London Calling 2023: MeOW: genome-wide identification of differentially methylated regions using Oxford Nanopore long-read sequencing data

Despite significant improvements in clinical genetic testing, nearly half of individuals with suspected genetic disorders remain undiagnosed. Oxford Nanopore long-read sequencing can identify disease-causing  variants missed by other methods. We developed MeOW, a program that quickly identifies genome-wide differentially methylated regions (DMRs) that may contribute to disease. MeOW successfully identified 100% of DMRs in individuals with known imprinting disorders, such as Prader–Willi syndrome, Angelman syndrome, and Beckwith–Wiedemann syndrome. When applied to a research cohort of individuals who remained undiagnosed after comprehensive clinical testing, MeOW revealed high-priority DMRs for further  evaluation. Our research shows that MeOW simplifies genome-wide analysis of challenging cases and  enables the identification of novel DMRs associated with human disease.