Multi-scale DNA language model improves 6 mA binding sites prediction

Abstract

DNA methylation at the N6 position of adenine (N6-methyladenine, 6 mA), which refers to the attachment of a methyl group to the N6 site of the adenine (A) of DNA, is an important epigenetic modification in prokaryotic and eukaryotic genomes. Accurately predicting the 6 mA binding sites can provide crucial insights into gene regulation, DNA repair, disease development and so on. Wet experiments are commonly used for analyzing 6 mA binding sites. However, they suffer from high cost and expensive time. Therefore, various deep learning methods have been widely used to predict 6 mA binding sites recently. In this study, we develop a framework based on multi-scale DNA language model named "iDNA6mA-MDL". "iDNA6mA-MDL" integrates multiple kmers and the nucleotide property and frequency method for feature embedding, which can capture a full range of DNA sequence context information. At the prediction stage, it also leverages DNABERT to compensate for the incomplete capture of global DNA information. Experiments show that our framework obtains average AUC of 0.981 on a classic 6 mA rice gene dataset, going beyond all existing advanced models under fivefold cross-validations. Moreover, "iDNA6mA-MDL" outperforms most of the popular state-of-the-art methods on another 11 6 mA datasets, demonstrating its effectiveness in 6 mA binding sites prediction.