Component Parts of Bacteriophage Virions Accurately Defined by a Machine-Learning Approach Built on Evolutionary Features

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  • Tze Y Thung
    Monash University
  • Murray E White
    Monash University
  • Wei Dai
    Monash University
  • Jonathan J Wilksch
    Monash University
  • Rebecca S Bamert
    Monash University
  • Andrea Rocker
    Monash University
  • Christopher J Stubenrauch
    Monash University
  • Daniel Williams
    Infection & Immunity ProgramBiomedicine Discovery InstituteMonash UniversityDepartment of Microbiology and VirologyCentre to Impact AMR
  • Cheng Huang
    Monash University
  • Ralf Schittelhelm
    Monash University
  • Jeremy J Barr
    Monash University
  • Eleanor Jameson
    School of Health and Life Sciences , Teesside University , Middlesbrough , UKThe University of Warwick
  • Sheena McGowan
    Monash University
  • Yanju Zhang
    Guilin University of Electronic Technology
  • Jiawei Wang
    Monash University
  • Rhys A Dunstan
    Monash University
  • Trevor Lithgow
    Monash University

Antimicrobial resistance (AMR) continues to evolve as a major threat to human health, and new strategies are required for the treatment of AMR infections. Bacteriophages (phages) that kill bacterial pathogens are being identified for use in phage therapies, with the intention to apply these bactericidal viruses directly into the infection sites in bespoke phage cocktails. Despite the great unsampled phage diversity for this purpose, an issue hampering the roll out of phage therapy is the poor quality annotation of many of the phage genomes, particularly for those from infrequently sampled environmental sources. We developed a computational tool called STEP3 to use the "evolutionary features" that can be recognized in genome sequences of diverse phages. These features, when integrated into an ensemble framework, achieved a stable and robust prediction performance when benchmarked against other prediction tools using phages from diverse sources. Validation of the prediction accuracy of STEP3 was conducted with high-resolution mass spectrometry analysis of two novel phages, isolated from a watercourse in the Southern Hemisphere. STEP3 provides a robust computational approach to distinguish specific and universal features in phages to improve the quality of phage cocktails and is available for use at http://step3.erc.monash.edu/. IMPORTANCE In response to the global problem of antimicrobial resistance, there are moves to use bacteriophages (phages) as therapeutic agents. Selecting which phages will be effective therapeutics relies on interpreting features contributing to shelf-life and applicability to diagnosed infections. However, the protein components of the phage virions that dictate these properties vary so much in sequence that best estimates suggest failure to recognize up to 90% of them. We have utilized this diversity in evolutionary features as an advantage, to apply machine learning for prediction accuracy for diverse components in phage virions. We benchmark this new tool showing the accurate recognition and evaluation of phage component parts using genome sequence data of phages from undersampled environments, where the richest diversity of phage still lies.

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Rhif yr erthygle0024221
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Dyddiad ar-lein cynnar27 Mai 2021
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 29 Meh 2021
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