Nucleic Acids Research, Vol 25, Issue 17 3389-3402, Copyright © 1997 by Oxford University Press
SF Altschul, TL Madden, AA Schaffer, J Zhang, Z Zhang, W Miller and DJ Lipman
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.
REVIEWS
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. altschul@ncbi.nlm.nih.gov
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