转录组数据的综合生物信息学分析揭示了帕金森病的分子复杂性和潜在治疗靶点

Qudsia Yousafi, Sawaira Asghar, Misbah Shaukat
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摘要

帕金森病(Parkinson's disease,PD)是一种进行性神经退行性疾病,影响着全球数百万人,在老龄人口中的发病率越来越高。在这项研究中,我们通过 GEOmnibus 检索了帕金森病的 mRNA 表达数据集 GSE165082。数据归一化后,共鉴定出 220 个下调基因和 354 个上调基因。利用 DAVID 工具进行的功能注释显示,这些 DEGs 主要富集在细胞分裂和蛋白质磷酸化等生物过程中,且主要定位于细胞质和细胞核。蛋白质结合和 ATP 结合这两种分子功能占主导地位。 此外,KEGG 通路分析还突显了它们在神经退行性疾病、癌症、老年痴呆症和冠状病毒疾病中的参与。INTERPRO 发现了犰狳型折叠和犰狳样螺旋结构域,SMART 发现了 TKc 结构域。转录因子 IRF1 由 FunRich 工具预测。发现上调基因在 6 个部位表达,即腭部、腹侧纹状体、多能干细胞、神经节、颅骨和睫状肌。使用 Cytoscape v 6.0 构建了蛋白质-蛋白质相互作用网络。十个中心基因 EFI3A、RPL28、SMG8.UPF2、XAF1、IFITM1、IFIT3、LY63、IFI3 和 LY6B。利用热图分析了枢纽基因在不同器官和免疫反应细胞中的表达模式,发现除肝脏外,EIF3 在几乎所有器官中都有表达。用 FunRich 工具预测了微RNA。最后,我们预测了RPL28、SMG8、UPF2和EIF3a的microRNA,这些microRNA可能会调控这些枢纽基因,从而为转录后基因调控提供了见解。这项全面的分析有助于我们了解帕金森病的分子机制,并为这一复杂而具有挑战性的疾病的未来研究和治疗开发奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrative bioinformatics analysis of transcriptomic data sheds light on the molecular complexity of parkinson's disease and potential therapeutic targets
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects millions of individuals worldwide, with an increasing prevalence in aging populations. In this study, we retrieved the mRNA expression dataset, GSE165082, for PD through GEOmnibus. Total of 220 downregulated and 354 upregulated genes were identified after data normalization. Functional annotation carried out by DAVID tools, revealed that these DEGs were mainly enriched in biological processes i.e., cell division and protein phosphorylation, and they were localized mostly cytoplasm and nucleus. Two molecular function protein binding and ATP binding were predominant.  Additionally KEGG pathway analysis highlighted their involvement in neurodegenerative, cancer, alzheimer's and coronavirus diseases. Armadillo-type fold and Armadillo-like helical domains were found by INTERPRO while TKc domain by SMART. Transcription factors IRF1 was predicted by FunRich tool. Upregulated genes were found expressed in 6 sites i.e., Palate, Ventral striatum, Pluripotent stem cells, Ganglia, Curtilage and Ciliary muscle. A protein-protein interaction network was constructed by using Cytoscape v 6.0. Ten hub genes EFI3A, RPL28, SMG8. UPF2, XAF1, IFITM1, IFIT3, LY63, IFI3 and LY6B were identified by Cytohubba. The expression patterns of hub genes across different organs and immune response cells using a heatmap and expression of EIF3 was found in almost all organs except liver. MicroRNA for were predicted by FunRich tool. Finally, we predicted microRNAs for RPL28, SMG8, UPF2 and EIF3a that could potentially regulate these hub genes, providing insights into post-transcriptional gene regulation. This comprehensive analysis contributes to our understanding of the molecular mechanisms underlying Parkinson's disease and provides a foundation for future research and therapeutic development in this complex and challenging condition
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