Parameters for accurate genome alignment

Martin C. Frith, Michiaki Hamada, Paul Horton

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Background: Genome sequence alignments form the basis of much research. Genome alignment depends on various mundane but critical choices, such as how to mask repeats and which score parameters to use. Surprisingly, there has been no large-scale assessment of these choices using real genomic data. Moreover, rigorous procedures to control the rate of spurious alignment have not been employed.Results: We have assessed 495 combinations of score parameters for alignment of animal, plant, and fungal genomes. As our gold-standard of accuracy, we used genome alignments implied by multiple alignments of proteins and of structural RNAs. We found the HOXD scoring schemes underlying alignments in the UCSC genome database to be far from optimal, and suggest better parameters. Higher values of the X-drop parameter are not always better. E-values accurately indicate the rate of spurious alignment, but only if tandem repeats are masked in a non-standard way. Finally, we show that γ-centroid (probabilistic) alignment can find highly reliable subsets of aligned bases.Conclusions: These results enable more accurate genome alignment, with reliability measures for local alignments and for individual aligned bases. This study was made possible by our new software, LAST, which can align vertebrate genomes in a few hours http://last.cbrc.jp/.

Original languageEnglish
Article number80
JournalBMC Bioinformatics
Volume11
DOIs
Publication statusPublished - 2010 Feb 9
Externally publishedYes

Fingerprint

Genome
Alignment
Genes
Fungal Genome
Plant Genome
Tandem Repeat Sequences
Sequence Alignment
Masks
Gold
Vertebrates
Software
Databases
RNA
Centroid
Scoring
Mask
Genomics
Animals
Research
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Structural Biology
  • Applied Mathematics

Cite this

Parameters for accurate genome alignment. / Frith, Martin C.; Hamada, Michiaki; Horton, Paul.

In: BMC Bioinformatics, Vol. 11, 80, 09.02.2010.

Research output: Contribution to journalArticle

Frith, Martin C. ; Hamada, Michiaki ; Horton, Paul. / Parameters for accurate genome alignment. In: BMC Bioinformatics. 2010 ; Vol. 11.
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