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      Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases

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      Virus Evolution
      Oxford University Press
      Ebola virus, evolution, transmission, outbreak sequencing

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          Abstract

          To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and to prevent new transmissions, rapid epidemiological tracing of cases and contacts was required. The ability to quickly identify unknown sources and chains of transmission is key to ending the EVD epidemic and of even greater importance in the context of recent reports of Ebola virus (EBOV) persistence in survivors. Phylogenetic analysis of complete EBOV genomes can provide important information on the source of any new infection. A local deep sequencing facility was established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The facility included all wetlab and computational resources to rapidly process EBOV diagnostic samples into full genome sequences. We produced 554 EBOV genomes from EVD cases across Sierra Leone. These genomes provided a detailed description of EBOV evolution and facilitated phylogenetic tracking of new EVD cases. Importantly, we show that linked genomic and epidemiological data can not only support contact tracing but also identify unconventional transmission chains involving body fluids, including semen. Rapid EBOV genome sequencing, when linked to epidemiological information and a comprehensive database of virus sequences across the outbreak, provided a powerful tool for public health epidemic control efforts.

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          Most cited references31

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          RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies

          Motivation: Phylogenies are increasingly used in all fields of medical and biological research. Moreover, because of the next-generation sequencing revolution, datasets used for conducting phylogenetic analyses grow at an unprecedented pace. RAxML (Randomized Axelerated Maximum Likelihood) is a popular program for phylogenetic analyses of large datasets under maximum likelihood. Since the last RAxML paper in 2006, it has been continuously maintained and extended to accommodate the increasingly growing input datasets and to serve the needs of the user community. Results: I present some of the most notable new features and extensions of RAxML, such as a substantial extension of substitution models and supported data types, the introduction of SSE3, AVX and AVX2 vector intrinsics, techniques for reducing the memory requirements of the code and a plethora of operations for conducting post-analyses on sets of trees. In addition, an up-to-date 50-page user manual covering all new RAxML options is available. Availability and implementation: The code is available under GNU GPL at https://github.com/stamatak/standard-RAxML. Contact: alexandros.stamatakis@h-its.org Supplementary information: Supplementary data are available at Bioinformatics online.
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            SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing.

            The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.
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              Bayesian Phylogenetics with BEAUti and the BEAST 1.7

              Computational evolutionary biology, statistical phylogenetics and coalescent-based population genetics are becoming increasingly central to the analysis and understanding of molecular sequence data. We present the Bayesian Evolutionary Analysis by Sampling Trees (BEAST) software package version 1.7, which implements a family of Markov chain Monte Carlo (MCMC) algorithms for Bayesian phylogenetic inference, divergence time dating, coalescent analysis, phylogeography and related molecular evolutionary analyses. This package includes an enhanced graphical user interface program called Bayesian Evolutionary Analysis Utility (BEAUti) that enables access to advanced models for molecular sequence and phenotypic trait evolution that were previously available to developers only. The package also provides new tools for visualizing and summarizing multispecies coalescent and phylogeographic analyses. BEAUti and BEAST 1.7 are open source under the GNU lesser general public license and available at http://beast-mcmc.googlecode.com and http://beast.bio.ed.ac.uk
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                Author and article information

                Contributors
                Journal
                Virus Evol
                Virus Evol
                vevolu
                Virus Evolution
                Oxford University Press
                2057-1577
                January 2016
                22 June 2016
                22 June 2016
                : 2
                : 1
                : vew016
                Affiliations
                [1 ]Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom
                [2 ]Wellcome Trust Sanger Institute, Hinxton, United Kingdom
                [3 ]Irrua Specialist Teaching Hospital, Institute of Lassa Fever Research and Control, Irrua, Nigeria
                [4 ]The European Mobile Laboratory Consortium, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
                [5 ]University of Makeni, Makeni, Sierra Leone
                [6 ]Institute of Evolutionary Biology, Ashworth Laboratories, Edinburgh, United Kingdom
                [7 ]Department of Zoology, University of Oxford, Oxford, UK
                [8 ]Sierra Leone Ministry of Health, Freetown, Sierra Leone
                [9 ]International Medical Corps, Los Angeles, CA, USA
                [10 ]Department of Medicine, Epidemic Diseases Research Group Oxford (ERGO), Centre for Tropical Medicine and Global Health Nuffield, University of Oxford, Oxford, United Kingdom
                [11 ]Republic of Sierra Leone Armed Forces, Freetown, Sierra Leone
                [12 ]Rare and Imported Pathogens Laboratory, Public Health England, United Kingdom
                [13 ]Thermo Fisher Scientific, South San Francisco, CA, USA
                [14 ]WHO Ebola Response Team, Geneva, Switzerland
                [15 ]Federal University, Oye-Ekit, Nigeria
                [16 ]Robert Koch Institute, Berlin, Germany
                [17 ]Public Health England, Porton Down, United Kingdom
                [18 ]Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
                [19 ]Bundeswehr Institute of Microbiology, Munich, Germany
                [20 ]National Institute for Infectious Diseases “L. Spallanzani”, Rome, Italy
                [21 ]Sierra Leone and Division of Global Health Protection, CDC Country Office, Georgia Center for Global Health Centers for Disease Control and Prevention, Atlanta, GA, USA
                [22 ]Fogarty International Center, NIH, Bethesda, MD, USA
                [23 ]Infection and Evolution, Centre for Immunology, Ashworth Laboratories, Edinburgh, United Kingdom
                [24 ]Division of Infection and Immunity, University College London, London, United Kingdom
                Author notes
                Article
                vew016
                10.1093/ve/vew016
                5499387
                28694998
                cbd5a392-1aff-46c3-8c37-c4f49d68e49e
                © The Author 2016. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Pages: 10
                Funding
                Funded by: Wellcome Trust 10.13039/100004440
                Award ID: 097997/Z/11/A and 097997/Z/11/Z
                Categories
                Rapid Communication

                ebola virus,evolution,transmission,outbreak sequencing
                ebola virus, evolution, transmission, outbreak sequencing

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