Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks.

Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks.

Publication date: Sep 21, 2023

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.

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Concepts Keywords
Epidemiological epidemiology
Genome genetics
Host genomics
Improved global health
Outbreaks viruses

Semantics

Type Source Name
disease IDO host
disease MESH infectious disease
pathway REACTOME Infectious disease
disease VO effective
disease MESH infection
disease IDO pathogen
disease VO LACK
disease VO frequency
disease VO Viruses

Original Article

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