title: Genome-wide decoding of hierarchical modular structure of transcriptional regulation by cis-element and expression clustering.
abstract: BACKGROUND
  A holistic approach to the study of cellular processes is identifying both gene-expression changes and regulatory elements promoting such changes. Cellular regulatory processes can be viewed as transcriptional modules (TMs), groups of coexpressed genes regulated by groups of transcription factors (TFs). We set out to devise a method that would identify TMs while avoiding arbitrary thresholds on TM sizes and number.
  
  
  METHODS
  Assuming that gene expression is determined by TFs that bind to the gene's promoter, clustering of genes based on TF binding sites (cis-elements) should create gene groups similar to those obtained by gene expression clustering. Intersections between the expression and cis-element-based gene clusters reveal TMs. Statistical significance assigned to each TM allows identification of regulatory units of any size.
  
  
  RESULTS
  Our method correctly identifies the number and sizes of TMs on simulated datasets. We demonstrate that yeast experimental TMs are biologically relevant by comparing them with MIPS and GO categories. Our modules are in statistically significant agreement with TMs from other research groups. This work suggests that there is no preferential division of biological processes into regulatory units; each degree of partitioning exhibits a slice of biological network revealing hierarchical modular organization of transcriptional regulation.
authors.affiliation: Bioinformatics Program, Boston University, Boston, MA 02215, USA. dleyfer@gnsbiotech.com
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Leyfer
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
mesh_terms: D000465:Algorithms; D002874:Chromosome Mapping / Q000379:methods*; D016000:Cluster Analysis; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics*; D005815:Genetic Code; D008957:Models, Genetic; D005810:Multigene Family / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*