Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable
Computational models of cardiac electrophysiology provided insights into arrhythmogenesis and paved the way towards tailored therapies in the last years. To fully leverage in-silico models in future research, these models need to be adapted to reflect pathologies, genetic alterations, or pharmacolog...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-01-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fbioe.2015.00209/full |
| _version_ | 1818479787929239552 |
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| author | Axel eLoewe Mathias eWilhelms Jochen eSchmid Mathias J. Krause Fathima eFischer Dierk eThomas Eberhard P. Scholz Olaf eDössel Gunnar eSeemann |
| author_facet | Axel eLoewe Mathias eWilhelms Jochen eSchmid Mathias J. Krause Fathima eFischer Dierk eThomas Eberhard P. Scholz Olaf eDössel Gunnar eSeemann |
| author_sort | Axel eLoewe |
| collection | DOAJ |
| description | Computational models of cardiac electrophysiology provided insights into arrhythmogenesis and paved the way towards tailored therapies in the last years. To fully leverage in-silico models in future research, these models need to be adapted to reflect pathologies, genetic alterations, or pharmacological effects, however. A common approach is to leave the structure of established models unaltered and estimate the values of a set of parameters. Today's high-throughput patch clamp data acquisition methods require robust, unsupervised algorithms that estimate parameters both accurate and reliably.In this work, two classes of optimization approaches are evaluated: gradient-based trust-region reflective and derivative-free particle swarm algorithms. Using synthetic input data and different ion current formulations from the Courtemanche et al. electrophysiological model of human atrial myocytes, we show that none of the two schemes alone succeeds to meet all requirements. Sequential combination of the two algorithms did improve the performance to some extent but not satisfactorily. Thus, we propose a novel hybrid approach coupling the two algorithms in each iteration. This hybrid approach yielded very accurate estimates with minimal dependency on the initial guess using synthetic input data for which a ground truth parameter set exists. When applied to measured data, the hybrid approach yielded the best fit, again with minimal variation. Using the proposed algorithm, a single run is sufficient to estimate the parameters. The degree of superiority over the other investigated algorithms in terms of accuracy and robustness depended on the type of current. In contrast to the non-hybrid approaches, the proposed method proved to be optimal for data of arbitrary signal to noise ratio. The hybrid algorithm proposed in this work provides an important tool to integrate experimental data into computational models both accurately and robustly allowing to assess the often non-intuitive consequences of ion channel-level changes on higher levels of integration. |
| first_indexed | 2024-12-10T11:15:22Z |
| format | Article |
| id | doaj.art-a573e6c9a87d49b6827dd09c2712d982 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-10T11:15:22Z |
| publishDate | 2016-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-a573e6c9a87d49b6827dd09c2712d9822022-12-22T01:51:13ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852016-01-01310.3389/fbioe.2015.00209170237Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliableAxel eLoewe0Mathias eWilhelms1Jochen eSchmid2Mathias J. Krause3Fathima eFischer4Dierk eThomas5Eberhard P. Scholz6Olaf eDössel7Gunnar eSeemann8Karlsruhe Institute of Technology (KIT)Karlsruhe Institute of Technology (KIT)Karlsruhe Institute of Technology (KIT)Karlsruhe Institute of Technology (KIT)University Hospital HeidelbergUniversity Hospital HeidelbergUniversity Hospital HeidelbergKarlsruhe Institute of Technology (KIT)Karlsruhe Institute of Technology (KIT)Computational models of cardiac electrophysiology provided insights into arrhythmogenesis and paved the way towards tailored therapies in the last years. To fully leverage in-silico models in future research, these models need to be adapted to reflect pathologies, genetic alterations, or pharmacological effects, however. A common approach is to leave the structure of established models unaltered and estimate the values of a set of parameters. Today's high-throughput patch clamp data acquisition methods require robust, unsupervised algorithms that estimate parameters both accurate and reliably.In this work, two classes of optimization approaches are evaluated: gradient-based trust-region reflective and derivative-free particle swarm algorithms. Using synthetic input data and different ion current formulations from the Courtemanche et al. electrophysiological model of human atrial myocytes, we show that none of the two schemes alone succeeds to meet all requirements. Sequential combination of the two algorithms did improve the performance to some extent but not satisfactorily. Thus, we propose a novel hybrid approach coupling the two algorithms in each iteration. This hybrid approach yielded very accurate estimates with minimal dependency on the initial guess using synthetic input data for which a ground truth parameter set exists. When applied to measured data, the hybrid approach yielded the best fit, again with minimal variation. Using the proposed algorithm, a single run is sufficient to estimate the parameters. The degree of superiority over the other investigated algorithms in terms of accuracy and robustness depended on the type of current. In contrast to the non-hybrid approaches, the proposed method proved to be optimal for data of arbitrary signal to noise ratio. The hybrid algorithm proposed in this work provides an important tool to integrate experimental data into computational models both accurately and robustly allowing to assess the often non-intuitive consequences of ion channel-level changes on higher levels of integration.http://journal.frontiersin.org/Journal/10.3389/fbioe.2015.00209/fullElectrophysiologypatch clampparameter estimationionic currentsParticle Swarm Optimizationhybrid optimzation |
| spellingShingle | Axel eLoewe Mathias eWilhelms Jochen eSchmid Mathias J. Krause Fathima eFischer Dierk eThomas Eberhard P. Scholz Olaf eDössel Gunnar eSeemann Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable Frontiers in Bioengineering and Biotechnology Electrophysiology patch clamp parameter estimation ionic currents Particle Swarm Optimization hybrid optimzation |
| title | Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable |
| title_full | Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable |
| title_fullStr | Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable |
| title_full_unstemmed | Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable |
| title_short | Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable |
| title_sort | parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable |
| topic | Electrophysiology patch clamp parameter estimation ionic currents Particle Swarm Optimization hybrid optimzation |
| url | http://journal.frontiersin.org/Journal/10.3389/fbioe.2015.00209/full |
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