OpenCell: Endogenous tagging for the cartography of human cellular organization.
Nathan H ChoKeith C CheverallsAndreas-David BrunnerKibeom KimAndré C MichaelisPreethi RaghavanHirofumi KobayashiLaura SavyJason Y LiHera CanajJames Y S KimEdna M StewartChristian GnannFrank McCarthyJoana P CabreraRachel M BrunettiBryant B ChhunGreg DingleMarco Y HeinBo HuangShalin B MehtaJonathan S WeissmanRafael Gómez-SjöbergDaniel N ItzhakLoïc Alain RoyerMatthias MannManuel D LeonettiPublished in: Science (New York, N.Y.) (2022)
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.
Keyphrases
- endothelial cells
- mass spectrometry
- induced pluripotent stem cells
- high resolution
- pluripotent stem cells
- single cell
- randomized controlled trial
- small molecule
- gene expression
- optical coherence tomography
- clinical trial
- big data
- liquid chromatography
- health information
- rna seq
- artificial intelligence
- protein protein
- binding protein
- bone marrow
- amino acid