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Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.

Martin Hunt1,2,3,4, Angie S Hinrichs5, Daniel Anderson1

  • 1European Molecular Biology Laboratory - European Bioinformatics Institute, Hinxton, UK.

Nature Methods
|February 9, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

This study introduces Viridian, a new tool to correct errors in SARS-CoV-2 genomes sequenced using tiled amplicons. This improves the accuracy of global phylogenetic trees, crucial for tracking virus evolution and variant spread.

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Area of Science:

  • Genomics
  • Virology
  • Bioinformatics

Background:

  • Most SARS-CoV-2 genomes were generated using tiled amplicons, a method prone to systematic errors.
  • These errors, often stemming from outdated amplicon schemes and sequencing limitations, impacted the accuracy of phylogenetic analyses.
  • The emergence of new SARS-CoV-2 variants necessitated updates to sequencing strategies, further complicating genome reconstruction.

Purpose of the Study:

  • To develop and validate a robust method for reconstructing high-quality SARS-CoV-2 genomes from amplicon sequencing data.
  • To generate an accurate global phylogenetic tree reflecting the evolutionary history of SARS-CoV-2.
  • To quantify the improvements in phylogenetic inference achieved by the new methodology.

Main Methods:

  • Utilized Viridian, a novel assembly tool designed to rigorously process amplicon sequence data.
  • Reconstructed SARS-CoV-2 genomes from public data available as of June 2024.
  • Constructed a global phylogenetic tree incorporating 4,471,579 samples.

    • Main Results:

    • Generated high-quality consensus sequences by addressing systematic errors inherent in amplicon sequencing.
    • Developed a comprehensive global phylogenetic tree of SARS-CoV-2, accessible via a public portal.
    • Validated the Viridian methodology through simulations and empirical data, demonstrating significant improvements in phylogenetic accuracy.

    Conclusions:

    • Viridian effectively corrects amplicon sequencing errors, leading to more reliable SARS-CoV-2 genome reconstruction.
    • The improved phylogenetic tree provides a more accurate representation of viral evolution and variant dynamics.
    • This work enhances our ability to track pandemics and understand pathogen evolution through accurate genomic data.