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

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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 leukaemias 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 IGH 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 characterization programs. Availability: iHMMune-align cross-platform Java executable and web interface are freely available to academic users and can be accessed at http://www.emi.unsw.edu.au/~ihmmune/ Contact:bgaeta@cse.unsw.edu.au