Journal
BIOINFORMATICS
Volume 28, Issue 12, Pages 1650-1651Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/bts240
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Funding
- National Library of Medicine (NIH) [LM04969]
- European Molecular Biology Laboratory
- European Commission [226073]
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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 similar to 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 similar to 5% less sensitive.
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