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

Bioinformatics
Marianne M LeeRalf Bundschuh

Abstract

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. 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 ...Continue Reading

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Citations

Jan 24, 2009·Bioinformatics·Inkyung Jung, Dongsup Kim
Dec 1, 2010·Bioinformatics·Yuheng LiRalf Bundschuh
Jan 13, 2010·Nucleic Acids Research·Mileidy W Gonzalez, William R Pearson
May 12, 2009·Nucleic Acids Research·Marianne M LeeRalf Bundschuh
Nov 28, 2013·Bioinformatics·Kazunori Yamada, Kentaro Tomii
Apr 5, 2011·Current Opinion in Structural Biology·Johannes Söding, Michael Remmert
Feb 7, 2013·Journal of Biomolecular Structure & Dynamics·Dmitry SuplatovVytas Švedas
Sep 14, 2013·Journal of Biomolecular Structure & Dynamics·Dmitry SuplatovVytas Svedas
Jan 1, 2013·F1000Research·Adwait Govind JoshiRamanathan Sowdhamini

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