The genetic landscape of a cell.
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.
Costanzo
Michael
M
Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Baryshnikova
Anastasia
A
Bellay
Jeremy
J
Kim
Yungil
Y
Spear
Eric D
ED
Sevier
Carolyn S
CS
Ding
Huiming
H
Koh
Judice L Y
JL
Toufighi
Kiana
K
Mostafavi
Sara
S
Prinz
Jeany
J
St Onge
Robert P
RP
VanderSluis
Benjamin
B
Makhnevych
Taras
T
Vizeacoumar
Franco J
FJ
Alizadeh
Solmaz
S
Bahr
Sondra
S
Brost
Renee L
RL
Chen
Yiqun
Y
Cokol
Murat
M
Deshpande
Raamesh
R
Li
Zhijian
Z
Lin
Zhen-Yuan
ZY
Liang
Wendy
W
Marback
Michaela
M
Paw
Jadine
J
San Luis
Bryan-Joseph
BJ
Shuteriqi
Ermira
E
Tong
Amy Hin Yan
AH
van Dyk
Nydia
N
Wallace
Iain M
IM
Whitney
Joseph A
JA
Weirauch
Matthew T
MT
Zhong
Guoqing
G
Zhu
Hongwei
H
Houry
Walid A
WA
Brudno
Michael
M
Ragibizadeh
Sasan
S
Papp
Balázs
B
Pál
Csaba
C
Roth
Frederick P
FP
Giaever
Guri
G
Nislow
Corey
C
Troyanskaya
Olga G
OG
Bussey
Howard
H
Bader
Gary D
GD
Gingras
Anne-Claude
AC
Morris
Quaid D
QD
Kim
Philip M
PM
Kaiser
Chris A
CA
Myers
Chad L
CL
Andrews
Brenda J
BJ
Boone
Charles
C
D019295:Computational Biology; D020440:Gene Duplication; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D056084:Genetic Fitness; D016681:Genome, Fungal; D053858:Metabolic Networks and Pathways; D009154:Mutation; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D029701:Saccharomyces cerevisiae Proteins