Discovery of regulatory elements in vertebrates through comparative genomics.
We have analyzed issues of reliability in studies in which comparative genomic approaches have been applied to the discovery of regulatory elements at a genome-wide level in vertebrates. We point out some potential problems with such studies, including difficulties in accurately identifying orthologous promoter regions. Many of these subtle analytical problems have become apparent only when studying the more complex vertebrate genomes. By determining motif reliability, we compared existing tools when applied to the discovery of vertebrate regulatory elements. We then used a statistical clustering method to produce a computational catalog of high quality putative regulatory elements from vertebrates, some of which are widely conserved among vertebrates and many of which are novel regulatory elements. The results provide a glimpse into the wealth of information that comparative genomics can yield and suggest the need for further improvement of genome-wide comparative computational techniques.
Prakash
Amol
A
Department of Computer Science and Engineering, Box 352350, University of Washington, Seattle, Washington 98195-2350, USA.
Tompa
Martin
M
D000465:Algorithms; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D017124:Conserved Sequence; D018983:DNA Footprinting / Q000379:methods; D019143:Evolution, Molecular; D023281:Genomics / Q000379:methods*; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014714:Vertebrates / Q000235:genetics*