A computational study of discrete mechanical tissue models

Pathmanathan, P.; Cooper, J.; Fletcher, A.; Mirams, G.; Murray, P.; Osborne, J.; Pitt-Francis, J.; Walter, Alex; Chapman, S. J.

doi:10.1088/1478-3975/6/3/036001

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.

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.

Is it time for in silico simulation of drug cardiac side effects? (2011)
Journal Article
Mirams, G. R., & Noble, D. (2011). Is it time for in silico simulation of drug cardiac side effects?. Annals of the New York Academy of Sciences, 1245(1), 44-47. https://doi.org/10.1111/j.1749-6632.2011.06324.x

Cardiac simulation is used to integrate information on drug action to predict side effects on the whole heart. Could simulation begin to replace animal models? © 2011 New York Academy of Sciences.

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.

Minimum Information about a Cardiac Electrophysiology Experiment (MICEE): Standardised reporting for model reproducibility, interoperability, and data sharing (2011)
Journal Article
Quinn, T. A., Granite, S., Allessie, M. A., Antzelevitch, C., Bollensdorff, C., Bub, G., …Kohl, P. (2011). Minimum Information about a Cardiac Electrophysiology Experiment (MICEE): Standardised reporting for model reproducibility, interoperability, and data sharing. Progress in Biophysics and Molecular Biology, 107(1), 4-10. https://doi.org/10.1016/j.pbiomolbio.2011.07.001

Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum Information... Read More about Minimum Information about a Cardiac Electrophysiology Experiment (MICEE): Standardised reporting for model reproducibility, interoperability, and data sharing.

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.

Novel approaches to assessing cardiac safety - Proceedings of a workshop: Regulators, industry and academia discuss the future of in silico cardiac modelling to predict the proarrhythmic safety of drugs (2011)
Journal Article
Fletcher, K., Shah, R. R., Thomas, A., Tobin, F., Rodriguez, B., Mirams, G. R., …Noble, D. (2011). Novel approaches to assessing cardiac safety - Proceedings of a workshop: Regulators, industry and academia discuss the future of in silico cardiac modelling to predict the proarrhythmic safety of drugs. Drug Safety, 34(5), 439-443. https://doi.org/10.2165/11591950-000000000-00000

The significant effect of the choice of ionic current integration method in cardiac electro-physiological simulations (2011)
Journal Article
Pathmanathan, P., Mirams, G. R., Southern, J., & Whiteley, J. P. (2011). The significant effect of the choice of ionic current integration method in cardiac electro-physiological simulations. International Journal for Numerical Methods in Biomedical Engineering, 27(11), 1751-1770. https://doi.org/10.1002/cnm.1438

Finite element (FE) cardiac electro-physiology solvers commonly have ionic current determined at mesh nodes but required element interiors. We consider two interpolation approaches: (i) ionic current interpolation (ICI), where nodal ionic currents ar... Read More about The significant effect of the choice of ionic current integration method in cardiac electro-physiological simulations.

Simulation of multiple ion channel block provides improved prediction of compounds’ clinical torsadogenic risk (2011)
Journal Article
Mirams, G. R., Cui, Y., Sher, A., Fink, M., Cooper, J., Heath, B. M., …Noble, D. (2011). Simulation of multiple ion channel block provides improved prediction of compounds’ clinical torsadogenic risk. Cardiovascular Research, 91(1), 53-61. https://doi.org/10.1093/cvr/cvr044

© 2011 The Author. Aims The level of inhibition of the human Ether - go-go-related gene (hERG) channel is one of the earliest preclinical markers used to predict the risk of a compound causing Torsade-de-Pointes (TdP) arrhythmias. While avoiding the... Read More about Simulation of multiple ion channel block provides improved prediction of compounds’ clinical torsadogenic risk.

A hybrid approach to multi-scale modelling of cancer (2010)
Journal Article
Osborne, J. M., Walter, A., Kershaw, S. K., Mirams, G. R., Fletcher, A. G., Pathmanathan, P., …Byrne, H. M. (2010). A hybrid approach to multi-scale modelling of cancer. Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, 368(1930), 5013-5028. https://doi.org/10.1098/rsta.2010.0173

In this paper, we review multi-scale models of solid tumour growth and discuss a middleout framework that tracks individual cells. By focusing on the cellular dynamics of a healthy colorectal crypt and its invasion by mutant, cancerous cells, we comp... Read More about A hybrid approach to multi-scale modelling of cancer.

Phenomenological modeling of cell-to-cell and beat-to-beat variability in isolated guinea pig ventricular myocytes (2010)
Conference Proceeding
Walmsley, J., Mirams, G., Bahoshy, M., Bollensdorff, C., Rodriguez, B., & Burrage, K. (2010). Phenomenological modeling of cell-to-cell and beat-to-beat variability in isolated guinea pig ventricular myocytes. In 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology, (1457-1460). https://doi.org/10.1109/IEMBS.2010.5626858

Experimental action potential (AP) recordings in isolated ventricular myoctes display significant temporal beatto- beat variability in morphology and duration. Furthermore, significant cell-to-cell differences in AP also exist even for isolated cells... Read More about Phenomenological modeling of cell-to-cell and beat-to-beat variability in isolated guinea pig ventricular myocytes.

Modelling spatially regulated ?-catenin dynamics and invasion in intestinal crypts (2010)
Journal Article
Murray, P. J., Kang, J. W., Mirams, G. R., Shin, S. Y., Byrne, H. M., Maini, P. K., & Cho, K. H. (2010). Modelling spatially regulated ?-catenin dynamics and invasion in intestinal crypts. Biophysical Journal, 99(3), 716-725. https://doi.org/10.1016/j.bpj.2010.05.016

Experimental data (e.g., genetic lineage and cell population studies) on intestinal crypts reveal that regulatory features of crypt behavior, such as control via morphogen gradients, are remarkably well conserved among numerous organisms (e.g., from... Read More about Modelling spatially regulated ?-catenin dynamics and invasion in intestinal crypts.

Multiscale modeling of colonic crypts and early colorectal cancer (2010)
Book Chapter
Fletcher, A. G., Mirams, G. R., Murray, P. J., Walter, A., Kang, J. W., Cho, K. H., …Byrne, H. M. (2010). Multiscale modeling of colonic crypts and early colorectal cancer. In T. S. Deisboeck, & G. Stamatakos (Eds.), Multiscale Cancer Modeling (111-131). CRC Press. https://doi.org/10.1201/b10407

© 2011 by Taylor & Francis Group, LLC. Colorectal cancer accounts for 13% of all cancers in the United Kingdom, with around 35,300 new diagnoses and 16,000 deaths occurring each year (http://info.cancerresearchuk.org). Colorectal cancer is predomin... Read More about Multiscale modeling of colonic crypts and early colorectal cancer.

An integrative computational model for intestinal tissue renewal (2009)
Journal Article
Van Leeuwen, I. M., Mirams, G. R., Walter, A., Fletcher, A., Murray, P., Osborne, J., …Byrne, H. M. (2009). An integrative computational model for intestinal tissue renewal. Cell Proliferation, 42(5), 617-636. https://doi.org/10.1111/j.1365-2184.2009.00627.x

Objectives: The luminal surface of the gut is lined with a monolayer of epithelial cells that acts as a nutrient absorptive engine and protective barrier. To maintain its integrity and functionality, the epithelium is renewed every few days. Theoreti... Read More about An integrative computational model for intestinal tissue renewal.

Chaste: A test-driven approach to software development for biological modelling (2009)
Journal Article
Pitt-Francis, J., Pathmanathan, P., Bernabeu, M. O., Bordas, R., Cooper, J., Fletcher, A. G., …Gavaghan, D. J. (2009). Chaste: A test-driven approach to software development for biological modelling. Computer Physics Communications, 180(12), 2452-2471. https://doi.org/10.1016/j.cpc.2009.07.019

Chaste ('Cancer, heart and soft-tissue environment') is a software library and a set of test suites for computational simulations in the domain of biology. Current functionality has arisen from modelling in the fields of cancer, cardiac physiology an... Read More about Chaste: A test-driven approach to software development for biological modelling.

A multiple timescale analysis of a mathematical model of the Wnt/?-catenin signalling pathway (2009)
Journal Article
Mirams, G. R., Byrne, H. M., & King, J. R. (2010). A multiple timescale analysis of a mathematical model of the Wnt/?-catenin signalling pathway. Journal of Mathematical Biology, 60(1), 131-160. https://doi.org/10.1007/s00285-009-0262-y

The Wnt signalling pathway is involved in stem cell maintenance, differentiation and tissue development. Its disregulation has also been implicated in many cancers. β-catenin is a protein that regulates both transcription of many genes and cell-cell... Read More about A multiple timescale analysis of a mathematical model of the Wnt/?-catenin signalling pathway.

A computational study of discrete mechanical tissue models (2009)
Journal Article
Pathmanathan, P., Cooper, J., Fletcher, A., Mirams, G., Murray, P., Osborne, J., …Chapman, S. J. (2009). A computational study of discrete mechanical tissue models. Physical Biology, 6(3), Article 036001. https://doi.org/10.1088/1478-3975/6/3/036001

A computational study of discrete 'cell-centre' approaches to modelling the evolution of a collection of cells is undertaken. The study focuses on the mechanical aspects of the tissue, in order to separate the passive mechanical response of the model... Read More about A computational study of discrete mechanical tissue models.

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