Parameter Identifiability of RNA Dynamics in PDE Transport Models of Fluorescence Recovery After Photobleaching

Abstract

The transport and localization of RNA molecules, crucial for cellular function and development, involve a combination of diffusion and active transport mechanisms. Here, we are motivated by understanding the dynamics of RNA in Xenopus laevis oocytes. Fluorescence Recovery After Photobleaching (FRAP) is an experimental technique that is widely used to investigate the dynamics of molecular movement within cells by observing the recovery of fluorescence intensity in a photobleached region over time. To advance the understanding of RNA dynamics, we develop a reaction-diffusion-advection partial differential equation (PDE) model integrating both transport and diffusion mechanisms. We propose a pipeline for identifiability analysis to assess the model's ability to uniquely determine parameter values from observed FRAP data. Based on profile likelihood analysis and reparametrization, we examine the relationship between non- identifiable parameters, which improves the robustness of parameter estimation. We find out that the identifiability of the four parameters of interest is not exactly the same in different regions of the cell. Specifically, transport velocity and diffusion coefficient are identifiable in all regions of the cell, while some combinations of binding rate and unbinding rate are found to be identifiable near the nucleus.