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3. Epidemiological and public health requirements for COVID-19 contact tracing apps and their evaluation

Author

Colizza, Vittoria, Grill, Eva, Mikolajczyk, Rafael, Cattuto, Ciro, Kucharski, Adam, Riley, Steven, Kendall, Michelle, Lythgoe, Katrina, Abeler-Dörner, Lucie, Wymant, Chris, Bonsall, David, Ferretti, Luca, and Fraser, Christophe

Subjects
Computer Science - Computers and Society, Computer Science - Social and Information Networks, Physics - Physics and Society, Quantitative Biology - Populations and Evolution
Abstract

Digital contact tracing is a public health intervention. It should be integrated with local health policy, provide rapid and accurate notifications to exposed individuals, and encourage high app uptake and adherence to quarantine. Real-time monitoring and evaluation of effectiveness of app-based contact tracing is key for improvement and public trust., Comment: 9 pages

Published
2021

4. Inferring HIV-1 transmission networks and sources of epidemic spread in Africa with deep-sequence phylogenetic analysis.

Author

Ratmann, Oliver, Grabowski, M Kate, Hall, Matthew, Golubchik, Tanya, Wymant, Chris, Abeler-Dörner, Lucie, Bonsall, David, Hoppe, Anne, Brown, Andrew Leigh, de Oliveira, Tulio, Gall, Astrid, Kellam, Paul, Pillay, Deenan, Kagaayi, Joseph, Kigozi, Godfrey, Quinn, Thomas C, Wawer, Maria J, Laeyendecker, Oliver, Serwadda, David, Gray, Ronald H, Fraser, Christophe, and PANGEA Consortium and Rakai Health Sciences Program

Subjects
PANGEA Consortium and Rakai Health Sciences Program, Humans, HIV-1, HIV Infections, Phylogeny, Base Sequence, Adolescent, Adult, Middle Aged, Africa, Young Adult, Epidemics, High-Throughput Nucleotide Sequencing
Abstract

To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these 'source' populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8-28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa.

Published
2019

5. The epidemiological impact of the NHS COVID-19 app

Author

Wymant, Chris, Ferretti, Luca, Tsallis, Daphne, Charalambides, Marcos, Abeler-Dörner, Lucie, Bonsall, David, Hinch, Robert, Kendall, Michelle, Milsom, Luke, Ayres, Matthew, Holmes, Chris, Briers, Mark, and Fraser, Christophe

Subjects
United Kingdom. National Health Service -- Technology application, Epidemics -- Control -- United Kingdom, Mobile applications -- Usage -- Health aspects, Technology application, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The COVID-19 pandemic has seen the emergence of digital contact tracing to help to prevent the spread of the disease. A mobile phone app records proximity events between app users, and when a user tests positive for COVID-19, their recent contacts can be notified instantly. Theoretical evidence has supported this new public health intervention.sup.1-6, but its epidemiological impact has remained uncertain.sup.7. Here we investigate the impact of the National Health Service (NHS) COVID-19 app for England and Wales, from its launch on 24 September 2020 to the end of December 2020. It was used regularly by approximately 16.5 million users (28% of the total population), and sent approximately 1.7 million exposure notifications: 4.2 per index case consenting to contact tracing. We estimated that the fraction of individuals notified by the app who subsequently showed symptoms and tested positive (the secondary attack rate (SAR)) was 6%, similar to the SAR for manually traced close contacts. We estimated the number of cases averted by the app using two complementary approaches: modelling based on the notifications and SAR gave an estimate of 284,000 (central 95% range of sensitivity analyses 108,000-450,000), and statistical comparison of matched neighbouring local authorities gave an estimate of 594,000 (95% confidence interval 317,000-914,000). Approximately one case was averted for each case consenting to notification of their contacts. We estimated that for every percentage point increase in app uptake, the number of cases could be reduced by 0.8% (using modelling) or 2.3% (using statistical analysis). These findings support the continued development and deployment of such apps in populations that are awaiting full protection from vaccines. Statistical analysis of COVID-19 transmission among users of a smartphone-based digital contact-tracing app suggests that such apps can be an effective measure for reducing disease spread., Author(s): Chris Wymant [sup.1] , Luca Ferretti [sup.1] , Daphne Tsallis [sup.2] , Marcos Charalambides [sup.3] , Lucie Abeler-Dörner [sup.1] , David Bonsall [sup.1] , Robert Hinch [sup.1] , Michelle [...]

Published
2021
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7. Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda

Author

Ayles, Helen, Bowden, Rory, Calvez, Vincent, Cohen, Myron, Dennis, Anne, Essex, Max, Fidler, Sarah, Frampton, Dan, Hayes, Richard, Herbeck, Josh, Kaleebu, Pontiano, Kityo, Cissy, Lingappa, Jairam, Novitsky, Vladimir, Paton, Nick, Rambaut, Andrew, Seeley, Janet, Ssemwanga, Deogratius, Tanser, Frank, Lutalo, Tom, Galiwango, Ronald, Makumbi, Fred, Sewankambo, Nelson K., Nabukalu, Dorean, Ndyanabo, Anthony, Ssekasanvu, Joseph, Nakawooya, Hadijja, Nakukumba, Jessica, Kigozi, Grace N., Nantume, Betty S., Resty, Nampijja, Kambasu, Jedidah, Nalugemwa, Margaret, Nakabuye, Regina, Ssebanobe, Lawrence, Nankinga, Justine, Kayiira, Adrian, Nanfuka, Gorreth, Ahimbisibwe, Ruth, Tomusange, Stephen, Galiwango, Ronald M., Nakalanzi, Margaret, Otobi, Joseph O., Ankunda, Denis, Ssembatya, Joseph L., Ssemanda, John B., Kato, Emmanuel, Kairania, Robert, Kisakye, Alice, Batte, James, Ludigo, James, Nampijja, Abisagi, Watya, Steven, Nehemia, Kighoma, Anyokot, Sr. Margaret, Mwinike, Joshua, Kibumba, George, Ssebowa, Paschal, Mondo, George, Wasswa, Francis, Nantongo, Agnes, Kakembo, Rebecca, Galiwango, Josephine, Ssemango, Geoffrey, Redd, Andrew D., Santelli, John, Kennedy, Caitlin E., Wagman, Jennifer, Tobian, Aaron, Ratmann, Oliver, Kagaayi, Joseph, Hall, Matthew, Golubchick, Tanya, Kigozi, Godfrey, Xi, Xiaoyue, Wymant, Chris, Nakigozi, Gertrude, Abeler-Dörner, Lucie, Bonsall, David, Gall, Astrid, Hoppe, Anne, Kellam, Paul, Bazaale, Jeremiah, Kalibbala, Sarah, Laeyendecker, Oliver, Lessler, Justin, Nalugoda, Fred, Chang, Larry W, de Oliveira, Tulio, Pillay, Deenan, Quinn, Thomas C, Reynolds, Steven J, Spencer, Simon E F, Ssekubugu, Robert, Serwadda, David, Wawer, Maria J, Gray, Ronald H, Fraser, Christophe, and Grabowski, M Kate

Published
2020
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8. Boosted Higgs Shapes

Author

Schlaffer, Matthias, Spannowsky, Michael, Takeuchi, Michihisa, Weiler, Andreas, and Wymant, Chris

Subjects
High Energy Physics - Phenomenology, High Energy Physics - Experiment
Abstract

The inclusive Higgs production rate through gluon fusion has been measured to be in agreement with the Standard Model (SM). We show that even if the inclusive Higgs production rate is very SM-like, a precise determination of the boosted Higgs transverse momentum shape offers the opportunity to see effects of natural new physics. These measurements are generically motivated by effective field theory arguments and specifically in extensions of the SM with a natural weak scale, like composite Higgs models and natural supersymmetry. We show in detail how a measurement at high transverse momentum of $H\to 2\ell+\mathbf{p}\!\!/_T$ via $H\to \tau\tau$ and $H\to WW^*$ could be performed and demonstrate that it offers a compelling alternative to the $t\bar t H$ channel. We discuss the sensitivity to new physics in the most challenging scenario of an exactly SM-like inclusive Higgs cross-section., Comment: 17 pages, 7 figures, 6 tables. Added references and minor clarifications. Matches published version

Published
2014
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9. Designing and recasting LHC analyses with MadAnalysis 5

Author

Conte, Eric, Dumont, Béranger, Fuks, Benjamin, and Wymant, Chris

Subjects
High Energy Physics - Phenomenology, High Energy Physics - Experiment
Abstract

We present an extension of the expert mode of the MadAnalysis 5 program dedicated to the design or reinterpretation of high-energy physics collider analyses. We detail the predefined classes, functions and methods available to the user and emphasize the most recent developments. The latter include the possible definition of multiple sub-analyses and a novel user-friendly treatment for the selection criteria. We illustrate this approach by two concrete examples: a CMS search for supersymmetric partners of the top quark and a phenomenological analysis targeting hadronically decaying monotop systems., Comment: 17 pages, 3 figures, 10 tables; version accepted by EPJC

Published
2014
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10. Signs of Susy

Author

Wymant, Chris

Subjects
High Energy Physics - Phenomenology, High Energy Physics - Experiment
Abstract

This doctoral thesis addresses aspects of Supersymmetry (Susy) phenomenology. In addition to previously published work, it contains introductions to the following topics: from classical mechanics to quantum field theory for the more casual reader, electroweak naturalness, the Higgs as a pseudo-Nambu-Goldstone boson, the MSSM and NMSSM, simple and less simple models of gauge-mediated Susy breaking (GMSB), collider searches for Susy and other new theories, transverse mass observables with missing energy, and Brazil-band plots. The previously published work is as follows. The optimally natural Higgs-stop sector in the MSSM in light of the 2012 discovery of a Higgs boson is derived, namely that of almost maximal mixing, with the scalar top partners almost as light as can be. The discovery is also interpreted numerically in the NMSSM, with greater emphasis placed on the visibility of the Higgs boson at the observed mass, i.e. on signal strengths. I investigate the role played by the mediation scale of GMSB: this is found to be as a control of the extent to which Yukawa couplings de-tune flavour-blind relations set by gauge couplings. Finally, issues relating to the discovery or exclusion of Susy at colliders are discussed. Bounds are derived for the masses of new particles from LHC searches for excesses of jets and missing energy without leptons, and compared to constraints arising from Higgs boson searches, for models of GMSB and the Constrained Minimal Supersymmetric Standard Model. I present a novel search strategy for new physics signatures with two neutral, stable particles, when such particles are produced by boosted decays. (Susy motivations include models with light gravitinos, pseudo-goldstinos, singlinos or new photinos.) The method is shown to produce sharp mass peaks that enhance the visibility of the signal, with mass reconstruction to 5% from O(100) events., Comment: Doctoral thesis, 86 pages + preamble + appendices + references, 28 figures. This article draws heavily from arXiv:1102.1589, arXiv:1103.1843, arXiv:1111.3365, arXiv:1203.3446, arXiv:1208.1737 and arXiv:1301.0345

Published
2013

11. Making The Most Of MET: Mass Reconstruction From Collimated Decays

Author

Spannowsky, Michael and Wymant, Chris

Subjects
High Energy Physics - Phenomenology, High Energy Physics - Experiment
Abstract

At hadron colliders invisible particles $\chi$ can be inferred only through observation of the transverse component of the vectorial sum of their momenta -- missing $E_T$ or MET -- preventing reconstruction of the masses of their mother particles. Here we outline situations where prior prejudice about the event kinematics allows one to make the most of MET by decomposing it into its expected sum of transverse contributions, each of which may be promoted to a full four-momentum approximating the associated $\chi$. Such prejudice arises when all $\chi$ in the event are expected to be light and (anti-)parallel to a visible object, due to spin-correlations, back-to-back decays or boosted decays. We focus on the last of these, with boosted semi-invisibly decaying neutralinos widely motivated in supersymmetry (in the presence of light gravitinos, singlinos, photini or pseudo-goldstini), and demonstrate our simple method's ability to reconstruct sharp mass peaks from the MET decomposition., Comment: 7 pages, 5 figures; v2 published in PRD - typos, references, comment added on the (non-)effect of additional hard radiation

Published
2013
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12. Partially (in)visible Higgs decays at the LHC

Author

Englert, Christoph, Spannowsky, Michael, and Wymant, Chris

Subjects
High Energy Physics - Phenomenology, High Energy Physics - Experiment
Abstract

Both Atlas and CMS have reported a discovery of a Standard Model-like Higgs boson $H$ of mass around 125 GeV. Consistency with the Standard Model implies the non-observation of non-SM like decay modes of the newly discovered particle. Sensitivity to such decay modes, especially when they involve partially invisible final states is currently beyond scrutiny of the LHC. We systematically study such decay channels in the form of $H\rightarrow AA\rightarrow jets+missing energy$, with $A$ a light scalar or scalar, and analyze to what extent these exotic branching fractions can be constrained by direct measurements at the LHC. While the analysis is challenging, constraints as good as ${BR}\lesssim 10%$ can be obtained., Comment: 8 pages, 6 figures; v2 typos, references, version published in PLB

Published
2012
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13. Optimising Stop Naturalness

Author

Wymant, Chris

Subjects
High Energy Physics - Phenomenology
Abstract

In supersymmetric models a large average stop mass $M_S$ is well known to both boost the lightest Higgs boson mass $m_{h}$ and also make radiative electroweak symmetry breaking unnaturally tuned. The case of `maximal mixing', where the stop trilinear mixing term $A_t$ is set to give $A_t^2/M_S^2 = 6$, allows the stops to be as light as possible for a given $m_h$. Here we make the distinction between minimal $M_S$ and optimal naturalness, showing that the latter occurs for less-than-maximal mixing. Lagrange constrained optimisation reveals that the two coincide closely in the Minimal Supersymmetric Standard Model (MSSM) -- optimally we have $5 < A_t^2/M_S^2 < 6$. We discuss why the two are not generally expected to coincide beyond the MSSM, and that even within the MSSM different models should not be compared based on the $M_S$ necessary to achieve a given $m_{h}$. The splitting between the two stop-mass eigenvalues $m_{\tilde{t}_2} - m_{\tilde{t}_1}$ is shown to be unconstrained by naturalness considerations., Comment: 14 pages, 3 figures. v2 and 3: extra content. v4: typos, PRD version

Published
2012
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14. The 125 GeV Higgs in the NMSSM in light of LHC results and astrophysics constraints

Author

Vasquez, Daniel Albornoz, Belanger, Genevieve, Boehm, Celine, Da Silva, Jonathan, Richardson, Peter, and Wymant, Chris

Subjects
High Energy Physics - Phenomenology, Astrophysics - Cosmology and Extragalactic Astrophysics, High Energy Physics - Experiment
Abstract

Recent LHC data suggest an excess in the Higgs decay channels into gamma gamma, W W and Z Z at roughly 125 GeV. The current excess in the diphoton channel is twice that expected from a Standard Model Higgs; whilst this may well change with more statistics, it is interesting to consider the implications should the result persist. Here, we assess whether the NMSSM with a neutralino dark matter candidate could explain this excess when astrophysical constraints (e.g. no overproduction of gamma rays and radio emission in the galaxy, no anomalous excess in the dark matter direct detection experiments and no dark matter overabundance) are imposed on the neutralino. This enables us to disregard unphysical regions of the parameter space even though the Higgs signal is compatible with the observed excess. The result of our analysis is that there are configurations of the parameter space which can explain the signal strength reported by the ATLAS and CMS collaborations for a Higgs mass within the required range. Should the observed signal strength finally be compatible with Standard Model expectations, it would be difficult to distinguish between the discovery of Standard Model Higgs and a SM-like Higgs from the NMSSM, unless one performs dedicated searches of very light Higgs bosons and possibly investigate peculiar signatures of supersymmetric particles. We also propose a new jets + missing E_T signal for the case where the LSP is a singlino-like neutralino., Comment: 9 pages, 9 figures; v2 references added, minor clarifications, version accepted by PRD

Published
2012
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15. Direct SUSY Searches at the LHC in the light of LEP Higgs Bounds

Author

Grellscheid, David, Jaeckel, Joerg, Khoze, Valentin V., Richardson, Peter, and Wymant, Chris

Subjects
High Energy Physics - Phenomenology
Abstract

In this note we compare the latest 1.04 fb^{-1} LHC searches for squarks and gluinos from jets and missing transverse momentum (MET) with constraints arising from the LEP Higgs bound. For General Gauge Mediation models with moderate values of tan(beta) we find that the zero-lepton MET searches of supersymmetry at the LHC are only starting to be competitive with the Higgs bounds from LEP. From this perspective and for such models, the SUSY searches at the LHC are still very much in the beginning., Comment: v2: comments and an update added, results unchanged, 15 pages, 5 figures

Published
2011
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16. RG Invariants, Unification and the Role of the Messenger Scale in General Gauge Mediation

Author

Jaeckel, Joerg, Khoze, Valentin V., and Wymant, Chris

Subjects
High Energy Physics - Phenomenology
Abstract

In General Gauge Mediation (GGM) all MSSM soft sfermion masses at a high scale M_mess can be parameterised by three a priori independent scales \Lambda_{S;1,2,3}(M_mess). (Similarly the gaugino masses are given by \Lambda_{G;1,2,3}(M_mess).) For the first two generations this parameterisation in terms of a set of running \Lambda_{S;1,2,3}(\mu) -- conveniently obtained from appropriate RG invariants -- continues to hold all the way down to the electroweak scale. This is not the case for the third generation because of the large Yukawa couplings. Together these two observations imply that the messenger scale is an additional parameter of GGM models. In models where all messengers are in complete GUT multiplets (without significant mass splittings), all \Lambda_{S,r} are equal at M_mess. Starting from the observable mass spectrum at the electroweak scale we present a strategy to determine if this unification occurs and at which scale. This approach uses data accessible at colliders to gain insight into high scale unification physics beyond the unification of gauge couplings., Comment: 17 pages, 6 figures. v2: updated Fig.1, citations added

Published
2011
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17. Mass Sum Rules and the Role of the Messenger Scale in General Gauge Mediation

Author

Jaeckel, Joerg, Khoze, Valentin V., and Wymant, Chris

Subjects
High Energy Physics - Phenomenology
Abstract

In General Gauge Mediation (GGM), supersymmetry breaking is communicated to the Standard Model (MSSM) sector via gauge interactions at a high scale which we refer to as the messenger scale. At this scale GGM predicts certain sum rules between the MSSM sfermion masses. We investigate the validity and the ultimate fate of these sum rules after RG evolution down to the electroweak scale where the mass spectrum will be probed at colliders. We find that the sum rules hold for the first two generations. However the third generation (where sfermions are lightest) violates one of the two sum rules by 10 to 50% over the explored parameter space. This constrains and quantifies the potential use of sum rules as a signature of gauge mediation. We also comment on the role played by the messenger scale in single- and multi-scale GGM models., Comment: 15 pages, 5 figures; v2: reference added

Published
2011
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20. Time to evaluate COVID-19 contact-tracing apps

Author

Colizza, Vittoria, Grill, Eva, Mikolajczyk, Rafael, Cattuto, Ciro, Kucharski, Adam, Riley, Steven, Kendall, Michelle, Lythgoe, Katrina, Bonsall, David, Wymant, Chris, Abeler-Dörner, Lucie, Ferretti, Luca, and Fraser, Christophe

Published
2021
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21. Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1

Author

Balakrishna, Suraj, primary, Loosli, Tom, additional, Zaheri, Maryam, additional, Frischknecht, Paul, additional, Huber, Michael, additional, Kusejko, Katharina, additional, Yerly, Sabine, additional, Leuzinger, Karoline, additional, Perreau, Matthieu, additional, Ramette, Alban, additional, Wymant, Chris, additional, Fraser, Christophe, additional, Kellam, Paul, additional, Gall, Astrid, additional, Hirsch, Hans H, additional, Stoeckle, Marcel, additional, Rauch, Andri, additional, Cavassini, Matthias, additional, Bernasconi, Enos, additional, Notter, Julia, additional, Calmy, Alexandra, additional, Günthard, Huldrych F, additional, Metzner, Karin J, additional, and Kouyos, Roger D, additional

Published
2023
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22. Estimating HIV Generation Time Distribution in Sub-Saharan Africa Using Phylogenetic Data from the Hptn071 Study

Author

Hinch, Rob, primary, Golubchik, Tanya, additional, Probert, William, additional, Bonsall, David, additional, Hall, Matthew, additional, Wymant, Chris, additional, Abeler- Dörner, Lucie, additional, Limbada, Mohammed, additional, Kosloff, Barry, additional, Schaap, Albertus, additional, de Cesare, Mariateresa, additional, MacIntyre-Cockett, George, additional, Simwinga, Musonda, additional, Fidler, Sarah, additional, Hayes, Richard J., additional, Ayles, Helen, additional, and Fraser, Christophe, additional

Published
2023
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23. Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1

Author

Balakrishna, Suraj, Loosli, Tom, Zaheri, Maryam, Frischknecht, Paul, Huber, Michael, Kusejko, Katharina, Yerly, Sabine, Leuzinger, Karoline, Perreau, Matthieu, Ramette, Alban, Wymant, Chris, Fraser, Christophe, Kellam, Paul, Gall, Astrid, Hirsch, Hans H, Stoeckle, Marcel, Rauch, Andri, Cavassini, Matthias, Bernasconi, Enos, Notter, Julia, Calmy, Alexandra, Günthard, Huldrych F, Metzner, Karin J, and Kouyos, Roger D

Subjects
Pharmacology, Microbiology (medical), Infectious Diseases, Pharmacology (medical), 610 Medizin und Gesundheit, 570 Biowissenschaften, Biologie
Abstract

BackgroundNext-generation sequencing (NGS) is gradually replacing Sanger sequencing (SS) as the primary method for HIV genotypic resistance testing. However, there are limited systematic data on comparability of these methods in a clinical setting for the presence of low-abundance drug resistance mutations (DRMs) and their dependency on the variant-calling thresholds.MethodsTo compare the HIV-DRMs detected by SS and NGS, we included participants enrolled in the Swiss HIV Cohort Study (SHCS) with SS and NGS sequences available with sample collection dates ≤7 days apart. We tested for the presence of HIV-DRMs and compared the agreement between SS and NGS at different variant-calling thresholds.ResultsWe included 594 pairs of SS and NGS from 527 SHCS participants. Males accounted for 80.5% of the participants, 76.3% were ART naive at sample collection and 78.1% of the sequences were subtype B. Overall, we observed a good agreement (Cohen’s kappa >0.80) for HIV-DRMs for variant-calling thresholds ≥5%. We observed an increase in low-abundance HIV-DRMs detected at lower thresholds [28/417 (6.7%) at 10%–25% to 293/812 (36.1%) at 1%–2% threshold]. However, such low-abundance HIV-DRMs were overrepresented in ART-naive participants and were in most cases not detected in previously sampled sequences suggesting high sequencing error for thresholds ConclusionsWe found high concordance between SS and NGS but also a substantial number of low-abundance HIV-DRMs detected only by NGS at lower variant-calling thresholds. Our findings suggest that a substantial fraction of the low-abundance HIV-DRMs detected at thresholds

Published
2023
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25. Estimating SARS-CoV-2 variant fitness and the impact of interventions in England using statistical and geo-spatial agent-based models

Author

Hinch, Robert, Panovska-Griffiths, Jasmina, Probert, William JM, Ferretti, Luca, Wymant, Chris, Di Lauro, Francesco, Baya, Nikolas, Ghafari, Mahan, Abeler-Dörner, Lucie, COVID-19 Genomics UK (COG-UK) Consortium, Fraser, Christophe, Hinch, Robert [0000-0003-3169-698X], Panovska-Griffiths, Jasmina [0000-0002-7720-1121], Probert, William JM [0000-0002-3437-759X], Baya, Nikolas [0000-0002-4681-374X], and Apollo - University of Cambridge Repository

Subjects
geo-spatial model, SARS-CoV-2, statistical model, virus variants, Communicable Disease Control, COVID-19, Humans, vaccinations, Seasons, agent-based model
Abstract

The SARS-CoV-2 epidemic has been extended by the evolution of more transmissible viral variants. In autumn 2020, the B.1.177 lineage became the dominant variant in England, before being replaced by the B.1.1.7 (Alpha) lineage in late 2020, with the sweep occurring at different times in each region. This period coincided with a large number of non-pharmaceutical interventions (e.g. lockdowns) to control the epidemic, making it difficult to estimate the relative transmissibility of variants. In this paper, we model the spatial spread of these variants in England using a meta-population agent-based model which correctly characterizes the regional variation in cases and distribution of variants. As a test of robustness, we additionally estimated the relative transmissibility of multiple variants using a statistical model based on the renewal equation, which simultaneously estimates the effective reproduction number R. Relative to earlier variants, the transmissibility of B.1.177 is estimated to have increased by 1.14 (1.12-1.16) and that of Alpha by 1.71 (1.65-1.77). The vaccination programme starting in December 2020 is also modelled. Counterfactual simulations demonstrate that the vaccination programme was essential for reopening in March 2021, and that if the January lockdown had started one month earlier, up to 30 k (24 k-38 k) deaths could have been prevented. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Published
2022

26. A highly virulent variant of HIV-1 circulating in the Netherlands

Author

Wymant, Chris, Bezemer, Daniela, Blanquart, François, Ferretti, Luca, et al, Günthard, Huldrych F, Kouyos, Roger D, University of Zurich, and Wymant, Chris

Subjects
10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 1000 Multidisciplinary, 610 Medicine & health
Published
2022

27. HIV-phyloTSI: Subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data

Author

Golubchik, Tanya, Abeler-Dörner, Lucie, Hall, Matthew, Wymant, Chris, Bonsall, David, Macintyre-Cockett, George, Thomson, Laura, Baeten, Jared, Celum, Connie, Galiwango, Ronald, Kosloff, Barry, Limbada, Mohammed, Mujugira, Andrew, Mugo, Nelly, Gall, Astrid, Blanquart, François, Bakker, Margreet, Bezemer, Daniela, Ong, Swee Hoe, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych, Kivelä, Pia, Kouyos, Roger, Meyer, Laurence, Porter, Kholoud, van Sighem, Ard, van der Valk, Mark, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Ayles, Helen, Burns, David, Fidler, Sarah, Grabowski, Mary Kate, Hayes, Richard, Herbeck, Joshua, Kagaayi, Joseph, Kaleebu, Pontiano, Lingappa, Jairam, Ssemwanga, Deogratius, Eshleman, Susan, Cohen, Myron, Ratmann, Oliver, Laeyendecker, Oliver, Fraser, Christophe, Blanquart, François, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and On behalf of the HPTN 071 (PopART) Phylogenetics protocol team, the BEEHIVE collaboration and the PANGEA consortium

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining duration of infection classify samples into recent and non-recent and are unable to give more granular TSI estimates. These binary classifications have a limited recency time window of several months, therefore requiring large sample sizes, and cannot assess the cumulative impact of an intervention. We developed a Random Forest Regression model, HIV-phyloTSI, that combines measures of within-host diversity and divergence to generate TSI estimates from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performed equally well for all major HIV subtypes based on data from African and European cohorts. We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.

Published
2022

28. Supplementary Figures and Materials from Estimating SARS-CoV-2 variant fitness and the impact of interventions in England using statistical and geo-spatial agent-based models

Author

Hinch, Robert, Panovska-Griffiths, Jasmina, Probert, William J. M., Ferretti, Luca, Wymant, Chris, Lauro, Francesco Di, Baya, Nikolas, Ghafari, Mahan, Abeler-Dörner, Lucie, Consortium, The COVID-19 Genomics UK (COG-UK), and Fraser, Christophe

Subjects
ComputingMethodologies_SIMULATIONANDMODELING, InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, ComputingMilieux_COMPUTERSANDEDUCATION, ComputerApplications_COMPUTERSINOTHERSYSTEMS
Abstract

All supplementary content referenced in the main article.

Published
2022
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29. Phylogenetic estimation of the viral fitness landscape of HIV-1 set-point viral load

Author

Zhao, Lele, Wymant, Chris, Blanquart, François, Golubchik, Tanya, Gall, Astrid, Bakker, Margreet, Bezemer, Daniela, Hall, Matthew, Hoe Ong, Swee, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Grabowski, M. Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F., Kivelä, Pia, Kouyos, Roger D., Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, van Sighem, Ard, van der Valk, Marc, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Ferretti, Luca, on behalf of the BEEHIVE Collaboration, Blanquart, François, University of Oxford, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory (EMBL), Amsterdam UMC - Amsterdam University Medical Center, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Johns Hopkins University (JHU), University hospital of Zurich [Zurich], Helsinki University Hospital [Finland] (HUS), National Institutes of Health [Bethesda] (NIH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University College of London [London] (UCL), Kymab Ltd, Cambridge, England, Medical Microbiology and Infection Prevention, Infectious diseases, AII - Infectious diseases, APH - Digital Health, APH - Personalized Medicine, APH - Global Health, Global Health, APH - Aging & Later Life, University of Zurich, Ferretti, Luca, HUS Internal Medicine and Rehabilitation, Department of Medicine, University of Helsinki, and Infektiosairauksien yksikkö

Subjects
11832 Microbiology and virology, between-host evolution, diagnosis, tansmission fitness, [SDV]Life Sciences [q-bio], 2404 Microbiology, antiretroviral therapy, 610 Medicine & health, heritability, Microbiology, initiation, 10234 Clinic for Infectious Diseases, virulence, [SDV] Life Sciences [q-bio], Virology, 2406 Virology, HIV-1, rna, ddc:610, 3111 Biomedicine, set-point viral load, 610 Medizin und Gesundheit, prognostic markers, time
Abstract

Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical optimum for the virus between 104 and 105 copies of viral RNA per ml. Here we aimed to detect transmission fitness differences between viruses from individuals with different SPVLs directly from phylogenetic trees inferred from whole-genome sequences. We used the local branching index (LBI) as a proxy for transmission fitness. We found that LBI is more sensitive to differences in infectiousness than to differences in the duration of the infectious state. By analysing subtype-B samples from the Bridging the Evolution and Epidemiology of HIV in Europe project, we inferred a significant positive relationship between SPVL and LBI up to approximately 105 copies/ml, with some evidence for a peak around this value of SPVL. This is evidence of selection against low values of SPVL in HIV-1 subtype-B strains, likely related to lower infectiousness, and perhaps a peak in the transmission fitness in the expected range of SPVL. The less prominent signatures of selection against higher SPVL could be explained by an inherent limit of the method or the deployment of antiretroviral therapy.

Published
2022

32. Modelling the effectiveness and social costs of daily lateral flow antigen tests versus quarantine in preventing onward transmission of COVID-19 from traced contacts

Author

Ferretti, Luca, primary, Wymant, Chris, additional, Nurtay, Anel, additional, Zhao, Lele, additional, Hinch, Robert, additional, Bonsall, David, additional, Kendall, Michelle, additional, Masel, Joanna, additional, Bell, John, additional, Hopkins, Susan, additional, Kilpatrick, A. Marm, additional, Peto, Tim, additional, Abeler-Dörner, Lucie, additional, and Fraser, Christophe, additional

Published
2021
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33. OpenABM-Covid19—An agent-based model for non-pharmaceutical interventions against COVID-19 including contact tracing

Author

Hinch, Robert, primary, Probert, William J. M., additional, Nurtay, Anel, additional, Kendall, Michelle, additional, Wymant, Chris, additional, Hall, Matthew, additional, Lythgoe, Katrina, additional, Bulas Cruz, Ana, additional, Zhao, Lele, additional, Stewart, Andrea, additional, Ferretti, Luca, additional, Montero, Daniel, additional, Warren, James, additional, Mather, Nicole, additional, Abueg, Matthew, additional, Wu, Neo, additional, Legat, Olivier, additional, Bentley, Katie, additional, Mead, Thomas, additional, Van-Vuuren, Kelvin, additional, Feldner-Busztin, Dylan, additional, Ristori, Tommaso, additional, Finkelstein, Anthony, additional, Bonsall, David G., additional, Abeler-Dörner, Lucie, additional, and Fraser, Christophe, additional

Published
2021
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35. OpenABM-Covid19 - an agent-based model for non-pharmaceutical interventions against COVID-19 including contact tracing

Author

Hinch, Robert, primary, Probert, William J M, additional, Nurtay, Anel, additional, Kendall, Michelle, additional, Wymant, Chris, additional, Hall, Matthew, additional, Lythgoe, Katrina, additional, Cruz, Ana Bulas, additional, Zhao, Lele, additional, Stewart, Andrea, additional, Ferretti, Luca, additional, Montero, Daniel, additional, Warren, James, additional, Mather, Nicole, additional, Abueg, Matthew, additional, Wu, Neo, additional, Finkelstein, Anthony, additional, Bonsall, David G, additional, Abeler-Dörner, Lucie, additional, and Fraser, Christophe, additional

Published
2020
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36. The timing of COVID-19 transmission

Author

Ferretti, Luca, primary, Ledda, Alice, additional, Wymant, Chris, additional, Zhao, Lele, additional, Ledda, Virginia, additional, Abeler-Dörner, Lucie, additional, Kendall, Michelle, additional, Nurtay, Anel, additional, Cheng, Hao-Yuan, additional, Ng, Ta-Chou, additional, Lin, Hsien-Ho, additional, Hinch, Rob, additional, Masel, Joanna, additional, Kilpatrick, A. Marm, additional, and Fraser, Christophe, additional

Published
2020
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39. Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda

Author

Ratmann, Oliver, primary, Kagaayi, Joseph, additional, Hall, Matthew, additional, Golubchick, Tanya, additional, Kigozi, Godfrey, additional, Xi, Xiaoyue, additional, Wymant, Chris, additional, Nakigozi, Gertrude, additional, Abeler-Dörner, Lucie, additional, Bonsall, David, additional, Gall, Astrid, additional, Hoppe, Anne, additional, Kellam, Paul, additional, Bazaale, Jeremiah, additional, Kalibbala, Sarah, additional, Laeyendecker, Oliver, additional, Lessler, Justin, additional, Nalugoda, Fred, additional, Chang, Larry W, additional, de Oliveira, Tulio, additional, Pillay, Deenan, additional, Quinn, Thomas C, additional, Reynolds, Steven J, additional, Spencer, Simon E F, additional, Ssekubugu, Robert, additional, Serwadda, David, additional, Wawer, Maria J, additional, Gray, Ronald H, additional, Fraser, Christophe, additional, Grabowski, M Kate, additional, Ayles, Helen, additional, Bowden, Rory, additional, Calvez, Vincent, additional, Cohen, Myron, additional, Dennis, Anne, additional, Essex, Max, additional, Fidler, Sarah, additional, Frampton, Dan, additional, Hayes, Richard, additional, Herbeck, Josh, additional, Kaleebu, Pontiano, additional, Kityo, Cissy, additional, Lingappa, Jairam, additional, Novitsky, Vladimir, additional, Paton, Nick, additional, Rambaut, Andrew, additional, Seeley, Janet, additional, Ssemwanga, Deogratius, additional, Tanser, Frank, additional, Lutalo, Tom, additional, Galiwango, Ronald, additional, Makumbi, Fred, additional, Sewankambo, Nelson K., additional, Nabukalu, Dorean, additional, Ndyanabo, Anthony, additional, Ssekasanvu, Joseph, additional, Nakawooya, Hadijja, additional, Nakukumba, Jessica, additional, Kigozi, Grace N., additional, Nantume, Betty S., additional, Resty, Nampijja, additional, Kambasu, Jedidah, additional, Nalugemwa, Margaret, additional, Nakabuye, Regina, additional, Ssebanobe, Lawrence, additional, Nankinga, Justine, additional, Kayiira, Adrian, additional, Nanfuka, Gorreth, additional, Ahimbisibwe, Ruth, additional, Tomusange, Stephen, additional, Galiwango, Ronald M., additional, Nakalanzi, Margaret, additional, Otobi, Joseph O., additional, Ankunda, Denis, additional, Ssembatya, Joseph L., additional, Ssemanda, John B., additional, Kato, Emmanuel, additional, Kairania, Robert, additional, Kisakye, Alice, additional, Batte, James, additional, Ludigo, James, additional, Nampijja, Abisagi, additional, Watya, Steven, additional, Nehemia, Kighoma, additional, Anyokot, Sr. Margaret, additional, Mwinike, Joshua, additional, Kibumba, George, additional, Ssebowa, Paschal, additional, Mondo, George, additional, Wasswa, Francis, additional, Nantongo, Agnes, additional, Kakembo, Rebecca, additional, Galiwango, Josephine, additional, Ssemango, Geoffrey, additional, Redd, Andrew D., additional, Santelli, John, additional, Kennedy, Caitlin E., additional, Wagman, Jennifer, additional, and Tobian, Aaron, additional

Published
2020
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40. Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052

Author

Zhang, Yinfeng, primary, Wymant, Chris, primary, Laeyendecker, Oliver, primary, Grabowski, M Kathryn, primary, Hall, Matthew, primary, Hudelson, Sarah, primary, Piwowar-Manning, Estelle, primary, McCauley, Marybeth, primary, Gamble, Theresa, primary, Hosseinipour, Mina C, primary, Kumarasamy, Nagalingeswaran, primary, Hakim, James G, primary, Kumwenda, Johnstone, primary, Mills, Lisa A, primary, Santos, Breno R, primary, Grinsztejn, Beatriz, primary, Pilotto, Jose H, primary, Chariyalertsak, Suwat, primary, Makhema, Joseph, primary, Chen, Ying Q, primary, Cohen, Myron S, primary, Fraser, Christophe, primary, and Eshleman, Susan H, primary

Published
2020
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41. Easy and accurate reconstruction of whole HIV genomes from short-read sequence data with shiver

Author

BEEHIVE Collaboration, Wymant, Chris, Blanquart, Francois, Golubchik, Tanya, Gall, Astrid, Bakker, Margreet, Bezemer, Daniela, Croucher, Nicholas J., Hall, Matthew, Hillebregt, Mariska, Ong, Swee Hoe, Ratmann, Oliver, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Fransen, Katrien, Gourlay, Annabelle, Grabowski, M. Kate, Gunsenheimer-Bartmeyer, Barbara, Gunthard, Huldrych F., Kivelä, Pia, Kouyos, Roger, Laeyendecker, Oliver, Liitsola, Kirsi, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Cornelissen, Marion, Kellam, Paul, Reiss, Peter, Fraser, Christophe, Institute for Particle Physics Phenomenology (IPPP), Durham University, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Evolution and Ecology Research Center, University of New South Wales [Sydney] (UNSW), Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Ecole Polytechnique Fédérale de Lausanne (EPFL), University College of London [London] (UCL), Universität Zürich [Zürich] = University of Zurich (UZH), Department of Infectious Diseases and Hospital Epidemiology [Zurich], University hospital of Zurich [Zurich], Department of Medicine, The Johns Hopkins University School of Medicine-Division of Infectious Diseases, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Center for Infection and Immunity Amsterdam (CINIMA), Wellcome Trust Genome Campus, Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Big Data Institute, University of Oxford, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), University of Cambridge [UK] (CAM), Laboratory of Experimental Virology - Department of Medical Microbiology [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Johns Hopkins University (JHU), Helsinki University Hospital [Finland] (HUS), Division of Intramural Research [Bethesda, MD, USA] (Cardiovascular Branch), National Institutes of Health [Bethesda] (NIH)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, THe BEEHIVE Collaboration, European Project: 339251,EC:FP7:ERC,ERC-2013-ADG,BEEHIVE(2014), AII - Infectious diseases, Medical Microbiology, APH - Aging & Later Life, Infectious diseases, Global Health, Clinicum, Infektiosairauksien yksikkö, HUS Inflammation Center, HUS Internal Medicine and Rehabilitation, and Bill & Melinda Gates Foundation

Subjects
0301 basic medicine, PROTEASE, Computer science, Sequence assembly, RECOMBINATION, Computational biology, Microbiology, Genome, DNA sequencing, diversity, Set (abstract data type), 03 medical and health sciences, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:610, mapping, TYPE-1, ComputingMilieux_MISCELLANEOUS, Sequence (medicine), Contig, IDENTIFICATION, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], BEEHIVE Collaboration, HIV, INSERTIONS, food and beverages, bioinformatics, TRANSFORM, GENE, Resources, 3. Good health, Identification (information), ALIGNMENT, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, HUMAN-IMMUNODEFICIENCY-VIRUS, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, genome assembly, next-generation sequencing, 3111 Biomedicine, 610 Medizin und Gesundheit, INHIBITORS, Reference genome
Abstract

International audience; Studying the evolution of viruses and their molecular epidemiology relies on accurate viral sequence data, so that small differences between similar viruses can be meaningfully interpreted. Despite its higher throughput and more detailed minority variant data, next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of large betweenand within-host diversity, including frequent indels, may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to pre-process reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with the user’s choice of existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We used shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read whole-genome data produced with the Illumina platform, for sixty-five existing publicly available samples and fifty new samples. We show the systematic superiority of mapping to shiver’s constructed reference compared with mapping the same reads to the closest of 3,249 real references: median values of 13 bases called differently and more accurately, 0 bases called differently and less accurately, and 205 bases of missing sequence recovered. We also successfully applied shiver to whole-genome samples of Hepatitis C Virus and Respiratory Syncytial Virus. shiver is publicly available from https://github.com/ChrisHIV/shiver.

Published
2018

44. HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences

Author

Ratmann, Oliver, Wymant, Chris, Colijn, Caroline, Danaviah, Siva, Essex, Max, Frost, Simon, Gall, Astrid, Gaseitsiwe, Simani, Grabowski, Mary, Gray, Ronald, Guindon, Stéphane, Von Haeseler, Arndt, Kaleebu, Pontiano, Kendall, Michelle, Kozlov, Alexey, Manasa, Justen, Minh, Bui Quang, Moyo, Sikhulile, Novitsky, Vlad, Nsubuga, Rebecca, Pillay, Sureshnee, Quinn, Thomas, Serwadda, David, Ssemwanga, Deogratius, Stamatakis, Alexandros, Trifinopoulos, Jana, Wawer, Maria, Brown, Andy Leigh, De Oliveira, Tulio, Pillay, Deenan, Fraser, Christophe, Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Botswana Harvard AIDS Institute Partnership, Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Africa Centre for Health and Population Studies, and University of KwaZulu-Natal (UKZN)-Medical Research Council of South Africa

Subjects
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract

International audience; To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the “Phylogenetics and Networks for Generalised HIV Epidemics in Africa” consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n = 2,833; MRC/UVRI Uganda, n = 701; Mochudi Prevention Project, n = 359; Africa Health Research Institute Resistance Cohort, n = 92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3′ end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences (NGS) has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.

Published
2017

45. Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052.

Author

Zhang, Yinfeng, Wymant, Chris, Laeyendecker, Oliver, Grabowski, M Kathryn, Hall, Matthew, Hudelson, Sarah, Piwowar-Manning, Estelle, McCauley, Marybeth, Gamble, Theresa, Hosseinipour, Mina C, Kumarasamy, Nagalingeswaran, Hakim, James G, Kumwenda, Johnstone, Mills, Lisa A, Santos, Breno R, Grinsztejn, Beatriz, Pilotto, Jose H, Chariyalertsak, Suwat, Makhema, Joseph, and Chen, Ying Q

Subjects
*HIV prevention, *COMPARATIVE studies, *GENOMES, *HIV, *PHYLOGENY, *BIOINFORMATICS, *SEROCONVERSION, *DESCRIPTIVE statistics, *SEQUENCE analysis
Abstract

Background Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. Methods Complete next-generation sequencing (NGS) data were obtained for 105 unique index–partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner , was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag , pol , env). Results Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. Conclusions We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data. [ABSTRACT FROM AUTHOR]

Published
2021
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47. A comprehensive genomics solution for HIV surveillance and clinical monitoring in a global health setting

Author

Bonsall, David, primary, Golubchik, Tanya, additional, Cesare, Mariateresa de, additional, Limbada, Mohammed, additional, Kosloff, Barry, additional, MacIntyre-Cockett, George, additional, Hall, Matthew, additional, Wymant, Chris, additional, Ansari, M Azim, additional, Abeler-Dörner, Lucie, additional, Schaap, Ab, additional, Brown, Anthony, additional, Barnes, Eleanor, additional, Piwowar-Manning, Estelle, additional, Wilson, Ethan, additional, Emel, Lynda, additional, Hayes, Richard, additional, Fidler, Sarah, additional, Ayles, Helen, additional, Bowden, Rory, additional, and Fraser, Christophe, additional

Published
2018
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50. PHYLOSCANNER: Inferring Transmission from Within- and Between-Host Pathogen Genetic Diversity.

Author

Wymant, Chris, Hall, Matthew, Ratmann, Oliver, Bonsall, David, Golubchik, Tanya, Cesare, Mariateresa de, Gall, Astrid, Cornelissen, Marion, Fraser, Christophe, and Consortium, STOP-HCV

Abstract

A central feature of pathogen genomics is that different infectious particles (virions and bacterial cells) within an infected individual may be genetically distinct, with patterns of relatedness among infectious particles being the result of both within-host evolution and transmission from one host to the next. Here, we present a new software tool, phyloscanner, which analyses pathogen diversity from multiple infected hosts. phyloscanner provides unprecedented resolution into the transmission process, allowing inference of the direction of transmission from sequence data alone. Multiply infected individuals are also identified, as they harbor subpopulations of infectious particles that are not connected by within-host evolution, except where recombinant types emerge. Low-level contamination is flagged and removed. We illustrate phyloscanner on both viral and bacterial pathogens, namely HIV-1 sequenced on Illumina and Roche 454 platforms, HCV sequenced with the Oxford Nanopore MinION platform and Streptococcus pneumoniae with sequences from multiple colonies per individual. [ABSTRACT FROM AUTHOR]

Published
2018
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