Identifying RNA ac⁴C Modification Sites via Pseudo-Nucleotide Fingerprint Encoding and Multi-Scale Feature...

RNA modifications, particularly N⁴-acetylcytidine (ac⁴C), play essential roles in gene regulation by influencing mRNA stability, translational efficiency, and cellular responses to stress. Aberrant ac⁴C modifications have been implicated in tumorigenesis and cancer progression, highlighting their potential as diagnostic biomarkers and therapeutic targets. However, existing computational approaches for predicting RNA modification sites often rely on fixed-scale features or shallow learning architectures, limiting their ability to model multiscale nucleotide interactions and long-range dependencies. To address these limitations, we introduce DFM-ac⁴C, a novel computational framework designed for the accurate prediction of ac⁴C modification sites. DFM-ac⁴C integrates pseudo-nucleotide fingerprint features derived from Kidera factors with global contextual embeddings generated by the Evo2 and DNAshape pretrained models. Leveraging an attention-based fusion architecture, the framework dynamically combines local sequence information, fingerprint descriptors, and global embeddings, enabling it to effectively capture the complex, multiscale characteristics of nucleotide interaction sites. Extensive performance evaluations demonstrate that DFM-ac⁴C significantly outperforms existing models, achieving outstanding predictive metrics, including an AUC of 96.76%, accuracy (ACC) of 90.49%, Matthew's correlation coefficient (MCC) of 0.8098, sensitivity (SEN) of 90.22%, and specificity (SPE) of 90.76%. These results underscore DFM-ac⁴C's effectiveness as a robust and efficient tool for RNA ac⁴C site identification. The complete dataset and source code supporting this study can be accessed freely from: https://github.com/BioAI-wym/DFM-ac4C .