Rockfish: A Transformer-based Model for Accurate 5-Methylcytosine Prediction from Nanopore Sequencing

DNA methylation plays a crucial role in various biological processes, including cell differentiation, ageing, and cancer development. The most important methylation in mammals is 5-methylcytosine (5mC) which is present in the context of CpG dinucleotides. Sequencing methods such as whole-genome bisulfite sequencing (WGBS) successfully detect 5mC DNA modifications. However, they suffer from the serious drawbacks of short read lengths and might introduce an amplification bias. Here we present Rockfish, a deep learning algorithm that significantly improves read-level 5mC detection by using Nanopore sequencing. Compared to other methods based on Nanopore sequencing, there is an increase in the single-base accuracy and the F1 measure of up to 5% and 12%, respectively. Furthermore, Rockfish shows a high correlation with WGBS and requires lower read depth while being computationally efficient. We deem that Rockfish is broadly applicable to study 5mC methylation in diverse organisms and disease systems to yield biological insights. ### Competing Interest Statement The authors have declared no competing interest.