title: Improvement in accuracy of multiple sequence alignment using novel group-to-group sequence alignment algorithm with piecewise linear gap cost.
abstract: BACKGROUND
  Multiple sequence alignment (MSA) is a useful tool in bioinformatics. Although many MSA algorithms have been developed, there is still room for improvement in accuracy and speed. In the alignment of a family of protein sequences, global MSA algorithms perform better than local ones in many cases, while local ones perform better than global ones when some sequences have long insertions or deletions (indels) relative to others. Many recent leading MSA algorithms have incorporated pairwise alignment information obtained from a mixture of sources into their scoring system to improve accuracy of alignment containing long indels.
  
  
  RESULTS
  We propose a novel group-to-group sequence alignment algorithm that uses a piecewise linear gap cost. We developed a program called PRIME, which employs our proposed algorithm to optimize the well-defined sum-of-pairs score. PRIME stands for Profile-based Randomized Iteration MEthod. We evaluated PRIME and some recent MSA programs using BAliBASE version 3.0 and PREFAB version 4.0 benchmarks. The results of benchmark tests showed that PRIME can construct accurate alignments comparable to the most accurate programs currently available, including L-INS-i of MAFFT, ProbCons, and T-Coffee.
  
  
  CONCLUSIONS
  PRIME enables users to construct accurate alignments without having to employ pairwise alignment information. PRIME is available at http://prime.cbrc.jp/.
authors.affiliation: Department of Computer Science, Graduate School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan. shinsuke@yama.info.waseda.ac.jp
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Gotoh
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamana
mesh_terms: D000465:Algorithms; D017124:Conserved Sequence; D016014:Linear Models; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods*; D017421:Sequence Analysis / Q000379:methods*; D017385:Sequence Homology