OpenCell: Endogenous tagging for the cartography of human cellular organization

Author:

Cho Nathan H.1ORCID,Cheveralls Keith C.1ORCID,Brunner Andreas-David2ORCID,Kim Kibeom1ORCID,Michaelis André C.2ORCID,Raghavan Preethi1ORCID,Kobayashi Hirofumi1ORCID,Savy Laura1,Li Jason Y.1,Canaj Hera1,Kim James Y. S.1ORCID,Stewart Edna M.1,Gnann Christian13ORCID,McCarthy Frank1ORCID,Cabrera Joana P.1ORCID,Brunetti Rachel M.4ORCID,Chhun Bryant B.1ORCID,Dingle Greg5ORCID,Hein Marco Y.1ORCID,Huang Bo146ORCID,Mehta Shalin B.1ORCID,Weissman Jonathan S.78ORCID,Gómez-Sjöberg Rafael1ORCID,Itzhak Daniel N.1,Royer Loïc A.1ORCID,Mann Matthias29ORCID,Leonetti Manuel D.1ORCID

Affiliation:

1. Chan Zuckerberg Biohub, San Francisco, CA, USA.

2. Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.

3. Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH–Royal Institute of Technology, Stockholm, Sweden.

4. Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.

5. Chan Zuckerberg Initiative, Redwood City, CA, USA.

6. Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.

7. Whitehead Institute, Koch Institute, Howard Hughes Medical Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

8. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.

9. NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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