tailieunhanh - Báo cáo y học: "Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action. | Hillenmeyer et al. Genome Biology 2010 11 R30 http 2010 11 3 R30 w Genome Biology METHOD _ Open Access Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action Maureen E Hillenmeyer1 2 Elke Ericson3 4 Ronald W Davis2 5 Corey Nislow4 6 Daphne Koller 7 and Guri Giaever 3 4 Abstract We systematically analyzed the relationships between gene fitness profiles co-fitness and drug inhibition profiles coinhibition 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. Background Yeast competitive fitness data constitute a unique genome-wide assay of the cellular response to environmental and chemical perturbations 1-8 . Here we systematically analyzed the largest fitness dataset available comprising measurements of the growth rates of barcoded pooled deletion strains in the presence of over 400 unique perturbations 1 and show that the dataset reveals novel aspects of cellular physiology and provides a valuable resource for systems biology. In the haploinsuffi-ciency profiling HIP assay consisting of all 6 000 heterozygous deletions where one copy of each gene is deleted most strains 97 grow at the rate of wild type 9 when assayed in parallel. In the presence of a drug the strain deleted for the drug target is specifically sensitized as measured by a decrease in growth rate as a result of a further decrease in functional gene dosage by the drug binding to the target protein. In this way fitness data allow identification of the potential drug target 3 4 10 . In the homozygous profiling HOP assay applied to