Gapped BLAST and PSI-BLAST: A New Generation of Protein Database Search Programs

Nucleic Acids Res. 1997 Sep 1;25(17):3389-402. doi: 10.1093/nar/25.17.3389.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Animals
  • DNA / chemistry*
  • Databases, Factual*
  • Humans
  • Molecular Sequence Data
  • Proteins / chemistry*
  • Sequence Alignment*
  • Software*

Substances

  • Proteins
  • DNA