From Pixels to Phenotypes: Integrating Image-Based Profiling with Cell Health Data Improves Interpretability
Seal S, Carreras-Puigvert J, Carpenter AE, Spjuth O, Bender A..
From Pixels to Phenotypes: Integrating Image-Based Profiling with Cell Health Data Improves Interpretability.
Molecular Biology of the Cell. 35, 3 (2024). DOI: 10.1091/mbc.E23-08-0298
Cell Painting assays generate morphological profiles that are versatile descriptors of biological systems and have been used to predict in vitro and in vivo drug effects. However, Cell Painting features are based on image statistics, and are, therefore, often not readily biologically interpretable. In this study, we introduce an approach that maps specific Cell Painting features into the BioMorph space using readouts from comprehensive Cell Health assays. We validated that the resulting BioMorph space effectively connected compounds not only with the morphological features associated with their bioactivity but with deeper insights into phenotypic characteristics and cellular processes associated with the given bioactivity. The BioMorph space revealed the mechanism of action for individual compounds, including dual-acting compounds such as emetine, an inhibitor of both protein synthesis and DNA replication. In summary, BioMorph space offers a more biologically relevant way to interpret cell morphological features from the Cell Painting assays and to generate hypotheses for experimental validation.