Bader Gary D, Hogue Christopher W V
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5.
Nat Biotechnol. 2002 Oct;20(10):991-7. doi: 10.1038/nbt1002-991.
High-throughput methods for detecting protein interactions, such as mass spectrometry and yeast two-hybrid assays, continue to produce vast amounts of data that may be exploited to infer protein function and regulation. As this article went to press, the pool of all published interaction information on Saccharomyces cerevisiae was 15,143 interactions among 4,825 proteins, and power-law scaling supports an estimate of 20,000 specific protein interactions. To investigate the biases, overlaps, and complementarities among these data, we have carried out an analysis of two high-throughput mass spectrometry (HMS)-based protein interaction data sets from budding yeast, comparing them to each other and to other interaction data sets. Our analysis reveals 198 interactions among 222 proteins common to both data sets, many of which reflect large multiprotein complexes. It also indicates that a "spoke" model that directly pairs bait proteins with associated proteins is roughly threefold more accurate than a "matrix" model that connects all proteins. In addition, we identify a large, previously unsuspected nucleolar complex of 148 proteins, including 39 proteins of unknown function. Our results indicate that existing large-scale protein interaction data sets are nonsaturating and that integrating many different experimental data sets yields a clearer biological view than any single method alone.
用于检测蛋白质相互作用的高通量方法，如质谱分析法和酵母双杂交试验，持续产生大量数据，这些数据可用于推断蛋白质的功能和调控机制。在本文付梓之时，已发表的关于酿酒酵母的所有相互作用信息库中，有4825个蛋白质之间存在15143种相互作用，幂律缩放支持对20000种特定蛋白质相互作用的估计。为了研究这些数据之间的偏差、重叠和互补性，我们对来自芽殖酵母的两个基于高通量质谱（HMS）的蛋白质相互作用数据集进行了分析，并将它们相互比较以及与其他相互作用数据集进行比较。我们的分析揭示了两个数据集中共有的222个蛋白质之间存在198种相互作用，其中许多反映了大型多蛋白复合物。这也表明，将诱饵蛋白与相关蛋白直接配对的“辐条”模型比连接所有蛋白质的“矩阵”模型的准确性大约高三倍。此外，我们鉴定出一个由148个蛋白质组成的、此前未被怀疑的大型核仁复合物，其中包括39个功能未知的蛋白质。我们的结果表明，现有的大规模蛋白质相互作用数据集尚未饱和，整合许多不同的实验数据集比任何单一方法能产生更清晰的生物学图景。
