부산대학교 도서관

• An equivalence testing procedure was implemented for gene expression data. • Culturing process does not affect the expression of CF lung disease modifier genes. • Over 90% of genes showed similar expression level across cultured HNE and HBE. • CF lung disease modifier genes have similar co-expression interaction pattern in cultured HNE and cultured HBE. Variation in respiratory response to cystic fibrosis (CF) small molecule therapies is due in part to the contribution of CF lung disease modifier genes. Cultured human bronchial epithelia (HBE) is the gold standard respiratory model for assessing CF therapeutic efficacy but it is hard to access. Cultured human nasal epithelia (HNE) is proposed as a more accessible surrogate model but it is unknown whether the expression profile of the modifier genes are comparable between HNE and HBE which we assess here. RNA-sequencing was conducted on paired cultured and fresh HNE and HBE (n = 71 samples) collected from 21 individuals with CF. Genome-wide gene expression was first compared between cultured and fresh cells and then between cultured HNE and HBE based on an equivalence testing procedure we implemented. The co-expression relationships of CFTR and CF lung disease modifier genes were compared between cultured HNE and HBE to determine equivalent interactions. The culturing process had little impact on the expression level of CF lung disease modifier genes. Over 90% of expressed genes showed significant equivalent expression level across cultured HNE and HBE (expression fold-change<2, FDR<0.1), including CFTR and CF lung disease modifier genes. The difference in co-expression relationships among these genes was not significant (p-value=0.99), suggesting their functional interactions are likely to be consistent in the two models. Cultured HNE recapitulates the expression profile of CF lung disease modifier genes in cultured HBE, suggesting the biological processes involving these genes are likely to be consistent across the two models. [ABSTRACT FROM AUTHOR]