title: Improving the sensitivity of the sequence profile method.
abstract: The sequence profile method (Gribskov M, McLachlan AD, Eisenberg D, 1987, Proc Natl Acad Sci USA 84:4355-4358) is a powerful tool to detect distant relationships between amino acid sequences. A profile is a table of position-specific scores and gap penalties, providing a generalized description of a protein motif, which can be used for sequence alignments and database searches instead of an individual sequence. A sequence profile is derived from a multiple sequence alignment. We have found 2 ways to improve the sensitivity of sequence profiles: (1) Sequence weights: Usage of individual weights for each sequence avoids bias toward closely related sequences. These weights are automatically assigned based on the distance of the sequences using a published procedure (Sibbald PR, Argos P, 1990, J Mol Biol 216:813-818). (2) Amino acid substitution table: In addition to the alignment, the construction of a profile also needs an amino acid substitution table. We have found that in some cases a new table, the BLOSUM45 table (Henikoff S, Henikoff JG, 1992, Proc Natl Acad Sci USA 89:10915-10919), is more sensitive than the original Dayhoff table or the modified Dayhoff table used in the current implementation. Profiles derived by the improved method are more sensitive and selective in a number of cases where previous methods have failed to completely separate true members from false positives.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
authors.forename: R
authors.initials: R
authors.lastname: Lüthy
authors.forename: I
authors.initials: I
authors.lastname: Xenarios
authors.forename: P
authors.initials: P
authors.lastname: Bucher
mesh_terms: D000595:Amino Acid Sequence; D005914:Globins / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry; D012680:Sensitivity and Specificity; D017421:Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D017385:Sequence Homology; D012984:Software
chemical_list: D006360:Heat-Shock Proteins; D005914:Globins; D016392:Proto-Oncogene Proteins pp60(c-src)