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  • Ma, YuqianDept Expt Immunobiol, Kings Coll London, London, England; , NIHR Biomed Res Ctr, Guys & St Thomas, NHS Foundation Trust, London, England; Kings College, London, England (author)

Genome-Wide Sequencing of Cellular microRNAs Identifies a Combinatorial Expression Signature Diagnostic of Sepsis

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013-10-16
  • Public Library of Science (PLoS),2013
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:oru-56628
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-56628URI
  • https://doi.org/10.1371/journal.pone.0075918DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • Rationale: Sepsis is a common cause of death in the intensive care unit with mortality up to 70% when accompanied by multiple organ dysfunction. Rapid diagnosis and the institution of appropriate antibiotic therapy and pressor support are therefore critical for survival. MicroRNAs are small non-coding RNAs that play an important role in the regulation of numerous cellular processes, including inflammation and immunity. Objectives: We hypothesized changes in expression of microRNAs during sepsis may be of diagnostic value in the intensive care unit (ICU). Methods: Massively parallel sequencing of microRNAs was utilised for screening microRNA candidates. Putative microRNAs were validated using quantitative real-time PCR (qRT-PCR). This study includes data from both a training cohort (UK) and an independent validation cohort (Sweden). A linear discriminant statistical model was employed to construct a diagnostic microRNA signature. Results: A panel of known and novel microRNAs were detectable in the blood of patients with sepsis. After qRT-PCR validation, microRNA miR-150 and miR-4772-5p-iso were able to discriminate between patients who have systemic inflammatory response syndrome and patients with sepsis. This finding was also validated in independent cohort with an average diagnostic accuracy of 86%. Fractionating the cellular components of blood reveals miR-4772-5p-iso is expressed differentially in monocytes. Functional experiments using primary human monocytes demonstrate that it expressed in response to TLR ligation. Conclusions: Taken together, these data provide a novel microRNA signature of sepsis that should allow rapid point-of-care diagnostic assessment of patients on ICU and also provide greater insight into the pathobiology of this severe disease.

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  • Vilanova, DavidR&D, Cepheid Europe, Maurens Scopont, France (author)
  • Atalar, KeremDept Expt Immunobiol, Kings Coll London, London, England; NIHR Biomed Res Ctr, Guys & St Thomas, NHS Fdn Trust, London, England; Kings College, London, England (author)
  • Delfour, OlivierR&D, Cepheid Europe, Maurens Scopont, France (author)
  • Edgeworth, JonathanNIHR Biomed Res Ctr, Guys & St Thomas, NHS Foundation Trust, London, England; Kings College, London, England (author)
  • Ostermann, MarliesNIHR Biomed Res Ctr, Guys & St Thomas, NHS Fdn Trust, London, England; Kings Coll London, London, England (author)
  • Hernandez-Fuentes, MariaDept Expt Immunobiol, Kings Coll, London, England; NIHR Biomed Res Ctr, Guys & St Thomas NHS Fdn Trust, London, England (author)
  • Razafimahatratra, SandrineR&D, Cepheid Europe, Maurens Scopont, France (author)
  • Michot, BernardR&D, Cepheid Europe, Maurens Scopont, France (author)
  • Persing, David H.Cepheid, Sunnyvale CA, USA (author)
  • Ziegler, IngridDept Infect Dis, Örebro University Hospital, Örebro, Sweden (author)
  • Toros, BiancaDept Lab Med, Örebro University Hospital, Örebro, Sweden (author)
  • Mölling, PaulaRegion Örebro län,Dept Lab Med(Swepub:oru)OUH-pa1mo (author)
  • Olcen, PerDept Lab Med, Örebro University Hospital, Örebro, Sweden (author)
  • Beale, RichardDiv Asthma Allergy & Lung Biol, Kings College, London, England; NIHR Biomed Res Ctr, Guys & St Thomas, NHS Foundation Trust, London, England (author)
  • Lord, Graham M.Dept Expt Immunobiol, Kings College, London, England; NIHR Biomed Res Ctr, Guys & St Thomas NHS Fdn Trust, London, England (author)
  • Dept Expt Immunobiol, Kings Coll London, London, England; , NIHR Biomed Res Ctr, Guys & St Thomas, NHS Foundation Trust, London, England; Kings College, London, EnglandR&D, Cepheid Europe, Maurens Scopont, France (creator_code:org_t)

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  • In:PLOS ONE: Public Library of Science (PLoS)8:101932-6203

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