@article {Piotrowski112557, author = {Jeff S. Piotrowski and Sheena C. Li and Raamesh Deshpande and Scott W. Simpkins and Justin Nelson and Yoko Yashiroda and Jacqueline M. Barber and Hamid Safizadeh and Erin Wilson and Hiroki Okada and Abraham A. Gebre and Karen Kubo and Nikko P. Torres and Marissa A. LeBlanc and Kerry Andrusiak and Reika Okamoto and Mami Yoshimura and Eva DeRango-Adem and Jolanda van Leeuwen and Katsuhiko Shirahige and Anastasia Baryshnikova and Grant W. Brown and Hiroyuki Hirano and Michael Costanzo and Brenda Andrews and Yoshikazu Ohya and Hiroyuki Osada and Minoru Yoshida and Chad L. Myers and Charles Boone}, title = {Functional Annotation of Chemical Libraries across Diverse Biological Processes}, elocation-id = {112557}, year = {2017}, doi = {10.1101/112557}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells to a compound, revealing chemical-genetic interactions that can elucidate a compound{\textquoteright}s mode of action. We developed a highly parallel and unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized, diagnostic mutant collection that is predictive all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode sequencing protocol, enabling assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened 7 different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.}, URL = {https://www.biorxiv.org/content/early/2017/02/28/112557}, eprint = {https://www.biorxiv.org/content/early/2017/02/28/112557.full.pdf}, journal = {bioRxiv} }