Morphological profiling data resource enables prediction of chemical compound properties

• Published in: iScience Vol. 28; no. 5; p. 112445
• Main Authors: Wolff, Christopher, Neuenschwander, Martin, Beese, Carsten Jörn, Sitani, Divya, Ramos, Maria C., Srovnalova, Alzbeta, Varela, María José, Polishchuk, Pavel, Skopelitou, Katholiki E., Škuta, Ctibor, Stechmann, Bahne, Brea, José, Clausen, Mads Hartvig, Dzubak, Petr, Fernández-Godino, Rosario, Genilloud, Olga, Hajduch, Marian, Loza, María Isabel, Lehmann, Martin, Peter von Kries, Jens, Sun, Han, Schmied, Christopher
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.05.2025; Elsevier
• Subjects: Chemistry; Chemistry
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2025.112445

Morphological profiling with the Cell Painting assay has emerged as a promising method in drug discovery research. The assay captures morphological changes across various cellular compartments enabling the rapid prediction of compound bioactivity. We present a comprehensive morphological profiling resource using the carefully curated and well-annotated EU-OPENSCREEN Bioactive compounds. The data were generated across four imaging sites with high-throughput confocal microscopes using the Hep G2 as well as the U2 OS cell lines. We employed an extensive assay optimization process to achieve high data quality across the different sites. An analysis of the extracted profiles validates the robustness of the generated data. We used this resource to compare the morphological features of the different cell lines. By correlating the profiles with overall activity, cellular toxicity, several specific mechanisms of action (MOAs), and protein targets, we demonstrate the dataset’s potential for facilitating more extensive exploration of MOAs. [Display omitted] •Cell Painting dataset based on 2464 EU-OPENSCREEN Bioactive compounds•Hep G2 datasets generated from four different imaging sites•Extensive assay optimization within and across sites yields high quality and reproducibility•Exploration of compound bioactivity and prediction of mechanisms of action Chemistry