Chan Zuckerberg Biohub, San Francisco, CA, USA.
Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Science. 2022 Mar 11;375(6585):eabi6983. doi: 10.1126/science.abi6983.
Elucidating the wiring diagram of the human cell is a central goal of the postgenomic era. We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. Our approach provides a data-driven description of the molecular and spatial networks that organize the proteome. Unsupervised clustering of these networks delineates functional communities that facilitate biological discovery. We found that remarkably precise functional information can be derived from protein localization patterns, which often contain enough information to identify molecular interactions, and that RNA binding proteins form a specific subgroup defined by unique interaction and localization properties. Paired with a fully interactive website (opencell.czbiohub.org), our work constitutes a resource for the quantitative cartography of human cellular organization.
阐明人类细胞的“接线图”是后基因组时代的核心目标。我们结合基因组工程、共聚焦活细胞成像、质谱分析和数据科学,系统绘制了人类蛋白质的定位和相互作用图谱。我们的方法为组织蛋白质组的分子和空间网络提供了数据驱动的描述。对这些网络进行无监督聚类可以划分出功能社区,从而促进生物学发现。我们发现,从蛋白质定位模式中可以衍生出非常精确的功能信息,这些信息通常足以识别分子相互作用,而且 RNA 结合蛋白形成了一个由独特的相互作用和定位特性定义的特定亚群。结合一个完全交互式的网站(opencell.czbiohub.org),我们的工作为人类细胞组织的定量制图构成了一个资源。