PT  - JOURNAL ARTICLE
AU  - Nazanin Zounemat Kermani
AU  - Stelios Pavlidis
AU  - Mansoor Saqi
AU  - Yike Guo
AU  - Paul Agapow
AU  - Chih-Hsi Kuo
AU  - Matthew Loza
AU  - Frederic Baribaud
AU  - Anthony Rowe
AU  - Ana Sousa
AU  - Bertrand De Meulder
AU  - Diane Lefaudeux
AU  - Louise Fleming
AU  - Julie Corfield
AU  - Richard Knowles
AU  - Charles Auffray
AU  - Ratko Djukanovic
AU  - Peter J. Sterk
AU  - Ian Adcock
AU  - Fan Chung
TI  - Further resolution of non-T2 asthma subtypes from high-throughput sputum transciptomics data in U-BIOPRED
AID  - 10.1183/13993003.congress-2018.PA606
DP  - 2018 Sep 15
TA  - European Respiratory Journal
PG  - PA606
VI  - 52
IP  - suppl 62
4099  - http://erj.ersjournals.com/content/52/suppl_62/PA606.short
4100  - http://erj.ersjournals.com/content/52/suppl_62/PA606.full
SO  - Eur Respir J2018 Sep 15; 52
AB  - Background: Precision medicine of asthma requires understanding of its heterogeneity and molecular pathophysiology.Aim: Three sputum-derived transcriptomic clusters (TACs) were previously identified [Kuo at al. Eur Respir J.2017, 49] in the U-BIOPRED cohort: TAC1 consisting of T2 high patients with eosinophilia, TAC2 with neutrophilia and inflammasome activation and TAC3, a more heterogeneous cluster with mostly paucigranulocytic patients. We further refine TAC3.Methods: Gaussian mixture modelling for model-based clustering was applied to sputum gene expression of 104 asthmatic participants from the adult cohort to substructure TAC3. Gene set variation analysis (GSVA) was used to explore the enrichment of gene signatures across the TACs.Results: We again produce the three TACs (TAC1 N=23, TAC2 N=24) but TAC3 was further split into two groups (TAC3a N=28, TAC3b N=29), distinguished by distinct neutrophils and macrophages density and enrichment of IL13 stimulation, inflammasome activation and OXPHOS gene signatures (Figure), as well as IL-4 and LPS-stimulated macrophage gene signatures. However, there were no distinguishing clinical features.Conclusion: Identification of sub-structure of sputum TACs, particularly of TAC3, will help towards improved targeted therapies.FootnotesCite this article as: European Respiratory Journal 2018 52: Suppl. 62, PA606.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).