title: HTJoinSolver: Human immunoglobulin VDJ partitioning using approximate dynamic programming constrained by conserved motifs.
abstract: BACKGROUND
  Partitioning 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  HTJoinSolver 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.
authors.affiliation: Division of Computational Bioscience, Center for Information Technology, NIH, 12 South Drive, Bethesda, MD, 20892, USA. druss@mail.nih.gov.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Russ
authors.affiliation: Division of Computational Bioscience, Center for Information Technology, NIH, 12 South Drive, Bethesda, MD, 20892, USA. hok@mail.nih.gov.
authors.forename: Kwan-Yuet
authors.initials: KY
authors.lastname: Ho
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, 40 Convent Drive, Bethesda, MD, 20892, USA. longon@mail.nih.gov.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Longo
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D015321:Gene Rearrangement; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012984:Software
chemical_list: D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region