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Whole genome sequencing (WGS)-based antimicrobial susceptibility testing (AST) is reliable, but requires bioinformatics skills. This study improved WGS-based AST tools, making them faster and easier to interpret for clinical use.

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Area of Science:

  • Microbiology
  • Genomics
  • Computational Biology

Background:

  • Whole genome sequencing (WGS)-based antimicrobial susceptibility testing (AST) offers a reliable alternative to traditional phenotypic AST.
  • WGS-based AST is currently limited by the need for specialized bioinformatics expertise and complex data interpretation.
  • Existing tools often require significant technical knowledge, hindering widespread adoption in routine diagnostics.

Purpose of the Study:

  • To enhance the speed and interpretability of WGS-based AST.
  • To develop an easily interpretable antibiogram output from WGS data.
  • To leverage freely accessible tools like ResFinder and PointFinder for broader usability.

Main Methods:

  • Rewriting ResFinder code for raw read processing using Kmer-based alignment.
  • Expanding and revising existing ResFinder and PointFinder databases.
  • Developing new databases, including a genotype-to-phenotype key and species-specific panels for in silico antibiograms.
  • Validating ResFinder 4.0 on diverse bacterial species (E. coli, Salmonella spp., C. jejuni, E. faecium, E. faecalis, S. aureus) from various sources and origins.

Main Results:

  • Achieved genotype-phenotype concordance of ≥95% for 46/51 Gram-negative and 25/32 Gram-positive antimicrobial/species combinations.
  • Discrepancies at lower concordance rates were primarily attributed to phenotypic interpretation criteria and sequence quality, not tool performance.
  • ResFinder 4.0 demonstrated high accuracy in predicting antimicrobial susceptibility from WGS data.

Conclusions:

  • WGS-based AST using ResFinder 4.0 provides reliable in silico antibiograms comparable to phenotypic AST.
  • The enhanced tool offers a more accessible and interpretable solution for WGS-based AST.
  • This advancement supports the routine clinical application of WGS for antimicrobial resistance surveillance and diagnostics.