STM-ac4C: a hybrid model for identification of N4-acetylcytidine (ac4C) in human mRNA based on selective kernel convolution, temporal convolutional network, and multi-head self-attention

Abstract

N4-acetylcysteine (ac4C) is a chemical modification in mRNAs that alters the structure and function of mRNA by adding an acetyl group to the N4 position of cytosine. Researchers have shown that ac4C is closely associated with the occurrence and development of various cancers. Therefore, accurate prediction of ac4C modification sites on human mRNA is crucial for revealing its role in diseases and developing new diagnostic and therapeutic strategies. However, existing deep learning models still have limitations in prediction accuracy and generalization ability, which restrict their effectiveness in handling complex biological sequence data. This paper introduces a deep learning-based model, STM-ac4C, for predicting ac4C modification sites on human mRNA. The model combines the advantages of selective kernel convolution, temporal convolutional networks, and multi-head self-attention mechanisms to effectively extract and integrate multi-level features of RNA sequences, thereby achieving high-precision prediction of ac4C sites. On the independent test dataset, STM-ac4C showed improvements of 1.81%, 3.5%, and 0.37% in accuracy, Matthews correlation coefficient, and area under the curve, respectively, compared to the existing state-of-the-art technologies. Moreover, its performance on additional balanced and imbalanced datasets also confirmed the model’s robustness and generalization ability. Various experimental results indicate that STM-ac4C outperforms existing methods in predictive performance. In summary, STM-ac4C excels in predicting ac4C modification sites on human mRNA, providing a powerful new tool for a deeper understanding of the biological significance of mRNA modifications and cancer treatment. Additionally, the model reveals key sequence features that influence the prediction of ac4C sites through sequence region impact analysis, offering new perspectives for future research. The source code and experimental data are available at https://github.com/ymy12341/STM-ac4C.