Analyzing fixed points of intracellular regulation networks with interrelated feedback topology

BMC Syst Biol. 2012 Jun 6:6:57. doi: 10.1186/1752-0509-6-57.

Abstract

Background: Modeling the dynamics of intracellular regulation networks by systems of ordinary differential equations has become a standard method in systems biology, and it has been shown that the behavior of these networks is often tightly connected to the network topology. We have recently introduced the circuit-breaking algorithm, a method that uses the network topology to construct a one-dimensional circuit-characteristic of the system. It was shown that this characteristic can be used for an efficient calculation of the system's fixed points.

Results: Here we extend previous work and show several connections between the circuit-characteristic and the stability of fixed points. In particular, we derive a sufficient condition on the characteristic for a fixed point to be unstable for certain graph structures and demonstrate that the characteristic does not contain the information to decide whether a fixed point is asymptotically stable. All statements are illustrated on biological network models.

Conclusions: Single feedback circuits and their role for complex dynamic behavior of biological networks have extensively been investigated, but a transfer of most of these concepts to more complex topologies is difficult. In this context, our algorithm is a powerful new approach for the analysis of regulation networks that goes beyond single isolated feedback circuits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cell Differentiation
  • Computer Graphics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / metabolism
  • Feedback, Physiological*
  • Hematopoietic Stem Cells / cytology
  • Intracellular Space / metabolism*
  • Models, Biological*
  • Repressor Proteins / metabolism
  • Tryptophan / metabolism

Substances

  • Escherichia coli Proteins
  • Repressor Proteins
  • Tryptophan