| Title: |
Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny |
| Authors: |
IMSSC Laboratory Network Consortium; Hunt, Martin; Hinrichs, Angie S; Anderson, Daniel; Karim, Lily; Dearlove, Bethany L; Knaggs, Jeff; Constantinides, Bede; Fowler, Philip W; Rodger, Gillian; Street, Teresa L; Lumley, Sheila F; Webster, Hermione; Sanderson, Theo; Ruis, Christopher; Maio, Nicola De; Amenga-Etego, Lucas N; Amuzu, Dominic SY; Avaro, Martin; Awandare, Gordon A; Ayivor-Djanie, Reuben; Bashton, Matthew; Batty, Elizabeth M; Bediako, Yaw; Belder, Denise De; Benedetti, Estefania; Bergthaler, Andreas; Boers, Stefan A; Campos, Josefina; Carr, Rosina Afua Ampomah; Cuba, Facundo; Dattero, Maria Elena; Dejnirattisai, Wanwissa; Dilthey, Alexander T; Duedu, Kwabena Obeng; Endler, Lukas; Engelmann, Ilka; Francisco, Ngiambudulu M; Fuchs, Jonas; Z., Etienne Gnimpieba; Groc, Soraya; Gyamfi, Jones; Heemskerk, Dennis; Houwaart, Torsten; Jarva, Hanna; Kant, Ravi; Kurkela, Satu; Lappalainen, Maija; Sironen, Tarja; Smura, Teemu; Vapalahti, Olli |
| Contributors: |
Medicum; HUSLAB; Research Programs Unit; HUS Diagnostic Center; Faculty Common Matters (Faculty of Medicine); Helsinki One Health (HOH); Department of Virology; Viral Zoonosis Research Unit; Emerging Infections Research Group; Veterinary Biosciences; Olli Pekka Vapalahti / Principal Investigator; Clinicum; Veterinary Microbiology and Epidemiology; HUS Chemistry and Microbiology |
| Publisher Information: |
Nature Research |
| Publication Year: |
2026 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Biochemistry; cell and molecular biology; Alignment |
| Description: |
The SARS-CoV-2 genome occupies a unique place in infection biology -- it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 3,960,704 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of March 2023, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. Phase 2 of our project will address the fact that the data in the public archives is heavily geographically biased towards the Global North. We therefore have contributed new raw data to ENA/SRA from many ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Open access funding provided by European Molecular Biology Laboratory (EMBL).; RIS: urn:9687427071904696493A765EFD190D7B; https://hdl.handle.net/10138/629367; 001684610600001 |
| Availability: |
https://hdl.handle.net/10138/629367 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.7101DE26 |
| Database: |
BASE |