Experimental and Bioinformatic Approaches to Studying DNA Methylation in Cancer

Simple Summary Aberrations of normal DNA methylation patterns are observed in many cancers and are associated with chromatin alterations, changes in gene expression and genomic instability, making the study of DNA methylation paramount to our understanding of cancer biology and evolution and the development of biomarkers. Here, we present an overview of genome-wide approaches for the analysis of DNA methylation with relevance to cancer research and clinics. DNA methylation is an essential epigenetic mark. Alterations of normal DNA methylation are a defining feature of cancer. Here, we review experimental and bioinformatic approaches to showcase the breadth and depth of information that this epigenetic mark provides for cancer research. First, we describe classical approaches for interrogating bulk DNA from cell populations as well as more recently developed approaches for single cells and multi-Omics. Second, we focus on the computational analysis from primary data processing to the identification of unique methylation signatures. Additionally, we discuss challenges such as sparse data and cellular heterogeneity.