Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action.
We systematically analyzed the relationships between gene fitness profiles (co-fitness) and drug inhibition profiles (co-inhibition) from several hundred chemogenomic screens in yeast. Co-fitness predicted gene functions distinct from those derived from other assays and identified conditionally dependent protein complexes. Co-inhibitory compounds were weakly correlated by structure and therapeutic class. We developed an algorithm predicting protein targets of chemical compounds and verified its accuracy with experimental testing. Fitness data provide a novel, systems-level perspective on the cell.
Hillenmeyer
Maureen E
ME
Biomedical Informatics, 251 Campus Drive, MSOB, Stanford University, Stanford, CA 94305, USA. maureenh@stanford.edu
Ericson
Elke
E
Davis
Ronald W
RW
Nislow
Corey
C
Koller
Daphne
D
Giaever
Guri
G
D000465:Algorithms; D027682:Cation Transport Proteins / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D000079922:Copper Transport Proteins; D016503:Drug Delivery Systems / Q000379:methods; D025141:Drug Resistance, Fungal / Q000235:genetics; D017353:Gene Deletion; D005800:Genes, Fungal / Q000187:drug effects / Q000235:genetics*; D056084:Genetic Fitness / Q000235:genetics*; D016681:Genome, Fungal / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D049490:Systems Biology / Q000379:methods*
C100359:COX17 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; C120810:EXO84 protein, S cerevisiae; D008565:Membrane Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D003024:Clozapine; D015739:Nocodazole