References of "Conzelmann, H"
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See detailAnalysis of an apoptotic core model focused on experimental design using artificial data.
Schlatter, R.; Conzelmann, H.; Gilles, E. D. et al

in IET Systems Biology (2009), 3(4), 255-65

The activation of caspases is a central mechanism in apoptosis. To gain further insights into complex processes like this, mathematical modelling using ordinary differential equations (ODEs) can be a very ... [more ▼]

The activation of caspases is a central mechanism in apoptosis. To gain further insights into complex processes like this, mathematical modelling using ordinary differential equations (ODEs) can be a very powerful research tool. Unfortunately, the lack of measurement data is a common problem in building such kinetic models, because it practically constrains the identifiability of the model parameters. An existing mathematical model of caspase activation during apoptosis was used in order to design future experimental setups that will help to maximise the obtained information. For this purpose, artificial measurement data are generated in silico to simulate potential experiments, and the model is fitted to this data. The model is also analysed using observability gramian and sensitivity analyses. The used analysis methods are compared. The artificial data approach allows one to make conclusions about system properties, identifiability of parameters and the potential information content of additional measurements for the used caspase activation model. The latter facilitates to improve the experimental design of further measurements significantly. The performed analyses reveal that several kinetic parameters are not at all, or only scarcely, identifiable, and that measurements of activated caspase 8 will maximally improve the parameter estimates. Furthermore, we can show that many assays with inhibitor of apoptosis protein (IAP) knockout cells only provide redundant information for our needs and as such do not have to be carried out. [less ▲]

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

in Systems biology (2004), 1(1), 159-69

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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