Congruence of mouse model to human in transcriptomic response

项目摘要/摘要 动物模型和体外细胞培养实验有助于替代人类研究和 加快基础和临床研究。关于非人类模型是否可以 很好地代表了人类，但还没有开发出足够的生物信息学工具来充分回答 问题。我们在这项提议中提出了以下目标，以在转录背景下提供答案：(1) 我们将开发一种转录相似性评分，将小鼠模型与参考人类研究进行比较 具有特定途径的分析；(2)我们将扩展该方法以允许同时分析 多种相互竞争的动物模型和人体研究，并开发下游生物信息学工具；(3)我们 将这些方法应用于乳腺癌和抑郁症的两个正在进行的小鼠模型，产生新的 假设并验证研究结果。这些目标的成功实现将为以下工作提供实际指导 许多疾病领域的科学家最好地利用动物模型来了解机制和寻求 新的治疗方法。

Project Summary/Abstract Animal models and in vitro cell culture experiments are instrumental to substitute for human studies and expedite basic and clinical research. There have been constant debates of whether non-human models can represent human well but no adequate bioinformatic tool has been developed to adequately answer the question. We propose the following aims in this proposal to provide an answer in the transcriptomic context: (1) We will develop a transcriptomic resemblance score comparing a mouse model to a reference human study with pathway-specific analysis; (2) We will extend the method to allow simultaneous resemblance analysis of multiple competing animal models and human studies, and develop downstream bioinformatics tools; (3) We will apply the methods to two on-going mouse models in breast cancer and depression, generate new hypotheses and validate the findings. Successful completion of these aims will provide practical guidance to scientists in many disease areas to best utilize animal models for understanding mechanisms and seeking novel treatments.