Fig. 2
Distribution and annotation of differentially methylated positions (DMPs) between advanced neoplasia and no neoplasia pools. A Manhattan plot for differential methylation. The -log10(p value) for the 741,310 probes analyzed are sorted by chromosome location. Significant DMPs (376) appear above the red dashed line (FDR 10%) B Volcano plot showing the -log10(p value) versus differences in methylation levels (Δbeta: obtained by subtracting the DNA methylation levels (beta-values) of NN from AN). Significant hypermethylated (Δbeta > 0) and hypomethylated (Δbeta < 0) positions appear highlighted in color and above the red dashed line (FDR 10%). C Distribution of the DMPs relative to CpG islands and functional genomic locations. D Enrichment of DMPs in relation to CpG island annotation and functional genomic regions. The color scale indicates the fold enrichment of all DMPs (gray), hypermethylated (red), and hypomethylated (blue) positions. The bolded numbers indicate annotations that are enriched with respect to the distribution of probes on the MethylationEPIC array (one-sided Fisher’s exact test p value < 0.05). Functional characterization of probes according to the Methylation EPIC Manifest: CpG island: region of at least 200bp with a CG content > 50% and an observed-to-expected CpG ratio ≥ 0.6; CpG island-shore: sequences 2 kb flanking the CpG island, CpG island-shelf: sequences 2 kb flanking shore regions, opensea: sequences located outside these regions, promoter regions (5′UTR, TSS200, TSS1500, and first exons), intragenic regions (gene body and 3′UTR), and intergenic regions. TSS200, TSS1500: 200 and 1500 bp upstream the transcription start site, respectively