Björklund Asa K, Light Sara, Hedin Linnea, Elofsson Arne
Department of Biochemistry and Biophysics, Center for Biological Membrane Research/Stockholm Bioinformatics Center, Stockholm University, Stockholm, Sweden.
Proteomics. 2008 Nov;8(22):4657-67. doi: 10.1002/pmic.200800150.
With recent publications of several large-scale protein-protein interaction (PPI) studies, the realization of the full yeast interaction network is getting closer. Here, we have analysed several yeast protein interaction datasets to understand their strengths and weaknesses. In particular, we investigate the effect of experimental biases on some of the protein properties suggested to be enriched in highly connected proteins. Finally, we use support vector machines (SVM) to assess the contribution of these properties to protein interactivity. We find that protein abundance is the most important factor for detecting interactions in tandem affinity purifications (TAP), while it is of less importance for Yeast Two Hybrid (Y2H) screens. Consequently, sequence conservation and/or essentiality of hubs may be related to their high abundance. Further, proteins with disordered structure are over-represented in Y2H screens and in one, but not the other, large-scale TAP assay. Hence, disordered regions may be important both in transient interactions and interactions in complexes. Finally, a few domain families seem to be responsible for a large part of all interactions. Most importantly, we show that there are method-specific biases in PPI experiments. Thus, care should be taken before drawing strong conclusions based on a single dataset.
随着近期几项大规模蛋白质-蛋白质相互作用（PPI）研究的发表，完整的酵母相互作用网络正日益接近实现。在此，我们分析了几个酵母蛋白质相互作用数据集，以了解它们的优缺点。特别是，我们研究了实验偏差对一些被认为在高连接性蛋白质中富集的蛋白质特性的影响。最后，我们使用支持向量机（SVM）来评估这些特性对蛋白质相互作用的贡献。我们发现，蛋白质丰度是在串联亲和纯化（TAP）中检测相互作用的最重要因素，而在酵母双杂交（Y2H）筛选中其重要性较低。因此，枢纽蛋白的序列保守性和/或必需性可能与其高丰度有关。此外，具有无序结构的蛋白质在Y2H筛选以及一项（而非另一项）大规模TAP实验中过度富集。因此，无序区域在瞬时相互作用和复合物中的相互作用中可能都很重要。最后，少数结构域家族似乎对所有相互作用的很大一部分负责。最重要的是，我们表明在PPI实验中存在方法特异性偏差。因此，在基于单个数据集得出强有力的结论之前应谨慎行事。
