Global pathogenomic analysis identifies known and novel genetic antimicrobial resistance determinants in twelve species
Hyun, J. C.; Monk, J. M.; Szubin, R.; Hefner, Y.; Palsson, B.
Show abstract
Surveillance programs for managing antimicrobial resistance (AMR) have yielded thousands of genomes suited for data-driven mechanism discovery. We present a workflow integrating pangenomics, gene annotation, and machine learning to identify AMR genes at scale. Applied to 12 species, 27,155 genomes, and 69 drugs, we 1) found AMR gene transfer mostly confined within related species, with 925 genes in multiple species but just eight in multiple phylogenetic classes, 2) demonstrated that discovery-oriented support vector machines outperform contemporary methods at recovering known AMR genes, recovering 263 genes compared to 145 by Pyseer, and 3) identified 142 novel AMR gene candidates. Validation of two candidates in E. coli BW25113 revealed cases of conditional resistance:{Delta} cycA conferred ciprofloxacin resistance in minimal media with D-serine, and frdD V111D conferred ampicillin resistance in the presence of ampC by modifying the overlapping promoter. We expect this approach to be adaptable to other species and phenotypes.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Antibiotic hypersensitivity signatures identify targets for attack in the Acinetobacter baumannii cell envelope 97%
- Escape mutations circumvent a tradeoff between resistance to beta-lactams and a beta-lactamase inhibitor 97%
- Increased antibiotic susceptibility in Neisseria gonorrhoeae through adaptation to the cervical environment 96%
Similar papers in this journal
- Genetic determinants facilitating the evolution of resistance to carbapenem antibiotics 97%
- Treatment history shapes the evolution of complex carbapenem-resistant phenotypes in Klebsiella spp. 97%
- Interpreting roles of mutations associated with the emergence of S. aureus USA300 strains using transcriptional regulatory network reconstruction 96%
Similar papers in this journal
- Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance 93%
- Molecular epidemiology of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire (UK) 2008-2018 92%
- Human reference gut microbiome comprising 5,414 prokaryotic species, including newly assembled genomes from under-represented Asian metagenomes 92%
Similar papers in this journal
- Integration of multi-modal measurements identifies critical mechanisms of tuberculosis drug action 96%
- Dual CRISPRi-Seq for genome-wide genetic interaction studies identifies key genes involved in the pneumococcal cell cycle 95%
- Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.