A multi-scale map of cell structure fusing protein images and interactions

Yue Qin, Edward L. Huttlin, Casper F. Winsnes, Maya L. Gosztyla, Ludivine Wacheul, Marcus R. Kelly, Steven M. Blue, Fan Zheng, Michael Chen, Leah V. Schaffer, Katherine Licon, Anna Bäckström, Laura Pontano Vaites, John J. Lee, Wei Ouyang, Sophie N. Liu, Tian Zhang, Erica Silva, Jisoo Park, Adriana Pitea, Jason F. Kreisberg, Steven P. Gygi, Jianzhu Ma, J. Wade Harper, Gene W. Yeo, Denis L. J. Lafontaine, Emma Lundberg () and Trey Ideker ()
Additional contact information
Yue Qin: University of California San Diego
Edward L. Huttlin: Harvard Medical School
Casper F. Winsnes: KTH Royal Institute of Technology
Maya L. Gosztyla: University of California San Diego
Ludivine Wacheul: Université Libre de Bruxelles (ULB)
Marcus R. Kelly: University of California San Diego
Steven M. Blue: University of California San Diego
Fan Zheng: University of California San Diego
Michael Chen: University of California San Diego
Leah V. Schaffer: University of California San Diego
Katherine Licon: University of California San Diego
Anna Bäckström: KTH Royal Institute of Technology
Laura Pontano Vaites: Harvard Medical School
John J. Lee: University of California San Diego
Wei Ouyang: KTH Royal Institute of Technology
Sophie N. Liu: University of California San Diego
Tian Zhang: Harvard Medical School
Erica Silva: University of California San Diego
Jisoo Park: University of California San Diego
Adriana Pitea: University of California San Diego
Jason F. Kreisberg: University of California San Diego
Steven P. Gygi: Harvard Medical School
Jianzhu Ma: Peking University
J. Wade Harper: Harvard Medical School
Gene W. Yeo: University of California San Diego
Denis L. J. Lafontaine: Université Libre de Bruxelles (ULB)
Emma Lundberg: KTH Royal Institute of Technology
Trey Ideker: University of California San Diego

Nature, 2021, vol. 600, issue 7889, 536-542

Abstract: Abstract The cell is a multi-scale structure with modular organization across at least four orders of magnitude1. Two central approaches for mapping this structure—protein fluorescent imaging and protein biophysical association—each generate extensive datasets, but of distinct qualities and resolutions that are typically treated separately2,3. Here we integrate immunofluorescence images in the Human Protein Atlas4 with affinity purifications in BioPlex5 to create a unified hierarchical map of human cell architecture. Integration is achieved by configuring each approach as a general measure of protein distance, then calibrating the two measures using machine learning. The map, known as the multi-scale integrated cell (MuSIC 1.0), resolves 69 subcellular systems, of which approximately half are to our knowledge undocumented. Accordingly, we perform 134 additional affinity purifications and validate subunit associations for the majority of systems. The map reveals a pre-ribosomal RNA processing assembly and accessory factors, which we show govern rRNA maturation, and functional roles for SRRM1 and FAM120C in chromatin and RPS3A in splicing. By integration across scales, MuSIC increases the resolution of imaging while giving protein interactions a spatial dimension, paving the way to incorporate diverse types of data in proteome-wide cell maps.

Date: 2021
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DOI: 10.1038/s41586-021-04115-9

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