Gene expression profiling in Venous thromboembolism: Insights from publicly available datasets

IF 2.6 4区生物学 Q2 BIOLOGY

Computational Biology and Chemistry Pub Date : 2024-10-11 DOI:10.1016/j.compbiolchem.2024.108246

Sunanda Arya, Rashi Khare, Iti Garg, Swati Srivastava

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Abstract

Background

Venous thromboembolism (VTE) is the third most common cardiovascular disease and is a major cause of mobility and mortality worldwide. VTE is a complex multifactorial disease and genetic mechanisms underlying its pathogenesis is yet to be completely elucidated. The aim of the present study was to identify hub genes and pathways involved in development and progression of blood clot during VTE using gene expression data from public repositories.

Methodology

Differential gene expression (DEG) data from two datasets, GSE48000 and GSE19151 were analysed using GEO2R tool. Gene expression data of VTE patients were compared to that of healthy controls using various bioinformatics tools.

Results

When the differentially expressed genes of the two datasets were compared, it was found that 19 genes were up-regulated while 134 genes were down-regulated. Gene ontology (GO) and pathway analysis revealed that pathways such as complement and coagulation cascade and B-cell receptor signalling along with DNA methylation, DNA alkylation and inflammatory genes were significantly up-regulated in VTE patients. On the other hand, differentially down-regulated genes included mitochondrial translation elongation, termination and biosysthesis along with heme biosynthesis, erythrocyte differentiation and homeostasis. The top 5 up-regulated hub genes obtained by protein-protein interaction (PPI) network analysis included MYC, FOS, SGK1, CR2 and CXCR4, whereas the top 5 down-regulated hub genes included MRPL13, MRPL3, MRPL11, RPS29 and RPL9. The up-regulated hub genes are functionally involved in maintain vascular integrity and complementation cascade while the down-regulated hub genes were mostly mitochondrial ribosomal proteins.

Conclusion

Present study highlights significantly enriched pathways and genes associated with VTE development and prognosis. The data hereby obtained could be used for designing newer diagnostic and therapeutic tools for VTE management.

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静脉血栓栓塞症的基因表达谱分析：从公开数据集中获得的启示

背景静脉血栓栓塞症（VTE）是第三大最常见的心血管疾病，也是全球流动性和死亡率的主要原因。VTE 是一种复杂的多因素疾病，其发病的遗传机制尚未完全阐明。本研究的目的是利用公共资料库中的基因表达数据，找出 VTE 期间血栓形成和发展过程中的枢纽基因和通路。方法利用 GEO2R 工具分析 GSE48000 和 GSE19151 两个数据集中的差异基因表达（DEG）数据。结果比较两个数据集的差异表达基因后发现，19 个基因上调，134 个基因下调。基因本体（GO）和通路分析显示，补体和凝血级联、B 细胞受体信号传导等通路以及 DNA 甲基化、DNA 烷基化和炎症基因在 VTE 患者中明显上调。另一方面，不同程度下调的基因包括线粒体翻译延伸、终止和生物合成，以及血红素生物合成、红细胞分化和稳态。通过蛋白-蛋白相互作用（PPI）网络分析获得的前5个上调中枢基因包括MYC、FOS、SGK1、CR2和CXCR4，而前5个下调中枢基因包括MRPL13、MRPL3、MRPL11、RPS29和RPL9。上调的中枢基因在功能上参与维持血管完整性和互补级联，而下调的中枢基因主要是线粒体核糖体蛋白。本研究获得的数据可用于设计新的 VTE 诊断和治疗工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Computational Biology and Chemistry 生物-计算机：跨学科应用

CiteScore

6.10

自引率

3.20%

发文量

142

审稿时长

24 days

期刊介绍： Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.