ORCID Profile
0000-0003-2525-1407
Current Organisations
EDF Research and Development
,
Universität Basel
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Publications
Author response: Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution
Publisher: eLife Sciences Publications, Ltd
Date: 20-08-2020
Author response: Establishment and stability of the latent HIV-1 DNA reservoir
Publisher: eLife Sciences Publications, Ltd
Date: 14-10-2016
Establishment and stability of the latent HIV-1 DNA reservoir
Publisher: Cold Spring Harbor Laboratory
Date: 18-05-2016
DOI: 10.1101/053983
Abstract: HIV-1 infection currently cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). To characterize establishment, turnover, and evolution of viral DNA reservoirs we deep-sequenced the p17gag region of the HIV-1 genome from s les obtained after 3-18 years of suppressive ART from 10 patients. For each of these patients, whole genome deep-sequencing data of HIV-1 RNA populations before onset of ART were available from 6-12 longitudinal plasma s les spanning 5-8 years of untreated infection. This enabled a detailed analysis of the dynamics and origin of proviral DNA during ART. A median of 14% (range 0-42%) of the p17gag DNA sequences were overtly defective due to G-to-A hypermutation. The remaining sequences were remarkably similar to previously observed RNA sequences and showed no evidence of evolution over many years of suppressive ART. Most sequences from the DNA reservoirs were very similar to viruses actively replicating in plasma (RNA sequences) shortly before start of ART. The results do not support persistent HIV-1 replication as a mechanism to maintain the HIV-1 reservoir during suppressive therapy. Rather, the data indicate that viral DNA variants are turning over as long as patients are untreated and that suppressive ART halts this turnover.
In-vivo mutation rates and fitness landscape of HIV-1
Publisher: Cold Spring Harbor Laboratory
Date: 21-03-2016
DOI: 10.1101/045039
Abstract: Mutation rates and fitness costs of deleterious mutations are difficult to measure in vivo but essential for a quantitative understanding of evolution. Using whole genome deep sequencing data from longitudinal s les during untreated HIV-1 infection, we estimated mutation rates and fitness costs in HIV-1 from the temporal dynamics of genetic variation. At approximately neutral sites, mutations accumulate with a rate of 1.2 x 10 -5 per site per day, in agreement with the rate measured in cell cultures. The rate from G to A is largest, followed by the other transitions C to T, T to C, and A to G, while transversions are more rare. At non-neutral sites, most mutations reduce virus replication using a model of mutation selection balance, we estimated the fitness cost of mutations at every site in the HIV-1 genome. About half of all nonsynonymous mutations have large fitness costs (greater than 10%), while most synonymous mutations have costs below 1%. The cost of synonymous mutations is especially low in most of gag and pol, while much higher costs are observed in important RNA structures and regulatory regions. The intrapatient fitness cost estimates are consistent across multiple patients, suggesting that the deleterious part of the fitness landscape is universal and explains a large fraction of global HIV-1 group M ersity.
SARS-CoV-2 Variants of Interest and Concern naming scheme conducive for global discourse
Publisher: Springer Science and Business Media LLC
Date: 09-06-2021
Future changes in hydrological extremes of a Mediterranean catchment: what can we say in an uncertainty context?
Publisher: Copernicus GmbH
Date: 23-03-2020
DOI: 10.5194/EGUSPHERE-EGU2020-13806
Abstract: & & & span& The Mediterranean region is a hot spot for climate change impact on the water cycle where water resources are anticipated to decrease and hydrological extremes to intensify while population and water use conflicts growth would keep rising. However, the analysis of the uncertainty related to hydrological projections is generally poorly quantified and difficult to translate to decision-makers. In this study, an in-depth analysis of projections and uncertainties for extreme high- and low-flows was performed. Climatic projections derived from a recent downscaling method over France (Adamont, Verfaillie et al., 2017) were used, and hydrological projections were produced on the H& #233 rault River catchment based on two different Radiative Concentration Pathways (RCPs), five global and regional climate model (GCM/RCM) couples, three hydrological models (HMs), and twenty-nine calibration schemes (Lemaitre-Basset et al., sub). This ensemble was analysed with the QUALYPSO approach (Evin et al., 2019) that allows transient uncertainty analysis of ensembles derived from incomplete GCM/RCM matrix. The quasi-ergodic analysis of variance (QE-ANOVA) used in QUALYPSO evaluates the contribution of each impact modelling step to the total uncertainty. For high-flows, GCMs and RCPs contribute the most to the total uncertainty at the short and long lead-time, respectively. For low-flows, HMs structure and calibration period are the most important sources of uncertainty across 2006-2100. While high-flow projections show a significant mean increase of 30% by 2085 compared to the historical period (confidence intervals: [-1% +64%]), low-flows would slightly decrease (-7%) by 2085, but with a higher uncertainty (confidence interval: [-24% +13%]). The time horizons for which a change (e.g. -50, -20, -10, & #8230 , +10, +20, +50%) in high- and low-flows intensity becomes robust (i.e. when more than 66% of the ensemble is above/below a given threshold) were also assessed. This provides strong messages to water managers of the H& #233 rault River catchment who can then anticipate the time needed to prepare and adapt to climate change impacts for extreme hydrological hazards.& /span& & & & & References:& & & & Evin, G., Hingray, B., Blanchet, J., Eckert, N., Morin, S., & Verfaillie, D. (2019). Partitioning Uncertainty Components of an Incomplete Ensemble of Climate Projections Using Data Augmentation. JOURNAL OF CLIMATE, 32, 18. 0.1175/JCLI-D-18-0606.1& & & & Lemaitre-Basset, T., Collet, L., Thirel, G., Parajka, J., Evin, G., Hingray, B. (submitted) Climate change impact and uncertainty analysis on hydrological extremes in a Mediterranean catchment. Hydrological Sciences Journal& & & & Verfaillie, D., D& #233 qu& #233 , M., Morin, S., & Lafaysse, M. (2017). The method ADAMONT v1.0 for statistical adjustment of climate projections applicable to energy balance land surface models. Geoscientific Model Development, 10(11), 4257& #8211 . 0.5194/gmd-10-4257-2017& &
Establishment and stability of the latent HIV-1 DNA reservoir
Publisher: eLife Sciences Publications, Ltd
Date: 15-11-2016
DOI: 10.7554/ELIFE.18889
Abstract: HIV-1 infection cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). In a previous paper ( xref ref-type="bibr" rid="bib43" Zanini et al, 2015 /xref ) we documented HIV-1 evolution in 10 untreated patients. Here we characterize establishment, turnover, and evolution of viral DNA reservoirs in the same patients after 3–18 years of suppressive ART. A median of 14% (range 0–42%) of the DNA sequences were defective due to G-to-A hypermutation. Remaining DNA sequences showed no evidence of evolution over years of suppressive ART. Most sequences from the DNA reservoirs were very similar to viruses actively replicating in plasma (RNA sequences) shortly before start of ART. The results do not support persistent HIV-1 replication as a mechanism to maintain the HIV-1 reservoir during suppressive therapy. Rather, the data indicate that DNA variants are turning over as long as patients are untreated and that suppressive ART halts this turnover.
Urgent need for a non-discriminatory and non-stigmatizing nomenclature for monkeypox virus
Publisher: Public Library of Science (PLoS)
Date: 23-08-2022
Rapid and consistent evolution of colistin resistance inPseudomonas aeruginosaduring morbidostat culture
Publisher: Cold Spring Harbor Laboratory
Date: 14-10-2016
DOI: 10.1101/080960
Abstract: Colistin is a last resort antibiotic commonly used against multidrug-resistant strains of Pseudomonas aeruginosa . To investigate the potential for in-situ evolution of resistance against colistin and map the molecular targets of colistin resistance, we exposed two P. aeruginosa isolates to colistin using a continuous culture device known as morbidostat. Colistin resistance emerged within two weeks along with highly stereotypic yet strain specific mutation patterns. The majority of mutations hit the prmAB two component signaling system and genes involved in lipopolysaccharide synthesis, including lpxC , pmrE , and migA . In seven out of 18 cultures, we observed mutations in mutS along with a mutator phenotype that seemed to facilitate resistance evolution.
Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 13-08-2020
DOI: 10.2807/1560-7917.ES.2020.25.32.2001410
Abstract: We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.
Rapid and Consistent Evolution of Colistin Resistance in Extensively Drug-Resistant Pseudomonas aeruginosa during Morbidostat Culture
Publisher: American Society for Microbiology
Date: 09-2017
DOI: 10.1128/AAC.00043-17
Abstract: Colistin is a last-resort antibiotic commonly used against multidrug-resistant strains of Pseudomonas aeruginosa . To investigate the potential for in situ evolution of resistance against colistin and to map the molecular targets of colistin resistance, we exposed two P. aeruginosa isolates to colistin using a continuous-culture device known as a morbidostat. As a result, colistin resistance reproducibly increased 10-fold within 10 days and 100-fold within 20 days, along with highly stereotypic yet strain-specific mutation patterns. The majority of mutations hit the pmrAB two-component signaling system and genes involved in lipopolysaccharide (LPS) synthesis, including lpxC , pmrE , and migA . We tracked the frequencies of all arising mutations by whole-genome deep sequencing every 3 to 4 days to obtain a detailed picture of the dynamics of resistance evolution, including competition and displacement among multiple resistant subpopulations. In 7 out of 18 cultures, we observed mutations in mutS along with a mutator phenotype that seemed to facilitate resistance evolution.
Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution
Publisher: eLife Sciences Publications, Ltd
Date: 02-09-2020
DOI: 10.7554/ELIFE.60067
Abstract: Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.
Related Organisations
Institut National De Recherche Pour L'Agriculture L'Alimentation Et L'Environnement
Location: France
Heriot-Watt University
Location: United Kingdom of Great Britain and Northern Ireland
Université De Strasbourg Ecole Et Observatoire Des Sciences De La Terre
Location: France
Kavli Institute For Theoretical Physics
Location: United States of America
Related Funding Activities
No related grants have been discovered for Richard Neher.