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

 
: Schofield, James P.R.; Bigler, Jeanette; Boedigheimer, Michael; Affleck, Karen; Taylor, Adam; Pavlidis, Stelios; Riley, John H.; Strazzeri, Fabio; Roberts, Graham; Brandsma, Joost; Bansal, Aruna T.; Nicholas, Ben; Xian, Yang; Rowe, Anthony; Corfield, Julie; Wilson, Susan J.; Ward, Jonathan A.; Lutter, René; Fleming, Louise; Shaw, Dominick E.; Per, Bakke; Caruso, Massimo; Dahlén, Sven-Erik; Fowler, Stephen J.; Hashimoto, Simone; Horváth, Ildikó; Howarth, Peter; Krug, Norbert; Montuschi, Paolo; Sanak, Marek; Sandstrom, Thomas; Singer, Florian; Sun, Kai; Pandis, Ioannis; Auffray, Charles; Meulder, Bertrand de; Lefaudeux, Diane; Knowles, Richard; Fitch, Neil; Sousa, Ana R.; Adcock, Ian M.; Chung, Kian Fan; Sterk, Peter J.; Skipp, Paul; Djukanović, Ratko

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European Respiratory Journal 52 (2018), Supplement 62, Abstract PA5435
ISSN: 0903-1936
ISSN: 1399-3003
European Respiratory Society (ERS International Congress) <2018, Paris>
Englisch
Abstract
Fraunhofer ITEM ()

Abstract
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.

: http://publica.fraunhofer.de/dokumente/N-559362.html