Journal Article

Empirical determination of effective gap penalties for sequence comparison

J.T. Reese and W.R. Pearson

in Bioinformatics

Volume 18, issue 11, pages 1500-1507
Published in print November 2002 | ISSN: 1367-4803
Published online November 2002 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/18.11.1500
Empirical determination of effective gap penalties for sequence comparison

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Motivation: No general theory guides the selection of gap penalties for local sequence alignment. We empirically determined the most effective gap penalties for protein sequence similarity searches with substitution matrices over a range of target evolutionary distances from 20 to 200 Point Accepted Mutations (PAMs).

Results: We embedded real and simulated homologs of protein sequences into a database and searched the database to determine the gap penalties that produced the best statistical significance for the distant homologs. The most effective penalty for the first residue in a gap (q+r) changes as a function of evolutionary distance, while the gap extension penalty for additional residues (r) does not. For these data, the optimal gap penalties for a given matrix scaled in 1/3 bit units (e.g. BLOSUM50, PAM200) are q=25−0.1 • (target PAM distance), r=5. Our results provide an empirical basis for selection of gap penalties and demonstrate how optimal gap penalties behave as a function of the target evolutionary distance of the substitution matrix. These gap penalties can improve expectation values by at least one order of magnitude when searching with short sequences, and improve the alignment of proteins containing short sequences repeated in tandem.

Contact: wrp@virginia.edu

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Subjects: Bioinformatics and Computational Biology

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