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PLoS Comput Biol. 2018 Dec 14;14(12):e1006258. doi: 10.1371/journal.pcbi.1006258. eCollection 2018 Dec.

Prediction of antibiotic resistance in Escherichia coli from large-scale pan-genome data.

Author information

1
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
2
Center for Computational Biology, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
3
Department for Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
4
Centre for Antibiotic Resistance Research at the University of Gothenburg, Gothenburg, Sweden.
5
Organismal and Evolutionary Biology Research Programme, Department of Computer Science, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
6
Helsinki Institute for Information Technology HIIT, Helsinki, Finland.
7
Department of Computer Science, University of Tartu, Tartu, Estonia.

Abstract

The emergence of microbial antibiotic resistance is a global health threat. In clinical settings, the key to controlling spread of resistant strains is accurate and rapid detection. As traditional culture-based methods are time consuming, genetic approaches have recently been developed for this task. The detection of antibiotic resistance is typically made by measuring a few known determinants previously identified from genome sequencing, and thus requires the prior knowledge of its biological mechanisms. To overcome this limitation, we employed machine learning models to predict resistance to 11 compounds across four classes of antibiotics from existing and novel whole genome sequences of 1936 E. coli strains. We considered a range of methods, and examined population structure, isolation year, gene content, and polymorphism information as predictors. Gradient boosted decision trees consistently outperformed alternative models with an average accuracy of 0.91 on held-out data (range 0.81-0.97). While the best models most frequently employed gene content, an average accuracy score of 0.79 could be obtained using population structure information alone. Single nucleotide variation data were less useful, and significantly improved prediction only for two antibiotics, including ciprofloxacin. These results demonstrate that antibiotic resistance in E. coli can be accurately predicted from whole genome sequences without a priori knowledge of mechanisms, and that both genomic and epidemiological data can be informative. This paves way to integrating machine learning approaches into diagnostic tools in the clinic.

PMID:
30550564
PMCID:
PMC6310291
DOI:
10.1371/journal.pcbi.1006258
[Indexed for MEDLINE]
Free PMC Article

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