AUTHOR=Chen Xi , Wang Wenjing , Xie Guangrui , Hontecillas Raquel , Verma Meghna , Leber Andrew , Bassaganya-Riera Josep , Abedi Vida TITLE=Multi-Resolution Sensitivity Analysis of Model of Immune Response to Helicobacter pylori Infection via Spatio-Temporal Metamodeling JOURNAL=Frontiers in Applied Mathematics and Statistics VOLUME=5 YEAR=2019 URL=https://www.frontiersin.org/journals/applied-mathematics-and-statistics/articles/10.3389/fams.2019.00004 DOI=10.3389/fams.2019.00004 ISSN=2297-4687 ABSTRACT=

Computational immunology studies the interactions between the components of the immune system that includes the interplay between regulatory and inflammatory elements. It provides a solid framework that aids the conversion of pre-clinical and clinical data into mathematical equations to enable modeling and in silico experimentation. The modeling-driven insights shed lights on some of the most pressing immunological questions and aid the design of fruitful validation experiments. A typical system of equations, mapping the interaction among various immunological entities and a pathogen, consists of a high-dimensional input parameter space that could drive the stochastic system outputs in unpredictable directions. In this paper, we perform spatio-temporal metamodel-based sensitivity analysis of immune response to Helicobacter pylori infection using the computational model developed by the ENteric Immune SImulator (ENISI). We propose a two-stage metamodel-based procedure to obtain the estimates of the Sobol' total and first-order indices for each input parameter, for quantifying their time-varying impacts on each output of interest. In particular, we fully reuse and exploit information from an existing simulated dataset, develop a novel sampling design for constructing the two-stage metamodels, and perform metamodel-based sensitivity analysis. The proposed procedure is scalable, easily interpretable, and adaptable to any multi-input multi-output complex systems of equations with a high-dimensional input parameter space.