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1. Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission

Author

Bengu, Nomonde, Cromhout, Gabriela, Adland, Emily, Govender, Katya, Herbert, Nicholas, Lim, Nicholas, Fillis, Rowena, Sprenger, Kenneth, Vieira, Vinicius, Kannie, Samantha, van Lobenstein, Jeroen, Chinniah, Kogielambal, Kapongo, Constant, Bhoola, Roopesh, Krishna, Malini, Mchunu, Noxolo, Pascucci, Giuseppe Rubens, Cotugno, Nicola, Palma, Paolo, Tagarro, Alfredo, Rojo, Pablo, Roider, Julia, Garcia-Guerrero, Maria C., Ochsenbauer, Christina, Groll, Andreas, Reddy, Kavidha, Giaquinto, Carlo, Rossi, Paolo, Hong, Seohyun, Dong, Krista, Ansari, M. Azim, Puertas, Maria C., Ndung’u, Thumbi, Capparelli, Edmund, Lichterfeld, Mathias, Martinez-Picado, Javier, Kappes, John C., Archary, Moherndran, and Goulder, Philip

Published
2024
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2. Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus

Author

Lin, Gu-Lung, Drysdale, Simon B., Snape, Matthew D., O’Connor, Daniel, Brown, Anthony, MacIntyre-Cockett, George, Mellado-Gomez, Esther, de Cesare, Mariateresa, Ansari, M. Azim, Bonsall, David, Bray, James E., Jolley, Keith A., Bowden, Rory, Aerssens, Jeroen, Bont, Louis, Openshaw, Peter J. M., Martinon-Torres, Federico, Nair, Harish, Golubchik, Tanya, and Pollard, Andrew J.

Published
2024
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3. HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol

Author

Arif, Ambreen, Hasnain, Aliya, Chaudhry, Auj, Asim, Muhammad, Shafqat, Muhammad Nabeel, Altaf, Abeer, Saba, Noor, Kemos, Polychronis, Ansari, M. Azim, Barnes, Eleanor, Metcalfe, Chris, Vickerman, Peter, Qureshi, Huma, Hamid, Saeed, Choudhry, Asad Ali, Niaz, Saad Khalid, Foster, Graham R., and Choudhry, Naheed

Published
2023
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4. Global prevalence and phylogeny of hepatitis B virus (HBV) drug and vaccine resistance mutations

Author

Mokaya, Jolynne, Vasylyeva, Tetyana I, Barnes, Eleanor, Ansari, M Azim, Pybus, Oliver G, and Matthews, Philippa C

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis, Chronic Liver Disease and Cirrhosis, Hepatitis - B, Liver Disease, Digestive Diseases, Infectious Diseases, Vaccine Related, Prevention, Genetics, HIV/AIDS, Immunization, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Antiviral Agents, DNA, Viral, Drug Resistance, Viral, Genotype, Hepatitis B Vaccines, Hepatitis B virus, Hepatitis B, Chronic, Humans, Mutation, Pharmaceutical Preparations, Phylogeny, Prevalence, Africa, entecavir, epidemiology, HBV, HBV vaccine, lamivudine, NAs, NUCs, prevention, RAMs, resistance, TDF, tenofovir, therapy, Microbiology, Gastroenterology & Hepatology, Clinical sciences, Medical microbiology
Abstract

Vaccination and anti-viral therapy with nucleos(t)ide analogues (NAs) are key approaches to reducing the morbidity, mortality and transmission of hepatitis B virus (HBV) infection. However, the efficacy of these interventions may be reduced by the emergence of drug resistance-associated mutations (RAMs) and/or vaccine escape mutations (VEMs). We have assimilated data on the global prevalence and distribution of HBV RAMs/VEMs from publicly available data and explored the evolution of these mutations. We analysed sequences downloaded from the HBV Database and calculated prevalence of 41 RAMs and 38 VEMs catalogued from published studies. We generated maximum likelihood phylogenetic trees and used treeBreaker to investigate the distribution and estimated the age of selected mutations across tree branches. RAM M204I/V had the highest prevalence, occurring in 3.8% (109/2838) of all HBV sequences in our data set, and a significantly higher rate in genotype C at 5.4% (60/1102, p = 0.0007). VEMs had an overall prevalence of 1.3% (37/2837) and had the highest prevalence in genotype C and in Asia at 2.2% (24/1102; p = 0.002) and 1.6% (34/2109; p = 0.009), respectively. Phylogenetic analysis suggested that RAM/VEMs can arise independently of treatment/vaccine exposure. In conclusion, HBV RAMs/VEMs have been found globally and across genotypes, with the highest prevalence observed in genotype C. Screening for genotype and for resistance-associated mutations may help to improve stratified patient treatment. As NAs and HBV vaccines are increasingly being deployed for HBV prevention and treatment, monitoring for resistance and advocating for better treatment regimens for HBV remains essential.

Published
2021

5. Genotyping and population characteristics of the China Kadoorie Biobank

Author

Walters, Robin G., Millwood, Iona Y., Lin, Kuang, Schmidt Valle, Dan, McDonnell, Pandora, Hacker, Alex, Avery, Daniel, Edris, Ahmed, Fry, Hannah, Cai, Na, Kretzschmar, Warren W., Ansari, M. Azim, Lyons, Paul A., Collins, Rory, Donnelly, Peter, Hill, Michael, Peto, Richard, Shen, Hongbing, Jin, Xin, Nie, Chao, Xu, Xun, Guo, Yu, Yu, Canqing, Lv, Jun, Clarke, Robert J., Li, Liming, and Chen, Zhengming

Published
2023
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6. Sustained aviraemia despite anti-retroviral therapy non-adherence in male children following in utero hiv transmission

Author

Bengu, Nomonde, primary, Cromhout, Gabriela, additional, Adland, Emily, additional, Govender, Katya, additional, Herbert, Nicholas, additional, Lim, Nicholas, additional, Fillis, Rowena, additional, Sprenger, Kenneth, additional, Vieira, Vinicius, additional, Kannie, Samantha, additional, van Lobenstein, Jeroen, additional, Chinniah, Kogielambal, additional, Kapongo, Constant, additional, Bhoola, Roopesh, additional, Krishna, Malini, additional, Mchunu, Noxolo, additional, Pascucci, Giuseppe Rubens, additional, Cotugno, Nicola, additional, Palma, Paolo, additional, Tagarro, Alfredo, additional, Rojo, Pablo, additional, Roider, Julia, additional, Garcia-Guerrero, Maria C., additional, Ochsenbauer, Christina, additional, Groll, Andreas, additional, Reddy, Kavidha, additional, Giaquinto, Carlo, additional, Rossi, Paolo, additional, Hong, Seohyun, additional, Dong, Krista, additional, Ansari, M. Azim, additional, Puertas, Maria C., additional, Ndung’u, Thumbi, additional, Capparelli, Edmund, additional, Lichterfeld, Mathias, additional, Martinez-Picado, Javier, additional, Kappes, John C., additional, Archary, Moherndran, additional, and Goulder, Philip, additional

Published
2024
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7. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Author

Ahern, David J, Ai, Zhichao, Ainsworth, Mark, Allan, Chris, Allcock, Alice, Angus, Brian, Ansari, M Azim, Arancibia-Cárcamo, Carolina, Aschenbrenner, Dominik, Attar, Moustafa, Baillie, J Kenneth, Barnes, Eleanor, Bashford-Rogers, Rachael, Bashyal, Archana, Beer, Sally, Berridge, Georgina, Beveridge, Amy, Bibi, Sagida, Bicanic, Tihana, Blackwell, Luke, Bowness, Paul, Brent, Andrew, Brown, Andrew, Broxholme, John, Buck, David, Burnham, Katie, Byrne, Helen, Camara, Susana, Ferreira, Ivan Candido, Charles, Philip, Chen, Wentao, Chen, Yi-Ling, Chong, Amanda, Clutterbuck, Elizabeth, Coles, Mark, Conlon, Christopher, Cornall, Richard, Cribbs, Adam, Curion, Fabiola, Davenport, Emma, Davidson, Neil, Davis, Simon, Dendrou, Calliope, Dequaire, Julie, Dib, Lea, Docker, James, Dold, Christina, Dong, Tao, Downes, Damien, Drakesmith, Hal, Dunachie, Susanna, Duncan, David, Eijsbouts, Chris, Esnouf, Robert, Espinosa, Alexis, Etherington, Rachel, Fairfax, Benjamin, Fairhead, Rory, Fang, Hai, Fassih, Shayan, Felle, Sally, Fernandez Mendoza, Maria, Ferreira, Ricardo, Fischer, Roman, Foord, Thomas, Forrow, Aden, Frater, John, Fries, Anastasia, Gallardo Sanchez, Veronica, Garner, Lucy, Geeves, Clementine, Georgiou, Dominique, Godfrey, Leila, Golubchik, Tanya, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Harrington, Heather, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Ho, Ling-Pei, Hoekzema, Renee, Hollis, Benjamin, Hughes, Jim, Hutton, Paula, Jackson-Wood, Matthew, Jainarayanan, Ashwin, James-Bott, Anna, Jansen, Kathrin, Jeffery, Katie, Jones, Elizabeth, Jostins, Luke, Kerr, Georgina, Kim, David, Klenerman, Paul, Knight, Julian, Kumar, Vinod, Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Linder, Aline, Lockett, Teresa, Lonie, Lorne, Lopopolo, Maria, Lukoseviciute, Martyna, Luo, Jian, Marinou, Spyridoula, Marsden, Brian, Martinez, Jose, Matthews, Philippa, Mazurczyk, Michalina, McGowan, Simon, McKechnie, Stuart, Mead, Adam, Mentzer, Alexander, Mi, Yuxin, Monaco, Claudia, Montadon, Ruddy, Napolitani, Giorgio, Nassiri, Isar, Novak, Alex, O'Brien, Darragh, O'Connor, Daniel, O'Donnell, Denise, Ogg, Graham, Overend, Lauren, Park, Inhye, Pavord, Ian, Peng, Yanchun, Penkava, Frank, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew, Powrie, Fiona, Psaila, Bethan, Quan, T Phuong, Repapi, Emmanouela, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Ritter, Thomas, Rollier, Christine, Rowland, Matthew, Ruehle, Fabian, Salio, Mariolina, Sansom, Stephen Nicholas, Sanches Peres, Raphael, Santos Delgado, Alberto, Sauka-Spengler, Tatjana, Schwessinger, Ron, Scozzafava, Giuseppe, Screaton, Gavin, Seigal, Anna, Semple, Malcolm, Sergeant, Martin, Simoglou Karali, Christina, Sims, David, Skelly, Donal, Slawinski, Hubert, Sobrinodiaz, Alberto, Sousos, Nikolaos, Stafford, Lizzie, Stockdale, Lisa, Strickland, Marie, Sumray, Otto, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Thongjuea, Supat, Thraves, Hannah, Todd, John, Tomic, Adriana, Tong, Orion, Trebes, Amy, Trzupek, Dominik, Tucci, Felicia Anna, Turtle, Lance, Udalova, Irina, Uhlig, Holm, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Voda, Alexandru, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Weinberger, Michael, Whalley, Justin, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Yuen Yeung, Hing, Yin, Zixi, Young, Rebecca, Youngs, Jonathan, Zhang, Ping, Zurke, Yasemin-Xiomara, Banning, Adrian, Antonopoulos, Alexios, Bajaj, Amrita, Kelion, Andrew, Deshpande, Aparna, Kardos, Attila, Hudson, Benjamin, Koo, Bon-Kwon, Shirodaria, Cheerag, Xie, Cheng, Kotanidis, Christos, Mahon, Ciara, Berry, Colin, Adlam, David, Newby, David, Connolly, Derek, Scaletta, Diane, Alexander, Donna, Nicol, Ed, McAlindon, Elisa, Oikonomou, Evangelos, Pugliese, Francesca, Pontone, Gianluca, Benedetti, Giulia, He, Guo-Wei, West, Henry, Kondo, Hidekazu, Benedek, Imre, Das, Intrajeet, Deanfield, John, Graby, John, Greenwood, John, Rodrigues, Jonathan, Ge, Junbo, Channon, Keith, Fabritz, Larissa, Fan, Li-Juan, Kingham, Lucy, Guglielmo, Marco, Lyasheva, Maria, Schmitt, Matthias, Beer, Meinrad, Anderson, Michelle, Desai, Milind, Marwan, Mohamed, Takahashi, Naohiko, Mehta, Nehal, Dai, Neng, Screaton, Nicholas, Sabharwal, Nikant, Maurovich-Horvat, Pál, Rao, Praveen, Kotronias, Rafail, Kharbanda, Rajesh, Preston, Rebecca, Wood, Richard, Blankstein, Ron, Rajani, Ronak, Mirsadraee, Saeed, Munir, Shahzad, Thomas, Sheena, Neubauer, Stefan, Klömpken, Steffen, Petersen, Steffen, Achenbach, Stephan, Anthony, Susan, Mak, Sze, Mittal, Tarun, Benedek, Theodora, Sharma, Vinoda, Lin, Wen-Hua, Kotanidis, Christos P, Rodrigues, Jonathan C L, O’Connor, Daniel, Siddique, Muhammad, Lockstone, Helen, Oikonomou, Evangelos K, Badi, Ileana, Lumley, Sheila F, Constantinides, Bede, Sanderson, Nicholas, Rodger, Gillian, Chau, Kevin K, Lodge, Archie, Tsakok, Maria, Gleeson, Fergus, Indrajeet, Das, Hudson, Benjamin J, Srivastava, Vivek, Farid, Shakil, Krasopoulos, George, Sayeed, Rana, Newby, David E, Channon, Keith M, and Antoniades, Charalambos

Published
2022
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8. Changes in the prevalence of hepatitis B and C viral infections in Sindh province, Pakistan: Findings from two sero‐surveys in 2007 and 2019.

Author

Alamneh, Tesfa Sewunet, Walker, Josephine G., Lim, Aaron G., Alam, Ejaz, Hamid, Saeed, Foster, Graham R., Choudhry, Naheed, Ansari, M. Azim, Qureshi, Huma, and Vickerman, Peter

Subjects
HEPATITIS C virus, HEPATITIS B virus, DISEASE prevalence, VIRUS diseases, HEPATITIS B
Abstract

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero‐surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)‐positive) prevalence and HCV exposure (HCV antibody (HCV‐Ab)‐positive) prevalence between two sero‐surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population‐attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2–2.9) in 2007 to 1.1% (95% CI: 0.8–1.3) in 2019, while HCV‐Ab prevalence increased from 5.1% (95% CI: 4.6%–5.5%) to 6.2% (95% CI: 5.6%–6.8%). The age and gender‐adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1–0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3–0.6) among adults over 2007–2019, while HCV‐Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2–0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2–1.7) in adults. HCV‐Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5–0.8) and higher (aOR = 0.5, 95%CI:0.3–0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2–2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9–3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6–2.7), being tattooed (aOR = 1.4, 95% CI: 1.0–1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0–1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7–48.4%). Overall HCV has increased over 2007–2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Castanet: a pipeline for rapid analysis of targeted multi-pathogen genomic data.

Author

Mayne, Richard, Secret, Shannah, Geoghegan, Cyndi, Trebes, Amy, Kean, Kai, Reid, Kaitlin, Lin, Gu-Lung, Ansari, M Azim, Cesare, Mariateresa de, Bonsall, David, Elliott, Ivo, Piazza, Paolo, Brown, Anthony, Bray, James, Knight, Julian C, Harvala, Heli, Breuer, Judith, Simmonds, Peter, Bowden, Rory J, and Golubchik, Tanya

Abstract

Motivation Target enrichment strategies generate genomic data from multiple pathogens in a single process, greatly improving sensitivity over metagenomic sequencing and enabling cost-effective, high-throughput surveillance and clinical applications. However, uptake by research and clinical laboratories is constrained by an absence of computational tools that are specifically designed for the analysis of multi-pathogen enrichment sequence data. Here we present an analysis pipeline, Castanet, for use with multi-pathogen enrichment sequencing data. Castanet is designed to work with short-read data produced by existing targeted enrichment strategies, but can be readily deployed on any BAM file generated by another methodology. Also included are an optional graphical interface and installer script. Results In addition to genome reconstruction, Castanet reports method-specific metrics that enable quantification of capture efficiency, estimation of pathogen load, differentiation of low-level positives from contamination, and assessment of sequencing quality. Castanet can be used as a traditional end-to-end pipeline for consensus generation, but its strength lies in the ability to process a flexible, pre-defined set of pathogens of interest directly from multi-pathogen enrichment experiments. In our tests, Castanet consensus sequences were accurate reconstructions of reference sequences, including in instances where multiple strains of the same pathogen were present. Castanet performs effectively on standard computers and can process the entire output of a 96-sample enrichment sequencing run (50M reads) using a single batch process command, in $<$2 h. Availability and implementation Source code freely available under GPL-3 license at https://github.com/MultipathogenGenomics/castanet , implemented in Python 3.10 and supported in Ubuntu Linux 22.04. The data underlying this article are available in Europe Nucleotide Archives, at https://www.ebi.ac.uk/ena/browser/view/PRJEB77004. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Inference of Host–Pathogen Interaction Matrices from Genome-Wide Polymorphism Data.

Author

Märkle, Hanna, John, Sona, Metzger, Lukas, Consortium, STOP-HCV, Ansari, M Azim, Pedergnana, Vincent, and Tellier, Aurélien

Subjects
SINGLE nucleotide polymorphisms, HEPATITIS C virus, LINKAGE disequilibrium, VIRAL mutation, HUMAN genes
Abstract

Host–pathogen coevolution is defined as the reciprocal evolutionary changes in both species due to genotype × genotype (G×G) interactions at the genetic level determining the outcome and severity of infection. While co-analyses of hosts and pathogen genomes (co-genome-wide association studies) allow us to pinpoint the interacting genes, these do not reveal which host genotype(s) is/are resistant to which pathogen genotype(s). The knowledge of this so-called infection matrix is important for agriculture and medicine. Building on established theories of host–pathogen interactions, we here derive four novel indices capturing the characteristics of the infection matrix. These indices can be computed from full genome polymorphism data of randomly sampled uninfected hosts, as well as infected hosts and their pathogen strains. We use these indices in an approximate Bayesian computation method to pinpoint loci with relevant G×G interactions and to infer their underlying interaction matrix. In a combined single nucleotide polymorphism dataset of 451 European humans and their infecting hepatitis C virus (HCV) strains and 503 uninfected individuals, we reveal a new human candidate gene for resistance to HCV and new virus mutations matching human genes. For two groups of significant human–HCV (G×G) associations, we infer a gene-for-gene infection matrix, which is commonly assumed to be typical of plant–pathogen interactions. Our model-based inference framework bridges theoretical models of G×G interactions with host and pathogen genomic data. It, therefore, paves the way for understanding the evolution of key G×G interactions underpinning HCV adaptation to the European human population after a recent expansion. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Prevalence of resistance-associated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population

Author

Zacharopoulou, Panagiota, primary, Lee, Ming, additional, Oliveira, Thiago, additional, Thornhill, John, additional, Robinson, Nicola, additional, Brown, Helen, additional, Kinloch, Sabine, additional, Goulder, Philip, additional, Fox, Julie, additional, Fidler, Sarah, additional, Ansari, M. Azim, additional, and Frater, John, additional

Published
2024
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14. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial

Author

Watson, Marion E.E., Song, Rinn, Cicconi, Paola, Minassian, Angela M., Bibi, Sagida, Kerridge, Simon, Singh, Nisha, Green, Catherine M., Douglas, Alexander D., Lawrie, Alison M., Clutterbuck, Elizabeth A., Frater, John, Ewer, Katie J, Ogbe, Ane, Pace, Mathew, Adele, Sandra, Adland, Emily, Alagaratnam, Jasmini, Aley, Parvinder K, Ali, Mohammad, Ansari, M Azim, Bara, Anna, Bittaye, Mustapha, Broadhead, Samantha, Brown, Anthony, Brown, Helen, Cappuccini, Federica, Cooney, Enya, Dejnirattisai, Wanwisa, Dold, Christina, Fairhead, Cassandra, Fok, Henry, Folegatti, Pedro M, Fowler, Jamie, Gibbs, Charlotte, Goodman, Anna L, Jenkin, Daniel, Jones, Mathew, Makinson, Rebecca, Marchevsky, Natalie G, Mujadidi, Yama F, Nguyen, Hanna, Parolini, Lucia, Petersen, Claire, Plested, Emma, Pollock, Katrina M, Ramasamy, Maheshi N, Rhead, Sarah, Robinson, Hannah, Robinson, Nicola, Rongkard, Patpong, Ryan, Fiona, Serrano, Sonia, Tipoe, Timothy, Voysey, Merryn, Waters, Anele, Zacharopoulou, Panagiota, Barnes, Eleanor, Dunachie, Susanna, Goulder, Philip, Klenerman, Paul, Screaton, Gavin R, Winston, Alan, Hill, Adrian V S, Gilbert, Sarah C, Pollard, Andrew J, Fidler, Sarah, Fox, Julie, and Lambe, Teresa

Published
2021
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15. Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus

Author

CTI Bont, Infectieziekten onderzoek1 (Bont), Zorg en O&O, Child Health, Infection & Immunity, Lin, Gu-Lung, Drysdale, Simon B, Snape, Matthew D, O'Connor, Daniel, Brown, Anthony, MacIntyre-Cockett, George, Mellado-Gomez, Esther, de Cesare, Mariateresa, Ansari, M Azim, Bonsall, David, Bray, James E, Jolley, Keith A, Bowden, Rory, Aerssens, Jeroen, Bont, Louis, Openshaw, Peter J M, Martinon-Torres, Federico, Nair, Harish, Golubchik, Tanya, Pollard, Andrew J, RESCEU Consortium, CTI Bont, Infectieziekten onderzoek1 (Bont), Zorg en O&O, Child Health, Infection & Immunity, Lin, Gu-Lung, Drysdale, Simon B, Snape, Matthew D, O'Connor, Daniel, Brown, Anthony, MacIntyre-Cockett, George, Mellado-Gomez, Esther, de Cesare, Mariateresa, Ansari, M Azim, Bonsall, David, Bray, James E, Jolley, Keith A, Bowden, Rory, Aerssens, Jeroen, Bont, Louis, Openshaw, Peter J M, Martinon-Torres, Federico, Nair, Harish, Golubchik, Tanya, Pollard, Andrew J, and RESCEU Consortium

Published
2024

17. Phylogenetic Analysis of Hepatitis C Virus Infections in a Large Belgian Cohort Using Next-Generation Sequencing of Full-Length Genomes

Author

Christensen, Kasper T., primary, Pierard, Florian, additional, Bonsall, David, additional, Bowden, Rory, additional, Barnes, Eleanor, additional, Florence, Eric, additional, Ansari, M. Azim, additional, Nguyen, Dung, additional, de Cesare, Mariateresa, additional, Nevens, Frederik, additional, Robaeys, Geert, additional, Schrooten, Yoeri, additional, Busschots, Dana, additional, Simmonds, Peter, additional, Vandamme, Anne-Mieke, additional, Van Wijngaerden, Eric, additional, Dierckx, Tim, additional, Cuypers, Lize, additional, and Van Laethem, Kristel, additional

Published
2023
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18. Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus

Author

Lin, Gu-Lung, Drysdale, Simon B., Snape, Matthew D., O’Connor, Daniel, Brown, Anthony, MacIntyre-Cockett, George, Mellado-Gomez, Esther, de Cesare, Mariateresa, Bonsall, David, Ansari, M. Azim, Öner, Deniz, Aerssens, Jeroen, Butler, Christopher, Bont, Louis, Openshaw, Peter, Martinón-Torres, Federico, Nair, Harish, Bowden, Rory, Golubchik, Tanya, and Pollard, Andrew J.

Published
2021
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20. Inference of recombination properties in bacteria from whole genomes

Author

Ansari, M. Azim, Didelot, Xavier, and Bowden, Rory

Subjects
579.3, Population genetics of bacteria, Bacterial speciation, Bacterial recombination, Coalescent theory, Gene-conversion recombination
Abstract

The concept of species in bacteria is a matter of contention. The current definition is based on DNA-DNA hybridisation and does not account for evolutionary forces that are important in demarcating species. In this thesis we investigate two evolutionary forces that are important in speciation in bacteria, propose novel statistical models for them and infer parameters of interest. We present the first attempt at inferring the bias in the recombination process from whole bacterial genomes. Despite empirical evidence that recombination is biased and theoretical results that this bias is important in speciation, it is usually ignored. We propose a coalescent based model that accounts for the bias in the recombination process. We use approximate Bayesian computation for inference and describe an efficient method for simulating from the model. We show that our method performs well on simulated datasets and is robust to slight misspecification of the history of the samples. Application of our method to a Bacillus cereus dataset shows that it contain evidence that the recombination process depends on the evolutionary distance between donors and recipients. We demonstrate that the rate of bias in the recombination process for this dataset is far lower than what theoretical studies require for the spontaneous generation of populations that can be called species under neutral model. Next we propose a model for occurrence of adaptive events on a phylogenetic tree. We use the model to infer the boundaries of clusters on a phylogenetic tree that correspond to ecologically distinct lineages. we characterise our method using simulated datasets and show that it is conservative in estimating the number of adaptive events. Finally we apply our method to two bacterial datasets of Salmonella enterica and Vibrionaceae. We show that there is decisive evidence that isolates in these datasets partition into numerous ecologically distinct lineages and use our method to delineate the boundaries of these lineages.

Published
2014

21. Prevalence of resistanceassociated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population.

Author

Zacharopoulou, Panagiota, Lee, Ming, Oliveira, Thiago, Thornhill, John, Robinson, Nicola, Brown, Helen, Kinloch, Sabine, Goulder, Philip, Fox, Julie, Fidler, Sarah, Ansari, M. Azim, and Frater, John

Subjects
HIV seroconversion, HIV infections, HIV infection transmission, INFECTION prevention, ANTIRETROVIRAL agents, INFECTION
Abstract

Broadly neutralising antibodies (bNAbs) targeting HIV show promise for both prevention of infection and treatment. Among these, 10-1074 has shown potential in neutralising a wide range of HIV strains. However, resistant viruses may limit the clinical efficacy of 10-1074. The prevalence of both de novo and emergent 10-1074 resistance will determine its use at a population level both to protect against HIV transmission and as an option for treatment. To help understand this further, we report the prevalence of pre-existing mutations associated with 10-1074 resistance in a bNAb-naive population of 157 individuals presenting to UK HIV centres with primary HIV infection, predominantly B clade, receiving antiretroviral treatment. Single genome analysis of HIV proviral envelope sequences showed that 29% of participants' viruses tested had at least one sequence with 10-1074 resistance-associated mutations. Mutations interfering with the glycan binding site at HIV Env position 332 accounted for 95% of all observed mutations. Subsequent analysis of a larger historic dataset of 2425 Bclade envelope sequences sampled from 1983 to 2019 revealed an increase of these mutations within the population over time. Clinical studies have shown that the presence of pre-existing bNAb mutations may predict diminished therapeutic effectiveness of 10-1074. Therefore, we emphasise the importance of screening for these mutations before initiating 10-1074 therapy, and to consider the implications of pre-existing resistance when designing prevention strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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22. A large-scale, multi-centre, prospective observational study to treat hepatitis C in Pakistan and assess resistance to antiviral drugs (HepFREEPak): study protocol

Author

Arif, Ambreen, primary, Hasnain, Aliya, additional, Chaudhry, Auj, additional, Asim, Muhammad, additional, Shafqat, Muhammad Nabeel, additional, Altaf, Abeer, additional, Saba, Noor, additional, Kemos, Polychronis, additional, Ansari, M. Azim, additional, Barnes, Eleanor, additional, Metcalfe, Chris, additional, Vickerman, Peter, additional, Qureshi, Huma, additional, Hamid, Saeed, additional, Choudhry, Asad Ali, additional, Niaz, Saad Khalid, additional, Foster, Graham R, additional, and Choudhry, Naheed, additional

Published
2023
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25. Strong sex bias in elite control of paediatric HIV infection

Author

Vieira, Vinicius A., Zuidewind, Peter, Muenchhoff, Maximilian, Roider, Julia, Millar, Jane, Clapson, Margaret, Van Zyl, Anriette, Shingadia, Delane, Adland, Emily, Athavale, Rohin, Grayson, Nicholas, Ansari, M. Azim, Brander, Christian, Guash, Claudia Fortuny, Naver, Lars, Puthanakit, Thanyawee, Songtaweesin, Wipaporn Natalie, Ananworanich, Jintanat, Peluso, Denise, Thomé, Beatriz, Pinto, Jorge, Jooste, Pieter, Tudor-Williams, Gareth, Cotton, Mark F., and Goulder, Philip

Published
2019
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28. Pan-genotypic probe-based enrichment to improve efficiency of Hepatitis B virus sequencing

Author

Lumley, Sheila F, primary, Jennings, Daisy, additional, Waddilove, Elizabeth, additional, Trebes, Amy, additional, Delphin, Marion, additional, Downs, Louise O, additional, MacIntyre-Cockett, George, additional, Wu, Yanxia, additional, Chaudron, Sandra, additional, de Lara, Catherine, additional, Chai, Haiting, additional, Maponga, Tongai G, additional, Martin, Jacqueline, additional, Collier, Jane, additional, Ip, Camilla LC, additional, Barnes, Eleanor, additional, Bonsall, David, additional, Piazza, Paolo, additional, Ansari, M. Azim, additional, and Matthews, Philippa C, additional

Published
2023
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29. Association between disease severity and co-detection of respiratory pathogens in infants with RSV infection

Author

Lin, Gu-Lung, primary, Drysdale, Simon B, additional, Snape, Matthew D, additional, O’Connor, Daniel, additional, Brown, Anthony, additional, MacIntyre-Cockett, George, additional, Mellado-Gomez, Esther, additional, de Cesare, Mariateresa, additional, Ansari, M Azim, additional, Bonsall, David, additional, Bray, James E, additional, Jolley, Keith A, additional, Bowden, Rory, additional, Aerssens, Jeroen, additional, Bont, Louis, additional, Openshaw, Peter J M, additional, Martinon-Torres, Federico, additional, Nair, Harish, additional, Golubchik, Tanya, additional, and Pollard, Andrew J, additional

Published
2023
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31. Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study

Author

Flower, Barnaby, primary, Hung, Le Manh, additional, Mccabe, Leanne, additional, Ansari, M Azim, additional, Le Ngoc, Chau, additional, Vo Thi, Thu, additional, Vu Thi Kim, Hang, additional, Nguyen Thi Ngoc, Phuong, additional, Phuong, Le Thanh, additional, Quang, Vo Minh, additional, Dang Trong, Thuan, additional, Le Thi, Thao, additional, Nguyen Bao, Tran, additional, Kingsley, Cherry, additional, Smith, David, additional, Hoglund, Richard M, additional, Tarning, Joel, additional, Kestelyn, Evelyne, additional, Pett, Sarah L, additional, van Doorn, Rogier, additional, Van Nuil, Jennifer Ilo, additional, Turner, Hugo, additional, Thwaites, Guy E, additional, Barnes, Eleanor, additional, Rahman, Motiur, additional, Walker, Ann Sarah, additional, Day, Jeremy N, additional, Chau, Nguyen VV, additional, and Cooke, Graham S, additional

Published
2023
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32. Author response: Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study

Author

Flower, Barnaby, primary, Hung, Le Manh, additional, Mccabe, Leanne, additional, Ansari, M Azim, additional, Le Ngoc, Chau, additional, Vo Thi, Thu, additional, Vu Thi Kim, Hang, additional, Nguyen Thi Ngoc, Phuong, additional, Phuong, Le Thanh, additional, Quang, Vo Minh, additional, Dang Trong, Thuan, additional, Le Thi, Thao, additional, Nguyen Bao, Tran, additional, Kingsley, Cherry, additional, Smith, David, additional, Hoglund, Richard M, additional, Tarning, Joel, additional, Kestelyn, Evelyne, additional, Pett, Sarah L, additional, van Doorn, Rogier, additional, Van Nuil, Jennifer Ilo, additional, Turner, Hugo, additional, Thwaites, Guy E, additional, Barnes, Eleanor, additional, Rahman, Motiur, additional, Walker, Ann Sarah, additional, Day, Jeremy N, additional, Chau, Nguyen VV, additional, and Cooke, Graham S, additional

Published
2022
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33. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Author

Kotanidis, Christos P, primary, Xie, Cheng, additional, Alexander, Donna, additional, Rodrigues, Jonathan C L, additional, Burnham, Katie, additional, Mentzer, Alexander, additional, O’Connor, Daniel, additional, Knight, Julian, additional, Siddique, Muhammad, additional, Lockstone, Helen, additional, Thomas, Sheena, additional, Kotronias, Rafail, additional, Oikonomou, Evangelos K, additional, Badi, Ileana, additional, Lyasheva, Maria, additional, Shirodaria, Cheerag, additional, Lumley, Sheila F, additional, Constantinides, Bede, additional, Sanderson, Nicholas, additional, Rodger, Gillian, additional, Chau, Kevin K, additional, Lodge, Archie, additional, Tsakok, Maria, additional, Gleeson, Fergus, additional, Adlam, David, additional, Rao, Praveen, additional, Indrajeet, Das, additional, Deshpande, Aparna, additional, Bajaj, Amrita, additional, Hudson, Benjamin J, additional, Srivastava, Vivek, additional, Farid, Shakil, additional, Krasopoulos, George, additional, Sayeed, Rana, additional, Ho, Ling-Pei, additional, Neubauer, Stefan, additional, Newby, David E, additional, Channon, Keith M, additional, Deanfield, John, additional, Antoniades, Charalambos, additional, Ahern, David J, additional, Ai, Zhichao, additional, Ainsworth, Mark, additional, Allan, Chris, additional, Allcock, Alice, additional, Angus, Brian, additional, Ansari, M Azim, additional, Arancibia-Cárcamo, Carolina, additional, Aschenbrenner, Dominik, additional, Attar, Moustafa, additional, Baillie, J Kenneth, additional, Barnes, Eleanor, additional, Bashford-Rogers, Rachael, additional, Bashyal, Archana, additional, Beer, Sally, additional, Berridge, Georgina, additional, Beveridge, Amy, additional, Bibi, Sagida, additional, Bicanic, Tihana, additional, Blackwell, Luke, additional, Bowness, Paul, additional, Brent, Andrew, additional, Brown, Andrew, additional, Broxholme, John, additional, Buck, David, additional, Byrne, Helen, additional, Camara, Susana, additional, Ferreira, Ivan Candido, additional, Charles, Philip, additional, Chen, Wentao, additional, Chen, Yi-Ling, additional, Chong, Amanda, additional, Clutterbuck, Elizabeth, additional, Coles, Mark, additional, Conlon, Christopher, additional, Cornall, Richard, additional, Cribbs, Adam, additional, Curion, Fabiola, additional, Davenport, Emma, additional, Davidson, Neil, additional, Davis, Simon, additional, Dendrou, Calliope, additional, Dequaire, Julie, additional, Dib, Lea, additional, Docker, James, additional, Dold, Christina, additional, Dong, Tao, additional, Downes, Damien, additional, Drakesmith, Hal, additional, Dunachie, Susanna, additional, Duncan, David, additional, Eijsbouts, Chris, additional, Esnouf, Robert, additional, Espinosa, Alexis, additional, Etherington, Rachel, additional, Fairfax, Benjamin, additional, Fairhead, Rory, additional, Fang, Hai, additional, Fassih, Shayan, additional, Felle, Sally, additional, Fernandez Mendoza, Maria, additional, Ferreira, Ricardo, additional, Fischer, Roman, additional, Foord, Thomas, additional, Forrow, Aden, additional, Frater, John, additional, Fries, Anastasia, additional, Gallardo Sanchez, Veronica, additional, Garner, Lucy, additional, Geeves, Clementine, additional, Georgiou, Dominique, additional, Godfrey, Leila, additional, Golubchik, Tanya, additional, Gomez Vazquez, Maria, additional, Green, Angie, additional, Harper, Hong, additional, Harrington, Heather, additional, Heilig, Raphael, additional, Hester, Svenja, additional, Hill, Jennifer, additional, Hinds, Charles, additional, Hird, Clare, additional, Hoekzema, Renee, additional, Hollis, Benjamin, additional, Hughes, Jim, additional, Hutton, Paula, additional, Jackson-Wood, Matthew, additional, Jainarayanan, Ashwin, additional, James-Bott, Anna, additional, Jansen, Kathrin, additional, Jeffery, Katie, additional, Jones, Elizabeth, additional, Jostins, Luke, additional, Kerr, Georgina, additional, Kim, David, additional, Klenerman, Paul, additional, Kumar, Vinod, additional, Kumar Sharma, Piyush, additional, Kurupati, Prathiba, additional, Kwok, Andrew, additional, Lee, Angela, additional, Linder, Aline, additional, Lockett, Teresa, additional, Lonie, Lorne, additional, Lopopolo, Maria, additional, Lukoseviciute, Martyna, additional, Luo, Jian, additional, Marinou, Spyridoula, additional, Marsden, Brian, additional, Martinez, Jose, additional, Matthews, Philippa, additional, Mazurczyk, Michalina, additional, McGowan, Simon, additional, McKechnie, Stuart, additional, Mead, Adam, additional, Mi, Yuxin, additional, Monaco, Claudia, additional, Montadon, Ruddy, additional, Napolitani, Giorgio, additional, Nassiri, Isar, additional, Novak, Alex, additional, O'Brien, Darragh, additional, O'Connor, Daniel, additional, O'Donnell, Denise, additional, Ogg, Graham, additional, Overend, Lauren, additional, Park, Inhye, additional, Pavord, Ian, additional, Peng, Yanchun, additional, Penkava, Frank, additional, Pereira Pinho, Mariana, additional, Perez, Elena, additional, Pollard, Andrew, additional, Powrie, Fiona, additional, Psaila, Bethan, additional, Quan, T Phuong, additional, Repapi, Emmanouela, additional, Revale, Santiago, additional, Silva-Reyes, Laura, additional, Richard, Jean-Baptiste, additional, Rich-Griffin, Charlotte, additional, Ritter, Thomas, additional, Rollier, Christine, additional, Rowland, Matthew, additional, Ruehle, Fabian, additional, Salio, Mariolina, additional, Sansom, Stephen Nicholas, additional, Sanches Peres, Raphael, additional, Santos Delgado, Alberto, additional, Sauka-Spengler, Tatjana, additional, Schwessinger, Ron, additional, Scozzafava, Giuseppe, additional, Screaton, Gavin, additional, Seigal, Anna, additional, Semple, Malcolm, additional, Sergeant, Martin, additional, Simoglou Karali, Christina, additional, Sims, David, additional, Skelly, Donal, additional, Slawinski, Hubert, additional, Sobrinodiaz, Alberto, additional, Sousos, Nikolaos, additional, Stafford, Lizzie, additional, Stockdale, Lisa, additional, Strickland, Marie, additional, Sumray, Otto, additional, Sun, Bo, additional, Taylor, Chelsea, additional, Taylor, Stephen, additional, Taylor, Adan, additional, Thongjuea, Supat, additional, Thraves, Hannah, additional, Todd, John, additional, Tomic, Adriana, additional, Tong, Orion, additional, Trebes, Amy, additional, Trzupek, Dominik, additional, Tucci, Felicia Anna, additional, Turtle, Lance, additional, Udalova, Irina, additional, Uhlig, Holm, additional, van Grinsven, Erinke, additional, Vendrell, Iolanda, additional, Verheul, Marije, additional, Voda, Alexandru, additional, Wang, Guanlin, additional, Wang, Lihui, additional, Wang, Dapeng, additional, Watkinson, Peter, additional, Watson, Robert, additional, Weinberger, Michael, additional, Whalley, Justin, additional, Witty, Lorna, additional, Wray, Katherine, additional, Xue, Luzheng, additional, Yuen Yeung, Hing, additional, Yin, Zixi, additional, Young, Rebecca, additional, Youngs, Jonathan, additional, Zhang, Ping, additional, Zurke, Yasemin-Xiomara, additional, Banning, Adrian, additional, Antonopoulos, Alexios, additional, Kelion, Andrew, additional, Kardos, Attila, additional, Hudson, Benjamin, additional, Koo, Bon-Kwon, additional, Kotanidis, Christos, additional, Mahon, Ciara, additional, Berry, Colin, additional, Newby, David, additional, Connolly, Derek, additional, Scaletta, Diane, additional, Nicol, Ed, additional, McAlindon, Elisa, additional, Oikonomou, Evangelos, additional, Pugliese, Francesca, additional, Pontone, Gianluca, additional, Benedetti, Giulia, additional, He, Guo-Wei, additional, West, Henry, additional, Kondo, Hidekazu, additional, Benedek, Imre, additional, Das, Intrajeet, additional, Graby, John, additional, Greenwood, John, additional, Rodrigues, Jonathan, additional, Ge, Junbo, additional, Channon, Keith, additional, Fabritz, Larissa, additional, Fan, Li-Juan, additional, Kingham, Lucy, additional, Guglielmo, Marco, additional, Schmitt, Matthias, additional, Beer, Meinrad, additional, Anderson, Michelle, additional, Desai, Milind, additional, Marwan, Mohamed, additional, Takahashi, Naohiko, additional, Mehta, Nehal, additional, Dai, Neng, additional, Screaton, Nicholas, additional, Sabharwal, Nikant, additional, Maurovich-Horvat, Pál, additional, Kharbanda, Rajesh, additional, Preston, Rebecca, additional, Wood, Richard, additional, Blankstein, Ron, additional, Rajani, Ronak, additional, Mirsadraee, Saeed, additional, Munir, Shahzad, additional, Klömpken, Steffen, additional, Petersen, Steffen, additional, Achenbach, Stephan, additional, Anthony, Susan, additional, Mak, Sze, additional, Mittal, Tarun, additional, Benedek, Theodora, additional, Sharma, Vinoda, additional, and Lin, Wen-Hua, additional

Published
2022
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34. T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study

Author

Angyal, Adrienn, primary, Longet, Stephanie, additional, Moore, Shona C, additional, Payne, Rebecca P, additional, Harding, Adam, additional, Tipton, Tom, additional, Rongkard, Patpong, additional, Ali, Mohammad, additional, Hering, Luisa M, additional, Meardon, Naomi, additional, Austin, James, additional, Brown, Rebecca, additional, Skelly, Donal, additional, Gillson, Natalie, additional, Dobson, Sue L, additional, Cross, Andrew, additional, Sandhar, Gurjinder, additional, Kilby, Jonathan A, additional, Tyerman, Jessica K, additional, Nicols, Alexander R, additional, Spegarova, Jarmila S, additional, Mehta, Hema, additional, Hornsby, Hailey, additional, Whitham, Rachel, additional, Conlon, Christopher P, additional, Jeffery, Katie, additional, Goulder, Philip, additional, Frater, John, additional, Dold, Christina, additional, Pace, Matthew, additional, Ogbe, Ane, additional, Brown, Helen, additional, Ansari, M Azim, additional, Adland, Emily, additional, Brown, Anthony, additional, Chand, Meera, additional, Shields, Adrian, additional, Matthews, Philippa C, additional, Hopkins, Susan, additional, Hall, Victoria, additional, James, William, additional, Rowland-Jones, Sarah L, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Richter, Alex, additional, Duncan, Christopher J A, additional, Barnes, Eleanor, additional, Carroll, Miles, additional, Turtle, Lance, additional, de Silva, Thushan I, additional, Watson, Adam, additional, Angyal, Adrienn, additional, Alhussni, Ahmed, additional, Nicols, Alexander, additional, Deeks, Alexandra, additional, Webb-Bridges, Alice, additional, Jämsén, Anni, additional, Chawla, Anu, additional, Duncan, Christopher, additional, Conlon, Christopher, additional, O'Donnell, Denise, additional, Weeks, Esme, additional, Abuelgasim, Hibatullah, additional, Xiao, Huiyuan, additional, Spegarova, Jarmila, additional, Holmes, Jennifer, additional, Haworth, Jenny, additional, Tyerman, Jessica, additional, Kilby, Jonathan, additional, Cutteridge, Joseph, additional, Lillie, Katy, additional, Romaniuk, Leigh, additional, Denly, Lucy, additional, Hering, Luisa, additional, Ansari, M. Azim, additional, Kasanyinga, Mwila, additional, Matthews, Philippa, additional, Payne, Rebecca, additional, Wilson, Robert, additional, Rowland-Jones, Sarah, additional, Thomas, Sarah, additional, Moore, Shona, additional, Gardiner, Siobhan, additional, Tucker, Stephanie, additional, Dobson, Sue, additional, Adlou, Syed, additional, de Silva, Thushan, additional, Lawrie, Allan, additional, Smith, Nikki, additional, Turton, Helena, additional, Zawia, Amira, additional, Bayley, Martin, additional, Fairman, Alex, additional, Harrington, Kate, additional, Kirk, Rosemary, additional, Marsh, Louise, additional, Watson, Lisa, additional, Wood, Steven, additional, Diffey, Benjamin, additional, Jones, Chris, additional, Lett, Lauren, additional, Platt, Gareth, additional, Subramaniam, Krishanthi, additional, Wootton, Daniel, additional, Payne, Brendan, additional, Hambleton, Sophie, additional, Kelly, Sinead, additional, Marston, Judith, additional, Poolan, Sonia, additional, Turner, Dianne, additional, Haniffa, Muzlifah, additional, Stephenson, Emily, additional, Adele, Sandra, additional, Akhter, Hossain Delowar, additional, Chinnakannan, Senthil, additional, de Lara, Catherine, additional, Donnison, Timothy, additional, Hackstein, Carl-Philipp, additional, Lee, Lian, additional, Lim, Nicholas, additional, Malone, Tom, additional, Phillips, Eloise, additional, Ramamurthy, Narayan, additional, Robinson, Nichola, additional, Sampson, Oliver, additional, Eyre, David, additional, Simmons, Beatrice, additional, Stafford, Lizzie, additional, Mentzer, Alexander, additional, Amini, Ali, additional, Arancibia-Cárcamo, Carolina, additional, Provine, Nicholas, additional, Travis, Simon, additional, Dimitriadis, Stavros, additional, Johnson, Sile, additional, Foulkes, Sarah, additional, Khawam, Jameel, additional, Wellington, Edgar, additional, Gilbert-Jaramillo, Javier, additional, Knight, Michael, additional, Dupont, Maeva, additional, Horner, Emily, additional, Thaventhiran, James, additional, and Chalk, Jeremy, additional

Published
2022
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35. Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: Results from a genome-wide case-control study

Author

Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U, Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, Von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Mattias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Ginanni Corradini, Stefano, Irving, William Lucien, Morling, Joanne R., Guha, Indra Neil, Barnes, Eleanor, Ansari, M. Azim, Quistrebert, Jocelyn, Valenti, Luca, Morgan, Marsha Yvonne, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, and Stickel, Felix

Subjects
Gastroenterology
Abstract

Objective: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-Analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44). Conclusion: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

Published
2022

36. Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for Hepatitis C: a single arm mechanistic pilot study

Author

Flower, Barnaby, primary, Hung, Le Manh, additional, McCabe, Leanne, additional, Ansari, M. Azim, additional, Le Ngoc, Chau, additional, Vo Thi, Thu, additional, Vu Thi Kim, Hang, additional, Nguyen Thi Ngoc, Phuong, additional, Phuong, Le Thanh, additional, Quang, Vo Minh, additional, Trong, Thuan Dang, additional, Le Thi, Thao, additional, Bao, Tran Nguyen, additional, Kingsley, Cherry, additional, Smith, David, additional, Hoglund, Richard M., additional, Tarning, Joel, additional, Kestelyn, Evelyne, additional, Pett, Sarah L, additional, van Doorn, Rogier, additional, van Nuil, Jennifer Ilo, additional, Turner, Hugo, additional, Thwaites, Guy, additional, Barnes, Eleanor, additional, Rahman, Motiur, additional, Walker, Ann Sarah, additional, Day, Jeremy, additional, Van Vinh Chau, Nguyen, additional, and Cooke, Graham S, additional

Published
2022
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37. Genetic variation inTERTmodifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study

Author

Buch, Stephan, primary, Innes, Hamish, additional, Lutz, Philipp Ludwig, additional, Nischalke, Hans Dieter, additional, Marquardt, Jens U, additional, Fischer, Janett, additional, Weiss, Karl Heinz, additional, Rosendahl, Jonas, additional, Marot, Astrid, additional, Krawczyk, Marcin, additional, Casper, Markus, additional, Lammert, Frank, additional, Eyer, Florian, additional, Vogel, Arndt, additional, Marhenke, Silke, additional, von Felden, Johann, additional, Sharma, Rohini, additional, Atkinson, Stephen Rahul, additional, McQuillin, Andrew, additional, Nattermann, Jacob, additional, Schafmayer, Clemens, additional, Franke, Andre, additional, Strassburg, Christian, additional, Rietschel, Marcella, additional, Altmann, Heidi, additional, Sulk, Stefan, additional, Thangapandi, Veera Raghavan, additional, Brosch, Mario, additional, Lackner, Carolin, additional, Stauber, Rudolf E, additional, Canbay, Ali, additional, Link, Alexander, additional, Reiberger, Thomas, additional, Mandorfer, Mattias, additional, Semmler, Georg, additional, Scheiner, Bernhard, additional, Datz, Christian, additional, Romeo, Stefano, additional, Ginanni Corradini, Stefano, additional, Irving, William Lucien, additional, Morling, Joanne R, additional, Guha, Indra Neil, additional, Barnes, Eleanor, additional, Ansari, M Azim, additional, Quistrebert, Jocelyn, additional, Valenti, Luca, additional, Müller, Sascha A, additional, Morgan, Marsha Yvonne, additional, Dufour, Jean-François, additional, Trebicka, Jonel, additional, Berg, Thomas, additional, Deltenre, Pierre, additional, Mueller, Sebastian, additional, Hampe, Jochen, additional, and Stickel, Felix, additional

Published
2022
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38. Recombinational Switching of the Clostridium difficile S-Layer and a Novel Glycosylation Gene Cluster Revealed by Large-Scale Whole-Genome Sequencing

Author

Dingle, Kate E., Didelot, Xavier, Ansari, M. Azim, Eyre, David W., Vaughan, Alison, Griffiths, David, Ip, Camilla L. C., Batty, Elizabeth M., Golubchik, Tanya, Bowden, Rory, Jolley, Keith A., Hood, Derek W., Fawley, Warren N., Walker, A. Sarah, Peto, Timothy E., Wilcox, Mark H., and Crook, Derrick W.

Published
2013
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39. Genetic variation in modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U, Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Mattias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Ginanni Corradini, Stefano, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, Stickel, Felix, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Buch, Stephan, Innes, Hamish, Lutz, Philipp Ludwig, Nischalke, Hans Dieter, Marquardt, Jens U, Fischer, Janett, Weiss, Karl Heinz, Rosendahl, Jonas, Marot, Astrid, Krawczyk, Marcin, Casper, Markus, Lammert, Frank, Eyer, Florian, Vogel, Arndt, Marhenke, Silke, von Felden, Johann, Sharma, Rohini, Atkinson, Stephen Rahul, McQuillin, Andrew, Nattermann, Jacob, Schafmayer, Clemens, Franke, Andre, Strassburg, Christian, Rietschel, Marcella, Altmann, Heidi, Sulk, Stefan, Thangapandi, Veera Raghavan, Brosch, Mario, Lackner, Carolin, Stauber, Rudolf E, Canbay, Ali, Link, Alexander, Reiberger, Thomas, Mandorfer, Mattias, Semmler, Georg, Scheiner, Bernhard, Datz, Christian, Romeo, Stefano, Ginanni Corradini, Stefano, Irving, William Lucien, Morling, Joanne R, Guha, Indra Neil, Barnes, Eleanor, Ansari, M Azim, Quistrebert, Jocelyn, Valenti, Luca, Müller, Sascha A, Morgan, Marsha Yvonne, Dufour, Jean-François, Trebicka, Jonel, Berg, Thomas, Deltenre, Pierre, Mueller, Sebastian, Hampe, Jochen, and Stickel, Felix

Abstract

Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Associations with variants rs738409 in and rs58542926 in previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in was associated with an increased leucocyte telomere length (p=2.12×10). This study identifies rs2242652 in as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

Published
2022

42. Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV

Author

Ogbe, Ane, primary, Pace, Matthew, additional, Bittaye, Mustapha, additional, Tipoe, Timothy, additional, Adele, Sandra, additional, Alagaratnam, Jasmini, additional, Aley, Parvinder K., additional, Ansari, M. Azim, additional, Bara, Anna, additional, Broadhead, Samantha, additional, Brown, Anthony, additional, Brown, Helen, additional, Cappuccini, Federica, additional, Cinardo, Paola, additional, Dejnirattisai, Wanwisa, additional, Ewer, Katie J., additional, Fok, Henry, additional, Folegatti, Pedro M., additional, Fowler, Jamie, additional, Godfrey, Leila, additional, Goodman, Anna L., additional, Jackson, Bethany, additional, Jenkin, Daniel, additional, Jones, Mathew, additional, Longet, Stephanie, additional, Makinson, Rebecca A., additional, Marchevsky, Natalie G., additional, Mathew, Moncy, additional, Mazzella, Andrea, additional, Mujadidi, Yama F., additional, Parolini, Lucia, additional, Petersen, Claire, additional, Plested, Emma, additional, Pollock, Katrina M., additional, Rajeswaran, Thurkka, additional, Ramasamy, Maheshi N., additional, Rhead, Sarah, additional, Robinson, Hannah, additional, Robinson, Nicola, additional, Sanders, Helen, additional, Serrano, Sonia, additional, Tipton, Tom, additional, Waters, Anele, additional, Zacharopoulou, Panagiota, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Goulder, Philip, additional, Klenerman, Paul, additional, Screaton, Gavin R., additional, Winston, Alan, additional, Hill, Adrian V.S., additional, Gilbert, Sarah C., additional, Carroll, Miles, additional, Pollard, Andrew J., additional, Fidler, Sarah, additional, Fox, Julie, additional, Lambe, Teresa, additional, and Frater, John, additional

Published
2022
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43. A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

Author

Ahern, David J., primary, Ai, Zhichao, additional, Ainsworth, Mark, additional, Allan, Chris, additional, Allcock, Alice, additional, Angus, Brian, additional, Ansari, M. Azim, additional, Arancibia-Cárcamo, Carolina V., additional, Aschenbrenner, Dominik, additional, Attar, Moustafa, additional, Baillie, J. Kenneth, additional, Barnes, Eleanor, additional, Bashford-Rogers, Rachael, additional, Bashyal, Archana, additional, Beer, Sally, additional, Berridge, Georgina, additional, Beveridge, Amy, additional, Bibi, Sagida, additional, Bicanic, Tihana, additional, Blackwell, Luke, additional, Bowness, Paul, additional, Brent, Andrew, additional, Brown, Andrew, additional, Broxholme, John, additional, Buck, David, additional, Burnham, Katie L., additional, Byrne, Helen, additional, Camara, Susana, additional, Candido Ferreira, Ivan, additional, Charles, Philip, additional, Chen, Wentao, additional, Chen, Yi-Ling, additional, Chong, Amanda, additional, Clutterbuck, Elizabeth A., additional, Coles, Mark, additional, Conlon, Christopher P., additional, Cornall, Richard, additional, Cribbs, Adam P., additional, Curion, Fabiola, additional, Davenport, Emma E., additional, Davidson, Neil, additional, Davis, Simon, additional, Dendrou, Calliope A., additional, Dequaire, Julie, additional, Dib, Lea, additional, Docker, James, additional, Dold, Christina, additional, Dong, Tao, additional, Downes, Damien, additional, Drakesmith, Hal, additional, Dunachie, Susanna J., additional, Duncan, David A., additional, Eijsbouts, Chris, additional, Esnouf, Robert, additional, Espinosa, Alexis, additional, Etherington, Rachel, additional, Fairfax, Benjamin, additional, Fairhead, Rory, additional, Fang, Hai, additional, Fassih, Shayan, additional, Felle, Sally, additional, Fernandez Mendoza, Maria, additional, Ferreira, Ricardo, additional, Fischer, Roman, additional, Foord, Thomas, additional, Forrow, Aden, additional, Frater, John, additional, Fries, Anastasia, additional, Gallardo Sanchez, Veronica, additional, Garner, Lucy C., additional, Geeves, Clementine, additional, Georgiou, Dominique, additional, Godfrey, Leila, additional, Golubchik, Tanya, additional, Gomez Vazquez, Maria, additional, Green, Angie, additional, Harper, Hong, additional, Harrington, Heather A., additional, Heilig, Raphael, additional, Hester, Svenja, additional, Hill, Jennifer, additional, Hinds, Charles, additional, Hird, Clare, additional, Ho, Ling-Pei, additional, Hoekzema, Renee, additional, Hollis, Benjamin, additional, Hughes, Jim, additional, Hutton, Paula, additional, Jackson-Wood, Matthew A., additional, Jainarayanan, Ashwin, additional, James-Bott, Anna, additional, Jansen, Kathrin, additional, Jeffery, Katie, additional, Jones, Elizabeth, additional, Jostins, Luke, additional, Kerr, Georgina, additional, Kim, David, additional, Klenerman, Paul, additional, Knight, Julian C., additional, Kumar, Vinod, additional, Kumar Sharma, Piyush, additional, Kurupati, Prathiba, additional, Kwok, Andrew, additional, Lee, Angela, additional, Linder, Aline, additional, Lockett, Teresa, additional, Lonie, Lorne, additional, Lopopolo, Maria, additional, Lukoseviciute, Martyna, additional, Luo, Jian, additional, Marinou, Spyridoula, additional, Marsden, Brian, additional, Martinez, Jose, additional, Matthews, Philippa C., additional, Mazurczyk, Michalina, additional, McGowan, Simon, additional, McKechnie, Stuart, additional, Mead, Adam, additional, Mentzer, Alexander J., additional, Mi, Yuxin, additional, Monaco, Claudia, additional, Montadon, Ruddy, additional, Napolitani, Giorgio, additional, Nassiri, Isar, additional, Novak, Alex, additional, O'Brien, Darragh P., additional, O'Connor, Daniel, additional, O'Donnell, Denise, additional, Ogg, Graham, additional, Overend, Lauren, additional, Park, Inhye, additional, Pavord, Ian, additional, Peng, Yanchun, additional, Penkava, Frank, additional, Pereira Pinho, Mariana, additional, Perez, Elena, additional, Pollard, Andrew J., additional, Powrie, Fiona, additional, Psaila, Bethan, additional, Quan, T. Phuong, additional, Repapi, Emmanouela, additional, Revale, Santiago, additional, Silva-Reyes, Laura, additional, Richard, Jean-Baptiste, additional, Rich-Griffin, Charlotte, additional, Ritter, Thomas, additional, Rollier, Christine S., additional, Rowland, Matthew, additional, Ruehle, Fabian, additional, Salio, Mariolina, additional, Sansom, Stephen Nicholas, additional, Sanches Peres, Raphael, additional, Santos Delgado, Alberto, additional, Sauka-Spengler, Tatjana, additional, Schwessinger, Ron, additional, Scozzafava, Giuseppe, additional, Screaton, Gavin, additional, Seigal, Anna, additional, Semple, Malcolm G., additional, Sergeant, Martin, additional, Simoglou Karali, Christina, additional, Sims, David, additional, Skelly, Donal, additional, Slawinski, Hubert, additional, Sobrinodiaz, Alberto, additional, Sousos, Nikolaos, additional, Stafford, Lizzie, additional, Stockdale, Lisa, additional, Strickland, Marie, additional, Sumray, Otto, additional, Sun, Bo, additional, Taylor, Chelsea, additional, Taylor, Stephen, additional, Taylor, Adan, additional, Thongjuea, Supat, additional, Thraves, Hannah, additional, Todd, John A., additional, Tomic, Adriana, additional, Tong, Orion, additional, Trebes, Amy, additional, Trzupek, Dominik, additional, Tucci, Felicia Anna, additional, Turtle, Lance, additional, Udalova, Irina, additional, Uhlig, Holm, additional, van Grinsven, Erinke, additional, Vendrell, Iolanda, additional, Verheul, Marije, additional, Voda, Alexandru, additional, Wang, Guanlin, additional, Wang, Lihui, additional, Wang, Dapeng, additional, Watkinson, Peter, additional, Watson, Robert, additional, Weinberger, Michael, additional, Whalley, Justin, additional, Witty, Lorna, additional, Wray, Katherine, additional, Xue, Luzheng, additional, Yeung, Hing Yuen, additional, Yin, Zixi, additional, Young, Rebecca K., additional, Youngs, Jonathan, additional, Zhang, Ping, additional, and Zurke, Yasemin-Xiomara, additional

Published
2022
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44. The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

Author

Innes, Hamish, Nischalke, Hans Dieter, Guha, Indra Neil, Weiss, Karl Heinz, Irving, Will, Gotthardt, Daniel, Barnes, Eleanor, Fischer, Janett, Ansari, M. Azim, Rosendahl, Jonas, Lin, Shang‐Kuan, Marot, Astrid, Pedergnana, Vincent, Casper, Markus, Benselin, Jennifer, Lammert, Frank, McLauchlan, John, Lutz, Philip L., Hamill, Victoria, Mueller, Sebastian, Morling, Joanne R., Semmler, Georg, Eyer, Florian, von Felden, Johann, Link, Alexander, Vogel, Arndt, Marquardt, Jens U., Sulk, Stefan, Trebicka, Jonel, Valenti, Luca, Datz, Christian, Reiberger, Thomas, Schafmayer, Clemens, Berg, Thomas, Deltenre, Pierre, Hampe, Jochen, Stickel, Felix, Buch, Stephan, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service de gastro-entérologie

Subjects
Liver Cirrhosis, Carcinoma, Hepatocellular, Hepatology, Liver Neoplasms, Membrane Proteins, SNP, Genomics, Hepatitis C, Polymorphism, Single Nucleotide, digestive system diseases, ddc, Chronic Liver Disease, Apolipoproteins E, Cirrhosis, Genetics, Humans, Genetic Predisposition to Disease, Liver cancer
Abstract

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol‐3‐phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol‐related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case‐control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP‐HCV), and one alcohol‐related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed‐effect meta‐analysis was used to determine the pooled effect size across all data sets. Across four case‐control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61‐0.84; P = 2.9 × 10−5). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45‐2.86; P = 3.1 × 10−6). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90‐1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84‐1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.

Published
2022
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45. 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

46. Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure

Author

Smith, David A., Fernandez-Antunez, Carlota, Magri, Andrea, Bowden, Rory, Chaturvedi, Nimisha, Fellay, Jacques, McLauchlan, John, Foster, Graham R., Irving, William L., Simmonds, Peter, Pedergnana, Vincent, Ramirez, Santseharay, Bukh, Jens, Barnes, Eleanor, Ansari, M. Azim, Ball, Jonathan, Brainard, Diana, Burgess, Gary, Cooke, Graham, Dillon, John, Gore, Charles, Guha, Neil, Halford, Rachel, Herath, Cham, Holmes, Chris, Howe, Anita, Hudson, Emma, Irving, William, Khakoo, Salim, Klenerman, Paul, Koletzki, Diana, Martin, Natasha, Massetto, Benedetta, Mbisa, Tamyo, McHutchison, John, McKeating, Jane, Miners, Alec, Murray, Andrea, Shaw, Peter, Spencer, Chris C. A., Targett-Adams, Paul, Thomson, Emma, Vickerman, Peter, Zitzmann, Nicole, Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford, University of Copenhagen = Københavns Universitet (UCPH), The Wellcome Trust Centre for Human Genetics [Oxford], Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Glasgow, Queen Mary University of London (QMUL), University of Nottingham, UK (UON), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), STOP-HCV Consortium, Ball, J., Brainard, D., Burgess, G., Cooke, G., Dillon, J., Gore, C., Guha, N., Halford, R., Herath, C., Holmes, C., Howe, A., Hudson, E., Irving, W., Khakoo, S., Klenerman, P., Koletzki, D., Martin, N., Massetto, B., Mbisa, T., McHutchison, J., McKeating, J., Miners, A., Murray, A., Shaw, P., Spencer, CCA, Targett-Adams, P., Thomson, E., Vickerman, P., and Zitzmann, N.

Subjects
ns2, Sofosbuvir, [SDV]Life Sciences [q-bio], viruses, General Physics and Astronomy, Genome-wide association study, resistance-associated substitutions, Hepacivirus, Viral Nonstructural Proteins, Chronic liver disease, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, Treatment Failure, 0303 health sciences, Multidisciplinary, Hepatitis C virus, virus diseases, Viral Load, Antivirals, 3. Good health, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Viral load, medicine.drug, Genotype, ribavirin, Science, Genome, Viral, Antiviral Agents/therapeutic use, Genome, Viral/genetics, Hepacivirus/drug effects, Hepacivirus/genetics, Hepacivirus/isolation & purification, Hepatitis C, Chronic/drug therapy, Hepatitis C, Chronic/virology, Humans, Polymorphism, Genetic, Sofosbuvir/therapeutic use, Viral Load/drug effects, Viral Load/genetics, Viral Nonstructural Proteins/genetics, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Article, Virus, 03 medical and health sciences, medicine, Potency, emergence, 030304 developmental biology, NS3, business.industry, Ribavirin, General Chemistry, biochemical phenomena, metabolism, and nutrition, Hepatitis C, Chronic, medicine.disease, Virology, infection, digestive system diseases, chemistry, Viral infection, protein, business
Abstract

Sofosbuvir is a common therapy in hepatitis C virus infection, which targets the NS5B polymerase. Here, Smith et al. analyze the association between whole genome HCV polymorphisms and sofosbuvir treatment failure and identify three common polymorphisms present in non-targeted NS2 and NS3 proteins associated with reduced treatment response., Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease, worldwide. With the development of direct-acting antivirals, treatment of chronically infected patients has become highly effective, although a subset of patients responds less well to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies, that targets the HCV NS5B polymerase. We use pre-treatment whole-genome sequences of HCV from 507 patients infected with HCV subtype 3a and treated with sofosbuvir containing regimens to detect viral polymorphisms associated with response to treatment. We find three common polymorphisms in non-targeted HCV NS2 and NS3 proteins are associated with reduced treatment response. These polymorphisms are enriched in post-treatment HCV sequences of patients unresponsive to treatment. They are also associated with lower reductions in viral load in the first week of therapy. Using in vitro short-term dose-response assays, these polymorphisms do not cause any reduction in sofosbuvir potency, suggesting an indirect mechanism of action in decreasing sofosbuvir efficacy. The identification of polymorphisms in NS2 and NS3 proteins associated with poor treatment outcomes emphasises the value of systematic genome-wide analyses of viruses in uncovering clinically relevant polymorphisms that impact treatment.

Published
2021

47. The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

Author

Innes, Hamish, primary, Nischalke, Hans Dieter, additional, Guha, Indra Neil, additional, Weiss, Karl Heinz, additional, Irving, Will, additional, Gotthardt, Daniel, additional, Barnes, Eleanor, additional, Fischer, Janett, additional, Ansari, M. Azim, additional, Rosendahl, Jonas, additional, Lin, Shang‐Kuan, additional, Marot, Astrid, additional, Pedergnana, Vincent, additional, Casper, Markus, additional, Benselin, Jennifer, additional, Lammert, Frank, additional, McLauchlan, John, additional, Lutz, Philip L., additional, Hamill, Victoria, additional, Mueller, Sebastian, additional, Morling, Joanne R., additional, Semmler, Georg, additional, Eyer, Florian, additional, von Felden, Johann, additional, Link, Alexander, additional, Vogel, Arndt, additional, Marquardt, Jens U., additional, Sulk, Stefan, additional, Trebicka, Jonel, additional, Valenti, Luca, additional, Datz, Christian, additional, Reiberger, Thomas, additional, Schafmayer, Clemens, additional, Berg, Thomas, additional, Deltenre, Pierre, additional, Hampe, Jochen, additional, Stickel, Felix, additional, and Buch, Stephan, additional

Published
2021
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48. Distinct patterns of within-host virus populations 2 between two subgroups of human respiratory syncytial 3 virus

Author

Lin, Gu-Lung, Drysdale, Simon B, Snape, Matthew D, O'Connor, Daniel P, Brown, Anthony, MacIntyre-Cockett, George, Mellado-Gomez, Esther, de Cesare, Mariateresa, Bonsall, David, Ansari, M Azim, Öner, Deniz, Aerssens, Jeroen, Butler, Christopher, Bont, Louis, Openshaw, Peter, Martinon-Torres, Federico, Nair, Harish, Bowden, Rory, Golubchik, Tanya, and Pollard, Andrew J

Subjects
viruses, respiratory system
Abstract

Human respiratory syncytial virus (RSV) is a major cause of lower respiratorytract infection in young children globally, but little is known about within-hostRSV diversity. Here, we characterised within-host RSV populations using deep sequencing data from 319 nasopharyngeal swabs collected during 2017–2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the twosubgroups.

Published
2021

49. An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+ T-cell-mediated immune control in adults

Author

Vieira, Vinicius A., primary, Adland, Emily, additional, Malone, David F. G., additional, Martin, Maureen P., additional, Groll, Andreas, additional, Ansari, M. Azim, additional, Garcia-Guerrero, Maria C., additional, Puertas, Mari C., additional, Muenchhoff, Maximilian, additional, Guash, Claudia Fortuny, additional, Brander, Christian, additional, Martinez-Picado, Javier, additional, Bamford, Alasdair, additional, Tudor-Williams, Gareth, additional, Ndung’u, Thumbi, additional, Walker, Bruce D., additional, Ramsuran, Veron, additional, Frater, John, additional, Jooste, Pieter, additional, Peppa, Dimitra, additional, Carrington, Mary, additional, and Goulder, Philip J. R., additional

Published
2021
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50. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Author

Payne, Rebecca P., primary, Longet, Stephanie, additional, Austin, James A., additional, Skelly, Donal T., additional, Dejnirattisai, Wanwisa, additional, Adele, Sandra, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Moore, Shona C., additional, Tipton, Tom, additional, Hering, Luisa M., additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R., additional, Gillson, Natalie, additional, Dobson, Susan L., additional, Amini, Ali, additional, Supasa, Piyada, additional, Cross, Andrew, additional, Bridges-Webb, Alice, additional, Reyes, Laura Silva, additional, Linder, Aline, additional, Sandhar, Gurjinder, additional, Kilby, Jonathan A., additional, Tyerman, Jessica K., additional, Altmann, Thomas, additional, Hornsby, Hailey, additional, Whitham, Rachel, additional, Phillips, Eloise, additional, Malone, Tom, additional, Hargreaves, Alexander, additional, Shields, Adrian, additional, Saei, Ayoub, additional, Foulkes, Sarah, additional, Stafford, Lizzie, additional, Johnson, Sile, additional, Wootton, Daniel G., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Frater, John, additional, Deeks, Alexandra S., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolsapaya, Juthathip, additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria, additional, Dold, Christina, additional, Duncan, Christopher J.A., additional, Richter, Alex, additional, Carroll, Miles, additional, Screaton, Gavin, additional, de Silva, Thushan I., additional, Turtle, Lance, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Abuelgasim, Hibatullah, additional, Adland, Emily, additional, Adlou, Syed, additional, Akther, Hossain Delowar, additional, Alhussni, Ahmed, additional, Ali, Mohammad, additional, Ansari, M. Azim, additional, Arancibia-Cárcamo, Carolina V., additional, Bayley, Martin, additional, Brown, Helen, additional, Chalk, Jeremy, additional, Chand, Meera, additional, Chawla, Anu, additional, Chinnakannan, Senthil, additional, Cutteridge, Joseph, additional, de Lara, Catherine, additional, Denly, Lucy, additional, Diffey, Ben, additional, Dimitriadis, Stavros, additional, Drake, Thomas M., additional, Donnison, Timothy, additional, Dupont, Maeva, additional, Eyre, David, additional, Fairman, Alex, additional, Gardiner, Siobhan, additional, Gilbert-Jarmillo, Javier, additional, Goulder, Philip, additional, Hackstein, Carl-Philipp, additional, Hambleton, Sophie, additional, Haniffa, Muzlifah, additional, Haworth, Jenny, additional, Holmes, Jennifer, additional, Horner, Emily, additional, Jämsén, Anni, additional, Jones, Chris, additional, Kasanyinga, Mwila, additional, Kelly, Sinead, additional, Kirk, Rosemary, additional, Knight, Michael L., additional, Lawrie, Allan, additional, Lee, Lian, additional, Lett, Lauren, additional, Lillie, Katy, additional, Lim, Nicholas, additional, Mehta, Hema, additional, Mentzer, Alexander J., additional, O’Donnell, Denise, additional, Ogbe, Ane, additional, Pace, Matthew, additional, Payne, Brendan A.I., additional, Platt, Gareth, additional, Poolan, Sonia, additional, Provine, Nicholas, additional, Ramamurthy, Narayan, additional, Robinson, Nichola, additional, Romaniuk, Leigh, additional, Rongkard, Patpong, additional, Sampson, Oliver L., additional, Simmons, Beatrice, additional, Spegarova, Jarmila S., additional, Stephenson, Emily, additional, Subramaniam, Kris, additional, Thaventhiran, James, additional, Thomas, Sarah, additional, Travis, Simon, additional, Tucker, Stephanie, additional, Turton, Helena, additional, Watson, Adam, additional, Watson, Lisa, additional, Weeks, Esme, additional, Wilson, Robert, additional, Wood, Steven, additional, Wright, Rachel, additional, Xiao, Huiyuan, additional, and Zawia, Amira A.T., additional

Published
2021
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