TY - JOUR T1 - Reference compounds for characterizing cellular injury in high-content cellular morphology assays JF - bioRxiv DO - 10.1101/2022.07.12.499781 SP - 2022.07.12.499781 AU - Jayme L. Dahlin AU - Bruce K. Hua AU - Beth E. Zucconi AU - Shawn D. Nelson, Jr. AU - Shantanu Singh AU - Anne E. Carpenter AU - Jonathan H. Shrimp AU - Evelyne Lima-Fernandes AU - Mathias J. Wawer AU - Lawrence P.W. Chung AU - Ayushi Agrawal AU - Mary O’Reilly AU - Dalia Barsyte-Lovejoy AU - Magdalena Szewczyk AU - Fengling Li AU - Parnian Lak AU - Matthew Cuellar AU - Philip A. Cole AU - Jordan L. Meier AU - Tim Thomas AU - Jonathan B. Baell AU - Peter J. Brown AU - Michael A. Walters AU - Paul A. Clemons AU - Stuart L. Schreiber AU - Bridget K. Wagner Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/07/14/2022.07.12.499781.abstract N2 - Robust, generalizable approaches to identify compounds efficiently with undesirable mechanisms of action in complex cellular assays remain elusive. Such a process would be useful for hit triage during high-throughput screening and, ultimately, predictive toxicology during drug development. We generated cell painting and cellular health profiles for 218 prototypical cytotoxic and nuisance compounds in U-2 OS cells in a concentration-response format. A diversity of compounds causing cellular damage produced bioactive cell painting morphologies, including cytoskeletal poisons, genotoxins, nonspecific electrophiles, and redox-active compounds. Further, we show that lower quality lysine acetyltransferase inhibitors and nonspecific electrophiles can be distinguished from more selective counterparts. We propose that the purposeful inclusion of cytotoxic and nuisance reference compounds such as those profiled in this Resource will help with assay optimization and compound prioritization in complex cellular assays like cell painting.Competing Interest StatementPA Cole is a cofounder of Acylin Therapeutics and has been a consultant to AbbVie which have had research programs in KAT inhibitors. AEC has ownership interest in, and serves on the Scientific Advisory Board of, Recursion which uses image-based data for drug discovery. PA Clemons is an advisor for Pfizer, Inc., and Belharra Therapeutics. The other authors hereby declare no conflicting interests pertaining to the material in this manuscript. ER -