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1. Sim2Ls: FAIR simulation workflows and data

Author

Hunt, Martin, Clark, Steven, Mejia, Daniel, Desai, Saaketh, and Strachan, Alejandro

Subjects
Computer Science - Digital Libraries
Abstract

Just like the scientific data they generate, simulation workflows for research should be findable, accessible, interoperable, and reusable (FAIR). However, while significant progress has been made towards FAIR data, the majority of science and engineering workflows used in research remain poorly documented and often unavailable, involving ad hoc scripts and manual steps, hindering reproducibility and stifling progress. We introduce Sim2Ls (pronounced simtools) and the Sim2L Python library that allow developers to create and share end-to-end computational workflows with well-defined and verified inputs and outputs. The Sim2L library makes Sim2Ls, their requirements, and their services discoverable, verifies inputs and outputs, and automatically stores results in a globally-accessible simulation cache and results database. This simulation ecosystem is available in nanoHUB, an open platform that also provides publication services for Sim2Ls, a computational environment for developers and users, and the hardware to execute runs and store results at no cost. We exemplify the use of Sim2Ls using two applications and discuss best practices towards FAIR simulation workflows and associated data., Comment: 23 pages, 5 figures

Published
2021
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3. A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates

Author

Fowler, Philip W, Wright, Carla, Spiers, Helen, Zhu, Tingting, Baeten, Elisabeth ML, Hoosdally, Sarah W, Cruz, Ana L Gibertoni, Roohi, Aysha, Kouchaki, Samaneh, Walker, Timothy M, Peto, Timothy EA, Miller, Grant, Lintott, Chris, Clifton, David, Crook, Derrick W, Walker, A Sarah, Barilar, Ivan, Battaglia, Simone, Borroni, Emanuele, Brandao, Angela Pires, Brankin, Alice, Cabibbe, Andrea Maurizio, Carter, Joshua, Cirillo, Daniela Maria, Claxton, Pauline, Clifton, David A, Cohen, Ted, Coronel, Jorge, Earle, Sarah G, Escuyer, Vincent, Ferrazoli, Lucilaine, Gao, George F, Gardy, Jennifer, Gharbia, Saheer, Ghisi, Kelen Teixeira, Ghodousi, Arash, Cruz, Ana Luıza Gibertoni, Grazian, Clara, Guthrie, Jennifer L, He, Wencong, Hoffmann, Harald, Hoosdally, Sarah J, Hunt, Martin, Iqbal, Zamin, Ismail, Nazir Ahmed, Jarrett, Lisa, Joseph, Lavania, Jou, Ruwen, Kambli, Priti, Knaggs, Jeff, Koch, Anastasia, Kohlerschmidt, Donna, Lachapelle, Alexander S, Lalvani, Ajit, Lapierre, Simon Grandjean, Laurenson, Ian F, Letcher, Brice, Lin, Wan-Hsuan, Liu, Chunfa, Liu, Dongxin, Malone, Kerri M, Mandal, Ayan, Matias, Daniela, Meintjes, Graeme, Mendes, Flavia Freitas, Merker, Matthias, Mihalic, Marina, Millard, James, Miotto, Paolo, Mistry, Nerges, Moore, David, Dreyer, Viola, Chetty, Darren, Musser, Kimberlee A, Ngcamu, Dumisani, Nhung, Hoang Ngoc, Grandjean, Louis, Nilgiriwala, Kayzad Soli, Nimmo, Camus, Okozi, Nana, Oliveira, Rosangela Siqueira, Omar, Shaheed Vally, Paton, Nicholas, Pinhata, Juliana Maira Watanabe, Plesnik, Sara, Puyen, Zully M, Rabodoarivelo, Marie Sylvianne, Rakotosamimanana, Niaina, Rancoita, Paola MV, Rathod, Priti, Robinson, Esther, Rodger, Gillian, Rodrigues, Camilla, Rodwell, Timothy C, and Santos-Lazaro, David

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Emerging Infectious Diseases, Infectious Diseases, Prevention, Antimicrobial Resistance, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Antitubercular Agents, Humans, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Tuberculosis, Volunteers, Zooniverse Volunteer Community, CRyPTIC Consortium, M. tuberculosis, antibiotics, citizen science, clinical microbiology, infectious disease, microbiology, tuberculosis, Biochemistry and Cell Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally, this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, each being present at a pre-determined concentration, thereby determining if the sample isresistant or susceptible to each sample. The minimum inhibitory concentration (MIC) of a drug is the lowestconcentration that inhibits growth and is a more useful quantity but requires each sample to be tested at a range ofconcentrations for each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is still an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11-17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing.

Published
2022

4. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis

Author

Walker, Timothy M, Miotto, Paolo, Köser, Claudio U, Fowler, Philip W, Knaggs, Jeff, Iqbal, Zamin, Hunt, Martin, Chindelevitch, Leonid, Farhat, Maha R, Cirillo, Daniela Maria, Comas, Iñaki, Posey, James, Omar, Shaheed V, Peto, Timothy EA, Suresh, Anita, Uplekar, Swapna, Laurent, Sacha, Colman, Rebecca E, Nathanson, Carl-Michael, Zignol, Matteo, Walker, Ann Sarah, Crook, Derrick W, Ismail, Nazir, Rodwell, Timothy C, Consortium, the SeqTreat Consortium CRyPTIC, Walker, A Sarah, Steyn, Adrie JC, Lalvani, Ajit, Baulard, Alain, Christoffels, Alan, Mendoza-Ticona, Alberto, Trovato, Alberto, Skrahina, Alena, Lachapelle, Alexander S, Brankin, Alice, Piatek, Amy, Cruz, Ana Gibertoni, Koch, Anastasia, Cabibbe, Andrea Maurizio, Spitaleri, Andrea, Brandao, Angela P, Chaiprasert, Angkana, Barbova, Anna, Van Rie, Annelies, Ghodousi, Arash, Bainomugisa, Arnold, Mandal, Ayan, Roohi, Aysha, Javid, Babak, Zhu, Baoli, Letcher, Brice, Rodrigues, Camilla, Nimmo, Camus, NATHANSON, Carl-Michael, Duncan, Carla, Coulter, Christopher, Utpatel, Christian, Liu, Chunfa, Grazian, Clara, Kong, Clare, Wilson, Daniel J, Matias, Daniela, Jorgensen, Danielle, Zimenkov, Danila, Chetty, Darren, Moore, David AJ, Clifton, David A, van Soolingen, Dick, Liu, Dongxin, Kohlerschmidt, Donna, Barreira, Draurio, Ngcamu, Dumisani, Lazaro, Elias David Santos, Kelly, Ellis, Borroni, Emanuele, Roycroft, Emma, Andre, Emmanuel, Böttger, Erik C, Robinson, Esther, Menardo, Fabrizio, Mendes, Flavia F, Jamieson, Frances B, Coll, Francesc, Gao, George Fu, Kasule, George W, Rossolini, Gian Maria, Rodger, Gillian, Smith, E Grace, Meintjes, Graeme, Thwaites, Guy, Hoffmann, Harald, Albert, Heidi, Cox, Helen, Laurenson, Ian F, and Arandjelovic, Irena

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Microbiology, Clinical Sciences, Tuberculosis, Infectious Diseases, Rare Diseases, Antimicrobial Resistance, Orphan Drug, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Antitubercular Agents, Drug Resistance, Ethambutol, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, World Health Organization, CRyPTIC Consortium, Seq&Treat Consortium, Immunology, Medical microbiology
Abstract

BackgroundMolecular diagnostics are considered the most promising route to achieving rapid, universal drug susceptibility testing for Mycobacterium tuberculosiscomplex (MTBC). We aimed to generate a WHO endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction.MethodsA candidate gene approach was used to identify mutations as associated with resistance, or consistent with susceptibility, for 13 WHO endorsed anti-tuberculosis drugs. 38,215 MTBC isolates with paired whole-genome sequencing and phenotypic drug susceptibility testing data were amassed from 45 countries. For each mutation, a contingency table of binary phenotypes and presence or absence of the mutation computed positive predictive value, and Fisher's exact tests generated odds ratios and Benjamini-Hochberg corrected p-values. Mutations were graded as Associated with Resistance if present in at least 5 isolates, if the odds ratio was >1 with a statistically significant corrected p-value, and if the lower bound of the 95% confidence interval on the positive predictive value for phenotypic resistance was >25%. A series of expert rules were applied for final confidence grading of each mutation.Findings15,667 associations were computed for 13,211 unique mutations linked to one or more drugs. 1,149/15,667 (7·3%) mutations were classified as associated with phenotypic resistance and 107/15,667 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was >80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were classified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs.InterpretationThis first WHO endorsed catalogue of molecular targets for MTBC drug susceptibility testing provides a global standard for resistance interpretation. Its existence should encourage the implementation of molecular diagnostics by National Tuberculosis Programmes.FundingUNITAID, Wellcome, MRC, BMGF.

Published
2022

5. Real-Time Multirate Multiband Amplification for Hearing Aids

Author

Sokolova, Alice, Sengupta, Dhiman, Hunt, Martin, Gupta, Rajesh, Aksanli, Baris, Harris, Fredric, and Garudadri, Harinath

Subjects
Information and Computing Sciences, Computer Vision and Multimedia Computation, Assistive Technology, Bioengineering, Ear, Hearing aids, digital signal processing, auditory system, channelization, wearable computers, speech processing, open source hardware, real-time systems, embedded software, research initiatives, Engineering, Technology, Information and computing sciences
Abstract

Hearing loss is a common problem affecting the quality of life for thousands of people. However, many individuals with hearing loss are dissatisfied with the quality of modern hearing aids. Amplification is the main method of compensating for hearing loss in modern hearing aids. One common amplification technique is dynamic range compression, which maps audio signals onto a person's hearing range using an amplification curve. However, due to the frequency dependent nature of the human cochlea, compression is often performed independently in different frequency bands. This paper presents a real-time multirate multiband amplification system for hearing aids, which includes a multirate channelizer for separating an audio signal into eleven standard audiometric frequency bands, and an automatic gain control system for accurate control of the steady state and dynamic behavior of audio compression as specified by ANSI standards. The spectral channelizer offers high frequency resolution with low latency of 5.4 ms and about 14× improvement in complexity over a baseline design. Our automatic gain control includes a closed-form solution for satisfying any designated attack and release times for any desired compression parameters. The increased frequency resolution and precise gain adjustment allow our system to more accurately fulfill audiometric hearing aid prescriptions.

Published
2022

8. Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing

Author

Allix-Béguec, Caroline, Arandjelovic, Irena, Bi, Lijun, Beckert, Patrick, Bonnet, Maryline, Bradley, Phelim, Cabibbe, Andrea M, Cancino-Muñoz, Irving, Caulfield, Mark J, Chaiprasert, Angkana, Cirillo, Daniela, Clifton, David, Comas, Iñaki, Crook, Derrick W, De Filippo, Maria Rosaria, de Neeling, Han, Diel, Roland, Drobniewski, Francis A, Faksri, Kiatichai, Farhat, Maha R, Fleming, Joy, Fowler, Philip, Fowler, Tom A, Gao, Qian, Gardy, Jennifer, Gascoyne-Binzi, Deborah, Cruz, Ana Gibertoni, Gil-Brusola, Ana, Golubchik, Tanya, Gonzalo, Ximena, Grandjean, Louis, He, Guangxue, Guthrie, Jennifer L, Hoosdally, Sarah, Hunt, Martin, Iqbal, Zamin, Ismail, Nazir, Johnston, James, Khanzada, Faisal Masood, Khor, Chiea Chuen, Kohl, Thomas A, Kong, Clare, Lipworth, Sam, Liu, Qingyun, Maphalala, Gugu, Martinez, Elena, Mathys, Vanessa, Merker, Matthias, Miotto, Paolo, Mistry, Nerges, Moore, David, Murray, Megan, Niemann, Stefan, Ong, Rick Twee-Hee, Peto, Tim EA, Posey, James E, Prammananan, Therdsak, Pym, Alexander, Rodrigues, Camilla, Rodrigues, Mabel, Rodwell, Timothy, Rossolini, Gian Maria, Padilla, Elisabeth Sánchez, Schito, Marco, Shen, Xin, Shendure, Jay, Sintchenko, Vitali, Sloutsky, Alex, Smith, E Grace, Snyder, Matthew, Soetaert, Karine, Starks, Angela M, Supply, Philip, Suriyapol, Prapat, Tahseen, Sabira, Tang, Patrick, Teo, Yik-Ying, Thuong, Thuong Nguyen Thuy, Thwaites, Guy, Tortoli, Enrico, Omar, Shaheed Vally, van Soolingen, Dick, Walker, A Sarah, Walker, Timothy M, Wilcox, Mark, Wilson, Daniel J, Wyllie, David, Yang, Yang, Zhang, Hongtai, Zhao, Yanlin, and Zhu, Baoli

Subjects
Genetics, Human Genome, Tuberculosis, Clinical Research, Patient Safety, Prevention, Rare Diseases, Infectious Diseases, Antimicrobial Resistance, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Antitubercular Agents, Drug Resistance, Bacterial, Ethambutol, Genome, Bacterial, Genotype, Humans, Isoniazid, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, Phenotype, Pyrazinamide, Rifampin, Whole Genome Sequencing, CRyPTIC Consortium and the 100, 000 Genomes Project, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThe World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear.MethodsWe obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance.ResultsA total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted.ConclusionsGenotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.).

Published
2018

10. Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Author

Bradnam, Keith R., Fass, Joseph N., Alexandrov, Anton, Baranay, Paul, Bechner, Michael, Birol, İnanç, Boisvert, Sébastien, Chapman, Jarrod A., Chapuis, Guillaume, Chikhi, Rayan, Chitsaz, Hamidreza, Chou, Wen-Chi, Corbeil, Jacques, Del Fabbro, Cristian, Docking, T. Roderick, Durbin, Richard, Earl, Dent, Emrich, Scott, Fedotov, Pavel, Fonseca, Nuno A., Ganapathy, Ganeshkumar, Gibbs, Richard A., Gnerre, Sante, Godzaridis, Élénie, Goldstein, Steve, Haimel, Matthias, Hall, Giles, Haussler, David, Hiatt, Joseph B., Ho, Isaac Y., Howard, Jason, Hunt, Martin, Jackman, Shaun D., Jaffe, David B, Jarvis, Erich, Jiang, Huaiyang, Kazakov, Sergey, Kersey, Paul J., Kitzman, Jacob O., Knight, James R., Koren, Sergey, Lam, Tak-Wah, Lavenier, Dominique, Laviolette, François, Li, Yingrui, Li, Zhenyu, Liu, Binghang, Liu, Yue, Luo, Ruibang, MacCallum, Iain, MacManes, Matthew D, Maillet, Nicolas, Melnikov, Sergey, Vieira, Bruno Miguel, Naquin, Delphine, Ning, Zemin, Otto, Thomas D., Paten, Benedict, Paulo, Octávio S., Phillippy, Adam M., Pina-Martins, Francisco, Place, Michael, Przybylski, Dariusz, Qin, Xiang, Qu, Carson, Ribeiro, Filipe J, Richards, Stephen, Rokhsar, Daniel S., Ruby, J. Graham, Scalabrin, Simone, Schatz, Michael C., Schwartz, David C., Sergushichev, Alexey, Sharpe, Ted, Shaw, Timothy I., Shendure, Jay, Shi, Yujian, Simpson, Jared T., Song, Henry, Tsarev, Fedor, Vezzi, Francesco, Vicedomini, Riccardo, Wang, Jun, Worley, Kim C., Yin, Shuangye, Yiu, Siu-Ming, Yuan, Jianying, Zhang, Guojie, Zhang, Hao, Zhou, Shiguo, and Korf, Ian F.

Subjects
Quantitative Biology - Genomics
Abstract

Background - The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results - In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions - Many current genome assemblers produced useful assemblies, containing a significant representation of their genes, regulatory sequences, and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another., Comment: Additional files available at http://korflab.ucdavis.edu/Datasets/Assemblathon/Assemblathon2/Additional_files/ Major changes 1. Accessions for the 3 read data sets have now been included 2. New file: spreadsheet containing details of all Study, Sample, Run, & Experiment identifiers 3. Made miscellaneous changes to address reviewers comments. DOIs added to GigaDB datasets

Published
2013
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14. Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Author

Bradnam, Keith R, Fass, Joseph N, Alexandrov, Anton, Baranay, Paul, Bechner, Michael, Birol, Inanç, Boisvert, Sébastien, Chapman, Jarrod A, Chapuis, Guillaume, Chikhi, Rayan, Chitsaz, Hamidreza, Chou, Wen-Chi, Corbeil, Jacques, Del Fabbro, Cristian, Docking, T, Durbin, Richard, Earl, Dent, Emrich, Scott, Fedotov, Pavel, Fonseca, Nuno A, Ganapathy, Ganeshkumar, Gibbs, Richard A, Gnerre, Sante, Godzaridis, Élénie, Goldstein, Steve, Haimel, Matthias, Hall, Giles, Haussler, David, Hiatt, Joseph B, Ho, Isaac Y, Howard, Jason, Hunt, Martin, Jackman, Shaun D, Jaffe, David B, Jarvis, Erich D, Jiang, Huaiyang, Kazakov, Sergey, Kersey, Paul J, Kitzman, Jacob O, Knight, James R, Koren, Sergey, Lam, Tak-Wah, Lavenier, Dominique, Laviolette, François, Li, Yingrui, Li, Zhenyu, Liu, Binghang, Liu, Yue, Luo, Ruibang, MacCallum, Iain, MacManes, Matthew D, Maillet, Nicolas, Melnikov, Sergey, Naquin, Delphine, Ning, Zemin, Otto, Thomas D, Paten, Benedict, Paulo, Octávio S, Phillippy, Adam M, Pina-Martins, Francisco, Place, Michael, Przybylski, Dariusz, Qin, Xiang, Qu, Carson, Ribeiro, Filipe J, Richards, Stephen, Rokhsar, Daniel S, Ruby, J, Scalabrin, Simone, Schatz, Michael C, Schwartz, David C, Sergushichev, Alexey, Sharpe, Ted, Shaw, Timothy I, Shendure, Jay, Shi, Yujian, Simpson, Jared T, Song, Henry, Tsarev, Fedor, Vezzi, Francesco, Vicedomini, Riccardo, Vieira, Bruno M, Wang, Jun, Worley, Kim C, Yin, Shuangye, Yiu, Siu-Ming, Yuan, Jianying, Zhang, Guojie, Zhang, Hao, Zhou, Shiguo, and Korf, Ian F

Abstract

Abstract Background The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.

Published
2013

17. Over-expansion of right ventricle to pulmonary artery conduits during transcatheter pulmonary valve placement

Author

Dana M. Boucek, Athar M. Qureshi, Varun Aggarwal, Zachary A. Spigel, Joyce Johnson, Robert G. Gray, and Mary Hunt Martin

Subjects
Pediatrics, Perinatology and Child Health, General Medicine, Cardiology and Cardiovascular Medicine
Abstract

Objectives: To determine the safety and feasibility of over-expansion of right ventricle to pulmonary artery conduits during transcatheter pulmonary valve placement. Background: Transcatheter pulmonary valve placement is an alternative to surgical pulmonary valve replacement. Traditionally, it was thought to be unsafe to expand a conduit to >110% of its original size. Methods: This retrospective cohort study from two centers includes patients with right ventricle to pulmonary artery conduits with attempted transcatheter pulmonary valve placement from 2010 to 2017. Demographic, procedural, echocardiographic and follow-up data, and complications were evaluated in control and overdilation (to >110% original conduit size) groups. Results: One hundred and seventy-two patients (51 overdilation and 121 control) had attempted transcatheter pulmonary valve placement (98% successful). The overdilation group was younger (11.2 versus 16.7 years, p < 0.001) with smaller conduits (15 versus 22 mm, p < 0.001); however, the final valve size was not significantly different (19.7 versus 20.2 mm, p = 0.2). Baseline peak echocardiographic gradient was no different (51.8 versus 55.6 mmHg, p = 0.3). Procedural complications were more frequent in overdilation (18%) than control (7%) groups (most successfully addressed during the procedure). One patient from each group required urgent surgical intervention, with no procedural mortality. Follow-up echocardiographic peak gradients were similar (24.1 versus 26 mmHg, p = 0.5). Conclusions: Over-expansion of right ventricle to pulmonary artery conduits during transcatheter pulmonary valve placement can be performed successfully. Procedural complications are more frequent with conduit overdilation, but there was no difference in the rate of life-threatening complications. There was no difference in valve function at most recent follow-up, and no difference in rate of reintervention. The long-term outcomes of transcatheter pulmonary valve placement with conduit over-expansion requires further study.

Published
2023
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19. Maturity biomarkers predicting storage performance of early-harvested yellow-fleshed kiwifruit identified using integrated multi-omics analysis

Author

Favre, Laurie, primary, Hunter, Donald A., additional, O’Donoghue, Erin M., additional, Erridge, Zoe A., additional, Napier, Nathanael J., additional, Cho, Jung, additional, Nangul, Agam, additional, O’Donnell, Kristie, additional, Pidakala, Paul, additional, Martin, Philip, additional, Somerfield, Sheryl D., additional, Hunt, Martin, additional, McGhie, Tony K., additional, Cooney, Janine M., additional, Saei, Ali, additional, David, Charles, additional, Chen, Ronan K.Y., additional, McKenzie, Marian J., additional, Brewster, Diane, additional, Gibon, Yves, additional, Heyes, Julian A., additional, Feng, Jinquan, additional, Lill, Ross E., additional, and Brummell, David A., additional

Published
2023
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22. Transcatheter and Surgical Aortic Valve Implantation in Children, Adolescents, and Young Adults With Congenital Heart Disease

Author

Dwight M. Robertson, Dana M. Boucek, Mary Hunt Martin, Robert G. Gray, Eric R. Griffiths, Aaron W. Eckhauser, Zhining Ou, Linda M. Lambert, Richard V. Williams, and S. Adil Husain

Subjects
Heart Defects, Congenital, Heart Valve Prosthesis Implantation, Transcatheter Aortic Valve Replacement, Young Adult, Treatment Outcome, Adolescent, Risk Factors, Aortic Valve, Humans, Aortic Valve Stenosis, Child, Cardiology and Cardiovascular Medicine, Retrospective Studies
Abstract

Transcatheter aortic valve implantation (TAVI) is common in adults but rare in children and adolescents. Since 2014, our institution has incorporated a transcatheter approach as an option for aortic valve replacement in this population. The purpose of this study was to compare short-term outcomes of TAVI with surgical aortic valve replacement (SAVR). This single-center, retrospective study included patients aged 10 to 21 years who had a native SAVR or TAVI between January 2010 to April 2020. Comparative analysis of baseline characteristics and a composite outcome (stroke within 6 months, readmission within 30 days, death) between SAVR and TAVI were made using chi-square test or Wilcoxon rank sum test, as appropriate. Of the 77 patients who underwent native aortic valve implantation during the study period (60 SAVR, 17 TAVI), 46 were aged 10 to 21 years (30 SAVR, 16 TAVI). Median follow-up was 3.8 years (interquartile range 1.5 to 4.9) for the SAVR group and 1.5 years (interquartile range 1.1 to 1.2) for the TAVI group. There was no difference in the composite outcome between groups. Patients in the SAVR group were more likely to have undergone concomitant surgical intervention and have longer intensive care unit and hospital stays. In conclusion, our study suggests similar short-term outcomes between SAVR and TAVI in children and young adults aged 10 to 21 years. Longer-term studies are essential to understand the utility of TAVI and to better consider the option of a transcatheter approach as an alternative to SAVR in the pediatric population.

Published
2022
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23. Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Author

Sonnenkalb, Lindsay, primary, Carter, Joshua James, additional, Spitaleri, Andrea, additional, Iqbal, Zamin, additional, Hunt, Martin, additional, Malone, Kerri Marie, additional, Utpatel, Christian, additional, Cirillo, Daniela Maria, additional, Rodrigues, Camilla, additional, Nilgiriwala, Kayzad Soli, additional, Fowler, Philip William, additional, Merker, Matthias, additional, Niemann, Stefan, additional, Barilar, Ivan, additional, Battaglia, Simone, additional, Borroni, Emanuele, additional, Brandao, Angela Pires, additional, Brankin, Alice, additional, Cabibbe, Andrea Maurizio, additional, Carter, Joshua, additional, Claxton, Pauline, additional, Clifton, David A, additional, Cohen, Ted, additional, Coronel, Jorge, additional, Crook, Derrick W, additional, Dreyer, Viola, additional, Earle, Sarah G, additional, Escuyer, Vincent, additional, Ferrazoli, Lucilaine, additional, Fowler, Philip W, additional, Fu Gao, George, additional, Gardy, Jennifer, additional, Gharbia, Saheer, additional, Ghisi, Kelen Teixeira, additional, Ghodousi, Arash, additional, Gibertoni Cruz, Ana Luíza, additional, Grandjean, Louis, additional, Grazian, Clara, additional, Groenheit, Ramona, additional, Guthrie, Jennifer L, additional, He, Wencong, additional, Hoffmann, Harald, additional, Hoosdally, Sarah J, additional, Ismail, Nazir Ahmed, additional, Jarrett, Lisa, additional, Joseph, Lavania, additional, Jou, Ruwen, additional, Kambli, Priti, additional, Khot, Rukhsar, additional, Knaggs, Jeff, additional, Koch, Anastasia, additional, Kohlerschmidt, Donna, additional, Kouchaki, Samaneh, additional, Lachapelle, Alexander S, additional, Lalvani, Ajit, additional, Grandjean Lapierre, Simon, additional, Laurenson, Ian F, additional, Letcher, Brice, additional, Lin, Wan-Hsuan, additional, Liu, Chunfa, additional, Liu, Dongxin, additional, Malone, Kerri M, additional, Mandal, Ayan, additional, Mansjö, Mikael, additional, Matias, Daniela, additional, Meintjes, Graeme, additional, de Freitas Mendes, Flávia, additional, Mihalic, Marina, additional, Millard, James, additional, Miotto, Paolo, additional, Mistry, Nerges, additional, Moore, David, additional, Musser, Kimberlee A, additional, Ngcamu, Dumisani, additional, Hoang, Ngoc Nhung, additional, Nimmo, Camus, additional, Okozi, Nana, additional, Oliveira, Rosangela Siqueira, additional, Omar, Shaheed Vally, additional, Paton, Nicholas, additional, Peto, Timothy EA, additional, Watanabe Pinhata, Juliana Maira, additional, Plesnik, Sara, additional, Puyen, Zully M, additional, Rabodoarivelo, Marie Sylvianne, additional, Rakotosamimanana, Niaina, additional, Rancoita, Paola MV, additional, Rathod, Priti, additional, Rodger, Gillian, additional, Rodwell, Timothy C, additional, Roohi, Eaysha, additional, Santos-Lazaro, David, additional, Shah, Sanchi, additional, Kohl, Thomas Andreas, additional, Smith, Grace, additional, Solano, Walter, additional, Supply, Philip, additional, Surve, Utkarsha, additional, Tahseen, Sabira, additional, Thuong, Nguyen Thuy Thuong, additional, Thwaites, Guy, additional, Todt, Katharina, additional, Trovato, Alberto, additional, Van Rie, Annelies, additional, Vijay, Srinivasan, additional, Walker, Timothy M, additional, Walker, Sarah A, additional, Warren, Robin, additional, Werngren, Jim, additional, Wijkander, Maria, additional, Wilkinson, Robert J, additional, Wilson, Daniel J, additional, Wintringer, Penelope, additional, Yu, Xin Xiao, additional, Yang, Yang, additional, Zhao, Yanlin, additional, Yao, Shen-Yuan, additional, and Zhu, Baoli, additional

Published
2023
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25. Hostile: accurate decontamination of microbial host sequences.

Author

Constantinides, Bede, Hunt, Martin, and Crook, Derrick W

Subjects
*DECONTAMINATION of food, *MORAL reasoning, *LEGAL reasoning
Abstract

Motivation Microbial sequences generated from clinical samples are often contaminated with human host sequences that must be removed for ethical and legal reasons. Care must be taken to excise host sequences without inadvertently removing target microbial sequences to the detriment of downstream analyses such as variant calling and de novo assembly. Results To facilitate accurate host decontamination of both short and long sequencing reads, we developed Hostile, a tool capable of accurate host read removal using a laptop. We demonstrate that our approach removes at least 99.6% of real human reads and retains at least 99.989% of simulated bacterial reads. Using Hostile with a masked reference genome further increases bacterial read retention (⁠ ≥ 99.997%) with negligible (⁠ ≤ 0.001%) reduction in human read removal performance. Compared with an existing tool, Hostile removes 21%–23% more human short reads and 21–43 times fewer bacterial reads, typically in less time. Availability and implementation Hostile is implemented as an MIT-licensed Python package available from https://github.com/bede/hostile together with supplementary material. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Author

Sonnenkalb, Lindsay, Carter, Joshua James, Spitaleri, Andrea, Iqbal, Zamin, Hunt, Martin, Malone, Kerri Marie, Utpatel, Christian, Cirillo, Daniela Maria, Rodrigues, Camilla, Nilgiriwala, Kayzad Soli, Fowler, Philip William, Merker, Matthias, Niemann, Stefan, Consortium, The Comprehensive Resistance Prediction for Tuberculosis: an International, Barilar, I, Battaglia, S, Borroni, E, Brandao, AP, Brankin, A, Cabibbe, AM, Carter, J, Claxton, P, Clifton, DA, Cohen, T, Coronel, J, Crook, DW, Dreyer, V, Earle, SG, Escuyer, V, Ferrazoli, L, Fowler, PW, Gao, G Fu, Gardy, J, Gharbia, S, Ghisi, KT, Ghodousi, A, Cruz, AL Gibertoni, Grandjean, L, Grazian, C, Groenheit, R, Guthrie, JL, He, W, Hoffmann, H, Hoosdally, SJ, Ismail, NA, Jarrett, L, Joseph, L, Jou, R, Kambli, P, Khot, R, Knaggs, J, Koch, A, Kohlerschmidt, D, Kouchaki, S, Lachapelle, AS, Lalvani, A, Lapierre, S Grandjean, Laurenson, IF, Letcher, B, Lin, WH, Liu, C, Liu, D, Malone, KM, Mandal, A, Mansjö, M, Matias, D, Meintjes, G, de Freitas Mendes, F, Mihalic, M, Millard, J, Miotto, P, Mistry, N, Moore, D, Musser, KA, Ngcamu, D, Hoang, NN, Nimmo, C, Okozi, N, Oliveira, RS, Omar, SV, Paton, N, Peto, TE, Pinhata, JM Watanabe, Plesnik, S, Puyen, ZM, Rabodoarivelo, MS, Rakotosamimanana, N, Rancoita, PM, Rathod, P, Rodger, G, Rodwell, TC, Roohi, E, Santos-Lazaro, D, Shah, S, Kohl, TA, Smith, G, Solano, W, Supply, P, Surve, U, Tahseen, S, and Thuong, NTT

Subjects
Model organisms, Human Biology & Physiology, FOS: Clinical medicine, Immunology, Infectious Disease
Abstract

Background: Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we combined experimental evolution, protein modelling, genome sequencing, and phenotypic data. Methods: For this in-vitro and in-silico data analysis, we used a novel in-vitro evolutionary model using subinhibitory drug concentrations to select bedaquiline-resistant and clofazimine-resistant mutants. We determined bedaquiline and clofazimine minimum inhibitory concentrations and did Illumina and PacBio sequencing to characterise selected mutants and establish a mutation catalogue. This catalogue also includes phenotypic and genotypic data of a global collection of more than 14 000 clinical Mycobacterium tuberculosis complex isolates, and publicly available data. We investigated variants implicated in bedaquiline resistance by protein modelling and dynamic simulations. Findings: We discerned 265 genomic variants implicated in bedaquiline resistance, with 250 (94%) variants affecting the transcriptional repressor (Rv0678) of the MmpS5–MmpL5 efflux system. We identified 40 new variants in vitro, and a new bedaquiline resistance mechanism caused by a large-scale genomic rearrangement. Additionally, we identified in vitro 15 (7%) of 208 mutations found in clinical bedaquiline-resistant isolates. From our in-vitro work, we detected 14 (16%) of 88 mutations so far identified as being associated with clofazimine resistance and also seen in clinically resistant strains, and catalogued 35 new mutations. Structural modelling of Rv0678 showed four major mechanisms of bedaquiline resistance: impaired DNA binding, reduction in protein stability, disruption of protein dimerisation, and alteration in affinity for its fatty acid ligand. Interpretation: Our findings advance the understanding of drug resistance mechanisms in M tuberculosis complex strains. We have established an extended mutation catalogue, comprising variants implicated in resistance and susceptibility to bedaquiline and clofazimine. Our data emphasise that genotypic testing can delineate clinical isolates with borderline phenotypes, which is essential for the design of effective treatments. Funding: Leibniz ScienceCampus Evolutionary Medicine of the Lung, Deutsche Forschungsgemeinschaft, Research Training Group 2501 TransEvo, Rhodes Trust, Stanford University Medical Scientist Training Program, National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Bill & Melinda Gates Foundation, Wellcome Trust, and Marie Skłodowska-Curie Actions.

Published
2023
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34. Selective pulmonary artery occlusion to treat hemoptysis associated with pulmonary venous obstruction

Author

Melissa S.W. Yamauchi, Mary Hunt Martin, Harlan R. Muntz, and Ronald W. Day

Subjects
Bronchoscopy, Hemoptysis, Pulmonary arterial hypertension, Pulmonary vein stenosis, Diseases of the respiratory system, RC705-779
Abstract

Hemoptysis may occur in patients with pulmonary venous obstruction and prominent decompressing vessels in the airways adjacent to the affected pulmonary veins. The options for treatment of hemoptysis are limited, particularly when efforts to alleviate pulmonary venous obstruction have failed. Here we describe a patient with hemoptysis associated with stenosis of the central left upper pulmonary vein and occlusion of the central left lower pulmonary vein. The left upper pulmonary vein was dilated with balloon catheters and a vascular plug was placed in the left lower pulmonary artery. Vascular engorgement regressed in the left bronchus and hemoptysis has not recurred for 4 years despite recurrence of left upper pulmonary vein stenosis. Selective occlusion of branch pulmonary arteries may be an effective option for the treatment of hemoptysis from bleeding in lung segments with inoperable pulmonary venous obstruction.

Published
2017
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35. Technical Report: GenoTyphi Implementation in Mykrobe

Author

Holt, Kathryn, Ingle, Danielle, Hawkey, Jane, Dyson, Zoe, and Hunt, Martin

Subjects
genotyping, typhi, typhoid
Abstract

The GenoTyphi genotyping scheme divides theSalmonella enterica serovarTyphi ("Typhi") population into 4 major lineages, and >75 different clades and subclades.The scheme was introduced in the paper"An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid", Wong et al, 2016, Nature Communications. Subsequent updates, including new genotypes and mutations conferring resistance to fluoroquinolones and azithromycin, are summarised in"Five years of GenoTyphi: updates to the global Salmonella Typhi genotyping framework", Dyson & Holt, 2021, Journal of Infectious Diseases. The original code that was made available for assigning GenoTyphi genotypes to Typhi genomes, implemented in Python, tookas input BAM or VCF files that the user has already generated by mapping Illumina reads to the reference genome for Typhi CT18. Here we describe a new kmer-based approach to assigning GenoTyphi genotypes to Typhi genomes, implemented in the Mykrobe open-source software platform and taking raw sequencing reads (FASTQ files) as input. This implementation also includes five newly defined genotypes, taking the total to n=87. We tested the new implementation on n=12,848 Typhi genomes, and found near-perfect concordance with the original mapping-based implementation. Code is available athttps://github.com/katholt/genotyphi(v2.0, doi: 10.5281/zenodo.7430538).

Published
2022
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37. Integrated multi-omic analysis of fruit maturity identifies biomarkers with drastic abundance shifts spanning the harvest period in ‘Royal Gala’ apple

Author

Favre, Laurie, primary, Hunter, Donald A., additional, O’Donoghue, Erin M., additional, Erridge, Zoe A., additional, Napier, Nathanael J., additional, Somerfield, Sheryl D., additional, Hunt, Martin, additional, McGhie, Tony K., additional, Cooney, Janine M., additional, Saei, Ali, additional, Chen, Ronan K.Y., additional, McKenzie, Marian J., additional, Brewster, Diane, additional, Martin, Harry, additional, Punter, Matt, additional, Carr, Bridie, additional, Tattersall, Anna, additional, Johnston, Jason W., additional, Gibon, Yves, additional, Heyes, Julian A., additional, Lill, Ross E., additional, and Brummell, David A., additional

Published
2022
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40. ABC of Lung Cancer

Author

Ian Hunt, Martin M. Muers, Tom Treasure, Ian Hunt, Martin M. Muers, Tom Treasure

Published
2009

41. A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics

Author

Brankin, Alice, Malone, Kerri, Barilar, Ivan, Battaglia, Simone, Borroni, Emanuele, Pires Brandao, Angela, Cabibbe, Andrea Maurizio, Carter, Joshua, Chetty, Darren, Cirillo, Daniela María, Claxton, Pauline, Clifton, David, Cohen, Ted, Coronel, Jorge, Crook, Derrick, Dreyer, Viola, Earle, Sarah, Escuyer, Vincent, Ferrazoli, Lucilaine, Gāo, George Fú, Gardy, Jennifer, Gharbia, Saheer, Teixeira Ghisi, Kelen, Ghodousi, Arash, Gibertoni Cruz, Ana Lúıza, Grandjean, Louis, Grazian, Clara, Groenheit, Ramona, Guthrie, Jennifer, He, Wencong, Hoffmann, Harald, J., Sarah, Hunt, Martin, Ismail, Nazir Ahmed, Jarrett, Lisa, Joseph, Lavania, Jou, Ruwen, Kambli, Priti, Khot, Rukhsar, Knaggs, Jeff, Koch, Anastasia, Kohlerschmidt, Donna, Kouchaki, Samaneh, Lachapelle, Alexander, Lalvani, Ajit, Grandjean Lapierre, Simon, Laurenson, Ian, Letcher, Brice, Lin, Wan-Hsuan, Liu, Chunfa, Liu, Dongxin, Mandal, Ayan, Mansjö, Mikael, Matias, Daniela, Meintjes, Graeme, de Freitas Mendes, Flávia, Merker, Matthias, Mihalic, Marina, Millard, James, Miotto, Paolo, Mistry, Nerges, Moore, David, Musser, Kimberlee A., Ngcamu, Dumisani, Ngoc Nhung, Hoang, Niemann, Stefan, Soli Nilgiriwala, Kayzad, Nimmo, Camus, O'Donnell, Max, Okozi, Nana, Siqueira Oliveira, Rosangela, Omar, Shaheed Vally, Paton, Nicholas, Peto, Timothy Ea, Watanabe Pinhata, Juliana Maira, Plesnik, Sara, Puyen, Zully, Rabodoarivelo, Marie, Rakotosamimanana, Niaina, Rancoita, Paola, Rathod, Priti, Robinson, Esther, Rodger, Gillian, Rodrigues, Camilla, Rodwell, Timothy, Roohi, Aysha, Santos-Lazaro, David, Shah, Sanchi, Kohl, Thomas Andreas, Smith, Grace, Solano, Walter, Spitaleri, Andrea, Supply, Philip, Steyn, Adrie, Surve, Utkarsha, Tahseen, Sabira, Thuong, Nguyen, Thwaites, Guy, Todt, Katharina, Trovato, Alberto, Utpatel, Christian, van Rie, Annelies, Vijay, Srinivasan, Walker, Timothy, Walker, A. Sarah, Warren, Robin M., Werngren, Jim, Wijkander, Maria, Wilkinson, Robert, Wilson, Daniel, Wintringer, Penelope, Xiao, Yu-Xin, Yang, Yang, Zhao, Yanlin, Yao, Shen-Yuan, Zhu, Baoli, Fowler, Philip, Iqbal, Zamin, Consortium, The CRyPTIC, University of Oxford, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Forschungszentrum Borstel - Research Center Borstel, IRCCS San Raffaele Scientific Institute [Milan, Italie], Casa de Oswaldo Cruz [Rio de Janeiro] (COC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Instituto Adolfo Lutz [São Paulo, Brazil], Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Africa Health Research Institute [Durban/Mtubatuba] (AHRI), University of Edinburgh, Yale School of Public Health (YSPH), Universidad Peruana de Ciencias Aplicadas (Lima) (UPC), Wadsworth Center, New York State Department of Health [Albany], Chinese Center for Disease Control and Prevention, Bill & Melinda Gates Foundation [Seattle], UK Health Security Agency [London] (UKHSA), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), University College of London [London] (UCL), University of New South Wales [Sydney] (UNSW), Public Health Agency of Sweden, University of British Columbia [Vancouver], Public Health Ontario - Santé publique Ontario, Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, National Institute for Communicable Diseases [Johannesburg] (NICD), Taipei Medical University, PD Hinduja Hospital & Research Institute, Mumbai, University of Cape Town, University of Surrey (UNIS), Imperial College London, Université de Montréal (UdeM), PRA Health sciences [Mumbai], London School of Hygiene and Tropical Medicine (LSHTM), Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), German Centre for Infection Research - partner site Hamburg-Lübeck-Borstel-Riems (DZIF), Columbia University Irving Medical Center (CUIMC), National University of Singapore (NUS), Socios En Salud [Lima, Peru], Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Foundation for Innovative New Diagnostics (FIND), University of California [San Diego] (UC San Diego), University of California (UC), Universidad Peruana Cayetano Heredia (UPCH), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), National TB control Program [Islamabad, Pakistan], University of Antwerp (UA), Stellenbosch University, Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, The Francis Crick Institute [London], Shanghai Jiao Tong University School of Medicine, Chinese Academy of Sciences [Beijing] (CAS), and Wellcome Trust (200205/Z/15/Z)Bill and Melinda Gates Foundation (OPP1133541)National Institute for Health Research Oxford Biomedical Research CentreNational Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial ResistanceWellcome Trust (203919/Z/16/Z)National Mega Project on Major Infectious Disease Prevention (2018ZX10103001)H2020 Marie Skłodowska-Curie Actions (EIPOD3)Unitaid (2019-32-FIND MDR)FAPESP (17/16082-7)FAPESP (2012/51756-5)National Natural Science Foundation of China (81991534)Beijing Municipal Science and Technology Commission (Z201100005520041)Wellcome Trust International Intermediate Fellowship (206724/Z/17/Z)Wellcome TrustSouth African Medical Research Councilthe Rhodes Trust and Stanford Medical Scientist Training Program (T32 GM007365)National Institute for Health Research (NIHR) Health Protection Research Unit in Respiratory Infections at Imperial College LondonFonds de Recherche en Santé du QuébecWellcome Trust (203583/Z/16/Z)Research Foundation Flanders (G0F8316N)Wellcome Trust (98316)Wellcome Trust (214321/Z/18/Z)Wellcome Trust (203135/Z/16/Z)National Research Foundation South Africa (64787)Wellcome Trust (201470/Z/16/Z)National Institute of Allergy and Infectious Diseases (1R01AI146338)GOSH (1R01AI146338)GOSH/ICH Biomedical Research CentreOxford Medical Research Council Doctoral Training Partnership (NDM Prize Studentship)Nuffield Department of Clinical MedicineSir Henry Dale Fellowship (101237/Z/13/B)The Robertson FoundationNIHRWellcome Trust (214560/Z/18/Z)Rhodes TrustWellcome Trust (FC0010218)UK Research and Innovation (FC0010218)Cancer Research UK (FC0010218)National Institutes of HealthCenters for Disease Control and PreventionUSAIDBill and Melinda Gates FoundationWellcome Trust (203141/Z/16/Z)NIHR Oxford Biomedical Research Centre (BRC BRC-1215-20008)Deutsches Zentrum für InfektionsforschungPublic Health ScotlandCenters for Disease Control and Prevention (U60OE000103)Division of Intramural Research, National Institute of Allergy and Infectious Diseases (AI-117312)

Subjects
General Immunology and Microbiology, General Neuroscience, Extensively Drug-Resistant Tuberculosis, Antitubercular Agents, Microbial Sensitivity Tests, Mycobacterium tuberculosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, General Biochemistry, Genetics and Molecular Biology, Phenotype, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Drug Resistance, Multiple, Bacterial, Mutation, Tuberculosis, Multidrug-Resistant, Humans, Rifampin, General Agricultural and Biological Sciences
Abstract

The Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) presents here a data compendium of 12,289 Mycobacterium tuberculosis global clinical isolates, all of which have undergone whole-genome sequencing and have had their minimum inhibitory concentrations to 13 antitubercular drugs measured in a single assay. It is the largest matched phenotypic and genotypic dataset for M. tuberculosis to date. Here, we provide a summary detailing the breadth of data collected, along with a description of how the isolates were selected, collected, and uniformly processed in CRyPTIC partner laboratories across 23 countries. The compendium contains 6,814 isolates resistant to at least 1 drug, including 2,129 samples that fully satisfy the clinical definitions of rifampicin resistant (RR), multidrug resistant (MDR), pre-extensively drug resistant (pre-XDR), or extensively drug resistant (XDR). The data are enriched for rare resistance-associated variants, and the current limits of genotypic prediction of resistance status (sensitive/resistant) are presented by using a genetic mutation catalogue, along with the presence of suspected resistance-conferring mutations for isolates resistant to the newly introduced drugs bedaquiline, clofazimine, delamanid, and linezolid. Finally, a case study of rifampicin monoresistance demonstrates how this compendium could be used to advance our genetic understanding of rare resistance phenotypes. The data compendium is fully open source and it is hoped that it will facilitate and inspire future research for years to come.

Published
2022
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42. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: A genotypic analysis

Author

Bill & Melinda Gates Foundation, Medical Research Council (UK), Wellcome Trust, Unitaid, Comas, Iñaki [0000-0001-5504-9408], Walker, Timothy M., Miotto, Paolo, Koser, Claudio U., Fowler, Philip W., Knaggs, Jeff, Iqbal, Zamin, Hunt, Martin, Chindelevitch, Leonid, Farhat, Maha, Cirillo, Daniela Maria, Comas, Iñaki, Posey, James, Omar, Shaheed V., Peto, Timothy Ea, Suresh, Anita, Uplekar, Swapna, Laurent, Sacha, Colman, Rebecca E., Nathanson, Carl-Michael, Zignol, Matteo, Walker, Ann Sarah, Crook, Derrick W., Ismail, Nazir, Rodwell, Timothy C., CRyPTIC Consortium, Seq&Treat Consortium, Bill & Melinda Gates Foundation, Medical Research Council (UK), Wellcome Trust, Unitaid, Comas, Iñaki [0000-0001-5504-9408], Walker, Timothy M., Miotto, Paolo, Koser, Claudio U., Fowler, Philip W., Knaggs, Jeff, Iqbal, Zamin, Hunt, Martin, Chindelevitch, Leonid, Farhat, Maha, Cirillo, Daniela Maria, Comas, Iñaki, Posey, James, Omar, Shaheed V., Peto, Timothy Ea, Suresh, Anita, Uplekar, Swapna, Laurent, Sacha, Colman, Rebecca E., Nathanson, Carl-Michael, Zignol, Matteo, Walker, Ann Sarah, Crook, Derrick W., Ismail, Nazir, Rodwell, Timothy C., CRyPTIC Consortium, and Seq&Treat Consortium

Abstract

Background: Molecular diagnostics are considered the most promising route to achieving rapid, universal drug susceptibility testing for Mycobacterium tuberculosiscomplex (MTBC). We aimed to generate a WHO endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: A candidate gene approach was used to identify mutations as associated with resistance, or consistent with susceptibility, for 13 WHO endorsed anti-tuberculosis drugs. 38,215 MTBC isolates with paired whole-genome sequencing and phenotypic drug susceptibility testing data were amassed from 45 countries. For each mutation, a contingency table of binary phenotypes and presence or absence of the mutation computed positive predictive value, and Fisher's exact tests generated odds ratios and Benjamini-Hochberg corrected p-values. Mutations were graded as Associated with Resistance if present in at least 5 isolates, if the odds ratio was >1 with a statistically significant corrected p-value, and if the lower bound of the 95% confidence interval on the positive predictive value for phenotypic resistance was >25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: 15,667 associations were computed for 13,211 unique mutations linked to one or more drugs. 1,149/15,667 (7·3%) mutations were classified as associated with phenotypic resistance and 107/15,667 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was >80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were classified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: This first WHO endorsed catalogue of molecular targets for MTBC drug susceptibility

Published
2022

43. Correction: MiR-277/4989 regulate transcriptional landscape during juvenile to adult transition in the parasitic helminth Schistosoma mansoni

Author

Protasio, Anna V., primary, Dongen, Stijn van, additional, Collins, Julie, additional, Quintais, Leonor, additional, Ribeiro, Diogo M., additional, Sessler, Florian, additional, Hunt, Martin, additional, Rinaldi, Gabriel, additional, Collins, James J., additional, Enright, Anton J., additional, and Berriman, Matthew, additional

Published
2022
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46. Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

Author

Aggarwal, Dinesh, Warne, Ben, Jahun, Aminu S., Hamilton, William L., Fieldman, Thomas, du Plessis, Louis, Hill, Verity, Blane, Beth, Watkins, Emmeline, Wright, Elizabeth, Hall, Grant, Ludden, Catherine, Myers, Richard, Hosmillo, Myra, Chaudhry, Yasmin, Pinckert, Malte L., Georgana, Iliana, Izuagbe, Rhys, Leek, Danielle, Nsonwu, Olisaeloka, Hughes, Gareth J., Packer, Simon, Page, Andrew J., Metaxaki, Marina, Fuller, Stewart, Weale, Gillian, Holgate, Jon, Brown, Christopher A., Orton, Alexandra, Douthwaite, Julie, Rees, Steve, Brown, Christopher, Clark, Roger, Jones, Daniel R., Kuenzi, Fred, Rankin, Jennifer, Waddell, Ian, Maxwell, Patrick, Matheson, Nicholas, Abell, Chris, Braithwaite, Vickie, Brierley, Craig, Crowcroft, Jon, Dahal, Aastha, Faulkner, Kathryn, Glover, Michael, Goodfellow, Ian, Greatorex, Jane, James, Laura, Lehner, Paul, Leslie, Ian, Liddell, Kathleen, Margolis, Ben, Morgan, Sally, Sheridan, Linda, Valletta, Sally, Vignoles, Anna, Vinnell, Martin, Wills, Mark, Hilborne, Sarah, Berry, Sarah, Kahkeshi, Mahin Bagheri, Hancock, Dawn, Winster, Jennifer, Enright, Jessica, Samworth, Richard, Samtani, Vijay, Ahmadi-Assalemi, Gabriela, Feather, Tom, Goodall, Robin, Hoensch, Steve, Johnson, Dean, Hunt, Martin, Mathieson, Nick, Nikitina, Katya, Sheldrake, Zara, Keen, Martin, Sato, Aris, Connor, David, Tolhurst, Jonathan, Williman, Jack, Hollamby, Victoria, Jordan, Sinead, Fatseas, Tania, Taylor, Peter, Georgiou, Christine, Caspersz, Michelle, McNulty, Claire, Davies, Richard, Clarke, Rebecca, Danaei, Darius, Dyer, Rory, Glew, Rob, Lambson, Oliver, Gibbs, Karen, Mozdzen, Barbara, Raub, Gabor, Radecki, Asako, White, Phil, Hughes, Robert, Gransden, Lucie, Ceaser, Matt, Sing, Robert, Wilson, Karl, Parlikad, Ajith, Dhada, Maharshi, Ridgman, Tom, Mungovan, Diane, Matthews, Steve, Searle, Paul, Mills, John, Neely, Andy, Henderson, Robert, Murphy, Edna, Russell, Matthew, Freeling, Anthony, Poppitt, Steve, Tynan, Jo, Knapton, James, Marchetti, Filippo, Angelis, Daniela De, Feltwell, Theresa, Hadjirin, Nazreen F., Jahun, Aminu, Pinckert, Malte, Shaw, Ashley, Chaudhry, Afzal, Brown, Nicholas M., Mactavous, Lenette, Hannan, Sophie, Hosaja, Aleksandra, Leong, Clare, Wright, Jo, Quinnell, Natalie, Workman, Chris, Ferris, Mark, Wright, Giles, Brooks, Ellena, Carabelli, Alessandro M., Churcher, Carol M., Galai, Katerina, Girgis, Sophia T., Gupta, Ravi K., McManus, Georgina M., Palmer, Sophie, Peacock, Sharon J., Smith, Kim S., Allara, Elias, Bibby, David, Bishop, Chloe, Bosworth, Andrew, Bradshaw, Daniel, Chalker, Vicki, Chand, Meera, Dabrera, Gavin, Ellaby, Nicholas, Gallagher, Eileen, Groves, Natalie, Harrison, Ian, Hartman, Hassan, Hopes, Richard, Hubb, Jonathan, Hutchings, Stephanie, Lackenby, Angie, Ledesma, Juan, Lee, David, Manesis, Nikos, Manso, Carmen, Mbisa, Tamyo, Miah, Shahjahan, Muir, Peter, Osman, Husam, Patel, Vineet, Pearson, Clare, Platt, Steven, Pymont, Hannah M., Ramsay, Mary, Robinson, Esther, Schaefer, Ulf, Thornton, Alicia, Twohig, Katherine A., Vipond, Ian B., Williams, David, Aigrain, Louise, Alderton, Alex, Amato, Roberto, Ariani, Cristina V., Barrett, Jeff, Bassett, Andrew R., Beale, Mathew A., Beaver, Charlotte, Bellis, Katherine L., Betteridge, Emma, Bonfield, James, Bronner, Iraad F., Chapman, Michael H. S., Danesh, John, Davies, Robert, Dorman, Matthew J., Drury, Eleanor, Durham, Jillian, Farr, Ben W., Foulser, Luke, Goncalves, Sonia, Goodwin, Scott, Gourtovaia, Marina, Jackson, David K., James, Keith, Jamrozy, Dorota, Johnston, Ian, Kane, Leanne, Kay, Sally, Keatley, Jon-Paul, Kwiatkowski, Dominic, Langford, Cordelia F., Lawniczak, Mara, Lensing, Stefanie V., Leonard, Steven, Letchford, Laura, Lewis, Kevin, Liddle, Jennifier, Livett, Rich, Lo, Stephanie, Makunin, Alex, Martincorena, Inigo, McCarthy, Shane, McGuigan, Samantha, Moll, Robin J., Nelson, Rachel, Oliver, Karen, Palmer, Steve, Park, Naomi R., Patel, Minal, Prestwood, Liam, Puethe, Christoph, Quail, Michael A., Rajan, Diana, Rajatileka, Shavanthi, Redshaw, Nicholas M., Scott, Carol, Shirley, Lesley, Sillitoe, John, Thurston, Scott A. J., Tonkin-Hill, Gerry, Tovar-Corona, Jaime M., Weldon, Danni, Whitwham, Andrew, Attwood, Stephen W., Zamudio, Marina Escalera, Francois, Sarah, Gutierrez, Bernardo, Kraemer, Moritz U. G., Raghwani, Jayna, Vasylyeva, Tetyana I., Zarebski, Alex E., Alikhan, Nabil-Fareed, Aydin, Alp, Baker, David J., de Oliveira Martins, Leonardo, Kay, Gemma L., Le-Viet, Thanh, Mather, Alison E., Meadows, Lizzie, O’Grady, Justin, Rudder, Steven, Trotter, Alexander J., Illingworth, Chris J., Jackson, Chris, Aranday-Cortes, Elihu, Asamaphan, Patawee, Broos, Alice, Carmichael, Stephen N., da Silva Filipe, Ana, Hughes, Joseph, Jesudason, Natasha G., Johnson, Natasha, Li, Kathy K., Mair, Daniel, Nichols, Jenna, Nickbakhsh, Seema, Niebel, Marc O., Nomikou, Kyriaki, Orton, Richard J., Robertson, David L., Shah, Rajiv N., Shepherd, James G., Singer, Joshua B., Starinskij, Igor, Thomson, Emma C., Tong, Lily, Vattipally, Sreenu, Ash, Amy, Koshy, Cherian, Cortes, Nick, Kidd, Stephen, Lynch, Jessica, Moore, Nathan, Mori, Matilde, Wise, Emma, Curran, Tanya, Fairley, Derek J., McKenna, James P., Adams, Helen, Bonsall, David, Fraser, Christophe, Golubchik, Tanya, Cogger, Benjamin J., Hassan-Ibrahim, Mohammed O., Malone, Cassandra S., Reynolds, Nicola, Wantoch, Michelle, Afifi, Safiah, Beer, Robert, John, Michaela, Maksimovic, Joshua, McCluggage, Kathryn, Morgan, Sian, Spellman, Karla, Bresner, Catherine, Connor, Thomas R., Fuller, William, Guest, Martyn, Gulliver, Huw, Kitchen, Christine, Marchbank, Angela, Merrick, Ian, Munn, Robert, Price, Anna, Southgate, Joel, Workman, Trudy, Patel, Amita, Snell, Luke B., Batra, Rahul, Charalampous, Themoula, Edgeworth, Jonathan, Nebbia, Gaia, Beckett, Angela H., Robson, Samuel C., Aanensen, David M., Abudahab, Khalil, Menegazzo, Mirko, Taylor, Ben E. W., Underwood, Anthony P., Yeats, Corin A., Berry, Louise, Boswell, Tim, Clark, Gemma, Fleming, Vicki M., Howson-Wells, Hannah C., Jones, Carl, Joseph, Amelia, Khakh, Manjinder, Lister, Michelle M., Smith, Wendy, Willingham, Iona, Bird, Paul, Fallon, Karlie, Helmer, Thomas, Holmes, Christopher, Tang, Julian, Blakey, Victoria, Campbell, Sharon, Raviprakash, Veena, Sheriff, Nicola, Williams, Lesley-Anne, Carlile, Matthew, Debebe, Johnny, Holmes, Nadine, Loose, Matthew W., Moore, Christopher, Sang, Fei, Wright, Victoria, Coll, Francesc, Betancor, Gilberto, Signell, Adrian W., Wilson, Harry D., Davis, Thomas, Eldirdiri, Sahar, Kenyon, Anita, Torok, M. Estee, Lowe, Hannah, Moses, Samuel, Bedford, Luke, Moore, Jonathan, Stonehouse, Susanne, Awan, Ali R., Fisher, Chloe L., BoYes, John, Atkinson, Laura, Breuer, Judith, Brown, Julianne R., Harris, Kathryn A., Lee, Jack C. D., Shah, Divya, Storey, Nathaniel, Flaviani, Flavia, Alcolea-Medina, Adela, Vernet, Gabrielle, Williams, Rebecca, Chapman, Michael R., Chatterton, Wendy, Heaney, Judith, Levett, Lisa J., Pusok, Monika, Xu-McCrae, Li, Bashton, Matthew, Smith, Darren, Young, Greg, Bolt, Frances, Cox, Alison, Holmes, Alison, Madona, Pinglawathee, Mookerjee, Siddharth, Price, James, Randell, Paul A., Boyd, Olivia, Nascimento, Fabricia F., Geidelberg, Lily, Johnson, Rob, Jorgensen, David, Ragonnet-Cronin, Manon, Rowan, Aileen, Siveroni, Igor, Taylor, Graham P., Volz, Erik M., Smollett, Katherine L., Loman, Nicholas J., McMurray, Claire, McNally, Alan, Nicholls, Sam, Poplawski, Radoslaw, Quick, Joshua, Rowe, Will, Stockton, Joanne, Nunez, Rocio T. Martinez, Breen, Cassie, Cowell, Angela, Mason, Jenifer, O’Toole, Elaine, Robinson, Trevor I., Watts, Joanne, Sluga, Graciela, Ahmad, Shazaad S. Y., George, Ryan P., Machin, Nicholas W., Halstead, Fenella, Hogsden, Wendy, Sivaprakasam, Venkat, Carden, Holli, Hale, Antony D., Harper, Katherine L., Macfarlane-Smith, Louissa R., Burton-Fanning, Shirelle, Collins, Jennifer, Eltringham, Gary, Payne, Brendan AI., Taha, Yusri, Waugh, Sheila, O’Brien, Sarah, Rushton, Steven, Blacow, Rachel, Bradley, Amanda, Maclean, Alasdair, Mollett, Guy, Dewar, Rebecca, McHugh, Martin P., Templeton, Kate E., Wastenge, Elizabeth, Coupland, Lindsay, Dervisevic, Samir, Meader, Emma J., Stanley, Rachael, Smith, Louise, Barton, Edward, Graham, Clive, Padgett, Debra, Scott, Garren, Greenaway, Jane, Swindells, Emma, McCann, Clare, Nelson, Andrew, Yew, Wen Chyin, Andersson, Monique, Crook, Derrick, Eyre, David, Justice, Anita, Peto, Timothy, Duckworth, Nichola, Sloan, Tim J., Walsh, Sarah, Bicknell, Kelly, Chauhan, Anoop J., Elliott, Scott, Glaysher, Sharon, Impey, Robert, Lloyd, Allyson, Wyllie, Sarah, Levene, Nick, Monaghan, Lynn, Bradley, Declan T., Wyatt, Tim, Curran, Martin D., Parmar, Surendra, Holden, Matthew T. G., Shaaban, Sharif, Adams, Alexander, Asad, Hibo, Birchley, Alec, Bull, Matthew, Coombes, Jason, Corden, Sally, Cottrell, Simon, Craine, Noel, Cronin, Michelle, Davies, Alisha, Lacy, Elen De, Downing, Fatima, Edwards, Sue, Evans, Johnathan M., Fina, Laia, Gaskin, Amy, Gatica-Wilcox, Bree, Gifford, Laura, Gilbert, Lauren, Graham, Lee, Heyburn, David, Hilvers, Ember, Howe, Robin, Jones, Hannah, Jones, Rachel, Jones, Sophie, Kumziene-SummerhaYes, Sara, McKerr, Caoimhe, Moore, Catherine, Morgan, Mari, Pacchiarini, Nicole, Perry, Malorie, Plimmer, Amy, Rey, Sara, Shankar, Giri, Taylor, Sarah, Watkins, Joanne, Williams, Chris, Casey, Anna, Ratcliffe, Liz, Acheson, Erwan, Molnar, Zoltan, Simpson, David A., Thompson, Thomas, Auckland, Cressida, Ellard, Sian, Jones, Christopher R., Knight, Bridget A., Masoli, Jane A. H., Haque, Tanzina, Hart, Jennifer, Irish-Tavares, Dianne, Mahungu, Tabitha W., Witele, Eric, Dadrah, Ashok, Fenton, Melisa L., Saluja, Tranprit, Symmonds, Amanda, Bourgeois, Yann, Scarlett, Garry P., Cook, Kate, Dent, Hannah, Fearn, Christopher, Goudarzi, Salman, Loveson, Katie F., Paul, Hannah, Evans, Cariad, Johnson, Kate, Partridge, David G., Raza, Mohammad, Baker, Paul, Bonner, Stephen, Essex, Sarah, Liggett, Steven, Lyons, Ronan A., Mahanama, Adhyana I. K., Saeed, Kordo, Samaraweera, Buddhini, Silveira, Siona, Wilson-Davies, Eleri, Emanuela, P., Bayzid, Nadua, Cotic, Marius, Ensell, Leah, Hartley, John A., Jannoo, Riaz, Karamani, Angeliki, Kristiansen, Mark, Lowe, Helen L., Roy, Sunando, Westhorpe, Adam P., Williams, Rachel J., Williams, Charlotte A., Jeremiah, Sarah, Prieto, Jacqui A., Berry, Lisa, Grammatopoulos, Dimitris, Jones, Katie, Pandey, Sarojini, Beggs, Andrew, Richter, Alex, Ashcroft, Fiona, Best, Angus, Crawford, Liam, Cumley, Nicola, Mayhew, Megan, Megram, Oliver, Mirza, Jeremy, Moles-Garcia, Emma, Percival, Benita, Bucca, Giselda, Hesketh, Andrew R., Smith, Colin P., Davidson, Rose K., Balcazar, Carlos E., Gallagher, Michael D., O’Toole, Áine, Rambaut, Andrew, Rooke, Stefan, Stanton, Thomas D., Williams, Thomas, Williamson, Kathleen A., Bewshea, Claire M., Farbos, Audrey, Harrison, James W., Jeffries, Aaron R., Manley, Robin, Michell, Stephen L., Michelsen, Michelle L., Sambles, Christine M., Studholme, David J., Temperton, Ben, Warwick-Dugdale, Joanna, Darby, Alistair C., Eccles, Richard, Gemmell, Matthew, Gregory, Richard, Haldenby, Sam T., Hiscox, Julian A., Hughes, Margaret, Iturriza-Gomara, Miren, Jackson, Kathryn A., Lucaci, Anita O., Nelson, Charlotte, Paterson, Steve, Rainbow, Lucille, Turtle, Lance, Vamos, Edith E., Webster, Hermione J., Whitehead, Mark, Wierzbicki, Claudia, Angyal, Adrienn, Brown, Rebecca, de Silva, Thushan I., Freeman, Timothy M., Gallis, Marta, Green, Luke R., Groves, Danielle C., Keeley, Alexander J., Lindsey, Benjamin B., Louka, Stavroula F., Parker, Matthew D., Parsons, Paul J., Smith, Nikki, Tucker, Rachel M., Wang, Dennis, Whiteley, Max, Wyles, Matthew, Zhang, Peijun, Alam, Mohammad T., Baxter, Laura, Bridgewater, Hannah E., Brown, Paul E., Cheng, Jeffrey K. J., Constantinidou, Chrystala, Frost, Lucy R., Ott, Sascha, Stark, Richard, Taylor-Joyce, Grace, Unnikrishnan, Meera, Cerda, Alberto C., Merrill, Tammy V., Wilson, Rebekah E., Ball, Jonathan, Chappell, Joseph G., McClure, Patrick C., Tsoleridis, Theocharis, Buck, David, de Cesare, Mariateresa, Green, Angie, MacIntyre-Cockett, George, Todd, John A., Trebes, Amy, Gunson, Rory N., Cormie, Claire, Dias, Joana, Forrest, Sally, Gill, Harmeet K., Higginson, Ellen E., Kermack, Leanne M., Maes, Mailis, Ruis, Chris, Sridhar, Sushmita, Young, Jamie, Howes, Rob, McFarlane, Duncan, Dougan, Gordon, Pybus, Oliver G., Maxwell, Patrick H., Weekes, Michael P., Illingworth, Chris, Harrison, Ewan M., Matheson, Nicholas J., Goodfellow, Ian G., The Cambridge Covid-19 testing Centre, University of Cambridge Asymptomatic COVID-19 Screening Programm, The COVID-19 Genomics UK (COG-UK) Consortium, Aggarwal, Dinesh [0000-0002-5938-8172], Warne, Ben [0000-0003-1326-0373], Hill, Verity [0000-0002-3509-8146], Pinckert, Malte [0000-0002-6072-5949], Leek, Danielle [0000-0001-5367-3354], Pybus, Oliver [0000-0001-6619-6112], Weekes, Michael [0000-0002-0030-2784], Apollo - University of Cambridge Repository, Jahun, Aminu S [0000-0002-4585-1701], Hamilton, William L [0000-0002-3330-353X], du Plessis, Louis [0000-0003-0352-6289], Blane, Beth [0000-0002-0996-9091], Wright, Elizabeth [0000-0002-8378-9072], Hall, Grant [0000-0003-3928-3979], Chaudhry, Yasmin [0000-0002-2386-3269], Pinckert, Malte L [0000-0002-6072-5949], Izuagbe, Rhys [0000-0001-8080-2510], Nsonwu, Olisaeloka [0000-0002-3024-700X], Hughes, Gareth J [0000-0002-3781-0117], Packer, Simon [0000-0002-9157-3650], Page, Andrew J [0000-0001-6919-6062], Metaxaki, Marina [0000-0002-4552-1622], Weale, Gillian [0000-0003-4728-5915], Brown, Christopher A [0000-0001-7773-0878], Peacock, Sharon J [0000-0002-1718-2782], Pybus, Oliver G [0000-0002-8797-2667], Weekes, Michael P [0000-0003-3196-5545], Harrison, Ewan M [0000-0003-2720-0507], Matheson, Nicholas J [0000-0002-3318-1851], Goodfellow, Ian G [0000-0002-9483-510X], Jahun, Aminu [0000-0002-4585-1701], Hosmillo, Myra [0000-0002-3514-7681], McFarlane, Duncan [0000-0002-1558-7823], Dougan, Gordon [0000-0003-0022-965X], Peacock, Sharon [0000-0002-1718-2782], Weekes, Michael [0000-0003-3196-5545], Illingworth, Christopher [0000-0002-0030-2784], Harrison, Ewan [0000-0003-2720-0507], Matheson, Nicholas [0000-0002-3318-1851], and Goodfellow, Ian [0000-0002-9483-510X]

Subjects
Universities, 631/326/325/2483, Science, education, University of Cambridge Asymptomatic COVID-19 Screening Programme Consortium, General Physics and Astronomy, Cambridge Covid-19 testing Centre, 45/23, Genome, Viral, General Biochemistry, Genetics and Molecular Biology, COVID-19 Genomics UK (COG-UK) Consortium, Risk Factors, The COVID-19 Genomics UK (COG-UK) Consortium, Humans, Students, Phylogeny, 631/326/596/4130, Multidisciplinary, SARS-CoV-2, article, COVID-19, virus diseases, C500, General Chemistry, Genomics, C700, 692/700/478/174, United Kingdom, The Cambridge Covid-19 testing Centre, RNA, Viral, 631/326/596/2562, Contact Tracing, 631/326/596/2563
Abstract

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics., Nature Communications, 13, ISSN:2041-1723

Published
2022

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