Nucleic Acids Research Advance Access originally published online on October 23, 2008
Nucleic Acids Research 2008 36(21):6664-6675; doi:10.1093/nar/gkn635
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Nucleic Acids Research, 2008, Vol. 36, No. 21 6664-6675
© 2008 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.
Computational Biology |
Genome bias influences amino acid choices: analysis of amino acid substitution and re-compilation of substitution matrices exclusive to an AT-biased genome
Computational and Functional Genomics Group & Sun Centre of Excellence in Medical Bioinformatics, Centre for DNA Fingerprinting and Diagnostics, EMBnet India Node, Hyderabad 500076, India
*To whom correspondence should be addressed. Tel: +91 40 27171503; Fax: +91 40 27155610; Email: akash{at}cdfd.org.in
Received April 1, 2008. Revised August 29, 2008. Accepted September 15, 2008.
The genomic era has seen a remarkable increase in the number of genomes being sequenced and annotated. Nonetheless, annotation remains a serious challenge for compositionally biased genomes. For the preliminary annotation, popular nucleotide and protein comparison methods such as BLAST are widely employed. These methods make use of matrices to score alignments such as the amino acid substitution matrices. Since a nucleotide bias leads to an overall bias in the amino acid composition of proteins, it is possible that a genome with nucleotide bias may have introduced atypical amino acid substitutions in its proteome. Consequently, standard matrices fail to perform well in sequence analysis of these genomes. To address this issue, we examined the amino acid substitution in the AT-rich genome of Plasmodium falciparum, chosen as a reference and reconstituted a substitution matrix in the genome's context. The matrix was used to generate protein sequence alignments for the parasite proteins that improved across the functional regions. We attribute this to the consistency that may have been achieved amid the target and background frequencies calculated exclusively in our study. This study has important implications on annotation of proteins that are of experimental interest but give poor sequence alignments with standard conventional matrices.