药源性急性肾损伤的关联靶标预测

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• 英文论文题名：The prediction of potential targets of drug-induced acute kidney injury
• 论文作者：陆冬 ; 郑明月 ; 罗小民
• 英文论文作者：Dong Lu ; Mingyue Zheng ; Xiaomin Luo ; Shanghai Institute of Materia Medica ; Chinese Academy of Sciences ; University of Chinese Academy of Sciences
• 年：2016
• 作者机构：中国科学院上海药物研究所;中国科学院大学;
• 论文关键词：急性肾损伤 ; 靶标基因 ; Fisher精确检验 ; 网络药理学
• 会议召开时间：2016-07-01
• 会议录名称：中国化学会第30届学术年会摘要集-第二十五分会：化学信息学与化学计量学
• 语种：中文
• 分类号：R692
• 学会代码：ZGHY
• 会议名称：中国化学会第30届学术年会-第二十五分会 ; 化学信息学与化学计量学
• 会议地点：中国辽宁大连
• 主办单位：中国化学会
• 学会名称：中国化学会
• 页数：1
• 文件大小：238k
• 原文格式：D
• 会议级别：全国

摘要

肾脏作为人体内药物代谢和排泄的重要器官,极易受到药物及其代谢产物所造成的毒性损害。在急性肾损伤的病例中,由药物暴露导致的发病比例高达19-25%[1]。药物导致的急性肾损伤,作用机制复杂,涉及到多种分子机制。开展药源性急性肾损伤的潜在关联靶标预测将有助于阐明其分子作用机制,并为预测化合物的肾脏毒性提供帮助。我们通过从现有数据库中搜集得到急性肾损伤的阳性化合物351个,阴性化合物680个,以及相关化合物作用的靶标基因,总计26390个。为了判断这些靶标基因与急性肾损伤是否存在非随机相关性,我们针对每一个靶标基因,利用Fisher精确检验[2]得到该靶标基因与急性肾损伤相关性的p-value值,该值越小,表明该基因与急性肾损伤的偶然相关的可能性越小。我们发现显著性排名前20的靶标基因中,有14个靶标基因与肾脏损害有关,其中5个有文献报道与急性肾损伤明确相关,其他排名靠前的靶标基因可能是急性肾损伤的潜在靶标。该方法具有较好的预测效果,有助于发现潜在的肾毒性关联靶标,并为其分子作用机制的研究提供帮助。
As the most important excretion organ in human body,the kidney is vulnerable to a variety of potential nephrotoxins,such as medications,diagnostic agents and environmental chemicals.In all cases of acute kidney injury(AKI),19-25%was caused by drug exposure.Nevertheless,the molecular mechanisms of AKI may differ between various nephrotoxins,involving many complex toxicity pathways.The prediction of potential targets of drug-induced AKI is helpful for elucidating the molecular mechanisms and predicting nephrotoxicity.The positive and negative chemicals of AKI was collected from public databases,and their interacting target gene was also extracted for further analysis.Fisher's exact test was adopted to examine the significance of the association between each target gene and AKI,and then these target genes were ranked by p-value which was calculated to measure the significance.The result showed that,among the top 20 target genes,there were 14 genes associating with kidney damage and 5 of these genes were explicitly associated with AKI according to the literature reports.The proposed method is effective to make prediction of targets of AKI and could contribute to the molecular mechanisms of nephrotoxicity.

引文

[1]Bonventre,J.V.,Vaidya,V.S.,Schmouder,R.,Feig,P.,and Dieterle,F.Nat.Biotechnol.2010,28:436-440.
    [2]Fisher,R.A.Journal of the Royal Statistical Society.1922,85(1):87-94.