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首页> 外文期刊>BMC Medical Genomics >Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks
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Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

机译：从关联基因网络揭示对哮喘和高血压合并症重要的新候选基因

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Hypertension and bronchial asthma are a major issue for people’s health. As of 2014, approximately one billion adults, or ~?22% of the world population, have had hypertension. As of 2011, 235–330 million people globally have been affected by asthma and approximately 250,000–345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension - 713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system. The application of methods of reconstruction and analysis of gene networks is a productive tool for studying the molecular mechanisms of comorbid conditions. The method put forth to rank genes by their importance to the comorbid condition of asthma and hypertension was employed that resulted in prediction of 10 genes, playing the key role in the development of the comorbid condition. The results can be utilised to plan experiments for identification of novel candidate genes along with searching for novel pharmacological targets.
机译：高血压和支气管哮喘是人们健康的主要问题。截至2014年，约有10亿成年人，约占世界人口的22％，患有高血压。截至2011年，全球有235-3.3亿人患有哮喘，每年约有25万-345,000人死于该疾病。由于这些疾病的合并症，使针对这些疾病的有效治疗方法的开发变得复杂。这通常是诊断和治疗的主要问题。因此，在这项研究中，已经开发出了用于分析这两种疾病合并症的生物信息学方法。因此，寻找与哮喘和高血压合并症相关的候选基因可以帮助阐明这两种疾病合并症的分子机制，并且对于基因分型和确定新药靶点也很有用。使用ANDSystem进行了与哮喘和高血压相关的基因网络的重建和分析。哮喘的基因网络包括755个基因/蛋白质和62,603个相互作用，而高血压的基因网络包括713个基因/蛋白质和45,479个相互作用。哮喘和高血压之间共有255个基因/蛋白质和9638个相互作用。提出了一种对涉及两种疾病合并症的基因进行排序的方法。该方法基于对基因进行重要性排名的9条标准，包括基因优先级的标准方法（Endeavor，ToppGene）以及考虑了关联基因网络的特征以及分析中已知多态性的原始标准。基因。根据提出的方法，在这两种疾病合并症的发展中，基因IL10，TLR4和CAT具有最高的优先级。另外，还揭示了凋亡基因和参与与中枢神经系统功能有关的生物过程的基因丰富了顶级基因。基因网络的重建和分析方法的应用是研究共病条件分子机制的有效工具。提出了根据基因在哮喘和高血压合并症中的重要性对基因进行排序的方法，该方法可预测10个基因，在合并症的发展中起关键作用。结果可用于计划实验，以鉴定新的候选基因以及寻找新的药理靶标。

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