Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Rapid heuristic inference of antibiotic resistance and susceptibility by genomic neighbor typing

View ORCID ProfileKarel Břinda, View ORCID ProfileAlanna Callendrello, View ORCID ProfileKevin C. Ma, View ORCID ProfileDerek R MacFadden, Themoula Charalampous, Robyn S Lee, View ORCID ProfileLauren Cowley, View ORCID ProfileCrista B Wadsworth, View ORCID ProfileYonatan H Grad, View ORCID ProfileGregory Kucherov, View ORCID ProfileJustin O’Grady, View ORCID ProfileMichael Baym, View ORCID ProfileWilliam P Hanage
doi: https://doi.org/10.1101/403204
Karel Břinda
1Center for Communicable Disease Dynamic, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
2Department of Biomedical Informatics and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Karel Břinda
  • For correspondence: kbrinda@hsph.harvard.edu
Alanna Callendrello
1Center for Communicable Disease Dynamic, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alanna Callendrello
Kevin C. Ma
3Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kevin C. Ma
Derek R MacFadden
1Center for Communicable Disease Dynamic, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
4Division of Infectious Diseases, Department of Medicine, University of Toronto, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Derek R MacFadden
Themoula Charalampous
5Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robyn S Lee
1Center for Communicable Disease Dynamic, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lauren Cowley
6Department of Biology and Biochemistry, University of Bath, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lauren Cowley
Crista B Wadsworth
7Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Crista B Wadsworth
Yonatan H Grad
3Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yonatan H Grad
Gregory Kucherov
8CNRS/LIGM Université Paris-Est, Marne-la-Vallée, France
9Skolkovo Institute of Science and Technology, Moscow, Russia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gregory Kucherov
Justin O’Grady
10Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
5Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Justin O’Grady
Michael Baym
2Department of Biomedical Informatics and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael Baym
William P Hanage
1Center for Communicable Disease Dynamic, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for William P Hanage
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Abstract

Surveillance of drug-resistant bacteria is essential for healthcare providers to deliver effective empiric antibiotic therapy. However, traditional molecular epidemiology does not typically occur on a timescale that could impact patient treatment and outcomes. Here we present a method called ‘genomic neighbor typing’ for inferring the phenotype of a bacterial sample by identifying its closest relatives in a database of genomes with metadata. We show that this technique can infer antibiotic susceptibility and resistance for both S. pneumoniae and N. gonorrhoeae. We implemented this with rapid k-mer matching, which, when used on Oxford Nanopore MinION data, can run in real time. This resulted in determination of resistance within ten minutes (sens/spec 91%/100% for S. pneumoniae and 81%/100% N. gonorrhoeae from isolates with a representative database) of sequencing starting, and for clinical metagenomic sputum samples (75%/100% for S. pneumoniae), within four hours of sample collection. This flexible approach has wide application to pathogen surveillance and may be used to greatly accelerate appropriate empirical antibiotic treatment.

Footnotes

  • https://github.com/c2-d2/rase-supplement

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted August 07, 2019.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Rapid heuristic inference of antibiotic resistance and susceptibility by genomic neighbor typing
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Rapid heuristic inference of antibiotic resistance and susceptibility by genomic neighbor typing
Karel Břinda, Alanna Callendrello, Kevin C. Ma, Derek R MacFadden, Themoula Charalampous, Robyn S Lee, Lauren Cowley, Crista B Wadsworth, Yonatan H Grad, Gregory Kucherov, Justin O’Grady, Michael Baym, William P Hanage
bioRxiv 403204; doi: https://doi.org/10.1101/403204
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Rapid heuristic inference of antibiotic resistance and susceptibility by genomic neighbor typing
Karel Břinda, Alanna Callendrello, Kevin C. Ma, Derek R MacFadden, Themoula Charalampous, Robyn S Lee, Lauren Cowley, Crista B Wadsworth, Yonatan H Grad, Gregory Kucherov, Justin O’Grady, Michael Baym, William P Hanage
bioRxiv 403204; doi: https://doi.org/10.1101/403204

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Bioinformatics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8767)
  • Bioengineering (6480)
  • Bioinformatics (23347)
  • Biophysics (11751)
  • Cancer Biology (9150)
  • Cell Biology (13255)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11370)
  • Epidemiology (2066)
  • Evolutionary Biology (15089)
  • Genetics (10402)
  • Genomics (14012)
  • Immunology (9122)
  • Microbiology (22050)
  • Molecular Biology (8780)
  • Neuroscience (47376)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8053)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2209)
  • Systems Biology (6016)
  • Zoology (1250)