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Bioinformatics Advance Access originally published online on April 10, 2008
Bioinformatics 2008 24(11):1339-1343; doi:10.1093/bioinformatics/btn130
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Simple is beautiful: a straightforward approach to improve the delineation of true and false positives in PSI-BLAST searches

Marianne M. Lee 1, Michael K. Chan 1,2,* and Ralf Bundschuh 1,3,*

1The Ohio State Biophysics Program, 2Departments of Biochemistry and Chemistry, Ohio State University, 484 W 12th Av. and 3Department of Physics, Ohio State University, 191 W Woodruff Av., Columbus OH 43210-1117, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: The deluge of biological information from different genomic initiatives and the rapid advancement in biotechnologies have made bioinformatics tools an integral part of modern biology. Among the widely used sequence alignment tools, BLAST and PSI-BLAST are arguably the most popular. PSI-BLAST, which uses an iterative profile position specific score matrix (PSSM)-based search strategy, is more sensitive than BLAST in detecting weak homologies, thus making it suitable for remote homolog detection. Many refinements have been made to improve PSI-BLAST, and its computational efficiency and high specificity have been much touted. Nevertheless, corruption of its profile via the incorporation of false positive sequences remains a major challenge.

Results: We have developed a simple and elegant approach to resolve the problem of model corruption in PSI-BLAST searches. We hypothesized that combining results from the first (least-corrupted) profile with results from later (most sensitive) iterations of PSI-BLAST provides a better discriminator for true and false hits. Accordingly, we have derived a formula that utilizes the E-values from these two PSI-BLAST iterations to obtain a figure of merit for rank-ordering the hits. Our verification results based on a ‘gold-standard’ test set indicate that this figure of merit does indeed delineate true positives from false positives better than PSI-BLAST E-values. Perhaps what is most notable about this strategy is that it is simple and straightforward to implement.

Contact: bundschuh{at}mps.ohio-state.edu

Associate Editor: Thomas Lengauer

Received on January 5, 2008; revised on February 28, 2008; accepted on April 7, 2008

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