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基于网络的方法突出抗高血压药物之间的相互作用:靶编码基因:疾病。

Network-based approach highlighting interplay among anti-hypertensives: target coding-genes: diseases.

机构信息

Centre for Molecular Modeling, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India.

出版信息

Sci Rep. 2020 Nov 19;10(1):20152. doi: 10.1038/s41598-020-76605-1.

Abstract

Elucidating the relation between the medicines: targets, targets: diseases and diseases: diseases are of fundamental significance as-is for societal benefit. Hypertension is one of the dangerous health conditions prevalent in society, is a risk factor for several other diseases if left untreated and anti-hypertensives (AHs) are the approved drugs to treat it. The goal of the study is to decipher the connection between hypertension with other health conditions, however, is challenging due to the large interactome. To fulfill the aim, the strategy involves prior clustering of the AHs into groups as per our previous method, followed by the analyzing functional association of the target coding-genes (tc-genes) and health conditions for each group. Following our recently published work where the AHs are clustered into six groups such that molecules having similar patterns come together, here, the distribution of molecular functions and the cellular components adopted by the tc-genes of each group are analyzed. The analyses indicate that kidney, heart, brain or lung related ailments are commonly associated with the tc-genes. The association of selective tc-genes to health conditions suggests a preference for certain health conditions despite many possibilities. Analyses of experimentally validated drug-drug combinations indicate the trend in successful AHs combinations. Clinically validated combinations bind different targets. Our study provides a promising methodology in a network-based approach that considers the influence of structural diversity of AHs to the functional perspective of tc-genes concerning the health conditions. The method could be extended to explore disease-disease relationships.

摘要

阐明药物

靶点、靶点:疾病和疾病:疾病之间的关系,对于社会利益而言,具有根本意义。高血压是社会中普遍存在的危险健康状况之一,如果不加以治疗,它会成为许多其他疾病的风险因素,而抗高血压药 (AHs) 是治疗高血压的批准药物。该研究的目的是破译高血压与其他健康状况之间的联系,但由于相互作用网络很大,这是具有挑战性的。为了实现这一目标,该策略涉及根据我们之前的方法将 AHs 预先聚类成组,然后分析每个组的目标编码基因 (tc-genes) 和健康状况之间的功能关联。根据我们最近发表的工作,将 AHs 聚类成六个组,使得具有相似模式的分子聚集在一起,在这里,分析了每个组的 tc-genes 采用的分子功能和细胞成分的分布。分析表明,肾脏、心脏、大脑或肺部相关疾病通常与 tc-genes 相关。尽管有许多可能性,但选择性 tc-genes 与健康状况的关联表明对某些健康状况的偏好。对经过实验验证的药物-药物组合的分析表明了成功的 AHs 组合的趋势。经过临床验证的组合结合不同的靶点。我们的研究提供了一种有前途的方法,即基于网络的方法,该方法考虑了 AHs 的结构多样性对 tc-genes 与健康状况的功能观点的影响。该方法可以扩展到探索疾病-疾病关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1ba/7677320/916caccfe850/41598_2020_76605_Fig1_HTML.jpg

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