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 Srikumar; Sondra 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

doi:10.1126/science.aaf1420

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

Science. 2016 Sep 23;353(6306):aaf1420. doi: 10.1126/science.aaf1420.

Authors

Michael Costanzo¹, Benjamin VanderSluis², Elizabeth N Koch³, Anastasia Baryshnikova⁴, Carles Pons³, Guihong Tan¹, Wen Wang³, Matej Usaj¹, Julia Hanchard⁵, Susan D Lee⁶, Vicent Pelechano⁷, Erin B Styles⁵, Maximilian Billmann⁸, Jolanda van Leeuwen¹, Nydia van Dyk¹, Zhen-Yuan Lin⁹, Elena Kuzmin⁵, Justin Nelson¹⁰, Jeff S Piotrowski¹¹, Tharan Srikumar¹², Sondra Bahr¹, Yiqun Chen¹, Raamesh Deshpande³, Christoph F Kurat¹, Sheena C Li¹¹, Zhijian Li¹, Mojca Mattiazzi Usaj¹, Hiroki Okada¹³, Natasha Pascoe⁵, Bryan-Joseph San Luis¹, Sara Sharifpoor¹, Emira Shuteriqi¹, Scott W Simpkins¹⁰, Jamie Snider¹, Harsha Garadi Suresh¹, Yizhao Tan¹, Hongwei Zhu¹, Noel Malod-Dognin¹⁴, Vuk Janjic¹⁵, Natasa Przulj¹⁶, Olga G Troyanskaya¹⁷, Igor Stagljar¹⁸, Tian Xia¹⁹, Yoshikazu Ohya¹³, Anne-Claude Gingras²⁰, Brian Raught¹², Michael Boutros⁸, Lars M Steinmetz²¹, Claire L Moore⁶, Adam P Rosebrock⁵, Amy A Caudy⁵, Chad L Myers²², Brenda Andrews²³, Charles Boone²⁴

Affiliations

¹ The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
² Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA. Simons Center for Data Analysis, Simons Foundation, 160 Fifth Avenue, New York, NY 10010, USA.
³ Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
⁴ Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
⁵ The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
⁶ Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
⁷ European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.
⁸ Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University, Heidelberg, Germany.
⁹ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto ON, Canada.
¹⁰ Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA. Program in Biomedical Informatics and Computational Biology, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
¹¹ The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Sciences (CSRS), Saitama, Japan.
¹² Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto ON, Canada.
¹³ Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan 277-8561.
¹⁴ Computer Science Deptartment, University College London, London WC1E 6BT, UK.
¹⁵ Department of Computing, Imperial College London, UK.
¹⁶ Computer Science Deptartment, University College London, London WC1E 6BT, UK. School of Computing (RAF), Union University, Belgrade, Serbia.
¹⁷ Simons Center for Data Analysis, Simons Foundation, 160 Fifth Avenue, New York, NY 10010, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
¹⁸ The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
¹⁹ Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA. School of Electronic Information and Communications, Huazhong University of Science and Technology, Wuhan, China, 430074.
²⁰ Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto ON, Canada.
²¹ European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany. Department of Genetics, School of Medicine and Stanford Genome Technology Center Stanford University, Palo Alto, CA 94304, USA.
²² Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA. Program in Biomedical Informatics and Computational Biology, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA. cmyers@cs.umn.edu brenda.andrews@utoronto.ca charlie.boone@utoronto.ca.
²³ The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. cmyers@cs.umn.edu brenda.andrews@utoronto.ca charlie.boone@utoronto.ca.
²⁴ The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1. Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Sciences (CSRS), Saitama, Japan. cmyers@cs.umn.edu brenda.andrews@utoronto.ca charlie.boone@utoronto.ca.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Epistasis, Genetic
Gene Regulatory Networks*
Genes, Essential
Genes, Fungal / physiology*
Genetic Pleiotropy / physiology*
Saccharomyces cerevisiae / genetics*
Saccharomyces cerevisiae Proteins / genetics*

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

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