Probabilistic Inference on Noisy Time Series (PINTS)

Clerx, Michael; Robinson, Martin; Lambert, Ben; Lei, Chon Lok; Ghosh, Sanmitra; Mirams, Gary R.; Gavaghan, David J.

doi:10.5334/jors.252

Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics (2024)
Journal Article
Mirams, G. R., Clerx, M., Whittaker, D. G., & Lei, C. L. (2024). Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics. Mathematics in Medical and Life Sciences, 1(1), Article 2375494. https://doi.org/10.1080/29937574.2024.2375494

Voltage-clamp waveforms are imposed in the patch-clamp electrophysiology technique to provoke ion currents, the particular waveform that is used is known as the “voltage-clamp protocol”. Designing protocols to probe and quantify how gating for a part... Read More about Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics.

Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics (2024)
Journal Article
Mirams, G. R., Clerx, M., Whittaker, D. G., & Lei, C. L. (2024). Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics. Mathematics in Medical and Life Sciences, 2024(1), Article 2375494. https://doi.org/10.1080/29937574.2024.2375494

Voltage-clamp waveforms are imposed in the patch-clamp electrophysiology technique to provoke ion currents, the particular waveform that is used is known as the “voltage-clamp protocol”. Designing protocols to probe and quantify how gating for a part... Read More about Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics.

Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings (2023)
Journal Article
Clark, A. P., Clerx, M., Wei, S., Lei, C. L., de Boer, T. P., Mirams, G. R., …Krogh-Madsen, T. (2023). Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings. EP-Europace, 25(9), Article euad243. https://doi.org/10.1093/europace/euad243

Aims
Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have become an essential tool to study arrhythmia mechanisms. Much of the foundational work on these cells, as well as the computational models built from the resultant data,... Read More about Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings.

Model-driven optimal experimental design for calibrating cardiac electrophysiology models (2023)
Journal Article
Lei, C. L., Clerx, M., Gavaghan, D. J., & Mirams, G. R. (2023). Model-driven optimal experimental design for calibrating cardiac electrophysiology models. Computer Methods and Programs in Biomedicine, 240, Article 107690. https://doi.org/10.1016/j.cmpb.2023.107690

Background and Objective: Models of the cardiomyocyte action potential have contributed immensely to the understanding of heart function, pathophysiology, and the origin of heart rhythm disturbances. However, action potential models are highly nonlin... Read More about Model-driven optimal experimental design for calibrating cardiac electrophysiology models.

Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment (2023)
Journal Article
Farm, H. J., Clerx, M., Cooper, F., Polonchuk, L., Wang, K., Gavaghan, D. J., & Lei, C. L. (2023). Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment. Frontiers in Pharmacology, 14, Article 1110555. https://doi.org/10.3389/fphar.2023.1110555

Reduction of the rapid delayed rectifier potassium current (IKr) via drug binding to the human Ether-à-go-go-Related Gene (hERG) channel is a well recognised mechanism that can contribute to an increased risk of Torsades de Pointes. Mathematical mode... Read More about Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment.

Autocorrelated measurement processes and inference for ordinary differential equation models of biological systems (2023)
Journal Article
Lambert, B., Lei, C. L., Robinson, M., Clerx, M., Creswell, R., Ghosh, S., …Gavaghan, D. J. (2023). Autocorrelated measurement processes and inference for ordinary differential equation models of biological systems. Journal of the Royal Society. Interface, 20(199), 20220725. https://doi.org/10.1098/rsif.2022.0725

Ordinary differential equation models are used to describe dynamic processes across biology. To perform likelihood-based parameter inference on these models, it is necessary to specify a statistical process representing the contribution of factors no... Read More about Autocorrelated measurement processes and inference for ordinary differential equation models of biological systems.

A Parameter Representing Missing Charge Should Be Considered when Calibrating Action Potential Models (2022)
Journal Article
Barral, Y. H. M., Shuttleworth, J., Clerx, M., Whittaker, D. G., Wang, K., Polonchuk, L., …Mirams, G. R. (2022). A Parameter Representing Missing Charge Should Be Considered when Calibrating Action Potential Models. Frontiers in Physiology, 13, Article 879035. https://doi.org/10.3389/fphys.2022.879035

Computational models of the electrical potential across a cell membrane are longstanding and vital tools in electrophysiology research and applications. These models describe how ionic currents, internal fluxes, and buffering interact to determine me... Read More about A Parameter Representing Missing Charge Should Be Considered when Calibrating Action Potential Models.

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., Mirams, G. R., & 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.

Immediate and Delayed Response of Simulated Human Atrial Myocytes to Clinically-Relevant Hypokalemia (2021)
Journal Article
Clerx, M., Mirams, G. R., Rogers, A. J., Narayan, S. M., & Giles, W. R. (2021). Immediate and Delayed Response of Simulated Human Atrial Myocytes to Clinically-Relevant Hypokalemia. Frontiers in Physiology, 12, Article 651162. https://doi.org/10.3389/fphys.2021.651162

Although plasma electrolyte levels are quickly and precisely regulated in the mammalian cardiovascular system, even small transient changes in K+, Na+, Ca2+, and/or Mg2+ can significantly alter physiological responses in the heart, blood vessels, and... Read More about Immediate and Delayed Response of Simulated Human Atrial Myocytes to Clinically-Relevant Hypokalemia.

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].

CellML 2.0 (2020)
Journal Article
Clerx, M., Cooling, M. T., Cooper, J., Garny, A., Moyle, K., Nickerson, D. P., …Sorby, H. (2020). CellML 2.0. Journal of Integrative Bioinformatics, 17(2-3), https://doi.org/10.1515/jib-2020-0021

We present here CellML 2.0, an XML-based language for describing and exchanging mathematical models of physiological systems. MathML embedded in CellML documents is used to define the underlying mathematics of models. Models consist of a network of r... Read More about CellML 2.0.

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.

Rapid characterisation of hERG channel kinetics II: temperature dependence (2019)
Journal Article
Lei, C. L., Clerx, M., Beattie, K. A., Melgari, D., Hancox, J. C., Gavaghan, D. J., …Mirams, G. R. (2019). Rapid characterisation of hERG channel kinetics II: temperature dependence. Biophysical Journal, 117(12), 2455-2470. https://doi.org/10.1101/609719

Ion channel behavior can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. These temperature-dependent changes in voltage-dependent ion channel... Read More about Rapid characterisation of hERG channel kinetics II: temperature dependence.

Four Ways to Fit an Ion Channel Model (2019)
Journal Article
Clerx, M., Beattie, K., Gavaghan, D., & Mirams, G. (2019). Four Ways to Fit an Ion Channel Model. Biophysical Journal, 117(12), 2420-2437. https://doi.org/10.1016/j.bpj.2019.08.001

© 2019 Biophysical Society Mathematical models of ionic currents are used to study the electrophysiology of the heart, brain, gut, and several other organs. Increasingly, these models are being used predictively in the clinic, for example, to predict... Read More about Four Ways to Fit an Ion Channel Model.

Rapid Characterization of hERG Channel Kinetics I: Using an Automated High-Throughput System (2019)
Journal Article
Lei, C. L., Clerx, M., Gavaghan, D. J., Polonchuk, L., Mirams, G. R., & Wang, K. (2019). Rapid Characterization of hERG Channel Kinetics I: Using an Automated High-Throughput System. Biophysical Journal, 117(12), 2438-2454. https://doi.org/10.1016/j.bpj.2019.07.029

Predicting how pharmaceuticals may affect heart rhythm is a crucial step in drug-development, and requires a deep understanding of a compound’s action on ion channels. In vitro hERG-channel current recordings are an important step in evaluating the p... Read More about Rapid Characterization of hERG Channel Kinetics I: Using an Automated High-Throughput System.

Probabilistic Inference on Noisy Time Series (PINTS) (2019)
Journal Article
Clerx, M., Robinson, M., Lambert, B., Lei, C. L., Ghosh, S., Mirams, G. R., & Gavaghan, D. J. (2019). Probabilistic Inference on Noisy Time Series (PINTS). Journal of Open Research Software, 7(1), 23. https://doi.org/10.5334/jors.252

Time series models are ubiquitous in science, arising in any situation where researchers seek to understand how a system’s behaviour changes over time. A key problem in time series modelling is inference; determining properties of the underlying syst... Read More about Probabilistic Inference on Noisy Time Series (PINTS).

All Outputs (17)