The Genetic Landscape of a Cell

Michael Costanzo(University of Toronto), Anastasia Baryshnikova(University of Toronto), Jeremy Bellay(University of Minnesota), Yungil Kim(University of Minnesota), Eric D. Spear(Massachusetts Institute of Technology), Carolyn S. Sevier(Massachusetts Institute of Technology), Huiming Ding(University of Toronto), Judice L.Y. Koh(University of Toronto), Kiana Toufighi(University of Toronto), Sara Mostafavi(University of Toronto), Jeany Prinz(University of Toronto), Robert P. St.Onge(Stanford University), Benjamin VanderSluis(University of Minnesota), Taras Makhnevych(University of Toronto), Franco J. Vizeacoumar(University of Toronto), Solmaz Alizadeh(University of Toronto), Sondra Bahr(University of Toronto), Renée L. Brost(University of Toronto), Yiqun Chen(University of Toronto), Murat Cokol(Harvard University), Raamesh Deshpande(University of Minnesota), Zhijian Li(University of Toronto), Zhen-Yuan Lin(Mount Sinai Hospital), Wendy Liang(University of Toronto), Michaela Marback(University of Toronto), Jadine Paw(University of Toronto), Bryan-Joseph San Luis(University of Toronto), Ermira Shuteriqi(University of Toronto), Amy H.Y. Tong(University of Toronto), Nydia van Dyk(University of Toronto), Iain M. Wallace(University of Toronto), Joseph A. Whitney(University of Toronto), Matthew T. Weirauch(University of California, Santa Cruz), Guoqing Zhong(University of Toronto), Hongwei Zhu(University of Toronto), Walid A. Houry(University of Toronto), Michael Brudno(University of Toronto), Sasan Ragibizadeh(York University), Balázs Papp(HUN-REN Szegedi Biológiai Kutatóközpont), Csaba Pál(HUN-REN Szegedi Biológiai Kutatóközpont), Frederick P. Roth(Harvard University), Guri Giaever(University of Toronto), Corey Nislow(University of Toronto), Olga G. Troyanskaya(Princeton University), Howard Bussey(McGill University), Gary D. Bader(University of Toronto), Anne‐Claude Gingras(Mount Sinai Hospital), Quaid Morris(University of Toronto), Philip M. Kim(University of Toronto), Chris A. Kaiser(Massachusetts Institute of Technology), Chad L. Myers(University of Minnesota), Brenda Andrews(University of Toronto), Charles Boone(University of Toronto)
Science
January 21, 2010
10.1126/science.1180823
Cited by 2,245Open Access
Full Text

Abstract

A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic genetic interactions, generating quantitative genetic interaction profiles for approximately 75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function. The global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification.

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