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Large-scale genomic survey with deep learning-based method reveals strain-level phage specificity determinants.

Yiyan Yang1, Keith Dufault-Thompson1, Wei Yan1

  • 1National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

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|April 22, 2024
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Summary

SpikeHunter, a new deep learning tool, identifies phage tailspike proteins crucial for targeting antibiotic-resistant bacteria. This advances phage therapy by predicting phage-host specificity based on bacterial polysaccharide receptors.

Keywords:
bacterial polysaccharidephage receptor-binding proteinphage therapyphage–host specificityserotype

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Area of Science:

  • Microbiology
  • Bioinformatics
  • Genomics

Background:

  • Phage therapy is a promising strategy against antimicrobial resistance.
  • Phage specificity, determined by receptor-binding proteins, is key but challenging to characterize due to phage diversity.
  • Existing tools for large-scale characterization of phage receptor-binding proteins are lacking.

Purpose of the Study:

  • To develop and present SpikeHunter, a deep learning method for characterizing phage tailspike proteins.
  • To analyze the association between tailspike proteins and bacterial polysaccharides.
  • To predict phage-host specificity.

Main Methods:

  • Utilized the ESM-2 protein language model to develop SpikeHunter.
  • Analyzed 787,566 bacterial genomes to identify phage-encoded tailspike proteins.
  • Correlated tailspike protein domains with bacterial polysaccharide receptors and phage-host specificity.

Main Results:

  • Identified 231,965 diverse phage tailspike proteins.
  • Found strong associations between 86.60% of identified proteins and specific bacterial polysaccharides.
  • Demonstrated that identical tailspike proteins can infect different bacterial species with similar receptors, highlighting the C-terminal domain's role in specificity.
  • Validated predictions against real-world phage therapy cases.

Conclusions:

  • SpikeHunter provides a method and database for understanding phage specificity determinants.
  • Enhances strain-level understanding of phage specificity.
  • Offers a framework for guiding phage selection in therapeutic applications.