@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{chaste_dtm, abstract = "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 from active effects such as cell-growth and cell division. Issues which arise when implementing these models are described, and a series of numerical mechanical experiments is performed. It is shown that discrete tissues modelled this way typically exhibit elastic-plastic behaviour under slow compression, and act as a brittle linear elastic solid under slow tension. Both overlapping spheres and Voronoi-tessellation-based models are examined, and the effect of different cell-cell interaction force laws on the bulk mechanical properties of the tissue is determined. This correspondence allows parameters in the cell-based model to be chosen to be compatible with bulk tissue measurements.", author = "P Pathmanathan and J Cooper and A Fletcher and G Mirams and P Murray and J Osborne and J Pitt-Francis and A Walter and S J Chapman", doi = "10.1088/1478-3975/6/3/036001", journal = "Physical Biology", number = "3", title = "A computational study of discrete mechanical tissue models", volume = "6", year = "2009", } @article{HPC, author = "Rafel Bordas, Bruno Carpentieri, Giorgio Fotia, Fabio Maggio, Ross Nobes, Joe Pitt-Francis and James Southern", journal = "Phil Trans Roy Soc (A)", title = "Simulation of Cardiac Electrophysiology on Next-Generation High-Performance Computers", 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{Chaste_paper, author = "Joe Pitt-Francis, Miguel O. Bernabeu, Jonathan Cooper, Alan Garny, Lee Momtahan, James Osborne, Pras Pathmanathan, Blanca Rodriguez, Jonathan P. Whiteley, David J. Gavaghan", doi = "10.1098/rsta.2008.0096", journal = "Phil Trans Roy Soc A", number = "1878", pages = "3111-3136", title = "Chaste: using agile programming techniques to develop computational biology software", volume = "366", year = "2008", }