From Pixels to Phenotypes: Integrating Image-Based Profiling with Cell Health Data Improves Interpretability.

Molecular biology of the cell
Authors
Abstract

Cell Painting assays generate morphological profiles that are versatile descriptors of biological systems and have been used to predict and drug effects. However, Cell Painting features extracted from classical software such as CellProfiler are based on statistical calculations and often not readily biologically interpretable. In this study, we propose a new feature space, which we call BioMorph, that maps these Cell Painting features with 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. Overall, BioMorph space offers a biologically relevant way to interpret the cell morphological features derived using software such as CellProfiler and to generate hypotheses for experimental validation.

Year of Publication
2024
Journal
Molecular biology of the cell
Pages
mbcE23080298
Date Published
01/2024
ISSN
1939-4586
DOI
10.1091/mbc.E23-08-0298
PubMed ID
38170589
Links