Deep6mA: A deep learning framework for exploring similar patterns in DNA N6-methyladenine sites across different species

N6-methyladenine (6mA) is an important DNA modification form associated with a wide range of biological processes. Identifying accurately 6mA sites on a genomic scale is crucial for under-standing of 6mA’s biological functions. However, the existing experimental techniques for detecting 6mA sites are cost-ineffective, which implies the great need of developing new computational methods for this problem. In this paper, we developed, without requiring any prior knowledge of 6mA and manually crafted sequence features, a deep learning framework named Deep6mA to identify DNA 6mA sites, and its performance is superior to other DNA 6mA prediction tools. Specifically, the 5-fold cross-validation on a benchmark dataset of rice gives the sensitivity and specificity of Deep6mA as 92.96% and 95.06%, respectively, and the overall prediction accuracy is 94%. Importantly, we find that the sequences with 6mA sites share similar patterns across different species. The model trained with rice data predicts well the 6mA sites of other three species: Arabidopsis thaliana, Fragaria vesca and Rosa chinensis with a prediction accuracy over 90%. In addition, we find that (1) 6mA tends to occur at GAGG motifs, which means the sequence near the 6mA site may be conservative; (2) 6mA is enriched in the TATA box of the promoter, which may be the main source of its regulating downstream gene expression.Author summary: DNA N6 methyladenine (6mA) is a newly recognized methylation modification in eukaryotes. It exists widely and conservatively in organisms, and its modification level changes dynamically in the whole life cycle. This study proposes an algorithm based on a deep learning framework including LSTM and CNN to predict 6mA sites. The results showed that our method could accurately predict the 6mA sites in different species, which means DNA sub-sequences containing 6mA sites among species have certain conservation. Importantly, we found that 6mA methylation in most different species is more likely to occur on the GAGG motif. In addition, we also found that 6mA is rich in the promoter’s TATA box, which may be a mechanism of regulating downstream gene expression.