Living systems integrate biochemical reactions that determine the functional state of each cell. Reactions are primarily mediated by proteins. In proteomic studies, these have been treated as independent entities, disregarding their higher-level organization into complexes that affects their activity and/or function and is thus of great interest for biological research. Here, we describe the implementation of an integrated technique to quantify cell-state-specific changes in the physical arrangement of protein complexes concurrently for thousands of proteins and hundreds of complexes. Applying this technique to a comparison of human cells in interphase and mitosis, we provide a systematic overview of mitotic proteome reorganization. The results recall key hallmarks of mitotic complex remodeling and suggest a model of nuclear pore complex disassembly, which we validate by orthogonal methods. To support the interpretation of quantitative SEC-SWATH-MS datasets, we extend the software CCprofiler and provide an interactive exploration tool, SECexplorer-cc.

生命系统整合了决定每个细胞功能状态的生化反应。反应主要由蛋白质介导。在蛋白质组学研究中，这些已被视为独立实体，无视它们的高层组织成为影响其活性和/或功能的复合物，因此对于生物学研究非常感兴趣。在这里，我们描述了一种集成技术的实现，该技术可以同时量化数千种蛋白质和数百种复合物的蛋白质复合物物理排列中的细胞状态特定变化。将该技术应用于相间和有丝分裂的人类细胞的比较，我们提供了有丝分裂蛋白质组重组的系统概述。结果回想了有丝分裂复合物重塑的关键特征，并提出了核孔复合物分解的模型，我们通过正交方法对其进行了验证。为支持对SEC-SWATH-MS定量数据集的解释，我们扩展了CCprofiler软件并提供了一个交互式探索工具SECexplorer-cc。