2022
DOI: 10.1002/psp4.12803
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Proarrhythmic risk assessment of drugs by dVm/dt shapes using the convolutional neural network

Abstract: Comprehensive in vitro Proarrhythmia Assay (CiPA) projects for assessing proarrhythmic drugs suggested a logistic regression model using qNet as the Torsades de Pointes (TdP) risk assessment biomarker, obtained from in silico simulation. However, using a single in silico feature, such as qNet, cannot reflect whole characteristics related to TdP in the entire action potential (AP) shape. Thus, this study proposed a deep convolutional neural network (CNN) model using differential action potential shapes to class… Show more

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Cited by 9 publications
(5 citation statements)
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References 39 publications
(110 reference statements)
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“…Second, timing offsets, for example between stimuli in the data to be fitted and the training data, can be accounted for using t 0 in (3) without retraining. Last but not least, the transmembrane potential gradient , recently highlighted in terms of proarrhythmic potential prediction ( Jeong et al, 2022 ), can be continuously derived and is not dependent on the temporal discretization.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Second, timing offsets, for example between stimuli in the data to be fitted and the training data, can be accounted for using t 0 in (3) without retraining. Last but not least, the transmembrane potential gradient , recently highlighted in terms of proarrhythmic potential prediction ( Jeong et al, 2022 ), can be continuously derived and is not dependent on the temporal discretization.…”
Section: Discussionmentioning
confidence: 99%
“…Last but not least, the transmembrane potential gradient , recently highlighted in terms of proarrhythmic potential prediction [Jeong et al, 2022 ], can be continuously derived and is not dependent on the temporal discretization.…”
Section: Emulatormentioning
confidence: 99%
“…between stimuli in the data to be fitted and the training data, can be accounted for using t 0 in (3) without retraining. Last but not least, the transmem-brane potential gradient ∂Vm ∂t , recently highlighted in terms of proarrhythmic potential prediction [Jeong et al, 2022], can be continuously derived and is not dependent on the temporal discretization.…”
Section: Emulatormentioning
confidence: 99%
“…To evaluate these risk factors, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has published S7B and E14 guidelines, which provide a framework for predicting cardiotoxicity assessment for drugs ( Cavero and Crumb, 2005 ). Unfortunately, the low specificity of ICH S7B/E14 leads to the undesirable regulation of drugs that are unlikely to cause cardiac arrhythmias ( Jeong et al, 2022 ). This is typically understood to result from focusing on only one of the many ion channels governing action potential (AP) formation ( Colatsky et al, 2016 ; Jeong et al, 2022 ).…”
Section: Introductionmentioning
confidence: 99%
“…Unfortunately, the low specificity of ICH S7B/E14 leads to the undesirable regulation of drugs that are unlikely to cause cardiac arrhythmias ( Jeong et al, 2022 ). This is typically understood to result from focusing on only one of the many ion channels governing action potential (AP) formation ( Colatsky et al, 2016 ; Jeong et al, 2022 ). To resolve this issue, the Comprehensive in vitro Proarrhythmia Assay (CiPA) project was proposed by the US Food and Drug Administration (FDA) and has grown into an international research project with the participation of the FDA and various researchers led by pharmaceutical companies.…”
Section: Introductionmentioning
confidence: 99%