Sputum gene signature comparison study between U-BIOPRED and Australia asthma cohorts

<b>Introduction:</b> The identification of asthma phenotypes is an evolving area. Analysis of sputum transcriptomics in U-BIOPRED defined three transcriptome-associated clusters (TACs) (Kuo C-HS, <i>et al</i>. Eur Respir J 2017) while Australia (NC-AU) proposed a six-gene signature (6GS) to identify inflammatory phenotypes (Baines K, <i>et al</i>. J Allergy Clin Immunol. 2014). Both studies identify different granulocytic inflammatory phenotypes in subjects with asthma in their corresponding populations. <b>Objective:</b> We aimed to assess the reproducibility of the TACs signatures in NC-AU cohort and the 6GS in U-BIOPRED. <b>Methods:</b> Microarray data from subjects with different granulocytic inflammatory phenotypes from two cohorts of asthma was analysed (U-BIOPRED: healthy control (HC) n=16; eosinophilic asthma (EA) n=42; neutrophilic asthma (NA) n=20 and paucigranulocytic asthma (PGA) n=26 | NC-AU: HC n=16; EA n=19; NA n=16; PGA n=18. We used gene set variation analysis to perform the comparison. <b>Results:</b> Adults with different granulocytic inflammatory phenotypes presented significantly different enrichment for the TACs and 6GS. In NC-AU, we confirmed that TAC1 signature was significantly enriched in EA compared to other phentoypes; TAC2 was enriched in NA compared to other phenotypes and HC; and TAC3 signature was significantly enriched in PGA compared to other phenotypes and HC. The inflammatory phenotypes from U-BIOPRED presented significant enrichment for the 6GS; EAvsNA(p&lt;.01); NA vs HC(p&lt;.01), vs EA(p&lt;.01) and vs PGA(p&lt;.01). <b>Conclusion:</b> Differences in gene expression in distinct inflammatory phenotypes can be reproduced in two distinct well-characterised asthma cohorts, providing validation across independent cohorts.