Parameter Identifiability in PDE Models of Fluorescence Recovery After Photobleaching

Abstract

Identifying unique parameters for mathematical models describing biological data can be challenging and often impossible. Parameter identifiability for partial differential equations models in cell biology is especially difficult given that many established in vivo measurements of protein dynamics average out the spatial dimensions. Here, we are motivated by recent experiments on the binding dynamics of the RNA-binding protein PTBP3 in RNP granules of frog oocytes based on fluorescence recovery after photobleaching (FRAP) measurements. FRAP is a widely-used experimental technique for probing protein dynamics in living cells, and is often modeled using simple reaction-diffusion models of the protein dynamics. We show that current methods of structural and practical parameter identifiability provide limited insights into identifiability of kinetic parameters for these PDE models and spatially-averaged FRAP data. We thus propose a pipeline for assessing parameter identifiability and for learning parameter combinations based on re-parametrization and profile likelihoods analysis. We show that this method is able to recover parameter combinations for synthetic FRAP datasets and investigate its application to real experimental data.

Keywords: FRAP; Parameter identifiability; Partial differential equations; Profile likelihood; RNA binding proteins.