GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in SKCM-TM

Skin Cutaneous Melanoma (Metastatic)

02 April 2015 | analyses__2015_04_02

Maintainer Information

Citation Information

Maintained by Juok Cho (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2015): GSEA Class2: Canonical Pathways enriched in each subtypes of mRNAseq_cNMF in SKCM-TM. Broad Institute of MIT and Harvard. doi:10.7908/C1VH5MZW

Overview

Introduction

This pipeline performs Gene Set Enrichment Analysis (GSEA) using The Broad Institute GSEA tool with MSigDB - Class2: Canonical Pathways gene sets. For a given phenotype subtype, it shows what pathways are significantly enriched in each subtype by comparing gene expression profiles between subtypes. Here, the phenotype is mRNAseq_cNMF subtypes in SKCM-TM. 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: 190
Number of samples: 367
Original number of Gene Sets: 404
Maximum gene set size: 388

Table 2. Get Full Table pheno data info

phenotype info
pheno.type: 1 - 3 :[ clus1 ] 138
pheno.type: 2 - 3 :[ clus2 ] 104
pheno.type: 3 - 3 :[ clus3 ] 125

For the expression subtypes of 18067 genes in 368 samples, GSEA found enriched gene sets in each cluster using 367 gene sets in MSigDB canonical pathways. Top enriched gene sets are listed as below.

clus1

Top enriched gene sets are BIOCARTA RACCYCD PATHWAY, KEGG CITRATE CYCLE TCA CYCLE, KEGG PENTOSE PHOSPHATE PATHWAY, KEGG OXIDATIVE PHOSPHORYLATION, KEGG SELENOAMINO ACID METABOLISM, KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM, KEGG INOSITOL PHOSPHATE METABOLISM, KEGG PYRUVATE METABOLISM, KEGG AMINOACYL TRNA BIOSYNTHESIS, KEGG RIBOSOME

And common core enriched genes are SDHA, SDHB, SDHC, ATP5A1, ATP5B, ATP5D, ATP5G1, ATP5G2, ATP5G3, ATP5H

clus2

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

And common core enriched genes are MAP3K14, NFKBIA, TNF, LAT, PIK3CG, PIK3R5, PRKCB, PTPRC, VAV1, VAV3

clus3

Top enriched gene sets are BIOCARTA NO1 PATHWAY, BIOCARTA AGR PATHWAY, BIOCARTA ALK PATHWAY, BIOCARTA NFAT PATHWAY, BIOCARTA EDG1 PATHWAY, BIOCARTA WNT PATHWAY, KEGG LYSINE DEGRADATION, KEGG ERBB SIGNALING PATHWAY, KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION, KEGG HEDGEHOG SIGNALING PATHWAY

And common core enriched genes are BMP2, BMP5, BMP7, BMPR1A, CHRD, SMAD1, SMAD5, TGFB2, TGFB3, THBS1

Results

Subtype clus1 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA RACCYCD PATHWAY	25	genes.ES.table	0.29	1.2	0.26	0.6	1	0.28	0.14	0.24	0.54	0.12
KEGG CITRATE CYCLE TCA CYCLE	29	genes.ES.table	0.55	1.9	0.016	0.048	0.14	0.59	0.19	0.48	0	0.007
KEGG PENTOSE PHOSPHATE PATHWAY	26	genes.ES.table	0.33	1	0.4	0.86	1	0.46	0.16	0.39	0.82	0.31
KEGG OXIDATIVE PHOSPHORYLATION	114	genes.ES.table	0.58	2.1	0.014	0.017	0.023	0.68	0.23	0.52	0	0.004
KEGG SELENOAMINO ACID METABOLISM	25	genes.ES.table	0.26	0.87	0.64	0.98	1	0.44	0.21	0.35	0.96	0.44
KEGG AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM	42	genes.ES.table	0.35	1.3	0.19	0.53	0.99	0.31	0.12	0.27	0.45	0.11
KEGG INOSITOL PHOSPHATE METABOLISM	52	genes.ES.table	0.22	0.86	0.69	0.96	1	0.19	0.074	0.18	0.95	0.42
KEGG PYRUVATE METABOLISM	38	genes.ES.table	0.28	0.94	0.49	0.87	1	0.37	0.17	0.31	0.84	0.29
KEGG AMINOACYL TRNA BIOSYNTHESIS	40	genes.ES.table	0.47	1.8	0.034	0.096	0.36	0.65	0.3	0.45	0	0.008
KEGG RIBOSOME	84	genes.ES.table	0.37	1	0.5	0.9	1	0.98	0.56	0.44	0.85	0.35

genes ES table in pathway: BIOCARTA RACCYCD PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ATP6V0A4	ATP6V0A4	ATP6V0A4	142	0.36	0.032	YES
2	ATP6V0D2	ATP6V0D2	ATP6V0D2	281	0.28	0.056	YES
3	COX6A2	COX6A2	COX6A2	630	0.2	0.059	YES
4	ATP6V0A1	ATP6V0A1	ATP6V0A1	881	0.16	0.063	YES
5	NDUFS7	NDUFS7	NDUFS7	995	0.15	0.074	YES
6	NDUFA8	NDUFA8	NDUFA8	1133	0.14	0.082	YES
7	ATP6V0C	ATP6V0C	ATP6V0C	1143	0.14	0.097	YES
8	ATP6AP1	ATP6AP1	ATP6AP1	1162	0.14	0.11	YES
9	NDUFS8	NDUFS8	NDUFS8	1306	0.13	0.12	YES
10	UQCRC1	UQCRC1	UQCRC1	1333	0.13	0.13	YES
11	SDHA	SDHA	SDHA	1409	0.12	0.14	YES
12	NDUFA7	NDUFA7	NDUFA7	1445	0.12	0.15	YES
13	NDUFB7	NDUFB7	NDUFB7	1458	0.12	0.16	YES
14	NDUFV1	NDUFV1	NDUFV1	1483	0.12	0.18	YES
15	ATP6V0B	ATP6V0B	ATP6V0B	1549	0.12	0.19	YES
16	ATP5G1	ATP5G1	ATP5G1	1554	0.12	0.2	YES
17	COX6A1	COX6A1	COX6A1	1569	0.11	0.21	YES
18	ATP6V1F	ATP6V1F	ATP6V1F	1680	0.11	0.22	YES
19	CYC1	CYC1	CYC1	1685	0.11	0.23	YES
20	ATP5D	ATP5D	ATP5D	1700	0.11	0.24	YES
21	NDUFV3	NDUFV3	NDUFV3	1729	0.11	0.25	YES
22	NDUFS6	NDUFS6	NDUFS6	1736	0.11	0.26	YES
23	COX5A	COX5A	COX5A	1756	0.11	0.27	YES
24	ATP6V0D1	ATP6V0D1	ATP6V0D1	1766	0.11	0.28	YES
25	NDUFA3	NDUFA3	NDUFA3	1773	0.11	0.3	YES
26	ATP12A	ATP12A	ATP12A	1820	0.1	0.3	YES
27	ATP6V1D	ATP6V1D	ATP6V1D	1838	0.1	0.32	YES
28	NDUFC2	NDUFC2	NDUFC2	1844	0.1	0.33	YES
29	ATP6V1B2	ATP6V1B2	ATP6V1B2	1848	0.1	0.34	YES
30	ATP5B	ATP5B	ATP5B	1862	0.1	0.35	YES
31	NDUFB1	NDUFB1	NDUFB1	1888	0.1	0.36	YES
32	COX5B	COX5B	COX5B	1891	0.1	0.37	YES
33	UQCR10	UQCR10	UQCR10	2038	0.094	0.37	YES
34	NDUFB4	NDUFB4	NDUFB4	2073	0.093	0.38	YES
35	COX8A	COX8A	COX8A	2207	0.089	0.38	YES
36	NDUFS2	NDUFS2	NDUFS2	2255	0.087	0.39	YES
37	COX6B1	COX6B1	COX6B1	2311	0.085	0.4	YES
38	UQCRQ	UQCRQ	UQCRQ	2318	0.085	0.4	YES
39	NDUFB9	NDUFB9	NDUFB9	2346	0.084	0.41	YES
40	ATP6V1E2	ATP6V1E2	ATP6V1E2	2374	0.083	0.42	YES
41	ATP5H	ATP5H	ATP5H	2442	0.081	0.43	YES
42	ATP6V1C1	ATP6V1C1	ATP6V1C1	2489	0.08	0.43	YES
43	ATP5G3	ATP5G3	ATP5G3	2544	0.078	0.44	YES
44	SDHB	SDHB	SDHB	2558	0.078	0.45	YES
45	NDUFA11	NDUFA11	NDUFA11	2568	0.078	0.45	YES
46	NDUFB10	NDUFB10	NDUFB10	2627	0.076	0.46	YES
47	COX6C	COX6C	COX6C	2638	0.075	0.47	YES
48	ATP6V1E1	ATP6V1E1	ATP6V1E1	2649	0.075	0.48	YES
49	NDUFA1	NDUFA1	NDUFA1	2683	0.074	0.48	YES
50	ATP6V1H	ATP6V1H	ATP6V1H	2735	0.073	0.49	YES
51	ATP5G2	ATP5G2	ATP5G2	2750	0.072	0.49	YES
52	UQCRHL	UQCRHL	UQCRHL	2845	0.07	0.5	YES
53	NDUFA6	NDUFA6	NDUFA6	2888	0.069	0.5	YES
54	NDUFA9	NDUFA9	NDUFA9	2893	0.069	0.51	YES
55	UQCRFS1	UQCRFS1	UQCRFS1	2911	0.069	0.52	YES
56	NDUFS3	NDUFS3	NDUFS3	2922	0.068	0.52	YES
57	ATP6V1G1	ATP6V1G1	ATP6V1G1	2969	0.068	0.53	YES
58	ATP5I	ATP5I	ATP5I	2971	0.068	0.54	YES
59	SDHC	SDHC	SDHC	3008	0.067	0.54	YES
60	NDUFA2	NDUFA2	NDUFA2	3301	0.059	0.53	YES
61	ATP4A	ATP4A	ATP4A	3324	0.059	0.54	YES
62	UQCRH	UQCRH	UQCRH	3499	0.055	0.53	YES
63	COX7A2L	COX7A2L	COX7A2L	3550	0.054	0.54	YES
64	NDUFB8	NDUFB8	NDUFB8	3569	0.054	0.54	YES
65	UQCRB	UQCRB	UQCRB	3607	0.053	0.55	YES
66	COX7A2	COX7A2	COX7A2	3769	0.05	0.54	YES
67	COX15	COX15	COX15	3934	0.046	0.54	YES
68	ATP5J2	ATP5J2	ATP5J2	3943	0.046	0.54	YES
69	ATP5J	ATP5J	ATP5J	3973	0.045	0.55	YES
70	COX4I1	COX4I1	COX4I1	3979	0.045	0.55	YES
71	COX7C	COX7C	COX7C	3996	0.045	0.56	YES
72	LHPP	LHPP	LHPP	4006	0.045	0.56	YES
73	NDUFB2	NDUFB2	NDUFB2	4008	0.045	0.56	YES
74	UQCR11	UQCR11	UQCR11	4024	0.044	0.57	YES
75	NDUFS5	NDUFS5	NDUFS5	4033	0.044	0.57	YES
76	ATP5A1	ATP5A1	ATP5A1	4144	0.042	0.57	YES
77	NDUFV2	NDUFV2	NDUFV2	4154	0.042	0.58	YES
78	NDUFA10	NDUFA10	NDUFA10	4704	0.032	0.55	NO
79	ATP5O	ATP5O	ATP5O	4707	0.032	0.55	NO
80	COX17	COX17	COX17	4827	0.03	0.55	NO
81	COX8C	COX8C	COX8C	4861	0.029	0.55	NO
82	NDUFAB1	NDUFAB1	NDUFAB1	4862	0.029	0.55	NO
83	NDUFC1	NDUFC1	NDUFC1	5059	0.025	0.55	NO
84	PPA2	PPA2	PPA2	5079	0.025	0.55	NO
85	NDUFS1	NDUFS1	NDUFS1	5130	0.024	0.55	NO
86	ATP5C1	ATP5C1	ATP5C1	5251	0.022	0.54	NO
87	ATP6V0E1	ATP6V0E1	ATP6V0E1	5287	0.021	0.54	NO
88	COX10	COX10	COX10	5336	0.02	0.54	NO
89	NDUFB3	NDUFB3	NDUFB3	5697	0.013	0.52	NO
90	NDUFB6	NDUFB6	NDUFB6	5749	0.012	0.52	NO
91	COX7B	COX7B	COX7B	5751	0.012	0.52	NO
92	ATP6V0E2	ATP6V0E2	ATP6V0E2	5858	0.01	0.52	NO
93	ATP5F1	ATP5F1	ATP5F1	6079	0.0058	0.51	NO
94	NDUFA4	NDUFA4	NDUFA4	6139	0.0046	0.5	NO
95	ATP6V1A	ATP6V1A	ATP6V1A	6280	0.0018	0.5	NO
96	UQCRC2	UQCRC2	UQCRC2	6499	-0.0024	0.49	NO
97	NDUFB5	NDUFB5	NDUFB5	6584	-0.0042	0.48	NO
98	ATP5L	ATP5L	ATP5L	6779	-0.0079	0.47	NO
99	TCIRG1	TCIRG1	TCIRG1	6837	-0.0089	0.47	NO
100	ATP5E	ATP5E	ATP5E	6864	-0.0096	0.47	NO
101	NDUFS4	NDUFS4	NDUFS4	7806	-0.029	0.42	NO
102	COX11	COX11	COX11	8366	-0.04	0.39	NO
103	ATP6V0A2	ATP6V0A2	ATP6V0A2	8498	-0.042	0.39	NO
104	NDUFA5	NDUFA5	NDUFA5	8721	-0.048	0.38	NO
105	ATP6V1B1	ATP6V1B1	ATP6V1B1	8982	-0.054	0.38	NO
106	COX6B2	COX6B2	COX6B2	9909	-0.075	0.33	NO
107	COX4I2	COX4I2	COX4I2	10068	-0.079	0.33	NO
108	PPA1	PPA1	PPA1	10130	-0.08	0.34	NO
109	NDUFA4L2	NDUFA4L2	NDUFA4L2	10404	-0.087	0.33	NO
110	SDHD	SDHD	SDHD	10992	-0.1	0.31	NO
111	ATP6V1G2	ATP6V1G2	ATP6V1G2	11545	-0.12	0.29	NO
112	ATP6V1C2	ATP6V1C2	ATP6V1C2	11782	-0.12	0.29	NO
113	COX7A1	COX7A1	COX7A1	14755	-0.23	0.15	NO
114	ATP4B	ATP4B	ATP4B	15435	-0.27	0.15	NO

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

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

genes ES table in pathway: KEGG CITRATE CYCLE TCA CYCLE

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	ACO2	ACO2	ACO2	961	0.16	0.019	YES
2	OGDHL	OGDHL	OGDHL	997	0.15	0.088	YES
3	SDHA	SDHA	SDHA	1409	0.12	0.12	YES
4	FH	FH	FH	1454	0.12	0.18	YES
5	IDH3G	IDH3G	IDH3G	1655	0.11	0.22	YES
6	PC	PC	PC	2199	0.089	0.23	YES
7	DLST	DLST	DLST	2234	0.088	0.27	YES
8	MDH2	MDH2	MDH2	2287	0.086	0.31	YES
9	PCK2	PCK2	PCK2	2344	0.084	0.34	YES
10	SUCLG1	SUCLG1	SUCLG1	2468	0.081	0.37	YES
11	CS	CS	CS	2525	0.079	0.41	YES
12	SDHB	SDHB	SDHB	2558	0.078	0.44	YES
13	MDH1	MDH1	MDH1	2729	0.073	0.47	YES
14	PDHA1	PDHA1	PDHA1	2840	0.07	0.49	YES
15	SDHC	SDHC	SDHC	3008	0.067	0.52	YES
16	OGDH	OGDH	OGDH	3067	0.065	0.54	YES
17	IDH3B	IDH3B	IDH3B	3432	0.057	0.55	YES
18	IDH1	IDH1	IDH1	3922	0.047	0.54	NO
19	IDH3A	IDH3A	IDH3A	4447	0.037	0.53	NO
20	ACO1	ACO1	ACO1	5412	0.018	0.49	NO
21	ACLY	ACLY	ACLY	5692	0.014	0.48	NO
22	PDHB	PDHB	PDHB	5775	0.012	0.48	NO
23	DLD	DLD	DLD	6512	-0.0027	0.44	NO
24	SUCLG2	SUCLG2	SUCLG2	6838	-0.009	0.42	NO
25	DLAT	DLAT	DLAT	7303	-0.018	0.41	NO
26	IDH2	IDH2	IDH2	7356	-0.02	0.41	NO
27	SUCLA2	SUCLA2	SUCLA2	9955	-0.076	0.31	NO
28	SDHD	SDHD	SDHD	10992	-0.1	0.3	NO
29	PCK1	PCK1	PCK1	14101	-0.2	0.22	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: KEGG CITRATE CYCLE TCA CYCLE.

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

genes ES table in pathway: KEGG PENTOSE PHOSPHATE PATHWAY

Table 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	PARS2	PARS2	PARS2	729	0.18	0.04	YES
2	NARS2	NARS2	NARS2	907	0.16	0.1	YES
3	AARS2	AARS2	AARS2	1622	0.11	0.11	YES
4	MARS2	MARS2	MARS2	1841	0.1	0.14	YES
5	SARS2	SARS2	SARS2	1843	0.1	0.19	YES
6	DARS2	DARS2	DARS2	2001	0.096	0.22	YES
7	CARS2	CARS2	CARS2	2046	0.094	0.26	YES
8	LARS2	LARS2	LARS2	2333	0.084	0.28	YES
9	EARS2	EARS2	EARS2	2668	0.075	0.3	YES
10	YARS2	YARS2	YARS2	2737	0.072	0.32	YES
11	FARSA	FARSA	FARSA	2857	0.07	0.35	YES
12	QARS	QARS	QARS	2939	0.068	0.37	YES
13	VARS2	VARS2	VARS2	2974	0.067	0.4	YES
14	VARS	VARS	VARS	3299	0.059	0.41	YES
15	AARS	AARS	AARS	3305	0.059	0.44	YES
16	NARS	NARS	NARS	3445	0.056	0.45	YES
17	SARS	SARS	SARS	3680	0.051	0.46	YES
18	WARS2	WARS2	WARS2	4196	0.042	0.45	YES
19	IARS2	IARS2	IARS2	4553	0.035	0.45	YES
20	YARS	YARS	YARS	4688	0.032	0.45	YES
21	FARS2	FARS2	FARS2	4764	0.031	0.46	YES
22	HARS2	HARS2	HARS2	5080	0.025	0.46	YES
23	WARS	WARS	WARS	5083	0.025	0.47	YES
24	GARS	GARS	GARS	5239	0.022	0.47	YES
25	MTFMT	MTFMT	MTFMT	5487	0.017	0.46	YES
26	MARS	MARS	MARS	5503	0.017	0.47	YES
27	HARS	HARS	HARS	6004	0.0074	0.44	NO
28	IARS	IARS	IARS	6128	0.0048	0.44	NO
29	FARSB	FARSB	FARSB	6410	-0.00072	0.42	NO
30	CARS	CARS	CARS	6423	-0.00087	0.42	NO
31	TARS	TARS	TARS	6503	-0.0025	0.42	NO
32	EPRS	EPRS	EPRS	6671	-0.006	0.42	NO
33	RARS	RARS	RARS	6836	-0.0089	0.41	NO
34	KARS	KARS	KARS	7181	-0.016	0.4	NO
35	LARS	LARS	LARS	7758	-0.027	0.38	NO
36	PSTK	PSTK	PSTK	7845	-0.029	0.39	NO
37	TARSL2	TARSL2	TARSL2	8888	-0.051	0.35	NO
38	DARS	DARS	DARS	9801	-0.072	0.33	NO
39	RARS2	RARS2	RARS2	10537	-0.09	0.33	NO
40	SEPSECS	SEPSECS	SEPSECS	13890	-0.2	0.23	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: KEGG PENTOSE PHOSPHATE PATHWAY.

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

genes ES table in pathway: KEGG OXIDATIVE PHOSPHORYLATION

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	SNCA	SNCA	SNCA	348	0.26	0.0073	YES
2	COX6A2	COX6A2	COX6A2	630	0.2	0.012	YES
3	SLC25A4	SLC25A4	SLC25A4	966	0.15	0.0098	YES
4	NDUFS7	NDUFS7	NDUFS7	995	0.15	0.024	YES
5	NDUFA8	NDUFA8	NDUFA8	1133	0.14	0.031	YES
6	NDUFS8	NDUFS8	NDUFS8	1306	0.13	0.035	YES
7	UQCRC1	UQCRC1	UQCRC1	1333	0.13	0.047	YES
8	SDHA	SDHA	SDHA	1409	0.12	0.056	YES
9	NDUFA7	NDUFA7	NDUFA7	1445	0.12	0.066	YES
10	NDUFB7	NDUFB7	NDUFB7	1458	0.12	0.078	YES
11	NDUFV1	NDUFV1	NDUFV1	1483	0.12	0.089	YES
12	VDAC2	VDAC2	VDAC2	1515	0.12	0.1	YES
13	ATP5G1	ATP5G1	ATP5G1	1554	0.12	0.11	YES
14	COX6A1	COX6A1	COX6A1	1569	0.11	0.12	YES
15	TH	TH	TH	1650	0.11	0.13	YES
16	CYC1	CYC1	CYC1	1685	0.11	0.14	YES
17	ATP5D	ATP5D	ATP5D	1700	0.11	0.15	YES
18	NDUFV3	NDUFV3	NDUFV3	1729	0.11	0.16	YES
19	NDUFS6	NDUFS6	NDUFS6	1736	0.11	0.17	YES
20	COX5A	COX5A	COX5A	1756	0.11	0.18	YES
21	NDUFA3	NDUFA3	NDUFA3	1773	0.11	0.19	YES
22	NDUFC2	NDUFC2	NDUFC2	1844	0.1	0.2	YES
23	ATP5B	ATP5B	ATP5B	1862	0.1	0.2	YES
24	NDUFB1	NDUFB1	NDUFB1	1888	0.1	0.21	YES
25	COX5B	COX5B	COX5B	1891	0.1	0.22	YES
26	UQCR10	UQCR10	UQCR10	2038	0.094	0.23	YES
27	NDUFB4	NDUFB4	NDUFB4	2073	0.093	0.23	YES
28	VDAC1	VDAC1	VDAC1	2087	0.093	0.24	YES
29	COX8A	COX8A	COX8A	2207	0.089	0.25	YES
30	NDUFS2	NDUFS2	NDUFS2	2255	0.087	0.25	YES
31	COX6B1	COX6B1	COX6B1	2311	0.085	0.26	YES
32	UQCRQ	UQCRQ	UQCRQ	2318	0.085	0.27	YES
33	NDUFB9	NDUFB9	NDUFB9	2346	0.084	0.27	YES
34	ATP5H	ATP5H	ATP5H	2442	0.081	0.28	YES
35	ATP5G3	ATP5G3	ATP5G3	2544	0.078	0.28	YES
36	SDHB	SDHB	SDHB	2558	0.078	0.29	YES
37	SLC25A5	SLC25A5	SLC25A5	2581	0.077	0.29	YES
38	SLC25A6	SLC25A6	SLC25A6	2623	0.076	0.3	YES
39	NDUFB10	NDUFB10	NDUFB10	2627	0.076	0.31	YES
40	COX6C	COX6C	COX6C	2638	0.075	0.31	YES
41	NDUFA1	NDUFA1	NDUFA1	2683	0.074	0.32	YES
42	ATP5G2	ATP5G2	ATP5G2	2750	0.072	0.32	YES
43	UQCRHL	UQCRHL	UQCRHL	2845	0.07	0.32	YES
44	NDUFA6	NDUFA6	NDUFA6	2888	0.069	0.33	YES
45	NDUFA9	NDUFA9	NDUFA9	2893	0.069	0.34	YES
46	UQCRFS1	UQCRFS1	UQCRFS1	2911	0.069	0.34	YES
47	NDUFS3	NDUFS3	NDUFS3	2922	0.068	0.35	YES
48	SDHC	SDHC	SDHC	3008	0.067	0.35	YES
49	NDUFA2	NDUFA2	NDUFA2	3301	0.059	0.34	YES
50	UBE2L3	UBE2L3	UBE2L3	3350	0.058	0.35	YES
51	UQCRH	UQCRH	UQCRH	3499	0.055	0.34	YES
52	UBB	UBB	UBB	3535	0.055	0.35	YES
53	COX7A2L	COX7A2L	COX7A2L	3550	0.054	0.35	YES
54	NDUFB8	NDUFB8	NDUFB8	3569	0.054	0.36	YES
55	PINK1	PINK1	PINK1	3570	0.054	0.36	YES
56	UQCRB	UQCRB	UQCRB	3607	0.053	0.37	YES
57	COX7A2	COX7A2	COX7A2	3769	0.05	0.36	YES
58	ATP5J	ATP5J	ATP5J	3973	0.045	0.36	YES
59	COX4I1	COX4I1	COX4I1	3979	0.045	0.36	YES
60	COX7C	COX7C	COX7C	3996	0.045	0.36	YES
61	NDUFB2	NDUFB2	NDUFB2	4008	0.045	0.37	YES
62	UQCR11	UQCR11	UQCR11	4024	0.044	0.37	YES
63	NDUFS5	NDUFS5	NDUFS5	4033	0.044	0.38	YES
64	ATP5A1	ATP5A1	ATP5A1	4144	0.042	0.37	YES
65	NDUFV2	NDUFV2	NDUFV2	4154	0.042	0.38	YES
66	NDUFA10	NDUFA10	NDUFA10	4704	0.032	0.35	NO
67	ATP5O	ATP5O	ATP5O	4707	0.032	0.35	NO
68	COX8C	COX8C	COX8C	4861	0.029	0.35	NO
69	NDUFAB1	NDUFAB1	NDUFAB1	4862	0.029	0.35	NO
70	NDUFC1	NDUFC1	NDUFC1	5059	0.025	0.34	NO
71	NDUFS1	NDUFS1	NDUFS1	5130	0.024	0.34	NO
72	VDAC3	VDAC3	VDAC3	5207	0.022	0.34	NO
73	ATP5C1	ATP5C1	ATP5C1	5251	0.022	0.34	NO
74	CYCS	CYCS	CYCS	5268	0.021	0.34	NO
75	PARK7	PARK7	PARK7	5695	0.013	0.32	NO
76	NDUFB3	NDUFB3	NDUFB3	5697	0.013	0.32	NO
77	NDUFB6	NDUFB6	NDUFB6	5749	0.012	0.32	NO
78	COX7B	COX7B	COX7B	5751	0.012	0.32	NO
79	HTRA2	HTRA2	HTRA2	5765	0.012	0.32	NO
80	UBA1	UBA1	UBA1	5782	0.012	0.32	NO
81	UBE2G2	UBE2G2	UBE2G2	5871	0.0099	0.32	NO
82	ATP5F1	ATP5F1	ATP5F1	6079	0.0058	0.31	NO
83	NDUFA4	NDUFA4	NDUFA4	6139	0.0046	0.3	NO
84	UBE2J2	UBE2J2	UBE2J2	6228	0.0029	0.3	NO
85	PPID	PPID	PPID	6416	-0.00076	0.29	NO
86	UQCRC2	UQCRC2	UQCRC2	6499	-0.0024	0.28	NO
87	NDUFB5	NDUFB5	NDUFB5	6584	-0.0042	0.28	NO
88	CASP9	CASP9	CASP9	6635	-0.0051	0.28	NO
89	ATP5E	ATP5E	ATP5E	6864	-0.0096	0.27	NO
90	NDUFS4	NDUFS4	NDUFS4	7806	-0.029	0.22	NO
91	NDUFA5	NDUFA5	NDUFA5	8721	-0.048	0.17	NO
92	UBE2G1	UBE2G1	UBE2G1	8722	-0.048	0.18	NO
93	COX6B2	COX6B2	COX6B2	9909	-0.075	0.12	NO
94	COX4I2	COX4I2	COX4I2	10068	-0.079	0.12	NO
95	SLC6A3	SLC6A3	SLC6A3	10240	-0.083	0.12	NO
96	NDUFA4L2	NDUFA4L2	NDUFA4L2	10404	-0.087	0.12	NO
97	SDHD	SDHD	SDHD	10992	-0.1	0.093	NO
98	UCHL1	UCHL1	UCHL1	11098	-0.1	0.098	NO
99	UBE2J1	UBE2J1	UBE2J1	11902	-0.13	0.067	NO
100	UBE2L6	UBE2L6	UBE2L6	12188	-0.14	0.065	NO
101	CASP3	CASP3	CASP3	12666	-0.15	0.055	NO
102	APAF1	APAF1	APAF1	12779	-0.16	0.064	NO
103	SLC18A2	SLC18A2	SLC18A2	13342	-0.18	0.052	NO
104	GPR37	GPR37	GPR37	13903	-0.2	0.041	NO
105	PARK2	PARK2	PARK2	13923	-0.2	0.06	NO
106	COX7A1	COX7A1	COX7A1	14755	-0.23	0.038	NO
107	UBA7	UBA7	UBA7	14961	-0.24	0.052	NO
108	LRRK2	LRRK2	LRRK2	15894	-0.3	0.031	NO
109	SLC18A1	SLC18A1	SLC18A1	17293	-0.41	-0.004	NO
110	SNCAIP	SNCAIP	SNCAIP	17507	-0.44	0.03	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: KEGG OXIDATIVE PHOSPHORYLATION.

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

genes ES table in pathway: KEGG SELENOAMINO ACID METABOLISM

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ARSG	ARSG	ARSG	55	0.46	0.038	YES
2	CTSL2	CTSL2	CTSL2	130	0.37	0.067	YES
3	ATP6V0A4	ATP6V0A4	ATP6V0A4	142	0.36	0.098	YES
4	ATP6V0D2	ATP6V0D2	ATP6V0D2	281	0.28	0.12	YES
5	CTSF	CTSF	CTSF	676	0.19	0.11	YES
6	GBA	GBA	GBA	702	0.19	0.13	YES
7	ATP6V0A1	ATP6V0A1	ATP6V0A1	881	0.16	0.13	YES
8	SORT1	SORT1	SORT1	923	0.16	0.14	YES
9	NAGLU	NAGLU	NAGLU	929	0.16	0.16	YES
10	CTNS	CTNS	CTNS	991	0.15	0.17	YES
11	ASAH1	ASAH1	ASAH1	1065	0.15	0.18	YES
12	ATP6V0C	ATP6V0C	ATP6V0C	1143	0.14	0.18	YES
13	ATP6AP1	ATP6AP1	ATP6AP1	1162	0.14	0.2	YES
14	PPT2	PPT2	PPT2	1214	0.14	0.2	YES
15	MCOLN1	MCOLN1	MCOLN1	1232	0.14	0.22	YES
16	PLA2G15	PLA2G15	PLA2G15	1236	0.13	0.23	YES
17	GLA	GLA	GLA	1256	0.13	0.24	YES
18	NPC1	NPC1	NPC1	1357	0.13	0.24	YES
19	CTSD	CTSD	CTSD	1399	0.12	0.25	YES
20	GM2A	GM2A	GM2A	1498	0.12	0.26	YES
21	ATP6V0B	ATP6V0B	ATP6V0B	1549	0.12	0.27	YES
22	CD63	CD63	CD63	1715	0.11	0.27	YES
23	HEXA	HEXA	HEXA	1748	0.11	0.27	YES
24	ATP6V0D1	ATP6V0D1	ATP6V0D1	1766	0.11	0.28	YES
25	NEU1	NEU1	NEU1	1771	0.11	0.29	YES
26	AP1S3	AP1S3	AP1S3	1915	0.099	0.29	YES
27	GGA1	GGA1	GGA1	2027	0.095	0.3	YES
28	CLTCL1	CLTCL1	CLTCL1	2062	0.094	0.3	YES
29	GLB1	GLB1	GLB1	2108	0.092	0.31	YES
30	CTSA	CTSA	CTSA	2149	0.09	0.31	YES
31	AP3M2	AP3M2	AP3M2	2177	0.09	0.32	YES
32	CLN3	CLN3	CLN3	2235	0.088	0.32	YES
33	ACP5	ACP5	ACP5	2266	0.087	0.33	YES
34	ABCB9	ABCB9	ABCB9	2424	0.082	0.33	YES
35	AP3B2	AP3B2	AP3B2	2485	0.08	0.33	YES
36	SMPD1	SMPD1	SMPD1	2498	0.08	0.34	YES
37	LAPTM4B	LAPTM4B	LAPTM4B	2580	0.077	0.34	YES
38	DNASE2B	DNASE2B	DNASE2B	2599	0.076	0.35	YES
39	CTSH	CTSH	CTSH	2600	0.076	0.35	YES
40	SGSH	SGSH	SGSH	2616	0.076	0.36	YES
41	NPC2	NPC2	NPC2	2631	0.076	0.37	YES
42	TPP1	TPP1	TPP1	2633	0.076	0.37	YES
43	ATP6V1H	ATP6V1H	ATP6V1H	2735	0.073	0.37	YES
44	NAGA	NAGA	NAGA	2739	0.072	0.38	YES
45	IGF2R	IGF2R	IGF2R	2828	0.071	0.38	YES
46	ARSA	ARSA	ARSA	2862	0.07	0.39	YES
47	AP3D1	AP3D1	AP3D1	2949	0.068	0.39	YES
48	CTSL1	CTSL1	CTSL1	2952	0.068	0.39	YES
49	AP1M1	AP1M1	AP1M1	2997	0.067	0.4	YES
50	GGA3	GGA3	GGA3	3007	0.067	0.4	YES
51	M6PR	M6PR	M6PR	3117	0.064	0.4	YES
52	AP1S1	AP1S1	AP1S1	3139	0.063	0.41	YES
53	CLTB	CLTB	CLTB	3270	0.06	0.4	NO
54	CTSZ	CTSZ	CTSZ	3533	0.055	0.4	NO
55	NAGPA	NAGPA	NAGPA	3543	0.054	0.4	NO
56	AP3S2	AP3S2	AP3S2	3580	0.054	0.4	NO
57	GGA2	GGA2	GGA2	3727	0.05	0.4	NO
58	GNPTG	GNPTG	GNPTG	3770	0.05	0.4	NO
59	PSAP	PSAP	PSAP	3947	0.046	0.39	NO
60	SLC11A2	SLC11A2	SLC11A2	4053	0.044	0.39	NO
61	ENTPD4	ENTPD4	ENTPD4	4511	0.036	0.37	NO
62	LAMP1	LAMP1	LAMP1	4675	0.033	0.36	NO
63	LAMP2	LAMP2	LAMP2	4684	0.032	0.37	NO
64	CTSB	CTSB	CTSB	4744	0.031	0.37	NO
65	GNPTAB	GNPTAB	GNPTAB	4838	0.03	0.36	NO
66	AP1B1	AP1B1	AP1B1	4864	0.029	0.36	NO
67	CTSK	CTSK	CTSK	4885	0.028	0.37	NO
68	DNASE2	DNASE2	DNASE2	4895	0.028	0.37	NO
69	CLTA	CLTA	CLTA	4897	0.028	0.37	NO
70	MAN2B1	MAN2B1	MAN2B1	4994	0.027	0.37	NO
71	AP1M2	AP1M2	AP1M2	5136	0.024	0.36	NO
72	HEXB	HEXB	HEXB	5149	0.024	0.36	NO
73	AP4M1	AP4M1	AP4M1	5523	0.016	0.34	NO
74	ABCA2	ABCA2	ABCA2	5734	0.013	0.33	NO
75	CLTC	CLTC	CLTC	5975	0.0079	0.32	NO
76	AGA	AGA	AGA	5981	0.0078	0.32	NO
77	AP3M1	AP3M1	AP3M1	6071	0.006	0.32	NO
78	GUSB	GUSB	GUSB	6268	0.0021	0.31	NO
79	SUMF1	SUMF1	SUMF1	6363	0.00039	0.3	NO
80	GNS	GNS	GNS	6529	-0.003	0.29	NO
81	CD68	CD68	CD68	6565	-0.0038	0.29	NO
82	TCIRG1	TCIRG1	TCIRG1	6837	-0.0089	0.28	NO
83	LAPTM4A	LAPTM4A	LAPTM4A	6906	-0.01	0.27	NO
84	GAA	GAA	GAA	6941	-0.011	0.27	NO
85	PPT1	PPT1	PPT1	7279	-0.018	0.26	NO
86	GALNS	GALNS	GALNS	7301	-0.018	0.26	NO
87	AP3S1	AP3S1	AP3S1	7784	-0.028	0.23	NO
88	SLC17A5	SLC17A5	SLC17A5	7996	-0.032	0.22	NO
89	LIPA	LIPA	LIPA	8028	-0.033	0.22	NO
90	AP4S1	AP4S1	AP4S1	8126	-0.035	0.22	NO
91	LGMN	LGMN	LGMN	8173	-0.036	0.22	NO
92	AP1S2	AP1S2	AP1S2	8435	-0.041	0.21	NO
93	AP1G1	AP1G1	AP1G1	8452	-0.041	0.21	NO
94	ATP6V0A2	ATP6V0A2	ATP6V0A2	8498	-0.042	0.22	NO
95	ARSB	ARSB	ARSB	9100	-0.056	0.19	NO
96	ACP2	ACP2	ACP2	9124	-0.056	0.19	NO
97	AP3B1	AP3B1	AP3B1	9243	-0.059	0.19	NO
98	AP4B1	AP4B1	AP4B1	9307	-0.06	0.19	NO
99	CLN5	CLN5	CLN5	9340	-0.061	0.19	NO
100	FUCA1	FUCA1	FUCA1	9409	-0.062	0.2	NO
101	SCARB2	SCARB2	SCARB2	9506	-0.065	0.2	NO
102	IDS	IDS	IDS	10091	-0.079	0.17	NO
103	CTSG	CTSG	CTSG	10615	-0.092	0.15	NO
104	HYAL1	HYAL1	HYAL1	10983	-0.1	0.14	NO
105	IDUA	IDUA	IDUA	11165	-0.11	0.14	NO
106	CD164	CD164	CD164	11319	-0.11	0.14	NO
107	SLC11A1	SLC11A1	SLC11A1	11374	-0.11	0.15	NO
108	AP4E1	AP4E1	AP4E1	12150	-0.14	0.12	NO
109	NAPSA	NAPSA	NAPSA	12567	-0.15	0.11	NO
110	CTSE	CTSE	CTSE	12684	-0.15	0.11	NO
111	CTSC	CTSC	CTSC	13489	-0.18	0.084	NO
112	CTSO	CTSO	CTSO	13540	-0.18	0.098	NO
113	GALC	GALC	GALC	13693	-0.19	0.11	NO
114	MANBA	MANBA	MANBA	13740	-0.19	0.12	NO
115	MFSD8	MFSD8	MFSD8	13846	-0.19	0.13	NO
116	CTSS	CTSS	CTSS	14474	-0.22	0.12	NO
117	LAPTM5	LAPTM5	LAPTM5	15199	-0.26	0.099	NO
118	CTSW	CTSW	CTSW	15812	-0.29	0.091	NO
119	LAMP3	LAMP3	LAMP3	16951	-0.38	0.061	NO

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

Figure S10. 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 AMINO SUGAR AND NUCLEOTIDE SUGAR METABOLISM

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	ERCC2	ERCC2	ERCC2	1345	0.13	-0.018	YES
2	LIG1	LIG1	LIG1	1574	0.11	0.021	YES
3	POLD1	POLD1	POLD1	1814	0.1	0.054	YES
4	POLD2	POLD2	POLD2	2157	0.09	0.076	YES
5	DDB1	DDB1	DDB1	2335	0.084	0.1	YES
6	POLE	POLE	POLE	2411	0.082	0.14	YES
7	GTF2H4	GTF2H4	GTF2H4	2507	0.079	0.17	YES
8	POLE4	POLE4	POLE4	2674	0.074	0.19	YES
9	DDB2	DDB2	DDB2	2902	0.069	0.21	YES
10	RAD23A	RAD23A	RAD23A	3089	0.065	0.23	YES
11	RFC5	RFC5	RFC5	4279	0.04	0.18	YES
12	CETN2	CETN2	CETN2	4646	0.033	0.18	YES
13	RFC2	RFC2	RFC2	4875	0.029	0.18	YES
14	RPA3	RPA3	RPA3	4970	0.027	0.18	YES
15	PCNA	PCNA	PCNA	5215	0.022	0.18	YES
16	GTF2H5	GTF2H5	GTF2H5	5469	0.017	0.17	YES
17	RBX1	RBX1	RBX1	5728	0.013	0.16	YES
18	CUL4A	CUL4A	CUL4A	5735	0.013	0.17	YES
19	ERCC1	ERCC1	ERCC1	5853	0.01	0.17	YES
20	RPA1	RPA1	RPA1	5971	0.0079	0.16	YES
21	RPA2	RPA2	RPA2	6037	0.0067	0.16	YES
22	POLD4	POLD4	POLD4	6669	-0.006	0.13	YES
23	RPA4	RPA4	RPA4	7002	-0.012	0.12	YES
24	XPC	XPC	XPC	7052	-0.014	0.12	YES
25	POLE3	POLE3	POLE3	7239	-0.017	0.12	YES
26	RFC1	RFC1	RFC1	7357	-0.02	0.12	YES
27	ERCC3	ERCC3	ERCC3	7593	-0.024	0.12	YES
28	GTF2H1	GTF2H1	GTF2H1	7605	-0.024	0.13	YES
29	POLE2	POLE2	POLE2	7747	-0.027	0.13	YES
30	RFC4	RFC4	RFC4	7854	-0.03	0.14	YES
31	POLD3	POLD3	POLD3	7966	-0.032	0.15	YES
32	MNAT1	MNAT1	MNAT1	8520	-0.043	0.14	YES
33	RFC3	RFC3	RFC3	8596	-0.045	0.15	YES
34	CDK7	CDK7	CDK7	8606	-0.045	0.17	YES
35	ERCC6	ERCC6	ERCC6	8729	-0.048	0.19	YES
36	GTF2H2	GTF2H2	GTF2H2	8878	-0.051	0.2	YES
37	CCNH	CCNH	CCNH	9323	-0.061	0.21	YES
38	ERCC5	ERCC5	ERCC5	10114	-0.08	0.2	YES
39	ERCC4	ERCC4	ERCC4	10348	-0.086	0.22	YES
40	ERCC8	ERCC8	ERCC8	11046	-0.1	0.23	YES
41	CUL4B	CUL4B	CUL4B	11414	-0.11	0.26	YES
42	GTF2H3	GTF2H3	GTF2H3	11442	-0.12	0.31	YES
43	XPA	XPA	XPA	11644	-0.12	0.36	YES

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

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

genes ES table in pathway: KEGG INOSITOL PHOSPHATE METABOLISM

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	POLR2L	POLR2L	POLR2L	825	0.17	0.07	YES
2	POLR1A	POLR1A	POLR1A	1989	0.096	0.071	YES
3	POLR3C	POLR3C	POLR3C	2455	0.081	0.1	YES
4	POLR2E	POLR2E	POLR2E	2554	0.078	0.15	YES
5	POLR2I	POLR2I	POLR2I	2686	0.074	0.19	YES
6	POLR1C	POLR1C	POLR1C	3296	0.059	0.2	YES
7	POLR2F	POLR2F	POLR2F	3302	0.059	0.24	YES
8	POLR3H	POLR3H	POLR3H	3335	0.059	0.28	YES
9	POLR3A	POLR3A	POLR3A	3902	0.047	0.28	YES
10	POLR2J	POLR2J	POLR2J	4062	0.044	0.3	YES
11	POLR2A	POLR2A	POLR2A	4093	0.043	0.33	YES
12	POLR1D	POLR1D	POLR1D	4456	0.037	0.33	YES
13	POLR3D	POLR3D	POLR3D	4642	0.033	0.34	YES
14	ZNRD1	ZNRD1	ZNRD1	5019	0.026	0.34	YES
15	POLR3K	POLR3K	POLR3K	5100	0.025	0.35	YES
16	POLR1E	POLR1E	POLR1E	5258	0.021	0.36	YES
17	POLR3B	POLR3B	POLR3B	5541	0.016	0.35	YES
18	POLR2G	POLR2G	POLR2G	6847	-0.0092	0.29	YES
19	POLR2C	POLR2C	POLR2C	7026	-0.013	0.29	YES
20	POLR3GL	POLR3GL	POLR3GL	7241	-0.017	0.29	YES
21	POLR2D	POLR2D	POLR2D	7321	-0.019	0.3	YES
22	POLR2B	POLR2B	POLR2B	7734	-0.027	0.29	YES
23	POLR2J2	POLR2J2	POLR2J2	8219	-0.036	0.29	YES
24	POLR2K	POLR2K	POLR2K	8422	-0.041	0.3	YES
25	POLR2J3	POLR2J3	POLR2J3	8778	-0.049	0.32	YES
26	POLR3G	POLR3G	POLR3G	9432	-0.063	0.33	YES
27	POLR1B	POLR1B	POLR1B	11278	-0.11	0.3	YES
28	POLR3F	POLR3F	POLR3F	11376	-0.11	0.37	YES

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

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

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	RENBP	RENBP	RENBP	310	0.27	0.048	YES
2	AMDHD2	AMDHD2	AMDHD2	354	0.25	0.11	YES
3	GALK1	GALK1	GALK1	534	0.22	0.15	YES
4	GALE	GALE	GALE	787	0.17	0.18	YES
5	CYB5R1	CYB5R1	CYB5R1	973	0.15	0.2	YES
6	NANS	NANS	NANS	1049	0.15	0.24	YES
7	GPI	GPI	GPI	1451	0.12	0.24	YES
8	PMM1	PMM1	PMM1	1532	0.12	0.27	YES
9	GNPDA1	GNPDA1	GNPDA1	1545	0.12	0.3	YES
10	HEXA	HEXA	HEXA	1748	0.11	0.31	YES
11	GMPPB	GMPPB	GMPPB	1954	0.098	0.32	YES
12	TSTA3	TSTA3	TSTA3	2133	0.091	0.33	YES
13	FUK	FUK	FUK	2176	0.09	0.35	YES
14	PGM1	PGM1	PGM1	2656	0.075	0.34	NO
15	GMPPA	GMPPA	GMPPA	3307	0.059	0.32	NO
16	MPI	MPI	MPI	3529	0.055	0.32	NO
17	GMDS	GMDS	GMDS	4227	0.041	0.3	NO
18	GALT	GALT	GALT	4603	0.034	0.28	NO
19	HK2	HK2	HK2	4624	0.034	0.29	NO
20	HEXB	HEXB	HEXB	5149	0.024	0.27	NO
21	CHIT1	CHIT1	CHIT1	5531	0.016	0.25	NO
22	PMM2	PMM2	PMM2	6014	0.0072	0.22	NO
23	NAGK	NAGK	NAGK	6041	0.0066	0.22	NO
24	HK1	HK1	HK1	6685	-0.0062	0.19	NO
25	CMAS	CMAS	CMAS	6962	-0.012	0.18	NO
26	NPL	NPL	NPL	7216	-0.017	0.17	NO
27	GNPNAT1	GNPNAT1	GNPNAT1	7514	-0.022	0.16	NO
28	GFPT1	GFPT1	GFPT1	7831	-0.029	0.15	NO
29	UXS1	UXS1	UXS1	8194	-0.036	0.14	NO
30	NANP	NANP	NANP	9130	-0.056	0.097	NO
31	UGP2	UGP2	UGP2	9251	-0.059	0.1	NO
32	GALK2	GALK2	GALK2	9401	-0.062	0.11	NO
33	GNE	GNE	GNE	9514	-0.065	0.12	NO
34	UAP1	UAP1	UAP1	10076	-0.079	0.11	NO
35	UGDH	UGDH	UGDH	10879	-0.099	0.088	NO
36	PGM3	PGM3	PGM3	12079	-0.13	0.054	NO
37	GNPDA2	GNPDA2	GNPDA2	12215	-0.14	0.08	NO
38	PGM2	PGM2	PGM2	12259	-0.14	0.11	NO
39	FPGT	FPGT	FPGT	12604	-0.15	0.13	NO
40	GFPT2	GFPT2	GFPT2	12850	-0.16	0.15	NO
41	GCK	GCK	GCK	14441	-0.22	0.12	NO
42	HK3	HK3	HK3	16525	-0.34	0.085	NO

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

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

genes ES table in pathway: KEGG AMINOACYL TRNA BIOSYNTHESIS

Table 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	MME	MME	MME	198	0.33	0.01	YES
2	PSEN2	PSEN2	PSEN2	299	0.27	0.022	YES
3	SNCA	SNCA	SNCA	348	0.26	0.036	YES
4	BACE2	BACE2	BACE2	471	0.23	0.044	YES
5	CACNA1D	CACNA1D	CACNA1D	623	0.2	0.048	YES
6	COX6A2	COX6A2	COX6A2	630	0.2	0.06	YES
7	MAPT	MAPT	MAPT	668	0.19	0.07	YES
8	CHP2	CHP2	CHP2	826	0.17	0.072	YES
9	FADD	FADD	FADD	964	0.16	0.074	YES
10	CDK5R1	CDK5R1	CDK5R1	965	0.15	0.084	YES
11	NDUFS7	NDUFS7	NDUFS7	995	0.15	0.092	YES
12	NDUFA8	NDUFA8	NDUFA8	1133	0.14	0.094	YES
13	NDUFS8	NDUFS8	NDUFS8	1306	0.13	0.092	YES
14	UQCRC1	UQCRC1	UQCRC1	1333	0.13	0.099	YES
15	APOE	APOE	APOE	1404	0.12	0.1	YES
16	SDHA	SDHA	SDHA	1409	0.12	0.11	YES
17	NDUFA7	NDUFA7	NDUFA7	1445	0.12	0.12	YES
18	NDUFB7	NDUFB7	NDUFB7	1458	0.12	0.12	YES
19	NDUFV1	NDUFV1	NDUFV1	1483	0.12	0.13	YES
20	ATP5G1	ATP5G1	ATP5G1	1554	0.12	0.13	YES
21	COX6A1	COX6A1	COX6A1	1569	0.11	0.14	YES
22	CYC1	CYC1	CYC1	1685	0.11	0.14	YES
23	ATP5D	ATP5D	ATP5D	1700	0.11	0.15	YES
24	NDUFV3	NDUFV3	NDUFV3	1729	0.11	0.15	YES
25	NDUFS6	NDUFS6	NDUFS6	1736	0.11	0.16	YES
26	COX5A	COX5A	COX5A	1756	0.11	0.16	YES
27	NDUFA3	NDUFA3	NDUFA3	1773	0.11	0.17	YES
28	NDUFC2	NDUFC2	NDUFC2	1844	0.1	0.17	YES
29	ATP5B	ATP5B	ATP5B	1862	0.1	0.18	YES
30	NDUFB1	NDUFB1	NDUFB1	1888	0.1	0.18	YES
31	COX5B	COX5B	COX5B	1891	0.1	0.19	YES
32	UQCR10	UQCR10	UQCR10	2038	0.094	0.19	YES
33	NDUFB4	NDUFB4	NDUFB4	2073	0.093	0.19	YES
34	CDK5	CDK5	CDK5	2150	0.09	0.19	YES
35	GRIN1	GRIN1	GRIN1	2161	0.09	0.2	YES
36	COX8A	COX8A	COX8A	2207	0.089	0.2	YES
37	NDUFS2	NDUFS2	NDUFS2	2255	0.087	0.2	YES
38	COX6B1	COX6B1	COX6B1	2311	0.085	0.21	YES
39	UQCRQ	UQCRQ	UQCRQ	2318	0.085	0.21	YES
40	CAPN1	CAPN1	CAPN1	2328	0.084	0.22	YES
41	NDUFB9	NDUFB9	NDUFB9	2346	0.084	0.22	YES
42	APH1A	APH1A	APH1A	2431	0.081	0.22	YES
43	ATP5H	ATP5H	ATP5H	2442	0.081	0.23	YES
44	ATP5G3	ATP5G3	ATP5G3	2544	0.078	0.22	YES
45	SDHB	SDHB	SDHB	2558	0.078	0.23	YES
46	NDUFB10	NDUFB10	NDUFB10	2627	0.076	0.23	YES
47	COX6C	COX6C	COX6C	2638	0.075	0.24	YES
48	NDUFA1	NDUFA1	NDUFA1	2683	0.074	0.24	YES
49	CHP	CHP	CHP	2722	0.073	0.24	YES
50	ATP5G2	ATP5G2	ATP5G2	2750	0.072	0.24	YES
51	UQCRHL	UQCRHL	UQCRHL	2845	0.07	0.24	YES
52	PSENEN	PSENEN	PSENEN	2846	0.07	0.25	YES
53	NDUFA6	NDUFA6	NDUFA6	2888	0.069	0.25	YES
54	NDUFA9	NDUFA9	NDUFA9	2893	0.069	0.25	YES
55	UQCRFS1	UQCRFS1	UQCRFS1	2911	0.069	0.26	YES
56	NDUFS3	NDUFS3	NDUFS3	2922	0.068	0.26	YES
57	SDHC	SDHC	SDHC	3008	0.067	0.26	YES
58	NDUFA2	NDUFA2	NDUFA2	3301	0.059	0.25	YES
59	GAPDH	GAPDH	GAPDH	3366	0.058	0.25	YES
60	UQCRH	UQCRH	UQCRH	3499	0.055	0.24	YES
61	CAPN2	CAPN2	CAPN2	3502	0.055	0.25	YES
62	COX7A2L	COX7A2L	COX7A2L	3550	0.054	0.25	YES
63	NDUFB8	NDUFB8	NDUFB8	3569	0.054	0.25	YES
64	UQCRB	UQCRB	UQCRB	3607	0.053	0.25	YES
65	APBB1	APBB1	APBB1	3669	0.052	0.25	YES
66	MAPK3	MAPK3	MAPK3	3683	0.051	0.25	YES
67	MAPK1	MAPK1	MAPK1	3690	0.051	0.26	YES
68	PLCB3	PLCB3	PLCB3	3724	0.051	0.26	YES
69	COX7A2	COX7A2	COX7A2	3769	0.05	0.26	YES
70	NCSTN	NCSTN	NCSTN	3909	0.047	0.25	YES
71	ATP5J	ATP5J	ATP5J	3973	0.045	0.25	YES
72	COX4I1	COX4I1	COX4I1	3979	0.045	0.26	YES
73	COX7C	COX7C	COX7C	3996	0.045	0.26	YES
74	NDUFB2	NDUFB2	NDUFB2	4008	0.045	0.26	YES
75	UQCR11	UQCR11	UQCR11	4024	0.044	0.26	YES
76	NDUFS5	NDUFS5	NDUFS5	4033	0.044	0.26	YES
77	CALML5	CALML5	CALML5	4047	0.044	0.27	YES
78	HSD17B10	HSD17B10	HSD17B10	4105	0.043	0.27	YES
79	ATP5A1	ATP5A1	ATP5A1	4144	0.042	0.27	YES
80	NDUFV2	NDUFV2	NDUFV2	4154	0.042	0.27	YES
81	ITPR3	ITPR3	ITPR3	4181	0.042	0.27	YES
82	ATP2A2	ATP2A2	ATP2A2	4471	0.037	0.26	NO
83	NDUFA10	NDUFA10	NDUFA10	4704	0.032	0.25	NO
84	ATP5O	ATP5O	ATP5O	4707	0.032	0.25	NO
85	CALML3	CALML3	CALML3	4749	0.031	0.25	NO
86	BAD	BAD	BAD	4823	0.03	0.24	NO
87	COX8C	COX8C	COX8C	4861	0.029	0.24	NO
88	NDUFAB1	NDUFAB1	NDUFAB1	4862	0.029	0.25	NO
89	NDUFC1	NDUFC1	NDUFC1	5059	0.025	0.24	NO
90	NDUFS1	NDUFS1	NDUFS1	5130	0.024	0.24	NO
91	PSEN1	PSEN1	PSEN1	5243	0.022	0.23	NO
92	ATP5C1	ATP5C1	ATP5C1	5251	0.022	0.23	NO
93	CYCS	CYCS	CYCS	5268	0.021	0.23	NO
94	NDUFB3	NDUFB3	NDUFB3	5697	0.013	0.21	NO
95	NDUFB6	NDUFB6	NDUFB6	5749	0.012	0.21	NO
96	COX7B	COX7B	COX7B	5751	0.012	0.21	NO
97	ATP5F1	ATP5F1	ATP5F1	6079	0.0058	0.19	NO
98	NDUFA4	NDUFA4	NDUFA4	6139	0.0046	0.19	NO
99	CALM3	CALM3	CALM3	6174	0.0039	0.18	NO
100	ATF6	ATF6	ATF6	6260	0.0022	0.18	NO
101	UQCRC2	UQCRC2	UQCRC2	6499	-0.0024	0.17	NO
102	CALM1	CALM1	CALM1	6570	-0.0039	0.16	NO
103	NDUFB5	NDUFB5	NDUFB5	6584	-0.0042	0.16	NO
104	CASP9	CASP9	CASP9	6635	-0.0051	0.16	NO
105	ATP5E	ATP5E	ATP5E	6864	-0.0096	0.15	NO
106	CACNA1S	CACNA1S	CACNA1S	7163	-0.016	0.13	NO
107	ADAM10	ADAM10	ADAM10	7198	-0.016	0.13	NO
108	RYR3	RYR3	RYR3	7263	-0.018	0.13	NO
109	GSK3B	GSK3B	GSK3B	7338	-0.019	0.13	NO
110	NDUFS4	NDUFS4	NDUFS4	7806	-0.029	0.1	NO
111	PPP3CC	PPP3CC	PPP3CC	8055	-0.034	0.091	NO
112	GRIN2D	GRIN2D	GRIN2D	8208	-0.036	0.084	NO
113	GNAQ	GNAQ	GNAQ	8269	-0.038	0.084	NO
114	GRIN2C	GRIN2C	GRIN2C	8341	-0.039	0.082	NO
115	ERN1	ERN1	ERN1	8369	-0.04	0.083	NO
116	NDUFA5	NDUFA5	NDUFA5	8721	-0.048	0.066	NO
117	NAE1	NAE1	NAE1	8904	-0.052	0.06	NO
118	PPP3R1	PPP3R1	PPP3R1	9131	-0.056	0.051	NO
119	LRP1	LRP1	LRP1	9224	-0.058	0.049	NO
120	ATP2A1	ATP2A1	ATP2A1	9363	-0.061	0.045	NO
121	TNFRSF1A	TNFRSF1A	TNFRSF1A	9435	-0.063	0.046	NO
122	GRIN2A	GRIN2A	GRIN2A	9882	-0.074	0.025	NO
123	COX6B2	COX6B2	COX6B2	9909	-0.075	0.029	NO
124	APP	APP	APP	9969	-0.076	0.03	NO
125	COX4I2	COX4I2	COX4I2	10068	-0.079	0.03	NO
126	IDE	IDE	IDE	10189	-0.082	0.028	NO
127	NDUFA4L2	NDUFA4L2	NDUFA4L2	10404	-0.087	0.022	NO
128	CALM2	CALM2	CALM2	10451	-0.088	0.025	NO
129	GRIN2B	GRIN2B	GRIN2B	10484	-0.089	0.029	NO
130	PPP3CB	PPP3CB	PPP3CB	10654	-0.093	0.026	NO
131	SDHD	SDHD	SDHD	10992	-0.1	0.013	NO
132	EIF2AK3	EIF2AK3	EIF2AK3	11061	-0.1	0.016	NO
133	BID	BID	BID	11345	-0.11	0.0074	NO
134	BACE1	BACE1	BACE1	11928	-0.13	-0.017	NO
135	PPP3CA	PPP3CA	PPP3CA	12571	-0.15	-0.043	NO
136	CASP3	CASP3	CASP3	12666	-0.15	-0.039	NO
137	APAF1	APAF1	APAF1	12779	-0.16	-0.035	NO
138	PPP3R2	PPP3R2	PPP3R2	12952	-0.16	-0.035	NO
139	ITPR2	ITPR2	ITPR2	13024	-0.16	-0.028	NO
140	ADAM17	ADAM17	ADAM17	13149	-0.17	-0.024	NO
141	CALML6	CALML6	CALML6	13242	-0.17	-0.019	NO
142	CACNA1F	CACNA1F	CACNA1F	13808	-0.19	-0.038	NO
143	CASP7	CASP7	CASP7	14102	-0.2	-0.041	NO
144	NOS1	NOS1	NOS1	14669	-0.23	-0.058	NO
145	COX7A1	COX7A1	COX7A1	14755	-0.23	-0.048	NO
146	CASP8	CASP8	CASP8	14891	-0.24	-0.04	NO
147	PLCB4	PLCB4	PLCB4	15058	-0.25	-0.034	NO
148	ATP2A3	ATP2A3	ATP2A3	15584	-0.28	-0.046	NO
149	PLCB2	PLCB2	PLCB2	15851	-0.29	-0.042	NO
150	ITPR1	ITPR1	ITPR1	15966	-0.3	-0.029	NO
151	LPL	LPL	LPL	16232	-0.32	-0.023	NO
152	TNF	TNF	TNF	16449	-0.33	-0.014	NO
153	CACNA1C	CACNA1C	CACNA1C	16534	-0.34	0.0029	NO
154	FAS	FAS	FAS	17353	-0.42	-0.016	NO
155	IL1B	IL1B	IL1B	17378	-0.42	0.0098	NO
156	PLCB1	PLCB1	PLCB1	17446	-0.43	0.034	NO

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

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

genes ES table in pathway: KEGG RIBOSOME

Table 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	ATP6V0A4	ATP6V0A4	ATP6V0A4	142	0.36	0.064	YES
2	ATP6V0D2	ATP6V0D2	ATP6V0D2	281	0.28	0.11	YES
3	ATP6V0A1	ATP6V0A1	ATP6V0A1	881	0.16	0.11	YES
4	ADCY9	ADCY9	ADCY9	933	0.16	0.14	YES
5	ATP6V0C	ATP6V0C	ATP6V0C	1143	0.14	0.16	YES
6	ATP6AP1	ATP6AP1	ATP6AP1	1162	0.14	0.19	YES
7	ATP6V0B	ATP6V0B	ATP6V0B	1549	0.12	0.19	YES
8	ATP6V1F	ATP6V1F	ATP6V1F	1680	0.11	0.2	YES
9	ATP6V0D1	ATP6V0D1	ATP6V0D1	1766	0.11	0.22	YES
10	ATP6V1D	ATP6V1D	ATP6V1D	1838	0.1	0.24	YES
11	ATP6V1B2	ATP6V1B2	ATP6V1B2	1848	0.1	0.26	YES
12	KDELR3	KDELR3	KDELR3	2358	0.083	0.24	YES
13	ATP6V1E2	ATP6V1E2	ATP6V1E2	2374	0.083	0.26	YES
14	ATP6V1C1	ATP6V1C1	ATP6V1C1	2489	0.08	0.27	YES
15	ACTG1	ACTG1	ACTG1	2643	0.075	0.28	YES
16	ATP6V1E1	ATP6V1E1	ATP6V1E1	2649	0.075	0.29	YES
17	ATP6V1H	ATP6V1H	ATP6V1H	2735	0.073	0.3	YES
18	TJP2	TJP2	TJP2	2836	0.07	0.31	YES
19	ATP6V1G1	ATP6V1G1	ATP6V1G1	2969	0.068	0.32	YES
20	KDELR1	KDELR1	KDELR1	3875	0.048	0.28	NO
21	ARF1	ARF1	ARF1	4021	0.045	0.28	NO
22	SEC61B	SEC61B	SEC61B	5073	0.025	0.22	NO
23	ATP6V0E1	ATP6V0E1	ATP6V0E1	5287	0.021	0.21	NO
24	SEC61A2	SEC61A2	SEC61A2	5629	0.014	0.2	NO
25	PRKACA	PRKACA	PRKACA	5677	0.014	0.2	NO
26	ACTB	ACTB	ACTB	5714	0.013	0.2	NO
27	ATP6V0E2	ATP6V0E2	ATP6V0E2	5858	0.01	0.19	NO
28	SEC61A1	SEC61A1	SEC61A1	6275	0.0019	0.17	NO
29	ATP6V1A	ATP6V1A	ATP6V1A	6280	0.0018	0.17	NO
30	PLCG1	PLCG1	PLCG1	6774	-0.0078	0.14	NO
31	TCIRG1	TCIRG1	TCIRG1	6837	-0.0089	0.14	NO
32	SEC61G	SEC61G	SEC61G	7086	-0.014	0.13	NO
33	ERO1L	ERO1L	ERO1L	7266	-0.018	0.13	NO
34	KDELR2	KDELR2	KDELR2	7353	-0.019	0.12	NO
35	GNAS	GNAS	GNAS	7902	-0.03	0.1	NO
36	ATP6V0A2	ATP6V0A2	ATP6V0A2	8498	-0.042	0.076	NO
37	ATP6V1B1	ATP6V1B1	ATP6V1B1	8982	-0.054	0.06	NO
38	CFTR	CFTR	CFTR	10202	-0.082	0.0088	NO
39	PDIA4	PDIA4	PDIA4	10928	-0.1	-0.011	NO
40	ATP6V1G2	ATP6V1G2	ATP6V1G2	11545	-0.12	-0.022	NO
41	ATP6V1C2	ATP6V1C2	ATP6V1C2	11782	-0.12	-0.0098	NO
42	TJP1	TJP1	TJP1	12239	-0.14	-0.0074	NO
43	SLC12A2	SLC12A2	SLC12A2	12389	-0.14	0.013	NO
44	PRKCB	PRKCB	PRKCB	13148	-0.17	0.0045	NO
45	PRKX	PRKX	PRKX	13366	-0.18	0.028	NO
46	PLCG2	PLCG2	PLCG2	14119	-0.2	0.027	NO
47	KCNQ1	KCNQ1	KCNQ1	14230	-0.21	0.063	NO
48	PRKCG	PRKCG	PRKCG	14691	-0.23	0.084	NO
49	PRKACB	PRKACB	PRKACB	14968	-0.24	0.12	NO
50	PRKCA	PRKCA	PRKCA	15451	-0.27	0.14	NO

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

Figure S20. 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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus2 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.25	0.74	0.81	0.79	1	0.31	0.31	0.22	0.8	0
BIOCARTA AT1R PATHWAY	32	genes.ES.table	0.38	1.4	0.13	0.17	0.96	0.062	0.052	0.059	0.13	0
BIOCARTA BCR PATHWAY	33	genes.ES.table	0.73	2	0.002	0.022	0.055	0.24	0.056	0.23	0	0.004
BIOCARTA BIOPEPTIDES PATHWAY	39	genes.ES.table	0.46	1.7	0.012	0.049	0.57	0.31	0.24	0.24	0.022	0
BIOCARTA HDAC PATHWAY	27	genes.ES.table	0.51	1.7	0.01	0.043	0.48	0.48	0.31	0.33	0	0
BIOCARTA EGF PATHWAY	30	genes.ES.table	0.52	1.7	0.016	0.045	0.46	0.53	0.34	0.35	0	0
BIOCARTA FAS PATHWAY	29	genes.ES.table	0.56	1.8	0	0.031	0.29	0.28	0.18	0.23	0	0
BIOCARTA FCER1 PATHWAY	37	genes.ES.table	0.64	1.9	0.004	0.025	0.23	0.24	0.11	0.22	0	0
BIOCARTA FMLP PATHWAY	34	genes.ES.table	0.57	1.9	0	0.026	0.2	0.29	0.22	0.23	0	0
BIOCARTA GH PATHWAY	26	genes.ES.table	0.57	1.7	0.02	0.046	0.55	0.19	0.076	0.18	0.02	0

genes ES table in pathway: BIOCARTA AGR 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	PTPRC	PTPRC	PTPRC	230	0.77	0.036	YES
2	NCF1	NCF1	NCF1	269	0.74	0.08	YES
3	VAV1	VAV1	VAV1	284	0.74	0.12	YES
4	PIK3CG	PIK3CG	PIK3CG	345	0.7	0.17	YES
5	WAS	WAS	WAS	385	0.68	0.21	YES
6	PRKCB	PRKCB	PRKCB	409	0.66	0.25	YES
7	DOCK2	DOCK2	DOCK2	410	0.66	0.29	YES
8	INPP5D	INPP5D	INPP5D	431	0.65	0.33	YES
9	FCGR1A	FCGR1A	FCGR1A	486	0.62	0.36	YES
10	RAC2	RAC2	RAC2	494	0.62	0.4	YES
11	PIK3R5	PIK3R5	PIK3R5	514	0.61	0.44	YES
12	HCK	HCK	HCK	588	0.57	0.47	YES
13	LAT	LAT	LAT	654	0.55	0.5	YES
14	SYK	SYK	SYK	771	0.5	0.53	YES
15	PLCG2	PLCG2	PLCG2	839	0.48	0.55	YES
16	FCGR3A	FCGR3A	FCGR3A	975	0.44	0.57	YES
17	LYN	LYN	LYN	1002	0.43	0.6	YES
18	FCGR2B	FCGR2B	FCGR2B	1202	0.38	0.61	YES
19	VAV3	VAV3	VAV3	1268	0.36	0.63	YES
20	FCGR2C	FCGR2C	FCGR2C	1504	0.31	0.64	YES
21	PIP5K1B	PIP5K1B	PIP5K1B	1644	0.28	0.65	YES
22	PRKCG	PRKCG	PRKCG	2145	0.22	0.63	NO
23	PIK3CD	PIK3CD	PIK3CD	2451	0.19	0.63	NO
24	FCGR2A	FCGR2A	FCGR2A	2779	0.16	0.62	NO
25	MARCKS	MARCKS	MARCKS	4253	0.088	0.54	NO
26	ARPC3	ARPC3	ARPC3	4336	0.085	0.54	NO
27	VASP	VASP	VASP	4517	0.08	0.54	NO
28	PIK3R3	PIK3R3	PIK3R3	4702	0.075	0.53	NO
29	PIK3R1	PIK3R1	PIK3R1	4757	0.074	0.54	NO
30	PIK3CA	PIK3CA	PIK3CA	4930	0.07	0.53	NO
31	ARF6	ARF6	ARF6	4958	0.069	0.53	NO
32	PPAP2B	PPAP2B	PPAP2B	5059	0.067	0.53	NO
33	ARPC2	ARPC2	ARPC2	5221	0.063	0.53	NO
34	PPAP2A	PPAP2A	PPAP2A	5257	0.062	0.53	NO
35	PAK1	PAK1	PAK1	5375	0.059	0.52	NO
36	PLD1	PLD1	PLD1	5452	0.058	0.52	NO
37	ARPC5	ARPC5	ARPC5	5591	0.055	0.52	NO
38	CDC42	CDC42	CDC42	5671	0.053	0.52	NO
39	LIMK2	LIMK2	LIMK2	5691	0.053	0.52	NO
40	DNM3	DNM3	DNM3	5727	0.052	0.52	NO
41	PIK3CB	PIK3CB	PIK3CB	5836	0.05	0.52	NO
42	SPHK1	SPHK1	SPHK1	5867	0.05	0.52	NO
43	RPS6KB1	RPS6KB1	RPS6KB1	5900	0.049	0.52	NO
44	AMPH	AMPH	AMPH	6024	0.046	0.52	NO
45	ARPC5L	ARPC5L	ARPC5L	6038	0.046	0.52	NO
46	PRKCD	PRKCD	PRKCD	6116	0.045	0.52	NO
47	MAP2K1	MAP2K1	MAP2K1	6134	0.045	0.52	NO
48	ARPC1B	ARPC1B	ARPC1B	6364	0.041	0.51	NO
49	ARPC4	ARPC4	ARPC4	6899	0.032	0.48	NO
50	SCIN	SCIN	SCIN	7151	0.028	0.47	NO
51	PIKFYVE	PIKFYVE	PIKFYVE	7238	0.027	0.47	NO
52	LIMK1	LIMK1	LIMK1	7588	0.022	0.45	NO
53	DNM2	DNM2	DNM2	7645	0.022	0.45	NO
54	CFL1	CFL1	CFL1	8463	0.011	0.4	NO
55	RAF1	RAF1	RAF1	8684	0.0083	0.39	NO
56	ASAP3	ASAP3	ASAP3	9004	0.0045	0.37	NO
57	WASF2	WASF2	WASF2	9125	0.0031	0.37	NO
58	PLD2	PLD2	PLD2	9787	-0.0046	0.33	NO
59	GSN	GSN	GSN	10172	-0.009	0.31	NO
60	MARCKSL1	MARCKSL1	MARCKSL1	10257	-0.0098	0.31	NO
61	MAPK3	MAPK3	MAPK3	10357	-0.011	0.3	NO
62	PLA2G6	PLA2G6	PLA2G6	10602	-0.014	0.29	NO
63	RAC1	RAC1	RAC1	11412	-0.023	0.24	NO
64	PIP5K1C	PIP5K1C	PIP5K1C	11497	-0.024	0.24	NO
65	DNM1L	DNM1L	DNM1L	11669	-0.025	0.23	NO
66	MAPK1	MAPK1	MAPK1	12160	-0.031	0.21	NO
67	CRKL	CRKL	CRKL	12203	-0.031	0.21	NO
68	WASL	WASL	WASL	12337	-0.033	0.2	NO
69	AKT1	AKT1	AKT1	12366	-0.033	0.2	NO
70	SPHK2	SPHK2	SPHK2	12550	-0.035	0.2	NO
71	ASAP1	ASAP1	ASAP1	12993	-0.041	0.17	NO
72	ARPC1A	ARPC1A	ARPC1A	13579	-0.048	0.14	NO
73	PLCG1	PLCG1	PLCG1	13619	-0.049	0.14	NO
74	AKT3	AKT3	AKT3	13688	-0.05	0.14	NO
75	VAV2	VAV2	VAV2	13764	-0.051	0.14	NO
76	AKT2	AKT2	AKT2	13834	-0.052	0.14	NO
77	PIP4K2B	PIP4K2B	PIP4K2B	14041	-0.055	0.14	NO
78	CRK	CRK	CRK	14161	-0.056	0.13	NO
79	PLA2G4D	PLA2G4D	PLA2G4D	14304	-0.059	0.13	NO
80	PIP5K1A	PIP5K1A	PIP5K1A	14585	-0.063	0.12	NO
81	PLA2G4A	PLA2G4A	PLA2G4A	14599	-0.064	0.12	NO
82	PRKCE	PRKCE	PRKCE	14650	-0.065	0.12	NO
83	CFL2	CFL2	CFL2	14754	-0.066	0.12	NO
84	MYO10	MYO10	MYO10	15075	-0.073	0.1	NO
85	ASAP2	ASAP2	ASAP2	15619	-0.084	0.08	NO
86	GAB2	GAB2	GAB2	15732	-0.088	0.08	NO
87	WASF1	WASF1	WASF1	16032	-0.096	0.069	NO
88	WASF3	WASF3	WASF3	16077	-0.098	0.073	NO
89	PLA2G4F	PLA2G4F	PLA2G4F	16159	-0.1	0.075	NO
90	PRKCA	PRKCA	PRKCA	16304	-0.11	0.073	NO
91	PIK3R2	PIK3R2	PIK3R2	16574	-0.12	0.066	NO
92	PPAP2C	PPAP2C	PPAP2C	16719	-0.12	0.065	NO
93	DNM1	DNM1	DNM1	16950	-0.14	0.061	NO

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

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

genes ES table in pathway: BIOCARTA AT1R PATHWAY

Table 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	TLR10	TLR10	TLR10	59	0.93	0.15	YES
2	TLR9	TLR9	TLR9	223	0.78	0.26	YES
3	TLR7	TLR7	TLR7	383	0.68	0.36	YES
4	TLR4	TLR4	TLR4	1075	0.41	0.39	YES
5	TLR6	TLR6	TLR6	1142	0.4	0.45	YES
6	TLR2	TLR2	TLR2	1298	0.36	0.5	YES
7	CD14	CD14	CD14	1486	0.31	0.54	YES
8	TLR3	TLR3	TLR3	1574	0.3	0.59	YES
9	NFKBIA	NFKBIA	NFKBIA	1804	0.26	0.62	YES
10	LY96	LY96	LY96	1835	0.25	0.66	YES
11	MAP3K14	MAP3K14	MAP3K14	1930	0.24	0.69	YES
12	MAP2K6	MAP2K6	MAP2K6	2700	0.16	0.67	NO
13	MYD88	MYD88	MYD88	3369	0.12	0.66	NO
14	TAB2	TAB2	TAB2	3778	0.1	0.65	NO
15	NFKB1	NFKB1	NFKB1	3941	0.099	0.66	NO
16	CHUK	CHUK	CHUK	4948	0.069	0.61	NO
17	MAP3K7	MAP3K7	MAP3K7	5013	0.068	0.62	NO
18	IKBKG	IKBKG	IKBKG	5521	0.057	0.6	NO
19	EIF2AK2	EIF2AK2	EIF2AK2	5561	0.056	0.61	NO
20	MAP3K1	MAP3K1	MAP3K1	5627	0.054	0.61	NO
21	IKBKB	IKBKB	IKBKB	6091	0.046	0.6	NO
22	FOS	FOS	FOS	6925	0.031	0.55	NO
23	JUN	JUN	JUN	6971	0.031	0.56	NO
24	MAP2K3	MAP2K3	MAP2K3	7115	0.029	0.55	NO
25	MAP2K4	MAP2K4	MAP2K4	7919	0.018	0.51	NO
26	MAPK14	MAPK14	MAPK14	9287	0.0011	0.44	NO
27	IRAK1	IRAK1	IRAK1	10770	-0.016	0.36	NO
28	RELA	RELA	RELA	10850	-0.017	0.35	NO
29	MAPK8	MAPK8	MAPK8	11238	-0.021	0.34	NO
30	TRAF6	TRAF6	TRAF6	11423	-0.023	0.33	NO
31	PGLYRP1	PGLYRP1	PGLYRP1	11596	-0.024	0.32	NO
32	ELK1	ELK1	ELK1	12058	-0.03	0.3	NO
33	TAB1	TAB1	TAB1	12374	-0.033	0.29	NO
34	TOLLIP	TOLLIP	TOLLIP	12375	-0.033	0.3	NO
35	TIRAP	TIRAP	TIRAP	12664	-0.037	0.29	NO
36	ECSIT	ECSIT	ECSIT	15364	-0.078	0.15	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 AT1R PATHWAY.

Figure S24. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA AT1R PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA BCR PATHWAY

Table 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	FASLG	FASLG	FASLG	63	0.92	0.11	YES
2	PRKCQ	PRKCQ	PRKCQ	90	0.9	0.22	YES
3	TNF	TNF	TNF	191	0.8	0.32	YES
4	PRKCB	PRKCB	PRKCB	409	0.66	0.39	YES
5	CEBPA	CEBPA	CEBPA	744	0.52	0.43	YES
6	MAPK13	MAPK13	MAPK13	763	0.51	0.49	YES
7	TNFRSF1B	TNFRSF1B	TNFRSF1B	969	0.44	0.54	YES
8	PRKCH	PRKCH	PRKCH	1370	0.34	0.56	YES
9	MAP3K5	MAP3K5	MAP3K5	1429	0.33	0.6	YES
10	FAS	FAS	FAS	1468	0.32	0.63	YES
11	NFKBIA	NFKBIA	NFKBIA	1804	0.26	0.65	YES
12	MAP3K14	MAP3K14	MAP3K14	1930	0.24	0.67	YES
13	PRKCG	PRKCG	PRKCG	2145	0.22	0.68	YES
14	MAP2K6	MAP2K6	MAP2K6	2700	0.16	0.67	NO
15	ETS1	ETS1	ETS1	3284	0.13	0.66	NO
16	BCL2	BCL2	BCL2	3823	0.1	0.64	NO
17	NFKB1	NFKB1	NFKB1	3941	0.099	0.65	NO
18	ETS2	ETS2	ETS2	4173	0.091	0.64	NO
19	CHUK	CHUK	CHUK	4948	0.069	0.61	NO
20	EGFR	EGFR	EGFR	5321	0.06	0.6	NO
21	MAP3K1	MAP3K1	MAP3K1	5627	0.054	0.59	NO
22	EGF	EGF	EGF	6023	0.046	0.57	NO
23	IKBKB	IKBKB	IKBKB	6091	0.046	0.57	NO
24	PRKCD	PRKCD	PRKCD	6116	0.045	0.58	NO
25	MAP2K1	MAP2K1	MAP2K1	6134	0.045	0.58	NO
26	PPP2CA	PPP2CA	PPP2CA	6421	0.04	0.57	NO
27	FOS	FOS	FOS	6925	0.031	0.55	NO
28	JUN	JUN	JUN	6971	0.031	0.55	NO
29	MAP2K3	MAP2K3	MAP2K3	7115	0.029	0.54	NO
30	SP1	SP1	SP1	7813	0.019	0.51	NO
31	MAP2K4	MAP2K4	MAP2K4	7919	0.018	0.5	NO
32	RIPK1	RIPK1	RIPK1	8153	0.015	0.49	NO
33	DAXX	DAXX	DAXX	8639	0.0089	0.47	NO
34	TNFRSF1A	TNFRSF1A	TNFRSF1A	8659	0.0086	0.47	NO
35	RAF1	RAF1	RAF1	8684	0.0083	0.47	NO
36	MAPK14	MAPK14	MAPK14	9287	0.0011	0.43	NO
37	MAPK3	MAPK3	MAPK3	10357	-0.011	0.38	NO
38	RELA	RELA	RELA	10850	-0.017	0.35	NO
39	MAPK8	MAPK8	MAPK8	11238	-0.021	0.33	NO
40	MAPK1	MAPK1	MAPK1	12160	-0.031	0.28	NO
41	HOXA7	HOXA7	HOXA7	12412	-0.034	0.27	NO
42	MAP2K7	MAP2K7	MAP2K7	14314	-0.059	0.18	NO
43	PRKCE	PRKCE	PRKCE	14650	-0.065	0.16	NO
44	HRAS	HRAS	HRAS	15565	-0.083	0.12	NO
45	PRKCA	PRKCA	PRKCA	16304	-0.11	0.097	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 BCR PATHWAY.

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

genes ES table in pathway: BIOCARTA BIOPEPTIDES PATHWAY

Table 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	TNF	TNF	TNF	191	0.8	0.12	YES
2	BIRC3	BIRC3	BIRC3	352	0.7	0.22	YES
3	TNFRSF1B	TNFRSF1B	TNFRSF1B	969	0.44	0.25	YES
4	ARHGDIB	ARHGDIB	ARHGDIB	1215	0.38	0.3	YES
5	MAP3K5	MAP3K5	MAP3K5	1429	0.33	0.34	YES
6	FAS	FAS	FAS	1468	0.32	0.38	YES
7	TRAF1	TRAF1	TRAF1	1749	0.27	0.41	YES
8	NFKBIA	NFKBIA	NFKBIA	1804	0.26	0.45	YES
9	MAP3K14	MAP3K14	MAP3K14	1930	0.24	0.48	YES
10	CFLAR	CFLAR	CFLAR	2206	0.21	0.5	YES
11	CASP8	CASP8	CASP8	2378	0.19	0.52	YES
12	CASP7	CASP7	CASP7	2830	0.16	0.52	YES
13	CASP3	CASP3	CASP3	3292	0.13	0.51	YES
14	TRADD	TRADD	TRADD	3735	0.11	0.5	YES
15	BCL2	BCL2	BCL2	3823	0.1	0.52	YES
16	NFKB1	NFKB1	NFKB1	3941	0.099	0.53	YES
17	LMNB1	LMNB1	LMNB1	4134	0.092	0.53	YES
18	BIRC2	BIRC2	BIRC2	4383	0.084	0.53	NO
19	CASP6	CASP6	CASP6	4703	0.075	0.52	NO
20	CHUK	CHUK	CHUK	4948	0.069	0.52	NO
21	RB1	RB1	RB1	4999	0.068	0.53	NO
22	XIAP	XIAP	XIAP	5398	0.059	0.52	NO
23	MAP3K1	MAP3K1	MAP3K1	5627	0.054	0.51	NO
24	APAF1	APAF1	APAF1	5806	0.051	0.51	NO
25	TRAF2	TRAF2	TRAF2	6068	0.046	0.5	NO
26	PRKCD	PRKCD	PRKCD	6116	0.045	0.51	NO
27	CDK11A	CDK11A	CDK11A	6233	0.043	0.51	NO
28	PAK2	PAK2	PAK2	7045	0.03	0.47	NO
29	BID	BID	BID	7191	0.028	0.46	NO
30	DFFB	DFFB	DFFB	7523	0.023	0.45	NO
31	CDK11B	CDK11B	CDK11B	7616	0.022	0.45	NO
32	BAG4	BAG4	BAG4	7875	0.018	0.44	NO
33	RIPK1	RIPK1	RIPK1	8153	0.015	0.42	NO
34	DAXX	DAXX	DAXX	8639	0.0089	0.4	NO
35	TNFRSF1A	TNFRSF1A	TNFRSF1A	8659	0.0086	0.4	NO
36	CASP9	CASP9	CASP9	8740	0.0077	0.39	NO
37	PSEN1	PSEN1	PSEN1	8755	0.0075	0.39	NO
38	RASA1	RASA1	RASA1	9699	-0.0034	0.34	NO
39	GSN	GSN	GSN	10172	-0.009	0.32	NO
40	NUMA1	NUMA1	NUMA1	10760	-0.016	0.29	NO
41	RELA	RELA	RELA	10850	-0.017	0.28	NO
42	MAPK8	MAPK8	MAPK8	11238	-0.021	0.27	NO
43	MDM2	MDM2	MDM2	11295	-0.021	0.27	NO
44	ACTG1	ACTG1	ACTG1	11418	-0.023	0.26	NO
45	SPTAN1	SPTAN1	SPTAN1	11422	-0.023	0.27	NO
46	CASP2	CASP2	CASP2	11588	-0.024	0.26	NO
47	PARP1	PARP1	PARP1	11812	-0.027	0.25	NO
48	CYCS	CYCS	CYCS	12628	-0.036	0.21	NO
49	DFFA	DFFA	DFFA	13147	-0.042	0.19	NO
50	PSEN2	PSEN2	PSEN2	13495	-0.047	0.18	NO
51	FADD	FADD	FADD	13543	-0.048	0.18	NO
52	CRADD	CRADD	CRADD	14160	-0.056	0.16	NO
53	LMNA	LMNA	LMNA	14219	-0.057	0.17	NO
54	MAP2K7	MAP2K7	MAP2K7	14314	-0.059	0.17	NO
55	PRKDC	PRKDC	PRKDC	14803	-0.068	0.15	NO
56	LMNB2	LMNB2	LMNB2	15461	-0.081	0.13	NO
57	PTK2	PTK2	PTK2	15839	-0.091	0.12	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 BIOPEPTIDES PATHWAY.

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

genes ES table in pathway: BIOCARTA HDAC PATHWAY

Table 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	CD3G	CD3G	CD3G	16	1	0.034	YES
2	ICOS	ICOS	ICOS	38	0.95	0.065	YES
3	CD40LG	CD40LG	CD40LG	42	0.95	0.097	YES
4	CD247	CD247	CD247	70	0.91	0.13	YES
5	PRKCQ	PRKCQ	PRKCQ	90	0.9	0.16	YES
6	CD3D	CD3D	CD3D	91	0.9	0.19	YES
7	CD8B	CD8B	CD8B	102	0.88	0.22	YES
8	CARD11	CARD11	CARD11	127	0.85	0.24	YES
9	LCK	LCK	LCK	129	0.85	0.27	YES
10	ZAP70	ZAP70	ZAP70	137	0.85	0.3	YES
11	PDCD1	PDCD1	PDCD1	139	0.84	0.33	YES
12	IFNG	IFNG	IFNG	146	0.84	0.36	YES
13	ITK	ITK	ITK	159	0.83	0.39	YES
14	CD3E	CD3E	CD3E	172	0.82	0.41	YES
15	TNF	TNF	TNF	191	0.8	0.44	YES
16	CD8A	CD8A	CD8A	228	0.77	0.46	YES
17	PTPRC	PTPRC	PTPRC	230	0.77	0.49	YES
18	CD28	CD28	CD28	240	0.76	0.52	YES
19	RASGRP1	RASGRP1	RASGRP1	246	0.76	0.54	YES
20	VAV1	VAV1	VAV1	284	0.74	0.56	YES
21	PIK3CG	PIK3CG	PIK3CG	345	0.7	0.58	YES
22	PTPN6	PTPN6	PTPN6	425	0.65	0.6	YES
23	PIK3R5	PIK3R5	PIK3R5	514	0.61	0.62	YES
24	MAP3K8	MAP3K8	MAP3K8	521	0.61	0.64	YES
25	IL10	IL10	IL10	580	0.58	0.66	YES
26	LAT	LAT	LAT	654	0.55	0.67	YES
27	CTLA4	CTLA4	CTLA4	738	0.52	0.68	YES
28	MAPK13	MAPK13	MAPK13	763	0.51	0.7	YES
29	GRAP2	GRAP2	GRAP2	796	0.5	0.71	YES
30	LCP2	LCP2	LCP2	877	0.47	0.73	YES
31	CD4	CD4	CD4	883	0.46	0.74	YES
32	VAV3	VAV3	VAV3	1268	0.36	0.73	YES
33	TEC	TEC	TEC	1316	0.35	0.74	YES
34	CSF2	CSF2	CSF2	1385	0.34	0.75	YES
35	NFKBIA	NFKBIA	NFKBIA	1804	0.26	0.74	NO
36	MAP3K14	MAP3K14	MAP3K14	1930	0.24	0.74	NO
37	NFATC2	NFATC2	NFATC2	2053	0.23	0.74	NO
38	PIK3CD	PIK3CD	PIK3CD	2451	0.19	0.72	NO
39	MALT1	MALT1	MALT1	2515	0.18	0.72	NO
40	NFATC1	NFATC1	NFATC1	2657	0.17	0.72	NO
41	PDK1	PDK1	PDK1	2916	0.15	0.71	NO
42	PPP3CC	PPP3CC	PPP3CC	3145	0.13	0.7	NO
43	NFKBIE	NFKBIE	NFKBIE	3302	0.12	0.7	NO
44	NCK1	NCK1	NCK1	3392	0.12	0.7	NO
45	CBLB	CBLB	CBLB	3517	0.12	0.7	NO
46	GRB2	GRB2	GRB2	3875	0.1	0.68	NO
47	NFKB1	NFKB1	NFKB1	3941	0.099	0.68	NO
48	BCL10	BCL10	BCL10	4186	0.09	0.67	NO
49	FYN	FYN	FYN	4295	0.087	0.67	NO
50	PPP3R2	PPP3R2	PPP3R2	4495	0.08	0.66	NO
51	PPP3CB	PPP3CB	PPP3CB	4562	0.079	0.66	NO
52	PIK3R3	PIK3R3	PIK3R3	4702	0.075	0.65	NO
53	PIK3R1	PIK3R1	PIK3R1	4757	0.074	0.65	NO
54	PIK3CA	PIK3CA	PIK3CA	4930	0.07	0.64	NO
55	CHUK	CHUK	CHUK	4948	0.069	0.64	NO
56	MAP3K7	MAP3K7	MAP3K7	5013	0.068	0.64	NO
57	NFATC3	NFATC3	NFATC3	5144	0.065	0.64	NO
58	PAK1	PAK1	PAK1	5375	0.059	0.63	NO
59	IKBKG	IKBKG	IKBKG	5521	0.057	0.62	NO
60	CDC42	CDC42	CDC42	5671	0.053	0.62	NO
61	SOS1	SOS1	SOS1	5695	0.053	0.62	NO
62	PIK3CB	PIK3CB	PIK3CB	5836	0.05	0.61	NO
63	NFKBIB	NFKBIB	NFKBIB	5962	0.048	0.6	NO
64	KRAS	KRAS	KRAS	6032	0.046	0.6	NO
65	IKBKB	IKBKB	IKBKB	6091	0.046	0.6	NO
66	MAP2K1	MAP2K1	MAP2K1	6134	0.045	0.6	NO
67	CBL	CBL	CBL	6293	0.042	0.59	NO
68	PPP3CA	PPP3CA	PPP3CA	6366	0.041	0.59	NO
69	NRAS	NRAS	NRAS	6488	0.039	0.58	NO
70	SOS2	SOS2	SOS2	6656	0.036	0.58	NO
71	FOS	FOS	FOS	6925	0.031	0.56	NO
72	JUN	JUN	JUN	6971	0.031	0.56	NO
73	PAK2	PAK2	PAK2	7045	0.03	0.56	NO
74	NFAT5	NFAT5	NFAT5	7140	0.028	0.55	NO
75	RHOA	RHOA	RHOA	7404	0.025	0.54	NO
76	DLG1	DLG1	DLG1	7532	0.023	0.53	NO
77	MAPK9	MAPK9	MAPK9	8062	0.016	0.5	NO
78	PPP3R1	PPP3R1	PPP3R1	8458	0.011	0.48	NO
79	MAPK11	MAPK11	MAPK11	8666	0.0085	0.47	NO
80	RAF1	RAF1	RAF1	8684	0.0083	0.47	NO
81	PAK3	PAK3	PAK3	9012	0.0043	0.45	NO
82	MAPK14	MAPK14	MAPK14	9287	0.0011	0.44	NO
83	MAPK3	MAPK3	MAPK3	10357	-0.011	0.38	NO
84	RELA	RELA	RELA	10850	-0.017	0.35	NO
85	GSK3B	GSK3B	GSK3B	11028	-0.018	0.34	NO
86	MAP2K2	MAP2K2	MAP2K2	11338	-0.022	0.33	NO
87	NCK2	NCK2	NCK2	11510	-0.024	0.32	NO
88	CHP	CHP	CHP	11529	-0.024	0.32	NO
89	MAPK1	MAPK1	MAPK1	12160	-0.031	0.28	NO
90	AKT1	AKT1	AKT1	12366	-0.033	0.27	NO
91	PAK7	PAK7	PAK7	13458	-0.046	0.21	NO
92	PLCG1	PLCG1	PLCG1	13619	-0.049	0.21	NO
93	AKT3	AKT3	AKT3	13688	-0.05	0.2	NO
94	VAV2	VAV2	VAV2	13764	-0.051	0.2	NO
95	AKT2	AKT2	AKT2	13834	-0.052	0.2	NO
96	MAP2K7	MAP2K7	MAP2K7	14314	-0.059	0.18	NO
97	NFATC4	NFATC4	NFATC4	15424	-0.08	0.12	NO
98	PAK6	PAK6	PAK6	15591	-0.084	0.11	NO
99	CDK4	CDK4	CDK4	16128	-0.1	0.083	NO
100	CBLC	CBLC	CBLC	16242	-0.1	0.08	NO
101	PIK3R2	PIK3R2	PIK3R2	16574	-0.12	0.066	NO
102	CHP2	CHP2	CHP2	16785	-0.13	0.058	NO
103	PAK4	PAK4	PAK4	17015	-0.14	0.05	NO
104	MAPK12	MAPK12	MAPK12	17735	-0.21	0.017	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 HDAC PATHWAY.

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

genes ES table in pathway: BIOCARTA EGF PATHWAY

Table 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	CD80	CD80	CD80	98	0.89	0.035	YES
2	TNF	TNF	TNF	191	0.8	0.067	YES
3	TLR9	TLR9	TLR9	223	0.78	0.1	YES
4	CXCL11	CXCL11	CXCL11	224	0.77	0.14	YES
5	TLR8	TLR8	TLR8	227	0.77	0.17	YES
6	CXCL9	CXCL9	CXCL9	280	0.74	0.2	YES
7	IL12B	IL12B	IL12B	315	0.72	0.23	YES
8	CXCL10	CXCL10	CXCL10	328	0.71	0.26	YES
9	PIK3CG	PIK3CG	PIK3CG	345	0.7	0.3	YES
10	CCL4	CCL4	CCL4	346	0.7	0.33	YES
11	CCL5	CCL5	CCL5	370	0.69	0.36	YES
12	TLR7	TLR7	TLR7	383	0.68	0.39	YES
13	CD86	CD86	CD86	455	0.64	0.41	YES
14	PIK3R5	PIK3R5	PIK3R5	514	0.61	0.44	YES
15	MAP3K8	MAP3K8	MAP3K8	521	0.61	0.47	YES
16	CCL3	CCL3	CCL3	602	0.57	0.49	YES
17	CD40	CD40	CD40	687	0.54	0.51	YES
18	MAPK13	MAPK13	MAPK13	763	0.51	0.53	YES
19	TICAM2	TICAM2	TICAM2	932	0.45	0.54	YES
20	IRF5	IRF5	IRF5	1061	0.41	0.55	YES
21	IL1B	IL1B	IL1B	1068	0.41	0.57	YES
22	TLR4	TLR4	TLR4	1075	0.41	0.59	YES
23	TLR6	TLR6	TLR6	1142	0.4	0.6	YES
24	TLR5	TLR5	TLR5	1172	0.39	0.62	YES
25	TLR1	TLR1	TLR1	1220	0.38	0.63	YES
26	TLR2	TLR2	TLR2	1298	0.36	0.64	YES
27	IL6	IL6	IL6	1324	0.35	0.66	YES
28	LBP	LBP	LBP	1469	0.32	0.66	YES
29	CD14	CD14	CD14	1486	0.31	0.68	YES
30	IL12A	IL12A	IL12A	1544	0.3	0.69	YES
31	TLR3	TLR3	TLR3	1574	0.3	0.7	YES
32	IRF7	IRF7	IRF7	1609	0.29	0.71	YES
33	STAT1	STAT1	STAT1	1655	0.28	0.72	YES
34	NFKBIA	NFKBIA	NFKBIA	1804	0.26	0.73	YES
35	LY96	LY96	LY96	1835	0.25	0.74	YES
36	IKBKE	IKBKE	IKBKE	1966	0.24	0.74	YES
37	IFNB1	IFNB1	IFNB1	2115	0.22	0.74	YES
38	CASP8	CASP8	CASP8	2378	0.19	0.74	YES
39	PIK3CD	PIK3CD	PIK3CD	2451	0.19	0.74	YES
40	MAP2K6	MAP2K6	MAP2K6	2700	0.16	0.73	YES
41	IFNAR2	IFNAR2	IFNAR2	2755	0.16	0.74	YES
42	IRAK4	IRAK4	IRAK4	2783	0.16	0.74	YES
43	TRAF3	TRAF3	TRAF3	3050	0.14	0.74	NO
44	MYD88	MYD88	MYD88	3369	0.12	0.72	NO
45	TAB2	TAB2	TAB2	3778	0.1	0.7	NO
46	NFKB1	NFKB1	NFKB1	3941	0.099	0.7	NO
47	IRF3	IRF3	IRF3	4563	0.079	0.67	NO
48	PIK3R3	PIK3R3	PIK3R3	4702	0.075	0.66	NO
49	PIK3R1	PIK3R1	PIK3R1	4757	0.074	0.67	NO
50	PIK3CA	PIK3CA	PIK3CA	4930	0.07	0.66	NO
51	CHUK	CHUK	CHUK	4948	0.069	0.66	NO
52	MAP3K7	MAP3K7	MAP3K7	5013	0.068	0.66	NO
53	IFNAR1	IFNAR1	IFNAR1	5087	0.066	0.66	NO
54	CTSK	CTSK	CTSK	5438	0.058	0.64	NO
55	IKBKG	IKBKG	IKBKG	5521	0.057	0.64	NO
56	IL8	IL8	IL8	5761	0.052	0.63	NO
57	PIK3CB	PIK3CB	PIK3CB	5836	0.05	0.63	NO
58	IKBKB	IKBKB	IKBKB	6091	0.046	0.62	NO
59	MAP2K1	MAP2K1	MAP2K1	6134	0.045	0.62	NO
60	FOS	FOS	FOS	6925	0.031	0.57	NO
61	JUN	JUN	JUN	6971	0.031	0.57	NO
62	MAP2K3	MAP2K3	MAP2K3	7115	0.029	0.57	NO
63	MAP2K4	MAP2K4	MAP2K4	7919	0.018	0.52	NO
64	MAPK9	MAPK9	MAPK9	8062	0.016	0.52	NO
65	RIPK1	RIPK1	RIPK1	8153	0.015	0.51	NO
66	MAPK11	MAPK11	MAPK11	8666	0.0085	0.48	NO
67	TICAM1	TICAM1	TICAM1	8706	0.0079	0.48	NO
68	SPP1	SPP1	SPP1	8897	0.0058	0.47	NO
69	MAPK14	MAPK14	MAPK14	9287	0.0011	0.45	NO
70	MAPK10	MAPK10	MAPK10	9703	-0.0034	0.43	NO
71	MAPK3	MAPK3	MAPK3	10357	-0.011	0.39	NO
72	IRAK1	IRAK1	IRAK1	10770	-0.016	0.37	NO
73	RELA	RELA	RELA	10850	-0.017	0.36	NO
74	MAPK8	MAPK8	MAPK8	11238	-0.021	0.34	NO
75	MAP2K2	MAP2K2	MAP2K2	11338	-0.022	0.34	NO
76	RAC1	RAC1	RAC1	11412	-0.023	0.34	NO
77	TRAF6	TRAF6	TRAF6	11423	-0.023	0.34	NO
78	MAPK1	MAPK1	MAPK1	12160	-0.031	0.3	NO
79	AKT1	AKT1	AKT1	12366	-0.033	0.29	NO
80	TAB1	TAB1	TAB1	12374	-0.033	0.29	NO
81	TOLLIP	TOLLIP	TOLLIP	12375	-0.033	0.29	NO
82	TIRAP	TIRAP	TIRAP	12664	-0.037	0.28	NO
83	FADD	FADD	FADD	13543	-0.048	0.23	NO
84	AKT3	AKT3	AKT3	13688	-0.05	0.22	NO
85	AKT2	AKT2	AKT2	13834	-0.052	0.22	NO
86	MAP2K7	MAP2K7	MAP2K7	14314	-0.059	0.19	NO
87	PIK3R2	PIK3R2	PIK3R2	16574	-0.12	0.072	NO
88	MAPK12	MAPK12	MAPK12	17735	-0.21	0.017	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 EGF PATHWAY.

Figure S32. 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 FAS 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	CD3G	CD3G	CD3G	16	1	0.092	YES
2	CD247	CD247	CD247	70	0.91	0.17	YES
3	CD3D	CD3D	CD3D	91	0.9	0.26	YES
4	LCK	LCK	LCK	129	0.85	0.33	YES
5	ZAP70	ZAP70	ZAP70	137	0.85	0.41	YES
6	CD3E	CD3E	CD3E	172	0.82	0.48	YES
7	PTPN7	PTPN7	PTPN7	261	0.75	0.55	YES
8	VAV1	VAV1	VAV1	284	0.74	0.61	YES
9	PIK3CG	PIK3CG	PIK3CG	345	0.7	0.68	YES
10	PRKCB	PRKCB	PRKCB	409	0.66	0.73	YES
11	LAT	LAT	LAT	654	0.55	0.77	YES
12	NFKBIA	NFKBIA	NFKBIA	1804	0.26	0.73	NO
13	NFATC2	NFATC2	NFATC2	2053	0.23	0.74	NO
14	NFATC1	NFATC1	NFATC1	2657	0.17	0.72	NO
15	PPP3CC	PPP3CC	PPP3CC	3145	0.13	0.7	NO
16	GRB2	GRB2	GRB2	3875	0.1	0.67	NO
17	NFKB1	NFKB1	NFKB1	3941	0.099	0.68	NO
18	FYN	FYN	FYN	4295	0.087	0.67	NO
19	PPP3CB	PPP3CB	PPP3CB	4562	0.079	0.66	NO
20	PIK3R1	PIK3R1	PIK3R1	4757	0.074	0.66	NO
21	PIK3CA	PIK3CA	PIK3CA	4930	0.07	0.65	NO
22	NFATC3	NFATC3	NFATC3	5144	0.065	0.65	NO
23	MAP3K1	MAP3K1	MAP3K1	5627	0.054	0.62	NO
24	SOS1	SOS1	SOS1	5695	0.053	0.63	NO
25	MAP2K1	MAP2K1	MAP2K1	6134	0.045	0.61	NO
26	PPP3CA	PPP3CA	PPP3CA	6366	0.041	0.6	NO
27	CALM2	CALM2	CALM2	6782	0.034	0.58	NO
28	FOS	FOS	FOS	6925	0.031	0.57	NO
29	JUN	JUN	JUN	6971	0.031	0.57	NO
30	CALM1	CALM1	CALM1	7074	0.029	0.57	NO
31	MAP2K4	MAP2K4	MAP2K4	7919	0.018	0.52	NO
32	RAF1	RAF1	RAF1	8684	0.0083	0.48	NO
33	RASA1	RASA1	RASA1	9699	-0.0034	0.43	NO
34	CALM3	CALM3	CALM3	9903	-0.0061	0.42	NO
35	MAPK3	MAPK3	MAPK3	10357	-0.011	0.39	NO
36	RELA	RELA	RELA	10850	-0.017	0.37	NO
37	MAPK8	MAPK8	MAPK8	11238	-0.021	0.35	NO
38	RAC1	RAC1	RAC1	11412	-0.023	0.34	NO
39	ELK1	ELK1	ELK1	12058	-0.03	0.31	NO
40	PLCG1	PLCG1	PLCG1	13619	-0.049	0.22	NO
41	SHC1	SHC1	SHC1	14115	-0.056	0.2	NO
42	NFATC4	NFATC4	NFATC4	15424	-0.08	0.14	NO
43	PRKCA	PRKCA	PRKCA	16304	-0.11	0.097	NO

Figure S33. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FAS PATHWAY.

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

genes ES table in pathway: BIOCARTA FCER1 PATHWAY

Table 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	CCR7	CCR7	CCR7	41	0.95	0.017	YES
2	CXCR5	CXCR5	CXCR5	79	0.91	0.033	YES
3	XCL2	XCL2	XCL2	80	0.9	0.051	YES
4	CXCL13	CXCL13	CXCL13	97	0.89	0.068	YES
5	CCR8	CCR8	CCR8	120	0.86	0.084	YES
6	GNGT2	GNGT2	GNGT2	124	0.85	0.1	YES
7	CCL19	CCL19	CCL19	128	0.85	0.12	YES
8	CCR4	CCR4	CCR4	132	0.85	0.14	YES
9	RASGRP2	RASGRP2	RASGRP2	136	0.85	0.15	YES
10	CCR2	CCR2	CCR2	145	0.84	0.17	YES
11	CXCR3	CXCR3	CXCR3	154	0.84	0.18	YES
12	ITK	ITK	ITK	159	0.83	0.2	YES
13	CXCR6	CXCR6	CXCR6	162	0.83	0.22	YES
14	XCL1	XCL1	XCL1	206	0.79	0.23	YES
15	CCR6	CCR6	CCR6	213	0.78	0.25	YES
16	CXCL11	CXCL11	CXCL11	224	0.77	0.26	YES
17	NCF1	NCF1	NCF1	269	0.74	0.28	YES
18	CXCL9	CXCL9	CXCL9	280	0.74	0.29	YES
19	VAV1	VAV1	VAV1	284	0.74	0.3	YES
20	CCR5	CCR5	CCR5	293	0.73	0.32	YES
21	CCL22	CCL22	CCL22	299	0.73	0.33	YES
22	CCR3	CCR3	CCR3	319	0.71	0.35	YES
23	CXCL10	CXCL10	CXCL10	328	0.71	0.36	YES
24	XCR1	XCR1	XCR1	333	0.71	0.37	YES
25	PIK3CG	PIK3CG	PIK3CG	345	0.7	0.39	YES
26	CCL4	CCL4	CCL4	346	0.7	0.4	YES
27	CCL4L2	CCL4L2	CCL4L2	358	0.69	0.42	YES
28	CCL5	CCL5	CCL5	370	0.69	0.43	YES
29	WAS	WAS	WAS	385	0.68	0.44	YES
30	PRKCB	PRKCB	PRKCB	409	0.66	0.45	YES
31	DOCK2	DOCK2	DOCK2	410	0.66	0.47	YES
32	FGR	FGR	FGR	479	0.63	0.48	YES
33	CCL8	CCL8	CCL8	485	0.62	0.49	YES
34	RAC2	RAC2	RAC2	494	0.62	0.5	YES
35	PIK3R5	PIK3R5	PIK3R5	514	0.61	0.51	YES
36	CCL25	CCL25	CCL25	552	0.59	0.52	YES
37	HCK	HCK	HCK	588	0.57	0.53	YES
38	CCL21	CCL21	CCL21	594	0.57	0.54	YES
39	CCL3	CCL3	CCL3	602	0.57	0.55	YES
40	CCR9	CCR9	CCR9	630	0.56	0.56	YES
41	CCL3L1	CCL3L1	CCL3L1	726	0.52	0.57	YES
42	CCL17	CCL17	CCL17	750	0.51	0.58	YES
43	JAK3	JAK3	JAK3	759	0.51	0.59	YES
44	CCL2	CCL2	CCL2	835	0.48	0.59	YES
45	CCL3L3	CCL3L3	CCL3L3	917	0.46	0.6	YES
46	PTK2B	PTK2B	PTK2B	940	0.45	0.6	YES
47	ELMO1	ELMO1	ELMO1	945	0.45	0.61	YES
48	CCL1	CCL1	CCL1	946	0.45	0.62	YES
49	CX3CR1	CX3CR1	CX3CR1	1001	0.43	0.63	YES
50	LYN	LYN	LYN	1002	0.43	0.64	YES
51	CXCL12	CXCL12	CXCL12	1008	0.43	0.64	YES
52	CXCR4	CXCR4	CXCR4	1011	0.43	0.65	YES
53	CCR1	CCR1	CCR1	1033	0.42	0.66	YES
54	CCL13	CCL13	CCL13	1168	0.39	0.66	YES
55	CCL23	CCL23	CCL23	1177	0.39	0.67	YES
56	PLCB2	PLCB2	PLCB2	1186	0.38	0.68	YES
57	ADCY4	ADCY4	ADCY4	1242	0.37	0.68	YES
58	CCL24	CCL24	CCL24	1245	0.37	0.69	YES
59	CCL14	CCL14	CCL14	1260	0.36	0.69	YES
60	VAV3	VAV3	VAV3	1268	0.36	0.7	YES
61	CCL16	CCL16	CCL16	1274	0.36	0.71	YES
62	JAK2	JAK2	JAK2	1365	0.34	0.71	YES
63	ADCY7	ADCY7	ADCY7	1497	0.31	0.71	YES
64	CCL18	CCL18	CCL18	1549	0.3	0.71	YES
65	GNG8	GNG8	GNG8	1593	0.29	0.72	YES
66	CXCL2	CXCL2	CXCL2	1614	0.29	0.72	YES
67	STAT1	STAT1	STAT1	1655	0.28	0.72	YES
68	CXCL14	CXCL14	CXCL14	1657	0.28	0.73	YES
69	CCL7	CCL7	CCL7	1664	0.28	0.74	YES
70	NFKBIA	NFKBIA	NFKBIA	1804	0.26	0.73	YES
71	CXCL16	CXCL16	CXCL16	1874	0.25	0.73	YES
72	PRKX	PRKX	PRKX	2026	0.23	0.73	YES
73	ARRB2	ARRB2	ARRB2	2089	0.22	0.73	YES
74	CXCR2	CXCR2	CXCR2	2094	0.22	0.74	YES
75	PIK3CD	PIK3CD	PIK3CD	2451	0.19	0.72	NO
76	CCL26	CCL26	CCL26	2550	0.18	0.72	NO
77	TIAM1	TIAM1	TIAM1	2577	0.18	0.72	NO
78	PREX1	PREX1	PREX1	2832	0.16	0.71	NO
79	RAP1A	RAP1A	RAP1A	2903	0.15	0.71	NO
80	ADRBK2	ADRBK2	ADRBK2	3148	0.13	0.7	NO
81	ADRBK1	ADRBK1	ADRBK1	3155	0.13	0.7	NO
82	CCL20	CCL20	CCL20	3229	0.13	0.7	NO
83	CXCL5	CXCL5	CXCL5	3247	0.13	0.7	NO
84	CCL11	CCL11	CCL11	3495	0.12	0.69	NO
85	GNG2	GNG2	GNG2	3610	0.11	0.68	NO
86	GRK5	GRK5	GRK5	3742	0.11	0.68	NO
87	STAT2	STAT2	STAT2	3749	0.11	0.68	NO
88	CCR10	CCR10	CCR10	3860	0.1	0.68	NO
89	GRB2	GRB2	GRB2	3875	0.1	0.68	NO
90	PRKACB	PRKACB	PRKACB	3923	0.1	0.68	NO
91	NFKB1	NFKB1	NFKB1	3941	0.099	0.68	NO
92	GNB3	GNB3	GNB3	3956	0.098	0.68	NO
93	GRK6	GRK6	GRK6	4035	0.096	0.68	NO
94	CXCR1	CXCR1	CXCR1	4156	0.091	0.67	NO
95	CXCL3	CXCL3	CXCL3	4196	0.09	0.67	NO
96	PIK3R3	PIK3R3	PIK3R3	4702	0.075	0.64	NO
97	CSK	CSK	CSK	4714	0.075	0.64	NO
98	PIK3R1	PIK3R1	PIK3R1	4757	0.074	0.64	NO
99	GNAI2	GNAI2	GNAI2	4845	0.072	0.64	NO
100	RAP1B	RAP1B	RAP1B	4848	0.072	0.64	NO
101	TIAM2	TIAM2	TIAM2	4878	0.071	0.64	NO
102	PIK3CA	PIK3CA	PIK3CA	4930	0.07	0.64	NO
103	CHUK	CHUK	CHUK	4948	0.069	0.64	NO
104	STAT5B	STAT5B	STAT5B	4969	0.069	0.64	NO
105	GNB5	GNB5	GNB5	5004	0.068	0.64	NO
106	ROCK1	ROCK1	ROCK1	5046	0.067	0.64	NO
107	CXCL1	CXCL1	CXCL1	5188	0.064	0.63	NO
108	CCL28	CCL28	CCL28	5200	0.063	0.63	NO
109	CCL15	CCL15	CCL15	5292	0.061	0.63	NO
110	PAK1	PAK1	PAK1	5375	0.059	0.63	NO
111	CX3CL1	CX3CL1	CX3CL1	5504	0.057	0.62	NO
112	IKBKG	IKBKG	IKBKG	5521	0.057	0.62	NO
113	GNG10	GNG10	GNG10	5612	0.055	0.62	NO
114	ADCY5	ADCY5	ADCY5	5669	0.053	0.61	NO
115	CDC42	CDC42	CDC42	5671	0.053	0.62	NO
116	SOS1	SOS1	SOS1	5695	0.053	0.62	NO
117	GNB4	GNB4	GNB4	5713	0.052	0.62	NO
118	IL8	IL8	IL8	5761	0.052	0.61	NO
119	PIK3CB	PIK3CB	PIK3CB	5836	0.05	0.61	NO
120	NFKBIB	NFKBIB	NFKBIB	5962	0.048	0.6	NO
121	STAT3	STAT3	STAT3	5983	0.047	0.6	NO
122	KRAS	KRAS	KRAS	6032	0.046	0.6	NO
123	IKBKB	IKBKB	IKBKB	6091	0.046	0.6	NO
124	ADCY2	ADCY2	ADCY2	6094	0.045	0.6	NO
125	PRKCD	PRKCD	PRKCD	6116	0.045	0.6	NO
126	MAP2K1	MAP2K1	MAP2K1	6134	0.045	0.6	NO
127	ARRB1	ARRB1	ARRB1	6382	0.04	0.59	NO
128	NRAS	NRAS	NRAS	6488	0.039	0.58	NO
129	GNG7	GNG7	GNG7	6579	0.037	0.58	NO
130	SOS2	SOS2	SOS2	6656	0.036	0.57	NO
131	PLCB1	PLCB1	PLCB1	6800	0.033	0.57	NO
132	GNGT1	GNGT1	GNGT1	6903	0.032	0.56	NO
133	ADCY1	ADCY1	ADCY1	7003	0.03	0.56	NO
134	RHOA	RHOA	RHOA	7404	0.025	0.54	NO
135	GNAI3	GNAI3	GNAI3	7494	0.024	0.53	NO
136	FOXO3	FOXO3	FOXO3	7555	0.023	0.53	NO
137	PRKCZ	PRKCZ	PRKCZ	7653	0.021	0.52	NO
138	SHC4	SHC4	SHC4	7961	0.017	0.51	NO
139	GNG5	GNG5	GNG5	8005	0.017	0.5	NO
140	PLCB4	PLCB4	PLCB4	8225	0.014	0.49	NO
141	GNG11	GNG11	GNG11	8326	0.013	0.49	NO
142	CXCL6	CXCL6	CXCL6	8340	0.013	0.49	NO
143	RAF1	RAF1	RAF1	8684	0.0083	0.47	NO
144	GNB1	GNB1	GNB1	9346	0.00035	0.43	NO
145	GRK7	GRK7	GRK7	9708	-0.0034	0.41	NO
146	MAPK3	MAPK3	MAPK3	10357	-0.011	0.37	NO
147	RELA	RELA	RELA	10850	-0.017	0.35	NO
148	GSK3B	GSK3B	GSK3B	11028	-0.018	0.34	NO
149	PRKACA	PRKACA	PRKACA	11160	-0.02	0.33	NO
150	RAC1	RAC1	RAC1	11412	-0.023	0.32	NO
151	BRAF	BRAF	BRAF	11716	-0.026	0.3	NO
152	PF4	PF4	PF4	11874	-0.028	0.29	NO
153	MAPK1	MAPK1	MAPK1	12160	-0.031	0.28	NO
154	CRKL	CRKL	CRKL	12203	-0.031	0.28	NO
155	WASL	WASL	WASL	12337	-0.033	0.27	NO
156	AKT1	AKT1	AKT1	12366	-0.033	0.27	NO
157	PXN	PXN	PXN	12388	-0.033	0.27	NO
158	GNB2	GNB2	GNB2	12563	-0.036	0.26	NO
159	ROCK2	ROCK2	ROCK2	12843	-0.039	0.24	NO
160	GNG4	GNG4	GNG4	13509	-0.047	0.21	NO
161	GSK3A	GSK3A	GSK3A	13555	-0.048	0.2	NO
162	AKT3	AKT3	AKT3	13688	-0.05	0.2	NO
163	VAV2	VAV2	VAV2	13764	-0.051	0.2	NO
164	AKT2	AKT2	AKT2	13834	-0.052	0.19	NO
165	SHC1	SHC1	SHC1	14115	-0.056	0.18	NO
166	CRK	CRK	CRK	14161	-0.056	0.18	NO
167	GNG12	GNG12	GNG12	14290	-0.058	0.17	NO
168	BCAR1	BCAR1	BCAR1	14622	-0.064	0.15	NO
169	PLCB3	PLCB3	PLCB3	14740	-0.066	0.15	NO
170	CCL27	CCL27	CCL27	15008	-0.072	0.14	NO
171	ADCY9	ADCY9	ADCY9	15457	-0.08	0.11	NO
172	HRAS	HRAS	HRAS	15565	-0.083	0.11	NO
173	PTK2	PTK2	PTK2	15839	-0.091	0.094	NO
174	GNAI1	GNAI1	GNAI1	15975	-0.095	0.088	NO
175	GRK4	GRK4	GRK4	15981	-0.095	0.09	NO
176	PPBP	PPBP	PPBP	16467	-0.11	0.065	NO
177	PIK3R2	PIK3R2	PIK3R2	16574	-0.12	0.062	NO
178	PARD3	PARD3	PARD3	16663	-0.12	0.059	NO
179	GNG3	GNG3	GNG3	17140	-0.15	0.035	NO
180	ADCY6	ADCY6	ADCY6	17257	-0.16	0.032	NO
181	SHC2	SHC2	SHC2	17530	-0.18	0.02	NO
182	ADCY8	ADCY8	ADCY8	17670	-0.2	0.017	NO
183	SHC3	SHC3	SHC3	17804	-0.22	0.014	NO

Figure S35. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA FCER1 PATHWAY.

Figure S36. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA FCER1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA FMLP PATHWAY

Table 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	DAPP1	DAPP1	DAPP1	53	0.93	0.044	YES
2	CD19	CD19	CD19	68	0.91	0.089	YES
3	CD79A	CD79A	CD79A	75	0.91	0.14	YES
4	BLNK	BLNK	BLNK	110	0.88	0.18	YES
5	CARD11	CARD11	CARD11	127	0.85	0.22	YES
6	CD72	CD72	CD72	220	0.78	0.25	YES
7	VAV1	VAV1	VAV1	284	0.74	0.29	YES
8	CR2	CR2	CR2	313	0.72	0.32	YES
9	PIK3CG	PIK3CG	PIK3CG	345	0.7	0.36	YES
10	CD79B	CD79B	CD79B	399	0.67	0.38	YES
11	BTK	BTK	BTK	403	0.67	0.42	YES
12	PRKCB	PRKCB	PRKCB	409	0.66	0.45	YES
13	PTPN6	PTPN6	PTPN6	425	0.65	0.48	YES
14	INPP5D	INPP5D	INPP5D	431	0.65	0.52	YES
15	RAC2	RAC2	RAC2	494	0.62	0.54	YES
16	PIK3R5	PIK3R5	PIK3R5	514	0.61	0.57	YES
17	PIK3AP1	PIK3AP1	PIK3AP1	589	0.57	0.6	YES
18	LILRB3	LILRB3	LILRB3	677	0.54	0.62	YES
19	SYK	SYK	SYK	771	0.5	0.64	YES
20	PLCG2	PLCG2	PLCG2	839	0.48	0.66	YES
21	LYN	LYN	LYN	1002	0.43	0.67	YES
22	CD22	CD22	CD22	1104	0.4	0.69	YES
23	FCGR2B	FCGR2B	FCGR2B	1202	0.38	0.7	YES
24	RASGRP3	RASGRP3	RASGRP3	1230	0.37	0.72	YES
25	VAV3	VAV3	VAV3	1268	0.36	0.74	YES
26	IFITM1	IFITM1	IFITM1	1441	0.32	0.74	YES
27	NFKBIA	NFKBIA	NFKBIA	1804	0.26	0.74	NO
28	NFATC2	NFATC2	NFATC2	2053	0.23	0.73	NO
29	PIK3CD	PIK3CD	PIK3CD	2451	0.19	0.72	NO
30	MALT1	MALT1	MALT1	2515	0.18	0.73	NO
31	NFATC1	NFATC1	NFATC1	2657	0.17	0.73	NO
32	PPP3CC	PPP3CC	PPP3CC	3145	0.13	0.71	NO
33	NFKBIE	NFKBIE	NFKBIE	3302	0.12	0.7	NO
34	GRB2	GRB2	GRB2	3875	0.1	0.68	NO
35	NFKB1	NFKB1	NFKB1	3941	0.099	0.68	NO
36	BCL10	BCL10	BCL10	4186	0.09	0.67	NO
37	PPP3R2	PPP3R2	PPP3R2	4495	0.08	0.66	NO
38	PPP3CB	PPP3CB	PPP3CB	4562	0.079	0.66	NO
39	PIK3R3	PIK3R3	PIK3R3	4702	0.075	0.65	NO
40	PIK3R1	PIK3R1	PIK3R1	4757	0.074	0.65	NO
41	PIK3CA	PIK3CA	PIK3CA	4930	0.07	0.65	NO
42	CHUK	CHUK	CHUK	4948	0.069	0.65	NO
43	NFATC3	NFATC3	NFATC3	5144	0.065	0.64	NO
44	IKBKG	IKBKG	IKBKG	5521	0.057	0.62	NO
45	SOS1	SOS1	SOS1	5695	0.053	0.62	NO
46	PIK3CB	PIK3CB	PIK3CB	5836	0.05	0.61	NO
47	NFKBIB	NFKBIB	NFKBIB	5962	0.048	0.61	NO
48	KRAS	KRAS	KRAS	6032	0.046	0.61	NO
49	IKBKB	IKBKB	IKBKB	6091	0.046	0.6	NO
50	MAP2K1	MAP2K1	MAP2K1	6134	0.045	0.6	NO
51	PPP3CA	PPP3CA	PPP3CA	6366	0.041	0.59	NO
52	NRAS	NRAS	NRAS	6488	0.039	0.59	NO
53	SOS2	SOS2	SOS2	6656	0.036	0.58	NO
54	FOS	FOS	FOS	6925	0.031	0.57	NO
55	JUN	JUN	JUN	6971	0.031	0.57	NO
56	NFAT5	NFAT5	NFAT5	7140	0.028	0.56	NO
57	PPP3R1	PPP3R1	PPP3R1	8458	0.011	0.49	NO
58	RAF1	RAF1	RAF1	8684	0.0083	0.48	NO
59	MAPK3	MAPK3	MAPK3	10357	-0.011	0.38	NO
60	RELA	RELA	RELA	10850	-0.017	0.36	NO
61	CD81	CD81	CD81	10919	-0.017	0.35	NO
62	GSK3B	GSK3B	GSK3B	11028	-0.018	0.35	NO
63	MAP2K2	MAP2K2	MAP2K2	11338	-0.022	0.33	NO
64	RAC1	RAC1	RAC1	11412	-0.023	0.33	NO
65	CHP	CHP	CHP	11529	-0.024	0.32	NO
66	MAPK1	MAPK1	MAPK1	12160	-0.031	0.29	NO
67	AKT1	AKT1	AKT1	12366	-0.033	0.28	NO
68	AKT3	AKT3	AKT3	13688	-0.05	0.21	NO
69	VAV2	VAV2	VAV2	13764	-0.051	0.21	NO
70	AKT2	AKT2	AKT2	13834	-0.052	0.21	NO
71	NFATC4	NFATC4	NFATC4	15424	-0.08	0.12	NO
72	PIK3R2	PIK3R2	PIK3R2	16574	-0.12	0.064	NO
73	CHP2	CHP2	CHP2	16785	-0.13	0.059	NO
74	RAC3	RAC3	RAC3	17836	-0.23	0.012	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: BIOCARTA FMLP PATHWAY.

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

genes ES table in pathway: BIOCARTA GH PATHWAY

Table 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	PRKCB	PRKCB	PRKCB	409	0.66	0.3	YES
2	PTK2B	PTK2B	PTK2B	940	0.45	0.49	YES
3	GRB2	GRB2	GRB2	3875	0.1	0.38	NO
4	PAK1	PAK1	PAK1	5375	0.059	0.32	NO
5	MAP3K1	MAP3K1	MAP3K1	5627	0.054	0.34	NO
6	SOS1	SOS1	SOS1	5695	0.053	0.36	NO
7	MAP2K1	MAP2K1	MAP2K1	6134	0.045	0.36	NO
8	CALM2	CALM2	CALM2	6782	0.034	0.34	NO
9	JUN	JUN	JUN	6971	0.031	0.34	NO
10	CALM1	CALM1	CALM1	7074	0.029	0.35	NO
11	MAP2K3	MAP2K3	MAP2K3	7115	0.029	0.36	NO
12	MAP2K4	MAP2K4	MAP2K4	7919	0.018	0.33	NO
13	RAF1	RAF1	RAF1	8684	0.0083	0.29	NO
14	MAPK14	MAPK14	MAPK14	9287	0.0011	0.26	NO
15	CALM3	CALM3	CALM3	9903	-0.0061	0.22	NO
16	MAPK3	MAPK3	MAPK3	10357	-0.011	0.2	NO
17	GNAQ	GNAQ	GNAQ	10643	-0.014	0.2	NO
18	MAPK8	MAPK8	MAPK8	11238	-0.021	0.17	NO
19	MAP2K2	MAP2K2	MAP2K2	11338	-0.022	0.18	NO
20	RAC1	RAC1	RAC1	11412	-0.023	0.19	NO
21	MAPK1	MAPK1	MAPK1	12160	-0.031	0.16	NO
22	CRKL	CRKL	CRKL	12203	-0.031	0.17	NO
23	SRC	SRC	SRC	12359	-0.033	0.18	NO
24	PLCG1	PLCG1	PLCG1	13619	-0.049	0.13	NO
25	SHC1	SHC1	SHC1	14115	-0.056	0.13	NO
26	BCAR1	BCAR1	BCAR1	14622	-0.064	0.14	NO
27	PRKCA	PRKCA	PRKCA	16304	-0.11	0.097	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Subtype clus3 enriched pathways

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

GeneSet(GS)	Size(#genes)	genes.ES.table	ES	NES	NOM.p.val	FDR.q.val	FWER.p.val	Tag..	Gene..	Signal	FDR..median.	glob.p.val
BIOCARTA NO1 PATHWAY	28	genes.ES.table	0.55	1.5	0.049	1	0.88	0.32	0.13	0.28	0.91	0.47
BIOCARTA AGR PATHWAY	35	genes.ES.table	0.5	1.5	0.055	1	0.86	0.31	0.24	0.24	1	0.52
BIOCARTA ALK PATHWAY	34	genes.ES.table	0.55	1.6	0.022	1	0.7	0.44	0.23	0.34	0.72	0.41
BIOCARTA NFAT PATHWAY	49	genes.ES.table	0.41	1.3	0.11	0.9	0.98	0.47	0.36	0.3	0.72	0.33
BIOCARTA EDG1 PATHWAY	26	genes.ES.table	0.48	1.3	0.14	0.98	0.98	0.31	0.15	0.26	0.78	0.38
BIOCARTA WNT PATHWAY	25	genes.ES.table	0.32	1.3	0.18	0.75	0.99	0.08	0.029	0.078	0.64	0.24
KEGG LYSINE DEGRADATION	43	genes.ES.table	0.31	1.4	0.12	1	0.97	0.12	0.15	0.099	0.82	0.4
KEGG ERBB SIGNALING PATHWAY	86	genes.ES.table	0.32	1.3	0.14	0.83	0.98	0.21	0.2	0.17	0.69	0.3
KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION	216	genes.ES.table	0.49	1.3	0.056	0.85	0.98	0.4	0.17	0.33	0.67	0.31
KEGG HEDGEHOG SIGNALING PATHWAY	52	genes.ES.table	0.48	1.3	0.14	0.84	0.98	0.36	0.18	0.3	0.7	0.3

genes ES table in pathway: BIOCARTA NO1 PATHWAY

Table S21. Get Full Table This table shows a Running Enrichment Score (RES) of each gene in this pathway, that is, the enrichment score at this point in the ranked list of genes. All genes are ranked by Signal-to-Noise (S2N), a measure of similarity as default and are used to obtain ES matrix of all genes. In this way, GSEA tool uses expression pattern of not only overlapped genes but also not-overlapped genes to produce ES matrix.

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TGFB2	TGFB2	TGFB2	127	0.49	0.035	YES
2	THBS4	THBS4	THBS4	207	0.45	0.069	YES
3	THBS2	THBS2	THBS2	256	0.43	0.1	YES
4	BMP2	BMP2	BMP2	260	0.43	0.14	YES
5	BMP6	BMP6	BMP6	278	0.42	0.18	YES
6	INHBA	INHBA	INHBA	326	0.41	0.21	YES
7	ID4	ID4	ID4	532	0.36	0.23	YES
8	LTBP1	LTBP1	LTBP1	580	0.36	0.26	YES
9	FST	FST	FST	586	0.36	0.28	YES
10	BMP5	BMP5	BMP5	994	0.3	0.29	YES
11	ID1	ID1	ID1	1206	0.28	0.3	YES
12	E2F5	E2F5	E2F5	1219	0.28	0.32	YES
13	ID3	ID3	ID3	1403	0.26	0.34	YES
14	ACVR2A	ACVR2A	ACVR2A	1481	0.25	0.35	YES
15	TGFB3	TGFB3	TGFB3	1581	0.25	0.37	YES
16	BMP8A	BMP8A	BMP8A	1744	0.23	0.38	YES
17	INHBB	INHBB	INHBB	1745	0.23	0.4	YES
18	ROCK2	ROCK2	ROCK2	1919	0.22	0.41	YES
19	DCN	DCN	DCN	1951	0.22	0.43	YES
20	SMAD9	SMAD9	SMAD9	2039	0.22	0.44	YES
21	BMPR1A	BMPR1A	BMPR1A	2197	0.21	0.45	YES
22	SMURF2	SMURF2	SMURF2	2372	0.2	0.46	YES
23	AMH	AMH	AMH	2525	0.19	0.46	YES
24	GDF6	GDF6	GDF6	2547	0.19	0.48	YES
25	BMP7	BMP7	BMP7	2577	0.19	0.49	YES
26	SMAD1	SMAD1	SMAD1	2602	0.18	0.51	YES
27	BMP8B	BMP8B	BMP8B	2653	0.18	0.52	YES
28	CHRD	CHRD	CHRD	2659	0.18	0.54	YES
29	SMAD5	SMAD5	SMAD5	2667	0.18	0.55	YES
30	THBS1	THBS1	THBS1	2737	0.18	0.56	YES
31	LEFTY1	LEFTY1	LEFTY1	3175	0.16	0.55	NO
32	COMP	COMP	COMP	3234	0.16	0.56	NO
33	BMP4	BMP4	BMP4	3777	0.14	0.54	NO
34	ROCK1	ROCK1	ROCK1	4329	0.12	0.52	NO
35	ACVR2B	ACVR2B	ACVR2B	4468	0.12	0.52	NO
36	ACVR1	ACVR1	ACVR1	4641	0.11	0.52	NO
37	THBS3	THBS3	THBS3	4660	0.11	0.53	NO
38	SMAD7	SMAD7	SMAD7	5134	0.1	0.52	NO
39	SMAD4	SMAD4	SMAD4	5291	0.097	0.51	NO
40	LEFTY2	LEFTY2	LEFTY2	5391	0.095	0.52	NO
41	INHBE	INHBE	INHBE	5478	0.092	0.52	NO
42	RPS6KB1	RPS6KB1	RPS6KB1	5725	0.087	0.51	NO
43	ZFYVE9	ZFYVE9	ZFYVE9	5936	0.082	0.51	NO
44	NODAL	NODAL	NODAL	6297	0.074	0.5	NO
45	PPP2R1B	PPP2R1B	PPP2R1B	6359	0.073	0.5	NO
46	RBL1	RBL1	RBL1	6527	0.069	0.5	NO
47	RBL2	RBL2	RBL2	7088	0.059	0.47	NO
48	ID2	ID2	ID2	7476	0.052	0.45	NO
49	ACVRL1	ACVRL1	ACVRL1	7783	0.046	0.44	NO
50	PPP2CB	PPP2CB	PPP2CB	7874	0.045	0.44	NO
51	TGFBR2	TGFBR2	TGFBR2	8312	0.038	0.42	NO
52	GDF5	GDF5	GDF5	8366	0.037	0.42	NO
53	SP1	SP1	SP1	8689	0.032	0.4	NO
54	INHBC	INHBC	INHBC	8880	0.028	0.39	NO
55	TFDP1	TFDP1	TFDP1	9047	0.026	0.39	NO
56	CUL1	CUL1	CUL1	9197	0.024	0.38	NO
57	CREBBP	CREBBP	CREBBP	9304	0.022	0.38	NO
58	CDKN2B	CDKN2B	CDKN2B	9341	0.021	0.38	NO
59	SKP1	SKP1	SKP1	9409	0.02	0.37	NO
60	TGFB1	TGFB1	TGFB1	9421	0.02	0.38	NO
61	E2F4	E2F4	E2F4	9561	0.018	0.37	NO
62	EP300	EP300	EP300	10385	0.0058	0.32	NO
63	TGFBR1	TGFBR1	TGFBR1	10528	0.0035	0.32	NO
64	AMHR2	AMHR2	AMHR2	10826	-0.00081	0.3	NO
65	PPP2CA	PPP2CA	PPP2CA	10854	-0.0011	0.3	NO
66	PITX2	PITX2	PITX2	11012	-0.0034	0.29	NO
67	SMAD2	SMAD2	SMAD2	11116	-0.0049	0.28	NO
68	PPP2R1A	PPP2R1A	PPP2R1A	11119	-0.005	0.28	NO
69	ZFYVE16	ZFYVE16	ZFYVE16	11155	-0.0056	0.28	NO
70	SMAD3	SMAD3	SMAD3	11211	-0.0064	0.28	NO
71	SMAD6	SMAD6	SMAD6	11799	-0.016	0.25	NO
72	BMPR2	BMPR2	BMPR2	11865	-0.017	0.25	NO
73	RHOA	RHOA	RHOA	12365	-0.025	0.22	NO
74	MAPK1	MAPK1	MAPK1	12409	-0.026	0.22	NO
75	RBX1	RBX1	RBX1	13061	-0.038	0.19	NO
76	MAPK3	MAPK3	MAPK3	13375	-0.044	0.17	NO
77	SMURF1	SMURF1	SMURF1	13654	-0.05	0.16	NO
78	ACVR1C	ACVR1C	ACVR1C	14739	-0.076	0.11	NO
79	GDF7	GDF7	GDF7	14788	-0.077	0.11	NO
80	RPS6KB2	RPS6KB2	RPS6KB2	15007	-0.083	0.11	NO
81	MYC	MYC	MYC	15047	-0.084	0.11	NO
82	BMPR1B	BMPR1B	BMPR1B	15077	-0.085	0.12	NO
83	TNF	TNF	TNF	17322	-0.25	0.015	NO
84	IFNG	IFNG	IFNG	17547	-0.29	0.028	NO

Figure S41. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA NO1 PATHWAY.

Figure S42. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA NO1 PATHWAY, this volcano plot shows how much they are up/down-regulated and significant. The significance was calculated by empirical bayesian fit

genes ES table in pathway: BIOCARTA AGR PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	TGFB2	TGFB2	TGFB2	127	0.49	0.1	YES
2	BMP2	BMP2	BMP2	260	0.43	0.19	YES
3	FZD1	FZD1	FZD1	525	0.36	0.25	YES
4	BMP5	BMP5	BMP5	994	0.3	0.29	YES
5	NKX2-5	NKX2-5	NKX2-5	1349	0.26	0.33	YES
6	TGFB3	TGFB3	TGFB3	1581	0.25	0.37	YES
7	BMPR1A	BMPR1A	BMPR1A	2197	0.21	0.38	YES
8	BMP7	BMP7	BMP7	2577	0.19	0.4	YES
9	SMAD1	SMAD1	SMAD1	2602	0.18	0.44	YES
10	CHRD	CHRD	CHRD	2659	0.18	0.48	YES
11	SMAD5	SMAD5	SMAD5	2667	0.18	0.52	YES
12	ATF2	ATF2	ATF2	3070	0.16	0.53	YES
13	BMP4	BMP4	BMP4	3777	0.14	0.52	YES
14	MAP3K7	MAP3K7	MAP3K7	3909	0.13	0.54	YES
15	APC	APC	APC	4194	0.12	0.55	YES
16	ACVR1	ACVR1	ACVR1	4641	0.11	0.55	NO
17	SMAD4	SMAD4	SMAD4	5291	0.097	0.54	NO
18	NOG	NOG	NOG	5950	0.082	0.52	NO
19	TGFBR2	TGFBR2	TGFBR2	8312	0.038	0.4	NO
20	GSK3B	GSK3B	GSK3B	8400	0.036	0.4	NO
21	TGFB1	TGFB1	TGFB1	9421	0.02	0.35	NO
22	RFC1	RFC1	RFC1	10058	0.01	0.31	NO
23	TGFBR1	TGFBR1	TGFBR1	10528	0.0035	0.29	NO
24	HNF1A	HNF1A	HNF1A	10903	-0.0017	0.27	NO
25	DVL1	DVL1	DVL1	11440	-0.01	0.24	NO
26	SMAD6	SMAD6	SMAD6	11799	-0.016	0.22	NO
27	BMPR2	BMPR2	BMPR2	11865	-0.017	0.22	NO
28	NPPA	NPPA	NPPA	12297	-0.024	0.2	NO
29	AXIN1	AXIN1	AXIN1	12874	-0.034	0.18	NO
30	GATA4	GATA4	GATA4	13200	-0.04	0.17	NO
31	TGFBR3	TGFBR3	TGFBR3	13500	-0.046	0.16	NO
32	CTNNB1	CTNNB1	CTNNB1	13993	-0.057	0.15	NO
33	MYL2	MYL2	MYL2	16418	-0.16	0.048	NO
34	WNT1	WNT1	WNT1	16825	-0.19	0.068	NO

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

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

genes ES table in pathway: BIOCARTA ALK PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ITGA1	ITGA1	ITGA1	357	0.4	0.09	YES
2	PAK3	PAK3	PAK3	434	0.38	0.19	YES
3	LAMA2	LAMA2	LAMA2	513	0.37	0.29	YES
4	LAMA4	LAMA4	LAMA4	874	0.31	0.35	YES
5	NRG1	NRG1	NRG1	1855	0.23	0.36	YES
6	EGFR	EGFR	EGFR	1984	0.22	0.41	YES
7	DMD	DMD	DMD	2366	0.2	0.44	YES
8	MAPK8	MAPK8	MAPK8	2391	0.2	0.5	YES
9	PAK7	PAK7	PAK7	3191	0.16	0.5	YES
10	UTRN	UTRN	UTRN	3999	0.13	0.49	YES
11	ITGB1	ITGB1	ITGB1	4285	0.12	0.5	YES
12	ACTA1	ACTA1	ACTA1	5736	0.086	0.45	NO
13	PTK2	PTK2	PTK2	5804	0.085	0.47	NO
14	MUSK	MUSK	MUSK	7545	0.051	0.38	NO
15	PAK2	PAK2	PAK2	8134	0.04	0.36	NO
16	GIT2	GIT2	GIT2	8179	0.04	0.37	NO
17	SP1	SP1	SP1	8689	0.032	0.35	NO
18	LAMA3	LAMA3	LAMA3	9201	0.024	0.33	NO
19	JUN	JUN	JUN	9232	0.023	0.33	NO
20	SRC	SRC	SRC	9234	0.023	0.34	NO
21	RAPSN	RAPSN	RAPSN	9268	0.022	0.34	NO
22	DAG1	DAG1	DAG1	9364	0.021	0.34	NO
23	PXN	PXN	PXN	9601	0.017	0.34	NO
24	RAC1	RAC1	RAC1	9959	0.012	0.32	NO
25	PAK6	PAK6	PAK6	11403	-0.0095	0.24	NO
26	DVL1	DVL1	DVL1	11440	-0.01	0.24	NO
27	CDC42	CDC42	CDC42	11790	-0.016	0.23	NO
28	MAPK1	MAPK1	MAPK1	12409	-0.026	0.2	NO
29	PAK1	PAK1	PAK1	12825	-0.033	0.19	NO
30	MAPK3	MAPK3	MAPK3	13375	-0.044	0.17	NO
31	CTTN	CTTN	CTTN	13460	-0.046	0.18	NO
32	CHRM1	CHRM1	CHRM1	13497	-0.046	0.19	NO
33	NRG2	NRG2	NRG2	13772	-0.052	0.18	NO
34	CHRNA1	CHRNA1	CHRNA1	15215	-0.09	0.13	NO
35	PAK4	PAK4	PAK4	15506	-0.1	0.14	NO

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

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

genes ES table in pathway: BIOCARTA NFAT PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	PRKG1	PRKG1	PRKG1	307	0.42	0.096	YES
2	BDKRB2	BDKRB2	BDKRB2	498	0.37	0.19	YES
3	TNNI1	TNNI1	TNNI1	1052	0.29	0.24	YES
4	VEGFA	VEGFA	VEGFA	1327	0.27	0.29	YES
5	RYR2	RYR2	RYR2	1365	0.26	0.36	YES
6	FLT1	FLT1	FLT1	1420	0.26	0.43	YES
7	PRKAR2B	PRKAR2B	PRKAR2B	1613	0.24	0.48	YES
8	PRKAR1B	PRKAR1B	PRKAR1B	2344	0.2	0.5	YES
9	KDR	KDR	KDR	2396	0.2	0.55	YES
10	PRKACB	PRKACB	PRKACB	3209	0.16	0.55	NO
11	PDE2A	PDE2A	PDE2A	5047	0.1	0.47	NO
12	ACTA1	ACTA1	ACTA1	5736	0.086	0.46	NO
13	PDE3B	PDE3B	PDE3B	6610	0.068	0.43	NO
14	NOS3	NOS3	NOS3	6961	0.061	0.43	NO
15	CALM2	CALM2	CALM2	6976	0.061	0.44	NO
16	PRKAR2A	PRKAR2A	PRKAR2A	7175	0.058	0.45	NO
17	FLT4	FLT4	FLT4	7769	0.047	0.43	NO
18	PRKAR1A	PRKAR1A	PRKAR1A	8255	0.038	0.41	NO
19	HSP90AA1	HSP90AA1	HSP90AA1	9154	0.024	0.37	NO
20	KNG1	KNG1	KNG1	9446	0.02	0.36	NO
21	PDE3A	PDE3A	PDE3A	9541	0.018	0.36	NO
22	CALM3	CALM3	CALM3	10673	0.0014	0.29	NO
23	CALM1	CALM1	CALM1	12205	-0.022	0.21	NO
24	CHRM1	CHRM1	CHRM1	13497	-0.046	0.16	NO
25	AKT1	AKT1	AKT1	14556	-0.07	0.12	NO
26	CHRNA1	CHRNA1	CHRNA1	15215	-0.09	0.1	NO
27	SLC7A1	SLC7A1	SLC7A1	15407	-0.098	0.12	NO
28	PRKG2	PRKG2	PRKG2	15459	-0.099	0.14	NO

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

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

genes ES table in pathway: BIOCARTA EDG1 PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ITGB3	ITGB3	ITGB3	86	0.52	0.031	YES
2	SDC2	SDC2	SDC2	160	0.47	0.059	YES
3	THBS4	THBS4	THBS4	207	0.45	0.086	YES
4	TNN	TNN	TNN	232	0.44	0.12	YES
5	THBS2	THBS2	THBS2	256	0.43	0.14	YES
6	ITGA2	ITGA2	ITGA2	319	0.41	0.17	YES
7	SV2A	SV2A	SV2A	325	0.41	0.2	YES
8	ITGA1	ITGA1	ITGA1	357	0.4	0.22	YES
9	CD36	CD36	CD36	489	0.37	0.24	YES
10	LAMA2	LAMA2	LAMA2	513	0.37	0.26	YES
11	COL11A2	COL11A2	COL11A2	657	0.34	0.28	YES
12	ITGA10	ITGA10	ITGA10	729	0.33	0.3	YES
13	RELN	RELN	RELN	800	0.32	0.32	YES
14	LAMA4	LAMA4	LAMA4	874	0.31	0.33	YES
15	ITGA8	ITGA8	ITGA8	911	0.31	0.35	YES
16	SPP1	SPP1	SPP1	1092	0.29	0.36	YES
17	IBSP	IBSP	IBSP	1197	0.28	0.37	YES
18	ITGA2B	ITGA2B	ITGA2B	1234	0.27	0.39	YES
19	LAMB1	LAMB1	LAMB1	1465	0.26	0.39	YES
20	COL4A6	COL4A6	COL4A6	1520	0.25	0.41	YES
21	COL5A2	COL5A2	COL5A2	1648	0.24	0.42	YES
22	COL1A2	COL1A2	COL1A2	1942	0.22	0.42	YES
23	ITGA11	ITGA11	ITGA11	2004	0.22	0.43	YES
24	ITGA4	ITGA4	ITGA4	2075	0.21	0.44	YES
25	ITGA9	ITGA9	ITGA9	2135	0.21	0.45	YES
26	COL2A1	COL2A1	COL2A1	2678	0.18	0.43	YES
27	ITGAV	ITGAV	ITGAV	2707	0.18	0.44	YES
28	THBS1	THBS1	THBS1	2737	0.18	0.45	YES
29	LAMC1	LAMC1	LAMC1	2743	0.18	0.46	YES
30	CHAD	CHAD	CHAD	2772	0.18	0.47	YES
31	ITGA6	ITGA6	ITGA6	2900	0.17	0.48	YES
32	ITGB6	ITGB6	ITGB6	3045	0.16	0.48	YES
33	COL6A1	COL6A1	COL6A1	3103	0.16	0.49	YES
34	COMP	COMP	COMP	3234	0.16	0.49	YES
35	COL11A1	COL11A1	COL11A1	3314	0.15	0.5	YES
36	ITGB8	ITGB8	ITGB8	3333	0.15	0.51	YES
37	COL6A2	COL6A2	COL6A2	3382	0.15	0.52	YES
38	ITGA5	ITGA5	ITGA5	3721	0.14	0.51	YES
39	COL5A1	COL5A1	COL5A1	3754	0.14	0.51	YES
40	COL3A1	COL3A1	COL3A1	3976	0.13	0.51	YES
41	ITGB5	ITGB5	ITGB5	4184	0.12	0.51	YES
42	COL4A1	COL4A1	COL4A1	4190	0.12	0.52	YES
43	ITGB1	ITGB1	ITGB1	4285	0.12	0.52	YES
44	COL5A3	COL5A3	COL5A3	4546	0.11	0.51	YES
45	TNR	TNR	TNR	4572	0.11	0.52	YES
46	ITGB4	ITGB4	ITGB4	4615	0.11	0.52	YES
47	LAMB4	LAMB4	LAMB4	4652	0.11	0.53	YES
48	THBS3	THBS3	THBS3	4660	0.11	0.54	YES
49	LAMA5	LAMA5	LAMA5	4825	0.11	0.54	YES
50	HMMR	HMMR	HMMR	4847	0.11	0.54	YES
51	SDC4	SDC4	SDC4	4875	0.11	0.55	YES
52	GP6	GP6	GP6	5070	0.1	0.54	YES
53	COL4A2	COL4A2	COL4A2	5163	0.1	0.54	YES
54	COL1A1	COL1A1	COL1A1	5195	0.099	0.55	YES
55	COL6A3	COL6A3	COL6A3	5267	0.097	0.55	YES
56	LAMB3	LAMB3	LAMB3	5403	0.094	0.55	NO
57	TNC	TNC	TNC	5551	0.091	0.55	NO
58	SV2C	SV2C	SV2C	6368	0.073	0.51	NO
59	SDC1	SDC1	SDC1	6484	0.07	0.51	NO
60	LAMC3	LAMC3	LAMC3	7503	0.052	0.45	NO
61	AGRN	AGRN	AGRN	7662	0.048	0.45	NO
62	FN1	FN1	FN1	8161	0.04	0.42	NO
63	LAMA3	LAMA3	LAMA3	9201	0.024	0.37	NO
64	DAG1	DAG1	DAG1	9364	0.021	0.36	NO
65	TNXB	TNXB	TNXB	9469	0.019	0.35	NO
66	LAMC2	LAMC2	LAMC2	10079	0.01	0.32	NO
67	COL6A6	COL6A6	COL6A6	10628	0.0022	0.29	NO
68	SDC3	SDC3	SDC3	10806	-0.00056	0.28	NO
69	CD47	CD47	CD47	11508	-0.011	0.24	NO
70	VWF	VWF	VWF	11889	-0.017	0.22	NO
71	SV2B	SV2B	SV2B	12055	-0.02	0.22	NO
72	HSPG2	HSPG2	HSPG2	12208	-0.022	0.21	NO
73	LAMB2	LAMB2	LAMB2	13416	-0.045	0.14	NO
74	COL4A4	COL4A4	COL4A4	14757	-0.076	0.074	NO
75	ITGA7	ITGA7	ITGA7	15496	-0.1	0.04	NO
76	CD44	CD44	CD44	15634	-0.11	0.04	NO
77	ITGA3	ITGA3	ITGA3	15802	-0.12	0.039	NO
78	GP5	GP5	GP5	17231	-0.24	-0.025	NO
79	LAMA1	LAMA1	LAMA1	17389	-0.26	-0.016	NO
80	GP1BA	GP1BA	GP1BA	17769	-0.34	-0.014	NO
81	ITGB7	ITGB7	ITGB7	17954	-0.43	0.0052	NO

Figure S49. Get High-res Image This plot shows mRNAseq_cNMF expression data heatmap (on the left) a RunningEnrichmentScore(RES) plot (on the top right) and a Signal2Noise(S2N) plot (on the bottom right) of genes in the pathway: BIOCARTA EDG1 PATHWAY.

Figure S50. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA EDG1 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 WNT PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	ITGB3	ITGB3	ITGB3	86	0.52	0.043	YES
2	ITGA2	ITGA2	ITGA2	319	0.41	0.068	YES
3	ITGA1	ITGA1	ITGA1	357	0.4	0.1	YES
4	SGCG	SGCG	SGCG	461	0.38	0.13	YES
5	LAMA2	LAMA2	LAMA2	513	0.37	0.16	YES
6	CDH2	CDH2	CDH2	558	0.36	0.19	YES
7	ITGA10	ITGA10	ITGA10	729	0.33	0.21	YES
8	ITGA8	ITGA8	ITGA8	911	0.31	0.23	YES
9	CTNNA3	CTNNA3	CTNNA3	1082	0.29	0.25	YES
10	GJA1	GJA1	GJA1	1120	0.28	0.27	YES
11	ITGA2B	ITGA2B	ITGA2B	1234	0.27	0.29	YES
12	RYR2	RYR2	RYR2	1365	0.26	0.31	YES
13	CACNA2D1	CACNA2D1	CACNA2D1	1569	0.25	0.32	YES
14	DSG2	DSG2	DSG2	1573	0.25	0.34	YES
15	CACNA1C	CACNA1C	CACNA1C	1816	0.23	0.35	YES
16	SGCB	SGCB	SGCB	1819	0.23	0.37	YES
17	ITGA11	ITGA11	ITGA11	2004	0.22	0.38	YES
18	ITGA4	ITGA4	ITGA4	2075	0.21	0.39	YES
19	ITGA9	ITGA9	ITGA9	2135	0.21	0.41	YES
20	CACNB4	CACNB4	CACNB4	2166	0.21	0.43	YES
21	ACTN2	ACTN2	ACTN2	2186	0.21	0.44	YES
22	CACNG4	CACNG4	CACNG4	2201	0.21	0.46	YES
23	DMD	DMD	DMD	2366	0.2	0.47	YES
24	CACNA2D3	CACNA2D3	CACNA2D3	2640	0.18	0.47	YES
25	ITGAV	ITGAV	ITGAV	2707	0.18	0.49	YES
26	CACNA2D4	CACNA2D4	CACNA2D4	2730	0.18	0.5	YES
27	ITGA6	ITGA6	ITGA6	2900	0.17	0.51	YES
28	ITGB6	ITGB6	ITGB6	3045	0.16	0.51	YES
29	ITGB8	ITGB8	ITGB8	3333	0.15	0.51	YES
30	ITGA5	ITGA5	ITGA5	3721	0.14	0.5	YES
31	TCF7L2	TCF7L2	TCF7L2	4080	0.13	0.5	YES
32	ITGB5	ITGB5	ITGB5	4184	0.12	0.5	YES
33	CACNB1	CACNB1	CACNB1	4226	0.12	0.51	YES
34	ITGB1	ITGB1	ITGB1	4285	0.12	0.52	YES
35	ITGB4	ITGB4	ITGB4	4615	0.11	0.51	NO
36	CACNB2	CACNB2	CACNB2	4975	0.1	0.5	NO
37	TCF7L1	TCF7L1	TCF7L1	5385	0.095	0.48	NO
38	DES	DES	DES	5634	0.089	0.48	NO
39	CACNG6	CACNG6	CACNG6	5694	0.087	0.48	NO
40	DSC2	DSC2	DSC2	5827	0.085	0.48	NO
41	JUP	JUP	JUP	7696	0.048	0.38	NO
42	ACTN4	ACTN4	ACTN4	8310	0.038	0.35	NO
43	CACNB3	CACNB3	CACNB3	8459	0.035	0.35	NO
44	CTNNA1	CTNNA1	CTNNA1	8834	0.029	0.33	NO
45	SLC8A1	SLC8A1	SLC8A1	8998	0.027	0.32	NO
46	DSP	DSP	DSP	9167	0.024	0.32	NO
47	DAG1	DAG1	DAG1	9364	0.021	0.31	NO
48	SGCA	SGCA	SGCA	9781	0.015	0.28	NO
49	LEF1	LEF1	LEF1	10472	0.0045	0.25	NO
50	ATP2A2	ATP2A2	ATP2A2	10861	-0.0012	0.23	NO
51	PKP2	PKP2	PKP2	10890	-0.0016	0.22	NO
52	CACNA1S	CACNA1S	CACNA1S	11370	-0.0088	0.2	NO
53	CTNNA2	CTNNA2	CTNNA2	12148	-0.022	0.16	NO
54	CACNA1D	CACNA1D	CACNA1D	13358	-0.044	0.094	NO
55	CACNA2D2	CACNA2D2	CACNA2D2	13552	-0.047	0.088	NO
56	ACTB	ACTB	ACTB	13778	-0.052	0.08	NO
57	CTNNB1	CTNNB1	CTNNB1	13993	-0.057	0.073	NO
58	ACTG1	ACTG1	ACTG1	14084	-0.059	0.074	NO
59	LMNA	LMNA	LMNA	14317	-0.064	0.066	NO
60	EMD	EMD	EMD	14347	-0.065	0.071	NO
61	SGCD	SGCD	SGCD	15054	-0.085	0.039	NO
62	CACNA1F	CACNA1F	CACNA1F	15282	-0.093	0.035	NO
63	ITGA7	ITGA7	ITGA7	15496	-0.1	0.032	NO
64	ACTN3	ACTN3	ACTN3	15577	-0.1	0.038	NO
65	ITGA3	ITGA3	ITGA3	15802	-0.12	0.036	NO
66	ACTN1	ACTN1	ACTN1	15904	-0.12	0.041	NO
67	TCF7	TCF7	TCF7	15941	-0.12	0.051	NO
68	CACNG3	CACNG3	CACNG3	17593	-0.3	-0.014	NO
69	ITGB7	ITGB7	ITGB7	17954	-0.43	0.0052	NO

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

Figure S52. Get High-res Image For the top 5 core enriched genes in the pathway: BIOCARTA WNT 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 LYSINE DEGRADATION

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	PDGFC	PDGFC	PDGFC	26	0.61	0.05	YES
2	HTR2A	HTR2A	HTR2A	146	0.48	0.084	YES
3	ADRB1	ADRB1	ADRB1	181	0.46	0.12	YES
4	PDGFA	PDGFA	PDGFA	187	0.46	0.16	YES
5	PLCB1	PLCB1	PLCB1	236	0.44	0.2	YES
6	PRKG1	PRKG1	PRKG1	307	0.42	0.23	YES
7	LPAR1	LPAR1	LPAR1	310	0.42	0.26	YES
8	PRKCA	PRKCA	PRKCA	527	0.36	0.28	YES
9	PDGFD	PDGFD	PDGFD	749	0.33	0.3	YES
10	ADCY8	ADCY8	ADCY8	1059	0.29	0.3	YES
11	TUBB1	TUBB1	TUBB1	1060	0.29	0.33	YES
12	GJA1	GJA1	GJA1	1120	0.28	0.35	YES
13	GRM5	GRM5	GRM5	1163	0.28	0.37	YES
14	PLCB4	PLCB4	PLCB4	1483	0.25	0.37	YES
15	GUCY1A3	GUCY1A3	GUCY1A3	1777	0.23	0.38	YES
16	EGFR	EGFR	EGFR	1984	0.22	0.38	YES
17	PDGFRA	PDGFRA	PDGFRA	2008	0.22	0.4	YES
18	GUCY1B3	GUCY1B3	GUCY1B3	2334	0.2	0.4	YES
19	TUBB2B	TUBB2B	TUBB2B	2386	0.2	0.41	YES
20	PRKACB	PRKACB	PRKACB	3209	0.16	0.38	NO
21	PDGFRB	PDGFRB	PDGFRB	3407	0.15	0.38	NO
22	ITPR1	ITPR1	ITPR1	3688	0.14	0.38	NO
23	HTR2C	HTR2C	HTR2C	4023	0.13	0.37	NO
24	GUCY1A2	GUCY1A2	GUCY1A2	4099	0.13	0.38	NO
25	TJP1	TJP1	TJP1	4251	0.12	0.38	NO
26	GRM1	GRM1	GRM1	4820	0.11	0.36	NO
27	DRD2	DRD2	DRD2	4851	0.11	0.37	NO
28	ADCY6	ADCY6	ADCY6	5181	0.099	0.36	NO
29	TUBA1A	TUBA1A	TUBA1A	5389	0.095	0.35	NO
30	MAP3K2	MAP3K2	MAP3K2	5632	0.089	0.35	NO
31	GNAS	GNAS	GNAS	5665	0.088	0.35	NO
32	GNAI1	GNAI1	GNAI1	5750	0.086	0.36	NO
33	ITPR2	ITPR2	ITPR2	6318	0.074	0.33	NO
34	SOS1	SOS1	SOS1	6766	0.065	0.31	NO
35	KRAS	KRAS	KRAS	6934	0.062	0.31	NO
36	PDGFB	PDGFB	PDGFB	6948	0.062	0.31	NO
37	MAP2K1	MAP2K1	MAP2K1	7378	0.054	0.29	NO
38	EGF	EGF	EGF	7388	0.054	0.3	NO
39	GNAQ	GNAQ	GNAQ	7477	0.052	0.3	NO
40	NRAS	NRAS	NRAS	7999	0.043	0.27	NO
41	HTR2B	HTR2B	HTR2B	8083	0.041	0.27	NO
42	GNA11	GNA11	GNA11	9044	0.026	0.22	NO
43	TUBA3E	TUBA3E	TUBA3E	9158	0.024	0.21	NO
44	SRC	SRC	SRC	9234	0.023	0.21	NO
45	GNAI3	GNAI3	GNAI3	9394	0.02	0.2	NO
46	MAP2K5	MAP2K5	MAP2K5	9420	0.02	0.2	NO
47	PRKCG	PRKCG	PRKCG	9547	0.018	0.2	NO
48	ADCY7	ADCY7	ADCY7	10141	0.0094	0.17	NO
49	SOS2	SOS2	SOS2	10177	0.0089	0.16	NO
50	PLCB3	PLCB3	PLCB3	10338	0.0065	0.16	NO
51	DRD1	DRD1	DRD1	10502	0.0039	0.15	NO
52	CDK1	CDK1	CDK1	10517	0.0037	0.15	NO
53	PRKACA	PRKACA	PRKACA	10534	0.0034	0.15	NO
54	TUBA3C	TUBA3C	TUBA3C	10622	0.0023	0.14	NO
55	RAF1	RAF1	RAF1	10632	0.0021	0.14	NO
56	ADCY5	ADCY5	ADCY5	11272	-0.0073	0.11	NO
57	TUBB	TUBB	TUBB	11595	-0.013	0.09	NO
58	MAPK7	MAPK7	MAPK7	11680	-0.014	0.086	NO
59	TUBA1B	TUBA1B	TUBA1B	12114	-0.021	0.064	NO
60	CSNK1D	CSNK1D	CSNK1D	12310	-0.024	0.055	NO
61	MAPK1	MAPK1	MAPK1	12409	-0.026	0.052	NO
62	PRKX	PRKX	PRKX	12640	-0.03	0.042	NO
63	GNAI2	GNAI2	GNAI2	12777	-0.032	0.037	NO
64	TUBA3D	TUBA3D	TUBA3D	12857	-0.034	0.035	NO
65	ADCY4	ADCY4	ADCY4	12893	-0.034	0.036	NO
66	MAPK3	MAPK3	MAPK3	13375	-0.044	0.013	NO
67	TUBB2A	TUBB2A	TUBB2A	13377	-0.044	0.017	NO
68	HRAS	HRAS	HRAS	13503	-0.046	0.014	NO
69	TUBB2C	TUBB2C	TUBB2C	13547	-0.047	0.015	NO
70	TUBAL3	TUBAL3	TUBAL3	13569	-0.048	0.018	NO
71	TUBB6	TUBB6	TUBB6	13658	-0.05	0.018	NO
72	PLCB2	PLCB2	PLCB2	14101	-0.059	-0.0021	NO
73	GRB2	GRB2	GRB2	14165	-0.061	-0.00046	NO
74	TUBB3	TUBB3	TUBB3	14223	-0.062	0.0016	NO
75	MAP2K2	MAP2K2	MAP2K2	14277	-0.063	0.004	NO
76	ITPR3	ITPR3	ITPR3	14547	-0.07	-0.005	NO
77	TUBA1C	TUBA1C	TUBA1C	15078	-0.086	-0.027	NO
78	ADCY9	ADCY9	ADCY9	15311	-0.094	-0.032	NO
79	PRKG2	PRKG2	PRKG2	15459	-0.099	-0.032	NO
80	TUBB8	TUBB8	TUBB8	16107	-0.13	-0.057	NO
81	ADCY1	ADCY1	ADCY1	16318	-0.15	-0.056	NO
82	TUBB4Q	TUBB4Q	TUBB4Q	16341	-0.15	-0.044	NO
83	TUBA4A	TUBA4A	TUBA4A	16845	-0.2	-0.056	NO
84	TUBA8	TUBA8	TUBA8	17297	-0.25	-0.06	NO
85	TUBB4	TUBB4	TUBB4	17857	-0.37	-0.059	NO
86	PRKCB	PRKCB	PRKCB	17924	-0.41	-0.028	NO
87	ADCY2	ADCY2	ADCY2	17937	-0.42	0.0062	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 LYSINE DEGRADATION.

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

genes ES table in pathway: KEGG ERBB SIGNALING PATHWAY

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

Rank	GENE	SYMBOL	DESC	LIST.LOC	S2N	RES	CORE_ENRICHMENT
1	GRIA2	GRIA2	GRIA2	3	0.71	0.091	YES
2	PLCB1	PLCB1	PLCB1	236	0.44	0.13	YES
3	GRIA1	GRIA1	GRIA1	251	0.44	0.19	YES
4	CAMK2B	CAMK2B	CAMK2B	439	0.38	0.23	YES
5	PRKCA	PRKCA	PRKCA	527	0.36	0.27	YES
6	ADCY8	ADCY8	ADCY8	1059	0.29	0.28	YES
7	GRM5	GRM5	GRM5	1163	0.28	0.31	YES
8	PLCB4	PLCB4	PLCB4	1483	0.25	0.32	YES
9	CACNA1C	CACNA1C	CACNA1C	1816	0.23	0.33	YES
10	PRKACB	PRKACB	PRKACB	3209	0.16	0.28	YES
11	GRIN2B	GRIN2B	GRIN2B	3401	0.15	0.28	YES
12	RAPGEF3	RAPGEF3	RAPGEF3	3403	0.15	0.3	YES
13	RPS6KA6	RPS6KA6	RPS6KA6	3441	0.15	0.32	YES
14	CAMK2D	CAMK2D	CAMK2D	3451	0.15	0.34	YES
15	CALML6	CALML6	CALML6	3568	0.14	0.35	YES
16	RPS6KA3	RPS6KA3	RPS6KA3	3650	0.14	0.36	YES
17	PPP1R12A	PPP1R12A	PPP1R12A	3683	0.14	0.38	YES
18	ITPR1	ITPR1	ITPR1	3688	0.14	0.4	YES
19	BRAF	BRAF	BRAF	4309	0.12	0.38	NO
20	PPP3CA	PPP3CA	PPP3CA	4470	0.12	0.38	NO
21	GRM1	GRM1	GRM1	4820	0.11	0.38	NO
22	GRIN2A	GRIN2A	GRIN2A	5061	0.1	0.38	NO
23	PPP3R2	PPP3R2	PPP3R2	5914	0.083	0.34	NO
24	ITPR2	ITPR2	ITPR2	6318	0.074	0.33	NO
25	PPP1CB	PPP1CB	PPP1CB	6389	0.072	0.33	NO
26	KRAS	KRAS	KRAS	6934	0.062	0.31	NO
27	CALM2	CALM2	CALM2	6976	0.061	0.32	NO
28	PPP1R1A	PPP1R1A	PPP1R1A	7276	0.056	0.31	NO
29	MAP2K1	MAP2K1	MAP2K1	7378	0.054	0.31	NO
30	GNAQ	GNAQ	GNAQ	7477	0.052	0.31	NO
31	RAP1A	RAP1A	RAP1A	7511	0.051	0.32	NO
32	PPP3R1	PPP3R1	PPP3R1	7684	0.048	0.31	NO
33	RAP1B	RAP1B	RAP1B	7992	0.043	0.3	NO
34	NRAS	NRAS	NRAS	7999	0.043	0.3	NO
35	GRIN2D	GRIN2D	GRIN2D	8483	0.035	0.28	NO
36	PPP3CB	PPP3CB	PPP3CB	9078	0.026	0.25	NO
37	CREBBP	CREBBP	CREBBP	9304	0.022	0.24	NO
38	PRKCG	PRKCG	PRKCG	9547	0.018	0.23	NO
39	PPP1CC	PPP1CC	PPP1CC	9945	0.012	0.21	NO
40	PLCB3	PLCB3	PLCB3	10338	0.0065	0.19	NO
41	EP300	EP300	EP300	10385	0.0058	0.19	NO
42	ATF4	ATF4	ATF4	10436	0.0051	0.19	NO
43	PRKACA	PRKACA	PRKACA	10534	0.0034	0.18	NO
44	RAF1	RAF1	RAF1	10632	0.0021	0.18	NO
45	CALM3	CALM3	CALM3	10673	0.0014	0.17	NO
46	CAMK2G	CAMK2G	CAMK2G	10943	-0.0024	0.16	NO
47	CALML3	CALML3	CALML3	11036	-0.0037	0.16	NO
48	CAMK4	CAMK4	CAMK4	11506	-0.011	0.13	NO
49	CALM1	CALM1	CALM1	12205	-0.022	0.094	NO
50	MAPK1	MAPK1	MAPK1	12409	-0.026	0.086	NO
51	PRKX	PRKX	PRKX	12640	-0.03	0.077	NO
52	ARAF	ARAF	ARAF	13357	-0.044	0.043	NO
53	MAPK3	MAPK3	MAPK3	13375	-0.044	0.048	NO
54	GRIN2C	GRIN2C	GRIN2C	13407	-0.044	0.052	NO
55	HRAS	HRAS	HRAS	13503	-0.046	0.052	NO
56	CALML5	CALML5	CALML5	13649	-0.05	0.05	NO
57	CHP	CHP	CHP	13920	-0.055	0.042	NO
58	PLCB2	PLCB2	PLCB2	14101	-0.059	0.04	NO
59	MAP2K2	MAP2K2	MAP2K2	14277	-0.063	0.038	NO
60	ITPR3	ITPR3	ITPR3	14547	-0.07	0.032	NO
61	PPP1CA	PPP1CA	PPP1CA	14807	-0.078	0.028	NO
62	CHP2	CHP2	CHP2	14860	-0.079	0.035	NO
63	PPP3CC	PPP3CC	PPP3CC	15154	-0.088	0.03	NO
64	RPS6KA2	RPS6KA2	RPS6KA2	15725	-0.11	0.013	NO
65	RPS6KA1	RPS6KA1	RPS6KA1	16299	-0.15	-0.00062	NO
66	CAMK2A	CAMK2A	CAMK2A	16620	-0.17	0.0034	NO
67	GRIN1	GRIN1	GRIN1	16782	-0.19	0.018	NO
68	PRKCB	PRKCB	PRKCB	17924	-0.41	0.0069	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 ERBB SIGNALING PATHWAY.

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

genes ES table in pathway: KEGG NEUROACTIVE LIGAND RECEPTOR INTERACTION

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	PDGFC	PDGFC	PDGFC	26	0.61	0.021	YES
2	ITGB3	ITGB3	ITGB3	86	0.52	0.036	YES
3	PDGFA	PDGFA	PDGFA	187	0.46	0.048	YES
4	SHC3	SHC3	SHC3	198	0.45	0.063	YES
5	THBS4	THBS4	THBS4	207	0.45	0.079	YES
6	TNN	TNN	TNN	232	0.44	0.094	YES
7	THBS2	THBS2	THBS2	256	0.43	0.11	YES
8	ITGA2	ITGA2	ITGA2	319	0.41	0.12	YES
9	ITGA1	ITGA1	ITGA1	357	0.4	0.13	YES
10	PAK3	PAK3	PAK3	434	0.38	0.14	YES
11	LAMA2	LAMA2	LAMA2	513	0.37	0.15	YES
12	PRKCA	PRKCA	PRKCA	527	0.36	0.16	YES
13	COL11A2	COL11A2	COL11A2	657	0.34	0.17	YES
14	ITGA10	ITGA10	ITGA10	729	0.33	0.18	YES
15	PDGFD	PDGFD	PDGFD	749	0.33	0.19	YES
16	HGF	HGF	HGF	797	0.32	0.2	YES
17	RELN	RELN	RELN	800	0.32	0.21	YES
18	FLNC	FLNC	FLNC	815	0.32	0.22	YES
19	LAMA4	LAMA4	LAMA4	874	0.31	0.23	YES
20	ITGA8	ITGA8	ITGA8	911	0.31	0.24	YES
21	SPP1	SPP1	SPP1	1092	0.29	0.24	YES
22	IBSP	IBSP	IBSP	1197	0.28	0.24	YES
23	ITGA2B	ITGA2B	ITGA2B	1234	0.27	0.25	YES
24	VEGFA	VEGFA	VEGFA	1327	0.27	0.26	YES
25	FLT1	FLT1	FLT1	1420	0.26	0.26	YES
26	LAMB1	LAMB1	LAMB1	1465	0.26	0.27	YES
27	COL4A6	COL4A6	COL4A6	1520	0.25	0.27	YES
28	COL5A2	COL5A2	COL5A2	1648	0.24	0.27	YES
29	PGF	PGF	PGF	1890	0.22	0.27	YES
30	ROCK2	ROCK2	ROCK2	1919	0.22	0.27	YES
31	COL1A2	COL1A2	COL1A2	1942	0.22	0.28	YES
32	EGFR	EGFR	EGFR	1984	0.22	0.29	YES
33	ITGA11	ITGA11	ITGA11	2004	0.22	0.29	YES
34	PDGFRA	PDGFRA	PDGFRA	2008	0.22	0.3	YES
35	ITGA4	ITGA4	ITGA4	2075	0.21	0.31	YES
36	ITGA9	ITGA9	ITGA9	2135	0.21	0.31	YES
37	ACTN2	ACTN2	ACTN2	2186	0.21	0.32	YES
38	MAPK8	MAPK8	MAPK8	2391	0.2	0.31	YES
39	KDR	KDR	KDR	2396	0.2	0.32	YES
40	MAPK10	MAPK10	MAPK10	2405	0.2	0.32	YES
41	COL2A1	COL2A1	COL2A1	2678	0.18	0.32	YES
42	ITGAV	ITGAV	ITGAV	2707	0.18	0.32	YES
43	THBS1	THBS1	THBS1	2737	0.18	0.32	YES
44	LAMC1	LAMC1	LAMC1	2743	0.18	0.33	YES
45	CHAD	CHAD	CHAD	2772	0.18	0.34	YES
46	ITGA6	ITGA6	ITGA6	2900	0.17	0.34	YES
47	VAV2	VAV2	VAV2	2933	0.17	0.34	YES
48	ITGB6	ITGB6	ITGB6	3045	0.16	0.34	YES
49	MYLK2	MYLK2	MYLK2	3062	0.16	0.34	YES
50	COL6A1	COL6A1	COL6A1	3103	0.16	0.35	YES
51	PAK7	PAK7	PAK7	3191	0.16	0.35	YES
52	COMP	COMP	COMP	3234	0.16	0.35	YES
53	COL11A1	COL11A1	COL11A1	3314	0.15	0.35	YES
54	TLN2	TLN2	TLN2	3315	0.15	0.36	YES
55	ITGB8	ITGB8	ITGB8	3333	0.15	0.36	YES
56	COL6A2	COL6A2	COL6A2	3382	0.15	0.37	YES
57	PDGFRB	PDGFRB	PDGFRB	3407	0.15	0.37	YES
58	BIRC2	BIRC2	BIRC2	3420	0.15	0.38	YES
59	PIK3CA	PIK3CA	PIK3CA	3542	0.14	0.37	YES
60	MYL10	MYL10	MYL10	3658	0.14	0.37	YES
61	PPP1R12A	PPP1R12A	PPP1R12A	3683	0.14	0.38	YES
62	ITGA5	ITGA5	ITGA5	3721	0.14	0.38	YES
63	COL5A1	COL5A1	COL5A1	3754	0.14	0.38	YES
64	COL3A1	COL3A1	COL3A1	3976	0.13	0.38	YES
65	MYLK	MYLK	MYLK	4051	0.13	0.38	YES
66	ARHGAP5	ARHGAP5	ARHGAP5	4170	0.12	0.37	YES
67	ITGB5	ITGB5	ITGB5	4184	0.12	0.38	YES
68	COL4A1	COL4A1	COL4A1	4190	0.12	0.38	YES
69	ITGB1	ITGB1	ITGB1	4285	0.12	0.38	YES
70	BRAF	BRAF	BRAF	4309	0.12	0.38	YES
71	ROCK1	ROCK1	ROCK1	4329	0.12	0.39	YES
72	XIAP	XIAP	XIAP	4331	0.12	0.39	YES
73	CRK	CRK	CRK	4420	0.12	0.39	YES
74	COL5A3	COL5A3	COL5A3	4546	0.11	0.39	YES
75	TNR	TNR	TNR	4572	0.11	0.39	YES
76	ITGB4	ITGB4	ITGB4	4615	0.11	0.39	YES
77	LAMB4	LAMB4	LAMB4	4652	0.11	0.39	YES
78	THBS3	THBS3	THBS3	4660	0.11	0.4	YES
79	DOCK1	DOCK1	DOCK1	4732	0.11	0.4	YES
80	LAMA5	LAMA5	LAMA5	4825	0.11	0.4	NO
81	SHC1	SHC1	SHC1	4947	0.1	0.39	NO
82	COL4A2	COL4A2	COL4A2	5163	0.1	0.38	NO
83	COL1A1	COL1A1	COL1A1	5195	0.099	0.39	NO
84	COL6A3	COL6A3	COL6A3	5267	0.097	0.39	NO
85	LAMB3	LAMB3	LAMB3	5403	0.094	0.38	NO
86	TNC	TNC	TNC	5551	0.091	0.38	NO
87	AKT3	AKT3	AKT3	5596	0.09	0.38	NO
88	PTK2	PTK2	PTK2	5804	0.085	0.37	NO
89	VCL	VCL	VCL	6216	0.076	0.35	NO
90	GRLF1	GRLF1	GRLF1	6241	0.075	0.35	NO
91	SHC2	SHC2	SHC2	6276	0.075	0.35	NO
92	ERBB2	ERBB2	ERBB2	6300	0.074	0.35	NO
93	PPP1CB	PPP1CB	PPP1CB	6389	0.072	0.35	NO
94	SOS1	SOS1	SOS1	6766	0.065	0.33	NO
95	PDGFB	PDGFB	PDGFB	6948	0.062	0.32	NO
96	CAV2	CAV2	CAV2	7005	0.061	0.32	NO
97	IGF1R	IGF1R	IGF1R	7212	0.057	0.31	NO
98	MAP2K1	MAP2K1	MAP2K1	7378	0.054	0.31	NO
99	EGF	EGF	EGF	7388	0.054	0.31	NO
100	MAPK9	MAPK9	MAPK9	7398	0.053	0.31	NO
101	LAMC3	LAMC3	LAMC3	7503	0.052	0.3	NO
102	RAP1A	RAP1A	RAP1A	7511	0.051	0.31	NO
103	ZYX	ZYX	ZYX	7567	0.05	0.31	NO
104	FLT4	FLT4	FLT4	7769	0.047	0.3	NO
105	MYLPF	MYLPF	MYLPF	7981	0.043	0.29	NO
106	RAP1B	RAP1B	RAP1B	7992	0.043	0.29	NO
107	CAV1	CAV1	CAV1	8072	0.041	0.28	NO
108	PAK2	PAK2	PAK2	8134	0.04	0.28	NO
109	FN1	FN1	FN1	8161	0.04	0.28	NO
110	VEGFC	VEGFC	VEGFC	8309	0.038	0.28	NO
111	ACTN4	ACTN4	ACTN4	8310	0.038	0.28	NO
112	GSK3B	GSK3B	GSK3B	8400	0.036	0.27	NO
113	IGF1	IGF1	IGF1	8685	0.032	0.26	NO
114	SHC4	SHC4	SHC4	8853	0.029	0.25	NO
115	LAMA3	LAMA3	LAMA3	9201	0.024	0.23	NO
116	JUN	JUN	JUN	9232	0.023	0.23	NO
117	SRC	SRC	SRC	9234	0.023	0.23	NO
118	TNXB	TNXB	TNXB	9469	0.019	0.22	NO
119	PIK3R1	PIK3R1	PIK3R1	9521	0.018	0.22	NO
120	PRKCG	PRKCG	PRKCG	9547	0.018	0.22	NO
121	PXN	PXN	PXN	9601	0.017	0.21	NO
122	PDPK1	PDPK1	PDPK1	9847	0.014	0.2	NO
123	PPP1CC	PPP1CC	PPP1CC	9945	0.012	0.2	NO
124	RAC1	RAC1	RAC1	9959	0.012	0.2	NO
125	LAMC2	LAMC2	LAMC2	10079	0.01	0.19	NO
126	VAV3	VAV3	VAV3	10165	0.009	0.18	NO
127	SOS2	SOS2	SOS2	10177	0.0089	0.18	NO
128	COL6A6	COL6A6	COL6A6	10628	0.0022	0.16	NO
129	RAF1	RAF1	RAF1	10632	0.0021	0.16	NO
130	BAD	BAD	BAD	10682	0.0013	0.16	NO
131	PIK3R2	PIK3R2	PIK3R2	10942	-0.0023	0.14	NO
132	CRKL	CRKL	CRKL	11014	-0.0034	0.14	NO
133	AKT2	AKT2	AKT2	11087	-0.0045	0.13	NO
134	FLNB	FLNB	FLNB	11149	-0.0055	0.13	NO
135	PAK6	PAK6	PAK6	11403	-0.0095	0.12	NO
136	CAPN2	CAPN2	CAPN2	11462	-0.01	0.11	NO
137	MYL9	MYL9	MYL9	11686	-0.014	0.1	NO
138	CDC42	CDC42	CDC42	11790	-0.016	0.097	NO
139	BCAR1	BCAR1	BCAR1	11859	-0.017	0.094	NO
140	VWF	VWF	VWF	11889	-0.017	0.092	NO
141	PIP5K1C	PIP5K1C	PIP5K1C	12127	-0.021	0.08	NO
142	ILK	ILK	ILK	12350	-0.025	0.068	NO
143	RHOA	RHOA	RHOA	12365	-0.025	0.069	NO
144	VASP	VASP	VASP	12386	-0.025	0.068	NO
145	MAPK1	MAPK1	MAPK1	12409	-0.026	0.068	NO
146	FIGF	FIGF	FIGF	12567	-0.029	0.06	NO
147	MYL12B	MYL12B	MYL12B	12666	-0.03	0.056	NO
148	PAK1	PAK1	PAK1	12825	-0.033	0.048	NO
149	PIK3R3	PIK3R3	PIK3R3	13103	-0.038	0.034	NO
150	ELK1	ELK1	ELK1	13137	-0.039	0.034	NO
151	DIAPH1	DIAPH1	DIAPH1	13347	-0.043	0.024	NO
152	MAPK3	MAPK3	MAPK3	13375	-0.044	0.024	NO
153	LAMB2	LAMB2	LAMB2	13416	-0.045	0.023	NO
154	FYN	FYN	FYN	13558	-0.048	0.017	NO
155	PTEN	PTEN	PTEN	13602	-0.048	0.016	NO
156	PIK3CG	PIK3CG	PIK3CG	13620	-0.049	0.017	NO
157	CCND3	CCND3	CCND3	13630	-0.049	0.018	NO
158	ACTB	ACTB	ACTB	13778	-0.052	0.012	NO
159	TLN1	TLN1	TLN1	13790	-0.052	0.013	NO
160	FLNA	FLNA	FLNA	13809	-0.053	0.014	NO
161	CTNNB1	CTNNB1	CTNNB1	13993	-0.057	0.006	NO
162	ACTG1	ACTG1	ACTG1	14084	-0.059	0.0031	NO
163	GRB2	GRB2	GRB2	14165	-0.061	0.00082	NO
164	BIRC3	BIRC3	BIRC3	14205	-0.061	0.00087	NO
165	PARVA	PARVA	PARVA	14354	-0.065	-0.0051	NO
166	MYL5	MYL5	MYL5	14455	-0.068	-0.0082	NO
167	AKT1	AKT1	AKT1	14556	-0.07	-0.011	NO
168	CCND2	CCND2	CCND2	14627	-0.072	-0.013	NO
169	COL4A4	COL4A4	COL4A4	14757	-0.076	-0.017	NO
170	MYL12A	MYL12A	MYL12A	14776	-0.076	-0.015	NO
171	PPP1CA	PPP1CA	PPP1CA	14807	-0.078	-0.014	NO
172	CCND1	CCND1	CCND1	15458	-0.099	-0.047	NO
173	ITGA7	ITGA7	ITGA7	15496	-0.1	-0.045	NO
174	PAK4	PAK4	PAK4	15506	-0.1	-0.042	NO
175	ACTN3	ACTN3	ACTN3	15577	-0.1	-0.042	NO
176	RAC3	RAC3	RAC3	15682	-0.11	-0.044	NO
177	PARVB	PARVB	PARVB	15718	-0.11	-0.042	NO
178	ITGA3	ITGA3	ITGA3	15802	-0.12	-0.042	NO
179	ACTN1	ACTN1	ACTN1	15904	-0.12	-0.044	NO
180	VEGFB	VEGFB	VEGFB	16081	-0.13	-0.049	NO
181	PIK3CB	PIK3CB	PIK3CB	16294	-0.15	-0.055	NO
182	MET	MET	MET	16308	-0.15	-0.051	NO
183	MYL2	MYL2	MYL2	16418	-0.16	-0.051	NO
184	RAPGEF1	RAPGEF1	RAPGEF1	16460	-0.16	-0.048	NO
185	VTN	VTN	VTN	16558	-0.16	-0.047	NO
186	BCL2	BCL2	BCL2	17073	-0.22	-0.068	NO
187	MYLK3	MYLK3	MYLK3	17165	-0.23	-0.065	NO
188	PIK3R5	PIK3R5	PIK3R5	17276	-0.25	-0.062	NO
189	VAV1	VAV1	VAV1	17316	-0.25	-0.055	NO
190	LAMA1	LAMA1	LAMA1	17389	-0.26	-0.049	NO
191	PARVG	PARVG	PARVG	17412	-0.27	-0.041	NO
192	RAC2	RAC2	RAC2	17451	-0.27	-0.033	NO
193	PRKCB	PRKCB	PRKCB	17924	-0.41	-0.045	NO
194	ITGB7	ITGB7	ITGB7	17954	-0.43	-0.031	NO
195	PIK3CD	PIK3CD	PIK3CD	17990	-0.45	-0.016	NO
196	RASGRF1	RASGRF1	RASGRF1	18025	-0.54	0.0013	NO

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

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

genes ES table in pathway: KEGG HEDGEHOG SIGNALING 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	AADAT	AADAT	AADAT	61	0.54	0.14	YES
2	BBOX1	BBOX1	BBOX1	100	0.52	0.28	YES
3	PLOD2	PLOD2	PLOD2	1121	0.28	0.3	YES
4	SETD7	SETD7	SETD7	2066	0.21	0.3	YES
5	AASS	AASS	AASS	2687	0.18	0.31	YES
6	AASDHPPT	AASDHPPT	AASDHPPT	3608	0.14	0.3	NO
7	ALDH3A2	ALDH3A2	ALDH3A2	5983	0.081	0.19	NO
8	SETD2	SETD2	SETD2	6099	0.079	0.21	NO
9	ASH1L	ASH1L	ASH1L	6807	0.064	0.18	NO
10	NSD1	NSD1	NSD1	6866	0.063	0.2	NO
11	ALDH7A1	ALDH7A1	ALDH7A1	6947	0.062	0.21	NO
12	DOT1L	DOT1L	DOT1L	7060	0.06	0.22	NO
13	SETD8	SETD8	SETD8	7143	0.058	0.23	NO
14	SUV420H1	SUV420H1	SUV420H1	7907	0.044	0.2	NO
15	AASDH	AASDH	AASDH	7989	0.043	0.21	NO
16	TMLHE	TMLHE	TMLHE	8342	0.037	0.2	NO
17	EHMT1	EHMT1	EHMT1	9124	0.025	0.16	NO
18	SETMAR	SETMAR	SETMAR	9278	0.022	0.16	NO
19	SUV39H2	SUV39H2	SUV39H2	9307	0.022	0.16	NO
20	WHSC1L1	WHSC1L1	WHSC1L1	9426	0.02	0.16	NO
21	WHSC1	WHSC1	WHSC1	9577	0.018	0.16	NO
22	PLOD1	PLOD1	PLOD1	9703	0.016	0.15	NO
23	OGDHL	OGDHL	OGDHL	10390	0.0058	0.12	NO
24	PLOD3	PLOD3	PLOD3	10478	0.0044	0.11	NO
25	ACAT1	ACAT1	ACAT1	10859	-0.0012	0.093	NO
26	SETD1A	SETD1A	SETD1A	10975	-0.0029	0.087	NO
27	EHMT2	EHMT2	EHMT2	11175	-0.0058	0.078	NO
28	SUV420H2	SUV420H2	SUV420H2	11243	-0.0069	0.076	NO
29	SETDB1	SETDB1	SETDB1	11262	-0.0071	0.077	NO
30	SETD1B	SETD1B	SETD1B	11376	-0.009	0.073	NO
31	ACAT2	ACAT2	ACAT2	12095	-0.021	0.038	NO
32	DLST	DLST	DLST	13021	-0.037	-0.0033	NO
33	GCDH	GCDH	GCDH	13680	-0.05	-0.026	NO
34	OGDH	OGDH	OGDH	13938	-0.056	-0.026	NO
35	HADHA	HADHA	HADHA	14196	-0.061	-0.024	NO
36	ALDH9A1	ALDH9A1	ALDH9A1	14546	-0.07	-0.025	NO
37	HADH	HADH	HADH	14849	-0.079	-0.02	NO
38	ECHS1	ECHS1	ECHS1	15173	-0.089	-0.015	NO
39	ALDH1B1	ALDH1B1	ALDH1B1	15596	-0.11	-0.0099	NO
40	SETDB2	SETDB2	SETDB2	15926	-0.12	0.005	NO
41	SUV39H1	SUV39H1	SUV39H1	16087	-0.13	0.032	NO
42	PIPOX	PIPOX	PIPOX	16232	-0.14	0.062	NO
43	ALDH2	ALDH2	ALDH2	16311	-0.15	0.096	NO

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

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

Fold change

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

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

Expression level

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

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

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

Significant gene list

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

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

Methods & Data

Input

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