Predicting S. aureus antimicrobial resistance with interpretable genomic space maps.

Journal: Molecular informatics
PMID:

Abstract

Increasing antimicrobial resistance (AMR) represents a global healthcare threat. To decrease the spread of AMR and associated mortality, methods for rapid selection of optimal antibiotic treatment are urgently needed. Machine learning (ML) models based on genomic data to predict resistant phenotypes can serve as a fast screening tool prior to phenotypic testing. Nonetheless, many existing ML methods lack interpretability. Therefore, we present a methodology for visualization of sequence space and AMR prediction based on the non-linear dimensionality reduction method - generative topographic mapping (GTM). This approach, applied to AMR data of >5000 S. aureus isolates retrieved from the PATRIC database, yielded GTM models with reasonable accuracy for all drugs (balanced accuracy values ≥0.75). The Generative Topographic Maps (GTMs) represent data in the form of illustrative maps of the genomic space and allow for antibiotic-wise comparison of resistant phenotypes. The maps were also found to be useful for the analysis of genetic determinants responsible for drug resistance. Overall, the GTM-based methodology is a useful tool for both the illustrative exploration of the genomic sequence space and AMR prediction.

Authors

  • Karina Pikalyova
    Laboratoire de Chémoinformatique, UMR 7140, Université de Strasbourg, 1 rue Blaise Pascal, Strasbourg, 67000, France.
  • Alexey Orlov
    Skolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, Russia.
  • Dragos Horvath
    Laboratoire de Chemoinformatique, UMR 7140, Université de Strasbourg , 1 rue Blaise Pascal, Strasbourg 67000, France.
  • Gilles Marcou
    Laboratoire de Chemoinformatique, UMR 7140, Université de Strasbourg , 1 rue Blaise Pascal, Strasbourg 67000, France.
  • Alexandre Varnek
    Laboratoire de Chemoinformatique, UMR 7140, Université de Strasbourg , 1 rue Blaise Pascal, Strasbourg 67000, France.