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Open Access Highly Accessed Methodology article

Structure, function, and behaviour of computational models in systems biology

Christian Knüpfer12*, Clemens Beckstein1, Peter Dittrich2 and Nicolas Le Novère3

Author Affiliations

1 Artificial Intelligence Group, University of Jena, Ernst-Abbe-Platz 2, Jena, Germany

2 Bio Systems Analysis Group, University of Jena, Ernst-Abbe-Platz 2, Jena, Germany

3 Le Novère lab, Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK

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BMC Systems Biology 2013, 7:43  doi:10.1186/1752-0509-7-43

Published: 31 May 2013

Abstract

Background

Systems Biology develops computational models in order to understand biological phenomena. The increasing number and complexity of such “bio-models” necessitate computer support for the overall modelling task. Computer-aided modelling has to be based on a formal semantic description of bio-models. But, even if computational bio-models themselves are represented precisely in terms of mathematical expressions their full meaning is not yet formally specified and only described in natural language.

Results

We present a conceptual framework – the meaning facets – which can be used to rigorously specify the semantics of bio-models. A bio-model has a dual interpretation: On the one hand it is a mathematical expression which can be used in computational simulations (intrinsic meaning). On the other hand the model is related to the biological reality (extrinsic meaning). We show that in both cases this interpretation should be performed from three perspectives: the meaning of the model’s components (structure), the meaning of the model’s intended use (function), and the meaning of the model’s dynamics (behaviour). In order to demonstrate the strengths of the meaning facets framework we apply it to two semantically related models of the cell cycle. Thereby, we make use of existing approaches for computer representation of bio-models as much as possible and sketch the missing pieces.

Conclusions

The meaning facets framework provides a systematic in-depth approach to the semantics of bio-models. It can serve two important purposes: First, it specifies and structures the information which biologists have to take into account if they build, use and exchange models. Secondly, because it can be formalised, the framework is a solid foundation for any sort of computer support in bio-modelling. The proposed conceptual framework establishes a new methodology for modelling in Systems Biology and constitutes a basis for computer-aided collaborative research.

Keywords:
System biology; Modelling and simulation; Knowledge representation; Semantics; Meaning facets; Philosophy of science