Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile
Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile
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DOI：
10.1016/j.cell.2005.08.031
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发表时间：
2005-11-04
期刊：
影响因子：
64.5
通讯作者：
Krogan, NJ
中科院分区：
文献类型：
--
作者：
Schuldiner, M;Collins, SR;Krogan, NJ
我们提出了一种生成和分析综合遗传相互作用图谱的策略，称为E-MAPs（上位微型阵列图谱），包括加重或减轻基因对之间相互作用的定量措施。对E-MAPs的解释至关重要的是它们的高密度特性，通过关注逻辑连接的基因子集和包括基本基因而成为可能。本文描述的是对酵母菌早期分泌途径中作用基因的E-MAP分析。分层聚类，结合新的分析策略和实验验证，揭示或澄清了许多蛋白质在广泛研究的过程中所起的作用，如鞘脂代谢和HDEL蛋白的保留。在更广泛的层面上，对E-MAP的分析描绘了通路组织和物理复合物的组成部分，并说明了各种分泌过程之间的相互联系。将这一策略扩展到酵母和高等真核生物中其他逻辑相关的基因亚群，将为生物系统的功能/组织原理提供重要的见解。
We present a strategy for generating and analyzing comprehensive genetic-interaction maps, termed E-MAPs (epistatic miniarray profiles), comprising quantitative measures of aggravating or alleviating interactions between gene pairs. Crucial to the interpretation of E-MAPs is their high-density nature made possible by focusing on logically connected gene subsets and including essential genes. Described here is the analysis of an E-MAP of genes acting in the yeast early secretory pathway. Hierarchical clustering, together with novel analytical strategies and experimental verification, revealed or clarified the role of many proteins involved in extensively studied processes such as sphingolipid metabolism and retention of HDEL proteins. At a broader level, analysis of the E-MAP delineated pathway organization and components of physical complexes and illustrated the interconnection between the various secretory processes. Extension of this strategy to other logically connected gene subsets in yeast and higher eukaryotes should provide critical insights into the functional/organizational principles of biological systems.