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Towards a proteome-scale map of the human protein-protein interaction network.

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.

Pubmed ID: 16189514


  • Rual JF
  • Venkatesan K
  • Hao T
  • Hirozane-Kishikawa T
  • Dricot A
  • Li N
  • Berriz GF
  • Gibbons FD
  • Dreze M
  • Ayivi-Guedehoussou N
  • Klitgord N
  • Simon C
  • Boxem M
  • Milstein S
  • Rosenberg J
  • Goldberg DS
  • Zhang LV
  • Wong SL
  • Franklin G
  • Li S
  • Albala JS
  • Lim J
  • Fraughton C
  • Llamosas E
  • Cevik S
  • Bex C
  • Lamesch P
  • Sikorski RS
  • Vandenhaute J
  • Zoghbi HY
  • Smolyar A
  • Bosak S
  • Sequerra R
  • Doucette-Stamm L
  • Cusick ME
  • Hill DE
  • Roth FP
  • Vidal M



Publication Data

October 20, 2005

Associated Grants

  • Agency: NHGRI NIH HHS, Id: P50 HG004233
  • Agency: NHGRI NIH HHS, Id: R01 HG001715
  • Agency: NCI NIH HHS, Id: R33 CA132073
  • Agency: NHGRI NIH HHS, Id: RC4 HG006066
  • Agency: NHGRI NIH HHS, Id: U01 HG001715
  • Agency: NHLBI NIH HHS, Id: U01 HL098166

Mesh Terms

  • Cloning, Molecular
  • Humans
  • Open Reading Frames
  • Protein Binding
  • Proteome
  • RNA
  • Saccharomyces cerevisiae
  • Two-Hybrid System Techniques