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Sequence determinant and functional relevance of 8-oxoguanine RNA modification unveiled from foundation-model-based predictor

  • Nanjing University of Chinese Medicine
  • Xi'an Jiaotong-Liverpool University
  • University of Liverpool
  • Institute of Systems

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

8-Oxoguanine (o8G) is an oxidative RNA modification that plays critical roles in cellular processes including stress responses and RNA integrity regulation. Notably, emerging evidence has implicated o8G modifications in cancer progression and development. However, research progress is limited by the lack of efficient high-throughput detection methods and computational tools for analyzing sequence distribution and regulatory mechanisms. Here, we present OBOE (foundation-model-based prediction of 8-oxoguanine sites), the first computational framework for o8G site prediction, developed by fine-tuning multiple pre-trained language models (DNABERT, RNABERT, BERT, and BioBERT). Benchmarking experiments demonstrated that OBOE significantly outperforms conventional machine learning methods, validating its superior capability in capturing RNA sequence features and modification patterns. Furthermore, we applied TF-MoDISCo to extract biologically meaningful motifs from model attributions, followed by validation of sequence similarity and enrichment using STREME and TOMTOM analysis. We identified recurrent GC-rich sequence motifs and CTC-like patterns associated with o8G modifications, suggesting potential cis -regulatory elements involved in oxidative stress responses. To facilitate model accessibility, we implemented two community resources: (1) a user-friendly web platform for online o8G prediction and (2) freely available source code and processed datasets.

Original languageEnglish
Article number102951
JournalMolecular Therapy Nucleic Acids
Volume37
Issue number2
DOIs
Publication statusPublished - 16 Jun 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • deep learning
  • first 8-oxoguanine (oG) predictor
  • genomic patterns
  • interpretable foundation model
  • motif discovery
  • MT: Bioinformatics
  • RNA modification
  • web server predictor

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