Identification of key drivers of antimicrobial resistance in using machine learning.

Journal: Canadian journal of microbiology
PMID:

Abstract

With antimicrobial resistance (AMR) rapidly evolving in pathogens, quick and accurate identification of genetic determinants of phenotypic resistance is essential for improving surveillance, stewardship, and clinical mitigation. Machine learning (ML) models show promise for AMR prediction in diagnostics but require a deep understanding of internal processes to use effectively. Our study utilised AMR gene, pangenomic, and predicted plasmid features from 647 and genomes across the One Health continuum, along with corresponding resistance phenotypes, to develop interpretive ML classifiers. Vancomycin resistance could be predicted with 99% accuracy with AMR gene features, 98% with pangenome features, and 96% with plasmid clusters. Top pangenome features overlapped with the resistance genes of the operon, which are often laterally transmitted via plasmids. Doxycycline resistance prediction achieved approximately 92% accuracy with pangenome features, with the top feature being elements of Tn conjugative transposon, a (M) carrier. Erythromycin resistance prediction models achieved about 90% accuracy, but top features were negatively correlated with resistance due to the confounding effect of population structure. This work demonstrates the importance of reviewing ML models' features to discern biological relevance even when achieving high-performance metrics. Our workflow offers the potential to propose hypotheses for experimental testing, enhancing the understanding of AMR mechanisms, which are crucial for combating the AMR crisis.

Authors

  • Jee In Kim
    Faculty of Computer Science, Dalhousie University, Halifax, NS, Canada.
  • Alexander Manuele
    Faculty of Computer Science, Dalhousie University, Halifax, NS, Canada.
  • Finlay Maguire
    Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Rahat Zaheer
    Agriculture and Agri-Food Canada, Lethbridge, AB, Canada.
  • Tim A McAllister
    Agriculture and Agri-Food Canada, Lethbridge, AB, Canada.
  • Robert G Beiko
    Faculty of Computer Science Dalhousie University Halifax NS Canada.