A deep learning algorithm to translate and classify cardiac electrophysiology: From induced pluripotent stem cell-derived cardiomyocytes to adult cardiac cells

Abstract

AbstractThe development of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has been a critical in vitro advance in the study of patient-specific physiology, pathophysiology and pharmacology. We designed a new deep learning multitask network approach intended to address the low throughput, high variability and immature phenotype of the iPSC-CM platform. It was trained using simulated action potential (AP) data and applied to classify cells into the drug-free and drugged categories and to predict the impact of electrophysiological perturbation across the continuum of aging from the immature iPSC-CMs to the adult ventricular myocytes. The phase of the AP extremely sensitive to perturbation due to a steep rise of the membrane resistance was found to contain the key information required for successful network multitasking. We also demonstrated successful translation of both experimental and simulated iPSC-CM AP data validating our network by prediction of experimental drug-induced effects on adult cardiomyocyte APs by the latter.