Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action

被引：114

作者：

Kapitzky, Laura ^{[1
]}

Beltrao, Pedro ^{[1
]}

Berens, Theresa J. ^{[2
]}

Gassner, Nadine ^{[3
]}

Zhou, Chunshui ^{[4
,5
]}

Wuester, Arthur ^{[1
,6
]}

Wu, Julie ^{[1
]}

Babu, M. Madan ^{[6
]}

Elledge, Stephen J. ^{[4
,5
]}

Toczyski, David ^{[2
]}

Lokey, R. Scott ^{[3
,7
]}

Krogan, Nevan J. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Inst QB3, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Biochem & Biophys, Canc Res Inst, San Francisco, CA 94158 USA

[3] Univ Calif Santa Cruz, UCSC Chem Screening Ctr, Santa Cruz, CA 95064 USA

[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[5] Brigham & Womens Hosp, Howard Hughes Med Inst, Div Genet, Boston, MA 02115 USA

[6] MRC Lab Mol Biol, Cambridge, England

[7] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA

来源：

MOLECULAR SYSTEMS BIOLOGY | 2010年 / 6卷

关键词：

chemogenomics; evolution; modularity; SACCHAROMYCES-CEREVISIAE GENOME; GENETIC INTERACTION MAP; SMALL MOLECULES; BIOACTIVE COMPOUNDS; OF-ACTION; CHEMICAL GENOMICS; FISSION YEAST; DISCOVERY; BIOLOGY; CELL;

D O I：

10.1038/msb.2010.107

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We present a cross-species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug scores (or D-scores), identifying mutants that are either sensitive or resistant to particular compounds. We found that compound-functional module relationships are more conserved than individual compound-gene interactions between these two species. Furthermore, we observed that combining data from both species allows for more accurate prediction of MoA. Finally, using this platform, we identified a novel small molecule that acts as a DNA damaging agent and demonstrate that its MoA is conserved in human cells. Molecular Systems Biology 6: 451; published online 21 December 2010; doi:10.1038/msb.2010.107

引用

页数：13

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