1. Large‐scale mapping of human protein–protein interactions by mass spectrometry
- Author
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Jean-Philippe Lambert, Brenda Muskat, Robert Kinach, Lynda Moore, Sally Lin Adams, Rod Taylor, Paul J. Taylor, Shudong Zhang, Kelly Hogue, Michael Moran, Linda McBroom-Cerajewski, Henry S. Duewel, Yinglun Sheng, Thodoros Topaloglou, Yuen Ho, Adrian Heilbut, Olga Ornatsky, Daniel Figeys, Gregg B. Morin, Yury V. Bukhman, Mohamed Abu-Farha, Martin Ethier, Hongyan Li, Ian I. Stewart, Peter Chu, Bonnie Kuehl, Katharine Gladwish, Michael Li, Moyez Dharsee, Liam O'Connor, Shane Climie, Mark D. Robinson, Karen Colwill, Rob M. Ewing, Fred Elisma, and Julian Vasilescu
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Immunoprecipitation ,human interactome ,Plasma protein binding ,Computational biology ,Biology ,Bioinformatics ,Mass spectrometry ,Article ,General Biochemistry, Genetics and Molecular Biology ,Protein–protein interaction ,03 medical and health sciences ,0302 clinical medicine ,Human interactome ,False positive paradox ,Humans ,030304 developmental biology ,0303 health sciences ,General Immunology and Microbiology ,Applied Mathematics ,Proteins ,Data set ,protein–protein interaction ,Computational Theory and Mathematics ,030220 oncology & carcinogenesis ,IP-HTMS ,Protein–protein interaction prediction ,General Agricultural and Biological Sciences ,Protein Binding ,Information Systems - Abstract
Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.
- Published
- 2007
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