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Accuracy of Different Bioinformatics Methods in Detecting Antibiotic Resistance and Virulence Factors from Staphylococcus aureus Whole-Genome Sequences

Mason, A; Foster, D; Bradley, P; Golubchik, T; Doumith, M; Gordon, NC; Pichon, B; ... Peto, T; + view all (2018) Accuracy of Different Bioinformatics Methods in Detecting Antibiotic Resistance and Virulence Factors from Staphylococcus aureus Whole-Genome Sequences. Journal of Clinical Microbiology , 56 (9) , Article e01815-17. 10.1128/JCM.01815-17. Green open access

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Abstract

In principle, whole-genome sequencing (WGS) can predict phenotypic resistance directly from a genotype, replacing laboratory-based tests. However, the contribution of different bioinformatics methods to genotype-phenotype discrepancies has not been systematically explored to date. We compared three WGS-based bioinformatics methods (Genefinder [read based], Mykrobe [de Bruijn graph based], and Typewriter [BLAST based]) for predicting the presence/absence of 83 different resistance determinants and virulence genes and overall antimicrobial susceptibility in 1,379 Staphylococcus aureus isolates previously characterized by standard laboratory methods (disc diffusion, broth and/or agar dilution, and PCR). In total, 99.5% (113,830/114,457) of individual resistance-determinant/virulence gene predictions were identical between all three methods, with only 627 (0.5%) discordant predictions, demonstrating high overall agreement (Fleiss' kappa = 0.98, P < 0.0001). Discrepancies when identified were in only one of the three methods for all genes except the cassette recombinase, ccrC(b). The genotypic antimicrobial susceptibility prediction matched the laboratory phenotype in 98.3% (14,224/14,464) of cases (2,720 [18.8%] resistant, 11,504 [79.5%] susceptible). There was greater disagreement between the laboratory phenotypes and the combined genotypic predictions (97 [0.7%] phenotypically susceptible, but all bioinformatic methods reported resistance; 89 [0.6%] phenotypically resistant, but all bioinformatics methods reported susceptible) than within the three bioinformatics methods (54 [0.4%] cases, 16 phenotypically resistant, 38 phenotypically susceptible). However, in 36/54 (67%) cases, the consensus genotype matched the laboratory phenotype. In this study, the choice between these three specific bioinformatic methods to identify resistance determinants or other genes in S. aureus did not prove critical, with all demonstrating high concordance with each other and phenotypic/molecular methods. However, each has some limitations; therefore, consensus methods provide some assurance.

Type: Article
Title: Accuracy of Different Bioinformatics Methods in Detecting Antibiotic Resistance and Virulence Factors from Staphylococcus aureus Whole-Genome Sequences
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/JCM.01815-17
Publisher version: https://doi.org/10.1128/JCM.01815-17
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Staphylococcus aureus, antibiotic resistance, bioinformatics, whole-genome sequencing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10047944
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