@Article{RSM:Wal2009,
  author =       "D.C. Walker and J. Southgate",
  title =        "The virtual cell--a candidate co-ordinator for
                 'middle-out' modelling of biological systems.",
  journal =      "Brief Bioinform",
  year =         "2009",
  month =        "Jul",
  volume =       "10",
  number =       "4",
  pages =        "450--461",
  robnote =      "Systems biology has traditionally used
                 either a 'top-down' or 'bottom-up' approach. However,
                 neither approach takes account of heterogeneity or
                 'noise', which is an inherent feature of cellular
                 behaviour and may have significant impact on system level
                 behaviour. We review existing approaches to modelling that
                 use cellular automata or agent-based methodologies, where
                 individual cells are represented as equivalent virtual
                 entities governed by simple rules. These paradigms allow a
                 direct one-to-one mapping between real and virtual cells
                 that can be exploited in terms of acquiring parameters
                 from experimental systems, or for model validation. Such
                 models are inherently extensible and can be integrated
                 with other modelling modalities (e.g. partial or ordinary
                 differential equations) to model multi-scale phenomena.
                 Alternatively, hierarchical agent models may be used to
                 explore the functions of biological systems across
                 temporal and spatial scales. This review examines
                 individual-based models and the application of the
                 paradigm to explore multi-scale phenomena in biology. In
                 so doing, it demonstrates how cellular-based models have
                 begun to play an important role in the development of
                 'middle-out' models, but with considerable potential for
                 future development.",
  bibdate =      "Tue Aug 25 23:18:17 2009",
}

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