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MOTIVATION Mathematical description of biological reaction networks by differential equations leads to large models whose parameters are calibrated in order to optimally explain experimental data. Often only parts of the model can be observed directly. Given a model that sufficiently describes the measured data, it is important to infer how well model(More)
Cellular signal transduction is governed by multiple feedback mechanisms to elicit robust cellular decisions. The specific contributions of individual feedback regulators, however, remain unclear. Based on extensive time-resolved data sets in primary erythroid progenitor cells, we established a dynamic pathway model to dissect the roles of the two(More)
Accurate estimation of parameters of biochemical models is required to characterize the dynamics of molecular processes. This problem is intimately linked to identifying the most informative experiments for accomplishing such tasks. While significant progress has been made, effective experimental strategies for parameter identification and for(More)
Cell surface receptors convert extracellular cues into receptor activation, thereby triggering intracellular signaling networks and controlling cellular decisions. A major unresolved issue is the identification of receptor properties that critically determine processing of ligand-encoded information. We show by mathematical modeling of quantitative data and(More)
Mathematical description of biological processes such as gene regulatory networks or signalling pathways by dynamic models utilising ordinary differential equations faces challenges if the model parameters like rate constants are estimated from incomplete and noisy experimental data. Typically, biological networks are only partially observed. Only a(More)
Due to the high complexity of biological data it is difficult to disentangle cellular processes relying only on intuitive interpretation of measurements. A Systems Biology approach that combines quantitative experimental data with dynamic mathematical modeling promises to yield deeper insights into these processes. Nevertheless, with growing complexity and(More)
Predicting a system’s behavior based on a mathematical model is a primary task in Systems Biology. If the model parameters are estimated from experimental data, the parameter uncertainty has to be translated into confidence intervals for model predictions. For dynamic models of biochemical networks, the nonlinearity in combination with the large number of(More)
MOTIVATION Modeling of dynamical systems using ordinary differential equations is a popular approach in the field of Systems Biology. The amount of experimental data that are used to build and calibrate these models is often limited. In this setting, the model parameters may not be uniquely determinable. Structural or a priori identifiability is a property(More)
Increasingly complex applications involve large datasets in combination with nonlinear and high-dimensional mathematical models. In this context, statistical inference is a challenging issue that calls for pragmatic approaches that take advantage of both Bayesian and frequentist methods. The elegance of Bayesian methodology is founded in the propagation of(More)
Systems biology aims for building quantitative models to address unresolved issues in molecular biology. In order to describe the behavior of biological cells adequately, gene regulatory networks (GRNs) are intensively investigated. As the validity of models built for GRNs depends crucially on the kinetic rates, various methods have been developed to(More)