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Large-scale mapping of human protein-protein interactions by mass spectrometry.


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.

SUBMITTER: Ewing RM 

PROVIDER: S-EPMC1847948 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Large-scale mapping of human protein-protein interactions by mass spectrometry.

Ewing Rob M RM   Chu Peter P   Elisma Fred F   Li Hongyan H   Taylor Paul P   Climie Shane S   McBroom-Cerajewski Linda L   Robinson Mark D MD   O'Connor Liam L   Li Michael M   Taylor Rod R   Dharsee Moyez M   Ho Yuen Y   Heilbut Adrian A   Moore Lynda L   Zhang Shudong S   Ornatsky Olga O   Bukhman Yury V YV   Ethier Martin M   Sheng Yinglun Y   Vasilescu Julian J   Abu-Farha Mohamed M   Lambert Jean-Philippe JP   Duewel Henry S HS   Stewart Ian I II   Kuehl Bonnie B   Hogue Kelly K   Colwill Karen K   Gladwish Katharine K   Muskat Brenda B   Kinach Robert R   Adams Sally-Lin SL   Moran Michael F MF   Morin Gregg B GB   Topaloglou Thodoros T   Figeys Daniel D  

Molecular systems biology 20070313


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 identi  ...[more]

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