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Quantifying gene network connectivity in silico: Scalability and accuracy of a modular approach
Journal article   Open access

Quantifying gene network connectivity in silico: Scalability and accuracy of a modular approach

Nirupama Yalamanchili, Daniel E. Zak, Babatunde A. Ogunnaike, James S. Schwaber, Andres Kriete and Boris N. Kholodenko
Systems biology, v 153(4), pp 236-246
01 Jul 2006
PMID: 16986625
url
https://europepmc.org/articles/pmc2346590View
Accepted (AM)Open Access (License Unspecified) Open

Abstract

connection coefficients gene networks modular approach reverse engineering
Large, complex datasets 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 analyzing 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, we are able to evaluate the accuracy of the modular approach and its sensitivity to key assumptions.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
Mathematical & Computational Biology
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