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Nucleic Acids Research Advance Access published online on May 8, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm209
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© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genomics

Comparative analysis of bacterial genomes: identification of divergent regions in mycobacterial strains using an anchor-based approach

Anchal Vishnoi1,*, Rahul Roy2 and Alok Bhattacharya1,3

1Center for Computational Biology and Bioinformatics, School of Information Technology, 2Indian Statistical Institute, New Delhi 110016, India and 3School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India

*To whom correspondence should be addressed. Tel: + 91 11 2671 7585; Fax: + 91 11 2671 7586; Email: anchalv{at}gmail.com, av1563{at}students.jnu.ac.in, alok0200{at}mail.jnu.ac.in

Received December 6, 2006. Revised March 19, 2007. Accepted March 26, 2007.

Comparative genomic approaches are useful in identifying molecular differences between organisms. Currently available methods fail to identify small changes in genomes, such as expansion of short repetitive motifs and to analyse divergent sequences. In this report, we describe an anchor-based whole genome comparison (ABWGC) method. ABWGC is based on random sampling of anchor sequences from one genome, followed by analysis of sampled and homologous regions from the target genome. The method was applied to compare two strains of Mycobacterium tuberculosis CDC1551 and H37Rv. ABWGC was able to identify a total of 104 indels including 20 expansion of short repetitive sequences and five recombination events. It included 18 new unidentified genomic differences. ABWGC also identified 188 SNPs including eight new ones. The method was also used to compare M. tuberculosis H37Rv and M. avium genomes. ABWGC was able to correctly pick 1002 additional indels (size >100 nt) between the two organisms in contrast to MUMmer, a popular tool for comparative genomics. ABWGC was able to identify correctly repeat expansion and indels in a set of simulated sequences. The study also revealed important role of small repeat expansion in the evolution of M. tuberculosis strains.


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