Paper

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

Setwart, Edna M, Hein, Marco Y, Kobayashi, Hirofumi, Chhun, Bryant B, Mann, Matthias, Michaelis, Andre C, Savy, Laura, Dingle, Greg, Raghavan, Preethi, Mccarthy, Frank, Cho, Nathan H, Brunetti, Rachel M, Cheveralls, Keith C, Leonetti, Manuel D, Li, Jason Y, Kim, Kibeom, Canaj, Hera, Gnann, Christian, Huang, Bo, Gomez-Sjoberg, Rafael, Royer, Loic A, Andreas-David Brunner, Cabrera, Joana P, Mehta, Shalin B, Itzhak, Daniel N, Kim, James Ys, Weissman, Jonathan S

2021

Overview

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 Statement J.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. Footnotes * https://opencell.czbiohub.org/

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Cartography / Cell Biology / Cell lines / CRISPR / Learning algorithms / Localization / Machine learning / Mass spectroscopy / Protein interaction / Proteins / Proteomes / RNA-binding protein