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基于生物信息学的帕金森病合并阻塞性睡眠呼吸暂停患者关键候选基因及信号通路的鉴定。

Bioinformatics-based identification of key candidate genes and signaling pathways in patients with Parkinson's disease and obstructive sleep apnea.

机构信息

Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.

Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China.

出版信息

Sleep Breath. 2024 Jun;28(3):1477-1489. doi: 10.1007/s11325-024-03003-6. Epub 2024 Feb 5.

Abstract

OBJECTIVES

Existing evidence exhibits that obstructive sleep apnea (OSA) is a potential consequence of Parkinson's disease (PD) or a contributor to PD progression. This investigation aimed to detect potential critical genes and molecular mechanisms underlying interactions between PD and OSA through bioinformatics analyses.

METHODS

The Gene Expression Omnibus (GEO) database was employed to obtain the expression profiles GSE20163 and GSE135917. The identification of common genes connected to PD and OSA was performed utilizing weighted gene co-expression network analysis and the R 4.0.4 program. The Cytoscape program was utilized to generate a network of protein-protein interactions (PPI), and the CytoHubba plugin was utilized to detect hub genes. Subsequently, functional enrichment analyses of the hub genes were conducted. Markers with increased diagnostic values for PD and OSA were confirmed using the GEO datasets GSE8397 and GSE38792.

RESULTS

Typically, 57 genes that are common were identified in PD and OSA. Among these common genes, the top 10 hub genes in the PPI network were chosen. The verified datasets confirmed the presence of three important genes: CADPS, CHGA, and SCG3. Functional enrichment analysis revealed that these hub genes mostly participate in GABAergic synapses.

CONCLUSION

Our findings suggest that CADPS, CHGA, and SCG3 are key genes involved in molecular mechanisms underlying interactions between OSA and PD. Functional enrichment of hub genes indicated a link between GABAergic synapses and the shared pathogenesis of PD and OSA. These candidate genes and corresponding pathways offer novel insights regarding biological targets that underlie the transcriptional connection between OSA and PD.

摘要

目的

现有证据表明,阻塞性睡眠呼吸暂停(OSA)是帕金森病(PD)的潜在后果,或是 PD 进展的促成因素。本研究旨在通过生物信息学分析,发现 PD 和 OSA 相互作用的潜在关键基因和分子机制。

方法

使用基因表达综合数据库(GEO)获取 GSE20163 和 GSE135917 表达谱数据。利用加权基因共表达网络分析和 R 4.0.4 程序识别与 PD 和 OSA 相关的共同基因。使用 Cytoscape 程序生成蛋白质-蛋白质相互作用(PPI)网络,并用 CytoHubba 插件检测枢纽基因。然后,对枢纽基因进行功能富集分析。使用 GEO 数据集 GSE8397 和 GSE38792 对 PD 和 OSA 的诊断标志物进行验证。

结果

通常情况下,在 PD 和 OSA 中鉴定出 57 个共同基因。在这些共同基因中,选择了 PPI 网络中的前 10 个枢纽基因。验证数据集证实了三个重要基因的存在:CADPS、CHGA 和 SCG3。功能富集分析表明,这些枢纽基因主要参与 GABA 能突触。

结论

我们的研究结果表明,CADPS、CHGA 和 SCG3 是 OSA 和 PD 相互作用分子机制中的关键基因。枢纽基因的功能富集表明 GABA 能突触与 PD 和 OSA 的共同发病机制之间存在联系。这些候选基因和相应的通路为 OSA 和 PD 之间转录关联的生物靶点提供了新的见解。

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