title: Information-theoretic analysis of the dynamics of an executable biological model.
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.
authors.affiliation: Institute for Systems Biology, Seattle, Washington, United States of America.
authors.forename: Avital
authors.initials: A
authors.lastname: Sadot
authors.forename: Septimia
authors.initials: S
authors.lastname: Sarbu
authors.forename: Juha
authors.initials: J
authors.lastname: Kesseli
authors.forename: Hila
authors.initials: H
authors.lastname: Amir-Kroll
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
authors.forename: Ilya
authors.initials: I
authors.lastname: Shmulevich
mesh_terms: D000465:Algorithms; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007257:Information Theory; D008954:Models, Biological; D056004:Molecular Dynamics Simulation