PT - JOURNAL ARTICLE AU - Nathan H. Cho AU - Keith C. Cheveralls AU - Andreas-David Brunner AU - Kibeom Kim AU - André C. Michaelis AU - Preethi Raghavan AU - Hirofumi Kobayashi AU - Laura Savy AU - Jason Y. Li AU - Hera Canaj AU - James Y.S. Kim AU - Edna M. Stewart AU - Christian Gnann AU - Frank McCarthy AU - Joana P. Cabrera AU - Rachel M. Brunetti AU - Bryant B. Chhun AU - Greg Dingle AU - Marco Y. Hein AU - Bo Huang AU - Shalin B. Mehta AU - Jonathan S. Weissman AU - Rafael Gómez-Sjöberg AU - Daniel N. Itzhak AU - Loic A. Royer AU - Matthias Mann AU - Manuel D. Leonetti TI - OpenCell: proteome-scale endogenous tagging enables the cartography of human cellular organization AID - 10.1101/2021.03.29.437450 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.03.29.437450 4099 - http://biorxiv.org/content/early/2021/12/08/2021.03.29.437450.short 4100 - http://biorxiv.org/content/early/2021/12/08/2021.03.29.437450.full AB - Elucidating the wiring diagram of the human cell is a central goal of the post-genomic 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, and uncovers that RNA-binding proteins form a specific sub-group defined by unique interaction and localization properties. Furthermore, we discover that remarkably precise functional information can be derived from protein localization patterns, which 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.Competing Interest StatementJ.S.W. declares outside interest in Chroma Therapeutics, KSQ Therapeutics, Maze Therapeutics, Amgen, Tessera Therapeutics and 5 AM Ventures. M. M. is an indirect shareholder in EvoSep Biosystems.