title: Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences.
abstract: Techniques of comparative genomics are being used to identify candidate functional DNA sequences, and objective evaluations are needed to assess their effectiveness. Different analytical methods score distinctive features of whole-genome alignments among human, mouse, and rat to predict functional regions. We evaluated three of these methods for their ability to identify the positions of known regulatory regions in the well-studied HBB gene complex. Two methods, multispecies conserved sequences and phastCons, quantify levels of conservation to estimate a likelihood that aligned DNA sequences are under purifying selection. A third function, regulatory potential (RP), measures the similarity of patterns in the alignments to those in known regulatory regions. The methods can correctly identify 50%-60% of noncoding positions in the HBB gene complex as regulatory or nonregulatory, with RP performing better than do other methods. When evaluated by the ability to discriminate genomic intervals, RP reaches a sensitivity of 0.78 and a true discovery rate of approximately 0.6. The performance is better on other reference sets; both phastCons and RP scores can capture almost all regulatory elements in those sets along with approximately 7% of the human genome.
authors: Center for Comparative Genomics and Bioinformatics, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors: David C
authors: DC
authors: King
authors: James
authors: J
authors: Taylor
authors: Laura
authors: L
authors: Elnitski
authors: Francesca
authors: F
authors: Chiaromonte
authors: Webb
authors: W
authors: Miller
authors: Ross C
authors: RC
authors: Hardison
mesh_terms: D000465:Algorithms; D000818:Animals; D016678:Genome; D005914:Globins / Q000235:genetics; D008322:Mammals / Q000235:genetics*; D012016:Reference Values; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment / Q000379:methods*; D012984:Software
chemical_list: D005914:Globins