Abstract
It is the mission of systems biology to investigate large biological networks (paradigmatic of cellular extension), and to explain their dynamics by means of mathematical models. Since these networks are far too complex to be modeled directly, they first must be decomposed into subnetworks of mathematically manageable size. This is often done by breaking the network down into quasi-independent modules. Different modularization strategies are applied, relying on functional (physiological) or on structural criteria (related to the topology of the network). This paper demonstrates that choosing a modularization strategy has far-reaching epistemic consequences: The modularization method predefines the kind of model that can be used to describe the network; by this it also predefines the explanatory goals that can be followed successfully. I further challenge the standard view that decomposition of a network according to structural criteria is neutral (while functional decomposition gives a biased picture) and demonstrate that also the choice of a structural criterion introduces a bias.
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Notes
- 1.
Stochastic models may serve as a more realistic substitute for kinetic models (which counterfactually assume continuity of matter). In these, reaction events, e.g., the transition of a particular molecule of a given molecular species, replace the reaction rates (Rao et al. 2002).
- 2.
See Krohs (2009b) for a reconstruction of theory structure in such cases.
- 3.
The citric acid cycle may serve as an example. It is delineated functionally (Krohs 2004: 173) and consequently forms a functional module. But each metabolic intermediate of the cycle is, besides its two edges within the cycle, also involved in many reactions that do not belong to the cycle but link it to other functional modules and help regulate the size of the pools of each of the intermediates (Kornberg 1965; Owen et al. 2002). By an analysis of a discrete model of the network, the external interactions are judged to be stronger than the internal ones. The functional module of the citric acid cycle is therefore not a structural module (Krohs 2009a).
- 4.
- 5.
Including stochastic approaches as mentioned in note 1.
- 6.
It may, however, count as a mechanistic explanation of the dynamic of the structural module. But as long as this dynamic is not itself interpreted physiologically – and thus the structural framework is given up in favor of a functional one – it is hard to see the biological relevance of such an explanation.
- 7.
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Acknowledgment
Support during the later stages of this work by the Deutsche Forschungsgemeinschaft (DFG), grant KR3662/1–1, is gratefully acknowledged.
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Krohs, U. (2010). Epistemic Consequences of Two Different Strategies for Decomposing Biological Networks. In: Suárez, M., Dorato, M., Rédei, M. (eds) EPSA Philosophical Issues in the Sciences. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3252-2_15
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