title: Deciphering transcriptional regulations coordinating the response to environmental changes.
abstract: BACKGROUND
  Gene co-expression evidenced as a response to environmental changes has shown that transcriptional activity is coordinated, which pinpoints the role of transcriptional regulatory networks (TRNs). Nevertheless, the prediction of TRNs based on the affinity of transcription factors (TFs) with binding sites (BSs) generally produces an over-estimation of the observable TF/BS relations within the network and therefore many of the predicted relations are spurious.
  
  
  RESULTS
  We present LOMBARDE, a bioinformatics method that extracts from a TRN determined from a set of predicted TF/BS affinities a subnetwork explaining a given set of observed co-expressions by choosing the TFs and BSs most likely to be involved in the co-regulation. LOMBARDE solves an optimization problem which selects confident paths within a given TRN that join a putative common regulator with two co-expressed genes via regulatory cascades. To evaluate the method, we used public data of Escherichia coli to produce a regulatory network that explained almost all observed co-expressions while using only 19 % of the input TF/BS affinities but including about 66 % of the independent experimentally validated regulations in the input data. When all known validated TF/BS affinities were integrated into the input data the precision of LOMBARDE increased significantly. The topological characteristics of the subnetwork that was obtained were similar to the characteristics described for known validated TRNs.
  
  
  CONCLUSIONS
  LOMBARDE provides a useful modeling scheme for deciphering the regulatory mechanisms that underlie the phenotypic responses of an organism to environmental challenges. The method can become a reliable tool for further research on genome-scale transcriptional regulation studies.
authors.affiliation: Center for Mathematical Modeling (UMI-CNRS 2807), Universidad de Chile, Santiago, Chile. viacuna@dim.uchile.cl.|Center for Genome Regulation, Universidad de Chile, Santiago, Chile. viacuna@dim.uchile.cl.
authors.forename: Vicente
authors.initials: V
authors.lastname: Acuña
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul University, Istanbul, Turkey. andres.aravena@istanbul.edu.tr.
authors.forename: Andrés
authors.initials: A
authors.lastname: Aravena
authors.affiliation: IRCCyN (UMR CNRS 6597), École Centrale de Nantes, Nantes, France. carito.guziolowski@irccyn.ec-nantes.fr.
authors.forename: Carito
authors.initials: C
authors.lastname: Guziolowski
authors.affiliation: LINA (UMR CNRS 6241), Université de Nantes, École des Mines de Nantes, Nantes, France. damien.eveillard@univ-nantes.fr.
authors.forename: Damien
authors.initials: D
authors.lastname: Eveillard
authors.affiliation: IRISA Project Dyliss (UMR CNRS 6074), Université de Rennes 1, Rennes, France. anne.siegel@irisa.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Siegel
authors.affiliation: Center for Mathematical Modeling (UMI-CNRS 2807), Universidad de Chile, Santiago, Chile. amaass@dim.uchile.cl.|Center for Genome Regulation, Universidad de Chile, Santiago, Chile. amaass@dim.uchile.cl.|Department of Mathematical Engineering, Universidad de Chile, Santiago, Chile. amaass@dim.uchile.cl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Maass
mesh_terms: D019295:Computational Biology / Q000379:methods*; D004777:Environment; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors