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

@article{lee_simple_2008, 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 (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.}, author = {Lee, Marianne M. and Chan, Michael K. and Bundschuh, Ralf }, citeulike-article-id = {2651271}, journal = {Bioinformatics}, keywords = {analysis, bioinformatics, psi-blast, sequence, statistics}, posted-at = {2008-04-11 01:32:11}, priority = {2}, title = {Simple is beautiful: a straightforward approach to improve the delineation of true and false positives in PSI-BLAST searches}, url = {http://bioinformatics.oxfordjournals.org/cgi/content/abstract/btn130v1}, year = {2008} }

TY - JOUR ID - lee_simple_2008 L3 - citeulike-article-id:2651271 TI - Simple is beautiful: a straightforward approach to improve the delineation of true and false positives in PSI-BLAST searches JF - Bioinformatics N2 - 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 (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. KW - analysis KW - bioinformatics KW - psi-blast KW - sequence KW - statistics AU - Lee, Marianne AU - Chan, Michael AU - Bundschuh, Ralf PY - 2008/// UR - http://bioinformatics.oxfordjournals.org/cgi/content/abstract/btn130v1 ER -