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  • Schofield, James P. R. (author)

Topological data analysis (TDA) of U-BIOPRED paediatric peripheral blood gene expression identified asthma phenotypes characterised by alternative splicing of glucocorticoid receptor (GR) mRNA

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • European Respiratory Society,2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-155991
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-155991URI
  • https://doi.org/10.1183/13993003.congress-2018.PA5435DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:140044375URI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Supplement: 62Meeting Abstract: PA5435
  • Background: Molecular stratification of childhood asthma could enable targeted therapy.Aims: Unbiased analysis of gene expression in paediatric severe (SA) and moderate/mild asthma (MA) blood samples to identify sub-phenotypes.Methods: Transcriptomic profiling by microarray analysis of blood from the U-BIOPRED paediatric cohort (Fleming ERJ 2015), pre- and school-age children, (SApre, n=62; MApre, n=42; SAsc, n=75 and MAsc, n=37). Topological data analysis (TDA) was used for unbiased clustering.Results: Sub-phenotypes, P1, P2, P3 and P4 were identified and are highlighted in the TDA network in the figure and a heatmap of selected variables. P1 (38% of the cohort, median 11 yrs) was characterised by low expression of glucocorticoid receptor (GR) mRNA splice variant with a long 3’ UTR (q = 2.43E-17), but no significant difference in the expression of glucocorticoid receptor (GR) mRNA splice variant with a short 3’ UTR. In P1, COX2 expression was up (q = 1.89E-06) and IFN-γ was down (q = 5.61E-06), characteristics of a decreased steroid response.Conclusion: Unbiased analysis of U-BIOPRED paediatric peripheral blood gene expression identified a sub-phenotype, P1, with an inhibited steroid response. P1 is associated with low expression of a splice variant of GR with a long 3’ UTR.

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  • Boedigheimer, Michael (author)
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  • Riley, John H. (author)
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  • Ward, Jonathan (author)
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  • Per, Bakke (author)
  • Caruso, Massimo (author)
  • Dahlen, Sven-Erik (author)
  • Fowler, Stephen (author)
  • Hashimoto, Simone (author)
  • Horvath, Ildiko (author)
  • Howarth, Peter (author)
  • Krug, Norbert (author)
  • Montuschi, Paolo (author)
  • Sanak, Marek (author)
  • Sandström, Thomas,1957-Umeå universitet(Swepub:umu)thsa0001 (author)
  • Singer, Florian (author)
  • Sun, Kai (author)
  • Pandis, Ioannis (author)
  • Auffray, Charles (author)
  • de Meulder, Bertrand (author)
  • Lefaudeux, Diane (author)
  • Knowles, Richard (author)
  • Fitch, Neil (author)
  • Sousa, Ana (author)
  • Adcock, Ian (author)
  • Chung, Kian Fan (author)
  • Sterk, Peter (author)
  • Skipp, Paul (author)
  • Djukanovic, Ratko (author)
  • Umeå universitet (creator_code:org_t)

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  • In:European Respiratory Journal: European Respiratory Society520903-19361399-3003

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