Abstract

Image-based morphological cell profiling combines high-content imaging with multiparametric analysis of cells, which allows for the collection of several hundred morphological features in an untargeted and unbiased manner. A popular morphological profiling method is the cell painting assay, in which cells are exposed to chemical or biological perturbations, the cells are then stained with six multiplexed fluorescent dyes, and finally automated microscopy is used to acquire high-content images in five channels. These six dyes reveal eight different cellular components that can be used to investigate the perturbed cellular state and subsequently interrogate a plethora of biological pathways.

This method has been previously used to study, among others, compound toxicity and mechanism of action of novel and existing compounds. In our work, expanding the canonical use of cell painting-based morphological profiling, we are exploring how this method can be used for establishing and characterising disease models, for the potential reversal of disease states with the help of drug repurposing screens and lastly for precision medicine.