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. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

S F Altschul 1, T L Madden 1, A A Schäffer 1, J Zhang 1, Z Zhang 1, W Miller 1, D J Lipman 1
PMCID: PMC146917  PMID: 9254694

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.

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Selected References

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