The Pharmacogenetic Phenome Compendium, A Chemical–Genetic Interaction Map

Development of new drugs is a complicated and difficult process, with many initially promising compounds falling by the wayside due to unforeseen off-target or genotype-specific effects. In an effort to address some of these problems a new paper by Breinig et. al. describes a high-throughput process for screening small molecules against a library of cancer cells with known gene knockouts in key signaling pathways. Using 384-well plates for testing the drug-cell combinations and an automated image analysis pipeline, the authors tracked changes in twenty different key drug-specific phenotypic features such as the cell count, shape, and DNA appearance.  Based on the drug-specific phenotypic differences the authors produced a chemical-genomic interaction map of the cancer cells.  These data were used to examine how drugs perturb genetic networks and to investigate cross-talk between pathways, as well as to explain some of the observed off-target activity and drug synergism. The group has released this data online as the Pharmacogenetic Phenome Compendium (PGPC) for other researchers to use.