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ReportsHigh-Quality Binary Protein Interaction Map of the Yeast Interactome Network ld r m,1,2,3*![]()
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
1 Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02115, USA. 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.
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.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)