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Cellular cardiac electrophysiology modeling with Chaste and CellML (2015)
Journal Article
Cooper, J., Spiteri, R. J., & Mirams, G. R. (2015). Cellular cardiac electrophysiology modeling with Chaste and CellML. Frontiers in Physiology, 5, Article 511. https://doi.org/10.3389/fphys.2014.00511

© 2015 Cooper, Spiteri and Mirams. Chaste is an open-source C++ library for computational biology that has well-developed cardiac electrophysiology tissue simulation support. In this paper, we introduce the features available for performing cardiac e... Read More about Cellular cardiac electrophysiology modeling with Chaste and CellML.

In silico pro-arrhythmia assessment: Can the results of the thorough QT study be predicted? (2014)
Journal Article
Mirams, G., Davies, M., Stott, J., Rodriguez, B., Cui, Y., Noble, D., Gavaghan, D., & Abi-Gerges, N. (2014). In silico pro-arrhythmia assessment: Can the results of the thorough QT study be predicted?. Journal of Pharmacological and Toxicological Methods, 70(3), 318. https://doi.org/10.1016/j.vascn.2014.03.033

In early drug development, high-throughput cardiac ion channel screening data are now available routinely and relatively cheaply. In-silico approaches that use these data have been proposed to predict the results of: later safety tests; human clinica... Read More about In silico pro-arrhythmia assessment: Can the results of the thorough QT study be predicted?.

Spatiotemporal Transitions in Cardiac Neuronal Co-Cultures (2014)
Presentation / Conference Contribution
A.B. Burton, R., Stephens, G., Sharkey, A., Bilton, S., Larsen, H., Kramer, H., Schmidt, C., Molina, C., Li, D., Mirams, G., Robinson, C., Paterson, D., & Bub, G. (2014, February). Spatiotemporal Transitions in Cardiac Neuronal Co-Cultures. Presented at 58th Annual Meeting Biophysical Society, San Francisco

A variety of arrhythmias have been attributed to formation of large scale patterns of excitation such as formation and break-up of spiral waves. We investigate the relationship between neuronal activity and evolution of macroscopic spatiotemporal dyn... Read More about Spatiotemporal Transitions in Cardiac Neuronal Co-Cultures.

Estimation of Conductivity Tensors from Human Ventricular Optical Mapping Recordings (2013)
Book Chapter
Walmsley, J., Mirams, G. R., Efimov, I. R., Burrage, K., & Rodriguez, B. (2013). Estimation of Conductivity Tensors from Human Ventricular Optical Mapping Recordings. In S. Ourselin, D. Rueckert, & N. Smith (Eds.), Functional Imaging and Modeling of the Heart: 7th International Conference, FIMH 2013, London, UK, June 20-22, 2013. Proceedings (224-231). Springer Verlag. https://doi.org/10.1007/978-3-642-38899-6_27

Experimental recordings of transmural activation in the human left ventricle show variability in recorded activation times. In this paper we demonstrate a framework for fitting the conductivity tensor of a monodomain model to reproduce activation tim... Read More about Estimation of Conductivity Tensors from Human Ventricular Optical Mapping Recordings.

Evaluation of an in silico cardiac safety assay: Using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge (2013)
Journal Article
Beattie, K. A., Luscombe, C., Williams, G., Munoz-Muriedas, J., Gavaghan, D. J., Cui, Y., & Mirams, G. R. (2013). Evaluation of an in silico cardiac safety assay: Using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge. Journal of Pharmacological and Toxicological Methods, 68(1), 88-96. https://doi.org/10.1016/j.vascn.2013.04.004

Introduction
Drugs that prolong the QT interval on the electrocardiogram present a major safety concern for pharmaceutical companies and regulatory agencies. Despite a range of assays performed to assess compound effects on the QT interval, QT prolo... Read More about Evaluation of an in silico cardiac safety assay: Using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge.

Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment (2013)
Journal Article
Elkins, R. C., Davies, M. R., Brough, S. J., Gavaghan, D. J., Cui, Y., Abi-Gerges, N., & Mirams, G. R. (2013). Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment. Journal of Pharmacological and Toxicological Methods, 68(1), 112-122. https://doi.org/10.1016/j.vascn.2013.04.007

Introduction: Unwanted drug interactions with ionic currents in the heart can lead to an increased pro-arrhythmic risk to patients in the clinic. It is therefore a priority for safety pharmacology teams to detect block of cardiac ion channels, and ne... Read More about Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment.

Chaste: An Open Source C++ Library for Computational Physiology and Biology (2013)
Journal Article
Mirams, G. R., Arthurs, C. J., Bernabeu, M. O., Bordas, R., Cooper, J., Corrias, A., …Gavaghan, D. J. (2013). Chaste: An Open Source C++ Library for Computational Physiology and Biology. PLoS Computational Biology, 9(3), e1002970. https://doi.org/10.1371/journal.pcbi.1002970

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac ele... Read More about Chaste: An Open Source C++ Library for Computational Physiology and Biology.

mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study (2013)
Journal Article
Walmsley, J., Rodriguez, J. F., Mirams, G. R., Burrage, K., Efimov, I. R., & Rodriguez, B. (2013). mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study. PLoS ONE, 8(2), Article e56359. https://doi.org/10.1371/journal.pone.0056359

Differences in mRNA expression levels have been observed in failing versus non-failing human hearts for several membrane channel proteins and accessory subunits. These differences may play a causal role in electrophysiological changes observed in hum... Read More about mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study.

Computational assessment of drug-induced effects on the electrocardiogram: From ion channel to body surface potentials (2013)
Journal Article
Zemzemi, N., Bernabeu, M. O., Saiz, J., Cooper, J., Pathmanathan, P., Mirams, G. R., …Rodriguez, B. (2013). Computational assessment of drug-induced effects on the electrocardiogram: From ion channel to body surface potentials. British Journal of Pharmacology, 168(3), 718-733. https://doi.org/10.1111/j.1476-5381.2012.02200.x

Background and Purpose: Understanding drug effects on the heart is key to safety pharmacology assessment and anti-arrhythmic therapy development. Here our goal is to demonstrate the ability of computational models to simulate the effect of drug actio... Read More about Computational assessment of drug-induced effects on the electrocardiogram: From ion channel to body surface potentials.

Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing (2012)
Journal Article
Mirams, G. R., Davies, M. R., Cui, Y., Kohl, P., & Noble, D. (2012). Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing. British Journal of Pharmacology, 167(5), 932-945. https://doi.org/10.1111/j.1476-5381.2012.02020.x

Concerns over cardiac side effects are the largest single cause of compound attrition during pharmaceutical drug development. For a number of years, biophysically detailed mathematical models of cardiac electrical activity have been used to explore h... Read More about Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing.

Evaluation of computational modelling as a preclinical proarrhythmic safety assay (2012)
Presentation / Conference Contribution
Mirams, G., Beattie, K., Cui, Y., Luscombe, C., Williams, G., Gavaghan, D., & McMahon, N. (2012, October). Evaluation of computational modelling as a preclinical proarrhythmic safety assay. Presented at Safety Pharmacology Society Annual Meeting, Phoenix, AZ

Many cardiac ion channels are prone to reduced current flow following blockade by pharmaceutical compounds. High throughput screening technologies now allow us to establish this reduction in activity routinely and relatively cheaply. It would be adva... Read More about Evaluation of computational modelling as a preclinical proarrhythmic safety assay.

A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt (2012)
Journal Article
Mirams, G. R., Fletcher, A. G., Maini, P. K., & Byrne, H. M. (2012). A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt. Journal of Theoretical Biology, 312, 143-156. https://doi.org/10.1016/j.jtbi.2012.08.002

The surface epithelium lining the intestinal tract renews itself rapidly by a coordinated programme of cell proliferation, migration and differentiation events that is initiated in the crypts of Lieberkühn. It is generally believed that colorectal ca... Read More about A theoretical investigation of the effect of proliferation and adhesion on monoclonal conversion in the colonic crypt.

Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG (2012)
Journal Article
Jonsson, M. K., Vos, M. A., Mirams, G. R., Duker, G., Sartipy, P., De Boer, T. P., & Van Veen, T. A. (2012). Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG. Journal of Molecular and Cellular Cardiology, 52(5), 998-1008. https://doi.org/10.1016/j.yjmcc.2012.02.002

Human embryonic stem cell-derived cardiomyocytes (hESC-CM) have been proposed as a new model for safety pharmacology. So far, a thorough description of their basic electrophysiology and extensive testing, and mechanistic explanations, of their overal... Read More about Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG.

Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: Models with two Aux/IAA and ARF proteins, and two target gene-sets (2011)
Journal Article
Bridge, L. J., Mirams, G. R., Kieffer, M. L., King, J. R., & Kepinski, S. (2012). Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: Models with two Aux/IAA and ARF proteins, and two target gene-sets. Mathematical Biosciences, 235(1), 32-44. https://doi.org/10.1016/j.mbs.2011.10.005

New models of gene transcriptional responses to auxin signalling in Arabidopsis are presented. This work extends a previous model of auxin signalling to include networks of gene-sets which may control developmental responses along auxin gradients. Ke... Read More about Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: Models with two Aux/IAA and ARF proteins, and two target gene-sets.

A local sensitivity analysis method for developing biological models with identifiable parameters: Application to cardiac ionic channel modelling (2011)
Journal Article
Sher, A. A., Wang, K., Wathen, A., Maybank, P. J., Mirams, G. R., Abramson, D., …Gavaghan, D. J. (2013). A local sensitivity analysis method for developing biological models with identifiable parameters: Application to cardiac ionic channel modelling. Future Generation Computer Systems, 29(2), 591-598. https://doi.org/10.1016/j.future.2011.09.006

Computational cardiac models provide important insights into the underlying mechanisms of heart function. Parameter estimation in these models is an ongoing challenge with many existing models being overparameterised. Sensitivity analysis presents a... Read More about A local sensitivity analysis method for developing biological models with identifiable parameters: Application to cardiac ionic channel modelling.

High-throughput functional curation of cellular electrophysiology models (2011)
Journal Article
Cooper, J., Mirams, G. R., & Niederer, S. A. (2011). High-throughput functional curation of cellular electrophysiology models. Progress in Biophysics and Molecular Biology, 107(1), 11-20. https://doi.org/10.1016/j.pbiomolbio.2011.06.003

Effective reuse of a quantitative mathematical model requires not just access to curated versions of the model equations, but also an understanding of the functional capabilities of the model, and the advisable scope of its application. To enable thi... Read More about High-throughput functional curation of cellular electrophysiology models.