Global sensitivity analysis used to interpret biological experimental results

J Math Biol. 2015 Jul;71(1):151-70. doi: 10.1007/s00285-014-0818-3. Epub 2014 Jul 25.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biofilms / growth & development
  • Computational Biology / methods*
  • Disease Models, Animal
  • Host-Pathogen Interactions / immunology
  • Humans
  • Mathematical Concepts
  • Methicillin-Resistant Staphylococcus aureus / immunology
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity
  • Methicillin-Resistant Staphylococcus aureus / physiology
  • Mice
  • Mice, Inbred Strains
  • Models, Biological*
  • Models, Immunological
  • Osteomyelitis / immunology
  • Staphylococcal Infections / immunology