Author: "Amandine Perrin" - Searchworks@Jio Institute Digital Library Search Results

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1. Correction: PPanGGOLiN: Depicting microbial diversity via a partitioned pangenome graph

Author: Guillaume Gautreau, Adelme Bazin, Mathieu Gachet, Rémi Planel, Laura Burlot, Mathieu Dubois, Amandine Perrin, Claudine Médigue, Alexandra Calteau, Stéphane Cruveiller, Catherine Matias, Christophe Ambroise, Eduardo P. C. Rocha, and David Vallenet
Subjects: Biology (General), QH301-705.5
Published: 2021

2. Phylogenetic background and habitat drive the genetic diversification of Escherichia coli.

Author: Marie Touchon, Amandine Perrin, Jorge André Moura de Sousa, Belinda Vangchhia, Samantha Burn, Claire L O'Brien, Erick Denamur, David Gordon, and Eduardo Pc Rocha
Subjects: Genetics, QH426-470
Abstract: Escherichia coli is mostly a commensal of birds and mammals, including humans, where it can act as an opportunistic pathogen. It is also found in water and sediments. We investigated the phylogeny, genetic diversification, and habitat-association of 1,294 isolates representative of the phylogenetic diversity of more than 5,000 isolates from the Australian continent. Since many previous studies focused on clinical isolates, we investigated mostly other isolates originating from humans, poultry, wild animals and water. These strains represent the species genetic diversity and reveal widespread associations between phylogroups and isolation sources. The analysis of strains from the same sequence types revealed very rapid change of gene repertoires in the very early stages of divergence, driven by the acquisition of many different types of mobile genetic elements. These elements also lead to rapid variations in genome size, even if few of their genes rise to high frequency in the species. Variations in genome size are associated with phylogroup and isolation sources, but the latter determine the number of MGEs, a marker of recent transfer, suggesting that gene flow reinforces the association of certain genetic backgrounds with specific habitats. After a while, the divergence of gene repertoires becomes linear with phylogenetic distance, presumably reflecting the continuous turnover of mobile element and the occasional acquisition of adaptive genes. Surprisingly, the phylogroups with smallest genomes have the highest rates of gene repertoire diversification and fewer but more diverse mobile genetic elements. This suggests that smaller genomes are associated with higher, not lower, turnover of genetic information. Many of these genomes are from freshwater isolates and have peculiar traits, including a specific capsule, suggesting adaptation to this environment. Altogether, these data contribute to explain why epidemiological clones tend to emerge from specific phylogenetic groups in the presence of pervasive horizontal gene transfer across the species.
Published: 2020
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3. PPanGGOLiN: Depicting microbial diversity via a partitioned pangenome graph.

Author: Guillaume Gautreau, Adelme Bazin, Mathieu Gachet, Rémi Planel, Laura Burlot, Mathieu Dubois, Amandine Perrin, Claudine Médigue, Alexandra Calteau, Stéphane Cruveiller, Catherine Matias, Christophe Ambroise, Eduardo P C Rocha, and David Vallenet
Subjects: Biology (General), QH301-705.5
Abstract: The use of comparative genomics for functional, evolutionary, and epidemiological studies requires methods to classify gene families in terms of occurrence in a given species. These methods usually lack multivariate statistical models to infer the partitions and the optimal number of classes and don't account for genome organization. We introduce a graph structure to model pangenomes in which nodes represent gene families and edges represent genomic neighborhood. Our method, named PPanGGOLiN, partitions nodes using an Expectation-Maximization algorithm based on multivariate Bernoulli Mixture Model coupled with a Markov Random Field. This approach takes into account the topology of the graph and the presence/absence of genes in pangenomes to classify gene families into persistent, cloud, and one or several shell partitions. By analyzing the partitioned pangenome graphs of isolate genomes from 439 species and metagenome-assembled genomes from 78 species, we demonstrate that our method is effective in estimating the persistent genome. Interestingly, it shows that the shell genome is a key element to understand genome dynamics, presumably because it reflects how genes present at intermediate frequencies drive adaptation of species, and its proportion in genomes is independent of genome size. The graph-based approach proposed by PPanGGOLiN is useful to depict the overall genomic diversity of thousands of strains in a compact structure and provides an effective basis for very large scale comparative genomics. The software is freely available at https://github.com/labgem/PPanGGOLiN.
Published: 2020
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4. IntegronFinder 2.0: Identification and Analysis of Integrons across Bacteria, with a Focus on Antibiotic Resistance in Klebsiella

Author: Bertrand Néron, Eloi Littner, Matthieu Haudiquet, Amandine Perrin, Jean Cury, and Eduardo P. C. Rocha
Subjects: integron, antibiotic resistance, bioinformatics, genomics, Biology (General), QH301-705.5
Abstract: Integrons are flexible gene-exchanging platforms that contain multiple cassettes encoding accessory genes whose order is shuffled by a specific integrase. Integrons embedded within mobile genetic elements often contain multiple antibiotic resistance genes that they spread among nosocomial pathogens and contribute to the current antibiotic resistance crisis. However, most integrons are presumably sedentary and encode a much broader diversity of functions. IntegronFinder is a widely used software to identify novel integrons in bacterial genomes, but has aged and lacks some useful functionalities to handle very large datasets of draft genomes or metagenomes. Here, we present IntegronFinder version 2. We have updated the code, improved its efficiency and usability, adapted the output to incomplete genome data, and added a few novel functions. We describe these changes and illustrate the relevance of the program by analyzing the distribution of integrons across more than 20,000 fully sequenced genomes. We also take full advantage of its novel capabilities to analyze close to 4000 Klebsiella pneumoniae genomes for the presence of integrons and antibiotic resistance genes within them. Our data show that K. pneumoniae has a large diversity of integrons and the largest mobile integron in our database of plasmids. The pangenome of these integrons contains a total of 165 different gene families with most of the largest families being related with resistance to numerous types of antibiotics. IntegronFinder is a free and open-source software available on multiple public platforms.
Published: 2022
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5. Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant: findings from the Icatibant Outcome Survey

Author: Werner Aberer, Marcus Maurer, Laurence Bouillet, Andrea Zanichelli, Teresa Caballero, Hilary J. Longhurst, Amandine Perrin, Irmgard Andresen, and for the IOS Study Group
Subjects: Hereditary angioedema, Icatibant, Breakthrough attacks, Prophylaxis, Bradykinin, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Background Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option. Methods Data on LTP use, attacks, and treatments were recorded. Attack characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP. Results Data on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while patients were using LTP. Attack rate, attack severity, and the distribution of attack sites were similar across all types of LTP used, and were comparable to the results found in patients who did not receive LTP. Attacks were successfully treated with icatibant; 82.5% of all breakthrough attacks were treated with a single icatibant injection without C1-INH rescue medication. Treatment outcomes were comparable for breakthrough attacks across all LTP types, and for attacks without LTP. Conclusions Patients who use LTP should be aware that breakthrough attacks can occur, and such attacks can be severe. Thus, patients with C1-INH-HAE using LTP should have emergency treatment readily available. Data from IOS show that icatibant is effective for the treatment of breakthrough attacks. Trial Registration NCT01034969
Published: 2017
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6. Evolutionary dynamics and genomic features of the Elizabethkingia anophelis 2015 to 2016 Wisconsin outbreak strain

Author: Amandine Perrin, Elise Larsonneur, Ainsley C. Nicholson, David J. Edwards, Kristin M. Gundlach, Anne M. Whitney, Christopher A. Gulvik, Melissa E. Bell, Olaya Rendueles, Jean Cury, Perrine Hugon, Dominique Clermont, Vincent Enouf, Vladimir Loparev, Phalasy Juieng, Timothy Monson, David Warshauer, Lina I. Elbadawi, Maroya Spalding Walters, Matthew B. Crist, Judith Noble-Wang, Gwen Borlaug, Eduardo P. C. Rocha, Alexis Criscuolo, Marie Touchon, Jeffrey P. Davis, Kathryn E. Holt, John R. McQuiston, and Sylvain Brisse
Subjects: Science
Abstract: Elizabethkingia anophelis is an emerging pathogen of high antimicrobial resistance. Perrin and colleagues sequenced isolates of a 2015/2016 E. anophelis outbreak in Wisconsin and found substantial genetic diversity, accelerated evolutionary rate and a disruptive mutation in the DNA repair gene mutY.
Published: 2017
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7. Assisted transcriptome reconstruction and splicing orthology

Author: Samuel Blanquart, Jean-Stéphane Varré, Paul Guertin, Amandine Perrin, Anne Bergeron, and Krister M. Swenson
Subjects: Transcriptome prediction, Splicing orthologs, Eukaryotes, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract: Abstract Background Transcriptome reconstruction, defined as the identification of all protein isoforms that may be expressed by a gene, is a notably difficult computational task. With real data, the best methods based on RNA-seq data identify barely 21 % of the expressed transcripts. While waiting for algorithms and sequencing techniques to improve — as has been strongly suggested in the literature — it is important to evaluate assisted transcriptome prediction; this is the question of how alternative transcription in one species performs as a predictor of protein isoforms in another relatively close species. Most evidence-based gene predictors use transcripts from other species to annotate a genome, but the predictive power of procedures that use exclusively transcripts from external species has never been quantified. The cornerstone of such an evaluation is the correct identification of pairs of transcripts with the same splicing patterns, called splicing orthologs. Results We propose a rigorous procedural definition of splicing orthologs, based on the identification of all ortholog pairs of splicing sites in the nucleotide sequences, and alignments at the protein level. Using our definition, we compared 24 382 human transcripts and 17 909 mouse transcripts from the highly curated CCDS database, and identified 11 122 splicing orthologs. In prediction mode, we show that human transcripts can be used to infer over 62 % of mouse protein isoforms. When restricting the predictions to transcripts known eight years ago, the percentage grows to 74 %. Using CCDS timestamped releases, we also analyze the evolution of the number of splicing orthologs over the last decade. Conclusions Alternative splicing is now recognized to play a major role in the protein diversity of eukaryotic organisms, but definitions of spliced isoform orthologs are still approximate. Here we propose a definition adapted to the subtle variations of conserved alternative splicing sites, and use it to validate numerous accurate orthologous isoform predictions.
Published: 2016
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8. Comparative genomics of carbapenemase-producingMorganella spp

Author: Rémy A. Bonnin, Elodie Creton, Amandine Perrin, Delphine Girlich, Cecile Emeraud, Agnès B. Jousset, Mathilde Duque, Katie Hopkins, Pierre Bogaerts, Youri Glupczynski, Niels Pfennigwerth, Marek Gniadkowski, Antoni Hendrickx, Kim van der Zwaluw, Petra Apfalter, Rainer Hartl, Vendula Heringova, Jaroslav Hrabak, Gerald Larrouy-Maumus, Eduardo P. C. Rocha, Thierry Naas, and Laurent Dortet
Abstract: BackgroundMorganellaare opportunistic pathogens involved in various infections. InMorganella, intrinsic resistance to multiple antibiotics including colistin combined with the emergence of carbapenemase-producers (CP) strongly limits the antimicrobial armamentarium.MethodsFrom 2013 to 2021, 172 highly drug-resistant (XDR)Morganellaisolates from 8 European countries and Canada, two reference strains from the Pasteur Institute collection and two susceptible isolates were characterized by WGS, antimicrobial susceptibility testing and biochemical tests. Complete genomes from Genbank (n=103) were included for genomic analysis. Intrinsic resistance mechanism to polymyxins was deciphered by combining genetic analysis with mass spectrometry on the lipid A.FindingsMorganellacould be separated into 4 species namedM. psychrotolerans, M. sibonii, M. morganiiand a new species represented by a unique strain.Morganella morganiiincluded two subspecies:M. morganiisubsp.morganii(the most prevalent) andM. morganiisubsp.intermedius. Intrinsic resistance to tetracycline and conservation of metabolic pathways correlated this refined taxonomy. CP were mostly identified among five ‘high-risk’ clones ofM. morganiisubsp.morganii. A single nucleotide polymorphism (SNP) cut-off of 100 was used to decipher outbreaks involving this species. Cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards the 172 XDRMorganellaspp. isolates of our collection (including 145 CP) except for metallo-β-lactamase-producers. The intrinsic resistance to polymyxins corresponds to the addition of L-Ara4N on the lipid A.InterpretationThis global characterization of the widest collection of XDRMorganellaspp. highlighted the need to clarify the taxonomy, deciphered intrinsic resistance mechanisms and paved the way for further genomic comparisons.FundingNoneRESEARCH IN CONTEXTEvidence before this studyOn January 28th2022, we have searched for the terms “Morganella” and “carbapenemase” in all published reports available in PubMed with no language restriction. We identified a total of 43 articles and most of them (41/43) corresponded to a report of a single isolate of carbapenemase-producingMorganella morganii. Only one article aimed to decipher the antimicrobial susceptibility on a collection ofProteus, ProvidenciaandMorganellaisolated from global hospitalized patients with intra-abdominal and urinary tract infections. However, this collection only included 7M. morganiiisolates. On March 2021, when we finished the inclusions in our collection, only 104 genomes ofMorganellaspp. were available in the NCBI database.Since September 2021, very few reports were published on carbapenemase-producing Morganella with the exception of a study from Xiang Get al. reported 40 multi-drug resistantM. morganiiisolates recovered from three hospitals in China from 2014 to 2020. Unfortunately, this collection included only two carbapenemase-producingM. morganiiisolates (one OXA-48 and one IMP-1). A report of KPC-producingM. morganiiin Japan and a longitudinal study of carbapemase-producing Enterobactrales in Taiwan that did not focused on Morganella.We also searched in PubMed for the terms ‘Morganella sibonii” or “Morganella psychrotolerans” in all published reports with no language restrictions. Our search identified a total of 20 articles. None of them was related to antimicrobial resistance and no study deciphered theMorganellaspp. epidemiology on clinical isolates.Added values of this studyThis global characterization involved the widest collection ofMorganellaspp. isolates ever reported (barely doubling the number ofMorganellaspp. genomes in Genbank). In addition, 145 isolates of this worldwide collection made of 172 multidrug resistantMorganellaspp. were carbapenemase producers for which therapeutic alternatives are scarce due to intrinsic resistance to last resort molecules, such as polymyxin.First, we found that cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards XDRMorganellaspp. isolates except for metallo-β-lactamase-producers.Then, we observed that carbapenemase-encoding genes were present in differentMorganellaspecies highlighting necessary changes in the taxonomy.Morganellagenus could be divided into 4 species namedM. psychrotolerans, M. sibonii, M. morganiiand a new species represented by a unique strain.Morganella morganiiincludes two subspecies:M. morganiisubsp.morganii(the most prevalent) andM. morganiisubsp.intermedius. We demonstrated that this refined taxonomy correlated with the intrinsic resistance to tetracycline, which was found only inM. sibonii, as well as several metabolic pathways (e.g. trehalose assimilation, type III (T3SS) and type IV secretion system (T6SS), etc.…).In addition, we highlighted five “high-risk” clones of carbapenemase-producingM. morganiisubsp.morganiithat have already disseminated worldwide. Combining whole genome sequencing (WGS) data with epidemiological investigations, we demonstrated that a cut-off of 100 single nucleotide polymorphisms (SNPs) could be used to discriminate clonally-related from sporadic independent isolates. This information is of the utmost importance since WGS is now considered as the reference method to identify and follow outbreaks.The intrinsic resistance ofMorganellaspp. to polymyxins was well-known but the underlying mechanism was unclear. Here, we demonstrated that the addition of L-Ara4N on the lipid A ofMorganellais involved.Implications of all the available evidenceThe identification of “high-risk” clones among highly-drug resistantMorganellaspp. paves the way of future investigations to better understand and hopefully limit the spread of these bugs. Additionally, our results identified new components and virulence factors of someMorganellaspecies (e.g. T6SS and T3SS inM. sibonii) that deserve further investigation since they might be implicated in the bacterial lifestyle of this genus.
Published: 2023
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9. BioConvert: a comprehensive format converter for life sciences

Author: Hugo Caro, Sulyvan Dollin, Anne Biton, Bryan Brancotte, Dimitri Desvillechabrol, Yoann Dufresne, Blaise Li, Etienne Kornobis, Frédéric Lemoine, Nicolas Maillet, Amandine Perrin, Nicolas Traut, Bertrand Néron, Thomas Cokelaer, Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Algorithmes pour les séquences biologiques - Sequence Bioinformatics, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Neuroanatomie Appliquée et Théorique / Applied and Theoretical Neuroanatomy (NAAT), France Génomique Consortium (ANR 10-INBS-09-08) and IBISA and the Biomics Platform of Institut Pasteur, Paris, France, and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: [INFO.INFO-DS]Computer Science [cs]/Data Structures and Algorithms [cs.DS], [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: Bioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To over-come these difficulties, we initiatedBioConvert, a collaborative project to facilitate the conversion of life science data from one format to another.BioConvertaggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently,BioConvertsupports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users,BioConvertcan also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface toBioConvert, hence allowing direct use for the community.
Published: 2023
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10. Safety and efficacy of sucroferric oxyhydroxide in pediatric patients with chronic kidney disease

Author: Raoul D. Nelson, Mihaela Balgradean, Carolyn Abitbol, Milica Enoiu, Marc Fila, Larry A. Greenbaum, Nikola Jeck, Sun Young Ahn, Rita D. Swinford, Günter Klaus, Larysa Wickman, Amandine Perrin, Augustina Jankauskiene, Sahar Fathallah-Shaykh, Ana Paredes, and Cristina Stoica
Subjects: Nephrology, Sucrose, medicine.medical_specialty, Adolescent, medicine.drug_class, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Ferric Compounds, Gastroenterology, 03 medical and health sciences, Hyperphosphatemia, 0302 clinical medicine, Renal Dialysis, Chronic kidney disease, Phosphate binder, Internal medicine, Post-hoc analysis, Humans, Medicine, Renal Insufficiency, Chronic, Sucroferric oxyhydroxide, Child, Adverse effect, Children, business.industry, Phosphorus, medicine.disease, Drug Combinations, Safety profile, Standard error, Tolerability, Pediatrics, Perinatology and Child Health, Original Article, business, Kidney disease
Abstract: Background Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety. Methods This phase 3, multicenter, randomized, open-label study investigated safety and efficacy of sucroferric oxyhydroxide (SFOH) in pediatric and adolescent subjects with CKD and hyperphosphatemia. Subjects were randomized to SFOH or calcium acetate (CaAc) for a 10-week dose titration (stage 1), followed by a 24-week safety extension (stage 2). Primary efficacy endpoint was change in serum phosphorus from baseline to the end of stage 1 in the SFOH group. Safety endpoints included treatment-emergent adverse events (TEAEs). Results Eighty-five subjects (2–18 years) were randomized and treated (SFOH, n = 66; CaAc, n = 19). Serum phosphorus reduction from baseline to the end of stage 1 in the overall SFOH group (least squares [LS] mean ± standard error [SE]) was − 0.488 ± 0.186 mg/dL; p = 0.011 (post hoc analysis). Significant reductions in serum phosphorus were observed in subjects aged ≥ 12 to ≤ 18 years (LS mean ± SE − 0.460 ± 0.195 mg/dL; p = 0.024) and subjects with serum phosphorus above age-related normal ranges at baseline (LS mean ± SE − 0.942 ± 0.246 mg/dL; p = 0.005). Similar proportions of subjects reported ≥ 1 TEAE in the SFOH (75.8%) and CaAc (73.7%) groups. Withdrawal due to TEAEs was more common with CaAc (31.6%) than with SFOH (18.2%). Conclusions SFOH effectively managed serum phosphorus in pediatric patients with a low pill burden and a safety profile consistent with that reported in adult patients.
Published: 2020
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11. Was the Last Bacterial Common Ancestor a Monoderm after All?

Author: Raphaël R. Léonard, Eric Sauvage, Valérian Lupo, Amandine Perrin, Damien Sirjacobs, Paulette Charlier, Frédéric Kerff, Denis Baurain, Integrative Biological Sciences (InBioS), Université de Liège, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This work was supported in part by the Belgian Program on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister’s Office, Science Policy programming (IAP no. P6/19). It also benefited from computational resources made available on the Tier-1 supercomputer of the Fédération Wallonie-Bruxelles, infrastructure funded by the Walloon Region under the grant agreement n°1117545, and on the 'durandal' grid computer, partially funded by two grants to DB (University of Liège 'Crédit de démarrage 2012' SFRD-12/04, and F.R.S.-FNRS 'Crédit de recherche 2014' CDR J.0080.15). R.R.L. and V.L. are the recipients of FRIA (Fonds de la Recherche pour l’Industrie et l’Agriculture) fellowships (F.R.S.-FNRS, Brussels, Belgium).
Subjects: bacterial evolution, cell-wall, outer membrane (OM), Bayesian inference (BI), phylogenomics, comparative genomics, ancestral traits, Bacteria, Gram-Negative Bacteria, Genetics, Bayes Theorem, Gram-Positive Bacteria, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Genetics (clinical), Phylogeny
Abstract: International audience; The very nature of the last bacterial common ancestor (LBCA), in particular the characteristics of its cell wall, is a critical issue to understand the evolution of life on earth. Although knowledge of the relationships between bacterial phyla has made progress with the advent of phylogenomics, many questions remain, including on the appearance or disappearance of the outer membrane of diderm bacteria (also called Gram-negative bacteria). The phylogenetic transition between monoderm (Gram-positive bacteria) and diderm bacteria, and the associated peptidoglycan expansion or reduction, requires clarification. Herein, using a phylogenomic tree of cultivated and characterized bacteria as an evolutionary framework and a literature review of their cell-wall characteristics, we used Bayesian ancestral state reconstruction to infer the cell-wall architecture of the LBCA. With the same phylogenomic tree, we further revisited the evolution of the division and cell-wall synthesis (dcw) gene cluster using homology- and model-based methods. Finally, extensive similarity searches were carried out to determine the phylogenetic distribution of the genes involved with the biosynthesis of the outer membrane in diderm bacteria. Quite unexpectedly, our analyses suggest that all cultivated and characterized bacteria might have evolved from a common ancestor with a monoderm cell-wall architecture. If true, this would indicate that the appearance of the outer membrane was not a unique event and that selective forces have led to the repeated adoption of such an architecture. Due to the lack of phenotypic information, our methodology cannot be applied to all extant bacteria. Consequently, our conclusion might change once enough information is made available to allow the use of an even more diverse organism selection.
Published: 2022
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12. PanACoTA: A modular tool for massive microbial comparative genomics

Author: Eduardo P. C. Rocha and Amandine Perrin
Subjects: Comparative genomics, Phylogenetic tree, Computer science, business.industry, Process (engineering), Genomics, Modular design, business, Adaptation (computer science), Gene, Data science, Genome
Abstract: The gene repertoires of microbial species, their pangenomes, evolve very fast. Their study facilitates the discrimination between lineages and reveals which genes drive their recent adaptation. It has therefore become a key topic of study in microbial evolution and genomics. Yet, the increase in the number of genomes available to certain species, now reaching many thousands, complicates the establishment of the basic building blocks of comparative genomics. Here, we present PanACoTA, a tool that allows to download all genomes of a species, build a database with those passing quality and redundancy controls, define uniform annotation, and use them to build a pangenome, several variants of core or persistent genomes, their alignments, and a rapid but accurate phylogenetic tree. While many programs have become available in the last few years to build pangenomes, we have focused on a method that tackles all the key steps of the process, from download to phylogenetic inference. This was conceived in a modular way, i.e. while all steps are integrated, they can also be run separately and multiple times to allow rapid and extensive exploration of the space of parameters of interest. The software is built in Python 3 and includes features to facilitate its installation and its future development. We believe PanACoTa is an interesting addition to the current set of bioinformatics software for comparative genomics, since it will accelerate and standardize the more routine parts of the work, allowing microbial genomicists to more quickly tackle their specific questions.
Published: 2020
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13. Interoperable medical data: the missing link for understanding COVID-19

Author: Denis C. Bauer, Seshadri S. Vasan, David Hansen, Amandine Perrin, Yatish Jain, L.S. Wilson, Sebastian Maurer-Stroh, Alejandro Metke-Jimenez, Kate Ebrill, Suma Tiruvayipati, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Macquarie University, National University of Singapore (NUS), Ministry of Health [Singapore], Yong Loo Lin School of Medicine [Singapore], Genome Institute of Singapore (GIS), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Collège doctoral [Sorbonne universités], Sorbonne Université (SU), University of York [York, UK], Genome Institute of Singapore (S.T.), Institut Pasteur (A.P.), Temasek Foundation (S.T.), Agency for Science, Technology and Research (S.T., S.M-S.), Coalition for Epidemic Preparedness Innovations (S.S.V.), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Collège Doctoral
Subjects: Knowledge management, Coronavirus disease 2019 (COVID-19), 040301 veterinary sciences, Computer science, genome sequence, [SDV]Life Sciences [q-bio], Interoperability, Ontology (information science), Global Health, SARS‐CoV‐2, 0403 veterinary science, 03 medical and health sciences, Resource (project management), COVID‐19, Component (UML), Influenza, Human, Controlled vocabulary, Health care, Animals, Humans, Medical history, ontology, 030304 developmental biology, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Data collection, General Veterinary, General Immunology and Microbiology, SARS-CoV-2, business.industry, COVID-19, 04 agricultural and veterinary sciences, General Medicine, patient information, Data science, 3. Good health, Workflow, Rapid Communications, business, Rapid Communication, GISAID
Abstract: International audience; Being able to link clinical outcomes to SARS-CoV-2 virus strains is a critical component of understanding COVID-19. Here, we discuss how current processes hamper sustainable data collection to enable meaningful analysis and insights. Following the 'Fast Healthcare Interoperable Resource' (FHIR) implementation guide, we introduce an ontology-based standard questionnaire to overcome these shortcomings and describe patient 'journeys' in coordination with the World Health Organization's recommendations. We identify steps in the clinical health data acquisition cycle and workflows that likely have the biggest impact in the data-driven understanding of this virus. Specifically, we recommend detailed symptoms and medical history using the FHIR standards. We have taken the first steps towards this by making patient status mandatory in GISAID ('Global Initiative on Sharing All Influenza Data'), immediately resulting in a measurable increase in the fraction of cases with useful patient information. The main remaining limitation is the lack of controlled vocabulary or a medical ontology.
Published: 2020
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14. Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study

Author: Linda H. Ficociello, Jacques Rottembourg, Amandine Perrin, Sebastian Walpen, Philip A. Kalra, Christoph Wanner, Manuela Stauss-Grabo, Denis Fouque, Jorge B. Cannata-Andía, Angel L.M. de Francisco, Marc G. Vervloet, Markus Ketteler, Piergiorgio Messa, Anja Derlet, Ioannis N Boletis, VU University Medical Center [Amsterdam], National and Kapodistrian University of Athens (NKUA), Hospital Universitario Marqués de Valdecilla [Santander], Salford Royal Hospital [Salford, UK], Robert-Bosch-Krankenhaus, University of Split, Università degli Studi di Milano [Milano] (UNIMI), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Würzburg = Universität Würzburg, Universidad de Oviedo [Oviedo], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, chronic kidney disease, end-stage kidney disease, haemodialysis, phosphate binder, peritoneal dialysis, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, Peritoneal dialysis, 03 medical and health sciences, Hyperphosphatemia, 0302 clinical medicine, Internal medicine, medicine, AcademicSubjects/MED00340, Dialysis, Transplantation, business.industry, Original Articles, medicine.disease, 3. Good health, Phosphate binder, Tolerability, Nephrology, Concomitant, Hemodialysis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract: Background The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis. Methods This non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels. Results The safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: −1.0 mg/dL, P Conclusions SFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden.
Published: 2020
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15. PPanGGOLiN: Depicting microbial diversity via a partitioned pangenome graph

Author: Adelme Bazin, Stéphane Cruveiller, Claudine Médigue, David Vallenet, Guillaume Gautreau, Rémi Planel, Eduardo P. C. Rocha, Mathieu Gachet, Amandine Perrin, Mathieu Dubois, Christophe Ambroise, Alexandra Calteau, Catherine Matias, Laura Burlot, Analyse Bio-Informatique pour la Génomique et le Métabolisme (LABGeM), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)-Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), Laboratoire de Probabilités, Statistique et Modélisation (LPSM (UMR_8001)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)-Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ED 515 - Complexité du vivant, Laboratoire de Probabilités, Statistiques et Modélisations (LPSM (UMR_8001)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), This research was supported in part by the IRTELIS and Phare PhD programs of the French Alternative Energies and Atomic Energy Commission (CEA) for GG and AB respectively, the French Government 'Investissements d’Avenir' programs (namely FRANCE GENOMIQUE [ANR-10-INBS-09-08], the INSTITUT FRANÇAIS DE BIOINFORMATIQUE [ANR-11-INBS-0013], and the Agence Nationale de la Recherche [Projet ANR-16-CE12-29 for EPCR])., We acknowledge Alexandre Renaux and Jonathan Mercier for their preliminary insights on pangenome graphs. We thank Mélanie Buy for drawing the PPanGGOLiN logo. Finally, we thank Guilhem Royer, Valentin Sabatet, Johan Rollin, Mohammed-Amin Madoui, Tom Delmont, Nicolas Pons and Pierre Peterlongo for all their advice along this work., Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)-Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), and Collège doctoral [Sorbonne universités]
Subjects: Computer science, [SDV]Life Sciences [q-bio], 01 natural sciences, Genome, 010104 statistics & probability, Database and Informatics Methods, Biology (General), Genome Evolution, Genomic organization, Data Management, 0303 health sciences, Markov random field, Applied Mathematics, Simulation and Modeling, Genomics, Genomic Databases, Physical Sciences, Engineering and Technology, Synthetic Biology, Algorithms, Research Article, Computer and Information Sciences, QH301-705.5, Computational biology, Research and Analysis Methods, Molecular Evolution, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Gene family, 0101 mathematics, Gene, Genome size, 030304 developmental biology, Taxonomy, Comparative genomics, Evolutionary Biology, Bacteria, Correction, Biology and Life Sciences, Computational Biology, 15. Life on land, Comparative Genomics, Synthetic Genomics, Genome Analysis, Biological Databases, Multivariate Analysis, Genome dynamics, Genome, Bacterial, Software, Mathematics
Abstract: The use of comparative genomics for functional, evolutionary, and epidemiological studies requires methods to classify gene families in terms of occurrence in a given species. These methods usually lack multivariate statistical models to infer the partitions and the optimal number of classes and don’t account for genome organization. We introduce a graph structure to model pangenomes in which nodes represent gene families and edges represent genomic neighborhood. Our method, named PPanGGOLiN, partitions nodes using an Expectation-Maximization algorithm based on multivariate Bernoulli Mixture Model coupled with a Markov Random Field. This approach takes into account the topology of the graph and the presence/absence of genes in pangenomes to classify gene families into persistent, cloud, and one or several shell partitions. By analyzing the partitioned pangenome graphs of isolate genomes from 439 species and metagenome-assembled genomes from 78 species, we demonstrate that our method is effective in estimating the persistent genome. Interestingly, it shows that the shell genome is a key element to understand genome dynamics, presumably because it reflects how genes present at intermediate frequencies drive adaptation of species, and its proportion in genomes is independent of genome size. The graph-based approach proposed by PPanGGOLiN is useful to depict the overall genomic diversity of thousands of strains in a compact structure and provides an effective basis for very large scale comparative genomics. The software is freely available at https://github.com/labgem/PPanGGOLiN., Author summary Microorganisms have the greatest biodiversity and evolutionary history on earth. At the genomic level, it is reflected by a highly variable gene content even among organisms from the same species which explains the ability of microbes to be pathogenic or to grow in specific environments. We developed a new method called PPanGGOLiN which accurately represents the genomic diversity of a species (i.e. its pangenome) using a compact graph structure. Based on this pangenome graph, we classify genes by a statistical method according to their occurrence in the genomes. This method allowed us to build pangenomes even for uncultivated species at an unprecedented scale. We applied our method on all available genomes in databanks in order to depict the overall diversity of hundreds of species. Overall, our work enables microbiologists to explore and visualize pangenomes alike a subway map.
Published: 2020
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16. FC024REAL-WORLD SAFETY AND EFFECTIVENESS OF SUCROFERRIC OXYHYDROXIDE IN PATIENTS UNDERGOING PERITONEAL DIALYSIS: AN INTERIM ANALYSIS OF THE VERIFIE STUDY

Author: Anja Derlet, Jorge B. Cannata-Andía, Linda H. Ficociello, Markus Ketteler, Jacques Rottembourg, Denis Fouque, Sebastian Walpen, Manuela Stauss-Grabo, Philip A. Kalra, Angel L.M. de Francisco, Marc G. Vervloet, Christoph Wanner, Amandine Perrin, Ioannis Boletis, and Piergiorgio Messa
Subjects: Transplantation, medicine.medical_specialty, Nephrology, business.industry, medicine.medical_treatment, Medicine, In patient, business, Interim analysis, Surgery, Peritoneal dialysis
Published: 2019
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17. Evolutionary dynamics and genomic features of the Elizabethkingia anophelis 2015 to 2016 Wisconsin outbreak strain

Author: Gwen Borlaug, Eduardo P. C. Rocha, Matthew B. Crist, Phalasy Juieng, Maroya Spalding Walters, Lina I Elbadawi, Elise Larsonneur, Kathryn E. Holt, Jeffrey P. Davis, Marie Touchon, Anne M. Whitney, David J. Edwards, John R. McQuiston, Alexis Criscuolo, Kristin M. Gundlach, Dominique Clermont, Timothy A. Monson, Vincent Enouf, Melissa Bell, David M. Warshauer, Perrine Hugon, Ainsley C. Nicholson, Vladimir N. Loparev, Olaya Rendueles, Amandine Perrin, Christopher A. Gulvik, Sylvain Brisse, Jean Cury, Judith Noble-Wang, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, University of Melbourne, Wisconsin State Laboratory of Hygiene [Madison] (WSLH), University of Wisconsin-Madison, Collection de l'Institut Pasteur (CIP), Institut Pasteur [Paris], Pasteur International Bioresources network (PIBNet), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Prévention et Thérapie Moléculaires des Maladies humaines, This work was supported by Institut Pasteur, French government’s Investissement d’Avenir program Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant ANR-10-LABX-62-IBEID), and the Advanced Molecular Detection (AMD) initiative at CDC. O.R. was supported by a fellowship from Fondation pour la Recherche Médicale (grant number ARF20150934077). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., We thank D. Mornico of Institut Pasteur and V. Nyak of CDC for assistance with submission of sequence data to public repositories. We would also like to thank the State Health Departments of Michigan and Illinois for contributing strains and information for the cases outside of the State of Wisconsin. The efforts of laboratory staff in both DHQP and DHCPP are greatly appreciated., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Rendueles, Olaya, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Bioinformatics and Sequence Analysis (BONSAI), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria), Institut Français de Bioinformatique - UMS CNRS 3601 (IFB-CORE), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Forest research, Northern research station, Forestry Commission, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus influenzae (Grippe)-Génétique moléculaire des virus à ARN (CNR), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), and Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8)
Subjects: 0301 basic medicine, Most recent common ancestor, MESH: Sequence Analysis, DNA, MESH: Mutation Rate, Elizabethkingia, General Physics and Astronomy, medicine.disease_cause, DNA Glycosylases, Disease Outbreaks, Mutation Rate, Flavobacteriaceae Infections, Bacterial genetics, MESH: Disease Outbreaks, MESH: Phylogeny, MESH: Flavobacteriaceae Infections / epidemiology, ComputingMilieux_MISCELLANEOUS, Phylogeny, Genetics, MESH: Bacterial Proteins / genetics, Multidisciplinary, MESH: Flavobacteriaceae / pathogenicity, Phylogenetic tree, Virulence, 3. Good health, MESH: Wisconsin / epidemiology, MESH: Flavobacteriaceae / genetics, Elizabethkingia anophelis, Pathogens, Flavobacteriaceae, food.ingredient, Science, 030106 microbiology, Bacterial genome size, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, food, Wisconsin, Bacterial Proteins, Phylogenetics, MESH: Virulence / genetics, medicine, Humans, MESH: Genome, Bacterial / genetics, Evolutionary dynamics, MESH: DNA Glycosylases / genetics, MESH: Humans, Outbreak, General Chemistry, Sequence Analysis, DNA, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, 030104 developmental biology, Bacterial genes, Evolutionary biology, MESH: Flavobacteriaceae Infections / microbiology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial infection, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Genome, Bacterial
Abstract: An atypically large outbreak of Elizabethkingia anophelis infections occurred in Wisconsin. Here we show that it was caused by a single strain with thirteen characteristic genomic regions. Strikingly, the outbreak isolates show an accelerated evolutionary rate and an atypical mutational spectrum. Six phylogenetic sub-clusters with distinctive temporal and geographic dynamics are revealed, and their last common ancestor existed approximately one year before the first recognized human infection. Unlike other E. anophelis, the outbreak strain had a disrupted DNA repair mutY gene caused by insertion of an integrative and conjugative element. This genomic change probably contributed to the high evolutionary rate of the outbreak strain and may have increased its adaptability, as many mutations in protein-coding genes occurred during the outbreak. This unique discovery of an outbreak caused by a naturally occurring mutator bacterial pathogen provides a dramatic example of the potential impact of pathogen evolutionary dynamics on infectious disease epidemiology., Elizabethkingia anophelis is an emerging pathogen of high antimicrobial resistance. Perrin and colleagues sequenced isolates of a 2015/2016 E. anophelis outbreak in Wisconsin and found substantial genetic diversity, accelerated evolutionary rate and a disruptive mutation in the DNA repair gene mutY.
Published: 2017
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18. FO047REAL-WORLD EFFECTIVENESS OF SUCROFERRIC OXYHYDROXIDE FOR SERUM PHOSPHORUS CONTROL IN DIALYSIS PATIENTS: AN INTERIM SUBGROUP ANALYSIS OF THE VERIFIE STUDY

Author: Marc G. Vervloet, Denis Fouque, Philip A. Kalra, Anja Derlet, Piergiorgio Messa, Markus Ketteler, Viatcheslav Rakov, Jacques Rottembourg, Jorge B. Cannata-Andía, Christoph Wanner, Amandine Perrin, Linda H. Ficociello, Sebastian Walpen, Ioannis Boletis, Manuela Stauss-Grabo, and Angel L.M. de Francisco
Subjects: Transplantation, medicine.medical_specialty, business.industry, Phosphorus, chemistry.chemical_element, Subgroup analysis, Dialysis patients, Gastroenterology, chemistry, Nephrology, Internal medicine, Interim, Medicine, Serum phosphorus, business
Published: 2018
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19. Achieving dietary recommendations and reducing greenhouse gas emissions: modelling diets to minimise the change from current intakes

Author: Graham W. Horgan, Amandine Perrin, Stephen Whybrow, Jennie I. Macdiarmid, The James Hutton Institute, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), The Rowett Institute, and University of Aberdeen
Subjects: Adult, Greenhouse Effect, Male, 0301 basic medicine, Population, Medicine (miscellaneous), Physical Therapy, Sports Therapy and Rehabilitation, Clinical nutrition, Environment, Modelling, Food Supply, Nutrition Policy, 03 medical and health sciences, 0302 clinical medicine, Nutrient, Environmental health, Linear programming, Greenhouse gas emissions, Humans, Medicine, Dietary recommendations, 030212 general & internal medicine, education, Greenhouse effect, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Research, Nutritional Requirements, Agriculture, Feeding Behavior, Nutrition Surveys, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, United Kingdom, Diet, Dietary Requirements, Food, Greenhouse gas, Sustainability, Female, sense organs, Energy Intake, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Sustainable diets
Abstract: International audience; Background: Average population dietary intakes do not reflect the wide diversity of dietary patterns across thepopulation. It is recognised that most people in the UK do not meet dietary recommendations and have diets witha high environmental impact, but changing dietary habits has proved very difficult. The purpose of this study wasto investigate the diversity in dietary changes needed to achieve a healthy diet and a healthy diet with lowergreenhouse gas emissions (GHGE) (referred to as a sustainable diet) by taking into account each individual’s currentdiet and then minimising the changes they need to make.Methods: Linear programming was used to construct two new diets for each adult in the UK National Diet andNutrition Survey (n = 1491) by minimising the changes to their current intake. Stepwise changes were applied until(i) dietary recommendations were achieved and (ii) dietary recommendations and a GHGE target were met. First,gradual changes (≤50 %) were made to the amount of any foods currently eaten. Second, new foods were addedto the diet. Third, greater reductions (≤75 %) were made to the amount of any food currently eaten and finally,foods were removed from the diet.Results: One person out of 1491 in the sample met all the dietary requirements based on their reported dietaryintake. Only 7.5 and 4.6 % of people achieved a healthy diet and a sustainable diet, respectively, by changing theamount of any food they currently ate by up to 50 %. The majority required changes to the amount of each foodeaten plus the addition of new foods. Fewer than 5 % had to remove foods they ate to meet recommendations.Sodium proved the most difficult nutrient recommendation to meet. The healthy diets and sustainable dietsproduced a 15 and 27 % reduction in greenhouse gas emissions respectively.Conclusions: Since healthy diets alone do not produce substantial reductions in greenhouse gas emissions, dietaryguidelines need to include recommendations for environmental sustainability. Minimising the shift from currentdietary intakes is likely to make dietary change more realistic and achievable
Published: 2016
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20. Time delays in the diagnosis and treatment of Fabry disease

Author: Pablo García-Pavía, Amandine Perrin, and Ricardo Reisin
Subjects: 0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Time delays, Delayed Diagnosis, High variability, 030105 genetics & heredity, Time-to-Treatment, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, In patient, Enzyme Replacement Therapy, Symptom onset, Young adult, Child, business.industry, General Medicine, Enzyme replacement therapy, medicine.disease, Fabry disease, Europe, Child, Preschool, Fabry Disease, Female, business, 030217 neurology & neurosurgery
Abstract: Background: The high variability in clinical manifestations of Fabry disease can lead to delays between symptom onset and correct diagnosis, and between correct diagnosis and initiation of enzyme replacement therapy. We investigated whether these delays have improved in recent years. Methods: Data were analyzed from the Fabry Outcome Survey (FOS; Shire; extracted August 2013) for “index patients”, defined as the first patient diagnosed with Fabry disease from a family with several or no additional members registered in FOS. Results: Periods analyzed: 2001–2006 versus 2007–2013, in patients overall and from Europe versus the rest of the world (ROW). Overall, 598 patients were diagnosed within the study periods. Median age (95% CI) at symptom onset in 2001–2006 and 2007–2013 was 7.0 (5.0–11.0) and 9.0 (6.0–11.0) in children, and 21.0 (15.0–28.0) and 31.0 (26.0–35.0) in adults, respectively. Overall, the delay in diagnosis did not improve, despite showing a trend towards earlier diagnosis in adults (median 14.0 [95% CI 9.0–20.0] vs. 10.5 [8.0–13.0] years) and children (5.0 [1.0–9.0] vs. 4.0 [0.0–8.0] years). In contrast, the delay in treatment onset significantly decreased from 2001–2006 to 2007–2013 in children (4.3 [2.0–7.0] vs. 1.0 [0.8–1.4] year; p < 0.001) and adults (2.1 [1.3–3.2] vs. 0.9 [0.8–1.1] years; p < 0.001). Geographically, the delay in treatment onset significantly decreased in the ROW among children (5.3 [4.2–8.0] vs. 1.0 [0.8–1.4] year; p < 0.001) and adults (5.4 [4.8–6.0] vs. 1.1 [0.9–1.1] year; p < 0.001), but it did not change in Europe. Conclusion: We found that the delay in diagnosis has not improved substantially whereas the delay in treatment onset has improved in recent years. pre-print 519 KB
Published: 2016

21. FP593REAL-WORLD SAFETY AND EFFECTIVENESS OF SUCROFERRIC OXYHYDROXIDE IN DIALYSIS PATIENTS: AN INTERIM ANALYSIS OF THE VERIFIE STUDY

Author: Piergiorgio Messa, Linda H. Ficociello, Jacques Rottembourg, Markus Ketteler, Philip A. Kalra, Christoph Wanner, Sebastian Walpen, Ioannis Boletis, Denis Fouque, Amandine Perrin, Jorge B. Cannata-Andía, Angel L.M. de Francisco, Manuela Stauss-Grabo, Marc G. Vervloet, Viatcheslav Rakov, and Anja Derlet
Subjects: Transplantation, medicine.medical_specialty, Nephrology, business.industry, medicine, Interim analysis, Intensive care medicine, Dialysis patients, business
Published: 2018
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22. Assisted transcriptome reconstruction and splicing orthology

Author: Anne Bergeron, Paul Guertin, Jean-Stéphane Varré, Samuel Blanquart, Amandine Perrin, Krister M. Swenson, Bioinformatics and Sequence Analysis (BONSAI), Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire de combinatoire et d'informatique mathématique [Montréal] (LaCIM), Centre de Recherches Mathématiques [Montréal] (CRM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Université du Québec à Montréal = University of Québec in Montréal (UQAM), Collège André-Grasset [Montréal], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Biologie Computationnelle (IBC), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AB is partially supported by Canada NSERC Grant number 05729-2014, and by Équipes associées Inria-FRQNT Grant number 188128. This research is supported by the Inria Associate Team program.Inria associated team CG-ALCODE (2014-2016), Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Eukaryotes, Proteomics, Genome, Transcriptome, MESH: RNA / metabolism, Mice, MESH: Proteins / chemistry, Protein Isoforms, MESH: Animals, Splicing orthologs, Genetics, MESH: Transcriptome, MESH: Alternative Splicing, MESH: Proteins / metabolism, Exons, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], RNA splicing, Transcriptome prediction, DNA microarray, MESH: RNA / chemistry, Algorithms, MESH: RNA / genetics, Biotechnology, MESH: Computational Biology, Gene isoform, lcsh:QH426-470, lcsh:Biotechnology, MESH: Protein Isoforms / genetics, Computational biology, Biology, MESH: Protein Isoforms / metabolism, 03 medical and health sciences, lcsh:TP248.13-248.65, MESH: Proteins / genetics, Animals, Humans, Gene, MESH: Mice, MESH: Protein Isoforms / chemistry, MESH: Humans, Alternative splicing, Computational Biology, Proteins, Alternative Splicing, lcsh:Genetics, 030104 developmental biology, MESH: Algorithms, RNA, MESH: Exons
Abstract: International audience; Background: Transcriptome reconstruction, defined as the identification of all protein isoforms that may be expressed by a gene, is a notably difficult computational task. With real data, the best methods based on RNA-seq data identify barely 21 % of the expressed transcripts. While waiting for algorithms and sequencing techniques to improve — as has been strongly suggested in the literature — it is important to evaluate assisted transcriptome prediction; this is the question of how alternative transcription in one species performs as a predictor of protein isoforms in another relatively close species. Most evidence-based gene predictors use transcripts from other species to annotate a genome, but the predictive power of procedures that use exclusively transcripts from external species has never been quantified. The cornerstone of such an evaluation is the correct identification of pairs of transcripts with the same splicing patterns, called splicing orthologs. Results: We propose a rigorous procedural definition of splicing orthologs, based on the identification of all ortholog pairs of splicing sites in the nucleotide sequences, and alignments at the protein level. Using our definition, we compared 24 382 human transcripts and 17 909 mouse transcripts from the highly curated CCDS database, and identified 11 122 splicing orthologs. In prediction mode, we show that human transcripts can be used to infer over 62 % of mouse protein isoforms. When restricting the predictions to transcripts known eight years ago, the percentage grows to 74 %. Using CCDS timestamped releases, we also analyze the evolution of the number of splicing orthologs over the last decade. Conclusions: Alternative splicing is now recognized to play a major role in the protein diversity of eukaryotic organisms, but definitions of spliced isoform orthologs are still approximate. Here we propose a definition adapted to the subtle variations of conserved alternative splicing sites, and use it to validate numerous accurate orthologous isoform predictions.
Published: 2016
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23. Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: cardiac outcomes after 10 years’ treatment

Author: Christoph Kampmann, Michael Beck, and Amandine Perrin
Subjects: medicine.medical_specialty, Lysosomal storage disorder, Cardiomyopathy, Left ventricular hypertrophy, Angina, Internal medicine, medicine, Genetics(clinical), Pharmacology (medical), cardiovascular diseases, Prospective cohort study, Genetics (clinical), Agalsidase alfa, Medicine(all), Fabry disease, Alpha-galactosidase, biology, business.industry, Research, General Medicine, Enzyme replacement therapy, medicine.disease, Endocrinology, Heart failure, Cardiology, biology.protein, business
Abstract: Background To explore long-term effects of agalsidase alfa on Fabry disease cardiomyopathy in adults. Methods Retrospective analysis of prospectively collected data at a single center in Mainz, Germany, revealed that 45 adult patients (21 men, 24 women) had received agalsidase alfa for approximately 10 years. Data were extracted for cardiac and heart failure status, echocardiographic evaluations of cardiac structure and function, and renal function at treatment start and during agalsidase alfa treatment. Results After 10 years of agalsidase alfa treatment, heart failure classification had improved by at least 1 class in 22/42 patients, and angina scores were stable or improved in 41/42 patients. During treatment, no patients without left ventricular hypertrophy (LVH) at treatment initiation developed LVH, and no patients with LVH at treatment initiation showed a decline in left ventricular mass. Conclusions Approximately 10 years of agalsidase alfa treatment appeared to have beneficial effects for controlling progression and improving some symptoms of Fabry-associated cardiomyopathy.
Published: 2015

24. O005 Improvement in hereditary angioedema diagnosis: Findings from the icatibant outcome survey

Author: Teresa Caballero, Amandine Perrin, Anete Sevciovic Grumach, Irmgard Andresen, Laurence Bouillet, Andrea Zanichelli, Markus Magerl, Anette Bygum, Marcus Maurer, Werner Aberer, and Hilary Longhurst
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Immunology, medicine.disease, Dermatology, Outcome (game theory), chemistry.chemical_compound, chemistry, Icatibant, Hereditary angioedema, medicine, Immunology and Allergy, business
Published: 2016
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25. Age at First Cardiac Symptoms in Fabry Disease: Association with a Chinese Hotspot Fabry Mutation (IVS4+919G>A), Classical Fabry Mutations, and Sex in a Taiwanese Population from the Fabry Outcome Survey (FOS)

Author: Hao-Chuan Liu, Hsiang-Yu Lin, Ting-Rong Hsu, Amandine Perrin, Dau-Ming Niu, Chia-Feng Yang, and Wen-Chung Yu
Subjects: Pediatrics, medicine.medical_specialty, Newborn screening, education.field_of_study, business.industry, Population, Enzyme replacement therapy, Left ventricular hypertrophy, medicine.disease, Chest pain, Fabry disease, Article, Cohort, Palpitations, medicine, medicine.symptom, business, education
Abstract: This is a descriptive analysis of a cohort of 59 Taiwanese patients with Fabry disease and either classical Fabry or cardiac variant IVS4+919G>A (IVS4) mutations from a disease registry, the Fabry Outcome Survey (FOS; sponsored by Shire). Most of our classical Fabry patients were symptomatic and were identified upon seeking medical advice at our clinics, whereas most of our IVS4 patients attended our clinics after newborn screening identified this mutation in their grandsons. The objective was to determine differences in cardiac manifestations between patients with classical Fabry or IVS4 mutations by comparing age at onset of selected cardiac symptoms. Data were extracted in August 2013 and analyzed retrospectively. Fifty-nine Taiwanese patients (median age at extract 60.7 years [range 15.0–86.9]; n = 36 [61%] male) with proven IVS4 (n = 41 [69%]) or classical Fabry mutations (n = 18 [31%]) had available data on cardiac symptoms. Of 55 (93%) patients with reported left ventricular hypertrophy (LVH), mean [SD] age (years) at first symptom was lower in classical Fabry males (30.0 [15.1]; n = 4) than classical Fabry females (49.6 [8.9]; n = 11; p
Published: 2015
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26. MP416EFFICACY OF ORAL IRON FOR TREATING IRON DEFICIENCY IN ANAEMIC PATIENTS WITH NON-DIALYSIS DEPENDENT CKD (ND-CKD)

Author: Iain C. Macdougall, Amandine Perrin, Andreas Bock, D Van Wyck, Yvonne Meier, Simon D. Roger, Carlo A. J. M. Gaillard, S Larroque, Fernando Carrera, and K-U Eckardt
Subjects: Transplantation, medicine.medical_specialty, Nephrology, Non dialysis dependent, business.industry, Internal medicine, medicine, Iron deficiency, medicine.disease, business, Gastroenterology
Published: 2017
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27. ProCARs: Progressive Reconstruction of Ancestral Gene Orders

Author: Amandine Perrin, Jean-Stéphane Varré, Samuel Blanquart, Aïda Ouangraoua, Bioinformatics and Sequence Analysis (BONSAI), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Genome, Models, Genetic, Research, Computational Biology, Boreoeutherian ancestor, Genomics, Animal Population Groups, Evolution, Molecular, Small phylogeny problem, Population Groups, [INFO.INFO-IR]Computer Science [cs]/Information Retrieval [cs.IR], Genetics, Animals, Humans, [INFO]Computer Science [cs], [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Ancestral gene orders reconstruction, Algorithms, Phylogeny, Biotechnology
Abstract: International audience; BACKGROUND:In the context of ancestral gene order reconstruction from extant genomes, there exist two main computational approaches: rearrangement-based, and homology-based methods. The rearrangement-based methods consist in minimizing a total rearrangement distance on the branches of a species tree. The homology-based methods consist in the detection of a set of potential ancestral contiguity features, followed by the assembling of these features into Contiguous Ancestral Regions (CARs).RESULTS:In this paper, we present a new homology-based method that uses a progressive approach for both the detection and the assembling of ancestral contiguity features into CARs. The method is based on detecting a set of potential ancestral adjacencies iteratively using the current set of CARs at each step, and constructing CARs progressively using a 2-phase assembling method.CONCLUSION:We show the usefulness of the method through a reconstruction of the boreoeutherian ancestral gene order, and a comparison with three other homology-based methods: AnGeS, InferCARs and GapAdj. The program, written in Python, and the dataset used in this paper are available at http://bioinfo.lifl.fr/procars/ webcite.
Published: 2014
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28. Early Versus Late Administration of Icatibant in Patients With Hereditary Angioedema

Author: Anette Bygum, Werner Aberer, Anete Sevciovic Grumach, Laurence Bouillet, Teresa Caballero, Irmgard Andresen, Amandine Perrin, Andrea Zanichelli, Marcus Maurer, and Hilary Longhurst
Subjects: medicine.medical_specialty, business.industry, Immunology, medicine.disease, Dermatology, chemistry.chemical_compound, chemistry, Icatibant, Hereditary angioedema, Immunology and Allergy, Medicine, In patient, business, Administration (government)
Published: 2017
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29. O004 Childhood presenting hereditary angioedema is diagnosed in adulthood by non-pediatric physicians: Icatibant outcome survey findings

Author: Andrea Zanichelli, Hilary Longhurst, Werner Aberer, Laurence Bouillet, Marcus Maurer, Teresa Caballero, Amandine Perrin, Anette Bygum, Anete Sevciovic Grumach, and Irmgard Andresen
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, business.industry, Immunology, medicine.disease, Outcome (game theory), chemistry.chemical_compound, chemistry, Icatibant, Hereditary angioedema, medicine, Physical therapy, Immunology and Allergy, business
Published: 2016
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30. Gender Analysis of Icatibant-Treatment Outcomes of Acute Angioedema Attacks in Patients with Hereditary Angioedema Type I and II: Results from the Icatibant Outcome Survey

Author: Hilary Longhurst, Laurence Bouillet, Marcus Maurer, Andrea Zanichelli, Teresa Caballero, Irmgard Andresen, Amandine Perrin, and Werner Aberer
Subjects: medicine.medical_specialty, Angioedema, business.industry, Immunology, Treatment outcome, Outcome (game theory), Dermatology, Hereditary Angioedema Type I, chemistry.chemical_compound, chemistry, Icatibant, medicine, Immunology and Allergy, Gender analysis, In patient, medicine.symptom, business
Published: 2016
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31. Taiwanese patients with the Chinese IVS4+919G>A mutation who underwent endomyocardial biopsy: Data from the Fabry Outcome Survey (FOS)

Author: Dau-Ming Niu, Amandine Perrin, Shih-Hsien Sung, Wen-Chung Yu, Ting-Rong Hsu, Fu-Pang Chang, and Tzu-Hung Chu
Subjects: medicine.medical_specialty, Endocrinology, business.industry, Endocrinology, Diabetes and Metabolism, Internal medicine, Mutation (genetic algorithm), Genetics, medicine, business, Molecular Biology, Biochemistry, Surgery, Endomyocardial biopsy
Published: 2015
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32. The Icatibant Outcome Survey: Characterizing Breakthrough Hereditary Angioedema Attacks In Patients Receiving Long-Term Prophylaxis

Author: Werner Aberer, Teresa Caballero, Marcus Maurer, Amandine Perrin, Laurence Bouillet, Andrea Zanichelli, and Hilary Longhurst
Subjects: Pediatrics, medicine.medical_specialty, business.industry, Immunology, Long term prophylaxis, medicine.disease, Outcome (game theory), chemistry.chemical_compound, chemistry, Icatibant, Anesthesia, Hereditary angioedema, medicine, Immunology and Allergy, In patient, business
Published: 2014
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33. Adverse cutaneous reactions due to glycopeptides-induced adverse cutaneous reactions

Author: Annick Barbaud, Philippe Trechot, Amandine Perrin, Nadine Petitpain, J. Luc Schmutz, and J. François Cuny
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Immunology, Immunology and Allergy, Medicine, business, Dermatology, Glycopeptide
Published: 2007
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34. A Clinical Study Provides the First Direct Evidence That Interindividual Variations in Fecal β-Lactamase Activity Affect the Gut Mycobiota Dynamics in Response to β-Lactam Antibiotics

Author: Delavy, Margot, Burdet, Charles, Sertour, Natacha, Devente, Savannah, Docquier, Jean-Denis, Grall, Nathalie, Volant, Stevenn, Ghozlane, Amine, Duval, Xavier, Mentré, France, D’enfert, Christophe, Bougnoux, Marie-Elisabeth, Study Group, Predires, Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Siena = University of Siena (UNISI), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], This work was supported by grants from Agence Nationale de la Recherche (FunComPath ANR-14-IFEC-0004 and PrediRes ANR-16-CE15-0022), the French Government’s Investissement d’Avenir program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases [ANR10-LABX-62-IBEID]), the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie action, Innovative Training Network (FunHoMic, Grant No. 812969) and Assistance Publique – Hôpitaux de Paris (CEREMI CRC13-179)., For the PrediRes study group: Charles Burdet (INSERM, Université de Paris APHP-Bichat Hospital), Erick Denamur (INSERM, Université de Paris), Xavier Duval (INSERM, Université de Paris, APHP-Bichat Hospital), Dusko Ehrlich (INRA Metagenopolis), France Mentré (INSERM, Université de Paris, APHP-Bichat Hospital), Eduardo P. C. Rocha (Institut Pasteur), Laurie Alla (INRA Metagenopolis), Emmanuelle Lechatelier (INRA Metagenopolis), Florence Levenez (INRA Metagenopolis), Nicolas Pons (INRA Metagenopolis), Benoît Quinquis (INRA Metagenopolis), Khadija Bourabha (INSERM), Antoine Bridier Nahmias (INSERM, Université de Paris), Olivier Clermont (INSERM, Université de Paris), Mélanie Magnan (INSERM, Université de Paris), Olivier Tenaillon (INSERM, Université de Paris), Camille d’Humières (INSERM, Université de Paris, APHP-Bichat Hospital, Institut Pasteur), Amandine Perrin (Institut Pasteur), Marie Touchon (Institut Pasteur), Dominique Rainteau (INSERM, Université Pierre et Marie Curie, APHP – Saint Antoine Hospital), Farid Ichou (ICAN), Philippe Lesnik (ICAN), Jimmy Mullaert (INSERM, Université de Paris, APHP – Bichat Hospital), Thu Thuy Nguyen (INSERM)., ANR-14-IFEC-0004,FunComPath,From fungal commensalism to pathogenicity:dissection of the colonization-to-infection shift of Candida albicans(2014), ANR-16-CE15-0022,PREDIRES,PREDIction de l'émergence de la RESistance bactérienne dans le microbiote intestinal humain lors d'un traitement antibiotique(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and European Project: 812969,H2020-MSCA-ITN-2018,FunHoMic(2019)
Subjects: beta-lactamases, healthy individuals, Virology, [SDV]Life Sciences [q-bio], Candida albicans, gut mycobiota, Microbiology, antibiotics
Abstract: International audience; Antibiotics disturb the intestinal bacterial microbiota, leading to gut dysbiosis and an increased risk for the overgrowth of opportunistic pathogens. It is not fully understood to what extent antibiotics affect the fungal fraction of the intestinal microbiota, the mycobiota. There is no report of the direct role of antibiotics in the overgrowth in healthy humans of the opportunistic pathogenic yeast Candida albicans. Here, we have explored the gut mycobiota of 22 healthy subjects before, during, and up to 6 months after a 3-day regimen of third-generation cephalosporins (3GCs). Using ITS1-targeted metagenomics, we highlighted the strong intra- and interindividual diversity of the healthy gut mycobiota. With a specific quantitative approach, we showed that C. albicans prevalence was much higher than previously reported, with all subjects but one being carriers of C. albicans, although with highly variable burdens. 3GCs significantly altered the mycobiota composition and the fungal load was increased both at short and long term. Both C. albicans relative and absolute abundances were increased but 3GCs did not reduce intersubject variability. Variations in C. albicans burden in response to 3GC treatment could be partly explained by changes in the levels of endogenous fecal β-lactamase activity, with subjects characterized by a high increase of β-lactamase activity displaying a lower increase of C. albicans levels. A same antibiotic treatment might thus affect differentially the gut mycobiota and C. albicans carriage, depending on the treated subject, suggesting a need to adjust the current risk factors for C. albicans overgrowth after a β-lactam treatment.IMPORTANCE Fungal infections are redoubtable healthcare-associated complications in immunocompromised patients. Particularly, the commensal intestinal yeast Candida albicans causes invasive infections in intensive care patients and is, therefore, associated with high mortality. These infections are preceded by an intestinal expansion of C. albicans before its translocation into the bloodstream. Antibiotics are a well-known risk factor for C. albicans overgrowth but the impact of antibiotic-induced dysbiosis on the human gut mycobiota—the fungal microbiota—and the understanding of the mechanisms involved in C. albicans overgrowth in humans are very limited. Our study shows that antibiotics increase the fungal proportion in the gut and disturb the fungal composition, especially C. albicans, in a subject-dependent manner. Indeed, variations across subjects in C. albicans burden in response to β-lactam treatment could be partly explained by changes in the levels of endogenous fecal β-lactamase activity. This highlighted a potential new key factor for C. albicans overgrowth. Thus, the significance of our research is in providing a better understanding of the factors behind C. albicans intestinal overgrowth, which might lead to new means to prevent life-threatening secondary infections.
Published: 2022
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35. COVID-Align: Accurate online alignment of hCoV-19 genomes using a profile HMM

Author: Olivier Gascuel, Luc Blassel, Frédéric Lemoine, Jakub Voznica, Bioinformatique évolutive - Evolutionary Bioinformatics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Ecole Doctorale Complexité du Vivant (ED515), Sorbonne Université (SU), Université de Paris (UP), LB PhD Grant: PRAIRIE (ANR-19-P3IA-0001), JV PhD Grant: École Normale Supérieure Paris-Saclay and ED Frontières de l'Innovation en Recherche et Education., Sincere thanks to Amandine Perrin and Fabien Mareuil (Institut Pasteur) for help, and the GISAID Team and all its Data Contributors for sharing their genome data., ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Cité (UPCité)
Subjects: 0106 biological sciences, Statistics and Probability, AcademicSubjects/SCI01060, Computer science, Interface (Java), Computational biology, 01 natural sciences, Biochemistry, Genome, 03 medical and health sciences, Software, Humans, 1000 Genomes Project, Hidden Markov model, Indel, Pandemics, Molecular Biology, 030304 developmental biology, 0303 health sciences, Multiple sequence alignment, SARS-CoV-2, business.industry, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], COVID-19, Computer Science Applications, Applications Note, Computational Mathematics, Computational Theory and Mathematics, Filter (video), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, 010606 plant biology & botany
Abstract: Motivation The first cases of the COVID-19 pandemic emerged in December 2019. Until the end of February 2020, the number of available genomes was below 1000 and their multiple alignment was easily achieved using standard approaches. Subsequently, the availability of genomes has grown dramatically. Moreover, some genomes are of low quality with sequencing/assembly errors, making accurate re-alignment of all genomes nearly impossible on a daily basis. A more efficient, yet accurate approach was clearly required to pursue all subsequent bioinformatics analyses of this crucial data. Results hCoV-19 genomes are highly conserved, with very few indels and no recombination. This makes the profile HMM approach particularly well suited to align new genomes, add them to an existing alignment and filter problematic ones. Using a core of ∼2500 high quality genomes, we estimated a profile using HMMER, and implemented this profile in COVID-Align, a user-friendly interface to be used online or as standalone via Docker. The alignment of 1000 genomes requires ∼50 minutes on our cluster. Moreover, COVID-Align provides summary statistics, which can be used to determine the sequencing quality and evolutionary novelty of input genomes (e.g. number of new mutations and indels). Availability and implementation https://covalign.pasteur.cloud, hub.docker.com/r/evolbioinfo/covid-align. Supplementary information Supplementary data are available at Bioinformatics online.
Published: 2020
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36. Modular prophage interactions driven by capsule serotype select for capsule loss under phage predation

Author: Amandine Buffet, Jorge A. Moura de Sousa, Matthieu Haudiquet, Eduardo P. C. Rocha, Olaya Rendueles, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Ecole Doctorale Frontiere de l’Innovation en Recherche et Education (ED 474 FIRE), Université de Paris (UP)-Université Paris sciences et lettres (PSL), MH is funded by an ANR JCJC (Agence national de recherche) grant [ANR 18 CE12 0001 01 ENCAPSULATION] awarded to OR. JAMS is supported by an ANR grant [ANR 16 CE12 0029 02 SALMOPROPHAGE] awarded to EPCR. The laboratory is funded by a Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant ANR-10-LABX-62-IBEID)., We thank Pedro Oliveira for making available the profiles for the RMS systems, Marie Touchon for help in the analysis of CRISPR, and Amandine Perrin for help with building pan-genomes., ANR-18-CE12-0001,ENCAPSULATION,Le rôle évolutif des capsules dans l'adaptation bactérienne(2018), ANR-16-CE12-0029,Salmo_prophages,Co-évolution des génomes bactériens et de leurs prophages: cooptation des prophages et conversion lysogenique chez Salmonella(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Cité (UPCité)-Université Paris sciences et lettres (PSL)
Subjects: Serotype, Species complex, Klebsiella, Klebsiella pneumoniae, Prophages, Population, Biology, Serogroup, Microbiology, Article, Microbial ecology, 03 medical and health sciences, Animals, Bacteriophages, education, Gene, Ecology, Evolution, Behavior and Systematics, Prophage, 030304 developmental biology, 2. Zero hunger, Infectivity, 0303 health sciences, education.field_of_study, Environmental microbiology, Bacteria, 030306 microbiology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Lytic cycle, Predatory Behavior, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: Klebsiella species are able to colonize a wide range of environments and include worrisome nosocomial pathogens. Here, we sought to determine the abundance and infectivity of prophages of Klebsiella to understand how the interactions between induced prophages and bacteria affect population dynamics and evolution. We identified many prophages in the species, placing these taxa among the top 5% of the most polylysogenic bacteria. We selected 35 representative strains of the Klebsiella pneumoniae species complex to establish a network of induced phage–bacteria interactions. This revealed that many prophages are able to enter the lytic cycle, and subsequently kill or lysogenize closely related Klebsiella strains. Although 60% of the tested strains could produce phages that infect at least one other strain, the interaction network of all pairwise cross-infections is very sparse and mostly organized in modules corresponding to the strains’ capsule serotypes. Accordingly, capsule mutants remain uninfected showing that the capsule is a key factor for successful infections. Surprisingly, experiments in which bacteria are predated by their own prophages result in accelerated loss of the capsule. Our results show that phage infectiousness defines interaction modules between small subsets of phages and bacteria in function of capsule serotype. This limits the role of prophages as competitive weapons because they can infect very few strains of the species complex. This should also restrict phage-driven gene flow across the species. Finally, the accelerated loss of the capsule in bacteria being predated by their own phages, suggests that phages drive serotype switch in nature.
Published: 2020
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37. Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

Author: Alm E., Broberg E.K., Connor T., Hodcroft E.B., Komissarov A.B., Maurer-Stroh S., Melidou A., Neher R.A., O'Toole A., Pereyaslov D., Beerenwinkel N., Posada-Cespedes S., Jablonski K.P., Ferreira P.F., Topolsky I., Avsic-Zupanc T., Korva M., Poljak M., Zakotnik S., Zorec T.M., Bragstad K., Hungnes O., Stene-Johansen K., Reusken C., Meijer A., Vennema H., Ruiz-Roldan L., Bracho M.A., Garcia-Gonzalez N., Chiner-Oms A., Cancino-Munoz I., Comas I., Goig G.A., Torres-Puente M., Lopez M.G., Martinez-Priego L., D'Auria G., Ruiz-Hueso P., Ferrus-Abad L., de Marco G., Galan-Vendrell I., Carbo-Ramirez S., Ruiz-Rodriguez P., Coscolla M., Polackova K., Kramna L., Cinek O., Richter J., Krashias G., Tryfonos C., Bashiardes S., Koptides D., Christodoulou C., Bartolini B., Gruber C.E., Di Caro A., Castilletti C., Stefani F., Rimoldi S.G., Romeri F., Salerno F., Polesello S., Nagy A., Jirincova H., Vecerova J., Novakova L., Cordey S., Murtskhvaladze M., Kotaria N., Schar T., Beisel C., Vugrek O., Rokic F., Trgovec-Greif L., Jurak I., Rukavina T., Sucic N., Schonning K., Karst S.M., Kirkegaard R.H., Michaelsen T.Y., Sorensen E.A., Knutson S., Brandt J., Le-Quy V., Sorensen T., Petersen C., Pedersen M.S., Larsen S.L., Skov M.N., Rasmussen M., Fonager J., Fomsgaard A., Maksyutov R.A., Gavrilova E.V., Pyankov O.V., Bodnev S.A., Tregubchak T.V., Shvalov A.N., Antonets D.V., Resende P.C., Goya S., Perrin A., Lee R.T., Yadahalli S., Han A.X., Russell C.A., Schmutz S., Zaheri M., Kufner V., Huber M., Trkola A., Antwerpen M., Walter M.C., van der Werf S., Gambaro F., Behillil S., Enouf V., Donati F., Ustinova M., Rovite V., Klovins J., Savicka O., Wienecke-Baldacchino A.K., Ragimbeau C., Fournier G., Mossong J., Aberle S.W., Haukland M., Enkirch T., Advani A., Karlberg M.L., Lindsjo O.K., Broddesson S., Slavikova M., Lickova M., Klempa B., Staronova E., Ticha E., Szemes T., Rusnakova D., Stadler T., Quer J., Anton A., Andres C., Pinana M., Garcia-Cehic D., Pumarola T., Izopet J., 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Rupnik M., Mahnic A., Walker A., Houwaart T., Wienemann T., Vasconcelos M.K., Strelow D., Jensen B.-E.O., Senff T., Hulse L., Adams O., Andree M., Hauka S., Feldt T., Keitel V., Kindgen-Milles D., Timm J., Pfeffer K., Dilthey A.T., Moore C., Ozdarendeli A., Pavel S.T.I., Yetiskin H., Aydin G., Holyavkin C., Uygut M.A., Cevik C., Shchetinin A., Gushchin V., Dinler-Doganay G., Doganay L., Kizilboga-Akgun T., Karacan I., Pancer K., Maes P., Marti-Carreras J., Wawina-Bokalanga T., Vanmechelen B., Thurmer A., Wedde M., Durrwald R., von Kleist M., Drechsel O., Wolff T., Fuchs S., Kmiecinski R., Michel J., Nitsche A., Casas I., Caballero M.I., Zaballos A., Jimenez P., Jimenez M., Fernandez S.M., Fernandez S.V., de la Plaza I.C., Fadeev A., Ivanova A., Sergeeva M., Stefanelli P., Estee Torok M., Hall G., da Silva Filipe A., Turtle L., Afifi S., McCluggage K., Beer R., Ledesma J., Maksimovic J., Spellman K., Hamilton W.L., Marchbank A., Southgate J.A., Underwood A., Taylor B., Yeats C., 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M., Bizta P., Belimezi M., Lambrechts L., Doymaz M.Z., Yazici M.K., Cetin N.S., Karaaslan E., Kallio-Kokko H., Virtanen J., Suvanto M., Nguyen P.T., Ellonen P., Hannula S., Kangas H., Sreenu V.B., Burian K., Terhes G., Gombos K., Gyenesei A., Urban P., Herczeg R., Jakab F., Kemenesi G., Toth G.E., Somogyi B., Zana B., Zeghbib S., Kuczmog A., Foldes F., Lanszki Z., Madai M., Papp H., Pereszlenyi C.I., Babinszky G.C., Dudas G., Csoma E., Abou Tayoun A.N., Alsheikh-Ali A.A., Loney T., Nowotny N., Abdul-Wahab O., Gonzalez-Candelas F., Andersen M.H., Taylor S., MARTI CARRERAS, Joan, Vanmechelen, Bert, Wawina, Tony, Medical Microbiology and Infection Prevention, AII - Infectious diseases, WHO European Region Sequencing Lab, GISAID EpiCoV Grp, Erik, Alm, Eeva K, Broberg, Thomas, Connor, Emma B, Hodcroft, Andrey B, Komissarov, Sebastian, Maurer-Stroh, Angeliki, Melidou, Richard A, Neher, Áine, O’Toole, Dmitriy, Pereyaslov, WHO European Region sequencing laboratories and GISAID EpiCoV group (Niko Beerenwinkel, The, Posada-Céspedes, Susana, Philipp, Kim, Jablonski, Falé Ferreira, Pedro, Topolsky, Ivan, Avšičžupanc, Tatjana, Korva, Miša, Poljak, Mario, Zakotnik, Samo, Tomaž, Zorec, Mark, Bragstad, Karoline, Hungnes, Olav, Stene-Johansen, Kathrine, Reusken, Chantal, Meijer, Adam, Vennema, Harry, Ruiz-Roldán, Lidia, Alma Bracho, María, García-González, Neri, Chiner-Oms, Álvaro, Cancino-Muñoz, Irving, Comas, Iñaki, A Goig, Galo, Torres-Puente, Manuela, G López, Mariana, Martínez-Priego, Llúcia, D’Auria, Giuseppe, LoretoFerrús-Abad, de Marco, Griselda, Galan-Vendrell, Inmaculada, Carbó-Ramirez, Sandra, Ruíz-Hueso, Paula, Coscollá, Mireia, Polackova, Katerina, Kramna, Lenka, Cinek, Ondrej, Richter, Jan, Krashias, George, Tryfonos, Christina, Bashiardes, Stavro, Koptides, Dana, Christodoulou, Christina, Bartolini, Barbara, Em Gruber, Cesare, Di Caro, Antonino, Castilletti, Concetta, Stefani, Fabrizio, Giordana Rimoldi, Sara, Romeri, Francesca, Salerno, Franco, Polesello, Stefano, Nagy, Alexander, Jirincova, Helena, Vecerova, Jaromira, Novakova, Ludmila, Cordey, Samuel, Murtskhvaladze, Marine, Kotaria, Nato, Schär, Tobia, Beisel, Christian, Vugrek, Oliver, Rokić, Filip, Trgovecgreif, Lovro, Jurak, Igor, Rukavina, Tomislav, Sučić, Neven, Schønning, Kristian, M Karst, Søren, H Kirkegaard, Rasmu, Y Michaelsen, Thoma, Aa Sørensen, Emil, Knutson, Simon, Brandt, Jakob, Le-Quy, Vang, Sørensen, Trine, Petersen, Celine, Schou Pedersen, Martin, Løkkegaard Larsen, Sanne, Nielsine Skov, Marianne, Rasmussen, Morten, Fonager, Jannik, Fomsgaard, Ander, Amirovich Maksyutov, Rinat, Vasil’Evna Gavrilova, Elena, Victorovich Pyankov, Oleg, Alexandrovich Bodnev, Sergey, Vladimirovna Tregubchak, Tatyana, Nikolayevich Shvalov, Alexander, Victorovich Antonets, Deni, Cristina Resende, Paola, Goya, Stephanie, Perrin, Amandine, Tc Lee, Raphael, Yadahalli, Shilpa, X Han, Alvin, A Russell, Colin, Schmutz, Stefan, Zaheri, Maryam, Kufner, Verena, Huber, Michael, Trkola, Alexandra, Antwerpen, Marku, C Walter, Mathia, van der Werf, Sylvie, Gambaro, Fabiana, Behillil, Sylvie, Enouf, Vincent, Donati, Flora, Ustinova, Monta, Rovite, Vita, Klovins, Jani, Savicka, Oksana, K Wienecke-Baldacchino, Anke, Ragimbeau, Catherine, Fournier, Guillaume, Mossong, Joël, W Aberle, Stephan, Haukland, Mattia, Enkirch, Theresa, Advani, Abdolreza, Lind Karlberg, Maria, Karlsson Lindsjö, Oskar, Broddesson, Sandra, Sláviková, Monika, Ličková, Martina, Klempa, Bori, Staroňová, Edita, Tichá, Elena, Szemes, Tomáš, Rusňáková, Diana, Stadler, Tanja, Quer, Josep, Anton, Andre, Andres, Cristina, Piñana, Maria, Garcia-Cehic, Damir, Pumarola, Toma, Izopet, Jacque, Gioula, Georgia, Exindari, Maria, Papa, Anna, Chatzidimitriou, Dimitrio, Metallidis, Symeon, Pappa, Stella, Macek Jr, Milan, Geryk, Jan, Brož, Petr, Briksí, Aleš, Hubáček, Petr, Dřevínek, Pavel, Zajac, Miroslav, Kvapil, Petr, Holub, Michal, Kvapilová, Kateřina, Novotný, Adam, Kašný, Martin, Klempt, Petr, Vapalahti, Olli, Smura, Teemu, Sironen, Tarja, Selhorst, Philippe, Anthony, Colin, Ariën, Kevin, Simon-Loriere, Etienne, Rabalski, Lukasz, Bienkowska-Szewczyk, Krystyna, Borges, Vítor, Isidro, Joana, Paulo Gomes, João, Guiomar, Raquel, Pechirra, Pedro, Costa, Inê, Duarte, Sílvia, Vieira, Luí, Pyrc, Krzysztof, S Zuckerman, Neta, Turdikulova, Shahlo, Abdullaev, Alisher, Dalimova, Dilbar, Abdurakhimov, Abror, Tagliabracci, Adriano, Alessandrini, Federica, Melchionda, Filomena, Onofri, Valerio, Turchi, Chiara, Bagnarelli, Patrizia, Menzo, Stefano, Caucci, Sara, Di Sante, Laura, Popa, Alexandra, Genger, Jakob-Wendelin, Agerer, Benedikt, Lercher, Alexander, Endler, Luka, Smyth, Mark, Penz, Thoma, Schuster, Michael, Senekowitsch, Martin, Laine, Jan, Bock, Christoph, Bergthaler, Andrea, Shevtsov, Alexandr, Kalendar, Ruslan, Ramanculov, Yerlan, Graf, Alexander, Muenchhoff, Maximilian, T Keppler, Oliver, Krebs, Stefan, Blum, Helmut, Marcello, Alessandro, Licastro, Danilo, D’Agaro, Pierlanfranco, Laubscher, Florian, Vidanovic, Dejan, Tesovic, Bojana, Volkening, Jeremy, Clementi, Nicola, Mancini, Nicasio, Rupnik, Maja, Mahnic, Aleksander, Walker, Andrea, Houwaart, Torsten, Wienemann, Tobia, Kohns Vasconcelos, Malte, Strelow, Daniel, Ole Jensen, Björn-Erik, Senff, Tina, Hülse, Lisanna, Adams, Ortwin, Andree, Marcel, Hauka, Sandra, Feldt, Torsten, Keitel, Verena, Kindgen-Milles, Detlef, Timm, Jörg, Pfeffer, Klau, T Dilthey, Alexander, Moore, Catherine, Ozdarendeli, Aykut, Terkis Islam Pavel, Shaikh, Yetiskin, Hazel, Aydin, Gunsu, Holyavkin, Can, Ali Uygut, Muhammet, Cevik, Ceren, Shchetinin, Alexey, Gushchin, Vladimir, Dinler-Doganay, Gizem, Doganay, Levent, Kizilboga-Akgun, Tugba, Karacan, Ilker, Pancer, Katarzyna, Maes, Piet, Martí-Carreras, Joan, Wawina-Bokalanga, Tony, Thürmer, Andrea, Wedde, Marianne, Dürrwald, Ralf, Von Kleist, Max, Drechsel, Oliver, Wolff, Thorsten, Fuchs, Stephan, Kmiecinski, Rene, Michel, Janine, Nitsche, Andrea, Casas, Inmaculada, Iglesias Caballero, María, Zaballos, Ángel, Jiménez, Pilar, Jiménez, Mercede, Monzón Fernández, Sara, Varona Fernández, Sarai, Cuesta De La Plaza, Isabel, Fadeev, Artem, Ivanova, Anna, Sergeeva, Mariia, Stefanelli, Paola, Estee Torok, M, Hall, Grant, da Silva Filipe, Ana, Turtle, Lance, Afifi, Safiah, Mccluggage, Kathryn, Beer, Robert, Ledesma, Juan, Maksimovic, Joshua, Spellman, Karla, L Hamilton, William, Marchbank, Angela, Alexander Southgate, Joel, Underwood, Anthony, Taylor, Ben, Yeats, Corin, Abudahab, Khalil, R Gemmell, Matthew, Eccles, Richard, Lucaci, Anita, Abigail Nelson, Charlotte, Rainbow, Lucille, Whitehead, Mark, Gregory, Richard, Haldenby, Sam, Paterson, Steve, A Hughes, Margaret, D Curran, Martin, Baker, David, Tucker, Rachel, R Green, Luke, Feltwell, Theresa, D Halstead, Fenella, Wyles, Matthew, S Jahun, Aminu, Y Ahmad, Shazaad S, Georgana, Iliana, Goodfellow, Ian, Yakovleva, Anna, W Meredith, Luke, Gavriil, Artemi, Raza Awan, Ali, Fisher, Chloe, Jonathan, European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), Cardiff University, Public Health Wales [Cardiff, Royaume uni], University of Basel (Unibas), Research Institute of Influenza, St. Petersburg, Russia, Agency for science, technology and research [Singapore] (A*STAR), National University of Singapore (NUS), University of Edinburgh, WHO Regional Office for Europe [Copenhagen], We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCoV Database used in the phylogenetic analysis. We gratefully acknowledge all the staff working with sample collection, sample preparation, sequencing, data analysis and data sharing in all laboratories in the WHO European Region for making this work possible, The WHO European Region sequencing laboratories and GISAID EpiCoV group*: Niko Beerenwinkel, Susana Posada-Céspedes, Kim Philipp Jablonski, Pedro Falé Ferreira, Ivan Topolsky, Tatjana Avšič-Županc, Miša Korva, Mario Poljak, Samo Zakotnik, Tomaž Mark Zorec, Karoline Bragstad, Olav Hungnes, Kathrine Stene-Johansen, Chantal Reusken, Adam Meijer, Harry Vennema, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Álvaro Chiner-Oms, Irving Cancino-Muñoz, Iñaki Comas, Galo A Goig, Manuela Torres-Puente, Mariana G López, Llúcia Martínez-Priego, Giuseppe D'Auria, Paula Ruíz-Hueso, Loreto Ferrús-Abad, Griselda de Marco, Inmaculada Galan-Vendrell, Sandra Carbó-Ramirez, Paula Ruiz-Rodriguez, Mireia Coscollá, Katerina Polackova, Lenka Kramna, Ondrej Cinek, Jan Richter, George Krashias, Christina Tryfonos, Stavros Bashiardes, Dana Koptides, Christina Christodoulou, Barbara Bartolini, Cesare Em Gruber, Antonino Di Caro, Concetta Castilletti, Fabrizio Stefani, Sara Giordana Rimoldi, Francesca Romeri, Franco Salerno, Stefano Polesello, Alexander Nagy, Helena Jirincova, Jaromira Vecerova, Ludmila Novakova, Samuel Cordey, Marine Murtskhvaladze, Nato Kotaria, Tobias Schär, Christian Beisel, Oliver Vugrek, Filip Rokić, Lovro Trgovec-Greif, Igor Jurak, Tomislav Rukavina, Neven Sučić, Kristian Schønning, Søren M Karst, Rasmus H Kirkegaard, Thomas Y Michaelsen, Emil Aa Sørensen, Simon Knutson, Jakob Brandt, Vang Le-Quy, Trine Sørensen, Celine Petersen, Martin Schou Pedersen, Sanne Løkkegaard Larsen, Marianne Nielsine Skov, Morten Rasmussen, Jannik Fonager, Anders Fomsgaard, Rinat Amirovich Maksyutov, Elena Vasil'Evna Gavrilova, Oleg Victorovich Pyankov, Sergey Alexandrovich Bodnev, Tatyana Vladimirovna Tregubchak, Alexander Nikolayevich Shvalov, Denis Victorovich Antonets, Paola Cristina Resende, Stephanie Goya, Amandine Perrin, Raphael Tc Lee, Shilpa Yadahalli, Alvin X Han, Colin A Russell, Stefan Schmutz, Maryam Zaheri, Verena Kufner, Michael Huber, Alexandra Trkola, Markus Antwerpen, Mathias C Walter, Sylvie van der Werf, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Flora Donati, Monta Ustinova, Vita Rovite, Janis Klovins, Oksana Savicka, Anke K Wienecke-Baldacchino, Catherine Ragimbeau, Guillaume Fournier, Joël Mossong, Stephan W Aberle, Mattias Haukland, Theresa Enkirch, Abdolreza Advani, Maria Lind Karlberg, Oskar Karlsson Lindsjö, Sandra Broddesson, Monika Sláviková, Martina Ličková, Boris Klempa, Edita Staroňová, Elena Tichá, Tomáš Szemes, Diana Rusňáková, Tanja Stadler, Josep Quer, Andres Anton, Cristina Andres, Maria Piñana, Damir Garcia-Cehic, Tomas Pumarola, Jacques Izopet, Georgia Gioula, Maria Exindari, Anna Papa, Dimitrios Chatzidimitriou, Symeon Metallidis, Stella Pappa, Milan Macek Jr, Jan Geryk, Petr Brož, Aleš Briksí, Petr Hubáček, Pavel Dřevínek, Miroslav Zajac, Petr Kvapil, Michal Holub, Kateřina Kvapilová, Adam Novotný, Martin Kašný, Petr Klempt, Olli Vapalahti, Teemu Smura, Tarja Sironen, Philippe Selhorst, Colin Anthony, Kevin Ariën, Etienne Simon-Loriere, Lukasz Rabalski, Krystyna Bienkowska-Szewczyk, Vítor Borges, Joana Isidro, João Paulo Gomes, Raquel Guiomar, Pedro Pechirra, Inês Costa, Sílvia Duarte, Luís Vieira, Krzysztof Pyrc, Neta S Zuckerman, Shahlo Turdikulova, Alisher Abdullaev, Dilbar Dalimova, Abror Abdurakhimov, Adriano Tagliabracci, Federica Alessandrini, Filomena Melchionda, Valerio Onofri, Chiara Turchi, Patrizia Bagnarelli, Stefano Menzo, Sara Caucci, Laura Di Sante, Alexandra Popa, Jakob-Wendelin Genger, Benedikt Agerer, Alexander Lercher, Lukas Endler, Mark Smyth, Thomas Penz, Michael Schuster, Martin Senekowitsch, Jan Laine, Christoph Bock, Andreas Bergthaler, Alexandr Shevtsov, Ruslan Kalendar, Yerlan Ramanculov, Alexander Graf, Maximilian Muenchhoff, Oliver T Keppler, 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Andreas Nitsche, Inmaculada Casas, María Iglesias Caballero, Ángel Zaballos, Pilar Jiménez, Mercedes Jiménez, Sara Monzón Fernández, Sarai Varona Fernández, Isabel Cuesta De La Plaza, Artem Fadeev, Anna Ivanova, Mariia Sergeeva, Paola Stefanelli, M Estee Torok, Grant Hall, Ana da Silva Filipe, Lance Turtle, Safiah Afifi, Kathryn Mccluggage, Robert Beer, Juan Ledesma, Joshua Maksimovic, Karla Spellman, William L Hamilton, Angela Marchbank, Joel Alexander Southgate, Anthony Underwood, Ben Taylor, Corin Yeats, Khalil Abudahab, Matthew R Gemmell, Richard Eccles, Anita Lucaci, Charlotte Abigail Nelson, Lucille Rainbow, Mark Whitehead, Richard Gregory, Sam Haldenby, Steve Paterson, Margaret A Hughes, Martin D Curran, David Baker, Rachel Tucker, Luke R Green, Theresa Feltwell, Fenella D Halstead, Matthew Wyles, Aminu S Jahun, Shazaad S Y Ahmad, Iliana Georgana, Ian Goodfellow, Anna Yakovleva, Luke W Meredith, Artemis Gavriil, Ali Raza Awan, Chloe Fisher, Jonathan Edgeworth, Jessica Lynch, Nathan Moore, Rebecca Williams, Stephen P Kidd, Nicholas Cortes, Kirstyn Brunker, John T Mccrone, Joshua Quick, Nichola Duckworth, Sarah Walsh, Tim Sloan, Catherine Ludden, Ryan P George, Gary Eltringham, Julianne R Brown, Elihu Aranday-Cortes, James G Shepherd, Joseph Hughes, Kathy K Li, Thomas C Williams, Natasha Johnson, Natasha Jesudason, Daniel Mair, Emma Thomson, Rajiv Shah, Yasmin A Parr, Stephen Carmichael, David L Robertson, Kyriaki Nomikou, Alice Broos, Marc Niebel, Katherine Smollett, Lily Tong, Shahjahan Miah, Anita Wittner, Nicole Phillips, Brendan Payne, Rebecca Dewar, Alison Holmes, Frances Bolt, James R Price, Siddharth Mookerjee, Dheeraj K Sethi, Will Potter, Rachael Stanley, Reenesh Prakash, Samir Dervisevic, Jonathan Clive Graham, Andrew Nelson, Darren Smith, Gregory R Young, Wen Chyin Yew, John A Todd, Amy Trebes, Monique Andersson, Matthew Bull, Joanne Watkins, Alec Birchley, Bree Gatica-Wilcox, Lauren Gilbert, Sara Kumžiene-Summerhayes, Sara Rey, Anoop Chauhan, Ethan Butcher, Kelly Bicknell, Scott Elliott, Sharon Glaysher, Angie Lackenby, David Bibby, Steven Platt, Hodan Mohamed, Nicholas William Machin, Jean Lutamyo Mbisa, Jonathan Evans, Malorie Perry, Nicole Pacchiarini, Sally Corden, Alexander Geraint Adams, Amy Gaskin, Jason Coombs, Lee John Graham, Simon Cottrell, Mari Morgan, Laura Gifford, Anastasia Kolyva, Steven John Rudder, Alexander J Trotter, Alison E Mather, Alp Aydin, Andrew J Page, Gemma L Kay, Leonardo de Oliveira Martins, Muhammad Yasir, Nabil-Fareed Alikhan, Nicholas M Thomson, Rachel Gilroy, Robert A Kingsley, Justin O'Grady, Ana Victoria Gutierrez, Maria Diaz, Thanh Le Viet, Ana P Tedim, Evelien M Adriaenssens, C Patrick Mcclure, Christopher Moore, Fei Sang, Gemma Clark, Hannah C Howson-Wells, Johnny Debebe, Jonathan Ball, Joseph Chappell, Manjinder Khakh, Matthew Carlile, Matthew Loose, Michelle M Lister, Nadine Holmes, Theocharis Tsoleridis, Vicki M Fleming, Victoria Wright, Wendy Smith, Michael D Gallagher, Matthew 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Lindsey, Danielle C Groves, Paul J Parsons, Martin P Mchugh, James Daniel Barnes, Carmen F Manso, Dimitris Grammatopoulos, Katja Elisabeth Menger, Ewan Harrison, Rory Gunson, Sharon J Peacock, Gabriel Gonzalez, Michael Carr, Lazar Mihaela, Odette Popovici, Mia Brytting, Catherine Bresner, William Fuller, Trudy Workman, Andreas F Mentis, Athanasios Kossyvakis, Timokratis Karamitros, Vasiliki Pogka, Antonios Kalliaropoulos, Elina Horefti, Aspasia Kontou, Beatriz Martinez-Gonzalez, Voula Labropoulou, Androniki Voulgari-Kokota, Maria Evangelidou, Panagiota Bizta, Maria Belimezi, Laurens Lambrechts, Mehmet Z Doymaz, Merve Kalkan Yazici, Nesibe S Cetin, Elif Karaaslan, Hannimari Kallio-Kokko, Jenni Virtanen, Maija Suvanto, Phuoc Truong Nguyen, Pekka Ellonen, Sari Hannula, Harri Kangas, Vattipally B Sreenu, Katalin Burián, Gabriella Terhes, Katalin Gombos, Attila Gyenesei, Péter Urbán, Róbert Herczeg, Ferenc Jakab, Gábor Kemenesi, Gábor Endre Tóth, Balázs Somogyi, Brigitta Zana, Safia Zeghbib, Anett Kuczmog, Fanni Földes, Zsófia Lanszki, Mónika Madai, Henrietta Papp, Ágnes Nagy, Csaba István Pereszlényi, Gergely Csaba Babinszky, Gábor Dudás, Eszter Csoma, Ahmad N Abou Tayoun, Alawi A Alsheikh-Ali, Tom Loney, Norbert Nowotny, Osama Abdul-Wahab, Fernando Gonzalez-Candelas, Martin H Andersen, Sarah Taylor, Comas, Iñaki [0000-0001-5504-9408], Alm, E., Broberg, E. K., Connor, T., Hodcroft, E. B., Komissarov, A. B., Maurer-Stroh, S., Melidou, A., Neher, R. A., O'Toole, A., Pereyaslov, D., Beerenwinkel, N., Posada-Cespedes, S., Jablonski, K. P., Ferreira, P. F., Topolsky, I., Avsic-Zupanc, T., Korva, M., Poljak, M., Zakotnik, S., Zorec, T. M., Bragstad, K., Hungnes, O., Stene-Johansen, K., Reusken, C., Meijer, A., Vennema, H., Ruiz-Roldan, L., Bracho, M. A., Garcia-Gonzalez, N., Chiner-Oms, A., Cancino-Munoz, I., Comas, I., Goig, G. A., Torres-Puente, M., Lopez, M. G., Martinez-Priego, L., D'Auria, G., Ruiz-Hueso, P., Ferrus-Abad, L., de Marco, G., Galan-Vendrell, I., Carbo-Ramirez, S., Ruiz-Rodriguez, P., Coscolla, M., Polackova, K., Kramna, L., Cinek, O., Richter, J., Krashias, G., Tryfonos, C., Bashiardes, S., Koptides, D., Christodoulou, C., Bartolini, B., Gruber, C. E., Di Caro, A., Castilletti, C., Stefani, F., Rimoldi, S. G., Romeri, F., Salerno, F., Polesello, S., Nagy, A., Jirincova, H., Vecerova, J., Novakova, L., Cordey, S., Murtskhvaladze, M., Kotaria, N., Schar, T., Beisel, C., Vugrek, O., Rokic, F., Trgovec-Greif, L., Jurak, I., Rukavina, T., Sucic, N., Schonning, K., Karst, S. M., Kirkegaard, R. H., Michaelsen, T. Y., Sorensen, E. A., Knutson, S., Brandt, J., Le-Quy, V., Sorensen, T., Petersen, C., Pedersen, M. S., Larsen, S. L., Skov, M. N., Rasmussen, M., Fonager, J., Fomsgaard, A., Maksyutov, R. A., Gavrilova, E. V., Pyankov, O. V., Bodnev, S. A., Tregubchak, T. V., Shvalov, A. N., Antonets, D. V., Resende, P. C., Goya, S., Perrin, A., Lee, R. T., Yadahalli, S., Han, A. X., Russell, C. A., Schmutz, S., Zaheri, M., Kufner, V., Huber, M., Trkola, A., Antwerpen, M., Walter, M. C., van der Werf, S., Gambaro, F., Behillil, S., Enouf, V., Donati, F., Ustinova, M., Rovite, V., Klovins, J., Savicka, O., Wienecke-Baldacchino, A. K., Ragimbeau, C., Fournier, G., Mossong, J., Aberle, S. W., Haukland, M., Enkirch, T., Advani, A., Karlberg, M. L., Lindsjo, O. K., Broddesson, S., Slavikova, M., Lickova, M., Klempa, B., Staronova, E., Ticha, E., Szemes, T., Rusnakova, D., Stadler, T., Quer, J., Anton, A., Andres, C., Pinana, M., Garcia-Cehic, D., Pumarola, T., Izopet, J., Gioula, G., Exindari, M., Papa, A., Chatzidimitriou, D., Metallidis, S., Pappa, S., Macek, M., Geryk, J., Broz, P., Briksi, A., Hubacek, P., Drevinek, P., Zajac, M., Kvapil, P., Holub, M., Kvapilova, K., Novotny, A., Kasny, M., Klempt, P., Vapalahti, O., Smura, T., Sironen, T., Selhorst, P., Anthony, C., Arien, K., Simon-Loriere, E., Rabalski, L., Bienkowska-Szewczyk, K., Borges, V., Isidro, J., Gomes, J. P., Guiomar, R., Pechirra, P., Costa, I., Duarte, S., Vieira, L., Pyrc, K., Zuckerman, N. S., Turdikulova, S., Abdullaev, A., Dalimova, D., Abdurakhimov, A., Tagliabracci, A., Alessandrini, F., Melchionda, F., Onofri, V., Turchi, C., Bagnarelli, P., Menzo, S., Caucci, S., Di Sante, L., Popa, A., Genger, J. -W., Agerer, B., Lercher, A., Endler, L., Smyth, M., Penz, T., Schuster, M., Senekowitsch, M., Laine, J., Bock, C., Bergthaler, A., Shevtsov, A., Kalendar, R., Ramanculov, Y., Graf, A., Muenchhoff, M., Keppler, O. T., Krebs, S., Blum, H., Marcello, A., Licastro, D., D'Agaro, P., Laubscher, F., Vidanovic, D., Tesovic, B., Volkening, J., Clementi, N., Mancini, N., Rupnik, M., Mahnic, A., Walker, A., Houwaart, T., Wienemann, T., Vasconcelos, M. K., Strelow, D., Jensen, B. -E. O., Senff, T., Hulse, L., Adams, O., Andree, M., Hauka, S., Feldt, T., Keitel, V., Kindgen-Milles, D., Timm, J., Pfeffer, K., Dilthey, A. T., Moore, C., Ozdarendeli, A., Pavel, S. T. I., Yetiskin, H., Aydin, G., Holyavkin, C., Uygut, M. A., Cevik, C., Shchetinin, A., Gushchin, V., Dinler-Doganay, G., Doganay, L., Kizilboga-Akgun, T., Karacan, I., Pancer, K., Maes, P., Marti-Carreras, J., Wawina-Bokalanga, T., Vanmechelen, B., Thurmer, A., Wedde, M., Durrwald, R., von Kleist, M., Drechsel, O., Wolff, T., Fuchs, S., Kmiecinski, R., Michel, J., Nitsche, A., Casas, I., Caballero, M. I., Zaballos, A., Jimenez, P., Jimenez, M., Fernandez, S. M., Fernandez, S. V., de la Plaza, I. C., Fadeev, A., Ivanova, A., Sergeeva, M., Stefanelli, P., Estee Torok, M., Hall, G., da Silva Filipe, A., Turtle, L., Afifi, S., Mccluggage, K., Beer, R., Ledesma, J., Maksimovic, J., Spellman, K., Hamilton, W. L., Marchbank, A., Southgate, J. A., Underwood, A., Taylor, B., Yeats, C., Abudahab, K., Gemmell, M. R., Eccles, R., Lucaci, A., Nelson, C. A., Rainbow, L., Whitehead, M., Gregory, R., Haldenby, S., Paterson, S., Hughes, M. A., Curran, M. D., Baker, D., Tucker, R., Green, L. R., Feltwell, T., Halstead, F. D., Wyles, M., Jahun, A. S., Ahmad, S. S. Y., Georgana, I., Goodfellow, I., Yakovleva, A., Meredith, L. W., Gavriil, A., Awan, A. R., Fisher, C., Edgeworth, J., Lynch, J., Moore, N., Williams, R., Kidd, S. P., Cortes, N., Brunker, K., Mccrone, J. T., Quick, J., Duckworth, N., Walsh, S., Sloan, T., Ludden, C., George, R. P., Eltringham, G., Brown, J. R., Aranday-Cortes, E., Shepherd, J. G., Hughes, J., Li, K. K., Williams, T. C., Johnson, N., Jesudason, N., Mair, D., Thomson, E., Shah, R., Parr, Y. A., Carmichael, S., Robertson, D. L., Nomikou, K., Broos, A., Niebel, M., Smollett, K., Tong, L., Miah, S., Wittner, A., Phillips, N., Payne, B., Dewar, R., Holmes, A., Bolt, F., Price, J. R., Mookerjee, S., Sethi, D. K., Potter, W., Stanley, R., Prakash, R., Dervisevic, S., Graham, J. C., Nelson, A., Smith, D., Young, G. R., Yew, W. C., Todd, J. A., Trebes, A., Andersson, M., Bull, M., Watkins, J., Birchley, A., Gatica-Wilcox, B., Gilbert, L., Kumziene-Summerhayes, S., Rey, S., Chauhan, A., Butcher, E., Bicknell, K., Elliott, S., Glaysher, S., Lackenby, A., Bibby, D., Platt, S., Mohamed, H., Machin, N. W., Mbisa, J. L., Evans, J., Perry, M., Pacchiarini, N., Corden, S., Adams, A. G., Gaskin, A., Coombs, J., Graham, L. J., Cottrell, S., Morgan, M., Gifford, L., Kolyva, A., Rudder, S. J., Trotter, A. J., Mather, A. E., Aydin, A., Page, A. J., Kay, G. L., de Oliveira Martins, L., Yasir, M., Alikhan, N. -F., Thomson, N. M., Gilroy, R., Kingsley, R. A., O'Grady, J., Gutierrez, A. V., Diaz, M., Viet, T. L., Tedim, A. P., Adriaenssens, E. M., Patrick Mcclure, C., Sang, F., Clark, G., Howson-Wells, H. C., Debebe, J., Ball, J., Chappell, J., Khakh, M., Carlile, M., Loose, M., Lister, M. M., Holmes, N., Tsoleridis, T., Fleming, V. M., Wright, V., Smith, W., Gallagher, M. D., Parker, M., Partridge, D. G., Evans, C., Baker, P., Essex, S., Liggett, S., Keeley, A. J., Bashton, M., Rooke, S., Dervisavic, S., Meader, E. J., Lopez, C. E. B., Angyal, A., Kristiansen, M., Tutill, H. J., Findlay, J., Mestek-Boukhibar, L., Forrest, L., Dyal, P., Williams, R. J., Panchbhaya, Y., Williams, C. A., Roy, S., Pandey, S., Stockton, J., Loman, N. J., Poplawski, R., Nicholls, S., Rowe, W. P. M., Khokhar, F., Pinckert, M. L., Hosmillo, M., Chaudhry, Y., Caller, L. G., Davidson, R. K., Griffith, L., Rambaut, A., Jackson, B., Colquhoun, R., Hill, V., Nichols, J., Asamaphan, P., Darby, A., Jackson, K. A., Iturriza-Gomara, M., Vamos, E. E., Green, A., Aanensen, D., Bonsall, D., Buck, D., Macintyre-Cockett, G., de Cesare, M., Pybus, O., Golubchik, T., Scarlett, G., Loveson, K. F., Robson, S. C., Beckett, A., Lindsey, B., Groves, D. C., Parsons, P. J., Mchugh, M. P., Barnes, J. D., Manso, C. F., Grammatopoulos, D., Menger, K. E., Harrison, E., Gunson, R., Peacock, S. J., Gonzalez, G., Carr, M., Mihaela, L., Popovici, O., Brytting, M., Bresner, C., Fuller, W., Workman, T., Mentis, A. F., Kossyvakis, A., Karamitros, T., Pogka, V., Kalliaropoulos, A., Horefti, E., Kontou, A., Martinez-Gonzalez, B., Labropoulou, V., Voulgari-Kokota, A., Evangelidou, M., Bizta, P., Belimezi, M., Lambrechts, L., Doymaz, M. Z., Yazici, M. K., Cetin, N. S., Karaaslan, E., Kallio-Kokko, H., Virtanen, J., Suvanto, M., Nguyen, P. T., Ellonen, P., Hannula, S., Kangas, H., Sreenu, V. B., Burian, K., Terhes, G., Gombos, K., Gyenesei, A., Urban, P., Herczeg, R., Jakab, F., Kemenesi, G., Toth, G. E., Somogyi, B., Zana, B., Zeghbib, S., Kuczmog, A., Foldes, F., Lanszki, Z., Madai, M., Papp, H., Pereszlenyi, C. I., Babinszky, G. C., Dudas, G., Csoma, E., Abou Tayoun, A. N., Alsheikh-Ali, A. A., Loney, T., Nowotny, N., Abdul-Wahab, O., Gonzalez-Candelas, F., Andersen, M. H., Taylor, S., European Centre for Disease Prevention and Control (ECDC), Public Health Wales Microbiology Cardiff, Faculty of Agriculture and Forestry, Department of Agricultural Sciences, and Institute of Biotechnology
Subjects: Infecções Respiratórias, 0301 basic medicine, MESH: Coronavirus Infections, Epidemiology, [SDV]Life Sciences [q-bio], Distribution (economics), Wastewater, MESH: Base Sequence, Severe Acute Respiratory Syndrome, MESH: World Health Organization, Pandemic, MESH: Coronavirus, MESH: COVID-19, Sequencing, Viral, Clade, Nomenclature, Genome, biology, COVID-19, Europe, NGS, SARS-CoV-2, WGS, nomenclature, sequencing, Base Sequence, Betacoronavirus, Coronavirus, Coronavirus Infections, Genome, Viral, Humans, Phylogeography, Pneumonia, Viral, RNA, Viral, RNA-Dependent RNA Polymerase, Spatio-Temporal Analysis, World Health Organization, Pandemics, C500, European region, 3. Good health, Geography, MESH: Phylogeography, MESH: RNA-Dependent RNA Polymerase, MESH: RNA, Viral, MESH: Betacoronavirus, Spatio-Temporal Analysi, MESH: Genome, Viral, Cartography, Human, Bioquímica, MESH: Pandemics, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronaviru, 030106 microbiology, 03 medical and health sciences, MESH: Spatio-Temporal Analysis, MESH: Severe Acute Respiratory Syndrome, Virology, MESH: SARS-CoV-2, Whole genome sequencing, MESH: Humans, Whole Genome Sequencing, Betacoronaviru, Coronavirus Infection, business.industry, Public Health, Environmental and Occupational Health, Pneumonia, biology.organism_classification, B900, 030104 developmental biology, MESH: Pneumonia, Viral, RNA, SARS_CoV-2, 3111 Biomedicine, MESH: Europe, Human medicine, business
Abstract: 8 páginas, 3 figuras, 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., We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCoV Database used in the phylogenetic analysis. We gratefully acknowledge all the staff working with sample collection, sample preparation, sequencing, data analysis and data sharing in all laboratories in the WHO European Region for making this work possible.
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