cncFinder: A graph-attention-network-based interpretable learning model to identify bifunctional long non-coding RNAs
Certain RNAs exhibit both protein-coding and regulatory non-coding functions, termed bifunctional RNAs or coding and non-coding RNAs. Long non-coding RNAs (lncRNAs), which play crucial roles in gene regulation and cellular processes, represent a major subset of bifunctional RNAs. Accurate identification of bifunctional lncRNAs is critical for advancing RNA biology and uncovering opportunities for biomarker discovery and therapeutic development. Here, we present cncFinder, a graph-attention-network-based model for predicting bifunctional lncRNAs. It transforms lncRNA sequences into k-mer graphs, encodes node features with Word2Vec, and employs graph attention network to capture higher-order sequence dependencies. On the testing dataset, cncFinder achieved superior performance, significantly outperforming state-of-the-art models. Its robustness and broad applicability were further confirmed through validation on cross-species datasets from mouse and fruit fly. Interpretability analysis revealed that cncFinder captured biologically meaningful motifs, including canonical start codons and Kozak-like elements. In a case study of LINC00961, cncFinder precisely detected an experimentally validated translation initiation motif, highlighting its biological relevance. To support broad accessibility, we developed a user-friendly web server. In summary, cncFinder advances predictive accuracy and interpretability, providing a powerful tool for systematic discovery of bifunctional lncRNAs and enabling new insights into RNA multifunctionality.
Authors
- Qiang Tang (ORCID: https://orcid.org/0000-0002-2744-2015)
- Min Shen
- Yang Yu
- Xu Jia
- Lin Zhang
- Juanjuan Kang
Institutions
- Chengdu Medical College (CN)
- Foshan Maternity and Child Health Care Hospital (CN)
- Shaoxing People's Hospital (CN)
- Chengdu University of Traditional Chinese Medicine (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- Molecular Therapy — Nucleic Acids
- Published
- 2025-12-26
- DOI
- https://doi.org/10.1016/j.omtn.2025.102812
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 0.00