Single-molecule, genome-scale analyses of DNA modifications: exposing the epigenome with next-generation technologies.

DNA modifications represent an integral part of the epigenome and they have a pivotal role in regulation of genome function. Despite the wide variety of analytical techniques that have been developed to detect DNA modifications, their investigation at the single-genome level is only beginning to emerge. In contrast to population-averaged analyses, single-molecule approaches potentially allow the mapping of epigenetic linkage between distantly located genomic regions, the locus-specific analysis of repetitive DNA elements, as well as determination of allele-specific DNA modification patterns. In this article, the properties of current single-molecule analyses of DNA modifications will be discussed and compared. In addition, the possible biomedical and discovery research applications of single-molecule epigenomics will be highlighted.