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Submitted on April 4, 2008
Accepted on August 1, 2008
High-Quality Binary Protein Interaction Map of the Yeast Interactome Network
Haiyuan Yu 1,Pascal Braun 1,Muhammed A. Yildirim 2,Irma Lemmens 3,Kavitha Venkatesan 1,Julie Sahalie 1,Tomoko Hirozane-Kishikawa 1,Fana Gebreab 1,Na Li 1,Nicolas Simonis 1,Tong Hao 1,Jean-François Rual 1,Amélie Dricot 1,Alexei Vazquez 4,Ryan R. Murray 1,Christophe Simon 1,Leah Tardivo 1,Stanley Tam 1,Nenad Svrzikapa 1,Changyu Fan 1,Anne-Sophie de Smet 3,Adriana Motyl 5,Michael E. Hudson 5,Juyong Park 6,Xiaofeng Xin 7,Michael E. Cusick 1,Troy Moore 8,Charlie Boone 7,Michael Snyder 5,Frederick P. Roth 9,Albert-László Barabási 6,Jan Tavernier 3,David E. Hill 1,Marc Vidal 1*
1 Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02115, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. 2 Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02115, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. 3 Department of Medical Protein Research, VIB, and Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium. 4 The Simons Center for Systems Biology, Institute for Advanced Studies, Princeton, NJ 08540, USA. 5 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06620, USA. 6 Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02115, USA.; Center for Complex Network Research and Departments of Physics, Biology and Computer Science, Northeastern University, Boston, MA 02115, USA. 7 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, Canada M5S 3E1. 8 Open Biosystems, Huntsville, AL 35806, USA. 9 Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02115, USA.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
* To whom correspondence should be addressed.
Marc Vidal , E-mail: marc_vidal{at}dfci.harvard.edu
These authors contributed equally to this work.
Current yeast interactome network maps contain several hundredmolecular complexes with limited and somewhat controversialrepresentation of direct binary interactions. We carried outa comparative quality assessment of current yeast interactomedata sets, demonstrating that high-throughput yeast two-hybrid(Y2H) provides high-quality binary interaction information.As a large fraction of the yeast binary interactome remainsto be mapped, we developed an empirically-controlled mappingframework to produce a "second-generation" high-quality high-throughputY2H 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 fundamentallydifferent and complementary nature resulting in networks withdifferent topological and biological properties. Compared toco-complex interactome models, this binary map is enriched fortransient signaling interactions and inter-complex connectionswith a highly significant clustering between essential proteins.Rather than correlating with essentiality, protein connectivitycorrelates with genetic pleiotropy.
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