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<p>Viral sequences in diverse environments remain largely uncharacterized, impeding our comprehension of their genetic makeup, biological interactions, and potential applications. This underscores an urgent need for innovative analytical methods. Here, we present the VirHost Hunter framework, which employs phage tails and lysins, bypassing the requirement for full genomes, for efficient and high-resolution host assignment. By harnessing Protein Language Models and Vision Transformers, VirHost Hunter captures protein functional homology despite sequence dissimilarity, significantly boosting prediction accuracy. In the scenario of disease-associated gut bacteria, the calibrated VirHost Hunter surpasses existing methods, doubling phage host assignments, expanding taxonomic reach, and revealing previously uncharacterized phages targeting gut bacteria, including <i>Akkermansia</i> and <i>Prevotella</i>. Therefore, we establish a gut phage lysin database, enabling the synthesis of a lysin that effectively and specifically targets an obesity-promoting bacterium. VirHost Hunter’s precision and scalability mark a significant leap forward in virome research and present a promising avenue for microbiome therapies.</p>

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High-resolution phage-host assignment through key proteins using large language models

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月20日

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  • Zhihua Du,
  • Min Li,
  • Kaihuang Lin,
  • Bo Xing,
  • Yuehua Ou,
  • Zihao Lin,
  • Wenchen Song,
  • Jie Chen,
  • Junhua Li,
  • Jianqiang Li,
  • Minfeng Xiao

摘要

Viral sequences in diverse environments remain largely uncharacterized, impeding our comprehension of their genetic makeup, biological interactions, and potential applications. This underscores an urgent need for innovative analytical methods. Here, we present the VirHost Hunter framework, which employs phage tails and lysins, bypassing the requirement for full genomes, for efficient and high-resolution host assignment. By harnessing Protein Language Models and Vision Transformers, VirHost Hunter captures protein functional homology despite sequence dissimilarity, significantly boosting prediction accuracy. In the scenario of disease-associated gut bacteria, the calibrated VirHost Hunter surpasses existing methods, doubling phage host assignments, expanding taxonomic reach, and revealing previously uncharacterized phages targeting gut bacteria, including Akkermansia and Prevotella. Therefore, we establish a gut phage lysin database, enabling the synthesis of a lysin that effectively and specifically targets an obesity-promoting bacterium. VirHost Hunter’s precision and scalability mark a significant leap forward in virome research and present a promising avenue for microbiome therapies.