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1.
Elife ; 102021 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-34212860

RESUMEN

The 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. The rationale for combining translation and classification tasks is because the most likely application of the deep learning technology we describe here is to translate iPSC-CMs following application of a perturbation. The deep learning network 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.


Asunto(s)
Algoritmos , Aprendizaje Profundo , Técnicas Electrofisiológicas Cardíacas , Miocitos Cardíacos/fisiología , Potenciales de Acción/fisiología , Diferenciación Celular/fisiología , Simulación por Computador , Canal de Potasio ERG1/genética , Canal de Potasio ERG1/metabolismo , Fenómenos Electrofisiológicos/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Células Madre Pluripotentes Inducidas/fisiología , Modelos Biológicos , Fenetilaminas/farmacología , Sulfonamidas/farmacología
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