Modular response analysis of cellular regulatory networks

J Theor Biol. 2002 Oct 21;218(4):507-20.

Abstract

The sheer complexity of intracellular regulatory networks, which involve signal transducing, metabolic, and genetic circuits, hampers our ability to carry out a quantitative analysis of their functions. Here, we describe an approach that greatly simplifies this type of analysis by capitalizing on the modular organization of such networks. Steady-state responses of the network as a whole are accounted for in terms of intermodular interactions between the modules alone; processes operating solely within modules need not be considered when analysing signal transfer through the entire network. The intermodular interactions are quantified through (local) response coefficients which populate an interaction map (matrix). This matrix can be derived from a biochemical or molecular biological analysis of (macro) molecular interactions that constitute the regulatory network. The approach is illustrated by two examples: (i) mitogenic signalling through the mitogen-activated protein kinase cascade in the epidermal growth factor receptor network and (ii) regulation of ammonium assimilation in Escherichia coli.

Publication types

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

MeSH terms

  • Animals
  • Cell Communication / physiology
  • Cell Physiological Phenomena*
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / metabolism
  • Escherichia coli / metabolism
  • MAP Kinase Signaling System
  • Models, Biological
  • Quaternary Ammonium Compounds / metabolism
  • Signal Transduction / physiology*

Substances

  • Quaternary Ammonium Compounds
  • Epidermal Growth Factor
  • ErbB Receptors