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1. Generation and transmission of interlineage recombinants in the SARS-CoV-2 pandemic

Author

Jackson, Ben, Boni, Maciej F., Bull, Matthew J., Colleran, Amy, Colquhoun, Rachel M., Darby, Alistair C., Haldenby, Sam, Hill, Verity, Lucaci, Anita, McCrone, John T., Nicholls, Samuel M., O’Toole, Áine, Pacchiarini, Nicole, Poplawski, Radoslaw, Scher, Emily, Todd, Flora, Webster, Hermione J., Whitehead, Mark, Wierzbicki, Claudia, Loman, Nicholas J., Connor, Thomas R., Robertson, David L., Pybus, Oliver G., and Rambaut, Andrew

Published
2021
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2. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Author

Koshy, Cherian, Wise, Emma, Cortes, Nick, Lynch, Jessica, Kidd, Stephen, Mori, Matilde, Fairley, Derek J., Curran, Tanya, McKenna, James P., Adams, Helen, Fraser, Christophe, Golubchik, Tanya, Bonsall, David, Moore, Catrin, Caddy, Sarah L., Khokhar, Fahad A., Wantoch, Michelle, Reynolds, Nicola, Warne, Ben, Maksimovic, Joshua, Spellman, Karla, McCluggage, Kathryn, John, Michaela, Beer, Robert, Afifi, Safiah, Morgan, Sian, Marchbank, Angela, Price, Anna, Kitchen, Christine, Gulliver, Huw, Merrick, Ian, Southgate, Joel, Guest, Martyn, Munn, Robert, Workman, Trudy, Connor, Thomas R., Fuller, William, Bresner, Catherine, Snell, Luke B., Charalampous, Themoula, Nebbia, Gaia, Batra, Rahul, Edgeworth, Jonathan, Robson, Samuel C., Beckett, Angela, Loveson, Katie F., Aanensen, David M., Underwood, Anthony P., Yeats, Corin A., Abudahab, Khalil, Taylor, Ben E.W., Menegazzo, Mirko, Clark, Gemma, Smith, Wendy, Khakh, Manjinder, Fleming, Vicki M., Lister, Michelle M., Howson-Wells, Hannah C., Berry, Louise, Boswell, Tim, Joseph, Amelia, Willingham, Iona, Bird, Paul, Helmer, Thomas, Fallon, Karlie, Holmes, Christopher, Tang, Julian, Raviprakash, Veena, Campbell, Sharon, Sheriff, Nicola, Loose, Matthew W., Holmes, Nadine, Moore, Christopher, Carlile, Matthew, Wright, Victoria, Sang, Fei, Debebe, Johnny, Coll, Francesc, Signell, Adrian W., Betancor, Gilberto, Wilson, Harry D., Feltwell, Theresa, Houldcroft, Charlotte J., Eldirdiri, Sahar, Kenyon, Anita, Davis, Thomas, Pybus, Oliver, du Plessis, Louis, Zarebski, Alex, Raghwani, Jayna, Kraemer, Moritz, Francois, Sarah, Attwood, Stephen, Vasylyeva, Tetyana, Torok, M. Estee, Hamilton, William L., Goodfellow, Ian G., Hall, Grant, Jahun, Aminu S., Chaudhry, Yasmin, Hosmillo, Myra, Pinckert, Malte L., Georgana, Iliana, Yakovleva, Anna, Meredith, Luke W., Moses, Samuel, Lowe, Hannah, Ryan, Felicity, Fisher, Chloe L., Awan, Ali R., Boyes, John, Breuer, Judith, Harris, Kathryn Ann, Brown, Julianne Rose, Shah, Divya, Atkinson, Laura, Lee, Jack C.D., Alcolea-Medina, Adela, Moore, Nathan, Cortes, Nicholas, Williams, Rebecca, Chapman, Michael R., Levett, Lisa J., Heaney, Judith, Smith, Darren L., Bashton, Matthew, Young, Gregory R., Allan, John, Loh, Joshua, Randell, Paul A., Cox, Alison, Madona, Pinglawathee, Holmes, Alison, Bolt, Frances, Price, James, Mookerjee, Siddharth, Rowan, Aileen, Taylor, Graham P., Ragonnet-Cronin, Manon, Nascimento, Fabricia F., Jorgensen, David, Siveroni, Igor, Johnson, Rob, Boyd, Olivia, Geidelberg, Lily, Volz, Erik M., Brunker, Kirstyn, Smollett, Katherine L., Loman, Nicholas J., Quick, Joshua, McMurray, Claire, Stockton, Joanne, Nicholls, Sam, Rowe, Will, Poplawski, Radoslaw, Martinez-Nunez, Rocio T., Mason, Jenifer, Robinson, Trevor I., O'Toole, Elaine, Watts, Joanne, Breen, Cassie, Cowell, Angela, Ludden, Catherine, Sluga, Graciela, Machin, Nicholas W., Ahmad, Shazaad S.Y., George, Ryan P., Halstead, Fenella, Sivaprakasam, Venkat, Thomson, Emma C., Shepherd, James G., Asamaphan, Patawee, Niebel, Marc O., Li, Kathy K., Shah, Rajiv N., Jesudason, Natasha G., Parr, Yasmin A., Tong, Lily, Broos, Alice, Mair, Daniel, Nichols, Jenna, Carmichael, Stephen N., Nomikou, Kyriaki, Aranday-Cortes, Elihu, Johnson, Natasha, Starinskij, Igor, da Silva Filipe, Ana, Robertson, David L., Orton, Richard J., Hughes, Joseph, Vattipally, Sreenu, Singer, Joshua B., Hale, Antony D., Macfarlane-Smith, Louissa R., Harper, Katherine L., Taha, Yusri, Payne, Brendan A.I., Burton-Fanning, Shirelle, Waugh, Sheila, Collins, Jennifer, Eltringham, Gary, Templeton, Kate E., McHugh, Martin P., Dewar, Rebecca, Wastenge, Elizabeth, Dervisevic, Samir, Stanley, Rachael, Prakash, Reenesh, Stuart, Claire, Elumogo, Ngozi, Sethi, Dheeraj K., Meader, Emma J., Coupland, Lindsay J., Potter, Will, Graham, Clive, Barton, Edward, Padgett, Debra, Scott, Garren, Swindells, Emma, Greenaway, Jane, Nelson, Andrew, Yew, Wen C., Resende Silva, Paola C., Andersson, Monique, Shaw, Robert, Peto, Timothy, Justice, Anita, Eyre, David, Crooke, Derrick, Hoosdally, Sarah, Sloan, Tim J., Duckworth, Nichola, Walsh, Sarah, Chauhan, Anoop J., Glaysher, Sharon, Bicknell, Kelly, Wyllie, Sarah, Butcher, Ethan, Elliott, Scott, Lloyd, Allyson, Impey, Robert, Levene, Nick, Monaghan, Lynn, Bradley, Declan T., Allara, Elias, Pearson, Clare, Muir, Peter, Vipond, Ian B., Hopes, Richard, Pymont, Hannah M., Hutchings, Stephanie, Curran, Martin D., Parmar, Surendra, Lackenby, Angie, Mbisa, Tamyo, Platt, Steven, Miah, Shahjahan, Bibby, David, Manso, Carmen, Hubb, Jonathan, Chand, Meera, Dabrera, Gavin, Ramsay, Mary, Bradshaw, Daniel, Thornton, Alicia, Myers, Richard, Schaefer, Ulf, Groves, Natalie, Gallagher, Eileen, Lee, David, Williams, David, Ellaby, Nicholas, Harrison, Ian, Hartman, Hassan, Manesis, Nikos, Patel, Vineet, Bishop, Chloe, Chalker, Vicki, Osman, Husam, Bosworth, Andrew, Robinson, Esther, Holden, Matthew T.G., Shaaban, Sharif, Birchley, Alec, Adams, Alexander, Davies, Alisha, Gaskin, Amy, Plimmer, Amy, Gatica-Wilcox, Bree, McKerr, Caoimhe, Moore, Catherine, Williams, Chris, Heyburn, David, De Lacy, Elen, Hilvers, Ember, Downing, Fatima, Shankar, Giri, Jones, Hannah, Asad, Hibo, Coombes, Jason, Watkins, Joanne, Evans, Johnathan M., Fina, Laia, Gifford, Laura, Gilbert, Lauren, Graham, Lee, Perry, Malorie, Morgan, Mari, Bull, Matthew, Cronin, Michelle, Pacchiarini, Nicole, Craine, Noel, Jones, Rachel, Howe, Robin, Corden, Sally, Rey, Sara, Kumziene-Summerhayes, Sara, Taylor, Sarah, Cottrell, Simon, Jones, Sophie, Edwards, Sue, O’Grady, Justin, Page, Andrew J., Wain, John, Webber, Mark A., Mather, Alison E., Baker, David J., Rudder, Steven, Yasir, Muhammad, Thomson, Nicholas M., Aydin, Alp, Tedim, Ana P., Kay, Gemma L., Trotter, Alexander J., Gilroy, Rachel A.J., Alikhan, Nabil-Fareed, de Oliveira Martins, Leonardo, Le-Viet, Thanh, Meadows, Lizzie, Kolyva, Anastasia, Diaz, Maria, Bell, Andrew, Gutierrez, Ana Victoria, Charles, Ian G., Adriaenssens, Evelien M., Kingsley, Robert A., Casey, Anna, Simpson, David A., Molnar, Zoltan, Thompson, Thomas, Acheson, Erwan, Masoli, Jane A.H., Knight, Bridget A., Hattersley, Andrew, Ellard, Sian, Auckland, Cressida, Mahungu, Tabitha W., Irish-Tavares, Dianne, Haque, Tanzina, Bourgeois, Yann, Scarlett, Garry P., Partridge, David G., Raza, Mohammad, Evans, Cariad, Johnson, Kate, Liggett, Steven, Baker, Paul, Essex, Sarah, Lyons, Ronan A., Caller, Laura G., Castellano, Sergi, Williams, Rachel J., Kristiansen, Mark, Roy, Sunando, Williams, Charlotte A., Dyal, Patricia L., Tutill, Helena J., Panchbhaya, Yasmin N., Forrest, Leysa M., Niola, Paola, Findlay, Jacqueline, Brooks, Tony T., Gavriil, Artemis, Mestek-Boukhibar, Lamia, Weeks, Sam, Pandey, Sarojini, Berry, Lisa, Jones, Katie, Richter, Alex, Beggs, Andrew, Smith, Colin P., Bucca, Giselda, Hesketh, Andrew R., Harrison, Ewan M., Peacock, Sharon J., Palmer, Sophie, Churcher, Carol M., Bellis, Katherine L., Girgis, Sophia T., Naydenova, Plamena, Blane, Beth, Sridhar, Sushmita, Ruis, Chris, Forrest, Sally, Cormie, Claire, Gill, Harmeet K., Dias, Joana, Higginson, Ellen E., Maes, Mailis, Young, Jamie, Kermack, Leanne M., Hadjirin, Nazreen F., Aggarwal, Dinesh, Griffith, Luke, Swingler, Tracey, Davidson, Rose K., Rambaut, Andrew, Williams, Thomas, Balcazar, Carlos E., Gallagher, Michael D., O'Toole, Áine, Rooke, Stefan, Jackson, Ben, Colquhoun, Rachel, Ashworth, Jordan, Hill, Verity, McCrone, J.T., Scher, Emily, Yu, Xiaoyu, Williamson, Kathleen A., Stanton, Thomas D., Michell, Stephen L., Bewshea, Claire M., Temperton, Ben, Michelsen, Michelle L., Warwick-Dugdale, Joanna, Manley, Robin, Farbos, Audrey, Harrison, James W., Sambles, Christine M., Studholme, David J., Jeffries, Aaron R., Darby, Alistair C., Hiscox, Julian A., Paterson, Steve, Iturriza-Gomara, Miren, Jackson, Kathryn A., Lucaci, Anita O., Vamos, Edith E., Hughes, Margaret, Rainbow, Lucille, Eccles, Richard, Nelson, Charlotte, Whitehead, Mark, Turtle, Lance, Haldenby, Sam T., Gregory, Richard, Gemmell, Matthew, Kwiatkowski, Dominic, de Silva, Thushan I., Smith, Nikki, Angyal, Adrienn, Lindsey, Benjamin B., Groves, Danielle C., Green, Luke R., Wang, Dennis, Freeman, Timothy M., Parker, Matthew D., Keeley, Alexander J., Parsons, Paul J., Tucker, Rachel M., Brown, Rebecca, Wyles, Matthew, Constantinidou, Chrystala, Unnikrishnan, Meera, Ott, Sascha, Cheng, Jeffrey K.J., Bridgewater, Hannah E., Frost, Lucy R., Taylor-Joyce, Grace, Stark, Richard, Baxter, Laura, Alam, Mohammad T., Brown, Paul E., McClure, Patrick C., Chappell, Joseph G., Tsoleridis, Theocharis, Ball, Jonathan, Grammatopoulos, Dimitris, Buck, David, Todd, John A., Green, Angie, Trebes, Amy, MacIntyre-Cockett, George, de Cesare, Mariateresa, Langford, Cordelia, Alderton, Alex, Amato, Roberto, Goncalves, Sonia, Jackson, David K., Johnston, Ian, Sillitoe, John, Palmer, Steve, Lawniczak, Mara, Berriman, Matt, Danesh, John, Livett, Rich, Shirley, Lesley, Farr, Ben, Quail, Mike, Thurston, Scott, Park, Naomi, Betteridge, Emma, Weldon, Danni, Goodwin, Scott, Nelson, Rachel, Beaver, Charlotte, Letchford, Laura, Jackson, David A., Foulser, Luke, McMinn, Liz, Prestwood, Liam, Kay, Sally, Kane, Leanne, Dorman, Matthew J., Martincorena, Inigo, Puethe, Christoph, Keatley, Jon-Paul, Tonkin-Hill, Gerry, Smith, Christen, Jamrozy, Dorota, Beale, Mathew A., Patel, Minal, Ariani, Cristina, Spencer-Chapman, Michael, Drury, Eleanor, Lo, Stephanie, Rajatileka, Shavanthi, Scott, Carol, James, Keith, Buddenborg, Sarah K., Berger, Duncan J., Patel, Gaurang, Garcia-Casado, Maria V., Dibling, Thomas, McGuigan, Samantha, Rogers, Hazel A., Hunter, Adam D., Souster, Emily, Neaverson, Alexandra S., Volz, Erik, McCrone, John T., O’Toole, Áine, Johnson, Robert, Rey, Sara M., Nicholls, Samuel M., Colquhoun, Rachel M., Shepherd, James, Pascall, David J., Shah, Rajiv, Jesudason, Natasha, Li, Kathy, Jarrett, Ruth, Goodfellow, Ian, and Pybus, Oliver G.

Published
2021
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3. Genomics-informed outbreak investigations of SARS-CoV-2 using civet

Author

O'Toole, Áine, Hill, Verity, Jackson, Ben, Dewar, Rebecca, Sahadeo, Nikita, Colquhoun, Rachel, Rooke, Stefan, McCrone, JT, Duggan, Kate, McHugh, Martin P, Nicholls, Samuel M, Poplawski, Radoslaw, COVID-19 Genomics UK (COG-UK) Consortium, COVID-19 Impact Project (Trinidad & Tobago Group), Aanensen, David, Holden, Matt, Connor, Tom, Loman, Nick, Goodfellow, Ian, Carrington, Christine VF, Templeton, Kate, Rambaut, Andrew, O'Toole, Áine [0000-0001-8083-474X], Jackson, Ben [0000-0002-9981-0649], Colquhoun, Rachel [0000-0002-5577-9897], McCrone, J T [0000-0002-9846-8917], Duggan, Kate [0000-0002-6709-4983], McHugh, Martin P [0000-0002-0370-3700], Nicholls, Samuel M [0000-0003-4081-065X], Poplawski, Radoslaw [0000-0002-9594-085X], Carrington, Christine V F [0000-0001-6533-9302], Apollo - University of Cambridge Repository, McCrone, JT [0000-0002-9846-8917], Carrington, Christine VF [0000-0001-6533-9302], University of St Andrews. School of Medicine, and University of St Andrews. Infection and Global Health Division

Subjects
MCC, SDG 3 - Good Health and Well-being, COVID-19 Genomics UK (COG-UK) Consortium, RA Public aspects of medicine, COVID-19, 3rd-DAS, COVID-19 Impact Project (Trinidad & Tobago Group), NIS, RA
Abstract

Funder: Trinidad and Tobago - UWI Research Development Impact Fund, The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 13 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background diversity, resolving the query into different 'catchments' and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus diversity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health.

Published
2022
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4. A phylogenetics and variant calling pipeline to support SARS-CoV-2 genomic epidemiology in the UK.

Author

Colquhoun, Rachel, O'Toole, Áine, Hill, Verity, McCrone, J T, Yu, Xiaoyu, Nicholls, Samuel M, Poplawski, Radoslaw, Whalley, Thomas, Groves, Natalie, Ellaby, Nicholas, Loman, Nick, Connor, Tom, and Rambaut, Andrew

Subjects
COVID-19 pandemic, SARS-CoV-2, QUALITY control, PHYLOGENY, COVID-19, SEQUENCE alignment
Abstract

In response to the escalating SARS-CoV-2 pandemic, in March 2020 the COVID-19 Genomics UK (COG-UK) consortium was established to enable national-scale genomic surveillance in the UK. By the end of 2020, 49% of all SARS-CoV-2 genome sequences globally had been generated as part of the COG-UK programme, and to date, this system has generated >3 million SARS-CoV-2 genomes. Rapidly and reliably analysing this unprecedented number of genomes was an enormous challenge. To fulfil this need and to inform public health decision-making, we developed a centralized pipeline that performs quality control, alignment, and variant calling and provides the global phylogenetic context of sequences. We present this pipeline and describe how we tailored it as the pandemic progressed to scale with the increasing amounts of data and to provide the most relevant analyses on a daily basis. [ABSTRACT FROM AUTHOR]

Published
2024
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5. SARS-CoV-2 within-host diversity and transmission

Author

Lythgoe, Katrina A., Hall, Matthew, Ferretti, Luca, de Cesare, Mariateresa, MacIntyre-Cockett, George, Trebes, Amy, Andersson, Monique, Otecko, Newton, Wise, Emma L., Moore, Nathan, Lynch, Jessica, Kidd, Stephen, Cortes, Nicholas, Mori, Matilde, Williams, Rebecca, Vernet, Gabrielle, Justice, Anita, Green, Angie, Nicholls, Samuel M., Ansari, M. Azim, Abeler-Dörner, Lucie, Moore, Catrin E., Peto, Timothy E. A., Eyre, David W., Shaw, Robert, Simmonds, Peter, Buck, David, Todd, John A., Connor, Thomas R., Ashraf, Shirin, da Silva Filipe, Ana, Shepherd, James, Thomson, Emma C., Bonsall, David, Fraser, Christophe, Golubchik, Tanya, The COVID-19 Genomics UK (COG-UK) Consortium, Bresner, Catherine, Fuller, William, Guest, Martyn, Kitchen, Christine, Marchbank, Angela, Merrick, Ian, Munn, Robert, Price, Anna, Southgate, Joel, Workman, Trudy, (OVSG), Oxford Virus Sequencing Analysis Group, consortium, The COVID-19 Genomics UK (COG-UK), Lythgoe, Katrina A [0000-0002-7089-7680], Hall, Matthew [0000-0002-2671-3864], Ferretti, Luca [0000-0001-7578-7301], de Cesare, Mariateresa [0000-0002-9847-1526], Trebes, Amy [0000-0002-3715-9109], Andersson, Monique [0000-0003-0619-1074], Wise, Emma L [0000-0002-0279-3900], Moore, Nathan [0000-0002-4279-2443], Lynch, Jessica [0000-0003-2015-9986], Kidd, Stephen [0000-0002-4504-4600], Mori, Matilde [0000-0001-9012-1911], Williams, Rebecca [0000-0002-8557-6337], Vernet, Gabrielle [0000-0001-9887-2824], Green, Angie [0000-0003-4386-9972], Nicholls, Samuel M [0000-0003-4081-065X], Ansari, M Azim [0000-0003-2790-8353], Abeler-Dörner, Lucie [0000-0003-3662-4192], Moore, Catrin E [0000-0002-8639-9846], Peto, Timothy EA [0000-0003-3477-8307], Shaw, Robert [0000-0003-3449-5876], Todd, John A [0000-0003-2740-8148], Connor, Thomas R [0000-0003-2394-6504], Ashraf, Shirin [0000-0002-6468-0258], da Silva Filipe, Ana [0000-0002-9442-2903], Shepherd, James [0000-0003-3915-048X], Thomson, Emma C [0000-0003-1482-0889], Bonsall, David [0000-0003-2187-0550], Fraser, Christophe [0000-0003-2399-9657], Golubchik, Tanya [0000-0003-2765-9828], and Apollo - University of Cambridge Repository

Subjects
Evolution, B100, B200, Genome, Viral, Biology, Virus, Bottleneck, law.invention, Coronavirus OC43, Human, 03 medical and health sciences, Phylogenetics, law, Pandemic, Humans, Online, RNA-Seq, Selection, Genetic, Research Articles, Phylogeny, 030304 developmental biology, Immune Evasion, 0303 health sciences, Family Characteristics, Multidisciplinary, Phylogenetic tree, 030306 microbiology, Coinfection, SARS-CoV-2, R-Articles, COVID-19, Genetic Variation, Microbio, Viral Load, C700, United Kingdom, Transmission (mechanics), Evolutionary biology, Mutation (genetic algorithm), Mutation, Spike Glycoprotein, Coronavirus, RNA, Viral, Coronavirus Infections, Viral load, Research Article
Abstract

Patterns and bottlenecks A year into the severe acute respiratory syndrome coronavirus 2 pandemic, we are experiencing waves of new variants emerging. Some of these variants have worrying functional implications, such as increased transmissibility or antibody treatment escape. Lythgoe et al. have undertaken in-depth sequencing of more than 1000 hospital patients' isolates to find out how the virus is mutating within individuals. Overall, there seem to be consistent and reproducible patterns of within-host virus diversity. The authors observed only one or two variants in most samples, but a few carried many variants. Although the evidence indicates strong purifying selection, including in the spike protein responsible for viral entry, the authors also saw evidence for transmission clusters associated with households and other possible superspreader events. After transmission, most variants fizzled out, but occasionally some initiated ongoing transmission and wider dissemination. Science, this issue p. eabg0821, More than a thousand deep-sequenced clinical samples from the UK reveal that SARS-CoV-2 has limited genetic diversity within most individuals., INTRODUCTION Genome sequencing at an unprecedented scale during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is helping to track spread of the virus and to identify new variants. Most of this work considers a single consensus sequence for each infected person. Here, we looked beneath the consensus to analyze genetic variation within viral populations making up an infection and studied the fate of within-host mutations when an infection is transmitted to a new individual. Within-host diversity offers the means to help confirm direct transmission and identify new variants of concern. RATIONALE We sequenced 1313 SARS-CoV-2 samples from the first wave of infection in the United Kingdom. We characterized within-host diversity and dynamics in the context of transmission and ongoing viral evolution. RESULTS Within-host diversity can be described by the number of intrahost single nucleotide variants (iSNVs) occurring above a given minor allele frequency (MAF) threshold. We found that in lower-viral-load samples, stochastic sampling effects resulted in a higher variance in MAFs, leading to more iSNVs being detected at any threshold. Based on a subset of 27 pairs of high-viral-load replicate RNA samples (>50,000 uniquely mapped veSEQ reads, corresponding to a cycle threshold of ~22), iSNVs with a minimum 3% MAF were highly reproducible. Comparing samples from two time points from 41 individuals, taken on average 6 days apart (interquartile ratio 2 to 10), we observed a dynamic process of iSNV generation and loss. Comparing iSNVs among 14 household contact pairs, we estimated transmission bottleneck sizes of one to eight viruses. Consensus differences between individuals in the same household, where sample depth allowed iSNV detection, were explained by the presence of an iSNV at the same site in the paired individual, consistent with direct transmission leading to fixation. We next focused on a set of 563 high-confidence iSNV sites that were variant in at least one high-viral-load sample (>50,000 uniquely mapped); low-confidence iSNVs unlikely to represent genomic diversity were excluded. Within-host diversity was limited in high-viral-load samples (mean 1.4 iSNVs per sample). Two exceptions, each with >14 iSNVs, showed variant frequencies consistent with coinfection or contamination. Overall, we estimated that 1 to 2% of samples in our dataset were coinfected and/or contaminated. Additionally, one sample was coinfected with another coronavirus (OC43), with no detectable impact on diversity. The ratio of nonsynonymous to synonymous (dN/dS) iSNVs was consistent with within-host purifying selection when estimated across the whole genome [dN/dS = 0.55, 95% confidence interval (95% CI) = 0.49 to 0.61] and for the Spike gene (dN/dS = 0.60, 95% CI = 0.45 to 0.82). Nevertheless, we observed Spike variants in multiple samples that have been shown to increase viral infectivity (L5F) or resistance to antibodies (G446V and A879V). We observed a strong association between high-confidence iSNVs and a consensus change on the phylogeny (153 cases), consistent with fixation after transmission or de novo mutations reaching consensus. Shared variants that never reached consensus (261 cases) were not phylogenetically associated. CONCLUSION Using robust methods to call within-host variants, we uncovered a consistent pattern of low within-host diversity, purifying selection, and narrow transmission bottlenecks. Within-host emergence of vaccine and therapeutic escape mutations is likely to be relatively rare, at least during early infection, when viral loads are high, but the observation of immune-escape variants in high-viral-load samples underlines the need for continued vigilance. Diagram showing low SARS-CoV-2 within-host genetic diversity and narrow transmission bottleneck. Individuals with high viral load typically have few, if any, within-host variants. Narrow transmission bottlenecks mean that the major variant in the source individual was typically transmitted and the minor variants lost. Occasionally, the minor variant was transmitted, leading to a consensus change, or multiple variants were transmitted, resulting in a mixed infection. Credit: FontAwesome, licensed under CC BY 4.0., Extensive global sampling and sequencing of the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have enabled researchers to monitor its spread and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals and how likely they are to be transmitted. To characterize within-host diversity and transmission, we deep-sequenced 1313 clinical samples from the United Kingdom. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high and by a narrow bottleneck at transmission. Most variants are either lost or occasionally fixed at the point of transmission, with minimal persistence of shared diversity, patterns that are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape SARS-CoV-2 variants are likely to arise infrequently but could spread rapidly if successfully transmitted.

Published
2021

6. Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package

Author

Griffiths, Emma J, primary, Timme, Ruth E, additional, Mendes, Catarina Inês, additional, Page, Andrew J, additional, Alikhan, Nabil-Fareed, additional, Fornika, Dan, additional, Maguire, Finlay, additional, Campos, Josefina, additional, Park, Daniel, additional, Olawoye, Idowu B, additional, Oluniyi, Paul E, additional, Anderson, Dominique, additional, Christoffels, Alan, additional, da Silva, Anders Gonçalves, additional, Cameron, Rhiannon, additional, Dooley, Damion, additional, Katz, Lee S, additional, Black, Allison, additional, Karsch-Mizrachi, Ilene, additional, Barrett, Tanya, additional, Johnston, Anjanette, additional, Connor, Thomas R, additional, Nicholls, Samuel M, additional, Witney, Adam A, additional, Tyson, Gregory H, additional, Tausch, Simon H, additional, Raphenya, Amogelang R, additional, Alcock, Brian, additional, Aanensen, David M, additional, Hodcroft, Emma, additional, Hsiao, William W L, additional, Vasconcelos, Ana Tereza R, additional, and MacCannell, Duncan R, additional

Published
2022
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7. CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Author

Nicholls, Samuel M., Poplawski, Radoslaw, Bull, Matthew J., Underwood, Anthony, Chapman, Michael, Abu-Dahab, Khalil, Taylor, Ben, Colquhoun, Rachel M., Rowe, Will P. M., Jackson, Ben, Hill, Verity, O’Toole, Áine, Rey, Sara, Southgate, Joel, Amato, Roberto, Livett, Rich, Gonçalves, Sónia, Harrison, Ewan M., Peacock, Sharon J., Aanensen, David M., Rambaut, Andrew, Connor, Thomas R., Loman, Nicholas J., The COVID-19 Genomics UK (COG-UK) Consortium, Bashton, Matthew, Smith, Darren, Nelson, Andrew, Young, Greg, McCann, Clare, Harrison, Ewan [0000-0003-2720-0507], Peacock, Sharon [0000-0002-1718-2782], and Apollo - University of Cambridge Repository

Subjects
QH301-705.5, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Genomics, Genome, Viral, Biology, QH426-470, Genome, User-Computer Interface, Pandemic, Genetics, Humans, Biology (General), Whole genome sequencing, Whole Genome Sequencing, SARS-CoV-2, C100, fungi, COVID-19, C500, Sequence Analysis, DNA, Cloud Computing, Data science, C900, United Kingdom, Metadata, B900, Editorial, Software deployment, Epidemiological Monitoring
Abstract

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network. Supplementary Information The online version contains supplementary material available at 10.1186/s13059-021-02395-y.

Published
2021
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8. Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK

Author

du Plessis, Louis, McCrone, John T., Zarebski, Alexander E., Hill, Verity, Ruis, Christopher, Gutierrez, Bernardo, Raghwani, Jayna, Ashworth, Jordan, Colquhoun, Rachel, Connor, Thomas R., Faria, Nuno R., Jackson, Ben, Loman, Nicholas J., O’Toole, Áine, Nicholls, Samuel M., Parag, Kris V., Scher, Emily, Vasylyeva, Tetyana I., Volz, Erik M., Watts, Alexander, Bogoch, Isaac I., Khan, Kamran, Aanensen, David M., Kraemer, Moritz U. G., Rambaut, Andrew, Pybus, Oliver G., COVID-19 Genomics UK (COG-UK) Consortium, Bashton, Matthew, Smith, Darren, Young, Greg, and Nelson, Andrew

Subjects
Lineage (genetic), Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Genome, Viral, Biology, Genome, Virus, law.invention, 03 medical and health sciences, 0302 clinical medicine, Communicable Diseases, Imported, Phylogenetics, law, Humans, 030212 general & internal medicine, Epidemics, Phylogeny, 030304 developmental biology, Chain of Infection, Travel, 0303 health sciences, Multidisciplinary, Phylogenetic tree, SARS-CoV-2, COVID-19, C700, United Kingdom, Transmission (mechanics), Evolutionary biology, Communicable Disease Control
Abstract

Lineage dynamics The scale of genome-sequencing efforts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented. The United Kingdom has contributed more than 26,000 sequences to this effort. This volume of data allowed du Plessis et al. to develop a detailed picture of the influxes of virus reaching U.K. shores as the pandemic developed during the first months of 2020 (see the Perspective by Nelson). Before lockdown, high travel volumes and few restrictions on international travel allowed more than 1000 lineages to become established. This accelerated local epidemic growth and exceeded contact tracing capacity. The authors were able to quantify the abundance, size distribution, and spatial range of the lineages that were transmitted. Transmission was highly heterogeneous, favoring some lineages that became widespread and subsequently harder to eliminate. This dire history indicates that rapid or even preemptive responses should have been used as they were elsewhere where containment was successful. Science , this issue p. 708 ; see also p. 680

Published
2021
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9. Additional file 1 of CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Author

Nicholls, Samuel M., Poplawski, Radoslaw, Bull, Matthew J., Underwood, Anthony, Chapman, Michael, Abu-Dahab, Khalil, Taylor, Ben, Colquhoun, Rachel M., Rowe, Will P. M., Jackson, Ben, Hill, Verity, O’Toole, Áine, Rey, Sara, Southgate, Joel, Amato, Roberto, Livett, Rich, Gonçalves, Sónia, Harrison, Ewan M., Peacock, Sharon J., Aanensen, David M., Rambaut, Andrew, Connor, Thomas R., and Loman, Nicholas J.

Abstract

Additional file 1. The COVID-19 Genomics UK (COG-UK) Consortium.

Published
2021
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10. Additional file 2 of CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Author

Nicholls, Samuel M., Poplawski, Radoslaw, Bull, Matthew J., Underwood, Anthony, Chapman, Michael, Abu-Dahab, Khalil, Taylor, Ben, Colquhoun, Rachel M., Rowe, Will P. M., Jackson, Ben, Hill, Verity, O’Toole, Áine, Rey, Sara, Southgate, Joel, Amato, Roberto, Livett, Rich, Gonçalves, Sónia, Harrison, Ewan M., Peacock, Sharon J., Aanensen, David M., Rambaut, Andrew, Connor, Thomas R., and Loman, Nicholas J.

Abstract

Additional file 2: Table 3. COG-UK full metadata standard.

Published
2021
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11. Evolution and epidemic spread of SARS-CoV-2 in Brazil

Author

Candido, Darlan S, Claro, Ingra M, de Jesus, Jaqueline G, Souza, William M, Moreira, Filipe RR, Dellicour, Simon, Mellan, Thomas A, du Plessis, Louis, Pereira, Rafael HM, Sales, Flavia CS, Manuli, Erika R, Thézé, Julien, Almeida, Luiz, Menezes, Mariane T, Voloch, Carolina M, Fumagalli, Marcilio J, Coletti, Thaís M, da Silva, Camila AM, Ramundo, Mariana S, Amorim, Mariene R, Hoeltgebaum, Henrique H, Mishra, Swapnil, Gill, Mandev S, Carvalho, Luiz M, Buss, Lewis F, Prete, Carlos A, Ashworth, Jordan, Nakaya, Helder I, Peixoto, Pedro S, Brady, Oliver J, Nicholls, Samuel M, Tanuri, Amilcar, Rossi, Átila D, Braga, Carlos KV, Gerber, Alexandra L, de C Guimarães, Ana Paula, Gaburo, Nelson, Alencar, Cecila Salete, Ferreira, Alessandro CS, Lima, Cristiano X, Levi, José Eduardo, Granato, Celso, Ferreira, Giulia M, Francisco, Ronaldo S, Granja, Fabiana, Garcia, Marcia T, Moretti, Maria Luiza, Perroud, Mauricio W, Castiñeiras, Terezinha MPP, Lazari, Carolina S, Hill, Sarah C, de Souza Santos, Andreza Aruska, Simeoni, Camila L, Forato, Julia, Sposito, Andrei C, Schreiber, Angelica Z, Santos, Magnun NN, de Sá, Camila Zolini, Souza, Renan P, Resende-Moreira, Luciana C, Teixeira, Mauro M, Hubner, Josy, Leme, Patricia AF, Moreira, Rennan G, Nogueira, Maurício L, Brazil-UK Centre for Arbovirus Discovery, Diagnosis, Genomics an, Ferguson, Neil M, Costa, Silvia F, Proenca-Modena, José Luiz, Vasconcelos, Ana Tereza R, Bhatt, Samir, Lemey, Philippe, Wu, Chieh-Hsi, Rambaut, Andrew, Loman, Nick J, Aguiar, Renato S, Pybus, Oliver G, Sabino, Ester C, and Faria, Nuno Rodrigues

Abstract

Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February and 11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average traveled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil and provides evidence that current interventions remain insufficient to keep virus transmission under control in this country.

Published
2020

13. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Author

Volz, Erik, primary, Hill, Verity, additional, McCrone, John T., additional, Price, Anna, additional, Jorgensen, David, additional, O’Toole, Áine, additional, Southgate, Joel, additional, Johnson, Robert, additional, Jackson, Ben, additional, Nascimento, Fabricia F., additional, Rey, Sara M., additional, Nicholls, Samuel M., additional, Colquhoun, Rachel M., additional, da Silva Filipe, Ana, additional, Shepherd, James, additional, Pascall, David J., additional, Shah, Rajiv, additional, Jesudason, Natasha, additional, Li, Kathy, additional, Jarrett, Ruth, additional, Pacchiarini, Nicole, additional, Bull, Matthew, additional, Geidelberg, Lily, additional, Siveroni, Igor, additional, Goodfellow, Ian, additional, Loman, Nicholas J., additional, Pybus, Oliver G., additional, Robertson, David L., additional, Thomson, Emma C., additional, Rambaut, Andrew, additional, Connor, Thomas R., additional, Koshy, Cherian, additional, Wise, Emma, additional, Cortes, Nick, additional, Lynch, Jessica, additional, Kidd, Stephen, additional, Mori, Matilde, additional, Fairley, Derek J., additional, Curran, Tanya, additional, McKenna, James P., additional, Adams, Helen, additional, Fraser, Christophe, additional, Golubchik, Tanya, additional, Bonsall, David, additional, Moore, Catrin, additional, Caddy, Sarah L., additional, Khokhar, Fahad A., additional, Wantoch, Michelle, additional, Reynolds, Nicola, additional, Warne, Ben, additional, Maksimovic, Joshua, additional, Spellman, Karla, additional, McCluggage, Kathryn, additional, John, Michaela, additional, Beer, Robert, additional, Afifi, Safiah, additional, Morgan, Sian, additional, Marchbank, Angela, additional, Kitchen, Christine, additional, Gulliver, Huw, additional, Merrick, Ian, additional, Guest, Martyn, additional, Munn, Robert, additional, Workman, Trudy, additional, Fuller, William, additional, Bresner, Catherine, additional, Snell, Luke B., additional, Charalampous, Themoula, additional, Nebbia, Gaia, additional, Batra, Rahul, additional, Edgeworth, Jonathan, additional, Robson, Samuel C., additional, Beckett, Angela, additional, Loveson, Katie F., additional, Aanensen, David M., additional, Underwood, Anthony P., additional, Yeats, Corin A., additional, Abudahab, Khalil, additional, Taylor, Ben E.W., additional, Menegazzo, Mirko, additional, Clark, Gemma, additional, Smith, Wendy, additional, Khakh, Manjinder, additional, Fleming, Vicki M., additional, Lister, Michelle M., additional, Howson-Wells, Hannah C., additional, Berry, Louise, additional, Boswell, Tim, additional, Joseph, Amelia, additional, Willingham, Iona, additional, Bird, Paul, additional, Helmer, Thomas, additional, Fallon, Karlie, additional, Holmes, Christopher, additional, Tang, Julian, additional, Raviprakash, Veena, additional, Campbell, Sharon, additional, Sheriff, Nicola, additional, Loose, Matthew W., additional, Holmes, Nadine, additional, Moore, Christopher, additional, Carlile, Matthew, additional, Wright, Victoria, additional, Sang, Fei, additional, Debebe, Johnny, additional, Coll, Francesc, additional, Signell, Adrian W., additional, Betancor, Gilberto, additional, Wilson, Harry D., additional, Feltwell, Theresa, additional, Houldcroft, Charlotte J., additional, Eldirdiri, Sahar, additional, Kenyon, Anita, additional, Davis, Thomas, additional, Pybus, Oliver, additional, du Plessis, Louis, additional, Zarebski, Alex, additional, Raghwani, Jayna, additional, Kraemer, Moritz, additional, Francois, Sarah, additional, Attwood, Stephen, additional, Vasylyeva, Tetyana, additional, Torok, M. Estee, additional, Hamilton, William L., additional, Goodfellow, Ian G., additional, Hall, Grant, additional, Jahun, Aminu S., additional, Chaudhry, Yasmin, additional, Hosmillo, Myra, additional, Pinckert, Malte L., additional, Georgana, Iliana, additional, Yakovleva, Anna, additional, Meredith, Luke W., additional, Moses, Samuel, additional, Lowe, Hannah, additional, Ryan, Felicity, additional, Fisher, Chloe L., additional, Awan, Ali R., additional, Boyes, John, additional, Breuer, Judith, additional, Harris, Kathryn Ann, additional, Brown, Julianne Rose, additional, Shah, Divya, additional, Atkinson, Laura, additional, Lee, Jack C.D., additional, Alcolea-Medina, Adela, additional, Moore, Nathan, additional, Cortes, Nicholas, additional, Williams, Rebecca, additional, Chapman, Michael R., additional, Levett, Lisa J., additional, Heaney, Judith, additional, Smith, Darren L., additional, Bashton, Matthew, additional, Young, Gregory R., additional, Allan, John, additional, Loh, Joshua, additional, Randell, Paul A., additional, Cox, Alison, additional, Madona, Pinglawathee, additional, Holmes, Alison, additional, Bolt, Frances, additional, Price, James, additional, Mookerjee, Siddharth, additional, Rowan, Aileen, additional, Taylor, Graham P., additional, Ragonnet-Cronin, Manon, additional, Johnson, Rob, additional, Boyd, Olivia, additional, Volz, Erik M., additional, Brunker, Kirstyn, additional, Smollett, Katherine L., additional, Quick, Joshua, additional, McMurray, Claire, additional, Stockton, Joanne, additional, Nicholls, Sam, additional, Rowe, Will, additional, Poplawski, Radoslaw, additional, Martinez-Nunez, Rocio T., additional, Mason, Jenifer, additional, Robinson, Trevor I., additional, O'Toole, Elaine, additional, Watts, Joanne, additional, Breen, Cassie, additional, Cowell, Angela, additional, Ludden, Catherine, additional, Sluga, Graciela, additional, Machin, Nicholas W., additional, Ahmad, Shazaad S.Y., additional, George, Ryan P., additional, Halstead, Fenella, additional, Sivaprakasam, Venkat, additional, Shepherd, James G., additional, Asamaphan, Patawee, additional, Niebel, Marc O., additional, Li, Kathy K., additional, Shah, Rajiv N., additional, Jesudason, Natasha G., additional, Parr, Yasmin A., additional, Tong, Lily, additional, Broos, Alice, additional, Mair, Daniel, additional, Nichols, Jenna, additional, Carmichael, Stephen N., additional, Nomikou, Kyriaki, additional, Aranday-Cortes, Elihu, additional, Johnson, Natasha, additional, Starinskij, Igor, additional, Orton, Richard J., additional, Hughes, Joseph, additional, Vattipally, Sreenu, additional, Singer, Joshua B., additional, Hale, Antony D., additional, Macfarlane-Smith, Louissa R., additional, Harper, Katherine L., additional, Taha, Yusri, additional, Payne, Brendan A.I., additional, Burton-Fanning, Shirelle, additional, Waugh, Sheila, additional, Collins, Jennifer, additional, Eltringham, Gary, additional, Templeton, Kate E., additional, McHugh, Martin P., additional, Dewar, Rebecca, additional, Wastenge, Elizabeth, additional, Dervisevic, Samir, additional, Stanley, Rachael, additional, Prakash, Reenesh, additional, Stuart, Claire, additional, Elumogo, Ngozi, additional, Sethi, Dheeraj K., additional, Meader, Emma J., additional, Coupland, Lindsay J., additional, Potter, Will, additional, Graham, Clive, additional, Barton, Edward, additional, Padgett, Debra, additional, Scott, Garren, additional, Swindells, Emma, additional, Greenaway, Jane, additional, Nelson, Andrew, additional, Yew, Wen C., additional, Resende Silva, Paola C., additional, Andersson, Monique, additional, Shaw, Robert, additional, Peto, Timothy, additional, Justice, Anita, additional, Eyre, David, additional, Crooke, Derrick, additional, Hoosdally, Sarah, additional, Sloan, Tim J., additional, Duckworth, Nichola, additional, Walsh, Sarah, additional, Chauhan, Anoop J., additional, Glaysher, Sharon, additional, Bicknell, Kelly, additional, Wyllie, Sarah, additional, Butcher, Ethan, additional, Elliott, Scott, additional, Lloyd, Allyson, additional, Impey, Robert, additional, Levene, Nick, additional, Monaghan, Lynn, additional, Bradley, Declan T., additional, Allara, Elias, additional, Pearson, Clare, additional, Muir, Peter, additional, Vipond, Ian B., additional, Hopes, Richard, additional, Pymont, Hannah M., additional, Hutchings, Stephanie, additional, Curran, Martin D., additional, Parmar, Surendra, additional, Lackenby, Angie, additional, Mbisa, Tamyo, additional, Platt, Steven, additional, Miah, Shahjahan, additional, Bibby, David, additional, Manso, Carmen, additional, Hubb, Jonathan, additional, Chand, Meera, additional, Dabrera, Gavin, additional, Ramsay, Mary, additional, Bradshaw, Daniel, additional, Thornton, Alicia, additional, Myers, Richard, additional, Schaefer, Ulf, additional, Groves, Natalie, additional, Gallagher, Eileen, additional, Lee, David, additional, Williams, David, additional, Ellaby, Nicholas, additional, Harrison, Ian, additional, Hartman, Hassan, additional, Manesis, Nikos, additional, Patel, Vineet, additional, Bishop, Chloe, additional, Chalker, Vicki, additional, Osman, Husam, additional, Bosworth, Andrew, additional, Robinson, Esther, additional, Holden, Matthew T.G., additional, Shaaban, Sharif, additional, Birchley, Alec, additional, Adams, Alexander, additional, Davies, Alisha, additional, Gaskin, Amy, additional, Plimmer, Amy, additional, Gatica-Wilcox, Bree, additional, McKerr, Caoimhe, additional, Moore, Catherine, additional, Williams, Chris, additional, Heyburn, David, additional, De Lacy, Elen, additional, Hilvers, Ember, additional, Downing, Fatima, additional, Shankar, Giri, additional, Jones, Hannah, additional, Asad, Hibo, additional, Coombes, Jason, additional, Watkins, Joanne, additional, Evans, Johnathan M., additional, Fina, Laia, additional, Gifford, Laura, additional, Gilbert, Lauren, additional, Graham, Lee, additional, Perry, Malorie, additional, Morgan, Mari, additional, Cronin, Michelle, additional, Craine, Noel, additional, Jones, Rachel, additional, Howe, Robin, additional, Corden, Sally, additional, Rey, Sara, additional, Kumziene-Summerhayes, Sara, additional, Taylor, Sarah, additional, Cottrell, Simon, additional, Jones, Sophie, additional, Edwards, Sue, additional, O’Grady, Justin, additional, Page, Andrew J., additional, Wain, John, additional, Webber, Mark A., additional, Mather, Alison E., additional, Baker, David J., additional, Rudder, Steven, additional, Yasir, Muhammad, additional, Thomson, Nicholas M., additional, Aydin, Alp, additional, Tedim, Ana P., additional, Kay, Gemma L., additional, Trotter, Alexander J., additional, Gilroy, Rachel A.J., additional, Alikhan, Nabil-Fareed, additional, de Oliveira Martins, Leonardo, additional, Le-Viet, Thanh, additional, Meadows, Lizzie, additional, Kolyva, Anastasia, additional, Diaz, Maria, additional, Bell, Andrew, additional, Gutierrez, Ana Victoria, additional, Charles, Ian G., additional, Adriaenssens, Evelien M., additional, Kingsley, Robert A., additional, Casey, Anna, additional, Simpson, David A., additional, Molnar, Zoltan, additional, Thompson, Thomas, additional, Acheson, Erwan, additional, Masoli, Jane A.H., additional, Knight, Bridget A., additional, Hattersley, Andrew, additional, Ellard, Sian, additional, Auckland, Cressida, additional, Mahungu, Tabitha W., additional, Irish-Tavares, Dianne, additional, Haque, Tanzina, additional, Bourgeois, Yann, additional, Scarlett, Garry P., additional, Partridge, David G., additional, Raza, Mohammad, additional, Evans, Cariad, additional, Johnson, Kate, additional, Liggett, Steven, additional, Baker, Paul, additional, Essex, Sarah, additional, Lyons, Ronan A., additional, Caller, Laura G., additional, Castellano, Sergi, additional, Williams, Rachel J., additional, Kristiansen, Mark, additional, Roy, Sunando, additional, Williams, Charlotte A., additional, Dyal, Patricia L., additional, Tutill, Helena J., additional, Panchbhaya, Yasmin N., additional, Forrest, Leysa M., additional, Niola, Paola, additional, Findlay, Jacqueline, additional, Brooks, Tony T., additional, Gavriil, Artemis, additional, Mestek-Boukhibar, Lamia, additional, Weeks, Sam, additional, Pandey, Sarojini, additional, Berry, Lisa, additional, Jones, Katie, additional, Richter, Alex, additional, Beggs, Andrew, additional, Smith, Colin P., additional, Bucca, Giselda, additional, Hesketh, Andrew R., additional, Harrison, Ewan M., additional, Peacock, Sharon J., additional, Palmer, Sophie, additional, Churcher, Carol M., additional, Bellis, Katherine L., additional, Girgis, Sophia T., additional, Naydenova, Plamena, additional, Blane, Beth, additional, Sridhar, Sushmita, additional, Ruis, Chris, additional, Forrest, Sally, additional, Cormie, Claire, additional, Gill, Harmeet K., additional, Dias, Joana, additional, Higginson, Ellen E., additional, Maes, Mailis, additional, Young, Jamie, additional, Kermack, Leanne M., additional, Hadjirin, Nazreen F., additional, Aggarwal, Dinesh, additional, Griffith, Luke, additional, Swingler, Tracey, additional, Davidson, Rose K., additional, Williams, Thomas, additional, Balcazar, Carlos E., additional, Gallagher, Michael D., additional, O'Toole, Áine, additional, Rooke, Stefan, additional, Colquhoun, Rachel, additional, Ashworth, Jordan, additional, McCrone, J.T., additional, Scher, Emily, additional, Yu, Xiaoyu, additional, Williamson, Kathleen A., additional, Stanton, Thomas D., additional, Michell, Stephen L., additional, Bewshea, Claire M., additional, Temperton, Ben, additional, Michelsen, Michelle L., additional, Warwick-Dugdale, Joanna, additional, Manley, Robin, additional, Farbos, Audrey, additional, Harrison, James W., additional, Sambles, Christine M., additional, Studholme, David J., additional, Jeffries, Aaron R., additional, Darby, Alistair C., additional, Hiscox, Julian A., additional, Paterson, Steve, additional, Iturriza-Gomara, Miren, additional, Jackson, Kathryn A., additional, Lucaci, Anita O., additional, Vamos, Edith E., additional, Hughes, Margaret, additional, Rainbow, Lucille, additional, Eccles, Richard, additional, Nelson, Charlotte, additional, Whitehead, Mark, additional, Turtle, Lance, additional, Haldenby, Sam T., additional, Gregory, Richard, additional, Gemmell, Matthew, additional, Kwiatkowski, Dominic, additional, de Silva, Thushan I., additional, Smith, Nikki, additional, Angyal, Adrienn, additional, Lindsey, Benjamin B., additional, Groves, Danielle C., additional, Green, Luke R., additional, Wang, Dennis, additional, Freeman, Timothy M., additional, Parker, Matthew D., additional, Keeley, Alexander J., additional, Parsons, Paul J., additional, Tucker, Rachel M., additional, Brown, Rebecca, additional, Wyles, Matthew, additional, Constantinidou, Chrystala, additional, Unnikrishnan, Meera, additional, Ott, Sascha, additional, Cheng, Jeffrey K.J., additional, Bridgewater, Hannah E., additional, Frost, Lucy R., additional, Taylor-Joyce, Grace, additional, Stark, Richard, additional, Baxter, Laura, additional, Alam, Mohammad T., additional, Brown, Paul E., additional, McClure, Patrick C., additional, Chappell, Joseph G., additional, Tsoleridis, Theocharis, additional, Ball, Jonathan, additional, Grammatopoulos, Dimitris, additional, Buck, David, additional, Todd, John A., additional, Green, Angie, additional, Trebes, Amy, additional, MacIntyre-Cockett, George, additional, de Cesare, Mariateresa, additional, Langford, Cordelia, additional, Alderton, Alex, additional, Amato, Roberto, additional, Goncalves, Sonia, additional, Jackson, David K., additional, Johnston, Ian, additional, Sillitoe, John, additional, Palmer, Steve, additional, Lawniczak, Mara, additional, Berriman, Matt, additional, Danesh, John, additional, Livett, Rich, additional, Shirley, Lesley, additional, Farr, Ben, additional, Quail, Mike, additional, Thurston, Scott, additional, Park, Naomi, additional, Betteridge, Emma, additional, Weldon, Danni, additional, Goodwin, Scott, additional, Nelson, Rachel, additional, Beaver, Charlotte, additional, Letchford, Laura, additional, Jackson, David A., additional, Foulser, Luke, additional, McMinn, Liz, additional, Prestwood, Liam, additional, Kay, Sally, additional, Kane, Leanne, additional, Dorman, Matthew J., additional, Martincorena, Inigo, additional, Puethe, Christoph, additional, Keatley, Jon-Paul, additional, Tonkin-Hill, Gerry, additional, Smith, Christen, additional, Jamrozy, Dorota, additional, Beale, Mathew A., additional, Patel, Minal, additional, Ariani, Cristina, additional, Spencer-Chapman, Michael, additional, Drury, Eleanor, additional, Lo, Stephanie, additional, Rajatileka, Shavanthi, additional, Scott, Carol, additional, James, Keith, additional, Buddenborg, Sarah K., additional, Berger, Duncan J., additional, Patel, Gaurang, additional, Garcia-Casado, Maria V., additional, Dibling, Thomas, additional, McGuigan, Samantha, additional, Rogers, Hazel A., additional, Hunter, Adam D., additional, Souster, Emily, additional, and Neaverson, Alexandra S., additional

Published
2021
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15. The PHA4GE SARS-CoV-2 Contextual Data Specification for Open Genomic Epidemiology

Author

Griffiths, Emma J., primary, Timme, Ruth E., additional, Page, Andrew J., additional, Alikhan, Nabil-Fareed, additional, Fornika, Dan, additional, Maguire, Finlay, additional, Mendes, Catarina Inês, additional, Tausch, Simon H., additional, Black, Allison, additional, Connor, Thomas R., additional, Tyson, Gregory H., additional, Aanensen, David M., additional, Alcock, Brian, additional, Campos, Josefina, additional, Christoffels, Alan, additional, Gonçalves da Silva, Anders, additional, Hodcroft, Emma, additional, Hsiao, William W.L., additional, Katz, Lee S., additional, Nicholls, Samuel M., additional, Oluniyi, Paul E., additional, Olawoye, Idowu B., additional, Raphenya, Amogelang R., additional, Vasconcelos, Ana Tereza R., additional, Witney, Adam A., additional, and MacCannell, Duncan R., additional

Published
2020
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16. Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity

Author

Volz, Erik, primary, Hill, Verity, additional, McCrone, John T., additional, Price, Anna, additional, Jorgensen, David, additional, O’Toole, Áine, additional, Southgate, Joel, additional, Johnson, Robert, additional, Jackson, Ben, additional, Nascimento, Fabricia F., additional, Rey, Sara M., additional, Nicholls, Samuel M., additional, Colquhoun, Rachel M., additional, da Silva Filipe, Ana, additional, Shepherd, James, additional, Pascall, David J., additional, Shah, Rajiv, additional, Jesudason, Natasha, additional, Li, Kathy, additional, Jarrett, Ruth, additional, Pacchiarini, Nicole, additional, Bull, Matthew, additional, Geidelberg, Lily, additional, Siveroni, Igor, additional, Goodfellow, Ian, additional, Loman, Nicholas J., additional, Pybus, Oliver G., additional, Robertson, David L., additional, Thomson, Emma C., additional, Rambaut, Andrew, additional, and Connor, Thomas R., additional

Published
2020
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18. Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK.

Author

Plessis, Louis du, McCrone, John T., Zarebski, Alexander E., Hill, Verity, Ruis, Christopher, Gutierrez, Bernardo, Raghwani, Jayna, Ashworth, Jordan, Colquhoun, Rachel, Connor, Thomas R., Faria, Nuno R., Jackson, Ben, Loman, Nicholas J., O’Toole, Áine, Nicholls, Samuel M., Parag, Kris V., Scher, Emily, Vasylyeva, Tetyana I., Volz, Erik M., and Watts, Alexander

Published
2021
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20. Recovery of gene haplotypes from a metagenome

Author

Nicholls, Samuel M., primary, Aubrey, Wayne, additional, Edwards, Arwyn, additional, Grave, Kurt de, additional, Huws, Sharon, additional, Schietgat, Leander, additional, Soares, André, additional, Creevey, Christopher J., additional, and Clare, Amanda, additional

Published
2017
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25. Genomics-informed outbreak investigations of SARS-CoV-2 using civet.

Author

O'Toole Á, Hill V, Jackson B, Dewar R, Sahadeo N, Colquhoun R, Rooke S, McCrone JT, Duggan K, McHugh MP, Nicholls SM, Poplawski R, Aanensen D, Holden M, Connor T, Loman N, Goodfellow I, Carrington CVF, Templeton K, and Rambaut A

Abstract

The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 13 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background diversity, resolving the query into different 'catchments' and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus diversity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 O’Toole et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2022
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26. CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.

Author

Nicholls SM, Poplawski R, Bull MJ, Underwood A, Chapman M, Abu-Dahab K, Taylor B, Colquhoun RM, Rowe WPM, Jackson B, Hill V, O'Toole Á, Rey S, Southgate J, Amato R, Livett R, Gonçalves S, Harrison EM, Peacock SJ, Aanensen DM, Rambaut A, Connor TR, and Loman NJ

Subjects
COVID-19 epidemiology, Epidemiological Monitoring, Genome, Viral, Humans, Sequence Analysis, DNA, United Kingdom, User-Computer Interface, Whole Genome Sequencing, Cloud Computing, Genomics organization & administration, SARS-CoV-2 genetics
Abstract

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.

Published
2021
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27. SARS-CoV-2 within-host diversity and transmission.

Author

Lythgoe KA, Hall M, Ferretti L, de Cesare M, MacIntyre-Cockett G, Trebes A, Andersson M, Otecko N, Wise EL, Moore N, Lynch J, Kidd S, Cortes N, Mori M, Williams R, Vernet G, Justice A, Green A, Nicholls SM, Ansari MA, Abeler-Dörner L, Moore CE, Peto TEA, Eyre DW, Shaw R, Simmonds P, Buck D, Todd JA, Connor TR, Ashraf S, da Silva Filipe A, Shepherd J, Thomson EC, Bonsall D, Fraser C, and Golubchik T

Subjects
COVID-19 immunology, Coinfection virology, Coronavirus Infections virology, Coronavirus OC43, Human, Family Characteristics, Genome, Viral, Humans, Immune Evasion, Mutation, Phylogeny, RNA, Viral genetics, RNA-Seq, SARS-CoV-2 pathogenicity, SARS-CoV-2 physiology, Selection, Genetic, Spike Glycoprotein, Coronavirus genetics, United Kingdom, Viral Load, COVID-19 transmission, COVID-19 virology, Genetic Variation, SARS-CoV-2 genetics
Abstract

Extensive global sampling and sequencing of the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have enabled researchers to monitor its spread and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals and how likely they are to be transmitted. To characterize within-host diversity and transmission, we deep-sequenced 1313 clinical samples from the United Kingdom. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high and by a narrow bottleneck at transmission. Most variants are either lost or occasionally fixed at the point of transmission, with minimal persistence of shared diversity, patterns that are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape SARS-CoV-2 variants are likely to arise infrequently but could spread rapidly if successfully transmitted., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Published
2021
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28. Evolution and epidemic spread of SARS-CoV-2 in Brazil.

Author

Candido DS, Claro IM, de Jesus JG, Souza WM, Moreira FRR, Dellicour S, Mellan TA, du Plessis L, Pereira RHM, Sales FCS, Manuli ER, Thézé J, Almeida L, Menezes MT, Voloch CM, Fumagalli MJ, Coletti TM, da Silva CAM, Ramundo MS, Amorim MR, Hoeltgebaum HH, Mishra S, Gill MS, Carvalho LM, Buss LF, Prete CA Jr, Ashworth J, Nakaya HI, Peixoto PS, Brady OJ, Nicholls SM, Tanuri A, Rossi ÁD, Braga CKV, Gerber AL, de C Guimarães AP, Gaburo N Jr, Alencar CS, Ferreira ACS, Lima CX, Levi JE, Granato C, Ferreira GM, Francisco RS Jr, Granja F, Garcia MT, Moretti ML, Perroud MW Jr, Castiñeiras TMPP, Lazari CS, Hill SC, de Souza Santos AA, Simeoni CL, Forato J, Sposito AC, Schreiber AZ, Santos MNN, de Sá CZ, Souza RP, Resende-Moreira LC, Teixeira MM, Hubner J, Leme PAF, Moreira RG, Nogueira ML, Ferguson NM, Costa SF, Proenca-Modena JL, Vasconcelos ATR, Bhatt S, Lemey P, Wu CH, Rambaut A, Loman NJ, Aguiar RS, Pybus OG, Sabino EC, and Faria NR

Subjects
Basic Reproduction Number, Bayes Theorem, Betacoronavirus classification, Brazil epidemiology, COVID-19, COVID-19 Testing, Cities epidemiology, Clinical Laboratory Techniques, Coronavirus Infections diagnosis, Coronavirus Infections prevention & control, Coronavirus Infections virology, Europe, Evolution, Molecular, Genome, Viral, Humans, Models, Genetic, Models, Statistical, Pandemics prevention & control, Phylogeny, Phylogeography, Pneumonia, Viral prevention & control, Pneumonia, Viral virology, SARS-CoV-2, Spatio-Temporal Analysis, Travel, Urban Population, Betacoronavirus genetics, Coronavirus Infections epidemiology, Coronavirus Infections transmission, Pneumonia, Viral epidemiology, Pneumonia, Viral transmission
Abstract

Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February and 11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average traveled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil and provides evidence that current interventions remain insufficient to keep virus transmission under control in this country., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Published
2020
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