a simple work flow for biologically inspired model reduction - application to early jak-stat signaling一个简单的工作流程,生物启发模型减少u2014u2014应用程序jak-stat早期信号.pdfVIP

Quaiser et al. BMC Systems Biology 2011, 5:30 /1752-0509/5/30 RESEARCH ARTICLE Open Access A simple work flow for biologically inspired model reduction - application to early JAK-STAT signaling Tom Quaiser 1,2, Anna Dittrich3,4, Fred Schaper3,4, Martin Mönnigmann1* Abstract Background: Modeling of biological pathways is a key issue in systems biology. When constructing a model, it is tempting to incorporate all known interactions of pathway species, which results in models with a large number of unknown parameters. Fortunately, unknown parameters need not necessarily be measured directly, but some parameter values can be estimated indirectly by fitting the model to experimental data. However, parameter fitting, or, more precisely, maximum likelihood parameter estimation, only provides valid results, if the complexity of the model is in balance with the amount and quality of the experimental data. If this is the case the model is said to be identifiable for the given data. If a model turns out to be unidentifiable, two steps can be taken. Either additional experiments need to be conducted, or the model has to be simplified. Results: We propose a systematic procedure for model simplification, which consists of the following steps: estimate the parameters of the model, create an identifiability ranking for the estimated parameters, and simplify the model based on the identifiability analysis results. These steps need to be applied iteratively until the resulting model is identifiable, or equivalently, until parameter variances are small. We choose parameter variances as stopping criterion, since they are concise and easy to interpret. For both, the parameter estimation and the calculation of parameter variances, multi-start parameter estimations are run on a parallel cluster. In contrast to related work in systems