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A synthesis of over 9,000 mass spectrometry experiments reveals the core set of human protein complexes

View ORCID ProfileKevin Drew, Chanjae Lee, Ryan L. Huizar, Fan Tu, Blake Borgeson, Claire D. McWhite, Yun Ma, John B. Wallingford, Edward M. Marcotte
doi: https://doi.org/10.1101/092361
Kevin Drew
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
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  • ORCID record for Kevin Drew
Chanjae Lee
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
2Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Ryan L. Huizar
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
2Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Fan Tu
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
2Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Blake Borgeson
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
2Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Claire D. McWhite
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
2Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Yun Ma
2Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
3The Otolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
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John B. Wallingford
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
2Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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Edward M. Marcotte
1Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA
2Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
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  • For correspondence: marcotte@icmb.utexas.edu
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Abstract

Macromolecular protein complexes carry out many of the essential functions of cells, and many genetic diseases arise from disrupting the functions of such complexes. Currently there is great interest in defining the complete set of human protein complexes, but recent published maps lack comprehensive coverage. Here, through the synthesis of over 9,000 published mass spectrometry experiments, we present hu.MAP, the most comprehensive and accurate human protein complex map to date, containing >4,600 total complexes, >7,700 proteins and >56,000 unique interactions, including thousands of confident protein interactions not identified by the original publications. hu.MAP accurately recapitulates known complexes withheld from the learning procedure, which was optimized with the aid of a new quantitative metric (k-cliques) for comparing sets of sets. The vast majority of complexes in our map are significantly enriched with literature annotations and the map overall shows improved coverage of many disease-associated proteins, as we describe in detail for ciliopathies. Using hu.MAP, we predicted and experimentally validated candidate ciliopathy disease genes in vivo in a model vertebrate, discovering CCDC138, WDR90, and KIAA1328 to be new cilia basal body/centriolar satellite proteins, and identifying ANKRD55 as a novel member of the intraflagellar transport machinery. By offering significant improvements to the accuracy and coverage of human protein complexes, hu.MAP (http://proteincomplexes.org) serves as a valuable resource for better understanding the core cellular functions of human proteins and helping to determine mechanistic foundations of human disease.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 07, 2016.
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A synthesis of over 9,000 mass spectrometry experiments reveals the core set of human protein complexes
Kevin Drew, Chanjae Lee, Ryan L. Huizar, Fan Tu, Blake Borgeson, Claire D. McWhite, Yun Ma, John B. Wallingford, Edward M. Marcotte
bioRxiv 092361; doi: https://doi.org/10.1101/092361
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A synthesis of over 9,000 mass spectrometry experiments reveals the core set of human protein complexes
Kevin Drew, Chanjae Lee, Ryan L. Huizar, Fan Tu, Blake Borgeson, Claire D. McWhite, Yun Ma, John B. Wallingford, Edward M. Marcotte
bioRxiv 092361; doi: https://doi.org/10.1101/092361

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