title: Utilization of the bootstrap method for determining confidence intervals of parameters for a model of MAP1B protein transport in axons.
abstract: This paper develops a model of axonal transport of MAP1B protein. The problem of determining parameter values for the proposed model utilizing limited available experimental data is addressed. We used a global minimum search algorithm to find parameter values that minimize the discrepancy between model predictions and published experimental results. By analyzing the best fit parameter values it was established that some processes can be dropped from the model without losing accuracy, thus a simplified version of the model was formulated. In particular, our analysis suggests that reversals in MAP1B transport are infrequent and can be neglected. The detachment of anterogradely-biased MAP1B from microtubules (MTs) and the attachment of retrogradely-biased MAP1B to MTs can also be neglected. An analytical solution for the simplified model was obtained. Confidence intervals for the determined parameters were found by bootstrapping model residuals. The resultant analysis heavily constrained the values of some parameters while showing that some could vary without significantly impacting model error. For example, our analysis suggests that, above a certain threshold value, the kinetic constant determining the rate of MAP1B transition from the retrograde pausing state to the off-track state has little impact on model error. On the contrary, the kinetic constant describing MAP1B transition from a pausing to a running state has great impact on model error.
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Kuznetsov
authors.affiliation: Dept. of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA. Electronic address: avkuznet@ncsu.edu.
authors.forename: A V
authors.initials: AV
authors.lastname: Kuznetsov
mesh_terms: D000465:Algorithms; D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism*; D016001:Confidence Intervals; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008962:Models, Theoretical; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport
chemical_list: D008869:Microtubule-Associated Proteins; C085284:microtubule-associated protein 1B
keywords: Bootstrapping; Neuron; Parameter determination; Resampling residuals; Slow axonal transport