Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Altschul, S F, Madden, T L, Schäffer, A A, Zhang, J, Zhang, Z, Miller, W, & Lipman, D J Nucleic Acids Res, 25(17):3389–3402, 1997.
abstract   bibtex   
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.
@Article{altschul97gapped,
  author    = {Altschul, S F and Madden, T L and Sch\"affer, A A and Zhang, J and Zhang, Z and Miller, W and Lipman, D J},
  title     = {Gapped {BLAST} and {PSI-BLAST}: a new generation of protein database search programs},
  journal   = {Nucleic Acids Res},
  year      = {1997},
  volume    = {25},
  number    = {17},
  pages     = {3389--3402},
  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.},
  pmid      = {9254694},
  timestamp = {2019.03.15},
}

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