@article{1873,
  keywords = {Genetic Engineering, Open Reading Frames, Cloning, Molecular, Gene Library},
  author = {Cheuk Ho and Leslie Magtanong and Sarah Barker and David Gresham and Shinichi Nishimura and Paramasivam Natarajan and Judice L Y Koh and Justin Porter and Christopher Gray and Raymond Andersen and Guri Giaever and Corey Nislow and Brenda Andrews and David Botstein and Todd Graham and Minoru Yoshida and Charles Boone},
  title = {A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds.},
  abstract = {<p>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.</p>},
  year = {2009},
  journal = {Nat Biotechnol},
  volume = {27},
  pages = {369-77},
  month = {04/2009},
  language = {eng},
}