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Bioinformatics Advance Access published online on April 26, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm147
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© The Author (2007). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

iHMMune-align: Hidden Markov model-based alignment and identification of germline genes in rearranged immunoglobulin gene sequences

Bruno A. Gaëta 1,2,*, Harald R. Malming 2, Katherine J. L. Jackson 1, Michael E. Bain 2, Patrick Wilson 3 and Andrew M. Collins 1

1School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052 Australia
2School of Computer Science and Engineering, The University of New South Wales, Sydney, NSW 2052 Australia
3Molecular Immunogenetics Program, the Oklahoma Medical Research Foundation, Oklahoma City, OK 73104 USA

*To whom correspondence should be addressed. Bruno A. Gaëta, E-mail: bgaeta{at}cse.unsw.edu.au, bgaeta{at}unsw.edu.au


  Abstract

Motivation: Immunoglobulin heavy chain (IGH) genes in mature B lymphocytes are the result of recombination of IGHV, IGHD and IGHJ germline genes, followed by somatic mutation. The correct identification of the germline genes that make up a variable VH domain is essential to our understanding of the process of antibody diversity generation as well as to clinical investigations of some leukemias and lymphomas.

Results: We have developed iHMMune-align, an alignment program that uses a hidden Markov model (HMM) to model the processes involved in human immunoglobulin heavy chain gene rearrangement and maturation. The performance of iHMMune-align was compared to that of other immunoglobulin gene alignment utilities using both clonally-related and randomly selected IGH sequences. This evaluation suggests that iHMMune-align provides a more accurate identification of component germline genes than other currently available IGH gene characterisation programs.

Availability: iHMMune-align cross-platform Java executable is freely available to academic users and can be downloaded from http://www.cse.unsw.edu.au/~binftools/iHMMuneAlign.zip

Associate Editor: Prof. Alfonoso Valencia

Received on September 17, 2006; revised on April 11, 2007; accepted on April 11, 2007

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