Piotrowski, J.S. et al. Nat. Chem. Biol. http://dx.doi.org/10.1038/nchembio.2436 (2017).

Chemical probes are valuable tools for studying protein function. Identifying the mechanisms of action of such compounds, however, is a major challenge. Piotrowski et al. report a high-throughput platform for screening for chemical probe function in yeast. The platform is based on the idea that if a compound targets a particular protein, this activity should resemble the genetic interaction profile resulting from loss-of-function mutations in the corresponding gene. The researchers created a set of barcoded yeast gene-deletion mutants in a drug-sensitized background, and then they used highly multiplexed barcode sequencing to simultaneously generate chemical genetic interaction profiles for hundreds of compounds. They compared these chemical genetic interaction profiles with available genetic interaction profiles to predict compound target pathways. This approach enabled them to screen more than 13,000 compounds and yielded functional information for 1,522 probes.