title: CAGER: classification analysis of gene expression regulation using multiple information sources.
abstract: BACKGROUND
  Many classification approaches have been applied to analyzing transcriptional regulation of gene expressions. These methods build models that can explain a gene's expression level from the regulatory elements (features) on its promoter sequence. Different types of features, such as experimentally verified binding motifs, motifs discovered by computer programs, or transcription factor binding data measured with Chromatin Immunoprecipitation (ChIP) assays, have been used towards this goal. Each type of features has been shown successful in modeling gene transcriptional regulation under certain conditions. However, no comparison has been made to evaluate the relative merit of these features. Furthermore, most publicly available classification tools were not designed specifically for modeling transcriptional regulation, and do not allow the user to combine different types of features.
  
  
  RESULTS
  In this study, we use a specific classification method, decision trees, to model transcriptional regulation in yeast with features based on predefined motifs, automatically identified motifs, ChlP-chip data, or their combinations. We compare the accuracies and stability of these models, and analyze their capabilities in identifying functionally related genes. Furthermore, we design and implement a user-friendly web server called CAGER (Classification Analysis of Gene Expression Regulation) that integrates several software components for automated analysis of transcriptional regulation using decision trees. Finally, we use CAGER to study the transcriptional regulation of Arabidopsis genes in response to abscisic acid, and report some interesting new results.
  
  
  CONCLUSIONS
  Models built with ChlP-chip data suffer from low accuracies when the condition under which gene expressions are measured is significantly different from the condition under which the ChIP experiment is conducted. Models built with automatically identified motifs can sometimes discover new features, but their modeling accuracies may have been over-estimated in previous studies. Furthermore, models built with automatically identified motifs are not stable with respect to noises. A combination of ChlP-chip data and predefined motifs can substantially improve modeling accuracies, and is effective in identifying true regulons. The CAGER web server, which is freely available at http://cic.cs.wustl.edu/CAGER/, allows the user to select combinations of different feature types for building decision trees, and interact with the models graphically. We believe that it will be a useful tool to facilitate the discovery of gene transcriptional regulatory networks.
authors.affiliation: Department of Computer Science and Engineering, Washington University, St. Louis, MO 63130, USA. jruan@cse.wustl.edu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ruan
authors.forename: Weixiong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D017360:Arabidopsis / Q000378:metabolism; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D003196:Computer Graphics; D004268:DNA-Binding Proteins; D003627:Data Interpretation, Statistical; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D005800:Genes, Fungal; D017343:Genes, Plant; D008954:Models, Biological; D008957:Models, Genetic; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D011381:Programming Languages; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D012984:Software; D012985:Software Design; D014158:Transcription, Genetic; D015854:Up-Regulation; D014584:User-Computer Interface
chemical_list: D004268:DNA-Binding Proteins