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

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; Theo Sanderson; Christopher Ruis; Nicola de Maio; Lucas N Amenga-Etego; Dominic S Y Amuzu; Martin Avaro; Gordon A Awandare; Reuben Ayivor-Djanie; Matthew Bashton; Elizabeth M Batty; Yaw Bediako; Denise De Belder; Estefania Benedetti; Andreas Bergthaler; Stefan A Boers; Josefina Campos; Rosina Afua Ampomah Carr; 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; 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; Tarja Sironen; Abay Sisay; Darren Smith; Teemu Smura; Piyada Supasa; Chayaporn Suphavilai; Jeremy Swann; Houriiyah Tegally; Bryan Tegomoh; Olli Vapalahti; Andreas Walker; Robert J Wilkinson; Carolyn Williamson; Tulio de Oliveira; Timothy E.A. Peto; Derrick Crook; Russell Corbett-Detig; Zamin Iqbal; IMSSC2 Laboratory Network Consortium

doi:10.1101/2024.04.29.591666

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

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, Theo Sanderson, Christopher Ruis, Nicola de Maio, Lucas N Amenga-Etego, Dominic S Y Amuzu, Martin Avaro, Gordon A Awandare, Reuben Ayivor-DjanieMatthew Bashton, Elizabeth M Batty, Yaw Bediako, Denise De Belder, Estefania Benedetti, Andreas Bergthaler, Stefan A Boers, Josefina Campos, Rosina Afua Ampomah Carr, 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, 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, Tarja Sironen, Abay Sisay, Darren Smith, Teemu Smura, Piyada Supasa, Chayaporn Suphavilai, Jeremy Swann, Houriiyah Tegally, Bryan Tegomoh, Olli Vapalahti, Andreas Walker, Robert J Wilkinson, Carolyn Williamson, Tulio de Oliveira, Timothy E.A. Peto, Derrick Crook, Russell Corbett-Detig, Zamin Iqbal, IMSSC2 Laboratory Network Consortium

Applied Sciences Department

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Abstract

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 countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

Original language	English
Publisher	bioRxiv
Pages	1-35
Number of pages	35
DOIs	https://doi.org/10.1101/2024.04.29.591666
Publication status	Submitted - 30 Apr 2024

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2024.04.29.591666v1.fullFinal published version, 2.32 MBLicence: CC BY

Cite this

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., de Maio, N., Amenga-Etego, L. N., Amuzu, D. S. Y., Avaro, M., Awandare, G. A., ... IMSSC2 Laboratory Network Consortium (2024). Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny. (pp. 1-35). bioRxiv. https://doi.org/10.1101/2024.04.29.591666

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abstract = "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 countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.",

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doi = "10.1101/2024.04.29.591666",

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Hunt, M, Hinrichs, AS, Anderson, D, Karim, L, Dearlove, BL, Knaggs, J, Constantinides, B, Fowler, PW, Rodger, G, Street, T, Lumley, S, Webster, H, Sanderson, T, Ruis, C, de Maio, N, Amenga-Etego, LN, Amuzu, DSY, Avaro, M, Awandare, GA, Ayivor-Djanie, R, Bashton, M, Batty, EM, Bediako, Y, De Belder, D, Benedetti, E, Bergthaler, A, Boers, SA, Campos, J, Carr, RAA, Cuba, F, Dattero, ME, Dejnirattisai, W, Dilthey, A, Duedu, KO, Endler, L, Engelmann, I, Francisco, NM, Fuchs, J, Gnimpieba, EZ, 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, KKK, Kurkela, S, Lappalainen, M, Lataretu, M, Liu, C, Malavige, GN, Mashe, T, Mongkolsapaya, J, Montes, B, Mora, JAM, Morang’a, CM, Mvula, B, Nagarajan, N, Nelson, A, Ngoi, JM, da Paixão, JP, Panning, M, Poklepovich, T, Quashie, PK, Ranasinghe, D, Russo, M, San, JE, Sanderson, ND, Scaria, V, Screaton, G, Sironen, T, Sisay, A, Smith, D, Smura, T, Supasa, P, Suphavilai, C, Swann, J, Tegally, H, Tegomoh, B, Vapalahti, O, Walker, A, Wilkinson, RJ, Williamson, C, de Oliveira, T, Peto, TEA, Crook, D, Corbett-Detig, R, Iqbal, Z & IMSSC2 Laboratory Network Consortium 2024 'Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny' bioRxiv, pp. 1-35. https://doi.org/10.1101/2024.04.29.591666

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T1 - Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny

AU - Hunt, Martin

AU - Hinrichs, Angie S

AU - Anderson, Daniel

AU - Karim, Lily

AU - Dearlove, Bethany L

AU - Knaggs, Jeff

AU - Constantinides, Bede

AU - Fowler, Philip W

AU - Rodger, Gillian

AU - Street, Teresa

AU - Lumley, Sheila

AU - Webster, Hermione

AU - Sanderson, Theo

AU - Ruis, Christopher

AU - de Maio, Nicola

AU - Amenga-Etego, Lucas N

AU - Amuzu, Dominic S Y

AU - Avaro, Martin

AU - Awandare, Gordon A

AU - Ayivor-Djanie, Reuben

AU - Bashton, Matthew

AU - Batty, Elizabeth M

AU - Bediako, Yaw

AU - De Belder, Denise

AU - Benedetti, Estefania

AU - Bergthaler, Andreas

AU - Boers, Stefan A

AU - Campos, Josefina

AU - Carr, Rosina Afua Ampomah

AU - Cuba, Facundo

AU - Dattero, Maria Elena

AU - Dejnirattisai, Wanwisa

AU - Dilthey, Alexander

AU - Duedu, Kwabena Obeng

AU - Endler, Lukas

AU - Engelmann, Ilka

AU - Francisco, Ngiambudulu M

AU - Fuchs, Jonas

AU - Gnimpieba, Etienne Z

AU - Groc, Soraya

AU - Gyamfi, Jones

AU - Heemskerk, Dennis

AU - Houwaart, Torsten

AU - Hsiao, Nei-Yuan

AU - Huska, Matthew

AU - Hölzer, Martin

AU - Iranzadeh, Arash

AU - Jarva, Hanna

AU - Jeewandara, Chandima

AU - Jolly, Bani

AU - Joseph, Rageema

AU - Kant, Ravi

AU - Ki, Karrie Ko Kwan

AU - Kurkela, Satu

AU - Lappalainen, Maija

AU - Lataretu, Marie

AU - Liu, Chang

AU - Malavige, Gathsaurie Neelika

AU - Mashe, Tapfumanei

AU - Mongkolsapaya, Juthathip

AU - Montes, Brigitte

AU - Mora, Jose Arturo Molina

AU - Morang’a, Collins M.

AU - Mvula, Bernard

AU - Nagarajan, Niranjan

AU - Nelson, Andrew

AU - Ngoi, Joyce M.

AU - da Paixão, Joana Paula

AU - Panning, Marcus

AU - Poklepovich, Tomas

AU - Quashie, Peter K.

AU - Ranasinghe, Diyanath

AU - Russo, Mara

AU - San, James Emmanuel

AU - Sanderson, Nicholas D.

AU - Scaria, Vinod

AU - Screaton, Gavin

AU - Sironen, Tarja

AU - Sisay, Abay

AU - Smith, Darren

AU - Smura, Teemu

AU - Supasa, Piyada

AU - Suphavilai, Chayaporn

AU - Swann, Jeremy

AU - Tegally, Houriiyah

AU - Tegomoh, Bryan

AU - Vapalahti, Olli

AU - Walker, Andreas

AU - Wilkinson, Robert J

AU - Williamson, Carolyn

AU - de Oliveira, Tulio

AU - Peto, Timothy E.A.

AU - Crook, Derrick

AU - Corbett-Detig, Russell

AU - Iqbal, Zamin

AU - IMSSC2 Laboratory Network Consortium

PY - 2024/4/30

Y1 - 2024/4/30

N2 - 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 countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

AB - 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 countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

U2 - 10.1101/2024.04.29.591666

DO - 10.1101/2024.04.29.591666

M3 - Preprint

C2 - 38746185

SP - 1

EP - 35

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

PB - bioRxiv

ER -