Application of machine learning to improve the efficiency of electrophysiological simulations used for the prediction of drug-induced ventricular arrhythmia

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  • dc.contributor.author Rodríguez-Belenguer, Pablo
  • dc.contributor.author Kopańska, Karolina
  • dc.contributor.author Llopis-Lorente, Jordi
  • dc.contributor.author Trenor, Beatriz
  • dc.contributor.author Saiz, Javier
  • dc.contributor.author Pastor Maeso, Manuel
  • dc.date.accessioned 2023-03-14T07:14:48Z
  • dc.date.available 2023-03-14T07:14:48Z
  • dc.date.issued 2023
  • dc.description.abstract Background and objective: In silico prediction of drug-induced ventricular arrhythmia often requires computationally intensive simulations, making its application tedious and non-interactive. This inconvenience can be mitigated using matrices of precomputed simulation results, allowing instantaneous computation of biomarkers such as action potential duration at 90% of the repolarisation (APD90). However, preparing such matrices can be computationally intensive for the method developers, limiting the range of simulated conditions. In this work, we aim to optimise the generation of these matrices so that they can be obtained with less effort and for a broader range of input values. Methods: Machine learning methods were applied, building models trained with only a small fraction of the originally simulated results. The predictive performances of the models were assessed by comparing their predicted values with the actual simulation results, using percentual mean absolute error and mean relative error, as well as the percentage of data with a relative error below 5%. Results: Our method obtained highly accurate estimations of the original values, leading to a nearly one hundred-fold decrease in computation time. This method also allows precomputing more complex matrices, describing the effect of more ion channels on the APD90. The best results were obtained by applying Support Vector Machine models, which yielded errors below 1% in most cases. This approach was further validated by predicting the APD90 of a set of 12 CiPA compounds and exporting the optimal settings for predicting APD90 using a different set of ion channels, always with satisfactory results. Conclusions: The proposed method effectively reduces the computational effort required to generate matrices of precomputed electrophysiological simulation values. The same approach can be applied in other fields where computationally costly simulations are applied repeatedly using slightly different input values.
  • dc.description.sponsorship The authors received funding from the eTRANSAFE project, Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777365, supported from European Union's Horizon 2020 and the EFPIA. We also received funding from the SimCardioTest supported by European Union’s Horizon 2020 research and innovation programme under grant agreement No 101016496. J.L.L. is being funded by the Ministerio de Ciencia, Innovacion y Universidades for the “Formacion de Profesorado Universitario” (Grant Reference: FPU18/01659). The work was also partially support by the Dirección General de Política Científica de la Generalitat Valenciana (PROMETEO/ 2020/043).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Rodríguez-Belenguer P, Kopańska K, Llopis-Lorente J, Trenor B, Saiz J, Pastor M. Application of machine learning to improve the efficiency of electrophysiological simulations used for the prediction of drug-induced ventricular arrhythmia. Comput Methods Programs Biomed. 2023 Mar;230:107345. DOI: 10.1016/j.cmpb.2023.107345
  • dc.identifier.doi http://dx.doi.org/10.1016/j.cmpb.2023.107345
  • dc.identifier.issn 0169-2607
  • dc.identifier.uri http://hdl.handle.net/10230/56212
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Comput Methods Programs Biomed. 2023 Mar;230:107345
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/777365
  • dc.rights © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.title Application of machine learning to improve the efficiency of electrophysiological simulations used for the prediction of drug-induced ventricular arrhythmia
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Departament de Medicina i Ciències de la Vida)
Articles (Hospital del Mar Research Institute)
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