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

Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2016): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in CESC-TP. Broad Institute of MIT and Harvard. doi:10.7908/C1ZP45GH

Overview

Introduction

This pipeline performs Gene Set Enrichment Analysis (GSEA) using The Broad Institute GSEA tool with MSigDB - Class2: Canonical Pathways gene sets. For a given phenotype subtype, it shows what pathways are significantly enriched in each subtype by comparing gene expression profiles between subtypes. Here, the phenotype is mRNAseq_cNMF subtypes having more than three samples and the input expression file "CESC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run. This pipeline has the following features:

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

Summary

Table 1. Get Full Table basic data info

basic data info
Number of Gene Sets: 716
Number of samples: 304
Original number of Gene Sets: 1320
Maximum gene set size: 933

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 4 :[ clus1 ] 61
pheno.type: 2 - 4 :[ clus2 ] 103
pheno.type: 3 - 4 :[ clus3 ] 69
pheno.type: 4 - 4 :[ clus4 ] 71

For the expression subtypes of 18187 genes in 305 samples, GSEA found enriched gene sets in each cluster using 304 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES, ST WNT BETA CATENIN PATHWAY, PID REELINPATHWAY, PID IGF1 PATHWAY, PID LIS1PATHWAY, PID HEDGEHOG GLIPATHWAY, PID HES HEYPATHWAY, REACTOME NEGATIVE REGULATION OF FGFR SIGNALING, REACTOME SIGNALING BY EGFR IN CANCER, REACTOME INSULIN RECEPTOR SIGNALLING CASCADE

And common core enriched genes are PIK3R1, AKT3, FGF1, FGF10, FGF17, FGF18, FGF19, FGF2, FGF7, FGF9

clus2

Top enriched gene sets are KEGG P53 SIGNALING PATHWAY, BIOCARTA EGF PATHWAY, BIOCARTA RACCYCD PATHWAY, BIOCARTA STRESS PATHWAY, BIOCARTA TNFR1 PATHWAY, BIOCARTA TOLL PATHWAY, PID ERBB1 RECEPTOR PROXIMAL PATHWAY, PID FOXOPATHWAY, PID PI3KCIPATHWAY, PID ECADHERIN NASCENTAJ PATHWAY

And common core enriched genes are SRC, PIK3CA, PIK3R1, CHUK, FOXO1, FOXO4, MAPK8, SFN, YWHAZ, EGFR

clus3

Top enriched gene sets are KEGG PURINE METABOLISM, KEGG SELENOAMINO ACID METABOLISM, KEGG N GLYCAN BIOSYNTHESIS, KEGG O GLYCAN BIOSYNTHESIS, KEGG SPHINGOLIPID METABOLISM, KEGG PEROXISOME, KEGG VASOPRESSIN REGULATED WATER REABSORPTION, KEGG VIBRIO CHOLERAE INFECTION, BIOCARTA RHO PATHWAY, PID RHOA REG PATHWAY

And common core enriched genes are ESR1, TFF1, XBP1, ATP6V0A4, ATP6V0E2, ATP6V1B1, ATP6V1C2, ATP6V1G2, CFTR, KCNQ1

clus4

Top enriched gene sets are KEGG RIBOSOME, KEGG PROTEASOME, KEGG NOD LIKE RECEPTOR SIGNALING PATHWAY, KEGG RIG I LIKE RECEPTOR SIGNALING PATHWAY, KEGG CYTOSOLIC DNA SENSING PATHWAY, BIOCARTA INTEGRIN PATHWAY, BIOCARTA PROTEASOME PATHWAY, BIOCARTA IL1R PATHWAY, ST TUMOR NECROSIS FACTOR PATHWAY, ST ERK1 ERK2 MAPK PATHWAY

And common core enriched genes are PSMA1, PSMA2, PSMA3, PSMA4, PSMA5, PSMA6, PSMA7, PSMA8, PSMB1, PSMB10

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
SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES	34	genes.ES.table	0.55	1.7	0.012	0.36	0.76	0.24	0.16	0.2	0.14	0.096
ST WNT BETA CATENIN PATHWAY	32	genes.ES.table	0.64	1.7	0.0062	0.41	0.73	0.28	0.04	0.27	0.15	0.1
PID REELINPATHWAY	28	genes.ES.table	0.65	2	0	0.68	0.26	0.25	0.095	0.23	0	0.13
PID IGF1 PATHWAY	30	genes.ES.table	0.49	1.8	0.01	0.36	0.59	0.13	0.14	0.12	0.093	0.092
PID LIS1PATHWAY	28	genes.ES.table	0.54	1.7	0.019	0.38	0.76	0.18	0.099	0.16	0.14	0.099
PID HEDGEHOG GLIPATHWAY	48	genes.ES.table	0.48	1.8	0.012	0.42	0.72	0.27	0.22	0.21	0.14	0.1
PID HES HEYPATHWAY	45	genes.ES.table	0.52	1.8	0.0021	0.41	0.68	0.22	0.12	0.2	0.13	0.1
REACTOME NEGATIVE REGULATION OF FGFR SIGNALING	31	genes.ES.table	0.69	1.9	0	0.4	0.39	0.42	0.17	0.35	0	0.095
REACTOME SIGNALING BY EGFR IN CANCER	103	genes.ES.table	0.41	1.8	0.0042	0.41	0.54	0.16	0.18	0.14	0.1	0.1
REACTOME INSULIN RECEPTOR SIGNALLING CASCADE	78	genes.ES.table	0.49	1.9	0	0.42	0.45	0.27	0.25	0.2	0	0.097

genes ES table in pathway: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES

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	FGFR1	FGFR1	FGFR1	115	0.46	0.044	YES
2	PDE1A	PDE1A	PDE1A	281	0.39	0.078	YES
3	FGF18	FGF18	FGF18	566	0.34	0.1	YES
4	ADCY5	ADCY5	ADCY5	620	0.33	0.13	YES
5	AKT3	AKT3	AKT3	644	0.32	0.17	YES
6	ADCY2	ADCY2	ADCY2	717	0.32	0.2	YES
7	FGF9	FGF9	FGF9	744	0.31	0.23	YES
8	KL	KL	KL	862	0.3	0.26	YES
9	ADCY1	ADCY1	ADCY1	900	0.3	0.29	YES
10	FGF2	FGF2	FGF2	992	0.28	0.31	YES
11	FGF7	FGF7	FGF7	1059	0.28	0.34	YES
12	PRKAR2B	PRKAR2B	PRKAR2B	1178	0.27	0.36	YES
13	FGF1	FGF1	FGF1	1270	0.26	0.39	YES
14	PDE1B	PDE1B	PDE1B	1278	0.26	0.42	YES
15	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.42	YES
16	IL17RD	IL17RD	IL17RD	1822	0.22	0.44	YES
17	FGFR2	FGFR2	FGFR2	1947	0.21	0.45	YES
18	CAMK4	CAMK4	CAMK4	2003	0.2	0.47	YES
19	FGF17	FGF17	FGF17	2262	0.19	0.48	YES
20	FGF19	FGF19	FGF19	2541	0.17	0.48	YES
21	FGF10	FGF10	FGF10	2885	0.15	0.48	YES
22	PRKACB	PRKACB	PRKACB	2950	0.15	0.49	YES
23	SPRY2	SPRY2	SPRY2	3020	0.15	0.5	YES
24	BRAF	BRAF	BRAF	3132	0.14	0.51	YES
25	PLCG1	PLCG1	PLCG1	3301	0.13	0.52	YES
26	FRS3	FRS3	FRS3	3630	0.12	0.51	NO
27	THEM4	THEM4	THEM4	4311	0.098	0.49	NO
28	ADCY4	ADCY4	ADCY4	4438	0.094	0.49	NO
29	FGF8	FGF8	FGF8	4518	0.092	0.5	NO
30	PRKCG	PRKCG	PRKCG	5175	0.076	0.47	NO
31	CDKN1B	CDKN1B	CDKN1B	5500	0.068	0.46	NO
32	PHLPP1	PHLPP1	PHLPP1	5753	0.063	0.45	NO
33	FRS2	FRS2	FRS2	6198	0.056	0.43	NO
34	CREB1	CREB1	CREB1	6780	0.047	0.4	NO
35	KRAS	KRAS	KRAS	6895	0.046	0.4	NO
36	FGFR4	FGFR4	FGFR4	6924	0.045	0.41	NO
37	PRKAR1B	PRKAR1B	PRKAR1B	6941	0.045	0.41	NO
38	TRIB3	TRIB3	TRIB3	7453	0.039	0.39	NO
39	SOS1	SOS1	SOS1	7703	0.036	0.38	NO
40	MAPK1	MAPK1	MAPK1	7890	0.034	0.37	NO
41	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.37	NO
42	CALM2	CALM2	CALM2	8463	0.028	0.35	NO
43	PPP2R1A	PPP2R1A	PPP2R1A	8770	0.025	0.33	NO
44	FOXO3	FOXO3	FOXO3	9054	0.022	0.32	NO
45	GSK3A	GSK3A	GSK3A	9285	0.02	0.31	NO
46	AKT1	AKT1	AKT1	9499	0.017	0.3	NO
47	RAF1	RAF1	RAF1	9849	0.014	0.28	NO
48	NR4A1	NR4A1	NR4A1	10042	0.012	0.27	NO
49	AKT2	AKT2	AKT2	10149	0.011	0.27	NO
50	BAD	BAD	BAD	10178	0.01	0.27	NO
51	MAPKAP1	MAPKAP1	MAPKAP1	10270	0.0092	0.26	NO
52	GRB2	GRB2	GRB2	10309	0.0088	0.26	NO
53	MLST8	MLST8	MLST8	10341	0.0086	0.26	NO
54	PRKAR1A	PRKAR1A	PRKAR1A	10541	0.0063	0.25	NO
55	NRAS	NRAS	NRAS	10673	0.0048	0.24	NO
56	RPS27A	RPS27A	RPS27A	10730	0.004	0.24	NO
57	TSC2	TSC2	TSC2	10803	0.0034	0.24	NO
58	MTOR	MTOR	MTOR	10838	0.0031	0.24	NO
59	KLB	KLB	KLB	10860	0.0029	0.23	NO
60	UBA52	UBA52	UBA52	10945	0.0019	0.23	NO
61	CALM3	CALM3	CALM3	11313	-0.0015	0.21	NO
62	CALM1	CALM1	CALM1	11478	-0.0033	0.2	NO
63	CBL	CBL	CBL	11512	-0.0037	0.2	NO
64	PPP2CA	PPP2CA	PPP2CA	11768	-0.0066	0.19	NO
65	AKT1S1	AKT1S1	AKT1S1	11818	-0.0073	0.18	NO
66	CASP9	CASP9	CASP9	11942	-0.0089	0.18	NO
67	HRAS	HRAS	HRAS	12032	-0.0097	0.18	NO
68	FOXO1	FOXO1	FOXO1	12119	-0.011	0.17	NO
69	YWHAB	YWHAB	YWHAB	12148	-0.011	0.17	NO
70	PPP2CB	PPP2CB	PPP2CB	12297	-0.013	0.16	NO
71	CDK1	CDK1	CDK1	12339	-0.013	0.16	NO
72	PRKCE	PRKCE	PRKCE	12628	-0.017	0.15	NO
73	SRC	SRC	SRC	12644	-0.017	0.15	NO
74	PRKCA	PRKCA	PRKCA	12673	-0.017	0.15	NO
75	GAB1	GAB1	GAB1	12719	-0.018	0.15	NO
76	MDM2	MDM2	MDM2	12761	-0.018	0.15	NO
77	MKNK1	MKNK1	MKNK1	13009	-0.022	0.14	NO
78	PRKACA	PRKACA	PRKACA	13050	-0.022	0.14	NO
79	FGF22	FGF22	FGF22	13126	-0.023	0.14	NO
80	MAP2K2	MAP2K2	MAP2K2	13178	-0.024	0.14	NO
81	PDPK1	PDPK1	PDPK1	13277	-0.026	0.13	NO
82	ADCY3	ADCY3	ADCY3	13685	-0.032	0.12	NO
83	ADCY6	ADCY6	ADCY6	13855	-0.036	0.11	NO
84	FOXO4	FOXO4	FOXO4	13968	-0.038	0.11	NO
85	SHC1	SHC1	SHC1	14024	-0.039	0.11	NO
86	ADRBK1	ADRBK1	ADRBK1	14240	-0.044	0.1	NO
87	CHUK	CHUK	CHUK	14332	-0.046	0.1	NO
88	RICTOR	RICTOR	RICTOR	14394	-0.047	0.1	NO
89	FGFR3	FGFR3	FGFR3	14450	-0.048	0.11	NO
90	FGF5	FGF5	FGF5	14570	-0.052	0.1	NO
91	MAPK3	MAPK3	MAPK3	14785	-0.057	0.1	NO
92	MAP2K1	MAP2K1	MAP2K1	14787	-0.057	0.11	NO
93	PRKCD	PRKCD	PRKCD	14952	-0.062	0.1	NO
94	ITPR3	ITPR3	ITPR3	14996	-0.063	0.11	NO
95	RPS6KB2	RPS6KB2	RPS6KB2	15082	-0.065	0.11	NO
96	ITPR2	ITPR2	ITPR2	15124	-0.067	0.12	NO
97	PTEN	PTEN	PTEN	15155	-0.067	0.12	NO
98	PRKAR2A	PRKAR2A	PRKAR2A	15810	-0.092	0.095	NO
99	ADCY9	ADCY9	ADCY9	15820	-0.093	0.1	NO
100	CDKN1A	CDKN1A	CDKN1A	16026	-0.1	0.1	NO
101	ADCY7	ADCY7	ADCY7	16490	-0.12	0.093	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: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES.

Figure S2. Get High-res Image For the top 5 core enriched genes in the pathway: SIG REGULATION OF THE ACTIN CYTOSKELETON BY RHO GTPASES, 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: ST WNT BETA CATENIN 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	MAP1B	MAP1B	MAP1B	10	0.62	0.2	YES
2	DAB1	DAB1	DAB1	234	0.4	0.32	YES
3	MAPK8IP1	MAPK8IP1	MAPK8IP1	939	0.29	0.38	YES
4	FYN	FYN	FYN	1226	0.26	0.45	YES
5	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.51	YES
6	RELN	RELN	RELN	1684	0.22	0.58	YES
7	GRIN2A	GRIN2A	GRIN2A	1725	0.22	0.65	YES
8	CDK5	CDK5	CDK5	5662	0.065	0.45	NO
9	CDK5R1	CDK5R1	CDK5R1	6422	0.052	0.43	NO
10	MAPT	MAPT	MAPT	6503	0.051	0.44	NO
11	VLDLR	VLDLR	VLDLR	6875	0.046	0.44	NO
12	LRP8	LRP8	LRP8	6982	0.044	0.44	NO
13	GSK3B	GSK3B	GSK3B	7055	0.044	0.45	NO
14	RAPGEF1	RAPGEF1	RAPGEF1	7838	0.035	0.42	NO
15	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.42	NO
16	LRPAP1	LRPAP1	LRPAP1	8055	0.032	0.43	NO
17	CRKL	CRKL	CRKL	8066	0.032	0.44	NO
18	MAPK8	MAPK8	MAPK8	8512	0.028	0.43	NO
19	ARHGEF2	ARHGEF2	ARHGEF2	8656	0.026	0.43	NO
20	AKT1	AKT1	AKT1	9499	0.017	0.39	NO
21	NCK2	NCK2	NCK2	9866	0.014	0.37	NO
22	ITGB1	ITGB1	ITGB1	10332	0.0086	0.35	NO
23	MAP2K7	MAP2K7	MAP2K7	11344	-0.0018	0.29	NO
24	PAFAH1B1	PAFAH1B1	PAFAH1B1	11348	-0.0018	0.29	NO
25	RAP1A	RAP1A	RAP1A	11469	-0.0033	0.29	NO
26	CBL	CBL	CBL	11512	-0.0037	0.29	NO
27	MAP3K11	MAP3K11	MAP3K11	12458	-0.015	0.24	NO
28	ITGA3	ITGA3	ITGA3	17571	-0.23	0.033	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: ST WNT BETA CATENIN PATHWAY.

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

genes ES table in pathway: PID REELINPATHWAY

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	FGFR1	FGFR1	FGFR1	115	0.46	0.091	YES
2	FGF18	FGF18	FGF18	566	0.34	0.14	YES
3	AKT3	AKT3	AKT3	644	0.32	0.2	YES
4	FGF9	FGF9	FGF9	744	0.31	0.26	YES
5	KL	KL	KL	862	0.3	0.32	YES
6	FGF2	FGF2	FGF2	992	0.28	0.37	YES
7	FGF7	FGF7	FGF7	1059	0.28	0.42	YES
8	FGF1	FGF1	FGF1	1270	0.26	0.47	YES
9	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.5	YES
10	FGFR2	FGFR2	FGFR2	1947	0.21	0.52	YES
11	FGF17	FGF17	FGF17	2262	0.19	0.55	YES
12	FGF19	FGF19	FGF19	2541	0.17	0.57	YES
13	FGF10	FGF10	FGF10	2885	0.15	0.58	YES
14	THEM4	THEM4	THEM4	4311	0.098	0.52	NO
15	FGF8	FGF8	FGF8	4518	0.092	0.53	NO
16	CDKN1B	CDKN1B	CDKN1B	5500	0.068	0.49	NO
17	PHLPP1	PHLPP1	PHLPP1	5753	0.063	0.49	NO
18	FRS2	FRS2	FRS2	6198	0.056	0.48	NO
19	CREB1	CREB1	CREB1	6780	0.047	0.45	NO
20	FGFR4	FGFR4	FGFR4	6924	0.045	0.46	NO
21	TRIB3	TRIB3	TRIB3	7453	0.039	0.44	NO
22	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.41	NO
23	FOXO3	FOXO3	FOXO3	9054	0.022	0.36	NO
24	GSK3A	GSK3A	GSK3A	9285	0.02	0.35	NO
25	AKT1	AKT1	AKT1	9499	0.017	0.34	NO
26	NR4A1	NR4A1	NR4A1	10042	0.012	0.31	NO
27	AKT2	AKT2	AKT2	10149	0.011	0.31	NO
28	BAD	BAD	BAD	10178	0.01	0.31	NO
29	MAPKAP1	MAPKAP1	MAPKAP1	10270	0.0092	0.31	NO
30	GRB2	GRB2	GRB2	10309	0.0088	0.31	NO
31	MLST8	MLST8	MLST8	10341	0.0086	0.31	NO
32	TSC2	TSC2	TSC2	10803	0.0034	0.28	NO
33	MTOR	MTOR	MTOR	10838	0.0031	0.28	NO
34	KLB	KLB	KLB	10860	0.0029	0.28	NO
35	AKT1S1	AKT1S1	AKT1S1	11818	-0.0073	0.23	NO
36	CASP9	CASP9	CASP9	11942	-0.0089	0.22	NO
37	FOXO1	FOXO1	FOXO1	12119	-0.011	0.22	NO
38	GAB1	GAB1	GAB1	12719	-0.018	0.19	NO
39	MDM2	MDM2	MDM2	12761	-0.018	0.19	NO
40	FGF22	FGF22	FGF22	13126	-0.023	0.18	NO
41	PDPK1	PDPK1	PDPK1	13277	-0.026	0.17	NO
42	FOXO4	FOXO4	FOXO4	13968	-0.038	0.14	NO
43	CHUK	CHUK	CHUK	14332	-0.046	0.13	NO
44	RICTOR	RICTOR	RICTOR	14394	-0.047	0.14	NO
45	FGFR3	FGFR3	FGFR3	14450	-0.048	0.14	NO
46	FGF5	FGF5	FGF5	14570	-0.052	0.15	NO
47	RPS6KB2	RPS6KB2	RPS6KB2	15082	-0.065	0.14	NO
48	PTEN	PTEN	PTEN	15155	-0.067	0.14	NO
49	CDKN1A	CDKN1A	CDKN1A	16026	-0.1	0.12	NO

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

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

genes ES table in pathway: PID IGF1 PATHWAY

Table 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	FGFR1	FGFR1	FGFR1	115	0.46	0.048	YES
2	PDE1A	PDE1A	PDE1A	281	0.39	0.085	YES
3	FGF18	FGF18	FGF18	566	0.34	0.11	YES
4	ADCY5	ADCY5	ADCY5	620	0.33	0.14	YES
5	AKT3	AKT3	AKT3	644	0.32	0.18	YES
6	ADCY2	ADCY2	ADCY2	717	0.32	0.22	YES
7	FGF9	FGF9	FGF9	744	0.31	0.25	YES
8	KL	KL	KL	862	0.3	0.28	YES
9	ADCY1	ADCY1	ADCY1	900	0.3	0.31	YES
10	FGF2	FGF2	FGF2	992	0.28	0.34	YES
11	FGF7	FGF7	FGF7	1059	0.28	0.37	YES
12	PRKAR2B	PRKAR2B	PRKAR2B	1178	0.27	0.39	YES
13	FGF1	FGF1	FGF1	1270	0.26	0.42	YES
14	PDE1B	PDE1B	PDE1B	1278	0.26	0.45	YES
15	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.46	YES
16	FGFR2	FGFR2	FGFR2	1947	0.21	0.46	YES
17	CAMK4	CAMK4	CAMK4	2003	0.2	0.48	YES
18	FGF17	FGF17	FGF17	2262	0.19	0.49	YES
19	FGF19	FGF19	FGF19	2541	0.17	0.5	YES
20	FGF10	FGF10	FGF10	2885	0.15	0.5	YES
21	PRKACB	PRKACB	PRKACB	2950	0.15	0.51	YES
22	PLCG1	PLCG1	PLCG1	3301	0.13	0.51	NO
23	FRS3	FRS3	FRS3	3630	0.12	0.5	NO
24	THEM4	THEM4	THEM4	4311	0.098	0.48	NO
25	ADCY4	ADCY4	ADCY4	4438	0.094	0.48	NO
26	FGF8	FGF8	FGF8	4518	0.092	0.49	NO
27	PRKCG	PRKCG	PRKCG	5175	0.076	0.46	NO
28	CDKN1B	CDKN1B	CDKN1B	5500	0.068	0.45	NO
29	PHLPP1	PHLPP1	PHLPP1	5753	0.063	0.44	NO
30	FRS2	FRS2	FRS2	6198	0.056	0.43	NO
31	CREB1	CREB1	CREB1	6780	0.047	0.4	NO
32	KRAS	KRAS	KRAS	6895	0.046	0.4	NO
33	FGFR4	FGFR4	FGFR4	6924	0.045	0.4	NO
34	PRKAR1B	PRKAR1B	PRKAR1B	6941	0.045	0.41	NO
35	TRIB3	TRIB3	TRIB3	7453	0.039	0.38	NO
36	SOS1	SOS1	SOS1	7703	0.036	0.38	NO
37	MAPK1	MAPK1	MAPK1	7890	0.034	0.37	NO
38	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.36	NO
39	CALM2	CALM2	CALM2	8463	0.028	0.34	NO
40	FOXO3	FOXO3	FOXO3	9054	0.022	0.31	NO
41	GSK3A	GSK3A	GSK3A	9285	0.02	0.3	NO
42	AKT1	AKT1	AKT1	9499	0.017	0.29	NO
43	RAF1	RAF1	RAF1	9849	0.014	0.28	NO
44	NR4A1	NR4A1	NR4A1	10042	0.012	0.27	NO
45	AKT2	AKT2	AKT2	10149	0.011	0.26	NO
46	BAD	BAD	BAD	10178	0.01	0.26	NO
47	MAPKAP1	MAPKAP1	MAPKAP1	10270	0.0092	0.26	NO
48	GRB2	GRB2	GRB2	10309	0.0088	0.26	NO
49	MLST8	MLST8	MLST8	10341	0.0086	0.26	NO
50	PRKAR1A	PRKAR1A	PRKAR1A	10541	0.0063	0.25	NO
51	NRAS	NRAS	NRAS	10673	0.0048	0.24	NO
52	TSC2	TSC2	TSC2	10803	0.0034	0.23	NO
53	MTOR	MTOR	MTOR	10838	0.0031	0.23	NO
54	KLB	KLB	KLB	10860	0.0029	0.23	NO
55	CALM3	CALM3	CALM3	11313	-0.0015	0.2	NO
56	CALM1	CALM1	CALM1	11478	-0.0033	0.2	NO
57	AKT1S1	AKT1S1	AKT1S1	11818	-0.0073	0.18	NO
58	CASP9	CASP9	CASP9	11942	-0.0089	0.17	NO
59	HRAS	HRAS	HRAS	12032	-0.0097	0.17	NO
60	FOXO1	FOXO1	FOXO1	12119	-0.011	0.17	NO
61	YWHAB	YWHAB	YWHAB	12148	-0.011	0.16	NO
62	CDK1	CDK1	CDK1	12339	-0.013	0.16	NO
63	PRKCE	PRKCE	PRKCE	12628	-0.017	0.14	NO
64	PRKCA	PRKCA	PRKCA	12673	-0.017	0.14	NO
65	GAB1	GAB1	GAB1	12719	-0.018	0.14	NO
66	MDM2	MDM2	MDM2	12761	-0.018	0.14	NO
67	PRKACA	PRKACA	PRKACA	13050	-0.022	0.13	NO
68	FGF22	FGF22	FGF22	13126	-0.023	0.13	NO
69	MAP2K2	MAP2K2	MAP2K2	13178	-0.024	0.13	NO
70	PDPK1	PDPK1	PDPK1	13277	-0.026	0.12	NO
71	ADCY3	ADCY3	ADCY3	13685	-0.032	0.11	NO
72	ADCY6	ADCY6	ADCY6	13855	-0.036	0.1	NO
73	FOXO4	FOXO4	FOXO4	13968	-0.038	0.099	NO
74	SHC1	SHC1	SHC1	14024	-0.039	0.1	NO
75	ADRBK1	ADRBK1	ADRBK1	14240	-0.044	0.094	NO
76	CHUK	CHUK	CHUK	14332	-0.046	0.094	NO
77	RICTOR	RICTOR	RICTOR	14394	-0.047	0.096	NO
78	FGFR3	FGFR3	FGFR3	14450	-0.048	0.099	NO
79	FGF5	FGF5	FGF5	14570	-0.052	0.098	NO
80	MAPK3	MAPK3	MAPK3	14785	-0.057	0.093	NO
81	MAP2K1	MAP2K1	MAP2K1	14787	-0.057	0.1	NO
82	PRKCD	PRKCD	PRKCD	14952	-0.062	0.098	NO
83	ITPR3	ITPR3	ITPR3	14996	-0.063	0.1	NO
84	RPS6KB2	RPS6KB2	RPS6KB2	15082	-0.065	0.11	NO
85	ITPR2	ITPR2	ITPR2	15124	-0.067	0.11	NO
86	PTEN	PTEN	PTEN	15155	-0.067	0.12	NO
87	PRKAR2A	PRKAR2A	PRKAR2A	15810	-0.092	0.093	NO
88	ADCY9	ADCY9	ADCY9	15820	-0.093	0.1	NO
89	CDKN1A	CDKN1A	CDKN1A	16026	-0.1	0.1	NO
90	ADCY7	ADCY7	ADCY7	16490	-0.12	0.093	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: PID IGF1 PATHWAY.

Figure S8. Get High-res Image For the top 5 core enriched genes in the pathway: PID IGF1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID LIS1PATHWAY

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	FGFR1	FGFR1	FGFR1	115	0.46	0.039	YES
2	PDE1A	PDE1A	PDE1A	281	0.39	0.069	YES
3	FGF18	FGF18	FGF18	566	0.34	0.087	YES
4	ADCY5	ADCY5	ADCY5	620	0.33	0.12	YES
5	AKT3	AKT3	AKT3	644	0.32	0.15	YES
6	ADCY2	ADCY2	ADCY2	717	0.32	0.17	YES
7	FGF9	FGF9	FGF9	744	0.31	0.2	YES
8	KL	KL	KL	862	0.3	0.23	YES
9	ADCY1	ADCY1	ADCY1	900	0.3	0.25	YES
10	FGF2	FGF2	FGF2	992	0.28	0.28	YES
11	FGF7	FGF7	FGF7	1059	0.28	0.3	YES
12	PRKAR2B	PRKAR2B	PRKAR2B	1178	0.27	0.32	YES
13	FGF1	FGF1	FGF1	1270	0.26	0.34	YES
14	PDE1B	PDE1B	PDE1B	1278	0.26	0.37	YES
15	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.37	YES
16	IL17RD	IL17RD	IL17RD	1822	0.22	0.38	YES
17	FGFR2	FGFR2	FGFR2	1947	0.21	0.4	YES
18	CAMK4	CAMK4	CAMK4	2003	0.2	0.41	YES
19	TRIM24	TRIM24	TRIM24	2165	0.2	0.42	YES
20	FGF17	FGF17	FGF17	2262	0.19	0.44	YES
21	FGF19	FGF19	FGF19	2541	0.17	0.44	YES
22	FGF10	FGF10	FGF10	2885	0.15	0.43	YES
23	PRKACB	PRKACB	PRKACB	2950	0.15	0.44	YES
24	SPRY2	SPRY2	SPRY2	3020	0.15	0.46	YES
25	BRAF	BRAF	BRAF	3132	0.14	0.46	YES
26	PLCG1	PLCG1	PLCG1	3301	0.13	0.47	YES
27	FRS3	FRS3	FRS3	3630	0.12	0.46	NO
28	THEM4	THEM4	THEM4	4311	0.098	0.43	NO
29	ADCY4	ADCY4	ADCY4	4438	0.094	0.44	NO
30	FGF8	FGF8	FGF8	4518	0.092	0.44	NO
31	PRKCG	PRKCG	PRKCG	5175	0.076	0.41	NO
32	CDKN1B	CDKN1B	CDKN1B	5500	0.068	0.4	NO
33	CPSF6	CPSF6	CPSF6	5688	0.065	0.4	NO
34	PHLPP1	PHLPP1	PHLPP1	5753	0.063	0.4	NO
35	GAB2	GAB2	GAB2	5867	0.061	0.4	NO
36	ZMYM2	ZMYM2	ZMYM2	6056	0.058	0.4	NO
37	FRS2	FRS2	FRS2	6198	0.056	0.39	NO
38	CREB1	CREB1	CREB1	6780	0.047	0.36	NO
39	KRAS	KRAS	KRAS	6895	0.046	0.36	NO
40	FGFR4	FGFR4	FGFR4	6924	0.045	0.37	NO
41	PRKAR1B	PRKAR1B	PRKAR1B	6941	0.045	0.37	NO
42	TRIB3	TRIB3	TRIB3	7453	0.039	0.35	NO
43	SOS1	SOS1	SOS1	7703	0.036	0.34	NO
44	MAPK1	MAPK1	MAPK1	7890	0.034	0.33	NO
45	FGFR1OP	FGFR1OP	FGFR1OP	7982	0.033	0.33	NO
46	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.33	NO
47	CALM2	CALM2	CALM2	8463	0.028	0.31	NO
48	PPP2R1A	PPP2R1A	PPP2R1A	8770	0.025	0.29	NO
49	FGFR1OP2	FGFR1OP2	FGFR1OP2	8887	0.023	0.29	NO
50	FOXO3	FOXO3	FOXO3	9054	0.022	0.28	NO
51	GSK3A	GSK3A	GSK3A	9285	0.02	0.27	NO
52	AKT1	AKT1	AKT1	9499	0.017	0.26	NO
53	RAF1	RAF1	RAF1	9849	0.014	0.24	NO
54	NR4A1	NR4A1	NR4A1	10042	0.012	0.23	NO
55	AKT2	AKT2	AKT2	10149	0.011	0.23	NO
56	BAD	BAD	BAD	10178	0.01	0.23	NO
57	MAPKAP1	MAPKAP1	MAPKAP1	10270	0.0092	0.22	NO
58	GRB2	GRB2	GRB2	10309	0.0088	0.22	NO
59	MLST8	MLST8	MLST8	10341	0.0086	0.22	NO
60	PRKAR1A	PRKAR1A	PRKAR1A	10541	0.0063	0.21	NO
61	NRAS	NRAS	NRAS	10673	0.0048	0.2	NO
62	RPS27A	RPS27A	RPS27A	10730	0.004	0.2	NO
63	TSC2	TSC2	TSC2	10803	0.0034	0.2	NO
64	MTOR	MTOR	MTOR	10838	0.0031	0.2	NO
65	KLB	KLB	KLB	10860	0.0029	0.2	NO
66	UBA52	UBA52	UBA52	10945	0.0019	0.19	NO
67	CALM3	CALM3	CALM3	11313	-0.0015	0.17	NO
68	CALM1	CALM1	CALM1	11478	-0.0033	0.16	NO
69	CBL	CBL	CBL	11512	-0.0037	0.16	NO
70	PPP2CA	PPP2CA	PPP2CA	11768	-0.0066	0.15	NO
71	AKT1S1	AKT1S1	AKT1S1	11818	-0.0073	0.14	NO
72	CASP9	CASP9	CASP9	11942	-0.0089	0.14	NO
73	HRAS	HRAS	HRAS	12032	-0.0097	0.13	NO
74	CUX1	CUX1	CUX1	12115	-0.011	0.13	NO
75	FOXO1	FOXO1	FOXO1	12119	-0.011	0.13	NO
76	YWHAB	YWHAB	YWHAB	12148	-0.011	0.13	NO
77	STAT5B	STAT5B	STAT5B	12269	-0.013	0.13	NO
78	PPP2CB	PPP2CB	PPP2CB	12297	-0.013	0.13	NO
79	CDK1	CDK1	CDK1	12339	-0.013	0.12	NO
80	PRKCE	PRKCE	PRKCE	12628	-0.017	0.11	NO
81	SRC	SRC	SRC	12644	-0.017	0.11	NO
82	PRKCA	PRKCA	PRKCA	12673	-0.017	0.11	NO
83	GAB1	GAB1	GAB1	12719	-0.018	0.11	NO
84	MDM2	MDM2	MDM2	12761	-0.018	0.11	NO
85	MKNK1	MKNK1	MKNK1	13009	-0.022	0.099	NO
86	PRKACA	PRKACA	PRKACA	13050	-0.022	0.099	NO
87	FGF22	FGF22	FGF22	13126	-0.023	0.097	NO
88	MAP2K2	MAP2K2	MAP2K2	13178	-0.024	0.097	NO
89	PDPK1	PDPK1	PDPK1	13277	-0.026	0.094	NO
90	ADCY3	ADCY3	ADCY3	13685	-0.032	0.074	NO
91	ADCY6	ADCY6	ADCY6	13855	-0.036	0.068	NO
92	STAT3	STAT3	STAT3	13907	-0.037	0.069	NO
93	FOXO4	FOXO4	FOXO4	13968	-0.038	0.07	NO
94	SHC1	SHC1	SHC1	14024	-0.039	0.071	NO
95	ADRBK1	ADRBK1	ADRBK1	14240	-0.044	0.063	NO
96	CHUK	CHUK	CHUK	14332	-0.046	0.063	NO
97	RICTOR	RICTOR	RICTOR	14394	-0.047	0.064	NO
98	FGFR3	FGFR3	FGFR3	14450	-0.048	0.066	NO
99	FGF5	FGF5	FGF5	14570	-0.052	0.064	NO
100	MAPK3	MAPK3	MAPK3	14785	-0.057	0.058	NO
101	MAP2K1	MAP2K1	MAP2K1	14787	-0.057	0.064	NO
102	PRKCD	PRKCD	PRKCD	14952	-0.062	0.061	NO
103	ITPR3	ITPR3	ITPR3	14996	-0.063	0.064	NO
104	RPS6KB2	RPS6KB2	RPS6KB2	15082	-0.065	0.066	NO
105	ITPR2	ITPR2	ITPR2	15124	-0.067	0.07	NO
106	PTEN	PTEN	PTEN	15155	-0.067	0.076	NO
107	BCR	BCR	BCR	15223	-0.07	0.079	NO
108	STAT1	STAT1	STAT1	15472	-0.079	0.073	NO
109	PRKAR2A	PRKAR2A	PRKAR2A	15810	-0.092	0.063	NO
110	ADCY9	ADCY9	ADCY9	15820	-0.093	0.072	NO
111	CDKN1A	CDKN1A	CDKN1A	16026	-0.1	0.071	NO
112	MYO18A	MYO18A	MYO18A	16196	-0.11	0.072	NO
113	ADCY7	ADCY7	ADCY7	16490	-0.12	0.068	NO
114	STAT5A	STAT5A	STAT5A	17669	-0.25	0.028	NO

Figure S9. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: PID LIS1PATHWAY.

Figure S10. Get High-res Image For the top 5 core enriched genes in the pathway: PID LIS1PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID HEDGEHOG GLIPATHWAY

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	FGFR1	FGFR1	FGFR1	115	0.46	0.12	YES
2	FGF18	FGF18	FGF18	566	0.34	0.18	YES
3	FGF9	FGF9	FGF9	744	0.31	0.26	YES
4	KL	KL	KL	862	0.3	0.33	YES
5	FGF2	FGF2	FGF2	992	0.28	0.4	YES
6	FGF7	FGF7	FGF7	1059	0.28	0.47	YES
7	FGF1	FGF1	FGF1	1270	0.26	0.52	YES
8	FGFR2	FGFR2	FGFR2	1947	0.21	0.54	YES
9	FGF17	FGF17	FGF17	2262	0.19	0.57	YES
10	FGF19	FGF19	FGF19	2541	0.17	0.61	YES
11	FGF10	FGF10	FGF10	2885	0.15	0.63	YES
12	SPRY2	SPRY2	SPRY2	3020	0.15	0.66	YES
13	BRAF	BRAF	BRAF	3132	0.14	0.69	YES
14	FGF8	FGF8	FGF8	4518	0.092	0.64	NO
15	FRS2	FRS2	FRS2	6198	0.056	0.56	NO
16	FGFR4	FGFR4	FGFR4	6924	0.045	0.53	NO
17	MAPK1	MAPK1	MAPK1	7890	0.034	0.49	NO
18	PPP2R1A	PPP2R1A	PPP2R1A	8770	0.025	0.45	NO
19	GRB2	GRB2	GRB2	10309	0.0088	0.37	NO
20	RPS27A	RPS27A	RPS27A	10730	0.004	0.34	NO
21	KLB	KLB	KLB	10860	0.0029	0.34	NO
22	UBA52	UBA52	UBA52	10945	0.0019	0.33	NO
23	CBL	CBL	CBL	11512	-0.0037	0.3	NO
24	PPP2CA	PPP2CA	PPP2CA	11768	-0.0066	0.29	NO
25	PPP2CB	PPP2CB	PPP2CB	12297	-0.013	0.26	NO
26	SRC	SRC	SRC	12644	-0.017	0.25	NO
27	MKNK1	MKNK1	MKNK1	13009	-0.022	0.24	NO
28	FGF22	FGF22	FGF22	13126	-0.023	0.24	NO
29	FGFR3	FGFR3	FGFR3	14450	-0.048	0.18	NO
30	FGF5	FGF5	FGF5	14570	-0.052	0.18	NO
31	MAPK3	MAPK3	MAPK3	14785	-0.057	0.19	NO

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

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

genes ES table in pathway: PID HES HEYPATHWAY

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	FGFR1	FGFR1	FGFR1	115	0.46	0.069	YES
2	PRKAA2	PRKAA2	PRKAA2	371	0.37	0.12	YES
3	FGF18	FGF18	FGF18	566	0.34	0.16	YES
4	FGF9	FGF9	FGF9	744	0.31	0.2	YES
5	KL	KL	KL	862	0.3	0.24	YES
6	FGF2	FGF2	FGF2	992	0.28	0.28	YES
7	FGF7	FGF7	FGF7	1059	0.28	0.32	YES
8	FGF1	FGF1	FGF1	1270	0.26	0.36	YES
9	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.38	YES
10	FGFR2	FGFR2	FGFR2	1947	0.21	0.39	YES
11	FGF17	FGF17	FGF17	2262	0.19	0.4	YES
12	FGF19	FGF19	FGF19	2541	0.17	0.42	YES
13	GRB10	GRB10	GRB10	2576	0.17	0.44	YES
14	SHC2	SHC2	SHC2	2829	0.16	0.45	YES
15	FGF10	FGF10	FGF10	2885	0.15	0.48	YES
16	PDE3B	PDE3B	PDE3B	3811	0.12	0.44	YES
17	DOK1	DOK1	DOK1	3836	0.11	0.46	YES
18	THEM4	THEM4	THEM4	4311	0.098	0.45	YES
19	CAB39L	CAB39L	CAB39L	4318	0.098	0.47	YES
20	PRKAG3	PRKAG3	PRKAG3	4402	0.095	0.48	YES
21	FGF8	FGF8	FGF8	4518	0.092	0.49	YES
22	INSR	INSR	INSR	5293	0.073	0.46	NO
23	PIK3C3	PIK3C3	PIK3C3	5888	0.061	0.43	NO
24	RHEB	RHEB	RHEB	5980	0.059	0.44	NO
25	STK11	STK11	STK11	6172	0.056	0.44	NO
26	FRS2	FRS2	FRS2	6198	0.056	0.44	NO
27	TLR9	TLR9	TLR9	6667	0.049	0.43	NO
28	STRADA	STRADA	STRADA	6700	0.049	0.43	NO
29	KRAS	KRAS	KRAS	6895	0.046	0.43	NO
30	FGFR4	FGFR4	FGFR4	6924	0.045	0.44	NO
31	RPTOR	RPTOR	RPTOR	7024	0.044	0.44	NO
32	EIF4B	EIF4B	EIF4B	7284	0.041	0.43	NO
33	TRIB3	TRIB3	TRIB3	7453	0.039	0.43	NO
34	PIK3R4	PIK3R4	PIK3R4	7690	0.037	0.42	NO
35	SOS1	SOS1	SOS1	7703	0.036	0.42	NO
36	PRKAG1	PRKAG1	PRKAG1	7809	0.035	0.42	NO
37	MAPK1	MAPK1	MAPK1	7890	0.034	0.42	NO
38	PPM1A	PPM1A	PPM1A	7893	0.034	0.43	NO
39	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.43	NO
40	PIK3CB	PIK3CB	PIK3CB	8402	0.029	0.41	NO
41	PIK3R2	PIK3R2	PIK3R2	8750	0.025	0.4	NO
42	PRKAB2	PRKAB2	PRKAB2	8955	0.023	0.39	NO
43	PRKAG2	PRKAG2	PRKAG2	9191	0.021	0.38	NO
44	RAF1	RAF1	RAF1	9849	0.014	0.35	NO
45	IRS1	IRS1	IRS1	9934	0.013	0.34	NO
46	AKT2	AKT2	AKT2	10149	0.011	0.33	NO
47	SHC3	SHC3	SHC3	10182	0.01	0.33	NO
48	IRS2	IRS2	IRS2	10279	0.0091	0.33	NO
49	GRB2	GRB2	GRB2	10309	0.0088	0.33	NO
50	MLST8	MLST8	MLST8	10341	0.0086	0.33	NO
51	EIF4G1	EIF4G1	EIF4G1	10524	0.0065	0.32	NO
52	NRAS	NRAS	NRAS	10673	0.0048	0.31	NO
53	EIF4EBP1	EIF4EBP1	EIF4EBP1	10691	0.0046	0.31	NO
54	TSC2	TSC2	TSC2	10803	0.0034	0.31	NO
55	MTOR	MTOR	MTOR	10838	0.0031	0.31	NO
56	KLB	KLB	KLB	10860	0.0029	0.3	NO
57	RPS6	RPS6	RPS6	10964	0.0018	0.3	NO
58	EIF4E	EIF4E	EIF4E	10986	0.0016	0.3	NO
59	EEF2K	EEF2K	EEF2K	11280	-0.0012	0.28	NO
60	PRKAB1	PRKAB1	PRKAB1	11556	-0.0043	0.27	NO
61	STRADB	STRADB	STRADB	11605	-0.0048	0.27	NO
62	TSC1	TSC1	TSC1	12009	-0.0095	0.25	NO
63	HRAS	HRAS	HRAS	12032	-0.0097	0.25	NO
64	YWHAB	YWHAB	YWHAB	12148	-0.011	0.24	NO
65	CDK1	CDK1	CDK1	12339	-0.013	0.23	NO
66	GAB1	GAB1	GAB1	12719	-0.018	0.22	NO
67	RPS6KB1	RPS6KB1	RPS6KB1	12978	-0.021	0.2	NO
68	FGF22	FGF22	FGF22	13126	-0.023	0.2	NO
69	MAP2K2	MAP2K2	MAP2K2	13178	-0.024	0.2	NO
70	PDPK1	PDPK1	PDPK1	13277	-0.026	0.2	NO
71	SHC1	SHC1	SHC1	14024	-0.039	0.16	NO
72	PRKAA1	PRKAA1	PRKAA1	14166	-0.042	0.16	NO
73	FGFR3	FGFR3	FGFR3	14450	-0.048	0.16	NO
74	FGF5	FGF5	FGF5	14570	-0.052	0.16	NO
75	MAPK3	MAPK3	MAPK3	14785	-0.057	0.16	NO
76	MAP2K1	MAP2K1	MAP2K1	14787	-0.057	0.16	NO
77	CAB39	CAB39	CAB39	14946	-0.062	0.17	NO
78	CRK	CRK	CRK	15265	-0.071	0.16	NO

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

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

genes ES table in pathway: REACTOME NEGATIVE REGULATION OF FGFR SIGNALING

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	FGFR1	FGFR1	FGFR1	115	0.46	0.08	YES
2	PRKAA2	PRKAA2	PRKAA2	371	0.37	0.14	YES
3	FGF18	FGF18	FGF18	566	0.34	0.19	YES
4	FGF9	FGF9	FGF9	744	0.31	0.24	YES
5	KL	KL	KL	862	0.3	0.28	YES
6	FGF2	FGF2	FGF2	992	0.28	0.33	YES
7	FGF7	FGF7	FGF7	1059	0.28	0.38	YES
8	FGF1	FGF1	FGF1	1270	0.26	0.42	YES
9	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.44	YES
10	FGFR2	FGFR2	FGFR2	1947	0.21	0.46	YES
11	FGF17	FGF17	FGF17	2262	0.19	0.48	YES
12	FGF19	FGF19	FGF19	2541	0.17	0.5	YES
13	FGF10	FGF10	FGF10	2885	0.15	0.5	YES
14	PDE3B	PDE3B	PDE3B	3811	0.12	0.48	YES
15	DOK1	DOK1	DOK1	3836	0.11	0.5	YES
16	THEM4	THEM4	THEM4	4311	0.098	0.49	YES
17	CAB39L	CAB39L	CAB39L	4318	0.098	0.5	YES
18	PRKAG3	PRKAG3	PRKAG3	4402	0.095	0.52	YES
19	FGF8	FGF8	FGF8	4518	0.092	0.53	YES
20	INSR	INSR	INSR	5293	0.073	0.5	NO
21	PIK3C3	PIK3C3	PIK3C3	5888	0.061	0.48	NO
22	RHEB	RHEB	RHEB	5980	0.059	0.48	NO
23	STK11	STK11	STK11	6172	0.056	0.48	NO
24	FRS2	FRS2	FRS2	6198	0.056	0.49	NO
25	TLR9	TLR9	TLR9	6667	0.049	0.48	NO
26	STRADA	STRADA	STRADA	6700	0.049	0.48	NO
27	FGFR4	FGFR4	FGFR4	6924	0.045	0.48	NO
28	RPTOR	RPTOR	RPTOR	7024	0.044	0.48	NO
29	EIF4B	EIF4B	EIF4B	7284	0.041	0.48	NO
30	TRIB3	TRIB3	TRIB3	7453	0.039	0.47	NO
31	PIK3R4	PIK3R4	PIK3R4	7690	0.037	0.47	NO
32	PRKAG1	PRKAG1	PRKAG1	7809	0.035	0.47	NO
33	PPM1A	PPM1A	PPM1A	7893	0.034	0.47	NO
34	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.47	NO
35	PIK3CB	PIK3CB	PIK3CB	8402	0.029	0.45	NO
36	PIK3R2	PIK3R2	PIK3R2	8750	0.025	0.44	NO
37	PRKAB2	PRKAB2	PRKAB2	8955	0.023	0.43	NO
38	PRKAG2	PRKAG2	PRKAG2	9191	0.021	0.42	NO
39	IRS1	IRS1	IRS1	9934	0.013	0.38	NO
40	AKT2	AKT2	AKT2	10149	0.011	0.37	NO
41	IRS2	IRS2	IRS2	10279	0.0091	0.37	NO
42	GRB2	GRB2	GRB2	10309	0.0088	0.37	NO
43	MLST8	MLST8	MLST8	10341	0.0086	0.37	NO
44	EIF4G1	EIF4G1	EIF4G1	10524	0.0065	0.36	NO
45	EIF4EBP1	EIF4EBP1	EIF4EBP1	10691	0.0046	0.35	NO
46	TSC2	TSC2	TSC2	10803	0.0034	0.35	NO
47	MTOR	MTOR	MTOR	10838	0.0031	0.34	NO
48	KLB	KLB	KLB	10860	0.0029	0.34	NO
49	RPS6	RPS6	RPS6	10964	0.0018	0.34	NO
50	EIF4E	EIF4E	EIF4E	10986	0.0016	0.34	NO
51	EEF2K	EEF2K	EEF2K	11280	-0.0012	0.32	NO
52	PRKAB1	PRKAB1	PRKAB1	11556	-0.0043	0.31	NO
53	STRADB	STRADB	STRADB	11605	-0.0048	0.31	NO
54	TSC1	TSC1	TSC1	12009	-0.0095	0.28	NO
55	GAB1	GAB1	GAB1	12719	-0.018	0.25	NO
56	RPS6KB1	RPS6KB1	RPS6KB1	12978	-0.021	0.24	NO
57	FGF22	FGF22	FGF22	13126	-0.023	0.24	NO
58	PDPK1	PDPK1	PDPK1	13277	-0.026	0.23	NO
59	PRKAA1	PRKAA1	PRKAA1	14166	-0.042	0.19	NO
60	FGFR3	FGFR3	FGFR3	14450	-0.048	0.18	NO
61	FGF5	FGF5	FGF5	14570	-0.052	0.19	NO
62	CAB39	CAB39	CAB39	14946	-0.062	0.18	NO

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

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

genes ES table in pathway: REACTOME SIGNALING BY EGFR IN CANCER

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	PDE1A	PDE1A	PDE1A	281	0.39	0.039	YES
2	ADCY5	ADCY5	ADCY5	620	0.33	0.066	YES
3	AKT3	AKT3	AKT3	644	0.32	0.11	YES
4	SH3GL2	SH3GL2	SH3GL2	709	0.32	0.15	YES
5	ADCY2	ADCY2	ADCY2	717	0.32	0.2	YES
6	ADCY1	ADCY1	ADCY1	900	0.3	0.23	YES
7	PRKAR2B	PRKAR2B	PRKAR2B	1178	0.27	0.25	YES
8	LRIG1	LRIG1	LRIG1	1182	0.27	0.28	YES
9	PDE1B	PDE1B	PDE1B	1278	0.26	0.32	YES
10	EGF	EGF	EGF	1480	0.24	0.34	YES
11	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.37	YES
12	CAMK4	CAMK4	CAMK4	2003	0.2	0.37	YES
13	ADAM12	ADAM12	ADAM12	2024	0.2	0.4	YES
14	SPRY1	SPRY1	SPRY1	2937	0.15	0.37	YES
15	PRKACB	PRKACB	PRKACB	2950	0.15	0.39	YES
16	SPRY2	SPRY2	SPRY2	3020	0.15	0.41	YES
17	PLCG1	PLCG1	PLCG1	3301	0.13	0.41	YES
18	THEM4	THEM4	THEM4	4311	0.098	0.37	NO
19	ADCY4	ADCY4	ADCY4	4438	0.094	0.37	NO
20	PRKCG	PRKCG	PRKCG	5175	0.076	0.34	NO
21	CDKN1B	CDKN1B	CDKN1B	5500	0.068	0.34	NO
22	PHLPP1	PHLPP1	PHLPP1	5753	0.063	0.33	NO
23	PAG1	PAG1	PAG1	6223	0.055	0.31	NO
24	CREB1	CREB1	CREB1	6780	0.047	0.29	NO
25	KRAS	KRAS	KRAS	6895	0.046	0.29	NO
26	PRKAR1B	PRKAR1B	PRKAR1B	6941	0.045	0.29	NO
27	TRIB3	TRIB3	TRIB3	7453	0.039	0.27	NO
28	SOS1	SOS1	SOS1	7703	0.036	0.26	NO
29	HSP90AA1	HSP90AA1	HSP90AA1	7875	0.034	0.26	NO
30	MAPK1	MAPK1	MAPK1	7890	0.034	0.26	NO
31	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.26	NO
32	AP2B1	AP2B1	AP2B1	8114	0.032	0.26	NO
33	CALM2	CALM2	CALM2	8463	0.028	0.24	NO
34	CLTA	CLTA	CLTA	8660	0.026	0.23	NO
35	FOXO3	FOXO3	FOXO3	9054	0.022	0.21	NO
36	AP2A2	AP2A2	AP2A2	9270	0.02	0.2	NO
37	GSK3A	GSK3A	GSK3A	9285	0.02	0.21	NO
38	AKT1	AKT1	AKT1	9499	0.017	0.2	NO
39	EPS15L1	EPS15L1	EPS15L1	9558	0.017	0.2	NO
40	AP2M1	AP2M1	AP2M1	9620	0.016	0.2	NO
41	RAF1	RAF1	RAF1	9849	0.014	0.18	NO
42	NR4A1	NR4A1	NR4A1	10042	0.012	0.18	NO
43	AKT2	AKT2	AKT2	10149	0.011	0.17	NO
44	STAM2	STAM2	STAM2	10157	0.01	0.17	NO
45	BAD	BAD	BAD	10178	0.01	0.17	NO
46	CLTC	CLTC	CLTC	10225	0.0097	0.17	NO
47	MAPKAP1	MAPKAP1	MAPKAP1	10270	0.0092	0.17	NO
48	GRB2	GRB2	GRB2	10309	0.0088	0.17	NO
49	MLST8	MLST8	MLST8	10341	0.0086	0.17	NO
50	PRKAR1A	PRKAR1A	PRKAR1A	10541	0.0063	0.16	NO
51	NRAS	NRAS	NRAS	10673	0.0048	0.15	NO
52	RPS27A	RPS27A	RPS27A	10730	0.004	0.15	NO
53	TSC2	TSC2	TSC2	10803	0.0034	0.15	NO
54	MTOR	MTOR	MTOR	10838	0.0031	0.14	NO
55	UBA52	UBA52	UBA52	10945	0.0019	0.14	NO
56	CALM3	CALM3	CALM3	11313	-0.0015	0.12	NO
57	AP2A1	AP2A1	AP2A1	11474	-0.0033	0.11	NO
58	CALM1	CALM1	CALM1	11478	-0.0033	0.11	NO
59	CBL	CBL	CBL	11512	-0.0037	0.11	NO
60	AKT1S1	AKT1S1	AKT1S1	11818	-0.0073	0.094	NO
61	CASP9	CASP9	CASP9	11942	-0.0089	0.088	NO
62	HGS	HGS	HGS	11963	-0.0091	0.089	NO
63	HRAS	HRAS	HRAS	12032	-0.0097	0.086	NO
64	FOXO1	FOXO1	FOXO1	12119	-0.011	0.083	NO
65	YWHAB	YWHAB	YWHAB	12148	-0.011	0.083	NO
66	CDK1	CDK1	CDK1	12339	-0.013	0.074	NO
67	ADAM17	ADAM17	ADAM17	12349	-0.013	0.076	NO
68	CDC42	CDC42	CDC42	12572	-0.016	0.066	NO
69	PRKCE	PRKCE	PRKCE	12628	-0.017	0.065	NO
70	SRC	SRC	SRC	12644	-0.017	0.066	NO
71	PRKCA	PRKCA	PRKCA	12673	-0.017	0.067	NO
72	GAB1	GAB1	GAB1	12719	-0.018	0.067	NO
73	MDM2	MDM2	MDM2	12761	-0.018	0.068	NO
74	EPS15	EPS15	EPS15	13015	-0.022	0.057	NO
75	PRKACA	PRKACA	PRKACA	13050	-0.022	0.058	NO
76	ADAM10	ADAM10	ADAM10	13120	-0.023	0.057	NO
77	MAP2K2	MAP2K2	MAP2K2	13178	-0.024	0.058	NO
78	CSK	CSK	CSK	13232	-0.025	0.058	NO
79	PDPK1	PDPK1	PDPK1	13277	-0.026	0.059	NO
80	EPN1	EPN1	EPN1	13478	-0.029	0.052	NO
81	AP2S1	AP2S1	AP2S1	13557	-0.03	0.052	NO
82	ADCY3	ADCY3	ADCY3	13685	-0.032	0.05	NO
83	STAM	STAM	STAM	13717	-0.033	0.052	NO
84	ADCY6	ADCY6	ADCY6	13855	-0.036	0.05	NO
85	FOXO4	FOXO4	FOXO4	13968	-0.038	0.049	NO
86	SH3KBP1	SH3KBP1	SH3KBP1	14009	-0.039	0.052	NO
87	SHC1	SHC1	SHC1	14024	-0.039	0.057	NO
88	ADRBK1	ADRBK1	ADRBK1	14240	-0.044	0.051	NO
89	CDC37	CDC37	CDC37	14261	-0.044	0.056	NO
90	CHUK	CHUK	CHUK	14332	-0.046	0.059	NO
91	RICTOR	RICTOR	RICTOR	14394	-0.047	0.062	NO
92	MAPK3	MAPK3	MAPK3	14785	-0.057	0.048	NO
93	MAP2K1	MAP2K1	MAP2K1	14787	-0.057	0.056	NO
94	PRKCD	PRKCD	PRKCD	14952	-0.062	0.056	NO
95	ITPR3	ITPR3	ITPR3	14996	-0.063	0.062	NO
96	RPS6KB2	RPS6KB2	RPS6KB2	15082	-0.065	0.067	NO
97	ITPR2	ITPR2	ITPR2	15124	-0.067	0.074	NO
98	PTEN	PTEN	PTEN	15155	-0.067	0.082	NO
99	PRKAR2A	PRKAR2A	PRKAR2A	15810	-0.092	0.058	NO
100	ADCY9	ADCY9	ADCY9	15820	-0.093	0.071	NO
101	CDKN1A	CDKN1A	CDKN1A	16026	-0.1	0.074	NO
102	ADCY7	ADCY7	ADCY7	16490	-0.12	0.065	NO
103	EGFR	EGFR	EGFR	17343	-0.2	0.046	NO

Figure S17. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: REACTOME SIGNALING BY EGFR IN CANCER.

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

genes ES table in pathway: REACTOME INSULIN RECEPTOR SIGNALLING CASCADE

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	FGFR1	FGFR1	FGFR1	115	0.46	0.056	YES
2	PRKAA2	PRKAA2	PRKAA2	371	0.37	0.093	YES
3	FGF18	FGF18	FGF18	566	0.34	0.13	YES
4	ATP6V1G2	ATP6V1G2	ATP6V1G2	608	0.33	0.17	YES
5	FGF9	FGF9	FGF9	744	0.31	0.21	YES
6	KL	KL	KL	862	0.3	0.24	YES
7	FGF2	FGF2	FGF2	992	0.28	0.27	YES
8	FGF7	FGF7	FGF7	1059	0.28	0.31	YES
9	FGF1	FGF1	FGF1	1270	0.26	0.33	YES
10	PIK3R1	PIK3R1	PIK3R1	1579	0.23	0.34	YES
11	ATP6V1E2	ATP6V1E2	ATP6V1E2	1923	0.21	0.35	YES
12	FGFR2	FGFR2	FGFR2	1947	0.21	0.38	YES
13	FGF17	FGF17	FGF17	2262	0.19	0.39	YES
14	FGF19	FGF19	FGF19	2541	0.17	0.4	YES
15	GRB10	GRB10	GRB10	2576	0.17	0.42	YES
16	SHC2	SHC2	SHC2	2829	0.16	0.43	YES
17	FGF10	FGF10	FGF10	2885	0.15	0.44	YES
18	PDE3B	PDE3B	PDE3B	3811	0.12	0.41	YES
19	DOK1	DOK1	DOK1	3836	0.11	0.42	YES
20	THEM4	THEM4	THEM4	4311	0.098	0.41	YES
21	CAB39L	CAB39L	CAB39L	4318	0.098	0.42	YES
22	ATP6V0A4	ATP6V0A4	ATP6V0A4	4376	0.096	0.43	YES
23	PRKAG3	PRKAG3	PRKAG3	4402	0.095	0.44	YES
24	FGF8	FGF8	FGF8	4518	0.092	0.45	YES
25	INSR	INSR	INSR	5293	0.073	0.42	NO
26	PIK3C3	PIK3C3	PIK3C3	5888	0.061	0.39	NO
27	RHEB	RHEB	RHEB	5980	0.059	0.4	NO
28	STK11	STK11	STK11	6172	0.056	0.39	NO
29	FRS2	FRS2	FRS2	6198	0.056	0.4	NO
30	TLR9	TLR9	TLR9	6667	0.049	0.38	NO
31	STRADA	STRADA	STRADA	6700	0.049	0.38	NO
32	KRAS	KRAS	KRAS	6895	0.046	0.38	NO
33	FGFR4	FGFR4	FGFR4	6924	0.045	0.38	NO
34	RPTOR	RPTOR	RPTOR	7024	0.044	0.39	NO
35	EIF4B	EIF4B	EIF4B	7284	0.041	0.38	NO
36	TRIB3	TRIB3	TRIB3	7453	0.039	0.37	NO
37	ATP6V0A2	ATP6V0A2	ATP6V0A2	7522	0.038	0.38	NO
38	PIK3R4	PIK3R4	PIK3R4	7690	0.037	0.37	NO
39	SOS1	SOS1	SOS1	7703	0.036	0.38	NO
40	PRKAG1	PRKAG1	PRKAG1	7809	0.035	0.37	NO
41	MAPK1	MAPK1	MAPK1	7890	0.034	0.37	NO
42	PPM1A	PPM1A	PPM1A	7893	0.034	0.38	NO
43	PIK3CA	PIK3CA	PIK3CA	8019	0.033	0.38	NO
44	PIK3CB	PIK3CB	PIK3CB	8402	0.029	0.36	NO
45	PIK3R2	PIK3R2	PIK3R2	8750	0.025	0.34	NO
46	PRKAB2	PRKAB2	PRKAB2	8955	0.023	0.34	NO
47	ATP6V1G1	ATP6V1G1	ATP6V1G1	9144	0.021	0.33	NO
48	PRKAG2	PRKAG2	PRKAG2	9191	0.021	0.33	NO
49	ATP6V1E1	ATP6V1E1	ATP6V1E1	9544	0.017	0.31	NO
50	RAF1	RAF1	RAF1	9849	0.014	0.3	NO
51	ATP6V1C1	ATP6V1C1	ATP6V1C1	9889	0.013	0.3	NO
52	IRS1	IRS1	IRS1	9934	0.013	0.29	NO
53	AKT2	AKT2	AKT2	10149	0.011	0.28	NO
54	SHC3	SHC3	SHC3	10182	0.01	0.28	NO
55	IRS2	IRS2	IRS2	10279	0.0091	0.28	NO
56	GRB2	GRB2	GRB2	10309	0.0088	0.28	NO
57	MLST8	MLST8	MLST8	10341	0.0086	0.28	NO
58	ATP6V1B2	ATP6V1B2	ATP6V1B2	10377	0.0081	0.28	NO
59	ATP6V0E1	ATP6V0E1	ATP6V0E1	10462	0.007	0.27	NO
60	EIF4G1	EIF4G1	EIF4G1	10524	0.0065	0.27	NO
61	NRAS	NRAS	NRAS	10673	0.0048	0.26	NO
62	EIF4EBP1	EIF4EBP1	EIF4EBP1	10691	0.0046	0.26	NO
63	TSC2	TSC2	TSC2	10803	0.0034	0.26	NO
64	ATP6V1H	ATP6V1H	ATP6V1H	10825	0.0032	0.26	NO
65	MTOR	MTOR	MTOR	10838	0.0031	0.26	NO
66	KLB	KLB	KLB	10860	0.0029	0.26	NO
67	RPS6	RPS6	RPS6	10964	0.0018	0.25	NO
68	EIF4E	EIF4E	EIF4E	10986	0.0016	0.25	NO
69	EEF2K	EEF2K	EEF2K	11280	-0.0012	0.23	NO
70	ATP6V1F	ATP6V1F	ATP6V1F	11300	-0.0014	0.23	NO
71	ATP6V1A	ATP6V1A	ATP6V1A	11338	-0.0018	0.23	NO
72	PRKAB1	PRKAB1	PRKAB1	11556	-0.0043	0.22	NO
73	ATP6V0B	ATP6V0B	ATP6V0B	11589	-0.0046	0.22	NO
74	STRADB	STRADB	STRADB	11605	-0.0048	0.22	NO
75	TSC1	TSC1	TSC1	12009	-0.0095	0.2	NO
76	HRAS	HRAS	HRAS	12032	-0.0097	0.2	NO
77	YWHAB	YWHAB	YWHAB	12148	-0.011	0.19	NO
78	CDK1	CDK1	CDK1	12339	-0.013	0.18	NO
79	GAB1	GAB1	GAB1	12719	-0.018	0.16	NO
80	RPS6KB1	RPS6KB1	RPS6KB1	12978	-0.021	0.15	NO
81	FGF22	FGF22	FGF22	13126	-0.023	0.15	NO
82	MAP2K2	MAP2K2	MAP2K2	13178	-0.024	0.15	NO
83	PDPK1	PDPK1	PDPK1	13277	-0.026	0.15	NO
84	ATP6V0D2	ATP6V0D2	ATP6V0D2	13347	-0.027	0.15	NO
85	ATP6V1C2	ATP6V1C2	ATP6V1C2	13537	-0.03	0.14	NO
86	ATP6V0C	ATP6V0C	ATP6V0C	13668	-0.032	0.14	NO
87	SHC1	SHC1	SHC1	14024	-0.039	0.12	NO
88	PRKAA1	PRKAA1	PRKAA1	14166	-0.042	0.12	NO
89	ATP6V0D1	ATP6V0D1	ATP6V0D1	14372	-0.047	0.12	NO
90	FGFR3	FGFR3	FGFR3	14450	-0.048	0.12	NO
91	FGF5	FGF5	FGF5	14570	-0.052	0.12	NO
92	MAPK3	MAPK3	MAPK3	14785	-0.057	0.12	NO
93	MAP2K1	MAP2K1	MAP2K1	14787	-0.057	0.12	NO
94	CAB39	CAB39	CAB39	14946	-0.062	0.12	NO
95	CRK	CRK	CRK	15265	-0.071	0.12	NO
96	ATP6V1B1	ATP6V1B1	ATP6V1B1	15614	-0.084	0.11	NO
97	ATP6V1D	ATP6V1D	ATP6V1D	15648	-0.086	0.12	NO
98	TCIRG1	TCIRG1	TCIRG1	17019	-0.16	0.064	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG P53 SIGNALING PATHWAY	67	genes.ES.table	0.44	1.7	0.012	0.81	0.89	0.39	0.27	0.28	0.42	0.24
BIOCARTA EGF PATHWAY	31	genes.ES.table	0.5	1.6	0.047	0.85	0.92	0.74	0.36	0.48	0.46	0.25
BIOCARTA RACCYCD PATHWAY	26	genes.ES.table	0.46	1.8	0.015	0.66	0.62	0.46	0.27	0.34	0.2	0.16
BIOCARTA STRESS PATHWAY	25	genes.ES.table	0.46	1.6	0.054	0.69	0.94	0.52	0.32	0.36	0.39	0.21
BIOCARTA TNFR1 PATHWAY	29	genes.ES.table	0.49	1.8	0.012	0.75	0.53	0.66	0.38	0.41	0.21	0.16
BIOCARTA TOLL PATHWAY	37	genes.ES.table	0.55	1.6	0.03	0.79	0.92	0.57	0.27	0.41	0.43	0.24
PID ERBB1 RECEPTOR PROXIMAL PATHWAY	35	genes.ES.table	0.54	1.9	0.0039	1	0.33	0.66	0.36	0.42	0	0.26
PID FOXOPATHWAY	48	genes.ES.table	0.45	1.9	0.0098	1	0.44	0.52	0.32	0.35	0	0.23
PID PI3KCIPATHWAY	49	genes.ES.table	0.58	1.6	0.039	0.77	0.92	0.53	0.22	0.42	0.42	0.23
PID ECADHERIN NASCENTAJ PATHWAY	39	genes.ES.table	0.43	1.9	0.016	0.82	0.47	0.36	0.2	0.29	0	0.17

genes ES table in pathway: KEGG P53 SIGNALING 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	GNAI1	GNAI1	GNAI1	640	0.29	0.11	YES
2	EGFR	EGFR	EGFR	1214	0.21	0.18	YES
3	NCK1	NCK1	NCK1	1604	0.18	0.24	YES
4	NCK2	NCK2	NCK2	2111	0.14	0.28	YES
5	PIK3CA	PIK3CA	PIK3CA	2339	0.13	0.33	YES
6	PIK3CD	PIK3CD	PIK3CD	2646	0.11	0.37	YES
7	PIK3R1	PIK3R1	PIK3R1	3266	0.089	0.38	YES
8	SRC	SRC	SRC	3423	0.084	0.41	YES
9	GNAI3	GNAI3	GNAI3	3732	0.074	0.43	YES
10	PIK3CB	PIK3CB	PIK3CB	3803	0.072	0.46	YES
11	STAT1	STAT1	STAT1	4508	0.056	0.45	YES
12	PTPN1	PTPN1	PTPN1	4789	0.05	0.46	YES
13	STAT3	STAT3	STAT3	4790	0.05	0.48	YES
14	GAB1	GAB1	GAB1	5048	0.045	0.49	YES
15	RASA1	RASA1	RASA1	5342	0.039	0.49	YES
16	HRAS	HRAS	HRAS	5501	0.037	0.5	YES
17	WASL	WASL	WASL	5530	0.037	0.52	YES
18	PTPN6	PTPN6	PTPN6	5716	0.034	0.52	YES
19	PIK3R2	PIK3R2	PIK3R2	5773	0.033	0.54	YES
20	GSN	GSN	GSN	6342	0.024	0.52	YES
21	MAPK1	MAPK1	MAPK1	6398	0.023	0.53	YES
22	SOS1	SOS1	SOS1	6440	0.023	0.54	YES
23	PIP5K1C	PIP5K1C	PIP5K1C	6548	0.021	0.54	YES
24	NRAS	NRAS	NRAS	6921	0.016	0.53	NO
25	GRB2	GRB2	GRB2	7468	0.0093	0.5	NO
26	KRAS	KRAS	KRAS	7824	0.0044	0.48	NO
27	PIK3R3	PIK3R3	PIK3R3	8252	-0.00091	0.46	NO
28	PLCG1	PLCG1	PLCG1	8304	-0.0015	0.46	NO
29	MAPK3	MAPK3	MAPK3	8347	-0.002	0.46	NO
30	PTPN11	PTPN11	PTPN11	8865	-0.0086	0.43	NO
31	TLN1	TLN1	TLN1	9652	-0.018	0.4	NO
32	SHC1	SHC1	SHC1	9703	-0.019	0.4	NO
33	PAK1	PAK1	PAK1	10593	-0.031	0.37	NO
34	PTK2	PTK2	PTK2	11294	-0.041	0.35	NO
35	EGF	EGF	EGF	12142	-0.054	0.33	NO

Figure S21. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: KEGG P53 SIGNALING PATHWAY.

Figure S22. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG P53 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: BIOCARTA EGF 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	MAPK10	MAPK10	MAPK10	454	0.34	0.084	YES
2	SFN	SFN	SFN	782	0.26	0.15	YES
3	SGK1	SGK1	SGK1	1289	0.2	0.19	YES
4	KAT2B	KAT2B	KAT2B	1508	0.18	0.23	YES
5	FASLG	FASLG	FASLG	1645	0.17	0.28	YES
6	BCL6	BCL6	BCL6	2455	0.12	0.28	YES
7	GADD45A	GADD45A	GADD45A	2796	0.11	0.29	YES
8	FBXO32	FBXO32	FBXO32	2798	0.11	0.32	YES
9	FOXO4	FOXO4	FOXO4	3050	0.097	0.34	YES
10	RBL2	RBL2	RBL2	3142	0.093	0.37	YES
11	CSNK1A1	CSNK1A1	CSNK1A1	3760	0.074	0.36	YES
12	BCL2L11	BCL2L11	BCL2L11	3776	0.073	0.38	YES
13	IKBKB	IKBKB	IKBKB	3971	0.068	0.39	YES
14	CSNK1G1	CSNK1G1	CSNK1G1	4211	0.062	0.4	YES
15	YWHAZ	YWHAZ	YWHAZ	4345	0.059	0.41	YES
16	CHUK	CHUK	CHUK	4718	0.051	0.4	YES
17	CSNK1G2	CSNK1G2	CSNK1G2	5033	0.045	0.4	YES
18	FOXO1	FOXO1	FOXO1	5175	0.042	0.41	YES
19	SOD2	SOD2	SOD2	5187	0.042	0.42	YES
20	RALB	RALB	RALB	5212	0.042	0.43	YES
21	MAPK8	MAPK8	MAPK8	5249	0.041	0.44	YES
22	EP300	EP300	EP300	5353	0.039	0.45	YES
23	RALA	RALA	RALA	5549	0.036	0.45	YES
24	CSNK1G3	CSNK1G3	CSNK1G3	5749	0.033	0.45	YES
25	SKP2	SKP2	SKP2	5893	0.031	0.45	YES
26	YWHAG	YWHAG	YWHAG	6266	0.025	0.44	NO
27	ZFAND5	ZFAND5	ZFAND5	6296	0.025	0.44	NO
28	YWHAQ	YWHAQ	YWHAQ	6738	0.019	0.43	NO
29	USP7	USP7	USP7	6993	0.015	0.42	NO
30	FOXO3	FOXO3	FOXO3	7087	0.014	0.42	NO
31	CREBBP	CREBBP	CREBBP	7247	0.012	0.41	NO
32	CCNB1	CCNB1	CCNB1	8055	0.0017	0.37	NO
33	YWHAH	YWHAH	YWHAH	8290	-0.0013	0.36	NO
34	CDK2	CDK2	CDK2	8329	-0.0018	0.35	NO
35	YWHAB	YWHAB	YWHAB	8331	-0.0019	0.35	NO
36	YWHAE	YWHAE	YWHAE	8915	-0.0093	0.32	NO
37	SIRT1	SIRT1	SIRT1	9103	-0.011	0.32	NO
38	PLK1	PLK1	PLK1	9220	-0.013	0.32	NO
39	XPO1	XPO1	XPO1	9249	-0.013	0.32	NO
40	RAN	RAN	RAN	9475	-0.016	0.31	NO
41	AKT1	AKT1	AKT1	9837	-0.021	0.3	NO
42	CDKN1B	CDKN1B	CDKN1B	11046	-0.037	0.24	NO
43	MAPK9	MAPK9	MAPK9	11285	-0.041	0.24	NO
44	CSNK1D	CSNK1D	CSNK1D	11320	-0.041	0.25	NO
45	CTNNB1	CTNNB1	CTNNB1	12156	-0.054	0.22	NO
46	CSNK1E	CSNK1E	CSNK1E	12745	-0.064	0.21	NO
47	MST1	MST1	MST1	14879	-0.12	0.14	NO
48	CAT	CAT	CAT	15332	-0.14	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 EGF PATHWAY.

Figure S24. 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 RACCYCD PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TIAM1	TIAM1	TIAM1	471	0.33	0.091	YES
2	JUP	JUP	JUP	1512	0.18	0.098	YES
3	ABI1	ABI1	ABI1	1917	0.15	0.13	YES
4	ITGB7	ITGB7	ITGB7	2133	0.14	0.17	YES
5	CTNND1	CTNND1	CTNND1	2196	0.14	0.21	YES
6	PIK3CA	PIK3CA	PIK3CA	2339	0.13	0.25	YES
7	WASF2	WASF2	WASF2	2679	0.11	0.27	YES
8	DLG1	DLG1	DLG1	2811	0.11	0.3	YES
9	RAC1	RAC1	RAC1	2855	0.1	0.33	YES
10	KLHL20	KLHL20	KLHL20	2896	0.1	0.36	YES
11	PIK3R1	PIK3R1	PIK3R1	3266	0.089	0.38	YES
12	SRC	SRC	SRC	3423	0.084	0.4	YES
13	ARF6	ARF6	ARF6	3614	0.078	0.41	YES
14	TJP1	TJP1	TJP1	3716	0.075	0.43	YES
15	CDC42	CDC42	CDC42	4531	0.055	0.41	NO
16	RAP1A	RAP1A	RAP1A	4848	0.048	0.41	NO
17	CDH1	CDH1	CDH1	5539	0.036	0.38	NO
18	NCKAP1	NCKAP1	NCKAP1	5584	0.036	0.39	NO
19	CSNK2A1	CSNK2A1	CSNK2A1	6127	0.027	0.37	NO
20	IQGAP1	IQGAP1	IQGAP1	6526	0.022	0.36	NO
21	PIP5K1C	PIP5K1C	PIP5K1C	6548	0.021	0.36	NO
22	AP1M1	AP1M1	AP1M1	6903	0.017	0.35	NO
23	CRK	CRK	CRK	6972	0.016	0.35	NO
24	ITGAE	ITGAE	ITGAE	7118	0.014	0.35	NO
25	MLLT4	MLLT4	MLLT4	7128	0.014	0.35	NO
26	CSNK2A2	CSNK2A2	CSNK2A2	8084	0.0012	0.3	NO
27	CTNNA1	CTNNA1	CTNNA1	8139	0.00056	0.3	NO
28	RAP1B	RAP1B	RAP1B	8228	-0.00057	0.29	NO
29	RAPGEF1	RAPGEF1	RAPGEF1	8888	-0.009	0.26	NO
30	CTTN	CTTN	CTTN	9335	-0.014	0.24	NO
31	RHOA	RHOA	RHOA	9786	-0.02	0.22	NO
32	AKT1	AKT1	AKT1	9837	-0.021	0.23	NO
33	ENAH	ENAH	ENAH	10182	-0.025	0.22	NO
34	CCND1	CCND1	CCND1	11965	-0.051	0.14	NO
35	CTNNB1	CTNNB1	CTNNB1	12156	-0.054	0.15	NO
36	NME1	NME1	NME1	12717	-0.064	0.14	NO
37	CSNK2B	CSNK2B	CSNK2B	12885	-0.067	0.15	NO
38	CYFIP2	CYFIP2	CYFIP2	16082	-0.18	0.04	NO
39	VAV2	VAV2	VAV2	16509	-0.21	0.092	NO

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

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

genes ES table in pathway: BIOCARTA STRESS PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MAP3K1	MAP3K1	MAP3K1	2139	0.14	-0.0081	YES
2	BAG4	BAG4	BAG4	2183	0.14	0.098	YES
3	CRADD	CRADD	CRADD	2343	0.13	0.19	YES
4	RB1	RB1	RB1	2897	0.1	0.24	YES
5	JUN	JUN	JUN	3246	0.09	0.29	YES
6	CASP3	CASP3	CASP3	3828	0.072	0.32	YES
7	PAK2	PAK2	PAK2	4219	0.062	0.35	YES
8	MAP2K4	MAP2K4	MAP2K4	4296	0.06	0.39	YES
9	MAPK8	MAPK8	MAPK8	5249	0.041	0.37	YES
10	TRADD	TRADD	TRADD	5382	0.039	0.39	YES
11	ARHGDIB	ARHGDIB	ARHGDIB	5471	0.037	0.42	YES
12	CASP2	CASP2	CASP2	5751	0.033	0.43	YES
13	LMNB2	LMNB2	LMNB2	6048	0.029	0.44	YES
14	RIPK1	RIPK1	RIPK1	6128	0.027	0.45	YES
15	TNFRSF1A	TNFRSF1A	TNFRSF1A	6406	0.023	0.46	YES
16	DFFA	DFFA	DFFA	6519	0.022	0.47	YES
17	PRKDC	PRKDC	PRKDC	6700	0.019	0.47	YES
18	LMNB1	LMNB1	LMNB1	6858	0.017	0.48	YES
19	LMNA	LMNA	LMNA	6894	0.017	0.49	YES
20	TNF	TNF	TNF	7154	0.014	0.48	NO
21	CASP8	CASP8	CASP8	8428	-0.0032	0.42	NO
22	PARP1	PARP1	PARP1	8491	-0.0041	0.42	NO
23	SPTAN1	SPTAN1	SPTAN1	9093	-0.011	0.39	NO
24	FADD	FADD	FADD	9423	-0.015	0.39	NO
25	MAP3K7	MAP3K7	MAP3K7	9501	-0.016	0.4	NO
26	TRAF2	TRAF2	TRAF2	9580	-0.017	0.4	NO
27	MADD	MADD	MADD	10285	-0.027	0.39	NO
28	DFFB	DFFB	DFFB	10317	-0.027	0.41	NO
29	PAK1	PAK1	PAK1	10593	-0.031	0.42	NO

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

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

genes ES table in pathway: BIOCARTA TNFR1 PATHWAY

Table 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	SFN	SFN	SFN	782	0.26	0.096	YES
2	CDKN1A	CDKN1A	CDKN1A	1908	0.15	0.11	YES
3	MAP3K5	MAP3K5	MAP3K5	2148	0.14	0.17	YES
4	TBC1D4	TBC1D4	TBC1D4	2362	0.13	0.23	YES
5	FOXO4	FOXO4	FOXO4	3050	0.097	0.24	YES
6	GSK3B	GSK3B	GSK3B	3363	0.086	0.27	YES
7	SRC	SRC	SRC	3423	0.084	0.31	YES
8	SLC2A4	SLC2A4	SLC2A4	3941	0.068	0.31	YES
9	PRKACA	PRKACA	PRKACA	4036	0.066	0.34	YES
10	PDPK1	PDPK1	PDPK1	4201	0.063	0.37	YES
11	YWHAZ	YWHAZ	YWHAZ	4345	0.059	0.39	YES
12	KPNA1	KPNA1	KPNA1	4669	0.052	0.4	YES
13	CHUK	CHUK	CHUK	4718	0.051	0.42	YES
14	RICTOR	RICTOR	RICTOR	5031	0.045	0.43	YES
15	FOXO1	FOXO1	FOXO1	5175	0.042	0.44	YES
16	MTOR	MTOR	MTOR	5993	0.029	0.42	NO
17	YWHAG	YWHAG	YWHAG	6266	0.025	0.41	NO
18	RAF1	RAF1	RAF1	6476	0.022	0.41	NO
19	PRKDC	PRKDC	PRKDC	6700	0.019	0.41	NO
20	MAPKAP1	MAPKAP1	MAPKAP1	6718	0.019	0.42	NO
21	YWHAQ	YWHAQ	YWHAQ	6738	0.019	0.43	NO
22	FOXO3	FOXO3	FOXO3	7087	0.014	0.42	NO
23	CASP9	CASP9	CASP9	7092	0.014	0.42	NO
24	AKT2	AKT2	AKT2	8059	0.0016	0.37	NO
25	YWHAH	YWHAH	YWHAH	8290	-0.0013	0.36	NO
26	YWHAB	YWHAB	YWHAB	8331	-0.0019	0.36	NO
27	YWHAE	YWHAE	YWHAE	8915	-0.0093	0.33	NO
28	GSK3A	GSK3A	GSK3A	9461	-0.016	0.31	NO
29	AKT1	AKT1	AKT1	9837	-0.021	0.3	NO
30	HSP90AA1	HSP90AA1	HSP90AA1	10250	-0.026	0.29	NO
31	CDKN1B	CDKN1B	CDKN1B	11046	-0.037	0.27	NO
32	MLST8	MLST8	MLST8	11531	-0.044	0.26	NO
33	BCL2L1	BCL2L1	BCL2L1	11607	-0.046	0.28	NO
34	BAD	BAD	BAD	13220	-0.074	0.23	NO
35	AKT3	AKT3	AKT3	13387	-0.078	0.26	NO

Figure S29. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA TNFR1 PATHWAY.

Figure S30. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA TNFR1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA TOLL PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CDKN1A	CDKN1A	CDKN1A	1908	0.15	0.0034	YES
2	PIK3CA	PIK3CA	PIK3CA	2339	0.13	0.071	YES
3	RAC1	RAC1	RAC1	2855	0.1	0.12	YES
4	RB1	RB1	RB1	2897	0.1	0.19	YES
5	NFKB1	NFKB1	NFKB1	3155	0.093	0.24	YES
6	PIK3R1	PIK3R1	PIK3R1	3266	0.089	0.3	YES
7	NFKBIA	NFKBIA	NFKBIA	3336	0.087	0.36	YES
8	IKBKB	IKBKB	IKBKB	3971	0.068	0.37	YES
9	IKBKG	IKBKG	IKBKG	4430	0.058	0.38	YES
10	CHUK	CHUK	CHUK	4718	0.051	0.41	YES
11	TFDP1	TFDP1	TFDP1	4858	0.048	0.43	YES
12	CDK6	CDK6	CDK6	4900	0.047	0.46	YES
13	HRAS	HRAS	HRAS	5501	0.037	0.46	NO
14	MAPK1	MAPK1	MAPK1	6398	0.023	0.42	NO
15	RAF1	RAF1	RAF1	6476	0.022	0.44	NO
16	RELA	RELA	RELA	7406	0.01	0.39	NO
17	CCNE1	CCNE1	CCNE1	7493	0.009	0.39	NO
18	CDK2	CDK2	CDK2	8329	-0.0018	0.35	NO
19	MAPK3	MAPK3	MAPK3	8347	-0.002	0.35	NO
20	RHOA	RHOA	RHOA	9786	-0.02	0.28	NO
21	AKT1	AKT1	AKT1	9837	-0.021	0.3	NO
22	PAK1	PAK1	PAK1	10593	-0.031	0.28	NO
23	CDKN1B	CDKN1B	CDKN1B	11046	-0.037	0.28	NO
24	CDK4	CDK4	CDK4	11458	-0.043	0.29	NO
25	CCND1	CCND1	CCND1	11965	-0.051	0.3	NO
26	E2F1	E2F1	E2F1	12681	-0.063	0.3	NO

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

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

genes ES table in pathway: PID ERBB1 RECEPTOR PROXIMAL 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	CDK5R1	CDK5R1	CDK5R1	466	0.34	0.16	YES
2	RPS6KA5	RPS6KA5	RPS6KA5	467	0.34	0.35	YES
3	RIT1	RIT1	RIT1	2330	0.13	0.32	YES
4	MEF2C	MEF2C	MEF2C	3737	0.074	0.28	YES
5	RUSC1	RUSC1	RUSC1	3886	0.07	0.31	YES
6	EHD4	EHD4	EHD4	3989	0.067	0.34	YES
7	MAP3K2	MAP3K2	MAP3K2	4040	0.066	0.38	YES
8	RAP1A	RAP1A	RAP1A	4848	0.048	0.36	YES
9	FOS	FOS	FOS	4849	0.048	0.39	YES
10	MAPK7	MAPK7	MAPK7	4989	0.046	0.41	YES
11	MAP2K1	MAP2K1	MAP2K1	5010	0.045	0.43	YES
12	MAPKAPK2	MAPKAPK2	MAPKAPK2	5225	0.042	0.44	YES
13	HRAS	HRAS	HRAS	5501	0.037	0.45	YES
14	EGR1	EGR1	EGR1	5719	0.034	0.45	YES
15	PRKCD	PRKCD	PRKCD	5892	0.031	0.46	YES
16	MAPK1	MAPK1	MAPK1	6398	0.023	0.45	NO
17	RAF1	RAF1	RAF1	6476	0.022	0.46	NO
18	BRAF	BRAF	BRAF	6849	0.017	0.44	NO
19	NRAS	NRAS	NRAS	6921	0.016	0.45	NO
20	MAP2K5	MAP2K5	MAP2K5	7198	0.013	0.44	NO
21	CREB1	CREB1	CREB1	7236	0.012	0.45	NO
22	SRF	SRF	SRF	7462	0.0094	0.44	NO
23	KRAS	KRAS	KRAS	7824	0.0044	0.42	NO
24	ELK1	ELK1	ELK1	7906	0.0036	0.42	NO
25	MAPK14	MAPK14	MAPK14	8102	0.001	0.41	NO
26	RAP1B	RAP1B	RAP1B	8228	-0.00057	0.4	NO
27	MAPK3	MAPK3	MAPK3	8347	-0.002	0.4	NO
28	NTF3	NTF3	NTF3	8571	-0.0051	0.39	NO
29	RPS6KA1	RPS6KA1	RPS6KA1	8789	-0.0078	0.38	NO
30	CDK5	CDK5	CDK5	10687	-0.033	0.29	NO
31	TRPV1	TRPV1	TRPV1	11255	-0.04	0.28	NO
32	MAP2K3	MAP2K3	MAP2K3	12894	-0.067	0.23	NO
33	MAP2K6	MAP2K6	MAP2K6	14320	-0.1	0.21	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: PID ERBB1 RECEPTOR PROXIMAL PATHWAY.

Figure S34. Get High-res Image For the top 5 core enriched genes in the pathway: PID ERBB1 RECEPTOR PROXIMAL PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID FOXOPATHWAY

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	TP53AIP1	TP53AIP1	TP53AIP1	116	0.53	0.18	YES
2	KAT2B	KAT2B	KAT2B	1508	0.18	0.17	YES
3	PPP1R13L	PPP1R13L	PPP1R13L	2033	0.14	0.19	YES
4	CDKN2A	CDKN2A	CDKN2A	2389	0.12	0.22	YES
5	MDM2	MDM2	MDM2	2934	0.1	0.22	YES
6	SETD8	SETD8	SETD8	3182	0.092	0.24	YES
7	ATR	ATR	ATR	3292	0.088	0.27	YES
8	GSK3B	GSK3B	GSK3B	3363	0.086	0.29	YES
9	CSNK1A1	CSNK1A1	CSNK1A1	3760	0.074	0.3	YES
10	CSNK1G1	CSNK1G1	CSNK1G1	4211	0.062	0.3	YES
11	DYRK2	DYRK2	DYRK2	4283	0.061	0.31	YES
12	RFWD2	RFWD2	RFWD2	4739	0.05	0.3	YES
13	PPM1D	PPM1D	PPM1D	4915	0.047	0.31	YES
14	CSNK1G2	CSNK1G2	CSNK1G2	5033	0.045	0.32	YES
15	MAPK8	MAPK8	MAPK8	5249	0.041	0.32	YES
16	SETD7	SETD7	SETD7	5258	0.041	0.34	YES
17	EP300	EP300	EP300	5353	0.039	0.35	YES
18	UBE2D1	UBE2D1	UBE2D1	5571	0.036	0.35	YES
19	CSNK1G3	CSNK1G3	CSNK1G3	5749	0.033	0.35	YES
20	CCNA2	CCNA2	CCNA2	5765	0.033	0.36	YES
21	PRKCD	PRKCD	PRKCD	5892	0.031	0.36	YES
22	SKP2	SKP2	SKP2	5893	0.031	0.38	YES
23	TP53	TP53	TP53	6016	0.029	0.38	YES
24	PPP2R4	PPP2R4	PPP2R4	6282	0.025	0.37	NO
25	FBXO11	FBXO11	FBXO11	6722	0.019	0.36	NO
26	RASSF1	RASSF1	RASSF1	6951	0.016	0.35	NO
27	USP7	USP7	USP7	6993	0.015	0.35	NO
28	CREBBP	CREBBP	CREBBP	7247	0.012	0.34	NO
29	YY1	YY1	YY1	7523	0.0086	0.33	NO
30	MDM4	MDM4	MDM4	7680	0.0065	0.32	NO
31	HUWE1	HUWE1	HUWE1	7700	0.0062	0.32	NO
32	CSE1L	CSE1L	CSE1L	7925	0.0033	0.31	NO
33	HIPK2	HIPK2	HIPK2	7938	0.0031	0.32	NO
34	PPP2CA	PPP2CA	PPP2CA	7992	0.0024	0.31	NO
35	E4F1	E4F1	E4F1	8034	0.0019	0.31	NO
36	MAPK14	MAPK14	MAPK14	8102	0.001	0.31	NO
37	KAT5	KAT5	KAT5	8253	-0.00091	0.3	NO
38	CDK2	CDK2	CDK2	8329	-0.0018	0.3	NO
39	TTC5	TTC5	TTC5	8470	-0.0038	0.29	NO
40	CHEK2	CHEK2	CHEK2	8862	-0.0086	0.27	NO
41	SMYD2	SMYD2	SMYD2	8988	-0.01	0.27	NO
42	RCHY1	RCHY1	RCHY1	9292	-0.014	0.26	NO
43	PIN1	PIN1	PIN1	9434	-0.015	0.25	NO
44	RPL11	RPL11	RPL11	9697	-0.019	0.25	NO
45	AKT1	AKT1	AKT1	9837	-0.021	0.25	NO
46	ABL1	ABL1	ABL1	9978	-0.022	0.25	NO
47	NEDD8	NEDD8	NEDD8	10437	-0.029	0.23	NO
48	CCNG1	CCNG1	CCNG1	10874	-0.035	0.22	NO
49	RPL5	RPL5	RPL5	10922	-0.036	0.23	NO
50	DAXX	DAXX	DAXX	11142	-0.039	0.23	NO
51	MAPK9	MAPK9	MAPK9	11285	-0.041	0.24	NO
52	CSNK1D	CSNK1D	CSNK1D	11320	-0.041	0.25	NO
53	ATM	ATM	ATM	11326	-0.041	0.26	NO
54	PRMT5	PRMT5	PRMT5	11853	-0.049	0.25	NO
55	CHEK1	CHEK1	CHEK1	12254	-0.056	0.25	NO
56	CSNK1E	CSNK1E	CSNK1E	12745	-0.064	0.25	NO
57	RPL23	RPL23	RPL23	13153	-0.073	0.25	NO
58	TRIM28	TRIM28	TRIM28	13301	-0.076	0.27	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: PID FOXOPATHWAY.

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

genes ES table in pathway: PID PI3KCIPATHWAY

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	NOD2	NOD2	NOD2	132	0.51	0.13	YES
2	IL1RN	IL1RN	IL1RN	136	0.51	0.26	YES
3	IL1RAP	IL1RAP	IL1RAP	836	0.26	0.29	YES
4	IL1A	IL1A	IL1A	983	0.24	0.35	YES
5	IRAK2	IRAK2	IRAK2	1148	0.22	0.4	YES
6	MAP3K8	MAP3K8	MAP3K8	1341	0.2	0.44	YES
7	TOLLIP	TOLLIP	TOLLIP	1738	0.16	0.46	YES
8	TMEM189-UBE2V1	TMEM189-UBE2V1	TMEM189-UBE2V1	1946	0.15	0.49	YES
9	BTRC	BTRC	BTRC	2457	0.12	0.49	YES
10	IRAK4	IRAK4	IRAK4	3572	0.079	0.45	YES
11	TAB3	TAB3	TAB3	3723	0.075	0.46	YES
12	MYD88	MYD88	MYD88	3814	0.072	0.48	YES
13	IKBKB	IKBKB	IKBKB	3971	0.068	0.49	YES
14	MAP2K4	MAP2K4	MAP2K4	4296	0.06	0.48	YES
15	IKBKG	IKBKG	IKBKG	4430	0.058	0.49	YES
16	TRAF6	TRAF6	TRAF6	4522	0.055	0.5	YES
17	PELI1	PELI1	PELI1	4606	0.054	0.51	YES
18	CHUK	CHUK	CHUK	4718	0.051	0.52	YES
19	IL1R1	IL1R1	IL1R1	4865	0.048	0.52	YES
20	MAP2K1	MAP2K1	MAP2K1	5010	0.045	0.53	YES
21	IRAK1	IRAK1	IRAK1	5841	0.032	0.49	NO
22	MAP3K3	MAP3K3	MAP3K3	6390	0.024	0.46	NO
23	TAB2	TAB2	TAB2	6565	0.021	0.46	NO
24	PELI3	PELI3	PELI3	7124	0.014	0.43	NO
25	TNIP2	TNIP2	TNIP2	7147	0.014	0.44	NO
26	TAB1	TAB1	TAB1	7327	0.011	0.43	NO
27	CUL1	CUL1	CUL1	7520	0.0086	0.42	NO
28	UBE2N	UBE2N	UBE2N	7525	0.0086	0.42	NO
29	NOD1	NOD1	NOD1	7729	0.0057	0.41	NO
30	RBX1	RBX1	RBX1	8740	-0.0074	0.36	NO
31	MAP3K7	MAP3K7	MAP3K7	9501	-0.016	0.32	NO
32	IL1B	IL1B	IL1B	9543	-0.017	0.32	NO
33	SKP1	SKP1	SKP1	10341	-0.028	0.29	NO
34	SQSTM1	SQSTM1	SQSTM1	10587	-0.031	0.28	NO
35	PELI2	PELI2	PELI2	13057	-0.07	0.16	NO
36	IL1R2	IL1R2	IL1R2	13816	-0.089	0.15	NO
37	RIPK2	RIPK2	RIPK2	14097	-0.097	0.16	NO
38	MAP2K6	MAP2K6	MAP2K6	14320	-0.1	0.17	NO
39	IRAK3	IRAK3	IRAK3	15463	-0.15	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: PID PI3KCIPATHWAY.

Figure S38. Get High-res Image For the top 5 core enriched genes in the pathway: PID PI3KCIPATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: PID ECADHERIN NASCENTAJ 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	S100A12	S100A12	S100A12	86	0.57	0.14	YES
2	S100B	S100B	S100B	617	0.3	0.18	YES
3	NLRC5	NLRC5	NLRC5	1525	0.18	0.18	YES
4	CYLD	CYLD	CYLD	1861	0.16	0.2	YES
5	HERC5	HERC5	HERC5	2050	0.14	0.23	YES
6	MAP3K1	MAP3K1	MAP3K1	2139	0.14	0.26	YES
7	IKBKE	IKBKE	IKBKE	2184	0.14	0.29	YES
8	IFIH1	IFIH1	IFIH1	2604	0.11	0.3	YES
9	NLRX1	NLRX1	NLRX1	2913	0.1	0.3	YES
10	IRF2	IRF2	IRF2	2988	0.098	0.32	YES
11	DDX58	DDX58	DDX58	3328	0.087	0.33	YES
12	NFKBIA	NFKBIA	NFKBIA	3336	0.087	0.35	YES
13	UBA7	UBA7	UBA7	3405	0.085	0.37	YES
14	IRF1	IRF1	IRF1	3597	0.078	0.38	YES
15	NFKBIB	NFKBIB	NFKBIB	3933	0.069	0.37	YES
16	IKBKB	IKBKB	IKBKB	3971	0.068	0.39	YES
17	TRAF3	TRAF3	TRAF3	3984	0.067	0.41	YES
18	UBE2L6	UBE2L6	UBE2L6	4155	0.064	0.41	YES
19	TBK1	TBK1	TBK1	4199	0.063	0.43	YES
20	IKBKG	IKBKG	IKBKG	4430	0.058	0.43	YES
21	TRAF6	TRAF6	TRAF6	4522	0.055	0.44	YES
22	SIKE1	SIKE1	SIKE1	4682	0.052	0.44	YES
23	CHUK	CHUK	CHUK	4718	0.051	0.45	YES
24	CASP10	CASP10	CASP10	4773	0.05	0.46	YES
25	TNFAIP3	TNFAIP3	TNFAIP3	4780	0.05	0.47	YES
26	UBE2D2	UBE2D2	UBE2D2	4999	0.046	0.47	YES
27	RNF135	RNF135	RNF135	5043	0.045	0.48	YES
28	EP300	EP300	EP300	5353	0.039	0.48	YES
29	IRF7	IRF7	IRF7	5377	0.039	0.48	YES
30	DHX58	DHX58	DHX58	5546	0.036	0.48	YES
31	UBE2D1	UBE2D1	UBE2D1	5571	0.036	0.49	YES
32	RIPK1	RIPK1	RIPK1	6128	0.027	0.47	NO
33	UBE2D3	UBE2D3	UBE2D3	6136	0.027	0.47	NO
34	IFNA1	IFNA1	IFNA1	7047	0.015	0.43	NO
35	CREBBP	CREBBP	CREBBP	7247	0.012	0.42	NO
36	RELA	RELA	RELA	7406	0.01	0.41	NO
37	RNF125	RNF125	RNF125	7926	0.0033	0.38	NO
38	HMGB1	HMGB1	HMGB1	8109	0.0009	0.38	NO
39	CASP8	CASP8	CASP8	8428	-0.0032	0.36	NO
40	TAX1BP1	TAX1BP1	TAX1BP1	8435	-0.0033	0.36	NO
41	UBE2K	UBE2K	UBE2K	8458	-0.0036	0.36	NO
42	TRIM25	TRIM25	TRIM25	8653	-0.0063	0.35	NO
43	ISG15	ISG15	ISG15	8946	-0.0096	0.34	NO
44	ATG5	ATG5	ATG5	9254	-0.013	0.32	NO
45	OTUD5	OTUD5	OTUD5	9263	-0.013	0.32	NO
46	NFKB2	NFKB2	NFKB2	9311	-0.014	0.33	NO
47	FADD	FADD	FADD	9423	-0.015	0.32	NO
48	PIN1	PIN1	PIN1	9434	-0.015	0.33	NO
49	TRAF2	TRAF2	TRAF2	9580	-0.017	0.32	NO
50	TANK	TANK	TANK	9686	-0.019	0.32	NO
51	ATG12	ATG12	ATG12	9892	-0.022	0.32	NO
52	SAA1	SAA1	SAA1	9906	-0.022	0.32	NO
53	UBA52	UBA52	UBA52	9927	-0.022	0.32	NO
54	MAVS	MAVS	MAVS	10659	-0.032	0.29	NO
55	PCBP2	PCBP2	PCBP2	11052	-0.038	0.28	NO
56	RPS27A	RPS27A	RPS27A	12016	-0.052	0.24	NO
57	APP	APP	APP	12199	-0.055	0.24	NO
58	IRF3	IRF3	IRF3	12243	-0.056	0.26	NO
59	DAK	DAK	DAK	12540	-0.061	0.26	NO
60	IFNB1	IFNB1	IFNB1	14154	-0.099	0.19	NO
61	AGER	AGER	AGER	14824	-0.12	0.18	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: PID ECADHERIN NASCENTAJ PATHWAY.

Figure S40. Get High-res Image For the top 5 core enriched genes in the pathway: PID ECADHERIN NASCENTAJ 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 PURINE METABOLISM	151	genes.ES.table	0.39	1.6	0.019	0.83	0.97	0.22	0.18	0.18	0.55	0.28
KEGG SELENOAMINO ACID METABOLISM	26	genes.ES.table	0.58	1.7	0.012	0.61	0.81	0.5	0.31	0.35	0.3	0.18
KEGG N GLYCAN BIOSYNTHESIS	46	genes.ES.table	0.53	1.8	0.0095	0.76	0.56	0.48	0.31	0.33	0.24	0.19
KEGG O GLYCAN BIOSYNTHESIS	29	genes.ES.table	0.61	1.5	0.042	0.66	0.98	0.59	0.18	0.48	0.48	0.2
KEGG SPHINGOLIPID METABOLISM	38	genes.ES.table	0.51	1.5	0.045	0.69	0.98	0.29	0.16	0.24	0.49	0.22
KEGG PEROXISOME	75	genes.ES.table	0.41	1.6	0.028	0.85	0.95	0.32	0.22	0.25	0.54	0.28
KEGG VASOPRESSIN REGULATED WATER REABSORPTION	42	genes.ES.table	0.47	1.8	0.0061	0.56	0.6	0.21	0.14	0.18	0.18	0.14
KEGG VIBRIO CHOLERAE INFECTION	52	genes.ES.table	0.58	2.2	0	0.085	0.056	0.23	0.097	0.21	0	0.027
BIOCARTA RHO PATHWAY	32	genes.ES.table	0.39	1.5	0.073	0.71	0.98	0.031	0.0011	0.031	0.51	0.23
PID RHOA REG PATHWAY	44	genes.ES.table	0.43	1.5	0.029	0.74	0.98	0.36	0.26	0.27	0.52	0.24

genes ES table in pathway: KEGG PURINE METABOLISM

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	CFTR	CFTR	CFTR	117	0.73	0.085	YES
2	KCNQ1	KCNQ1	KCNQ1	171	0.68	0.17	YES
3	ATP6V1B1	ATP6V1B1	ATP6V1B1	353	0.57	0.23	YES
4	ATP6V1C2	ATP6V1C2	ATP6V1C2	474	0.52	0.29	YES
5	MUC2	MUC2	MUC2	539	0.5	0.35	YES
6	PRKCG	PRKCG	PRKCG	743	0.43	0.39	YES
7	ATP6V0A4	ATP6V0A4	ATP6V0A4	912	0.39	0.43	YES
8	KDELR3	KDELR3	KDELR3	938	0.38	0.47	YES
9	SLC12A2	SLC12A2	SLC12A2	979	0.37	0.52	YES
10	ATP6V1G2	ATP6V1G2	ATP6V1G2	1311	0.31	0.54	YES
11	PRKCA	PRKCA	PRKCA	1701	0.26	0.55	YES
12	ATP6V0E2	ATP6V0E2	ATP6V0E2	1770	0.26	0.58	YES
13	TCIRG1	TCIRG1	TCIRG1	4020	0.11	0.47	NO
14	KDELR2	KDELR2	KDELR2	4338	0.095	0.46	NO
15	PDIA4	PDIA4	PDIA4	4653	0.085	0.45	NO
16	KDELR1	KDELR1	KDELR1	4930	0.078	0.45	NO
17	ADCY9	ADCY9	ADCY9	5598	0.059	0.42	NO
18	ARF1	ARF1	ARF1	7389	0.025	0.32	NO
19	SEC61B	SEC61B	SEC61B	7396	0.025	0.33	NO
20	ATP6AP1	ATP6AP1	ATP6AP1	7516	0.023	0.32	NO
21	GNAS	GNAS	GNAS	7687	0.02	0.32	NO
22	SEC61A1	SEC61A1	SEC61A1	7774	0.019	0.31	NO
23	SEC61A2	SEC61A2	SEC61A2	7880	0.017	0.31	NO
24	ATP6V0A1	ATP6V0A1	ATP6V0A1	8416	0.0093	0.28	NO
25	ATP6V0A2	ATP6V0A2	ATP6V0A2	8810	0.0038	0.26	NO
26	ATP6V0B	ATP6V0B	ATP6V0B	9089	0.00019	0.24	NO
27	ACTG1	ACTG1	ACTG1	9218	-0.0018	0.24	NO
28	TJP1	TJP1	TJP1	9361	-0.0038	0.23	NO
29	TJP2	TJP2	TJP2	9552	-0.0065	0.22	NO
30	SEC61G	SEC61G	SEC61G	10844	-0.026	0.15	NO
31	ATP6V0E1	ATP6V0E1	ATP6V0E1	11015	-0.028	0.15	NO
32	ATP6V0D1	ATP6V0D1	ATP6V0D1	11270	-0.031	0.14	NO
33	ATP6V0C	ATP6V0C	ATP6V0C	11356	-0.033	0.14	NO
34	ATP6V1C1	ATP6V1C1	ATP6V1C1	11467	-0.034	0.14	NO
35	PRKACB	PRKACB	PRKACB	11598	-0.036	0.13	NO
36	ACTB	ACTB	ACTB	11957	-0.042	0.12	NO
37	ATP6V1A	ATP6V1A	ATP6V1A	12247	-0.047	0.11	NO
38	PRKACA	PRKACA	PRKACA	12438	-0.05	0.1	NO
39	ATP6V1F	ATP6V1F	ATP6V1F	12781	-0.057	0.091	NO
40	ATP6V1H	ATP6V1H	ATP6V1H	12951	-0.06	0.09	NO
41	ATP6V1E1	ATP6V1E1	ATP6V1E1	13469	-0.072	0.07	NO
42	PLCG1	PLCG1	PLCG1	13891	-0.082	0.057	NO
43	ATP6V1G1	ATP6V1G1	ATP6V1G1	13910	-0.082	0.066	NO
44	ATP6V1B2	ATP6V1B2	ATP6V1B2	14134	-0.088	0.065	NO
45	PRKCB	PRKCB	PRKCB	14160	-0.089	0.075	NO
46	ATP6V1D	ATP6V1D	ATP6V1D	14195	-0.09	0.084	NO
47	ADCY3	ADCY3	ADCY3	14479	-0.099	0.081	NO
48	ATP6V1E2	ATP6V1E2	ATP6V1E2	14782	-0.11	0.078	NO
49	ERO1L	ERO1L	ERO1L	15095	-0.12	0.076	NO
50	PRKX	PRKX	PRKX	16431	-0.2	0.028	NO
51	PLCG2	PLCG2	PLCG2	16900	-0.25	0.034	NO
52	ATP6V0D2	ATP6V0D2	ATP6V0D2	17170	-0.29	0.055	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 PURINE METABOLISM.

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

genes ES table in pathway: KEGG SELENOAMINO ACID METABOLISM

Table 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	MGAT3	MGAT3	MGAT3	379	0.56	0.11	YES
2	ST6GAL1	ST6GAL1	ST6GAL1	407	0.55	0.23	YES
3	ALG11	ALG11	ALG11	1196	0.33	0.26	YES
4	MGAT4A	MGAT4A	MGAT4A	1493	0.28	0.31	YES
5	MAN1C1	MAN1C1	MAN1C1	1743	0.26	0.36	YES
6	DPM3	DPM3	DPM3	2716	0.17	0.34	YES
7	DPAGT1	DPAGT1	DPAGT1	3410	0.13	0.33	YES
8	ALG5	ALG5	ALG5	3484	0.13	0.36	YES
9	ALG10B	ALG10B	ALG10B	3542	0.13	0.38	YES
10	FUT8	FUT8	FUT8	3855	0.11	0.39	YES
11	ALG1	ALG1	ALG1	3922	0.11	0.42	YES
12	STT3A	STT3A	STT3A	4051	0.1	0.43	YES
13	ALG8	ALG8	ALG8	4081	0.1	0.45	YES
14	ALG14	ALG14	ALG14	4450	0.091	0.45	YES
15	MGAT5	MGAT5	MGAT5	4625	0.086	0.46	YES
16	ALG13	ALG13	ALG13	4678	0.085	0.48	YES
17	ALG9	ALG9	ALG9	4689	0.085	0.5	YES
18	MAN2A2	MAN2A2	MAN2A2	5112	0.072	0.49	YES
19	ALG12	ALG12	ALG12	5299	0.067	0.5	YES
20	ALG10	ALG10	ALG10	5313	0.067	0.51	YES
21	MGAT4B	MGAT4B	MGAT4B	5316	0.066	0.53	YES
22	ALG6	ALG6	ALG6	5563	0.06	0.53	YES
23	STT3B	STT3B	STT3B	6379	0.043	0.49	NO
24	MOGS	MOGS	MOGS	6398	0.043	0.5	NO
25	B4GALT1	B4GALT1	B4GALT1	6426	0.042	0.51	NO
26	RPN2	RPN2	RPN2	6614	0.039	0.51	NO
27	DAD1	DAD1	DAD1	6748	0.036	0.51	NO
28	RPN1	RPN1	RPN1	6958	0.033	0.5	NO
29	ALG2	ALG2	ALG2	6971	0.033	0.51	NO
30	MAN1A2	MAN1A2	MAN1A2	7671	0.02	0.48	NO
31	RFT1	RFT1	RFT1	7719	0.02	0.48	NO
32	DDOST	DDOST	DDOST	8243	0.012	0.45	NO
33	MAN1B1	MAN1B1	MAN1B1	8517	0.0077	0.44	NO
34	GANAB	GANAB	GANAB	8849	0.0032	0.42	NO
35	MAN1A1	MAN1A1	MAN1A1	9561	-0.0066	0.38	NO
36	DPM2	DPM2	DPM2	10448	-0.02	0.34	NO
37	MGAT5B	MGAT5B	MGAT5B	10656	-0.023	0.33	NO
38	ALG3	ALG3	ALG3	10722	-0.024	0.34	NO
39	MGAT2	MGAT2	MGAT2	10745	-0.024	0.34	NO
40	MAN2A1	MAN2A1	MAN2A1	10876	-0.026	0.34	NO
41	DPM1	DPM1	DPM1	11263	-0.031	0.32	NO
42	B4GALT3	B4GALT3	B4GALT3	11277	-0.032	0.33	NO
43	MGAT1	MGAT1	MGAT1	11786	-0.039	0.31	NO
44	DOLPP1	DOLPP1	DOLPP1	12350	-0.049	0.29	NO
45	B4GALT2	B4GALT2	B4GALT2	12684	-0.055	0.29	NO
46	TUSC3	TUSC3	TUSC3	13511	-0.073	0.26	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 SELENOAMINO ACID METABOLISM.

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

genes ES table in pathway: KEGG N GLYCAN BIOSYNTHESIS

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	AQP2	AQP2	AQP2	46	0.88	0.16	YES
2	CREB3L1	CREB3L1	CREB3L1	110	0.74	0.3	YES
3	CREB3L4	CREB3L4	CREB3L4	1577	0.28	0.27	YES
4	ADCY6	ADCY6	ADCY6	1705	0.26	0.31	YES
5	AVPR2	AVPR2	AVPR2	1870	0.24	0.35	YES
6	CREB5	CREB5	CREB5	1905	0.24	0.39	YES
7	DYNC2LI1	DYNC2LI1	DYNC2LI1	2174	0.22	0.42	YES
8	AQP4	AQP4	AQP4	2190	0.22	0.46	YES
9	CREB3L2	CREB3L2	CREB3L2	2617	0.18	0.47	YES
10	CREB3L3	CREB3L3	CREB3L3	3249	0.14	0.46	NO
11	CREB3	CREB3	CREB3	4245	0.098	0.42	NO
12	NSF	NSF	NSF	4547	0.088	0.42	NO
13	ADCY9	ADCY9	ADCY9	5598	0.059	0.38	NO
14	VAMP2	VAMP2	VAMP2	5607	0.059	0.39	NO
15	RAB11B	RAB11B	RAB11B	6990	0.032	0.32	NO
16	RAB5A	RAB5A	RAB5A	7461	0.024	0.3	NO
17	GNAS	GNAS	GNAS	7687	0.02	0.29	NO
18	RAB5C	RAB5C	RAB5C	7876	0.018	0.28	NO
19	DCTN1	DCTN1	DCTN1	9499	-0.0059	0.19	NO
20	DYNC1LI2	DYNC1LI2	DYNC1LI2	9744	-0.0095	0.18	NO
21	ARHGDIA	ARHGDIA	ARHGDIA	9872	-0.011	0.18	NO
22	CREB1	CREB1	CREB1	10154	-0.016	0.16	NO
23	DYNLL2	DYNLL2	DYNLL2	10180	-0.016	0.16	NO
24	RAB11A	RAB11A	RAB11A	10389	-0.019	0.16	NO
25	DYNC1LI1	DYNC1LI1	DYNC1LI1	11079	-0.029	0.12	NO
26	DYNC1I2	DYNC1I2	DYNC1I2	11288	-0.032	0.12	NO
27	RAB5B	RAB5B	RAB5B	11311	-0.032	0.12	NO
28	DCTN5	DCTN5	DCTN5	11434	-0.034	0.12	NO
29	DYNC2H1	DYNC2H1	DYNC2H1	11493	-0.034	0.13	NO
30	PRKACB	PRKACB	PRKACB	11598	-0.036	0.13	NO
31	STX4	STX4	STX4	12011	-0.043	0.11	NO
32	PRKACA	PRKACA	PRKACA	12438	-0.05	0.099	NO
33	DCTN6	DCTN6	DCTN6	12725	-0.056	0.094	NO
34	DYNC1H1	DYNC1H1	DYNC1H1	12871	-0.059	0.097	NO
35	DCTN2	DCTN2	DCTN2	13010	-0.061	0.1	NO
36	DCTN4	DCTN4	DCTN4	13542	-0.073	0.086	NO
37	ARHGDIB	ARHGDIB	ARHGDIB	14181	-0.089	0.067	NO
38	DYNLL1	DYNLL1	DYNLL1	14201	-0.09	0.083	NO
39	ADCY3	ADCY3	ADCY3	14479	-0.099	0.086	NO
40	PRKX	PRKX	PRKX	16431	-0.2	0.017	NO
41	DYNC1I1	DYNC1I1	DYNC1I1	16442	-0.2	0.055	NO
42	AQP3	AQP3	AQP3	16554	-0.22	0.089	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 N GLYCAN BIOSYNTHESIS.

Figure S46. 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 O GLYCAN BIOSYNTHESIS

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	C4BPB	C4BPB	C4BPB	30	0.93	0.11	YES
2	FOXA2	FOXA2	FOXA2	115	0.74	0.2	YES
3	FOXA3	FOXA3	FOXA3	118	0.73	0.29	YES
4	TFF1	TFF1	TFF1	228	0.64	0.36	YES
5	SHH	SHH	SHH	257	0.62	0.43	YES
6	SFTPA2	SFTPA2	SFTPA2	564	0.49	0.47	YES
7	SERPINA1	SERPINA1	SERPINA1	884	0.39	0.5	YES
8	NR2F2	NR2F2	NR2F2	946	0.38	0.55	YES
9	NFIB	NFIB	NFIB	1280	0.32	0.57	YES
10	ESR1	ESR1	ESR1	1346	0.31	0.6	YES
11	XBP1	XBP1	XBP1	1522	0.28	0.63	YES
12	FOXA1	FOXA1	FOXA1	1843	0.25	0.64	YES
13	CYP2C18	CYP2C18	CYP2C18	2658	0.18	0.62	NO
14	COL18A1	COL18A1	COL18A1	2903	0.16	0.62	NO
15	KLK3	KLK3	KLK3	3486	0.13	0.6	NO
16	SCGB1A1	SCGB1A1	SCGB1A1	3725	0.12	0.61	NO
17	BRCA1	BRCA1	BRCA1	4151	0.1	0.6	NO
18	CDKN1B	CDKN1B	CDKN1B	4358	0.094	0.6	NO
19	POU2F1	POU2F1	POU2F1	4476	0.09	0.6	NO
20	AR	AR	AR	4564	0.087	0.6	NO
21	NKX3-1	NKX3-1	NKX3-1	5844	0.054	0.54	NO
22	APOB	APOB	APOB	6131	0.048	0.53	NO
23	NFIA	NFIA	NFIA	7080	0.031	0.48	NO
24	PRDM15	PRDM15	PRDM15	7380	0.025	0.47	NO
25	NDUFV3	NDUFV3	NDUFV3	7665	0.02	0.46	NO
26	CEBPB	CEBPB	CEBPB	8255	0.012	0.42	NO
27	FOS	FOS	FOS	8479	0.0084	0.41	NO
28	SP1	SP1	SP1	8543	0.0074	0.41	NO
29	ATP5J	ATP5J	ATP5J	9304	-0.0032	0.37	NO
30	SOD1	SOD1	SOD1	9422	-0.0049	0.36	NO
31	EP300	EP300	EP300	9795	-0.01	0.34	NO
32	AP1B1	AP1B1	AP1B1	10127	-0.015	0.33	NO
33	CREBBP	CREBBP	CREBBP	10253	-0.017	0.32	NO
34	NCOA3	NCOA3	NCOA3	12436	-0.05	0.21	NO
35	PISD	PISD	PISD	12812	-0.057	0.2	NO
36	NFIC	NFIC	NFIC	12866	-0.058	0.2	NO
37	SFTPA1	SFTPA1	SFTPA1	14327	-0.094	0.13	NO
38	NRIP1	NRIP1	NRIP1	14380	-0.096	0.14	NO
39	DSCAM	DSCAM	DSCAM	14429	-0.097	0.15	NO
40	JUN	JUN	JUN	14769	-0.11	0.14	NO
41	VTN	VTN	VTN	15935	-0.17	0.099	NO
42	SFTPD	SFTPD	SFTPD	16343	-0.2	0.1	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 O GLYCAN BIOSYNTHESIS.

Figure S48. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG O 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 SPHINGOLIPID 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	TFF1	TFF1	TFF1	228	0.64	0.091	YES
2	NR0B1	NR0B1	NR0B1	1074	0.35	0.1	YES
3	AXIN2	AXIN2	AXIN2	1109	0.34	0.16	YES
4	NR0B2	NR0B2	NR0B2	1146	0.34	0.21	YES
5	C3	C3	C3	1201	0.33	0.26	YES
6	ESR1	ESR1	ESR1	1346	0.31	0.3	YES
7	XBP1	XBP1	XBP1	1522	0.28	0.34	YES
8	PDIA2	PDIA2	PDIA2	1956	0.24	0.35	YES
9	PGR	PGR	PGR	2240	0.21	0.37	YES
10	GREB1	GREB1	GREB1	2296	0.2	0.4	YES
11	ESR2	ESR2	ESR2	2572	0.18	0.41	YES
12	ABCA3	ABCA3	ABCA3	2828	0.17	0.43	YES
13	COL18A1	COL18A1	COL18A1	2903	0.16	0.45	YES
14	LCOR	LCOR	LCOR	3348	0.14	0.45	NO
15	BRCA1	BRCA1	BRCA1	4151	0.1	0.42	NO
16	APBB1	APBB1	APBB1	4405	0.093	0.42	NO
17	NCOR1	NCOR1	NCOR1	4793	0.082	0.41	NO
18	MPG	MPG	MPG	5203	0.07	0.4	NO
19	POU4F1	POU4F1	POU4F1	5981	0.051	0.37	NO
20	NCOA7	NCOA7	NCOA7	6105	0.049	0.37	NO
21	LMO4	LMO4	LMO4	6516	0.04	0.35	NO
22	NCOR2	NCOR2	NCOR2	6752	0.036	0.34	NO
23	DDX17	DDX17	DDX17	7050	0.031	0.33	NO
24	SRA1	SRA1	SRA1	7107	0.03	0.34	NO
25	MED1	MED1	MED1	7116	0.03	0.34	NO
26	CTSD	CTSD	CTSD	7334	0.026	0.33	NO
27	EBAG9	EBAG9	EBAG9	7370	0.026	0.33	NO
28	PRDM15	PRDM15	PRDM15	7380	0.025	0.34	NO
29	CALCOCO1	CALCOCO1	CALCOCO1	7463	0.024	0.34	NO
30	NDUFV3	NDUFV3	NDUFV3	7665	0.02	0.33	NO
31	ANP32A	ANP32A	ANP32A	7666	0.02	0.33	NO
32	NCOA2	NCOA2	NCOA2	7833	0.018	0.33	NO
33	STAT5A	STAT5A	STAT5A	7893	0.017	0.33	NO
34	CEBPB	CEBPB	CEBPB	8255	0.012	0.31	NO
35	HDAC1	HDAC1	HDAC1	8339	0.01	0.3	NO
36	UBA3	UBA3	UBA3	8575	0.0069	0.29	NO
37	NCOA1	NCOA1	NCOA1	8866	0.003	0.28	NO
38	MTA1	MTA1	MTA1	9206	-0.0015	0.26	NO
39	ATP5J	ATP5J	ATP5J	9304	-0.0032	0.25	NO
40	CHUK	CHUK	CHUK	9376	-0.0041	0.25	NO
41	SOD1	SOD1	SOD1	9422	-0.0049	0.25	NO
42	PHB2	PHB2	PHB2	9514	-0.0061	0.24	NO
43	PRL	PRL	PRL	9639	-0.0078	0.24	NO
44	EP300	EP300	EP300	9795	-0.01	0.23	NO
45	AP1B1	AP1B1	AP1B1	10127	-0.015	0.22	NO
46	SAFB	SAFB	SAFB	10268	-0.017	0.21	NO
47	PCNA	PCNA	PCNA	10486	-0.02	0.2	NO
48	HDAC4	HDAC4	HDAC4	10542	-0.021	0.2	NO
49	DDX54	DDX54	DDX54	10599	-0.022	0.2	NO
50	UBE2M	UBE2M	UBE2M	10754	-0.025	0.2	NO
51	HSF2	HSF2	HSF2	11148	-0.03	0.18	NO
52	SMAD4	SMAD4	SMAD4	11247	-0.031	0.18	NO
53	TRIM59	TRIM59	TRIM59	11273	-0.031	0.19	NO
54	SET	SET	SET	11926	-0.042	0.16	NO
55	CD82	CD82	CD82	12216	-0.047	0.15	NO
56	NCOA3	NCOA3	NCOA3	12436	-0.05	0.14	NO
57	NEDD8	NEDD8	NEDD8	12584	-0.053	0.14	NO
58	KLRC3	KLRC3	KLRC3	13391	-0.07	0.11	NO
59	NRIP1	NRIP1	NRIP1	14380	-0.096	0.073	NO
60	DSCAM	DSCAM	DSCAM	14429	-0.097	0.086	NO
61	JUN	JUN	JUN	14769	-0.11	0.085	NO
62	CCND1	CCND1	CCND1	15912	-0.17	0.049	NO
63	MYC	MYC	MYC	17859	-0.47	0.017	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 SPHINGOLIPID METABOLISM.

Figure S50. 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 PEROXISOME

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	GGT1	GGT1	GGT1	852	0.4	0.11	YES
2	PAPSS2	PAPSS2	PAPSS2	855	0.4	0.26	YES
3	GGT6	GGT6	GGT6	1376	0.3	0.34	YES
4	GGT7	GGT7	GGT7	1963	0.24	0.4	YES
5	CTH	CTH	CTH	2001	0.23	0.49	YES
6	CBS	CBS	CBS	2564	0.18	0.53	YES
7	HEMK1	HEMK1	HEMK1	3229	0.14	0.55	YES
8	AHCYL2	AHCYL2	AHCYL2	4202	0.099	0.53	YES
9	SCLY	SCLY	SCLY	5032	0.075	0.51	YES
10	AHCYL1	AHCYL1	AHCYL1	5157	0.071	0.53	YES
11	SEPHS2	SEPHS2	SEPHS2	5506	0.062	0.54	YES
12	WBSCR22	WBSCR22	WBSCR22	5528	0.061	0.56	YES
13	MAT2A	MAT2A	MAT2A	5614	0.059	0.58	YES
14	AHCY	AHCY	AHCY	6611	0.039	0.54	NO
15	SEPHS1	SEPHS1	SEPHS1	7326	0.026	0.51	NO
16	TRMT11	TRMT11	TRMT11	7592	0.022	0.5	NO
17	LCMT1	LCMT1	LCMT1	7886	0.017	0.49	NO
18	LCMT2	LCMT2	LCMT2	7939	0.016	0.5	NO
19	METTL2B	METTL2B	METTL2B	8106	0.014	0.49	NO
20	METTL6	METTL6	METTL6	9439	-0.005	0.42	NO
21	PAPSS1	PAPSS1	PAPSS1	9538	-0.0064	0.42	NO
22	MAT1A	MAT1A	MAT1A	9952	-0.012	0.4	NO
23	MAT2B	MAT2B	MAT2B	10316	-0.018	0.39	NO
24	MARS	MARS	MARS	10970	-0.028	0.36	NO
25	MARS2	MARS2	MARS2	12124	-0.045	0.32	NO
26	GGT5	GGT5	GGT5	12228	-0.047	0.33	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 PEROXISOME.

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

genes ES table in pathway: KEGG VASOPRESSIN REGULATED WATER REABSORPTION

Table 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	MGAT3	MGAT3	MGAT3	379	0.56	0.055	YES
2	ST6GAL1	ST6GAL1	ST6GAL1	407	0.55	0.13	YES
3	ALG11	ALG11	ALG11	1196	0.33	0.13	YES
4	MGAT4A	MGAT4A	MGAT4A	1493	0.28	0.15	YES
5	MAN1C1	MAN1C1	MAN1C1	1743	0.26	0.17	YES
6	ST8SIA2	ST8SIA2	ST8SIA2	1953	0.24	0.19	YES
7	SEC24D	SEC24D	SEC24D	2507	0.19	0.19	YES
8	GMPPB	GMPPB	GMPPB	2660	0.18	0.2	YES
9	DPM3	DPM3	DPM3	2716	0.17	0.22	YES
10	GMPPA	GMPPA	GMPPA	2915	0.16	0.24	YES
11	UGGT2	UGGT2	UGGT2	3307	0.14	0.23	YES
12	B4GALT4	B4GALT4	B4GALT4	3349	0.14	0.25	YES
13	B4GALT5	B4GALT5	B4GALT5	3370	0.13	0.26	YES
14	PGM3	PGM3	PGM3	3402	0.13	0.28	YES
15	DPAGT1	DPAGT1	DPAGT1	3410	0.13	0.3	YES
16	ALG5	ALG5	ALG5	3484	0.13	0.31	YES
17	ALG10B	ALG10B	ALG10B	3542	0.13	0.33	YES
18	MLEC	MLEC	MLEC	3679	0.12	0.34	YES
19	EDEM3	EDEM3	EDEM3	3789	0.12	0.34	YES
20	FUT8	FUT8	FUT8	3855	0.11	0.36	YES
21	ALG1	ALG1	ALG1	3922	0.11	0.37	YES
22	STT3A	STT3A	STT3A	4051	0.1	0.37	YES
23	ALG8	ALG8	ALG8	4081	0.1	0.39	YES
24	SEC13	SEC13	SEC13	4441	0.091	0.38	YES
25	ALG14	ALG14	ALG14	4450	0.091	0.39	YES
26	MGAT5	MGAT5	MGAT5	4625	0.086	0.39	YES
27	ALG13	ALG13	ALG13	4678	0.085	0.4	YES
28	ALG9	ALG9	ALG9	4689	0.085	0.41	YES
29	EDEM2	EDEM2	EDEM2	5239	0.069	0.39	YES
30	ALG12	ALG12	ALG12	5299	0.067	0.4	YES
31	ALG10	ALG10	ALG10	5313	0.067	0.41	YES
32	MGAT4B	MGAT4B	MGAT4B	5316	0.066	0.42	YES
33	ALG6	ALG6	ALG6	5563	0.06	0.41	YES
34	PMM1	PMM1	PMM1	5592	0.06	0.42	YES
35	GNPNAT1	GNPNAT1	GNPNAT1	5649	0.058	0.42	YES
36	MOGS	MOGS	MOGS	6398	0.043	0.38	NO
37	B4GALT1	B4GALT1	B4GALT1	6426	0.042	0.39	NO
38	RPN2	RPN2	RPN2	6614	0.039	0.38	NO
39	PMM2	PMM2	PMM2	6663	0.038	0.39	NO
40	PDIA3	PDIA3	PDIA3	6696	0.037	0.39	NO
41	DAD1	DAD1	DAD1	6748	0.036	0.39	NO
42	UGGT1	UGGT1	UGGT1	6758	0.036	0.4	NO
43	SAR1B	SAR1B	SAR1B	6809	0.035	0.4	NO
44	CANX	CANX	CANX	6908	0.034	0.4	NO
45	RPN1	RPN1	RPN1	6958	0.033	0.4	NO
46	ALG2	ALG2	ALG2	6971	0.033	0.4	NO
47	PREB	PREB	PREB	7252	0.028	0.39	NO
48	MPI	MPI	MPI	7324	0.026	0.39	NO
49	SEC31A	SEC31A	SEC31A	7377	0.026	0.39	NO
50	CALR	CALR	CALR	7513	0.023	0.39	NO
51	MAN1A2	MAN1A2	MAN1A2	7671	0.02	0.38	NO
52	RFT1	RFT1	RFT1	7719	0.02	0.38	NO
53	LMAN1	LMAN1	LMAN1	7903	0.017	0.37	NO
54	MCFD2	MCFD2	MCFD2	7926	0.017	0.37	NO
55	SEC24C	SEC24C	SEC24C	7940	0.016	0.38	NO
56	DDOST	DDOST	DDOST	8243	0.012	0.36	NO
57	MAN1B1	MAN1B1	MAN1B1	8517	0.0077	0.35	NO
58	PRKCSH	PRKCSH	PRKCSH	8754	0.0046	0.33	NO
59	GANAB	GANAB	GANAB	8849	0.0032	0.33	NO
60	MAN1A1	MAN1A1	MAN1A1	9561	-0.0066	0.29	NO
61	DOLK	DOLK	DOLK	10278	-0.018	0.25	NO
62	DPM2	DPM2	DPM2	10448	-0.02	0.25	NO
63	ALG3	ALG3	ALG3	10722	-0.024	0.24	NO
64	MGAT2	MGAT2	MGAT2	10745	-0.024	0.24	NO
65	MAN2A1	MAN2A1	MAN2A1	10876	-0.026	0.23	NO
66	ST8SIA6	ST8SIA6	ST8SIA6	11056	-0.029	0.23	NO
67	DPM1	DPM1	DPM1	11263	-0.031	0.22	NO
68	B4GALT3	B4GALT3	B4GALT3	11277	-0.032	0.22	NO
69	MANEA	MANEA	MANEA	11416	-0.033	0.22	NO
70	SEC23A	SEC23A	SEC23A	11601	-0.036	0.22	NO
71	MGAT1	MGAT1	MGAT1	11786	-0.039	0.21	NO
72	SEC24B	SEC24B	SEC24B	11865	-0.041	0.21	NO
73	DOLPP1	DOLPP1	DOLPP1	12350	-0.049	0.19	NO
74	B4GALT2	B4GALT2	B4GALT2	12684	-0.055	0.18	NO
75	TUSC3	TUSC3	TUSC3	13511	-0.073	0.14	NO
76	EDEM1	EDEM1	EDEM1	14357	-0.095	0.11	NO
77	B4GALT6	B4GALT6	B4GALT6	15112	-0.12	0.086	NO
78	MGAT4C	MGAT4C	MGAT4C	16298	-0.19	0.047	NO
79	GFPT2	GFPT2	GFPT2	17720	-0.42	0.025	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 VASOPRESSIN REGULATED WATER REABSORPTION.

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

genes ES table in pathway: KEGG VIBRIO CHOLERAE INFECTION

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	MUC13	MUC13	MUC13	16	1	0.069	YES
2	MUC5B	MUC5B	MUC5B	26	0.96	0.13	YES
3	B3GNT3	B3GNT3	B3GNT3	186	0.67	0.17	YES
4	GCNT3	GCNT3	GCNT3	246	0.63	0.21	YES
5	MUC16	MUC16	MUC16	316	0.59	0.25	YES
6	ST6GAL1	ST6GAL1	ST6GAL1	407	0.55	0.28	YES
7	GALNT12	GALNT12	GALNT12	460	0.53	0.31	YES
8	GALNTL6	GALNTL6	GALNTL6	515	0.5	0.34	YES
9	B3GNT7	B3GNT7	B3GNT7	521	0.5	0.38	YES
10	MUC2	MUC2	MUC2	539	0.5	0.41	YES
11	MUC6	MUC6	MUC6	642	0.46	0.44	YES
12	GALNT9	GALNT9	GALNT9	705	0.44	0.46	YES
13	GALNT6	GALNT6	GALNT6	841	0.4	0.48	YES
14	B3GNT6	B3GNT6	B3GNT6	1047	0.36	0.5	YES
15	GALNTL1	GALNTL1	GALNTL1	1112	0.34	0.52	YES
16	GALNT7	GALNT7	GALNT7	1178	0.34	0.54	YES
17	MUC4	MUC4	MUC4	1260	0.32	0.55	YES
18	GCNT1	GCNT1	GCNT1	1318	0.31	0.57	YES
19	ST6GALNAC4	ST6GALNAC4	ST6GALNAC4	1583	0.28	0.58	YES
20	MUC12	MUC12	MUC12	1736	0.26	0.58	YES
21	B3GNTL1	B3GNTL1	B3GNTL1	1840	0.25	0.6	YES
22	GALNT5	GALNT5	GALNT5	2073	0.22	0.6	YES
23	GALNT10	GALNT10	GALNT10	2401	0.2	0.59	NO
24	GALNT8	GALNT8	GALNT8	2981	0.16	0.57	NO
25	C1GALT1	C1GALT1	C1GALT1	3155	0.14	0.57	NO
26	GALNT3	GALNT3	GALNT3	3296	0.14	0.57	NO
27	B4GALT5	B4GALT5	B4GALT5	3370	0.13	0.58	NO
28	B3GNT2	B3GNT2	B3GNT2	4196	0.1	0.54	NO
29	C1GALT1C1	C1GALT1C1	C1GALT1C1	4388	0.094	0.54	NO
30	ST3GAL2	ST3GAL2	ST3GAL2	6906	0.034	0.4	NO
31	ST3GAL3	ST3GAL3	ST3GAL3	10046	-0.014	0.23	NO
32	WBSCR17	WBSCR17	WBSCR17	10703	-0.024	0.19	NO
33	GALNT11	GALNT11	GALNT11	11379	-0.033	0.16	NO
34	MUC21	MUC21	MUC21	11724	-0.038	0.14	NO
35	B3GNT9	B3GNT9	B3GNT9	11770	-0.039	0.14	NO
36	GALNTL2	GALNTL2	GALNTL2	12494	-0.052	0.11	NO
37	GALNT13	GALNT13	GALNT13	12541	-0.052	0.11	NO
38	ST6GALNAC3	ST6GALNAC3	ST6GALNAC3	12710	-0.056	0.1	NO
39	ST3GAL1	ST3GAL1	ST3GAL1	13681	-0.077	0.053	NO
40	GALNT2	GALNT2	GALNT2	14015	-0.085	0.041	NO
41	GALNT1	GALNT1	GALNT1	15181	-0.13	-0.015	NO
42	MUC15	MUC15	MUC15	16215	-0.19	-0.059	NO
43	ST6GALNAC2	ST6GALNAC2	ST6GALNAC2	16703	-0.23	-0.07	NO
44	MUCL1	MUCL1	MUCL1	16713	-0.23	-0.055	NO
45	B3GNT5	B3GNT5	B3GNT5	16716	-0.23	-0.039	NO
46	GALNT14	GALNT14	GALNT14	16770	-0.24	-0.026	NO
47	GCNT4	GCNT4	GCNT4	17275	-0.31	-0.033	NO
48	B3GNT4	B3GNT4	B3GNT4	17544	-0.36	-0.023	NO
49	B3GNT8	B3GNT8	B3GNT8	17614	-0.38	-0.00018	NO
50	GALNTL4	GALNTL4	GALNTL4	17822	-0.45	0.019	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 VIBRIO CHOLERAE INFECTION.

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

genes ES table in pathway: BIOCARTA RHO PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	MPV17L	MPV17L	MPV17L	583	0.48	0.022	YES
2	SLC27A2	SLC27A2	SLC27A2	624	0.46	0.072	YES
3	PIPOX	PIPOX	PIPOX	887	0.39	0.1	YES
4	PECR	PECR	PECR	899	0.39	0.15	YES
5	PHYH	PHYH	PHYH	962	0.37	0.19	YES
6	DDO	DDO	DDO	1016	0.36	0.22	YES
7	ACSL5	ACSL5	ACSL5	1130	0.34	0.26	YES
8	AGXT	AGXT	AGXT	1504	0.28	0.27	YES
9	DECR2	DECR2	DECR2	1984	0.23	0.27	YES
10	PEX11G	PEX11G	PEX11G	2251	0.21	0.28	YES
11	CAT	CAT	CAT	2369	0.2	0.29	YES
12	FAR2	FAR2	FAR2	2414	0.19	0.31	YES
13	NUDT12	NUDT12	NUDT12	2687	0.18	0.32	YES
14	ABCD3	ABCD3	ABCD3	2706	0.17	0.34	YES
15	NOS2	NOS2	NOS2	2739	0.17	0.36	YES
16	PXMP2	PXMP2	PXMP2	2767	0.17	0.37	YES
17	PEX11A	PEX11A	PEX11A	3046	0.15	0.38	YES
18	CRAT	CRAT	CRAT	3217	0.14	0.38	YES
19	PXMP4	PXMP4	PXMP4	3317	0.14	0.39	YES
20	BAAT	BAAT	BAAT	3590	0.12	0.39	YES
21	PEX7	PEX7	PEX7	3808	0.11	0.39	YES
22	GSTK1	GSTK1	GSTK1	3943	0.11	0.4	YES
23	IDH1	IDH1	IDH1	4044	0.1	0.4	YES
24	HMGCL	HMGCL	HMGCL	4076	0.1	0.41	YES
25	ACSL4	ACSL4	ACSL4	4317	0.096	0.41	NO
26	PEX11B	PEX11B	PEX11B	4929	0.078	0.39	NO
27	HACL1	HACL1	HACL1	4969	0.077	0.39	NO
28	HAO2	HAO2	HAO2	5015	0.076	0.4	NO
29	ACOX2	ACOX2	ACOX2	5097	0.073	0.4	NO
30	MLYCD	MLYCD	MLYCD	5362	0.065	0.4	NO
31	PEX6	PEX6	PEX6	5416	0.064	0.4	NO
32	AMACR	AMACR	AMACR	5608	0.059	0.4	NO
33	ACOT8	ACOT8	ACOT8	5777	0.055	0.39	NO
34	PEX2	PEX2	PEX2	5946	0.052	0.39	NO
35	PEX1	PEX1	PEX1	6061	0.05	0.39	NO
36	SCP2	SCP2	SCP2	6113	0.049	0.39	NO
37	GNPAT	GNPAT	GNPAT	6127	0.048	0.4	NO
38	ABCD1	ABCD1	ABCD1	6263	0.046	0.4	NO
39	ABCD4	ABCD4	ABCD4	6395	0.043	0.39	NO
40	PRDX5	PRDX5	PRDX5	6730	0.037	0.38	NO
41	PEX16	PEX16	PEX16	6827	0.035	0.38	NO
42	ACOX1	ACOX1	ACOX1	6865	0.034	0.38	NO
43	PEX26	PEX26	PEX26	7227	0.028	0.36	NO
44	ACAA1	ACAA1	ACAA1	7320	0.026	0.36	NO
45	IDH2	IDH2	IDH2	7659	0.02	0.34	NO
46	HSD17B4	HSD17B4	HSD17B4	7660	0.02	0.35	NO
47	ECH1	ECH1	ECH1	7908	0.017	0.33	NO
48	ACSL3	ACSL3	ACSL3	8197	0.013	0.32	NO
49	PEX19	PEX19	PEX19	9291	-0.0029	0.26	NO
50	SOD1	SOD1	SOD1	9422	-0.0049	0.25	NO
51	EHHADH	EHHADH	EHHADH	9949	-0.012	0.22	NO
52	MPV17	MPV17	MPV17	10421	-0.019	0.2	NO
53	PMVK	PMVK	PMVK	10461	-0.02	0.2	NO
54	SLC25A17	SLC25A17	SLC25A17	10560	-0.021	0.2	NO
55	AGPS	AGPS	AGPS	10595	-0.022	0.2	NO
56	PEX10	PEX10	PEX10	11283	-0.032	0.16	NO
57	PEX13	PEX13	PEX13	11347	-0.032	0.16	NO
58	PRDX1	PRDX1	PRDX1	11394	-0.033	0.17	NO
59	PAOX	PAOX	PAOX	11963	-0.042	0.14	NO
60	PEX12	PEX12	PEX12	12077	-0.044	0.14	NO
61	DHRS4	DHRS4	DHRS4	12157	-0.045	0.14	NO
62	PEX3	PEX3	PEX3	12264	-0.047	0.14	NO
63	PEX5	PEX5	PEX5	12333	-0.049	0.14	NO
64	PEX14	PEX14	PEX14	12582	-0.053	0.13	NO
65	FAR1	FAR1	FAR1	13679	-0.077	0.081	NO
66	ACOX3	ACOX3	ACOX3	14035	-0.086	0.071	NO
67	ABCD2	ABCD2	ABCD2	14037	-0.086	0.081	NO
68	SOD2	SOD2	SOD2	14305	-0.093	0.077	NO
69	NUDT19	NUDT19	NUDT19	14831	-0.11	0.061	NO
70	MVK	MVK	MVK	14980	-0.12	0.066	NO
71	ACSL1	ACSL1	ACSL1	15319	-0.13	0.062	NO
72	XDH	XDH	XDH	15618	-0.15	0.063	NO
73	ACSL6	ACSL6	ACSL6	16065	-0.18	0.058	NO
74	EPHX2	EPHX2	EPHX2	16901	-0.25	0.041	NO
75	CROT	CROT	CROT	16923	-0.26	0.069	NO

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

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

genes ES table in pathway: PID RHOA REG PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CP	CP	CP	151	0.7	0.12	YES
2	ATP6V1B1	ATP6V1B1	ATP6V1B1	353	0.57	0.22	YES
3	ATP6V1C2	ATP6V1C2	ATP6V1C2	474	0.52	0.31	YES
4	SLC40A1	SLC40A1	SLC40A1	535	0.5	0.4	YES
5	ATP6V0A4	ATP6V0A4	ATP6V0A4	912	0.39	0.46	YES
6	ATP6V1G2	ATP6V1G2	ATP6V1G2	1311	0.31	0.49	YES
7	SLC46A1	SLC46A1	SLC46A1	2608	0.18	0.46	NO
8	HEPH	HEPH	HEPH	3518	0.13	0.43	NO
9	FLVCR1	FLVCR1	FLVCR1	3519	0.13	0.45	NO
10	TCIRG1	TCIRG1	TCIRG1	4020	0.11	0.45	NO
11	FTH1	FTH1	FTH1	4546	0.088	0.43	NO
12	CYBRD1	CYBRD1	CYBRD1	4705	0.084	0.44	NO
13	STEAP3	STEAP3	STEAP3	5252	0.068	0.42	NO
14	ATP6V0A2	ATP6V0A2	ATP6V0A2	8810	0.0038	0.23	NO
15	ATP6V0B	ATP6V0B	ATP6V0B	9089	0.00019	0.21	NO
16	FTL	FTL	FTL	10054	-0.014	0.16	NO
17	ABCG2	ABCG2	ABCG2	10664	-0.023	0.13	NO
18	ATP6V0E1	ATP6V0E1	ATP6V0E1	11015	-0.028	0.12	NO
19	ATP6V0D1	ATP6V0D1	ATP6V0D1	11270	-0.031	0.11	NO
20	ATP6V0C	ATP6V0C	ATP6V0C	11356	-0.033	0.11	NO
21	ATP6V1C1	ATP6V1C1	ATP6V1C1	11467	-0.034	0.11	NO
22	TFRC	TFRC	TFRC	11609	-0.036	0.11	NO
23	ATP6V1A	ATP6V1A	ATP6V1A	12247	-0.047	0.086	NO
24	MCOLN1	MCOLN1	MCOLN1	12780	-0.057	0.067	NO
25	ATP6V1F	ATP6V1F	ATP6V1F	12781	-0.057	0.078	NO
26	ATP6V1H	ATP6V1H	ATP6V1H	12951	-0.06	0.08	NO
27	ATP6V1E1	ATP6V1E1	ATP6V1E1	13469	-0.072	0.065	NO
28	HMOX2	HMOX2	HMOX2	13855	-0.081	0.059	NO
29	ATP6V1G1	ATP6V1G1	ATP6V1G1	13910	-0.082	0.072	NO
30	ATP6V1B2	ATP6V1B2	ATP6V1B2	14134	-0.088	0.076	NO
31	ATP6V1D	ATP6V1D	ATP6V1D	14195	-0.09	0.09	NO
32	ATP6V1E2	ATP6V1E2	ATP6V1E2	14782	-0.11	0.078	NO
33	HMOX1	HMOX1	HMOX1	15256	-0.13	0.077	NO
34	TF	TF	TF	15659	-0.15	0.083	NO
35	ATP6V0D2	ATP6V0D2	ATP6V0D2	17170	-0.29	0.055	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus4 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
KEGG RIBOSOME	85	genes.ES.table	0.67	1.6	0.055	0.24	0.92	0.91	0.3	0.63	0.13	0.037
KEGG PROTEASOME	43	genes.ES.table	0.64	1.8	0.006	0.14	0.59	0.86	0.32	0.58	0.042	0.026
KEGG NOD LIKE RECEPTOR SIGNALING PATHWAY	62	genes.ES.table	0.66	1.8	0.0042	0.14	0.6	0.37	0.087	0.34	0.042	0.026
KEGG RIG I LIKE RECEPTOR SIGNALING PATHWAY	58	genes.ES.table	0.49	1.7	0.019	0.2	0.84	0.31	0.15	0.26	0.096	0.031
KEGG CYTOSOLIC DNA SENSING PATHWAY	44	genes.ES.table	0.63	1.7	0.019	0.19	0.8	0.32	0.1	0.28	0.088	0.032
BIOCARTA INTEGRIN PATHWAY	38	genes.ES.table	0.56	2	0.0042	0.25	0.21	0.29	0.13	0.25	0	0.063
BIOCARTA PROTEASOME PATHWAY	28	genes.ES.table	0.62	1.7	0.0098	0.21	0.84	0.79	0.32	0.53	0.097	0.034
BIOCARTA IL1R PATHWAY	33	genes.ES.table	0.6	1.7	0.008	0.19	0.79	0.27	0.075	0.25	0.085	0.031
ST TUMOR NECROSIS FACTOR PATHWAY	28	genes.ES.table	0.6	1.9	0.0099	0.16	0.44	0.46	0.22	0.36	0	0.038
ST ERK1 ERK2 MAPK PATHWAY	31	genes.ES.table	0.46	1.7	0.019	0.19	0.77	0.23	0.14	0.2	0.079	0.033

genes ES table in pathway: KEGG RIBOSOME

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	KIFC3	KIFC3	KIFC3	209	0.38	0.2	YES
2	SPHK1	SPHK1	SPHK1	971	0.2	0.27	YES
3	FBXO6	FBXO6	FBXO6	1282	0.17	0.34	YES
4	FKBP9	FKBP9	FKBP9	2192	0.11	0.35	YES
5	KIF13A	KIF13A	KIF13A	2714	0.087	0.37	YES
6	CCT5	CCT5	CCT5	2715	0.087	0.42	YES
7	CCT2	CCT2	CCT2	3096	0.074	0.44	YES
8	CCT4	CCT4	CCT4	3310	0.069	0.47	YES
9	CCT7	CCT7	CCT7	3346	0.068	0.5	YES
10	CCT6A	CCT6A	CCT6A	3361	0.068	0.54	YES
11	CCT3	CCT3	CCT3	4345	0.047	0.51	YES
12	TCP1	TCP1	TCP1	4446	0.045	0.53	YES
13	NOP56	NOP56	NOP56	4600	0.043	0.55	YES
14	CCT8	CCT8	CCT8	5172	0.033	0.53	NO
15	FBXW5	FBXW5	FBXW5	5455	0.028	0.53	NO
16	FBXW2	FBXW2	FBXW2	6331	0.015	0.49	NO
17	LONP2	LONP2	LONP2	7667	-0.0021	0.42	NO
18	AP3M1	AP3M1	AP3M1	8147	-0.0088	0.4	NO
19	FBXO4	FBXO4	FBXO4	8501	-0.014	0.38	NO
20	FBXW7	FBXW7	FBXW7	8585	-0.015	0.39	NO
21	FBXL3	FBXL3	FBXL3	8831	-0.018	0.38	NO
22	XRN2	XRN2	XRN2	9091	-0.022	0.38	NO
23	USP11	USP11	USP11	10596	-0.044	0.32	NO
24	FBXL5	FBXL5	FBXL5	10651	-0.045	0.35	NO
25	FBXW4	FBXW4	FBXW4	10854	-0.049	0.36	NO
26	ARFGEF2	ARFGEF2	ARFGEF2	12216	-0.076	0.33	NO

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

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

genes ES table in pathway: KEGG PROTEASOME

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	PSMB9	PSMB9	PSMB9	1474	0.15	-0.03	YES
2	PSMB7	PSMB7	PSMB7	2195	0.11	-0.034	YES
3	PSMD12	PSMD12	PSMD12	2234	0.1	-0.0011	YES
4	AURKA	AURKA	AURKA	2296	0.1	0.03	YES
5	CDC20	CDC20	CDC20	2489	0.096	0.051	YES
6	SKP2	SKP2	SKP2	2504	0.096	0.082	YES
7	PSMA6	PSMA6	PSMA6	2634	0.09	0.1	YES
8	PSMB8	PSMB8	PSMB8	2771	0.085	0.13	YES
9	PSMC1	PSMC1	PSMC1	2979	0.078	0.14	YES
10	UBE2D1	UBE2D1	UBE2D1	3093	0.074	0.16	YES
11	PSME2	PSME2	PSME2	3172	0.072	0.18	YES
12	PLK1	PLK1	PLK1	3218	0.071	0.2	YES
13	PSMA4	PSMA4	PSMA4	3394	0.067	0.21	YES
14	RPS27A	RPS27A	RPS27A	3437	0.066	0.23	YES
15	PSMD14	PSMD14	PSMD14	3444	0.065	0.25	YES
16	PSMA2	PSMA2	PSMA2	3454	0.065	0.28	YES
17	PSMB5	PSMB5	PSMB5	3633	0.06	0.29	YES
18	PSMB10	PSMB10	PSMB10	3723	0.058	0.3	YES
19	PSMD8	PSMD8	PSMD8	3751	0.058	0.32	YES
20	PSMB2	PSMB2	PSMB2	3813	0.057	0.33	YES
21	PSMD9	PSMD9	PSMD9	3825	0.056	0.35	YES
22	PSMC6	PSMC6	PSMC6	3846	0.056	0.37	YES
23	PSMA3	PSMA3	PSMA3	3998	0.053	0.38	YES
24	PSMA7	PSMA7	PSMA7	4189	0.05	0.38	YES
25	UBE2C	UBE2C	UBE2C	4324	0.048	0.39	YES
26	PTTG1	PTTG1	PTTG1	4330	0.047	0.41	YES
27	PSMA1	PSMA1	PSMA1	4373	0.047	0.42	YES
28	CDC27	CDC27	CDC27	4398	0.046	0.44	YES
29	PSMA5	PSMA5	PSMA5	4466	0.045	0.45	YES
30	UBA52	UBA52	UBA52	4551	0.043	0.46	YES
31	CDC16	CDC16	CDC16	4706	0.041	0.46	YES
32	PSMD6	PSMD6	PSMD6	4766	0.04	0.47	YES
33	PSMB3	PSMB3	PSMB3	4805	0.039	0.48	YES
34	AURKB	AURKB	AURKB	4827	0.038	0.5	YES
35	PSMB1	PSMB1	PSMB1	4839	0.038	0.51	YES
36	PSMD3	PSMD3	PSMD3	4876	0.038	0.52	YES
37	PSMA8	PSMA8	PSMA8	4877	0.038	0.53	YES
38	PSMB4	PSMB4	PSMB4	4900	0.037	0.54	YES
39	PSME1	PSME1	PSME1	4913	0.037	0.55	YES
40	PSMD13	PSMD13	PSMD13	5034	0.035	0.56	YES
41	PSMC4	PSMC4	PSMC4	5058	0.035	0.57	YES
42	PSMD7	PSMD7	PSMD7	5089	0.034	0.58	YES
43	PSMD11	PSMD11	PSMD11	5373	0.03	0.57	YES
44	PSMD2	PSMD2	PSMD2	5534	0.027	0.57	YES
45	PSMC3	PSMC3	PSMC3	5724	0.024	0.57	YES
46	PSMD4	PSMD4	PSMD4	5746	0.024	0.58	YES
47	PSMB6	PSMB6	PSMB6	5841	0.022	0.58	YES
48	PSMC5	PSMC5	PSMC5	6120	0.018	0.57	NO
49	PSMD1	PSMD1	PSMD1	6250	0.016	0.57	NO
50	PSMC2	PSMC2	PSMC2	6383	0.015	0.57	NO
51	ANAPC1	ANAPC1	ANAPC1	6584	0.012	0.56	NO
52	PSMD5	PSMD5	PSMD5	6639	0.011	0.56	NO
53	PSMF1	PSMF1	PSMF1	6828	0.0085	0.55	NO
54	ANAPC10	ANAPC10	ANAPC10	6909	0.0075	0.55	NO
55	CDC26	CDC26	CDC26	7300	0.0026	0.53	NO
56	ANAPC11	ANAPC11	ANAPC11	7634	-0.0016	0.51	NO
57	CDC23	CDC23	CDC23	7705	-0.0028	0.51	NO
58	ANAPC5	ANAPC5	ANAPC5	8264	-0.01	0.48	NO
59	PSMD10	PSMD10	PSMD10	8325	-0.011	0.48	NO
60	ANAPC2	ANAPC2	ANAPC2	8528	-0.014	0.48	NO
61	PSME4	PSME4	PSME4	9691	-0.03	0.42	NO
62	UBE2E1	UBE2E1	UBE2E1	9830	-0.032	0.42	NO
63	ANAPC4	ANAPC4	ANAPC4	9926	-0.034	0.43	NO
64	ANAPC7	ANAPC7	ANAPC7	12165	-0.075	0.33	NO

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

Figure S64. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG PROTEASOME, 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 NOD LIKE RECEPTOR SIGNALING 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	CAV1	CAV1	CAV1	65	0.5	0.16	YES
2	PXN	PXN	PXN	640	0.25	0.2	YES
3	ACTN1	ACTN1	ACTN1	804	0.22	0.27	YES
4	ITGA1	ITGA1	ITGA1	958	0.21	0.33	YES
5	BCAR1	BCAR1	BCAR1	1249	0.17	0.36	YES
6	SHC1	SHC1	SHC1	1368	0.16	0.41	YES
7	ITGB1	ITGB1	ITGB1	1469	0.15	0.46	YES
8	HRAS	HRAS	HRAS	1652	0.14	0.49	YES
9	ACTN3	ACTN3	ACTN3	1839	0.13	0.52	YES
10	ZYX	ZYX	ZYX	1986	0.12	0.55	YES
11	MAP2K1	MAP2K1	MAP2K1	2312	0.1	0.56	YES
12	VCL	VCL	VCL	3280	0.07	0.53	NO
13	FYN	FYN	FYN	3476	0.065	0.54	NO
14	BCR	BCR	BCR	4151	0.05	0.52	NO
15	TLN1	TLN1	TLN1	4295	0.048	0.53	NO
16	CRKL	CRKL	CRKL	4636	0.042	0.52	NO
17	CAPNS2	CAPNS2	CAPNS2	4690	0.041	0.54	NO
18	CAPN1	CAPN1	CAPN1	4918	0.037	0.54	NO
19	PTK2	PTK2	PTK2	4961	0.036	0.54	NO
20	CAPNS1	CAPNS1	CAPNS1	4969	0.036	0.56	NO
21	RAPGEF1	RAPGEF1	RAPGEF1	5825	0.023	0.52	NO
22	RHOA	RHOA	RHOA	6132	0.018	0.5	NO
23	ACTN2	ACTN2	ACTN2	6360	0.015	0.5	NO
24	GRB2	GRB2	GRB2	6655	0.011	0.48	NO
25	RAP1A	RAP1A	RAP1A	7537	-0.0004	0.44	NO
26	MAPK3	MAPK3	MAPK3	7755	-0.0037	0.42	NO
27	MAPK8	MAPK8	MAPK8	7918	-0.0058	0.42	NO
28	MAPK1	MAPK1	MAPK1	8287	-0.011	0.4	NO
29	CSK	CSK	CSK	8339	-0.011	0.4	NO
30	MAP2K2	MAP2K2	MAP2K2	8466	-0.013	0.4	NO
31	ROCK1	ROCK1	ROCK1	8612	-0.015	0.4	NO
32	JUN	JUN	JUN	9302	-0.025	0.37	NO
33	SRC	SRC	SRC	10479	-0.042	0.31	NO
34	RAF1	RAF1	RAF1	10553	-0.044	0.32	NO
35	SOS1	SOS1	SOS1	10556	-0.044	0.34	NO
36	TNS1	TNS1	TNS1	11254	-0.056	0.32	NO
37	ACTA1	ACTA1	ACTA1	12071	-0.072	0.3	NO
38	PPP1R12B	PPP1R12B	PPP1R12B	14054	-0.13	0.23	NO

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

Figure S66. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG NOD LIKE RECEPTOR 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 RIG I LIKE RECEPTOR SIGNALING 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	MAPK11	MAPK11	MAPK11	1207	0.18	-0.018	YES
2	PSMB9	PSMB9	PSMB9	1474	0.15	0.0094	YES
3	PSMB7	PSMB7	PSMB7	2195	0.11	-0.001	YES
4	PSMD12	PSMD12	PSMD12	2234	0.1	0.026	YES
5	EXOSC6	EXOSC6	EXOSC6	2248	0.1	0.054	YES
6	EXOSC3	EXOSC3	EXOSC3	2624	0.09	0.058	YES
7	PSMA6	PSMA6	PSMA6	2634	0.09	0.082	YES
8	EXOSC4	EXOSC4	EXOSC4	2673	0.088	0.1	YES
9	PSMB8	PSMB8	PSMB8	2771	0.085	0.12	YES
10	PSMC1	PSMC1	PSMC1	2979	0.078	0.13	YES
11	PSME2	PSME2	PSME2	3172	0.072	0.14	YES
12	PSMA4	PSMA4	PSMA4	3394	0.067	0.15	YES
13	RPS27A	RPS27A	RPS27A	3437	0.066	0.16	YES
14	PSMD14	PSMD14	PSMD14	3444	0.065	0.18	YES
15	PSMA2	PSMA2	PSMA2	3454	0.065	0.2	YES
16	PSMB5	PSMB5	PSMB5	3633	0.06	0.2	YES
17	HSPA8	HSPA8	HSPA8	3698	0.059	0.22	YES
18	PSMB10	PSMB10	PSMB10	3723	0.058	0.23	YES
19	PSMD8	PSMD8	PSMD8	3751	0.058	0.25	YES
20	PSMB2	PSMB2	PSMB2	3813	0.057	0.26	YES
21	PSMD9	PSMD9	PSMD9	3825	0.056	0.27	YES
22	PSMC6	PSMC6	PSMC6	3846	0.056	0.29	YES
23	MAPK14	MAPK14	MAPK14	3906	0.055	0.3	YES
24	PSMA3	PSMA3	PSMA3	3998	0.053	0.31	YES
25	EXOSC5	EXOSC5	EXOSC5	4128	0.051	0.32	YES
26	PABPC1	PABPC1	PABPC1	4135	0.051	0.33	YES
27	PSMA7	PSMA7	PSMA7	4189	0.05	0.34	YES
28	PSMA1	PSMA1	PSMA1	4373	0.047	0.34	YES
29	PSMA5	PSMA5	PSMA5	4466	0.045	0.35	YES
30	EXOSC2	EXOSC2	EXOSC2	4514	0.044	0.36	YES
31	UBA52	UBA52	UBA52	4551	0.043	0.37	YES
32	PSMD6	PSMD6	PSMD6	4766	0.04	0.37	YES
33	PSMB3	PSMB3	PSMB3	4805	0.039	0.38	YES
34	PSMB1	PSMB1	PSMB1	4839	0.038	0.39	YES
35	HSPA1B	HSPA1B	HSPA1B	4869	0.038	0.4	YES
36	PSMD3	PSMD3	PSMD3	4876	0.038	0.4	YES
37	PSMA8	PSMA8	PSMA8	4877	0.038	0.42	YES
38	PSMB4	PSMB4	PSMB4	4900	0.037	0.42	YES
39	PSME1	PSME1	PSME1	4913	0.037	0.43	YES
40	EXOSC7	EXOSC7	EXOSC7	4957	0.036	0.44	YES
41	PSMD13	PSMD13	PSMD13	5034	0.035	0.45	YES
42	PSMC4	PSMC4	PSMC4	5058	0.035	0.46	YES
43	PSMD7	PSMD7	PSMD7	5089	0.034	0.46	YES
44	PSMD11	PSMD11	PSMD11	5373	0.03	0.46	YES
45	PSMD2	PSMD2	PSMD2	5534	0.027	0.45	YES
46	PSMC3	PSMC3	PSMC3	5724	0.024	0.45	YES
47	PSMD4	PSMD4	PSMD4	5746	0.024	0.46	YES
48	PSMB6	PSMB6	PSMB6	5841	0.022	0.46	YES
49	EXOSC1	EXOSC1	EXOSC1	5899	0.022	0.46	YES
50	DIS3	DIS3	DIS3	5948	0.021	0.46	YES
51	YWHAZ	YWHAZ	YWHAZ	5985	0.02	0.47	YES
52	MAPKAPK2	MAPKAPK2	MAPKAPK2	6050	0.019	0.47	YES
53	PSMC5	PSMC5	PSMC5	6120	0.018	0.47	YES
54	PSMD1	PSMD1	PSMD1	6250	0.016	0.47	YES
55	TNPO1	TNPO1	TNPO1	6351	0.015	0.46	YES
56	ANP32A	ANP32A	ANP32A	6352	0.015	0.47	YES
57	PSMC2	PSMC2	PSMC2	6383	0.015	0.47	YES
58	PARN	PARN	PARN	6412	0.014	0.47	YES
59	YWHAB	YWHAB	YWHAB	6446	0.014	0.48	YES
60	PSMD5	PSMD5	PSMD5	6639	0.011	0.47	NO
61	AKT1	AKT1	AKT1	6645	0.011	0.47	NO
62	PSMF1	PSMF1	PSMF1	6828	0.0085	0.46	NO
63	NUP214	NUP214	NUP214	7413	0.0012	0.43	NO
64	PRKCA	PRKCA	PRKCA	7707	-0.0028	0.42	NO
65	EIF4G1	EIF4G1	EIF4G1	7772	-0.0038	0.41	NO
66	HNRNPD	HNRNPD	HNRNPD	7851	-0.0051	0.41	NO
67	EXOSC8	EXOSC8	EXOSC8	7987	-0.0066	0.4	NO
68	XPO1	XPO1	XPO1	8040	-0.0073	0.4	NO
69	EXOSC9	EXOSC9	EXOSC9	8217	-0.0098	0.4	NO
70	PSMD10	PSMD10	PSMD10	8325	-0.011	0.39	NO
71	ZFP36	ZFP36	ZFP36	8982	-0.02	0.36	NO
72	PSME4	PSME4	PSME4	9691	-0.03	0.33	NO
73	DCP2	DCP2	DCP2	10064	-0.036	0.32	NO
74	ELAVL1	ELAVL1	ELAVL1	10280	-0.039	0.32	NO
75	XRN1	XRN1	XRN1	10552	-0.044	0.32	NO
76	KHSRP	KHSRP	KHSRP	10760	-0.047	0.32	NO
77	HSPB1	HSPB1	HSPB1	10995	-0.051	0.32	NO
78	DCP1A	DCP1A	DCP1A	11206	-0.055	0.32	NO
79	ZFP36L1	ZFP36L1	ZFP36L1	12023	-0.071	0.3	NO
80	TNFSF13	TNFSF13	TNFSF13	12133	-0.074	0.31	NO
81	PRKCD	PRKCD	PRKCD	12297	-0.077	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: KEGG RIG I LIKE RECEPTOR SIGNALING PATHWAY.

Figure S68. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG RIG I LIKE RECEPTOR 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 CYTOSOLIC DNA SENSING 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	RPL3L	RPL3L	RPL3L	178	0.4	0.022	YES
2	RPL36A	RPL36A	RPL36A	773	0.23	0.0075	YES
3	MAPK11	MAPK11	MAPK11	1207	0.18	-0.0026	YES
4	PSMB9	PSMB9	PSMB9	1474	0.15	-0.0052	YES
5	RPSAP9	RPSAP9	RPSAP9	1704	0.14	-0.007	YES
6	RPS26	RPS26	RPS26	1955	0.12	-0.011	YES
7	NUP37	NUP37	NUP37	1991	0.12	-0.004	YES
8	GEMIN7	GEMIN7	GEMIN7	2066	0.11	0.00091	YES
9	RPL37	RPL37	RPL37	2166	0.11	0.004	YES
10	PSMB7	PSMB7	PSMB7	2195	0.11	0.011	YES
11	RPL39	RPL39	RPL39	2210	0.11	0.019	YES
12	PSMD12	PSMD12	PSMD12	2234	0.1	0.026	YES
13	RPS17	RPS17	RPS17	2246	0.1	0.034	YES
14	EXOSC6	EXOSC6	EXOSC6	2248	0.1	0.042	YES
15	RPL26L1	RPL26L1	RPL26L1	2345	0.1	0.044	YES
16	RPL28	RPL28	RPL28	2360	0.1	0.052	YES
17	RPL18A	RPL18A	RPL18A	2404	0.099	0.057	YES
18	RPS2	RPS2	RPS2	2410	0.099	0.065	YES
19	RPL35	RPL35	RPL35	2456	0.097	0.07	YES
20	RPL38	RPL38	RPL38	2463	0.097	0.077	YES
21	RPS16	RPS16	RPS16	2480	0.096	0.084	YES
22	RPL13	RPL13	RPL13	2611	0.091	0.084	YES
23	EXOSC3	EXOSC3	EXOSC3	2624	0.09	0.091	YES
24	PSMA6	PSMA6	PSMA6	2634	0.09	0.097	YES
25	RPS10	RPS10	RPS10	2663	0.089	0.1	YES
26	RPS5	RPS5	RPS5	2665	0.089	0.11	YES
27	EXOSC4	EXOSC4	EXOSC4	2673	0.088	0.12	YES
28	PSMB8	PSMB8	PSMB8	2771	0.085	0.12	YES
29	RPL27	RPL27	RPL27	2799	0.084	0.12	YES
30	TNKS1BP1	TNKS1BP1	TNKS1BP1	2850	0.082	0.13	YES
31	RPL8	RPL8	RPL8	2882	0.082	0.13	YES
32	GEMIN6	GEMIN6	GEMIN6	2893	0.081	0.14	YES
33	RPL12	RPL12	RPL12	2908	0.08	0.14	YES
34	SNRPD2	SNRPD2	SNRPD2	2910	0.08	0.15	YES
35	PSMC1	PSMC1	PSMC1	2979	0.078	0.15	YES
36	RPS3	RPS3	RPS3	2993	0.078	0.16	YES
37	RPL4	RPL4	RPL4	3061	0.076	0.16	YES
38	RPL7A	RPL7A	RPL7A	3155	0.072	0.16	YES
39	PSME2	PSME2	PSME2	3172	0.072	0.16	YES
40	RPS19	RPS19	RPS19	3177	0.072	0.17	YES
41	SNRPF	SNRPF	SNRPF	3181	0.072	0.18	YES
42	RPL18	RPL18	RPL18	3194	0.071	0.18	YES
43	RPS18	RPS18	RPS18	3244	0.07	0.18	YES
44	EDC3	EDC3	EDC3	3282	0.07	0.19	YES
45	RPLP1	RPLP1	RPLP1	3286	0.069	0.19	YES
46	RPL29	RPL29	RPL29	3296	0.069	0.2	YES
47	PRMT5	PRMT5	PRMT5	3318	0.069	0.2	YES
48	RPS29	RPS29	RPS29	3335	0.068	0.21	YES
49	RPS24	RPS24	RPS24	3344	0.068	0.21	YES
50	RPS21	RPS21	RPS21	3352	0.068	0.22	YES
51	PSMA4	PSMA4	PSMA4	3394	0.067	0.22	YES
52	EIF4A1	EIF4A1	EIF4A1	3414	0.066	0.22	YES
53	RPS27A	RPS27A	RPS27A	3437	0.066	0.23	YES
54	PSMD14	PSMD14	PSMD14	3444	0.065	0.23	YES
55	PSMA2	PSMA2	PSMA2	3454	0.065	0.24	YES
56	RPS28	RPS28	RPS28	3495	0.064	0.24	YES
57	RPL23	RPL23	RPL23	3511	0.064	0.24	YES
58	RPL31	RPL31	RPL31	3534	0.063	0.25	YES
59	RPL6	RPL6	RPL6	3544	0.063	0.25	YES
60	RPS9	RPS9	RPS9	3605	0.061	0.26	YES
61	PSMB5	PSMB5	PSMB5	3633	0.06	0.26	YES
62	RPL17	RPL17	RPL17	3645	0.06	0.26	YES
63	RPS25	RPS25	RPS25	3670	0.06	0.26	YES
64	LSM5	LSM5	LSM5	3671	0.06	0.27	YES
65	RPS14	RPS14	RPS14	3675	0.059	0.28	YES
66	RPL7	RPL7	RPL7	3676	0.059	0.28	YES
67	HSPA8	HSPA8	HSPA8	3698	0.059	0.28	YES
68	PSMB10	PSMB10	PSMB10	3723	0.058	0.29	YES
69	PSMD8	PSMD8	PSMD8	3751	0.058	0.29	YES
70	RPS15A	RPS15A	RPS15A	3788	0.057	0.29	YES
71	RPLP0	RPLP0	RPLP0	3790	0.057	0.3	YES
72	CLNS1A	CLNS1A	CLNS1A	3791	0.057	0.3	YES
73	RPS7	RPS7	RPS7	3802	0.057	0.3	YES
74	PSMB2	PSMB2	PSMB2	3813	0.057	0.31	YES
75	RPL13A	RPL13A	RPL13A	3823	0.056	0.31	YES
76	PSMD9	PSMD9	PSMD9	3825	0.056	0.32	YES
77	RPLP2	RPLP2	RPLP2	3829	0.056	0.32	YES
78	PSMC6	PSMC6	PSMC6	3846	0.056	0.32	YES
79	RPSA	RPSA	RPSA	3882	0.056	0.33	YES
80	RPL32	RPL32	RPL32	3897	0.055	0.33	YES
81	RPL30	RPL30	RPL30	3898	0.055	0.34	YES
82	RPL14	RPL14	RPL14	3899	0.055	0.34	YES
83	MAPK14	MAPK14	MAPK14	3906	0.055	0.34	YES
84	RPS12	RPS12	RPS12	3946	0.054	0.35	YES
85	PSMA3	PSMA3	PSMA3	3998	0.053	0.35	YES
86	RPS20	RPS20	RPS20	4035	0.053	0.35	YES
87	NUP107	NUP107	NUP107	4111	0.051	0.35	YES
88	CNOT3	CNOT3	CNOT3	4123	0.051	0.35	YES
89	EXOSC5	EXOSC5	EXOSC5	4128	0.051	0.36	YES
90	PABPC1	PABPC1	PABPC1	4135	0.051	0.36	YES
91	PSMA7	PSMA7	PSMA7	4189	0.05	0.36	YES
92	RPL23A	RPL23A	RPL23A	4201	0.05	0.36	YES
93	RPL11	RPL11	RPL11	4268	0.048	0.37	YES
94	PSMA1	PSMA1	PSMA1	4373	0.047	0.36	YES
95	PPP2R1A	PPP2R1A	PPP2R1A	4399	0.046	0.37	YES
96	RPL26	RPL26	RPL26	4423	0.046	0.37	YES
97	RPS13	RPS13	RPS13	4437	0.045	0.37	YES
98	PSMA5	PSMA5	PSMA5	4466	0.045	0.37	YES
99	PHAX	PHAX	PHAX	4492	0.044	0.38	YES
100	EXOSC2	EXOSC2	EXOSC2	4514	0.044	0.38	YES
101	UBA52	UBA52	UBA52	4551	0.043	0.38	YES
102	GEMIN5	GEMIN5	GEMIN5	4559	0.043	0.38	YES
103	RPS11	RPS11	RPS11	4582	0.043	0.38	YES
104	RPL27A	RPL27A	RPL27A	4584	0.043	0.39	YES
105	RPL21	RPL21	RPL21	4609	0.042	0.39	YES
106	RPS23	RPS23	RPS23	4626	0.042	0.39	YES
107	RPL37A	RPL37A	RPL37A	4644	0.042	0.4	YES
108	RPL10A	RPL10A	RPL10A	4685	0.041	0.4	YES
109	RPL34	RPL34	RPL34	4686	0.041	0.4	YES
110	LSM6	LSM6	LSM6	4691	0.041	0.4	YES
111	RPS8	RPS8	RPS8	4762	0.04	0.4	YES
112	PSMD6	PSMD6	PSMD6	4766	0.04	0.4	YES
113	ETF1	ETF1	ETF1	4797	0.039	0.41	YES
114	PSMB3	PSMB3	PSMB3	4805	0.039	0.41	YES
115	RPL10	RPL10	RPL10	4822	0.038	0.41	YES
116	PSMB1	PSMB1	PSMB1	4839	0.038	0.41	YES
117	HSPA1B	HSPA1B	HSPA1B	4869	0.038	0.41	YES
118	EIF4A3	EIF4A3	EIF4A3	4875	0.038	0.42	YES
119	PSMD3	PSMD3	PSMD3	4876	0.038	0.42	YES
120	PSMA8	PSMA8	PSMA8	4877	0.038	0.42	YES
121	RPL41	RPL41	RPL41	4894	0.037	0.42	YES
122	PSMB4	PSMB4	PSMB4	4900	0.037	0.43	YES
123	RPS6	RPS6	RPS6	4902	0.037	0.43	YES
124	PSME1	PSME1	PSME1	4913	0.037	0.43	YES
125	SNRPG	SNRPG	SNRPG	4924	0.037	0.44	YES
126	RPL19	RPL19	RPL19	4932	0.037	0.44	YES
127	NUP93	NUP93	NUP93	4948	0.036	0.44	YES
128	EXOSC7	EXOSC7	EXOSC7	4957	0.036	0.44	YES
129	RPS3A	RPS3A	RPS3A	4979	0.036	0.44	YES
130	RPL36	RPL36	RPL36	4984	0.036	0.45	YES
131	SNRPD1	SNRPD1	SNRPD1	5023	0.035	0.45	YES
132	PSMD13	PSMD13	PSMD13	5034	0.035	0.45	YES
133	PSMC4	PSMC4	PSMC4	5058	0.035	0.45	YES
134	PSMD7	PSMD7	PSMD7	5089	0.034	0.45	YES
135	PPP2CA	PPP2CA	PPP2CA	5136	0.033	0.45	YES
136	NUP155	NUP155	NUP155	5186	0.033	0.45	YES
137	RPL5	RPL5	RPL5	5198	0.032	0.45	YES
138	MAGOH	MAGOH	MAGOH	5215	0.032	0.46	YES
139	RPL24	RPL24	RPL24	5260	0.031	0.46	YES
140	SNUPN	SNUPN	SNUPN	5269	0.031	0.46	YES
141	NUP153	NUP153	NUP153	5276	0.031	0.46	YES
142	FAU	FAU	FAU	5302	0.031	0.46	YES
143	EIF4B	EIF4B	EIF4B	5332	0.03	0.46	YES
144	GEMIN4	GEMIN4	GEMIN4	5349	0.03	0.46	YES
145	PSMD11	PSMD11	PSMD11	5373	0.03	0.46	YES
146	PAIP1	PAIP1	PAIP1	5387	0.029	0.47	YES
147	RPS4X	RPS4X	RPS4X	5388	0.029	0.47	YES
148	RPL3	RPL3	RPL3	5521	0.027	0.46	YES
149	PSMD2	PSMD2	PSMD2	5534	0.027	0.46	YES
150	SNRPE	SNRPE	SNRPE	5568	0.026	0.46	YES
151	AAAS	AAAS	AAAS	5605	0.026	0.46	YES
152	PATL1	PATL1	PATL1	5608	0.026	0.47	YES
153	LSM2	LSM2	LSM2	5615	0.026	0.47	YES
154	RNPS1	RNPS1	RNPS1	5655	0.025	0.47	YES
155	PSMC3	PSMC3	PSMC3	5724	0.024	0.47	YES
156	RPS15	RPS15	RPS15	5741	0.024	0.47	YES
157	NUP62	NUP62	NUP62	5743	0.024	0.47	YES
158	PSMD4	PSMD4	PSMD4	5746	0.024	0.47	YES
159	RPS27	RPS27	RPS27	5838	0.023	0.47	NO
160	PSMB6	PSMB6	PSMB6	5841	0.022	0.47	NO
161	SNRPB	SNRPB	SNRPB	5868	0.022	0.47	NO
162	EXOSC1	EXOSC1	EXOSC1	5899	0.022	0.47	NO
163	DIS3	DIS3	DIS3	5948	0.021	0.47	NO
164	YWHAZ	YWHAZ	YWHAZ	5985	0.02	0.47	NO
165	MAPKAPK2	MAPKAPK2	MAPKAPK2	6050	0.019	0.47	NO
166	LSM3	LSM3	LSM3	6073	0.019	0.47	NO
167	NUP85	NUP85	NUP85	6088	0.019	0.47	NO
168	EDC4	EDC4	EDC4	6109	0.019	0.47	NO
169	PSMC5	PSMC5	PSMC5	6120	0.018	0.47	NO
170	NUP188	NUP188	NUP188	6135	0.018	0.47	NO
171	RPL22	RPL22	RPL22	6210	0.017	0.47	NO
172	PSMD1	PSMD1	PSMD1	6250	0.016	0.47	NO
173	SEH1L	SEH1L	SEH1L	6312	0.016	0.46	NO
174	TNPO1	TNPO1	TNPO1	6351	0.015	0.46	NO
175	ANP32A	ANP32A	ANP32A	6352	0.015	0.46	NO
176	PSMC2	PSMC2	PSMC2	6383	0.015	0.46	NO
177	PARN	PARN	PARN	6412	0.014	0.46	NO
178	YWHAB	YWHAB	YWHAB	6446	0.014	0.46	NO
179	NUP50	NUP50	NUP50	6605	0.012	0.45	NO
180	PSMD5	PSMD5	PSMD5	6639	0.011	0.45	NO
181	SNRPD3	SNRPD3	SNRPD3	6642	0.011	0.45	NO
182	AKT1	AKT1	AKT1	6645	0.011	0.46	NO
183	SMN2	SMN2	SMN2	6740	0.0098	0.45	NO
184	TGS1	TGS1	TGS1	6789	0.0091	0.45	NO
185	NCBP1	NCBP1	NCBP1	6798	0.009	0.45	NO
186	PSMF1	PSMF1	PSMF1	6828	0.0085	0.45	NO
187	LSM4	LSM4	LSM4	6841	0.0083	0.45	NO
188	RPL35A	RPL35A	RPL35A	6922	0.0073	0.44	NO
189	RAE1	RAE1	RAE1	6998	0.0062	0.44	NO
190	RPL15	RPL15	RPL15	7311	0.0024	0.42	NO
191	SMG5	SMG5	SMG5	7383	0.0016	0.42	NO
192	NUP214	NUP214	NUP214	7413	0.0012	0.42	NO
193	CNOT10	CNOT10	CNOT10	7594	-0.0011	0.41	NO
194	PRKCA	PRKCA	PRKCA	7707	-0.0028	0.4	NO
195	EIF4G1	EIF4G1	EIF4G1	7772	-0.0038	0.4	NO
196	HNRNPD	HNRNPD	HNRNPD	7851	-0.0051	0.39	NO
197	RANBP2	RANBP2	RANBP2	7942	-0.0061	0.39	NO
198	NUP205	NUP205	NUP205	7964	-0.0063	0.39	NO
199	EXOSC8	EXOSC8	EXOSC8	7987	-0.0066	0.39	NO
200	NUPL1	NUPL1	NUPL1	7988	-0.0067	0.39	NO
201	RBM8A	RBM8A	RBM8A	7998	-0.0068	0.39	NO
202	XPO1	XPO1	XPO1	8040	-0.0073	0.39	NO
203	EXOSC9	EXOSC9	EXOSC9	8217	-0.0098	0.38	NO
204	PSMD10	PSMD10	PSMD10	8325	-0.011	0.37	NO
205	CNOT2	CNOT2	CNOT2	8335	-0.011	0.37	NO
206	POM121	POM121	POM121	8568	-0.015	0.36	NO
207	SMG1	SMG1	SMG1	8570	-0.015	0.36	NO
208	NUPL2	NUPL2	NUPL2	8631	-0.015	0.36	NO
209	NUP35	NUP35	NUP35	8666	-0.016	0.36	NO
210	LSM1	LSM1	LSM1	8976	-0.02	0.34	NO
211	ZFP36	ZFP36	ZFP36	8982	-0.02	0.35	NO
212	NUP54	NUP54	NUP54	8990	-0.02	0.35	NO
213	DDX20	DDX20	DDX20	9140	-0.022	0.34	NO
214	PPP2R2A	PPP2R2A	PPP2R2A	9319	-0.025	0.33	NO
215	DDX6	DDX6	DDX6	9448	-0.027	0.33	NO
216	PSME4	PSME4	PSME4	9691	-0.03	0.32	NO
217	WDR77	WDR77	WDR77	9820	-0.032	0.31	NO
218	SMG6	SMG6	SMG6	9883	-0.033	0.31	NO
219	NUP133	NUP133	NUP133	9974	-0.034	0.31	NO
220	CNOT4	CNOT4	CNOT4	9995	-0.034	0.31	NO
221	UPF3A	UPF3A	UPF3A	10063	-0.036	0.31	NO
222	DCP2	DCP2	DCP2	10064	-0.036	0.31	NO
223	TPR	TPR	TPR	10124	-0.036	0.31	NO
224	NUP88	NUP88	NUP88	10158	-0.037	0.31	NO
225	CNOT6	CNOT6	CNOT6	10159	-0.037	0.32	NO
226	C2orf29	C2orf29	C2orf29	10215	-0.038	0.32	NO
227	DCPS	DCPS	DCPS	10275	-0.039	0.32	NO
228	ELAVL1	ELAVL1	ELAVL1	10280	-0.039	0.32	NO
229	RQCD1	RQCD1	RQCD1	10394	-0.041	0.32	NO
230	XRN1	XRN1	XRN1	10552	-0.044	0.31	NO
231	NUP210	NUP210	NUP210	10574	-0.044	0.31	NO
232	EIF4E	EIF4E	EIF4E	10707	-0.046	0.31	NO
233	RPL9	RPL9	RPL9	10708	-0.046	0.31	NO
234	KHSRP	KHSRP	KHSRP	10760	-0.047	0.31	NO
235	CNOT7	CNOT7	CNOT7	10764	-0.047	0.32	NO
236	SMG7	SMG7	SMG7	10894	-0.05	0.31	NO
237	UPF2	UPF2	UPF2	10900	-0.05	0.32	NO
238	NUP43	NUP43	NUP43	10978	-0.051	0.32	NO
239	HSPB1	HSPB1	HSPB1	10995	-0.051	0.32	NO
240	NCBP2	NCBP2	NCBP2	11081	-0.053	0.32	NO
241	DCP1A	DCP1A	DCP1A	11206	-0.055	0.32	NO
242	SMN1	SMN1	SMN1	11466	-0.06	0.31	NO
243	CASC3	CASC3	CASC3	11547	-0.062	0.31	NO
244	ZFP36L1	ZFP36L1	ZFP36L1	12023	-0.071	0.29	NO
245	CNOT8	CNOT8	CNOT8	12048	-0.072	0.29	NO
246	TNFSF13	TNFSF13	TNFSF13	12133	-0.074	0.29	NO
247	PRKCD	PRKCD	PRKCD	12297	-0.077	0.29	NO
248	UPF3B	UPF3B	UPF3B	12301	-0.077	0.3	NO
249	DCP1B	DCP1B	DCP1B	12603	-0.085	0.29	NO
250	EIF4A2	EIF4A2	EIF4A2	13004	-0.094	0.27	NO
251	GSPT2	GSPT2	GSPT2	13367	-0.1	0.26	NO
252	FAM153A	FAM153A	FAM153A	13395	-0.1	0.27	NO

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

Figure S70. Get High-res Image For the top 5 core enriched genes in the pathway: KEGG CYTOSOLIC DNA SENSING 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 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	PSMB9	PSMB9	PSMB9	1474	0.15	-0.027	YES
2	PSMB7	PSMB7	PSMB7	2195	0.11	-0.029	YES
3	PSMD12	PSMD12	PSMD12	2234	0.1	0.0065	YES
4	CDC20	CDC20	CDC20	2489	0.096	0.026	YES
5	PSMA6	PSMA6	PSMA6	2634	0.09	0.05	YES
6	PSMB8	PSMB8	PSMB8	2771	0.085	0.073	YES
7	PSMC1	PSMC1	PSMC1	2979	0.078	0.089	YES
8	UBE2D1	UBE2D1	UBE2D1	3093	0.074	0.11	YES
9	PSME2	PSME2	PSME2	3172	0.072	0.13	YES
10	PSMA4	PSMA4	PSMA4	3394	0.067	0.14	YES
11	RPS27A	RPS27A	RPS27A	3437	0.066	0.16	YES
12	PSMD14	PSMD14	PSMD14	3444	0.065	0.19	YES
13	PSMA2	PSMA2	PSMA2	3454	0.065	0.21	YES
14	PSMB5	PSMB5	PSMB5	3633	0.06	0.22	YES
15	PSMB10	PSMB10	PSMB10	3723	0.058	0.24	YES
16	PSMD8	PSMD8	PSMD8	3751	0.058	0.26	YES
17	PSMB2	PSMB2	PSMB2	3813	0.057	0.27	YES
18	PSMD9	PSMD9	PSMD9	3825	0.056	0.29	YES
19	PSMC6	PSMC6	PSMC6	3846	0.056	0.31	YES
20	PSMA3	PSMA3	PSMA3	3998	0.053	0.32	YES
21	PSMA7	PSMA7	PSMA7	4189	0.05	0.33	YES
22	CCNB1	CCNB1	CCNB1	4205	0.05	0.34	YES
23	UBE2C	UBE2C	UBE2C	4324	0.048	0.36	YES
24	PTTG1	PTTG1	PTTG1	4330	0.047	0.37	YES
25	PSMA1	PSMA1	PSMA1	4373	0.047	0.38	YES
26	CDC27	CDC27	CDC27	4398	0.046	0.4	YES
27	PSMA5	PSMA5	PSMA5	4466	0.045	0.41	YES
28	UBA52	UBA52	UBA52	4551	0.043	0.42	YES
29	CDC16	CDC16	CDC16	4706	0.041	0.43	YES
30	PSMD6	PSMD6	PSMD6	4766	0.04	0.44	YES
31	PSMB3	PSMB3	PSMB3	4805	0.039	0.45	YES
32	PSMB1	PSMB1	PSMB1	4839	0.038	0.46	YES
33	PSMD3	PSMD3	PSMD3	4876	0.038	0.48	YES
34	PSMA8	PSMA8	PSMA8	4877	0.038	0.49	YES
35	PSMB4	PSMB4	PSMB4	4900	0.037	0.5	YES
36	PSME1	PSME1	PSME1	4913	0.037	0.51	YES
37	PSMD13	PSMD13	PSMD13	5034	0.035	0.52	YES
38	PSMC4	PSMC4	PSMC4	5058	0.035	0.53	YES
39	PSMD7	PSMD7	PSMD7	5089	0.034	0.54	YES
40	PSMD11	PSMD11	PSMD11	5373	0.03	0.54	YES
41	MAD2L1	MAD2L1	MAD2L1	5505	0.027	0.54	YES
42	PSMD2	PSMD2	PSMD2	5534	0.027	0.55	YES
43	PSMC3	PSMC3	PSMC3	5724	0.024	0.54	YES
44	PSMD4	PSMD4	PSMD4	5746	0.024	0.55	YES
45	BUB3	BUB3	BUB3	5779	0.023	0.56	YES
46	PSMB6	PSMB6	PSMB6	5841	0.022	0.56	YES
47	PSMC5	PSMC5	PSMC5	6120	0.018	0.55	NO
48	PSMD1	PSMD1	PSMD1	6250	0.016	0.55	NO
49	PSMC2	PSMC2	PSMC2	6383	0.015	0.55	NO
50	ANAPC1	ANAPC1	ANAPC1	6584	0.012	0.54	NO
51	PSMD5	PSMD5	PSMD5	6639	0.011	0.54	NO
52	PSMF1	PSMF1	PSMF1	6828	0.0085	0.54	NO
53	ANAPC10	ANAPC10	ANAPC10	6909	0.0075	0.54	NO
54	CDC26	CDC26	CDC26	7300	0.0026	0.51	NO
55	ANAPC11	ANAPC11	ANAPC11	7634	-0.0016	0.5	NO
56	CDC23	CDC23	CDC23	7705	-0.0028	0.49	NO
57	ANAPC5	ANAPC5	ANAPC5	8264	-0.01	0.47	NO
58	PSMD10	PSMD10	PSMD10	8325	-0.011	0.47	NO
59	BUB1B	BUB1B	BUB1B	8344	-0.012	0.47	NO
60	ANAPC2	ANAPC2	ANAPC2	8528	-0.014	0.46	NO
61	CDK1	CDK1	CDK1	9018	-0.021	0.44	NO
62	PSME4	PSME4	PSME4	9691	-0.03	0.42	NO
63	UBE2E1	UBE2E1	UBE2E1	9830	-0.032	0.42	NO
64	ANAPC4	ANAPC4	ANAPC4	9926	-0.034	0.43	NO
65	ANAPC7	ANAPC7	ANAPC7	12165	-0.075	0.33	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 INTEGRIN PATHWAY.

Figure S72. 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 PROTEASOME PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	CCNA1	CCNA1	CCNA1	1426	0.16	-0.023	YES
2	PSMB9	PSMB9	PSMB9	1474	0.15	0.028	YES
3	PSMB7	PSMB7	PSMB7	2195	0.11	0.026	YES
4	PSMD12	PSMD12	PSMD12	2234	0.1	0.061	YES
5	SKP2	SKP2	SKP2	2504	0.096	0.08	YES
6	PSMA6	PSMA6	PSMA6	2634	0.09	0.1	YES
7	PSMB8	PSMB8	PSMB8	2771	0.085	0.13	YES
8	CKS1B	CKS1B	CKS1B	2921	0.08	0.15	YES
9	PSMC1	PSMC1	PSMC1	2979	0.078	0.17	YES
10	PSME2	PSME2	PSME2	3172	0.072	0.18	YES
11	PSMA4	PSMA4	PSMA4	3394	0.067	0.2	YES
12	RPS27A	RPS27A	RPS27A	3437	0.066	0.22	YES
13	PSMD14	PSMD14	PSMD14	3444	0.065	0.24	YES
14	PSMA2	PSMA2	PSMA2	3454	0.065	0.26	YES
15	CDKN1A	CDKN1A	CDKN1A	3455	0.065	0.28	YES
16	PSMB5	PSMB5	PSMB5	3633	0.06	0.3	YES
17	PSMB10	PSMB10	PSMB10	3723	0.058	0.31	YES
18	CDK2	CDK2	CDK2	3747	0.058	0.33	YES
19	PSMD8	PSMD8	PSMD8	3751	0.058	0.35	YES
20	PSMB2	PSMB2	PSMB2	3813	0.057	0.37	YES
21	PSMD9	PSMD9	PSMD9	3825	0.056	0.39	YES
22	PSMC6	PSMC6	PSMC6	3846	0.056	0.41	YES
23	PSMA3	PSMA3	PSMA3	3998	0.053	0.42	YES
24	PSMA7	PSMA7	PSMA7	4189	0.05	0.42	YES
25	PSMA1	PSMA1	PSMA1	4373	0.047	0.43	YES
26	PSMA5	PSMA5	PSMA5	4466	0.045	0.44	YES
27	UBA52	UBA52	UBA52	4551	0.043	0.45	YES
28	PSMD6	PSMD6	PSMD6	4766	0.04	0.45	YES
29	PSMB3	PSMB3	PSMB3	4805	0.039	0.46	YES
30	PSMB1	PSMB1	PSMB1	4839	0.038	0.48	YES
31	PSMD3	PSMD3	PSMD3	4876	0.038	0.49	YES
32	PSMB4	PSMB4	PSMB4	4900	0.037	0.5	YES
33	PSME1	PSME1	PSME1	4913	0.037	0.51	YES
34	PSMD13	PSMD13	PSMD13	5034	0.035	0.52	YES
35	PSMC4	PSMC4	PSMC4	5058	0.035	0.53	YES
36	PSMD7	PSMD7	PSMD7	5089	0.034	0.54	YES
37	PSMD11	PSMD11	PSMD11	5373	0.03	0.53	YES
38	CCNA2	CCNA2	CCNA2	5493	0.028	0.54	YES
39	PSMD2	PSMD2	PSMD2	5534	0.027	0.54	YES
40	PSMC3	PSMC3	PSMC3	5724	0.024	0.54	YES
41	PSMD4	PSMD4	PSMD4	5746	0.024	0.55	YES
42	CCNE1	CCNE1	CCNE1	5807	0.023	0.55	YES
43	PSMB6	PSMB6	PSMB6	5841	0.022	0.56	YES
44	CUL1	CUL1	CUL1	5974	0.021	0.56	NO
45	PSMC5	PSMC5	PSMC5	6120	0.018	0.56	NO
46	PSMD1	PSMD1	PSMD1	6250	0.016	0.56	NO
47	PSMC2	PSMC2	PSMC2	6383	0.015	0.56	NO
48	PSMD5	PSMD5	PSMD5	6639	0.011	0.55	NO
49	PSMF1	PSMF1	PSMF1	6828	0.0085	0.54	NO
50	PSMD10	PSMD10	PSMD10	8325	-0.011	0.46	NO
51	SKP1	SKP1	SKP1	8644	-0.016	0.45	NO
52	CDKN1B	CDKN1B	CDKN1B	13568	-0.11	0.21	NO
53	CCNE2	CCNE2	CCNE2	13738	-0.11	0.24	NO

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

Figure S74. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA PROTEASOME 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 IL1R 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	MYC	MYC	MYC	604	0.26	0.037	YES
2	CCNA1	CCNA1	CCNA1	1426	0.16	0.035	YES
3	PSMB9	PSMB9	PSMB9	1474	0.15	0.074	YES
4	PKMYT1	PKMYT1	PKMYT1	1620	0.14	0.1	YES
5	CDK7	CDK7	CDK7	2010	0.12	0.12	YES
6	PSMB7	PSMB7	PSMB7	2195	0.11	0.14	YES
7	PSMD12	PSMD12	PSMD12	2234	0.1	0.16	YES
8	SKP2	SKP2	SKP2	2504	0.096	0.17	YES
9	PSMA6	PSMA6	PSMA6	2634	0.09	0.19	YES
10	PSMB8	PSMB8	PSMB8	2771	0.085	0.21	YES
11	CKS1B	CKS1B	CKS1B	2921	0.08	0.22	YES
12	PSMC1	PSMC1	PSMC1	2979	0.078	0.24	YES
13	PSME2	PSME2	PSME2	3172	0.072	0.25	YES
14	PSMA4	PSMA4	PSMA4	3394	0.067	0.25	YES
15	RPS27A	RPS27A	RPS27A	3437	0.066	0.27	YES
16	PSMD14	PSMD14	PSMD14	3444	0.065	0.29	YES
17	PSMA2	PSMA2	PSMA2	3454	0.065	0.3	YES
18	CDKN1A	CDKN1A	CDKN1A	3455	0.065	0.32	YES
19	PSMB5	PSMB5	PSMB5	3633	0.06	0.33	YES
20	PSMB10	PSMB10	PSMB10	3723	0.058	0.34	YES
21	CDK2	CDK2	CDK2	3747	0.058	0.35	YES
22	PSMD8	PSMD8	PSMD8	3751	0.058	0.37	YES
23	PSMB2	PSMB2	PSMB2	3813	0.057	0.38	YES
24	PSMD9	PSMD9	PSMD9	3825	0.056	0.4	YES
25	PSMC6	PSMC6	PSMC6	3846	0.056	0.41	YES
26	PSMA3	PSMA3	PSMA3	3998	0.053	0.42	YES
27	PSMA7	PSMA7	PSMA7	4189	0.05	0.42	YES
28	PSMA1	PSMA1	PSMA1	4373	0.047	0.42	YES
29	PSMA5	PSMA5	PSMA5	4466	0.045	0.43	YES
30	UBA52	UBA52	UBA52	4551	0.043	0.44	YES
31	CDC25A	CDC25A	CDC25A	4632	0.042	0.44	YES
32	PSMD6	PSMD6	PSMD6	4766	0.04	0.45	YES
33	PSMB3	PSMB3	PSMB3	4805	0.039	0.46	YES
34	PSMB1	PSMB1	PSMB1	4839	0.038	0.46	YES
35	MNAT1	MNAT1	MNAT1	4851	0.038	0.47	YES
36	PSMD3	PSMD3	PSMD3	4876	0.038	0.48	YES
37	PSMB4	PSMB4	PSMB4	4900	0.037	0.49	YES
38	PSME1	PSME1	PSME1	4913	0.037	0.5	YES
39	PSMD13	PSMD13	PSMD13	5034	0.035	0.5	YES
40	PSMC4	PSMC4	PSMC4	5058	0.035	0.51	YES
41	PSMD7	PSMD7	PSMD7	5089	0.034	0.52	YES
42	PSMD11	PSMD11	PSMD11	5373	0.03	0.51	YES
43	CCNA2	CCNA2	CCNA2	5493	0.028	0.51	YES
44	PSMD2	PSMD2	PSMD2	5534	0.027	0.52	YES
45	PSMC3	PSMC3	PSMC3	5724	0.024	0.52	YES
46	PSMD4	PSMD4	PSMD4	5746	0.024	0.52	YES
47	CCNE1	CCNE1	CCNE1	5807	0.023	0.52	YES
48	PSMB6	PSMB6	PSMB6	5841	0.022	0.53	YES
49	CUL1	CUL1	CUL1	5974	0.021	0.53	NO
50	PSMC5	PSMC5	PSMC5	6120	0.018	0.52	NO
51	PSMD1	PSMD1	PSMD1	6250	0.016	0.52	NO
52	PSMC2	PSMC2	PSMC2	6383	0.015	0.52	NO
53	PSMD5	PSMD5	PSMD5	6639	0.011	0.51	NO
54	PSMF1	PSMF1	PSMF1	6828	0.0085	0.5	NO
55	MAX	MAX	MAX	7936	-0.006	0.44	NO
56	PSMD10	PSMD10	PSMD10	8325	-0.011	0.42	NO
57	SKP1	SKP1	SKP1	8644	-0.016	0.41	NO
58	CCNH	CCNH	CCNH	9540	-0.028	0.36	NO
59	RB1	RB1	RB1	11797	-0.067	0.26	NO
60	CDKN1B	CDKN1B	CDKN1B	13568	-0.11	0.19	NO
61	CCNE2	CCNE2	CCNE2	13738	-0.11	0.21	NO
62	WEE1	WEE1	WEE1	13755	-0.12	0.24	NO

Figure S75. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA IL1R PATHWAY.

Figure S76. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA IL1R 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: ST TUMOR NECROSIS FACTOR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PSMB9	PSMB9	PSMB9	1474	0.15	-0.015	YES
2	PSMB7	PSMB7	PSMB7	2195	0.11	-0.0087	YES
3	PSMD12	PSMD12	PSMD12	2234	0.1	0.034	YES
4	PSMA6	PSMA6	PSMA6	2634	0.09	0.051	YES
5	PSMB8	PSMB8	PSMB8	2771	0.085	0.08	YES
6	PSMC1	PSMC1	PSMC1	2979	0.078	0.1	YES
7	PSME2	PSME2	PSME2	3172	0.072	0.12	YES
8	PSMA4	PSMA4	PSMA4	3394	0.067	0.14	YES
9	RPS27A	RPS27A	RPS27A	3437	0.066	0.16	YES
10	PSMD14	PSMD14	PSMD14	3444	0.065	0.19	YES
11	PSMA2	PSMA2	PSMA2	3454	0.065	0.22	YES
12	CHEK1	CHEK1	CHEK1	3560	0.062	0.24	YES
13	PSMB5	PSMB5	PSMB5	3633	0.06	0.26	YES
14	PSMB10	PSMB10	PSMB10	3723	0.058	0.28	YES
15	PSMD8	PSMD8	PSMD8	3751	0.058	0.31	YES
16	PSMB2	PSMB2	PSMB2	3813	0.057	0.33	YES
17	PSMD9	PSMD9	PSMD9	3825	0.056	0.35	YES
18	PSMC6	PSMC6	PSMC6	3846	0.056	0.38	YES
19	PSMA3	PSMA3	PSMA3	3998	0.053	0.39	YES
20	PSMA7	PSMA7	PSMA7	4189	0.05	0.4	YES
21	PSMA1	PSMA1	PSMA1	4373	0.047	0.41	YES
22	PSMA5	PSMA5	PSMA5	4466	0.045	0.42	YES
23	UBA52	UBA52	UBA52	4551	0.043	0.44	YES
24	CDC25A	CDC25A	CDC25A	4632	0.042	0.45	YES
25	PSMD6	PSMD6	PSMD6	4766	0.04	0.46	YES
26	PSMB3	PSMB3	PSMB3	4805	0.039	0.48	YES
27	PSMB1	PSMB1	PSMB1	4839	0.038	0.49	YES
28	PSMD3	PSMD3	PSMD3	4876	0.038	0.51	YES
29	PSMA8	PSMA8	PSMA8	4877	0.038	0.52	YES
30	PSMB4	PSMB4	PSMB4	4900	0.037	0.54	YES
31	PSME1	PSME1	PSME1	4913	0.037	0.55	YES
32	PSMD13	PSMD13	PSMD13	5034	0.035	0.56	YES
33	PSMC4	PSMC4	PSMC4	5058	0.035	0.57	YES
34	PSMD7	PSMD7	PSMD7	5089	0.034	0.59	YES
35	PSMD11	PSMD11	PSMD11	5373	0.03	0.58	YES
36	PSMD2	PSMD2	PSMD2	5534	0.027	0.59	YES
37	PSMC3	PSMC3	PSMC3	5724	0.024	0.59	YES
38	PSMD4	PSMD4	PSMD4	5746	0.024	0.6	YES
39	PSMB6	PSMB6	PSMB6	5841	0.022	0.6	YES
40	PSMC5	PSMC5	PSMC5	6120	0.018	0.59	NO
41	PSMD1	PSMD1	PSMD1	6250	0.016	0.59	NO
42	PSMC2	PSMC2	PSMC2	6383	0.015	0.59	NO
43	PSMD5	PSMD5	PSMD5	6639	0.011	0.58	NO
44	PSMF1	PSMF1	PSMF1	6828	0.0085	0.58	NO
45	CHEK2	CHEK2	CHEK2	7532	-0.00038	0.54	NO
46	PSMD10	PSMD10	PSMD10	8325	-0.011	0.5	NO
47	PSME4	PSME4	PSME4	9691	-0.03	0.44	NO
48	ATM	ATM	ATM	12079	-0.073	0.34	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: ST TUMOR NECROSIS FACTOR PATHWAY.

Figure S78. Get High-res Image For the top 5 core enriched genes in the pathway: ST TUMOR NECROSIS FACTOR 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: ST ERK1 ERK2 MAPK PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PSMB9	PSMB9	PSMB9	1474	0.15	-0.013	YES
2	PSMB7	PSMB7	PSMB7	2195	0.11	-0.0046	YES
3	PSMD12	PSMD12	PSMD12	2234	0.1	0.04	YES
4	PSMA6	PSMA6	PSMA6	2634	0.09	0.058	YES
5	PSMB8	PSMB8	PSMB8	2771	0.085	0.089	YES
6	PSMC1	PSMC1	PSMC1	2979	0.078	0.11	YES
7	PSME2	PSME2	PSME2	3172	0.072	0.13	YES
8	PSMA4	PSMA4	PSMA4	3394	0.067	0.15	YES
9	RPS27A	RPS27A	RPS27A	3437	0.066	0.18	YES
10	PSMD14	PSMD14	PSMD14	3444	0.065	0.21	YES
11	PSMA2	PSMA2	PSMA2	3454	0.065	0.24	YES
12	PSMB5	PSMB5	PSMB5	3633	0.06	0.25	YES
13	PSMB10	PSMB10	PSMB10	3723	0.058	0.27	YES
14	CDK2	CDK2	CDK2	3747	0.058	0.3	YES
15	PSMD8	PSMD8	PSMD8	3751	0.058	0.32	YES
16	PSMB2	PSMB2	PSMB2	3813	0.057	0.35	YES
17	PSMD9	PSMD9	PSMD9	3825	0.056	0.37	YES
18	PSMC6	PSMC6	PSMC6	3846	0.056	0.39	YES
19	PSMA3	PSMA3	PSMA3	3998	0.053	0.41	YES
20	PSMA7	PSMA7	PSMA7	4189	0.05	0.42	YES
21	PSMA1	PSMA1	PSMA1	4373	0.047	0.43	YES
22	PSMA5	PSMA5	PSMA5	4466	0.045	0.45	YES
23	UBA52	UBA52	UBA52	4551	0.043	0.46	YES
24	PSMD6	PSMD6	PSMD6	4766	0.04	0.47	YES
25	PSMB3	PSMB3	PSMB3	4805	0.039	0.48	YES
26	CDC6	CDC6	CDC6	4828	0.038	0.5	YES
27	PSMB1	PSMB1	PSMB1	4839	0.038	0.52	YES
28	PSMD3	PSMD3	PSMD3	4876	0.038	0.53	YES
29	PSMA8	PSMA8	PSMA8	4877	0.038	0.55	YES
30	PSMB4	PSMB4	PSMB4	4900	0.037	0.56	YES
31	PSME1	PSME1	PSME1	4913	0.037	0.58	YES
32	PSMD13	PSMD13	PSMD13	5034	0.035	0.59	YES
33	PSMC4	PSMC4	PSMC4	5058	0.035	0.6	YES
34	PSMD7	PSMD7	PSMD7	5089	0.034	0.62	YES
35	PSMD11	PSMD11	PSMD11	5373	0.03	0.61	YES
36	PSMD2	PSMD2	PSMD2	5534	0.027	0.62	YES
37	PSMC3	PSMC3	PSMC3	5724	0.024	0.62	YES
38	PSMD4	PSMD4	PSMD4	5746	0.024	0.63	YES
39	PSMB6	PSMB6	PSMB6	5841	0.022	0.63	YES
40	PSMC5	PSMC5	PSMC5	6120	0.018	0.62	NO
41	PSMD1	PSMD1	PSMD1	6250	0.016	0.62	NO
42	PSMC2	PSMC2	PSMC2	6383	0.015	0.62	NO
43	PSMD5	PSMD5	PSMD5	6639	0.011	0.61	NO
44	PSMF1	PSMF1	PSMF1	6828	0.0085	0.61	NO
45	PSMD10	PSMD10	PSMD10	8325	-0.011	0.53	NO
46	PSME4	PSME4	PSME4	9691	-0.03	0.47	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: ST ERK1 ERK2 MAPK PATHWAY.

Figure S80. Get High-res Image For the top 5 core enriched genes in the pathway: ST ERK1 ERK2 MAPK PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Methods & Data

Input

Gene set database = c2.cp.v4.0.symbols.gmt
Expression data file = CESC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Phenotype data file = CESC-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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