The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Science. 2014 Apr 11;344(6180):208-11. doi: 10.1126/science.1250217.
Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes.
对体内细胞对干扰的反应进行全基因组表征对于理解细胞如何在压力下存活是至关重要的。确定小分子干扰的蛋白质和途径会通过揭示药物作用的机制来影响生物学和医学。我们使用了一种酵母化学基因组学平台，该平台定量测量了每个基因对体内化合物抗性的要求，以系统和无偏倚的方式对 3250 种小分子进行了分析。我们确定了 317 种特定干扰 121 个基因功能的化合物，并对特定化合物的作用机制进行了描述。全面分析表明，细胞对小分子的反应是有限的，可以用 45 个主要化学基因组特征的网络来描述。我们的结果为发现基因、化学物质和生物过程之间的功能相互作用提供了资源。
