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Science
Vol. 322 no. 5898 pp. 104-110
DOI: 10.1126/science.1158684
  • Report

High-Quality Binary Protein Interaction Map of the Yeast Interactome Network

  1. Marc Vidal1,2,

+ Author Affiliations

  1. 1 Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  2. 2 Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  3. 3 School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
  4. 4 Department of Medical Protein Research, VIB, and Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
  5. 5 The Simons Center for Systems Biology, Institute for Advanced Studies, Princeton, NJ 08540, USA.
  6. 6 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06620, USA.
  7. 7 Center for Complex Network Research and Departments of Physics, Biology, and Computer Science, Northeastern University, Boston, MA 02115, USA.
  8. 8 Banting and Best Department of Medical Research and Department of Medical Genetics and Microbiology, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
  9. 9 Open Biosystems, Huntsville, AL 35806, USA.
  10. 10 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  1. To whom correspondence should be addressed. E-mail: marc_vidal@dfci.harvard.edu
  • * These authors contributed equally to this work.

Current yeast interactome network maps contain several hundred molecular complexes with limited and somewhat controversial representation of direct binary interactions. We carried out a comparative quality assessment of current yeast interactome data sets, demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information. Because a large fraction of the yeast binary interactome remains to be mapped, we developed an empirically controlled mapping framework to produce a “second-generation” high-quality, high-throughput Y2H data set covering ∼20% of all yeast binary interactions. Both Y2H and affinity purification followed by mass spectrometry (AP/MS) data are of equally high quality but of a fundamentally different and complementary nature, resulting in networks with different topological and biological properties. Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions and intercomplex connections with a highly significant clustering between essential proteins. Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy.

    • Received for publication 4 April 2008.
    • Accepted for publication 1 August 2008.

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