Abstract
DNA methylations, such as 5-methylcytosine (5mC), are crucial in biological processes, and aberrant methylations are strongly linked to various human diseases. Genomic 5mC is not randomly distributed but exhibits a strong association with genomic sequences. Thus, various computational methods were developed to predict 5mC status based on DNA sequences. These methods generated promising achievements and overcome the limitations of experimental approaches. However, few studies have comprehensively investigated the dependency of 5mC on genomic sequences, and most existing methods focus on specific genomic regions. In this work, we introduce Deep5mC, a deep learning transformer-based method designed to predict 5mC methylations. Deep5mC leverages long-range dependencies within genomic sequences to estimate the probability of cytosine methylations. Through cross-chromosome evaluation, Deep5mC achieves Matthew's correlation coefficient over 0.86 and F1-score over 0.93, substantially outperforming state-of-the-art methods. Deep5mC not only confirms the influence of long-range sequence context on 5mC prediction but also paves the way for further studying 5mC-sequence dependency across species and in human diseases.