OpenCell: proteome-scale endogenous tagging enables the cartography of human cellular organization

Elucidating the wiring diagram of the human cell is one of the central goals of the post-genomic era. Here, we integrate 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, and uncovers that RNA-binding proteins form a specific sub-group defined by unique interaction and localization properties. Furthermore, we discover that localization patterns are remarkably predictive of protein function and often contain enough information to identify molecular interactions. Paired with a fully interactive website (opencell.czbiohub.org), we provide a resource for the quantitative cartography of human cellular organization.