Ten simple rules for training scientists to make better software
(2024)
Journal Article
Gallagher, K., Creswell, R., Lambert, B., Robinson, M., Lei, C. L., Mirams, G. R., & Gavaghan, D. J. (2024). Ten simple rules for training scientists to make better software. PLoS Computational Biology, 20(9), Article e1012410. https://doi.org/10.1371/journal.pcbi.1012410
All Outputs (95)
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/10.1080/29937574.2024.2375494Voltage-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, 1(1), Article 2375494. https://doi.org/10.1080/29937574.2024.2375494Voltage-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.
Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies (2024)
Journal Article
Grandits, T., Augustin, C. M., Haase, G., Jost, N., Mirams, G. R., Niederer, S. A., …Jung, A. (2024). Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies. eLife, 12, Article RP91911. https://doi.org/10.7554/elife.91911.3Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimen... Read More about Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies.
Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation (2024)
Journal Article
Ayagama, T., Charles, P. D., Bose, S. J., Boland, B., Priestman, D. A., Aston, D., …Burton, R. A. (2024). Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation. iScience, 27(6), Article 109609. https://doi.org/10.1016/j.isci.2024.109609Endolysosomes (EL) are known for their role in regulating both intracellular trafficking and proteostasis. EL facilitate the elimination of damaged membranes, protein aggregates, membranous organelles and play an important role in calcium signaling.... Read More about Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation.
Understanding the impact of numerical solvers on inference for differential equation models (2024)
Journal Article
Creswell, R., Shepherd, K. M., Lambert, B., Mirams, G. R., Lei, C. L., Tavener, S., Robinson, M., & Gavaghan, D. J. (2024). Understanding the impact of numerical solvers on inference for differential equation models. Journal of the Royal Society, Interface, 21(212), Article 20230369. https://doi.org/10.1098/rsif.2023.0369Most ordinary differential equation (ODE) models used to describe biological or physical systems must be solved approximately using numerical methods. Perniciously, even those solvers that seem sufficiently accurate for the forward problem, i.e. for... Read More about Understanding the impact of numerical solvers on inference for differential equation models.
Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes (2024)
Journal Article
Raniga, K., Nasir, A., Vo, N. T., Vaidyanathan, R., Dickerson, S., Hilcove, S., Mosqueira, D., Mirams, G. R., Clements, P., Hicks, R., Pointon, A., Stebbeds, W., Francis, J., & Denning, C. (2024). Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes. Cell Stem Cell, 31(3), 292-311. https://doi.org/10.1016/j.stem.2024.01.007Advances in hiPSC isolation and reprogramming and hPSC-CM differentiation have prompted their therapeutic application and utilization for evaluating potential cardiovascular safety liabilities. In this perspective, we showcase key efforts toward the... Read More about Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes.
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/s11538-023-01224-6When 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.
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.16250Background 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.
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/euad243Aims
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.2023.107690Background 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.
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.2023.107690Background 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.
Using many different voltage protocols to characterise discrepancy in mathematical ion channel models (2023)
Journal Article
Shuttleworth, J. G., Lok Lei, C., Windley, M., Hill, A. P., Perry, M. D., Preston, S., & Mirams, G. R. (2023). Using many different voltage protocols to characterise discrepancy in mathematical ion channel models. Biophysical Journal, 122(3, Suppl. 1), 242a. https://doi.org/10.1016/j.bpj.2022.11.1415The Kv11.1 protein encoded by the hERG gene forms the primary subunit of a voltage-sensitive ion channel responsible for IKr in cardiomyocytes. Mathematical models of the macroscopic current are fitted to data from patch-clamp experiments - in which... Read More about Using many different voltage protocols to characterise discrepancy in mathematical ion channel models.
Uncertainty and error in SARS-CoV-2 epidemiological parameters inferred from population-level epidemic models (2022)
Journal Article
Whittaker, D. G., Herrera-Reyes, A. D., Hendrix, M., Owen, M. R., Band, L. R., Mirams, G. R., …Preston, S. P. (2023). Uncertainty and error in SARS-CoV-2 epidemiological parameters inferred from population-level epidemic models. Journal of Theoretical Biology, 558, Article 111337. https://doi.org/10.1016/j.jtbi.2022.111337During the SARS-CoV2 pandemic, epidemic models have been central to policy-making. Public health responses have been shaped by model-based projections and inferences, especially related to the impact of various non-pharmaceutical interventions. Accom... Read More about Uncertainty and error in SARS-CoV-2 epidemiological parameters inferred from population-level epidemic models.
Nuanced Interactions between AKAP79 and STIM1 with Orai1 Ca 2+ Channels at Endoplasmic Reticulum-Plasma Membrane Junctions Sustain NFAT Activation (2022)
Journal Article
Lin, Y.-P., Scappini, E., Landaverde, C., Parekh-Glitsch, F., Tucker, C. J., Mirams, G. R., & Parekh, A. B. (2022). Nuanced Interactions between AKAP79 and STIM1 with Orai1 Ca 2+ Channels at Endoplasmic Reticulum-Plasma Membrane Junctions Sustain NFAT Activation. Molecular and Cellular Biology, 42(11), Article e00175-22. https://doi.org/10.1128/mcb.00175-22A-kinase anchoring protein 79 (AKAP79) is a human scaffolding protein that organizes Ca2+/calmodulin-dependent protein phosphatase calcineurin, calmodulin, cAMP-dependent protein kinase, protein kinase C, and the transcription factor nuclear factor o... Read More about Nuanced Interactions between AKAP79 and STIM1 with Orai1 Ca 2+ Channels at Endoplasmic Reticulum-Plasma Membrane Junctions Sustain NFAT Activation.
Models of the cardiac L-type calcium current: A quantitative review (2022)
Journal Article
Agrawal, A., Wang, K., Polonchuk, L., Cooper, J., Hendrix, M., Gavaghan, D. J., …Clerx, M. (2022). Models of the cardiac L-type calcium current: A quantitative review. Wiley Interdisciplinary Reviews: Mechanisms of Disease, 15(1), Article e1581. https://doi.org/10.1002/wsbm.1581The L-type calcium current ((Formula presented.)) plays a critical role in cardiac electrophysiology, and models of (Formula presented.) are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modeling (Form... Read More about Models of the cardiac L-type calcium current: A quantitative review.
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.2022.0193Mathematical 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.
cellmlmanip and chaste_codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians (2022)
Journal Article
Hendrix, M., Clerx, M., Tamuri, A. U., Keating, S. M., Johnstone, R. H., Cooper, J., & Mirams, G. R. (2022). cellmlmanip and chaste_codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians. Wellcome Open Research, 6, Article 261. https://doi.org/10.12688/wellcomeopenres.17206.2Hundreds of different mathematical models have been proposed for describing electrophysiology of various cell types. These models are quite complex (nonlinear systems of typically tens of ODEs and sometimes hundreds of parameters) and software packag... Read More about cellmlmanip and chaste_codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians.
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.2022.879035Computational 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.
chaste codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians (2022)
Journal Article
Hendrix, M., Clerx, M., Tamuri, A. U., Keating, S. M., Johnstone, R. H., Cooper, J., & Mirams, G. R. (2022). chaste codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians. Wellcome Open Research, 6, Article 261. https://doi.org/10.12688/wellcomeopenres.17206.1Hundreds of different mathematical models have been proposed for describing electrophysiology of various cell types. These models are quite complex (nonlinear systems of typically tens of ODEs and sometimes hundreds of parameters) and software packag... Read More about chaste codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians.