Global sensitivity analysis used to interpret biological experimental results
- 25 July 2014
- journal article
- Published by Springer Science and Business Media LLC in Journal of Mathematical Biology
- Vol. 71 (1), 151-170
- https://doi.org/10.1007/s00285-014-0818-3
Abstract
Modeling host/pathogen interactions provides insight into immune defects that allow bacteria to overwhelm the host, mechanisms that allow vaccine strategies to be successful, and illusive interactions between immune components that govern the immune response to a challenge. However, even simplified models require a fairly high dimensional parameter space to be explored. Here we use global sensitivity analysis for parameters in a simple model for biofilm infections in mice. The results indicate which parameters are insignificant and are ‘frozen’ to yield a reduced model. The reduced model replicates the full model with high accuracy, using approximately half of the parameter space. We used the sensitivity to investigate the results of the combined biological and mathematical experiments for osteomyelitis. We are able to identify parts of the compartmentalized immune system that were responsible for each of the experimental outcomes. This model is one example for a technique that can be used generally.Keywords
This publication has 49 references indexed in Scilit:
- Mathematical modeling of the immune system recognition to mammary carcinoma antigenBMC Bioinformatics, 2012
- Suppression of the Inflammatory Immune Response Prevents the Development of Chronic Biofilm Infection Due to Methicillin-Resistant Staphylococcus aureusInfection and Immunity, 2011
- Murine Immune Response to a Chronic Staphylococcus aureus Biofilm InfectionInfection and Immunity, 2011
- Resolution of Staphylococcus aureus Biofilm Infection Using Vaccination and Antibiotic TreatmentInfection and Immunity, 2011
- Vaccine development inStaphylococcus aureus: taking the biofilm phenotype into considerationFEMS Immunology & Medical Microbiology, 2010
- A methodology for performing global uncertainty and sensitivity analysis in systems biologyJournal of Theoretical Biology, 2008
- A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administrationJournal of Theoretical Biology, 2006
- A reduced mathematical model of the acute inflammatory response: I. Derivation of model and analysis of anti-inflammationJournal of Theoretical Biology, 2006
- Identification of Staphylococcus aureus Proteins Recognized by the Antibody-Mediated Immune Response to a Biofilm InfectionInfection and Immunity, 2006
- Making best use of model evaluations to compute sensitivity indicesComputer Physics Communications, 2002