MST-m6A: A Novel Multi-Scale Transformer-based Framework for Accurate Prediction of m6A Modification Sites Across Diverse Cellular Contexts

Abstract

N6-methyladenosine (m6A) modification, a prevalent epigenetic mark in eukaryotic cells, is crucial in regulating gene expression and RNA metabolism. Accurately identifying m6A modification sites is essential for understanding their functions within biological processes and the intricate mechanisms that regulate them. Recent advances in high-throughput sequencing technologies have enabled the generation of extensive datasets characterizing m6A modification sites at single-nucleotide resolution, leading to the development of computational methods for identifying m6A RNA modification sites. However, most current methods focus on specific cell lines, limiting their generalizability and practical application across diverse biological contexts. To address the limitation, we propose MST-m6A, a novel approach for identifying m6A modification sites with higher accuracy across various cell lines and tissues. MST-m6A utilizes a multi-scale transformer-based architecture, employing dual k-mer tokenization to capture rich feature representations and global contextual information from RNA sequences at multiple levels of granularity. These representations are then effectively combined using a channel fusion mechanism and further processed by a convolutional neural network to enhance prediction accuracy. Rigorous validation demonstrates that MST-m6A significantly outperforms conventional machine learning models, deep learning models, and state-of-the-art predictors. We anticipate that the high precision and cross-cell-type adaptability of MST-m6A will provide valuable insights into m6A biology and facilitate advancements in related fields. The proposed approach is available at https://github.com/cbbl-skku-org/MST-m6A/ for prediction and reproducibility purposes.

Keywords: BERT; N6-methyladenosine modification; convolutional neural network; feature fusion; transformer.