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Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome

View ORCID ProfileEdward L. Huttlin, Raphael J. Bruckner, Jose Navarrete-Perea, Joe R. Cannon, Kurt Baltier, Fana Gebreab, Melanie P. Gygi, Alexandra Thornock, Gabriela Zarraga, Stanley Tam, John Szpyt, Alexandra Panov, Hannah Parzen, Sipei Fu, Arvene Golbazi, Eila Maenpaa, Keegan Stricker, Sanjukta Guha Thakurta, Ramin Rad, Joshua Pan, View ORCID ProfileDavid P. Nusinow, View ORCID ProfileJoao A. Paulo, View ORCID ProfileDevin K. Schweppe, Laura Pontano Vaites, View ORCID ProfileJ. Wade Harper, Steven P. Gygi
doi: https://doi.org/10.1101/2020.01.19.905109
Edward L. Huttlin
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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  • ORCID record for Edward L. Huttlin
  • For correspondence: edward_huttlin@hms.harvard.edu wade_harper@hms.harvard.edu steven_gygi@hms.harvard.edu
Raphael J. Bruckner
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
3ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA, 02115, USA
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Jose Navarrete-Perea
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Joe R. Cannon
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
4Merck, West Point, PA, 19486, USA
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Kurt Baltier
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
5IQ Proteomics, Cambridge, MA, 02139, USA
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Fana Gebreab
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Melanie P. Gygi
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Alexandra Thornock
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Gabriela Zarraga
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
6Vor Biopharma, Cambridge, MA, 02142, USA
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Stanley Tam
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
7Rubius Therapeutics, Cambridge, MA, 02139, USA
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John Szpyt
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Alexandra Panov
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Hannah Parzen
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
8RPS North America, South Kingstown, RI, 02879, USA
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Sipei Fu
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Arvene Golbazi
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Eila Maenpaa
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Keegan Stricker
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Sanjukta Guha Thakurta
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Ramin Rad
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Joshua Pan
2Broad Institute, Cambridge, MA, 02s142, USA
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David P. Nusinow
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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  • ORCID record for David P. Nusinow
Joao A. Paulo
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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Devin K. Schweppe
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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  • ORCID record for Devin K. Schweppe
Laura Pontano Vaites
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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J. Wade Harper
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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  • For correspondence: edward_huttlin@hms.harvard.edu wade_harper@hms.harvard.edu steven_gygi@hms.harvard.edu
Steven P. Gygi
1Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA
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  • For correspondence: edward_huttlin@hms.harvard.edu wade_harper@hms.harvard.edu steven_gygi@hms.harvard.edu
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SUMMARY

Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome. Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. The first, BioPlex 3.0, results from affinity purification of 10,128 human proteins – half the proteome – in 293T cells and includes 118,162 interactions among 14,586 proteins; the second results from 5,522 immunoprecipitations in HCT116 cells. These networks model the interactome at unprecedented scale, encoding protein function, localization, and complex membership. Their comparison validates thousands of interactions and reveals extensive customization of each network. While shared interactions reside in core complexes and involve essential proteins, cell-specific interactions bridge conserved complexes, likely ‘rewiring’ each cell’s interactome. Interactions are gained and lost in tandem among proteins of shared function as the proteome remodels to produce each cell’s phenotype. Viewable interactively online through BioPlexExplorer, these networks define principles of proteome organization and enable unknown protein characterization.

Footnotes

  • ↵# Lead Contact: steven_gygi{at}hms.harvard.edu

  • https://bioplex.hms.harvard.edu

  • https://bioplex.hms.harvard.edu/bioPlexExplorer

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 19, 2020.
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Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome
Edward L. Huttlin, Raphael J. Bruckner, Jose Navarrete-Perea, Joe R. Cannon, Kurt Baltier, Fana Gebreab, Melanie P. Gygi, Alexandra Thornock, Gabriela Zarraga, Stanley Tam, John Szpyt, Alexandra Panov, Hannah Parzen, Sipei Fu, Arvene Golbazi, Eila Maenpaa, Keegan Stricker, Sanjukta Guha Thakurta, Ramin Rad, Joshua Pan, David P. Nusinow, Joao A. Paulo, Devin K. Schweppe, Laura Pontano Vaites, J. Wade Harper, Steven P. Gygi
bioRxiv 2020.01.19.905109; doi: https://doi.org/10.1101/2020.01.19.905109
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Dual Proteome-scale Networks Reveal Cell-specific Remodeling of the Human Interactome
Edward L. Huttlin, Raphael J. Bruckner, Jose Navarrete-Perea, Joe R. Cannon, Kurt Baltier, Fana Gebreab, Melanie P. Gygi, Alexandra Thornock, Gabriela Zarraga, Stanley Tam, John Szpyt, Alexandra Panov, Hannah Parzen, Sipei Fu, Arvene Golbazi, Eila Maenpaa, Keegan Stricker, Sanjukta Guha Thakurta, Ramin Rad, Joshua Pan, David P. Nusinow, Joao A. Paulo, Devin K. Schweppe, Laura Pontano Vaites, J. Wade Harper, Steven P. Gygi
bioRxiv 2020.01.19.905109; doi: https://doi.org/10.1101/2020.01.19.905109

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