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用于化学基因组学筛选的自动化细胞:化合物与环境筛选系统(ACCESS)

The automated cell: compound and environment screening system (ACCESS) for chemogenomic screening.

作者信息

Proctor Michael, Urbanus Malene L, Fung Eula L, Jaramillo Daniel F, Davis Ronald W, Nislow Corey, Giaever Guri

机构信息

Stanford Genome Technology Center, Palo Alto, CA, USA.

出版信息

Methods Mol Biol. 2011;759:239-69. doi: 10.1007/978-1-61779-173-4_15.

DOI:10.1007/978-1-61779-173-4_15
PMID:21863492
Abstract

The automated cell, compound and environment screening system (ACCESS) was developed as an automated platform for chemogenomic research. In the yeast Saccharomyces cerevisiae, a number of genomic screens rely on the modulation of gene dose to determine the mode of action of bioactive compounds or the effects of environmental/compound perturbations. These and other phenotypic experiments have been shown to benefit from high-resolution growth curves and a highly automated controlled environment system that enables a wide range of multi-well assays that can be run over many days without any manual intervention. Furthermore, precise control of drug dosing, timing of drug exposure, and precise timing of cell harvesting at specific generation times are important for optimal results. Some of these benefits include the ability to derive fine distinctions between growth rates of mutant strains (1) and the discovery of novel compounds and drug targets (2). The automation has also enabled large-scale screening projects with over 100,000 unique compounds screened to date including a thousand genome-wide screens (3). The ACCESS system also has a diverse set of software tools to enable users to set up, run, annotate, and evaluate complex screens with minimal training.

摘要

自动化细胞、化合物和环境筛选系统(ACCESS)是作为化学基因组学研究的自动化平台而开发的。在酿酒酵母中,许多基因组筛选依赖于基因剂量的调节,以确定生物活性化合物的作用模式或环境/化合物扰动的影响。这些以及其他表型实验已被证明受益于高分辨率生长曲线和高度自动化的受控环境系统,该系统能够进行广泛的多孔测定,且无需任何人工干预即可连续运行多天。此外,精确控制药物给药、药物暴露时间以及在特定世代时间精确收获细胞的时间对于获得最佳结果很重要。其中一些好处包括能够区分突变菌株生长速率之间的细微差异(1)以及发现新型化合物和药物靶点(2)。自动化还使得大规模筛选项目成为可能,迄今为止已筛选了超过100,000种独特化合物,包括一千次全基因组筛选(3)。ACCESS系统还拥有各种各样的软件工具,使用户能够在最少培训的情况下设置、运行、注释和评估复杂的筛选。

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