title: Adjusting scoring matrices to correct overextended alignments.
abstract: BACKGROUND
  Sequence similarity searches performed with BLAST, SSEARCH and FASTA achieve high sensitivity by using scoring matrices (e.g. BLOSUM62) that target low identity (<33%) alignments. Although such scoring matrices can effectively identify distant homologs, they can also produce local alignments that extend beyond the homologous regions.
  
  
  RESULTS
  We measured local alignment start/stop boundary accuracy using a set of queries where the correct alignment boundaries were known, and found that 7% of BLASTP and 8% of SSEARCH alignment boundaries were overextended. Overextended alignments include non-homologous sequences; they occur most frequently between sequences that are more closely related (>33% identity). Adjusting the scoring matrix to reflect the identity of the homologous sequence can correct higher identity overextended alignment boundaries. In addition, the scoring matrix that produced a correct alignment could be reliably predicted based on the sequence identity seen in the original BLOSUM62 alignment. Realigning with the predicted scoring matrix corrected 37% of all overextended alignments, resulting in more correct alignments than using BLOSUM62 alone.
authors.affiliation: Department of Molecular, Cell and Developmental Biology and Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Mills
authors.forename: William R
authors.initials: WR
authors.lastname: Pearson
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D008969:Molecular Sequence Data; D056510:Position-Specific Scoring Matrices; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid
chemical_list: D011506:Proteins