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The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life

机译:利用基因本体术语和KEGG通路富集分析药物半衰期

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摘要

A drug’s biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO) terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347), monoamine transmembrane transporter activity (GO:0008504), negative regulation of synaptic transmission (GO:0050805), neuroactive ligand-receptor interaction (hsa04080), serotonergic synapse (hsa04726), and linoleic acid metabolism (hsa00591), among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives.
机译:药物的生物半衰期是指人体代谢或消除初始药物剂量的50%所需的时间。正确测量给定药物的半衰期有助于安全,准确地使用该药物。在这项研究中,我们调查了哪些基因本体论(GO)术语和生物学途径与药物半衰期的确定高度相关。根据已知GO术语和KEGG途径的富集得分,对具有已知半衰期的被研究药物进行分析。这些分数表明药物靶向的是哪些GO术语或KEGG途径。使用特征选择方法(最小冗余最大相关性)分析这些GO术语和KEGG途径并鉴定重要的GO术语和途径,例如不依赖钠的有机阴离子跨膜转运蛋白活性(GO:0015347),单胺跨膜转运蛋白活性( GO:0008504),突触传递的负调控(GO:0050805),神经活性配体-受体相互作用(hsa04080),血清素能突触(hsa04726)和亚油酸代谢(hsa00591)等。该分析证实了我们的结果,并可能为研究药物半衰期和建立有效的预测药物半衰期的计算方法的新方法提供证据。

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