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Decoding the interconnected splicing patterns of hepatitis B virus and host using large language and deep learning

Chun Shen Lim1,2,3, Chris M Brown1,2,3

  • 1Department of Biochemistry, Faculty of Biomedical Sciences, University of Otago, Dunedin, New Zealand.

Microbial Genomics
|January 16, 2026
PubMed
Summary
This summary is machine-generated.

Hepatitis B virus (HBV) splicing efficiency, not just the amount of spliced RNA, strongly correlates with disease progression. Artificial intelligence models reveal unique HBV splicing patterns, aiding understanding of viral persistence.

Keywords:
artificial intelligencedeep sequencinglarge language modelsplicing efficiencyvirus–host coevolution

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Area of Science:

  • Virology
  • Genomics
  • Bioinformatics

Background:

  • Hepatitis B virus (HBV) infection is a leading cause of liver cancer and death.
  • HBV's compact genome utilizes extensive alternative splicing, contributing to immune evasion and hindering functional cures.
  • Understanding HBV splicing is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the correlation between HBV splicing efficiency and disease progression.
  • To decode the sequence determinants of HBV splicing using AI models.
  • To analyze context- and genotype-specific splicing patterns in HBV.

Main Methods:

  • Quantified HBV splicing efficiency from 279 RNA-sequencing libraries.
  • Applied AI models (SpliceBERT, OpenSpliceAI) to 4,706 HBV genomes.
  • Performed motif conservation and splicing propensity analyses.

Main Results:

  • HBV splicing efficiency correlates more strongly with disease progression than the proportion of spliced HBV RNA.
  • HBV splice donor sites resemble host sites, while acceptor sites are more cryptic.
  • Identified context- and genotype-specific splicing patterns, suggesting sequence-based regulation.

Conclusions:

  • HBV splicing efficiency is a more significant indicator of disease progression than previously thought.
  • AI models effectively decode viral splicing patterns, revealing unique HBV splice site characteristics.
  • HBV splicing patterns may reflect coevolution with hosts, supporting viral persistence and immune evasion.