title: Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus.
abstract: In 2014, Western Africa experienced an unanticipated explosion of Ebola virus infections. What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. We used transcriptome data for peripheral blood taken from infected and convalescent recovering patients to identify early stage host factors that are associated with acute illness and those that differentiate patient survival from fatality.
  
  
  
  The data demonstrate that individuals who succumbed to the disease show stronger upregulation of interferon signalling and acute phase responses compared to survivors during the acute phase of infection. Particularly notable is the strong upregulation of albumin and fibrinogen genes, which suggest significant liver pathology. Cell subtype prediction using messenger RNA expression patterns indicated that NK-cell populations increase in patients who survive infection. By selecting genes whose expression properties discriminated between fatal cases and survivors, we identify a small panel of responding genes that act as strong predictors of patient outcome, independent of viral load.
  
  
  
  Transcriptomic analysis of the host response to pathogen infection using blood samples taken during an outbreak situation can provide multiple levels of information on both disease state and mechanisms of pathogenesis. Host biomarkers were identified that provide high predictive value under conditions where other predictors, such as viral load, are poor prognostic indicators. The data suggested that rapid analysis of the host response to infection in an outbreak situation can provide valuable information to guide an understanding of disease outcome and mechanisms of disease.
authors.affiliation: National Institute of Health Research, Health Protection Research Unit In Emerging and Zoonotic Infections, Liverpool, UK.|Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Microbiology, School of Medicine, National Emerging and Infectious Diseases Laboratories, Bioinformatics Program, Boston University, Boston, MA, 02118, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Speranza
authors.affiliation: Heinrich Pette Institute - Leibniz Institute for Experimental Virology, 20251, Hamburg, Germany.|Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.|German Center for Infection Research (DZIF), partner site Hamburg, Germany.
authors.forename: César
authors.initials: C
authors.lastname: Muñoz-Fontela
authors.affiliation: Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Haldenby
authors.affiliation: National Institute of Health Research, Health Protection Research Unit In Emerging and Zoonotic Infections, Liverpool, UK.|Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.
authors.forename: Natasha Y
authors.initials: NY
authors.lastname: Rickett
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.
authors.forename: Isabel
authors.initials: I
authors.lastname: Garcia-Dorival
authors.affiliation: Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Public Health England, Porton Down, Wiltshire, SP4 0JG, UK.
authors.forename: Yper
authors.initials: Y
authors.lastname: Hall
authors.affiliation: National Institute of Health Research, Health Protection Research Unit In Emerging and Zoonotic Infections, Liverpool, UK.|Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.
authors.forename: Elsa-Gayle
authors.initials: EG
authors.lastname: Zekeng
authors.affiliation: Heinrich Pette Institute - Leibniz Institute for Experimental Virology, 20251, Hamburg, Germany.|Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Lüdtke
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK.
authors.forename: Dong
authors.initials: D
authors.lastname: Xia
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.
authors.forename: Romy
authors.initials: R
authors.lastname: Kerber
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Krumkamp
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.
authors.forename: Sophie
authors.initials: S
authors.lastname: Duraffour
authors.affiliation: Bordeaux Hospital University Center (CHU) -INSERM U1219- Bordeaux University, Bordeaux, France.
authors.forename: Daouda
authors.initials: D
authors.lastname: Sissoko
authors.affiliation: Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
authors.forename: John
authors.initials: J
authors.lastname: Kenny
authors.affiliation: Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
authors.forename: Nichola
authors.initials: N
authors.lastname: Rockliffe
authors.affiliation: Defence Science Technology Laboratories (Porton Down), Porton Down, Salisbury, UK.
authors.forename: E Diane
authors.initials: ED
authors.lastname: Williamson
authors.affiliation: Defence Science Technology Laboratories (Porton Down), Porton Down, Salisbury, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Laws
authors.affiliation: Hôpital National Donka service des Maladies infectieuses et Tropicales, Conakry, Guinea.
authors.forename: Magassouba
authors.initials: M
authors.lastname: N'Faly
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Matthews
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.|German Center for Infection Research (DZIF), partner site Hamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Günther
authors.affiliation: Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Cossins
authors.affiliation: Médecins Sans Frontières (MSF), Brussels, Belgium.
authors.forename: Armand
authors.initials: A
authors.lastname: Sprecher
authors.affiliation: Department of Microbiology, School of Medicine, National Emerging and Infectious Diseases Laboratories, Bioinformatics Program, Boston University, Boston, MA, 02118, USA. jhconnor@bu.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Connor
authors.affiliation: Public Health England, Porton Down, Wiltshire, SP4 0JG, UK. Miles.Carroll@phe.gov.uk.|National Institute of Health Research in Emerging and Zoonotic Infections, Porton Down, SP4 0JQ, Salisbury, UK. Miles.Carroll@phe.gov.uk.
authors.forename: Miles W
authors.initials: MW
authors.lastname: Carroll
authors.affiliation: National Institute of Health Research, Health Protection Research Unit In Emerging and Zoonotic Infections, Liverpool, UK. julian.hiscox@liverpool.ac.uk.|Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, UK. julian.hiscox@liverpool.ac.uk.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Hiscox
mesh_terms: D016000:Cluster Analysis; D060085:Coinfection; D019295:Computational Biology / Q000379:methods; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D029043:Ebolavirus; D020869:Gene Expression Profiling; D016701:Guinea; D019142:Hemorrhagic Fever, Ebola / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D063868:Patient Outcome Assessment; D012372:ROC Curve; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome; D019562:Viral Load
chemical_list: D007372:Interferons