Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny
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Martin Hunt Angie S Hinrichs Daniel Anderson Lily Karim Bethany L Dearlove Jeff Knaggs Bede Constantinides Philip W Fowler Gillian Rodger Teresa Street Sheila Lumley Hermione Webster Theodore Sanderson Christopher Ruis Benjamin Kotzen Nicola de Maio Lucas N Amenga-Etego Dominic SY Amuzu Martin Avaro Gordon A Awandare Reuben Ayivor-Djanie Timothy Barkham Matthew Bashton Elizabeth M Batty Yaw Bediako Denise De Belder Estefania Benedetti Andreas Bergthaler Stefan A Boers Josefina Campos Rosina Afua Ampomah Carr Yuan Yi Constance Chen Facundo Cuba Maria Elena Dattero Wanwisa Dejnirattisai Alexander Dilthey Kwabena Obeng Duedu Lukas Endler Ilka Engelmann Ngiambudulu M Francisco Jonas Fuchs Etienne Z Gnimpieba Soraya Groc Jones Gyamfi Dennis Heemskerk Torsten Houwaart Nei-Yuan Hsiao Matthew Huska Martin Hölzer Arash Iranzadeh Hanna Jarva Chandima Jeewandara Bani Jolly Rageema Joseph Ravi Kant Karrie Ko Kwan Ki Satu Kurkela Maija Lappalainen Marie Lataretu Jacob Lemieux Chang Liu Gathsaurie Neelika Malavige Tapfumanei Mashe Juthathip Mongkolsapaya Brigitte Montes Jose Arturo Molina Mora Collins M Morang'a Bernard Mvula Niranjan Nagarajan Andrew Nelson Joyce M Ngoi Joana Paula da Paixão Marcus Panning Tomas Poklepovich Peter K Quashie Diyanath Ranasinghe Mara Russo James Emmanuel San Nicholas D Sanderson Vinod Scaria Gavin Screaton October Michael Sessions Tarja Sironen Abay Sisay Darren Smith Teemu Smura Piyada Supasa Chayaporn Suphavilai Jeremy Swann Houriiyah Tegally Bryan Tegomoh Olli Vapalahti Andreas Walker Robert Wilkinson Carolyn Williamson Xavier Zair IMSSC Laboratory Network Consortium Tulio de Oliveira Timothy Ea Peto Derrick Crook Russell Corbett-Detig Zamin Iqbal
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Abstract
The majority of SARS-CoV-2 genomes obtained during the pandemic were derived by amplifying overlapping windows of the genome ('tiled amplicons'), reconstructing their sequences and fitting them together. This leads to systematic errors in genomes unless the software is both aware of the amplicon scheme and of the error modes of amplicon sequencing. Additionally, over time, amplicon schemes need to be updated as new mutations in the virus interfere with the primer binding sites at the end of amplicons. Thus, waves of variants swept the world during the pandemic and were followed by waves of systematic errors in the genomes, which had significant impacts on the inferred phylogenetic tree.Here we reconstruct the genomes from all public data as of June 2024 using an assembly tool called Viridian ( https://github.com/iqbal-lab-org/viridian ), developed to rigorously process amplicon sequence data. With these high-quality consensus sequences we provide a global phylogenetic tree of 4,471,579 samples, viewable at https://viridian.taxonium.org . We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny.
Journal details
Journal
Nature Methods
Volume
23
Issue number
3
Pages
653-662
Available online
Publication date
Full text links
Publisher website (DOI)
10.1038/s41592-025-02947-1
Europe PubMed Central
41663577
Pubmed
41663577
Publishing history
The publication was previously a preprint.
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