title: A global genetic interaction network maps a wiring diagram of cellular function.
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.
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Michael
authors.initials: M
authors.lastname: Costanzo
authors.affiliation: 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.
authors.forename: Benjamin
authors.initials: B
authors.lastname: VanderSluis
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Koch
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Baryshnikova
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
authors.forename: Carles
authors.initials: C
authors.lastname: Pons
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Guihong
authors.initials: G
authors.lastname: Tan
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Matej
authors.initials: M
authors.lastname: Usaj
authors.affiliation: 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.
authors.forename: Julia
authors.initials: J
authors.lastname: Hanchard
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Lee
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.
authors.forename: Vicent
authors.initials: V
authors.lastname: Pelechano
authors.affiliation: 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.
authors.forename: Erin B
authors.initials: EB
authors.lastname: Styles
authors.affiliation: Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University, Heidelberg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Billmann
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Jolanda
authors.initials: J
authors.lastname: van Leeuwen
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Nydia
authors.initials: N
authors.lastname: van Dyk
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto ON, Canada.
authors.forename: Zhen-Yuan
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Elena
authors.initials: E
authors.lastname: Kuzmin
authors.affiliation: 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.
authors.forename: Justin
authors.initials: J
authors.lastname: Nelson
authors.affiliation: 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.
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Piotrowski
authors.affiliation: Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto ON, Canada.
authors.forename: Tharan
authors.initials: T
authors.lastname: Srikumar
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Sondra
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authors.lastname: Bahr
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
authors.forename: Raamesh
authors.initials: R
authors.lastname: Deshpande
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Christoph F
authors.initials: CF
authors.lastname: Kurat
authors.affiliation: 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.
authors.forename: Sheena C
authors.initials: SC
authors.lastname: Li
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Mojca Mattiazzi
authors.initials: MM
authors.lastname: Usaj
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan 277-8561.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Okada
authors.affiliation: 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.
authors.forename: Natasha
authors.initials: N
authors.lastname: Pascoe
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Bryan-Joseph
authors.initials: BJ
authors.lastname: San Luis
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Sara
authors.initials: S
authors.lastname: Sharifpoor
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Emira
authors.initials: E
authors.lastname: Shuteriqi
authors.affiliation: 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.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Simpkins
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Jamie
authors.initials: J
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authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Harsha Garadi
authors.initials: HG
authors.lastname: Suresh
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Yizhao
authors.initials: Y
authors.lastname: Tan
authors.affiliation: The Donnelly Centre, University of Toronto, 160 College Street, Toronto ON, Canada M5S 3E1.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Computer Science Deptartment, University College London, London WC1E 6BT, UK.
authors.forename: Noel
authors.initials: N
authors.lastname: Malod-Dognin
authors.affiliation: Department of Computing, Imperial College London, UK.
authors.forename: Vuk
authors.initials: V
authors.lastname: Janjic
authors.affiliation: Computer Science Deptartment, University College London, London WC1E 6BT, UK. School of Computing (RAF), Union University, Belgrade, Serbia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Przulj
authors.affiliation: 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.
authors.forename: Olga G
authors.initials: OG
authors.lastname: Troyanskaya
authors.affiliation: 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.
authors.forename: Igor
authors.initials: I
authors.lastname: Stagljar
authors.affiliation: 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.
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan 277-8561.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ohya
authors.affiliation: 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.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
authors.affiliation: Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto ON, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.affiliation: Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
authors.affiliation: 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.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Moore
authors.affiliation: 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.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Rosebrock
authors.affiliation: 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.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Caudy
authors.affiliation: 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.
authors.forename: Chad L
authors.initials: CL
authors.lastname: Myers
authors.affiliation: 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.
authors.forename: Brenda
authors.initials: B
authors.lastname: Andrews
authors.affiliation: 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.
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
mesh_terms: D004843:Epistasis, Genetic; D053263:Gene Regulatory Networks; D020043:Genes, Essential; D005800:Genes, Fungal / Q000502:physiology*; D058685:Genetic Pleiotropy / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D029701:Saccharomyces cerevisiae Proteins