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

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.

Pubmed ID: 17353931

Authors

  • Ewing RM
  • Chu P
  • Elisma F
  • Li H
  • Taylor P
  • Climie S
  • McBroom-Cerajewski L
  • Robinson MD
  • O'Connor L
  • Li M
  • Taylor R
  • Dharsee M
  • Ho Y
  • Heilbut A
  • Moore L
  • Zhang S
  • Ornatsky O
  • Bukhman YV
  • Ethier M
  • Sheng Y
  • Vasilescu J
  • Abu-Farha M
  • Lambert JP
  • Duewel HS
  • Stewart II
  • Kuehl B
  • Hogue K
  • Colwill K
  • Gladwish K
  • Muskat B
  • Kinach R
  • Adams SL
  • Moran MF
  • Morin GB
  • Topaloglou T
  • Figeys D

Journal

Molecular systems biology

Publication Data

March 13, 2007

Associated Grants

None

Mesh Terms

  • Humans
  • Immunoprecipitation
  • Protein Binding
  • Proteins
  • Spectrometry, Mass, Electrospray Ionization