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      Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa.

      1 , 2 , 3 , 4 , 3 , 5 , 6 , 3 , 7 , 7 , 8 , 9 , 10 , 10 , 10 , 9 , 11 , 12 , 9 , 13 , 14 , 11 , 15 , 16 , 17 , 18 , 19 , 19 , 19 , 9 , 19 , 20 , 10 , 21 , 22 , 18 , 23 , 24 , 25 , 16 , 18 , 18 , 18 , 10 , 9 , 14 , 26 , 18 , 18 , 27 , 28 , 9 , 18 , 11 , 9 , 29 , 30 , 9 , 15 , 20 , 19 , 31 , 18 , 25 , 29 , 31 , 9 , 9 , 11 , 10 , 10 , 10 , 10 , 11 , 26 , 32 , 9 , 9 , 33 , 19 ,   34 , 35 , 18 , 11 , 18 , 18 , 14 , 14 , 9 ,   9 , 10 , 9 , 36 , 8 , 9 , 25 , 14 , 18 , 19 , 37 , 4 , 38 , 3 , 39 , 40 , 11 , 41 , 42 , 4 , 43 , 44 , 45 , 46 , 46 , 46 , 47 , 48 , 49 , 50 , 51 , 27 , 18 , 32 , 19 , 14 , 25 , 11 , 52 , 19 , 25 , 44 , 11
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          Abstract

          West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.

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          Fast gapped-read alignment with Bowtie 2.

          As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
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            MrBayes 3.2: Efficient Bayesian Phylogenetic Inference and Model Choice Across a Large Model Space

            Since its introduction in 2001, MrBayes has grown in popularity as a software package for Bayesian phylogenetic inference using Markov chain Monte Carlo (MCMC) methods. With this note, we announce the release of version 3.2, a major upgrade to the latest official release presented in 2003. The new version provides convergence diagnostics and allows multiple analyses to be run in parallel with convergence progress monitored on the fly. The introduction of new proposals and automatic optimization of tuning parameters has improved convergence for many problems. The new version also sports significantly faster likelihood calculations through streaming single-instruction-multiple-data extensions (SSE) and support of the BEAGLE library, allowing likelihood calculations to be delegated to graphics processing units (GPUs) on compatible hardware. Speedup factors range from around 2 with SSE code to more than 50 with BEAGLE for codon problems. Checkpointing across all models allows long runs to be completed even when an analysis is prematurely terminated. New models include relaxed clocks, dating, model averaging across time-reversible substitution models, and support for hard, negative, and partial (backbone) tree constraints. Inference of species trees from gene trees is supported by full incorporation of the Bayesian estimation of species trees (BEST) algorithms. Marginal model likelihoods for Bayes factor tests can be estimated accurately across the entire model space using the stepping stone method. The new version provides more output options than previously, including samples of ancestral states, site rates, site d N /d S rations, branch rates, and node dates. A wide range of statistics on tree parameters can also be output for visualization in FigTree and compatible software.
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              Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences

              Increased reliance on computational approaches in the life sciences has revealed grave concerns about how accessible and reproducible computation-reliant results truly are. Galaxy http://usegalaxy.org, an open web-based platform for genomic research, addresses these problems. Galaxy automatically tracks and manages data provenance and provides support for capturing the context and intent of computational methods. Galaxy Pages are interactive, web-based documents that provide users with a medium to communicate a complete computational analysis.
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                Author and article information

                Journal
                Nature
                Nature
                1476-4687
                0028-0836
                Aug 6 2015
                : 524
                : 7563
                Affiliations
                [1 ] 1] Public Health England, Porton Down, Wiltshire SP4 0JG, UK [2] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] University of Southampton, South General Hospital, Southampton SO16 6YD, UK.
                [2 ] Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
                [3 ] Institute of Infection and Global Health, University of Liverpool, Liverpool L69 2BE, UK.
                [4 ] Public Health England, Porton Down, Wiltshire SP4 0JG, UK.
                [5 ] 1] Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK [2] Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA [3] Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 2FL, UK.
                [6 ] 1] Public Health England, Porton Down, Wiltshire SP4 0JG, UK [2] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
                [7 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée, Conakry, Guinea [3] Institut National de Santé Publique, Conakry, Guinea.
                [8 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Institute of Tropical Medicine, B-2000 Antwerp, Belgium.
                [9 ] 1] Public Health England, Porton Down, Wiltshire SP4 0JG, UK [2] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
                [10 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria.
                [11 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany.
                [12 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Swiss Tropical and Public Health Institute, University of Basel, CH-4002 Basel, Switzerland.
                [13 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany.
                [14 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Institute of Virology, Philipps University Marburg, 35043 Marburg, Germany.
                [15 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] National Reference Center for Viral Hemorrhagic Fevers, 69365 Lyon, France [3] Laboratoire P4 Inserm-Jean Mérieux, US003 Inserm, 69365 Lyon, France.
                [16 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Department of Biology, University of Antwerp, B-2020 Antwerp, Belgium.
                [17 ] 1] Public Health England, Porton Down, Wiltshire SP4 0JG, UK [2] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] Institute of Infection and Global Health, University of Liverpool, Liverpool L69 2BE, UK.
                [18 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Robert Koch Institute, 13353 Berlin, Germany.
                [19 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] National Institute for Infectious Diseases (INMI) Lazzaro Spallanzani, 00149 Rome, Italy.
                [20 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Friedrich Loeffler Institute, Federal Research Institute for Animal Health, 17493 Greifswald, Insel Riems, Germany.
                [21 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] KU Leuven Rega institute, B-3000 Leuven, Belgium.
                [22 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany [3] Redeemer's University, Osun State, Nigeria.
                [23 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28029 Madrid, Spain.
                [24 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] National Reference Center for Viral Hemorrhagic Fevers, 69365 Lyon, France [3] Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, 69365 Lyon, France.
                [25 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Bundeswehr Institute of Microbiology, 80937 Munich, Germany.
                [26 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] National Center for Epidemiology, National Biosafety Laboratory, H-1097 Budapest, Hungary.
                [27 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
                [28 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Public Health Agency of Sweden, 171 82 Solna, Sweden.
                [29 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Heinrich Pette Institute - Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
                [30 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] KU Leuven Rega institute, B-3000 Leuven, Belgium.
                [31 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany [3] Institute of Virology, University of Bonn, 53127 Bonn, Germany.
                [32 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Federal Office for Civil Protection, Spiez Laboratory, CH-3700 Spiez, Switzerland.
                [33 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Bundeswehr Hospital, 22049 Hamburg, Germany.
                [34 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Institute of Virology and Immunology, CH-3147 Mittelhäusern, Switzerland.
                [35 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Janssen-Cilag, SE-192 07 Sollentuna, Sweden.
                [36 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Thünen Institute, D-22767 Hamburg, Germany.
                [37 ] Eurice - European Research and Project Office GmbH, 10115 Berlin, Germany.
                [38 ] Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK.
                [39 ] Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK.
                [40 ] Department of Infection and Population Health, University College London, London WC1E 6JB, UK.
                [41 ] Research IT, University of Bristol, Bristol BS8 1HH, UK.
                [42 ] Advanced Computing Research Centre, University of Bristol, Bristol BS8 1HH, UK.
                [43 ] Ministry of Health Guinea, Conakry, Guinea.
                [44 ] World Health Organization, 1211 Geneva 27, Switzerland.
                [45 ] World Health Organization, Conakry, Guinea.
                [46 ] Médecins Sans Frontières, B-1050 Brussels, Belgium.
                [47 ] Section Prévention et Lutte contre la Maladie à la Direction Préfectorale de la Santé de Guéckédou, Guéckédou, Guinea.
                [48 ] Université Gamal Abdel Nasser de Conakry, CHU Donka, Conakry, Guinea.
                [49 ] Health and Sustainable Development Foundation, Conakry, Guinea.
                [50 ] Institut National de Santé Publique, Conakry, Guinea.
                [51 ] Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée, Conakry, Guinea.
                [52 ] 1] The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany [2] Laboratoire P4 Inserm-Jean Mérieux, US003 Inserm, 69365 Lyon, France.
                Article
                nature14594
                10.1038/nature14594
                26083749
                62d48487-ba48-4362-8685-2b856f101fb8
                History

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