title: Frameshift alignment: statistics and post-genomic applications.
abstract: BACKGROUND
  The alignment of DNA sequences to proteins, allowing for frameshifts, is a classic method in sequence analysis. It can help identify pseudogenes (which accumulate mutations), analyze raw DNA and RNA sequence data (which may have frameshift sequencing errors), investigate ribosomal frameshifts, etc. Often, however, only ad hoc approximations or simulations are available to provide the statistical significance of a frameshift alignment score.
  
  
  RESULTS
  We describe a method to estimate statistical significance of frameshift alignments, similar to classic BLAST statistics. (BLAST presently does not permit its alignments to include frameshifts.) We also illustrate the continuing usefulness of frameshift alignment with two 'post-genomic' applications: (i) when finding pseudogenes within the human genome, frameshift alignments show that most anciently conserved non-coding human elements are recent pseudogenes with conserved ancestral genes; and (ii) when analyzing metagenomic DNA reads from polluted soil, frameshift alignments show that most alignable metagenomic reads contain frameshifts, suggesting that metagenomic analysis needs to use frameshift alignment to derive accurate results.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA and Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
authors.forename: Sergey L
authors.initials: SL
authors.lastname: Sheetlin
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA and Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
authors.forename: Yonil
authors.initials: Y
authors.lastname: Park
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA and Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Frith
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA and Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
authors.forename: John L
authors.initials: JL
authors.lastname: Spouge
mesh_terms: D000465:Algorithms; D003627:Data Interpretation, Statistical; D016368:Frameshift Mutation; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D056186:Metagenomics; D011544:Pseudogenes; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D017423:Sequence Analysis, RNA; D012984:Software