Systematic Analysis and Accurate Identification of DNA N4-Methylcytosine Sites by Deep Learning

DNA N⁴-methylcytosine (4mC) is a pivotal epigenetic modification that plays an essential role in DNA replication, repair, expression and differentiation. To gain insight into the biological functions of 4mC, it is critical to identify their modification sites in the genomics. Recently, deep learning has become increasingly popular in recent years and frequently employed for the 4mC site identification. However, a systematic analysis of how to build predictive models using deep learning techniques is still lacking. In this work, we first summarized all existing deep learning-based predictors and systematically analyzed their models, features and datasets, etc. Then, using a typical standard dataset with three species (A. thaliana, C. elegans, and D. melanogaster), we assessed the contribution of different model architectures, encoding methods and the attention mechanism in establishing a deep learning-based model for the 4mC site prediction. After a series of optimizations, convolutional-recurrent neural network architecture using the one-hot encoding and attention mechanism achieved the best overall prediction performance. Extensive comparison experiments were conducted based on the same dataset. This work will be helpful for researchers who would like to build the 4mC prediction models using deep learning in the future.