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High-Quality Binary Protein Interaction Map of the Yeast Interactome Network
Haiyuan Yu,1,2*Pascal Braun,1,2*Muhammed A. Yldrm,1,2,3*Irma Lemmens,4Kavitha Venkatesan,1,2Julie Sahalie,1,2Tomoko Hirozane-Kishikawa,1,2Fana Gebreab,1,2Na Li,1,2Nicolas Simonis,1,2Tong Hao,1,2Jean-François Rual,1,2Amélie Dricot,1,2Alexei Vazquez,5Ryan R. Murray,1,2Christophe Simon,1,2Leah Tardivo,1,2Stanley Tam,1,2Nenad Svrzikapa,1,2Changyu Fan,1,2Anne-Sophie de Smet,4Adriana Motyl,6Michael E. Hudson,6Juyong Park,1,7Xiaofeng Xin,8Michael E. Cusick,1,2Troy Moore,9Charlie Boone,8Michael Snyder,6Frederick P. Roth,1,10Albert-László Barabási,1,7Jan Tavernier,4David E. Hill,1,2Marc Vidal1,2
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) screening provides high-quality binary interaction information.Because 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 intercomplex connectionswith a highly significant clustering between essential proteins.Rather than correlating with essentiality, protein connectivitycorrelates with genetic pleiotropy.
1 Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02115, USA. 2 Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. 3 School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. 4 Department of Medical Protein Research, VIB, and Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium. 5 The Simons Center for Systems Biology, Institute for Advanced Studies, Princeton, NJ 08540, USA. 6 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06620, USA. 7 Center for Complex Network Research and Departments of Physics, Biology, and Computer Science, Northeastern University, Boston, MA 02115, USA. 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 Open Biosystems, Huntsville, AL 35806, USA. 10 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: marc_vidal{at}dfci.harvard.edu
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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. 
To whom correspondence should be addressed. E-mail: 
