Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Science. 2010 Jan 22;327(5964):425-31. doi: 10.1126/science.1180823.
A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic genetic interactions, generating quantitative genetic interaction profiles for approximately 75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function. The global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification.
通过检测 540 万个基因-基因对的合成遗传相互作用,构建了一个全基因组遗传相互作用图谱,为酿酒酵母(Saccharomyces cerevisiae)中约 75%的所有基因生成了定量遗传相互作用图谱。基于遗传相互作用图谱的网络揭示了细胞的功能图谱,其中具有相似生物学过程的基因在连贯的子集中聚集在一起,高度相关的图谱描绘了特定的途径来定义基因功能。全局网络识别所有生物过程之间的功能交叉连接,绘制出细胞的多效性电路图。遗传相互作用程度与许多不同的基因属性相关,这可能为其他生物体中的遗传网络枢纽提供信息。我们还证明,广泛和无偏的遗传景观映射为解释化学遗传相互作用和药物靶点识别提供了关键。