Tonight I watched the London Calling 2023 session entitled “Genome-wide single-molecule analysis of DNA methylation by nanopore sequencing reveals heterogeneous patterns” presented by Lyndsay Kerr from the University of Edinburgh in the UK. They spoke about the novel way of analyzing methylation patterns from single-molecule reads. Kerr explained that DNA methylation is a “repressive epigenetic mark” because normally it is associated with a gene being repressed. Unusual methylation patterns have been detected in disease. In the past, single-molecule data from short-read sequencing has been analyzed for methylation patterns. Kerr defined low and high heterogeneity regions based on the diversity of methylation at a site. To study the correlation in methylation state between nearest-neighbour CpGs and to quantify heterogeneity, Kerr used the Nanopore data set for GM 24385, a normal lymphoblastoid cell line. Kerr took the reads and aligned them to the regions of “high heterogeneity.” Kerr found that high heterogeneity regions are enriched in heterochromatin. They found distance-dependent correlations between neighbouring CpGs suggestive of periodic methylation patterns. Since Kerr’s background is in mathematics, they developed a series of ways to calculate the correlation between high heterogeneity reads and distance between sites. The plots revealed periodic patterns and associations with heterochromatin regions. I wonder if in bacterial similar situations will be discovered!
