Gapped BLAST and PSLBLAST: a new generation of protein database search programs

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 It approximately three times the speed of the original. n addition, a method is introduced for automatically mnbining statistically significant alignments proiuced by BLAST into a position-specific score matrix, ind searching the database using this matrix. The esulting Position-Specific Iterated BLAST (PSI3LAST) program runs a i approximately the same ;peed per iteration as gapped BLAST, but in many ases is much more sensitive to weak but biologically slevant sequence similarities. PSI-BLAST is used to Incover several new and Snteresting members of the 3RCT superfamily.