References of "IEE Proceedings - Systems Biology"
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See detailRobustness properties of apoptosis models with respect to parameter variations and intrinsic noise
Eißing, Thomas; Allgöwer, Frank; Bullinger, Eric ULg

in IEE Proceedings - Systems Biology (2005), 152(4), 221228

Analyses of different robustness aspects for models of the direct signal transduction pathway of receptor-induced apoptosis is presented. Apoptosis is a form of programmed cell death, removing unwanted ... [more ▼]

Analyses of different robustness aspects for models of the direct signal transduction pathway of receptor-induced apoptosis is presented. Apoptosis is a form of programmed cell death, removing unwanted cells within multicellular organisms to maintain a proper balance between cell reproduction and death. Its signalling pathway includes an activation feedback loop that generates bistable behaviour, where the two steady states can be seen as `life' and `death'. Inherent robustness, widely recognised in biological systems, is of major importance in apoptosis signalling, as it guarantees the same cell fate for similar conditions. First, the influence of the stochastic nature of reactions indicating a role for inhibition reactions as noise filters and justifying a deterministic approach in the further analyses is evaluated. Second, the robustness of the bistable threshold with respect to parameter changes is evaluated by statistical methods, showing the need to balance both the forward and the back part of the activation loop. These analyses can also discriminate between the models favouring the model consistent with novel biological findings. The parameter robustness analyses are also applicable to other signal transduction networks, as several have been shown to display bistable behaviour. These methods therefore have a range of possible applications in systems biology not only to measure robustness, but also for model discrimination. [less ▲]

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See detailReduction of mathematical models of signal transduction networks: simulation-based approach applied to EGF receptor signalling
Conzelmann, Holger; Saez-Rodriguez, Julio; Sauter, Thomas et al

in IEE Proceedings - Systems Biology (2004), 1(1), 159-169

Biological systems and, in particular, cellular signal transduction pathways are characterised by their high complexity. Mathematical models describing these processes might be of great help to gain ... [more ▼]

Biological systems and, in particular, cellular signal transduction pathways are characterised by their high complexity. Mathematical models describing these processes might be of great help to gain qualitative and, most importantly, quantitative knowledge about such complex systems. However, a detailed mathematical description of these systems leads to nearly unmanageably large models, especially when combining models of different signalling pathways to study cross-talk phenomena. Therefore, simplification of models becomes very important. Different methods are available for model reduction of biological models. Importantly, most of the common model reduction methods cannot be applied to cellular signal transduction pathways. Using as an example the epidermal growth factor (EGF) signalling pathway, we discuss how quantitative methods like system analysis and simulation studies can help to suitably reduce models and additionally give new insights into the signal transmission and processing of the cell [less ▲]

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