Document Type

Article

Publication Date

July 2006

Comments

This article has been peer reviewed. It is the author's final version prior to publication in Systems Biology 153(4):236-246, July 2006. The published version is available from the IET Digital Library at http://scitation.aip.org/getabs/servlet/GetabsServlet?prog=normal&id=IPSBDJ000153000004000236000001&idtype=cvips&gifs=Yes. Copyright © 2006 by the Institution of Engineering and Technology.

Abstract

Large, complex data sets that are generated from microarray experiments, create a need for systematic analysis techniques to unravel the underlying connectivity of gene regulatory networks. A modular approach, previously proposed by Kholodenko and co-workers, helps to scale down the network complexity into more computationally manageable entities called modules. A functional module includes a gene's mRNA, promoter and resulting products, thus encompassing a large set of interacting states. The essential elements of this approach are described in detail for a three-gene model network and later extended to a ten-gene model network, demonstrating scalability. The network architecture is identified by analysing in silico steady-state changes in the activities of only the module outputs, communicating intermediates, that result from specific perturbations applied to the network modules one at a time. These steady-state changes form the system response matrix, which is used to compute the network connectivity or network interaction map. By employing a known biochemical network, the accuracy of the modular approach and its sensitivity to key assumptions are evaluated.

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