title: PSI-BLAST pseudocounts and the minimum description length principle.
abstract: Position specific score matrices (PSSMs) are derived from multiple sequence alignments to aid in the recognition of distant protein sequence relationships. The PSI-BLAST protein database search program derives the column scores of its PSSMs with the aid of pseudocounts, added to the observed amino acid counts in a multiple alignment column. In the absence of theory, the number of pseudocounts used has been a completely empirical parameter. This article argues that the minimum description length principle can motivate the choice of this parameter. Specifically, for realistic alignments, the principle supports the practice of using a number of pseudocounts essentially independent of alignment size. However, it also implies that more highly conserved columns should use fewer pseudocounts, increasing the inter-column contrast of the implied PSSMs. A new method for calculating pseudocounts that significantly improves PSI-BLAST's; retrieval accuracy is now employed by default.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD 20894, USA. altschul@ncbi.nlm.nih.gov
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Altschul
authors.forename: E Michael
authors.initials: EM
authors.lastname: Gertz
authors.forename: Richa
authors.initials: R
authors.lastname: Agarwala
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Yi-Kuo
authors.initials: YK
authors.lastname: Yu
mesh_terms: D030562:Databases, Protein; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*