Estimating Global Methylation and Erasure Using Low-Coverage Whole-Genome Bisulfite Sequencing (WGBS)

Abstract Whole-genome bisulfite sequencing (WGBS) is a popular method for characterizing cytosine methylation because it fully quantitative and has base-pair resolution. While WGBS prohibitively expensive experiments involving many samples, low-coverage can accurately determine global erasure at similar cost to high-performance liquid chromatography (HPLC) or enzyme-linked immunosorbent assays (ELISA). Moreover, the capacity distinguish between in different contexts (e.g., CG, CHH, CHG), tolerate low-input material (<100 cells), detect presence of overrepresented DNA originating from mitochondria amplified ribosomal DNA. In addition describing library construction quantitation approach, here we detail computational methods predict accuracy using empirical bootstrap samplers theoretical estimators those used election polling. Using examples, further demonstrate how non-independent sampling cytosines alter precision error calculation provide improve this.