Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Genome sequencing can offer critical insight into pathogen spread in viral outbreaks, but existing transmission inference methods use simplistic evolutionary models and only incorporate a portion of available genetic data. Here, we develop a robust evolutionary model for transmission reconstruction that tracks the genetic composition of within-host viral populations over time and the lineages transmitted between hosts. We confirm that our model reliably describes within-host variant frequencies in a dataset of 134,682 SARS-CoV-2 deep-sequenced genomes from Massachusetts, USA. We then demonstrate that our reconstruction approach infers transmissions more accurately than two leading methods on synthetic data, as well as in a controlled outbreak of bovine respiratory syncytial virus and an epidemiologically-investigated SARS-CoV-2 outbreak in South Africa. Finally, we apply our transmission reconstruction tool to 5,692 outbreaks among the 134,682 Massachusetts genomes. Our methods and results demonstrate the utility of within-host variation for transmission inference of SARS-CoV-2 and other pathogens, and provide an adaptable mathematical framework for tracking within-host evolution.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593003 | PMC |
| http://dx.doi.org/10.1101/2023.10.14.23297039 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Phylodynamic estimation of the within-host evolutionary rate of extended-spectrum beta-lactamase-producing Enterobacterales.
Microb Genom
September 2025
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Despite their clinical relevance, the within-host evolution of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales is still poorly understood. To estimate the within-host evolutionary rates of ESBL-producing and species complex, we fitted phylodynamic models to genomic sequence data of longitudinally collected rectal swabs from 63 colonized hospital patients. We estimated an average within-host evolutionary rate of 7.
View Article and Find Full Text PDFNaturally acquired promoter variation influences Streptococcus pneumoniae infection outcomes.
Cell Host Microbe
August 2025
Division of Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address:
Streptococcus pneumoniae colonizes human airways, where it acquires sugars from glycosylated mucins using glycoside hydrolases and sugar transport systems. This study identifies widespread nucleotide sequence variation in the promoter of a pneumococcal operon encoding a glycan scavenging system. We identify 78 promoter sequence patterns across 21,155 genomes, with variation clustered within a stretch of adenines, where mutations accumulate via strand slippage during DNA replication.
View Article and Find Full Text PDFHost prior exposure augments heterogeneity in gene expression in both host and pathogen during infection.
bioRxiv
August 2025
Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
Variability in acquired protection, whether from prior pathogen exposure or vaccination, is increasingly recognized as a key determinant of host population-level variation in disease traits. It remains unclear whether this extends to the within-host physiological environment and what the consequences are for reinfecting pathogens. Here, we asked whether prior pathogen exposure of hosts induces gene expression heterogeneity in the host and/or pathogen during infection.
View Article and Find Full Text PDFViral expansion after transfer is a primary driver of influenza A virus transmission bottlenecks.
PLoS Biol
September 2025
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GeorgiaUnited States of America.
For many viruses, narrow bottlenecks acting during transmission sharply reduce genetic diversity in a recipient host relative to the donor. Since genetic diversity represents adaptive potential, such losses of diversity are thought to limit the opportunity for viral populations to undergo antigenic change and other adaptive processes. Thus, a detailed picture of evolutionary dynamics during transmission is critical to understanding the forces driving viral evolution at an epidemiologic scale.
View Article and Find Full Text PDFInvestigating alveolar macrophages in an human ex vivo precision-cut lung slice model of SARS-CoV-2 infection using Raman spectroscopy-A case study.
Clin Transl Med
September 2025
Leibniz Institute of Photonic Technology, Member of Leibniz Health Technologies, Member of the Leibniz Centre for Photonics in Infection Research (LPI), Jena, Germany.
Background: Alveolar macrophages (AMs) are crucial innate immune cells that play important roles during infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Ex vivo human precision-cut lung slices (PCLSs) are well-suited models to study immune reactions and biochemical changes within host cells as well as to follow functional macrophage phenotype plasticity within complex tissue environment. Raman spectroscopy emerged in recent years as a powerful method for label-free cell characterization.
View Article and Find Full Text PDF