Yu Shuhao, Zheng Lulu, Li Yun, Li Chunyan, Ma Chenchen, Li Yixue, Li Xuan, Hao Pei
Key Lab of Systems Biology/Key Laboratory of Synthetic Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, PR China.
BMC Syst Biol. 2012;6 Suppl 3(Suppl 3):S18. doi: 10.1186/1752-0509-6-S3-S18. Epub 2012 Dec 17.
Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism.
We developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery. We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning.
We developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology.
动物模型是研究人类疾病病因和寻找治疗方法不可或缺的工具。动物模型的科学价值取决于对人类疾病的准确模拟。本研究的主要目标是开发一种跨物种方法，利用动物模型的表达数据来评估与人类疾病的相似性，并评估药物分子在药物研究中的效率。因此，我们希望揭示在病理学、毒理学、药物重新定位和药物作用机制研究中跨物种比较基因表达谱是可行且有用的。
我们开发了一种跨物种分析方法，通过利用公共数据库中现有的动物基因表达数据来分析动物模型与人类疾病的相似性以及在药物研究中的有效性，并挖掘了一些有助于药物研究的有意义信息，如潜在的候选药物、可能的药物重新定位、副作用和药理学分析。新的动物模型在用于药物发现之前可以通过我们的方法进行评估。我们将该方法应用于几例已知的动物模型表达谱案例，并获得了一些有助于药物研究的有用信息。我们发现曲古抑菌素A和其他一些组蛋白去乙酰化酶在基因表达水平上可能在不同细胞系和物种间有非常相似的反应。小鼠缺氧模型可以准确模拟人类缺氧，而小鼠糖尿病药物模型可能存在一些局限性。阿尔茨海默病转基因小鼠是一个有用的模型，我们深入分析了该案例中一些药物的生物学机制。此外，所有案例都可以为药物发现和药物重新定位提供一些思路。
我们开发了一种新的跨物种基因表达模块比较方法，利用动物模型的表达数据来分析动物模型在药物研究中的有效性。此外，通过数据整合，我们的方法可应用于药物研究，如潜在的候选药物、可能的药物重新定位、副作用和药理学信息。
