DNA methylation, which is the addition of a methyl group to the cytosine of a CpG dinucleotide, is one of the most widely studied epigenetic modifications in development and disease. Changes in DNA methylation are vital for normal development and differentiation, whilst aberrant methylation is involved in many diseases. As interest in epigenetics, and particularly DNA methylation has grown, measurement technologies have rapidly evolved in scale and resolution. Whole genome bisulfite-sequencing (WGBS) is considered the gold-standard for measuring methylation across the genome, however it is still too costly for many applications. Consequently, for human studies, Illumina methylation arrays have emerged as a popular alternative for studies that require large numbers of samples, such as disease association studies.
Illumina methylation arrays have been shown to be robust and reproducible and the analysis methods are very mature, however, they only cover up to 0.03% of the ~30 million CpGs in the human genome. Consequently, WGBS is still preferred for certain applications. However, the analysis of WGBS data remains challenging at several levels. In this talk, I will describe how sodium bisulfite treatment is employed to measure methylation using both arrays and sequencing. I will explain the challenges associated with the analysis of WGBS data, from read mapping to finding differentially methylated loci. I will also cover some of the popular methods and tools that are currently being used in WGBS analysis pipelines.