ArticleNature methods2026
Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.
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Article in Nature methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19citing papers in PubMed
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Who cites it
19 citing papers in PubMed.
- Identification and masking of artifactual and misleading within-host variants in deep-sequencing SARS-CoV-2 data.Molecular biology and evolution · 2026Article
- SARS-CoV-2 saltational events are recurrent and trace to persistent human infections.bioRxiv : the preprint server for biology · 2026Article
- Rate variation and recurrent sequence errors in pandemic-scale phylogenetics.Nature methods · 2026Article
- Biological causes and impacts of rugged tree landscapes in phylodynamic inference.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Pandemic-Scale Ancestral Recombination Graph for SARS-CoV-2.bioRxiv : the preprint server for biology · 2025Article
- Article
- Highly Recurrent Multinucleotide Mutations in SARS-CoV-2.Molecular biology and evolution · 2025Article
- Tsbrowse: an interactive browser for ancestral recombination graphs.Bioinformatics (Oxford, England) · 2025Article
- UShER-TB: Scalable, Comprehensive, Accessible Phylogenomic Analysis ofmedRxiv : the preprint server for health sciences · 2025Article
- CREMSA: compressed indexing of (ultra) large multiple sequence alignments.Bioinformatics (Oxford, England) · 2025Article
- Biological causes and impacts of rugged tree landscapes in phylodynamic inference.bioRxiv : the preprint server for biology · 2025Article
- The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and RNA structure.Nucleic acids research · 2025Article
- Article
- Epidemic-induced local awareness behavior inferred from surveys and genetic sequence data.Nature communications · 2025Article
- Analysis-ready VCF at Biobank scale using Zarr.bioRxiv : the preprint server for biology · 2025Article
- The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and RNA structure.bioRxiv : the preprint server for biology · 2025Article
- Analysis-ready VCF at Biobank scale using Zarr.GigaScience · 2025Article
- Genome data artifacts and functional studies of deletion repair in the BA.1 SARS-CoV-2 spike protein.Virus evolution · 2025Article
- Recombination Events Among SARS-CoV-2 Omicron Subvariants: Impact on Spike Interaction With ACE2 Receptor and Neutralizing Antibodies.Evolutionary bioinformatics online · 2024Article
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Authors and funding
102 authors.
Martin HuntEuropean Molecular Biology Laboratory - European Bioinformatics Institute, Hinxton, UK.ORCID http://orcid.org/0000-0002-8060-4335
Angie S HinrichsGenomics Institute, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID http://orcid.org/0000-0002-1697-1130
Daniel AndersonEuropean Molecular Biology Laboratory - European Bioinformatics Institute, Hinxton, UK.ORCID http://orcid.org/0000-0003-4422-9520
Lily KarimGenomics Institute, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID http://orcid.org/0000-0002-4972-7513
Bethany L DearloveInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-3653-4592
Jeff KnaggsEuropean Molecular Biology Laboratory - European Bioinformatics Institute, Hinxton, UK.ORCID http://orcid.org/0000-0002-1206-0583
Bede ConstantinidesNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-3480-3819
Philip W FowlerNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-0912-4483
Gillian RodgerNuffield Department of Medicine, University of Oxford, Oxford, UK.
Teresa StreetNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-8491-240X
Sheila LumleyNuffield Department of Medicine, University of Oxford, Oxford, UK.
Hermione WebsterNuffield Department of Medicine, University of Oxford, Oxford, UK.
Theo SandersonFrancis Crick Institute, London, UK.
Christopher RuisVictor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, Cambridge, UK.
Benjamin KotzenDepartment of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0009-0007-2886-8521
Nicola de MaioEuropean Molecular Biology Laboratory - European Bioinformatics Institute, Hinxton, UK.ORCID http://orcid.org/0000-0002-1776-8564
Lucas N Amenga-EtegoWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.
Dominic S Y AmuzuWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.ORCID http://orcid.org/0000-0002-8920-0708
Martin AvaroServicio de Virus Respiratorios, Instituto Nacional Enfermedades Infecciosas, ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
Gordon A AwandareWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.
Reuben Ayivor-DjanieBiomanufacturing Group, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.ORCID http://orcid.org/0000-0003-0323-5473
Timothy BarkhamTan Tock Seng Hospital, Singapore, Singapore.
Matthew BashtonThe Hub for Biotechnology in the Built Environment, Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-6847-1525
Elizabeth M BattyCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Yaw BediakoWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.
Denise De BelderUnidad Operativa Centro Nacional de Genómica y Bioinformática, ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
Estefania BenedettiServicio de Virus Respiratorios, Instituto Nacional Enfermedades Infecciosas, ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
Andreas BergthalerInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-0597-1976
Stefan A BoersCenter of Infectious Diseases, Medical Microbiology and Infection Control, Leiden University Medical Centre, Albinusdreef 2, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-1560-6799
Josefina CamposUnidad Operativa Centro Nacional de Genómica y Bioinformática, ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
Rosina Afua Ampomah CarrDepartment of Biomedical Sciences, University of Health and Allied Sciences, Ho, Ghana.ORCID http://orcid.org/0000-0001-8391-5633
Yuan Yi Constance ChenTan Tock Seng Hospital, Singapore, Singapore.
Facundo CubaUnidad Operativa Centro Nacional de Genómica y Bioinformática, ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
Maria Elena DatteroServicio de Virus Respiratorios, Instituto Nacional Enfermedades Infecciosas, ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
Wanwisa DejnirattisaiDivision of Emerging Infectious Disease, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkoknoi, Thailand.
Alexander DiltheyInstitute of Medical Microbiology and Hospital Hygiene, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.ORCID http://orcid.org/0000-0002-6394-4581
Kwabena Obeng DueduDepartment of Biomedical Sciences, University of Health and Allied Sciences, Ho, Ghana.ORCID http://orcid.org/0000-0001-5816-5172
Lukas EndlerInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-9115-8756
Ilka EngelmannPathogenesis and Control of Chronic and Emerging Infections, Univ Montpellier, INSERM, Virology Laboratory, CHU Montpellier, Montpellier, France.ORCID http://orcid.org/0000-0001-7489-3786
Ngiambudulu M FranciscoGrupo de Investigação Microbiana e Imunológica, Instituto Nacional de Investigação em Saúde (National Institute for Health Research), Luanda, Angola.ORCID http://orcid.org/0000-0003-3255-8968
Jonas FuchsInstitute of Virology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-1974-212X
Etienne Z GnimpiebaBiomedical Engineering Department, University of South Dakota, Sioux Falls, SD, USA.ORCID http://orcid.org/0000-0002-5338-084X
Soraya GrocVirology Laboratory, CHU Montpellier, Montpellier, France.
Jones GyamfiDepartment of Biomedical Sciences, University of Health and Allied Sciences, Ho, Ghana.ORCID http://orcid.org/0000-0003-3785-9487
Dennis HeemskerkCenter of Infectious Diseases, Medical Microbiology and Infection Control, Leiden University Medical Centre, Albinusdreef 2, Leiden, The Netherlands.ORCID http://orcid.org/0009-0009-6761-8888
Torsten HouwaartInstitute of Medical Microbiology and Hospital Hygiene, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Nei-Yuan HsiaoDivison of Medical Virology, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa.
Matthew HuskaGenome Competence Center (MF1), Robert Koch Institute, Nordufer 20, Berlin, Germany.ORCID http://orcid.org/0000-0002-0912-745X
Martin HölzerGenome Competence Center (MF1), Robert Koch Institute, Nordufer 20, Berlin, Germany.
Arash IranzadehComputational Biology Division, University of Cape Town, Cape Town, South Africa.
Hanna JarvaHUS Diagnostic Center, Clinical Microbiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.ORCID http://orcid.org/0000-0002-9154-354X
Chandima JeewandaraInstitute of Allergology and Immunology, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka.
Bani JollyKarkinos Healthcare Private Limited (KHPL), Aurbis Business Parks, Bellandur, Bengaluru, India.
Rageema JosephDivison of Medical Virology, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa.
Ravi KantDepartment of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0003-3878-9775
Karrie Ko Kwan KiDepartment of Microbiology, Singapore General Hospital, Singapore, Singapore.ORCID http://orcid.org/0000-0002-5968-1870
Satu KurkelaHUS Diagnostic Center, Clinical Microbiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.ORCID http://orcid.org/0000-0003-2911-3212
Maija LappalainenHUS Diagnostic Center, Clinical Microbiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Marie LataretuGenome Competence Center (MF1), Robert Koch Institute, Nordufer 20, Berlin, Germany.ORCID http://orcid.org/0000-0002-3637-5870
Jacob LemieuxDepartment of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
Chang LiuChinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
Gathsaurie Neelika MalavigeInstitute of Allergology and Immunology, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka.ORCID http://orcid.org/0000-0001-9201-0449
Tapfumanei MasheHealth System Strengthening Unit, World Health Organisation, Harare, Zimbabwe.
Juthathip MongkolsapayaMahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
Brigitte MontesVirology Laboratory, CHU Montpellier, Montpellier, France.ORCID http://orcid.org/0000-0003-2866-4274
Jose Arturo Molina MoraCentro de investigación en Enfermedades Tropicales & Facultad de Microbiologia, Universidad de Costa Rica, San José, Costa Rica.ORCID http://orcid.org/0000-0001-9764-4192
Collins M Morang'aWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.
Bernard MvulaPublic Health Institute of Malawi, Ministry of Health, Malawi, Malawi.
Niranjan NagarajanGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.ORCID http://orcid.org/0000-0003-0850-5604
Andrew NelsonDepartment of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
Joyce M NgoiWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.
Joana Paula da PaixãoGrupo de Investigação Microbiana e Imunológica, Instituto Nacional de Investigação em Saúde (National Institute for Health Research), Luanda, Angola.
Marcus PanningInstitute of Virology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-3596-5964
Tomas PoklepovichUnidad Operativa Centro Nacional de Genómica y Bioinformática, ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
Peter K QuashieWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.ORCID http://orcid.org/0000-0003-4114-5460
Diyanath RanasingheInstitute of Allergology and Immunology, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka.ORCID http://orcid.org/0000-0001-5151-8908
Mara RussoServicio de Virus Respiratorios, Instituto Nacional Enfermedades Infecciosas, ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.
James Emmanuel SanDuke Human Vaccine Institute, Duke University, Durham, NC, England.ORCID http://orcid.org/0000-0002-5736-664X
Nicholas D SandersonNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-6370-1961
Vinod ScariaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Gavin ScreatonNuffield Department of Medicine, University of Oxford, Oxford, UK.
October Michael SessionsSaw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
Tarja SironenDepartment of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Abay SisayDepartment of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Darren SmithThe Hub for Biotechnology in the Built Environment, Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
Teemu SmuraDepartment of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Piyada SupasaChinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
Chayaporn SuphavilaiGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Jeremy SwannNuffield Department of Medicine, University of Oxford, Oxford, UK.
Houriiyah TegallyCentre for Epidemic Response and Innovation (CERI), Stellenbosch University, Stellenbosch, South Africa.
Bryan TegomohCentre de Coordination des Opérations d'Urgences de Santé Publique, Ministere de Sante Publique, Yaoundé, Cameroun.ORCID http://orcid.org/0000-0002-8763-6516
Olli VapalahtiDepartment of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0003-2270-6824
Andreas WalkerInstitute of Virology, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.ORCID http://orcid.org/0000-0002-8736-0863
Robert J WilkinsonFrancis Crick Institute, London, UK.ORCID http://orcid.org/0000-0002-2753-1800
Carolyn WilliamsonDivison of Medical Virology, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa.ORCID http://orcid.org/0000-0003-0125-1226
Xavier ZairSaw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
IMSSC Laboratory Network Consortium
Tulio de OliveiraCentre for Epidemic Response and Innovation (CERI), Stellenbosch University, Stellenbosch, South Africa.ORCID http://orcid.org/0000-0002-3027-5254
Timothy Ea PetoNuffield Department of Medicine, University of Oxford, Oxford, UK.
Derrick CrookNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-0590-2850
Russell Corbett-DetigGenomics Institute, University of California, Santa Cruz, Santa Cruz, CA, USA.ORCID http://orcid.org/0000-0001-6535-2478
Zamin IqbalEuropean Molecular Biology Laboratory - European Bioinformatics Institute, Hinxton, UK. zi245@bath.ac.uk.ORCID http://orcid.org/0000-0001-8466-7547
Funding
The UCSC Genome BrowserU24HG002371 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI Maximilian Haeussler · 2022 to 2026
$17.6MOrigins, Functional, and Evolutionary Consequences of Genomic VariationR35GM128932 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI Russell Corbett-Detig · 2018 to 2026
$3.2MUCSC Graduate Program in Genome SciencesT32HG012344 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI Angela Norie Brooks, Christopher Vollmers · 2022 to 2026
$1.5MAcademy of Finland (Suomen Akatemia) 336490DH | National Institute for Health Research (NIHR) NIHR200915NHGRI NIH HHS U24 HG002371U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC) BAA 200-2021-11554.U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) T32HG012344U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 5P20GM103443-20U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM128932Wellcome Trust (Wellcome) 210918/Z/18/ZWellcome Trust (Wellcome) 222574,
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.
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COVID-19Genome, ViralPhylogenySARS-CoV-2HumansPandemicsSoftware
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