Identification of species-specific RNA N6-methyladinosine modification sites from RNA sequences.

ABSTRACT

N6-methyladinosine (m6A) modification is the most abundant co-transcriptional modification in eukaryotic RNA and plays important roles in cellular regulation. Traditional high-throughput sequencing experiments used to explore functional mechanisms are time-consuming and labor-intensive, and most of the proposed methods focused on limited species types. To further understand the relevant biological mechanisms among different species with the same RNA modification, it is necessary to develop a computational scheme that can be applied to different species. To achieve this, we proposed an attention-based deep learning method, adaptive-m6A, which consists of convolutional neural network, bi-directional long short-term memory and an attention mechanism, to identify m6A sites in multiple species. In addition, three conventional machine learning (ML) methods, including support vector machine, random forest and logistic regression classifiers, were considered in this work. In addition to the performance of ML methods for multi-species prediction, the optimal performance of adaptive-m6A yielded an accuracy of 0.9832 and the area under the receiver operating characteristic curve of 0.98. Moreover, the motif analysis and cross-validation among different species were conducted to test the robustness of one model towards multiple species, which helped improve our understanding about the sequence characteristics and biological functions of RNA modifications in different species.