title: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSI-BLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. altschul@ncbi.nlm.nih.gov
authors.forename: S F
authors.initials: SF
authors.lastname: Altschul
authors.forename: T L
authors.initials: TL
authors.lastname: Madden
authors.forename: A A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Miller
authors.forename: D J
authors.initials: DJ
authors.lastname: Lipman
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000737:chemistry*; D016208:Databases, Factual; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D012984:Software
chemical_list: D011506:Proteins; D004247:DNA