Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods
As cardiac cell models become increasingly complex, a correspondingly complex ‘genealogy’ of inherited parameter values has also emerged. The result has been the loss of a direct link between model parameters and experimental data, limiting both reproducibility and the ability to re-fit to new data....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2015-01-01
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| Series: | Royal Society Open Science |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.150499 |
| _version_ | 1819006333119102976 |
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| author | Aidan C. Daly David J. Gavaghan Chris Holmes Jonathan Cooper |
| author_facet | Aidan C. Daly David J. Gavaghan Chris Holmes Jonathan Cooper |
| author_sort | Aidan C. Daly |
| collection | DOAJ |
| description | As cardiac cell models become increasingly complex, a correspondingly complex ‘genealogy’ of inherited parameter values has also emerged. The result has been the loss of a direct link between model parameters and experimental data, limiting both reproducibility and the ability to re-fit to new data. We examine the ability of approximate Bayesian computation (ABC) to infer parameter distributions in the seminal action potential model of Hodgkin and Huxley, for which an immediate and documented connection to experimental results exists. The ability of ABC to produce tight posteriors around the reported values for the gating rates of sodium and potassium ion channels validates the precision of this early work, while the highly variable posteriors around certain voltage dependency parameters suggests that voltage clamp experiments alone are insufficient to constrain the full model. Despite this, Hodgkin and Huxley's estimates are shown to be competitive with those produced by ABC, and the variable behaviour of posterior parametrized models under complex voltage protocols suggests that with additional data the model could be fully constrained. This work will provide the starting point for a full identifiability analysis of commonly used cardiac models, as well as a template for informative, data-driven parametrization of newly proposed models. |
| first_indexed | 2024-12-21T00:07:01Z |
| format | Article |
| id | doaj.art-d8b906e7047f43858c2ae84f3e8033bb |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-12-21T00:07:01Z |
| publishDate | 2015-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-d8b906e7047f43858c2ae84f3e8033bb2022-12-21T19:22:27ZengThe Royal SocietyRoyal Society Open Science2054-57032015-01-0121210.1098/rsos.150499150499Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methodsAidan C. DalyDavid J. GavaghanChris HolmesJonathan CooperAs cardiac cell models become increasingly complex, a correspondingly complex ‘genealogy’ of inherited parameter values has also emerged. The result has been the loss of a direct link between model parameters and experimental data, limiting both reproducibility and the ability to re-fit to new data. We examine the ability of approximate Bayesian computation (ABC) to infer parameter distributions in the seminal action potential model of Hodgkin and Huxley, for which an immediate and documented connection to experimental results exists. The ability of ABC to produce tight posteriors around the reported values for the gating rates of sodium and potassium ion channels validates the precision of this early work, while the highly variable posteriors around certain voltage dependency parameters suggests that voltage clamp experiments alone are insufficient to constrain the full model. Despite this, Hodgkin and Huxley's estimates are shown to be competitive with those produced by ABC, and the variable behaviour of posterior parametrized models under complex voltage protocols suggests that with additional data the model could be fully constrained. This work will provide the starting point for a full identifiability analysis of commonly used cardiac models, as well as a template for informative, data-driven parametrization of newly proposed models.https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.150499hodgkin huxleyapproximate bayesian computationidentifiabilitycardiac cell modellingfunctional curationparameter fitting |
| spellingShingle | Aidan C. Daly David J. Gavaghan Chris Holmes Jonathan Cooper Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods Royal Society Open Science hodgkin huxley approximate bayesian computation identifiability cardiac cell modelling functional curation parameter fitting |
| title | Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods |
| title_full | Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods |
| title_fullStr | Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods |
| title_full_unstemmed | Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods |
| title_short | Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods |
| title_sort | hodgkin huxley revisited reparametrization and identifiability analysis of the classic action potential model with approximate bayesian methods |
| topic | hodgkin huxley approximate bayesian computation identifiability cardiac cell modelling functional curation parameter fitting |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.150499 |
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