title: Incorporating the amino acid properties to predict the significance of missense mutations.
abstract: Determining if missense mutations are deleterious is critical for the analysis of genes implicated in disease. However, the mutational effects of many missense mutations in databases like the Breast Cancer Information Core are unclassified. Several approaches have emerged recently to determine such mutational effects but none have utilized amino acid property indices. We modified a previously described phylogenetic approach by first classifying benign substitutions based on the assumption that missense mutations that are maintained in orthologs are unlikely to affect function. A consensus conservation score based on 16 amino acid properties was used to characterize the remaining substitutions. This approach was evaluated with experimentally verified T4 lysozyme missense mutations and is shown to be able to sieve out putative biochemical and structurally important residues. The use of amino acid properties can enhance the prediction of biochemical and structurally important residues and thus also predict the significance of missense mutations.
authors.affiliation: Bioinformatics Institute, 30 Biopolis Street, Singapore, 138671, Singapore. leetc@bii-sg.org
authors.forename: Tze-Chuen
authors.initials: TC
authors.lastname: Lee
authors.forename: Ann S G
authors.initials: AS
authors.lastname: Lee
authors.forename: Kuo-Bin
authors.initials: KB
authors.lastname: Li
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D019313:BRCA1 Protein / Q000737:chemistry* / Q000235:genetics*; D017122:Bacteriophage T4 / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry / Q000235:genetics; D020125:Mutation, Missense
chemical_list: D000596:Amino Acids; D019313:BRCA1 Protein; D009113:Muramidase