Abstract
PSI-BLAST is an iterative program to search a database for proteins with distant similarity to a query sequence. We investigated over a dozen modifications to the methods used in PSI-BLAST, with the goal of improving accuracy in finding true positive matches. To evaluate performance we used a set of 103 queries for which the true positives in yeast had been annotated by human experts, and a popular measure of retrieval accuracy (ROC) that can be normalized to take on values between 0 (worst) and 1 (best). The modifications we consider novel improve the ROC score from 0.758 +/- 0.005 to 0.895 +/- 0.003. This does not include the benefits from four modifications we included in the 'baseline' version, even though they were not implemented in PSI-BLAST version 2.0. The improvement in accuracy was confirmed on a small second test set. This test involved analyzing three protein families with curated lists of true positives from the non-redundant protein database. The modification that accounts for the majority of the improvement is the use, for each database sequence, of a position-specific scoring system tuned to that sequence's amino acid composition. The use of composition-based statistics is particularly beneficial for large-scale automated applications of PSI-BLAST.
Keywords
False positive paradoxSimilarity (geometry)Set (abstract data type)Sequence (biology)BiologyComputer scienceDatabaseTest setData miningInformation retrievalStatisticsArtificial intelligenceMathematicsGenetics
MeSH Terms
AlgorithmsAmino AcidsAnimalsComputational BiologyDatabasesFactualHumansInformation Storage and RetrievalProteinsReproducibility of ResultsSensitivity and SpecificitySequence AlignmentSoftware
Affiliated Institutions
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Publication Info
- Year
- 2001
- Type
- review
- Volume
- 29
- Issue
- 14
- Pages
- 2994-3005
- Citations
- 1381
- Access
- Closed
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Cite This
A. A. Schaffer
(2001).
Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements.
Nucleic Acids Research
, 29
(14)
, 2994-3005.
https://doi.org/10.1093/nar/29.14.2994
Identifiers
- DOI
- 10.1093/nar/29.14.2994
- PMID
- 11452024
- PMCID
- PMC55814