The Genetic Landscape of a Cell

被引：1570

作者：

Costanzo, Michael ^{[2
,3
]}

Baryshnikova, Anastasia ^{[2
,3
]}

Bellay, Jeremy ^{[1
]}

Kim, Yungil ^{[1
]}

Spear, Eric D. ^{[4
]}

Sevier, Carolyn S. ^{[4
]}

Ding, Huiming ^{[2
,3
]}

Koh, Judice L. Y. ^{[2
,3
]}

Toufighi, Kiana ^{[2
,3
]}

Mostafavi, Sara ^{[3
,5
]}

Prinz, Jeany ^{[2
,3
]}

Onge, Robert P. St. ^{[6
]}

VanderSluis, Benjamin

Makhnevych, Taras ^{[7
]}

Vizeacoumar, Franco J. ^{[2
,3
]}

Alizadeh, Solmaz ^{[2
,3
]}

Bahr, Sondra ^{[2
,3
]}

Brost, Renee L. ^{[2
,3
]}

Chen, Yiqun ^{[2
,3
]}

Cokol, Murat ^{[8
]}

Deshpande, Raamesh ^{[1
]}

Li, Zhijian ^{[2
,3
]}

Lin, Zhen-Yuan ^{[9
]}

Liang, Wendy ^{[2
,3
]}

Marback, Michaela ^{[2
,3
]}

Paw, Jadine ^{[2
,3
]}

Luis, Bryan-Joseph San ^{[2
,3
]}

Shuteriqi, Ermira ^{[2
,3
]}

Tong, Amy Hin Yan ^{[2
,3
]}

van Dyk, Nydia ^{[2
,3
]}

Wallace, Iain M. ^{[2
,3
,10
]}

Whitney, Joseph A. ^{[3
,5
]}

Weirauch, Matthew T. ^{[11
]}

Zhong, Guoqing ^{[2
,3
]}

Zhu, Hongwei ^{[2
,3
]}

Houry, Walid A.

Brudno, Michael ^{[3
,5
]}

Ragibizadeh, Sasan ^{[12
]}

Papp, Balazs ^{[13
]}

Pal, Csaba ^{[13
]}

Roth, Frederick P. ^{[8
]}

Giaever, Guri ^{[2
,10
]}

Nislow, Corey ^{[2
,3
]}

Troyanskaya, Olga G. ^{[14
]}

Bussey, Howard ^{[15
]}

Bader, Gary D. ^{[2
,3
]}

Gingras, Anne-Claude ^{[9
]}

Morris, Quaid D. ^{[2
,3
,5
]}

Kim, Philip M. ^{[2
,3
]}

Kaiser, Chris A. ^{[4
]}

机构：

[1] Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN 55455 USA

[2] Univ Toronto, Dept Mol Genet, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada

[3] Univ Toronto, Banting & Best Dept Med Res, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada

[4] MIT, Dept Biol, Cambridge, MA 02142 USA

[5] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 2E4, Canada

[6] Stanford Univ, Dept Biochem, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA

[7] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada

[8] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[9] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[10] Univ Toronto, Dept Pharm, Toronto, ON M5S 3E1, Canada

[11] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[12] S&P Robot Inc, N York, ON M3J 2V8, Canada

[13] Biol Res Ctr, Inst Biochem, H-6701 Szeged, Hungary

[14] Princeton Univ, Dept Comp Sci, Lewis Sigler Inst Integrat Genom, Carl Icahn Lab, Princeton, NJ 08544 USA

[15] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada

来源：

SCIENCE | 2010年 / 327卷 / 5964期

基金：

加拿大健康研究院;

关键词：

SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORKS; TRANSFER-RNA; PROTEIN; EVOLUTION; INTERACTOME; EXOCYTOSIS; PATHWAYS; REVEALS; MAP;

D O I：

10.1126/science.1180823

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 similar to 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.

引用

页码：425 / 431

页数：7

共 34 条

[1] LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway
Chen, EJ
Kaiser, CA
[J]. JOURNAL OF CELL BIOLOGY, 2003, 161 (02) : 333 - 347
[2] Perspective: Evolution and detection of genetic robustness
de Visser, JAGM
Hermisson, J
Wagner, GP
Meyers, LA
Bagheri, HC
Blanchard, JL
Chao, L
Cheverud, JM
Elena, SF
Fontana, W
Gibson, G
Hansen, TF
Krakauer, D
Lewontin, RC
Ofria, C
Rice, SH
von Dassow, G
Wagner, A
Whitlock, MC
[J]. EVOLUTION, 2003, 57 (09) : 1959 - 1972
[3] Systematic Mapping of Genetic Interaction Networks
Dixon, Scott J.
Costanzo, Michael
Baryshnikova, Anastasia
Andrews, Brenda
Boone, Charles
[J]. ANNUAL REVIEW OF GENETICS, 2009, 43 : 601 - 625
[4] Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae
Dunham, MJ
Badrane, H
Ferea, T
Adams, J
Brown, PO
Rosenzweig, F
Botstein, D
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (25) : 16144 - 16149
[5] Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis
Esberg, Anders
Huang, Bo
Johansson, Marcus J. O.
Bystrom, Anders S.
[J]. MOLECULAR CELL, 2006, 24 (01) : 139 - 148
[6] Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers.
Fong, Peter C.
Boss, David S.
Yap, Timothy A.
Tutt, Andrew
Wu, Peijun
Mergui-Roelvink, Marja
Mortimer, Peter
Swaisland, Helen
Lau, Alan
O'Connor, Mark J.
Ashworth, Alan
Carmichael, James
Kaye, Stan B.
Schellens, Jan H. M.
de Bono, Johann S.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (02) : 123 - 134
[7] A simple dependence between protein evolution rate and the number of protein-protein interactions
Fraser, HB
Wall, DP
Hirsh, AE
[J]. BMC EVOLUTIONARY BIOLOGY, 2003, 3 (1)
[8] Proteome survey reveals modularity of the yeast cell machinery
Gavin, AC
Aloy, P
Grandi, P
Krause, R
Boesche, M
Marzioch, M
Rau, C
Jensen, LJ
Bastuck, S
Dümpelfeld, B
Edelmann, A
Heurtier, MA
Hoffman, V
Hoefert, C
Klein, K
Hudak, M
Michon, AM
Schelder, M
Schirle, M
Remor, M
Rudi, T
Hooper, S
Bauer, A
Bouwmeester, T
Casari, G
Drewes, G
Neubauer, G
Rick, JM
Kuster, B
Bork, P
Russell, RB
Superti-Furga, G
[J]. NATURE, 2006, 440 (7084) : 631 - 636
[9] Robust interactions
Hartwell, L
[J]. SCIENCE, 2004, 303 (5659) : 774 - 775
[10] Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis
Huber, Alexandre
Bodenmiller, Bernd
Uotila, Aino
Stahl, Michael
Wanka, Stefanie
Gerrits, Bertran
Aebersold, Ruedi
Loewith, Robbie
[J]. GENES & DEVELOPMENT, 2009, 23 (16) : 1929 - 1943

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