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An Integrated Pipeline for Combining in vitro Data and Mathematical Models Using a Bayesian Parameter Inference Approach to Characterize Spatio-temporal Chemokine Gradient Formation

Kalogiros, Dimitris I.; Russell, Matthew; Bonneuil, Willy; Frattolin, Jennifer; Watson, Daniel; Moore Jr, James E.; Kypraios, Theodore; Brook, Bindi S.

Authors

Willy Bonneuil

Jennifer Frattolin

Daniel Watson

James E. Moore Jr



Abstract

All protective and pathogenic immune and inflammatory responses rely heavily on leukocyte migration and localization. Chemokines are secreted chemoattractants that orchestrate the positioning and migration of leukocytes through concentration gradients. The mechanisms underlying chemokine gradient establishment and control include physical as well as biological phenomena. Mathematical models offer the potential to both understand this complexity and suggest interventions to modulate immune function. Constructing models that have powerful predictive capability relies on experimental data to estimate model parameters accurately, but even with a reductionist approach, most experiments include multiple cell types, competing interdependent processes and considerable uncertainty. Therefore, we propose the use of reduced modelling and experimental frameworks in complement, to minimize the number of parameters to be estimated. We present a Bayesian optimization framework that accounts for advection and diffusion of a chemokine surrogate and the chemokine CCL19, transport processes that are known to contribute to the establishment of spatio-temporal chemokine gradients. Three examples are provided that demonstrate the estimation of the governing parameters as well as the underlying uncertainty.

This study demonstrates how a synergistic approach between experimental and computational modelling benefits from the Bayesian approach to provide a robust analysis of chemokine transport. It provides a building block for a larger research effort to gain holistic insight and generate novel and testable hypotheses in chemokine biology and leukocyte trafficking.

Citation

Kalogiros, D. I., Russell, M., Bonneuil, W., Frattolin, J., Watson, D., Moore Jr, J. E., …Brook, B. S. (2019). An Integrated Pipeline for Combining in vitro Data and Mathematical Models Using a Bayesian Parameter Inference Approach to Characterize Spatio-temporal Chemokine Gradient Formation. Frontiers in Immunology, 10, https://doi.org/10.3389/fimmu.2019.01986

Journal Article Type Article
Acceptance Date Aug 6, 2019
Online Publication Date Oct 11, 2019
Publication Date Oct 11, 2019
Deposit Date Oct 11, 2019
Publicly Available Date Oct 15, 2019
Journal Frontiers in Immunology
Electronic ISSN 1664-3224
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 10
Article Number 1986
DOI https://doi.org/10.3389/fimmu.2019.01986
Keywords Chemokine transport dynamics, Microfluidic device, Model validation, Bayesian parameter inference, sequential Bayesian updating, MCMC methods, Partial Differential Equations
Public URL https://nottingham-repository.worktribe.com/output/2444912
Publisher URL https://www.frontiersin.org/articles/10.3389/fimmu.2019.01986/full

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