Integration of Genome-Wide DNA Methylation and Transcription Uncovered Aberrant Methylation-Regulated Genes and Pathways in the Peripheral Blood Mononuclear Cells of Systemic Sclerosis

Figure 2

Identification of DNA methylation differences between systemic sclerosis and normal. (a) Volcano plot of the differential DNA methylation analysis. X-axis: mean β-value difference; y-axis: BH-adjusted p values for each probe (- log10 scale). The vertical dotted lines represent 12% change in β-values. The horizontal dotted line represents the significant cutoff of p < 0.05. Seven genes, ANKFY1, FAM49B, GNG7, INPP5A, LAX, PITPNM2, and VOPP1, showed both significant hypermethylation and hypomethylation (see text and Supplementary Table 2). (b) Two-dimensional hierarchical clustering was performed using the differential Infinium DNA methylation probes across all samples (n = 37). Probes are in rows; samples are in columns. (c) Proportions of probes from genes with associated CpG islands, shelf, shore, and open sea (left) and proportions of probes from genes with associated probe locations, categorized as gene body, intergenic, 3’UTR, 5’UTR, exon, TSS1500, and TSS200 (right). (d) Canonical pathway analysis of the differentially expressed genes in PBMC from SSc patients as compared with normal controls. Statistically significant pathways were shown. The y-axis indicates percentage of differential expression genes involved in the pathway. The y-axis shows BH-adjusted p-value of enrichment analysis.

(a)

(b)

(c)

(d)