title: Genome-wide functional element detection using pairwise statistical alignment outperforms multiple genome footprinting techniques.
abstract: BACKGROUND
  Comparative genomic sequence analysis is a powerful approach for identifying putative functional elements in silico. The availability of full-genome sequences from many vertebrate species has resulted in the development of popular tools, for example, the phastCons software package that search large numbers of genomes to identify conserved elements. While phastCons can analyze many genomes simultaneously, it ignores potentially informative insertion and deletion events and relies on a fixed, precomputed multiple sequence alignment.
  
  
  RESULTS
  We have developed a new method, GRAPeFoot, which simultaneously aligns two full genomes and annotates a set of conserved regions exhibiting reduced rates of insertion, deletion and substitution mutations. We tested GRAPeFoot using the human and mouse genomes and compared its performance to a set of phastCons predictions hosted on the UCSC genome browser. Our results demonstrate that despite the use of only two genomes, GRAPeFoot identified constrained elements at rates comparable with phastCons, which analyzed data from 28 vertebrate genomes. This study demonstrates how integrated modelling of substitutions, indels and purifying selection allows a pairwise analysis to exhibit a sensitivity similar to a heuristic analysis of many genomes.
  
  
  BACKGROUND
  The GRAPeFoot software and set of genome-wide functional element predictions are freely available to download online at http://www.stats.ox.ac.uk/ approximately satija/GRAPeFoot/.
authors.affiliation: Department of Statistics, Oxford University, Oxford, UK. satija@stats.ox.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Satija
authors.forename: J
authors.initials: J
authors.lastname: Hein
authors.forename: G A
authors.initials: GA
authors.lastname: Lunter
mesh_terms: D000818:Animals; D018983:DNA Footprinting; D016678:Genome; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D012372:ROC Curve; D016415:Sequence Alignment / Q000379:methods*; D012984:Software