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Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics (2023)
Journal Article
Shuttleworth, J. G., Lei, C. L., Whittaker, D. G., Windley, M. J., Hill, A. P., Preston, S. P., & Mirams, G. R. (2024). Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics. Bulletin of Mathematical Biology, 86(1), Article 2. https://doi.org/10.1007/s11538-023-01224-6

When using mathematical models to make quantitative predictions for clinical or industrial use, it is important that predictions come with a reliable estimate of their accuracy (uncertainty quantification). Because models of complex biological system... Read More about Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics.

Ion channel model reduction using manifold boundaries (2022)
Journal Article
Whittaker, D. G., Wang, J., Shuttleworth, J., Venkateshappa, R., Kemp, J. M., Claydon, T. W., & Mirams, G. R. (2022). Ion channel model reduction using manifold boundaries. Journal of the Royal Society, Interface, 19(193), Article 20220193. https://doi.org/10.1098/rsif.2022.0193

Mathematical models of voltage-gated ion channels are used in basic research, industrial and clinical settings. These models range in complexity, but typically contain numerous variables representing the proportion of channels in a given state, and p... Read More about Ion channel model reduction using manifold boundaries.

A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer (2021)
Journal Article
Lei, C. L., Fabbri, A., Whittaker, D. G., Clerx, M., Windley, M. J., Hill, A. P., …de Boer, T. P. (2021). A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer. Wellcome Open Research, 5, 1-34. https://doi.org/10.12688/wellcomeopenres.15968.2

Automated patch-clamp platforms are widely used and vital tools in both academia and industry to enable high-throughput studies such as drug screening. A leak current to ground occurs whenever the seal between a pipette and cell (or internal solution... Read More about A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer.

Electrophysiological characterization of the hERG R56Q LQTS variant and targeted rescue by the activator RPR260243 (2021)
Journal Article
Kemp, J. M., Whittaker, D. G., Venkateshappa, R., Pang, Z. K., Johal, R., Sergeev, V., …Claydon, T. W. (2021). Electrophysiological characterization of the hERG R56Q LQTS variant and targeted rescue by the activator RPR260243. Journal of General Physiology, 153(10), Article e202112923. https://doi.org/10.1085/jgp.202112923

Human Ether-à-go-go (hERG) channels contribute to cardiac repolarization, and inherited variants or drug block are associated with long QT syndrome type 2 (LQTS2) and arrhythmia. Therefore, hERG activator compounds present a therapeutic opportunity f... Read More about Electrophysiological characterization of the hERG R56Q LQTS variant and targeted rescue by the activator RPR260243.

Cardiac TdP risk stratification modelling of anti-infective compounds including chloroquine and hydroxychloroquine (2021)
Journal Article
Whittaker, D. G., Capel, R. A., Hendrix, M., Chan, X. H. S., Herring, N., White, N. J., …Burton, R. A. B. (2021). Cardiac TdP risk stratification modelling of anti-infective compounds including chloroquine and hydroxychloroquine. Royal Society Open Science, 8(4), https://doi.org/10.1098/rsos.210235

Hydroxychloroquine (HCQ), the hydroxyl derivative of chloroquine (CQ), is widely used in the treatment of rheumatological conditions (systemic lupus erythematosus, rheumatoid arthritis) and is being studied for the treatment and prevention of COVID-1... Read More about Cardiac TdP risk stratification modelling of anti-infective compounds including chloroquine and hydroxychloroquine.

A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer [version 1; peer review: 2 approved with reservations] (2020)
Journal Article
Lei, C. L., Fabbri, A., Whittaker, D. G., Clerx, M., Windley, M. J., Hill, A. P., …de Boer, T. P. (2020). A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer [version 1; peer review: 2 approved with reservations]. Wellcome Open Research, 5, Article 152. https://doi.org/10.12688/wellcomeopenres.15968.1

Automated patch-clamp platforms are widely used and vital tools in both academia and industry to enable high-throughput studies such as drug screening. A leak current to ground occurs whenever the seal between a pipette and cell (or internal solution... Read More about A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer [version 1; peer review: 2 approved with reservations].

Considering discrepancy when calibrating a mechanistic electrophysiology model (2020)
Journal Article
Wilkinson, R. D., Worden, K., Walmsley, J., Dos Santos, R. W., Riabiz, M., Pathmanathan, P., …Whittaker, D. G. (2020). Considering discrepancy when calibrating a mechanistic electrophysiology model. Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, 378(2173), 20190349. https://doi.org/10.1098/rsta.2019.0349

Uncertainty quantification (UQ) is a vital step in using mathematical models and simulations to take decisions. The field of cardiac simulation has begun to explore and adopt UQ methods to characterize uncertainty in model inputs and how that propaga... Read More about Considering discrepancy when calibrating a mechanistic electrophysiology model.

Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments (2020)
Journal Article
Clerx, M., Lei, C. L., Whittaker, D. G., Gavaghan, D. J., de Boer, T. P., & Mirams, G. R. (2020). Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments. Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, 378(2173), Article 20190348. https://doi.org/10.1098/rsta.2019.0348

Mathematical models of ion channels, which constitute indispensable components of action potential models, are commonly constructed by fitting to whole-cell patch-clamp data. In a previous study, we fitted cell-specific models to hERG1a (Kv11.1) reco... Read More about Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments.

Calibration of ionic and cellular cardiac electrophysiology models (2020)
Journal Article
Whittaker, D. G., Clerx, M., Lei, C. L., Christini, D. J., & Mirams, G. R. (2020). Calibration of ionic and cellular cardiac electrophysiology models. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 12(4), https://doi.org/10.1002/wsbm.1482

© 2020 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc. Cardiac electrophysiology models are among the most mature and well-studied mathematical models of biological systems. This maturity is bringing new challenge... Read More about Calibration of ionic and cellular cardiac electrophysiology models.