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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)
Dynamical models of cellular processes promise to yield new insights into the underlying systems and their biological interpretation. The processes are usually nonlinear, high dimensional, and time-resolved experimental data of the processes are sparse. Therefore, parameter estimation faces the challenges of structural and practical nonidentifiability.(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)
UNLABELLED Modeling of dynamical systems using ordinary differential equations is a popular approach in the field of systems biology. Two of the most critical steps in this approach are to construct dynamical models of biochemical reaction networks for large datasets and complex experimental conditions and to perform efficient and reliable parameter(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)
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)
Complex intracellular signalling networks integrate extracellular signals and convert them into cellular responses. In cancer cells, the tightly regulated and fine-tuned dynamics of information processing in signalling networks is altered, leading to uncontrolled cell proliferation, survival and migration. Systems biology combines mathematical modelling(More)
Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) share a frequent constitutive activation of JAK (Janus kinase)/STAT signaling pathway. Because of complex, nonlinear relations within the pathway, key dynamic properties remained to be identified to predict possible strategies for intervention. We report the development of(More)