Three million images and morphological profiles of cells treated with matched chemical and genetic perturbations

NATURE METHODS(2024)

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Abstract
The identification of genetic and chemical perturbations with similar impacts on cell morphology can elucidate compounds' mechanisms of action or novel regulators of genetic pathways. Research on methods for identifying such similarities has lagged due to a lack of carefully designed and well-annotated image sets of cells treated with chemical and genetic perturbations. Here we create such a Resource dataset, CPJUMP1, in which each perturbed gene's product is a known target of at least two chemical compounds in the dataset. We systematically explore the directionality of correlations among perturbations that target the same protein encoded by a given gene, and we find that identifying matches between chemical and genetic perturbations is a challenging task. Our dataset and baseline analyses provide a benchmark for evaluating methods that measure perturbation similarities and impact, and more generally, learn effective representations of cellular state from microscopy images. Such advancements would accelerate the applications of image-based profiling of cellular states, such as uncovering drug mode of action or probing functional genomics. The CPJUMP1 Resource comprises Cell Painting images and profiles of 75 million cells treated with hundreds of chemical and genetic perturbations. The dataset enables exploration of their relationships and lays the foundation for the development of advanced methods to match perturbations.
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Key words
cells,morphological profiles,images
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