PLOS ONE:中国树鼩全基因组解析完成

摘要 : 中科院昆明动物研究所张云研究员课题组与深圳华大基因研究院合作，解析了新型实验动物中国树鼩的全基因组，系统评估了树鼩作为药物研发实验动物的特征和优势。研究近日发表于《公共科学图书馆·综合》。

中科院昆明动物研究所张云研究员课题组与深圳华大基因研究院合作，解析了新型实验动物中国树鼩的全基因组，系统评估了树鼩作为药物研发实验动物的特征和优势。研究近日发表于《公共科学图书馆·综合》。

研究不仅为中国树鼩用于新药研发的药效学、药理学和毒理学评价提供了系统的基础信息数据和科学依据，而且揭示了特定药物研发中使用树鼩作为实验动物的独特优势。

据介绍，目前药物研发中广泛使用的大鼠、小鼠等啮齿类动物与人种属差异较大，获得的研究结果经常与人相距甚远，造成药物研发在大量投入后失败。树鼩是灵长类动物近亲，作为实验动物具有个体小、繁殖快、易于饲养等有利特点。

科研人员首先开发了一种可用于药物靶标预测和基于模型药靶评价的有效方法，进一步在基因组和转录组层面上对中国树鼩进行了系统全面的药物靶标预测和分析。

在获得的3482种中国树鼩药物靶标蛋白质中，排名最高的446种蛋白质和总得分最高的1049种蛋白质包含了许多与肿瘤治疗、抑郁症、衰老及机能减退、心血管疾病和代谢性疾病药物靶标相关的人类同源分子。与目前广泛使用的小鼠药物靶蛋白相比，50%以上的中国树鼩药物靶蛋白与人类药物靶蛋白的相似性更高。

同时，药物靶标确认实验证实了与心血管疾病药物研发密切相关的蛋白酶激活受体在树鼩血小板上的表达模式与人类血小板一致。

原文摘要：

Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing

Feng Zhao, Xiaolong Guo, Yanjie Wang, Jie Liu, Wen-hui Lee, Yun Zhang

The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.

作者：中国科学报

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