PEA-m6A: an ensemble learning framework for accurately predicting N6-methyladenosine modifications in plants

Abstract N 6-methyladenosine (m6A), which is the mostly prevalent modification in eukaryotic mRNAs, is involved in gene expression regulation and many RNA metabolism processes. Accurate prediction of m6A modification is important for understanding its molecular mechanisms in different biological contexts. However, most existing models have limited range of application and are species-centric. Here we present PEA-m6A, a unified, modularized and parameterized framework that can streamline m6A-Seq data analysis for predicting m6A-modified regions in plant genomes. The PEA-m6A framework builds ensemble learning-based m6A prediction models with statistic-based and deep learning-driven features, achieving superior performance with an improvement of 6.7% to 23.3% in the area under precision-recall curve compared with state-of-the-art regional-scale m6A predictor WeakRM in 12 plant species. Especially, PEA-m6A is capable of leveraging knowledge from pretrained models via transfer learning, representing an innovation in that it can improve prediction accuracy of m6A modifications under small-sample training tasks. PEA-m6A also has a strong capability for generalization, making it suitable for application in within- and cross-species m6A prediction. Overall, this study presents a promising m6A prediction tool, PEA-m6A, with outstanding performance in terms of its accuracy, flexibility, transferability, and generalization ability. PEA-m6A has been packaged using Galaxy and Docker technologies for ease of use and is publicly available at https://github.com/cma2015/PEA-m6A.