Cell Painting transfer increases screening hit rate

Drug discovery uses high throughput screening to identify compounds that interact with a molecular target or that alter a phenotype favorably. The cautious selection of molecules used for such a screening is instrumental, and is tightly related to the hit rate. In this work, we wondered if Cell Painting, a general purpose image-based assay, could be used as an efficient proxy for compound selection, thus increasing the success rate of a specific assay. To this end, we considered Cell Painting images with 30,000 molecules treatments, and selected compounds that produced a visual effect close to the positive control of an assay, by using the Frechet Inception Distance. We then compared the hit rates of such a preselection with what was actually obtained in real screening campaigns. As a result, Cell Painting would have permitted a significant increase in the success rate and, even for one of the assays, would have allowed to reach 80% of the hits with ten times fewer compounds to test. We conclude that images of a Cell Painting assay can be directly used for compound selection prior to screening, and we provide a simple quantitative approach in order to do so.