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COPD 相关同源基因的预测和富集分析:利用果蝇对人类 COPD 基因组反应进行建模的潜力。

Prediction and enrichment analyses of the COPD-related orthologs: potential for modeling of human COPD genomic responses with the fruit fly.

机构信息

Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, Larissa, Greece.

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2022 Jan 1;322(1):R77-R82. doi: 10.1152/ajpregu.00092.2021. Epub 2021 Dec 8.

DOI:10.1152/ajpregu.00092.2021
PMID:34877887
Abstract

The significant similarities in airway epithelial cells between mammals and the fruit fly have rendered the latter an important model organism for studies of chronic inflammatory lung diseases. Focusing on the chronic obstructive pulmonary disease (COPD), we here mapped human gene orthologs associated with this disease in to identify functionally equivalent genes for immediate, further screening with the fruit fly model. The DIOPT-DIST tool was accessed for the prediction of the COPD-associated orthologs between humans and . Enrichment analyses with respect to pathways of the retrieved functional homologs were performed using the ToppFun and FlyMine tools, identifying 73 unique human genes as well as 438 fruit fly genes. The ToppFun analysis verified that the human gene list is associated with COPD phenotypes. Furthermore, the FlyMine investigation highlighted that the genes are functionally connected mainly with the "ABC-family proteins mediated transport" and the "β-catenin-independent WNT signaling pathway." These results suggest an evolutionarily conserved role toward responses to inhaled toxicants and CO in both species. We reason that the predicted orthologous genes should be further studied in the models of cigarette smoke-induced COPD.

摘要

哺乳动物和果蝇的气道上皮细胞存在显著的相似性,这使得后者成为研究慢性炎症性肺部疾病的重要模式生物。本文聚焦于慢性阻塞性肺疾病(COPD),我们在此将与人类 COPD 相关的基因直系同源物映射到 中,以鉴定功能等效的基因,用于立即在果蝇模型中进行进一步筛选。使用 DIOPT-DIST 工具预测人类和 之间的 COPD 相关直系同源物。使用 ToppFun 和 FlyMine 工具对检索到的功能同源物的途径进行富集分析,鉴定出 73 个独特的人类基因和 438 个果蝇基因。ToppFun 分析证实,人类基因列表与 COPD 表型相关。此外,FlyMine 研究强调,果蝇的 基因主要与“ABC 家族蛋白介导的运输”和“β-连环蛋白非依赖性 WNT 信号通路”功能相关。这些结果表明,在这两个物种中,对吸入性毒物和 CO 的反应存在进化上保守的作用。我们认为,预测的直系同源物基因应在香烟烟雾诱导的 COPD 的 模型中进一步研究。

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