@article {2435, title = {A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds}, journal = {Nature Biotechnology}, volume = {27}, number = {4}, year = {2009}, note = {ISI Document Delivery No.: 430EOTimes Cited: 27Cited Reference Count: 60Ho, Cheuk Hei Magtanong, Leslie Barker, Sarah L. Gresham, David Nishimura, Shinichi Natarajan, Paramasivam Koh, Judice L. Y. Porter, Justin Gray, Christopher A. Andersen, Raymond J. Giaever, Guri Nislow, Corey Andrews, Brenda Botstein, David Graham, Todd R. Yoshida, Minoru Boone, Charles}, month = {Apr}, pages = {369-377}, type = {Article}, abstract = {We present a yeast chemical-genomics approach designed to identify genes that when mutated confer drug resistance, thereby providing insight about the modes of action of compounds. We developed a molecular barcoded yeast open reading frame (MoBY-ORF) library in which each gene, controlled by its native promoter and terminator, is cloned into a centromere-based vector along with two unique oligonucleotide barcodes. The MoBY-ORF resource has numerous genetic and chemical-genetic applications, but here we focus on cloning wild-type versions of mutant drug-resistance genes using a complementation strategy and on simultaneously assaying the fitness of all transformants with barcode microarrays. The complementation cloning was validated by mutation detection using whole-genome yeast tiling microarrays, which identified unique polymorphisms associated with a drug-resistant mutant. We used the MoBY-ORF library to identify the genetic basis of several drug-resistant mutants and in this analysis discovered a new class of sterol-binding compounds.}, keywords = {1, 2, 3-BETA-D-GLUCAN SYNTHASE, CYCLOHEXIMIDE, DELETION MUTANTS, ELONGATION-FACTOR, GENE-DELETION, MAMMALIAN PROTEIN, ORDERED ARRAYS, OVEREXPRESSION STRAINS, resistance, SACCHAROMYCES-CEREVISIAE GENOME, SPONGE THEONELLA SP}, isbn = {1087-0156}, url = {://000264971800023}, author = {Ho, C. H. and Magtanong, L. and Barker, S. L. and Gresham, D. and Nishimura, S. and Natarajan, P. and Koh, J. L. Y. and Porter, J. and Gray, C. A. and Andersen, R. J. and Giaever, G. and Nislow, C. and Andrews, B. and Botstein, D. and Graham, T. R. and Yoshida, M. and Boone, C.} }