A global genetic interaction network maps a wiring diagram of cellular function

Michael Costanzo, Benjamin VanderSluis, Elizabeth N. Koch, Anastasia Baryshnikova, Carles Pons, Guihong Tan, Wen Wang, Matej Usaj, Julia Hanchard, Susan D. Lee, Vicent Pelechano, Erin B. Styles, Maximilian Billmann, Jolanda Van Leeuwen, Nydia Van Dyk, Zhen Yuan Lin, Elena Kuzmin, Justin Nelson, Jeff S. Piotrowski, Tharan SrikumarSondra Bahr, Yiqun Chen, Raamesh Deshpande, Christoph F. Kurat, Sheena C. Li, Zhijian Li, Mojca Mattiazzi Usaj, Hiroki Okada, Natasha Pascoe, Bryan Joseph San Luis, Sara Sharifpoor, Emira Shuteriqi, Scott W. Simpkins, Jamie Snider, Harsha Garadi Suresh, Yizhao Tan, Hongwei Zhu, Noel Malod-Dognin, Vuk Janjic, Natasa Przulj, Olga G. Troyanskaya, Igor Stagljar, Tian Xia, Yoshikazu Ohya, Anne Claude Gingras, Brian Raught, Michael Boutros, Lars M. Steinmetz, Claire L. Moore, Adam P. Rosebrock, Amy A. Caudy, Chad L. Myers, Brenda Andrews, Charles Boone

Research output: Contribution to journalArticle

363 Scopus citations

Abstract

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell.

Original languageEnglish (US)
Article number1420
JournalScience
Volume353
Issue number6306
DOIs
StatePublished - Sep 23 2016

All Science Journal Classification (ASJC) codes

  • General

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    Costanzo, M., VanderSluis, B., Koch, E. N., Baryshnikova, A., Pons, C., Tan, G., Wang, W., Usaj, M., Hanchard, J., Lee, S. D., Pelechano, V., Styles, E. B., Billmann, M., Van Leeuwen, J., Van Dyk, N., Lin, Z. Y., Kuzmin, E., Nelson, J., Piotrowski, J. S., ... Boone, C. (2016). A global genetic interaction network maps a wiring diagram of cellular function. Science, 353(6306), [1420]. https://doi.org/10.1126/science.aaf1420