Title: "Investigating the TCR-activated Erk-MAPK Signaling Pathway Through a Comparative Study of Parameter Sensitivity Analyses"
Speaker: Dr. Ann Rundell, Weldon School of Biomedical Engineering, Purdue University
Place: Mechanical Engineering (ME) 161; Tuesday, 4:30pm


Parameter estimation is a major challenge for mathematical modeling biological systems. Given the uncertainties associated with model parameters, it is important to understand how sensitive the model output is to variations in parameter values. While a local sensitivity analysis determines the model sensitivity to parameter variations over a localized region around the nominal parameter values, a global sensitivity analysis (GSA) investigates the sensitivity over the entire parameter space. Using a T cell receptor-activated Erk-MAPK signaling pathway model as an example, this presentation will provide a comparative study of a variety of different sensitivity analysis techniques. These techniques include: local sensitivity analysis, existing GSA methods of PRCC, Sobol's, extended FAST, as well as a weighted average of local sensitivities, and a new GSA method to extract global parameter sensitivities from a parameter identification routine. Results of this study revealed critical reactions in the signaling pathway and their impact on the signaling dynamics, and provided insights into embedded regulatory mechanisms such as feedback loops in the pathway. From this study, a recommendation emerges for a general sensitivity analysis strategy to efficiently and reliably infer quantitative, dynamic as well as topological properties from Systems Biology models.

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