Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome

Clinical Epigenetics

Table 2 Gene set enrichment analysis details are reported for DPMs (hypo- and hypermethylated genes) and DMRs

	Enriched pathways	Pathway ID	Overlap	P value	Combined score	Overlapping genes
Hypermethylated probes	Glycosphingolipid biosynthesis	HSA-00603	3/14	0.001	2.29	ST3GAL1, GBGT1, ST3GAL2
	FoxO signal pathway	HSA-04068	8/133	0.003	2.60	MAPK10, USP7, AKT2, STAT3, PTEN, FOXO3, SKP2, GABARAP
	Insulin signalling pathway	HSA-04910	8/139	0.004	2.49	MAPK10, PTPN1, SHC2, AKT2, PRKAK1B, FASN, TSC2, CRKL
Hypomethylated probes	PI3K-Akt signalling	HSA_04151	16/341	0.006	3.46	CSF-1R, CDKN1B, TNXB, VWF, LAMA1, FLT4, THBS1, PTK2, LPAR5, PPP2R2B, PPP2R2D, MAPK1, COL6A6, FGFR1, BCL2L1, ITGA9
Hypomethylated probes	Focal adhesion	HSA_04510	12/202	0.01	3.26	MAPK10, TNXB, VWF, ROCK2, LAMA1, FLT4, PXN, MAPK1, COL6A6, THBS1, PTK2, ITGA9
DMRs	Sphingolipid metabolism	HSA_00600	2/120	0.003	4.54	CERS3, CERS1
DMRs	Sphingolipid signalling pathway	HSA_047071	1/47	0.001	5.36	CERS3

Overlap indicates the number of hits from the differentially methylated gene sets compared to the KEGG gene set library, while “overlapping genes” column contains names of these hits. Differentially expressed genes between normal and WS fibroblasts in Cheung HH dataset [30] are reported. Enriched pathways were selected based on the P value. Combined score is a multiplication of the P value computed using Fisher’s exact test with the z-score of the deviation from the expected rank (see “Methods” for details)

ISSN: 1868-7083