Journal article
Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis
- Abstract:
- The rise of antibiotic-resistant bacteria has led to an urgent need for rapid detection of drug resistance in clinical samples, and improvements in global surveillance. Here we show how de Bruijn graph representation of bacterial diversity can be used to identify species and resistance profiles of clinical isolates. We implement this method for Staphylococcus aureus and Mycobacterium tuberculosis in a software package ('Mykrobe predictor') that takes raw sequence data as input, and generates a clinician-friendly report within 3 minutes on a laptop. For S. aureus, the error rates of our method are comparable to gold-standard phenotypic methods, with sensitivity/specificity of 99.1%/99.6% across 12 antibiotics (using an independent validation set, n=470). For M. tuberculosis, our method predicts resistance with sensitivity/specificity of 82.6%/98.5% (independent validation set, n=1,609); sensitivity is lower here, probably because of limited understanding of the underlying genetic mechanisms. We give evidence that minor alleles improve detection of extremely drug-resistant strains, and demonstrate feasibility of the use of emerging single-molecule nanopore sequencing techniques for these purposes.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.9MB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms10063
Authors
+ National Institute for Health Research
More from this funder
- Funding agency for:
- Peto, T
- Crook, D
- Grant:
- Senior Investigator Award
- Senior Investigator Award
- G0800778
+ Wellcome Trust/Royal Society Sir Henry Dale Fellowship
More from this funder
- Funding agency for:
- Wilson, D
- Iqbal, Z
- Grant:
- 101237/Z/13/Z
- 102541/Z/13/Z
+ Medical Research Council
More from this funder
- Funding agency for:
- Earle, S
- Grant:
- funded prize studentship to the Nuffield Department of Medicine
+ Wellcome Trust
More from this funder
- Funding agency for:
- Bradley, P
- McVean, G
- Grant:
- PhD studentship
- 100956/Z/13/Z
- UK Clinical Research Collaboration 087646/Z/08/Z
- Core Award Grant Number 090532/Z/09/Z
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Communications More from this journal
- Volume:
- 6
- Pages:
- 10063-10063
- Publication date:
- 2015-12-21
- Acceptance date:
- 2015-10-28
- DOI:
- EISSN:
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2041-1723
- Pubs id:
-
pubs:581535
- UUID:
-
uuid:0ab1313e-cb99-43e4-8fde-c3a0b7331d3f
- Local pid:
-
pubs:581535
- Source identifiers:
-
581535
- Deposit date:
-
2016-01-12
Terms of use
- Copyright holder:
- Bradley et al
- Copyright date:
- 2015
- Notes:
- Author(s) retain copyright; published by Nature Publishing Group under license. This work is licensed under a Creative Commons Attribution 4.0 International License. This is the publisher's version of the article. The final version is available online from Nature Publishing Group at: [10.1038/ncomms10063]
- Licence:
- CC Attribution (CC BY)
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