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一个系统的哺乳动物遗传相互作用地图揭示了基因敏感性潜在的路径

Michael C Bassik¹, Martin Kampmann, Robert Jan Lebbink

¹Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94122, USA. bassik@cmp.ucsf.edu

|February 12, 2013

概括

这项研究引入了一种新方法,用于在哺乳动物细胞中创建详细的基因相互作用 (GI) 地图. 这些地图有助于了解基因功能,并识别治疗的潜在协同作用药物组合.

科学领域:

遗传学是一个遗传学.
分子生物学分子生物学
系统生物学系统生物学

背景情况:

基因相互作用 (GI) 地图通过测量基因之间的依赖关系来系统地探索基因功能.
以前的胃肠道地图构造是有限的,特别是在哺乳动物系统中.
了解基因功能对于生物研究和治疗开发至关重要.

研究的目的:

为哺乳动物细胞开发高密度遗传相互作用绘制策略.
通过GI地图识别新的基因功能和途径.
探索GI地图在治疗应用中的潜力.

主要方法:

使用超复杂的聚合shRNA库 (25个shRNA/基因) 的两阶段方法.
识别特定表型的高可靠性命中基因和有效的shRNA.
通过构建双shRNA库来系统测量遗传相互作用 (GI).

主要成果:

在哺乳动物细胞中构建高密度GI图.
概述已知的途径和发现新的见解,包括COPI的非正典作用.
确定RPS25和不同的哺乳动物TRAPP复合体的专门作用.
一个GI地图的演示,专注于辛的敏感性.

结论:

开发的策略可以快速生成哺乳动物的GI地图.
胃肠道图是定义基因功能的强大工具.
这种方法可以为基于协同作用的基因对的组合疗法的设计提供信息.

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