Towards a proteome-scale map of the human protein-protein interaction network
Towards a proteome-scale map of the human protein-protein interaction network
复制标题
DOI：
10.1038/nature04209
复制
发表时间：
2005-10-20
期刊：
影响因子：
64.8
通讯作者：
Vidal, M
中科院分区：
文献类型：
--
作者：
Rual, JF;Venkatesan, K;Vidal, M
蛋白质 - 蛋白质相互作用的系统性图谱绘制，即“相互作用组”图谱绘制，始于模式生物，从明确的生物学过程开始（1,2），然后扩展到蛋白质组规模（3 - 7）。尽管远未完成，但此类图谱已经揭示了相互作用组网络的全局拓扑结构和动态特征，这些特征与已知的生物学特性相关（8,9），这表明人类相互作用组图谱将在系统层面深入了解发育和疾病机制。在此我们描述了人类二元蛋白质 - 蛋白质相互作用的蛋白质组规模图谱的初始版本。利用一种严格的、高通量的酵母双杂交系统，我们对大约8100个当前可用的Gateway克隆开放阅读框的产物之间的成对相互作用进行了检测，并发现了大约2800种相互作用。这个被称为CCSB - HI1的数据集，经独立的共亲和纯化分析显示，其验证率约为78%，并且与其他生物学属性显著相关。CCSB - HI1数据集使测试范围内可用的二元相互作用集增加了约70%，并揭示了与100多种疾病相关蛋白的300多种新联系。这项工作是迈向系统性和综合性人类相互作用组项目的重要一步。
Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes(1,2) and then expanding to the scale of the proteome(3-7). Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties(8,9), suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of similar to 8,100 currently available Gateway-cloned open reading frames and detected similar to 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of similar to 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by similar to 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.