title: Quantifying gene network connectivity in silico: scalability and accuracy of a modular approach.
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.
authors.affiliation: School of Biomedical Engineering and Health Sciences, Drexel University, Philadelphia, PA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Yalamanchili
authors.forename: D E
authors.initials: DE
authors.lastname: Zak
authors.forename: B A
authors.initials: BA
authors.lastname: Ogunnaike
authors.forename: J S
authors.initials: JS
authors.lastname: Schwaber
authors.forename: A
authors.initials: A
authors.lastname: Kriete
authors.forename: B N
authors.initials: BN
authors.lastname: Kholodenko
mesh_terms: D000465:Algorithms; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors