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
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 to reconstruct outbreaks 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 stable among repeated serial samples from the same host, is 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.
Dunn Helen、Kendall Michelle、Hatcher James、Williams Charlotte、Goldstein Richard A.、Didelot Xavier、Breuer Judith、Storey Nathaniel、Williams Rachel、Harris Kathryn、Ortiz Arturo Torres、Grandjean Louis、Roy Sunando
Department of Microbiology, Great Ormond Street HospitalDepartment of Statistics, University of WarwickDepartment of Microbiology, Great Ormond Street HospitalUCL Genomics, Institute of Child HealthUCL Genomics, Institute of Child HealthDepartment of Statistics, University of WarwickDepartment of Infection, Immunity and Inflammation, Institute of Child HealthDepartment of Microbiology, Great Ormond Street HospitalUCL Genomics, Institute of Child HealthDepartment of Microbiology, Great Ormond Street Hospital||Department of Virology, East South East London Pathology Partnership, Royal London HospitalDepartment of Infectious Diseases, Imperial College LondonDepartment of Infection, Immunity and Inflammation, Institute of Child HealthDepartment of Infection, Immunity and Inflammation, Institute of Child Health
医学研究方法预防医学微生物学
Phylogeneticswithin-host diversitytransmissioninfectious diseasesSARS- CoV-2
Dunn Helen,Kendall Michelle,Hatcher James,Williams Charlotte,Goldstein Richard A.,Didelot Xavier,Breuer Judith,Storey Nathaniel,Williams Rachel,Harris Kathryn,Ortiz Arturo Torres,Grandjean Louis,Roy Sunando.Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/2022.06.07.495142.点此复制
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