title: PSI-Search: iterative HOE-reduced profile SSEARCH searching.
abstract: Iterative similarity searches with PSI-BLAST position-specific score matrices (PSSMs) find many more homologs than single searches, but PSSMs can be contaminated when homologous alignments are extended into unrelated protein domains-homologous over-extension (HOE). PSI-Search combines an optimal Smith-Waterman local alignment sequence search, using SSEARCH, with the PSI-BLAST profile construction strategy. An optional sequence boundary-masking procedure, which prevents alignments from being extended after they are initially included, can reduce HOE errors in the PSSM profile. Preventing HOE improves selectivity for both PSI-BLAST and PSI-Search, but PSI-Search has ~4-fold better selectivity than PSI-BLAST and similar sensitivity at 50% and 60% family coverage. PSI-Search is also produces 2- for 4-fold fewer false-positives than JackHMMER, but is ~5% less sensitive.
  
  
  METHODS
  PSI-Search is available from the authors as a standalone implementation written in Perl for Linux-compatible platforms. It is also available through a web interface (www.ebi.ac.uk/Tools/sss/psisearch) and SOAP and REST Web Services (www.ebi.ac.uk/Tools/webservices).
authors.affiliation: EMBL - European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Li
authors.forename: Hamish
authors.initials: H
authors.lastname: McWilliam
authors.forename: Mickael
authors.initials: M
authors.lastname: Goujon
authors.forename: Andrew
authors.initials: A
authors.lastname: Cowley
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lopez
authors.forename: William R
authors.initials: WR
authors.lastname: Pearson
mesh_terms: D020816:Amino Acid Motifs; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D020407:Internet; D011381:Programming Languages; D016415:Sequence Alignment / Q000379:methods*; D012984:Software