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Bioinformatics Advance Access published online on April 10, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl112
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© The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received December 15, 2005
Revised March 20, 2006
Accepted March 21, 2006

Article

AuberGene - a sensitive genome alignment tool

Radek Szklarczyk 1 and Jaap Heringa 1 *

1 Centre for Integrative Bioinformatics VU (IBIVU), Faculty of Sciences and Faculty of Earth and Life Sciences, Vrije Universiteit, De Boelelaan 1081A, 1081 HV Amsterdam, The Netherlands

* To whom correspondence should be addressed.
Jaap Heringa, E-mail: heringa{at}cs.vu.nl


  Abstract

Motivation: The accumulation of genome sequences will only accelerate in the coming years. We aim to use this abundance of data to improve the quality of genomic alignments and devised a method which is capable of detecting regions evolving under weak or no evolutionary constraints.

Results: We describe a genome alignment program AuberGene, which explores the idea of transitivity of local alignments. Assessment of the program was done based on a 2Mbp genomic region containing the CFTR gene of 13 species. In this region, we can identify 53% of human sequence sharing common ancestry with mouse, as compared to 44% found using the usual pairwise alignment. Between human and tetraodon 93 orthologous exons are found, as compared to 77 detected by the pairwise human-tetraodon comparison.

AuberGene allows the user to 1) identify distant, previously undetected, conserved orthogonal regions such as ORFs or regulatory regions; 2) identify neutrally evolving regions in related species which are often overlooked by other alignment programs; 3) recognize false orthologous genomic regions. The increased sensitivity of the method is not obtained at the cost of reduced specificity. Our results suggest that, over the CFTR region, human shares 10% more sequence with mouse than previously thought (approximately 50%, instead of 40% found with the pairwise alignment).

Availability: The source code and tracks for UCSC Genome Browser generated with the program are available from http://www.ibivu.cs.vu.nl/programs/aubergenewww.

Associate Editor: Dmitrij Frishman
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