药物重新定位
转录组
医学
基因
药品
组蛋白
候选基因
重新调整用途
计算生物学
生物信息学
药理学
基因表达
遗传学
生物
生态学
作者
Renaud Felten,Tao Ye,Cédric Schleiss,Benno Schwikowski,Jean Sibilia,Fanny Monneaux,Hélène Dumortier,Roland Jönsson,Christopher J. Lessard,Fai Ng,Tsutomu Takeuchi,Xavier Mariette,Jacques-Éric Gottenberg
出处
期刊:Rheumatology
[Oxford University Press]
日期:2023-03-03
卷期号:62 (11): 3715-3723
被引量:2
标识
DOI:10.1093/rheumatology/kead096
摘要
Abstract Objectives To date, no immunomodulatory drug has demonstrated its efficacy in primary SS (pSS). We sought to analyse potential commonalities between pSS transcriptomic signatures and signatures of various drugs or specific knock-in or knock-down genes. Methods Gene expression from peripheral blood samples of patients with pSS was compared with that of healthy controls in two cohorts and three public databases. In each of the five datasets, we analysed the 150 most up- and downregulated genes between pSS patients and controls with regard to the differentially expressed genes resulting from the biological action on nine cell lines of 2837 drugs, 2160 knock-in and 3799 knock-down genes in the Connectivity Map database. Results We analysed 1008 peripheral blood transcriptomes from five independent studies (868 patients with pSS and 140 healthy controls). Eleven drugs could represent potential candidate drugs, with histone deacetylases and PI3K inhibitors among the most significantly associated. Twelve knock-in genes were associated with a pSS-like profile and 23 knock-down genes were associated with a pSS-revert profile. Most of those genes (28/35, 80%) were interferon-regulated. Conclusion This first drug repositioning transcriptomic approach in SS confirms the interest of targeting interferons and identifies histone deacetylases and PI3K inhibitors as potential therapeutic targets.
科研通智能强力驱动
Strongly Powered by AbleSci AI