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Science 303 (5659): 808-813

Copyright © 2004 by the American Association for the Advancement of Science

Global Mapping of the Yeast Genetic Interaction Network

Amy Hin Yan Tong,1,2* Guillaume Lesage,3* Gary D. Bader,4 Huiming Ding,1 Hong Xu,1,2 Xiaofeng Xin,1,2 James Young,6 Gabriel F. Berriz,7 Renee L. Brost,1 Michael Chang,5 YiQun Chen,1 Xin Cheng,1 Gordon Chua,1 Helena Friesen,2 Debra S. Goldberg,7 Jennifer Haynes,2 Christine Humphries,2 Grace He,1 Shamiza Hussein,3 Lizhu Ke,1 Nevan Krogan,1,2 Zhijian Li,1,2 Joshua N. Levinson,3 Hong Lu,1 Patrice Ménard,3 Christella Munyana,3 Ainslie B. Parsons,1,2 Owen Ryan,1 Raffi Tonikian,1,2 Tania Roberts,5 Anne-Marie Sdicu,3 Jesse Shapiro,3 Bilal Sheikh,1 Bernhard Suter,8 Sharyl L. Wong,7 Lan V. Zhang,7 Hongwei Zhu,1 Christopher G. Burd,9 Sean Munro,10 Chris Sander,4 Jasper Rine,8 Jack Greenblatt,1,2 Matthias Peter,11 Anthony Bretscher,6 Graham Bell,3 Frederick P. Roth,7 Grant W. Brown,5 Brenda Andrews,2{dagger} Howard Bussey,3{dagger} Charles Boone1,2{dagger}

Abstract: A genetic interaction network containing ~1000 genes and ~4000 interactions was mapped by crossing mutations in 132 different query genes into a set of ~4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.

1 Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6.
2 Department of Medical Genetics and Microbiology, University of Toronto, Toronto, ON, Canada M5S 1A8.
3 Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, QC, Canada H3A 1B1.
4 Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10021, USA.
5 Department of Biochemistry, University of Toronto, Toronto, ON, Canada M5S 1A8.
6 Department of Molecular Biology and Genetics, 351 Biotechnology Building, Cornell University, Ithaca, NY 14853, USA.
7 Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, 250 Longwood Avenue, Boston, MA 02115, USA.
8 Department of Molecular & Cell Biology, University of California, 16 Barker Hall, Berkeley, CA 94720–3202, USA.
9 University of Pennsylvania School of Medicine, Department of Cell and Developmental Biology, 421 Curie Boulevard, BRB 2/3, Room 1010, Philadelphia, PA 19104–6058, USA.
10 MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK.
11 Institute of Biochemistry, HPM G8.0, ETH Hoenggerberg, 8093, Zurich, Switzerland.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: brenda.andrews{at} (B.A.); howard.bussey{at} (H.B.); charlie.boone{at} (C.B.)

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The Intra-S Phase Checkpoint Protein Tof1 Collaborates with the Helicase Rrm3 and the F-box Protein Dia2 to Maintain Genome Stability in Saccharomyces cerevisiae.
N. K. Bairwa, B. K. Mohanty, R. Stamenova, M. J. Curcio, and D. Bastia (2011)
J. Biol. Chem. 286, 2445-2454
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A constraint network of interactions: protein-protein interaction analysis of the yeast type II phosphatase Ptc1p and its adaptor protein Nbp2p.
A. Hruby, M. Zapatka, S. Heucke, L. Rieger, Y. Wu, U. Nussbaumer, S. Timmermann, A. Dunkler, and N. Johnsson (2011)
J. Cell Sci. 124, 35-46
   Abstract »    Full Text »    PDF »
Type 2C Protein Phosphatases in Fungi.
J. Arino, A. Casamayor, and A. Gonzalez (2011)
Eukaryot. Cell 10, 21-33
   Abstract »    Full Text »    PDF »
Literature curation of protein interactions: measuring agreement across major public databases.
A. L. Turinsky, S. Razick, B. Turner, I. M. Donaldson, and S. J. Wodak (2010)
Database 2010, baq026
   Abstract »    Full Text »    PDF »
Vesicle trafficking maintains nuclear shape in Saccharomyces cerevisiae during membrane proliferation.
M. T. Webster, J. M. McCaffery, and O. Cohen-Fix (2010)
J. Cell Biol. 191, 1079-1088
   Abstract »    Full Text »    PDF »
The Eukaryotic Translation Elongation Factor 1B{gamma} Has a Non-guanine Nucleotide Exchange Factor Role in Protein Metabolism.
A. M. Esposito and T. G. Kinzy (2010)
J. Biol. Chem. 285, 37995-38004
   Abstract »    Full Text »    PDF »
Derepression of INO1 Transcription Requires Cooperation between the Ino2p-Ino4p Heterodimer and Cbf1p and Recruitment of the ISW2 Chromatin-Remodeling Complex.
A. Shetty and J. M. Lopes (2010)
Eukaryot. Cell 9, 1845-1855
   Abstract »    Full Text »    PDF »

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