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1.	Schofield, James P. R., et al. (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 2018 In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52 Journal article (other academic/artistic)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.

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Type of publication: journal article (1)

Type of content: other academic/artistic (1)

Author/Editor: Riley, John H. (1); De Meulder, Bertrand (1); Auffray, Charles (1); Caruso, Massimo (1); Corfield, Julie (1); Horvath, Ildiko (1); show more...; Krug, Norbert (1); Sun, Kai (1); Sandström, Thomas, 1 ... (1); Montuschi, Paolo (1); Lutter, René (1); Djukanovic, Ratko (1); Howarth, Peter (1); Skipp, Paul (1); Sanak, Marek (1); Chung, Kian Fan (1); Shaw, Dominick (1); Fleming, Louise (1); Roberts, Graham (1); Knowles, Richard (1); Bansal, Aruna (1); Pandis, Ioannis (1); Singer, Florian (1); Adcock, Ian (1); Dahlen, Sven-Erik (1); Pavlidis, Stelios (1); Sterk, Peter (1); Wilson, Susan (1); Brandsma, Joost (1); Schofield, James P.R ... (1); Strazzeri, Fabio (1); Lefaudeux, Diane (1); Nicholas, Ben (1); Xian, Yang (1); Rowe, Anthony (1); Ward, Jonathan (1); Hashimoto, Simone (1); Sousa, Ana (1); Fowler, Stephen (1); Bigler, Jeanette (1); Boedigheimer, Michae ... (1); Affleck, Karen (1); Taylor, Adam (1); Per, Bakke (1); Fitch, Neil (1); show less...

University: Umeå University (1); Karolinska Institutet (1)

Language: English (1)

Research subject (UKÄ/SCB): Medical and Health Sciences (1)

Year: 2018 (1)

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