Information-theoretic analysis of the dynamics of an executable biological model

PLoS One. 2013;8(3):e59303. doi: 10.1371/journal.pone.0059303. Epub 2013 Mar 19.

Abstract

To facilitate analysis and understanding of biological systems, large-scale data are often integrated into models using a variety of mathematical and computational approaches. Such models describe the dynamics of the biological system and can be used to study the changes in the state of the system over time. For many model classes, such as discrete or continuous dynamical systems, there exist appropriate frameworks and tools for analyzing system dynamics. However, the heterogeneous information that encodes and bridges molecular and cellular dynamics, inherent to fine-grained molecular simulation models, presents significant challenges to the study of system dynamics. In this paper, we present an algorithmic information theory based approach for the analysis and interpretation of the dynamics of such executable models of biological systems. We apply a normalized compression distance (NCD) analysis to the state representations of a model that simulates the immune decision making and immune cell behavior. We show that this analysis successfully captures the essential information in the dynamics of the system, which results from a variety of events including proliferation, differentiation, or perturbations such as gene knock-outs. We demonstrate that this approach can be used for the analysis of executable models, regardless of the modeling framework, and for making experimentally quantifiable predictions.

MeSH terms

  • Algorithms*
  • Humans
  • Immunity, Cellular / immunology*
  • Information Theory*
  • Models, Biological*
  • Molecular Dynamics Simulation*

Grants and funding

This work was supported by the Academy of Finland project number 132877 (MN) and 251937 (JK) and by the Luxembourg Centre for Systems Biomedicine and the University of Luxembourg and GETA – Graduate School in Electronics, Telecommunications and Automation, from Aalto University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.