NO
53	HMGCS2	HMGCS2	HMGCS2	13191	-0.055	0.09	NO
54	CYP7A1	CYP7A1	CYP7A1	13484	-0.06	0.082	NO
55	MMP1	MMP1	MMP1	13907	-0.069	0.068	NO
56	GK	GK	GK	14246	-0.077	0.059	NO
57	PDPK1	PDPK1	PDPK1	14642	-0.086	0.049	NO
58	ACSL4	ACSL4	ACSL4	15259	-0.1	0.028	NO
59	CPT1A	CPT1A	CPT1A	15506	-0.11	0.03	NO
60	CYP4A11	CYP4A11	CYP4A11	16257	-0.14	0.0075	NO
61	APOA5	APOA5	APOA5	17392	-0.23	-0.024	NO
62	SLC27A2	SLC27A2	SLC27A2	17567	-0.25	-0.0011	NO
63	CD36	CD36	CD36	17947	-0.32	0.02	NO

Figure S91. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION.

Figure S92. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG HISTIDINE METABOLISM

Table S47. 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	ALDOB	ALDOB	ALDOB	185	0.52	0.19	YES
2	PFKFB1	PFKFB1	PFKFB1	1065	0.25	0.24	YES
3	FBP1	FBP1	FBP1	2337	0.14	0.22	YES
4	MTMR7	MTMR7	MTMR7	2369	0.14	0.28	YES
5	HK2	HK2	HK2	2392	0.14	0.33	YES
6	PFKFB2	PFKFB2	PFKFB2	3013	0.11	0.34	YES
7	ALDOC	ALDOC	ALDOC	3085	0.11	0.37	YES
8	FUK	FUK	FUK	3261	0.1	0.4	YES
9	PHPT1	PHPT1	PHPT1	3663	0.09	0.42	YES
10	KHK	KHK	KHK	4655	0.065	0.39	YES
11	GMPPA	GMPPA	GMPPA	4703	0.064	0.41	YES
12	MPI	MPI	MPI	4820	0.061	0.43	YES
13	FPGT	FPGT	FPGT	5342	0.052	0.42	NO
14	PFKL	PFKL	PFKL	5816	0.043	0.41	NO
15	PMM1	PMM1	PMM1	6055	0.04	0.41	NO
16	MTMR2	MTMR2	MTMR2	6925	0.028	0.37	NO
17	SORD	SORD	SORD	7791	0.016	0.33	NO
18	PFKFB4	PFKFB4	PFKFB4	8947	0.0021	0.27	NO
19	AKR1B1	AKR1B1	AKR1B1	9068	0.00032	0.26	NO
20	PFKP	PFKP	PFKP	9164	-0.00088	0.26	NO
21	TSTA3	TSTA3	TSTA3	9793	-0.0083	0.23	NO
22	PFKFB3	PFKFB3	PFKFB3	9835	-0.0087	0.23	NO
23	TPI1	TPI1	TPI1	11143	-0.025	0.17	NO
24	MTMR6	MTMR6	MTMR6	11219	-0.026	0.17	NO
25	GMPPB	GMPPB	GMPPB	11632	-0.032	0.16	NO
26	PMM2	PMM2	PMM2	11802	-0.034	0.17	NO
27	PFKM	PFKM	PFKM	13794	-0.066	0.083	NO
28	AKR1B10	AKR1B10	AKR1B10	13870	-0.068	0.11	NO
29	MTMR1	MTMR1	MTMR1	14041	-0.072	0.12	NO
30	GMDS	GMDS	GMDS	14325	-0.079	0.14	NO
31	HK1	HK1	HK1	15042	-0.098	0.14	NO
32	HK3	HK3	HK3	15332	-0.11	0.16	NO

Figure S93. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG HISTIDINE METABOLISM.

Figure S94. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG HISTIDINE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG GLUTATHIONE METABOLISM

Table S48. 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	GSTM5	GSTM5	GSTM5	384	0.39	0.06	YES
2	GSTO2	GSTO2	GSTO2	582	0.33	0.12	YES
3	ADH1B	ADH1B	ADH1B	903	0.27	0.16	YES
4	MGST1	MGST1	MGST1	1155	0.24	0.19	YES
5	ALDH3A1	ALDH3A1	ALDH3A1	1292	0.22	0.23	YES
6	AKR1C1	AKR1C1	AKR1C1	1779	0.18	0.24	YES
7	GSTT1	GSTT1	GSTT1	1977	0.16	0.26	YES
8	CYP2S1	CYP2S1	CYP2S1	2038	0.16	0.29	YES
9	ALDH3B1	ALDH3B1	ALDH3B1	2259	0.15	0.31	YES
10	CYP2E1	CYP2E1	CYP2E1	2308	0.14	0.34	YES
11	CYP3A43	CYP3A43	CYP3A43	2352	0.14	0.37	YES
12	GSTM1	GSTM1	GSTM1	2608	0.13	0.38	YES
13	GSTM3	GSTM3	GSTM3	2667	0.12	0.4	YES
14	GSTZ1	GSTZ1	GSTZ1	2699	0.12	0.43	YES
15	EPHX1	EPHX1	EPHX1	2719	0.12	0.45	YES
16	AKR1C3	AKR1C3	AKR1C3	2779	0.12	0.47	YES
17	CYP1A1	CYP1A1	CYP1A1	2852	0.12	0.49	YES
18	ALDH3B2	ALDH3B2	ALDH3B2	3378	0.099	0.49	YES
19	GSTM2	GSTM2	GSTM2	3409	0.098	0.5	YES
20	GSTP1	GSTP1	GSTP1	3722	0.088	0.51	YES
21	AKR1C2	AKR1C2	AKR1C2	3761	0.087	0.52	YES
22	MGST3	MGST3	MGST3	3855	0.084	0.53	YES
23	MGST2	MGST2	MGST2	4394	0.07	0.52	YES
24	GSTM4	GSTM4	GSTM4	4584	0.066	0.52	YES
25	CYP3A5	CYP3A5	CYP3A5	4607	0.066	0.54	YES
26	GSTO1	GSTO1	GSTO1	4769	0.062	0.54	YES
27	GSTA1	GSTA1	GSTA1	5443	0.05	0.51	NO
28	ALDH1A3	ALDH1A3	ALDH1A3	5510	0.049	0.52	NO
29	CYP2C8	CYP2C8	CYP2C8	5808	0.043	0.51	NO
30	GSTK1	GSTK1	GSTK1	6611	0.032	0.48	NO
31	DHDH	DHDH	DHDH	6622	0.031	0.48	NO
32	CYP2F1	CYP2F1	CYP2F1	7627	0.018	0.43	NO
33	ADH6	ADH6	ADH6	7994	0.013	0.41	NO
34	ADH5	ADH5	ADH5	9667	-0.0069	0.32	NO
35	GSTA4	GSTA4	GSTA4	10519	-0.018	0.28	NO
36	GSTT2	GSTT2	GSTT2	11270	-0.027	0.24	NO
37	AKR1C4	AKR1C4	AKR1C4	11952	-0.036	0.21	NO
38	ADH1A	ADH1A	ADH1A	12769	-0.048	0.18	NO
39	CYP3A7	CYP3A7	CYP3A7	14216	-0.077	0.12	NO
40	ADH1C	ADH1C	ADH1C	15069	-0.098	0.09	NO
41	CYP1B1	CYP1B1	CYP1B1	15767	-0.12	0.078	NO
42	CYP2C18	CYP2C18	CYP2C18	16099	-0.14	0.088	NO
43	ADH7	ADH7	ADH7	16474	-0.16	0.1	NO

Figure S95. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLUTATHIONE METABOLISM.

Figure S96. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLUTATHIONE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG ETHER LIPID METABOLISM

Table S49. 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	ARHGEF16	ARHGEF16	ARHGEF16	83	0.68	0.23	YES
2	ARHGEF5	ARHGEF5	ARHGEF5	208	0.5	0.39	YES
3	MYLK	MYLK	MYLK	794	0.28	0.46	YES
4	ARHGEF10	ARHGEF10	ARHGEF10	2164	0.15	0.44	NO
5	ARHGEF1	ARHGEF1	ARHGEF1	2682	0.12	0.45	NO
6	ARHGEF19	ARHGEF19	ARHGEF19	3896	0.083	0.41	NO
7	ARHGEF4	ARHGEF4	ARHGEF4	4015	0.08	0.43	NO
8	MYL7	MYL7	MYL7	4647	0.065	0.42	NO
9	PPP1R12B	PPP1R12B	PPP1R12B	6256	0.037	0.34	NO
10	ARHGEF2	ARHGEF2	ARHGEF2	6461	0.034	0.34	NO
11	GNA12	GNA12	GNA12	6615	0.032	0.35	NO
12	ARHGAP5	ARHGAP5	ARHGAP5	6680	0.031	0.36	NO
13	ARHGEF6	ARHGEF6	ARHGEF6	8597	0.0061	0.25	NO
14	PKN1	PKN1	PKN1	8781	0.0042	0.24	NO
15	ARHGEF18	ARHGEF18	ARHGEF18	9226	-0.0017	0.22	NO
16	GNAQ	GNAQ	GNAQ	9913	-0.0097	0.19	NO
17	ARHGEF17	ARHGEF17	ARHGEF17	10002	-0.011	0.18	NO
18	ARHGEF7	ARHGEF7	ARHGEF7	11125	-0.025	0.13	NO
19	PRKCA	PRKCA	PRKCA	11783	-0.034	0.11	NO
20	GNB1	GNB1	GNB1	11903	-0.035	0.11	NO
21	ROCK1	ROCK1	ROCK1	12615	-0.046	0.09	NO
22	ARHGEF12	ARHGEF12	ARHGEF12	13152	-0.055	0.079	NO
23	ARHGEF3	ARHGEF3	ARHGEF3	14085	-0.073	0.054	NO
24	PLCB1	PLCB1	PLCB1	14634	-0.086	0.053	NO
25	ARHGEF15	ARHGEF15	ARHGEF15	14860	-0.092	0.073	NO
26	ARHGEF11	ARHGEF11	ARHGEF11	15197	-0.1	0.09	NO
27	ARHGEF9	ARHGEF9	ARHGEF9	15339	-0.11	0.12	NO
28	PRKCB	PRKCB	PRKCB	15885	-0.13	0.13	NO

Figure S97. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG ETHER LIPID METABOLISM.

Figure S98. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG ETHER LIPID METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG PROPANOATE METABOLISM

Table S50. 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	PPAP2C	PPAP2C	PPAP2C	54	0.74	0.16	YES
2	ENPP2	ENPP2	ENPP2	151	0.58	0.29	YES
3	PLD1	PLD1	PLD1	170	0.54	0.42	YES
4	PLA2G7	PLA2G7	PLA2G7	671	0.31	0.46	YES
5	LPCAT2	LPCAT2	LPCAT2	976	0.26	0.5	YES
6	PLA2G1B	PLA2G1B	PLA2G1B	2173	0.15	0.47	YES
7	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	2323	0.14	0.49	YES
8	PPAP2A	PPAP2A	PPAP2A	2344	0.14	0.52	YES
9	PLD2	PLD2	PLD2	3441	0.097	0.49	NO
10	PLA2G5	PLA2G5	PLA2G5	4130	0.077	0.47	NO
11	PLA2G6	PLA2G6	PLA2G6	4364	0.071	0.47	NO
12	PPAP2B	PPAP2B	PPAP2B	4403	0.07	0.48	NO
13	PLA2G12A	PLA2G12A	PLA2G12A	5014	0.058	0.46	NO
14	PAFAH2	PAFAH2	PAFAH2	6346	0.036	0.4	NO
15	CHPT1	CHPT1	CHPT1	6775	0.03	0.38	NO
16	PLA2G2D	PLA2G2D	PLA2G2D	6861	0.028	0.38	NO
17	AGPS	AGPS	AGPS	9972	-0.01	0.22	NO
18	PAFAH1B3	PAFAH1B3	PAFAH1B3	10996	-0.023	0.17	NO
19	PLA2G12B	PLA2G12B	PLA2G12B	11059	-0.024	0.17	NO
20	PAFAH1B1	PAFAH1B1	PAFAH1B1	12260	-0.04	0.11	NO
21	LPCAT1	LPCAT1	LPCAT1	12956	-0.051	0.086	NO
22	PLA2G3	PLA2G3	PLA2G3	14933	-0.094	-0.00028	NO
23	LPCAT4	LPCAT4	LPCAT4	15838	-0.13	-0.021	NO
24	PLA2G10	PLA2G10	PLA2G10	15860	-0.13	0.0067	NO
25	PAFAH1B2	PAFAH1B2	PAFAH1B2	15999	-0.13	0.03	NO
26	PLA2G2A	PLA2G2A	PLA2G2A	17067	-0.2	0.017	NO
27	PLA2G4A	PLA2G4A	PLA2G4A	17298	-0.22	0.056	NO

Figure S99. 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 PROPANOATE METABOLISM.

Figure S100. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PROPANOATE METABOLISM, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Methods & Data

Input

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