Estimates of statistical significance for comparison of individual positions in multiple sequence alignments

Background: Profile-based analysis of multiple sequence alignments (MSA) allows for accurate comparison of protein families. Here, we address the problems of detecting statistically confident dissimilarities between (1) MSA position and a set of predicted residue frequencies, and (2) between two MSA positions. These problems are important for (i) evaluation and optimization of methods predicting residue occurrence at protein positions; (ii) detection of potentially misaligned regions in automatically produced alignments and their further refinement; and (iii) detection of sites that determine functional or structural specificity in two related families. Results: For problems (1) and (2), we propose analytical estimates of P-value and apply them to the detection of significant positional dissimilarities in various experimental situations. (a) We compare structure-based predictions of residue propensities at a protein position to the actual residue frequencies in the MSA of homologs. (b...

• Type: Journal
• Year: 2004
• Where: BMCBI
• Authors: Ruslan Sadreyev, Nick V. Grishin
• Keywords: BMCBI 2004, Msa Positions, Multiple Sequence Alignments, Residue Frequencies