Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences

David C. King, James Taylor, Laura Elnitski, Francesca Chiaromonte, Webb Miller, Ross Cameron Hardison

Research output: Contribution to journalArticle

157 Citations (Scopus)

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 ∼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 ∼7% of the human genome.

Original languageEnglish (US)
Pages (from-to)1051-1060
Number of pages10
JournalGenome research
Volume15
Issue number8
DOIs
StatePublished - Aug 1 2005

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Genome
Nucleic Acid Regulatory Sequences
Conserved Sequence
Human Genome
Genomics
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

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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 ∼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 ∼7{\%} of the human genome.",
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Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences. / King, David C.; Taylor, James; Elnitski, Laura; Chiaromonte, Francesca; Miller, Webb; Hardison, Ross Cameron.

In: Genome research, Vol. 15, No. 8, 01.08.2005, p. 1051-1060.

Research output: Contribution to journalArticle

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