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

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• These errors, often stemming from outdated amplicon schemes and sequencing limitations, impacted the accuracy of phylogenetic analyses.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.