Abstract
Cardiomyocytes derived from human induced pluripotent stem (iPS) cells enable the study of cardiac physiology and the developmental testing of new therapeutic drugs in a human setting. In parallel, machine learning methods are being applied to biomedical science in unprecedented ways. Machine learning has been used to distinguish healthy from diseased cardiomyocytes using calcium (Ca2+) transient signals. Most Ca2+ transient signals are obtained via terminal assays that do not permit longitudinal studies, although some recently developed options can circumvent these concerns. Here, we describe the use of machine learning to identify healthy and diseased cardiomyocytes according to their contractility profiles, which are derived from brightfield videos. This noncontact, label-free approach allows for the continued cultivation of cells after they have been evaluated for use in other assays and can be readily extended to organs-on-chip. To demonstrate utility, we assessed contractility profiles of cardiomyocytes obtained from patients with Timothy Syndrome (TS), a long QT disease which can lead to fatal arrhythmias, and from healthy individuals. The videos were processed and classified using machine learning methods and their performance was evaluated according to several parameters. The trained algorithms were able to distinguish the TS cardiomyocytes from healthy controls and classify two different healthy controls. The proposed computational machine learning evaluation of human iPS cell-derived cardiomyocytes' contractility profiles has the potential to identify other genetic proarrhythmic events, screen therapeutic agents for inducing or suppressing long QT events, and predict drug-target interactions. The same approach could be readily extended to the evaluation of engineered cardiac tissues within single-tissue and multi-tissue organs-on-chip.