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首页> 外文期刊>BMC Medical Genomics >Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem
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Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem

机译：使用ANDSystem分析关联基因网络，通过涉及淋巴水肿来区分参与内皮细胞凋亡的基因的优先级

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Currently, more than 150 million people worldwide suffer from lymphedema. It is a chronic progressive disease characterized by high-protein edema of various parts of the body due to defects in lymphatic drainage. Molecular-genetic mechanisms of the disease are still poorly understood. Beginning of a clinical manifestation of primary lymphedema in middle age and the development of secondary lymphedema after treatment of breast cancer can be genetically determined. Disruption of endothelial cell apoptosis can be considered as one of the factors contributing to the development of lymphedema. However, a study of the relationship between genes associated with lymphedema and genes involved in endothelial apoptosis, in the associative gene network was not previously conducted. In the current work, we used well-known methods (ToppGene and Endeavour), as well as methods previously developed by us, to prioritize genes involved in endothelial apoptosis and to find potential participants of molecular-genetic mechanisms of lymphedema among them. Original methods of prioritization took into account the overrepresented Gene Ontology biological processes, the centrality of vertices in the associative gene network, describing the interactions of endothelial apoptosis genes with genes associated with lymphedema, and the association of the analyzed genes with diseases that are comorbid to lymphedema. An assessment of the quality of prioritization was performed using criteria, which involved an analysis of the enrichment of the top-most priority genes by genes, which are known to have simultaneous interactions with lymphedema and endothelial cell apoptosis, as well as by genes differentially expressed in murine model of lymphedema. In particular, among genes involved in endothelial apoptosis, KDR, TNF, TEK, BMPR2, SERPINE1, IL10, CD40LG, CCL2, FASLG and ABL1 had the highest priority. The identified priority genes can be considered as candidates for genotyping in the studies involving the search for associations with lymphedema. Analysis of interactions of these genes in the associative gene network of lymphedema can improve understanding of mechanisms of interaction between endothelial apoptosis and lymphangiogenesis, and shed light on the role of disturbance of these processes in the development of edema, chronic inflammation and connective tissue transformation during the progression of the disease.
机译：目前，全世界有超过1.5亿人患有淋巴水肿。它是一种慢性进行性疾病，其特征是由于淋巴引流缺陷导致身体各个部位出现高蛋白水肿。对该疾病的分子遗传机制仍知之甚少。可以从遗传角度确定中年原发性淋巴水肿的临床表现的开始以及乳腺癌治疗后继发性淋巴水肿的发展。内皮细胞凋亡的破坏可以被认为是导致淋巴水肿发展的因素之一。但是，以前尚未在关联基因网络中进行过与淋巴水肿相关的基因和与内皮细胞凋亡相关的基因之间的关系的研究。在当前的工作中，我们使用了众所周知的方法（ToppGene和Endeavour）以及我们先前开发的方法来对参与内皮细胞凋亡的基因进行优先排序，并在其中寻找潜在的淋巴水肿分子遗传机制的参与者。优先级排序的原始方法考虑了过度代表的基因本体论生物学过程，顶点在关联基因网络中的中心地位，描述了内皮细胞凋亡基因与与淋巴水肿相关的基因之间的相互作用以及所分析的基因与并发疾病的相关性淋巴水肿。使用标准进行了优先级质量的评估，其中涉及对最优先基因的富集进行分析，这些基因与淋巴水肿和内皮细胞凋亡以及差异表达的基因同时发生相互作用。在小鼠淋巴水肿模型中。特别是，在涉及内皮细胞凋亡的基因中，KDR，TNF，TEK，BMPR2，SERPINE1，IL10，CD40LG，CCL2，FASLG和ABL1具有最高优先级。在涉及寻找与淋巴水肿相关性的研究中，可以将鉴定出的优先级基因视为基因分型的候选者。在淋巴水肿的相关基因网络中分析这些基因的相互作用可以增进对内皮细胞凋亡与淋巴血管生成之间相互作用机制的了解，并阐明这些过程的紊乱在水肿发展过程中的作用，慢性炎症和结缔组织转化。疾病的进展。

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