Parameter identifiability in PDE models of fluorescence recovery after photobleaching

Fuente: arXiv
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Main Authors: Ciocanel, Maria-Veronica, Ding, Lee, Mastromatteo, Lucas, Reichheld, Sarah, Cabral, Sarah, Mowry, Kimberly, Sandstede, Bjorn
Format: Preprint
Published: 2023
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author Ciocanel, Maria-Veronica
Ding, Lee
Mastromatteo, Lucas
Reichheld, Sarah
Cabral, Sarah
Mowry, Kimberly
Sandstede, Bjorn
author_facet Ciocanel, Maria-Veronica
Ding, Lee
Mastromatteo, Lucas
Reichheld, Sarah
Cabral, Sarah
Mowry, Kimberly
Sandstede, Bjorn
contents 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 \textit{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.
format Preprint
id arxiv_https___arxiv_org_abs_2307_15857
institution arXiv
publishDate 2023
record_format arxiv
spellingShingle Parameter identifiability in PDE models of fluorescence recovery after photobleaching
Ciocanel, Maria-Veronica
Ding, Lee
Mastromatteo, Lucas
Reichheld, Sarah
Cabral, Sarah
Mowry, Kimberly
Sandstede, Bjorn
Quantitative Methods
Dynamical Systems
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 \textit{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.
title Parameter identifiability in PDE models of fluorescence recovery after photobleaching
topic Quantitative Methods
Dynamical Systems
url https://arxiv.org/abs/2307.15857