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Science 327 (5964): 425-431

Copyright © 2010 by the American Association for the Advancement of Science

The Genetic Landscape of a Cell

Michael Costanzo,1,2,* Anastasia Baryshnikova,1,2,* Jeremy Bellay,3 Yungil Kim,3 Eric D. Spear,4 Carolyn S. Sevier,4 Huiming Ding,1,2 Judice L.Y. Koh,1,2 Kiana Toufighi,1,2 Sara Mostafavi,1,5 Jeany Prinz,1,2 Robert P. St. Onge,6 Benjamin VanderSluis,3 Taras Makhnevych,7 Franco J. Vizeacoumar,1,2 Solmaz Alizadeh,1,2 Sondra Bahr,1,2 Renee L. Brost,1,2 Yiqun Chen,1,2 Murat Cokol,8 Raamesh Deshpande,3 Zhijian Li,1,2 Zhen-Yuan Lin,9 Wendy Liang,1,2 Michaela Marback,1,2 Jadine Paw,1,2 Bryan-Joseph San Luis,1,2 Ermira Shuteriqi,1,2 Amy Hin Yan Tong,1,2 Nydia van Dyk,1,2 Iain M. Wallace,1,2,10 Joseph A. Whitney,1,5 Matthew T. Weirauch,11 Guoqing Zhong,1,2 Hongwei Zhu,1,2 Walid A. Houry,7 Michael Brudno,1,5 Sasan Ragibizadeh,12 Balázs Papp,13 Csaba Pál,13 Frederick P. Roth,8 Guri Giaever,2,10 Corey Nislow,1,2 Olga G. Troyanskaya,14 Howard Bussey,15 Gary D. Bader,1,2 Anne-Claude Gingras,9 Quaid D. Morris,1,2,5 Philip M. Kim,1,2 Chris A. Kaiser,4 Chad L. Myers,3,{dagger} Brenda J. Andrews,1,2,{dagger} Charles Boone1,2,{dagger}

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 ~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.

1 Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
2 Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
3 Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
4 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
5 Department of Computer Science, University of Toronto, Toronto, Ontario M5S 2E4, Canada.
6 Department of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA.
7 Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
8 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
9 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
10 Department of Pharmacy, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
11 Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA.
12 S&P Robotics, Inc., 1181 Finch Avenue West, North York, Ontario M3J 2V8, Canada.
13 Institute of Biochemistry, Biological Research Center, H-6701 Szeged, Hungary.
14 Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Carl Icahn Laboratory, Princeton University, Princeton, NJ 08544, USA.
15 Biology Department, McGill University, Montreal, Quebec H3A 1B1, Canada.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: cmyers{at}cs.umn.edu (C.L.M.); brenda.andrews{at}utoronto.ca (B.J.A.); charlie.boone{at}utoronto.ca (C.B.)


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C. D. Putnam, S. R. Allen-Soltero, S. L. Martinez, J. E. Chan, T. K. Hayes, and R. D. Kolodner (2012)
PNAS 109, E3251-E3259
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The SNF2 family ATPase LSH promotes phosphorylation of H2AX and efficient repair of DNA double-strand breaks in mammalian cells.
J. Burrage, A. Termanis, A. Geissner, K. Myant, K. Gordon, and I. Stancheva (2012)
J. Cell Sci. 125, 5524-5534
   Abstract »    Full Text »    PDF »
Variance in Epistasis Links Gene Regulation and Evolutionary Rate in the Yeast Genetic Interaction Network.
J. L. Fierst and P. C. Phillips (2012)
Genome Biol Evol 4, 1080-1087
   Abstract »    Full Text »    PDF »
Biological function through network topology: a survey of the human diseasome.
V. Janjic and N. Przulj (2012)
Briefings in Functional Genomics 11, 522-532
   Abstract »    Full Text »    PDF »
Proteome-wide Analysis of Lysine Acetylation Suggests its Broad Regulatory Scope in Saccharomyces cerevisiae.
P. Henriksen, S. A. Wagner, B. T. Weinert, S. Sharma, G. Bacinskaja, M. Rehman, A. H. Juffer, T. C. Walther, M. Lisby, and C. Choudhary (2012)
Mol. Cell. Proteomics 11, 1510-1522
   Abstract »    Full Text »    PDF »

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