Faculty, Staff and Student Publications

Publication Date

11-1-2025

Journal

Briefings in Bioinformatics

DOI

10.1093/bib/bbaf690

PMID

41451538

PMCID

PMC12741562

PubMedCentral® Posted Date

12-26-2025

PubMedCentral® Full Text Version

Post-print

Abstract

RNA modification, which is evolutionarily conserved, is crucial for modulating various biological functions and disease pathogenesis. High resolution transcriptome-wide mapping of RNA modifications has facilitated both data resources and computational prediction of RNA modification. While these prediction algorithms are promising, they are limited in interpretability or generalizability, or the capacity for discovering novel post-transcriptional regulations. Here, we present NetRNApan, a deep learning framework for RNA modification site prediction, motif discovery and trans-regulatory factor identification. Using m5U profiles generated by FICC-seq and miCLIP-seq technologies and single-base resolution m6A sites from multiple experiments as cases, we demonstrated the accuracy of NetRNApan with more efficient and interpretive feature representations. For m5U modification, we uncovered five representative clusters with consensus motifs that may be essential by decoding the informative characteristics detected by NetRNApan. Furthermore, NetRNApan revealed interesting trans-regulatory factors and provided a protein-binding perspective for investigating the function of RNA modifications. Specifically, we discovered 21 potential functional RNA-binding proteins (RBPs) whose binding sites were significantly linked to the extracted top-scoring motifs for m5U modification. Two examples are ANKHD1 and RBM4 with potential regulatory function of m5U modifications. Meanwhile, the analysis of convolution layer parameters within the model offers valuable insights into the regulation of m6A in humans. Collectively, NetRNApan demonstrated high accuracy, interpretability and generalizability for study of RNA modification and mRNA regulation. NetRNApan is freely available at https://github.com/bsml320/NetRNApan.

Keywords

RNA Processing, Post-Transcriptional, RNA-Binding Proteins, Humans, RNA, Deep Learning, Computational Biology, Algorithms, Software, Binding Sites

Published Open-Access

yes

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