Prediction of missense mutation functionality depends on both the algorithm and sequence alignment employed.

ABSTRACT: Multiple algorithms are used to predict the impact of missense mutations on protein structure and function using algorithm-generated sequence alignments or manually curated alignments. We compared the accuracy with native alignment of SIFT, Align-GVGD, PolyPhen-2, and Xvar when generating functionality predictions of well-characterized missense mutations (n = 267) within the BRCA1, MSH2, MLH1, and TP53 genes. We also evaluated the impact of the alignment employed on predictions from these algorithms (except Xvar) when supplied the same four alignments including alignments automatically generated by (1) SIFT, (2) Polyphen-2, (3) Uniprot, and (4) a manually curated alignment tuned for Align-GVGD. Alignments differ in sequence composition and evolutionary depth. Data-based receiver operating

SUBMITTER: Hicks S 

PROVIDER: S-EPMC4154965 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature