Email updates

Keep up to date with the latest news and content from BMC Bioinformatics and BioMed Central.

Open Access Highly Accessed Research article

Parameters for accurate genome alignment

Martin C Frith1*, Michiaki Hamada12 and Paul Horton1

Author Affiliations

1 Computational Biology Research Center, Institute for Advanced Industrial Science and Technology, Tokyo 135-0064, Japan

2 Mizuho Information & Research Institute, Inc. 2-3 Kanda-Nishikicho, Chiyoda-ku, Tokyo 101-8443, Japan

For all author emails, please log on.

BMC Bioinformatics 2010, 11:80  doi:10.1186/1471-2105-11-80

Published: 9 February 2010

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/ webcite.