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Elife ; 102021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212860

RESUMO

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.


Assuntos
Algoritmos , Aprendizado Profundo , Técnicas Eletrofisiológicas Cardíacas , Miócitos Cardíacos/fisiologia , Potenciais de Ação/fisiologia , Diferenciação Celular/fisiologia , Simulação por Computador , Canal de Potássio ERG1/genética , Canal de Potássio ERG1/metabolismo , Fenômenos Eletrofisiológicos/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Modelos Biológicos , Fenetilaminas/farmacologia , Sulfonamidas/farmacologia
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