Article abstract

Nature Methods 6, 83 - 90 (2009)
Published online: 7 December 2008 | doi:10.1038/nmeth.1280

An empirical framework for binary interactome mapping

Kavitha Venkatesan1,2,12,13, Jean-François Rual1,2,12,13, Alexei Vazquez1,3,4,13, Ulrich Stelzl5,6,13, Irma Lemmens7,13, Tomoko Hirozane-Kishikawa1,2, Tong Hao1,2, Martina Zenkner5, Xiaofeng Xin8, Kwang-Il Goh1,3,9, Muhammed A Yildirim1,2,10, Nicolas Simonis1,2, Kathrin Heinzmann1,2,12, Fana Gebreab1,2, Julie M Sahalie1,2, Sebiha Cevik1,2,12, Christophe Simon1,2,12, Anne-Sophie de Smet7, Elizabeth Dann1,2, Alex Smolyar1,2, Arunachalam Vinayagam5, Haiyuan Yu1,2, David Szeto1,2, Heather Borick1,2,12, Amélie Dricot1,2, Niels Klitgord1,2,12, Ryan R Murray1,2, Chenwei Lin1,2, Maciej Lalowski5,12, Jan Timm5, Kirstin Rau5, Charles Boone8, Pascal Braun1,2, Michael E Cusick1,2, Frederick P Roth1,11, David E Hill1,2, Jan Tavernier7, Erich E Wanker5, Albert-László Barabási1,3,12 & Marc Vidal1,2

Several attempts have been made to systematically map protein-protein interaction, or 'interactome', networks. However, it remains difficult to assess the quality and coverage of existing data sets. Here we describe a framework that uses an empirically-based approach to rigorously dissect quality parameters of currently available human interactome maps. Our results indicate that high-throughput yeast two-hybrid (HT-Y2H) interactions for human proteins are more precise than literature-curated interactions supported by a single publication, suggesting that HT-Y2H is suitable to map a significant portion of the human interactome. We estimate that the human interactome contains ~130,000 binary interactions, most of which remain to be mapped. Similar to estimates of DNA sequence data quality and genome size early in the Human Genome Project, estimates of protein interaction data quality and interactome size are crucial to establish the magnitude of the task of comprehensive human interactome mapping and to elucidate a path toward this goal.

  1. Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
  2. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
  3. Center for Complex Network Research and Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, Indiana 46556, USA.
  4. The Simons Center for Systems Biology, Institute for Advanced Study, Einstein Drive, Princeton, New Jersey 08540, USA.
  5. Max Delbrück Center for Molecular Medicine, Robert-Roessle-Straße 10, D-13125 Berlin, Germany.
  6. Otto-Warburg Laboratory, Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, D-14195 Berlin, Germany.
  7. Department of Medical Protein Research, Vlaams Instituut voor Biotechnologie, and Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Albert Baertsoenkaai 3, 9000 Ghent, Belgium.
  8. Banting and Best Department of Medical Research and Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  9. Department of Physics, Korea University, 1 Anam-dong 5-ga, Seongbuk-gu, Seoul 136-713, Korea.
  10. School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, Massachusetts 02138, USA.
  11. Department of Biochemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA.
  12. Present addresses: Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (K.V.), Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA (J.-F.R.), Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, UK (K.H.), University College Dublin, School of Biomolecular and Biomedical Science, Belfield, Dublin 4, Ireland (S.C.), Genome Exploration Research Group, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan (C.S.), Department of Biological Sciences, Clemson University, 132 Long Hall, Clemson, South Carolina 29634, USA (H.B.), Bioinformatics Program, Boston University, 24 Cummington Street, Boston, Massachusetts 02215, USA (N.K.), Protein Chemistry/Proteomics/Peptide Synthesis and Array Unit, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, FI-00014 Helsinki, Finland (M.L.) and Center for Complex Network Research and Departments of Physics, Biology and Computer Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA (A.-L.B.).
  13. These authors contributed equally to this work.

Correspondence to: Marc Vidal1,2 e-mail:

Correspondence to: Albert-László Barabási1,3,12 e-mail:

Correspondence to: Erich E Wanker5 e-mail:

Correspondence to: Jan Tavernier7 e-mail:


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