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Using substitution probabilities to improve position-specific scoring matrices

by: Jorja G Henikoff, Steven Henikoff
Comput. Appl. Biosci., Vol. 12, No. 2. (1 April 1996), pp. 135-143.


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Each column of amino acids in a multiple alignment of protein sequences can be represented as a vector of 20 amino acid counts. For alignment and searching applications, the count vector is an imperfect representation of a position, because the observed sequences are an incomplete sample of the full set of related sequences. One general solution to this problem is to model unobserved sequences by adding artificial pseudo-counts' to the observed counts. We introduce a simple method for computing pseudo-counts that combines the diversity observed in each alignment position with amino acid substitution probabilities. In extensive empirical tests, this position-based method out-performed other pseudo-count methods and was a substantial improvement over the traditional average score method used for constructing profiles. 10.1093/bioinformatics/12.2.135


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