Single-cell RNA-Sequencing Co-Expression Analysis with CFTR in Lung Tissue
crossref(2024)
摘要
Background While cystic fibrosis is caused by loss-of-function variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) , other modifier genes have been shown to associate with disease severity. Co-expression of modifiers with CFTR in normal tissue indicates a cooperative relationship and suggests the potential for compensation in the presence of CFTR dysfunction. We examined the co-expression relationships with CFTR in the lung using single cell RNA sequencing to pinpoint cell types and their modifiers involved in the forced expiratory volume in 1 second (FEV1)-based cystic fibrosis lung phenotype and support target cell-type prioritization for therapy [1][1].
Methods SmartSeq2 single cell RNA sequencing data from non-cystic fibrosis lung tissue was used for evaluation of co-expression with CFTR and modifier genes. Zero-inflated negative binomial model was used to formally test the co-expression association. 10X Chromium based single cell RNA sequencing data from both cystic fibrosis and non-cystic fibrosis studies were assessed graphically to confirm conclusions from the SmartSeq2 primary analysis.
Results Differentiating basal, club and alveolar epithelial type 2 cells were found to have high proportions of cells expressing CFTR as well as the greatest number of significant co-expression relationships with the modifiers. In particular, among alveolar epithelial type 2 cells, we observed a strong co-expression trio relationship between CFTR, SLC6A14 and SLC26A9 (p < 0.05).
Conclusions CFTR-modifier gene co-expression suggests basal, club and alveolar epithelial type 2 cells show coordinated expression. Alveolar epithelial type 2 cells showed strong co-expression evidence with two of the most established cystic fibrosis modifier genes.
### Competing Interest Statement
CW, KK, AW and LS declare no conflicts of interest. FR acts as a consultant for Vertex Pharmaceuticals.
[1]: #ref-1
更多查看译文
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要