Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks
- Imperial College London, United Kingdom
- University of Warwick, United Kingdom
- Great Ormond Street Hospital, United Kingdom
- University College London, United Kingdom
Abstract
Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts. Although within-host genetic diversity is common among a wide variety of pathogens, conventional whole-genome sequencing phylogenetic approaches exclusively use consensus sequences, which consider only the most prevalent nucleotide at each position and therefore fail to capture low frequency variation within samples. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is partially maintained among repeated serial samples from the same host, it can transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.
Data availability
Samples sequenced as part of this study have been submitted to the European Nucleotide Archive under accession PRJEB53224.Sample metadata is included in Supplementary file 1.All custom code used in this article can be accessed at https://github.com/arturotorreso/scov2_withinHost.git.
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Within-host diversity improves phylogenetic reconstruction of SARS-CoV-2 outbreaksEuropean Nucleotide Archive, PRJEB53224.
Article and author information
Author details
Arturo Torres Ortiz
Richard A Goldstein
Funding
Wellcome Trust (201470/Z/16/Z)
- Louis Grandjean
National Institute of Allergy and Infectious Diseases (1R01AI146338)
- Louis Grandjean
NIHR
- Xavier Didelot
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- James M McCaw, University of Melbourne, Australia
Version history
- Preprint posted: June 7, 2022 (view preprint)
- Received: October 22, 2022
- Accepted: September 20, 2023
- Accepted Manuscript published: September 21, 2023 (version 1)
- Version of Record published: October 26, 2023 (version 2)
Copyright
© 2023, Torres Ortiz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks
eLife 12:e84384.
https://doi.org/10.7554/eLife.84384
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