Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny
Issued Date
2026-01-01
Resource Type
ISSN
15487091
eISSN
15487105
Scopus ID
2-s2.0-105029877354
Pubmed ID
41663577
Journal Title
Nature Methods
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Methods (2026)
Suggested Citation
Hunt M., Hinrichs A.S., Anderson D., Karim L., Dearlove B.L., Knaggs J., Constantinides B., Fowler P.W., Rodger G., Street T., Lumley S., Webster H., Sanderson T., Ruis C., Kotzen B., de Maio N., Amenga-Etego L.N., Amuzu D.S.Y., Avaro M., Awandare G.A., Ayivor-Djanie R., Barkham T., Bashton M., Batty E.M., Bediako Y., De Belder D., Benedetti E., Bergthaler A., Boers S.A., Campos J., Carr R.A.A., Chen Y.Y.C., Cuba F., Dattero M.E., Dejnirattisai W., Dilthey A., Duedu K.O., Endler L., Engelmann I., Francisco N.M., Fuchs J., Gnimpieba E.Z., Groc S., Gyamfi J., Heemskerk D., Houwaart T., Hsiao N.Y., Huska M., Hölzer M., Iranzadeh A., Jarva H., Jeewandara C., Jolly B., Joseph R., Kant R., Ki K.K.K., Kurkela S., Lappalainen M., Lataretu M., Lemieux J., Liu C., Malavige G.N., Mashe T., Mongkolsapaya J., Montes B., Mora J.A.M., Morang’a C.M., Mvula B., Nagarajan N., Nelson A., Ngoi J.M., da Paixão J.P., Panning M., Poklepovich T., Quashie P.K., Ranasinghe D., Russo M., San J.E., Sanderson N.D., Scaria V., Screaton G., Sessions O.M., Sironen T., Sisay A., Smith D., Smura T., Supasa P., Suphavilai C., Swann J., Tegally H., Tegomoh B., Vapalahti O., Walker A., Wilkinson R.J., Williamson C., Zair X., Tiemann C., Tewald F., Szabados F., Schwanz T. Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny. Nature Methods (2026). doi:10.1038/s41592-025-02947-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115157
Title
Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny
Author(s)
Hunt M.
Hinrichs A.S.
Anderson D.
Karim L.
Dearlove B.L.
Knaggs J.
Constantinides B.
Fowler P.W.
Rodger G.
Street T.
Lumley S.
Webster H.
Sanderson T.
Ruis C.
Kotzen B.
de Maio N.
Amenga-Etego L.N.
Amuzu D.S.Y.
Avaro M.
Awandare G.A.
Ayivor-Djanie R.
Barkham T.
Bashton M.
Batty E.M.
Bediako Y.
De Belder D.
Benedetti E.
Bergthaler A.
Boers S.A.
Campos J.
Carr R.A.A.
Chen Y.Y.C.
Cuba F.
Dattero M.E.
Dejnirattisai W.
Dilthey A.
Duedu K.O.
Endler L.
Engelmann I.
Francisco N.M.
Fuchs J.
Gnimpieba E.Z.
Groc S.
Gyamfi J.
Heemskerk D.
Houwaart T.
Hsiao N.Y.
Huska M.
Hölzer M.
Iranzadeh A.
Jarva H.
Jeewandara C.
Jolly B.
Joseph R.
Kant R.
Ki K.K.K.
Kurkela S.
Lappalainen M.
Lataretu M.
Lemieux J.
Liu C.
Malavige G.N.
Mashe T.
Mongkolsapaya J.
Montes B.
Mora J.A.M.
Morang’a C.M.
Mvula B.
Nagarajan N.
Nelson A.
Ngoi J.M.
da Paixão J.P.
Panning M.
Poklepovich T.
Quashie P.K.
Ranasinghe D.
Russo M.
San J.E.
Sanderson N.D.
Scaria V.
Screaton G.
Sessions O.M.
Sironen T.
Sisay A.
Smith D.
Smura T.
Supasa P.
Suphavilai C.
Swann J.
Tegally H.
Tegomoh B.
Vapalahti O.
Walker A.
Wilkinson R.J.
Williamson C.
Zair X.
Tiemann C.
Tewald F.
Szabados F.
Schwanz T.
Hinrichs A.S.
Anderson D.
Karim L.
Dearlove B.L.
Knaggs J.
Constantinides B.
Fowler P.W.
Rodger G.
Street T.
Lumley S.
Webster H.
Sanderson T.
Ruis C.
Kotzen B.
de Maio N.
Amenga-Etego L.N.
Amuzu D.S.Y.
Avaro M.
Awandare G.A.
Ayivor-Djanie R.
Barkham T.
Bashton M.
Batty E.M.
Bediako Y.
De Belder D.
Benedetti E.
Bergthaler A.
Boers S.A.
Campos J.
Carr R.A.A.
Chen Y.Y.C.
Cuba F.
Dattero M.E.
Dejnirattisai W.
Dilthey A.
Duedu K.O.
Endler L.
Engelmann I.
Francisco N.M.
Fuchs J.
Gnimpieba E.Z.
Groc S.
Gyamfi J.
Heemskerk D.
Houwaart T.
Hsiao N.Y.
Huska M.
Hölzer M.
Iranzadeh A.
Jarva H.
Jeewandara C.
Jolly B.
Joseph R.
Kant R.
Ki K.K.K.
Kurkela S.
Lappalainen M.
Lataretu M.
Lemieux J.
Liu C.
Malavige G.N.
Mashe T.
Mongkolsapaya J.
Montes B.
Mora J.A.M.
Morang’a C.M.
Mvula B.
Nagarajan N.
Nelson A.
Ngoi J.M.
da Paixão J.P.
Panning M.
Poklepovich T.
Quashie P.K.
Ranasinghe D.
Russo M.
San J.E.
Sanderson N.D.
Scaria V.
Screaton G.
Sessions O.M.
Sironen T.
Sisay A.
Smith D.
Smura T.
Supasa P.
Suphavilai C.
Swann J.
Tegally H.
Tegomoh B.
Vapalahti O.
Walker A.
Wilkinson R.J.
Williamson C.
Zair X.
Tiemann C.
Tewald F.
Szabados F.
Schwanz T.
Author's Affiliation
University of Oxford
University of California, Berkeley
University of Cambridge
Imperial College London
National University of Singapore
Massachusetts General Hospital
Helsingin Yliopisto
Duke University
University of Michigan Medical School
University of Cape Town
Leids Universitair Medisch Centrum
University of KwaZulu-Natal
Stellenbosch University
Universitätsklinikum Freiburg
John Radcliffe Hospital
Universitätsmedizin Mainz
NUS Yong Loo Lin School of Medicine
Academy of Scientific and Innovative Research (AcSIR)
University of Northumbria
Addis Ababa University
Nuffield Department of Medicine
University of Ghana
Universitätsklinikum Düsseldorf
Centre Hospitalier Universitaire de Montpellier
Singapore General Hospital
Siriraj Hospital
Universidad de Costa Rica
Robert Koch Institute
Teesside University
Tan Tock Seng Hospital
Birmingham City University
Baskin School of Engineering
NIHR Oxford Biomedical Research Centre
The Francis Crick Institute
International Centre for Genetic Engineering and Biotechnology
European Molecular Biology Laboratory
University of Sri Jayewardenepura
A-Star, Genome Institute of Singapore
Mahidol Oxford Tropical Medicine Research Unit
University of Health and Allied Sciences, Ghana
Medizinische Universitat Wien, Zentrum für Pathophysiologie, Infektiologie und Immunologie
Ministry of Health Malawai
Department of Veterinary Medicine
Administracion Nacional de Laboratorios E Institutos de Salud Dr. Carlos G. Malbran
Instituto Nacional de Enfermedades Infecciosas
Akademickie Centrum Medycyny Morskiej i Tropikalnej
Pathogenèse et Contrôle des Infections Chroniques
WHO Regional Office for Africa
CARE Foundation
Department of Biomedical Engineering
Instituto Nacional de Investigação em Saúde
NEBRASKA DEPARTMENT OF HEALTH & HUMAN SERVICES
Ministère de la Santé Publique
Labor Krone
Labor Enders
Laborarztpraxis Osnabrück
Karkinos Healthcare Private Limited (KHPL)
University of California, Berkeley
University of Cambridge
Imperial College London
National University of Singapore
Massachusetts General Hospital
Helsingin Yliopisto
Duke University
University of Michigan Medical School
University of Cape Town
Leids Universitair Medisch Centrum
University of KwaZulu-Natal
Stellenbosch University
Universitätsklinikum Freiburg
John Radcliffe Hospital
Universitätsmedizin Mainz
NUS Yong Loo Lin School of Medicine
Academy of Scientific and Innovative Research (AcSIR)
University of Northumbria
Addis Ababa University
Nuffield Department of Medicine
University of Ghana
Universitätsklinikum Düsseldorf
Centre Hospitalier Universitaire de Montpellier
Singapore General Hospital
Siriraj Hospital
Universidad de Costa Rica
Robert Koch Institute
Teesside University
Tan Tock Seng Hospital
Birmingham City University
Baskin School of Engineering
NIHR Oxford Biomedical Research Centre
The Francis Crick Institute
International Centre for Genetic Engineering and Biotechnology
European Molecular Biology Laboratory
University of Sri Jayewardenepura
A-Star, Genome Institute of Singapore
Mahidol Oxford Tropical Medicine Research Unit
University of Health and Allied Sciences, Ghana
Medizinische Universitat Wien, Zentrum für Pathophysiologie, Infektiologie und Immunologie
Ministry of Health Malawai
Department of Veterinary Medicine
Administracion Nacional de Laboratorios E Institutos de Salud Dr. Carlos G. Malbran
Instituto Nacional de Enfermedades Infecciosas
Akademickie Centrum Medycyny Morskiej i Tropikalnej
Pathogenèse et Contrôle des Infections Chroniques
WHO Regional Office for Africa
CARE Foundation
Department of Biomedical Engineering
Instituto Nacional de Investigação em Saúde
NEBRASKA DEPARTMENT OF HEALTH & HUMAN SERVICES
Ministère de la Santé Publique
Labor Krone
Labor Enders
Laborarztpraxis Osnabrück
Karkinos Healthcare Private Limited (KHPL)
Corresponding Author(s)
Other Contributor(s)
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.