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The effectiveness of position- and composition-specific gap costs for protein similarity searches

Authors
Journal
Bioinformatics
1367-4803
Publisher
Oxford University Press
Publication Date
Volume
24
Issue
13
Identifiers
DOI: 10.1093/bioinformatics/btn171
Keywords
  • Ismb 2008 Conference Proceedings 19–23 July 2008
  • Toronto
  • Original Papers
  • Sequence Analysis And Alignment
Disciplines
  • Biology

Abstract

Motivation: The flexibility in gap cost enjoyed by hidden Markov models (HMMs) is expected to afford them better retrieval accuracy than position-specific scoring matrices (PSSMs). We attempt to quantify the effect of more general gap parameters by separately examining the influence of position- and composition-specific gap scores, as well as by comparing the retrieval accuracy of the PSSMs constructed using an iterative procedure to that of the HMMs provided by Pfam and SUPERFAMILY, curated ensembles of multiple alignments. Results: We found that position-specific gap penalties have an advantage over uniform gap costs. We did not explore optimizing distinct uniform gap costs for each query. For Pfam, PSSMs iteratively constructed from seeds based on HMM consensus sequences perform equivalently to HMMs that were adjusted to have constant gap transition probabilities, albeit with much greater variance. We observed no effect of composition-specific gap costs on retrieval performance. These results suggest possible improvements to the PSI-BLAST protein database search program. Availability: The scripts for performing evaluations are available upon request from the authors. Contact: [email protected]

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