title: Domain enhanced lookup time accelerated BLAST.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  DELTA-BLAST is a useful program for the detection of remote protein homologs. It is available under the "Protein BLAST" link at http://blast.ncbi.nlm.nih.gov.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894, USA. boratyng@ncbi.nlm.nih.gov
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Boratyn
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Richa
authors.initials: R
authors.lastname: Agarwala
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Altschul
authors.forename: David J
authors.initials: DJ
authors.lastname: Lipman
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Madden
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D020407:Internet; D017434:Protein Structure, Tertiary; D012372:ROC Curve; D015203:Reproducibility of Results; D057386:Search Engine / Q000379:methods*; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods; D017386:Sequence Homology, Amino Acid; D012984:Software; D013997:Time Factors