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Domain enhanced lookup time accelerated BLAST

Grzegorz M Boratyn*, Alejandro A Schäffer, Richa Agarwala, Stephen F Altschul, David J Lipman and Thomas L Madden

Author Affiliations

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, 8600 Rockville Pike, Bethesda, MD 20894, USA

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Biology Direct 2012, 7:12  doi:10.1186/1745-6150-7-12

Published: 17 April 2012



BLAST is a commonly-used software package for comparing a query sequence to a database of known sequences; in this study, we focus on protein sequences. Position-specific-iterated BLAST (PSI-BLAST) iteratively searches a protein sequence database, using the matches in round i to construct a position-specific score matrix (PSSM) for searching the database in round i + 1. Biegert and Söding developed Context-sensitive BLAST (CS-BLAST), which combines information from searching the sequence database with information derived from a library of short protein profiles to achieve better homology detection than PSI-BLAST, which builds its PSSMs from scratch.


We describe a new method, called domain enhanced lookup time accelerated BLAST (DELTA-BLAST), which searches a database of pre-constructed PSSMs before searching a protein-sequence database, to yield better homology detection. For its PSSMs, DELTA-BLAST employs a subset of NCBI’s Conserved Domain Database (CDD). On a test set derived from ASTRAL, with one round of searching, DELTA-BLAST achieves a ROC5000 of 0.270 vs. 0.116 for CS-BLAST. The performance advantage diminishes in iterated searches, but DELTA-BLAST continues to achieve better ROC scores than CS-BLAST.


DELTA-BLAST is a useful program for the detection of remote protein homologs. It is available under the “Protein BLAST” link at webcite.


This article was reviewed by Arcady Mushegian, Nick V. Grishin, and Frank Eisenhaber.