title: Real-time, portable genome sequencing for Ebola surveillance.
abstract: The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10(-3) and 1.42 × 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.
authors: Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.
authors: Joshua
authors: J
authors: Quick
authors: Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.
authors: Nicholas J
authors: NJ
authors: Loman
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Sophie
authors: S
authors: Duraffour
authors: Ontario Institute for Cancer Research, Toronto, Canada.|Department of Computer Science, University of Toronto, Toronto, Canada.
authors: Jared T
authors: JT
authors: Simpson
authors: European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
authors: Ettore
authors: E
authors: Severi
authors: National Infection Service, Public Health England, London, UK.
authors: Lauren
authors: L
authors: Cowley
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Joseph Akoi
authors: JA
authors: Bore
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Raymond
authors: R
authors: Koundouno
authors: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK.
authors: Gytis
authors: G
authors: Dudas
authors: National Infection Service, Public Health England, London, UK.
authors: Amy
authors: A
authors: Mikhail
authors: Postgraduate Training for Applied Epidemiology (PAE, German FETP), Robert Koch Institute, Berlin, Germany.
authors: Nobila
authors: N
authors: Ouédraogo
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Public Health England, Porton Down, Wiltshire SP4 0JG, UK.
authors: Babak
authors: B
authors: Afrough
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors: Amadou
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authors: Bah
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Jonathan Hj
authors: JH
authors: Baum
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Beate
authors: B
authors: Becker-Ziaja
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Robert Koch Institute, Berlin, Germany.
authors: Jan-Peter
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authors: Boettcher
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Mar
authors: M
authors: Cabeza-Cabrerizo
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Alvaro
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authors: Camino-Sanchez
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|University College London, London, UK.
authors: Lisa L
authors: LL
authors: Carter
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Juiliane
authors: J
authors: Doerrbecker
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Paul-Ehrlich-Institut, Division of Veterinary Medicine, Langen, Germany.
authors: Theresa
authors: T
authors: Enkirch
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors: Isabel Graciela García
authors: IGG
authors: Dorival
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Robert Koch Institute, Berlin, Germany.
authors: Nicole
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authors: Hetzelt
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Robert Koch Institute, Berlin, Germany.
authors: Julia
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authors: Hinzmann
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Tobias
authors: T
authors: Holm
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Laboratory for Clinical and Epidemiological Virology, Department of Microbiology and Immunology, KU Leuven, Belgium.
authors: Liana Eleni
authors: LE
authors: Kafetzopoulou
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Ministry of Health Guinea, Conakry, Guinea.
authors: Michel
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authors: Koropogui
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Kenya Medical Research Institute, Nairobi, Kenya.
authors: Abigail
authors: A
authors: Kosgey
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Public Health England, Porton Down, Wiltshire SP4 0JG, UK.
authors: Eeva
authors: E
authors: Kuisma
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Public Health England, Porton Down, Wiltshire SP4 0JG, UK.
authors: Christopher H
authors: CH
authors: Logue
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors: Antonio
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authors: Mazzarelli
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Sarah
authors: S
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authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Friedrich-Loeffler-Institute, Greifswald, Germany.
authors: Marc
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authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Robert Koch Institute, Berlin, Germany.
authors: Janine
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authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Public Health England, Porton Down, Wiltshire SP4 0JG, UK.
authors: Didier
authors: D
authors: Ngabo
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Katja
authors: K
authors: Nitzsche
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Elisa
authors: E
authors: Pallash
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Livia Victoria
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authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Spiez Laboratory, Spiez, Switzerland.
authors: Jasmine
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authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Janssen-Cilag, Stockholm, Sweden.
authors: Johanna Gabriella
authors: JG
authors: Repits
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, L69 7BE.
authors: Natasha Yasmin
authors: NY
authors: Rickett
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Robert Koch Institute, Berlin, Germany.
authors: Andrea
authors: A
authors: Sachse
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Institute of Virology, Technische Universität München, Munich, Germany.
authors: Katrin
authors: K
authors: Singethan
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Public Health England, Porton Down, Wiltshire SP4 0JG, UK.
authors: Inês
authors: I
authors: Vitoriano
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Rahel L
authors: RL
authors: Yemanaberhan
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, L69 7BE.
authors: Elsa G
authors: EG
authors: Zekeng
authors: Public Health Agency of Canada, Winnipeg, Canada.
authors: Racine
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authors: Trina
authors: Public Health Agency of Canada, Winnipeg, Canada.
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authors: Institut Pasteur Dakar, Dakar, Senegal.
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authors: Sandia National Laboratories, Albuquerque, New Mexico, USA.|Ratoma Ebola Diagnostic Center, Conakry, Guinea.
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authors: Sandia National Laboratories, Albuquerque, New Mexico, USA.|Ratoma Ebola Diagnostic Center, Conakry, Guinea.
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authors: Expertise France, Laboratoire K-plan de Forecariah en Guinée, Paris, France.
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authors: Expertise France, Laboratoire K-plan de Forecariah en Guinée, Paris, France.
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authors: Fédération des Laboratoires - HIA Bégin, Paris, France.|Laboratoire de Biologie - Centre de Traitement des Soignants, Conakry, Guinée.
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authors: World Health Organization, Conakry, Guinea.
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authors: World Health Organization, Conakry, Guinea.
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authors: RB
authors: Pallawo
authors: London School of Hygiene and Tropical Medicine, London, UK.
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authors: GJ
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authors: Norwegian Institute of Public Health, Oslo, Norway.|European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
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authors: World Health Organization, Conakry, Guinea.
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authors: I
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authors: Public Health Wales, Cardiff, UK.|European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.
authors: Christopher J
authors: CJ
authors: Williams
authors: Ministry of Health Guinea, Conakry, Guinea.
authors: Facinet
authors: F
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authors: Public Health England, Porton Down, Wiltshire SP4 0JG, UK.
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authors: Lewandowski
authors: Defence Science and Technology Laboratory (Dstl) Porton Down, Salisbury SP4 0JQ, UK.
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authors: J
authors: Taylor
authors: Defence Science and Technology Laboratory (Dstl) Porton Down, Salisbury SP4 0JQ, UK.
authors: Philip
authors: P
authors: Rachwal
authors: Oxford Nanopore Technologies, Oxford, UK.
authors: Daniel
authors: D
authors: Turner
authors: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, L69 7BE.
authors: Georgios
authors: G
authors: Pollakis
authors: Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, L69 7BE.
authors: Julian A
authors: JA
authors: Hiscox
authors: Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
authors: David A
authors: DA
authors: Matthews
authors: Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.|Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham, UK.
authors: Matthew K
authors: MK
authors: O'Shea
authors: Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham, UK.
authors: Andrew McD
authors: AM
authors: Johnston
authors: Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham, UK.
authors: Duncan
authors: D
authors: Wilson
authors: Centre of Defence Pathology, Royal Centre of Defence Medicine, Birmingham UK.
authors: Emma
authors: E
authors: Hutley
authors: Queen Elizabeth Hospital, Birmingham, UK.
authors: Erasmus
authors: E
authors: Smit
authors: National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors: Antonino
authors: A
authors: Di Caro
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bundeswehr Institute of Microbiology, Munich, Germany.
authors: Roman
authors: R
authors: Woelfel
authors: Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bundeswehr Institute of Microbiology, Munich, Germany.
authors: Kilian
authors: K
authors: Stoecker
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bundeswehr Institute of Microbiology, Munich, Germany.
authors: Erna
authors: E
authors: Fleischmann
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Martin
authors: M
authors: Gabriel
authors: Defence Science and Technology Laboratory (Dstl) Porton Down, Salisbury SP4 0JQ, UK.
authors: Simon A
authors: SA
authors: Weller
authors: Institut National de Santé Publique, Conakry, Guinea.
authors: Lamine
authors: L
authors: Koivogui
authors: World Health Organization, Conakry, Guinea.
authors: Boubacar
authors: B
authors: Diallo
authors: Ministry of Health Guinea, Conakry, Guinea.
authors: Sakoba
authors: S
authors: Keita
authors: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK.|Fogarty International Center, National Institutes of Health, Bethesda, USA.|Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 2FL, UK.
authors: Andrew
authors: A
authors: Rambaut
authors: World Health Organization, Conakry, Guinea.
authors: Pierre
authors: P
authors: Formenty
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors: Stephan
authors: S
authors: Gunther
authors: The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.|Public Health England, Porton Down, Wiltshire SP4 0JG, UK.|University of Southampton, South General Hospital, Southampton SO16 6YD, UK.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, PHE Porton Down, UK.
authors: Miles W
authors: MW
authors: Carroll
mesh_terms: D000401:Aircraft; D004196:Disease Outbreaks / Q000706:statistics & numerical data; D029043:Ebolavirus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D062665:Epidemiological Monitoring; D016679:Genome, Viral / Q000235:genetics*; D016701:Guinea / Q000453:epidemiology; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D016296:Mutagenesis / Q000235:genetics; D059645:Mutation Rate; D017422:Sequence Analysis, DNA / Q000295:instrumentation* / Q000379:methods*; D013997:Time Factors