Congruence of mouse model to human in transcriptomic response

小鼠模型与人类转录组反应的一致性

• 批准号: 9768543
• 负责人: George C. Tseng
• 金额: $ 20.29万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768543
• 关键词: Admixture; Agreement; Animal Model; Animals; Applications Grants; Area; Basic Science; Bioinformatics; CDH1 gene; Cell Culture Techniques; Cells; Chronic; Clinical Research; Computer software; Corticosterone; Data; Databases; Disease; Feedback; Funding; Future; Genes; Genomics; Genotype; Homologous Gene; Human; In Vitro; Inflammatory; Investigation; Knockout Mice; Knowledge Extraction; Lobular Carcinoma; Measures; Mental Depression; Methods; Methylation; MicroRNAs; Mus; Outcome; Paper; Pathway interactions; Pattern; Population Heterogeneity; Recurrence; Research; Research Personnel; Sample Size; Scientist; Series; Structure; System; Techniques; Time; Validation; Work; bioinformatics tool; cancer subtypes; cell type; chromosomal location; cohort; cost; depression model; disease mechanisms study; drug discovery; experimental study; genome-wide; human study; human tissue; improved; in vivo; instrument; malignant breast neoplasm; model development; mouse model; new therapeutic target; novel; novel therapeutic intervention; precision medicine; response; text searching; therapeutic target; transcriptomics

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.

项目概要/摘要 动物模型和体外细胞培养实验有助于替代人体研究和 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，但尚未开发出足够的生物信息工具来充分回答这个问题 问题。我们在本提案中提出以下目标，以在转录组学背景下提供答案：（1） 我们将开发一个转录组相似性评分，将小鼠模型与参考人类研究进行比较 进行路径特异性分析； (2) 我们将扩展该方法以允许同时进行相似性分析 多种竞争动物模型和人体研究，并开发下游生物信息学工具； (3) 我们 将把这些方法应用于两种正在进行的乳腺癌和抑郁症小鼠模型，产生新的 假设并验证研究结果。这些目标的成功实现将为 许多疾病领域的科学家最好地利用动物模型来理解机制并寻求 新的治疗方法。