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Principled simulation of cell proliferation dynamics using the CoSMoS approach

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Abstract

A collaboration between cancer biologists and academic software engineers has been exploring the development of an agent-based simulator to inform and support work on the dynamics of cell proliferation in the study of prostate disorders. The research has influenced and been informed by the CoSMoS project. This paper presents the simulation project (which is not yet complete). We reflect on the reality of following CoSMoS principles; we describe the domain exploration and show how software modelling approaches (here, Petri nets, state diagrams) can be used to express both biological and software models. We explore fitness for purpose and consider ways to present a fitness argument. We consider issues in choosing simulation media and mapping from domain models through to code. The implementation emphasis is on traceability to support reuse and extension of the simulator, as well as demonstrable fitness for purpose. Initial work on calibration is presented. We discuss the calibration results, that both support and challenge the design and assumptions captured in the domain modelling and development activities.

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Notes

  1. See http://www.omg.org/spec/UML/.

  2. The GSN standard is available at http://www.goalstructuringnotation.info/documents/GSN_Standard.pdf. Here, the argument structure diagrams are created using the Artoo argumentation tool, http://www.ycil.org.uk/argumentation-tool/.

  3. http://golang.org/.

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Acknowledgments

Fiona Polack’s contribution includes work undertaken for the EPSRC CoSMoS project, grants EP/E053505/1 and EP/E049419/1. Alastair Droop’s contribution has been funded through the Maitland Lab’s Yorkshire Cancer Research platform grant, and from the EPSRC TRANSIT “bridging the gap” funding through the York Centre for Complex Systems Analysis (grant EP/F032749/1). We would like to thank Professor Norman Maitland and the staff of the Maitland Lab, Department of Biology, University of York, for their ongoing involvement in this project: the research underlying this paper is funded by a range of organisations notably Yorkshire Cancer Research. We also acknowledge significant contributions to the biological domain from Biology interns Sarah Greener and Emily Pollard; and to the simulation development and theory by Computer Science undergraduate project students, Jon Low, Nikola Nikolov and Codrin Oprea; and YCCSA Summerschool students Livia Dia (2013) and Andrei Simionescu (2012). The Wellcome Trust funded biological materials and the 2012 summer internship through York’s C2D2 grant.

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Authors and Affiliations

  1. YCCSA/Department of Computer Science, University of York, York, YO10 5DD, UK

    Fiona Polack

  2. Cancer Research UK Leeds Centre, University of Leeds, Leeds, UK

    Alastair Droop

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  1. Fiona Polack
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  2. Alastair Droop
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Correspondence to Fiona Polack.

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Polack, F., Droop, A. Principled simulation of cell proliferation dynamics using the CoSMoS approach. Nat Comput 14, 63–82 (2015). https://doi.org/10.1007/s11047-014-9468-z

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