title: Differential regulation enrichment analysis via the integration of transcriptional regulatory network and gene expression data.
abstract: BACKGROUND
  Although many gene set analysis methods have been proposed to explore associations between a phenotype and a group of genes sharing common biological functions or involved in the same biological process, the underlying biological mechanisms of identified gene sets are typically unexplained.
  
  
  RESULTS
  We propose a method called Differential Regulation-based enrichment Analysis for GENe sets (DRAGEN) to identify gene sets in which a significant proportion of genes have their transcriptional regulatory patterns changed in a perturbed phenotype. We conduct comprehensive simulation studies to demonstrate the capability of our method in identifying differentially regulated gene sets. We further apply our method to three human microarray expression datasets, two with hormone treated and control samples and one concerning different cell cycle phases. Results indicate that the capability of DRAGEN in identifying phenotype-associated gene sets is significantly superior to those of four existing methods for analyzing differentially expressed gene sets. We conclude that the proposed differential regulation enrichment analysis method, though exploratory in nature, complements the existing gene set analysis methods and provides a promising new direction for the interpretation of gene expression data.
  
  
  METHODS
  The program of DRAGEN is freely available at http://bioinfo.au.tsinghua.edu.cn/dragen/.
  
  
  BACKGROUND
  ruijiang@tsinghua.edu.cn or jiang@cs.ucr.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST; Department of Automation, Tsinghua University, Beijing 100084, China, Department of Computer Science and Engineering, University of California, Riverside, CA 92521, USA, Department of Statistics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Shining
authors.initials: S
authors.lastname: Ma
authors.affiliation: MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST; Department of Automation, Tsinghua University, Beijing 100084, China, Department of Computer Science and Engineering, University of California, Riverside, CA 92521, USA, Department of Statistics, Stanford University, Stanford, CA 94305, USA MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST; Department of Automation, Tsinghua University, Beijing 100084, China, Department of Computer Science and Engineering, University of California, Riverside, CA 92521, USA, Department of Statistics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST; Department of Automation, Tsinghua University, Beijing 100084, China, Department of Computer Science and Engineering, University of California, Riverside, CA 92521, USA, Department of Statistics, Stanford University, Stanford, CA 94305, USA MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST; Department of Automation, Tsinghua University, Beijing 100084, China, Department of Computer Science and Engineering, University of California, Riverside, CA 92521, USA, Department of Statistics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Jiang
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics; D012984:Software
chemical_list: D029968:Escherichia coli Proteins