@article{, abstract = "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 and soft-tissue mechanics. It is released under the LGPL 2.1 licence. Chaste has been developed using agile programming methods. The project began in 2005 when it was reasoned that the modelling of a variety of physiological phenomena required both a generic mathematical modelling framework, and a generic computational/simulation framework. The Chaste project evolved from the Integrative Biology (IB) e-Science Project, an inter-institutional project aimed at developing a suitable IT infrastructure to support physiome-level computational modelling, with a primary focus on cardiac and cancer modelling.", author = "J Pitt-Francis, P Pathmanathan, MO Bernabeu, R Bordas, J Cooper, AG Fletcher, GR Mirams, P Murray, JM Osborne, A Walter, SJ Chapman, A Garny, I van Leeuwen, PK Maini, B Rodríguez, SL Waters, JP Whiteley, HM Byrne and DJ Gavaghan", journal = "Computer Physics Communications", title = "Chaste: A test-driven approach to software development for biological modelling", volume = "(in press)", year = "2009", } @article{, abstract = "The generalised minimal residual (GMRES) method is a common choice for solving the large non-symmetric linear systems that arise when numerically computing solutions of incompressible nonlinear elasticity problems using the finite element method. Analytic results on the performance of GMRES are available on linear problems such as linear elasticity or Stokes' flow (where the matrices in the corresponding linear systems are symmetric), or on the nonlinear problem of Navier-Stokes' flow (where the matrix is block-symmetric/block-skew-symmetric); however there has been very little investigation into GMRES performance in incompressible nonlinear elasticity problems, where the nonlinearity of the incompressibility constraint means the matrix is not block-symmetric/block-skew-symmetric. In this short paper we identify one feature of the problem formulation which has a huge impact on unpreconditioned GMRES-convergence. We explain that it is important to ensure that the matrices are perturbations of a block-skew-symmetric matrix rather than a perturbation of a block-symmetric matrix. This relates to the choice of sign before the incompressibility constraint integral in the weak formulation (with both choices being mathematically equivalent). The incorrect choice is shown to have a hugely detrimental effect on total computation time.", author = "P Pathmanathan, JP Whiteley, SJ Chapman and DJ Gavaghan", journal = "Journal of Applied Mechanics", title = "A Note on the Effect of the Choice of Weak Form on GMRES Convergence for Incompressible Nonlinear Elasticity Problems", volume = "(in press)", year = "2009", } @article{cancerchaste1, abstract = "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. Theoretical models are powerful tools that can be used to test hypotheses concerning the regulation of the renewal process, to investigate how its dysfunction can lead to loss of homeostasis and neoplasia, and to identify potential therapeutic interventions. Here we propose a new multiscale model for crypt dynamics that links phenomena occurring at the subcellular, cellular and tissue levels of organisation. Methods: At the subcellular level, deterministic models characterise molecular networks, such as cell-cycle control and Wnt signalling. The output of these models determines the behaviour of each epithelial cell in response to intra-, inter- and extra-cellular cues. The modular nature of the model enables us to modify easily individual assumptions and analyse their effects on the system as a whole. Results: We perform virtual microdissection and labelling-index experiments, evaluate the impact of various model extensions, obtain new insight into clonal expansion in the crypt, and compare our predictions with recent mtDNA mutation data. Conclusions: We demonstrate that relaxing the assumption that stem cell positions are fixed enables clonal expansion and niche succession to occur. We also predict that the presence of extracellular factors near the base of the crypt alone suffices to explain the observed spatial variation in nuclear beta-catenin levels along the crypt axis.", author = "IMM van Leeuwen, GR Mirams, A Walter, A Fletcher, P Murray, J Osborne, S Varma, SJ Young, J Cooper, B Doyle, J Pitt-Francis, L Momtahan, P Pathmanathan, JP Whiteley, SJ Chapman, DJ Gavaghan, OE Jensen, JR King, PK Maini, SL Waters, HM Byrne", journal = "Cell Proliferation", keywords = "Wnt signalling, Crypt dynamics, Cell cycle, Colorectal cancer, Stem cells", title = "An integrative computational model for intestinal tissue renewal", year = "2009", } @article{Chaste2, author = "Bernabeu MO, Bordas R, Pathmanathan P, Pitt-Francis J, Cooper J, Garny A, Gavaghan DJ, Rodriguez B, Southern JA, Whiteley JP", doi = "10.1098/rsta.2008.0309", journal = "Phil Trans Roy Soc (A)", month = "May", number = "1895", pages = "1907-1930", title = "Chaste: Incorporating a Novel Multiscale Spatial and Temporal Algorithm into a Large Scale Open Source Library", volume = "367", year = "2009", } @article{, abstract = "Cardiac modelling is the area of physiome modelling where the available simulation software is perhaps most mature, and it therefore provides an excellent starting point for considering the software requirements for the wider physiome community. In this paper, we will begin by introducing some of the most advanced existing software packages for simulating cardiac electrical activity. We consider the software development methods used in producing codes of this type, and discuss their use of numerical algorithms, relative computational efficiency, usability, robustness and extensibility.We then go on to describe a class of software development methodologies known as test-driven agile methods and argue that such methods are more suitable for scientific software development than the traditional academic approaches. A case study is a project of our own, Cancer, Heart and Soft Tissue Environment, which is a library of computational biology software that began as an experiment in the use of agile programming methods. We present our experiences with a review of our progress thus far, focusing on the advantages and disadvantages of this new approach compared with the development methods used in some existing packages.We conclude by considering whether the likely wider needs of the cardiac modelling community are currently being met and suggest that, in order to respond effectively to changing requirements, it is essential that these codes should be more malleable. Such codes will allow for reliable extensions to include both detailed mathematical models—of the heart and other organs—and more efficient numerical techniques that are currently being developed by many research groups worldwide.", author = "J Pitt-Francis, MO Bernabeu, JC, A Garny, L Momtahan, J Osborne, P Pathmanathan, B Rodriguez, JP Whiteley and DJ Gavaghan", journal = "Philosophical Transactions of the Royal Society A", pages = "3111-3136.", title = "Chaste: Using Agile Programming Techniques to Develop Computational Biology Software", volume = "366(1878)", year = "2008", } @article{, abstract = "Breast cancer is one of the biggest killers in the western world, and early diagnosis is essential for improved prognosis. The shape of the breast varies hugely between the scenarios of magnetic resonance (MR) imaging (patient lies prone, breast hanging down under gravity), X-ray mammography (breast strongly compressed) and ultrasound or biopsy/surgery (patient lies supine), rendering image fusion an extremely difficult task. This paper is concerned with the use of the finite-element method and nonlinear elasticity to build a 3-D, patient-specific, anatomically accurate model of the breast. The model is constructed from MR images and can be deformed to simulate breast shape and predict tumor location during mammography or biopsy/surgery. Two extensions of the standard elasticity problem need to be solved: an inverse elasticity problem (arising from the fact that only a deformed, stressed, state is known initially), and the contact problem of modeling compression. The model is used for craniocaudal mediolateral oblique mammographic image matching, and a number of numerical experiments are performed", author = "P Pathmanathan, DJ Gavaghan, JP Whiteley, SJ Chapman and JM Brady", journal = "IEEE Transactions on Biomedical Engineering", pages = "2471-2480", title = "Predicting tumor location by modeling the deformation of the breast", volume = "55(10)", year = "2008", }