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特应性皮炎的综合转录组全基因组分析,用于药物重定位。

Integrative transcriptome-wide analysis of atopic dermatitis for drug repositioning.

机构信息

Department of Life Sciences, Dongguk University-Seoul, 04620, Seoul, Republic of Korea.

Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA, 90089, USA.

出版信息

Commun Biol. 2022 Jun 22;5(1):615. doi: 10.1038/s42003-022-03564-w.

Abstract

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, which significantly impact the quality of life. Transcriptome-wide association study (TWAS) was conducted to estimate both transcriptomic and genomic features of AD and detected significant associations between 31 expression quantitative loci and 25 genes. Our results replicated well-known genetic markers for AD, as well as 4 novel associated genes. Next, transcriptome meta-analysis was conducted with 5 studies retrieved from public databases and identified 5 additional novel susceptibility genes for AD. Applying the connectivity map to the results from TWAS and meta-analysis, robustly enriched perturbations were identified and their chemical or functional properties were analyzed. Here, we report the first research on integrative approaches for an AD, combining TWAS and transcriptome meta-analysis. Together, our findings could provide a comprehensive understanding of the pathophysiologic mechanisms of AD and suggest potential drug candidates as alternative treatment options.

摘要

特应性皮炎(AD)是最常见的炎症性皮肤病之一,严重影响生活质量。本研究进行了全转录组关联研究(TWAS),以评估 AD 的转录组和基因组特征,并检测到 31 个表达数量性状基因座和 25 个基因之间的显著关联。我们的结果复制了 AD 的众所周知的遗传标记,以及 4 个新的相关基因。接下来,通过对从公共数据库检索到的 5 项研究进行转录组荟萃分析,确定了 AD 的另外 5 个新的易感基因。应用连接组学将 TWAS 和荟萃分析的结果进行整合,鉴定出稳健富集的扰动,并对其化学或功能特性进行了分析。在这里,我们报告了首次整合 TWAS 和转录组荟萃分析的 AD 研究。综上所述,我们的研究结果可以提供对 AD 病理生理机制的全面理解,并为潜在的药物候选物作为替代治疗方案提供依据。

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