Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network.
BACKGROUND
It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems.


RESULTS
Using Boolean network models as an exemplar, we present a new technique to identify subsystems, based on their dynamical properties. The main part of the method depends only on the stable dynamics (attractors) of the system, thus requiring no prior knowledge of the underlying network. However, knowledge of the logical relationships between the network components can be used to describe how each subsystem is regulated. To demonstrate its applicability to genetic regulatory systems, we apply the method to a model of the Drosophila segment polarity network, providing a detailed breakdown of the system.


CONCLUSIONS
We have designed a technique for decomposing any set of discrete-state, discrete-time attractors into subsystems. Having a suitable mathematical model also allows us to describe how each subsystem is regulated and how robust each subsystem is against perturbations. However, since the subsystems are found directly from the attractors, a mathematical model or underlying network topology is not necessarily required to identify them, potentially allowing the method to be applied directly to experimental expression data.
Irons
David J
DJ
Department of Computer Science, University of Sheffield, UK. d.irons@sheffield.ac.uk
Monk
Nicholas A M
NA
D000465:Algorithms; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D016000:Cluster Analysis; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D025461:Feedback, Physiological / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000502:physiology*; D017344:Genes, Insect / Q000502:physiology; D008957:Models, Genetic; D017711:Nonlinear Dynamics; D049490:Systems Biology / Q000379:methods*
D029721:Drosophila Proteins