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Nonlinear mixed-effects models to analyze actin dynamics in dendritic spines
Di Credico, Gioia
Pelucchi, Silvia
PAULI, FRANCESCO
Stringhi, Ramona
Marcello, Elena
Edefonti, Valeria
2024
Abstract
Fluorescence recovery after photobleaching (FRAP) is used to study actin-turnover in dendritic spines providing recovery_trajectories over time within a nested data structure (i.e. spine/neuron/culture). Statistical approaches to FRAP usually_consider one-phase association models to estimate recovery-curve-specific parameters and test statistical hypotheses on_curve parameters either at the spine or neuron level, ignoring the nested data structure. However, this approach leads to_pseudoreplication concerns. We propose a nonlinear mixed-effects model to integrate the one-phase association model_estimate with nested data structure of FRAP experiments; this allowed us to model heteroscedasticity with an exponential_variance function, accounting for the different effects of the experimental condition, and autocorrelation structure over time with_an autoregressive model. We used this approach to evaluate the effect of the downregulation of the actin-binding protein CAP2_on actin dynamics. Our model was able to capture the higher variance, thus increased instability, of actin cytoskeleton upon_CAP2 down-regulation. We developed an R-based Shiny application, termed FRApp, to fit the statistical models introduced_without requiring programming expertise._
Source
Gioia Di Credico, Silvia Pelucchi, Francesco Pauli, Ramona Stringhi, Elena Marcello, and Valeria Edefonti, "Nonlinear mixed-effects models to analyze actin dynamics in dendritic spines", Trieste, EUT Edizioni Università di Trieste, 2024
Languages
en
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
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