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Outputs (20)

Reproducible model development in the Cardiac Electrophysiology Web Lab (2018)
Journal Article
Daly, A. C., Clerx, M., Beattie, K. A., Cooper, J., Gavaghan, D. J., & Mirams, G. R. (2018). Reproducible model development in the Cardiac Electrophysiology Web Lab. Progress in Biophysics and Molecular Biology, 139, 3-14. https://doi.org/10.1016/j.pbiomolbio.2018.05.011

The modelling of the electrophysiology of cardiac cells is one of the most mature areas of systems biology. This extended concentration of research effort brings with it new challenges, foremost among which is that of choosing which of these models i... Read More about Reproducible model development in the Cardiac Electrophysiology Web Lab.

Representation of multiple cellular phenotypes within tissue-level simulations of cardiac electrophysiology (2018)
Journal Article
Bowler, L. A., Gavaghan, D. J., Mirams, G. R., & Whiteley, J. P. (2019). Representation of multiple cellular phenotypes within tissue-level simulations of cardiac electrophysiology. Bulletin of Mathematical Biology, 81(1), 7–38. https://doi.org/10.1007/s11538-018-0516-1

Distinct electrophysiological phenotypes are exhibited 1 by biological cells that have differentiated into particular cell types. The usual approach when simulating the cardiac electrophysiology of tissue that includes different cell types is to mode... Read More about Representation of multiple cellular phenotypes within tissue-level simulations of cardiac electrophysiology.

Defining vitamin D status using multi-metabolite mathematical modelling: a pregnancy perspective (2019)
Journal Article
Beentjes, C., Taylor-King, J., Bayani, A., Davis, C., Dunster, J., Jabbari, S., …Tamblyn, J. (2019). Defining vitamin D status using multi-metabolite mathematical modelling: a pregnancy perspective. Journal of Steroid Biochemistry and Molecular Biology, 190, 152-160. https://doi.org/10.1016/j.jsbmb.2019.03.024

Vitamin D deficiency is linked to adverse pregnancy outcomes such as pre-eclampsia (PET) but remains defined by serum measurement of 25-hydroxyvitamin D3 (25(OH)D3) alone. To identify broader changes in vitamin D metabolism during normal and PET preg... Read More about Defining vitamin D status using multi-metabolite mathematical modelling: a pregnancy perspective.

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.

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.

Selective recruitment of different Ca2+-dependent transcription factors by STIM1-Orai1 channel clusters (2019)
Journal Article
Lin, Y., Bakowski, D., Mirams, G. R., & Parekh, A. B. (2019). Selective recruitment of different Ca2+-dependent transcription factors by STIM1-Orai1 channel clusters. Nature Communications, 10(1), Article 2516. https://doi.org/10.1038/s41467-019-10329-3

© 2019, The Author(s). Store-operated Ca2+ entry, involving endoplasmic reticulum Ca2+ sensing STIM proteins and plasma membrane Orai1 channels, is a widespread and evolutionary conserved Ca2+ influx pathway. This form of Ca2+ influx occurs at discre... Read More about Selective recruitment of different Ca2+-dependent transcription factors by STIM1-Orai1 channel clusters.

General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy (2019)
Journal Article
Li, Z., Mirams, G. R., Yoshinaga, T., Ridder, B. J., Han, X., Chen, J. E., …Strauss, D. G. (2020). General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy. Clinical Pharmacology and Therapeutics, 107(1), 102-111. https://doi.org/10.1002/cpt.1647

This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and... Read More about General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy.

Use of Patient Health Records to Quantify Drug-Related Pro-arrhythmic Risk (2020)
Journal Article
Davies, M. R., Martinec, M., Walls, R., Schwarz, R., Mirams, G. R., Wang, K., …Polonchuk, L. (2020). Use of Patient Health Records to Quantify Drug-Related Pro-arrhythmic Risk. Cell Reports Medicine, 1(5), Article 100076. https://doi.org/10.1016/j.xcrm.2020.100076

There is an increasing expectation that computational approaches may supplement existing human decision-making. Frontloading of models for cardiac safety prediction is no exception to this trend, and ongoing regulatory initiatives propose use of high... Read More about Use of Patient Health Records to Quantify Drug-Related Pro-arrhythmic Risk.

Development, Implementation and Testing of a Multicellular Dynamic Action Potential Clamp Simulator for Drug Cardiac Safety Assessment (2020)
Presentation / Conference Contribution
Camporesi, M., Bartolucci, C., Lei, C. L., Mirams, G. R., De Boer, T. P., & Severi, S. (2020). Development, Implementation and Testing of a Multicellular Dynamic Action Potential Clamp Simulator for Drug Cardiac Safety Assessment. . https://doi.org/10.22489/CinC.2020.416

© 2020 Creative Commons; the authors hold their copyright. As drugs can be multichannel blockers it is important to assess their cardiac safety taking into account multiple currents. In silico action potential (AP) models have been proposed for being... Read More about Development, Implementation and Testing of a Multicellular Dynamic Action Potential Clamp Simulator for Drug Cardiac Safety Assessment.

Neural Network Differential Equations For Ion Channel Modelling (2021)
Journal Article
Lei, C. L., & Mirams, G. R. (2021). Neural Network Differential Equations For Ion Channel Modelling. Frontiers in Physiology, 12, Article 708944. https://doi.org/10.3389/fphys.2021.708944

Mathematical models of cardiac ion channels have been widely used to study and predict the behaviour of ion currents. Typically models are built using biophysically-based mechanistic principles such as Hodgkin-Huxley or Markov state transitions. Thes... Read More about Neural Network Differential Equations For Ion Channel Modelling.

Exorcising Malthusian ghosts: Vaccinating the Nexus to advance integrated water, energy and food resource resilience (2021)
Journal Article
Kemp, P. S., Acuto, M., Larcom, S., Lumbroso, D., & Owen, M. R. (2022). Exorcising Malthusian ghosts: Vaccinating the Nexus to advance integrated water, energy and food resource resilience. Current Research in Environmental Sustainability, 4, Article 100108. https://doi.org/10.1016/j.crsust.2021.100108

Water-Energy-Food (WEF) Nexus interactions vary from seemingly negative and intractable wicked problems to opportunities for enhanced sustainability. The aim of this paper is to review the current state of understanding on WEF resource interactions a... Read More about Exorcising Malthusian ghosts: Vaccinating the Nexus to advance integrated water, energy and food resource resilience.

A Quantitative Systems Pharmacology Perspective on the Importance of Parameter Identifiability (2022)
Journal Article
Sher, A., Niederer, S. A., Mirams, G. R., Kirpichnikova, A., Allen, R., Pathmanathan, P., …Noble, D. (2022). A Quantitative Systems Pharmacology Perspective on the Importance of Parameter Identifiability. Bulletin of Mathematical Biology, 84(3), Article 39. https://doi.org/10.1007/s11538-021-00982-5

There is an inherent tension in Quantitative Systems Pharmacology (QSP) between the need to incorporate mathematical descriptions of complex physiology and drug targets with the necessity of developing robust, predictive and well-constrained models.... Read More about A Quantitative Systems Pharmacology Perspective on the Importance of Parameter Identifiability.

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.

Modelling the emergence of cities and urban patterning using coupled integro-differential equations (2022)
Journal Article
Whiteley, T. D., Avitabile, D., Siebers, P. O., Robinson, D., & Owen, M. R. (2022). Modelling the emergence of cities and urban patterning using coupled integro-differential equations. Journal of the Royal Society, Interface, 19(190), Article 20220176. https://doi.org/10.1098/rsif.2022.0176

Human residential population distributions show patterns of higher density clustering around local services such as shops and places of employment, displaying characteristic length scales; Fourier transforms and spatial autocorrelation show the lengt... Read More about Modelling the emergence of cities and urban patterning using coupled integro-differential equations.

The role of mathematical models in designing mechanopharmacological therapies for asthma (2022)
Journal Article
Irons, L., & Brook, B. S. (2022). The role of mathematical models in designing mechanopharmacological therapies for asthma. Frontiers in Systems Biology, 2, Article 929426. https://doi.org/10.3389/fsysb.2022.929426

Healthy lung function depends on a complex system of interactions which regulate the mechanical and biochemical environment of individual cells to the whole organ. Perturbations from these regulated processes give rise to significant lung dysfunction... Read More about The role of mathematical models in designing mechanopharmacological therapies for asthma.

The impact of uncertainty in hERG binding mechanism on in silico predictions of drug-induced proarrhythmic risk (2023)
Journal Article
Lei, C. L., Whittaker, D. G., & Mirams, G. R. (2024). The impact of uncertainty in hERG binding mechanism on in silico predictions of drug-induced proarrhythmic risk. British Journal of Pharmacology, 181(7), 987-1004. https://doi.org/10.1111/bph.16250

Background and Purpose Drug-induced reduction of the rapid delayed rectifier potassium current carried by the human Ether-à-go-go-Related Gene (hERG) channel is associated with increased risk of arrhythmias. Recent updates to drug safety regulatory... Read More about The impact of uncertainty in hERG binding mechanism on in silico predictions of drug-induced proarrhythmic risk.

Computational Cardiac Safety Testing (2023)
Book Chapter
Mirams, G. R. (2023). Computational Cardiac Safety Testing. In F. J. Hock, M. R. Gralinski, & M. K. Pugsley (Eds.), Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays (1-33). Springer. https://doi.org/10.1007/978-3-030-73317-9_137-1

In recent years, computational cardiac electrophysiology simulations using mathematical models have begun to be used in industrial and regulatory assessment of the proarrhythmic risk of candidate drug compounds. The aim of this chapter is to equip th... Read More about Computational Cardiac Safety Testing.