Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes
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 co...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2017-06-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20167490 |
| _version_ | 1797280684613566464 |
|---|---|
| author | Kevin Drew Chanjae Lee Ryan L Huizar Fan Tu Blake Borgeson Claire D McWhite Yun Ma John B Wallingford Edward M Marcotte |
| author_facet | Kevin Drew Chanjae Lee Ryan L Huizar Fan Tu Blake Borgeson Claire D McWhite Yun Ma John B Wallingford Edward M Marcotte |
| author_sort | Kevin Drew |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T16:44:50Z |
| format | Article |
| id | doaj.art-f3ad75b364974deeae77b34a7463352b |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T16:44:50Z |
| publishDate | 2017-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-f3ad75b364974deeae77b34a7463352b2024-03-03T07:05:17ZengSpringer NatureMolecular Systems Biology1744-42922017-06-01136n/an/a10.15252/msb.20167490Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexesKevin Drew0Chanjae Lee1Ryan L Huizar2Fan Tu3Blake Borgeson4Claire D McWhite5Yun Ma6John B Wallingford7Edward M Marcotte8Center for Systems and Synthetic Biology Institute for Cellular and Molecular Biology University of Texas at Austin Austin TX USACenter for Systems and Synthetic Biology Institute for Cellular and Molecular Biology University of Texas at Austin Austin TX USACenter for Systems and Synthetic Biology Institute for Cellular and Molecular Biology University of Texas at Austin Austin TX USACenter for Systems and Synthetic Biology Institute for Cellular and Molecular Biology University of Texas at Austin Austin TX USACenter for Systems and Synthetic Biology Institute for Cellular and Molecular Biology University of Texas at Austin Austin TX USACenter for Systems and Synthetic Biology Institute for Cellular and Molecular Biology University of Texas at Austin Austin TX USADepartment of Molecular Biosciences University of Texas at Austin Austin TX USACenter for Systems and Synthetic Biology Institute for Cellular and Molecular Biology University of Texas at Austin Austin TX USACenter for Systems and Synthetic Biology Institute for Cellular and Molecular Biology University of Texas at Austin Austin TX USAAbstract 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.https://doi.org/10.15252/msb.20167490ciliaciliopathyhuman interactomemass spectrometryprotein complexesproteomics |
| spellingShingle | Kevin Drew Chanjae Lee Ryan L Huizar Fan Tu Blake Borgeson Claire D McWhite Yun Ma John B Wallingford Edward M Marcotte Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes Molecular Systems Biology cilia ciliopathy human interactome mass spectrometry protein complexes proteomics |
| title | Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes |
| title_full | Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes |
| title_fullStr | Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes |
| title_full_unstemmed | Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes |
| title_short | Integration of over 9,000 mass spectrometry experiments builds a global map of human protein complexes |
| title_sort | integration of over 9 000 mass spectrometry experiments builds a global map of human protein complexes |
| topic | cilia ciliopathy human interactome mass spectrometry protein complexes proteomics |
| url | https://doi.org/10.15252/msb.20167490 |
| work_keys_str_mv | AT kevindrew integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes AT chanjaelee integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes AT ryanlhuizar integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes AT fantu integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes AT blakeborgeson integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes AT clairedmcwhite integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes AT yunma integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes AT johnbwallingford integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes AT edwardmmarcotte integrationofover9000massspectrometryexperimentsbuildsaglobalmapofhumanproteincomplexes |