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

Thyroid Adenocarcinoma (Primary solid tumor)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in THCA-TP. Broad Institute of MIT and Harvard. doi:10.7908/C19S1Q53

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 THCA-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: 501
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 4 :[ clus1 ] 168
pheno.type: 2 - 4 :[ clus2 ] 157
pheno.type: 3 - 4 :[ clus3 ] 59
pheno.type: 4 - 4 :[ clus4 ] 117

For the expression subtypes of 17991 genes in 502 samples, GSEA found enriched gene sets in each cluster using 501 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA G1 PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA HIVNEF PATHWAY, BIOCARTA RACCYCD PATHWAY, KEGG PYRIMIDINE METABOLISM, KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES, KEGG RIBOSOME, KEGG DNA REPLICATION, KEGG NUCLEOTIDE EXCISION REPAIR, KEGG HOMOLOGOUS RECOMBINATION

And common core enriched genes are CCND1, CDKN1A, CDKN2A, TGFB2, ACTG1, BAG4, BID, BIRC2, BIRC3, CASP6

clus2

Top enriched gene sets are BIOCARTA GH PATHWAY, BIOCARTA VEGF PATHWAY, KEGG CITRATE CYCLE TCA CYCLE, KEGG FATTY ACID METABOLISM, KEGG OXIDATIVE PHOSPHORYLATION, KEGG GLYCINE SERINE AND THREONINE METABOLISM, KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION, KEGG LYSINE DEGRADATION, KEGG ARGININE AND PROLINE METABOLISM, KEGG STARCH AND SUCROSE METABOLISM

And common core enriched genes are ACAT1, ALDH1B1, ALDH2, ALDH7A1, ALDH9A1, ECHS1, HADH, HADHA, ABAT, ACADS

clus3

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA ALK PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA BCR PATHWAY, BIOCARTA BIOPEPTIDES PATHWAY, BIOCARTA G1 PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA INFLAM PATHWAY, BIOCARTA EGF PATHWAY

And common core enriched genes are CEBPA, MAP2K6, NFATC1, NFATC2, PRKCA, PRKCB, ACAP1, ADRB2, ADRB3, AGAP2

clus4

Top enriched gene sets are BIOCARTA ALK PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA ERK PATHWAY, KEGG GLYCEROPHOSPHOLIPID METABOLISM, KEGG ETHER LIPID METABOLISM, KEGG ARACHIDONIC ACID METABOLISM, KEGG SPLICEOSOME, KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION, KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT, KEGG NOTCH SIGNALING PATHWAY

And common core enriched genes are LEF1, TCF7, RET, RXRG, TCF7L2, ACIN1, BAT1, BUD31, CCDC12, CDC5L

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 G1 PATHWAY	27	genes.ES.table	0.57	1.6	0.032	0.47	0.7	0.3	0.16	0.25	0.28	0.14
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.43	1.3	0.18	0.95	0.96	0.45	0.27	0.33	0.72	0.33
BIOCARTA HIVNEF PATHWAY	57	genes.ES.table	0.48	1.7	0.026	0.85	0.39	0.46	0.28	0.33	0	0.29
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.35	1.4	0.12	0.99	0.96	0.44	0.29	0.31	0.74	0.35
KEGG PYRIMIDINE METABOLISM	97	genes.ES.table	0.32	1.3	0.11	0.88	0.96	0.3	0.21	0.24	0.67	0.29
KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES	25	genes.ES.table	0.56	1.3	0.093	0.81	0.97	0.24	0.064	0.22	0.62	0.26
KEGG RIBOSOME	84	genes.ES.table	0.5	1.2	0.31	0.97	0.99	0.82	0.38	0.51	0.8	0.36
KEGG DNA REPLICATION	35	genes.ES.table	0.57	1.6	0.072	0.6	0.6	0.46	0.24	0.35	0.32	0.2
KEGG NUCLEOTIDE EXCISION REPAIR	43	genes.ES.table	0.32	1.3	0.22	0.86	0.98	0.28	0.24	0.21	0.69	0.28
KEGG HOMOLOGOUS RECOMBINATION	27	genes.ES.table	0.58	1.5	0.076	0.5	0.84	0.48	0.24	0.36	0.34	0.13

genes ES table in pathway: BIOCARTA G1 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	BIRC3	BIRC3	BIRC3	311	0.43	0.097	YES
2	MAP3K5	MAP3K5	MAP3K5	1008	0.24	0.12	YES
3	FAS	FAS	FAS	1039	0.24	0.19	YES
4	BID	BID	BID	1042	0.24	0.25	YES
5	RASA1	RASA1	RASA1	1791	0.16	0.25	YES
6	GSN	GSN	GSN	1908	0.15	0.28	YES
7	CFLAR	CFLAR	CFLAR	1937	0.14	0.32	YES
8	BAG4	BAG4	BAG4	2423	0.12	0.32	YES
9	CASP6	CASP6	CASP6	2904	0.093	0.32	YES
10	LMNB1	LMNB1	LMNB1	3108	0.085	0.33	YES
11	MAP3K1	MAP3K1	MAP3K1	3110	0.085	0.36	YES
12	TNFRSF1B	TNFRSF1B	TNFRSF1B	3181	0.082	0.38	YES
13	TNF	TNF	TNF	3328	0.077	0.39	YES
14	LMNA	LMNA	LMNA	3436	0.073	0.4	YES
15	PRKDC	PRKDC	PRKDC	3585	0.068	0.41	YES
16	PAK2	PAK2	PAK2	3611	0.067	0.43	YES
17	TNFRSF1A	TNFRSF1A	TNFRSF1A	4102	0.054	0.41	YES
18	FADD	FADD	FADD	4129	0.054	0.43	YES
19	NFKB1	NFKB1	NFKB1	4218	0.052	0.44	YES
20	RELA	RELA	RELA	4252	0.051	0.45	YES
21	ACTG1	ACTG1	ACTG1	4361	0.049	0.46	YES
22	BIRC2	BIRC2	BIRC2	4362	0.049	0.47	YES
23	LMNB2	LMNB2	LMNB2	4668	0.043	0.46	YES
24	CASP7	CASP7	CASP7	4750	0.042	0.47	YES
25	DFFA	DFFA	DFFA	4877	0.039	0.47	YES
26	MAP3K14	MAP3K14	MAP3K14	4968	0.038	0.48	YES
27	CHUK	CHUK	CHUK	5159	0.034	0.48	NO
28	CASP2	CASP2	CASP2	5442	0.03	0.47	NO
29	PRKCD	PRKCD	PRKCD	5459	0.029	0.48	NO
30	PSEN1	PSEN1	PSEN1	5711	0.026	0.47	NO
31	SPTAN1	SPTAN1	SPTAN1	5944	0.022	0.46	NO
32	APAF1	APAF1	APAF1	6164	0.019	0.45	NO
33	PTK2	PTK2	PTK2	6194	0.019	0.46	NO
34	CASP3	CASP3	CASP3	6225	0.018	0.46	NO
35	MAPK8	MAPK8	MAPK8	6627	0.013	0.44	NO
36	MDM2	MDM2	MDM2	6733	0.012	0.44	NO
37	MAP2K7	MAP2K7	MAP2K7	6908	0.01	0.43	NO
38	XIAP	XIAP	XIAP	7063	0.0085	0.43	NO
39	NUMA1	NUMA1	NUMA1	7621	0.0023	0.4	NO
40	CASP8	CASP8	CASP8	7794	0.00018	0.39	NO
41	RB1	RB1	RB1	7915	-0.0011	0.38	NO
42	TRADD	TRADD	TRADD	8177	-0.0041	0.37	NO
43	PSEN2	PSEN2	PSEN2	8852	-0.012	0.33	NO
44	CDK11A	CDK11A	CDK11A	8997	-0.014	0.33	NO
45	TRAF1	TRAF1	TRAF1	9038	-0.014	0.33	NO
46	CDK11B	CDK11B	CDK11B	9040	-0.014	0.33	NO
47	RIPK1	RIPK1	RIPK1	9219	-0.017	0.33	NO
48	DAXX	DAXX	DAXX	9249	-0.017	0.33	NO
49	DFFB	DFFB	DFFB	9311	-0.018	0.33	NO
50	PARP1	PARP1	PARP1	9913	-0.024	0.3	NO
51	ARHGDIB	ARHGDIB	ARHGDIB	10180	-0.028	0.3	NO
52	NFKBIA	NFKBIA	NFKBIA	10889	-0.038	0.27	NO
53	TRAF2	TRAF2	TRAF2	11284	-0.044	0.26	NO
54	CRADD	CRADD	CRADD	12480	-0.065	0.21	NO
55	CYCS	CYCS	CYCS	12827	-0.073	0.21	NO
56	CASP9	CASP9	CASP9	13609	-0.094	0.19	NO
57	BCL2	BCL2	BCL2	15690	-0.2	0.13	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 G1 PATHWAY.

Figure S2. 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 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	CTSE	CTSE	CTSE	331	0.42	0.029	YES
2	NAPSA	NAPSA	NAPSA	454	0.38	0.066	YES
3	NPC1	NPC1	NPC1	822	0.28	0.076	YES
4	ATP6V0D2	ATP6V0D2	ATP6V0D2	823	0.28	0.11	YES
5	CTSL2	CTSL2	CTSL2	841	0.27	0.14	YES
6	ACP5	ACP5	ACP5	886	0.27	0.16	YES
7	CTSC	CTSC	CTSC	893	0.26	0.2	YES
8	SLC11A1	SLC11A1	SLC11A1	1026	0.24	0.22	YES
9	CTSK	CTSK	CTSK	1124	0.23	0.24	YES
10	CTSH	CTSH	CTSH	1416	0.19	0.24	YES
11	CD68	CD68	CD68	1485	0.18	0.26	YES
12	CTSS	CTSS	CTSS	1494	0.18	0.28	YES
13	DNASE2B	DNASE2B	DNASE2B	1513	0.18	0.3	YES
14	LAMP3	LAMP3	LAMP3	1715	0.16	0.3	YES
15	IGF2R	IGF2R	IGF2R	1922	0.15	0.31	YES
16	SLC17A5	SLC17A5	SLC17A5	2007	0.14	0.32	YES
17	IDS	IDS	IDS	2178	0.13	0.33	YES
18	CTSA	CTSA	CTSA	2681	0.1	0.31	YES
19	HEXB	HEXB	HEXB	2942	0.092	0.3	YES
20	TCIRG1	TCIRG1	TCIRG1	2999	0.089	0.31	YES
21	AP3S1	AP3S1	AP3S1	3036	0.087	0.32	YES
22	CTSD	CTSD	CTSD	3071	0.086	0.33	YES
23	LAPTM5	LAPTM5	LAPTM5	3087	0.086	0.34	YES
24	PSAP	PSAP	PSAP	3134	0.084	0.34	YES
25	TPP1	TPP1	TPP1	3239	0.08	0.35	YES
26	GM2A	GM2A	GM2A	3267	0.079	0.35	YES
27	AP4E1	AP4E1	AP4E1	3400	0.074	0.36	YES
28	NAGA	NAGA	NAGA	3477	0.072	0.36	YES
29	MANBA	MANBA	MANBA	3493	0.071	0.37	YES
30	CTSB	CTSB	CTSB	3518	0.07	0.37	YES
31	ENTPD4	ENTPD4	ENTPD4	3522	0.07	0.38	YES
32	MAN2B1	MAN2B1	MAN2B1	3603	0.067	0.38	YES
33	LAMP2	LAMP2	LAMP2	3665	0.065	0.39	YES
34	AP1S3	AP1S3	AP1S3	3716	0.064	0.39	YES
35	GGA3	GGA3	GGA3	3768	0.062	0.4	YES
36	NPC2	NPC2	NPC2	3848	0.06	0.4	YES
37	FUCA1	FUCA1	FUCA1	3910	0.059	0.4	YES
38	LIPA	LIPA	LIPA	4052	0.056	0.4	YES
39	ATP6V0A2	ATP6V0A2	ATP6V0A2	4119	0.054	0.4	YES
40	SCARB2	SCARB2	SCARB2	4167	0.053	0.41	YES
41	CLTA	CLTA	CLTA	4223	0.052	0.41	YES
42	ARSA	ARSA	ARSA	4298	0.05	0.41	YES
43	AP1S1	AP1S1	AP1S1	4344	0.049	0.41	YES
44	ARSB	ARSB	ARSB	4380	0.048	0.42	YES
45	LAPTM4B	LAPTM4B	LAPTM4B	4424	0.048	0.42	YES
46	LAMP1	LAMP1	LAMP1	4461	0.047	0.42	YES
47	PPT1	PPT1	PPT1	4462	0.047	0.43	YES
48	GNPTAB	GNPTAB	GNPTAB	4602	0.044	0.42	YES
49	GLB1	GLB1	GLB1	4640	0.044	0.43	YES
50	ASAH1	ASAH1	ASAH1	4744	0.042	0.43	NO
51	CTNS	CTNS	CTNS	4879	0.039	0.42	NO
52	CLTC	CLTC	CLTC	5100	0.035	0.42	NO
53	SLC11A2	SLC11A2	SLC11A2	5180	0.034	0.42	NO
54	GBA	GBA	GBA	5261	0.033	0.41	NO
55	NEU1	NEU1	NEU1	5345	0.031	0.41	NO
56	MCOLN1	MCOLN1	MCOLN1	5404	0.03	0.41	NO
57	AP1M2	AP1M2	AP1M2	5419	0.03	0.42	NO
58	ABCB9	ABCB9	ABCB9	5635	0.027	0.41	NO
59	NAGPA	NAGPA	NAGPA	5688	0.026	0.41	NO
60	AP4M1	AP4M1	AP4M1	5834	0.024	0.4	NO
61	GGA2	GGA2	GGA2	5870	0.024	0.4	NO
62	M6PR	M6PR	M6PR	5932	0.022	0.4	NO
63	AP1S2	AP1S2	AP1S2	6015	0.021	0.4	NO
64	AGA	AGA	AGA	6027	0.021	0.4	NO
65	CD63	CD63	CD63	6101	0.02	0.4	NO
66	LAPTM4A	LAPTM4A	LAPTM4A	6103	0.02	0.4	NO
67	GUSB	GUSB	GUSB	6320	0.017	0.39	NO
68	GNS	GNS	GNS	6418	0.016	0.39	NO
69	GGA1	GGA1	GGA1	6536	0.015	0.38	NO
70	AP3M1	AP3M1	AP3M1	6613	0.014	0.38	NO
71	AP3D1	AP3D1	AP3D1	6687	0.013	0.38	NO
72	HEXA	HEXA	HEXA	6840	0.011	0.37	NO
73	MFSD8	MFSD8	MFSD8	7000	0.0094	0.36	NO
74	ATP6AP1	ATP6AP1	ATP6AP1	7136	0.0077	0.36	NO
75	AP1G1	AP1G1	AP1G1	7188	0.0072	0.35	NO
76	AP1B1	AP1B1	AP1B1	7229	0.0066	0.35	NO
77	CLN3	CLN3	CLN3	7259	0.0063	0.35	NO
78	CTSG	CTSG	CTSG	7358	0.0053	0.35	NO
79	CTSL1	CTSL1	CTSL1	7834	-0.00022	0.32	NO
80	SMPD1	SMPD1	SMPD1	7991	-0.002	0.31	NO
81	ATP6V0A1	ATP6V0A1	ATP6V0A1	8078	-0.0029	0.31	NO
82	ACP2	ACP2	ACP2	8196	-0.0043	0.3	NO
83	ATP6V0C	ATP6V0C	ATP6V0C	8264	-0.005	0.3	NO
84	SUMF1	SUMF1	SUMF1	8399	-0.0067	0.29	NO
85	SORT1	SORT1	SORT1	8462	-0.0074	0.29	NO
86	AP1M1	AP1M1	AP1M1	8470	-0.0075	0.29	NO
87	GALNS	GALNS	GALNS	8647	-0.0094	0.28	NO
88	GAA	GAA	GAA	8697	-0.0098	0.28	NO
89	ATP6V1H	ATP6V1H	ATP6V1H	8871	-0.012	0.27	NO
90	GNPTG	GNPTG	GNPTG	9197	-0.016	0.25	NO
91	CLTB	CLTB	CLTB	9260	-0.017	0.25	NO
92	SGSH	SGSH	SGSH	9341	-0.018	0.25	NO
93	AP3B1	AP3B1	AP3B1	9565	-0.02	0.24	NO
94	CTSW	CTSW	CTSW	10129	-0.027	0.21	NO
95	DNASE2	DNASE2	DNASE2	10216	-0.029	0.21	NO
96	PLA2G15	PLA2G15	PLA2G15	10266	-0.029	0.21	NO
97	CTSF	CTSF	CTSF	10296	-0.029	0.21	NO
98	ATP6V0D1	ATP6V0D1	ATP6V0D1	10387	-0.03	0.21	NO
99	CTSO	CTSO	CTSO	10532	-0.032	0.2	NO
100	CD164	CD164	CD164	10542	-0.032	0.21	NO
101	CTSZ	CTSZ	CTSZ	10587	-0.033	0.21	NO
102	ATP6V0A4	ATP6V0A4	ATP6V0A4	10851	-0.037	0.2	NO
103	NAGLU	NAGLU	NAGLU	10958	-0.039	0.2	NO
104	AP3S2	AP3S2	AP3S2	11754	-0.051	0.16	NO
105	GALC	GALC	GALC	11935	-0.055	0.16	NO
106	ABCA2	ABCA2	ABCA2	11955	-0.055	0.16	NO
107	AP3B2	AP3B2	AP3B2	12247	-0.06	0.15	NO
108	ATP6V0B	ATP6V0B	ATP6V0B	12267	-0.061	0.16	NO
109	AP3M2	AP3M2	AP3M2	12273	-0.061	0.16	NO
110	CLN5	CLN5	CLN5	13273	-0.085	0.12	NO
111	LGMN	LGMN	LGMN	13602	-0.093	0.11	NO
112	GLA	GLA	GLA	13732	-0.097	0.11	NO
113	PPT2	PPT2	PPT2	14138	-0.11	0.1	NO
114	AP4B1	AP4B1	AP4B1	14448	-0.12	0.099	NO
115	CLTCL1	CLTCL1	CLTCL1	14538	-0.13	0.11	NO
116	AP4S1	AP4S1	AP4S1	14950	-0.15	0.1	NO
117	ARSG	ARSG	ARSG	15546	-0.19	0.091	NO
118	IDUA	IDUA	IDUA	15647	-0.2	0.11	NO
119	HYAL1	HYAL1	HYAL1	15711	-0.2	0.13	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 FAS PATHWAY.

Figure S4. 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 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	POLE2	POLE2	POLE2	739	0.3	0.088	YES
2	MCM4	MCM4	MCM4	1176	0.22	0.16	YES
3	POLD1	POLD1	POLD1	1985	0.14	0.18	YES
4	PRIM2	PRIM2	PRIM2	2005	0.14	0.24	YES
5	RNASEH1	RNASEH1	RNASEH1	2030	0.14	0.3	YES
6	MCM6	MCM6	MCM6	2076	0.14	0.35	YES
7	MCM2	MCM2	MCM2	2148	0.13	0.41	YES
8	MCM5	MCM5	MCM5	2528	0.11	0.43	YES
9	PRIM1	PRIM1	PRIM1	3088	0.086	0.44	YES
10	RFC3	RFC3	RFC3	3223	0.08	0.47	YES
11	PCNA	PCNA	PCNA	3441	0.073	0.49	YES
12	FEN1	FEN1	FEN1	3625	0.066	0.5	YES
13	POLE	POLE	POLE	3748	0.063	0.52	YES
14	POLA2	POLA2	POLA2	3822	0.061	0.55	YES
15	RFC4	RFC4	RFC4	3898	0.06	0.57	YES
16	RPA3	RPA3	RPA3	4265	0.051	0.57	YES
17	RNASEH2A	RNASEH2A	RNASEH2A	4857	0.04	0.56	NO
18	MCM3	MCM3	MCM3	5673	0.026	0.52	NO
19	MCM7	MCM7	MCM7	5723	0.026	0.53	NO
20	LIG1	LIG1	LIG1	5743	0.025	0.54	NO
21	RFC5	RFC5	RFC5	6052	0.021	0.53	NO
22	POLE3	POLE3	POLE3	6121	0.02	0.54	NO
23	RNASEH2B	RNASEH2B	RNASEH2B	6344	0.017	0.53	NO
24	RPA1	RPA1	RPA1	6490	0.015	0.53	NO
25	RFC2	RFC2	RFC2	6917	0.01	0.51	NO
26	POLD3	POLD3	POLD3	7006	0.0093	0.51	NO
27	POLD4	POLD4	POLD4	7222	0.0067	0.5	NO
28	RFC1	RFC1	RFC1	7243	0.0065	0.5	NO
29	DNA2	DNA2	DNA2	7926	-0.0012	0.46	NO
30	SSBP1	SSBP1	SSBP1	8045	-0.0025	0.46	NO
31	RPA2	RPA2	RPA2	8354	-0.0061	0.44	NO
32	RNASEH2C	RNASEH2C	RNASEH2C	10512	-0.032	0.34	NO
33	POLE4	POLE4	POLE4	11487	-0.047	0.3	NO
34	POLD2	POLD2	POLD2	12132	-0.058	0.29	NO
35	RPA4	RPA4	RPA4	12785	-0.072	0.29	NO

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

Figure S6. 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 RACCYCD 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	CDKN2A	CDKN2A	CDKN2A	195	0.5	0.079	YES
2	SHC3	SHC3	SHC3	196	0.5	0.17	YES
3	RUNX1	RUNX1	RUNX1	465	0.38	0.22	YES
4	TGFB2	TGFB2	TGFB2	774	0.29	0.26	YES
5	BCL2L1	BCL2L1	BCL2L1	1565	0.18	0.24	YES
6	TGFBR1	TGFBR1	TGFBR1	1583	0.18	0.27	YES
7	E2F2	E2F2	E2F2	1710	0.16	0.3	YES
8	AKT3	AKT3	AKT3	1915	0.15	0.31	YES
9	PIK3CA	PIK3CA	PIK3CA	2089	0.14	0.33	YES
10	CDKN1A	CDKN1A	CDKN1A	2150	0.13	0.35	YES
11	BRAF	BRAF	BRAF	2356	0.12	0.36	YES
12	GAB2	GAB2	GAB2	2486	0.11	0.37	YES
13	SHC2	SHC2	SHC2	2593	0.11	0.38	YES
14	PIK3R5	PIK3R5	PIK3R5	2702	0.1	0.4	YES
15	CCND1	CCND1	CCND1	2787	0.099	0.41	YES
16	MAPK1	MAPK1	MAPK1	2935	0.092	0.42	YES
17	PIK3R1	PIK3R1	PIK3R1	3021	0.088	0.43	YES
18	PIK3CD	PIK3CD	PIK3CD	3143	0.084	0.44	YES
19	PIK3R2	PIK3R2	PIK3R2	3443	0.073	0.43	YES
20	STAT5A	STAT5A	STAT5A	3517	0.07	0.44	YES
21	BCR	BCR	BCR	3892	0.06	0.43	NO
22	NFKB1	NFKB1	NFKB1	4218	0.052	0.42	NO
23	RELA	RELA	RELA	4252	0.051	0.43	NO
24	MYC	MYC	MYC	4466	0.047	0.43	NO
25	TGFB3	TGFB3	TGFB3	4496	0.046	0.43	NO
26	CDK4	CDK4	CDK4	4963	0.038	0.42	NO
27	NRAS	NRAS	NRAS	5030	0.036	0.42	NO
28	PIK3CG	PIK3CG	PIK3CG	5083	0.036	0.42	NO
29	HDAC2	HDAC2	HDAC2	5087	0.036	0.43	NO
30	CHUK	CHUK	CHUK	5159	0.034	0.43	NO
31	CBL	CBL	CBL	5239	0.033	0.43	NO
32	CRK	CRK	CRK	5314	0.032	0.43	NO
33	PIK3CB	PIK3CB	PIK3CB	5360	0.031	0.44	NO
34	PTPN11	PTPN11	PTPN11	5395	0.03	0.44	NO
35	SMAD3	SMAD3	SMAD3	6066	0.021	0.41	NO
36	SHC1	SHC1	SHC1	6128	0.02	0.41	NO
37	TGFB1	TGFB1	TGFB1	6136	0.02	0.41	NO
38	ARAF	ARAF	ARAF	6378	0.016	0.4	NO
39	TP53	TP53	TP53	6482	0.015	0.4	NO
40	MAP2K1	MAP2K1	MAP2K1	6596	0.014	0.39	NO
41	MDM2	MDM2	MDM2	6733	0.012	0.39	NO
42	KRAS	KRAS	KRAS	6868	0.011	0.38	NO
43	E2F3	E2F3	E2F3	7131	0.0077	0.37	NO
44	SOS2	SOS2	SOS2	7240	0.0065	0.36	NO
45	CRKL	CRKL	CRKL	7511	0.0036	0.35	NO
46	CDKN1B	CDKN1B	CDKN1B	7757	0.00062	0.34	NO
47	STAT5B	STAT5B	STAT5B	7764	0.00052	0.34	NO
48	CTBP1	CTBP1	CTBP1	7780	0.00036	0.33	NO
49	MAPK3	MAPK3	MAPK3	7908	-0.0011	0.33	NO
50	RB1	RB1	RB1	7915	-0.0011	0.33	NO
51	SMAD4	SMAD4	SMAD4	7990	-0.0019	0.32	NO
52	GRB2	GRB2	GRB2	8205	-0.0045	0.31	NO
53	RAF1	RAF1	RAF1	8358	-0.0061	0.3	NO
54	ABL1	ABL1	ABL1	8507	-0.0079	0.3	NO
55	MAP2K2	MAP2K2	MAP2K2	8669	-0.0096	0.29	NO
56	AKT1	AKT1	AKT1	8925	-0.013	0.28	NO
57	MECOM	MECOM	MECOM	10506	-0.032	0.2	NO
58	NFKBIA	NFKBIA	NFKBIA	10889	-0.038	0.18	NO
59	IKBKB	IKBKB	IKBKB	10916	-0.038	0.19	NO
60	SOS1	SOS1	SOS1	10950	-0.039	0.19	NO
61	CTBP2	CTBP2	CTBP2	11197	-0.042	0.19	NO
62	HRAS	HRAS	HRAS	11336	-0.044	0.19	NO
63	IKBKG	IKBKG	IKBKG	12041	-0.057	0.16	NO
64	AKT2	AKT2	AKT2	12069	-0.057	0.17	NO
65	HDAC1	HDAC1	HDAC1	12781	-0.072	0.14	NO
66	CBLB	CBLB	CBLB	12939	-0.076	0.14	NO
67	BAD	BAD	BAD	13235	-0.084	0.14	NO
68	CBLC	CBLC	CBLC	13311	-0.086	0.16	NO
69	SHC4	SHC4	SHC4	14005	-0.11	0.14	NO
70	TGFBR2	TGFBR2	TGFBR2	14178	-0.11	0.15	NO
71	CDK6	CDK6	CDK6	15132	-0.16	0.12	NO
72	PIK3R3	PIK3R3	PIK3R3	15728	-0.2	0.12	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 RACCYCD PATHWAY.

Figure S8. 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 PYRIMIDINE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CCNA1	CCNA1	CCNA1	25	0.76	0.23	YES
2	CDKN2A	CDKN2A	CDKN2A	195	0.5	0.38	YES
3	CDKN2B	CDKN2B	CDKN2B	389	0.4	0.49	YES
4	TGFB2	TGFB2	TGFB2	774	0.29	0.56	YES
5	CDKN1A	CDKN1A	CDKN1A	2150	0.13	0.52	YES
6	CCND1	CCND1	CCND1	2787	0.099	0.52	YES
7	CCNE1	CCNE1	CCNE1	2847	0.096	0.55	YES
8	CDK2	CDK2	CDK2	2929	0.093	0.57	YES
9	GSK3B	GSK3B	GSK3B	3658	0.066	0.55	NO
10	TGFB3	TGFB3	TGFB3	4496	0.046	0.52	NO
11	CDK4	CDK4	CDK4	4963	0.038	0.5	NO
12	SMAD3	SMAD3	SMAD3	6066	0.021	0.45	NO
13	TGFB1	TGFB1	TGFB1	6136	0.02	0.45	NO
14	TP53	TP53	TP53	6482	0.015	0.44	NO
15	CDKN1B	CDKN1B	CDKN1B	7757	0.00062	0.36	NO
16	RB1	RB1	RB1	7915	-0.0011	0.36	NO
17	SMAD4	SMAD4	SMAD4	7990	-0.0019	0.35	NO
18	ATM	ATM	ATM	8043	-0.0025	0.35	NO
19	ABL1	ABL1	ABL1	8507	-0.0079	0.33	NO
20	DHFR	DHFR	DHFR	8546	-0.0083	0.33	NO
21	TFDP1	TFDP1	TFDP1	8735	-0.01	0.32	NO
22	ATR	ATR	ATR	10035	-0.026	0.26	NO
23	HDAC1	HDAC1	HDAC1	12781	-0.072	0.13	NO
24	CDK1	CDK1	CDK1	13119	-0.08	0.13	NO
25	SKP2	SKP2	SKP2	13196	-0.083	0.15	NO
26	CDK6	CDK6	CDK6	15132	-0.16	0.096	NO
27	CDC25A	CDC25A	CDC25A	15689	-0.2	0.13	NO

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

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

genes ES table in pathway: KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES

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	SFN	SFN	SFN	57	0.65	0.079	YES
2	PMAIP1	PMAIP1	PMAIP1	116	0.57	0.15	YES
3	CDKN2A	CDKN2A	CDKN2A	195	0.5	0.2	YES
4	PERP	PERP	PERP	768	0.29	0.21	YES
5	FAS	FAS	FAS	1039	0.24	0.22	YES
6	BID	BID	BID	1042	0.24	0.26	YES
7	ZMAT3	ZMAT3	ZMAT3	1058	0.24	0.28	YES
8	CCNE2	CCNE2	CCNE2	1196	0.22	0.3	YES
9	TP73	TP73	TP73	1288	0.21	0.32	YES
10	SERPINB5	SERPINB5	SERPINB5	1375	0.2	0.34	YES
11	CHEK2	CHEK2	CHEK2	1388	0.2	0.37	YES
12	THBS1	THBS1	THBS1	1449	0.19	0.39	YES
13	RRM2	RRM2	RRM2	1537	0.18	0.41	YES
14	BBC3	BBC3	BBC3	1670	0.17	0.42	YES
15	DDB2	DDB2	DDB2	1684	0.16	0.44	YES
16	GADD45A	GADD45A	GADD45A	1919	0.15	0.44	YES
17	CDKN1A	CDKN1A	CDKN1A	2150	0.13	0.45	YES
18	GTSE1	GTSE1	GTSE1	2281	0.12	0.46	YES
19	TNFRSF10B	TNFRSF10B	TNFRSF10B	2443	0.12	0.46	YES
20	TP53I3	TP53I3	TP53I3	2708	0.1	0.46	YES
21	CCNB2	CCNB2	CCNB2	2726	0.1	0.47	YES
22	SESN3	SESN3	SESN3	2749	0.1	0.48	YES
23	CD82	CD82	CD82	2779	0.099	0.5	YES
24	CCND1	CCND1	CCND1	2787	0.099	0.51	YES
25	CCNE1	CCNE1	CCNE1	2847	0.096	0.52	YES
26	CDK2	CDK2	CDK2	2929	0.093	0.52	YES
27	SESN2	SESN2	SESN2	3235	0.08	0.52	NO
28	BAX	BAX	BAX	3381	0.075	0.52	NO
29	CCNG1	CCNG1	CCNG1	3607	0.067	0.51	NO
30	RRM2B	RRM2B	RRM2B	3795	0.062	0.51	NO
31	CCNG2	CCNG2	CCNG2	3911	0.059	0.51	NO
32	EI24	EI24	EI24	3980	0.057	0.52	NO
33	CHEK1	CHEK1	CHEK1	4354	0.049	0.5	NO
34	CCND3	CCND3	CCND3	4688	0.043	0.49	NO
35	CDK4	CDK4	CDK4	4963	0.038	0.48	NO
36	RFWD2	RFWD2	RFWD2	5307	0.032	0.46	NO
37	SHISA5	SHISA5	SHISA5	6049	0.021	0.42	NO
38	SERPINE1	SERPINE1	SERPINE1	6143	0.02	0.42	NO
39	APAF1	APAF1	APAF1	6164	0.019	0.42	NO
40	CASP3	CASP3	CASP3	6225	0.018	0.42	NO
41	TP53	TP53	TP53	6482	0.015	0.41	NO
42	MDM2	MDM2	MDM2	6733	0.012	0.4	NO
43	CCND2	CCND2	CCND2	7573	0.0028	0.35	NO
44	CASP8	CASP8	CASP8	7794	0.00018	0.34	NO
45	ATM	ATM	ATM	8043	-0.0025	0.32	NO
46	SIAH1	SIAH1	SIAH1	8447	-0.0073	0.3	NO
47	PTEN	PTEN	PTEN	8466	-0.0075	0.3	NO
48	CCNB1	CCNB1	CCNB1	9012	-0.014	0.27	NO
49	LRDD	LRDD	LRDD	9099	-0.015	0.27	NO
50	CCNB3	CCNB3	CCNB3	9637	-0.021	0.24	NO
51	TSC2	TSC2	TSC2	9729	-0.022	0.24	NO
52	SESN1	SESN1	SESN1	9847	-0.024	0.24	NO
53	PPM1D	PPM1D	PPM1D	10016	-0.026	0.23	NO
54	ATR	ATR	ATR	10035	-0.026	0.23	NO
55	RCHY1	RCHY1	RCHY1	10734	-0.035	0.2	NO
56	TP53AIP1	TP53AIP1	TP53AIP1	12191	-0.059	0.12	NO
57	GADD45B	GADD45B	GADD45B	12193	-0.06	0.13	NO
58	MDM4	MDM4	MDM4	12414	-0.064	0.13	NO
59	IGFBP3	IGFBP3	IGFBP3	12454	-0.064	0.13	NO
60	CYCS	CYCS	CYCS	12827	-0.073	0.12	NO
61	CDK1	CDK1	CDK1	13119	-0.08	0.12	NO
62	CASP9	CASP9	CASP9	13609	-0.094	0.1	NO
63	IGF1	IGF1	IGF1	13713	-0.097	0.11	NO
64	CDK6	CDK6	CDK6	15132	-0.16	0.047	NO
65	GADD45G	GADD45G	GADD45G	15830	-0.21	0.035	NO
66	RPRM	RPRM	RPRM	16578	-0.28	0.028	NO
67	BAI1	BAI1	BAI1	17291	-0.39	0.038	NO

Figure S11. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES.

Figure S12. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG GLYCOSPHINGOLIPID BIOSYNTHESIS LACTO AND NEOLACTO SERIES, 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 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	CCNA1	CCNA1	CCNA1	25	0.76	0.067	YES
2	SFN	SFN	SFN	57	0.65	0.12	YES
3	CDKN2A	CDKN2A	CDKN2A	195	0.5	0.16	YES
4	BUB1	BUB1	BUB1	357	0.41	0.19	YES
5	CDKN2B	CDKN2B	CDKN2B	389	0.4	0.22	YES
6	CDC45	CDC45	CDC45	499	0.36	0.25	YES
7	TGFB2	TGFB2	TGFB2	774	0.29	0.26	YES
8	ORC1L	ORC1L	ORC1L	843	0.27	0.28	YES
9	PKMYT1	PKMYT1	PKMYT1	1131	0.23	0.29	YES
10	MCM4	MCM4	MCM4	1176	0.22	0.3	YES
11	CCNE2	CCNE2	CCNE2	1196	0.22	0.32	YES
12	E2F1	E2F1	E2F1	1281	0.21	0.34	YES
13	ORC6L	ORC6L	ORC6L	1373	0.2	0.35	YES
14	CHEK2	CHEK2	CHEK2	1388	0.2	0.37	YES
15	CDC6	CDC6	CDC6	1532	0.18	0.38	YES
16	E2F2	E2F2	E2F2	1710	0.16	0.38	YES
17	MAD2L1	MAD2L1	MAD2L1	1913	0.15	0.38	YES
18	GADD45A	GADD45A	GADD45A	1919	0.15	0.39	YES
19	MCM6	MCM6	MCM6	2076	0.14	0.4	YES
20	MCM2	MCM2	MCM2	2148	0.13	0.41	YES
21	CDKN1A	CDKN1A	CDKN1A	2150	0.13	0.42	YES
22	CDC25B	CDC25B	CDC25B	2315	0.12	0.42	YES
23	ESPL1	ESPL1	ESPL1	2397	0.12	0.43	YES
24	RBL1	RBL1	RBL1	2438	0.12	0.43	YES
25	MCM5	MCM5	MCM5	2528	0.11	0.44	YES
26	CCNB2	CCNB2	CCNB2	2726	0.1	0.44	YES
27	MAD2L2	MAD2L2	MAD2L2	2785	0.099	0.44	YES
28	CCND1	CCND1	CCND1	2787	0.099	0.45	YES
29	TFDP2	TFDP2	TFDP2	2840	0.096	0.46	YES
30	CCNE1	CCNE1	CCNE1	2847	0.096	0.46	YES
31	CDK2	CDK2	CDK2	2929	0.093	0.47	YES
32	CDK7	CDK7	CDK7	2937	0.092	0.48	YES
33	MAD1L1	MAD1L1	MAD1L1	3050	0.087	0.48	YES
34	ANAPC1	ANAPC1	ANAPC1	3125	0.084	0.48	YES
35	YWHAH	YWHAH	YWHAH	3324	0.077	0.48	YES
36	PCNA	PCNA	PCNA	3441	0.073	0.48	YES
37	YWHAG	YWHAG	YWHAG	3494	0.071	0.48	YES
38	PRKDC	PRKDC	PRKDC	3585	0.068	0.48	YES
39	GSK3B	GSK3B	GSK3B	3658	0.066	0.48	YES
40	CCNA2	CCNA2	CCNA2	3705	0.064	0.49	YES
41	CDC7	CDC7	CDC7	3928	0.059	0.48	NO
42	CDKN2D	CDKN2D	CDKN2D	3997	0.057	0.48	NO
43	CHEK1	CHEK1	CHEK1	4354	0.049	0.47	NO
44	TTK	TTK	TTK	4359	0.049	0.47	NO
45	MYC	MYC	MYC	4466	0.047	0.47	NO
46	TGFB3	TGFB3	TGFB3	4496	0.046	0.47	NO
47	EP300	EP300	EP300	4547	0.045	0.47	NO
48	CCND3	CCND3	CCND3	4688	0.043	0.47	NO
49	CDK4	CDK4	CDK4	4963	0.038	0.46	NO
50	YWHAZ	YWHAZ	YWHAZ	5061	0.036	0.46	NO
51	HDAC2	HDAC2	HDAC2	5087	0.036	0.46	NO
52	SMAD2	SMAD2	SMAD2	5129	0.035	0.46	NO
53	ORC3L	ORC3L	ORC3L	5297	0.032	0.45	NO
54	MCM3	MCM3	MCM3	5673	0.026	0.43	NO
55	YWHAQ	YWHAQ	YWHAQ	5697	0.026	0.43	NO
56	MCM7	MCM7	MCM7	5723	0.026	0.43	NO
57	SMAD3	SMAD3	SMAD3	6066	0.021	0.42	NO
58	TGFB1	TGFB1	TGFB1	6136	0.02	0.42	NO
59	SMC3	SMC3	SMC3	6222	0.018	0.41	NO
60	CCNH	CCNH	CCNH	6448	0.016	0.4	NO
61	TP53	TP53	TP53	6482	0.015	0.4	NO
62	RBL2	RBL2	RBL2	6518	0.015	0.4	NO
63	MDM2	MDM2	MDM2	6733	0.012	0.39	NO
64	YWHAB	YWHAB	YWHAB	6744	0.012	0.39	NO
65	RBX1	RBX1	RBX1	6851	0.011	0.38	NO
66	FZR1	FZR1	FZR1	6923	0.01	0.38	NO
67	STAG1	STAG1	STAG1	7005	0.0093	0.38	NO
68	ORC4L	ORC4L	ORC4L	7055	0.0087	0.38	NO
69	E2F3	E2F3	E2F3	7131	0.0077	0.37	NO
70	WEE1	WEE1	WEE1	7192	0.0071	0.37	NO
71	BUB3	BUB3	BUB3	7251	0.0064	0.37	NO
72	CCND2	CCND2	CCND2	7573	0.0028	0.35	NO
73	CDC27	CDC27	CDC27	7704	0.0012	0.34	NO
74	CDKN1B	CDKN1B	CDKN1B	7757	0.00062	0.34	NO
75	CDC16	CDC16	CDC16	7796	0.00014	0.34	NO
76	SKP1	SKP1	SKP1	7888	-0.00084	0.33	NO
77	RB1	RB1	RB1	7915	-0.0011	0.33	NO
78	SMAD4	SMAD4	SMAD4	7990	-0.0019	0.33	NO
79	ATM	ATM	ATM	8043	-0.0025	0.32	NO
80	RAD21	RAD21	RAD21	8136	-0.0035	0.32	NO
81	SMC1A	SMC1A	SMC1A	8270	-0.005	0.31	NO
82	BUB1B	BUB1B	BUB1B	8292	-0.0054	0.31	NO
83	CDC25C	CDC25C	CDC25C	8302	-0.0055	0.31	NO
84	STAG2	STAG2	STAG2	8359	-0.0061	0.31	NO
85	CUL1	CUL1	CUL1	8440	-0.0072	0.3	NO
86	ABL1	ABL1	ABL1	8507	-0.0079	0.3	NO
87	TFDP1	TFDP1	TFDP1	8735	-0.01	0.29	NO
88	PLK1	PLK1	PLK1	8753	-0.01	0.29	NO
89	YWHAE	YWHAE	YWHAE	8756	-0.01	0.29	NO
90	ANAPC5	ANAPC5	ANAPC5	8837	-0.012	0.29	NO
91	CREBBP	CREBBP	CREBBP	8882	-0.012	0.29	NO
92	ANAPC7	ANAPC7	ANAPC7	8996	-0.014	0.28	NO
93	CCNB1	CCNB1	CCNB1	9012	-0.014	0.28	NO
94	CCNB3	CCNB3	CCNB3	9637	-0.021	0.25	NO
95	E2F4	E2F4	E2F4	9750	-0.022	0.24	NO
96	ANAPC10	ANAPC10	ANAPC10	9842	-0.024	0.24	NO
97	ORC5L	ORC5L	ORC5L	9987	-0.025	0.24	NO
98	ATR	ATR	ATR	10035	-0.026	0.24	NO
99	ANAPC11	ANAPC11	ANAPC11	10061	-0.026	0.24	NO
100	ZBTB17	ZBTB17	ZBTB17	10322	-0.03	0.22	NO
101	PTTG1	PTTG1	PTTG1	10392	-0.031	0.22	NO
102	CDKN1C	CDKN1C	CDKN1C	10743	-0.035	0.21	NO
103	CDC23	CDC23	CDC23	10779	-0.036	0.21	NO
104	SMC1B	SMC1B	SMC1B	10963	-0.039	0.2	NO
105	ORC2L	ORC2L	ORC2L	11001	-0.039	0.2	NO
106	CDC14A	CDC14A	CDC14A	11423	-0.046	0.18	NO
107	ANAPC2	ANAPC2	ANAPC2	11731	-0.051	0.17	NO
108	ANAPC4	ANAPC4	ANAPC4	11917	-0.054	0.16	NO
109	CDC26	CDC26	CDC26	11941	-0.055	0.17	NO
110	GADD45B	GADD45B	GADD45B	12193	-0.06	0.16	NO
111	E2F5	E2F5	E2F5	12325	-0.062	0.16	NO
112	HDAC1	HDAC1	HDAC1	12781	-0.072	0.14	NO
113	CDC14B	CDC14B	CDC14B	12878	-0.074	0.14	NO
114	CDC20	CDC20	CDC20	12958	-0.077	0.14	NO
115	ANAPC13	ANAPC13	ANAPC13	13081	-0.08	0.14	NO
116	CDK1	CDK1	CDK1	13119	-0.08	0.15	NO
117	SKP2	SKP2	SKP2	13196	-0.083	0.15	NO
118	CDK6	CDK6	CDK6	15132	-0.16	0.058	NO
119	PTTG2	PTTG2	PTTG2	15661	-0.2	0.047	NO
120	CDC25A	CDC25A	CDC25A	15689	-0.2	0.063	NO
121	GADD45G	GADD45G	GADD45G	15830	-0.21	0.074	NO
122	CDKN2C	CDKN2C	CDKN2C	15884	-0.21	0.091	NO
123	WEE2	WEE2	WEE2	16655	-0.29	0.074	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 RIBOSOME.

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

genes ES table in pathway: KEGG DNA REPLICATION

Table 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	BRCA2	BRCA2	BRCA2	706	0.3	0.1	YES
2	RAD51	RAD51	RAD51	796	0.28	0.23	YES
3	XRCC2	XRCC2	XRCC2	856	0.27	0.35	YES
4	RAD51L1	RAD51L1	RAD51L1	1816	0.15	0.37	YES
5	BLM	BLM	BLM	1933	0.14	0.43	YES
6	POLD1	POLD1	POLD1	1985	0.14	0.5	YES
7	EME1	EME1	EME1	2456	0.11	0.52	YES
8	RAD54L	RAD54L	RAD54L	3153	0.083	0.52	YES
9	RAD54B	RAD54B	RAD54B	3757	0.063	0.52	YES
10	MRE11A	MRE11A	MRE11A	3922	0.059	0.54	YES
11	NBN	NBN	NBN	4164	0.053	0.55	YES
12	RPA3	RPA3	RPA3	4265	0.051	0.57	YES
13	RAD50	RAD50	RAD50	4383	0.048	0.58	YES
14	RPA1	RPA1	RPA1	6490	0.015	0.47	NO
15	TOP3B	TOP3B	TOP3B	6825	0.011	0.46	NO
16	MUS81	MUS81	MUS81	6858	0.011	0.46	NO
17	POLD3	POLD3	POLD3	7006	0.0093	0.46	NO
18	POLD4	POLD4	POLD4	7222	0.0067	0.45	NO
19	SSBP1	SSBP1	SSBP1	8045	-0.0025	0.4	NO
20	TOP3A	TOP3A	TOP3A	8046	-0.0026	0.41	NO
21	RPA2	RPA2	RPA2	8354	-0.0061	0.39	NO
22	XRCC3	XRCC3	XRCC3	10236	-0.029	0.3	NO
23	RAD52	RAD52	RAD52	10305	-0.03	0.31	NO
24	SHFM1	SHFM1	SHFM1	11765	-0.052	0.25	NO
25	POLD2	POLD2	POLD2	12132	-0.058	0.26	NO
26	RAD51L3	RAD51L3	RAD51L3	12639	-0.068	0.26	NO
27	RPA4	RPA4	RPA4	12785	-0.072	0.29	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 DNA REPLICATION.

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

genes ES table in pathway: KEGG NUCLEOTIDE EXCISION REPAIR

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	BIRC3	BIRC3	BIRC3	311	0.43	0.037	YES
2	TNFRSF10A	TNFRSF10A	TNFRSF10A	452	0.38	0.078	YES
3	IL1RAP	IL1RAP	IL1RAP	459	0.38	0.12	YES
4	IL1A	IL1A	IL1A	934	0.26	0.13	YES
5	FAS	FAS	FAS	1039	0.24	0.16	YES
6	BID	BID	BID	1042	0.24	0.19	YES
7	IRAK2	IRAK2	IRAK2	1178	0.22	0.21	YES
8	CSF2RB	CSF2RB	CSF2RB	1221	0.22	0.23	YES
9	ENDOD1	ENDOD1	ENDOD1	1278	0.21	0.26	YES
10	TNFRSF10C	TNFRSF10C	TNFRSF10C	1333	0.2	0.28	YES
11	BCL2L1	BCL2L1	BCL2L1	1565	0.18	0.29	YES
12	AKT3	AKT3	AKT3	1915	0.15	0.29	YES
13	CFLAR	CFLAR	CFLAR	1937	0.14	0.3	YES
14	PIK3CA	PIK3CA	PIK3CA	2089	0.14	0.31	YES
15	CAPN2	CAPN2	CAPN2	2103	0.14	0.33	YES
16	MYD88	MYD88	MYD88	2118	0.13	0.35	YES
17	IL1R1	IL1R1	IL1R1	2185	0.13	0.36	YES
18	IL1B	IL1B	IL1B	2208	0.13	0.37	YES
19	TNFRSF10B	TNFRSF10B	TNFRSF10B	2443	0.12	0.38	YES
20	PIK3R5	PIK3R5	PIK3R5	2702	0.1	0.37	YES
21	CASP6	CASP6	CASP6	2904	0.093	0.38	YES
22	PIK3R1	PIK3R1	PIK3R1	3021	0.088	0.38	YES
23	CAPN1	CAPN1	CAPN1	3111	0.085	0.38	YES
24	PIK3CD	PIK3CD	PIK3CD	3143	0.084	0.39	YES
25	NTRK1	NTRK1	NTRK1	3220	0.08	0.4	YES
26	TNF	TNF	TNF	3328	0.077	0.4	YES
27	BAX	BAX	BAX	3381	0.075	0.41	YES
28	PIK3R2	PIK3R2	PIK3R2	3443	0.073	0.42	YES
29	PRKAR2A	PRKAR2A	PRKAR2A	3471	0.072	0.42	YES
30	TNFSF10	TNFSF10	TNFSF10	3534	0.07	0.43	YES
31	CHP	CHP	CHP	3576	0.068	0.44	YES
32	TNFRSF1A	TNFRSF1A	TNFRSF1A	4102	0.054	0.41	NO
33	FADD	FADD	FADD	4129	0.054	0.42	NO
34	NFKB1	NFKB1	NFKB1	4218	0.052	0.42	NO
35	RELA	RELA	RELA	4252	0.051	0.42	NO
36	BIRC2	BIRC2	BIRC2	4362	0.049	0.42	NO
37	PRKAR1B	PRKAR1B	PRKAR1B	4489	0.046	0.42	NO
38	CASP7	CASP7	CASP7	4750	0.042	0.42	NO
39	DFFA	DFFA	DFFA	4877	0.039	0.41	NO
40	MAP3K14	MAP3K14	MAP3K14	4968	0.038	0.41	NO
41	PIK3CG	PIK3CG	PIK3CG	5083	0.036	0.41	NO
42	PPP3CA	PPP3CA	PPP3CA	5137	0.035	0.41	NO
43	CHUK	CHUK	CHUK	5159	0.034	0.42	NO
44	PIK3CB	PIK3CB	PIK3CB	5360	0.031	0.41	NO
45	TNFRSF10D	TNFRSF10D	TNFRSF10D	5692	0.026	0.39	NO
46	PPP3CB	PPP3CB	PPP3CB	6064	0.021	0.38	NO
47	PRKX	PRKX	PRKX	6161	0.019	0.37	NO
48	APAF1	APAF1	APAF1	6164	0.019	0.37	NO
49	CASP3	CASP3	CASP3	6225	0.018	0.37	NO
50	TP53	TP53	TP53	6482	0.015	0.36	NO
51	XIAP	XIAP	XIAP	7063	0.0085	0.33	NO
52	PPP3R1	PPP3R1	PPP3R1	7270	0.0062	0.32	NO
53	PRKAR1A	PRKAR1A	PRKAR1A	7600	0.0026	0.3	NO
54	CASP8	CASP8	CASP8	7794	0.00018	0.29	NO
55	ATM	ATM	ATM	8043	-0.0025	0.28	NO
56	TRADD	TRADD	TRADD	8177	-0.0041	0.27	NO
57	AKT1	AKT1	AKT1	8925	-0.013	0.23	NO
58	IRAK4	IRAK4	IRAK4	9179	-0.016	0.22	NO
59	RIPK1	RIPK1	RIPK1	9219	-0.017	0.22	NO
60	DFFB	DFFB	DFFB	9311	-0.018	0.21	NO
61	NFKBIA	NFKBIA	NFKBIA	10889	-0.038	0.13	NO
62	IKBKB	IKBKB	IKBKB	10916	-0.038	0.13	NO
63	CASP10	CASP10	CASP10	11010	-0.04	0.13	NO
64	TRAF2	TRAF2	TRAF2	11284	-0.044	0.12	NO
65	IRAK1	IRAK1	IRAK1	11672	-0.05	0.11	NO
66	ENDOG	ENDOG	ENDOG	11789	-0.052	0.11	NO
67	PRKACA	PRKACA	PRKACA	11873	-0.053	0.11	NO
68	IKBKG	IKBKG	IKBKG	12041	-0.057	0.11	NO
69	AKT2	AKT2	AKT2	12069	-0.057	0.12	NO
70	PPP3CC	PPP3CC	PPP3CC	12493	-0.065	0.1	NO
71	PRKAR2B	PRKAR2B	PRKAR2B	12765	-0.071	0.094	NO
72	EXOG	EXOG	EXOG	12821	-0.073	0.1	NO
73	CYCS	CYCS	CYCS	12827	-0.073	0.11	NO
74	AIFM1	AIFM1	AIFM1	13170	-0.082	0.1	NO
75	BAD	BAD	BAD	13235	-0.084	0.11	NO
76	CASP9	CASP9	CASP9	13609	-0.094	0.098	NO
77	NGF	NGF	NGF	13816	-0.1	0.1	NO
78	IL3RA	IL3RA	IL3RA	13905	-0.1	0.11	NO
79	IRAK3	IRAK3	IRAK3	14345	-0.12	0.099	NO
80	CHP2	CHP2	CHP2	15167	-0.16	0.074	NO
81	BCL2	BCL2	BCL2	15690	-0.2	0.07	NO
82	PIK3R3	PIK3R3	PIK3R3	15728	-0.2	0.094	NO
83	PRKACB	PRKACB	PRKACB	16288	-0.25	0.094	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 NUCLEOTIDE EXCISION REPAIR.

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

genes ES table in pathway: KEGG HOMOLOGOUS RECOMBINATION

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	PIK3CA	PIK3CA	PIK3CA	2089	0.14	-0.021	YES
2	CDKN1A	CDKN1A	CDKN1A	2150	0.13	0.068	YES
3	CCND1	CCND1	CCND1	2787	0.099	0.1	YES
4	CCNE1	CCNE1	CCNE1	2847	0.096	0.17	YES
5	CDK2	CDK2	CDK2	2929	0.093	0.23	YES
6	MAPK1	MAPK1	MAPK1	2935	0.092	0.29	YES
7	PIK3R1	PIK3R1	PIK3R1	3021	0.088	0.35	YES
8	NFKB1	NFKB1	NFKB1	4218	0.052	0.32	YES
9	RELA	RELA	RELA	4252	0.051	0.35	YES
10	CDK4	CDK4	CDK4	4963	0.038	0.34	YES
11	CHUK	CHUK	CHUK	5159	0.034	0.35	YES
12	RHOA	RHOA	RHOA	6274	0.018	0.3	NO
13	RAC1	RAC1	RAC1	6517	0.015	0.3	NO
14	CDKN1B	CDKN1B	CDKN1B	7757	0.00062	0.23	NO
15	MAPK3	MAPK3	MAPK3	7908	-0.0011	0.22	NO
16	RB1	RB1	RB1	7915	-0.0011	0.22	NO
17	RAF1	RAF1	RAF1	8358	-0.0061	0.2	NO
18	TFDP1	TFDP1	TFDP1	8735	-0.01	0.19	NO
19	AKT1	AKT1	AKT1	8925	-0.013	0.19	NO
20	NFKBIA	NFKBIA	NFKBIA	10889	-0.038	0.11	NO
21	IKBKB	IKBKB	IKBKB	10916	-0.038	0.13	NO
22	HRAS	HRAS	HRAS	11336	-0.044	0.14	NO
23	IKBKG	IKBKG	IKBKG	12041	-0.057	0.14	NO
24	PAK1	PAK1	PAK1	14080	-0.11	0.1	NO
25	CDK6	CDK6	CDK6	15132	-0.16	0.16	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 HOMOLOGOUS RECOMBINATION.

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

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 GH PATHWAY	26	genes.ES.table	0.53	1.4	0.1	0.51	0.94	0.19	0.077	0.18	0.4	0.11
BIOCARTA VEGF PATHWAY	28	genes.ES.table	0.45	1.3	0.19	0.55	0.97	0.21	0.13	0.19	0.46	0.13
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.49	1.3	0.25	0.52	0.98	0.69	0.35	0.45	0.43	0.11
KEGG FATTY ACID METABOLISM	38	genes.ES.table	0.44	1.3	0.18	0.51	0.98	0.63	0.28	0.45	0.42	0.1
KEGG OXIDATIVE PHOSPHORYLATION	113	genes.ES.table	0.53	1.5	0.13	0.47	0.84	0.77	0.32	0.53	0.33	0.11
KEGG GLYCINE SERINE AND THREONINE METABOLISM	28	genes.ES.table	0.59	1.4	0.083	0.56	0.94	0.57	0.21	0.45	0.43	0.14
KEGG VALINE LEUCINE AND ISOLEUCINE DEGRADATION	43	genes.ES.table	0.56	1.6	0.076	0.41	0.75	0.86	0.3	0.6	0.28	0.096
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.48	1.7	0.017	0.33	0.32	0.46	0.26	0.34	0	0.11
KEGG ARGININE AND PROLINE METABOLISM	51	genes.ES.table	0.47	1.4	0.059	0.62	0.92	0.45	0.21	0.36	0.46	0.18
KEGG STARCH AND SUCROSE METABOLISM	32	genes.ES.table	0.49	1.3	0.14	0.53	0.98	0.22	0.056	0.21	0.44	0.11

genes ES table in pathway: BIOCARTA GH 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	OGDHL	OGDHL	OGDHL	102	0.77	0.17	YES
2	ALDH1B1	ALDH1B1	ALDH1B1	1405	0.27	0.16	YES
3	ALDH2	ALDH2	ALDH2	1498	0.26	0.21	YES
4	SETMAR	SETMAR	SETMAR	2120	0.19	0.22	YES
5	ACAT1	ACAT1	ACAT1	2188	0.18	0.26	YES
6	ALDH9A1	ALDH9A1	ALDH9A1	2609	0.16	0.27	YES
7	AASS	AASS	AASS	2784	0.15	0.29	YES
8	AADAT	AADAT	AADAT	2823	0.14	0.32	YES
9	SETD8	SETD8	SETD8	2862	0.14	0.36	YES
10	OGDH	OGDH	OGDH	3241	0.13	0.36	YES
11	GCDH	GCDH	GCDH	3421	0.12	0.38	YES
12	ALDH7A1	ALDH7A1	ALDH7A1	3796	0.1	0.38	YES
13	ECHS1	ECHS1	ECHS1	3911	0.098	0.4	YES
14	SUV420H1	SUV420H1	SUV420H1	4174	0.09	0.4	YES
15	SETDB2	SETDB2	SETDB2	4460	0.082	0.41	YES
16	PLOD1	PLOD1	PLOD1	4467	0.081	0.42	YES
17	AASDH	AASDH	AASDH	4592	0.078	0.44	YES
18	TMLHE	TMLHE	TMLHE	4643	0.077	0.45	YES
19	HADH	HADH	HADH	4669	0.076	0.47	YES
20	WHSC1	WHSC1	WHSC1	4762	0.074	0.48	YES
21	HADHA	HADHA	HADHA	5086	0.066	0.48	NO
22	SUV39H2	SUV39H2	SUV39H2	6033	0.047	0.43	NO
23	NSD1	NSD1	NSD1	6465	0.039	0.42	NO
24	DLST	DLST	DLST	6648	0.036	0.42	NO
25	SETD2	SETD2	SETD2	6961	0.031	0.41	NO
26	SETD1B	SETD1B	SETD1B	7350	0.025	0.39	NO
27	EHMT1	EHMT1	EHMT1	7463	0.023	0.39	NO
28	SUV39H1	SUV39H1	SUV39H1	7741	0.019	0.38	NO
29	PLOD3	PLOD3	PLOD3	7750	0.019	0.38	NO
30	SETD1A	SETD1A	SETD1A	8039	0.015	0.37	NO
31	AASDHPPT	AASDHPPT	AASDHPPT	8370	0.0099	0.35	NO
32	DOT1L	DOT1L	DOT1L	8372	0.0099	0.36	NO
33	PLOD2	PLOD2	PLOD2	8385	0.0098	0.36	NO
34	WHSC1L1	WHSC1L1	WHSC1L1	9437	-0.0056	0.3	NO
35	SETDB1	SETDB1	SETDB1	9841	-0.011	0.28	NO
36	ALDH3A2	ALDH3A2	ALDH3A2	9982	-0.013	0.28	NO
37	ACAT2	ACAT2	ACAT2	10566	-0.022	0.25	NO
38	ASH1L	ASH1L	ASH1L	10610	-0.023	0.25	NO
39	EHMT2	EHMT2	EHMT2	11163	-0.032	0.23	NO
40	SUV420H2	SUV420H2	SUV420H2	12358	-0.057	0.17	NO
41	BBOX1	BBOX1	BBOX1	12816	-0.071	0.16	NO
42	SETD7	SETD7	SETD7	13862	-0.11	0.13	NO
43	PIPOX	PIPOX	PIPOX	16828	-0.43	0.064	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 GH PATHWAY.

Figure S22. 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 VEGF 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	HMGCS2	HMGCS2	HMGCS2	461	0.49	0.084	YES
2	ACSM5	ACSM5	ACSM5	532	0.46	0.18	YES
3	OXCT2	OXCT2	OXCT2	895	0.36	0.24	YES
4	ALDH1B1	ALDH1B1	ALDH1B1	1405	0.27	0.27	YES
5	ALDH2	ALDH2	ALDH2	1498	0.26	0.32	YES
6	BDH1	BDH1	BDH1	1527	0.25	0.38	YES
7	ACSM3	ACSM3	ACSM3	1609	0.24	0.43	YES
8	ACAT1	ACAT1	ACAT1	2188	0.18	0.44	YES
9	ACADS	ACADS	ACADS	2325	0.18	0.47	YES
10	AACS	AACS	AACS	2558	0.16	0.49	YES
11	L2HGDH	L2HGDH	L2HGDH	2598	0.16	0.52	YES
12	ALDH9A1	ALDH9A1	ALDH9A1	2609	0.16	0.56	YES
13	PDHA1	PDHA1	PDHA1	3048	0.14	0.56	YES
14	ABAT	ABAT	ABAT	3277	0.12	0.58	YES
15	HMGCS1	HMGCS1	HMGCS1	3531	0.11	0.59	YES
16	GAD1	GAD1	GAD1	3770	0.1	0.6	YES
17	ALDH7A1	ALDH7A1	ALDH7A1	3796	0.1	0.62	YES
18	ECHS1	ECHS1	ECHS1	3911	0.098	0.64	YES
19	OXCT1	OXCT1	OXCT1	4352	0.085	0.63	YES
20	HADH	HADH	HADH	4669	0.076	0.63	YES
21	HADHA	HADHA	HADHA	5086	0.066	0.62	YES
22	AKR1B10	AKR1B10	AKR1B10	5171	0.064	0.63	YES
23	ACSM2A	ACSM2A	ACSM2A	5175	0.064	0.64	YES
24	HMGCL	HMGCL	HMGCL	5426	0.058	0.64	YES
25	ALDH5A1	ALDH5A1	ALDH5A1	5612	0.054	0.64	YES
26	PDHB	PDHB	PDHB	6076	0.046	0.63	NO
27	BDH2	BDH2	BDH2	8421	0.0093	0.5	NO
28	ALDH3A2	ALDH3A2	ALDH3A2	9982	-0.013	0.42	NO
29	ACAT2	ACAT2	ACAT2	10566	-0.022	0.39	NO
30	ACSM1	ACSM1	ACSM1	13748	-0.11	0.24	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 VEGF PATHWAY.

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

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

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	ACACB	ACACB	ACACB	841	0.38	0.048	YES
2	ALDH1B1	ALDH1B1	ALDH1B1	1405	0.27	0.084	YES
3	ALDH2	ALDH2	ALDH2	1498	0.26	0.14	YES
4	ALDH6A1	ALDH6A1	ALDH6A1	1687	0.23	0.19	YES
5	LDHAL6A	LDHAL6A	LDHAL6A	1820	0.22	0.24	YES
6	ACAT1	ACAT1	ACAT1	2188	0.18	0.26	YES
7	EHHADH	EHHADH	EHHADH	2299	0.18	0.3	YES
8	ACSS1	ACSS1	ACSS1	2455	0.17	0.34	YES
9	ALDH9A1	ALDH9A1	ALDH9A1	2609	0.16	0.37	YES
10	SUCLG1	SUCLG1	SUCLG1	2885	0.14	0.39	YES
11	ACADM	ACADM	ACADM	3108	0.13	0.41	YES
12	ABAT	ABAT	ABAT	3277	0.12	0.43	YES
13	LDHB	LDHB	LDHB	3284	0.12	0.46	YES
14	MLYCD	MLYCD	MLYCD	3330	0.12	0.49	YES
15	PCCB	PCCB	PCCB	3506	0.11	0.51	YES
16	PCCA	PCCA	PCCA	3684	0.11	0.52	YES
17	ALDH7A1	ALDH7A1	ALDH7A1	3796	0.1	0.55	YES
18	ECHS1	ECHS1	ECHS1	3911	0.098	0.56	YES
19	SUCLA2	SUCLA2	SUCLA2	3974	0.096	0.58	YES
20	ACACA	ACACA	ACACA	4723	0.075	0.56	YES
21	ACSS2	ACSS2	ACSS2	4749	0.074	0.58	YES
22	HIBCH	HIBCH	HIBCH	4759	0.074	0.6	YES
23	SUCLG2	SUCLG2	SUCLG2	5037	0.067	0.6	YES
24	HADHA	HADHA	HADHA	5086	0.066	0.61	YES
25	MCEE	MCEE	MCEE	5280	0.062	0.62	YES
26	MUT	MUT	MUT	5768	0.052	0.6	NO
27	ACSS3	ACSS3	ACSS3	8675	0.006	0.44	NO
28	ALDH3A2	ALDH3A2	ALDH3A2	9982	-0.013	0.37	NO
29	ACAT2	ACAT2	ACAT2	10566	-0.022	0.35	NO
30	LDHA	LDHA	LDHA	14076	-0.12	0.18	NO
31	LDHAL6B	LDHAL6B	LDHAL6B	14374	-0.14	0.2	NO

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

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

genes ES table in pathway: KEGG FATTY ACID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	HMGCS2	HMGCS2	HMGCS2	461	0.49	0.048	YES
2	AOX1	AOX1	AOX1	787	0.39	0.088	YES
3	OXCT2	OXCT2	OXCT2	895	0.36	0.14	YES
4	ALDH1B1	ALDH1B1	ALDH1B1	1405	0.27	0.15	YES
5	ALDH2	ALDH2	ALDH2	1498	0.26	0.18	YES
6	ALDH6A1	ALDH6A1	ALDH6A1	1687	0.23	0.2	YES
7	ACADSB	ACADSB	ACADSB	1991	0.2	0.22	YES
8	BCAT2	BCAT2	BCAT2	2086	0.19	0.24	YES
9	ACAD8	ACAD8	ACAD8	2151	0.19	0.27	YES
10	ACAT1	ACAT1	ACAT1	2188	0.18	0.29	YES
11	MCCC2	MCCC2	MCCC2	2235	0.18	0.32	YES
12	EHHADH	EHHADH	EHHADH	2299	0.18	0.34	YES
13	ACADS	ACADS	ACADS	2325	0.18	0.36	YES
14	ALDH9A1	ALDH9A1	ALDH9A1	2609	0.16	0.37	YES
15	DBT	DBT	DBT	2774	0.15	0.38	YES
16	BCKDHB	BCKDHB	BCKDHB	2947	0.14	0.4	YES
17	ACADM	ACADM	ACADM	3108	0.13	0.41	YES
18	IVD	IVD	IVD	3125	0.13	0.43	YES
19	HSD17B10	HSD17B10	HSD17B10	3138	0.13	0.44	YES
20	ABAT	ABAT	ABAT	3277	0.12	0.46	YES
21	PCCB	PCCB	PCCB	3506	0.11	0.46	YES
22	HMGCS1	HMGCS1	HMGCS1	3531	0.11	0.48	YES
23	DLD	DLD	DLD	3541	0.11	0.49	YES
24	PCCA	PCCA	PCCA	3684	0.11	0.5	YES
25	HIBADH	HIBADH	HIBADH	3732	0.1	0.51	YES
26	ALDH7A1	ALDH7A1	ALDH7A1	3796	0.1	0.52	YES
27	ECHS1	ECHS1	ECHS1	3911	0.098	0.53	YES
28	HADHB	HADHB	HADHB	3955	0.097	0.55	YES
29	BCKDHA	BCKDHA	BCKDHA	3982	0.096	0.56	YES
30	OXCT1	OXCT1	OXCT1	4352	0.085	0.55	YES
31	HADH	HADH	HADH	4669	0.076	0.54	YES
32	AUH	AUH	AUH	4754	0.074	0.55	YES
33	HIBCH	HIBCH	HIBCH	4759	0.074	0.56	YES
34	HADHA	HADHA	HADHA	5086	0.066	0.55	YES
35	MCCC1	MCCC1	MCCC1	5133	0.065	0.56	YES
36	MCEE	MCEE	MCEE	5280	0.062	0.56	YES
37	HMGCL	HMGCL	HMGCL	5426	0.058	0.56	YES
38	MUT	MUT	MUT	5768	0.052	0.55	NO
39	ACAA1	ACAA1	ACAA1	6116	0.045	0.54	NO
40	ALDH3A2	ALDH3A2	ALDH3A2	9982	-0.013	0.32	NO
41	ACAT2	ACAT2	ACAT2	10566	-0.022	0.3	NO
42	ACAA2	ACAA2	ACAA2	13579	-0.098	0.14	NO
43	IL4I1	IL4I1	IL4I1	17674	-0.69	0.017	NO

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

Figure S28. 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 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	ATP4A	ATP4A	ATP4A	202	0.65	0.04	YES
2	COX4I2	COX4I2	COX4I2	695	0.41	0.046	YES
3	ATP6V1G2	ATP6V1G2	ATP6V1G2	852	0.37	0.067	YES
4	COX7A1	COX7A1	COX7A1	1096	0.32	0.079	YES
5	ATP6V0E2	ATP6V0E2	ATP6V0E2	1163	0.3	0.099	YES
6	NDUFA4L2	NDUFA4L2	NDUFA4L2	1910	0.21	0.074	YES
7	NDUFB1	NDUFB1	NDUFB1	2333	0.17	0.064	YES
8	ATP6V1B1	ATP6V1B1	ATP6V1B1	2337	0.17	0.078	YES
9	ATP6V1E2	ATP6V1E2	ATP6V1E2	2342	0.17	0.092	YES
10	COX8A	COX8A	COX8A	2538	0.16	0.093	YES
11	COX7B	COX7B	COX7B	2543	0.16	0.11	YES
12	NDUFB2	NDUFB2	NDUFB2	2575	0.16	0.12	YES
13	COX10	COX10	COX10	2577	0.16	0.13	YES
14	ATP5G1	ATP5G1	ATP5G1	2655	0.15	0.14	YES
15	COX8C	COX8C	COX8C	2679	0.15	0.15	YES
16	COX6A1	COX6A1	COX6A1	2853	0.14	0.15	YES
17	NDUFA3	NDUFA3	NDUFA3	2917	0.14	0.16	YES
18	ATP5H	ATP5H	ATP5H	2952	0.14	0.17	YES
19	ATP4B	ATP4B	ATP4B	2961	0.14	0.18	YES
20	NDUFA5	NDUFA5	NDUFA5	2996	0.14	0.19	YES
21	COX6C	COX6C	COX6C	3030	0.14	0.2	YES
22	NDUFA1	NDUFA1	NDUFA1	3047	0.14	0.2	YES
23	NDUFA8	NDUFA8	NDUFA8	3087	0.13	0.21	YES
24	ATP6V1C2	ATP6V1C2	ATP6V1C2	3090	0.13	0.22	YES
25	CYC1	CYC1	CYC1	3192	0.13	0.23	YES
26	COX5B	COX5B	COX5B	3225	0.13	0.24	YES
27	UQCRHL	UQCRHL	UQCRHL	3261	0.12	0.24	YES
28	ATP5I	ATP5I	ATP5I	3347	0.12	0.25	YES
29	NDUFA2	NDUFA2	NDUFA2	3369	0.12	0.26	YES
30	ATP5J	ATP5J	ATP5J	3386	0.12	0.27	YES
31	UQCRQ	UQCRQ	UQCRQ	3499	0.11	0.27	YES
32	ATP5D	ATP5D	ATP5D	3552	0.11	0.28	YES
33	NDUFV2	NDUFV2	NDUFV2	3564	0.11	0.28	YES
34	NDUFB3	NDUFB3	NDUFB3	3569	0.11	0.29	YES
35	ATP5B	ATP5B	ATP5B	3585	0.11	0.3	YES
36	ATP5J2	ATP5J2	ATP5J2	3618	0.11	0.31	YES
37	NDUFB7	NDUFB7	NDUFB7	3654	0.11	0.31	YES
38	UQCR11	UQCR11	UQCR11	3694	0.11	0.32	YES
39	UQCR10	UQCR10	UQCR10	3705	0.11	0.33	YES
40	COX17	COX17	COX17	3735	0.1	0.34	YES
41	NDUFC2	NDUFC2	NDUFC2	3758	0.1	0.34	YES
42	UQCRH	UQCRH	UQCRH	3854	0.1	0.34	YES
43	SDHD	SDHD	SDHD	3867	0.1	0.35	YES
44	NDUFS7	NDUFS7	NDUFS7	3899	0.099	0.36	YES
45	ATP5G3	ATP5G3	ATP5G3	3922	0.098	0.36	YES
46	NDUFA6	NDUFA6	NDUFA6	3935	0.098	0.37	YES
47	NDUFA7	NDUFA7	NDUFA7	3996	0.096	0.38	YES
48	COX15	COX15	COX15	4013	0.095	0.38	YES
49	ATP5O	ATP5O	ATP5O	4034	0.095	0.39	YES
50	COX5A	COX5A	COX5A	4074	0.094	0.4	YES
51	ATP5E	ATP5E	ATP5E	4107	0.093	0.4	YES
52	ATP6V0B	ATP6V0B	ATP6V0B	4114	0.092	0.41	YES
53	ATP5C1	ATP5C1	ATP5C1	4150	0.091	0.41	YES
54	NDUFV3	NDUFV3	NDUFV3	4158	0.091	0.42	YES
55	NDUFS6	NDUFS6	NDUFS6	4220	0.089	0.42	YES
56	COX4I1	COX4I1	COX4I1	4244	0.088	0.43	YES
57	NDUFB5	NDUFB5	NDUFB5	4359	0.085	0.43	YES
58	COX11	COX11	COX11	4367	0.084	0.44	YES
59	COX7A2	COX7A2	COX7A2	4386	0.084	0.44	YES
60	NDUFB6	NDUFB6	NDUFB6	4411	0.083	0.45	YES
61	ATP5F1	ATP5F1	ATP5F1	4483	0.081	0.45	YES
62	ATP5A1	ATP5A1	ATP5A1	4491	0.081	0.46	YES
63	NDUFS2	NDUFS2	NDUFS2	4515	0.08	0.46	YES
64	NDUFS3	NDUFS3	NDUFS3	4558	0.079	0.46	YES
65	UQCRFS1	UQCRFS1	UQCRFS1	4566	0.079	0.47	YES
66	NDUFB10	NDUFB10	NDUFB10	4573	0.079	0.48	YES
67	NDUFC1	NDUFC1	NDUFC1	4576	0.079	0.48	YES
68	COX6B1	COX6B1	COX6B1	4611	0.078	0.49	YES
69	UQCRC2	UQCRC2	UQCRC2	4612	0.078	0.49	YES
70	ATP6V1H	ATP6V1H	ATP6V1H	4626	0.078	0.5	YES
71	SDHC	SDHC	SDHC	4668	0.077	0.5	YES
72	ATP6V0D1	ATP6V0D1	ATP6V0D1	4768	0.074	0.5	YES
73	NDUFA4	NDUFA4	NDUFA4	4817	0.072	0.51	YES
74	LHPP	LHPP	LHPP	4853	0.072	0.51	YES
75	COX7C	COX7C	COX7C	4868	0.071	0.51	YES
76	NDUFB8	NDUFB8	NDUFB8	4939	0.07	0.52	YES
77	UQCRB	UQCRB	UQCRB	4968	0.069	0.52	YES
78	NDUFA9	NDUFA9	NDUFA9	5006	0.068	0.52	YES
79	NDUFA10	NDUFA10	NDUFA10	5203	0.063	0.52	YES
80	NDUFS8	NDUFS8	NDUFS8	5249	0.062	0.52	YES
81	NDUFB4	NDUFB4	NDUFB4	5250	0.062	0.52	YES
82	ATP5G2	ATP5G2	ATP5G2	5326	0.06	0.52	YES
83	NDUFV1	NDUFV1	NDUFV1	5400	0.059	0.53	YES
84	SDHA	SDHA	SDHA	5439	0.058	0.53	YES
85	ATP6V1D	ATP6V1D	ATP6V1D	5522	0.056	0.53	YES
86	NDUFB9	NDUFB9	NDUFB9	5629	0.054	0.53	YES
87	NDUFS4	NDUFS4	NDUFS4	5664	0.054	0.53	YES
88	ATP6V0E1	ATP6V0E1	ATP6V0E1	5825	0.051	0.52	NO
89	ATP5L	ATP5L	ATP5L	5861	0.05	0.53	NO
90	NDUFS1	NDUFS1	NDUFS1	6173	0.044	0.51	NO
91	UQCRC1	UQCRC1	UQCRC1	6208	0.044	0.51	NO
92	SDHB	SDHB	SDHB	6214	0.043	0.52	NO
93	NDUFAB1	NDUFAB1	NDUFAB1	6323	0.041	0.51	NO
94	PPA2	PPA2	PPA2	6387	0.04	0.51	NO
95	ATP6AP1	ATP6AP1	ATP6AP1	6690	0.035	0.5	NO
96	NDUFA11	NDUFA11	NDUFA11	6995	0.03	0.48	NO
97	ATP6V1C1	ATP6V1C1	ATP6V1C1	7384	0.024	0.47	NO
98	ATP6V0C	ATP6V0C	ATP6V0C	7987	0.016	0.43	NO
99	ATP6V1G1	ATP6V1G1	ATP6V1G1	8817	0.0037	0.39	NO
100	ATP6V0A1	ATP6V0A1	ATP6V0A1	8897	0.0025	0.38	NO
101	COX7A2L	COX7A2L	COX7A2L	8995	0.0012	0.38	NO
102	ATP6V1F	ATP6V1F	ATP6V1F	9317	-0.0039	0.36	NO
103	NDUFS5	NDUFS5	NDUFS5	9572	-0.0074	0.35	NO
104	ATP6V0A4	ATP6V0A4	ATP6V0A4	10857	-0.027	0.28	NO
105	ATP6V1A	ATP6V1A	ATP6V1A	11029	-0.03	0.27	NO
106	ATP6V1E1	ATP6V1E1	ATP6V1E1	11724	-0.042	0.23	NO
107	ATP6V0A2	ATP6V0A2	ATP6V0A2	12727	-0.068	0.18	NO
108	PPA1	PPA1	PPA1	13403	-0.091	0.15	NO
109	ATP12A	ATP12A	ATP12A	13843	-0.11	0.14	NO
110	ATP6V1B2	ATP6V1B2	ATP6V1B2	13986	-0.12	0.14	NO
111	TCIRG1	TCIRG1	TCIRG1	15295	-0.21	0.082	NO
112	ATP6V0D2	ATP6V0D2	ATP6V0D2	16677	-0.4	0.037	NO
113	COX6B2	COX6B2	COX6B2	16952	-0.45	0.057	NO

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

Figure S30. 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 GLYCINE SERINE AND THREONINE METABOLISM

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	CKMT2	CKMT2	CKMT2	279	0.58	0.057	YES
2	AGMAT	AGMAT	AGMAT	491	0.48	0.1	YES
3	GATM	GATM	GATM	760	0.4	0.14	YES
4	ALDH4A1	ALDH4A1	ALDH4A1	872	0.37	0.18	YES
5	CKMT1B	CKMT1B	CKMT1B	893	0.36	0.22	YES
6	CKB	CKB	CKB	1168	0.3	0.25	YES
7	MAOB	MAOB	MAOB	1197	0.3	0.28	YES
8	ALDH1B1	ALDH1B1	ALDH1B1	1405	0.27	0.3	YES
9	CKMT1A	CKMT1A	CKMT1A	1487	0.26	0.33	YES
10	ALDH2	ALDH2	ALDH2	1498	0.26	0.36	YES
11	NOS1	NOS1	NOS1	1510	0.25	0.39	YES
12	SAT2	SAT2	SAT2	2381	0.17	0.37	YES
13	ARG1	ARG1	ARG1	2422	0.17	0.38	YES
14	GAMT	GAMT	GAMT	2545	0.16	0.4	YES
15	ALDH9A1	ALDH9A1	ALDH9A1	2609	0.16	0.41	YES
16	GOT1	GOT1	GOT1	2651	0.15	0.43	YES
17	NAGS	NAGS	NAGS	2858	0.14	0.44	YES
18	P4HA3	P4HA3	P4HA3	2916	0.14	0.45	YES
19	GOT2	GOT2	GOT2	3422	0.12	0.44	YES
20	CPS1	CPS1	CPS1	3484	0.12	0.45	YES
21	PYCRL	PYCRL	PYCRL	3563	0.11	0.46	YES
22	MAOA	MAOA	MAOA	3700	0.11	0.46	YES
23	ALDH7A1	ALDH7A1	ALDH7A1	3796	0.1	0.47	YES
24	ASL	ASL	ASL	4307	0.086	0.45	NO
25	PYCR1	PYCR1	PYCR1	4335	0.086	0.46	NO
26	ARG2	ARG2	ARG2	4535	0.08	0.46	NO
27	OAT	OAT	OAT	4918	0.07	0.45	NO
28	GLUL	GLUL	GLUL	5965	0.048	0.4	NO
29	ALDH18A1	ALDH18A1	ALDH18A1	6515	0.038	0.37	NO
30	AMD1	AMD1	AMD1	6838	0.033	0.36	NO
31	ACY1	ACY1	ACY1	6970	0.031	0.35	NO
32	NOS3	NOS3	NOS3	7359	0.025	0.34	NO
33	ADC	ADC	ADC	8645	0.0065	0.26	NO
34	NOS2	NOS2	NOS2	8829	0.0035	0.25	NO
35	ALDH3A2	ALDH3A2	ALDH3A2	9982	-0.013	0.19	NO
36	P4HA1	P4HA1	P4HA1	10299	-0.018	0.18	NO
37	PYCR2	PYCR2	PYCR2	11105	-0.031	0.14	NO
38	ASS1	ASS1	ASS1	12189	-0.053	0.082	NO
39	GLUD1	GLUD1	GLUD1	12223	-0.054	0.086	NO
40	SMS	SMS	SMS	12493	-0.06	0.079	NO
41	ABP1	ABP1	ABP1	12706	-0.067	0.076	NO
42	SRM	SRM	SRM	12983	-0.077	0.07	NO
43	LAP3	LAP3	LAP3	13319	-0.088	0.062	NO
44	GLUD2	GLUD2	GLUD2	13474	-0.094	0.065	NO
45	ODC1	ODC1	ODC1	13824	-0.11	0.059	NO
46	DAO	DAO	DAO	13857	-0.11	0.072	NO
47	P4HA2	P4HA2	P4HA2	14433	-0.14	0.058	NO
48	GLS	GLS	GLS	15120	-0.2	0.044	NO
49	PRODH	PRODH	PRODH	15931	-0.28	0.034	NO
50	CKM	CKM	CKM	16061	-0.3	0.064	NO
51	GLS2	GLS2	GLS2	16291	-0.34	0.094	NO

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

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

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

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	PYGM	PYGM	PYGM	36	0.92	0.055	YES
2	PPARGC1A	PPARGC1A	PPARGC1A	82	0.8	0.1	YES
3	SLC2A4	SLC2A4	SLC2A4	117	0.75	0.15	YES
4	IRS4	IRS4	IRS4	168	0.69	0.19	YES
5	GCK	GCK	GCK	204	0.64	0.22	YES
6	GYS2	GYS2	GYS2	345	0.55	0.25	YES
7	PPP1R3C	PPP1R3C	PPP1R3C	776	0.39	0.25	YES
8	ACACB	ACACB	ACACB	841	0.38	0.27	YES
9	IRS1	IRS1	IRS1	954	0.35	0.28	YES
10	PRKACB	PRKACB	PRKACB	1083	0.32	0.3	YES
11	MAPK10	MAPK10	MAPK10	1385	0.27	0.3	YES
12	CALML6	CALML6	CALML6	1425	0.26	0.31	YES
13	SOCS2	SOCS2	SOCS2	1582	0.24	0.32	YES
14	PIK3R3	PIK3R3	PIK3R3	1741	0.22	0.32	YES
15	PHKG1	PHKG1	PHKG1	1903	0.21	0.33	YES
16	PRKAA2	PRKAA2	PRKAA2	2087	0.19	0.33	YES
17	PCK1	PCK1	PCK1	2207	0.18	0.33	YES
18	SH2B2	SH2B2	SH2B2	2260	0.18	0.34	YES
19	PHKB	PHKB	PHKB	2346	0.17	0.35	YES
20	AKT2	AKT2	AKT2	2753	0.15	0.33	NO
21	BAD	BAD	BAD	2992	0.14	0.33	NO
22	FOXO1	FOXO1	FOXO1	3045	0.14	0.33	NO
23	CBLB	CBLB	CBLB	3264	0.12	0.33	NO
24	HK1	HK1	HK1	3457	0.12	0.32	NO
25	MAPK8	MAPK8	MAPK8	3809	0.1	0.31	NO
26	PRKAR2A	PRKAR2A	PRKAR2A	4071	0.094	0.3	NO
27	FASN	FASN	FASN	4550	0.079	0.28	NO
28	ACACA	ACACA	ACACA	4723	0.075	0.28	NO
29	GYS1	GYS1	GYS1	4755	0.074	0.28	NO
30	PRKAB2	PRKAB2	PRKAB2	4797	0.073	0.28	NO
31	PPP1R3D	PPP1R3D	PPP1R3D	5161	0.064	0.26	NO
32	SOS2	SOS2	SOS2	5511	0.057	0.25	NO
33	TSC2	TSC2	TSC2	5513	0.056	0.25	NO
34	EIF4E	EIF4E	EIF4E	5528	0.056	0.26	NO
35	PRKAG2	PRKAG2	PRKAG2	5786	0.051	0.24	NO
36	SOCS4	SOCS4	SOCS4	6007	0.047	0.23	NO
37	SOS1	SOS1	SOS1	6296	0.042	0.22	NO
38	PDPK1	PDPK1	PDPK1	6393	0.04	0.22	NO
39	TSC1	TSC1	TSC1	6501	0.038	0.21	NO
40	PPP1CC	PPP1CC	PPP1CC	6503	0.038	0.22	NO
41	INSR	INSR	INSR	6508	0.038	0.22	NO
42	PRKCZ	PRKCZ	PRKCZ	6795	0.033	0.2	NO
43	RPS6KB2	RPS6KB2	RPS6KB2	6867	0.032	0.2	NO
44	PRKAG1	PRKAG1	PRKAG1	7043	0.029	0.2	NO
45	RPS6KB1	RPS6KB1	RPS6KB1	7195	0.027	0.19	NO
46	MAPK9	MAPK9	MAPK9	7238	0.027	0.19	NO
47	RPTOR	RPTOR	RPTOR	7365	0.025	0.18	NO
48	MAPK3	MAPK3	MAPK3	7369	0.025	0.18	NO
49	PRKAA1	PRKAA1	PRKAA1	7495	0.023	0.18	NO
50	SHC2	SHC2	SHC2	7603	0.021	0.17	NO
51	AKT1	AKT1	AKT1	7634	0.021	0.17	NO
52	MKNK2	MKNK2	MKNK2	7683	0.02	0.17	NO
53	PRKACA	PRKACA	PRKACA	7719	0.019	0.17	NO
54	RAF1	RAF1	RAF1	7855	0.017	0.16	NO
55	RHOQ	RHOQ	RHOQ	7921	0.016	0.16	NO
56	PHKG2	PHKG2	PHKG2	7923	0.016	0.16	NO
57	CRK	CRK	CRK	8104	0.014	0.15	NO
58	CALM1	CALM1	CALM1	8114	0.014	0.15	NO
59	SORBS1	SORBS1	SORBS1	8224	0.012	0.15	NO
60	EIF4E2	EIF4E2	EIF4E2	8228	0.012	0.15	NO
61	IKBKB	IKBKB	IKBKB	8415	0.0094	0.14	NO
62	CALM3	CALM3	CALM3	8499	0.0084	0.13	NO
63	MAP2K2	MAP2K2	MAP2K2	8524	0.008	0.13	NO
64	RAPGEF1	RAPGEF1	RAPGEF1	8526	0.008	0.13	NO
65	LIPE	LIPE	LIPE	8905	0.0024	0.11	NO
66	PIK3CB	PIK3CB	PIK3CB	8910	0.0024	0.11	NO
67	PRKAB1	PRKAB1	PRKAB1	9018	0.00088	0.11	NO
68	PCK2	PCK2	PCK2	9034	0.00058	0.11	NO
69	PPP1R3B	PPP1R3B	PPP1R3B	9146	-0.0012	0.1	NO
70	MTOR	MTOR	MTOR	9289	-0.0034	0.092	NO
71	FLOT2	FLOT2	FLOT2	9304	-0.0037	0.091	NO
72	EXOC7	EXOC7	EXOC7	9364	-0.0047	0.088	NO
73	PPP1CA	PPP1CA	PPP1CA	9389	-0.0051	0.087	NO
74	ARAF	ARAF	ARAF	9444	-0.0056	0.085	NO
75	KRAS	KRAS	KRAS	9642	-0.0084	0.074	NO
76	BRAF	BRAF	BRAF	9685	-0.009	0.072	NO
77	NRAS	NRAS	NRAS	9689	-0.0091	0.073	NO
78	PDE3A	PDE3A	PDE3A	9690	-0.0091	0.073	NO
79	MAP2K1	MAP2K1	MAP2K1	9821	-0.011	0.067	NO
80	PRKX	PRKX	PRKX	9833	-0.011	0.067	NO
81	PRKAR1A	PRKAR1A	PRKAR1A	10090	-0.015	0.053	NO
82	RPS6	RPS6	RPS6	10205	-0.016	0.048	NO
83	GRB2	GRB2	GRB2	10500	-0.021	0.033	NO
84	SOCS1	SOCS1	SOCS1	10528	-0.022	0.033	NO
85	FLOT1	FLOT1	FLOT1	11078	-0.031	0.0038	NO
86	INPP5K	INPP5K	INPP5K	11081	-0.031	0.0055	NO
87	PHKA1	PHKA1	PHKA1	11228	-0.034	-0.00058	NO
88	PRKCI	PRKCI	PRKCI	11287	-0.035	-0.0017	NO
89	PTPN1	PTPN1	PTPN1	11407	-0.036	-0.0061	NO
90	PPP1CB	PPP1CB	PPP1CB	11479	-0.038	-0.0078	NO
91	PKLR	PKLR	PKLR	11547	-0.039	-0.0091	NO
92	MKNK1	MKNK1	MKNK1	11834	-0.044	-0.022	NO
93	CRKL	CRKL	CRKL	11837	-0.044	-0.02	NO
94	FBP1	FBP1	FBP1	11846	-0.044	-0.018	NO
95	GSK3B	GSK3B	GSK3B	11852	-0.045	-0.015	NO
96	RHEB	RHEB	RHEB	11981	-0.048	-0.019	NO
97	PHKA2	PHKA2	PHKA2	12277	-0.055	-0.032	NO
98	SHC4	SHC4	SHC4	12306	-0.056	-0.03	NO
99	SHC1	SHC1	SHC1	12646	-0.065	-0.046	NO
100	PYGB	PYGB	PYGB	12855	-0.073	-0.053	NO
101	PIK3R2	PIK3R2	PIK3R2	13001	-0.077	-0.056	NO
102	CALM2	CALM2	CALM2	13062	-0.079	-0.054	NO
103	CBL	CBL	CBL	13107	-0.081	-0.052	NO
104	MAPK1	MAPK1	MAPK1	13122	-0.081	-0.048	NO
105	HK2	HK2	HK2	13153	-0.082	-0.044	NO
106	EIF4EBP1	EIF4EBP1	EIF4EBP1	13383	-0.09	-0.052	NO
107	CBLC	CBLC	CBLC	13555	-0.098	-0.055	NO
108	PRKAR1B	PRKAR1B	PRKAR1B	13655	-0.1	-0.054	NO
109	PIK3R1	PIK3R1	PIK3R1	13675	-0.1	-0.049	NO
110	ELK1	ELK1	ELK1	13875	-0.11	-0.053	NO
111	TRIP10	TRIP10	TRIP10	13950	-0.12	-0.05	NO
112	PRKAR2B	PRKAR2B	PRKAR2B	14085	-0.12	-0.05	NO
113	SOCS3	SOCS3	SOCS3	14238	-0.13	-0.051	NO
114	AKT3	AKT3	AKT3	14361	-0.14	-0.049	NO
115	SREBF1	SREBF1	SREBF1	14491	-0.15	-0.047	NO
116	PIK3CA	PIK3CA	PIK3CA	14548	-0.15	-0.041	NO
117	PYGL	PYGL	PYGL	15188	-0.2	-0.064	NO
118	IRS2	IRS2	IRS2	15267	-0.21	-0.055	NO
119	PIK3CG	PIK3CG	PIK3CG	15557	-0.24	-0.057	NO
120	PTPRF	PTPRF	PTPRF	15622	-0.25	-0.045	NO
121	INPP5D	INPP5D	INPP5D	15878	-0.28	-0.042	NO
122	CALML3	CALML3	CALML3	15948	-0.28	-0.028	NO
123	PDE3B	PDE3B	PDE3B	16375	-0.35	-0.031	NO
124	SHC3	SHC3	SHC3	16530	-0.38	-0.016	NO
125	PIK3CD	PIK3CD	PIK3CD	16753	-0.41	-0.0032	NO
126	PIK3R5	PIK3R5	PIK3R5	17120	-0.48	0.0062	NO
127	HK3	HK3	HK3	17638	-0.67	0.019	NO

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

Figure S34. 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 LYSINE DEGRADATION

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	GNMT	GNMT	GNMT	186	0.67	0.095	YES
2	GLDC	GLDC	GLDC	230	0.62	0.19	YES
3	PSAT1	PSAT1	PSAT1	381	0.53	0.27	YES
4	CTH	CTH	CTH	571	0.45	0.33	YES
5	AOC2	AOC2	AOC2	670	0.42	0.39	YES
6	GATM	GATM	GATM	760	0.4	0.45	YES
7	DMGDH	DMGDH	DMGDH	891	0.36	0.5	YES
8	MAOB	MAOB	MAOB	1197	0.3	0.53	YES
9	PSPH	PSPH	PSPH	1724	0.23	0.54	YES
10	GCAT	GCAT	GCAT	1823	0.22	0.56	YES
11	GAMT	GAMT	GAMT	2545	0.16	0.55	YES
12	AOC3	AOC3	AOC3	2592	0.16	0.57	YES
13	PHGDH	PHGDH	PHGDH	2837	0.14	0.58	YES
14	ALAS2	ALAS2	ALAS2	3395	0.12	0.57	YES
15	DLD	DLD	DLD	3541	0.11	0.58	YES
16	MAOA	MAOA	MAOA	3700	0.11	0.59	YES
17	ALAS1	ALAS1	ALAS1	3978	0.096	0.59	NO
18	BHMT	BHMT	BHMT	4894	0.071	0.55	NO
19	SRR	SRR	SRR	6856	0.032	0.44	NO
20	SHMT1	SHMT1	SHMT1	7789	0.018	0.39	NO
21	CBS	CBS	CBS	8143	0.013	0.38	NO
22	GLYCTK	GLYCTK	GLYCTK	8390	0.0097	0.36	NO
23	SHMT2	SHMT2	SHMT2	11690	-0.042	0.19	NO
24	CHDH	CHDH	CHDH	13588	-0.099	0.096	NO
25	DAO	DAO	DAO	13857	-0.11	0.099	NO
26	SDS	SDS	SDS	13915	-0.11	0.11	NO
27	SARDH	SARDH	SARDH	15908	-0.28	0.047	NO
28	PIPOX	PIPOX	PIPOX	16828	-0.43	0.064	NO

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

Figure S36. 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 ARGININE AND PROLINE METABOLISM

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	SLC2A4	SLC2A4	SLC2A4	117	0.75	0.2	YES
2	GHR	GHR	GHR	604	0.44	0.3	YES
3	HNF1A	HNF1A	HNF1A	830	0.38	0.39	YES
4	IRS1	IRS1	IRS1	954	0.35	0.48	YES
5	PRKCA	PRKCA	PRKCA	1389	0.27	0.53	YES
6	RPS6KA1	RPS6KA1	RPS6KA1	3973	0.096	0.41	NO
7	SRF	SRF	SRF	5673	0.053	0.34	NO
8	SOS1	SOS1	SOS1	6296	0.042	0.31	NO
9	INSR	INSR	INSR	6508	0.038	0.31	NO
10	PLCG1	PLCG1	PLCG1	6681	0.035	0.31	NO
11	PRKCB	PRKCB	PRKCB	7368	0.025	0.28	NO
12	MAPK3	MAPK3	MAPK3	7369	0.025	0.29	NO
13	RAF1	RAF1	RAF1	7855	0.017	0.26	NO
14	MAP2K1	MAP2K1	MAP2K1	9821	-0.011	0.16	NO
15	STAT5B	STAT5B	STAT5B	9963	-0.013	0.15	NO
16	GRB2	GRB2	GRB2	10500	-0.021	0.13	NO
17	SOCS1	SOCS1	SOCS1	10528	-0.022	0.13	NO
18	GH1	GH1	GH1	11990	-0.048	0.066	NO
19	SHC1	SHC1	SHC1	12646	-0.065	0.047	NO
20	MAPK1	MAPK1	MAPK1	13122	-0.081	0.043	NO
21	JAK2	JAK2	JAK2	13142	-0.082	0.065	NO
22	PTPN6	PTPN6	PTPN6	13211	-0.084	0.085	NO
23	PIK3R1	PIK3R1	PIK3R1	13675	-0.1	0.088	NO
24	STAT5A	STAT5A	STAT5A	14513	-0.15	0.083	NO
25	PIK3CA	PIK3CA	PIK3CA	14548	-0.15	0.12	NO
26	PIK3CG	PIK3CG	PIK3CG	15557	-0.24	0.14	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 ARGININE AND PROLINE METABOLISM.

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

genes ES table in pathway: KEGG STARCH AND SUCROSE 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	PPARGC1A	PPARGC1A	PPARGC1A	82	0.8	0.038	YES
2	HAP1	HAP1	HAP1	105	0.76	0.077	YES
3	ITPR1	ITPR1	ITPR1	328	0.56	0.094	YES
4	COX4I2	COX4I2	COX4I2	695	0.41	0.095	YES
5	DNAI2	DNAI2	DNAI2	1021	0.33	0.094	YES
6	COX7A1	COX7A1	COX7A1	1096	0.32	0.11	YES
7	DNALI1	DNALI1	DNALI1	1253	0.29	0.11	YES
8	NDUFA4L2	NDUFA4L2	NDUFA4L2	1910	0.21	0.088	YES
9	CLTCL1	CLTCL1	CLTCL1	1982	0.2	0.094	YES
10	NDUFB1	NDUFB1	NDUFB1	2333	0.17	0.084	YES
11	VDAC3	VDAC3	VDAC3	2395	0.17	0.089	YES
12	CYCS	CYCS	CYCS	2416	0.17	0.097	YES
13	PPARG	PPARG	PPARG	2485	0.16	0.1	YES
14	COX8A	COX8A	COX8A	2538	0.16	0.11	YES
15	COX7B	COX7B	COX7B	2543	0.16	0.12	YES
16	NDUFB2	NDUFB2	NDUFB2	2575	0.16	0.12	YES
17	ATP5G1	ATP5G1	ATP5G1	2655	0.15	0.13	YES
18	COX8C	COX8C	COX8C	2679	0.15	0.13	YES
19	DNAL1	DNAL1	DNAL1	2795	0.15	0.13	YES
20	COX6A1	COX6A1	COX6A1	2853	0.14	0.14	YES
21	NDUFA3	NDUFA3	NDUFA3	2917	0.14	0.14	YES
22	ATP5H	ATP5H	ATP5H	2952	0.14	0.15	YES
23	SLC25A4	SLC25A4	SLC25A4	2981	0.14	0.15	YES
24	NDUFA5	NDUFA5	NDUFA5	2996	0.14	0.16	YES
25	COX6C	COX6C	COX6C	3030	0.14	0.16	YES
26	NDUFA1	NDUFA1	NDUFA1	3047	0.14	0.17	YES
27	NDUFA8	NDUFA8	NDUFA8	3087	0.13	0.18	YES
28	CYC1	CYC1	CYC1	3192	0.13	0.18	YES
29	COX5B	COX5B	COX5B	3225	0.13	0.18	YES
30	UQCRHL	UQCRHL	UQCRHL	3261	0.12	0.19	YES
31	NDUFA2	NDUFA2	NDUFA2	3369	0.12	0.19	YES
32	ATP5J	ATP5J	ATP5J	3386	0.12	0.19	YES
33	PLCB4	PLCB4	PLCB4	3405	0.12	0.2	YES
34	UQCRQ	UQCRQ	UQCRQ	3499	0.11	0.2	YES
35	ATP5D	ATP5D	ATP5D	3552	0.11	0.2	YES
36	NDUFV2	NDUFV2	NDUFV2	3564	0.11	0.21	YES
37	NDUFB3	NDUFB3	NDUFB3	3569	0.11	0.21	YES
38	ATP5B	ATP5B	ATP5B	3585	0.11	0.22	YES
39	NDUFB7	NDUFB7	NDUFB7	3654	0.11	0.22	YES
40	UQCR11	UQCR11	UQCR11	3694	0.11	0.22	YES
41	UQCR10	UQCR10	UQCR10	3705	0.11	0.23	YES
42	NDUFC2	NDUFC2	NDUFC2	3758	0.1	0.23	YES
43	UQCRH	UQCRH	UQCRH	3854	0.1	0.23	YES
44	SDHD	SDHD	SDHD	3867	0.1	0.23	YES
45	NDUFS7	NDUFS7	NDUFS7	3899	0.099	0.24	YES
46	ATP5G3	ATP5G3	ATP5G3	3922	0.098	0.24	YES
47	NDUFA6	NDUFA6	NDUFA6	3935	0.098	0.25	YES
48	NDUFA7	NDUFA7	NDUFA7	3996	0.096	0.25	YES
49	ATP5O	ATP5O	ATP5O	4034	0.095	0.25	YES
50	COX5A	COX5A	COX5A	4074	0.094	0.25	YES
51	CREB3L1	CREB3L1	CREB3L1	4097	0.093	0.26	YES
52	ATP5E	ATP5E	ATP5E	4107	0.093	0.26	YES
53	ATP5C1	ATP5C1	ATP5C1	4150	0.091	0.26	YES
54	DNAL4	DNAL4	DNAL4	4155	0.091	0.27	YES
55	NDUFV3	NDUFV3	NDUFV3	4158	0.091	0.27	YES
56	NDUFS6	NDUFS6	NDUFS6	4220	0.089	0.28	YES
57	COX4I1	COX4I1	COX4I1	4244	0.088	0.28	YES
58	NDUFB5	NDUFB5	NDUFB5	4359	0.085	0.28	YES
59	COX7A2	COX7A2	COX7A2	4386	0.084	0.28	YES
60	NDUFB6	NDUFB6	NDUFB6	4411	0.083	0.28	YES
61	SLC25A5	SLC25A5	SLC25A5	4474	0.081	0.28	YES
62	ATP5F1	ATP5F1	ATP5F1	4483	0.081	0.29	YES
63	ATP5A1	ATP5A1	ATP5A1	4491	0.081	0.29	YES
64	PLCB1	PLCB1	PLCB1	4502	0.081	0.29	YES
65	NDUFS2	NDUFS2	NDUFS2	4515	0.08	0.3	YES
66	DNAH3	DNAH3	DNAH3	4554	0.079	0.3	YES
67	NDUFS3	NDUFS3	NDUFS3	4558	0.079	0.3	YES
68	UQCRFS1	UQCRFS1	UQCRFS1	4566	0.079	0.31	YES
69	NDUFB10	NDUFB10	NDUFB10	4573	0.079	0.31	YES
70	NDUFC1	NDUFC1	NDUFC1	4576	0.079	0.32	YES
71	COX6B1	COX6B1	COX6B1	4611	0.078	0.32	YES
72	UQCRC2	UQCRC2	UQCRC2	4612	0.078	0.32	YES
73	DNAI1	DNAI1	DNAI1	4629	0.077	0.32	YES
74	SDHC	SDHC	SDHC	4668	0.077	0.33	YES
75	NDUFA4	NDUFA4	NDUFA4	4817	0.072	0.32	YES
76	COX7C	COX7C	COX7C	4868	0.071	0.32	YES
77	POLR2J	POLR2J	POLR2J	4873	0.071	0.33	YES
78	NDUFB8	NDUFB8	NDUFB8	4939	0.07	0.33	YES
79	UQCRB	UQCRB	UQCRB	4968	0.069	0.33	YES
80	NDUFA9	NDUFA9	NDUFA9	5006	0.068	0.33	YES
81	POLR2G	POLR2G	POLR2G	5029	0.068	0.33	YES
82	NDUFA10	NDUFA10	NDUFA10	5203	0.063	0.33	YES
83	NDUFS8	NDUFS8	NDUFS8	5249	0.062	0.33	YES
84	NDUFB4	NDUFB4	NDUFB4	5250	0.062	0.33	YES
85	CASP9	CASP9	CASP9	5256	0.062	0.33	YES
86	ATP5G2	ATP5G2	ATP5G2	5326	0.06	0.33	YES
87	NDUFV1	NDUFV1	NDUFV1	5400	0.059	0.33	YES
88	SDHA	SDHA	SDHA	5439	0.058	0.33	YES
89	HDAC1	HDAC1	HDAC1	5459	0.058	0.34	YES
90	NDUFB9	NDUFB9	NDUFB9	5629	0.054	0.33	NO
91	NDUFS4	NDUFS4	NDUFS4	5664	0.054	0.33	NO
92	AP2S1	AP2S1	AP2S1	5888	0.049	0.32	NO
93	POLR2F	POLR2F	POLR2F	6098	0.046	0.31	NO
94	NDUFS1	NDUFS1	NDUFS1	6173	0.044	0.31	NO
95	UQCRC1	UQCRC1	UQCRC1	6208	0.044	0.31	NO
96	SDHB	SDHB	SDHB	6214	0.043	0.31	NO
97	NDUFAB1	NDUFAB1	NDUFAB1	6323	0.041	0.31	NO
98	TAF4B	TAF4B	TAF4B	6521	0.038	0.3	NO
99	CREB3L2	CREB3L2	CREB3L2	6616	0.036	0.29	NO
100	SOD1	SOD1	SOD1	6718	0.034	0.29	NO
101	SLC25A31	SLC25A31	SLC25A31	6976	0.03	0.28	NO
102	CREB3L4	CREB3L4	CREB3L4	7014	0.03	0.28	NO
103	PPID	PPID	PPID	7069	0.029	0.28	NO
104	POLR2K	POLR2K	POLR2K	7326	0.025	0.26	NO
105	VDAC2	VDAC2	VDAC2	7485	0.023	0.26	NO
106	POLR2L	POLR2L	POLR2L	7538	0.022	0.25	NO
107	DCTN2	DCTN2	DCTN2	7599	0.021	0.25	NO
108	TBPL1	TBPL1	TBPL1	7839	0.018	0.24	NO
109	UCP1	UCP1	UCP1	8025	0.015	0.23	NO
110	POLR2C	POLR2C	POLR2C	8074	0.014	0.23	NO
111	CREB1	CREB1	CREB1	8156	0.013	0.22	NO
112	POLR2I	POLR2I	POLR2I	8299	0.011	0.22	NO
113	SIN3A	SIN3A	SIN3A	8346	0.01	0.21	NO
114	NRF1	NRF1	NRF1	8484	0.0086	0.21	NO
115	CLTB	CLTB	CLTB	8633	0.0066	0.2	NO
116	DCTN1	DCTN1	DCTN1	8877	0.0028	0.18	NO
117	AP2A2	AP2A2	AP2A2	8925	0.0022	0.18	NO
118	POLR2H	POLR2H	POLR2H	8974	0.0015	0.18	NO
119	COX7A2L	COX7A2L	COX7A2L	8995	0.0012	0.18	NO
120	DCTN4	DCTN4	DCTN4	9009	0.001	0.18	NO
121	TBP	TBP	TBP	9019	0.00086	0.18	NO
122	POLR2A	POLR2A	POLR2A	9100	-0.00042	0.17	NO
123	CREBBP	CREBBP	CREBBP	9109	-0.00058	0.17	NO
124	GNAQ	GNAQ	GNAQ	9127	-0.00088	0.17	NO
125	CLTC	CLTC	CLTC	9130	-0.0009	0.17	NO
126	SLC25A6	SLC25A6	SLC25A6	9134	-0.001	0.17	NO
127	NDUFS5	NDUFS5	NDUFS5	9572	-0.0074	0.15	NO
128	VDAC1	VDAC1	VDAC1	9784	-0.01	0.14	NO
129	POLR2E	POLR2E	POLR2E	9799	-0.01	0.14	NO
130	POLR2B	POLR2B	POLR2B	9863	-0.012	0.13	NO
131	DNAH2	DNAH2	DNAH2	10190	-0.016	0.12	NO
132	TFAM	TFAM	TFAM	10193	-0.016	0.12	NO
133	AP2B1	AP2B1	AP2B1	10228	-0.017	0.12	NO
134	TAF4	TAF4	TAF4	10364	-0.019	0.11	NO
135	RCOR1	RCOR1	RCOR1	10367	-0.019	0.11	NO
136	PLCB3	PLCB3	PLCB3	10496	-0.021	0.1	NO
137	CREB3	CREB3	CREB3	10718	-0.025	0.092	NO
138	REST	REST	REST	11363	-0.036	0.058	NO
139	TP53	TP53	TP53	11370	-0.036	0.059	NO
140	SP1	SP1	SP1	11468	-0.038	0.056	NO
141	HDAC2	HDAC2	HDAC2	11550	-0.039	0.054	NO
142	EP300	EP300	EP300	12016	-0.049	0.03	NO
143	IFT57	IFT57	IFT57	12160	-0.052	0.025	NO
144	AP2M1	AP2M1	AP2M1	12166	-0.052	0.027	NO
145	GPX1	GPX1	GPX1	12257	-0.055	0.025	NO
146	AP2A1	AP2A1	AP2A1	12557	-0.063	0.011	NO
147	POLR2D	POLR2D	POLR2D	12589	-0.064	0.013	NO
148	CLTA	CLTA	CLTA	12603	-0.064	0.016	NO
149	APAF1	APAF1	APAF1	12631	-0.065	0.018	NO
150	HTT	HTT	HTT	12849	-0.072	0.0092	NO
151	BAX	BAX	BAX	12876	-0.074	0.012	NO
152	HIP1	HIP1	HIP1	13040	-0.078	0.0066	NO
153	POLR2J2	POLR2J2	POLR2J2	13218	-0.085	0.0012	NO
154	CASP3	CASP3	CASP3	13377	-0.09	-0.003	NO
155	DNAH1	DNAH1	DNAH1	13647	-0.1	-0.013	NO
156	SOD2	SOD2	SOD2	13895	-0.11	-0.021	NO
157	DLG4	DLG4	DLG4	14267	-0.13	-0.034	NO
158	CASP8	CASP8	CASP8	14378	-0.14	-0.033	NO
159	GRIN1	GRIN1	GRIN1	14552	-0.15	-0.035	NO
160	BBC3	BBC3	BBC3	15420	-0.23	-0.072	NO
161	CREB3L3	CREB3L3	CREB3L3	15568	-0.24	-0.067	NO
162	POLR2J3	POLR2J3	POLR2J3	15590	-0.24	-0.055	NO
163	TGM2	TGM2	TGM2	16615	-0.39	-0.092	NO
164	BDNF	BDNF	BDNF	16637	-0.39	-0.073	NO
165	PLCB2	PLCB2	PLCB2	16758	-0.41	-0.058	NO
166	COX6B2	COX6B2	COX6B2	16952	-0.45	-0.045	NO
167	CREB5	CREB5	CREB5	17903	-0.95	-0.048	NO
168	GRM5	GRM5	GRM5	17915	-0.98	0.0032	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 STARCH AND SUCROSE METABOLISM.

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

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 NO1 PATHWAY	28	genes.ES.table	0.62	1.5	0.047	0.075	0.85	0.25	0.15	0.21	0.053	0
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.6	1.6	0.013	0.041	0.58	0.17	0.066	0.16	0.019	0
BIOCARTA ALK PATHWAY	33	genes.ES.table	0.54	1.6	0.034	0.053	0.73	0.18	0.1	0.16	0.034	0
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.43	1.4	0.089	0.091	0.9	0.094	0.17	0.078	0.069	0
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.73	1.9	0	0.023	0.038	0.24	0.14	0.21	0	0.006
BIOCARTA BIOPEPTIDES PATHWAY	38	genes.ES.table	0.49	1.6	0.041	0.048	0.69	0.21	0.2	0.17	0.029	0
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.54	1.6	0.043	0.052	0.73	0.41	0.3	0.29	0.035	0
BIOCARTA HDAC PATHWAY	26	genes.ES.table	0.66	1.8	0.0022	0.018	0.19	0.23	0.12	0.2	0	0
BIOCARTA INFLAM PATHWAY	25	genes.ES.table	0.83	1.6	0	0.047	0.66	0.72	0.1	0.64	0.028	0
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.54	1.6	0.035	0.047	0.66	0.13	0.14	0.12	0.028	0

genes ES table in pathway: BIOCARTA NO1 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	IL2RG	IL2RG	IL2RG	251	0.83	0.028	YES
2	CCR5	CCR5	CCR5	298	0.8	0.066	YES
3	IL2RA	IL2RA	IL2RA	316	0.78	0.1	YES
4	ACAP1	ACAP1	ACAP1	349	0.76	0.14	YES
5	IL2RB	IL2RB	IL2RB	560	0.66	0.16	YES
6	CXCR2	CXCR2	CXCR2	618	0.63	0.19	YES
7	AGAP2	AGAP2	AGAP2	643	0.62	0.22	YES
8	PDGFRA	PDGFRA	PDGFRA	650	0.62	0.25	YES
9	ADRB2	ADRB2	ADRB2	756	0.58	0.28	YES
10	RET	RET	RET	807	0.56	0.3	YES
11	NTRK1	NTRK1	NTRK1	1045	0.5	0.31	YES
12	CXCR4	CXCR4	CXCR4	1049	0.5	0.34	YES
13	HSPA6	HSPA6	HSPA6	1082	0.48	0.36	YES
14	DNM1	DNM1	DNM1	1168	0.46	0.38	YES
15	ADRB3	ADRB3	ADRB3	1285	0.44	0.4	YES
16	CSF1R	CSF1R	CSF1R	1432	0.41	0.41	YES
17	PIP5K1B	PIP5K1B	PIP5K1B	1780	0.34	0.41	YES
18	HLA-F	HLA-F	HLA-F	1839	0.34	0.42	YES
19	HLA-G	HLA-G	HLA-G	1878	0.33	0.43	YES
20	CXCR1	CXCR1	CXCR1	2117	0.29	0.44	YES
21	ARRB2	ARRB2	ARRB2	2125	0.29	0.45	YES
22	LDLR	LDLR	LDLR	2254	0.27	0.46	YES
23	DAB2	DAB2	DAB2	2485	0.25	0.46	YES
24	HLA-B	HLA-B	HLA-B	2788	0.21	0.45	YES
25	ARRB1	ARRB1	ARRB1	2943	0.2	0.45	YES
26	EHD3	EHD3	EHD3	2944	0.2	0.46	YES
27	HLA-C	HLA-C	HLA-C	2979	0.19	0.47	YES
28	SMAP2	SMAP2	SMAP2	3025	0.19	0.48	YES
29	HLA-E	HLA-E	HLA-E	3188	0.18	0.48	YES
30	PSD	PSD	PSD	3204	0.18	0.48	YES
31	RAB31	RAB31	RAB31	3267	0.17	0.49	YES
32	GRK6	GRK6	GRK6	3336	0.16	0.49	YES
33	HLA-A	HLA-A	HLA-A	3449	0.16	0.5	YES
34	SH3KBP1	SH3KBP1	SH3KBP1	3486	0.15	0.5	YES
35	PLD1	PLD1	PLD1	3491	0.15	0.51	YES
36	SH3GL2	SH3GL2	SH3GL2	3901	0.13	0.49	NO
37	ADRBK2	ADRBK2	ADRBK2	3925	0.13	0.5	NO
38	ADRBK1	ADRBK1	ADRBK1	3954	0.13	0.5	NO
39	PARD6A	PARD6A	PARD6A	4001	0.12	0.5	NO
40	TFRC	TFRC	TFRC	4634	0.094	0.48	NO
41	ASAP1	ASAP1	ASAP1	4712	0.09	0.48	NO
42	KIT	KIT	KIT	4819	0.086	0.47	NO
43	SMURF2	SMURF2	SMURF2	4837	0.085	0.48	NO
44	ARF6	ARF6	ARF6	4866	0.084	0.48	NO
45	GRK5	GRK5	GRK5	4945	0.081	0.48	NO
46	IQSEC3	IQSEC3	IQSEC3	5023	0.078	0.48	NO
47	CBLB	CBLB	CBLB	5270	0.069	0.47	NO
48	HSPA2	HSPA2	HSPA2	5425	0.065	0.46	NO
49	CBL	CBL	CBL	5537	0.061	0.46	NO
50	PLD2	PLD2	PLD2	5609	0.059	0.46	NO
51	SMURF1	SMURF1	SMURF1	5738	0.056	0.45	NO
52	CBLC	CBLC	CBLC	5747	0.056	0.46	NO
53	GIT2	GIT2	GIT2	5764	0.056	0.46	NO
54	EHD1	EHD1	EHD1	5886	0.053	0.46	NO
55	HSPA1A	HSPA1A	HSPA1A	5974	0.051	0.45	NO
56	HSPA8	HSPA8	HSPA8	6002	0.05	0.45	NO
57	F2R	F2R	F2R	6055	0.049	0.45	NO
58	HSPA1B	HSPA1B	HSPA1B	6267	0.044	0.44	NO
59	EHD2	EHD2	EHD2	6309	0.043	0.44	NO
60	SRC	SRC	SRC	6389	0.041	0.44	NO
61	ADRB1	ADRB1	ADRB1	6495	0.04	0.44	NO
62	AP2A2	AP2A2	AP2A2	6499	0.04	0.44	NO
63	MET	MET	MET	6575	0.038	0.44	NO
64	CDC42	CDC42	CDC42	6640	0.037	0.44	NO
65	ARAP2	ARAP2	ARAP2	6749	0.035	0.43	NO
66	ACAP3	ACAP3	ACAP3	6779	0.034	0.43	NO
67	ERBB3	ERBB3	ERBB3	6895	0.033	0.43	NO
68	RAB11FIP1	RAB11FIP1	RAB11FIP1	7051	0.03	0.42	NO
69	EPS15	EPS15	EPS15	7142	0.029	0.42	NO
70	AP2S1	AP2S1	AP2S1	7200	0.028	0.41	NO
71	VTA1	VTA1	VTA1	7212	0.028	0.41	NO
72	DNM3	DNM3	DNM3	7266	0.027	0.41	NO
73	IQSEC1	IQSEC1	IQSEC1	7267	0.027	0.41	NO
74	SH3GLB1	SH3GLB1	SH3GLB1	7638	0.023	0.39	NO
75	EEA1	EEA1	EEA1	7803	0.021	0.39	NO
76	TRAF6	TRAF6	TRAF6	7905	0.02	0.38	NO
77	ERBB4	ERBB4	ERBB4	7941	0.019	0.38	NO
78	PIKFYVE	PIKFYVE	PIKFYVE	7952	0.019	0.38	NO
79	PIP5K1A	PIP5K1A	PIP5K1A	8040	0.018	0.38	NO
80	WWP1	WWP1	WWP1	8060	0.018	0.38	NO
81	ARFGAP1	ARFGAP1	ARFGAP1	8114	0.017	0.37	NO
82	EGF	EGF	EGF	8266	0.016	0.37	NO
83	DNM2	DNM2	DNM2	8311	0.015	0.36	NO
84	STAM2	STAM2	STAM2	8504	0.013	0.36	NO
85	MDM2	MDM2	MDM2	8543	0.012	0.35	NO
86	EHD4	EHD4	EHD4	8723	0.011	0.34	NO
87	VPS4B	VPS4B	VPS4B	8945	0.0085	0.33	NO
88	VPS37C	VPS37C	VPS37C	9210	0.006	0.32	NO
89	SH3GL1	SH3GL1	SH3GL1	9292	0.0054	0.31	NO
90	RAB11FIP5	RAB11FIP5	RAB11FIP5	9424	0.0042	0.31	NO
91	STAMBP	STAMBP	STAMBP	9584	0.0028	0.3	NO
92	ARFGAP3	ARFGAP3	ARFGAP3	9628	0.0023	0.3	NO
93	ACAP2	ACAP2	ACAP2	9636	0.0022	0.29	NO
94	ARAP1	ARAP1	ARAP1	9656	0.0019	0.29	NO
95	NEDD4	NEDD4	NEDD4	9722	0.0013	0.29	NO
96	PSD4	PSD4	PSD4	9743	0.0011	0.29	NO
97	ITCH	ITCH	ITCH	9842	9.6e-06	0.28	NO
98	AP2M1	AP2M1	AP2M1	9846	-0.000023	0.28	NO
99	DNM1L	DNM1L	DNM1L	9883	-0.00041	0.28	NO
100	IQSEC2	IQSEC2	IQSEC2	9921	-0.00068	0.28	NO
101	AP2A1	AP2A1	AP2A1	9958	-0.0009	0.28	NO
102	USP8	USP8	USP8	9960	-0.00094	0.28	NO
103	RAB11A	RAB11A	RAB11A	9982	-0.0011	0.28	NO
104	ARAP3	ARAP3	ARAP3	10059	-0.0018	0.27	NO
105	CHMP4B	CHMP4B	CHMP4B	10082	-0.002	0.27	NO
106	RUFY1	RUFY1	RUFY1	10258	-0.0035	0.26	NO
107	RAB22A	RAB22A	RAB22A	10322	-0.004	0.26	NO
108	RABEP1	RABEP1	RABEP1	10347	-0.0042	0.26	NO
109	VPS25	VPS25	VPS25	10428	-0.005	0.25	NO
110	VPS36	VPS36	VPS36	10442	-0.005	0.25	NO
111	SMAP1	SMAP1	SMAP1	10446	-0.0051	0.25	NO
112	PDCD6IP	PDCD6IP	PDCD6IP	10638	-0.0067	0.24	NO
113	STAM	STAM	STAM	10640	-0.0067	0.24	NO
114	RAB5A	RAB5A	RAB5A	10664	-0.007	0.24	NO
115	RAB5C	RAB5C	RAB5C	10669	-0.007	0.24	NO
116	CLTC	CLTC	CLTC	10771	-0.0079	0.24	NO
117	VPS45	VPS45	VPS45	10806	-0.0082	0.23	NO
118	PRKCI	PRKCI	PRKCI	10894	-0.0089	0.23	NO
119	ASAP2	ASAP2	ASAP2	10984	-0.0098	0.22	NO
120	HGS	HGS	HGS	11059	-0.01	0.22	NO
121	PSD3	PSD3	PSD3	11119	-0.011	0.22	NO
122	VPS37A	VPS37A	VPS37A	11158	-0.011	0.22	NO
123	GRK7	GRK7	GRK7	11206	-0.012	0.22	NO
124	CHMP4A	CHMP4A	CHMP4A	11343	-0.013	0.21	NO
125	VPS37B	VPS37B	VPS37B	11353	-0.013	0.21	NO
126	RAB4A	RAB4A	RAB4A	11362	-0.013	0.21	NO
127	PIP5K1C	PIP5K1C	PIP5K1C	11493	-0.014	0.2	NO
128	RAB5B	RAB5B	RAB5B	11639	-0.016	0.2	NO
129	SNF8	SNF8	SNF8	11658	-0.016	0.2	NO
130	GIT1	GIT1	GIT1	11702	-0.016	0.19	NO
131	PIP4K2B	PIP4K2B	PIP4K2B	11847	-0.018	0.19	NO
132	ASAP3	ASAP3	ASAP3	11849	-0.018	0.19	NO
133	CHMP6	CHMP6	CHMP6	11918	-0.018	0.18	NO
134	LDLRAP1	LDLRAP1	LDLRAP1	12042	-0.019	0.18	NO
135	TSG101	TSG101	TSG101	12055	-0.019	0.18	NO
136	ARFGAP2	ARFGAP2	ARFGAP2	12097	-0.02	0.18	NO
137	RNF41	RNF41	RNF41	12098	-0.02	0.18	NO
138	CLTB	CLTB	CLTB	12204	-0.02	0.17	NO
139	VPS24	VPS24	VPS24	12361	-0.022	0.16	NO
140	AP2B1	AP2B1	AP2B1	12366	-0.022	0.17	NO
141	ZFYVE20	ZFYVE20	ZFYVE20	12486	-0.023	0.16	NO
142	CHMP2B	CHMP2B	CHMP2B	12581	-0.024	0.16	NO
143	RAB11FIP2	RAB11FIP2	RAB11FIP2	12649	-0.025	0.15	NO
144	FAM125B	FAM125B	FAM125B	12740	-0.026	0.15	NO
145	RAB11FIP4	RAB11FIP4	RAB11FIP4	12890	-0.027	0.14	NO
146	EPN1	EPN1	EPN1	12960	-0.028	0.14	NO
147	PARD6G	PARD6G	PARD6G	13024	-0.029	0.14	NO
148	EPN2	EPN2	EPN2	13081	-0.029	0.14	NO
149	RAB11FIP3	RAB11FIP3	RAB11FIP3	13105	-0.029	0.14	NO
150	CHMP5	CHMP5	CHMP5	13295	-0.031	0.13	NO
151	CHMP2A	CHMP2A	CHMP2A	13372	-0.032	0.13	NO
152	FAM125A	FAM125A	FAM125A	13376	-0.032	0.13	NO
153	CHMP1B	CHMP1B	CHMP1B	13523	-0.034	0.12	NO
154	PARD3	PARD3	PARD3	13524	-0.034	0.12	NO
155	NEDD4L	NEDD4L	NEDD4L	13686	-0.036	0.12	NO
156	EGFR	EGFR	EGFR	13721	-0.036	0.12	NO
157	VPS28	VPS28	VPS28	13802	-0.037	0.11	NO
158	CLTA	CLTA	CLTA	13813	-0.037	0.11	NO
159	SH3GLB2	SH3GLB2	SH3GLB2	14245	-0.042	0.092	NO
160	KDR	KDR	KDR	14338	-0.044	0.088	NO
161	RAB11B	RAB11B	RAB11B	14380	-0.044	0.088	NO
162	VPS4A	VPS4A	VPS4A	14407	-0.045	0.089	NO
163	HSPA1L	HSPA1L	HSPA1L	14729	-0.049	0.074	NO
164	IGF1R	IGF1R	IGF1R	14902	-0.052	0.067	NO
165	AGAP1	AGAP1	AGAP1	15285	-0.059	0.048	NO
166	CHMP4C	CHMP4C	CHMP4C	15953	-0.074	0.014	NO
167	PRKCZ	PRKCZ	PRKCZ	16259	-0.083	0.0015	NO
168	CLTCL1	CLTCL1	CLTCL1	16488	-0.091	-0.0067	NO
169	PARD6B	PARD6B	PARD6B	16565	-0.094	-0.0062	NO
170	PSD2	PSD2	PSD2	16612	-0.096	-0.0039	NO
171	FLT1	FLT1	FLT1	16644	-0.098	-0.00073	NO
172	VPS37D	VPS37D	VPS37D	16672	-0.099	0.0028	NO
173	DNAJC6	DNAJC6	DNAJC6	16696	-0.1	0.0065	NO
174	FGFR2	FGFR2	FGFR2	16697	-0.1	0.012	NO
175	GRK4	GRK4	GRK4	17307	-0.14	-0.016	NO
176	EPN3	EPN3	EPN3	17308	-0.14	-0.0085	NO
177	FGFR4	FGFR4	FGFR4	17406	-0.15	-0.0063	NO
178	SH3GL3	SH3GL3	SH3GL3	17777	-0.21	-0.016	NO
179	GRK1	GRK1	GRK1	17847	-0.24	-0.0082	NO
180	FGFR3	FGFR3	FGFR3	17934	-0.3	0.0021	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 NO1 PATHWAY.

Figure S42. 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 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	FLT3	FLT3	FLT3	4	1.2	0.15	YES
2	PIK3CG	PIK3CG	PIK3CG	375	0.74	0.22	YES
3	PIK3R5	PIK3R5	PIK3R5	420	0.72	0.31	YES
4	PIM2	PIM2	PIM2	675	0.61	0.37	YES
5	SPI1	SPI1	SPI1	912	0.54	0.42	YES
6	PIK3CD	PIK3CD	PIK3CD	1261	0.44	0.46	YES
7	CCNA1	CCNA1	CCNA1	1984	0.31	0.46	YES
8	PIM1	PIM1	PIM1	1991	0.31	0.49	YES
9	MYC	MYC	MYC	2004	0.31	0.53	YES
10	LEF1	LEF1	LEF1	2365	0.26	0.54	YES
11	RUNX1T1	RUNX1T1	RUNX1T1	2465	0.25	0.57	YES
12	RUNX1	RUNX1	RUNX1	2768	0.21	0.58	YES
13	CEBPA	CEBPA	CEBPA	2920	0.2	0.59	YES
14	TCF7	TCF7	TCF7	2948	0.2	0.62	YES
15	EIF4EBP1	EIF4EBP1	EIF4EBP1	3013	0.19	0.64	YES
16	STAT5A	STAT5A	STAT5A	4425	0.1	0.57	NO
17	KIT	KIT	KIT	4819	0.086	0.56	NO
18	NRAS	NRAS	NRAS	5091	0.076	0.55	NO
19	PML	PML	PML	5292	0.068	0.55	NO
20	NFKB1	NFKB1	NFKB1	5447	0.064	0.55	NO
21	KRAS	KRAS	KRAS	5490	0.062	0.55	NO
22	GRB2	GRB2	GRB2	5507	0.062	0.56	NO
23	TCF7L1	TCF7L1	TCF7L1	5613	0.059	0.56	NO
24	IKBKG	IKBKG	IKBKG	5639	0.059	0.57	NO
25	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.57	NO
26	PIK3CA	PIK3CA	PIK3CA	5963	0.051	0.56	NO
27	STAT3	STAT3	STAT3	6237	0.044	0.55	NO
28	SOS1	SOS1	SOS1	6474	0.04	0.55	NO
29	PIK3R1	PIK3R1	PIK3R1	6696	0.036	0.54	NO
30	CHUK	CHUK	CHUK	7462	0.025	0.5	NO
31	IKBKB	IKBKB	IKBKB	7593	0.023	0.49	NO
32	TCF7L2	TCF7L2	TCF7L2	7634	0.023	0.49	NO
33	RELA	RELA	RELA	7714	0.022	0.49	NO
34	RARA	RARA	RARA	8340	0.015	0.46	NO
35	RPS6KB2	RPS6KB2	RPS6KB2	8667	0.011	0.44	NO
36	STAT5B	STAT5B	STAT5B	9212	0.006	0.41	NO
37	RPS6KB1	RPS6KB1	RPS6KB1	9296	0.0054	0.41	NO
38	MTOR	MTOR	MTOR	9671	0.0018	0.39	NO
39	MAPK1	MAPK1	MAPK1	10793	-0.0081	0.33	NO
40	RAF1	RAF1	RAF1	10794	-0.0081	0.33	NO
41	MAP2K2	MAP2K2	MAP2K2	10838	-0.0084	0.33	NO
42	ARAF	ARAF	ARAF	11383	-0.013	0.3	NO
43	AKT1	AKT1	AKT1	11525	-0.014	0.29	NO
44	PIK3R2	PIK3R2	PIK3R2	11530	-0.015	0.29	NO
45	JUP	JUP	JUP	11952	-0.018	0.27	NO
46	PIK3R3	PIK3R3	PIK3R3	11985	-0.019	0.27	NO
47	HRAS	HRAS	HRAS	12373	-0.022	0.25	NO
48	AKT3	AKT3	AKT3	12459	-0.023	0.25	NO
49	SOS2	SOS2	SOS2	12666	-0.025	0.24	NO
50	MAPK3	MAPK3	MAPK3	13627	-0.035	0.19	NO
51	ZBTB16	ZBTB16	ZBTB16	14084	-0.04	0.17	NO
52	CCND1	CCND1	CCND1	14762	-0.05	0.14	NO
53	BAD	BAD	BAD	15295	-0.059	0.12	NO
54	PIK3CB	PIK3CB	PIK3CB	15473	-0.063	0.12	NO
55	BRAF	BRAF	BRAF	16429	-0.089	0.074	NO
56	AKT2	AKT2	AKT2	16685	-0.099	0.072	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 AGR PATHWAY.

Figure S44. 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 ALK 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	NCF1C	NCF1C	NCF1C	108	0.99	0.22	YES
2	NCF2	NCF2	NCF2	704	0.6	0.33	YES
3	FPR1	FPR1	FPR1	779	0.57	0.45	YES
4	CAMK1G	CAMK1G	CAMK1G	1481	0.4	0.51	YES
5	MAP2K6	MAP2K6	MAP2K6	1754	0.35	0.57	YES
6	NFATC1	NFATC1	NFATC1	1995	0.31	0.63	YES
7	NFATC2	NFATC2	NFATC2	2135	0.29	0.69	YES
8	PLCB1	PLCB1	PLCB1	3724	0.14	0.63	NO
9	NFKBIA	NFKBIA	NFKBIA	3751	0.14	0.66	NO
10	NFKB1	NFKB1	NFKB1	5447	0.064	0.58	NO
11	NFATC3	NFATC3	NFATC3	5449	0.064	0.6	NO
12	PPP3CC	PPP3CC	PPP3CC	5556	0.061	0.6	NO
13	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.6	NO
14	CAMK1	CAMK1	CAMK1	6340	0.042	0.58	NO
15	CALM1	CALM1	CALM1	7463	0.025	0.53	NO
16	RELA	RELA	RELA	7714	0.022	0.52	NO
17	CALM3	CALM3	CALM3	7834	0.02	0.52	NO
18	MAP2K3	MAP2K3	MAP2K3	8074	0.018	0.51	NO
19	GNB1	GNB1	GNB1	8260	0.016	0.5	NO
20	PPP3CA	PPP3CA	PPP3CA	8388	0.014	0.5	NO
21	NFATC4	NFATC4	NFATC4	8490	0.013	0.49	NO
22	ELK1	ELK1	ELK1	8540	0.012	0.49	NO
23	PPP3CB	PPP3CB	PPP3CB	8597	0.012	0.49	NO
24	PAK1	PAK1	PAK1	8760	0.01	0.49	NO
25	RAC1	RAC1	RAC1	8813	0.0097	0.48	NO
26	MAP3K1	MAP3K1	MAP3K1	9380	0.0046	0.46	NO
27	CALM2	CALM2	CALM2	10425	-0.0049	0.4	NO
28	MAPK1	MAPK1	MAPK1	10793	-0.0081	0.38	NO
29	RAF1	RAF1	RAF1	10794	-0.0081	0.38	NO
30	MAP2K2	MAP2K2	MAP2K2	10838	-0.0084	0.38	NO
31	MAPK14	MAPK14	MAPK14	11830	-0.017	0.33	NO
32	HRAS	HRAS	HRAS	12373	-0.022	0.3	NO
33	MAPK3	MAPK3	MAPK3	13627	-0.035	0.24	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 ALK PATHWAY.

Figure S46. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA ALK 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 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	FASLG	FASLG	FASLG	134	0.95	0.15	YES
2	TNF	TNF	TNF	422	0.72	0.26	YES
3	PRKCB	PRKCB	PRKCB	478	0.69	0.37	YES
4	HOXA7	HOXA7	HOXA7	925	0.53	0.44	YES
5	PRKCG	PRKCG	PRKCG	1427	0.41	0.48	YES
6	MAP2K6	MAP2K6	MAP2K6	1754	0.35	0.52	YES
7	TNFRSF1B	TNFRSF1B	TNFRSF1B	2334	0.26	0.53	YES
8	PRKCA	PRKCA	PRKCA	2486	0.25	0.56	YES
9	MAP3K14	MAP3K14	MAP3K14	2756	0.22	0.58	YES
10	CEBPA	CEBPA	CEBPA	2920	0.2	0.61	YES
11	ETS1	ETS1	ETS1	3587	0.15	0.6	YES
12	NFKBIA	NFKBIA	NFKBIA	3751	0.14	0.61	YES
13	FAS	FAS	FAS	3758	0.14	0.63	YES
14	ETS2	ETS2	ETS2	5073	0.076	0.57	NO
15	NFKB1	NFKB1	NFKB1	5447	0.064	0.56	NO
16	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.55	NO
17	PRKCH	PRKCH	PRKCH	5863	0.054	0.56	NO
18	FOS	FOS	FOS	6115	0.047	0.55	NO
19	TNFRSF1A	TNFRSF1A	TNFRSF1A	6188	0.045	0.56	NO
20	DAXX	DAXX	DAXX	6529	0.039	0.54	NO
21	RIPK1	RIPK1	RIPK1	6702	0.036	0.54	NO
22	SP1	SP1	SP1	6780	0.034	0.54	NO
23	PRKCE	PRKCE	PRKCE	6822	0.034	0.55	NO
24	MAP3K5	MAP3K5	MAP3K5	7339	0.026	0.52	NO
25	CHUK	CHUK	CHUK	7462	0.025	0.52	NO
26	IKBKB	IKBKB	IKBKB	7593	0.023	0.52	NO
27	RELA	RELA	RELA	7714	0.022	0.51	NO
28	MAPK13	MAPK13	MAPK13	7826	0.021	0.51	NO
29	MAP2K3	MAP2K3	MAP2K3	8074	0.018	0.5	NO
30	EGF	EGF	EGF	8266	0.016	0.49	NO
31	JUN	JUN	JUN	9332	0.0051	0.43	NO
32	MAP3K1	MAP3K1	MAP3K1	9380	0.0046	0.43	NO
33	PPP2CA	PPP2CA	PPP2CA	9879	-0.00036	0.4	NO
34	PRKCD	PRKCD	PRKCD	10364	-0.0043	0.38	NO
35	MAPK1	MAPK1	MAPK1	10793	-0.0081	0.35	NO
36	RAF1	RAF1	RAF1	10794	-0.0081	0.36	NO
37	MAPK14	MAPK14	MAPK14	11830	-0.017	0.3	NO
38	MAP2K7	MAP2K7	MAP2K7	12023	-0.019	0.29	NO
39	MAP2K4	MAP2K4	MAP2K4	12150	-0.02	0.29	NO
40	HRAS	HRAS	HRAS	12373	-0.022	0.28	NO
41	PRKCQ	PRKCQ	PRKCQ	13332	-0.032	0.23	NO
42	MAPK3	MAPK3	MAPK3	13627	-0.035	0.22	NO
43	EGFR	EGFR	EGFR	13721	-0.036	0.22	NO
44	MAPK8	MAPK8	MAPK8	14013	-0.039	0.21	NO
45	BCL2	BCL2	BCL2	14515	-0.046	0.19	NO

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

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

genes ES table in pathway: BIOCARTA BCR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CD79A	CD79A	CD79A	24	1.2	0.19	YES
2	CD79B	CD79B	CD79B	171	0.9	0.34	YES
3	BTK	BTK	BTK	226	0.85	0.47	YES
4	VAV1	VAV1	VAV1	325	0.78	0.6	YES
5	PRKCB	PRKCB	PRKCB	478	0.69	0.7	YES
6	NFATC1	NFATC1	NFATC1	1995	0.31	0.67	YES
7	NFATC2	NFATC2	NFATC2	2135	0.29	0.71	YES
8	PRKCA	PRKCA	PRKCA	2486	0.25	0.74	YES
9	LYN	LYN	LYN	3686	0.14	0.69	NO
10	NFATC3	NFATC3	NFATC3	5449	0.064	0.6	NO
11	GRB2	GRB2	GRB2	5507	0.062	0.61	NO
12	PPP3CC	PPP3CC	PPP3CC	5556	0.061	0.62	NO
13	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.61	NO
14	FOS	FOS	FOS	6115	0.047	0.6	NO
15	SOS1	SOS1	SOS1	6474	0.04	0.59	NO
16	SHC1	SHC1	SHC1	7013	0.031	0.57	NO
17	SYK	SYK	SYK	7422	0.026	0.55	NO
18	CALM1	CALM1	CALM1	7463	0.025	0.55	NO
19	CALM3	CALM3	CALM3	7834	0.02	0.53	NO
20	PPP3CA	PPP3CA	PPP3CA	8388	0.014	0.5	NO
21	NFATC4	NFATC4	NFATC4	8490	0.013	0.5	NO
22	ELK1	ELK1	ELK1	8540	0.012	0.5	NO
23	PPP3CB	PPP3CB	PPP3CB	8597	0.012	0.5	NO
24	RAC1	RAC1	RAC1	8813	0.0097	0.49	NO
25	JUN	JUN	JUN	9332	0.0051	0.46	NO
26	MAP3K1	MAP3K1	MAP3K1	9380	0.0046	0.46	NO
27	PLCG1	PLCG1	PLCG1	9573	0.0028	0.45	NO
28	CALM2	CALM2	CALM2	10425	-0.0049	0.4	NO
29	RAF1	RAF1	RAF1	10794	-0.0081	0.38	NO
30	BLNK	BLNK	BLNK	11052	-0.01	0.37	NO
31	MAPK14	MAPK14	MAPK14	11830	-0.017	0.33	NO
32	MAPK3	MAPK3	MAPK3	13627	-0.035	0.24	NO
33	MAPK8	MAPK8	MAPK8	14013	-0.039	0.22	NO

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

Figure S50. 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 BIOPEPTIDES PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PIK3CG	PIK3CG	PIK3CG	375	0.74	0.068	YES
2	PIK3R5	PIK3R5	PIK3R5	420	0.72	0.15	YES
3	PRKCB	PRKCB	PRKCB	478	0.69	0.23	YES
4	IGF1	IGF1	IGF1	482	0.69	0.32	YES
5	PDGFRA	PDGFRA	PDGFRA	650	0.62	0.38	YES
6	E2F2	E2F2	E2F2	945	0.52	0.43	YES
7	PIK3CD	PIK3CD	PIK3CD	1261	0.44	0.46	YES
8	PRKCG	PRKCG	PRKCG	1427	0.41	0.5	YES
9	CDKN2A	CDKN2A	CDKN2A	1807	0.34	0.52	YES
10	PLCG2	PLCG2	PLCG2	1917	0.32	0.55	YES
11	CAMK2A	CAMK2A	CAMK2A	2383	0.26	0.56	YES
12	PRKCA	PRKCA	PRKCA	2486	0.25	0.58	YES
13	CALML3	CALML3	CALML3	2582	0.24	0.61	YES
14	CDK6	CDK6	CDK6	3595	0.15	0.57	NO
15	PDGFRB	PDGFRB	PDGFRB	3831	0.13	0.57	NO
16	CALML6	CALML6	CALML6	4612	0.095	0.54	NO
17	NRAS	NRAS	NRAS	5091	0.076	0.52	NO
18	KRAS	KRAS	KRAS	5490	0.062	0.5	NO
19	GRB2	GRB2	GRB2	5507	0.062	0.51	NO
20	PDGFA	PDGFA	PDGFA	5568	0.06	0.52	NO
21	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.51	NO
22	PIK3CA	PIK3CA	PIK3CA	5963	0.051	0.51	NO
23	TP53	TP53	TP53	6262	0.044	0.5	NO
24	SOS1	SOS1	SOS1	6474	0.04	0.49	NO
25	SHC4	SHC4	SHC4	6505	0.039	0.49	NO
26	PIK3R1	PIK3R1	PIK3R1	6696	0.036	0.48	NO
27	SHC1	SHC1	SHC1	7013	0.031	0.47	NO
28	PTEN	PTEN	PTEN	7164	0.029	0.47	NO
29	CAMK2G	CAMK2G	CAMK2G	7175	0.028	0.47	NO
30	RB1	RB1	RB1	7285	0.027	0.47	NO
31	CALM1	CALM1	CALM1	7463	0.025	0.46	NO
32	SHC3	SHC3	SHC3	7588	0.023	0.46	NO
33	CALM3	CALM3	CALM3	7834	0.02	0.44	NO
34	CAMK2D	CAMK2D	CAMK2D	8110	0.017	0.43	NO
35	EGF	EGF	EGF	8266	0.016	0.42	NO
36	MDM2	MDM2	MDM2	8543	0.012	0.41	NO
37	CDKN1A	CDKN1A	CDKN1A	9073	0.0074	0.38	NO
38	PLCG1	PLCG1	PLCG1	9573	0.0028	0.35	NO
39	MTOR	MTOR	MTOR	9671	0.0018	0.35	NO
40	E2F3	E2F3	E2F3	10184	-0.0028	0.32	NO
41	CALM2	CALM2	CALM2	10425	-0.0049	0.31	NO
42	MAPK1	MAPK1	MAPK1	10793	-0.0081	0.29	NO
43	RAF1	RAF1	RAF1	10794	-0.0081	0.29	NO
44	MAP2K2	MAP2K2	MAP2K2	10838	-0.0084	0.29	NO
45	PDGFB	PDGFB	PDGFB	10885	-0.0088	0.29	NO
46	ARAF	ARAF	ARAF	11383	-0.013	0.26	NO
47	AKT1	AKT1	AKT1	11525	-0.014	0.25	NO
48	PIK3R2	PIK3R2	PIK3R2	11530	-0.015	0.26	NO
49	PIK3R3	PIK3R3	PIK3R3	11985	-0.019	0.23	NO
50	HRAS	HRAS	HRAS	12373	-0.022	0.21	NO
51	AKT3	AKT3	AKT3	12459	-0.023	0.21	NO
52	SOS2	SOS2	SOS2	12666	-0.025	0.2	NO
53	CDK4	CDK4	CDK4	13083	-0.029	0.18	NO
54	MAPK3	MAPK3	MAPK3	13627	-0.035	0.16	NO
55	TGFA	TGFA	TGFA	13637	-0.035	0.16	NO
56	EGFR	EGFR	EGFR	13721	-0.036	0.16	NO
57	CCND1	CCND1	CCND1	14762	-0.05	0.11	NO
58	IGF1R	IGF1R	IGF1R	14902	-0.052	0.11	NO
59	PIK3CB	PIK3CB	PIK3CB	15473	-0.063	0.082	NO
60	SHC2	SHC2	SHC2	15678	-0.067	0.079	NO
61	BRAF	BRAF	BRAF	16429	-0.089	0.047	NO
62	AKT2	AKT2	AKT2	16685	-0.099	0.045	NO
63	CAMK2B	CAMK2B	CAMK2B	17809	-0.22	0.0091	NO

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

Figure S52. 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 G1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CAMK4	CAMK4	CAMK4	53	1.1	0.16	YES
2	PIK3CG	PIK3CG	PIK3CG	375	0.74	0.26	YES
3	IGF1	IGF1	IGF1	482	0.69	0.36	YES
4	PRKAR2B	PRKAR2B	PRKAR2B	1366	0.42	0.37	YES
5	HAND2	HAND2	HAND2	1437	0.41	0.43	YES
6	CAMK1G	CAMK1G	CAMK1G	1481	0.4	0.49	YES
7	GATA4	GATA4	GATA4	1546	0.39	0.54	YES
8	NFATC1	NFATC1	NFATC1	1995	0.31	0.57	YES
9	NFATC2	NFATC2	NFATC2	2135	0.29	0.6	YES
10	EDN1	EDN1	EDN1	2152	0.29	0.64	YES
11	ACTA1	ACTA1	ACTA1	2689	0.22	0.65	YES
12	AGT	AGT	AGT	2981	0.19	0.66	YES
13	FGF2	FGF2	FGF2	3316	0.17	0.67	YES
14	LIF	LIF	LIF	3537	0.15	0.68	YES
15	PRKACB	PRKACB	PRKACB	5029	0.078	0.61	NO
16	NFATC3	NFATC3	NFATC3	5449	0.064	0.59	NO
17	PPP3CC	PPP3CC	PPP3CC	5556	0.061	0.6	NO
18	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.59	NO
19	PIK3CA	PIK3CA	PIK3CA	5963	0.051	0.59	NO
20	CAMK1	CAMK1	CAMK1	6340	0.042	0.58	NO
21	PIK3R1	PIK3R1	PIK3R1	6696	0.036	0.56	NO
22	HBEGF	HBEGF	HBEGF	7104	0.029	0.54	NO
23	CALM1	CALM1	CALM1	7463	0.025	0.53	NO
24	CALM3	CALM3	CALM3	7834	0.02	0.51	NO
25	FKBP1A	FKBP1A	FKBP1A	7861	0.02	0.51	NO
26	PPP3CA	PPP3CA	PPP3CA	8388	0.014	0.48	NO
27	NPPA	NPPA	NPPA	8440	0.014	0.48	NO
28	NFATC4	NFATC4	NFATC4	8490	0.013	0.48	NO
29	PPP3CB	PPP3CB	PPP3CB	8597	0.012	0.48	NO
30	RPS6KB1	RPS6KB1	RPS6KB1	9296	0.0054	0.44	NO
31	CSNK1A1	CSNK1A1	CSNK1A1	10141	-0.0024	0.39	NO
32	CREBBP	CREBBP	CREBBP	10381	-0.0045	0.38	NO
33	CALM2	CALM2	CALM2	10425	-0.0049	0.38	NO
34	GSK3B	GSK3B	GSK3B	10786	-0.0081	0.36	NO
35	MAPK1	MAPK1	MAPK1	10793	-0.0081	0.36	NO
36	RAF1	RAF1	RAF1	10794	-0.0081	0.36	NO
37	CALR	CALR	CALR	10810	-0.0082	0.36	NO
38	PRKAR2A	PRKAR2A	PRKAR2A	11432	-0.014	0.33	NO
39	AKT1	AKT1	AKT1	11525	-0.014	0.33	NO
40	CTF1	CTF1	CTF1	11790	-0.017	0.32	NO
41	MAPK14	MAPK14	MAPK14	11830	-0.017	0.32	NO
42	HRAS	HRAS	HRAS	12373	-0.022	0.29	NO
43	PRKAR1A	PRKAR1A	PRKAR1A	12796	-0.026	0.27	NO
44	MAPK3	MAPK3	MAPK3	13627	-0.035	0.23	NO
45	MAPK8	MAPK8	MAPK8	14013	-0.039	0.21	NO
46	PRKAR1B	PRKAR1B	PRKAR1B	14425	-0.045	0.2	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: BIOCARTA G1 PATHWAY.

Figure S54. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA G1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA HDAC PATHWAY

Table 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	HGF	HGF	HGF	367	0.75	0.097	YES
2	PIK3CG	PIK3CG	PIK3CG	375	0.74	0.21	YES
3	PIK3R5	PIK3R5	PIK3R5	420	0.72	0.32	YES
4	PAK3	PAK3	PAK3	1188	0.46	0.35	YES
5	PIK3CD	PIK3CD	PIK3CD	1261	0.44	0.42	YES
6	EGLN3	EGLN3	EGLN3	1390	0.42	0.48	YES
7	TGFB3	TGFB3	TGFB3	1833	0.34	0.51	YES
8	FIGF	FIGF	FIGF	3005	0.19	0.47	NO
9	ETS1	ETS1	ETS1	3587	0.15	0.46	NO
10	TGFB1	TGFB1	TGFB1	4518	0.099	0.42	NO
11	NRAS	NRAS	NRAS	5091	0.076	0.4	NO
12	HIF1A	HIF1A	HIF1A	5274	0.069	0.4	NO
13	RAP1B	RAP1B	RAP1B	5328	0.067	0.41	NO
14	ARNT2	ARNT2	ARNT2	5406	0.065	0.42	NO
15	KRAS	KRAS	KRAS	5490	0.062	0.42	NO
16	GRB2	GRB2	GRB2	5507	0.062	0.43	NO
17	RAPGEF1	RAPGEF1	RAPGEF1	5580	0.06	0.44	NO
18	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.43	NO
19	PIK3CA	PIK3CA	PIK3CA	5963	0.051	0.43	NO
20	GAB1	GAB1	GAB1	6187	0.045	0.43	NO
21	PAK2	PAK2	PAK2	6231	0.044	0.43	NO
22	VHL	VHL	VHL	6368	0.042	0.43	NO
23	SOS1	SOS1	SOS1	6474	0.04	0.43	NO
24	PAK7	PAK7	PAK7	6545	0.039	0.43	NO
25	MET	MET	MET	6575	0.038	0.44	NO
26	CDC42	CDC42	CDC42	6640	0.037	0.44	NO
27	PIK3R1	PIK3R1	PIK3R1	6696	0.036	0.44	NO
28	RAP1A	RAP1A	RAP1A	6748	0.035	0.45	NO
29	CRKL	CRKL	CRKL	6776	0.034	0.45	NO
30	RBX1	RBX1	RBX1	7610	0.023	0.41	NO
31	CUL2	CUL2	CUL2	8185	0.016	0.38	NO
32	EGLN2	EGLN2	EGLN2	8542	0.012	0.36	NO
33	PAK1	PAK1	PAK1	8760	0.01	0.35	NO
34	RAC1	RAC1	RAC1	8813	0.0097	0.35	NO
35	TGFB2	TGFB2	TGFB2	8957	0.0084	0.34	NO
36	JUN	JUN	JUN	9332	0.0051	0.32	NO
37	EP300	EP300	EP300	9595	0.0027	0.31	NO
38	ARNT	ARNT	ARNT	9703	0.0016	0.3	NO
39	SLC2A1	SLC2A1	SLC2A1	10336	-0.0041	0.27	NO
40	CREBBP	CREBBP	CREBBP	10381	-0.0045	0.26	NO
41	TCEB1	TCEB1	TCEB1	10572	-0.0062	0.26	NO
42	PTPN11	PTPN11	PTPN11	10656	-0.0069	0.25	NO
43	MAPK1	MAPK1	MAPK1	10793	-0.0081	0.24	NO
44	RAF1	RAF1	RAF1	10794	-0.0081	0.25	NO
45	MAP2K2	MAP2K2	MAP2K2	10838	-0.0084	0.24	NO
46	EPAS1	EPAS1	EPAS1	10855	-0.0085	0.24	NO
47	PDGFB	PDGFB	PDGFB	10885	-0.0088	0.24	NO
48	ARAF	ARAF	ARAF	11383	-0.013	0.22	NO
49	AKT1	AKT1	AKT1	11525	-0.014	0.21	NO
50	PIK3R2	PIK3R2	PIK3R2	11530	-0.015	0.22	NO
51	EGLN1	EGLN1	EGLN1	11818	-0.017	0.2	NO
52	FH	FH	FH	11970	-0.018	0.2	NO
53	PIK3R3	PIK3R3	PIK3R3	11985	-0.019	0.2	NO
54	AKT3	AKT3	AKT3	12459	-0.023	0.18	NO
55	SOS2	SOS2	SOS2	12666	-0.025	0.17	NO
56	FLCN	FLCN	FLCN	12929	-0.028	0.16	NO
57	VEGFB	VEGFB	VEGFB	13421	-0.033	0.14	NO
58	CRK	CRK	CRK	13532	-0.034	0.14	NO
59	MAPK3	MAPK3	MAPK3	13627	-0.035	0.14	NO
60	TGFA	TGFA	TGFA	13637	-0.035	0.14	NO
61	TCEB2	TCEB2	TCEB2	14268	-0.043	0.11	NO
62	VEGFC	VEGFC	VEGFC	14917	-0.052	0.084	NO
63	PAK4	PAK4	PAK4	15269	-0.059	0.074	NO
64	PIK3CB	PIK3CB	PIK3CB	15473	-0.063	0.072	NO
65	PGF	PGF	PGF	15648	-0.067	0.073	NO
66	VEGFA	VEGFA	VEGFA	16163	-0.08	0.057	NO
67	BRAF	BRAF	BRAF	16429	-0.089	0.056	NO
68	PAK6	PAK6	PAK6	16545	-0.094	0.064	NO
69	AKT2	AKT2	AKT2	16685	-0.099	0.072	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: BIOCARTA HDAC PATHWAY.

Figure S56. 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 INFLAM PATHWAY

Table S29. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CD40LG	CD40LG	CD40LG	19	1.2	0.039	YES
2	CD3G	CD3G	CD3G	42	1.1	0.075	YES
3	ICOS	ICOS	ICOS	57	1.1	0.11	YES
4	GRAP2	GRAP2	GRAP2	68	1	0.15	YES
5	CD28	CD28	CD28	93	1	0.18	YES
6	CTLA4	CTLA4	CTLA4	99	1	0.21	YES
7	ITK	ITK	ITK	102	1	0.25	YES
8	IL10	IL10	IL10	109	0.98	0.28	YES
9	CD247	CD247	CD247	127	0.96	0.31	YES
10	CD3D	CD3D	CD3D	139	0.94	0.34	YES
11	PDCD1	PDCD1	PDCD1	140	0.94	0.38	YES
12	ZAP70	ZAP70	ZAP70	143	0.94	0.41	YES
13	IFNG	IFNG	IFNG	182	0.89	0.44	YES
14	CD3E	CD3E	CD3E	203	0.87	0.46	YES
15	LCK	LCK	LCK	224	0.85	0.49	YES
16	VAV1	VAV1	VAV1	325	0.78	0.51	YES
17	PTPRC	PTPRC	PTPRC	352	0.76	0.54	YES
18	RASGRP1	RASGRP1	RASGRP1	353	0.76	0.56	YES
19	CD8A	CD8A	CD8A	365	0.75	0.59	YES
20	PIK3CG	PIK3CG	PIK3CG	375	0.74	0.61	YES
21	PIK3R5	PIK3R5	PIK3R5	420	0.72	0.64	YES
22	TNF	TNF	TNF	422	0.72	0.66	YES
23	CD8B	CD8B	CD8B	438	0.71	0.68	YES
24	CARD11	CARD11	CARD11	567	0.65	0.7	YES
25	IL2	IL2	IL2	642	0.62	0.72	YES
26	LAT	LAT	LAT	877	0.55	0.72	YES
27	LCP2	LCP2	LCP2	1025	0.5	0.73	YES
28	PAK3	PAK3	PAK3	1188	0.46	0.74	YES
29	CSF2	CSF2	CSF2	1250	0.45	0.75	YES
30	PIK3CD	PIK3CD	PIK3CD	1261	0.44	0.76	YES
31	CD4	CD4	CD4	1331	0.43	0.77	YES
32	NFATC1	NFATC1	NFATC1	1995	0.31	0.75	NO
33	MAP3K8	MAP3K8	MAP3K8	2065	0.3	0.75	NO
34	NFATC2	NFATC2	NFATC2	2135	0.29	0.76	NO
35	PDK1	PDK1	PDK1	2260	0.27	0.76	NO
36	NFKBIE	NFKBIE	NFKBIE	2543	0.24	0.76	NO
37	MAP3K14	MAP3K14	MAP3K14	2756	0.22	0.75	NO
38	PTPN6	PTPN6	PTPN6	3193	0.18	0.73	NO
39	NFKBIA	NFKBIA	NFKBIA	3751	0.14	0.7	NO
40	MAPK12	MAPK12	MAPK12	4202	0.11	0.68	NO
41	MALT1	MALT1	MALT1	4399	0.1	0.68	NO
42	MAPK11	MAPK11	MAPK11	4582	0.096	0.67	NO
43	BCL10	BCL10	BCL10	4818	0.086	0.66	NO
44	NRAS	NRAS	NRAS	5091	0.076	0.65	NO
45	CBLB	CBLB	CBLB	5270	0.069	0.64	NO
46	NFKB1	NFKB1	NFKB1	5447	0.064	0.63	NO
47	NFATC3	NFATC3	NFATC3	5449	0.064	0.63	NO
48	KRAS	KRAS	KRAS	5490	0.062	0.63	NO
49	GRB2	GRB2	GRB2	5507	0.062	0.64	NO
50	CBL	CBL	CBL	5537	0.061	0.64	NO
51	PPP3CC	PPP3CC	PPP3CC	5556	0.061	0.64	NO
52	CHP2	CHP2	CHP2	5577	0.06	0.64	NO
53	IKBKG	IKBKG	IKBKG	5639	0.059	0.64	NO
54	CBLC	CBLC	CBLC	5747	0.056	0.63	NO
55	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.63	NO
56	PIK3CA	PIK3CA	PIK3CA	5963	0.051	0.62	NO
57	FOS	FOS	FOS	6115	0.047	0.62	NO
58	TEC	TEC	TEC	6147	0.046	0.62	NO
59	NCK1	NCK1	NCK1	6150	0.046	0.62	NO
60	PAK2	PAK2	PAK2	6231	0.044	0.62	NO
61	SOS1	SOS1	SOS1	6474	0.04	0.6	NO
62	PAK7	PAK7	PAK7	6545	0.039	0.6	NO
63	CDC42	CDC42	CDC42	6640	0.037	0.6	NO
64	PIK3R1	PIK3R1	PIK3R1	6696	0.036	0.59	NO
65	PPP3R1	PPP3R1	PPP3R1	6817	0.034	0.59	NO
66	FYN	FYN	FYN	7012	0.031	0.58	NO
67	CHUK	CHUK	CHUK	7462	0.025	0.55	NO
68	IKBKB	IKBKB	IKBKB	7593	0.023	0.55	NO
69	RELA	RELA	RELA	7714	0.022	0.54	NO
70	RHOA	RHOA	RHOA	7819	0.021	0.54	NO
71	MAPK13	MAPK13	MAPK13	7826	0.021	0.54	NO
72	MAP3K7	MAP3K7	MAP3K7	8037	0.018	0.53	NO
73	PPP3CA	PPP3CA	PPP3CA	8388	0.014	0.51	NO
74	NFATC4	NFATC4	NFATC4	8490	0.013	0.5	NO
75	PPP3CB	PPP3CB	PPP3CB	8597	0.012	0.5	NO
76	PAK1	PAK1	PAK1	8760	0.01	0.49	NO
77	JUN	JUN	JUN	9332	0.0051	0.46	NO
78	PLCG1	PLCG1	PLCG1	9573	0.0028	0.44	NO
79	VAV2	VAV2	VAV2	10010	-0.0014	0.42	NO
80	NFKBIB	NFKBIB	NFKBIB	10453	-0.0052	0.39	NO
81	GSK3B	GSK3B	GSK3B	10786	-0.0081	0.38	NO
82	MAPK1	MAPK1	MAPK1	10793	-0.0081	0.38	NO
83	RAF1	RAF1	RAF1	10794	-0.0081	0.38	NO
84	MAP2K2	MAP2K2	MAP2K2	10838	-0.0084	0.37	NO
85	AKT1	AKT1	AKT1	11525	-0.014	0.34	NO
86	PIK3R2	PIK3R2	PIK3R2	11530	-0.015	0.34	NO
87	MAPK14	MAPK14	MAPK14	11830	-0.017	0.32	NO
88	PIK3R3	PIK3R3	PIK3R3	11985	-0.019	0.31	NO
89	CHP	CHP	CHP	12011	-0.019	0.31	NO
90	MAP2K7	MAP2K7	MAP2K7	12023	-0.019	0.31	NO
91	AKT3	AKT3	AKT3	12459	-0.023	0.29	NO
92	SOS2	SOS2	SOS2	12666	-0.025	0.28	NO
93	NCK2	NCK2	NCK2	12728	-0.026	0.27	NO
94	NFAT5	NFAT5	NFAT5	13058	-0.029	0.26	NO
95	CDK4	CDK4	CDK4	13083	-0.029	0.26	NO
96	PRKCQ	PRKCQ	PRKCQ	13332	-0.032	0.24	NO
97	DLG1	DLG1	DLG1	13547	-0.034	0.23	NO
98	MAPK3	MAPK3	MAPK3	13627	-0.035	0.23	NO
99	MAPK9	MAPK9	MAPK9	13763	-0.037	0.22	NO
100	VAV3	VAV3	VAV3	14302	-0.043	0.19	NO
101	PAK4	PAK4	PAK4	15269	-0.059	0.14	NO
102	PIK3CB	PIK3CB	PIK3CB	15473	-0.063	0.13	NO
103	PAK6	PAK6	PAK6	16545	-0.094	0.076	NO
104	AKT2	AKT2	AKT2	16685	-0.099	0.072	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: BIOCARTA INFLAM PATHWAY.

Figure S58. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA INFLAM 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 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	PLA2G2D	PLA2G2D	PLA2G2D	34	1.1	0.096	YES
2	SH2D2A	SH2D2A	SH2D2A	142	0.94	0.17	YES
3	PIK3CG	PIK3CG	PIK3CG	375	0.74	0.22	YES
4	PLA2G2A	PLA2G2A	PLA2G2A	401	0.73	0.29	YES
5	PIK3R5	PIK3R5	PIK3R5	420	0.72	0.35	YES
6	PRKCB	PRKCB	PRKCB	478	0.69	0.41	YES
7	RAC2	RAC2	RAC2	791	0.57	0.44	YES
8	PLA2G4A	PLA2G4A	PLA2G4A	1175	0.46	0.46	YES
9	PIK3CD	PIK3CD	PIK3CD	1261	0.44	0.49	YES
10	PRKCG	PRKCG	PRKCG	1427	0.41	0.52	YES
11	PLA2G5	PLA2G5	PLA2G5	1507	0.39	0.55	YES
12	PLCG2	PLCG2	PLCG2	1917	0.32	0.55	YES
13	NFATC1	NFATC1	NFATC1	1995	0.31	0.57	YES
14	PTGS2	PTGS2	PTGS2	2036	0.3	0.6	YES
15	NFATC2	NFATC2	NFATC2	2135	0.29	0.62	YES
16	PRKCA	PRKCA	PRKCA	2486	0.25	0.62	YES
17	PLA2G1B	PLA2G1B	PLA2G1B	3229	0.17	0.6	NO
18	PLA2G2F	PLA2G2F	PLA2G2F	3293	0.17	0.61	NO
19	PLA2G10	PLA2G10	PLA2G10	3738	0.14	0.59	NO
20	MAPK12	MAPK12	MAPK12	4202	0.11	0.58	NO
21	MAPK11	MAPK11	MAPK11	4582	0.096	0.56	NO
22	PLA2G3	PLA2G3	PLA2G3	4842	0.085	0.56	NO
23	NRAS	NRAS	NRAS	5091	0.076	0.55	NO
24	NOS3	NOS3	NOS3	5115	0.075	0.56	NO
25	NFATC3	NFATC3	NFATC3	5449	0.064	0.54	NO
26	KRAS	KRAS	KRAS	5490	0.062	0.55	NO
27	PPP3CC	PPP3CC	PPP3CC	5556	0.061	0.55	NO
28	CHP2	CHP2	CHP2	5577	0.06	0.55	NO
29	MAP2K1	MAP2K1	MAP2K1	5798	0.055	0.54	NO
30	PIK3CA	PIK3CA	PIK3CA	5963	0.051	0.54	NO
31	SRC	SRC	SRC	6389	0.041	0.52	NO
32	SPHK1	SPHK1	SPHK1	6501	0.04	0.52	NO
33	CDC42	CDC42	CDC42	6640	0.037	0.51	NO
34	PIK3R1	PIK3R1	PIK3R1	6696	0.036	0.51	NO
35	MAPKAPK2	MAPKAPK2	MAPKAPK2	6756	0.035	0.51	NO
36	PPP3R1	PPP3R1	PPP3R1	6817	0.034	0.51	NO
37	MAPK13	MAPK13	MAPK13	7826	0.021	0.46	NO
38	PPP3CA	PPP3CA	PPP3CA	8388	0.014	0.43	NO
39	NFATC4	NFATC4	NFATC4	8490	0.013	0.42	NO
40	PPP3CB	PPP3CB	PPP3CB	8597	0.012	0.42	NO
41	RAC1	RAC1	RAC1	8813	0.0097	0.41	NO
42	PLCG1	PLCG1	PLCG1	9573	0.0028	0.36	NO
43	HSPB1	HSPB1	HSPB1	10598	-0.0064	0.31	NO
44	MAPK1	MAPK1	MAPK1	10793	-0.0081	0.3	NO
45	RAF1	RAF1	RAF1	10794	-0.0081	0.3	NO
46	MAP2K2	MAP2K2	MAP2K2	10838	-0.0084	0.3	NO
47	RAC3	RAC3	RAC3	11131	-0.011	0.28	NO
48	MAPKAPK3	MAPKAPK3	MAPKAPK3	11233	-0.012	0.28	NO
49	AKT1	AKT1	AKT1	11525	-0.014	0.26	NO
50	PIK3R2	PIK3R2	PIK3R2	11530	-0.015	0.26	NO
51	MAPK14	MAPK14	MAPK14	11830	-0.017	0.25	NO
52	PIK3R3	PIK3R3	PIK3R3	11985	-0.019	0.24	NO
53	CHP	CHP	CHP	12011	-0.019	0.24	NO
54	SPHK2	SPHK2	SPHK2	12077	-0.02	0.24	NO
55	AKT3	AKT3	AKT3	12459	-0.023	0.22	NO
56	NFAT5	NFAT5	NFAT5	13058	-0.029	0.19	NO
57	CASP9	CASP9	CASP9	13474	-0.033	0.17	NO
58	MAPK3	MAPK3	MAPK3	13627	-0.035	0.16	NO
59	PTK2	PTK2	PTK2	13640	-0.035	0.16	NO
60	PXN	PXN	PXN	13973	-0.039	0.15	NO
61	KDR	KDR	KDR	14338	-0.044	0.13	NO
62	PLA2G6	PLA2G6	PLA2G6	14553	-0.047	0.13	NO
63	BAD	BAD	BAD	15295	-0.059	0.09	NO
64	PIK3CB	PIK3CB	PIK3CB	15473	-0.063	0.085	NO
65	SHC2	SHC2	SHC2	15678	-0.067	0.08	NO
66	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	15728	-0.068	0.083	NO
67	PLA2G12A	PLA2G12A	PLA2G12A	16047	-0.077	0.072	NO
68	VEGFA	VEGFA	VEGFA	16163	-0.08	0.072	NO
69	AKT2	AKT2	AKT2	16685	-0.099	0.052	NO
70	PLA2G2E	PLA2G2E	PLA2G2E	16717	-0.1	0.059	NO
71	PLA2G12B	PLA2G12B	PLA2G12B	17139	-0.13	0.046	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: BIOCARTA EGF PATHWAY.

Figure S60. 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

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 ALK PATHWAY	33	genes.ES.table	0.41	1.1	0.31	1	1	0.18	0.12	0.16	1	0.62
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.27	0.91	0.56	1	1	0.38	0.28	0.27	1	0.84
BIOCARTA ERK PATHWAY	26	genes.ES.table	0.4	1.2	0.3	1	1	0.15	0.16	0.13	1	0.65
KEGG GLYCEROPHOSPHOLIPID METABOLISM	71	genes.ES.table	0.31	1	0.39	1	1	0.31	0.19	0.25	1	0.75
KEGG ETHER LIPID METABOLISM	29	genes.ES.table	0.49	1.3	0.12	1	0.98	0.41	0.17	0.34	1	0.76
KEGG ARACHIDONIC ACID METABOLISM	47	genes.ES.table	0.52	1.3	0.15	1	0.99	0.4	0.15	0.35	1	0.53
KEGG SPLICEOSOME	125	genes.ES.table	0.32	1.4	0.13	1	0.93	0.64	0.43	0.37	1	0.72
KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION	216	genes.ES.table	0.43	1.1	0.28	1	1	0.3	0.11	0.27	1	0.62
KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT	37	genes.ES.table	0.32	1.2	0.28	1	1	0.14	0.1	0.12	1	0.63
KEGG NOTCH SIGNALING PATHWAY	45	genes.ES.table	0.35	1.3	0.18	1	0.98	0.38	0.29	0.27	1	0.68

genes ES table in pathway: BIOCARTA ALK 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	RXRG	RXRG	RXRG	160	0.44	0.18	YES
2	RET	RET	RET	253	0.39	0.33	YES
3	TCF7	TCF7	TCF7	620	0.27	0.42	YES
4	LEF1	LEF1	LEF1	1175	0.18	0.47	YES
5	TCF7L2	TCF7L2	TCF7L2	2987	0.082	0.4	NO
6	MYC	MYC	MYC	3931	0.059	0.37	NO
7	CCND1	CCND1	CCND1	5053	0.039	0.33	NO
8	CTNNB1	CTNNB1	CTNNB1	5631	0.032	0.31	NO
9	RXRB	RXRB	RXRB	7043	0.018	0.24	NO
10	TPM3	TPM3	TPM3	7766	0.011	0.2	NO
11	MAP2K2	MAP2K2	MAP2K2	8173	0.0072	0.18	NO
12	CDH1	CDH1	CDH1	8845	0.00098	0.14	NO
13	RXRA	RXRA	RXRA	9076	-0.001	0.13	NO
14	TP53	TP53	TP53	9135	-0.0015	0.13	NO
15	MAPK3	MAPK3	MAPK3	9846	-0.008	0.094	NO
16	PAX8	PAX8	PAX8	10223	-0.012	0.078	NO
17	MAPK1	MAPK1	MAPK1	10444	-0.014	0.072	NO
18	TPR	TPR	TPR	11496	-0.025	0.023	NO
19	TFG	TFG	TFG	11813	-0.028	0.017	NO
20	MAP2K1	MAP2K1	MAP2K1	12459	-0.037	-0.0033	NO
21	KRAS	KRAS	KRAS	12721	-0.04	-0.0012	NO
22	TCF7L1	TCF7L1	TCF7L1	13210	-0.048	-0.0085	NO
23	NCOA4	NCOA4	NCOA4	13494	-0.053	-0.0024	NO
24	CCDC6	CCDC6	CCDC6	14187	-0.067	-0.013	NO
25	NRAS	NRAS	NRAS	14678	-0.08	-0.0076	NO
26	BRAF	BRAF	BRAF	15018	-0.09	0.011	NO
27	NTRK1	NTRK1	NTRK1	15216	-0.097	0.04	NO
28	PPARG	PPARG	PPARG	17479	-0.27	0.027	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 ALK PATHWAY.

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA ALK 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 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	HSPA1L	HSPA1L	HSPA1L	1776	0.14	-0.062	YES
2	SNRPA	SNRPA	SNRPA	2878	0.085	-0.1	YES
3	CTNNBL1	CTNNBL1	CTNNBL1	3551	0.067	-0.12	YES
4	PUF60	PUF60	PUF60	3602	0.066	-0.1	YES
5	U2AF1	U2AF1	U2AF1	3636	0.065	-0.087	YES
6	CCDC12	CCDC12	CCDC12	3668	0.064	-0.071	YES
7	HNRNPA1	HNRNPA1	HNRNPA1	3752	0.063	-0.059	YES
8	SF3A2	SF3A2	SF3A2	3832	0.061	-0.046	YES
9	THOC1	THOC1	THOC1	3910	0.059	-0.034	YES
10	SFRS5	SFRS5	SFRS5	3960	0.058	-0.021	YES
11	PRPF40B	PRPF40B	PRPF40B	4008	0.057	-0.0079	YES
12	HNRNPA1L2	HNRNPA1L2	HNRNPA1L2	4038	0.056	0.006	YES
13	XAB2	XAB2	XAB2	4084	0.055	0.019	YES
14	LSM7	LSM7	LSM7	4223	0.052	0.026	YES
15	RBMX	RBMX	RBMX	4344	0.05	0.033	YES
16	PRPF6	PRPF6	PRPF6	4455	0.048	0.04	YES
17	RBM22	RBM22	RBM22	4542	0.047	0.048	YES
18	MAGOH	MAGOH	MAGOH	4601	0.046	0.057	YES
19	SNRNP70	SNRNP70	SNRNP70	4614	0.046	0.069	YES
20	SNRPF	SNRPF	SNRPF	4615	0.046	0.082	YES
21	SYF2	SYF2	SYF2	4686	0.044	0.09	YES
22	PRPF38A	PRPF38A	PRPF38A	4859	0.042	0.092	YES
23	SFRS2B	SFRS2B	SFRS2B	4948	0.04	0.098	YES
24	PQBP1	PQBP1	PQBP1	4976	0.04	0.11	YES
25	SNRPD1	SNRPD1	SNRPD1	4981	0.04	0.12	YES
26	RBM17	RBM17	RBM17	5046	0.039	0.13	YES
27	SNRPE	SNRPE	SNRPE	5097	0.039	0.13	YES
28	SFRS6	SFRS6	SFRS6	5193	0.037	0.14	YES
29	SART1	SART1	SART1	5196	0.037	0.15	YES
30	PRPF3	PRPF3	PRPF3	5468	0.034	0.14	YES
31	BAT1	BAT1	BAT1	5497	0.034	0.15	YES
32	SF3A1	SF3A1	SF3A1	5516	0.034	0.16	YES
33	PPIE	PPIE	PPIE	5523	0.034	0.17	YES
34	SF3A3	SF3A3	SF3A3	5625	0.032	0.17	YES
35	LSM6	LSM6	LSM6	5661	0.032	0.18	YES
36	TRA2B	TRA2B	TRA2B	5712	0.031	0.18	YES
37	SFRS7	SFRS7	SFRS7	5729	0.031	0.19	YES
38	PRPF31	PRPF31	PRPF31	5877	0.03	0.19	YES
39	CHERP	CHERP	CHERP	6032	0.028	0.19	YES
40	U2AF2	U2AF2	U2AF2	6042	0.028	0.2	YES
41	SF3B2	SF3B2	SF3B2	6049	0.028	0.21	YES
42	ACIN1	ACIN1	ACIN1	6062	0.028	0.21	YES
43	TRA2A	TRA2A	TRA2A	6086	0.027	0.22	YES
44	SNRPD2	SNRPD2	SNRPD2	6171	0.026	0.22	YES
45	DDX42	DDX42	DDX42	6183	0.026	0.23	YES
46	ISY1	ISY1	ISY1	6224	0.026	0.23	YES
47	SF3B14	SF3B14	SF3B14	6228	0.026	0.24	YES
48	THOC2	THOC2	THOC2	6334	0.025	0.24	YES
49	SFRS3	SFRS3	SFRS3	6361	0.024	0.25	YES
50	LSM2	LSM2	LSM2	6400	0.024	0.25	YES
51	SFRS4	SFRS4	SFRS4	6423	0.024	0.26	YES
52	LSM4	LSM4	LSM4	6508	0.023	0.26	YES
53	SFRS2	SFRS2	SFRS2	6509	0.023	0.26	YES
54	SLU7	SLU7	SLU7	6541	0.022	0.27	YES
55	TCERG1	TCERG1	TCERG1	6617	0.022	0.27	YES
56	SF3B1	SF3B1	SF3B1	6671	0.021	0.27	YES
57	HNRNPC	HNRNPC	HNRNPC	6726	0.021	0.28	YES
58	SFRS13A	SFRS13A	SFRS13A	6789	0.02	0.28	YES
59	RBM8A	RBM8A	RBM8A	6918	0.019	0.28	YES
60	CDC5L	CDC5L	CDC5L	6931	0.019	0.28	YES
61	SF3B4	SF3B4	SF3B4	6940	0.018	0.28	YES
62	DDX5	DDX5	DDX5	6948	0.018	0.29	YES
63	USP39	USP39	USP39	6950	0.018	0.29	YES
64	SNRPD3	SNRPD3	SNRPD3	6961	0.018	0.3	YES
65	SNRPA1	SNRPA1	SNRPA1	6967	0.018	0.3	YES
66	SFRS1	SFRS1	SFRS1	6968	0.018	0.31	YES
67	SR140	SR140	SR140	7017	0.018	0.31	YES
68	SNRNP200	SNRNP200	SNRNP200	7078	0.017	0.31	YES
69	CWC15	CWC15	CWC15	7222	0.016	0.31	YES
70	BUD31	BUD31	BUD31	7224	0.016	0.31	YES
71	NHP2L1	NHP2L1	NHP2L1	7331	0.015	0.31	YES
72	SNRPG	SNRPG	SNRPG	7489	0.013	0.31	YES
73	EIF4A3	EIF4A3	EIF4A3	7550	0.013	0.31	YES
74	RBM25	RBM25	RBM25	7613	0.012	0.31	YES
75	SNRPB2	SNRPB2	SNRPB2	7625	0.012	0.31	YES
76	HNRNPA3	HNRNPA3	HNRNPA3	7653	0.012	0.31	YES
77	SNRPB	SNRPB	SNRPB	7701	0.011	0.31	YES
78	SFRS9	SFRS9	SFRS9	7704	0.011	0.31	YES
79	PRPF4	PRPF4	PRPF4	7715	0.011	0.32	YES
80	HNRNPM	HNRNPM	HNRNPM	7733	0.011	0.32	YES
81	HNRNPU	HNRNPU	HNRNPU	7951	0.0092	0.31	NO
82	HSPA1B	HSPA1B	HSPA1B	7997	0.0087	0.31	NO
83	PRPF19	PRPF19	PRPF19	8033	0.0084	0.31	NO
84	LSM5	LSM5	LSM5	8038	0.0084	0.31	NO
85	HNRNPK	HNRNPK	HNRNPK	8104	0.0078	0.31	NO
86	LSM3	LSM3	LSM3	8107	0.0077	0.31	NO
87	ZMAT2	ZMAT2	ZMAT2	8143	0.0074	0.31	NO
88	PLRG1	PLRG1	PLRG1	8221	0.0068	0.31	NO
89	SNRNP40	SNRNP40	SNRNP40	8222	0.0068	0.31	NO
90	DDX23	DDX23	DDX23	8292	0.0061	0.31	NO
91	THOC4	THOC4	THOC4	8312	0.006	0.31	NO
92	DHX38	DHX38	DHX38	8313	0.006	0.31	NO
93	SF3B3	SF3B3	SF3B3	8561	0.0034	0.3	NO
94	DHX16	DHX16	DHX16	8566	0.0034	0.3	NO
95	PRPF8	PRPF8	PRPF8	8672	0.0027	0.29	NO
96	SNRPC	SNRPC	SNRPC	8676	0.0027	0.29	NO
97	CRNKL1	CRNKL1	CRNKL1	8876	0.00067	0.28	NO
98	PPIH	PPIH	PPIH	9054	-0.00089	0.27	NO
99	DHX15	DHX15	DHX15	9582	-0.0057	0.25	NO
100	EFTUD2	EFTUD2	EFTUD2	9686	-0.0066	0.24	NO
101	CDC40	CDC40	CDC40	9851	-0.008	0.24	NO
102	PRPF38B	PRPF38B	PRPF38B	9970	-0.0091	0.23	NO
103	PCBP1	PCBP1	PCBP1	10305	-0.012	0.22	NO
104	SF3B5	SF3B5	SF3B5	10391	-0.013	0.21	NO
105	PPIL1	PPIL1	PPIL1	10511	-0.014	0.21	NO
106	SNW1	SNW1	SNW1	10590	-0.015	0.21	NO
107	SMNDC1	SMNDC1	SMNDC1	10751	-0.017	0.21	NO
108	WBP11	WBP11	WBP11	10758	-0.017	0.21	NO
109	MAGOHB	MAGOHB	MAGOHB	11018	-0.02	0.2	NO
110	TXNL4A	TXNL4A	TXNL4A	11181	-0.022	0.2	NO
111	PRPF40A	PRPF40A	PRPF40A	11305	-0.023	0.2	NO
112	PHF5A	PHF5A	PHF5A	11379	-0.024	0.2	NO
113	AQR	AQR	AQR	11627	-0.026	0.19	NO
114	BCAS2	BCAS2	BCAS2	11697	-0.027	0.2	NO
115	DHX8	DHX8	DHX8	11831	-0.029	0.2	NO
116	DDX46	DDX46	DDX46	12026	-0.031	0.2	NO
117	HSPA2	HSPA2	HSPA2	12094	-0.032	0.2	NO
118	NAA38	NAA38	NAA38	12457	-0.037	0.19	NO
119	NCBP1	NCBP1	NCBP1	12615	-0.039	0.19	NO
120	HSPA1A	HSPA1A	HSPA1A	12803	-0.041	0.19	NO
121	HSPA8	HSPA8	HSPA8	12879	-0.042	0.2	NO
122	PRPF18	PRPF18	PRPF18	13139	-0.047	0.2	NO
123	THOC3	THOC3	THOC3	14704	-0.08	0.13	NO
124	HSPA6	HSPA6	HSPA6	14799	-0.083	0.15	NO
125	SNRNP27	SNRNP27	SNRNP27	15122	-0.093	0.16	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 AT1R PATHWAY.

Figure S64. 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 ERK 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	PLA2G12B	PLA2G12B	PLA2G12B	149	0.45	0.14	YES
2	PLA2G2E	PLA2G2E	PLA2G2E	666	0.26	0.2	YES
3	PPAP2C	PPAP2C	PPAP2C	827	0.23	0.27	YES
4	PLA2G10	PLA2G10	PLA2G10	1104	0.19	0.32	YES
5	CHPT1	CHPT1	CHPT1	1348	0.17	0.37	YES
6	PAFAH1B3	PAFAH1B3	PAFAH1B3	2073	0.12	0.36	YES
7	PLA2G5	PLA2G5	PLA2G5	2265	0.11	0.39	YES
8	PLA2G6	PLA2G6	PLA2G6	2375	0.1	0.42	YES
9	LPCAT4	LPCAT4	LPCAT4	2430	0.1	0.45	YES
10	PPAP2A	PPAP2A	PPAP2A	2845	0.086	0.46	YES
11	PPAP2B	PPAP2B	PPAP2B	3000	0.082	0.48	YES
12	ENPP2	ENPP2	ENPP2	3130	0.078	0.49	YES
13	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	5158	0.038	0.39	NO
14	LPCAT2	LPCAT2	LPCAT2	6175	0.026	0.35	NO
15	PLD2	PLD2	PLD2	8028	0.0084	0.25	NO
16	PLA2G4A	PLA2G4A	PLA2G4A	9237	-0.0024	0.18	NO
17	PLA2G3	PLA2G3	PLA2G3	9473	-0.0045	0.17	NO
18	PAFAH1B1	PAFAH1B1	PAFAH1B1	10762	-0.017	0.1	NO
19	PLA2G12A	PLA2G12A	PLA2G12A	11039	-0.02	0.093	NO
20	AGPS	AGPS	AGPS	12811	-0.042	0.0084	NO
21	PAFAH1B2	PAFAH1B2	PAFAH1B2	13501	-0.053	-0.012	NO
22	PLA2G2D	PLA2G2D	PLA2G2D	13680	-0.056	-0.0032	NO
23	PLA2G7	PLA2G7	PLA2G7	14692	-0.08	-0.033	NO
24	PLD1	PLD1	PLD1	15016	-0.09	-0.02	NO
25	PAFAH2	PAFAH2	PAFAH2	15051	-0.091	0.0084	NO
26	PLA2G2F	PLA2G2F	PLA2G2F	15092	-0.092	0.037	NO
27	PLA2G2A	PLA2G2A	PLA2G2A	15487	-0.11	0.051	NO
28	LPCAT1	LPCAT1	LPCAT1	15589	-0.11	0.082	NO
29	PLA2G1B	PLA2G1B	PLA2G1B	16375	-0.15	0.089	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 ERK PATHWAY.

Figure S66. 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: KEGG GLYCEROPHOSPHOLIPID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	DTX4	DTX4	DTX4	896	0.22	0.038	YES
2	DTX1	DTX1	DTX1	900	0.22	0.12	YES
3	DLL1	DLL1	DLL1	1882	0.13	0.12	YES
4	NUMBL	NUMBL	NUMBL	1977	0.12	0.17	YES
5	DLL4	DLL4	DLL4	2268	0.11	0.19	YES
6	MAML3	MAML3	MAML3	2471	0.099	0.22	YES
7	NOTCH4	NOTCH4	NOTCH4	2497	0.098	0.26	YES
8	HES5	HES5	HES5	2813	0.087	0.28	YES
9	CTBP2	CTBP2	CTBP2	3242	0.074	0.28	YES
10	NOTCH3	NOTCH3	NOTCH3	3485	0.069	0.3	YES
11	NOTCH2	NOTCH2	NOTCH2	3568	0.067	0.32	YES
12	JAG2	JAG2	JAG2	3688	0.064	0.34	YES
13	DVL1	DVL1	DVL1	4002	0.057	0.34	YES
14	MAML2	MAML2	MAML2	4438	0.049	0.34	YES
15	HDAC1	HDAC1	HDAC1	5064	0.039	0.32	YES
16	DTX3	DTX3	DTX3	5077	0.039	0.33	YES
17	CIR1	CIR1	CIR1	5142	0.038	0.35	YES
18	CTBP1	CTBP1	CTBP1	5435	0.035	0.34	NO
19	MAML1	MAML1	MAML1	5845	0.03	0.33	NO
20	KAT2A	KAT2A	KAT2A	6125	0.027	0.33	NO
21	DVL2	DVL2	DVL2	6141	0.027	0.34	NO
22	CREBBP	CREBBP	CREBBP	6928	0.019	0.3	NO
23	LFNG	LFNG	LFNG	6954	0.018	0.31	NO
24	PSEN2	PSEN2	PSEN2	6987	0.018	0.31	NO
25	RFNG	RFNG	RFNG	6991	0.018	0.32	NO
26	PSENEN	PSENEN	PSENEN	7234	0.016	0.31	NO
27	RBPJ	RBPJ	RBPJ	8588	0.0032	0.24	NO
28	NCSTN	NCSTN	NCSTN	8742	0.002	0.23	NO
29	EP300	EP300	EP300	8950	-0.000017	0.22	NO
30	JAG1	JAG1	JAG1	9174	-0.0018	0.21	NO
31	PSEN1	PSEN1	PSEN1	9378	-0.0036	0.2	NO
32	DVL3	DVL3	DVL3	9608	-0.006	0.19	NO
33	NOTCH1	NOTCH1	NOTCH1	9761	-0.0073	0.18	NO
34	HDAC2	HDAC2	HDAC2	9828	-0.0078	0.18	NO
35	APH1A	APH1A	APH1A	9919	-0.0086	0.18	NO
36	NCOR2	NCOR2	NCOR2	10205	-0.011	0.17	NO
37	SNW1	SNW1	SNW1	10590	-0.015	0.15	NO
38	DTX2	DTX2	DTX2	10774	-0.017	0.15	NO
39	DTX3L	DTX3L	DTX3L	11222	-0.022	0.13	NO
40	KAT2B	KAT2B	KAT2B	12318	-0.035	0.086	NO
41	NUMB	NUMB	NUMB	12548	-0.038	0.088	NO
42	ADAM17	ADAM17	ADAM17	12793	-0.041	0.091	NO
43	PTCRA	PTCRA	PTCRA	14417	-0.072	0.029	NO
44	HES1	HES1	HES1	15943	-0.13	-0.0046	NO
45	DLL3	DLL3	DLL3	17553	-0.29	0.023	NO

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

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

genes ES table in pathway: KEGG ETHER LIPID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TCF7	TCF7	TCF7	620	0.27	0.024	YES
2	PVRL4	PVRL4	PVRL4	698	0.26	0.076	YES
3	LEF1	LEF1	LEF1	1175	0.18	0.089	YES
4	TGFBR1	TGFBR1	TGFBR1	1206	0.18	0.13	YES
5	RAC2	RAC2	RAC2	1551	0.15	0.14	YES
6	MET	MET	MET	1684	0.14	0.16	YES
7	PVRL1	PVRL1	PVRL1	1892	0.13	0.18	YES
8	EGFR	EGFR	EGFR	1974	0.12	0.2	YES
9	FYN	FYN	FYN	2196	0.11	0.22	YES
10	SORBS1	SORBS1	SORBS1	2399	0.1	0.23	YES
11	PTPRM	PTPRM	PTPRM	2545	0.096	0.24	YES
12	IGF1R	IGF1R	IGF1R	2584	0.094	0.26	YES
13	BAIAP2	BAIAP2	BAIAP2	2645	0.092	0.27	YES
14	ERBB2	ERBB2	ERBB2	2801	0.087	0.28	YES
15	SRC	SRC	SRC	2850	0.086	0.3	YES
16	PTPRF	PTPRF	PTPRF	2881	0.085	0.32	YES
17	TCF7L2	TCF7L2	TCF7L2	2987	0.082	0.33	YES
18	MLLT4	MLLT4	MLLT4	3138	0.077	0.34	YES
19	PVRL2	PVRL2	PVRL2	3465	0.069	0.33	YES
20	WASF1	WASF1	WASF1	3509	0.068	0.35	YES
21	SMAD3	SMAD3	SMAD3	3512	0.068	0.36	YES
22	INSR	INSR	INSR	3737	0.063	0.36	YES
23	SSX2IP	SSX2IP	SSX2IP	4100	0.055	0.35	YES
24	LMO7	LMO7	LMO7	4106	0.055	0.36	YES
25	ACTN1	ACTN1	ACTN1	4555	0.047	0.35	NO
26	PTPRB	PTPRB	PTPRB	4876	0.042	0.34	NO
27	CTNNB1	CTNNB1	CTNNB1	5631	0.032	0.31	NO
28	CSNK2A2	CSNK2A2	CSNK2A2	5636	0.032	0.31	NO
29	ACTN4	ACTN4	ACTN4	5857	0.03	0.31	NO
30	VCL	VCL	VCL	6044	0.028	0.3	NO
31	CTNNA1	CTNNA1	CTNNA1	6052	0.028	0.31	NO
32	TJP1	TJP1	TJP1	6090	0.027	0.31	NO
33	CSNK2B	CSNK2B	CSNK2B	6570	0.022	0.29	NO
34	CREBBP	CREBBP	CREBBP	6928	0.019	0.27	NO
35	RAC1	RAC1	RAC1	7557	0.013	0.24	NO
36	WASF2	WASF2	WASF2	7659	0.012	0.24	NO
37	RHOA	RHOA	RHOA	7979	0.009	0.22	NO
38	TGFBR2	TGFBR2	TGFBR2	8196	0.007	0.21	NO
39	PARD3	PARD3	PARD3	8475	0.0043	0.2	NO
40	IQGAP1	IQGAP1	IQGAP1	8534	0.0037	0.2	NO
41	CDH1	CDH1	CDH1	8845	0.00098	0.18	NO
42	EP300	EP300	EP300	8950	-0.000017	0.17	NO
43	PTPN6	PTPN6	PTPN6	9030	-0.00073	0.17	NO
44	PVRL3	PVRL3	PVRL3	9377	-0.0036	0.15	NO
45	SMAD4	SMAD4	SMAD4	9380	-0.0036	0.15	NO
46	WASL	WASL	WASL	9571	-0.0055	0.14	NO
47	SNAI2	SNAI2	SNAI2	9678	-0.0065	0.14	NO
48	MAPK3	MAPK3	MAPK3	9846	-0.008	0.13	NO
49	CDC42	CDC42	CDC42	9873	-0.0081	0.13	NO
50	ACP1	ACP1	ACP1	10163	-0.011	0.12	NO
51	ACTG1	ACTG1	ACTG1	10187	-0.011	0.12	NO
52	MAPK1	MAPK1	MAPK1	10444	-0.014	0.1	NO
53	CTNND1	CTNND1	CTNND1	10862	-0.018	0.086	NO
54	FGFR1	FGFR1	FGFR1	11147	-0.021	0.074	NO
55	CSNK2A1	CSNK2A1	CSNK2A1	11823	-0.029	0.043	NO
56	CTNNA3	CTNNA3	CTNNA3	12091	-0.032	0.035	NO
57	WAS	WAS	WAS	12541	-0.038	0.018	NO
58	ACTB	ACTB	ACTB	12557	-0.038	0.025	NO
59	SMAD2	SMAD2	SMAD2	12857	-0.042	0.018	NO
60	FER	FER	FER	13054	-0.045	0.017	NO
61	ACTN3	ACTN3	ACTN3	13171	-0.047	0.02	NO
62	TCF7L1	TCF7L1	TCF7L1	13210	-0.048	0.029	NO
63	MAP3K7	MAP3K7	MAP3K7	13312	-0.05	0.034	NO
64	PTPRJ	PTPRJ	PTPRJ	13375	-0.05	0.041	NO
65	CTNNA2	CTNNA2	CTNNA2	13441	-0.052	0.049	NO
66	FARP2	FARP2	FARP2	13489	-0.052	0.058	NO
67	YES1	YES1	YES1	13693	-0.056	0.058	NO
68	NLK	NLK	NLK	13820	-0.059	0.064	NO
69	PTPN1	PTPN1	PTPN1	14108	-0.065	0.062	NO
70	SNAI1	SNAI1	SNAI1	15163	-0.095	0.024	NO
71	WASF3	WASF3	WASF3	16666	-0.17	-0.024	NO
72	ACTN2	ACTN2	ACTN2	17014	-0.2	0.000082	NO
73	RAC3	RAC3	RAC3	17350	-0.25	0.035	NO

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

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

genes ES table in pathway: KEGG ARACHIDONIC ACID METABOLISM

Table 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	GRM4	GRM4	GRM4	100	0.5	0.13	YES
2	SCNN1G	SCNN1G	SCNN1G	339	0.35	0.21	YES
3	GNB3	GNB3	GNB3	504	0.3	0.28	YES
4	ADCY8	ADCY8	ADCY8	539	0.29	0.36	YES
5	TAS1R3	TAS1R3	TAS1R3	1359	0.17	0.36	YES
6	TRPM5	TRPM5	TRPM5	1434	0.16	0.4	YES
7	TAS2R14	TAS2R14	TAS2R14	1781	0.14	0.42	YES
8	SCNN1B	SCNN1B	SCNN1B	2132	0.11	0.43	YES
9	CACNA1A	CACNA1A	CACNA1A	2191	0.11	0.46	YES
10	TAS2R19	TAS2R19	TAS2R19	2227	0.11	0.48	YES
11	TAS2R4	TAS2R4	TAS2R4	2242	0.11	0.51	YES
12	ADCY4	ADCY4	ADCY4	2472	0.099	0.53	YES
13	GNG3	GNG3	GNG3	2481	0.098	0.55	YES
14	TAS2R5	TAS2R5	TAS2R5	3494	0.069	0.51	NO
15	TAS2R20	TAS2R20	TAS2R20	4018	0.057	0.5	NO
16	PRKACA	PRKACA	PRKACA	4441	0.048	0.49	NO
17	ADCY6	ADCY6	ADCY6	5060	0.039	0.47	NO
18	TAS2R31	TAS2R31	TAS2R31	5266	0.036	0.46	NO
19	SCNN1A	SCNN1A	SCNN1A	6611	0.022	0.4	NO
20	TAS2R10	TAS2R10	TAS2R10	6958	0.018	0.38	NO
21	TAS2R13	TAS2R13	TAS2R13	7637	0.012	0.35	NO
22	ACCN1	ACCN1	ACCN1	7965	0.0091	0.33	NO
23	TAS2R3	TAS2R3	TAS2R3	8624	0.003	0.3	NO
24	PDE1A	PDE1A	PDE1A	9904	-0.0084	0.23	NO
25	PRKX	PRKX	PRKX	10150	-0.011	0.22	NO
26	GNB1	GNB1	GNB1	10447	-0.014	0.2	NO
27	PLCB2	PLCB2	PLCB2	11131	-0.021	0.17	NO
28	GNAS	GNAS	GNAS	12146	-0.032	0.12	NO
29	TAS2R50	TAS2R50	TAS2R50	12989	-0.044	0.087	NO
30	ITPR3	ITPR3	ITPR3	13478	-0.052	0.074	NO
31	TAS1R1	TAS1R1	TAS1R1	13996	-0.063	0.062	NO
32	KCNB1	KCNB1	KCNB1	14388	-0.071	0.06	NO
33	TAS2R43	TAS2R43	TAS2R43	14723	-0.081	0.063	NO
34	TAS2R46	TAS2R46	TAS2R46	14789	-0.083	0.082	NO
35	PRKACB	PRKACB	PRKACB	16119	-0.14	0.044	NO
36	CACNA1B	CACNA1B	CACNA1B	17171	-0.22	0.045	NO

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

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

genes ES table in pathway: KEGG SPLICEOSOME

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	PLA2G12B	PLA2G12B	PLA2G12B	149	0.45	0.069	YES
2	CYP2C8	CYP2C8	CYP2C8	167	0.44	0.14	YES
3	CYP2E1	CYP2E1	CYP2E1	273	0.37	0.2	YES
4	CBR3	CBR3	CBR3	647	0.27	0.23	YES
5	PLA2G2E	PLA2G2E	PLA2G2E	666	0.26	0.27	YES
6	GGT6	GGT6	GGT6	808	0.23	0.3	YES
7	LTC4S	LTC4S	LTC4S	842	0.23	0.34	YES
8	ALOX12B	ALOX12B	ALOX12B	1101	0.19	0.36	YES
9	PLA2G10	PLA2G10	PLA2G10	1104	0.19	0.39	YES
10	ALOX12	ALOX12	ALOX12	1362	0.17	0.4	YES
11	CYP4A11	CYP4A11	CYP4A11	1429	0.16	0.43	YES
12	HPGDS	HPGDS	HPGDS	1653	0.14	0.44	YES
13	PTGDS	PTGDS	PTGDS	1937	0.13	0.45	YES
14	GPX2	GPX2	GPX2	1963	0.12	0.47	YES
15	ALOX15B	ALOX15B	ALOX15B	2087	0.12	0.48	YES
16	PLA2G5	PLA2G5	PLA2G5	2265	0.11	0.49	YES
17	GGT5	GGT5	GGT5	2306	0.11	0.5	YES
18	PLA2G6	PLA2G6	PLA2G6	2375	0.1	0.52	YES
19	PTGS2	PTGS2	PTGS2	2649	0.092	0.52	YES
20	TBXAS1	TBXAS1	TBXAS1	3987	0.058	0.45	NO
21	GGT7	GGT7	GGT7	4200	0.053	0.45	NO
22	GPX4	GPX4	GPX4	4311	0.051	0.45	NO
23	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	5158	0.038	0.41	NO
24	EPHX2	EPHX2	EPHX2	5286	0.036	0.41	NO
25	PTGS1	PTGS1	PTGS1	7520	0.013	0.29	NO
26	GPX1	GPX1	GPX1	9137	-0.0015	0.2	NO
27	PLA2G4A	PLA2G4A	PLA2G4A	9237	-0.0024	0.2	NO
28	PLA2G3	PLA2G3	PLA2G3	9473	-0.0045	0.18	NO
29	LTA4H	LTA4H	LTA4H	10329	-0.012	0.14	NO
30	PTGES2	PTGES2	PTGES2	10437	-0.014	0.13	NO
31	PLA2G12A	PLA2G12A	PLA2G12A	11039	-0.02	0.1	NO
32	GPX7	GPX7	GPX7	11237	-0.022	0.096	NO
33	CBR1	CBR1	CBR1	11336	-0.023	0.095	NO
34	PTGIS	PTGIS	PTGIS	12999	-0.044	0.0096	NO
35	PLA2G2D	PLA2G2D	PLA2G2D	13680	-0.056	-0.019	NO
36	AKR1C3	AKR1C3	AKR1C3	14337	-0.07	-0.043	NO
37	GGT1	GGT1	GGT1	14599	-0.077	-0.045	NO
38	ALOX15	ALOX15	ALOX15	15021	-0.09	-0.053	NO
39	PLA2G2F	PLA2G2F	PLA2G2F	15092	-0.092	-0.041	NO
40	ALOX5	ALOX5	ALOX5	15332	-0.1	-0.037	NO
41	CYP4F3	CYP4F3	CYP4F3	15466	-0.1	-0.027	NO
42	PLA2G2A	PLA2G2A	PLA2G2A	15487	-0.11	-0.0096	NO
43	CYP2U1	CYP2U1	CYP2U1	15892	-0.12	-0.011	NO
44	CYP2C9	CYP2C9	CYP2C9	15969	-0.13	0.0068	NO
45	GPX3	GPX3	GPX3	16315	-0.14	0.012	NO
46	PLA2G1B	PLA2G1B	PLA2G1B	16375	-0.15	0.035	NO
47	PTGES	PTGES	PTGES	17637	-0.32	0.019	NO

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

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

genes ES table in pathway: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION

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	SNAP25	SNAP25	SNAP25	403	0.33	0.11	YES
2	STX1B	STX1B	STX1B	736	0.25	0.18	YES
3	STX19	STX19	STX19	915	0.22	0.26	YES
4	VAMP5	VAMP5	VAMP5	1651	0.14	0.28	YES
5	VAMP4	VAMP4	VAMP4	1820	0.13	0.32	YES
6	USE1	USE1	USE1	4058	0.056	0.22	NO
7	VAMP8	VAMP8	VAMP8	4124	0.054	0.23	NO
8	VAMP1	VAMP1	VAMP1	4529	0.047	0.23	NO
9	STX16	STX16	STX16	4733	0.044	0.23	NO
10	TSNARE1	TSNARE1	TSNARE1	5085	0.039	0.23	NO
11	VAMP2	VAMP2	VAMP2	5795	0.03	0.2	NO
12	SNAP47	SNAP47	SNAP47	5979	0.028	0.2	NO
13	SNAP23	SNAP23	SNAP23	6639	0.022	0.18	NO
14	VAMP3	VAMP3	VAMP3	6660	0.021	0.18	NO
15	STX8	STX8	STX8	7074	0.017	0.17	NO
16	STX4	STX4	STX4	7772	0.011	0.13	NO
17	STX3	STX3	STX3	7966	0.0091	0.12	NO
18	BET1L	BET1L	BET1L	8392	0.0052	0.1	NO
19	STX5	STX5	STX5	8769	0.0017	0.082	NO
20	STX10	STX10	STX10	10182	-0.011	0.0077	NO
21	STX6	STX6	STX6	10336	-0.012	0.004	NO
22	STX7	STX7	STX7	10834	-0.018	-0.017	NO
23	VTI1A	VTI1A	VTI1A	11778	-0.028	-0.058	NO
24	STX12	STX12	STX12	11907	-0.03	-0.054	NO
25	STX17	STX17	STX17	12109	-0.032	-0.053	NO
26	GOSR1	GOSR1	GOSR1	12248	-0.034	-0.047	NO
27	BET1	BET1	BET1	12456	-0.037	-0.044	NO
28	STX18	STX18	STX18	12484	-0.037	-0.032	NO
29	VTI1B	VTI1B	VTI1B	12521	-0.037	-0.019	NO
30	GOSR2	GOSR2	GOSR2	12590	-0.038	-0.0077	NO
31	YKT6	YKT6	YKT6	12849	-0.042	-0.0057	NO
32	STX1A	STX1A	STX1A	13542	-0.054	-0.023	NO
33	VAMP7	VAMP7	VAMP7	13746	-0.057	-0.012	NO
34	SEC22B	SEC22B	SEC22B	14616	-0.078	-0.031	NO
35	BNIP1	BNIP1	BNIP1	15041	-0.09	-0.019	NO
36	STX2	STX2	STX2	15849	-0.12	-0.016	NO
37	STX11	STX11	STX11	17713	-0.34	0.014	NO

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

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

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

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	NGFR	NGFR	NGFR	38	0.61	0.37	YES
2	EGFR	EGFR	EGFR	1974	0.12	0.34	YES
3	IGF1R	IGF1R	IGF1R	2584	0.094	0.36	YES
4	SRC	SRC	SRC	2850	0.086	0.4	YES
5	MYC	MYC	MYC	3931	0.059	0.37	NO
6	ELK1	ELK1	ELK1	4343	0.05	0.38	NO
7	PDGFRA	PDGFRA	PDGFRA	5161	0.038	0.36	NO
8	SHC1	SHC1	SHC1	5371	0.035	0.37	NO
9	STAT3	STAT3	STAT3	6387	0.024	0.32	NO
10	MAP2K2	MAP2K2	MAP2K2	8173	0.0072	0.23	NO
11	PPP2CA	PPP2CA	PPP2CA	8421	0.0049	0.22	NO
12	GRB2	GRB2	GRB2	9551	-0.0054	0.16	NO
13	MAPK3	MAPK3	MAPK3	9846	-0.008	0.15	NO
14	PTPRR	PTPRR	PTPRR	9862	-0.0081	0.15	NO
15	RAF1	RAF1	RAF1	9923	-0.0086	0.15	NO
16	MKNK2	MKNK2	MKNK2	10025	-0.0096	0.15	NO
17	MAPK1	MAPK1	MAPK1	10444	-0.014	0.14	NO
18	GNB1	GNB1	GNB1	10447	-0.014	0.15	NO
19	ITGB1	ITGB1	ITGB1	10609	-0.015	0.15	NO
20	MKNK1	MKNK1	MKNK1	11142	-0.021	0.13	NO
21	SOS1	SOS1	SOS1	11569	-0.026	0.12	NO
22	GNAS	GNAS	GNAS	12146	-0.032	0.11	NO
23	NGF	NGF	NGF	12389	-0.036	0.12	NO
24	MAP2K1	MAP2K1	MAP2K1	12459	-0.037	0.14	NO
25	RPS6KA1	RPS6KA1	RPS6KA1	16148	-0.14	0.014	NO
26	RPS6KA5	RPS6KA5	RPS6KA5	16302	-0.14	0.093	NO

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

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: KEGG NOTCH SIGNALING PATHWAY

Table 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	IFNE	IFNE	IFNE	56	0.57	0.12	YES
2	IFNA1	IFNA1	IFNA1	202	0.41	0.21	YES
3	IFNA13	IFNA13	IFNA13	304	0.36	0.28	YES
4	IFNA8	IFNA8	IFNA8	305	0.36	0.36	YES
5	IKBKE	IKBKE	IKBKE	1900	0.13	0.3	NO
6	MAP3K1	MAP3K1	MAP3K1	2098	0.12	0.32	NO
7	TMEM173	TMEM173	TMEM173	2709	0.09	0.3	NO
8	TANK	TANK	TANK	3174	0.076	0.29	NO
9	IRF3	IRF3	IRF3	3209	0.075	0.31	NO
10	CASP8	CASP8	CASP8	3783	0.062	0.29	NO
11	MAPK10	MAPK10	MAPK10	4062	0.056	0.29	NO
12	IRF7	IRF7	IRF7	4154	0.054	0.29	NO
13	MAPK11	MAPK11	MAPK11	4756	0.043	0.27	NO
14	FADD	FADD	FADD	4781	0.043	0.28	NO
15	CASP10	CASP10	CASP10	5068	0.039	0.27	NO
16	OTUD5	OTUD5	OTUD5	5650	0.032	0.25	NO
17	MAPK14	MAPK14	MAPK14	5728	0.031	0.25	NO
18	RELA	RELA	RELA	6094	0.027	0.23	NO
19	RNF125	RNF125	RNF125	6367	0.024	0.22	NO
20	IKBKB	IKBKB	IKBKB	6534	0.023	0.22	NO
21	DAK	DAK	DAK	6668	0.021	0.22	NO
22	TBKBP1	TBKBP1	TBKBP1	7298	0.015	0.19	NO
23	NFKBIB	NFKBIB	NFKBIB	7658	0.012	0.17	NO
24	TRIM25	TRIM25	TRIM25	8191	0.007	0.14	NO
25	DHX58	DHX58	DHX58	8399	0.0051	0.13	NO
26	NLRX1	NLRX1	NLRX1	8970	-0.00022	0.098	NO
27	IKBKG	IKBKG	IKBKG	8986	-0.00035	0.097	NO
28	TRADD	TRADD	TRADD	9333	-0.0032	0.078	NO
29	PIN1	PIN1	PIN1	9427	-0.004	0.074	NO
30	MAPK13	MAPK13	MAPK13	9464	-0.0044	0.073	NO
31	TRAF2	TRAF2	TRAF2	9797	-0.0075	0.056	NO
32	DDX3X	DDX3X	DDX3X	9882	-0.0082	0.053	NO
33	DDX58	DDX58	DDX58	10007	-0.0095	0.049	NO
34	TBK1	TBK1	TBK1	10078	-0.01	0.047	NO
35	MAVS	MAVS	MAVS	10413	-0.014	0.031	NO
36	RIPK1	RIPK1	RIPK1	10580	-0.015	0.025	NO
37	AZI2	AZI2	AZI2	11681	-0.027	-0.03	NO
38	NFKB1	NFKB1	NFKB1	11691	-0.027	-0.024	NO
39	ATG5	ATG5	ATG5	11739	-0.028	-0.021	NO
40	CYLD	CYLD	CYLD	11755	-0.028	-0.016	NO
41	TNF	TNF	TNF	11986	-0.03	-0.022	NO
42	MAPK9	MAPK9	MAPK9	12551	-0.038	-0.045	NO
43	DDX3Y	DDX3Y	DDX3Y	12569	-0.038	-0.037	NO
44	IFIH1	IFIH1	IFIH1	13168	-0.047	-0.06	NO
45	MAP3K7	MAP3K7	MAP3K7	13312	-0.05	-0.057	NO
46	ISG15	ISG15	ISG15	13795	-0.058	-0.071	NO
47	IL8	IL8	IL8	13804	-0.058	-0.058	NO
48	ATG12	ATG12	ATG12	13905	-0.061	-0.051	NO
49	MAPK12	MAPK12	MAPK12	14070	-0.064	-0.045	NO
50	NFKBIA	NFKBIA	NFKBIA	14194	-0.067	-0.037	NO
51	TRAF6	TRAF6	TRAF6	14258	-0.068	-0.026	NO
52	CHUK	CHUK	CHUK	14643	-0.078	-0.03	NO
53	SIKE1	SIKE1	SIKE1	15404	-0.1	-0.049	NO
54	MAPK8	MAPK8	MAPK8	15763	-0.12	-0.043	NO
55	CXCL10	CXCL10	CXCL10	15977	-0.13	-0.026	NO
56	IL12A	IL12A	IL12A	16290	-0.14	-0.012	NO
57	IFNB1	IFNB1	IFNB1	16373	-0.15	0.017	NO
58	TRAF3	TRAF3	TRAF3	16391	-0.15	0.049	NO
59	IL12B	IL12B	IL12B	16756	-0.17	0.068	NO

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

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

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 = THCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = THCA-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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