Abstract
BackgroundPartitioning the human immunoglobulin variable region into variable (V), diversity (D), and joining (J) segments is a common sequence analysis step. We introduce a novel approximate dynamic programming method that uses conserved immunoglobulin gene motifs to improve performance of aligning V-segments of rearranged immunoglobulin (Ig) genes. Our new algorithm enhances the former JOINSOLVER algorithm by processing sequences with insertions and/or deletions (indels) and improves the efficiency for large datasets provided by high throughput sequencing.ResultsIn our simulations, which include rearrangements with indels, the V-matching success rate improved from 61% for partial alignments of sequences with indels in the original algorithm to over 99% in the approximate algorithm. An improvement in the alignment of human VDJ rearrangements over the initial JOINSOLVER algorithm was also seen when compared to the Stanford.S22 human Ig dataset with an online VDJ partitioning software evaluation tool.ConclusionsHTJoinSolver can rapidly identify V- and J-segments with indels to high accuracy for mutated sequences when the mutation probability is around 30% and 20% respectively. The D-segment is much harder to fit even at 20% mutation probability. For all segments, the probability of correctly matching V, D, and J increases with our alignment score.
Highlights
Partitioning the human immunoglobulin variable region into variable (V), diversity (D), and joining (J) segments is a common sequence analysis step
Diversity in the antigen-binding region of Ig provides an appropriate immune response to the wide array of pathogens confronting individuals. This diversity is generated by VDJ recombination, which joins a Variable (V) gene segment, a Diversity (D) gene segment, and a Joining (J) gene segment from distant regions of DNA to potentially create about 10 billion different antibodies, each of which binds to a distinct epitope
We introduce a sequence alignment algorithm that approximates the results of a dynamic programming (DP) algorithm, which can save up to 98% of the computational time
Summary
Partitioning the human immunoglobulin variable region into variable (V), diversity (D), and joining (J) segments is a common sequence analysis step. Diversity in the antigen-binding region of Ig provides an appropriate immune response to the wide array of pathogens confronting individuals. This diversity is generated by VDJ recombination, which joins a Variable (V) gene segment, a Diversity (D) gene segment, and a Joining (J) gene segment from distant regions of DNA to potentially create about 10 billion different antibodies, each of which binds to a distinct epitope.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.