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Steady state approach to model gene regulatory networks-simulation of microarray experiments

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Title Steady state approach to model gene regulatory networks-simulation of microarray experiments
 
Creator RAWOOL, SUBODH B
VENKATESH, KV
 
Subject microarray modeling
genetic regulatory network
steady state modeling
gal network
saccharomyces cerevisiae
 
Description Genetic regulatory networks (GRN) represent complex interactions between genes brought about through proteins that they code for. Quantification of expression levels in GRN either through experiments or theoretical modeling is a challenging task. Recently, microarray experiments have gained importance in evaluating GRN at the genome level. Microarray experiments yield log fold change in mRNA abundance which is helpful in deciphering connectivity in GRN. Current approaches such as data mining, Boolean or Bayesian modeling and combined use of expression and location data are useful in analyzing microarray data. However, these methodologies lack underlying mechanistic details present in GRN. We present here a steady state gene expression simulator (SSGES) which sets up steady state equations and simulates the response for a given network structure of a GRN. SSGES includes mechanistic details such as stoichiometry, protein–DNA and protein–protein interactions, translocation of regulatory proteins and autoregulation. SSGES can be used to simulate the response of a GRN in terms of fractional transcription and protein expression. SSGES can also be used to generate log fold change in mRNA abundance and protein expression implying that it is useful to simulate microarray type experiments. We have demonstrated these capabilities of SSGES by modeling the steady state response of GAL regulatory system in Saccharomyces cerevisiae. We have demonstrated that the predicted data qualitatively matched the microarray data obtained experimentally by Ideker et al. [Ideker, T., Thorsson, V., Ranish, J.A., Christmas, R., Buhler, J., Eng, J.K., Bumgarner, R., Goodlett, D.R., Aebersold, R., Hood, L., 2001. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 292, 929–934]. SSGES is available from authors upon request.
 
Publisher Elsevier
 
Date 2009-03-09T07:47:46Z
2011-11-25T18:57:13Z
2011-12-26T13:07:06Z
2011-12-27T05:55:08Z
2009-03-09T07:47:46Z
2011-11-25T18:57:13Z
2011-12-26T13:07:06Z
2011-12-27T05:55:08Z
2007
 
Type Article
 
Identifier Biosystems 90(3), 636-655
0303-2647
http://dx.doi.org/10.1016/j.biosystems.2007.02.003
http://hdl.handle.net/10054/917
http://dspace.library.iitb.ac.in/xmlui/handle/10054/917
 
Language en