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Nucleic Acids Research Advance Access published online on October 26, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl731
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Published by Oxford University Press 2006

Computational Biology

Retrieval accuracy, statistical significance and compositional similarity in protein sequence database searches

Yi-Kuo Yu, E. Michael Gertz, Richa Agarwala, Alejandro A. Schäffer and Stephen F. Altschul*

National Center for Biotechnology Information, National Library of Medicine NIH, DHHS, Bethesda, MD 20894, USA

*To whom correspondence should be addressed. Tel: +301 435 7803; Fax: +301 480 2288; Email: altschul{at}ncbi.nlm.nih.gov

Received July 27, 2006. Revised September 15, 2006. Accepted September 21, 2006.

Protein sequence database search programs may be evaluated both for their retrieval accuracy—the ability to separate meaningful from chance similarities—and for the accuracy of their statistical assessments of reported alignments. However, methods for improving statistical accuracy can degrade retrieval accuracy by discarding compositional evidence of sequence relatedness. This evidence may be preserved by combining essentially independent measures of alignment and compositional similarity into a unified measure of sequence similarity. A version of the BLAST protein database search program, modified to employ this new measure, outperforms the baseline program in both retrieval and statistical accuracy on ASTRAL, a SCOP-based test set.


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