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

Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)

21 August 2015 | analyses__2015_08_21

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in KIRP-TP. Broad Institute of MIT and Harvard. doi:10.7908/C18C9VGC

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 KIRP-TP. This pipeline has the following features:

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

Summary

Table 1. Get Full Table basic data info

basic data info
Number of Gene Sets: 192
Number of samples: 290
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 ] 34
pheno.type: 2 - 4 :[ clus2 ] 97
pheno.type: 3 - 4 :[ clus3 ] 67
pheno.type: 4 - 4 :[ clus4 ] 92

For the expression subtypes of 17999 genes in 291 samples, GSEA found enriched gene sets in each cluster using 290 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AT1R PATHWAY, BIOCARTA BCR PATHWAY, BIOCARTA HDAC PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA FAS PATHWAY, BIOCARTA FCER1 PATHWAY, BIOCARTA FMLP PATHWAY, BIOCARTA GH PATHWAY

And common core enriched genes are PIK3CG, KIT, NTRK1, BID, BIRC3, CASP7, FAS, NFKB1, NFKBIA, TNF

clus2

Top enriched gene sets are BIOCARTA ALK PATHWAY, BIOCARTA DEATH PATHWAY, KEGG HISTIDINE METABOLISM, KEGG SPHINGOLIPID METABOLISM, KEGG RNA DEGRADATION, KEGG SPLICEOSOME, KEGG ERBB SIGNALING PATHWAY, KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT, KEGG CARDIAC MUSCLE CONTRACTION, KEGG HEDGEHOG SIGNALING PATHWAY

And common core enriched genes are BMP2, BMP4, BMP7, CLDN15, CLDN18, CLDN19, CLDN20, CLDN3, CLDN6, CLDN7

clus3

Top enriched gene sets are KEGG GLYCOLYSIS GLUCONEOGENESIS, KEGG CITRATE CYCLE TCA CYCLE, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG FRUCTOSE AND MANNOSE METABOLISM, KEGG FATTY ACID METABOLISM, KEGG STEROID HORMONE BIOSYNTHESIS, KEGG OXIDATIVE PHOSPHORYLATION, KEGG PYRIMIDINE METABOLISM, KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM, KEGG GLYCINE SERINE AND THREONINE METABOLISM

And common core enriched genes are ACAA1, EHHADH, HMGCL, PIPOX, ACAT1, ACAT2, ALDH1B1, ALDH2, ALDH3A2, ALDH7A1

clus4

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA G1 PATHWAY, BIOCARTA ERK PATHWAY, BIOCARTA MPR PATHWAY, BIOCARTA INTEGRIN PATHWAY, BIOCARTA VEGF PATHWAY, KEGG N GLYCAN BIOSYNTHESIS, KEGG CALCIUM SIGNALING PATHWAY, KEGG CELL CYCLE, KEGG OOCYTE MEIOSIS

And common core enriched genes are CCND1, CDH1, LEF1, TCF7L1, CDK1, MYC, RET, RXRA, RXRG, ACTN2

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 NO1 PATHWAY	28	genes.ES.table	0.58	1.3	0.21	0.24	0.98	0.46	0.19	0.38	0.2	0
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.45	1.7	0.037	0.055	0.58	0.56	0.41	0.33	0.028	0
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.7	1.9	0	0.018	0.14	0.42	0.18	0.35	0	0
BIOCARTA HDAC PATHWAY	26	genes.ES.table	0.64	2	0	0.023	0.047	0.15	0.048	0.15	0	0.003
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.5	1.6	0.032	0.075	0.69	0.73	0.41	0.43	0.043	0
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.49	1.5	0.092	0.12	0.88	0.18	0.15	0.16	0.086	0
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.48	1.7	0.037	0.055	0.58	0.38	0.33	0.26	0.028	0
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.69	1.9	0.0021	0.017	0.12	0.4	0.18	0.33	0	0
BIOCARTA FMLP PATHWAY	35	genes.ES.table	0.58	1.9	0.0021	0.02	0.1	0.34	0.24	0.26	0	0
BIOCARTA GH PATHWAY	25	genes.ES.table	0.56	1.7	0.014	0.035	0.42	0.4	0.24	0.3	0	0

genes ES table in pathway: BIOCARTA NO1 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	CXCR2	CXCR2	CXCR2	32	0.66	0.038	YES
2	IL2RA	IL2RA	IL2RA	36	0.66	0.078	YES
3	CXCR1	CXCR1	CXCR1	69	0.62	0.11	YES
4	PDGFRA	PDGFRA	PDGFRA	113	0.59	0.15	YES
5	IL2RG	IL2RG	IL2RG	281	0.51	0.17	YES
6	CCR5	CCR5	CCR5	304	0.5	0.2	YES
7	AGAP2	AGAP2	AGAP2	411	0.46	0.22	YES
8	IL2RB	IL2RB	IL2RB	459	0.45	0.24	YES
9	KIT	KIT	KIT	577	0.42	0.26	YES
10	ACAP1	ACAP1	ACAP1	581	0.42	0.29	YES
11	ADRB3	ADRB3	ADRB3	671	0.39	0.31	YES
12	HSPA6	HSPA6	HSPA6	849	0.36	0.32	YES
13	NTRK1	NTRK1	NTRK1	864	0.36	0.34	YES
14	CXCR4	CXCR4	CXCR4	950	0.34	0.36	YES
15	ADRB2	ADRB2	ADRB2	1190	0.3	0.36	YES
16	CSF1R	CSF1R	CSF1R	1291	0.29	0.37	YES
17	HLA-G	HLA-G	HLA-G	1502	0.26	0.38	YES
18	ADRBK2	ADRBK2	ADRBK2	1605	0.25	0.39	YES
19	SMAP2	SMAP2	SMAP2	1691	0.24	0.4	YES
20	LDLR	LDLR	LDLR	1760	0.23	0.41	YES
21	CBLC	CBLC	CBLC	1795	0.23	0.42	YES
22	ARRB1	ARRB1	ARRB1	1998	0.21	0.42	YES
23	IQSEC3	IQSEC3	IQSEC3	2036	0.2	0.43	YES
24	PSD3	PSD3	PSD3	2128	0.2	0.44	YES
25	ARRB2	ARRB2	ARRB2	2264	0.18	0.44	YES
26	RAB31	RAB31	RAB31	2411	0.17	0.44	YES
27	F2R	F2R	F2R	2519	0.17	0.45	YES
28	EHD3	EHD3	EHD3	2613	0.16	0.45	YES
29	VPS37B	VPS37B	VPS37B	2992	0.14	0.44	YES
30	ARAP2	ARAP2	ARAP2	3068	0.14	0.44	YES
31	RET	RET	RET	3231	0.13	0.44	YES
32	CBLB	CBLB	CBLB	3251	0.13	0.45	YES
33	HLA-F	HLA-F	HLA-F	3508	0.11	0.44	YES
34	GRK5	GRK5	GRK5	3526	0.11	0.44	YES
35	HLA-E	HLA-E	HLA-E	3621	0.11	0.45	YES
36	HSPA2	HSPA2	HSPA2	3825	0.1	0.44	YES
37	SH3KBP1	SH3KBP1	SH3KBP1	4017	0.095	0.44	YES
38	MET	MET	MET	4052	0.094	0.44	YES
39	HLA-B	HLA-B	HLA-B	4244	0.087	0.44	YES
40	ASAP1	ASAP1	ASAP1	4271	0.086	0.44	YES
41	HSPA1A	HSPA1A	HSPA1A	4308	0.085	0.44	YES
42	ARAP3	ARAP3	ARAP3	4352	0.084	0.44	YES
43	DNM3	DNM3	DNM3	4396	0.083	0.45	YES
44	SMURF2	SMURF2	SMURF2	4475	0.081	0.45	YES
45	ARF6	ARF6	ARF6	4607	0.077	0.44	YES
46	HSPA1B	HSPA1B	HSPA1B	4717	0.074	0.44	YES
47	RNF41	RNF41	RNF41	4733	0.073	0.45	YES
48	TRAF6	TRAF6	TRAF6	4788	0.072	0.45	YES
49	LDLRAP1	LDLRAP1	LDLRAP1	4792	0.072	0.45	YES
50	PSD4	PSD4	PSD4	4803	0.071	0.46	YES
51	ADRB1	ADRB1	ADRB1	4824	0.071	0.46	YES
52	CBL	CBL	CBL	4873	0.07	0.46	YES
53	ACAP2	ACAP2	ACAP2	4966	0.068	0.46	YES
54	EHD4	EHD4	EHD4	5006	0.066	0.46	YES
55	ERBB3	ERBB3	ERBB3	5041	0.066	0.46	YES
56	DNAJC6	DNAJC6	DNAJC6	5102	0.064	0.46	YES
57	ADRBK1	ADRBK1	ADRBK1	5141	0.063	0.47	YES
58	HLA-C	HLA-C	HLA-C	5220	0.062	0.46	YES
59	GRK6	GRK6	GRK6	5228	0.061	0.47	YES
60	SMURF1	SMURF1	SMURF1	5334	0.059	0.47	NO
61	MDM2	MDM2	MDM2	5365	0.058	0.47	NO
62	EHD2	EHD2	EHD2	5657	0.053	0.46	NO
63	CHMP1B	CHMP1B	CHMP1B	5658	0.053	0.46	NO
64	GIT2	GIT2	GIT2	5672	0.052	0.46	NO
65	ARAP1	ARAP1	ARAP1	5829	0.05	0.46	NO
66	CDC42	CDC42	CDC42	5836	0.05	0.46	NO
67	EGFR	EGFR	EGFR	5884	0.049	0.46	NO
68	HLA-A	HLA-A	HLA-A	5924	0.048	0.46	NO
69	PRKCI	PRKCI	PRKCI	6230	0.042	0.44	NO
70	RAB11FIP2	RAB11FIP2	RAB11FIP2	6263	0.042	0.44	NO
71	EPS15	EPS15	EPS15	6452	0.039	0.44	NO
72	VPS37D	VPS37D	VPS37D	6473	0.038	0.44	NO
73	RAB11FIP1	RAB11FIP1	RAB11FIP1	6475	0.038	0.44	NO
74	SH3GLB1	SH3GLB1	SH3GLB1	6479	0.038	0.44	NO
75	IGF1R	IGF1R	IGF1R	6746	0.034	0.43	NO
76	ARFGAP3	ARFGAP3	ARFGAP3	6764	0.034	0.43	NO
77	HSPA1L	HSPA1L	HSPA1L	6848	0.033	0.43	NO
78	CHMP2B	CHMP2B	CHMP2B	6967	0.031	0.42	NO
79	RAB5B	RAB5B	RAB5B	7151	0.029	0.41	NO
80	PDCD6IP	PDCD6IP	PDCD6IP	7313	0.027	0.41	NO
81	PLD2	PLD2	PLD2	7332	0.027	0.41	NO
82	EEA1	EEA1	EEA1	7347	0.027	0.41	NO
83	PIP5K1C	PIP5K1C	PIP5K1C	7452	0.025	0.4	NO
84	KDR	KDR	KDR	7483	0.025	0.4	NO
85	VPS37C	VPS37C	VPS37C	7527	0.024	0.4	NO
86	VTA1	VTA1	VTA1	7547	0.024	0.4	NO
87	ZFYVE20	ZFYVE20	ZFYVE20	7661	0.023	0.4	NO
88	WWP1	WWP1	WWP1	7737	0.022	0.4	NO
89	DAB2	DAB2	DAB2	7791	0.021	0.39	NO
90	RAB5A	RAB5A	RAB5A	7833	0.02	0.39	NO
91	HSPA8	HSPA8	HSPA8	7956	0.019	0.39	NO
92	VPS36	VPS36	VPS36	7977	0.019	0.39	NO
93	VPS4B	VPS4B	VPS4B	8025	0.018	0.38	NO
94	SMAP1	SMAP1	SMAP1	8092	0.018	0.38	NO
95	RABEP1	RABEP1	RABEP1	8232	0.016	0.38	NO
96	VPS25	VPS25	VPS25	8266	0.016	0.38	NO
97	PIP5K1A	PIP5K1A	PIP5K1A	8310	0.015	0.37	NO
98	STAM	STAM	STAM	8329	0.015	0.37	NO
99	FAM125B	FAM125B	FAM125B	8389	0.015	0.37	NO
100	IQSEC1	IQSEC1	IQSEC1	8452	0.014	0.37	NO
101	CHMP5	CHMP5	CHMP5	8553	0.013	0.36	NO
102	ITCH	ITCH	ITCH	8595	0.012	0.36	NO
103	EHD1	EHD1	EHD1	8702	0.011	0.36	NO
104	PIKFYVE	PIKFYVE	PIKFYVE	8814	0.0099	0.35	NO
105	EPN2	EPN2	EPN2	8870	0.0093	0.35	NO
106	RAB4A	RAB4A	RAB4A	8950	0.0085	0.34	NO
107	ASAP2	ASAP2	ASAP2	8997	0.008	0.34	NO
108	TFRC	TFRC	TFRC	9068	0.0073	0.34	NO
109	STAM2	STAM2	STAM2	9168	0.0063	0.33	NO
110	PIP5K1B	PIP5K1B	PIP5K1B	9208	0.0059	0.33	NO
111	CHMP4B	CHMP4B	CHMP4B	9252	0.0055	0.33	NO
112	AGAP1	AGAP1	AGAP1	9370	0.0041	0.32	NO
113	RAB5C	RAB5C	RAB5C	9383	0.004	0.32	NO
114	ASAP3	ASAP3	ASAP3	9526	0.0026	0.32	NO
115	AP2A1	AP2A1	AP2A1	9607	0.0016	0.31	NO
116	TSG101	TSG101	TSG101	9699	0.00063	0.31	NO
117	RAB11A	RAB11A	RAB11A	9809	-0.00059	0.3	NO
118	AP2S1	AP2S1	AP2S1	9851	-0.00099	0.3	NO
119	CLTA	CLTA	CLTA	9865	-0.0011	0.3	NO
120	IQSEC2	IQSEC2	IQSEC2	9872	-0.0012	0.3	NO
121	RAB22A	RAB22A	RAB22A	9884	-0.0014	0.3	NO
122	VPS24	VPS24	VPS24	9918	-0.0017	0.29	NO
123	USP8	USP8	USP8	9940	-0.0019	0.29	NO
124	VPS37A	VPS37A	VPS37A	10012	-0.0027	0.29	NO
125	CLTC	CLTC	CLTC	10051	-0.0031	0.29	NO
126	RAB11FIP4	RAB11FIP4	RAB11FIP4	10167	-0.004	0.28	NO
127	SRC	SRC	SRC	10239	-0.0047	0.28	NO
128	AP2B1	AP2B1	AP2B1	10389	-0.0064	0.27	NO
129	ARFGAP2	ARFGAP2	ARFGAP2	10436	-0.0069	0.27	NO
130	DNM1L	DNM1L	DNM1L	10515	-0.0076	0.26	NO
131	SH3GL1	SH3GL1	SH3GL1	10517	-0.0077	0.26	NO
132	GRK7	GRK7	GRK7	10608	-0.0086	0.26	NO
133	PARD3	PARD3	PARD3	10691	-0.0097	0.26	NO
134	EPN1	EPN1	EPN1	10714	-0.0099	0.26	NO
135	PARD6B	PARD6B	PARD6B	10773	-0.01	0.25	NO
136	AP2M1	AP2M1	AP2M1	10907	-0.012	0.24	NO
137	VPS4A	VPS4A	VPS4A	11129	-0.014	0.23	NO
138	RAB11B	RAB11B	RAB11B	11159	-0.014	0.23	NO
139	RUFY1	RUFY1	RUFY1	11195	-0.015	0.23	NO
140	CHMP4A	CHMP4A	CHMP4A	11211	-0.015	0.23	NO
141	CLTCL1	CLTCL1	CLTCL1	11290	-0.016	0.23	NO
142	AP2A2	AP2A2	AP2A2	11308	-0.016	0.23	NO
143	FLT1	FLT1	FLT1	11527	-0.018	0.22	NO
144	CHMP6	CHMP6	CHMP6	11575	-0.019	0.22	NO
145	VPS45	VPS45	VPS45	11755	-0.021	0.21	NO
146	PLD1	PLD1	PLD1	12072	-0.024	0.19	NO
147	FGFR4	FGFR4	FGFR4	12207	-0.026	0.18	NO
148	RAB11FIP5	RAB11FIP5	RAB11FIP5	12297	-0.026	0.18	NO
149	NEDD4L	NEDD4L	NEDD4L	12339	-0.027	0.18	NO
150	HGS	HGS	HGS	13129	-0.037	0.14	NO
151	PRKCZ	PRKCZ	PRKCZ	13169	-0.038	0.14	NO
152	ARFGAP1	ARFGAP1	ARFGAP1	13206	-0.038	0.14	NO
153	PIP4K2B	PIP4K2B	PIP4K2B	13413	-0.041	0.13	NO
154	DNM2	DNM2	DNM2	13414	-0.041	0.13	NO
155	CLTB	CLTB	CLTB	13443	-0.041	0.13	NO
156	CHMP4C	CHMP4C	CHMP4C	13582	-0.044	0.13	NO
157	FAM125A	FAM125A	FAM125A	13743	-0.046	0.12	NO
158	CHMP2A	CHMP2A	CHMP2A	13801	-0.047	0.12	NO
159	ACAP3	ACAP3	ACAP3	13879	-0.048	0.12	NO
160	VPS28	VPS28	VPS28	13927	-0.049	0.12	NO
161	ERBB4	ERBB4	ERBB4	14122	-0.052	0.11	NO
162	STAMBP	STAMBP	STAMBP	14157	-0.053	0.11	NO
163	EPN3	EPN3	EPN3	14236	-0.054	0.11	NO
164	PARD6A	PARD6A	PARD6A	14297	-0.055	0.11	NO
165	FGFR2	FGFR2	FGFR2	14399	-0.057	0.11	NO
166	RAB11FIP3	RAB11FIP3	RAB11FIP3	14448	-0.058	0.11	NO
167	SNF8	SNF8	SNF8	14763	-0.064	0.098	NO
168	NEDD4	NEDD4	NEDD4	14840	-0.066	0.098	NO
169	SH3GLB2	SH3GLB2	SH3GLB2	15386	-0.08	0.072	NO
170	GIT1	GIT1	GIT1	15556	-0.085	0.067	NO
171	DNM1	DNM1	DNM1	15805	-0.094	0.059	NO
172	PSD	PSD	PSD	15824	-0.095	0.064	NO
173	EGF	EGF	EGF	15870	-0.097	0.067	NO
174	PARD6G	PARD6G	PARD6G	16044	-0.1	0.064	NO
175	SH3GL3	SH3GL3	SH3GL3	16314	-0.12	0.056	NO
176	GRK4	GRK4	GRK4	16378	-0.12	0.059	NO
177	FGFR3	FGFR3	FGFR3	16811	-0.15	0.044	NO
178	PSD2	PSD2	PSD2	17024	-0.17	0.042	NO
179	SH3GL2	SH3GL2	SH3GL2	17256	-0.19	0.041	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 NO1 PATHWAY.

Figure S2. 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 AT1R 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	TNF	TNF	TNF	233	0.53	0.12	YES
2	BIRC3	BIRC3	BIRC3	960	0.34	0.17	YES
3	TNFRSF1B	TNFRSF1B	TNFRSF1B	1037	0.33	0.25	YES
4	MAP3K5	MAP3K5	MAP3K5	1612	0.25	0.28	YES
5	ARHGDIB	ARHGDIB	ARHGDIB	1841	0.22	0.33	YES
6	MAP3K1	MAP3K1	MAP3K1	3297	0.12	0.28	YES
7	BAG4	BAG4	BAG4	3337	0.12	0.31	YES
8	NFKBIA	NFKBIA	NFKBIA	3867	0.1	0.31	YES
9	GSN	GSN	GSN	3946	0.097	0.33	YES
10	NFKB1	NFKB1	NFKB1	3971	0.096	0.35	YES
11	BID	BID	BID	4068	0.093	0.37	YES
12	CASP7	CASP7	CASP7	4250	0.087	0.38	YES
13	MAPK8	MAPK8	MAPK8	4370	0.083	0.4	YES
14	FAS	FAS	FAS	4402	0.082	0.42	YES
15	TNFRSF1A	TNFRSF1A	TNFRSF1A	4562	0.078	0.43	YES
16	APAF1	APAF1	APAF1	5057	0.065	0.42	YES
17	BCL2	BCL2	BCL2	5168	0.062	0.43	YES
18	RB1	RB1	RB1	5353	0.058	0.43	YES
19	MDM2	MDM2	MDM2	5365	0.058	0.45	YES
20	RIPK1	RIPK1	RIPK1	5729	0.051	0.44	YES
21	PAK2	PAK2	PAK2	5783	0.051	0.45	YES
22	CRADD	CRADD	CRADD	5875	0.049	0.46	YES
23	CFLAR	CFLAR	CFLAR	5892	0.049	0.47	YES
24	PRKCD	PRKCD	PRKCD	6086	0.045	0.47	YES
25	MAP3K14	MAP3K14	MAP3K14	6115	0.044	0.48	YES
26	BIRC2	BIRC2	BIRC2	6485	0.038	0.47	NO
27	RELA	RELA	RELA	6534	0.037	0.48	NO
28	CDK11A	CDK11A	CDK11A	6720	0.035	0.47	NO
29	LMNB1	LMNB1	LMNB1	7003	0.031	0.47	NO
30	TRAF1	TRAF1	TRAF1	7091	0.03	0.47	NO
31	RASA1	RASA1	RASA1	7154	0.029	0.47	NO
32	PARP1	PARP1	PARP1	7222	0.028	0.48	NO
33	PSEN1	PSEN1	PSEN1	7349	0.027	0.48	NO
34	CDK11B	CDK11B	CDK11B	7555	0.024	0.47	NO
35	CASP2	CASP2	CASP2	7684	0.022	0.47	NO
36	CASP3	CASP3	CASP3	7713	0.022	0.47	NO
37	LMNA	LMNA	LMNA	8271	0.016	0.45	NO
38	PRKDC	PRKDC	PRKDC	8381	0.015	0.44	NO
39	PSEN2	PSEN2	PSEN2	8430	0.014	0.44	NO
40	CASP9	CASP9	CASP9	8663	0.012	0.44	NO
41	XIAP	XIAP	XIAP	8852	0.0096	0.43	NO
42	CHUK	CHUK	CHUK	8926	0.0087	0.42	NO
43	DAXX	DAXX	DAXX	9331	0.0045	0.4	NO
44	LMNB2	LMNB2	LMNB2	9336	0.0045	0.4	NO
45	FADD	FADD	FADD	9464	0.0032	0.4	NO
46	DFFA	DFFA	DFFA	9619	0.0015	0.39	NO
47	TRAF2	TRAF2	TRAF2	9813	-0.00064	0.38	NO
48	NUMA1	NUMA1	NUMA1	9836	-0.00088	0.38	NO
49	SPTAN1	SPTAN1	SPTAN1	9892	-0.0015	0.38	NO
50	ACTG1	ACTG1	ACTG1	10521	-0.0077	0.34	NO
51	CASP8	CASP8	CASP8	11146	-0.014	0.31	NO
52	MAP2K7	MAP2K7	MAP2K7	12337	-0.027	0.25	NO
53	CASP6	CASP6	CASP6	13132	-0.037	0.22	NO
54	TRADD	TRADD	TRADD	13249	-0.039	0.22	NO
55	CYCS	CYCS	CYCS	13394	-0.041	0.22	NO
56	PTK2	PTK2	PTK2	14600	-0.061	0.17	NO
57	DFFB	DFFB	DFFB	14732	-0.064	0.18	NO

Figure S3. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA AT1R PATHWAY.

Figure S4. 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 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	PIK3CG	PIK3CG	PIK3CG	54	0.64	0.092	YES
2	FLT3	FLT3	FLT3	216	0.54	0.16	YES
3	PIK3R5	PIK3R5	PIK3R5	292	0.5	0.23	YES
4	KIT	KIT	KIT	577	0.42	0.28	YES
5	RUNX1	RUNX1	RUNX1	752	0.38	0.33	YES
6	CCNA1	CCNA1	CCNA1	817	0.36	0.38	YES
7	SPI1	SPI1	SPI1	979	0.34	0.42	YES
8	RUNX1T1	RUNX1T1	RUNX1T1	1176	0.31	0.45	YES
9	LEF1	LEF1	LEF1	1182	0.3	0.5	YES
10	TCF7	TCF7	TCF7	1342	0.28	0.53	YES
11	ZBTB16	ZBTB16	ZBTB16	1577	0.25	0.56	YES
12	PIM2	PIM2	PIM2	1655	0.24	0.59	YES
13	CEBPA	CEBPA	CEBPA	2177	0.19	0.59	YES
14	PIK3CD	PIK3CD	PIK3CD	2560	0.16	0.59	YES
15	STAT5A	STAT5A	STAT5A	3048	0.14	0.58	NO
16	NFKB1	NFKB1	NFKB1	3971	0.096	0.55	NO
17	PML	PML	PML	4224	0.088	0.55	NO
18	PIK3CA	PIK3CA	PIK3CA	4304	0.085	0.55	NO
19	STAT3	STAT3	STAT3	4985	0.067	0.53	NO
20	RARA	RARA	RARA	5025	0.066	0.53	NO
21	MYC	MYC	MYC	5809	0.05	0.5	NO
22	PIK3R1	PIK3R1	PIK3R1	5992	0.047	0.49	NO
23	KRAS	KRAS	KRAS	6005	0.046	0.5	NO
24	PIM1	PIM1	PIM1	6150	0.044	0.5	NO
25	MAPK1	MAPK1	MAPK1	6275	0.042	0.5	NO
26	MAP2K1	MAP2K1	MAP2K1	6295	0.041	0.5	NO
27	RELA	RELA	RELA	6534	0.037	0.5	NO
28	PIK3CB	PIK3CB	PIK3CB	6841	0.033	0.48	NO
29	MTOR	MTOR	MTOR	6859	0.033	0.49	NO
30	STAT5B	STAT5B	STAT5B	6946	0.031	0.49	NO
31	GRB2	GRB2	GRB2	7037	0.03	0.49	NO
32	AKT3	AKT3	AKT3	7264	0.028	0.48	NO
33	AKT1	AKT1	AKT1	7964	0.019	0.44	NO
34	RAF1	RAF1	RAF1	8047	0.018	0.44	NO
35	SOS2	SOS2	SOS2	8133	0.017	0.44	NO
36	NRAS	NRAS	NRAS	8216	0.016	0.44	NO
37	CHUK	CHUK	CHUK	8926	0.0087	0.4	NO
38	TCF7L2	TCF7L2	TCF7L2	9070	0.0073	0.39	NO
39	BRAF	BRAF	BRAF	9147	0.0064	0.39	NO
40	JUP	JUP	JUP	9245	0.0056	0.38	NO
41	SOS1	SOS1	SOS1	9734	0.00026	0.36	NO
42	MAPK3	MAPK3	MAPK3	9797	-0.00052	0.35	NO
43	IKBKB	IKBKB	IKBKB	10080	-0.0033	0.34	NO
44	IKBKG	IKBKG	IKBKG	10531	-0.0078	0.31	NO
45	ARAF	ARAF	ARAF	10562	-0.0081	0.31	NO
46	RPS6KB1	RPS6KB1	RPS6KB1	11028	-0.013	0.29	NO
47	AKT2	AKT2	AKT2	11065	-0.014	0.29	NO
48	RPS6KB2	RPS6KB2	RPS6KB2	12142	-0.025	0.23	NO
49	PIK3R2	PIK3R2	PIK3R2	13041	-0.036	0.19	NO
50	MAP2K2	MAP2K2	MAP2K2	13345	-0.04	0.18	NO
51	BAD	BAD	BAD	14352	-0.056	0.13	NO
52	EIF4EBP1	EIF4EBP1	EIF4EBP1	14722	-0.064	0.12	NO
53	CCND1	CCND1	CCND1	14772	-0.064	0.12	NO
54	HRAS	HRAS	HRAS	15391	-0.08	0.1	NO
55	PIK3R3	PIK3R3	PIK3R3	15706	-0.09	0.098	NO
56	TCF7L1	TCF7L1	TCF7L1	17303	-0.19	0.038	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 BCR PATHWAY.

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

genes ES table in pathway: BIOCARTA HDAC PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PIK3CG	PIK3CG	PIK3CG	54	0.64	0.069	YES
2	CSF2RB	CSF2RB	CSF2RB	151	0.57	0.13	YES
3	IRAK3	IRAK3	IRAK3	218	0.54	0.18	YES
4	TNF	TNF	TNF	233	0.53	0.24	YES
5	PIK3R5	PIK3R5	PIK3R5	292	0.5	0.29	YES
6	IL1B	IL1B	IL1B	656	0.4	0.32	YES
7	IL1A	IL1A	IL1A	693	0.39	0.36	YES
8	NTRK1	NTRK1	NTRK1	864	0.36	0.39	YES
9	BIRC3	BIRC3	BIRC3	960	0.34	0.42	YES
10	IL1RAP	IL1RAP	IL1RAP	1558	0.26	0.42	YES
11	IRAK2	IRAK2	IRAK2	1833	0.22	0.43	YES
12	TNFRSF10A	TNFRSF10A	TNFRSF10A	1969	0.21	0.44	YES
13	NGF	NGF	NGF	2003	0.21	0.47	YES
14	TNFSF10	TNFSF10	TNFSF10	2175	0.19	0.48	YES
15	PIK3CD	PIK3CD	PIK3CD	2560	0.16	0.48	YES
16	PRKAR2B	PRKAR2B	PRKAR2B	2821	0.15	0.48	YES
17	PRKAR2A	PRKAR2A	PRKAR2A	3240	0.13	0.47	YES
18	MYD88	MYD88	MYD88	3341	0.12	0.48	YES
19	PRKACB	PRKACB	PRKACB	3414	0.12	0.49	YES
20	IL1R1	IL1R1	IL1R1	3491	0.12	0.5	YES
21	IL3RA	IL3RA	IL3RA	3541	0.11	0.5	YES
22	NFKBIA	NFKBIA	NFKBIA	3867	0.1	0.5	YES
23	NFKB1	NFKB1	NFKB1	3971	0.096	0.5	YES
24	BID	BID	BID	4068	0.093	0.51	YES
25	CASP7	CASP7	CASP7	4250	0.087	0.51	YES
26	PIK3CA	PIK3CA	PIK3CA	4304	0.085	0.51	YES
27	TNFRSF10D	TNFRSF10D	TNFRSF10D	4394	0.083	0.52	YES
28	FAS	FAS	FAS	4402	0.082	0.53	YES
29	TNFRSF1A	TNFRSF1A	TNFRSF1A	4562	0.078	0.53	NO
30	IRAK4	IRAK4	IRAK4	4962	0.068	0.51	NO
31	PRKX	PRKX	PRKX	5043	0.066	0.52	NO
32	APAF1	APAF1	APAF1	5057	0.065	0.52	NO
33	BCL2	BCL2	BCL2	5168	0.062	0.52	NO
34	CAPN1	CAPN1	CAPN1	5356	0.058	0.52	NO
35	TNFRSF10C	TNFRSF10C	TNFRSF10C	5408	0.057	0.52	NO
36	RIPK1	RIPK1	RIPK1	5729	0.051	0.51	NO
37	CFLAR	CFLAR	CFLAR	5892	0.049	0.51	NO
38	PIK3R1	PIK3R1	PIK3R1	5992	0.047	0.51	NO
39	MAP3K14	MAP3K14	MAP3K14	6115	0.044	0.5	NO
40	PPP3CA	PPP3CA	PPP3CA	6217	0.043	0.5	NO
41	BIRC2	BIRC2	BIRC2	6485	0.038	0.49	NO
42	PPP3CB	PPP3CB	PPP3CB	6522	0.038	0.5	NO
43	RELA	RELA	RELA	6534	0.037	0.5	NO
44	CASP10	CASP10	CASP10	6656	0.036	0.5	NO
45	ATM	ATM	ATM	6761	0.034	0.49	NO
46	PPP3R1	PPP3R1	PPP3R1	6827	0.033	0.49	NO
47	PIK3CB	PIK3CB	PIK3CB	6841	0.033	0.5	NO
48	AKT3	AKT3	AKT3	7264	0.028	0.48	NO
49	CHP	CHP	CHP	7519	0.024	0.46	NO
50	PRKAR1A	PRKAR1A	PRKAR1A	7678	0.022	0.46	NO
51	CASP3	CASP3	CASP3	7713	0.022	0.46	NO
52	AKT1	AKT1	AKT1	7964	0.019	0.45	NO
53	PRKACA	PRKACA	PRKACA	8252	0.016	0.43	NO
54	CASP9	CASP9	CASP9	8663	0.012	0.41	NO
55	XIAP	XIAP	XIAP	8852	0.0096	0.4	NO
56	CHUK	CHUK	CHUK	8926	0.0087	0.4	NO
57	BCL2L1	BCL2L1	BCL2L1	9314	0.0048	0.38	NO
58	TP53	TP53	TP53	9422	0.0036	0.37	NO
59	FADD	FADD	FADD	9464	0.0032	0.37	NO
60	CAPN2	CAPN2	CAPN2	9478	0.003	0.37	NO
61	PPP3CC	PPP3CC	PPP3CC	9553	0.0023	0.37	NO
62	DFFA	DFFA	DFFA	9619	0.0015	0.36	NO
63	TNFRSF10B	TNFRSF10B	TNFRSF10B	9692	0.00076	0.36	NO
64	TRAF2	TRAF2	TRAF2	9813	-0.00064	0.35	NO
65	ENDOD1	ENDOD1	ENDOD1	9873	-0.0012	0.35	NO
66	IKBKB	IKBKB	IKBKB	10080	-0.0033	0.34	NO
67	BAX	BAX	BAX	10358	-0.006	0.32	NO
68	IKBKG	IKBKG	IKBKG	10531	-0.0078	0.31	NO
69	AKT2	AKT2	AKT2	11065	-0.014	0.29	NO
70	CASP8	CASP8	CASP8	11146	-0.014	0.28	NO
71	EXOG	EXOG	EXOG	11218	-0.015	0.28	NO
72	IRAK1	IRAK1	IRAK1	12176	-0.025	0.23	NO
73	PIK3R2	PIK3R2	PIK3R2	13041	-0.036	0.19	NO
74	CASP6	CASP6	CASP6	13132	-0.037	0.18	NO
75	TRADD	TRADD	TRADD	13249	-0.039	0.18	NO
76	CYCS	CYCS	CYCS	13394	-0.041	0.18	NO
77	PRKAR1B	PRKAR1B	PRKAR1B	13880	-0.048	0.16	NO
78	AIFM1	AIFM1	AIFM1	13898	-0.048	0.16	NO
79	BAD	BAD	BAD	14352	-0.056	0.14	NO
80	DFFB	DFFB	DFFB	14732	-0.064	0.13	NO
81	PIK3R3	PIK3R3	PIK3R3	15706	-0.09	0.085	NO
82	ENDOG	ENDOG	ENDOG	16751	-0.14	0.042	NO
83	CHP2	CHP2	CHP2	17581	-0.23	0.022	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 HDAC PATHWAY.

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

genes ES table in pathway: BIOCARTA EGF PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PIK3CG	PIK3CG	PIK3CG	54	0.64	0.22	YES
2	CAMK1G	CAMK1G	CAMK1G	173	0.56	0.4	YES
3	IGF1	IGF1	IGF1	435	0.45	0.55	YES
4	NFATC2	NFATC2	NFATC2	865	0.36	0.64	YES
5	NFATC1	NFATC1	NFATC1	2521	0.17	0.61	NO
6	PIK3CA	PIK3CA	PIK3CA	4304	0.085	0.54	NO
7	MEF2D	MEF2D	MEF2D	4927	0.068	0.53	NO
8	YWHAH	YWHAH	YWHAH	5724	0.052	0.5	NO
9	PIK3R1	PIK3R1	PIK3R1	5992	0.047	0.5	NO
10	PPP3CA	PPP3CA	PPP3CA	6217	0.043	0.51	NO
11	PPP3CB	PPP3CB	PPP3CB	6522	0.038	0.5	NO
12	MAPK14	MAPK14	MAPK14	6528	0.037	0.51	NO
13	IGF1R	IGF1R	IGF1R	6746	0.034	0.51	NO
14	MEF2A	MEF2A	MEF2A	7186	0.029	0.5	NO
15	MAPK7	MAPK7	MAPK7	7370	0.026	0.5	NO
16	CABIN1	CABIN1	CABIN1	7489	0.025	0.5	NO
17	CALM3	CALM3	CALM3	7577	0.024	0.5	NO
18	CALM2	CALM2	CALM2	7962	0.019	0.49	NO
19	AKT1	AKT1	AKT1	7964	0.019	0.5	NO
20	CALM1	CALM1	CALM1	8743	0.011	0.46	NO
21	PPP3CC	PPP3CC	PPP3CC	9553	0.0023	0.41	NO
22	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	10091	-0.0034	0.38	NO
23	MAP2K6	MAP2K6	MAP2K6	10717	-0.0099	0.35	NO
24	CAMK1	CAMK1	CAMK1	13902	-0.048	0.19	NO
25	HDAC5	HDAC5	HDAC5	13952	-0.049	0.2	NO
26	INSR	INSR	INSR	14435	-0.057	0.2	NO

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

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

genes ES table in pathway: BIOCARTA ERK PATHWAY

Table 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	CCL22	CCL22	CCL22	11	0.76	0.019	YES
2	CXCL5	CXCL5	CXCL5	19	0.71	0.038	YES
3	CXCR2	CXCR2	CXCR2	32	0.66	0.054	YES
4	CCL23	CCL23	CCL23	37	0.66	0.071	YES
5	CCR4	CCR4	CCR4	43	0.65	0.088	YES
6	CCL13	CCL13	CCL13	52	0.64	0.1	YES
7	PIK3CG	PIK3CG	PIK3CG	54	0.64	0.12	YES
8	CXCR1	CXCR1	CXCR1	69	0.62	0.14	YES
9	CCR7	CCR7	CCR7	70	0.62	0.15	YES
10	CXCL6	CXCL6	CXCL6	73	0.62	0.17	YES
11	CXCR6	CXCR6	CXCR6	86	0.61	0.18	YES
12	CCR2	CCR2	CCR2	126	0.58	0.2	YES
13	IL8	IL8	IL8	131	0.58	0.21	YES
14	CCL18	CCL18	CCL18	135	0.58	0.23	YES
15	ITK	ITK	ITK	162	0.56	0.24	YES
16	PF4	PF4	PF4	169	0.56	0.26	YES
17	CXCL1	CXCL1	CXCL1	196	0.55	0.27	YES
18	CCL7	CCL7	CCL7	217	0.54	0.28	YES
19	CXCL3	CXCL3	CXCL3	219	0.54	0.3	YES
20	CXCL2	CXCL2	CXCL2	273	0.51	0.31	YES
21	PF4V1	PF4V1	PF4V1	287	0.5	0.32	YES
22	PIK3R5	PIK3R5	PIK3R5	292	0.5	0.33	YES
23	CCR5	CCR5	CCR5	304	0.5	0.34	YES
24	CCR3	CCR3	CCR3	312	0.49	0.36	YES
25	FGR	FGR	FGR	333	0.48	0.37	YES
26	CCR1	CCR1	CCR1	342	0.48	0.38	YES
27	CCL21	CCL21	CCL21	351	0.48	0.39	YES
28	CXCR5	CXCR5	CXCR5	371	0.47	0.4	YES
29	CCL24	CCL24	CCL24	382	0.47	0.42	YES
30	CCL11	CCL11	CCL11	386	0.47	0.43	YES
31	GNGT2	GNGT2	GNGT2	393	0.47	0.44	YES
32	DOCK2	DOCK2	DOCK2	401	0.46	0.45	YES
33	VAV1	VAV1	VAV1	428	0.46	0.46	YES
34	CCR6	CCR6	CCR6	436	0.45	0.47	YES
35	CCL4L2	CCL4L2	CCL4L2	447	0.45	0.48	YES
36	HCK	HCK	HCK	511	0.43	0.49	YES
37	PRKCB	PRKCB	PRKCB	548	0.42	0.5	YES
38	NCF1	NCF1	NCF1	550	0.42	0.51	YES
39	GNG2	GNG2	GNG2	554	0.42	0.52	YES
40	CCL4	CCL4	CCL4	622	0.41	0.53	YES
41	TIAM1	TIAM1	TIAM1	630	0.41	0.54	YES
42	CXCR3	CXCR3	CXCR3	649	0.4	0.55	YES
43	CCL2	CCL2	CCL2	668	0.4	0.56	YES
44	PPBP	PPBP	PPBP	669	0.4	0.57	YES
45	CCL28	CCL28	CCL28	722	0.38	0.58	YES
46	WAS	WAS	WAS	730	0.38	0.59	YES
47	CCL17	CCL17	CCL17	733	0.38	0.6	YES
48	CCL20	CCL20	CCL20	736	0.38	0.61	YES
49	RASGRP2	RASGRP2	RASGRP2	882	0.36	0.61	YES
50	CCL5	CCL5	CCL5	898	0.35	0.62	YES
51	XCR1	XCR1	XCR1	903	0.35	0.62	YES
52	CXCR4	CXCR4	CXCR4	950	0.34	0.63	YES
53	XCL2	XCL2	XCL2	1015	0.34	0.64	YES
54	ELMO1	ELMO1	ELMO1	1029	0.33	0.64	YES
55	CCL3L1	CCL3L1	CCL3L1	1046	0.33	0.65	YES
56	RAC2	RAC2	RAC2	1048	0.33	0.66	YES
57	XCL1	XCL1	XCL1	1098	0.32	0.67	YES
58	CCL26	CCL26	CCL26	1101	0.32	0.67	YES
59	CCL3	CCL3	CCL3	1126	0.31	0.68	YES
60	CCL19	CCL19	CCL19	1235	0.3	0.68	YES
61	PREX1	PREX1	PREX1	1284	0.29	0.69	YES
62	CCR8	CCR8	CCR8	1331	0.28	0.69	YES
63	CXCL9	CXCL9	CXCL9	1337	0.28	0.7	YES
64	GNB4	GNB4	GNB4	1353	0.28	0.71	YES
65	PLCB2	PLCB2	PLCB2	1415	0.27	0.71	YES
66	CCL14	CCL14	CCL14	1421	0.27	0.72	YES
67	CCL8	CCL8	CCL8	1446	0.27	0.72	YES
68	ADRBK2	ADRBK2	ADRBK2	1605	0.25	0.72	YES
69	CCL3L3	CCL3L3	CCL3L3	1658	0.24	0.72	YES
70	CX3CR1	CX3CR1	CX3CR1	1756	0.23	0.72	YES
71	LYN	LYN	LYN	1799	0.23	0.73	YES
72	CXCL12	CXCL12	CXCL12	1864	0.22	0.73	YES
73	JAK3	JAK3	JAK3	1956	0.21	0.73	YES
74	ARRB1	ARRB1	ARRB1	1998	0.21	0.73	YES
75	CXCL16	CXCL16	CXCL16	2005	0.21	0.74	YES
76	ARRB2	ARRB2	ARRB2	2264	0.18	0.73	NO
77	CXCL10	CXCL10	CXCL10	2296	0.18	0.73	NO
78	PIK3CD	PIK3CD	PIK3CD	2560	0.16	0.72	NO
79	GNGT1	GNGT1	GNGT1	2639	0.16	0.72	NO
80	CCR9	CCR9	CCR9	2910	0.14	0.71	NO
81	ADCY7	ADCY7	ADCY7	3329	0.12	0.69	NO
82	PTK2B	PTK2B	PTK2B	3335	0.12	0.69	NO
83	PRKACB	PRKACB	PRKACB	3414	0.12	0.69	NO
84	GRK5	GRK5	GRK5	3526	0.11	0.69	NO
85	GNAI1	GNAI1	GNAI1	3623	0.11	0.69	NO
86	SHC4	SHC4	SHC4	3750	0.1	0.68	NO
87	RAP1A	RAP1A	RAP1A	3785	0.1	0.68	NO
88	NFKBIA	NFKBIA	NFKBIA	3867	0.1	0.68	NO
89	NFKB1	NFKB1	NFKB1	3971	0.096	0.68	NO
90	CXCL11	CXCL11	CXCL11	4012	0.095	0.68	NO
91	CXCL13	CXCL13	CXCL13	4135	0.091	0.67	NO
92	PIK3CA	PIK3CA	PIK3CA	4304	0.085	0.66	NO
93	JAK2	JAK2	JAK2	4351	0.084	0.66	NO
94	SHC3	SHC3	SHC3	4524	0.079	0.66	NO
95	GNAI2	GNAI2	GNAI2	4601	0.077	0.66	NO
96	ADCY5	ADCY5	ADCY5	4621	0.077	0.66	NO
97	ADCY4	ADCY4	ADCY4	4667	0.075	0.66	NO
98	STAT2	STAT2	STAT2	4794	0.072	0.65	NO
99	STAT3	STAT3	STAT3	4985	0.067	0.64	NO
100	SHC2	SHC2	SHC2	4986	0.067	0.64	NO
101	PRKX	PRKX	PRKX	5043	0.066	0.64	NO
102	RAP1B	RAP1B	RAP1B	5101	0.064	0.64	NO
103	ADRBK1	ADRBK1	ADRBK1	5141	0.063	0.64	NO
104	GRK6	GRK6	GRK6	5228	0.061	0.64	NO
105	CSK	CSK	CSK	5330	0.059	0.63	NO
106	GNG10	GNG10	GNG10	5419	0.057	0.63	NO
107	CRKL	CRKL	CRKL	5508	0.056	0.63	NO
108	FOXO3	FOXO3	FOXO3	5699	0.052	0.62	NO
109	PLCB1	PLCB1	PLCB1	5712	0.052	0.62	NO
110	CXCL14	CXCL14	CXCL14	5794	0.05	0.61	NO
111	CDC42	CDC42	CDC42	5836	0.05	0.61	NO
112	STAT1	STAT1	STAT1	5848	0.049	0.61	NO
113	PIK3R1	PIK3R1	PIK3R1	5992	0.047	0.61	NO
114	KRAS	KRAS	KRAS	6005	0.046	0.61	NO
115	PRKCD	PRKCD	PRKCD	6086	0.045	0.6	NO
116	ROCK1	ROCK1	ROCK1	6127	0.044	0.6	NO
117	GNAI3	GNAI3	GNAI3	6227	0.042	0.6	NO
118	RAC1	RAC1	RAC1	6233	0.042	0.6	NO
119	MAPK1	MAPK1	MAPK1	6275	0.042	0.6	NO
120	MAP2K1	MAP2K1	MAP2K1	6295	0.041	0.6	NO
121	GNB1	GNB1	GNB1	6510	0.038	0.59	NO
122	RELA	RELA	RELA	6534	0.037	0.59	NO
123	RHOA	RHOA	RHOA	6703	0.035	0.58	NO
124	PIK3CB	PIK3CB	PIK3CB	6841	0.033	0.57	NO
125	STAT5B	STAT5B	STAT5B	6946	0.031	0.57	NO
126	GNG12	GNG12	GNG12	6952	0.031	0.57	NO
127	ADCY2	ADCY2	ADCY2	7010	0.031	0.56	NO
128	GRB2	GRB2	GRB2	7037	0.03	0.56	NO
129	ROCK2	ROCK2	ROCK2	7226	0.028	0.55	NO
130	AKT3	AKT3	AKT3	7264	0.028	0.55	NO
131	GNG7	GNG7	GNG7	7355	0.027	0.55	NO
132	PXN	PXN	PXN	7502	0.025	0.54	NO
133	TIAM2	TIAM2	TIAM2	7698	0.022	0.53	NO
134	CRK	CRK	CRK	7744	0.022	0.53	NO
135	GSK3B	GSK3B	GSK3B	7770	0.021	0.53	NO
136	CCR10	CCR10	CCR10	7837	0.02	0.52	NO
137	AKT1	AKT1	AKT1	7964	0.019	0.52	NO
138	ADCY8	ADCY8	ADCY8	7997	0.019	0.52	NO
139	RAF1	RAF1	RAF1	8047	0.018	0.51	NO
140	SOS2	SOS2	SOS2	8133	0.017	0.51	NO
141	NRAS	NRAS	NRAS	8216	0.016	0.5	NO
142	GNB2	GNB2	GNB2	8240	0.016	0.5	NO
143	PRKACA	PRKACA	PRKACA	8252	0.016	0.5	NO
144	SHC1	SHC1	SHC1	8457	0.014	0.49	NO
145	GNG5	GNG5	GNG5	8543	0.013	0.49	NO
146	WASL	WASL	WASL	8796	0.01	0.48	NO
147	PAK1	PAK1	PAK1	8825	0.0098	0.47	NO
148	CHUK	CHUK	CHUK	8926	0.0087	0.47	NO
149	BRAF	BRAF	BRAF	9147	0.0064	0.46	NO
150	GNG11	GNG11	GNG11	9449	0.0033	0.44	NO
151	SOS1	SOS1	SOS1	9734	0.00026	0.42	NO
152	MAPK3	MAPK3	MAPK3	9797	-0.00052	0.42	NO
153	IKBKB	IKBKB	IKBKB	10080	-0.0033	0.4	NO
154	CX3CL1	CX3CL1	CX3CL1	10196	-0.0043	0.4	NO
155	ADCY6	ADCY6	ADCY6	10327	-0.0057	0.39	NO
156	ADCY9	ADCY9	ADCY9	10409	-0.0066	0.39	NO
157	IKBKG	IKBKG	IKBKG	10531	-0.0078	0.38	NO
158	GRK7	GRK7	GRK7	10608	-0.0086	0.38	NO
159	GNB5	GNB5	GNB5	10684	-0.0096	0.37	NO
160	PARD3	PARD3	PARD3	10691	-0.0097	0.37	NO
161	AKT2	AKT2	AKT2	11065	-0.014	0.35	NO
162	VAV3	VAV3	VAV3	11109	-0.014	0.35	NO
163	GSK3A	GSK3A	GSK3A	11344	-0.017	0.34	NO
164	NFKBIB	NFKBIB	NFKBIB	11794	-0.021	0.31	NO
165	PLCB4	PLCB4	PLCB4	11928	-0.022	0.3	NO
166	PIK3R2	PIK3R2	PIK3R2	13041	-0.036	0.24	NO
167	BCAR1	BCAR1	BCAR1	13117	-0.037	0.24	NO
168	PRKCZ	PRKCZ	PRKCZ	13169	-0.038	0.24	NO
169	VAV2	VAV2	VAV2	13405	-0.041	0.23	NO
170	PLCB3	PLCB3	PLCB3	13657	-0.045	0.21	NO
171	PTK2	PTK2	PTK2	14600	-0.061	0.16	NO
172	CCL15	CCL15	CCL15	14607	-0.061	0.16	NO
173	GNG4	GNG4	GNG4	15280	-0.077	0.13	NO
174	CCL16	CCL16	CCL16	15283	-0.077	0.13	NO
175	HRAS	HRAS	HRAS	15391	-0.08	0.12	NO
176	GNB3	GNB3	GNB3	15677	-0.089	0.11	NO
177	PIK3R3	PIK3R3	PIK3R3	15706	-0.09	0.11	NO
178	GNG3	GNG3	GNG3	16009	-0.1	0.098	NO
179	CCL25	CCL25	CCL25	16180	-0.11	0.091	NO
180	GRK4	GRK4	GRK4	16378	-0.12	0.083	NO
181	CCL27	CCL27	CCL27	16456	-0.12	0.082	NO
182	ADCY1	ADCY1	ADCY1	16510	-0.13	0.083	NO

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

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

genes ES table in pathway: BIOCARTA FAS PATHWAY

Table S7. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	FCER1A	FCER1A	FCER1A	15	0.72	0.068	YES
2	PIK3CG	PIK3CG	PIK3CG	54	0.64	0.13	YES
3	PLA2G2D	PLA2G2D	PLA2G2D	55	0.64	0.19	YES
4	TNF	TNF	TNF	233	0.53	0.23	YES
5	MS4A2	MS4A2	MS4A2	284	0.51	0.27	YES
6	PIK3R5	PIK3R5	PIK3R5	292	0.5	0.32	YES
7	BTK	BTK	BTK	302	0.5	0.36	YES
8	PLA2G4A	PLA2G4A	PLA2G4A	314	0.49	0.41	YES
9	CSF2	CSF2	CSF2	365	0.48	0.45	YES
10	VAV1	VAV1	VAV1	428	0.46	0.49	YES
11	PRKCB	PRKCB	PRKCB	548	0.42	0.53	YES
12	LCP2	LCP2	LCP2	572	0.42	0.56	YES
13	FCER1G	FCER1G	FCER1G	698	0.39	0.59	YES
14	RAC2	RAC2	RAC2	1048	0.33	0.6	YES
15	SYK	SYK	SYK	1431	0.27	0.61	YES
16	INPP5D	INPP5D	INPP5D	1491	0.26	0.63	YES
17	LYN	LYN	LYN	1799	0.23	0.64	YES
18	MAPK13	MAPK13	MAPK13	1869	0.22	0.65	YES
19	PIK3CD	PIK3CD	PIK3CD	2560	0.16	0.63	NO
20	GAB2	GAB2	GAB2	2974	0.14	0.62	NO
21	PLA2G2A	PLA2G2A	PLA2G2A	3339	0.12	0.61	NO
22	PLCG2	PLCG2	PLCG2	3844	0.1	0.59	NO
23	PIK3CA	PIK3CA	PIK3CA	4304	0.085	0.57	NO
24	MAPK8	MAPK8	MAPK8	4370	0.083	0.58	NO
25	PLA2G5	PLA2G5	PLA2G5	5027	0.066	0.55	NO
26	PDK1	PDK1	PDK1	5052	0.065	0.55	NO
27	MAP2K3	MAP2K3	MAP2K3	5163	0.063	0.55	NO
28	PIK3R1	PIK3R1	PIK3R1	5992	0.047	0.51	NO
29	KRAS	KRAS	KRAS	6005	0.046	0.52	NO
30	PRKCD	PRKCD	PRKCD	6086	0.045	0.52	NO
31	RAC1	RAC1	RAC1	6233	0.042	0.51	NO
32	MAPK1	MAPK1	MAPK1	6275	0.042	0.51	NO
33	MAP2K1	MAP2K1	MAP2K1	6295	0.041	0.52	NO
34	MAPK14	MAPK14	MAPK14	6528	0.037	0.51	NO
35	PIK3CB	PIK3CB	PIK3CB	6841	0.033	0.49	NO
36	GRB2	GRB2	GRB2	7037	0.03	0.48	NO
37	AKT3	AKT3	AKT3	7264	0.028	0.47	NO
38	MAP2K4	MAP2K4	MAP2K4	7314	0.027	0.47	NO
39	PLA2G12B	PLA2G12B	PLA2G12B	7680	0.022	0.46	NO
40	AKT1	AKT1	AKT1	7964	0.019	0.44	NO
41	RAF1	RAF1	RAF1	8047	0.018	0.44	NO
42	SOS2	SOS2	SOS2	8133	0.017	0.44	NO
43	NRAS	NRAS	NRAS	8216	0.016	0.43	NO
44	PRKCA	PRKCA	PRKCA	8662	0.012	0.41	NO
45	SOS1	SOS1	SOS1	9734	0.00026	0.35	NO
46	MAPK3	MAPK3	MAPK3	9797	-0.00052	0.34	NO
47	LAT	LAT	LAT	9928	-0.0019	0.34	NO
48	FYN	FYN	FYN	10495	-0.0074	0.31	NO
49	MAPK11	MAPK11	MAPK11	10711	-0.0099	0.3	NO
50	MAP2K6	MAP2K6	MAP2K6	10717	-0.0099	0.3	NO
51	AKT2	AKT2	AKT2	11065	-0.014	0.28	NO
52	VAV3	VAV3	VAV3	11109	-0.014	0.28	NO
53	MAPK10	MAPK10	MAPK10	11560	-0.019	0.25	NO
54	PRKCE	PRKCE	PRKCE	11839	-0.021	0.24	NO
55	PLA2G1B	PLA2G1B	PLA2G1B	12188	-0.025	0.22	NO
56	MAP2K7	MAP2K7	MAP2K7	12337	-0.027	0.22	NO
57	MAPK9	MAPK9	MAPK9	12895	-0.034	0.19	NO
58	PIK3R2	PIK3R2	PIK3R2	13041	-0.036	0.19	NO
59	PLA2G10	PLA2G10	PLA2G10	13154	-0.037	0.18	NO
60	MAP2K2	MAP2K2	MAP2K2	13345	-0.04	0.18	NO
61	VAV2	VAV2	VAV2	13405	-0.041	0.18	NO
62	PLA2G12A	PLA2G12A	PLA2G12A	13446	-0.041	0.18	NO
63	JMJD7-PLA2G4B	JMJD7-PLA2G4B	JMJD7-PLA2G4B	13886	-0.048	0.16	NO
64	PLCG1	PLCG1	PLCG1	15004	-0.07	0.1	NO
65	PIK3R3	PIK3R3	PIK3R3	15706	-0.09	0.072	NO
66	PLA2G6	PLA2G6	PLA2G6	16395	-0.12	0.045	NO
67	RAC3	RAC3	RAC3	17370	-0.2	0.0098	NO
68	MAPK12	MAPK12	MAPK12	17692	-0.26	0.016	NO

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

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

genes ES table in pathway: BIOCARTA FCER1 PATHWAY

Table S8. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PIK3CG	PIK3CG	PIK3CG	54	0.64	0.11	YES
2	PIK3R5	PIK3R5	PIK3R5	292	0.5	0.19	YES
3	RUNX1	RUNX1	RUNX1	752	0.38	0.23	YES
4	TGFB2	TGFB2	TGFB2	1647	0.24	0.22	YES
5	CBLC	CBLC	CBLC	1795	0.23	0.26	YES
6	TGFB3	TGFB3	TGFB3	2380	0.18	0.26	YES
7	PIK3CD	PIK3CD	PIK3CD	2560	0.16	0.28	YES
8	TGFBR2	TGFBR2	TGFBR2	2944	0.14	0.28	YES
9	GAB2	GAB2	GAB2	2974	0.14	0.3	YES
10	STAT5A	STAT5A	STAT5A	3048	0.14	0.32	YES
11	CBLB	CBLB	CBLB	3251	0.13	0.34	YES
12	TGFB1	TGFB1	TGFB1	3607	0.11	0.34	YES
13	SHC4	SHC4	SHC4	3750	0.1	0.35	YES
14	NFKBIA	NFKBIA	NFKBIA	3867	0.1	0.36	YES
15	NFKB1	NFKB1	NFKB1	3971	0.096	0.37	YES
16	CDKN1B	CDKN1B	CDKN1B	4066	0.094	0.38	YES
17	PIK3CA	PIK3CA	PIK3CA	4304	0.085	0.38	YES
18	CDKN1A	CDKN1A	CDKN1A	4337	0.084	0.4	YES
19	TGFBR1	TGFBR1	TGFBR1	4491	0.08	0.4	YES
20	SHC3	SHC3	SHC3	4524	0.079	0.42	YES
21	CDK6	CDK6	CDK6	4551	0.078	0.43	YES
22	CBL	CBL	CBL	4873	0.07	0.42	YES
23	SHC2	SHC2	SHC2	4986	0.067	0.43	YES
24	CDKN2A	CDKN2A	CDKN2A	5297	0.06	0.42	YES
25	RB1	RB1	RB1	5353	0.058	0.43	YES
26	MDM2	MDM2	MDM2	5365	0.058	0.44	YES
27	CRKL	CRKL	CRKL	5508	0.056	0.44	YES
28	BCR	BCR	BCR	5560	0.054	0.45	YES
29	MYC	MYC	MYC	5809	0.05	0.44	YES
30	CTBP2	CTBP2	CTBP2	5821	0.05	0.45	YES
31	PTPN11	PTPN11	PTPN11	5914	0.048	0.46	YES
32	PIK3R1	PIK3R1	PIK3R1	5992	0.047	0.46	YES
33	KRAS	KRAS	KRAS	6005	0.046	0.47	YES
34	MAPK1	MAPK1	MAPK1	6275	0.042	0.46	YES
35	MAP2K1	MAP2K1	MAP2K1	6295	0.041	0.46	YES
36	SMAD3	SMAD3	SMAD3	6336	0.04	0.47	YES
37	RELA	RELA	RELA	6534	0.037	0.47	NO
38	PIK3CB	PIK3CB	PIK3CB	6841	0.033	0.46	NO
39	STAT5B	STAT5B	STAT5B	6946	0.031	0.46	NO
40	SMAD4	SMAD4	SMAD4	6956	0.031	0.46	NO
41	HDAC1	HDAC1	HDAC1	7028	0.03	0.46	NO
42	GRB2	GRB2	GRB2	7037	0.03	0.47	NO
43	AKT3	AKT3	AKT3	7264	0.028	0.46	NO
44	CRK	CRK	CRK	7744	0.022	0.44	NO
45	AKT1	AKT1	AKT1	7964	0.019	0.43	NO
46	E2F3	E2F3	E2F3	8005	0.018	0.43	NO
47	RAF1	RAF1	RAF1	8047	0.018	0.43	NO
48	SOS2	SOS2	SOS2	8133	0.017	0.43	NO
49	NRAS	NRAS	NRAS	8216	0.016	0.43	NO
50	SHC1	SHC1	SHC1	8457	0.014	0.42	NO
51	CHUK	CHUK	CHUK	8926	0.0087	0.39	NO
52	BRAF	BRAF	BRAF	9147	0.0064	0.38	NO
53	HDAC2	HDAC2	HDAC2	9200	0.006	0.38	NO
54	BCL2L1	BCL2L1	BCL2L1	9314	0.0048	0.37	NO
55	TP53	TP53	TP53	9422	0.0036	0.37	NO
56	SOS1	SOS1	SOS1	9734	0.00026	0.35	NO
57	MAPK3	MAPK3	MAPK3	9797	-0.00052	0.35	NO
58	CTBP1	CTBP1	CTBP1	9955	-0.0022	0.34	NO
59	IKBKB	IKBKB	IKBKB	10080	-0.0033	0.33	NO
60	ABL1	ABL1	ABL1	10256	-0.0049	0.32	NO
61	CDK4	CDK4	CDK4	10312	-0.0055	0.32	NO
62	IKBKG	IKBKG	IKBKG	10531	-0.0078	0.31	NO
63	ARAF	ARAF	ARAF	10562	-0.0081	0.31	NO
64	AKT2	AKT2	AKT2	11065	-0.014	0.28	NO
65	PIK3R2	PIK3R2	PIK3R2	13041	-0.036	0.18	NO
66	MAP2K2	MAP2K2	MAP2K2	13345	-0.04	0.17	NO
67	BAD	BAD	BAD	14352	-0.056	0.12	NO
68	CCND1	CCND1	CCND1	14772	-0.064	0.11	NO
69	MECOM	MECOM	MECOM	15242	-0.075	0.099	NO
70	HRAS	HRAS	HRAS	15391	-0.08	0.11	NO
71	PIK3R3	PIK3R3	PIK3R3	15706	-0.09	0.1	NO
72	E2F2	E2F2	E2F2	16488	-0.13	0.083	NO

Figure S15. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FCER1 PATHWAY.

Figure S16. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA FMLP PATHWAY

Table S9. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MAP4K1	MAP4K1	MAP4K1	535	0.43	0.041	YES
2	FOS	FOS	FOS	906	0.35	0.078	YES
3	RPS6KA5	RPS6KA5	RPS6KA5	993	0.34	0.13	YES
4	MAP3K5	MAP3K5	MAP3K5	1612	0.25	0.14	YES
5	TGFB2	TGFB2	TGFB2	1647	0.24	0.17	YES
6	MAP3K8	MAP3K8	MAP3K8	1669	0.24	0.21	YES
7	MAP3K13	MAP3K13	MAP3K13	1817	0.23	0.24	YES
8	MAPK13	MAPK13	MAPK13	1869	0.22	0.28	YES
9	CEBPA	CEBPA	CEBPA	2177	0.19	0.29	YES
10	TGFB3	TGFB3	TGFB3	2380	0.18	0.31	YES
11	RPS6KA2	RPS6KA2	RPS6KA2	2717	0.16	0.31	YES
12	MAPK4	MAPK4	MAPK4	2916	0.14	0.33	YES
13	JUN	JUN	JUN	3095	0.13	0.34	YES
14	MAP3K9	MAP3K9	MAP3K9	3184	0.13	0.36	YES
15	MAP3K1	MAP3K1	MAP3K1	3297	0.12	0.37	YES
16	TGFB1	TGFB1	TGFB1	3607	0.11	0.37	YES
17	NFKBIA	NFKBIA	NFKBIA	3867	0.1	0.37	YES
18	NFKB1	NFKB1	NFKB1	3971	0.096	0.38	YES
19	MAPK8	MAPK8	MAPK8	4370	0.083	0.37	YES
20	TGFBR1	TGFBR1	TGFBR1	4491	0.08	0.38	YES
21	MEF2D	MEF2D	MEF2D	4927	0.068	0.37	YES
22	MAP2K3	MAP2K3	MAP2K3	5163	0.063	0.36	YES
23	RPS6KA1	RPS6KA1	RPS6KA1	5348	0.058	0.36	YES
24	MAP3K2	MAP3K2	MAP3K2	5492	0.056	0.36	YES
25	MAX	MAX	MAX	5661	0.052	0.36	YES
26	RPS6KA3	RPS6KA3	RPS6KA3	5725	0.052	0.37	YES
27	RIPK1	RIPK1	RIPK1	5729	0.051	0.38	YES
28	PAK2	PAK2	PAK2	5783	0.051	0.38	YES
29	MYC	MYC	MYC	5809	0.05	0.39	YES
30	SP1	SP1	SP1	5834	0.05	0.4	YES
31	STAT1	STAT1	STAT1	5848	0.049	0.4	YES
32	RAPGEF2	RAPGEF2	RAPGEF2	5895	0.048	0.41	YES
33	MAP3K6	MAP3K6	MAP3K6	5936	0.048	0.42	YES
34	MAP3K14	MAP3K14	MAP3K14	6115	0.044	0.41	YES
35	RAC1	RAC1	RAC1	6233	0.042	0.41	YES
36	MAPK1	MAPK1	MAPK1	6275	0.042	0.42	YES
37	MAP2K1	MAP2K1	MAP2K1	6295	0.041	0.42	YES
38	MAP3K3	MAP3K3	MAP3K3	6440	0.039	0.42	YES
39	MAPK14	MAPK14	MAPK14	6528	0.037	0.42	YES
40	RELA	RELA	RELA	6534	0.037	0.43	YES
41	CREB1	CREB1	CREB1	6645	0.036	0.43	YES
42	ATF2	ATF2	ATF2	6758	0.034	0.43	YES
43	RPS6KA4	RPS6KA4	RPS6KA4	6789	0.034	0.43	YES
44	MAPKAPK5	MAPKAPK5	MAPKAPK5	6928	0.032	0.43	YES
45	GRB2	GRB2	GRB2	7037	0.03	0.43	YES
46	MAP3K7	MAP3K7	MAP3K7	7097	0.03	0.43	YES
47	MEF2A	MEF2A	MEF2A	7186	0.029	0.43	YES
48	MAPK6	MAPK6	MAPK6	7228	0.028	0.43	YES
49	MAP2K4	MAP2K4	MAP2K4	7314	0.027	0.43	YES
50	ELK1	ELK1	ELK1	7352	0.027	0.43	YES
51	MAPK7	MAPK7	MAPK7	7370	0.026	0.44	YES
52	RAF1	RAF1	RAF1	8047	0.018	0.4	NO
53	SHC1	SHC1	SHC1	8457	0.014	0.38	NO
54	MAP3K4	MAP3K4	MAP3K4	8581	0.012	0.38	NO
55	PAK1	PAK1	PAK1	8825	0.0098	0.36	NO
56	MAP4K4	MAP4K4	MAP4K4	8832	0.0098	0.37	NO
57	MAP3K11	MAP3K11	MAP3K11	8920	0.0088	0.36	NO
58	CHUK	CHUK	CHUK	8926	0.0087	0.36	NO
59	BRAF	BRAF	BRAF	9147	0.0064	0.35	NO
60	MAP2K5	MAP2K5	MAP2K5	9330	0.0045	0.34	NO
61	DAXX	DAXX	DAXX	9331	0.0045	0.34	NO
62	MKNK2	MKNK2	MKNK2	9667	0.00098	0.33	NO
63	MAPK3	MAPK3	MAPK3	9797	-0.00052	0.32	NO
64	TRAF2	TRAF2	TRAF2	9813	-0.00064	0.32	NO
65	MAPKAPK3	MAPKAPK3	MAPKAPK3	9838	-0.00089	0.32	NO
66	MAP4K5	MAP4K5	MAP4K5	10055	-0.0031	0.3	NO
67	IKBKB	IKBKB	IKBKB	10080	-0.0033	0.3	NO
68	LOC729991-MEF2B	LOC729991-MEF2B	LOC729991-MEF2B	10091	-0.0034	0.3	NO
69	ARAF	ARAF	ARAF	10562	-0.0081	0.28	NO
70	MAPKAPK2	MAPKAPK2	MAPKAPK2	10644	-0.0091	0.28	NO
71	MAPK11	MAPK11	MAPK11	10711	-0.0099	0.27	NO
72	MAP2K6	MAP2K6	MAP2K6	10717	-0.0099	0.28	NO
73	MKNK1	MKNK1	MKNK1	10764	-0.01	0.28	NO
74	RPS6KB1	RPS6KB1	RPS6KB1	11028	-0.013	0.26	NO
75	MAPK10	MAPK10	MAPK10	11560	-0.019	0.24	NO
76	RPS6KB2	RPS6KB2	RPS6KB2	12142	-0.025	0.21	NO
77	MAP2K7	MAP2K7	MAP2K7	12337	-0.027	0.2	NO
78	MAPK9	MAPK9	MAPK9	12895	-0.034	0.18	NO
79	TRADD	TRADD	TRADD	13249	-0.039	0.16	NO
80	MAP2K2	MAP2K2	MAP2K2	13345	-0.04	0.16	NO
81	MAP3K12	MAP3K12	MAP3K12	13362	-0.04	0.17	NO
82	MAP3K10	MAP3K10	MAP3K10	13563	-0.043	0.16	NO
83	MAP4K3	MAP4K3	MAP4K3	14929	-0.068	0.1	NO
84	HRAS	HRAS	HRAS	15391	-0.08	0.087	NO
85	MAP4K2	MAP4K2	MAP4K2	15726	-0.091	0.084	NO
86	MAPK12	MAPK12	MAPK12	17692	-0.26	0.016	NO

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

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

genes ES table in pathway: BIOCARTA GH PATHWAY

Table 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	TNF	TNF	TNF	233	0.53	0.079	YES
2	ACSL5	ACSL5	ACSL5	444	0.45	0.15	YES
3	SOCS3	SOCS3	SOCS3	1032	0.33	0.17	YES
4	TNFRSF1B	TNFRSF1B	TNFRSF1B	1037	0.33	0.23	YES
5	POMC	POMC	POMC	1241	0.3	0.27	YES
6	AGRP	AGRP	AGRP	1464	0.27	0.3	YES
7	LEP	LEP	LEP	1602	0.25	0.34	YES
8	PRKCQ	PRKCQ	PRKCQ	1896	0.22	0.36	YES
9	CD36	CD36	CD36	2126	0.2	0.38	YES
10	SLC2A4	SLC2A4	SLC2A4	2182	0.19	0.41	YES
11	CPT1C	CPT1C	CPT1C	2800	0.15	0.4	YES
12	PCK1	PCK1	PCK1	3166	0.13	0.41	YES
13	IRS1	IRS1	IRS1	3331	0.12	0.42	YES
14	LEPR	LEPR	LEPR	3476	0.12	0.43	YES
15	CAMKK1	CAMKK1	CAMKK1	3696	0.11	0.44	YES
16	IRS2	IRS2	IRS2	3766	0.1	0.45	YES
17	NFKBIA	NFKBIA	NFKBIA	3867	0.1	0.46	YES
18	NFKBIE	NFKBIE	NFKBIE	3929	0.098	0.48	YES
19	NFKB1	NFKB1	NFKB1	3971	0.096	0.49	YES
20	G6PC	G6PC	G6PC	4261	0.087	0.49	YES
21	JAK2	JAK2	JAK2	4351	0.084	0.5	YES
22	MAPK8	MAPK8	MAPK8	4370	0.083	0.52	YES
23	PRKAB1	PRKAB1	PRKAB1	4499	0.08	0.52	YES
24	TNFRSF1A	TNFRSF1A	TNFRSF1A	4562	0.078	0.53	YES
25	ACSL4	ACSL4	ACSL4	4572	0.078	0.55	YES
26	STAT3	STAT3	STAT3	4985	0.067	0.53	NO
27	RXRA	RXRA	RXRA	5409	0.057	0.52	NO
28	PTPN11	PTPN11	PTPN11	5914	0.048	0.5	NO
29	RELA	RELA	RELA	6534	0.037	0.47	NO
30	MTOR	MTOR	MTOR	6859	0.033	0.46	NO
31	AKT3	AKT3	AKT3	7264	0.028	0.44	NO
32	SLC2A1	SLC2A1	SLC2A1	7266	0.028	0.45	NO
33	ACSL6	ACSL6	ACSL6	7425	0.026	0.44	NO
34	ADIPOR2	ADIPOR2	ADIPOR2	7682	0.022	0.43	NO
35	ADIPOR1	ADIPOR1	ADIPOR1	7853	0.02	0.43	NO
36	AKT1	AKT1	AKT1	7964	0.019	0.42	NO
37	CHUK	CHUK	CHUK	8926	0.0087	0.37	NO
38	PRKAA1	PRKAA1	PRKAA1	9037	0.0076	0.37	NO
39	CAMKK2	CAMKK2	CAMKK2	9343	0.0044	0.35	NO
40	ACSL3	ACSL3	ACSL3	9434	0.0035	0.35	NO
41	PRKAG2	PRKAG2	PRKAG2	9586	0.0018	0.34	NO
42	TRAF2	TRAF2	TRAF2	9813	-0.00064	0.32	NO
43	IKBKB	IKBKB	IKBKB	10080	-0.0033	0.31	NO
44	PRKAA2	PRKAA2	PRKAA2	10449	-0.007	0.29	NO
45	IKBKG	IKBKG	IKBKG	10531	-0.0078	0.29	NO
46	PRKAG1	PRKAG1	PRKAG1	10709	-0.0099	0.28	NO
47	PPARGC1A	PPARGC1A	PPARGC1A	10983	-0.013	0.27	NO
48	RXRB	RXRB	RXRB	11038	-0.013	0.27	NO
49	AKT2	AKT2	AKT2	11065	-0.014	0.27	NO
50	MAPK10	MAPK10	MAPK10	11560	-0.019	0.24	NO
51	NFKBIB	NFKBIB	NFKBIB	11794	-0.021	0.23	NO
52	STK11	STK11	STK11	12038	-0.024	0.22	NO
53	RXRG	RXRG	RXRG	12156	-0.025	0.22	NO
54	CPT1A	CPT1A	CPT1A	12180	-0.025	0.22	NO
55	ACSL1	ACSL1	ACSL1	12875	-0.034	0.19	NO
56	MAPK9	MAPK9	MAPK9	12895	-0.034	0.2	NO
57	TRADD	TRADD	TRADD	13249	-0.039	0.18	NO
58	CPT1B	CPT1B	CPT1B	14142	-0.052	0.14	NO
59	PPARA	PPARA	PPARA	14282	-0.055	0.14	NO
60	PCK2	PCK2	PCK2	15172	-0.073	0.11	NO
61	G6PC2	G6PC2	G6PC2	15327	-0.078	0.11	NO
62	ACACB	ACACB	ACACB	15520	-0.084	0.12	NO
63	PRKAB2	PRKAB2	PRKAB2	16251	-0.11	0.097	NO

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

Figure S20. 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

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 ALK PATHWAY	32	genes.ES.table	0.42	1.2	0.19	1	0.99	0.22	0.15	0.19	1	0.81
BIOCARTA DEATH PATHWAY	32	genes.ES.table	0.3	1.2	0.28	1	1	0.16	0.18	0.13	1	0.79
KEGG HISTIDINE METABOLISM	28	genes.ES.table	0.34	0.83	0.67	1	1	0.32	0.25	0.24	1	0.7
KEGG SPHINGOLIPID METABOLISM	36	genes.ES.table	0.28	0.83	0.71	1	1	0.11	0.099	0.1	1	0.6
KEGG RNA DEGRADATION	56	genes.ES.table	0.2	0.92	0.54	1	1	0.036	0.034	0.035	1	0.78
KEGG SPLICEOSOME	125	genes.ES.table	0.22	0.91	0.51	1	1	1	0.79	0.22	1	0.63
KEGG ERBB SIGNALING PATHWAY	86	genes.ES.table	0.2	0.75	0.83	1	1	0.07	0.091	0.064	1	0.7
KEGG SNARE INTERACTIONS IN VESICULAR TRANSPORT	37	genes.ES.table	0.28	1.1	0.36	1	1	0.14	0.13	0.12	1	0.72
KEGG CARDIAC MUSCLE CONTRACTION	62	genes.ES.table	0.33	1	0.45	1	1	0.16	0.085	0.15	1	0.69
KEGG HEDGEHOG SIGNALING PATHWAY	53	genes.ES.table	0.42	1.1	0.28	1	1	0.36	0.22	0.28	1	0.77

genes ES table in pathway: BIOCARTA ALK 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	IGSF5	IGSF5	IGSF5	55	0.63	0.036	YES
2	MYH3	MYH3	MYH3	132	0.56	0.066	YES
3	PRKCG	PRKCG	PRKCG	266	0.49	0.088	YES
4	MYH7B	MYH7B	MYH7B	319	0.48	0.12	YES
5	MYH8	MYH8	MYH8	436	0.44	0.14	YES
6	RAB3B	RAB3B	RAB3B	526	0.42	0.16	YES
7	CLDN9	CLDN9	CLDN9	558	0.42	0.18	YES
8	PRKCQ	PRKCQ	PRKCQ	665	0.39	0.2	YES
9	CLDN7	CLDN7	CLDN7	796	0.37	0.21	YES
10	CLDN3	CLDN3	CLDN3	804	0.37	0.24	YES
11	CLDN18	CLDN18	CLDN18	851	0.36	0.26	YES
12	CLDN15	CLDN15	CLDN15	1173	0.31	0.26	YES
13	CLDN19	CLDN19	CLDN19	1208	0.3	0.27	YES
14	CLDN20	CLDN20	CLDN20	1391	0.28	0.28	YES
15	TJP3	TJP3	TJP3	1437	0.27	0.29	YES
16	GNAI1	GNAI1	GNAI1	1460	0.27	0.31	YES
17	CLDN6	CLDN6	CLDN6	1551	0.26	0.32	YES
18	MAGI2	MAGI2	MAGI2	1609	0.26	0.33	YES
19	OCLN	OCLN	OCLN	1993	0.22	0.32	NO
20	MYH1	MYH1	MYH1	2200	0.2	0.33	NO
21	MYH4	MYH4	MYH4	2471	0.18	0.32	NO
22	CLDN4	CLDN4	CLDN4	2919	0.16	0.31	NO
23	LLGL2	LLGL2	LLGL2	3216	0.14	0.3	NO
24	CLDN23	CLDN23	CLDN23	3425	0.13	0.3	NO
25	PRKCZ	PRKCZ	PRKCZ	3597	0.12	0.29	NO
26	MLLT4	MLLT4	MLLT4	3691	0.12	0.3	NO
27	MYL5	MYL5	MYL5	4178	0.1	0.28	NO
28	CASK	CASK	CASK	4276	0.098	0.28	NO
29	PRKCI	PRKCI	PRKCI	4322	0.096	0.28	NO
30	MAGI1	MAGI1	MAGI1	4481	0.091	0.28	NO
31	TJP2	TJP2	TJP2	4565	0.088	0.28	NO
32	CLDN14	CLDN14	CLDN14	4698	0.085	0.27	NO
33	TJP1	TJP1	TJP1	4718	0.084	0.28	NO
34	PARD6B	PARD6B	PARD6B	4735	0.083	0.28	NO
35	EXOC4	EXOC4	EXOC4	4923	0.078	0.28	NO
36	MYH14	MYH14	MYH14	5270	0.069	0.26	NO
37	PARD6A	PARD6A	PARD6A	5325	0.068	0.26	NO
38	KRAS	KRAS	KRAS	5426	0.065	0.26	NO
39	CRB3	CRB3	CRB3	5549	0.062	0.26	NO
40	AMOTL1	AMOTL1	AMOTL1	5681	0.059	0.25	NO
41	CLDN2	CLDN2	CLDN2	5823	0.056	0.25	NO
42	CLDN1	CLDN1	CLDN1	5841	0.056	0.25	NO
43	EPB41L1	EPB41L1	EPB41L1	6044	0.051	0.24	NO
44	AKT2	AKT2	AKT2	6096	0.05	0.24	NO
45	MYL12B	MYL12B	MYL12B	6196	0.048	0.24	NO
46	LLGL1	LLGL1	LLGL1	6508	0.041	0.23	NO
47	MRAS	MRAS	MRAS	6538	0.04	0.23	NO
48	AKT1	AKT1	AKT1	6749	0.036	0.22	NO
49	CSDA	CSDA	CSDA	6802	0.035	0.22	NO
50	TJAP1	TJAP1	TJAP1	6971	0.031	0.21	NO
51	SYMPK	SYMPK	SYMPK	7030	0.03	0.21	NO
52	PRKCA	PRKCA	PRKCA	7250	0.026	0.2	NO
53	F11R	F11R	F11R	7434	0.023	0.19	NO
54	CTTN	CTTN	CTTN	7483	0.021	0.19	NO
55	MPP5	MPP5	MPP5	7640	0.019	0.18	NO
56	RHOA	RHOA	RHOA	7797	0.016	0.17	NO
57	EPB41L2	EPB41L2	EPB41L2	8232	0.0086	0.15	NO
58	SPTAN1	SPTAN1	SPTAN1	8258	0.0082	0.15	NO
59	CTNNA1	CTNNA1	CTNNA1	8293	0.0077	0.15	NO
60	SRC	SRC	SRC	8515	0.0041	0.13	NO
61	MYL12A	MYL12A	MYL12A	8518	0.004	0.13	NO
62	ASH1L	ASH1L	ASH1L	8612	0.0024	0.13	NO
63	ACTB	ACTB	ACTB	8728	0.00023	0.12	NO
64	AKT3	AKT3	AKT3	8775	-0.00056	0.12	NO
65	RRAS	RRAS	RRAS	8788	-0.0008	0.12	NO
66	MAGI3	MAGI3	MAGI3	8850	-0.0018	0.12	NO
67	EXOC3	EXOC3	EXOC3	9080	-0.0059	0.1	NO
68	RAB13	RAB13	RAB13	9185	-0.0076	0.098	NO
69	CDC42	CDC42	CDC42	9280	-0.0091	0.093	NO
70	MYL9	MYL9	MYL9	9449	-0.012	0.085	NO
71	PPP2R1A	PPP2R1A	PPP2R1A	9590	-0.014	0.078	NO
72	CSNK2B	CSNK2B	CSNK2B	9745	-0.017	0.07	NO
73	MYLPF	MYLPF	MYLPF	9831	-0.018	0.066	NO
74	RRAS2	RRAS2	RRAS2	10009	-0.021	0.058	NO
75	GNAI3	GNAI3	GNAI3	10040	-0.021	0.057	NO
76	MYH2	MYH2	MYH2	10058	-0.022	0.058	NO
77	MYH10	MYH10	MYH10	10090	-0.022	0.057	NO
78	PTEN	PTEN	PTEN	10274	-0.025	0.049	NO
79	CLDN16	CLDN16	CLDN16	10275	-0.025	0.05	NO
80	YES1	YES1	YES1	10535	-0.029	0.038	NO
81	CTNNB1	CTNNB1	CTNNB1	10740	-0.033	0.028	NO
82	INADL	INADL	INADL	10770	-0.033	0.028	NO
83	CSNK2A2	CSNK2A2	CSNK2A2	10890	-0.035	0.024	NO
84	PPP2R2D	PPP2R2D	PPP2R2D	11043	-0.038	0.018	NO
85	PARD3	PARD3	PARD3	11106	-0.039	0.017	NO
86	VAPA	VAPA	VAPA	11168	-0.04	0.016	NO
87	GNAI2	GNAI2	GNAI2	11219	-0.041	0.015	NO
88	PPP2R1B	PPP2R1B	PPP2R1B	11348	-0.043	0.011	NO
89	ZAK	ZAK	ZAK	11400	-0.044	0.011	NO
90	ACTG1	ACTG1	ACTG1	11418	-0.044	0.012	NO
91	PARD6G	PARD6G	PARD6G	11427	-0.044	0.015	NO
92	CSNK2A1	CSNK2A1	CSNK2A1	11596	-0.047	0.0081	NO
93	PPP2CB	PPP2CB	PPP2CB	11847	-0.052	-0.0027	NO
94	PPP2CA	PPP2CA	PPP2CA	11851	-0.052	0.00033	NO
95	EPB41L3	EPB41L3	EPB41L3	11885	-0.053	0.0017	NO
96	ACTN4	ACTN4	ACTN4	11904	-0.053	0.004	NO
97	MPDZ	MPDZ	MPDZ	11915	-0.053	0.0066	NO
98	CLDN10	CLDN10	CLDN10	11919	-0.053	0.0097	NO
99	CLDN8	CLDN8	CLDN8	12264	-0.06	-0.0058	NO
100	MYH9	MYH9	MYH9	13269	-0.083	-0.057	NO
101	CGN	CGN	CGN	13303	-0.084	-0.054	NO
102	NRAS	NRAS	NRAS	13499	-0.09	-0.059	NO
103	ACTN1	ACTN1	ACTN1	13598	-0.093	-0.059	NO
104	EPB41	EPB41	EPB41	13717	-0.096	-0.06	NO
105	CDK4	CDK4	CDK4	13727	-0.097	-0.054	NO
106	PRKCD	PRKCD	PRKCD	13895	-0.1	-0.057	NO
107	MYH15	MYH15	MYH15	13957	-0.1	-0.054	NO
108	PPP2R2A	PPP2R2A	PPP2R2A	14164	-0.11	-0.059	NO
109	ACTN2	ACTN2	ACTN2	14193	-0.11	-0.054	NO
110	CLDN5	CLDN5	CLDN5	14718	-0.14	-0.075	NO
111	MYH7	MYH7	MYH7	15458	-0.18	-0.1	NO
112	HCLS1	HCLS1	HCLS1	15696	-0.2	-0.11	NO
113	CLDN11	CLDN11	CLDN11	15927	-0.21	-0.11	NO
114	ACTN3	ACTN3	ACTN3	16013	-0.22	-0.098	NO
115	JAM3	JAM3	JAM3	16311	-0.24	-0.1	NO
116	JAM2	JAM2	JAM2	16643	-0.26	-0.1	NO
117	CTNNA3	CTNNA3	CTNNA3	16866	-0.29	-0.097	NO
118	PRKCE	PRKCE	PRKCE	17106	-0.32	-0.091	NO
119	PRKCH	PRKCH	PRKCH	17137	-0.32	-0.073	NO
120	CTNNA2	CTNNA2	CTNNA2	17219	-0.33	-0.058	NO
121	MYH11	MYH11	MYH11	17391	-0.35	-0.045	NO
122	PRKCB	PRKCB	PRKCB	17594	-0.4	-0.032	NO
123	PPP2R2B	PPP2R2B	PPP2R2B	17623	-0.4	-0.0094	NO
124	PPP2R2C	PPP2R2C	PPP2R2C	17812	-0.48	0.0095	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 ALK PATHWAY.

Figure S22. 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 DEATH 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	NOG	NOG	NOG	195	0.52	0.13	YES
2	BMP4	BMP4	BMP4	374	0.46	0.24	YES
3	SMAD6	SMAD6	SMAD6	637	0.4	0.34	YES
4	NPPA	NPPA	NPPA	2393	0.19	0.29	YES
5	BMP2	BMP2	BMP2	2435	0.19	0.34	YES
6	FZD1	FZD1	FZD1	2455	0.19	0.39	YES
7	BMP7	BMP7	BMP7	2743	0.17	0.42	YES
8	HNF1A	HNF1A	HNF1A	3857	0.11	0.38	NO
9	TGFB2	TGFB2	TGFB2	3862	0.11	0.42	NO
10	SMAD4	SMAD4	SMAD4	5216	0.07	0.36	NO
11	WNT1	WNT1	WNT1	5284	0.069	0.37	NO
12	DVL1	DVL1	DVL1	5842	0.056	0.36	NO
13	AXIN1	AXIN1	AXIN1	5922	0.054	0.37	NO
14	TGFBR3	TGFBR3	TGFBR3	6948	0.032	0.32	NO
15	BMPR1A	BMPR1A	BMPR1A	7371	0.024	0.3	NO
16	SMAD5	SMAD5	SMAD5	7608	0.019	0.3	NO
17	TGFBR2	TGFBR2	TGFBR2	8442	0.0053	0.25	NO
18	GSK3B	GSK3B	GSK3B	8743	-0.000065	0.23	NO
19	BMPR2	BMPR2	BMPR2	8839	-0.0016	0.23	NO
20	TGFB3	TGFB3	TGFB3	9610	-0.014	0.19	NO
21	SMAD1	SMAD1	SMAD1	9791	-0.018	0.18	NO
22	MAP3K7	MAP3K7	MAP3K7	9963	-0.02	0.18	NO
23	RFC1	RFC1	RFC1	10451	-0.028	0.16	NO
24	CTNNB1	CTNNB1	CTNNB1	10740	-0.033	0.15	NO
25	TGFBR1	TGFBR1	TGFBR1	12616	-0.068	0.066	NO
26	APC	APC	APC	13420	-0.087	0.045	NO
27	CHRD	CHRD	CHRD	13570	-0.092	0.062	NO
28	ACVR1	ACVR1	ACVR1	14313	-0.12	0.052	NO
29	TGFB1	TGFB1	TGFB1	14517	-0.12	0.075	NO
30	BMP5	BMP5	BMP5	14767	-0.14	0.098	NO
31	GATA4	GATA4	GATA4	14998	-0.15	0.12	NO
32	ATF2	ATF2	ATF2	15016	-0.15	0.16	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 DEATH PATHWAY.

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

genes ES table in pathway: KEGG HISTIDINE METABOLISM

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	TNFRSF25	TNFRSF25	TNFRSF25	460	0.44	0.15	YES
2	BCL2	BCL2	BCL2	2066	0.22	0.15	YES
3	TNFSF10	TNFSF10	TNFSF10	2209	0.2	0.23	YES
4	TNFSF12	TNFSF12	TNFSF12	2431	0.19	0.29	YES
5	DFFB	DFFB	DFFB	3244	0.14	0.3	YES
6	TRAF2	TRAF2	TRAF2	5365	0.067	0.21	NO
7	TRADD	TRADD	TRADD	5474	0.064	0.23	NO
8	GAS2	GAS2	GAS2	5898	0.055	0.23	NO
9	RIPK1	RIPK1	RIPK1	6359	0.044	0.22	NO
10	CASP9	CASP9	CASP9	6568	0.04	0.23	NO
11	CYCS	CYCS	CYCS	6642	0.038	0.24	NO
12	APAF1	APAF1	APAF1	6765	0.036	0.25	NO
13	TNFRSF10B	TNFRSF10B	TNFRSF10B	7233	0.026	0.23	NO
14	LMNA	LMNA	LMNA	7261	0.026	0.24	NO
15	BIRC2	BIRC2	BIRC2	7912	0.014	0.21	NO
16	MAP3K14	MAP3K14	MAP3K14	8044	0.012	0.21	NO
17	CASP6	CASP6	CASP6	8177	0.0095	0.2	NO
18	SPTAN1	SPTAN1	SPTAN1	8258	0.0082	0.2	NO
19	NFKB1	NFKB1	NFKB1	8333	0.0072	0.2	NO
20	XIAP	XIAP	XIAP	9462	-0.012	0.14	NO
21	RELA	RELA	RELA	9647	-0.015	0.14	NO
22	FADD	FADD	FADD	9695	-0.016	0.14	NO
23	CHUK	CHUK	CHUK	10702	-0.032	0.1	NO
24	NFKBIA	NFKBIA	NFKBIA	11370	-0.043	0.082	NO
25	CASP8	CASP8	CASP8	11473	-0.045	0.095	NO
26	CASP3	CASP3	CASP3	11764	-0.05	0.099	NO
27	CFLAR	CFLAR	CFLAR	11941	-0.054	0.11	NO
28	CASP7	CASP7	CASP7	12352	-0.062	0.11	NO
29	DFFA	DFFA	DFFA	13080	-0.078	0.1	NO
30	CASP10	CASP10	CASP10	13946	-0.1	0.099	NO
31	TNFRSF10A	TNFRSF10A	TNFRSF10A	14899	-0.14	0.1	NO
32	BIRC3	BIRC3	BIRC3	15193	-0.16	0.16	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 HISTIDINE METABOLISM.

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

genes ES table in pathway: KEGG SPHINGOLIPID 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	BMP6	BMP6	BMP6	144	0.55	0.056	YES
2	WNT2	WNT2	WNT2	208	0.52	0.11	YES
3	WNT5A	WNT5A	WNT5A	303	0.48	0.16	YES
4	BMP8B	BMP8B	BMP8B	314	0.48	0.22	YES
5	BMP4	BMP4	BMP4	374	0.46	0.27	YES
6	WNT7B	WNT7B	WNT7B	386	0.46	0.32	YES
7	SHH	SHH	SHH	846	0.36	0.34	YES
8	GLI3	GLI3	GLI3	1021	0.33	0.37	YES
9	WNT10B	WNT10B	WNT10B	1624	0.26	0.36	YES
10	BMP8A	BMP8A	BMP8A	2251	0.2	0.35	YES
11	WNT16	WNT16	WNT16	2362	0.19	0.37	YES
12	BMP2	BMP2	BMP2	2435	0.19	0.39	YES
13	BMP7	BMP7	BMP7	2743	0.17	0.39	YES
14	WNT4	WNT4	WNT4	2764	0.17	0.41	YES
15	SMO	SMO	SMO	3165	0.14	0.4	YES
16	STK36	STK36	STK36	3246	0.14	0.41	YES
17	PRKX	PRKX	PRKX	3525	0.13	0.41	YES
18	WNT3	WNT3	WNT3	3781	0.12	0.41	YES
19	HHIP	HHIP	HHIP	3875	0.11	0.42	YES
20	PRKACB	PRKACB	PRKACB	4611	0.087	0.39	NO
21	LRP2	LRP2	LRP2	4686	0.085	0.4	NO
22	PTCH1	PTCH1	PTCH1	4709	0.084	0.4	NO
23	CSNK1E	CSNK1E	CSNK1E	5010	0.076	0.4	NO
24	WNT1	WNT1	WNT1	5284	0.069	0.39	NO
25	WNT9A	WNT9A	WNT9A	5634	0.06	0.38	NO
26	CSNK1D	CSNK1D	CSNK1D	6711	0.037	0.32	NO
27	SUFU	SUFU	SUFU	6857	0.034	0.32	NO
28	BTRC	BTRC	BTRC	6951	0.032	0.32	NO
29	CSNK1G2	CSNK1G2	CSNK1G2	7182	0.028	0.31	NO
30	IHH	IHH	IHH	7360	0.024	0.3	NO
31	WNT7A	WNT7A	WNT7A	7539	0.02	0.29	NO
32	RAB23	RAB23	RAB23	8482	0.0047	0.24	NO
33	GSK3B	GSK3B	GSK3B	8743	-0.000065	0.22	NO
34	PTCH2	PTCH2	PTCH2	9040	-0.0051	0.21	NO
35	CSNK1G1	CSNK1G1	CSNK1G1	9096	-0.0061	0.21	NO
36	WNT11	WNT11	WNT11	9594	-0.014	0.18	NO
37	CSNK1A1	CSNK1A1	CSNK1A1	10080	-0.022	0.16	NO
38	PRKACA	PRKACA	PRKACA	10307	-0.026	0.15	NO
39	WNT8B	WNT8B	WNT8B	11218	-0.041	0.1	NO
40	WNT2B	WNT2B	WNT2B	11241	-0.041	0.1	NO
41	CSNK1G3	CSNK1G3	CSNK1G3	11340	-0.043	0.1	NO
42	CSNK1A1L	CSNK1A1L	CSNK1A1L	13245	-0.082	0.0073	NO
43	FBXW11	FBXW11	FBXW11	14357	-0.12	-0.041	NO
44	WNT5B	WNT5B	WNT5B	14545	-0.13	-0.036	NO
45	GAS1	GAS1	GAS1	14680	-0.13	-0.028	NO
46	BMP5	BMP5	BMP5	14767	-0.14	-0.017	NO
47	WNT9B	WNT9B	WNT9B	15418	-0.18	-0.032	NO
48	WNT6	WNT6	WNT6	16010	-0.22	-0.04	NO
49	GLI1	GLI1	GLI1	16117	-0.22	-0.02	NO
50	ZIC2	ZIC2	ZIC2	16222	-0.23	0.0011	NO
51	GLI2	GLI2	GLI2	16519	-0.26	0.014	NO
52	DHH	DHH	DHH	16762	-0.28	0.033	NO
53	WNT10A	WNT10A	WNT10A	16934	-0.3	0.058	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 SPHINGOLIPID METABOLISM.

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

genes ES table in pathway: KEGG RNA DEGRADATION

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	STX1A	STX1A	STX1A	1045	0.33	0.04	YES
2	VAMP1	VAMP1	VAMP1	1101	0.32	0.13	YES
3	SNAP25	SNAP25	SNAP25	1205	0.3	0.22	YES
4	STX1B	STX1B	STX1B	2095	0.21	0.23	YES
5	STX19	STX19	STX19	2309	0.2	0.28	YES
6	STX2	STX2	STX2	3300	0.14	0.26	NO
7	STX16	STX16	STX16	3914	0.11	0.26	NO
8	VAMP2	VAMP2	VAMP2	4503	0.09	0.26	NO
9	STX10	STX10	STX10	5221	0.07	0.24	NO
10	VAMP4	VAMP4	VAMP4	5319	0.068	0.26	NO
11	VAMP5	VAMP5	VAMP5	5401	0.066	0.27	NO
12	STX8	STX8	STX8	5789	0.057	0.27	NO
13	YKT6	YKT6	YKT6	7085	0.029	0.2	NO
14	TSNARE1	TSNARE1	TSNARE1	7381	0.024	0.19	NO
15	STX18	STX18	STX18	7592	0.02	0.19	NO
16	STX17	STX17	STX17	7743	0.017	0.18	NO
17	BET1	BET1	BET1	7902	0.014	0.18	NO
18	GOSR1	GOSR1	GOSR1	8096	0.011	0.17	NO
19	STX4	STX4	STX4	8761	-0.00034	0.14	NO
20	VAMP8	VAMP8	VAMP8	8766	-0.00041	0.14	NO
21	BET1L	BET1L	BET1L	9111	-0.0064	0.12	NO
22	STX5	STX5	STX5	9651	-0.015	0.092	NO
23	SNAP47	SNAP47	SNAP47	9812	-0.018	0.088	NO
24	VTI1B	VTI1B	VTI1B	10270	-0.025	0.07	NO
25	STX3	STX3	STX3	10399	-0.027	0.071	NO
26	STX7	STX7	STX7	10596	-0.03	0.07	NO
27	VAMP3	VAMP3	VAMP3	10603	-0.03	0.078	NO
28	STX12	STX12	STX12	12020	-0.055	0.016	NO
29	USE1	USE1	USE1	12095	-0.056	0.029	NO
30	GOSR2	GOSR2	GOSR2	12236	-0.06	0.039	NO
31	SNAP23	SNAP23	SNAP23	12364	-0.062	0.05	NO
32	STX6	STX6	STX6	13422	-0.087	0.018	NO
33	SEC22B	SEC22B	SEC22B	14351	-0.12	0.0018	NO
34	BNIP1	BNIP1	BNIP1	14463	-0.12	0.033	NO
35	VTI1A	VTI1A	VTI1A	14488	-0.12	0.069	NO
36	VAMP7	VAMP7	VAMP7	14594	-0.13	0.1	NO
37	STX11	STX11	STX11	16892	-0.29	0.061	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 RNA DEGRADATION.

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

genes ES table in pathway: KEGG SPLICEOSOME

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	WNT2	WNT2	WNT2	208	0.52	0.051	YES
2	WNT5A	WNT5A	WNT5A	303	0.48	0.1	YES
3	BMP4	BMP4	BMP4	374	0.46	0.15	YES
4	WNT7B	WNT7B	WNT7B	386	0.46	0.21	YES
5	SHH	SHH	SHH	846	0.36	0.23	YES
6	AXIN2	AXIN2	AXIN2	897	0.35	0.27	YES
7	GLI3	GLI3	GLI3	1021	0.33	0.3	YES
8	WNT10B	WNT10B	WNT10B	1624	0.26	0.3	YES
9	WNT16	WNT16	WNT16	2362	0.19	0.28	YES
10	BMP2	BMP2	BMP2	2435	0.19	0.3	YES
11	FZD1	FZD1	FZD1	2455	0.19	0.32	YES
12	WNT4	WNT4	WNT4	2764	0.17	0.32	YES
13	FZD4	FZD4	FZD4	3164	0.14	0.32	YES
14	SMO	SMO	SMO	3165	0.14	0.33	YES
15	STK36	STK36	STK36	3246	0.14	0.34	YES
16	APC2	APC2	APC2	3559	0.13	0.34	YES
17	WNT3	WNT3	WNT3	3781	0.12	0.34	YES
18	HHIP	HHIP	HHIP	3875	0.11	0.35	YES
19	FZD8	FZD8	FZD8	3911	0.11	0.36	YES
20	DVL2	DVL2	DVL2	3993	0.11	0.37	YES
21	FZD2	FZD2	FZD2	4069	0.1	0.38	YES
22	FZD9	FZD9	FZD9	4128	0.1	0.39	YES
23	PTCH1	PTCH1	PTCH1	4709	0.084	0.37	NO
24	WNT1	WNT1	WNT1	5284	0.069	0.34	NO
25	TCF7L2	TCF7L2	TCF7L2	5339	0.067	0.35	NO
26	WNT9A	WNT9A	WNT9A	5634	0.06	0.34	NO
27	DVL1	DVL1	DVL1	5842	0.056	0.34	NO
28	AXIN1	AXIN1	AXIN1	5922	0.054	0.34	NO
29	SUFU	SUFU	SUFU	6857	0.034	0.29	NO
30	WNT7A	WNT7A	WNT7A	7539	0.02	0.25	NO
31	TP53	TP53	TP53	7935	0.014	0.23	NO
32	DVL3	DVL3	DVL3	8260	0.0082	0.22	NO
33	FZD6	FZD6	FZD6	8540	0.0038	0.2	NO
34	GSK3B	GSK3B	GSK3B	8743	-0.000065	0.19	NO
35	PTCH2	PTCH2	PTCH2	9040	-0.0051	0.17	NO
36	WNT11	WNT11	WNT11	9594	-0.014	0.14	NO
37	TCF7	TCF7	TCF7	9914	-0.019	0.13	NO
38	FZD3	FZD3	FZD3	10486	-0.028	0.1	NO
39	CTNNB1	CTNNB1	CTNNB1	10740	-0.033	0.09	NO
40	WNT8B	WNT8B	WNT8B	11218	-0.041	0.069	NO
41	WNT2B	WNT2B	WNT2B	11241	-0.041	0.072	NO
42	APC	APC	APC	13420	-0.087	-0.039	NO
43	TCF7L1	TCF7L1	TCF7L1	14046	-0.11	-0.061	NO
44	WNT5B	WNT5B	WNT5B	14545	-0.13	-0.073	NO
45	FZD7	FZD7	FZD7	14702	-0.14	-0.066	NO
46	FZD5	FZD5	FZD5	14774	-0.14	-0.053	NO
47	WNT9B	WNT9B	WNT9B	15418	-0.18	-0.068	NO
48	WNT6	WNT6	WNT6	16010	-0.22	-0.075	NO
49	GLI1	GLI1	GLI1	16117	-0.22	-0.054	NO
50	GLI2	GLI2	GLI2	16519	-0.26	-0.046	NO
51	WNT10A	WNT10A	WNT10A	16934	-0.3	-0.034	NO
52	FZD10	FZD10	FZD10	17306	-0.34	-0.013	NO
53	LEF1	LEF1	LEF1	17696	-0.42	0.016	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 SPLICEOSOME.

Figure S32. 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 ERBB SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TNNI3	TNNI3	TNNI3	32	0.67	0.067	YES
2	COX6B2	COX6B2	COX6B2	69	0.62	0.13	YES
3	CACNB2	CACNB2	CACNB2	184	0.53	0.17	YES
4	MYL3	MYL3	MYL3	646	0.4	0.19	YES
5	CACNA2D3	CACNA2D3	CACNA2D3	947	0.34	0.21	YES
6	CACNA2D2	CACNA2D2	CACNA2D2	997	0.33	0.24	YES
7	CACNB3	CACNB3	CACNB3	1030	0.33	0.27	YES
8	CACNB1	CACNB1	CACNB1	1362	0.28	0.28	YES
9	CACNA2D4	CACNA2D4	CACNA2D4	1490	0.27	0.3	YES
10	COX8C	COX8C	COX8C	1524	0.27	0.33	YES
11	CACNG6	CACNG6	CACNG6	3344	0.14	0.24	NO
12	CACNA1D	CACNA1D	CACNA1D	3648	0.12	0.23	NO
13	TPM1	TPM1	TPM1	3916	0.11	0.23	NO
14	CACNG4	CACNG4	CACNG4	4132	0.1	0.23	NO
15	CACNA1F	CACNA1F	CACNA1F	4504	0.09	0.22	NO
16	FXYD2	FXYD2	FXYD2	4508	0.09	0.23	NO
17	COX7A1	COX7A1	COX7A1	5385	0.066	0.18	NO
18	SLC9A1	SLC9A1	SLC9A1	5537	0.063	0.18	NO
19	TPM2	TPM2	TPM2	7763	0.017	0.06	NO
20	COX6A1	COX6A1	COX6A1	8680	0.0012	0.0086	NO
21	ATP2A2	ATP2A2	ATP2A2	9130	-0.0066	-0.016	NO
22	COX4I1	COX4I1	COX4I1	9345	-0.01	-0.027	NO
23	COX5B	COX5B	COX5B	9710	-0.016	-0.045	NO
24	TNNT2	TNNT2	TNNT2	9776	-0.017	-0.047	NO
25	ATP1A1	ATP1A1	ATP1A1	9988	-0.02	-0.057	NO
26	COX7A2	COX7A2	COX7A2	10018	-0.021	-0.056	NO
27	UQCR10	UQCR10	UQCR10	10085	-0.022	-0.058	NO
28	COX6C	COX6C	COX6C	10265	-0.025	-0.065	NO
29	UQCR11	UQCR11	UQCR11	10288	-0.025	-0.064	NO
30	UQCRC1	UQCRC1	UQCRC1	10317	-0.026	-0.063	NO
31	COX6B1	COX6B1	COX6B1	10893	-0.035	-0.091	NO
32	COX5A	COX5A	COX5A	11099	-0.038	-0.099	NO
33	TPM3	TPM3	TPM3	11120	-0.039	-0.096	NO
34	COX8A	COX8A	COX8A	11290	-0.042	-0.1	NO
35	ATP1A4	ATP1A4	ATP1A4	11569	-0.046	-0.11	NO
36	TNNC1	TNNC1	TNNC1	11823	-0.052	-0.12	NO
37	CACNB4	CACNB4	CACNB4	12041	-0.055	-0.13	NO
38	COX7C	COX7C	COX7C	12089	-0.056	-0.12	NO
39	CYC1	CYC1	CYC1	12239	-0.06	-0.13	NO
40	UQCRB	UQCRB	UQCRB	12273	-0.06	-0.12	NO
41	ATP1B1	ATP1B1	ATP1B1	12511	-0.066	-0.13	NO
42	SLC8A1	SLC8A1	SLC8A1	12747	-0.07	-0.14	NO
43	UQCRQ	UQCRQ	UQCRQ	13053	-0.078	-0.14	NO
44	COX7B	COX7B	COX7B	13141	-0.08	-0.14	NO
45	SLC9A6	SLC9A6	SLC9A6	13465	-0.088	-0.15	NO
46	TPM4	TPM4	TPM4	13553	-0.092	-0.14	NO
47	UQCRH	UQCRH	UQCRH	13649	-0.094	-0.14	NO
48	COX7A2L	COX7A2L	COX7A2L	13778	-0.098	-0.14	NO
49	UQCRFS1	UQCRFS1	UQCRFS1	13954	-0.1	-0.14	NO
50	UQCRHL	UQCRHL	UQCRHL	14213	-0.11	-0.14	NO
51	ATP1B3	ATP1B3	ATP1B3	15447	-0.18	-0.19	NO
52	MYH7	MYH7	MYH7	15458	-0.18	-0.17	NO
53	RYR2	RYR2	RYR2	15612	-0.19	-0.16	NO
54	ATP1B2	ATP1B2	ATP1B2	15695	-0.2	-0.15	NO
55	ATP1A2	ATP1A2	ATP1A2	16158	-0.23	-0.15	NO
56	CACNA2D1	CACNA2D1	CACNA2D1	16518	-0.26	-0.14	NO
57	COX4I2	COX4I2	COX4I2	16593	-0.26	-0.12	NO
58	CACNA1S	CACNA1S	CACNA1S	17052	-0.31	-0.12	NO
59	ACTC1	ACTC1	ACTC1	17407	-0.36	-0.098	NO
60	COX6A2	COX6A2	COX6A2	17505	-0.37	-0.066	NO
61	CACNA1C	CACNA1C	CACNA1C	17569	-0.39	-0.03	NO
62	ATP1A3	ATP1A3	ATP1A3	17880	-0.52	0.0056	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 ERBB SIGNALING PATHWAY.

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

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

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	TAS2R4	TAS2R4	TAS2R4	163	0.54	0.065	YES
2	GNG3	GNG3	GNG3	269	0.49	0.13	YES
3	TAS2R5	TAS2R5	TAS2R5	355	0.47	0.19	YES
4	TAS2R14	TAS2R14	TAS2R14	720	0.38	0.22	YES
5	TAS2R10	TAS2R10	TAS2R10	1183	0.31	0.24	YES
6	TAS2R19	TAS2R19	TAS2R19	1294	0.29	0.27	YES
7	GNB3	GNB3	GNB3	1403	0.28	0.3	YES
8	SCNN1A	SCNN1A	SCNN1A	1451	0.27	0.34	YES
9	TAS1R1	TAS1R1	TAS1R1	1536	0.26	0.37	YES
10	TAS2R3	TAS2R3	TAS2R3	1600	0.26	0.4	YES
11	TAS2R20	TAS2R20	TAS2R20	1843	0.24	0.42	YES
12	TAS2R13	TAS2R13	TAS2R13	2439	0.19	0.41	YES
13	CACNA1A	CACNA1A	CACNA1A	2616	0.18	0.43	YES
14	PRKX	PRKX	PRKX	3525	0.13	0.4	NO
15	KCNB1	KCNB1	KCNB1	4031	0.11	0.38	NO
16	PRKACB	PRKACB	PRKACB	4611	0.087	0.36	NO
17	ITPR3	ITPR3	ITPR3	5174	0.071	0.34	NO
18	ADCY6	ADCY6	ADCY6	5688	0.059	0.32	NO
19	TAS2R50	TAS2R50	TAS2R50	6023	0.052	0.31	NO
20	TAS2R31	TAS2R31	TAS2R31	6163	0.049	0.31	NO
21	GNAS	GNAS	GNAS	7515	0.021	0.24	NO
22	GNB1	GNB1	GNB1	9773	-0.017	0.11	NO
23	PRKACA	PRKACA	PRKACA	10307	-0.026	0.085	NO
24	TAS2R43	TAS2R43	TAS2R43	10858	-0.034	0.059	NO
25	ACCN1	ACCN1	ACCN1	11129	-0.039	0.05	NO
26	TAS1R3	TAS1R3	TAS1R3	12198	-0.059	-0.0018	NO
27	PLCB2	PLCB2	PLCB2	13669	-0.095	-0.071	NO
28	ADCY8	ADCY8	ADCY8	14247	-0.11	-0.087	NO
29	TRPM5	TRPM5	TRPM5	15303	-0.17	-0.12	NO
30	CACNA1B	CACNA1B	CACNA1B	15791	-0.2	-0.12	NO
31	GRM4	GRM4	GRM4	16373	-0.24	-0.12	NO
32	SCNN1G	SCNN1G	SCNN1G	16572	-0.26	-0.096	NO
33	ADCY4	ADCY4	ADCY4	16886	-0.29	-0.073	NO
34	SCNN1B	SCNN1B	SCNN1B	17435	-0.36	-0.054	NO
35	PDE1A	PDE1A	PDE1A	17947	-0.61	0.0019	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 SNARE INTERACTIONS IN VESICULAR TRANSPORT.

Figure S36. 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 CARDIAC MUSCLE CONTRACTION

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	PAPOLB	PAPOLB	PAPOLB	547	0.42	0.087	YES
2	ENO3	ENO3	ENO3	611	0.4	0.2	YES
3	EXOSC8	EXOSC8	EXOSC8	3236	0.14	0.091	NO
4	PAPD7	PAPD7	PAPD7	4301	0.097	0.059	NO
5	LSM5	LSM5	LSM5	4358	0.095	0.083	NO
6	CNOT4	CNOT4	CNOT4	4559	0.088	0.097	NO
7	NAA38	NAA38	NAA38	5738	0.058	0.047	NO
8	CNOT6L	CNOT6L	CNOT6L	6035	0.051	0.045	NO
9	ENO2	ENO2	ENO2	6040	0.051	0.06	NO
10	CNOT3	CNOT3	CNOT3	6195	0.048	0.064	NO
11	DCP2	DCP2	DCP2	6417	0.043	0.064	NO
12	XRN1	XRN1	XRN1	6436	0.042	0.075	NO
13	LSM7	LSM7	LSM7	6771	0.036	0.066	NO
14	EDC4	EDC4	EDC4	6961	0.032	0.065	NO
15	DCP1A	DCP1A	DCP1A	7249	0.026	0.056	NO
16	EXOSC10	EXOSC10	EXOSC10	7437	0.022	0.052	NO
17	CNOT2	CNOT2	CNOT2	7643	0.019	0.046	NO
18	DIS3	DIS3	DIS3	7972	0.013	0.031	NO
19	PARN	PARN	PARN	8048	0.012	0.03	NO
20	LSM4	LSM4	LSM4	8102	0.011	0.03	NO
21	CNOT6	CNOT6	CNOT6	8436	0.0054	0.013	NO
22	EDC3	EDC3	EDC3	8440	0.0053	0.015	NO
23	EXOSC9	EXOSC9	EXOSC9	8509	0.0042	0.012	NO
24	ZCCHC7	ZCCHC7	ZCCHC7	8616	0.0024	0.0069	NO
25	CNOT10	CNOT10	CNOT10	8655	0.0017	0.0052	NO
26	PAPOLA	PAPOLA	PAPOLA	9097	-0.0061	-0.018	NO
27	EXOSC2	EXOSC2	EXOSC2	9326	-0.0097	-0.028	NO
28	LSM1	LSM1	LSM1	9493	-0.012	-0.033	NO
29	DCP1B	DCP1B	DCP1B	9593	-0.014	-0.035	NO
30	XRN2	XRN2	XRN2	9652	-0.015	-0.034	NO
31	DDX6	DDX6	DDX6	9846	-0.018	-0.04	NO
32	SKIV2L	SKIV2L	SKIV2L	9889	-0.019	-0.036	NO
33	ENO1	ENO1	ENO1	10140	-0.023	-0.044	NO
34	EXOSC7	EXOSC7	EXOSC7	10838	-0.034	-0.073	NO
35	PAPOLG	PAPOLG	PAPOLG	11122	-0.039	-0.078	NO
36	CNOT7	CNOT7	CNOT7	11177	-0.04	-0.07	NO
37	MPHOSPH6	MPHOSPH6	MPHOSPH6	11408	-0.044	-0.07	NO
38	PNPT1	PNPT1	PNPT1	11411	-0.044	-0.058	NO
39	LSM3	LSM3	LSM3	11587	-0.047	-0.055	NO
40	EXOSC1	EXOSC1	EXOSC1	11826	-0.052	-0.053	NO
41	CNOT1	CNOT1	CNOT1	11944	-0.054	-0.045	NO
42	LSM6	LSM6	LSM6	12185	-0.058	-0.042	NO
43	TTC37	TTC37	TTC37	12274	-0.06	-0.03	NO
44	SKIV2L2	SKIV2L2	SKIV2L2	12430	-0.064	-0.02	NO
45	EXOSC4	EXOSC4	EXOSC4	12459	-0.064	-0.0037	NO
46	DCPS	DCPS	DCPS	12526	-0.066	0.011	NO
47	LSM2	LSM2	LSM2	12593	-0.067	0.026	NO
48	EXOSC3	EXOSC3	EXOSC3	12817	-0.072	0.034	NO
49	EXOSC6	EXOSC6	EXOSC6	13372	-0.086	0.028	NO
50	EXOSC5	EXOSC5	EXOSC5	13456	-0.088	0.048	NO
51	WDR61	WDR61	WDR61	13919	-0.1	0.051	NO
52	C1D	C1D	C1D	13923	-0.1	0.08	NO
53	PATL1	PATL1	PATL1	14044	-0.11	0.1	NO
54	HSPD1	HSPD1	HSPD1	14121	-0.11	0.13	NO
55	HSPA9	HSPA9	HSPA9	14635	-0.13	0.14	NO
56	RQCD1	RQCD1	RQCD1	15326	-0.17	0.15	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 CARDIAC MUSCLE CONTRACTION.

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

genes ES table in pathway: KEGG HEDGEHOG SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CAMK2B	CAMK2B	CAMK2B	85	0.59	0.035	YES
2	WNT2	WNT2	WNT2	208	0.52	0.062	YES
3	PRKCG	PRKCG	PRKCG	266	0.49	0.092	YES
4	WNT5A	WNT5A	WNT5A	303	0.48	0.12	YES
5	WNT7B	WNT7B	WNT7B	386	0.46	0.15	YES
6	ADCY2	ADCY2	ADCY2	412	0.45	0.18	YES
7	MC1R	MC1R	MC1R	551	0.42	0.2	YES
8	KITLG	KITLG	KITLG	745	0.38	0.21	YES
9	TYR	TYR	TYR	838	0.36	0.23	YES
10	EDNRB	EDNRB	EDNRB	1329	0.29	0.22	YES
11	GNAI1	GNAI1	GNAI1	1460	0.27	0.23	YES
12	EDN1	EDN1	EDN1	1525	0.26	0.24	YES
13	CALML6	CALML6	CALML6	1586	0.26	0.26	YES
14	WNT10B	WNT10B	WNT10B	1624	0.26	0.27	YES
15	KIT	KIT	KIT	2109	0.21	0.26	YES
16	CALML3	CALML3	CALML3	2235	0.2	0.27	YES
17	WNT16	WNT16	WNT16	2362	0.19	0.27	YES
18	FZD1	FZD1	FZD1	2455	0.19	0.28	YES
19	WNT4	WNT4	WNT4	2764	0.17	0.27	NO
20	MITF	MITF	MITF	2901	0.16	0.28	NO
21	FZD4	FZD4	FZD4	3164	0.14	0.27	NO
22	PRKX	PRKX	PRKX	3525	0.13	0.26	NO
23	WNT3	WNT3	WNT3	3781	0.12	0.25	NO
24	FZD8	FZD8	FZD8	3911	0.11	0.25	NO
25	DVL2	DVL2	DVL2	3993	0.11	0.26	NO
26	FZD2	FZD2	FZD2	4069	0.1	0.26	NO
27	FZD9	FZD9	FZD9	4128	0.1	0.26	NO
28	CREB3L4	CREB3L4	CREB3L4	4142	0.1	0.27	NO
29	PRKACB	PRKACB	PRKACB	4611	0.087	0.25	NO
30	CREB3L2	CREB3L2	CREB3L2	4755	0.083	0.25	NO
31	DCT	DCT	DCT	4972	0.077	0.24	NO
32	WNT1	WNT1	WNT1	5284	0.069	0.23	NO
33	TCF7L2	TCF7L2	TCF7L2	5339	0.067	0.23	NO
34	KRAS	KRAS	KRAS	5426	0.065	0.23	NO
35	HRAS	HRAS	HRAS	5483	0.064	0.23	NO
36	GNAQ	GNAQ	GNAQ	5588	0.061	0.23	NO
37	WNT9A	WNT9A	WNT9A	5634	0.06	0.23	NO
38	ADCY6	ADCY6	ADCY6	5688	0.059	0.23	NO
39	DVL1	DVL1	DVL1	5842	0.056	0.22	NO
40	CAMK2D	CAMK2D	CAMK2D	6155	0.049	0.21	NO
41	PLCB3	PLCB3	PLCB3	6334	0.045	0.2	NO
42	CREB1	CREB1	CREB1	6634	0.038	0.19	NO
43	ADCY9	ADCY9	ADCY9	6804	0.035	0.18	NO
44	PRKCA	PRKCA	PRKCA	7250	0.026	0.16	NO
45	WNT3A	WNT3A	WNT3A	7316	0.025	0.16	NO
46	GNAS	GNAS	GNAS	7515	0.021	0.15	NO
47	CALM2	CALM2	CALM2	7519	0.021	0.15	NO
48	WNT7A	WNT7A	WNT7A	7539	0.02	0.15	NO
49	RAF1	RAF1	RAF1	7716	0.017	0.14	NO
50	EP300	EP300	EP300	8077	0.011	0.12	NO
51	CREBBP	CREBBP	CREBBP	8174	0.0096	0.12	NO
52	DVL3	DVL3	DVL3	8260	0.0082	0.11	NO
53	ADCY7	ADCY7	ADCY7	8311	0.0074	0.11	NO
54	CALM1	CALM1	CALM1	8372	0.0065	0.1	NO
55	FZD6	FZD6	FZD6	8540	0.0038	0.096	NO
56	GSK3B	GSK3B	GSK3B	8743	-0.000065	0.085	NO
57	CAMK2G	CAMK2G	CAMK2G	9089	-0.006	0.066	NO
58	WNT11	WNT11	WNT11	9594	-0.014	0.039	NO
59	TCF7	TCF7	TCF7	9914	-0.019	0.022	NO
60	CREB3	CREB3	CREB3	10025	-0.021	0.018	NO
61	GNAI3	GNAI3	GNAI3	10040	-0.021	0.018	NO
62	MAPK1	MAPK1	MAPK1	10203	-0.024	0.011	NO
63	PRKACA	PRKACA	PRKACA	10307	-0.026	0.0067	NO
64	FZD3	FZD3	FZD3	10486	-0.028	-0.0014	NO
65	MAP2K2	MAP2K2	MAP2K2	10538	-0.029	-0.0023	NO
66	CTNNB1	CTNNB1	CTNNB1	10740	-0.033	-0.011	NO
67	POMC	POMC	POMC	10752	-0.033	-0.0099	NO
68	MAPK3	MAPK3	MAPK3	10944	-0.036	-0.018	NO
69	WNT8B	WNT8B	WNT8B	11218	-0.041	-0.031	NO
70	GNAI2	GNAI2	GNAI2	11219	-0.041	-0.028	NO
71	WNT2B	WNT2B	WNT2B	11241	-0.041	-0.026	NO
72	NRAS	NRAS	NRAS	13499	-0.09	-0.15	NO
73	PLCB2	PLCB2	PLCB2	13669	-0.095	-0.15	NO
74	MAP2K1	MAP2K1	MAP2K1	13975	-0.1	-0.16	NO
75	TCF7L1	TCF7L1	TCF7L1	14046	-0.11	-0.16	NO
76	CALM3	CALM3	CALM3	14083	-0.11	-0.15	NO
77	ADCY8	ADCY8	ADCY8	14247	-0.11	-0.15	NO
78	PLCB1	PLCB1	PLCB1	14534	-0.13	-0.16	NO
79	WNT5B	WNT5B	WNT5B	14545	-0.13	-0.15	NO
80	FZD7	FZD7	FZD7	14702	-0.14	-0.15	NO
81	ASIP	ASIP	ASIP	14716	-0.14	-0.14	NO
82	FZD5	FZD5	FZD5	14774	-0.14	-0.14	NO
83	ADCY5	ADCY5	ADCY5	14807	-0.14	-0.13	NO
84	WNT9B	WNT9B	WNT9B	15418	-0.18	-0.15	NO
85	TYRP1	TYRP1	TYRP1	15514	-0.18	-0.15	NO
86	CAMK2A	CAMK2A	CAMK2A	15615	-0.19	-0.14	NO
87	WNT6	WNT6	WNT6	16010	-0.22	-0.15	NO
88	PLCB4	PLCB4	PLCB4	16609	-0.26	-0.16	NO
89	ADCY4	ADCY4	ADCY4	16886	-0.29	-0.16	NO
90	WNT10A	WNT10A	WNT10A	16934	-0.3	-0.14	NO
91	FZD10	FZD10	FZD10	17306	-0.34	-0.14	NO
92	CREB3L3	CREB3L3	CREB3L3	17521	-0.38	-0.13	NO
93	PRKCB	PRKCB	PRKCB	17594	-0.4	-0.11	NO
94	LEF1	LEF1	LEF1	17696	-0.42	-0.083	NO
95	ADCY1	ADCY1	ADCY1	17761	-0.46	-0.057	NO
96	GNAO1	GNAO1	GNAO1	17835	-0.49	-0.028	NO
97	CREB3L1	CREB3L1	CREB3L1	17911	-0.55	0.0039	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 HEDGEHOG SIGNALING PATHWAY.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG HEDGEHOG 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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG GLYCOLYSIS GLUCONEOGENESIS	57	genes.ES.table	0.53	1.7	0.0088	0.054	0.5	0.51	0.18	0.42	0	0
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.81	1.9	0	0.013	0.09	0.9	0.17	0.75	0	0.001
KEGG PENTOSE PHOSPHATE PATHWAY	25	genes.ES.table	0.47	1.4	0.1	0.19	0.9	0.6	0.22	0.47	0.14	0.003
KEGG FRUCTOSE AND MANNOSE METABOLISM	32	genes.ES.table	0.56	1.7	0.015	0.052	0.5	0.34	0.11	0.31	0.011	0
KEGG FATTY ACID METABOLISM	40	genes.ES.table	0.71	1.9	0.0043	0.017	0.079	0.78	0.15	0.66	0	0.001
KEGG STEROID HORMONE BIOSYNTHESIS	48	genes.ES.table	0.64	1.6	0.017	0.11	0.72	0.4	0.084	0.36	0.064	0.001
KEGG OXIDATIVE PHOSPHORYLATION	112	genes.ES.table	0.68	1.9	0.006	0.014	0.088	0.82	0.19	0.67	0	0.001
KEGG PYRIMIDINE METABOLISM	96	genes.ES.table	0.36	1.6	0.056	0.12	0.77	0.24	0.15	0.2	0.076	0.001
KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM	30	genes.ES.table	0.7	1.8	0.0041	0.03	0.27	0.53	0.11	0.48	0	0
KEGG GLYCINE SERINE AND THREONINE METABOLISM	30	genes.ES.table	0.8	1.8	0	0.027	0.23	0.6	0.068	0.56	0	0

genes ES table in pathway: KEGG GLYCOLYSIS GLUCONEOGENESIS

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	HAO2	HAO2	HAO2	1	0.85	0.086	YES
2	DAO	DAO	DAO	6	0.75	0.16	YES
3	PIPOX	PIPOX	PIPOX	20	0.63	0.22	YES
4	AGXT	AGXT	AGXT	48	0.55	0.28	YES
5	MPV17L	MPV17L	MPV17L	374	0.3	0.29	YES
6	EHHADH	EHHADH	EHHADH	389	0.29	0.32	YES
7	PXMP2	PXMP2	PXMP2	428	0.28	0.34	YES
8	DHRS4	DHRS4	DHRS4	615	0.23	0.36	YES
9	PAOX	PAOX	PAOX	623	0.22	0.38	YES
10	MLYCD	MLYCD	MLYCD	661	0.22	0.4	YES
11	DECR2	DECR2	DECR2	726	0.21	0.42	YES
12	SLC27A2	SLC27A2	SLC27A2	794	0.2	0.43	YES
13	DDO	DDO	DDO	854	0.19	0.45	YES
14	ACSL1	ACSL1	ACSL1	862	0.19	0.47	YES
15	ACAA1	ACAA1	ACAA1	878	0.18	0.48	YES
16	EPHX2	EPHX2	EPHX2	949	0.18	0.5	YES
17	PECI	PECI	PECI	964	0.17	0.51	YES
18	HMGCL	HMGCL	HMGCL	965	0.17	0.53	YES
19	PHYH	PHYH	PHYH	1053	0.16	0.54	YES
20	PEX11G	PEX11G	PEX11G	1084	0.16	0.56	YES
21	IDH2	IDH2	IDH2	1299	0.14	0.56	YES
22	HACL1	HACL1	HACL1	1319	0.14	0.57	YES
23	MVK	MVK	MVK	1426	0.13	0.58	YES
24	CRAT	CRAT	CRAT	1440	0.13	0.59	YES
25	ECH1	ECH1	ECH1	1666	0.12	0.59	YES
26	ACOX3	ACOX3	ACOX3	1704	0.11	0.6	YES
27	SOD2	SOD2	SOD2	1809	0.11	0.61	YES
28	PEX7	PEX7	PEX7	1823	0.11	0.62	YES
29	PEX3	PEX3	PEX3	1842	0.11	0.63	YES
30	CAT	CAT	CAT	1868	0.11	0.64	YES
31	PRDX1	PRDX1	PRDX1	1939	0.1	0.64	YES
32	FAR2	FAR2	FAR2	1984	0.1	0.65	YES
33	SCP2	SCP2	SCP2	2162	0.094	0.65	YES
34	IDH1	IDH1	IDH1	2259	0.091	0.65	YES
35	BAAT	BAAT	BAAT	2278	0.091	0.66	YES
36	PRDX5	PRDX5	PRDX5	2309	0.089	0.67	YES
37	PECR	PECR	PECR	2428	0.085	0.67	YES
38	PEX26	PEX26	PEX26	2494	0.083	0.68	YES
39	ACSL5	ACSL5	ACSL5	2537	0.082	0.68	YES
40	SOD1	SOD1	SOD1	2657	0.078	0.68	YES
41	ACOX1	ACOX1	ACOX1	2744	0.075	0.68	YES
42	GSTK1	GSTK1	GSTK1	2772	0.074	0.69	YES
43	HSD17B4	HSD17B4	HSD17B4	2832	0.073	0.7	YES
44	PEX11A	PEX11A	PEX11A	2924	0.07	0.7	YES
45	ACOT8	ACOT8	ACOT8	3165	0.064	0.69	YES
46	MPV17	MPV17	MPV17	3257	0.062	0.69	YES
47	ABCD3	ABCD3	ABCD3	3283	0.061	0.7	YES
48	PMVK	PMVK	PMVK	3396	0.058	0.7	YES
49	AMACR	AMACR	AMACR	3466	0.056	0.7	YES
50	XDH	XDH	XDH	3513	0.055	0.7	YES
51	PEX5	PEX5	PEX5	3580	0.054	0.7	YES
52	NUDT19	NUDT19	NUDT19	3598	0.053	0.71	YES
53	PEX10	PEX10	PEX10	3719	0.05	0.7	NO
54	PEX13	PEX13	PEX13	4154	0.041	0.68	NO
55	ABCD1	ABCD1	ABCD1	4190	0.04	0.69	NO
56	PEX16	PEX16	PEX16	4306	0.038	0.68	NO
57	ABCD4	ABCD4	ABCD4	4570	0.034	0.67	NO
58	PEX11B	PEX11B	PEX11B	4993	0.027	0.65	NO
59	PEX14	PEX14	PEX14	4995	0.027	0.66	NO
60	PEX19	PEX19	PEX19	5274	0.022	0.64	NO
61	NUDT12	NUDT12	NUDT12	6057	0.011	0.6	NO
62	AGPS	AGPS	AGPS	6413	0.0056	0.58	NO
63	PXMP4	PXMP4	PXMP4	6566	0.0034	0.57	NO
64	GNPAT	GNPAT	GNPAT	7036	-0.0032	0.55	NO
65	ACSL3	ACSL3	ACSL3	7168	-0.0052	0.54	NO
66	SLC25A17	SLC25A17	SLC25A17	7199	-0.0057	0.54	NO
67	PEX6	PEX6	PEX6	7207	-0.0058	0.54	NO
68	PEX12	PEX12	PEX12	7609	-0.011	0.52	NO
69	PEX2	PEX2	PEX2	7751	-0.013	0.51	NO
70	ABCD2	ABCD2	ABCD2	8935	-0.031	0.45	NO
71	ACSL6	ACSL6	ACSL6	9061	-0.033	0.44	NO
72	PEX1	PEX1	PEX1	10146	-0.049	0.39	NO
73	CROT	CROT	CROT	11630	-0.077	0.31	NO
74	ACSL4	ACSL4	ACSL4	12155	-0.088	0.29	NO
75	FAR1	FAR1	FAR1	12703	-0.1	0.27	NO
76	NOS2	NOS2	NOS2	15824	-0.22	0.12	NO

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

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

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

Table 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	EARS2	EARS2	EARS2	1605	0.12	-0.027	YES
2	LARS2	LARS2	LARS2	1665	0.12	0.031	YES
3	FARS2	FARS2	FARS2	1920	0.1	0.072	YES
4	WARS2	WARS2	WARS2	1950	0.1	0.12	YES
5	PARS2	PARS2	PARS2	1965	0.1	0.18	YES
6	MARS2	MARS2	MARS2	2050	0.098	0.22	YES
7	DARS2	DARS2	DARS2	2416	0.086	0.25	YES
8	YARS2	YARS2	YARS2	2764	0.074	0.27	YES
9	AARS	AARS	AARS	2830	0.073	0.3	YES
10	NARS2	NARS2	NARS2	2901	0.071	0.34	YES
11	NARS	NARS	NARS	3212	0.063	0.35	YES
12	CARS2	CARS2	CARS2	3388	0.058	0.37	YES
13	HARS2	HARS2	HARS2	3470	0.056	0.4	YES
14	KARS	KARS	KARS	3484	0.056	0.43	YES
15	YARS	YARS	YARS	3541	0.054	0.45	YES
16	SEPSECS	SEPSECS	SEPSECS	3667	0.052	0.47	YES
17	PSTK	PSTK	PSTK	3984	0.045	0.48	YES
18	VARS2	VARS2	VARS2	4094	0.042	0.5	YES
19	IARS2	IARS2	IARS2	4121	0.042	0.52	YES
20	SARS2	SARS2	SARS2	4142	0.041	0.54	YES
21	QARS	QARS	QARS	4161	0.041	0.56	YES
22	VARS	VARS	VARS	4183	0.04	0.58	YES
23	FARSA	FARSA	FARSA	4363	0.038	0.59	YES
24	FARSB	FARSB	FARSB	4626	0.033	0.59	YES
25	HARS	HARS	HARS	4688	0.032	0.6	YES
26	IARS	IARS	IARS	4795	0.03	0.62	YES
27	MTFMT	MTFMT	MTFMT	4832	0.03	0.63	YES
28	SARS	SARS	SARS	4862	0.029	0.64	YES
29	GARS	GARS	GARS	4914	0.028	0.66	YES
30	RARS2	RARS2	RARS2	4934	0.028	0.67	YES
31	RARS	RARS	RARS	5099	0.025	0.67	YES
32	WARS	WARS	WARS	5407	0.02	0.67	NO
33	CARS	CARS	CARS	6014	0.012	0.64	NO
34	TARS	TARS	TARS	6080	0.011	0.64	NO
35	MARS	MARS	MARS	6380	0.0061	0.63	NO
36	DARS	DARS	DARS	6759	0.00074	0.61	NO
37	AARS2	AARS2	AARS2	6981	-0.0024	0.6	NO
38	LARS	LARS	LARS	7184	-0.0055	0.59	NO
39	TARSL2	TARSL2	TARSL2	7676	-0.012	0.57	NO
40	EPRS	EPRS	EPRS	7916	-0.015	0.56	NO

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

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

genes ES table in pathway: KEGG PENTOSE PHOSPHATE 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	AOX1	AOX1	AOX1	71	0.52	0.071	YES
2	ABAT	ABAT	ABAT	137	0.43	0.13	YES
3	ALDH6A1	ALDH6A1	ALDH6A1	246	0.35	0.17	YES
4	ALDH1B1	ALDH1B1	ALDH1B1	346	0.31	0.21	YES
5	EHHADH	EHHADH	EHHADH	389	0.29	0.25	YES
6	ACAT1	ACAT1	ACAT1	622	0.23	0.27	YES
7	PCCA	PCCA	PCCA	748	0.2	0.3	YES
8	ACADS	ACADS	ACADS	816	0.19	0.32	YES
9	HIBCH	HIBCH	HIBCH	819	0.19	0.35	YES
10	ECHS1	ECHS1	ECHS1	823	0.19	0.38	YES
11	ACAA1	ACAA1	ACAA1	878	0.18	0.4	YES
12	BCAT2	BCAT2	BCAT2	935	0.18	0.42	YES
13	HMGCL	HMGCL	HMGCL	965	0.17	0.44	YES
14	ALDH2	ALDH2	ALDH2	982	0.17	0.47	YES
15	IL4I1	IL4I1	IL4I1	1015	0.17	0.49	YES
16	MCEE	MCEE	MCEE	1028	0.17	0.51	YES
17	PCCB	PCCB	PCCB	1065	0.16	0.54	YES
18	AUH	AUH	AUH	1096	0.16	0.56	YES
19	OXCT1	OXCT1	OXCT1	1109	0.16	0.58	YES
20	ACAA2	ACAA2	ACAA2	1134	0.16	0.6	YES
21	HADH	HADH	HADH	1154	0.15	0.62	YES
22	OXCT2	OXCT2	OXCT2	1165	0.15	0.64	YES
23	MCCC1	MCCC1	MCCC1	1191	0.15	0.66	YES
24	ACADM	ACADM	ACADM	1310	0.14	0.68	YES
25	ACADSB	ACADSB	ACADSB	1396	0.13	0.69	YES
26	ACAT2	ACAT2	ACAT2	1479	0.13	0.7	YES
27	MUT	MUT	MUT	1481	0.13	0.72	YES
28	ACAD8	ACAD8	ACAD8	1520	0.12	0.74	YES
29	HIBADH	HIBADH	HIBADH	1635	0.12	0.75	YES
30	ALDH7A1	ALDH7A1	ALDH7A1	1918	0.1	0.75	YES
31	ALDH9A1	ALDH9A1	ALDH9A1	1923	0.1	0.76	YES
32	MCCC2	MCCC2	MCCC2	1954	0.1	0.78	YES
33	HADHA	HADHA	HADHA	2146	0.095	0.78	YES
34	IVD	IVD	IVD	2207	0.093	0.79	YES
35	HSD17B10	HSD17B10	HSD17B10	2330	0.088	0.8	YES
36	HADHB	HADHB	HADHB	2351	0.088	0.81	YES
37	ALDH3A2	ALDH3A2	ALDH3A2	2514	0.082	0.81	YES
38	DLD	DLD	DLD	2580	0.08	0.82	YES
39	BCKDHA	BCKDHA	BCKDHA	2632	0.078	0.82	YES
40	BCKDHB	BCKDHB	BCKDHB	2708	0.076	0.83	YES
41	DBT	DBT	DBT	3269	0.062	0.81	NO
42	HMGCS2	HMGCS2	HMGCS2	3726	0.05	0.79	NO
43	HMGCS1	HMGCS1	HMGCS1	8257	-0.02	0.54	NO

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

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

genes ES table in pathway: KEGG FRUCTOSE AND MANNOSE METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PIPOX	PIPOX	PIPOX	20	0.63	0.13	YES
2	BBOX1	BBOX1	BBOX1	96	0.48	0.23	YES
3	ALDH1B1	ALDH1B1	ALDH1B1	346	0.31	0.28	YES
4	ACAT1	ACAT1	ACAT1	622	0.23	0.31	YES
5	GCDH	GCDH	GCDH	737	0.21	0.34	YES
6	OGDHL	OGDHL	OGDHL	800	0.2	0.38	YES
7	ECHS1	ECHS1	ECHS1	823	0.19	0.42	YES
8	ALDH2	ALDH2	ALDH2	982	0.17	0.45	YES
9	HADH	HADH	HADH	1154	0.15	0.47	YES
10	AADAT	AADAT	AADAT	1313	0.14	0.49	YES
11	ACAT2	ACAT2	ACAT2	1479	0.13	0.51	YES
12	ALDH7A1	ALDH7A1	ALDH7A1	1918	0.1	0.51	YES
13	ALDH9A1	ALDH9A1	ALDH9A1	1923	0.1	0.53	YES
14	HADHA	HADHA	HADHA	2146	0.095	0.53	YES
15	TMLHE	TMLHE	TMLHE	2197	0.093	0.55	YES
16	ALDH3A2	ALDH3A2	ALDH3A2	2514	0.082	0.55	YES
17	OGDH	OGDH	OGDH	2776	0.074	0.55	YES
18	DLST	DLST	DLST	2839	0.073	0.56	YES
19	PLOD1	PLOD1	PLOD1	3044	0.067	0.57	YES
20	AASDHPPT	AASDHPPT	AASDHPPT	5480	0.019	0.43	NO
21	PLOD3	PLOD3	PLOD3	5842	0.014	0.42	NO
22	AASS	AASS	AASS	7361	-0.0082	0.33	NO
23	SETDB2	SETDB2	SETDB2	7845	-0.014	0.31	NO
24	EHMT2	EHMT2	EHMT2	8135	-0.019	0.3	NO
25	SETD1A	SETD1A	SETD1A	8185	-0.02	0.3	NO
26	SETD7	SETD7	SETD7	8865	-0.03	0.27	NO
27	AASDH	AASDH	AASDH	9116	-0.034	0.26	NO
28	SETD2	SETD2	SETD2	9148	-0.034	0.27	NO
29	SUV39H2	SUV39H2	SUV39H2	9185	-0.035	0.27	NO
30	SETMAR	SETMAR	SETMAR	9404	-0.038	0.27	NO
31	SETDB1	SETDB1	SETDB1	9636	-0.041	0.26	NO
32	PLOD2	PLOD2	PLOD2	9733	-0.043	0.27	NO
33	NSD1	NSD1	NSD1	9880	-0.045	0.27	NO
34	SUV39H1	SUV39H1	SUV39H1	10643	-0.058	0.24	NO
35	SUV420H2	SUV420H2	SUV420H2	11244	-0.069	0.22	NO
36	EHMT1	EHMT1	EHMT1	11313	-0.07	0.23	NO
37	DOT1L	DOT1L	DOT1L	11661	-0.077	0.23	NO
38	SETD8	SETD8	SETD8	11714	-0.078	0.24	NO
39	SUV420H1	SUV420H1	SUV420H1	12412	-0.094	0.22	NO
40	WHSC1	WHSC1	WHSC1	12563	-0.098	0.23	NO
41	WHSC1L1	WHSC1L1	WHSC1L1	12614	-0.099	0.25	NO
42	ASH1L	ASH1L	ASH1L	12774	-0.1	0.26	NO
43	SETD1B	SETD1B	SETD1B	13736	-0.13	0.24	NO

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

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

genes ES table in pathway: KEGG FATTY ACID METABOLISM

Table 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	DNASE2B	DNASE2B	DNASE2B	144	0.42	0.037	YES
2	ACP5	ACP5	ACP5	306	0.32	0.062	YES
3	ATP6V0D2	ATP6V0D2	ATP6V0D2	308	0.32	0.097	YES
4	CTSE	CTSE	CTSE	637	0.22	0.1	YES
5	HYAL1	HYAL1	HYAL1	645	0.22	0.12	YES
6	CTSS	CTSS	CTSS	723	0.21	0.14	YES
7	CD68	CD68	CD68	883	0.18	0.15	YES
8	CTSH	CTSH	CTSH	1142	0.15	0.16	YES
9	PLA2G15	PLA2G15	PLA2G15	1254	0.14	0.16	YES
10	CTSB	CTSB	CTSB	1263	0.14	0.18	YES
11	NAGLU	NAGLU	NAGLU	1354	0.14	0.19	YES
12	AP1M2	AP1M2	AP1M2	1412	0.13	0.2	YES
13	CTSL2	CTSL2	CTSL2	1418	0.13	0.21	YES
14	NEU1	NEU1	NEU1	1508	0.12	0.22	YES
15	ATP6V0D1	ATP6V0D1	ATP6V0D1	1509	0.12	0.24	YES
16	FUCA1	FUCA1	FUCA1	1515	0.12	0.25	YES
17	MCOLN1	MCOLN1	MCOLN1	1517	0.12	0.26	YES
18	CTSD	CTSD	CTSD	1593	0.12	0.27	YES
19	LAPTM5	LAPTM5	LAPTM5	1662	0.12	0.28	YES
20	CTSA	CTSA	CTSA	1700	0.12	0.29	YES
21	ATP6V0C	ATP6V0C	ATP6V0C	1814	0.11	0.3	YES
22	GM2A	GM2A	GM2A	1816	0.11	0.31	YES
23	LGMN	LGMN	LGMN	1858	0.11	0.32	YES
24	LIPA	LIPA	LIPA	1859	0.11	0.33	YES
25	ARSA	ARSA	ARSA	1998	0.1	0.33	YES
26	NAGPA	NAGPA	NAGPA	2001	0.1	0.34	YES
27	SLC17A5	SLC17A5	SLC17A5	2157	0.094	0.34	YES
28	CTSW	CTSW	CTSW	2248	0.092	0.35	YES
29	AP1S1	AP1S1	AP1S1	2276	0.091	0.35	YES
30	TPP1	TPP1	TPP1	2319	0.089	0.36	YES
31	CTSK	CTSK	CTSK	2362	0.087	0.37	YES
32	ASAH1	ASAH1	ASAH1	2371	0.087	0.38	YES
33	ATP6V0B	ATP6V0B	ATP6V0B	2425	0.085	0.38	YES
34	NPC2	NPC2	NPC2	2432	0.085	0.39	YES
35	CLTCL1	CLTCL1	CLTCL1	2433	0.085	0.4	YES
36	ATP6V0A1	ATP6V0A1	ATP6V0A1	2497	0.083	0.41	YES
37	CTSL1	CTSL1	CTSL1	2513	0.082	0.42	YES
38	GBA	GBA	GBA	2598	0.08	0.42	YES
39	HEXA	HEXA	HEXA	2603	0.079	0.43	YES
40	ATP6V1H	ATP6V1H	ATP6V1H	2624	0.079	0.43	YES
41	GNPTG	GNPTG	GNPTG	2698	0.077	0.44	YES
42	GGA2	GGA2	GGA2	2699	0.077	0.45	YES
43	GLB1	GLB1	GLB1	2729	0.076	0.45	YES
44	GALNS	GALNS	GALNS	2747	0.075	0.46	YES
45	SUMF1	SUMF1	SUMF1	2792	0.074	0.46	YES
46	CLN3	CLN3	CLN3	2811	0.073	0.47	YES
47	SMPD1	SMPD1	SMPD1	2836	0.073	0.48	YES
48	GLA	GLA	GLA	2871	0.072	0.48	YES
49	LAMP1	LAMP1	LAMP1	2890	0.071	0.49	YES
50	CTNS	CTNS	CTNS	2927	0.07	0.5	YES
51	ACP2	ACP2	ACP2	2933	0.07	0.5	YES
52	SLC11A1	SLC11A1	SLC11A1	3002	0.068	0.51	YES
53	HEXB	HEXB	HEXB	3035	0.067	0.51	YES
54	CTSZ	CTSZ	CTSZ	3103	0.066	0.52	YES
55	ARSB	ARSB	ARSB	3236	0.062	0.52	YES
56	AP1B1	AP1B1	AP1B1	3244	0.062	0.52	YES
57	LAMP2	LAMP2	LAMP2	3343	0.06	0.52	YES
58	CD63	CD63	CD63	3441	0.057	0.52	YES
59	IGF2R	IGF2R	IGF2R	3482	0.056	0.53	YES
60	GNS	GNS	GNS	3487	0.056	0.53	YES
61	AGA	AGA	AGA	3508	0.055	0.54	YES
62	DNASE2	DNASE2	DNASE2	3539	0.054	0.54	YES
63	AP1M1	AP1M1	AP1M1	3666	0.052	0.54	YES
64	AP3S1	AP3S1	AP3S1	3669	0.052	0.55	YES
65	AP3S2	AP3S2	AP3S2	4130	0.042	0.52	NO
66	NAPSA	NAPSA	NAPSA	4149	0.041	0.53	NO
67	AP1S2	AP1S2	AP1S2	4164	0.041	0.53	NO
68	CLN5	CLN5	CLN5	4296	0.039	0.53	NO
69	CLTC	CLTC	CLTC	4367	0.038	0.53	NO
70	GAA	GAA	GAA	4405	0.037	0.53	NO
71	PPT2	PPT2	PPT2	4460	0.036	0.53	NO
72	AP1G1	AP1G1	AP1G1	4493	0.036	0.53	NO
73	MANBA	MANBA	MANBA	4522	0.035	0.53	NO
74	ATP6AP1	ATP6AP1	ATP6AP1	4603	0.034	0.53	NO
75	CLTA	CLTA	CLTA	4789	0.03	0.53	NO
76	PSAP	PSAP	PSAP	4819	0.03	0.53	NO
77	CD164	CD164	CD164	4864	0.029	0.53	NO
78	CTSO	CTSO	CTSO	5121	0.025	0.52	NO
79	CLTB	CLTB	CLTB	5163	0.024	0.52	NO
80	LAPTM4A	LAPTM4A	LAPTM4A	5217	0.023	0.52	NO
81	AP3D1	AP3D1	AP3D1	5317	0.022	0.51	NO
82	PPT1	PPT1	PPT1	5583	0.018	0.5	NO
83	AP3B1	AP3B1	AP3B1	5901	0.013	0.48	NO
84	NPC1	NPC1	NPC1	5960	0.012	0.48	NO
85	MAN2B1	MAN2B1	MAN2B1	6082	0.011	0.48	NO
86	GUSB	GUSB	GUSB	6106	0.01	0.48	NO
87	NAGA	NAGA	NAGA	6214	0.0086	0.47	NO
88	SCARB2	SCARB2	SCARB2	6483	0.0046	0.46	NO
89	GALC	GALC	GALC	6816	-0.000059	0.44	NO
90	SORT1	SORT1	SORT1	7048	-0.0034	0.43	NO
91	CTSC	CTSC	CTSC	7062	-0.0037	0.42	NO
92	ARSG	ARSG	ARSG	7130	-0.0047	0.42	NO
93	ATP6V0A2	ATP6V0A2	ATP6V0A2	7174	-0.0053	0.42	NO
94	M6PR	M6PR	M6PR	7195	-0.0056	0.42	NO
95	GNPTAB	GNPTAB	GNPTAB	7245	-0.0065	0.42	NO
96	SGSH	SGSH	SGSH	7464	-0.0096	0.41	NO
97	LAPTM4B	LAPTM4B	LAPTM4B	7897	-0.015	0.38	NO
98	AP3M1	AP3M1	AP3M1	8013	-0.017	0.38	NO
99	MFSD8	MFSD8	MFSD8	8388	-0.022	0.36	NO
100	GGA1	GGA1	GGA1	8465	-0.024	0.36	NO
101	ENTPD4	ENTPD4	ENTPD4	8870	-0.03	0.34	NO
102	AP4E1	AP4E1	AP4E1	9014	-0.032	0.34	NO
103	AP4M1	AP4M1	AP4M1	9211	-0.035	0.33	NO
104	AP3M2	AP3M2	AP3M2	9478	-0.039	0.32	NO
105	AP4B1	AP4B1	AP4B1	9695	-0.042	0.31	NO
106	CTSF	CTSF	CTSF	9974	-0.046	0.3	NO
107	TCIRG1	TCIRG1	TCIRG1	10180	-0.05	0.29	NO
108	GGA3	GGA3	GGA3	10465	-0.054	0.28	NO
109	AP4S1	AP4S1	AP4S1	10965	-0.064	0.26	NO
110	SLC11A2	SLC11A2	SLC11A2	11656	-0.077	0.23	NO
111	ABCA2	ABCA2	ABCA2	11908	-0.082	0.23	NO
112	AP1S3	AP1S3	AP1S3	12191	-0.089	0.22	NO
113	ABCB9	ABCB9	ABCB9	12350	-0.092	0.22	NO
114	CTSG	CTSG	CTSG	13070	-0.11	0.19	NO
115	IDS	IDS	IDS	13538	-0.12	0.18	NO
116	IDUA	IDUA	IDUA	13658	-0.13	0.19	NO
117	LAMP3	LAMP3	LAMP3	13903	-0.14	0.19	NO
118	AP3B2	AP3B2	AP3B2	14445	-0.16	0.17	NO
119	ATP6V0A4	ATP6V0A4	ATP6V0A4	15938	-0.22	0.11	NO

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

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

genes ES table in pathway: KEGG STEROID HORMONE BIOSYNTHESIS

Table 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	PKLR	PKLR	PKLR	16	0.65	0.11	YES
2	PCK1	PCK1	PCK1	31	0.6	0.21	YES
3	LDHD	LDHD	LDHD	149	0.41	0.28	YES
4	PC	PC	PC	326	0.32	0.32	YES
5	ALDH1B1	ALDH1B1	ALDH1B1	346	0.31	0.37	YES
6	HAGHL	HAGHL	HAGHL	409	0.28	0.42	YES
7	ME1	ME1	ME1	489	0.26	0.46	YES
8	ACAT1	ACAT1	ACAT1	622	0.23	0.49	YES
9	PCK2	PCK2	PCK2	655	0.22	0.53	YES
10	HAGH	HAGH	HAGH	832	0.19	0.55	YES
11	ALDH2	ALDH2	ALDH2	982	0.17	0.57	YES
12	GRHPR	GRHPR	GRHPR	1041	0.16	0.6	YES
13	MDH1	MDH1	MDH1	1386	0.13	0.6	YES
14	ACAT2	ACAT2	ACAT2	1479	0.13	0.62	YES
15	ACSS2	ACSS2	ACSS2	1611	0.12	0.63	YES
16	PDHA1	PDHA1	PDHA1	1894	0.1	0.63	YES
17	ALDH7A1	ALDH7A1	ALDH7A1	1918	0.1	0.65	YES
18	ALDH9A1	ALDH9A1	ALDH9A1	1923	0.1	0.67	YES
19	MDH2	MDH2	MDH2	2181	0.094	0.67	YES
20	ME3	ME3	ME3	2340	0.088	0.67	YES
21	PDHB	PDHB	PDHB	2378	0.087	0.69	YES
22	ACOT12	ACOT12	ACOT12	2441	0.085	0.7	YES
23	ALDH3A2	ALDH3A2	ALDH3A2	2514	0.082	0.71	YES
24	DLD	DLD	DLD	2580	0.08	0.72	YES
25	LDHB	LDHB	LDHB	2642	0.078	0.73	YES
26	DLAT	DLAT	DLAT	2917	0.071	0.72	YES
27	ACSS1	ACSS1	ACSS1	3000	0.068	0.73	YES
28	ME2	ME2	ME2	3776	0.049	0.7	NO
29	ACYP2	ACYP2	ACYP2	4311	0.038	0.67	NO
30	AKR1B1	AKR1B1	AKR1B1	4551	0.035	0.67	NO
31	ACACB	ACACB	ACACB	6420	0.0055	0.56	NO
32	PKM2	PKM2	PKM2	6805	0.000099	0.54	NO
33	LDHA	LDHA	LDHA	7267	-0.0069	0.52	NO
34	ACACA	ACACA	ACACA	7423	-0.0091	0.51	NO
35	ACYP1	ACYP1	ACYP1	9499	-0.039	0.4	NO
36	GLO1	GLO1	GLO1	9573	-0.04	0.4	NO
37	LDHAL6B	LDHAL6B	LDHAL6B	14773	-0.17	0.14	NO
38	LDHAL6A	LDHAL6A	LDHAL6A	15480	-0.2	0.14	NO

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

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

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

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	ADH6	ADH6	ADH6	160	0.4	0.058	YES
2	CYP4A11	CYP4A11	CYP4A11	179	0.39	0.12	YES
3	ALDH1B1	ALDH1B1	ALDH1B1	346	0.31	0.16	YES
4	EHHADH	EHHADH	EHHADH	389	0.29	0.21	YES
5	ACAT1	ACAT1	ACAT1	622	0.23	0.23	YES
6	GCDH	GCDH	GCDH	737	0.21	0.26	YES
7	ACADS	ACADS	ACADS	816	0.19	0.29	YES
8	ECHS1	ECHS1	ECHS1	823	0.19	0.32	YES
9	CPT2	CPT2	CPT2	836	0.19	0.35	YES
10	ACSL1	ACSL1	ACSL1	862	0.19	0.38	YES
11	ACAA1	ACAA1	ACAA1	878	0.18	0.41	YES
12	PECI	PECI	PECI	964	0.17	0.43	YES
13	CYP4A22	CYP4A22	CYP4A22	969	0.17	0.46	YES
14	ALDH2	ALDH2	ALDH2	982	0.17	0.49	YES
15	ACADL	ACADL	ACADL	994	0.17	0.51	YES
16	ACAA2	ACAA2	ACAA2	1134	0.16	0.53	YES
17	HADH	HADH	HADH	1154	0.15	0.56	YES
18	ACADM	ACADM	ACADM	1310	0.14	0.57	YES
19	ACADSB	ACADSB	ACADSB	1396	0.13	0.59	YES
20	ACAT2	ACAT2	ACAT2	1479	0.13	0.6	YES
21	ACOX3	ACOX3	ACOX3	1704	0.11	0.61	YES
22	ADH5	ADH5	ADH5	1874	0.11	0.62	YES
23	ALDH7A1	ALDH7A1	ALDH7A1	1918	0.1	0.63	YES
24	ALDH9A1	ALDH9A1	ALDH9A1	1923	0.1	0.65	YES
25	HADHA	HADHA	HADHA	2146	0.095	0.65	YES
26	ACADVL	ACADVL	ACADVL	2244	0.092	0.66	YES
27	HADHB	HADHB	HADHB	2351	0.088	0.67	YES
28	ALDH3A2	ALDH3A2	ALDH3A2	2514	0.082	0.68	YES
29	ACSL5	ACSL5	ACSL5	2537	0.082	0.69	YES
30	CPT1A	CPT1A	CPT1A	2622	0.079	0.7	YES
31	DCI	DCI	DCI	2675	0.077	0.7	YES
32	ADH4	ADH4	ADH4	2908	0.071	0.7	NO
33	ACSL3	ACSL3	ACSL3	7168	-0.0052	0.47	NO
34	ADH1B	ADH1B	ADH1B	8521	-0.025	0.4	NO
35	ACSL6	ACSL6	ACSL6	9061	-0.033	0.37	NO
36	ADH1C	ADH1C	ADH1C	10229	-0.051	0.32	NO
37	ADH1A	ADH1A	ADH1A	10753	-0.06	0.3	NO
38	ACSL4	ACSL4	ACSL4	12155	-0.088	0.23	NO
39	CPT1B	CPT1B	CPT1B	13460	-0.12	0.18	NO
40	CPT1C	CPT1C	CPT1C	17847	-0.44	0.0075	NO

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

Figure S54. 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 PYRIMIDINE METABOLISM

Table S28. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	AOX1	AOX1	AOX1	71	0.52	0.08	YES
2	DDC	DDC	DDC	80	0.51	0.16	YES
3	KMO	KMO	KMO	163	0.4	0.22	YES
4	ACMSD	ACMSD	ACMSD	265	0.34	0.27	YES
5	ALDH1B1	ALDH1B1	ALDH1B1	346	0.31	0.32	YES
6	EHHADH	EHHADH	EHHADH	389	0.29	0.36	YES
7	HAAO	HAAO	HAAO	417	0.28	0.41	YES
8	ACAT1	ACAT1	ACAT1	622	0.23	0.43	YES
9	GCDH	GCDH	GCDH	737	0.21	0.46	YES
10	OGDHL	OGDHL	OGDHL	800	0.2	0.49	YES
11	ECHS1	ECHS1	ECHS1	823	0.19	0.52	YES
12	ALDH2	ALDH2	ALDH2	982	0.17	0.54	YES
13	IL4I1	IL4I1	IL4I1	1015	0.17	0.56	YES
14	HADH	HADH	HADH	1154	0.15	0.58	YES
15	AADAT	AADAT	AADAT	1313	0.14	0.59	YES
16	ACAT2	ACAT2	ACAT2	1479	0.13	0.6	YES
17	ABP1	ABP1	ABP1	1679	0.12	0.61	YES
18	MAOB	MAOB	MAOB	1844	0.11	0.62	YES
19	CAT	CAT	CAT	1868	0.11	0.64	YES
20	ALDH7A1	ALDH7A1	ALDH7A1	1918	0.1	0.65	YES
21	ALDH9A1	ALDH9A1	ALDH9A1	1923	0.1	0.67	YES
22	WARS2	WARS2	WARS2	1950	0.1	0.68	YES
23	AFMID	AFMID	AFMID	2074	0.097	0.69	YES
24	HADHA	HADHA	HADHA	2146	0.095	0.7	YES
25	ALDH3A2	ALDH3A2	ALDH3A2	2514	0.082	0.7	NO
26	OGDH	OGDH	OGDH	2776	0.074	0.69	NO
27	CYP1B1	CYP1B1	CYP1B1	3762	0.049	0.64	NO
28	MAOA	MAOA	MAOA	3785	0.049	0.65	NO
29	WARS	WARS	WARS	5407	0.02	0.56	NO
30	AANAT	AANAT	AANAT	5748	0.015	0.55	NO
31	IDO1	IDO1	IDO1	7060	-0.0037	0.48	NO
32	INMT	INMT	INMT	11349	-0.071	0.25	NO
33	IDO2	IDO2	IDO2	12160	-0.088	0.22	NO
34	CYP1A1	CYP1A1	CYP1A1	13189	-0.11	0.18	NO
35	TDO2	TDO2	TDO2	13514	-0.12	0.18	NO
36	TPH1	TPH1	TPH1	15360	-0.2	0.11	NO
37	ASMT	ASMT	ASMT	15903	-0.22	0.12	NO

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

Figure S56. 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 ALANINE ASPARTATE AND GLUTAMATE METABOLISM

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	COX6A2	COX6A2	COX6A2	82	0.5	0.042	YES
2	ATP6V0D2	ATP6V0D2	ATP6V0D2	308	0.32	0.058	YES
3	ATP6V1B1	ATP6V1B1	ATP6V1B1	513	0.26	0.071	YES
4	ATP5G1	ATP5G1	ATP5G1	1180	0.15	0.047	YES
5	COX17	COX17	COX17	1238	0.15	0.057	YES
6	SDHB	SDHB	SDHB	1259	0.14	0.07	YES
7	UQCRQ	UQCRQ	UQCRQ	1261	0.14	0.083	YES
8	LHPP	LHPP	LHPP	1328	0.14	0.092	YES
9	NDUFAB1	NDUFAB1	NDUFAB1	1364	0.14	0.1	YES
10	PPA2	PPA2	PPA2	1437	0.13	0.11	YES
11	UQCRHL	UQCRHL	UQCRHL	1444	0.13	0.12	YES
12	ATP5G3	ATP5G3	ATP5G3	1490	0.13	0.13	YES
13	UQCRC2	UQCRC2	UQCRC2	1496	0.12	0.14	YES
14	UQCRC1	UQCRC1	UQCRC1	1502	0.12	0.15	YES
15	ATP6V0D1	ATP6V0D1	ATP6V0D1	1509	0.12	0.16	YES
16	NDUFS1	NDUFS1	NDUFS1	1531	0.12	0.17	YES
17	NDUFB2	NDUFB2	NDUFB2	1545	0.12	0.18	YES
18	SDHA	SDHA	SDHA	1567	0.12	0.2	YES
19	NDUFS4	NDUFS4	NDUFS4	1600	0.12	0.2	YES
20	NDUFA9	NDUFA9	NDUFA9	1630	0.12	0.21	YES
21	ATP6V1B2	ATP6V1B2	ATP6V1B2	1671	0.12	0.22	YES
22	CYC1	CYC1	CYC1	1684	0.12	0.23	YES
23	COX7B	COX7B	COX7B	1739	0.11	0.24	YES
24	UQCRFS1	UQCRFS1	UQCRFS1	1764	0.11	0.25	YES
25	ATP6V0C	ATP6V0C	ATP6V0C	1814	0.11	0.26	YES
26	NDUFB6	NDUFB6	NDUFB6	1831	0.11	0.26	YES
27	NDUFS2	NDUFS2	NDUFS2	1833	0.11	0.27	YES
28	NDUFB3	NDUFB3	NDUFB3	1857	0.11	0.28	YES
29	NDUFB10	NDUFB10	NDUFB10	1863	0.11	0.29	YES
30	UQCRH	UQCRH	UQCRH	1881	0.1	0.3	YES
31	NDUFV1	NDUFV1	NDUFV1	1888	0.1	0.31	YES
32	ATP6V1F	ATP6V1F	ATP6V1F	1922	0.1	0.32	YES
33	ATP5F1	ATP5F1	ATP5F1	1933	0.1	0.33	YES
34	SDHD	SDHD	SDHD	1949	0.1	0.34	YES
35	COX5A	COX5A	COX5A	1976	0.1	0.34	YES
36	COX4I1	COX4I1	COX4I1	1986	0.1	0.35	YES
37	NDUFA2	NDUFA2	NDUFA2	2006	0.1	0.36	YES
38	ATP6V0E2	ATP6V0E2	ATP6V0E2	2007	0.1	0.37	YES
39	ATP5B	ATP5B	ATP5B	2046	0.098	0.38	YES
40	COX10	COX10	COX10	2092	0.096	0.38	YES
41	NDUFS8	NDUFS8	NDUFS8	2096	0.096	0.39	YES
42	ATP5I	ATP5I	ATP5I	2104	0.096	0.4	YES
43	NDUFB5	NDUFB5	NDUFB5	2141	0.095	0.41	YES
44	NDUFS6	NDUFS6	NDUFS6	2155	0.094	0.41	YES
45	NDUFA3	NDUFA3	NDUFA3	2169	0.094	0.42	YES
46	NDUFA10	NDUFA10	NDUFA10	2187	0.094	0.43	YES
47	NDUFB1	NDUFB1	NDUFB1	2191	0.094	0.44	YES
48	NDUFS7	NDUFS7	NDUFS7	2240	0.092	0.44	YES
49	UQCR10	UQCR10	UQCR10	2262	0.091	0.45	YES
50	COX6A1	COX6A1	COX6A1	2277	0.091	0.46	YES
51	COX7A2	COX7A2	COX7A2	2290	0.09	0.47	YES
52	PPA1	PPA1	PPA1	2292	0.09	0.47	YES
53	ATP5A1	ATP5A1	ATP5A1	2313	0.089	0.48	YES
54	ATP6V0B	ATP6V0B	ATP6V0B	2425	0.085	0.48	YES
55	NDUFB9	NDUFB9	NDUFB9	2442	0.085	0.49	YES
56	SDHC	SDHC	SDHC	2477	0.083	0.5	YES
57	ATP6V0A1	ATP6V0A1	ATP6V0A1	2497	0.083	0.5	YES
58	ATP5J	ATP5J	ATP5J	2509	0.082	0.51	YES
59	ATP6V1E1	ATP6V1E1	ATP6V1E1	2562	0.081	0.51	YES
60	NDUFB4	NDUFB4	NDUFB4	2563	0.081	0.52	YES
61	COX5B	COX5B	COX5B	2595	0.08	0.53	YES
62	ATP6V1H	ATP6V1H	ATP6V1H	2624	0.079	0.53	YES
63	NDUFA1	NDUFA1	NDUFA1	2636	0.078	0.54	YES
64	COX7C	COX7C	COX7C	2676	0.077	0.54	YES
65	NDUFB8	NDUFB8	NDUFB8	2680	0.077	0.55	YES
66	NDUFV2	NDUFV2	NDUFV2	2695	0.077	0.56	YES
67	ATP5E	ATP5E	ATP5E	2705	0.076	0.56	YES
68	NDUFS5	NDUFS5	NDUFS5	2732	0.076	0.57	YES
69	NDUFA8	NDUFA8	NDUFA8	2803	0.074	0.57	YES
70	COX8A	COX8A	COX8A	2809	0.073	0.58	YES
71	UQCRB	UQCRB	UQCRB	2821	0.073	0.58	YES
72	NDUFA7	NDUFA7	NDUFA7	2854	0.072	0.59	YES
73	UQCR11	UQCR11	UQCR11	2897	0.071	0.59	YES
74	ATP5C1	ATP5C1	ATP5C1	2949	0.07	0.6	YES
75	COX6C	COX6C	COX6C	2955	0.069	0.6	YES
76	ATP6V1C1	ATP6V1C1	ATP6V1C1	2957	0.069	0.61	YES
77	NDUFB7	NDUFB7	NDUFB7	2961	0.069	0.62	YES
78	NDUFC1	NDUFC1	NDUFC1	2997	0.068	0.62	YES
79	NDUFS3	NDUFS3	NDUFS3	3015	0.068	0.62	YES
80	ATP6V0E1	ATP6V0E1	ATP6V0E1	3030	0.068	0.63	YES
81	COX15	COX15	COX15	3071	0.067	0.63	YES
82	NDUFC2	NDUFC2	NDUFC2	3079	0.066	0.64	YES
83	ATP5J2	ATP5J2	ATP5J2	3089	0.066	0.64	YES
84	COX7A2L	COX7A2L	COX7A2L	3093	0.066	0.65	YES
85	ATP5O	ATP5O	ATP5O	3111	0.066	0.66	YES
86	NDUFA11	NDUFA11	NDUFA11	3147	0.064	0.66	YES
87	ATP6V1D	ATP6V1D	ATP6V1D	3217	0.063	0.66	YES
88	ATP5H	ATP5H	ATP5H	3285	0.061	0.66	YES
89	ATP5D	ATP5D	ATP5D	3289	0.061	0.67	YES
90	ATP5L	ATP5L	ATP5L	3368	0.059	0.67	YES
91	ATP6V1A	ATP6V1A	ATP6V1A	3370	0.059	0.68	YES
92	NDUFA4	NDUFA4	NDUFA4	3395	0.058	0.68	YES
93	NDUFA6	NDUFA6	NDUFA6	3589	0.053	0.67	NO
94	COX6B1	COX6B1	COX6B1	3695	0.051	0.67	NO
95	ATP5G2	ATP5G2	ATP5G2	4329	0.038	0.64	NO
96	ATP6V1G1	ATP6V1G1	ATP6V1G1	4339	0.038	0.64	NO
97	ATP6AP1	ATP6AP1	ATP6AP1	4603	0.034	0.63	NO
98	ATP6V1E2	ATP6V1E2	ATP6V1E2	4916	0.028	0.62	NO
99	NDUFV3	NDUFV3	NDUFV3	5216	0.023	0.6	NO
100	COX11	COX11	COX11	5241	0.023	0.6	NO
101	NDUFA5	NDUFA5	NDUFA5	6418	0.0055	0.54	NO
102	ATP6V0A2	ATP6V0A2	ATP6V0A2	7174	-0.0053	0.5	NO
103	NDUFA4L2	NDUFA4L2	NDUFA4L2	9066	-0.033	0.39	NO
104	ATP4B	ATP4B	ATP4B	9247	-0.035	0.39	NO
105	COX4I2	COX4I2	COX4I2	10151	-0.049	0.34	NO
106	TCIRG1	TCIRG1	TCIRG1	10180	-0.05	0.34	NO
107	COX8C	COX8C	COX8C	10185	-0.05	0.35	NO
108	COX7A1	COX7A1	COX7A1	11352	-0.071	0.29	NO
109	ATP6V1G2	ATP6V1G2	ATP6V1G2	11955	-0.083	0.26	NO
110	ATP6V1C2	ATP6V1C2	ATP6V1C2	15156	-0.18	0.1	NO
111	ATP6V0A4	ATP6V0A4	ATP6V0A4	15938	-0.22	0.078	NO
112	COX6B2	COX6B2	COX6B2	17707	-0.39	0.015	NO

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

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

genes ES table in pathway: KEGG GLYCINE SERINE AND THREONINE METABOLISM

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	PCK1	PCK1	PCK1	31	0.6	0.16	YES
2	PC	PC	PC	326	0.32	0.23	YES
3	PCK2	PCK2	PCK2	655	0.22	0.27	YES
4	OGDHL	OGDHL	OGDHL	800	0.2	0.32	YES
5	SDHB	SDHB	SDHB	1259	0.14	0.33	YES
6	ACO2	ACO2	ACO2	1293	0.14	0.36	YES
7	IDH2	IDH2	IDH2	1299	0.14	0.4	YES
8	SUCLG2	SUCLG2	SUCLG2	1324	0.14	0.44	YES
9	SUCLG1	SUCLG1	SUCLG1	1368	0.14	0.47	YES
10	MDH1	MDH1	MDH1	1386	0.13	0.51	YES
11	SDHA	SDHA	SDHA	1567	0.12	0.53	YES
12	ACO1	ACO1	ACO1	1647	0.12	0.56	YES
13	FH	FH	FH	1744	0.11	0.58	YES
14	PDHA1	PDHA1	PDHA1	1894	0.1	0.6	YES
15	SDHD	SDHD	SDHD	1949	0.1	0.63	YES
16	MDH2	MDH2	MDH2	2181	0.094	0.64	YES
17	IDH3G	IDH3G	IDH3G	2220	0.093	0.66	YES
18	IDH1	IDH1	IDH1	2259	0.091	0.69	YES
19	PDHB	PDHB	PDHB	2378	0.087	0.7	YES
20	IDH3B	IDH3B	IDH3B	2449	0.084	0.72	YES
21	SDHC	SDHC	SDHC	2477	0.083	0.74	YES
22	DLD	DLD	DLD	2580	0.08	0.76	YES
23	OGDH	OGDH	OGDH	2776	0.074	0.77	YES
24	DLST	DLST	DLST	2839	0.073	0.78	YES
25	DLAT	DLAT	DLAT	2917	0.071	0.8	YES
26	SUCLA2	SUCLA2	SUCLA2	3034	0.067	0.81	YES
27	CS	CS	CS	3604	0.053	0.79	NO
28	IDH3A	IDH3A	IDH3A	5575	0.018	0.69	NO
29	ACLY	ACLY	ACLY	7212	-0.0059	0.6	NO

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

Figure S60. 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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus4 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA NO1 PATHWAY	28	genes.ES.table	0.68	1.5	0.045	0.6	0.85	0.46	0.072	0.43	0.4	0.19
BIOCARTA G1 PATHWAY	27	genes.ES.table	0.63	1.7	0.0038	0.5	0.45	0.41	0.2	0.33	0	0.15
BIOCARTA ERK PATHWAY	27	genes.ES.table	0.52	1.5	0.089	0.59	0.88	0.22	0.12	0.2	0.41	0.18
BIOCARTA MPR PATHWAY	32	genes.ES.table	0.52	1.7	0.03	0.48	0.57	0.16	0.049	0.15	0.22	0.14
BIOCARTA INTEGRIN PATHWAY	37	genes.ES.table	0.43	1.5	0.074	0.55	0.79	0.35	0.25	0.26	0.34	0.16
BIOCARTA VEGF PATHWAY	28	genes.ES.table	0.62	1.7	0.023	0.59	0.57	0.43	0.24	0.33	0.27	0.18
KEGG N GLYCAN BIOSYNTHESIS	45	genes.ES.table	0.42	1.4	0.14	0.61	0.91	0.11	0.09	0.1	0.45	0.18
KEGG CALCIUM SIGNALING PATHWAY	165	genes.ES.table	0.5	1.4	0.037	0.58	0.92	0.36	0.14	0.32	0.43	0.17
KEGG CELL CYCLE	123	genes.ES.table	0.53	1.6	0.05	0.52	0.72	0.37	0.2	0.3	0.31	0.15
KEGG OOCYTE MEIOSIS	105	genes.ES.table	0.5	1.6	0.027	0.44	0.65	0.29	0.16	0.24	0.23	0.11

genes ES table in pathway: BIOCARTA NO1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	LEF1	LEF1	LEF1	265	0.47	0.13	YES
2	RET	RET	RET	384	0.43	0.26	YES
3	TCF7L1	TCF7L1	TCF7L1	592	0.39	0.36	YES
4	RXRG	RXRG	RXRG	947	0.33	0.45	YES
5	CDH1	CDH1	CDH1	1031	0.32	0.54	YES
6	RXRA	RXRA	RXRA	2084	0.2	0.54	YES
7	MYC	MYC	MYC	2144	0.2	0.6	YES
8	CCND1	CCND1	CCND1	2674	0.16	0.62	YES
9	BRAF	BRAF	BRAF	3676	0.11	0.6	NO
10	MAP2K1	MAP2K1	MAP2K1	4159	0.095	0.6	NO
11	TPR	TPR	TPR	5242	0.068	0.56	NO
12	NRAS	NRAS	NRAS	5816	0.058	0.55	NO
13	MAP2K2	MAP2K2	MAP2K2	6768	0.041	0.5	NO
14	CCDC6	CCDC6	CCDC6	6899	0.039	0.51	NO
15	NCOA4	NCOA4	NCOA4	8007	0.022	0.46	NO
16	MAPK3	MAPK3	MAPK3	8364	0.017	0.44	NO
17	TCF7L2	TCF7L2	TCF7L2	8370	0.017	0.45	NO
18	TPM3	TPM3	TPM3	8650	0.013	0.43	NO
19	TCF7	TCF7	TCF7	8911	0.0087	0.42	NO
20	MAPK1	MAPK1	MAPK1	9156	0.0053	0.41	NO
21	CTNNB1	CTNNB1	CTNNB1	9301	0.0034	0.4	NO
22	RXRB	RXRB	RXRB	9509	0.00069	0.39	NO
23	TP53	TP53	TP53	9885	-0.0054	0.37	NO
24	NTRK1	NTRK1	NTRK1	10635	-0.018	0.34	NO
25	TFG	TFG	TFG	10646	-0.018	0.34	NO
26	PPARG	PPARG	PPARG	11734	-0.036	0.29	NO
27	KRAS	KRAS	KRAS	11955	-0.04	0.29	NO
28	PAX8	PAX8	PAX8	15343	-0.14	0.15	NO

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

Figure S62. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NO1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA G1 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	CTNNA2	CTNNA2	CTNNA2	210	0.49	0.053	YES
2	LEF1	LEF1	LEF1	265	0.47	0.11	YES
3	CTNNA3	CTNNA3	CTNNA3	336	0.45	0.17	YES
4	TCF7L1	TCF7L1	TCF7L1	592	0.39	0.21	YES
5	PVRL4	PVRL4	PVRL4	639	0.38	0.25	YES
6	SNAI2	SNAI2	SNAI2	662	0.38	0.3	YES
7	CDH1	CDH1	CDH1	1031	0.32	0.32	YES
8	SNAI1	SNAI1	SNAI1	1038	0.31	0.36	YES
9	PTPRB	PTPRB	PTPRB	1269	0.29	0.39	YES
10	ACTN3	ACTN3	ACTN3	1383	0.27	0.42	YES
11	WASF3	WASF3	WASF3	1593	0.25	0.44	YES
12	ACTN2	ACTN2	ACTN2	1658	0.24	0.47	YES
13	FER	FER	FER	1931	0.22	0.48	YES
14	FGFR1	FGFR1	FGFR1	2997	0.14	0.44	NO
15	VCL	VCL	VCL	3650	0.11	0.42	NO
16	FYN	FYN	FYN	4255	0.092	0.4	NO
17	INSR	INSR	INSR	4572	0.083	0.39	NO
18	TGFBR1	TGFBR1	TGFBR1	4682	0.081	0.4	NO
19	ACTN1	ACTN1	ACTN1	5262	0.068	0.38	NO
20	CSNK2A1	CSNK2A1	CSNK2A1	5279	0.068	0.38	NO
21	WASF1	WASF1	WASF1	5499	0.063	0.38	NO
22	FARP2	FARP2	FARP2	5625	0.061	0.38	NO
23	SSX2IP	SSX2IP	SSX2IP	5719	0.059	0.38	NO
24	IQGAP1	IQGAP1	IQGAP1	5799	0.058	0.39	NO
25	EGFR	EGFR	EGFR	5815	0.058	0.39	NO
26	CSNK2A2	CSNK2A2	CSNK2A2	6056	0.053	0.39	NO
27	ACTN4	ACTN4	ACTN4	6274	0.049	0.38	NO
28	EP300	EP300	EP300	7193	0.034	0.34	NO
29	CREBBP	CREBBP	CREBBP	7291	0.033	0.33	NO
30	MAP3K7	MAP3K7	MAP3K7	7344	0.032	0.34	NO
31	PTPRM	PTPRM	PTPRM	7380	0.032	0.34	NO
32	SMAD3	SMAD3	SMAD3	7702	0.026	0.32	NO
33	ACTG1	ACTG1	ACTG1	7834	0.025	0.32	NO
34	PARD3	PARD3	PARD3	8003	0.022	0.31	NO
35	ACP1	ACP1	ACP1	8170	0.02	0.31	NO
36	NLK	NLK	NLK	8304	0.018	0.3	NO
37	CTNND1	CTNND1	CTNND1	8350	0.017	0.3	NO
38	MAPK3	MAPK3	MAPK3	8364	0.017	0.3	NO
39	TCF7L2	TCF7L2	TCF7L2	8370	0.017	0.3	NO
40	PVRL3	PVRL3	PVRL3	8559	0.014	0.3	NO
41	SMAD2	SMAD2	SMAD2	8570	0.014	0.3	NO
42	TCF7	TCF7	TCF7	8911	0.0087	0.28	NO
43	YES1	YES1	YES1	8936	0.0084	0.28	NO
44	MAPK1	MAPK1	MAPK1	9156	0.0053	0.27	NO
45	CTNNB1	CTNNB1	CTNNB1	9301	0.0034	0.26	NO
46	SRC	SRC	SRC	9466	0.0012	0.25	NO
47	PVRL1	PVRL1	PVRL1	10019	-0.0076	0.22	NO
48	CSNK2B	CSNK2B	CSNK2B	10314	-0.012	0.21	NO
49	TGFBR2	TGFBR2	TGFBR2	10441	-0.014	0.2	NO
50	CTNNA1	CTNNA1	CTNNA1	10491	-0.015	0.2	NO
51	IGF1R	IGF1R	IGF1R	10813	-0.02	0.18	NO
52	PVRL2	PVRL2	PVRL2	10916	-0.022	0.18	NO
53	PTPN1	PTPN1	PTPN1	11147	-0.026	0.17	NO
54	CDC42	CDC42	CDC42	11309	-0.029	0.17	NO
55	PTPRF	PTPRF	PTPRF	11377	-0.03	0.17	NO
56	WASF2	WASF2	WASF2	11537	-0.033	0.16	NO
57	TJP1	TJP1	TJP1	11682	-0.036	0.16	NO
58	ACTB	ACTB	ACTB	11837	-0.038	0.16	NO
59	SMAD4	SMAD4	SMAD4	11908	-0.039	0.16	NO
60	RHOA	RHOA	RHOA	12179	-0.045	0.15	NO
61	BAIAP2	BAIAP2	BAIAP2	12289	-0.047	0.15	NO
62	PTPN6	PTPN6	PTPN6	12479	-0.051	0.14	NO
63	PTPRJ	PTPRJ	PTPRJ	12506	-0.051	0.15	NO
64	MLLT4	MLLT4	MLLT4	12632	-0.054	0.15	NO
65	ERBB2	ERBB2	ERBB2	13692	-0.08	0.1	NO
66	SORBS1	SORBS1	SORBS1	13850	-0.084	0.1	NO
67	RAC1	RAC1	RAC1	13924	-0.087	0.11	NO
68	WASL	WASL	WASL	14401	-0.1	0.098	NO
69	WAS	WAS	WAS	14442	-0.1	0.11	NO
70	RAC2	RAC2	RAC2	15172	-0.13	0.087	NO
71	LMO7	LMO7	LMO7	15269	-0.14	0.1	NO
72	MET	MET	MET	15790	-0.17	0.093	NO
73	RAC3	RAC3	RAC3	16470	-0.22	0.084	NO

Figure S63. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA G1 PATHWAY.

Figure S64. 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 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	CCNE1	CCNE1	CCNE1	368	0.44	0.14	YES
2	CDK1	CDK1	CDK1	446	0.42	0.29	YES
3	SKP2	SKP2	SKP2	1428	0.27	0.33	YES
4	CDKN2B	CDKN2B	CDKN2B	2402	0.18	0.34	YES
5	TGFB1	TGFB1	TGFB1	2494	0.17	0.4	YES
6	CCND1	CCND1	CCND1	2674	0.16	0.44	YES
7	DHFR	DHFR	DHFR	2921	0.14	0.48	YES
8	TGFB2	TGFB2	TGFB2	2927	0.14	0.54	YES
9	TGFB3	TGFB3	TGFB3	3126	0.13	0.57	YES
10	CDC25A	CDC25A	CDC25A	3581	0.11	0.59	YES
11	CCNA1	CCNA1	CCNA1	3622	0.11	0.63	YES
12	CDK4	CDK4	CDK4	4318	0.09	0.62	NO
13	CDKN2A	CDKN2A	CDKN2A	6268	0.049	0.53	NO
14	ABL1	ABL1	ABL1	6491	0.046	0.54	NO
15	CDKN1B	CDKN1B	CDKN1B	7611	0.028	0.48	NO
16	SMAD3	SMAD3	SMAD3	7702	0.026	0.49	NO
17	TFDP1	TFDP1	TFDP1	9005	0.0075	0.42	NO
18	ATM	ATM	ATM	9178	0.0051	0.41	NO
19	CDK2	CDK2	CDK2	9423	0.0016	0.4	NO
20	RB1	RB1	RB1	9527	0.00043	0.39	NO
21	GSK3B	GSK3B	GSK3B	9532	0.00037	0.39	NO
22	TP53	TP53	TP53	9885	-0.0054	0.37	NO
23	HDAC1	HDAC1	HDAC1	9924	-0.006	0.37	NO
24	ATR	ATR	ATR	10934	-0.022	0.32	NO
25	SMAD4	SMAD4	SMAD4	11908	-0.039	0.28	NO
26	CDK6	CDK6	CDK6	12367	-0.049	0.28	NO
27	CDKN1A	CDKN1A	CDKN1A	14230	-0.096	0.21	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: BIOCARTA MPR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	KDR	KDR	KDR	122	0.53	0.14	YES
2	FLT4	FLT4	FLT4	224	0.48	0.27	YES
3	NOS3	NOS3	NOS3	310	0.46	0.39	YES
4	VEGFA	VEGFA	VEGFA	509	0.41	0.49	YES
5	FLT1	FLT1	FLT1	684	0.37	0.58	YES
6	PRKCB	PRKCB	PRKCB	2542	0.17	0.52	YES
7	EIF2S3	EIF2S3	EIF2S3	2846	0.15	0.55	YES
8	SHC1	SHC1	SHC1	3271	0.13	0.56	YES
9	EIF1AX	EIF1AX	EIF1AX	3293	0.13	0.59	YES
10	PTK2	PTK2	PTK2	4023	0.099	0.58	YES
11	EIF2S2	EIF2S2	EIF2S2	4045	0.099	0.6	YES
12	PIK3CA	PIK3CA	PIK3CA	4286	0.091	0.62	YES
13	EIF2S1	EIF2S1	EIF2S1	5903	0.056	0.54	NO
14	PIK3CG	PIK3CG	PIK3CG	6076	0.053	0.55	NO
15	EIF1	EIF1	EIF1	6405	0.047	0.54	NO
16	ELAVL1	ELAVL1	ELAVL1	6506	0.046	0.55	NO
17	HIF1A	HIF1A	HIF1A	6839	0.04	0.54	NO
18	VHL	VHL	VHL	7299	0.033	0.52	NO
19	PXN	PXN	PXN	7355	0.032	0.53	NO
20	EIF2B4	EIF2B4	EIF2B4	7892	0.024	0.51	NO
21	ARNT	ARNT	ARNT	7911	0.024	0.51	NO
22	EIF2B1	EIF2B1	EIF2B1	9296	0.0035	0.44	NO
23	EIF2B3	EIF2B3	EIF2B3	10149	-0.0097	0.39	NO
24	EIF2B2	EIF2B2	EIF2B2	10205	-0.011	0.39	NO
25	EIF2B5	EIF2B5	EIF2B5	11427	-0.031	0.33	NO
26	PRKCA	PRKCA	PRKCA	11846	-0.038	0.32	NO
27	PIK3R1	PIK3R1	PIK3R1	11889	-0.039	0.33	NO
28	PLCG1	PLCG1	PLCG1	12306	-0.047	0.32	NO

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

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

genes ES table in pathway: BIOCARTA INTEGRIN PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CDC25C	CDC25C	CDC25C	113	0.54	0.14	YES
2	PGR	PGR	PGR	333	0.45	0.25	YES
3	CDK1	CDK1	CDK1	446	0.42	0.36	YES
4	MYT1	MYT1	MYT1	814	0.35	0.43	YES
5	CCNB1	CCNB1	CCNB1	879	0.34	0.52	YES
6	PRKAR2A	PRKAR2A	PRKAR2A	3028	0.14	0.44	NO
7	PRKAR2B	PRKAR2B	PRKAR2B	4050	0.098	0.4	NO
8	ACTA1	ACTA1	ACTA1	4469	0.086	0.4	NO
9	ACTR2	ACTR2	ACTR2	5388	0.066	0.37	NO
10	ACTR3	ACTR3	ACTR3	5441	0.064	0.39	NO
11	ARPC2	ARPC2	ARPC2	6648	0.043	0.33	NO
12	PRKAR1A	PRKAR1A	PRKAR1A	7735	0.026	0.28	NO
13	GNAS	GNAS	GNAS	8249	0.019	0.25	NO
14	MAPK3	MAPK3	MAPK3	8364	0.017	0.25	NO
15	CAP1	CAP1	CAP1	8590	0.014	0.24	NO
16	ARPC5	ARPC5	ARPC5	8643	0.013	0.24	NO
17	PIN1	PIN1	PIN1	8827	0.01	0.24	NO
18	MAPK1	MAPK1	MAPK1	9156	0.0053	0.22	NO
19	ARPC1A	ARPC1A	ARPC1A	9379	0.0023	0.21	NO
20	SRC	SRC	SRC	9466	0.0012	0.2	NO
21	ARPC3	ARPC3	ARPC3	9959	-0.0066	0.18	NO
22	GNB1	GNB1	GNB1	10451	-0.014	0.15	NO
23	HRAS	HRAS	HRAS	10660	-0.018	0.15	NO
24	PAQR5	PAQR5	PAQR5	10693	-0.019	0.15	NO
25	ARPC4	ARPC4	ARPC4	11883	-0.039	0.095	NO
26	PRKAR1B	PRKAR1B	PRKAR1B	12961	-0.061	0.051	NO
27	PAQR7	PAQR7	PAQR7	13676	-0.079	0.033	NO
28	RPS6KA1	RPS6KA1	RPS6KA1	14532	-0.11	0.014	NO
29	ARPC1B	ARPC1B	ARPC1B	14921	-0.12	0.025	NO
30	PRKACB	PRKACB	PRKACB	14923	-0.12	0.058	NO
31	GNAI1	GNAI1	GNAI1	16072	-0.19	0.045	NO
32	GNGT1	GNGT1	GNGT1	16511	-0.22	0.082	NO

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

Figure S70. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA INTEGRIN 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 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	UBE2QL1	UBE2QL1	UBE2QL1	120	0.53	0.047	YES
2	UBE2C	UBE2C	UBE2C	526	0.4	0.065	YES
3	KLHL13	KLHL13	KLHL13	715	0.36	0.091	YES
4	CDC20	CDC20	CDC20	738	0.36	0.13	YES
5	SOCS1	SOCS1	SOCS1	773	0.36	0.16	YES
6	SKP2	SKP2	SKP2	1428	0.27	0.15	YES
7	NHLRC1	NHLRC1	NHLRC1	2281	0.18	0.12	YES
8	RHOBTB2	RHOBTB2	RHOBTB2	2332	0.18	0.14	YES
9	NEDD4	NEDD4	NEDD4	2478	0.17	0.14	YES
10	SAE1	SAE1	SAE1	2829	0.15	0.14	YES
11	ANAPC1	ANAPC1	ANAPC1	2845	0.15	0.16	YES
12	UBE2S	UBE2S	UBE2S	2901	0.15	0.17	YES
13	BRCA1	BRCA1	BRCA1	2970	0.14	0.18	YES
14	FBXW11	FBXW11	FBXW11	3441	0.12	0.16	YES
15	PIAS3	PIAS3	PIAS3	3455	0.12	0.17	YES
16	PIAS2	PIAS2	PIAS2	3535	0.12	0.18	YES
17	PIAS4	PIAS4	PIAS4	3607	0.11	0.19	YES
18	UBA2	UBA2	UBA2	3787	0.11	0.19	YES
19	CUL4B	CUL4B	CUL4B	3899	0.1	0.19	YES
20	HERC1	HERC1	HERC1	3963	0.1	0.2	YES
21	UBE2A	UBE2A	UBE2A	3986	0.1	0.21	YES
22	UBE2B	UBE2B	UBE2B	4112	0.096	0.21	YES
23	CDC27	CDC27	CDC27	4324	0.09	0.21	YES
24	ANAPC10	ANAPC10	ANAPC10	4337	0.09	0.22	YES
25	UBA1	UBA1	UBA1	4349	0.09	0.22	YES
26	UBE2D1	UBE2D1	UBE2D1	4359	0.089	0.23	YES
27	PIAS1	PIAS1	PIAS1	4591	0.083	0.23	YES
28	CUL7	CUL7	CUL7	4603	0.083	0.24	YES
29	FANCL	FANCL	FANCL	4604	0.083	0.24	YES
30	UBE2O	UBE2O	UBE2O	4629	0.082	0.25	YES
31	WWP1	WWP1	WWP1	4862	0.077	0.25	YES
32	UBA6	UBA6	UBA6	4887	0.076	0.25	YES
33	UBR5	UBR5	UBR5	4922	0.075	0.26	YES
34	KEAP1	KEAP1	KEAP1	5029	0.073	0.26	YES
35	CUL2	CUL2	CUL2	5050	0.072	0.27	YES
36	TRIP12	TRIP12	TRIP12	5106	0.071	0.27	YES
37	SKP1	SKP1	SKP1	5150	0.07	0.28	YES
38	HUWE1	HUWE1	HUWE1	5154	0.07	0.28	YES
39	UBE2U	UBE2U	UBE2U	5232	0.069	0.28	YES
40	TRAF6	TRAF6	TRAF6	5305	0.068	0.29	YES
41	XIAP	XIAP	XIAP	5375	0.066	0.29	YES
42	FBXO4	FBXO4	FBXO4	5558	0.062	0.29	YES
43	UBE2D2	UBE2D2	UBE2D2	5654	0.06	0.29	YES
44	TRIM37	TRIM37	TRIM37	5687	0.06	0.29	YES
45	UBE2K	UBE2K	UBE2K	5827	0.058	0.29	YES
46	CUL3	CUL3	CUL3	5829	0.058	0.3	YES
47	UBE2L6	UBE2L6	UBE2L6	5872	0.057	0.3	YES
48	DDB1	DDB1	DDB1	5955	0.055	0.3	YES
49	BIRC6	BIRC6	BIRC6	6006	0.054	0.3	YES
50	SYVN1	SYVN1	SYVN1	6070	0.053	0.3	YES
51	UBE2M	UBE2M	UBE2M	6242	0.05	0.3	NO
52	TCEB1	TCEB1	TCEB1	6306	0.049	0.3	NO
53	CDC23	CDC23	CDC23	6449	0.047	0.3	NO
54	PRPF19	PRPF19	PRPF19	6629	0.043	0.29	NO
55	CUL5	CUL5	CUL5	6682	0.043	0.29	NO
56	RCHY1	RCHY1	RCHY1	6720	0.042	0.3	NO
57	UBE2W	UBE2W	UBE2W	6730	0.042	0.3	NO
58	CBL	CBL	CBL	6808	0.04	0.3	NO
59	HERC4	HERC4	HERC4	6814	0.04	0.3	NO
60	UBE2Q1	UBE2Q1	UBE2Q1	6883	0.039	0.3	NO
61	UBE3A	UBE3A	UBE3A	6998	0.037	0.3	NO
62	UBE2H	UBE2H	UBE2H	7038	0.037	0.3	NO
63	MID1	MID1	MID1	7069	0.036	0.3	NO
64	TRIM32	TRIM32	TRIM32	7199	0.034	0.3	NO
65	UBE2F	UBE2F	UBE2F	7209	0.034	0.3	NO
66	VHL	VHL	VHL	7299	0.033	0.3	NO
67	UBE2N	UBE2N	UBE2N	7348	0.032	0.3	NO
68	ERCC8	ERCC8	ERCC8	7482	0.03	0.3	NO
69	HERC2	HERC2	HERC2	7604	0.028	0.29	NO
70	BIRC3	BIRC3	BIRC3	7651	0.027	0.29	NO
71	ITCH	ITCH	ITCH	7744	0.026	0.29	NO
72	CDC26	CDC26	CDC26	7767	0.026	0.29	NO
73	UBE2D3	UBE2D3	UBE2D3	7774	0.026	0.29	NO
74	UBE2E1	UBE2E1	UBE2E1	7828	0.025	0.29	NO
75	UBE4B	UBE4B	UBE4B	7835	0.025	0.3	NO
76	RFWD2	RFWD2	RFWD2	7858	0.024	0.3	NO
77	FZR1	FZR1	FZR1	7907	0.024	0.3	NO
78	UBE2J1	UBE2J1	UBE2J1	8014	0.022	0.29	NO
79	MDM2	MDM2	MDM2	8098	0.021	0.29	NO
80	CUL4A	CUL4A	CUL4A	8226	0.019	0.28	NO
81	ANAPC5	ANAPC5	ANAPC5	8325	0.018	0.28	NO
82	SIAH1	SIAH1	SIAH1	8593	0.014	0.27	NO
83	UBE2Z	UBE2Z	UBE2Z	8836	0.0098	0.26	NO
84	FBXW8	FBXW8	FBXW8	9129	0.0057	0.24	NO
85	KLHL9	KLHL9	KLHL9	9204	0.0047	0.24	NO
86	PML	PML	PML	9208	0.0046	0.24	NO
87	CDC34	CDC34	CDC34	9260	0.0039	0.23	NO
88	UBOX5	UBOX5	UBOX5	9299	0.0034	0.23	NO
89	BIRC2	BIRC2	BIRC2	9448	0.0014	0.22	NO
90	HERC3	HERC3	HERC3	9833	-0.0043	0.2	NO
91	UBE2R2	UBE2R2	UBE2R2	9968	-0.0067	0.2	NO
92	CUL1	CUL1	CUL1	10074	-0.0085	0.19	NO
93	RNF7	RNF7	RNF7	10087	-0.0087	0.19	NO
94	UBE4A	UBE4A	UBE4A	10125	-0.0094	0.19	NO
95	FBXW7	FBXW7	FBXW7	10171	-0.01	0.19	NO
96	TCEB2	TCEB2	TCEB2	10323	-0.012	0.18	NO
97	UBE2G1	UBE2G1	UBE2G1	10423	-0.014	0.18	NO
98	SOCS3	SOCS3	SOCS3	10483	-0.015	0.18	NO
99	UBE2Q2	UBE2Q2	UBE2Q2	10511	-0.016	0.18	NO
100	ANAPC7	ANAPC7	ANAPC7	10532	-0.016	0.18	NO
101	UBE2NL	UBE2NL	UBE2NL	10545	-0.016	0.18	NO
102	CDC16	CDC16	CDC16	10601	-0.017	0.18	NO
103	DET1	DET1	DET1	10652	-0.018	0.17	NO
104	UBE3B	UBE3B	UBE3B	10703	-0.019	0.17	NO
105	UBE2E3	UBE2E3	UBE2E3	10756	-0.02	0.17	NO
106	PARK2	PARK2	PARK2	10879	-0.021	0.17	NO
107	UBE2I	UBE2I	UBE2I	11037	-0.024	0.16	NO
108	ANAPC11	ANAPC11	ANAPC11	11086	-0.025	0.16	NO
109	UBE2G2	UBE2G2	UBE2G2	11224	-0.027	0.16	NO
110	SMURF2	SMURF2	SMURF2	11387	-0.03	0.15	NO
111	RBX1	RBX1	RBX1	11399	-0.03	0.15	NO
112	SMURF1	SMURF1	SMURF1	11753	-0.037	0.14	NO
113	UBE3C	UBE3C	UBE3C	11772	-0.037	0.14	NO
114	WWP2	WWP2	WWP2	11905	-0.039	0.14	NO
115	ANAPC4	ANAPC4	ANAPC4	12430	-0.05	0.11	NO
116	FBXO2	FBXO2	FBXO2	12461	-0.05	0.11	NO
117	NEDD4L	NEDD4L	NEDD4L	12505	-0.051	0.12	NO
118	UBE2L3	UBE2L3	UBE2L3	12944	-0.06	0.098	NO
119	UBA3	UBA3	UBA3	13107	-0.064	0.096	NO
120	ANAPC2	ANAPC2	ANAPC2	13384	-0.071	0.087	NO
121	STUB1	STUB1	STUB1	13406	-0.072	0.093	NO
122	MGRN1	MGRN1	MGRN1	13534	-0.076	0.094	NO
123	CBLB	CBLB	CBLB	13574	-0.076	0.099	NO
124	MAP3K1	MAP3K1	MAP3K1	13634	-0.078	0.1	NO
125	UBE2J2	UBE2J2	UBE2J2	13748	-0.081	0.11	NO
126	PPIL2	PPIL2	PPIL2	13764	-0.082	0.11	NO
127	UBE2E2	UBE2E2	UBE2E2	13822	-0.084	0.12	NO
128	ANAPC13	ANAPC13	ANAPC13	13830	-0.084	0.13	NO
129	AIRE	AIRE	AIRE	14353	-0.1	0.11	NO
130	UBA7	UBA7	UBA7	14638	-0.11	0.1	NO
131	UBE2D4	UBE2D4	UBE2D4	14660	-0.11	0.11	NO
132	DDB2	DDB2	DDB2	15680	-0.16	0.071	NO
133	CBLC	CBLC	CBLC	17889	-0.57	0.0052	NO

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

Figure S72. 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 N GLYCAN BIOSYNTHESIS

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	BUB1	BUB1	BUB1	25	0.65	0.043	YES
2	ADCY1	ADCY1	ADCY1	39	0.62	0.084	YES
3	CDC25C	CDC25C	CDC25C	113	0.54	0.12	YES
4	CCNB2	CCNB2	CCNB2	141	0.52	0.15	YES
5	PGR	PGR	PGR	333	0.45	0.17	YES
6	CCNE1	CCNE1	CCNE1	368	0.44	0.2	YES
7	CDK1	CDK1	CDK1	446	0.42	0.22	YES
8	PTTG1	PTTG1	PTTG1	478	0.41	0.25	YES
9	CHP2	CHP2	CHP2	515	0.4	0.27	YES
10	SGOL1	SGOL1	SGOL1	587	0.39	0.29	YES
11	ADCY4	ADCY4	ADCY4	630	0.38	0.32	YES
12	MAD2L1	MAD2L1	MAD2L1	677	0.37	0.34	YES
13	CDC20	CDC20	CDC20	738	0.36	0.36	YES
14	CCNB1	CCNB1	CCNB1	879	0.34	0.38	YES
15	CCNE2	CCNE2	CCNE2	1002	0.32	0.39	YES
16	CAMK2A	CAMK2A	CAMK2A	1094	0.31	0.4	YES
17	ESPL1	ESPL1	ESPL1	1216	0.29	0.42	YES
18	PLK1	PLK1	PLK1	1268	0.29	0.44	YES
19	AURKA	AURKA	AURKA	1337	0.28	0.45	YES
20	PKMYT1	PKMYT1	PKMYT1	1582	0.25	0.45	YES
21	CPEB1	CPEB1	CPEB1	1962	0.21	0.45	YES
22	SMC1B	SMC1B	SMC1B	2004	0.21	0.46	YES
23	ITPR1	ITPR1	ITPR1	2074	0.2	0.47	YES
24	ITPR2	ITPR2	ITPR2	2125	0.2	0.48	YES
25	MAPK12	MAPK12	MAPK12	2292	0.18	0.48	YES
26	ADCY8	ADCY8	ADCY8	2454	0.17	0.48	YES
27	FBXO5	FBXO5	FBXO5	2556	0.17	0.49	YES
28	ANAPC1	ANAPC1	ANAPC1	2845	0.15	0.48	YES
29	RPS6KA6	RPS6KA6	RPS6KA6	2894	0.15	0.49	YES
30	FBXO43	FBXO43	FBXO43	2958	0.14	0.5	YES
31	FBXW11	FBXW11	FBXW11	3441	0.12	0.48	NO
32	SMC3	SMC3	SMC3	3447	0.12	0.49	NO
33	PTTG2	PTTG2	PTTG2	3862	0.1	0.47	NO
34	PPP2R5E	PPP2R5E	PPP2R5E	3991	0.1	0.47	NO
35	MAP2K1	MAP2K1	MAP2K1	4159	0.095	0.47	NO
36	MAD2L2	MAD2L2	MAD2L2	4189	0.094	0.47	NO
37	CDC27	CDC27	CDC27	4324	0.09	0.47	NO
38	PPP2R5D	PPP2R5D	PPP2R5D	4335	0.09	0.48	NO
39	ANAPC10	ANAPC10	ANAPC10	4337	0.09	0.48	NO
40	ADCY5	ADCY5	ADCY5	4493	0.086	0.48	NO
41	SKP1	SKP1	SKP1	5150	0.07	0.45	NO
42	SMC1A	SMC1A	SMC1A	5202	0.069	0.45	NO
43	PPP3R1	PPP3R1	PPP3R1	5297	0.068	0.45	NO
44	RPS6KA3	RPS6KA3	RPS6KA3	5703	0.06	0.43	NO
45	PPP2R1B	PPP2R1B	PPP2R1B	5927	0.056	0.42	NO
46	SLK	SLK	SLK	6021	0.054	0.42	NO
47	CDC23	CDC23	CDC23	6449	0.047	0.4	NO
48	PPP2R5C	PPP2R5C	PPP2R5C	6472	0.046	0.4	NO
49	PPP1CB	PPP1CB	PPP1CB	6643	0.043	0.39	NO
50	PPP1CC	PPP1CC	PPP1CC	6646	0.043	0.4	NO
51	CALM3	CALM3	CALM3	6693	0.042	0.4	NO
52	PPP3CC	PPP3CC	PPP3CC	6713	0.042	0.4	NO
53	YWHAB	YWHAB	YWHAB	6716	0.042	0.4	NO
54	PPP2CA	PPP2CA	PPP2CA	6991	0.037	0.39	NO
55	CAMK2G	CAMK2G	CAMK2G	7746	0.026	0.35	NO
56	CDC26	CDC26	CDC26	7767	0.026	0.35	NO
57	PRKACA	PRKACA	PRKACA	7826	0.025	0.35	NO
58	CALML6	CALML6	CALML6	7842	0.025	0.35	NO
59	YWHAQ	YWHAQ	YWHAQ	7890	0.024	0.35	NO
60	YWHAZ	YWHAZ	YWHAZ	7987	0.022	0.34	NO
61	PPP2CB	PPP2CB	PPP2CB	8321	0.018	0.32	NO
62	ANAPC5	ANAPC5	ANAPC5	8325	0.018	0.33	NO
63	ADCY6	ADCY6	ADCY6	8356	0.017	0.32	NO
64	MAPK3	MAPK3	MAPK3	8364	0.017	0.33	NO
65	PPP2R1A	PPP2R1A	PPP2R1A	8621	0.013	0.31	NO
66	YWHAG	YWHAG	YWHAG	8744	0.011	0.31	NO
67	PPP2R5A	PPP2R5A	PPP2R5A	9079	0.0065	0.29	NO
68	PPP3CB	PPP3CB	PPP3CB	9116	0.0059	0.29	NO
69	MAPK1	MAPK1	MAPK1	9156	0.0053	0.28	NO
70	ADCY7	ADCY7	ADCY7	9247	0.0042	0.28	NO
71	CHP	CHP	CHP	9346	0.0028	0.28	NO
72	CDK2	CDK2	CDK2	9423	0.0016	0.27	NO
73	PPP3CA	PPP3CA	PPP3CA	9835	-0.0044	0.25	NO
74	CUL1	CUL1	CUL1	10074	-0.0085	0.24	NO
75	PPP1CA	PPP1CA	PPP1CA	10179	-0.01	0.23	NO
76	ANAPC7	ANAPC7	ANAPC7	10532	-0.016	0.21	NO
77	BTRC	BTRC	BTRC	10596	-0.017	0.21	NO
78	CDC16	CDC16	CDC16	10601	-0.017	0.21	NO
79	IGF1R	IGF1R	IGF1R	10813	-0.02	0.2	NO
80	ANAPC11	ANAPC11	ANAPC11	11086	-0.025	0.19	NO
81	CALM2	CALM2	CALM2	11174	-0.026	0.18	NO
82	RBX1	RBX1	RBX1	11399	-0.03	0.17	NO
83	CALM1	CALM1	CALM1	11913	-0.04	0.15	NO
84	YWHAH	YWHAH	YWHAH	12327	-0.048	0.13	NO
85	IGF1	IGF1	IGF1	12349	-0.048	0.13	NO
86	ANAPC4	ANAPC4	ANAPC4	12430	-0.05	0.13	NO
87	YWHAE	YWHAE	YWHAE	12563	-0.052	0.12	NO
88	PPP2R5B	PPP2R5B	PPP2R5B	12906	-0.06	0.11	NO
89	CAMK2D	CAMK2D	CAMK2D	12971	-0.061	0.11	NO
90	ANAPC2	ANAPC2	ANAPC2	13384	-0.071	0.091	NO
91	SPDYA	SPDYA	SPDYA	13471	-0.074	0.091	NO
92	ITPR3	ITPR3	ITPR3	13641	-0.079	0.087	NO
93	REC8	REC8	REC8	13732	-0.081	0.087	NO
94	ANAPC13	ANAPC13	ANAPC13	13830	-0.084	0.087	NO
95	PRKX	PRKX	PRKX	13920	-0.086	0.088	NO
96	CALML3	CALML3	CALML3	14069	-0.091	0.086	NO
97	RPS6KA1	RPS6KA1	RPS6KA1	14532	-0.11	0.067	NO
98	RPS6KA2	RPS6KA2	RPS6KA2	14568	-0.11	0.073	NO
99	PRKACB	PRKACB	PRKACB	14923	-0.12	0.061	NO
100	PLCZ1	PLCZ1	PLCZ1	15202	-0.13	0.055	NO
101	ADCY9	ADCY9	ADCY9	15224	-0.14	0.063	NO
102	AR	AR	AR	16555	-0.23	0.0036	NO
103	ADCY2	ADCY2	ADCY2	17004	-0.28	-0.0023	NO
104	STAG3	STAG3	STAG3	17089	-0.3	0.013	NO
105	CAMK2B	CAMK2B	CAMK2B	17864	-0.55	0.0066	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 N GLYCAN BIOSYNTHESIS.

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

genes ES table in pathway: KEGG CALCIUM SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	BUB1	BUB1	BUB1	25	0.65	0.038	YES
2	CDC25C	CDC25C	CDC25C	113	0.54	0.065	YES
3	CCNB2	CCNB2	CCNB2	141	0.52	0.095	YES
4	TTK	TTK	TTK	150	0.51	0.12	YES
5	BUB1B	BUB1B	BUB1B	182	0.5	0.15	YES
6	CCNE1	CCNE1	CCNE1	368	0.44	0.17	YES
7	CDK1	CDK1	CDK1	446	0.42	0.19	YES
8	PTTG1	PTTG1	PTTG1	478	0.41	0.21	YES
9	MAD2L1	MAD2L1	MAD2L1	677	0.37	0.22	YES
10	CDC20	CDC20	CDC20	738	0.36	0.24	YES
11	ORC6L	ORC6L	ORC6L	769	0.36	0.26	YES
12	CDC6	CDC6	CDC6	785	0.35	0.28	YES
13	CCNB1	CCNB1	CCNB1	879	0.34	0.3	YES
14	CCNA2	CCNA2	CCNA2	919	0.33	0.32	YES
15	CCNE2	CCNE2	CCNE2	1002	0.32	0.33	YES
16	ESPL1	ESPL1	ESPL1	1216	0.29	0.34	YES
17	PLK1	PLK1	PLK1	1268	0.29	0.35	YES
18	RBL1	RBL1	RBL1	1339	0.28	0.36	YES
19	CDC45	CDC45	CDC45	1409	0.27	0.38	YES
20	E2F2	E2F2	E2F2	1417	0.27	0.39	YES
21	SKP2	SKP2	SKP2	1428	0.27	0.41	YES
22	PKMYT1	PKMYT1	PKMYT1	1582	0.25	0.41	YES
23	CDKN2C	CDKN2C	CDKN2C	1682	0.24	0.42	YES
24	MCM4	MCM4	MCM4	1693	0.24	0.44	YES
25	E2F1	E2F1	E2F1	1708	0.24	0.45	YES
26	ORC1L	ORC1L	ORC1L	1902	0.22	0.45	YES
27	SMC1B	SMC1B	SMC1B	2004	0.21	0.46	YES
28	MYC	MYC	MYC	2144	0.2	0.46	YES
29	MCM6	MCM6	MCM6	2156	0.2	0.47	YES
30	CDKN2B	CDKN2B	CDKN2B	2402	0.18	0.47	YES
31	TGFB1	TGFB1	TGFB1	2494	0.17	0.48	YES
32	CCND1	CCND1	CCND1	2674	0.16	0.48	YES
33	WEE1	WEE1	WEE1	2750	0.16	0.48	YES
34	ANAPC1	ANAPC1	ANAPC1	2845	0.15	0.48	YES
35	TGFB2	TGFB2	TGFB2	2927	0.14	0.49	YES
36	TGFB3	TGFB3	TGFB3	3126	0.13	0.48	YES
37	CHEK1	CHEK1	CHEK1	3154	0.13	0.49	YES
38	PRKDC	PRKDC	PRKDC	3216	0.13	0.5	YES
39	SMC3	SMC3	SMC3	3447	0.12	0.49	YES
40	MCM2	MCM2	MCM2	3506	0.12	0.49	YES
41	CDC25B	CDC25B	CDC25B	3568	0.12	0.5	YES
42	TFDP2	TFDP2	TFDP2	3572	0.12	0.5	YES
43	CDC25A	CDC25A	CDC25A	3581	0.11	0.51	YES
44	GADD45B	GADD45B	GADD45B	3600	0.11	0.52	YES
45	CDK7	CDK7	CDK7	3609	0.11	0.52	YES
46	CCNA1	CCNA1	CCNA1	3622	0.11	0.53	YES
47	PTTG2	PTTG2	PTTG2	3862	0.1	0.52	NO
48	E2F3	E2F3	E2F3	4111	0.096	0.51	NO
49	MAD2L2	MAD2L2	MAD2L2	4189	0.094	0.52	NO
50	CDK4	CDK4	CDK4	4318	0.09	0.51	NO
51	CDC27	CDC27	CDC27	4324	0.09	0.52	NO
52	ANAPC10	ANAPC10	ANAPC10	4337	0.09	0.52	NO
53	CCNH	CCNH	CCNH	4536	0.084	0.52	NO
54	ORC3L	ORC3L	ORC3L	4899	0.076	0.5	NO
55	STAG1	STAG1	STAG1	4930	0.075	0.5	NO
56	SKP1	SKP1	SKP1	5150	0.07	0.5	NO
57	ORC2L	ORC2L	ORC2L	5151	0.07	0.5	NO
58	SMC1A	SMC1A	SMC1A	5202	0.069	0.5	NO
59	E2F5	E2F5	E2F5	5454	0.064	0.49	NO
60	PCNA	PCNA	PCNA	5683	0.06	0.48	NO
61	HDAC2	HDAC2	HDAC2	6060	0.053	0.46	NO
62	CDKN2A	CDKN2A	CDKN2A	6268	0.049	0.46	NO
63	BUB3	BUB3	BUB3	6312	0.049	0.46	NO
64	RAD21	RAD21	RAD21	6419	0.047	0.45	NO
65	CDC23	CDC23	CDC23	6449	0.047	0.45	NO
66	ABL1	ABL1	ABL1	6491	0.046	0.46	NO
67	YWHAB	YWHAB	YWHAB	6716	0.042	0.44	NO
68	STAG2	STAG2	STAG2	6868	0.039	0.44	NO
69	CDKN2D	CDKN2D	CDKN2D	6925	0.038	0.44	NO
70	EP300	EP300	EP300	7193	0.034	0.42	NO
71	GADD45A	GADD45A	GADD45A	7215	0.034	0.43	NO
72	CREBBP	CREBBP	CREBBP	7291	0.033	0.42	NO
73	CDKN1B	CDKN1B	CDKN1B	7611	0.028	0.41	NO
74	SMAD3	SMAD3	SMAD3	7702	0.026	0.4	NO
75	CCND3	CCND3	CCND3	7717	0.026	0.4	NO
76	CDC26	CDC26	CDC26	7767	0.026	0.4	NO
77	YWHAQ	YWHAQ	YWHAQ	7890	0.024	0.4	NO
78	FZR1	FZR1	FZR1	7907	0.024	0.4	NO
79	YWHAZ	YWHAZ	YWHAZ	7987	0.022	0.4	NO
80	ORC4L	ORC4L	ORC4L	8052	0.022	0.39	NO
81	ORC5L	ORC5L	ORC5L	8082	0.021	0.39	NO
82	MDM2	MDM2	MDM2	8098	0.021	0.39	NO
83	MCM3	MCM3	MCM3	8145	0.02	0.39	NO
84	GADD45G	GADD45G	GADD45G	8275	0.018	0.39	NO
85	ANAPC5	ANAPC5	ANAPC5	8325	0.018	0.38	NO
86	E2F4	E2F4	E2F4	8530	0.015	0.37	NO
87	SMAD2	SMAD2	SMAD2	8570	0.014	0.37	NO
88	YWHAG	YWHAG	YWHAG	8744	0.011	0.36	NO
89	CDC14A	CDC14A	CDC14A	8981	0.0079	0.35	NO
90	TFDP1	TFDP1	TFDP1	9005	0.0075	0.35	NO
91	ATM	ATM	ATM	9178	0.0051	0.34	NO
92	CDK2	CDK2	CDK2	9423	0.0016	0.33	NO
93	RB1	RB1	RB1	9527	0.00043	0.32	NO
94	GSK3B	GSK3B	GSK3B	9532	0.00037	0.32	NO
95	TP53	TP53	TP53	9885	-0.0054	0.3	NO
96	HDAC1	HDAC1	HDAC1	9924	-0.006	0.3	NO
97	CDC7	CDC7	CDC7	9941	-0.0062	0.3	NO
98	CUL1	CUL1	CUL1	10074	-0.0085	0.29	NO
99	MCM5	MCM5	MCM5	10433	-0.014	0.27	NO
100	ANAPC7	ANAPC7	ANAPC7	10532	-0.016	0.27	NO
101	CDC16	CDC16	CDC16	10601	-0.017	0.27	NO
102	ATR	ATR	ATR	10934	-0.022	0.25	NO
103	ANAPC11	ANAPC11	ANAPC11	11086	-0.025	0.24	NO
104	RBL2	RBL2	RBL2	11178	-0.026	0.24	NO
105	RBX1	RBX1	RBX1	11399	-0.03	0.23	NO
106	SMAD4	SMAD4	SMAD4	11908	-0.039	0.2	NO
107	YWHAH	YWHAH	YWHAH	12327	-0.048	0.18	NO
108	CDK6	CDK6	CDK6	12367	-0.049	0.18	NO
109	ANAPC4	ANAPC4	ANAPC4	12430	-0.05	0.18	NO
110	YWHAE	YWHAE	YWHAE	12563	-0.052	0.18	NO
111	CDC14B	CDC14B	CDC14B	12732	-0.056	0.17	NO
112	ZBTB17	ZBTB17	ZBTB17	12999	-0.061	0.16	NO
113	ANAPC2	ANAPC2	ANAPC2	13384	-0.071	0.14	NO
114	SFN	SFN	SFN	13409	-0.072	0.14	NO
115	ANAPC13	ANAPC13	ANAPC13	13830	-0.084	0.13	NO
116	MCM7	MCM7	MCM7	13961	-0.088	0.12	NO
117	CHEK2	CHEK2	CHEK2	14043	-0.091	0.13	NO
118	CDKN1A	CDKN1A	CDKN1A	14230	-0.096	0.12	NO
119	CCNB3	CCNB3	CCNB3	16424	-0.22	0.011	NO
120	MAD1L1	MAD1L1	MAD1L1	16460	-0.22	0.022	NO
121	CDKN1C	CDKN1C	CDKN1C	17227	-0.32	-0.0014	NO
122	CCND2	CCND2	CCND2	17247	-0.32	0.017	NO
123	WEE2	WEE2	WEE2	17580	-0.4	0.022	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 CALCIUM SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG CELL CYCLE

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	BUB1	BUB1	BUB1	25	0.65	0.055	YES
2	ADCY1	ADCY1	ADCY1	39	0.62	0.11	YES
3	CDC25C	CDC25C	CDC25C	113	0.54	0.15	YES
4	CCNB2	CCNB2	CCNB2	141	0.52	0.19	YES
5	PGR	PGR	PGR	333	0.45	0.22	YES
6	PDE3B	PDE3B	PDE3B	402	0.43	0.25	YES
7	CDK1	CDK1	CDK1	446	0.42	0.29	YES
8	PDE3A	PDE3A	PDE3A	521	0.4	0.32	YES
9	ADCY4	ADCY4	ADCY4	630	0.38	0.34	YES
10	MAD2L1	MAD2L1	MAD2L1	677	0.37	0.38	YES
11	CCNB1	CCNB1	CCNB1	879	0.34	0.39	YES
12	CCNA2	CCNA2	CCNA2	919	0.33	0.42	YES
13	ADCY3	ADCY3	ADCY3	1069	0.31	0.44	YES
14	PLK1	PLK1	PLK1	1268	0.29	0.45	YES
15	PKMYT1	PKMYT1	PKMYT1	1582	0.25	0.46	YES
16	CPEB1	CPEB1	CPEB1	1962	0.21	0.45	YES
17	PIK3R3	PIK3R3	PIK3R3	2252	0.19	0.45	YES
18	MAPK12	MAPK12	MAPK12	2292	0.18	0.47	YES
19	ADCY8	ADCY8	ADCY8	2454	0.17	0.47	YES
20	ANAPC1	ANAPC1	ANAPC1	2845	0.15	0.46	YES
21	RPS6KA6	RPS6KA6	RPS6KA6	2894	0.15	0.47	YES
22	CDC25B	CDC25B	CDC25B	3568	0.12	0.44	YES
23	CDC25A	CDC25A	CDC25A	3581	0.11	0.45	YES
24	MAPK8	MAPK8	MAPK8	3611	0.11	0.46	YES
25	CCNA1	CCNA1	CCNA1	3622	0.11	0.47	YES
26	BRAF	BRAF	BRAF	3676	0.11	0.48	YES
27	MAP2K1	MAP2K1	MAP2K1	4159	0.095	0.46	YES
28	MAD2L2	MAD2L2	MAD2L2	4189	0.094	0.47	YES
29	PIK3CA	PIK3CA	PIK3CA	4286	0.091	0.47	YES
30	CDC27	CDC27	CDC27	4324	0.09	0.47	YES
31	ANAPC10	ANAPC10	ANAPC10	4337	0.09	0.48	YES
32	ADCY5	ADCY5	ADCY5	4493	0.086	0.48	NO
33	MAPK9	MAPK9	MAPK9	5093	0.072	0.45	NO
34	AKT3	AKT3	AKT3	5435	0.065	0.44	NO
35	RPS6KA3	RPS6KA3	RPS6KA3	5703	0.06	0.43	NO
36	PIK3CG	PIK3CG	PIK3CG	6076	0.053	0.41	NO
37	CDC23	CDC23	CDC23	6449	0.047	0.4	NO
38	ARAF	ARAF	ARAF	6719	0.042	0.38	NO
39	HSP90AA1	HSP90AA1	HSP90AA1	6947	0.038	0.38	NO
40	PIK3R2	PIK3R2	PIK3R2	7032	0.037	0.37	NO
41	CDC26	CDC26	CDC26	7767	0.026	0.34	NO
42	PRKACA	PRKACA	PRKACA	7826	0.025	0.33	NO
43	FZR1	FZR1	FZR1	7907	0.024	0.33	NO
44	ANAPC5	ANAPC5	ANAPC5	8325	0.018	0.31	NO
45	ADCY6	ADCY6	ADCY6	8356	0.017	0.31	NO
46	MAPK3	MAPK3	MAPK3	8364	0.017	0.31	NO
47	MAPK14	MAPK14	MAPK14	8793	0.01	0.29	NO
48	MAPK11	MAPK11	MAPK11	8961	0.0081	0.28	NO
49	MAPK1	MAPK1	MAPK1	9156	0.0053	0.27	NO
50	ADCY7	ADCY7	ADCY7	9247	0.0042	0.26	NO
51	CDK2	CDK2	CDK2	9423	0.0016	0.25	NO
52	GNAI3	GNAI3	GNAI3	9649	-0.0013	0.24	NO
53	GNAI2	GNAI2	GNAI2	10085	-0.0086	0.22	NO
54	AKT2	AKT2	AKT2	10177	-0.01	0.21	NO
55	ANAPC7	ANAPC7	ANAPC7	10532	-0.016	0.2	NO
56	CDC16	CDC16	CDC16	10601	-0.017	0.19	NO
57	IGF1R	IGF1R	IGF1R	10813	-0.02	0.18	NO
58	PIK3CB	PIK3CB	PIK3CB	10950	-0.023	0.18	NO
59	ANAPC11	ANAPC11	ANAPC11	11086	-0.025	0.17	NO
60	RAF1	RAF1	RAF1	11560	-0.033	0.15	NO
61	PIK3R1	PIK3R1	PIK3R1	11889	-0.039	0.13	NO
62	KRAS	KRAS	KRAS	11955	-0.04	0.13	NO
63	AKT1	AKT1	AKT1	12005	-0.042	0.13	NO
64	IGF1	IGF1	IGF1	12349	-0.048	0.12	NO
65	ANAPC4	ANAPC4	ANAPC4	12430	-0.05	0.12	NO
66	ANAPC2	ANAPC2	ANAPC2	13384	-0.071	0.072	NO
67	SPDYA	SPDYA	SPDYA	13471	-0.074	0.074	NO
68	ANAPC13	ANAPC13	ANAPC13	13830	-0.084	0.061	NO
69	PRKX	PRKX	PRKX	13920	-0.086	0.063	NO
70	RPS6KA1	RPS6KA1	RPS6KA1	14532	-0.11	0.038	NO
71	RPS6KA2	RPS6KA2	RPS6KA2	14568	-0.11	0.046	NO
72	PRKACB	PRKACB	PRKACB	14923	-0.12	0.036	NO
73	PIK3CD	PIK3CD	PIK3CD	15084	-0.13	0.039	NO
74	ADCY9	ADCY9	ADCY9	15224	-0.14	0.042	NO
75	MAPK10	MAPK10	MAPK10	15436	-0.15	0.043	NO
76	GNAI1	GNAI1	GNAI1	16072	-0.19	0.024	NO
77	PIK3R5	PIK3R5	PIK3R5	16394	-0.21	0.024	NO
78	CCNB3	CCNB3	CCNB3	16424	-0.22	0.041	NO
79	MAPK13	MAPK13	MAPK13	16692	-0.25	0.048	NO
80	ADCY2	ADCY2	ADCY2	17004	-0.28	0.055	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 CELL CYCLE.

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

genes ES table in pathway: KEGG OOCYTE MEIOSIS

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	ITGA1	ITGA1	ITGA1	750	0.36	0.075	YES
2	ACTN3	ACTN3	ACTN3	1383	0.27	0.13	YES
3	ACTN2	ACTN2	ACTN2	1658	0.24	0.19	YES
4	CAPNS2	CAPNS2	CAPNS2	2290	0.18	0.22	YES
5	CAV1	CAV1	CAV1	2792	0.15	0.24	YES
6	SHC1	SHC1	SHC1	3271	0.13	0.26	YES
7	PPP1R12B	PPP1R12B	PPP1R12B	3375	0.12	0.29	YES
8	MAPK8	MAPK8	MAPK8	3611	0.11	0.32	YES
9	VCL	VCL	VCL	3650	0.11	0.35	YES
10	PTK2	PTK2	PTK2	4023	0.099	0.36	YES
11	MAP2K1	MAP2K1	MAP2K1	4159	0.095	0.38	YES
12	FYN	FYN	FYN	4255	0.092	0.41	YES
13	ACTA1	ACTA1	ACTA1	4469	0.086	0.42	YES
14	ACTN1	ACTN1	ACTN1	5262	0.068	0.4	NO
15	CRKL	CRKL	CRKL	5699	0.06	0.4	NO
16	ITGB1	ITGB1	ITGB1	6478	0.046	0.37	NO
17	MAP2K2	MAP2K2	MAP2K2	6768	0.041	0.37	NO
18	CSK	CSK	CSK	6870	0.039	0.38	NO
19	ROCK1	ROCK1	ROCK1	6911	0.039	0.39	NO
20	SOS1	SOS1	SOS1	7010	0.037	0.39	NO
21	PXN	PXN	PXN	7355	0.032	0.38	NO
22	TNS1	TNS1	TNS1	7440	0.031	0.39	NO
23	MAPK3	MAPK3	MAPK3	8364	0.017	0.34	NO
24	RAPGEF1	RAPGEF1	RAPGEF1	8705	0.012	0.33	NO
25	RAP1A	RAP1A	RAP1A	8716	0.012	0.33	NO
26	MAPK1	MAPK1	MAPK1	9156	0.0053	0.31	NO
27	SRC	SRC	SRC	9466	0.0012	0.29	NO
28	HRAS	HRAS	HRAS	10660	-0.018	0.23	NO
29	GRB2	GRB2	GRB2	11345	-0.029	0.2	NO
30	RAF1	RAF1	RAF1	11560	-0.033	0.2	NO
31	CAPNS1	CAPNS1	CAPNS1	11693	-0.036	0.21	NO
32	RHOA	RHOA	RHOA	12179	-0.045	0.19	NO
33	BCR	BCR	BCR	12182	-0.045	0.21	NO
34	JUN	JUN	JUN	13338	-0.07	0.17	NO
35	ZYX	ZYX	ZYX	13992	-0.089	0.16	NO
36	BCAR1	BCAR1	BCAR1	14104	-0.092	0.18	NO
37	CAPN1	CAPN1	CAPN1	14284	-0.098	0.21	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 OOCYTE MEIOSIS.

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