Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae
Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae
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DOI：
10.1074/mcp.m600381-mcp200
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发表时间：
2007-03-01
影响因子：
7
通讯作者：
Krogan, Nevan J.
中科院分区：
文献类型：
--
作者：
Collins, Sean R.;Kemmeren, Patrick;Krogan, Nevan J.
定义蛋白质复合物对细胞生物学的几乎所有方面都至关重要。最近在酿酒酵母中进行的两项亲和纯化/质谱研究极大地增加了可用的蛋白质相互作用数据。然而，由于假阳性的存在，这类高通量相互作用组的实际效用大大降低。在此，我们创建了一种新的概率度量标准，它利用了这些数据的高密度，包括单个关联的存在和不存在，为每个潜在的蛋白质 - 蛋白质相互作用提供了相对置信度的度量。这种分析在很大程度上克服了高通量免疫沉淀实验中固有的噪声。例如，在源自这两项研究的相互作用数据通用库（BioGRID）中的12,122个二元相互作用中，我们将7504个标记为置信度明显较低。此外，应用我们的度量标准和严格的截断值，我们确定了一组9074个相互作用（包括12,122个相互作用中没有的4456个），其准确性与传统的小规模方法相当。最后，我们使用层次聚类将蛋白质组织成连贯的多亚基复合物。因此，这项工作以一种生物界易于获取的形式提供了一个高度准确的酵母物理相互作用图谱。
Defining protein complexes is critical to virtually all aspects of cell biology. Two recent affinity purification/mass spectrometry studies in Saccharomyces cerevisiae have vastly increased the available protein interaction data. The practical utility of such high throughput interaction sets, however, is substantially decreased by the presence of false positives. Here we created a novel probabilistic metric that takes advantage of the high density of these data, including both the presence and absence of individual associations, to provide a measure of the relative confidence of each potential protein-protein interaction. This analysis largely overcomes the noise inherent in high throughput immunoprecipitation experiments. For example, of the 12,122 binary interactions in the general repository of interaction data (BioGRID) derived from these two studies, we marked 7504 as being of substantially lower confidence. Additionally, applying our metric and a stringent cutoff we identified a set of 9074 interactions (including 4456 that were not among the 12,122 interactions) with accuracy comparable to that of conventional small scale methodologies. Finally we organized proteins into coherent multisubunit complexes using hierarchical clustering. This work thus provides a highly accurate physical interaction map of yeast in a format that is readily accessible to the biological community.