NCM 2023 Singapore: Direct detection of DNA modifications in human cancer genomes

Epigenomic aberration is one of the hallmarks of cancer genomes. Global hypomethylation, aberrant hypermethylation at transcriptional regulatory regions (e.g. promoters, enhancers) and loss of imprinting have been widely revealed by short-read sequencing and methylation microarrays, but it can be difficult to assess the detailed modification status on a long, continuous read. Here we evaluated the accuracy and feasibility of native DNA sequencing using PromethION from Oxford Nanopore Technologies to detect a long-ranged and haplotype-resolved methylation level in the cancer genome. In addition, we propose the importance of integrated analysis of cytosine modifications to consider the dynamics of 5-methylcytosine and its oxidation derivatives.