PSI-BLAST pseudocounts and the minimum description length principle.
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.
Altschul
Stephen F
SF
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD 20894, USA. altschul@ncbi.nlm.nih.gov
Gertz
E Michael
EM
Agarwala
Richa
R
Schäffer
Alejandro A
AA
Yu
Yi-Kuo
YK
D030562:Databases, Protein; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*