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基于系统生物学方法的芯片数据分析鉴定 HELLP 综合征诊断生物标志物的枢纽基因

Bioinformatics analysis of microarray data to identify hub genes, as diagnostic biomarker of HELLP syndrome: System biology approach.

机构信息

Assistant Professor of Obstetrics and Gynecology, Department of Gynecology and Obstetrics, Yasuj University of Medical Sciences, Yasuj, Iran.

Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

出版信息

J Obstet Gynaecol Res. 2022 Oct;48(10):2493-2504. doi: 10.1111/jog.15363. Epub 2022 Jul 22.

Abstract

BACKGROUND

HELLP syndrome is one of the disorders characterized by hemolysis, increased liver enzymes and decreased platelet count. So far, many molecular pathways and genes have been identified in relation to the pathogenesis of this syndrome; however, the main cause of the incidence and progression of the disease has not been identified. Using the biological system approach is a way to target patients by identifying genes and molecular pathways. In this study, we investigated genes and important molecular factors in the pathogenesis of HELLP syndrome.

MATERIAL AND METHODS

In this study, the microarray dataset was downloaded from Gene Expression Omnibus (GEO) database and analyzed using the GEO2R online tool for identifying differentially expressed genes (DEGs). Enrichment analysis of DEGs was evaluated using the Enrichr database. Then, protein-protein interaction (PPI) networks were constructed via the STRING database; they were visualized by Cytoscape. Then the STRING database was used to construct PPI networks. The hub genes were recognized using the cytoHubba. Ultimately, the interaction of the miRNA-hub genes and drug-hub genes were also evaluated.

RESULT

After analysis, it was found that some genes with the highest degree of connectivity are involved in the pathogenesis of HELLP syndrome, which are known as the hub genes. These genes are as follows: KIT, JAK2, LEP, EP300, HIST1H4L, HIST1H4F, HIST1H4H, MMP9, THBS2, and ADAMTS3. Has-miR-34a-5p was also most associated with hub genes.

CONCLUSION

Finally, it can be said, that the identification of genes and molecular pathways in HELLP syndrome can be helpful in identifying the pathogenesis pathways of the disease, and designing therapeutic targets.

摘要

背景

HELLP 综合征是一种以溶血、肝酶升高和血小板减少为特征的疾病。迄今为止,已经发现了许多与该综合征发病机制相关的分子途径和基因;然而,疾病发生和进展的主要原因尚未确定。使用生物系统方法是通过识别基因和分子途径来靶向患者的一种方法。在这项研究中,我们研究了 HELLP 综合征发病机制中的基因和重要的分子因素。

材料和方法

本研究从基因表达综合数据库(GEO)下载微阵列数据集,并使用 GEO2R 在线工具分析以鉴定差异表达基因(DEGs)。使用 Enrichr 数据库评估 DEGs 的富集分析。然后,通过 STRING 数据库构建蛋白质-蛋白质相互作用(PPI)网络;通过 Cytoscape 可视化。然后使用 STRING 数据库构建 PPI 网络。使用 cytoHubba 识别枢纽基因。最终,还评估了 miRNA-枢纽基因和药物-枢纽基因的相互作用。

结果

分析后发现,一些连接度最高的基因参与了 HELLP 综合征的发病机制,这些基因被称为枢纽基因。这些基因如下:KIT、JAK2、LEP、EP300、HIST1H4L、HIST1H4F、HIST1H4H、MMP9、THBS2 和 ADAMTS3。Has-miR-34a-5p 也与枢纽基因最相关。

结论

最后,可以说,HELLP 综合征中基因和分子途径的鉴定有助于鉴定疾病的发病机制途径,并设计治疗靶点。

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