Mapping the cellular response to small molecules using chemogenomic fitness signatures.
Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes.
The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Anna Y
AY
Lee
Robert P
RP
St Onge
Michael J
MJ
Proctor
Iain M
IM
Wallace
Aaron H
AH
Nile
Paul A
PA
Spagnuolo
Yulia
Y
Jitkova
Marcela
M
Gronda
Yan
Y
Wu
Moshe K
MK
Kim
Kahlin
K
Cheung-Ong
Nikko P
NP
Torres
Eric D
ED
Spear
Mitchell K L
MK
Han
Ulrich
U
Schlecht
Sundari
S
Suresh
Geoffrey
G
Duby
Lawrence E
LE
Heisler
Anuradha
A
Surendra
Eula
E
Fung
Malene L
ML
Urbanus
Marinella
M
Gebbia
Elena
E
Lissina
Molly
M
Miranda
Jennifer H
JH
Chiang
Ana Maria
AM
Aparicio
Mahel
M
Zeghouf
Ronald W
RW
Davis
Jacqueline
J
Cherfils
Marc
M
Boutry
Chris A
CA
Kaiser
Carolyn L
CL
Cummins
William S
WS
Trimble
Grant W
GW
Brown
Aaron D
AD
Schimmer
Vytas A
VA
Bankaitis
Corey
C
Nislow
Gary D
GD
Bader
Guri
G
Giaever
D045744:Cell Line, Tumor; D002477:Cells / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004351:Drug Resistance / Q000235:genetics*; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study / Q000379:methods*; D057895:Haploinsufficiency; D006801:Humans; D010597:Pharmacogenetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology*
D054852:Small Molecule Libraries