title: Machine learning plus optical flow: a simple and sensitive method to detect cardioactive drugs.
abstract: Current preclinical screening methods do not adequately detect cardiotoxicity. Using human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs), more physiologically relevant preclinical or patient-specific screening to detect potential cardiotoxic effects of drug candidates may be possible. However, one of the persistent challenges for developing a high-throughput drug screening platform using iPS-CMs is the need to develop a simple and reliable method to measure key electrophysiological and contractile parameters. To address this need, we have developed a platform that combines machine learning paired with brightfield optical flow as a simple and robust tool that can automate the detection of cardiomyocyte drug effects. Using three cardioactive drugs of different mechanisms, including those with primarily electrophysiological effects, we demonstrate the general applicability of this screening method to detect subtle changes in cardiomyocyte contraction. Requiring only brightfield images of cardiomyocyte contractions, we detect changes in cardiomyocyte contraction comparable to - and even superior to - fluorescence readouts. This automated method serves as a widely applicable screening tool to characterize the effects of drugs on cardiomyocyte function.
authors.affiliation: Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697.
authors.forename: Eugene K
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130.
authors.forename: Yosuke K
authors.initials: YK
authors.lastname: Kurokawa
authors.affiliation: Department of Statistics, California Polytechnic State University, San Luis Obispo, San Luis Obispo, CA 93410.
authors.forename: Robin
authors.initials: R
authors.lastname: Tu
authors.affiliation: 1] Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130 [2] Department of Energy, Environment, and Chemical Engineering, Washington University in St. Louis, St. Louis, MO 63130.
authors.forename: Steven C
authors.initials: SC
authors.lastname: George
authors.affiliation: 1] Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697 [2] Department of Chemical Engineering and Material Science, University of California, Irvine, Irvine, CA 92697.
authors.forename: Michelle
authors.initials: M
authors.lastname: Khine
mesh_terms: D002316:Cardiotonic Agents / Q000494:pharmacology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000502:physiology; D000069550:Machine Learning; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D055096:Optical Devices
chemical_list: D002316:Cardiotonic Agents