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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
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2018 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
European Respiratory Society , 2018. Vol. 52
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:umu:diva-155991DOI: 10.1183/13993003.congress-2018.PA5435ISI: 000455567107185OAI: oai:DiVA.org:umu-155991DiVA, id: diva2:1286606
Conference
28th International Congress of the European-Respiratory-Society (ERS), SEP 15-19, 2018, Paris, FRANCE
Note

Supplement: 62

Meeting Abstract: PA5435

Available from: 2019-02-07 Created: 2019-02-07 Last updated: 2019-02-07Bibliographically approved

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Sandström, Thomas

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