Methylseqdesign: A Framework For Methyl-Seq Genome-Wide Power Calculation And Study Design Issues

Bisulfite DNA methylation sequencing (Methyl-Seq) becomes one of the most important technologies to study methylation level difference at a genome-wide scale. Due to the complexity and large scale of methyl-Seq data, power calculation and study design method have not been developed. Here, we propose a "Methyl-SeqDesign" framework for power calculation and study design of MethylSeq experiments by utilizing information from pilot data. Differential methylation analysis is based on a beta-binomial model. Power calculation is achieved using mixture model fitting of p-values from pilot data and a parametric bootstrap procedure. To circumvent the issue of existing tens of millions of methylation sites, we focus on the inference of pre-specified targeted regions. The performance of the method was evaluated with simulations. Two real examples are analyzed to illustrate our method. An R package "MethylSeqDesign" to implement this method is publicly available.