SuSPect: enhanced prediction of single amino acid variant (SAV) phenotype using network features - PubMed (original) (raw)

SuSPect: enhanced prediction of single amino acid variant (SAV) phenotype using network features

Christopher M Yates et al. J Mol Biol. 2014.

Abstract

Whole-genome and exome sequencing studies reveal many genetic variants between individuals, some of which are linked to disease. Many of these variants lead to single amino acid variants (SAVs), and accurate prediction of their phenotypic impact is important. Incorporating sequence conservation and network-level features, we have developed a method, SuSPect (Disease-Susceptibility-based SAV Phenotype Prediction), for predicting how likely SAVs are to be associated with disease. SuSPect performs significantly better than other available batch methods on the VariBench benchmarking dataset, with a balanced accuracy of 82%. SuSPect is available at www.sbg.bio.ic.ac.uk/suspect. The Web site has been implemented in Perl and SQLite and is compatible with modern browsers. An SQLite database of possible missense variants in the human proteome is available to download at www.sbg.bio.ic.ac.uk/suspect/download.html.

Keywords: SAV; SuSPect; missense mutation; nsSNP; protein–protein interaction.

Copyright © 2014. Published by Elsevier Ltd.

PubMed Disclaimer

Figures

None

Graphical abstract

Fig. 1

Fig. 1

Performance of five versions of SuSPect compared to seven other methods.

Fig. 2

Fig. 2

Distribution of SuSPect-FS scores for disease-associated (red) and neutral (blue) SAVs in the VariBench test set. The two sets of SAVs have significantly different distributions (Wilcoxon test, p < 2.2 × 10− 16).

Similar articles

Cited by

References

    1. The 1000 Genomes Project Consortium A map of human genome variation from population-scale sequencing. Nature. 2010;467:1061–1073. - PMC - PubMed
    1. Stranger B.E., Stahl E.A., Raj T. Progress and promise of genome-wide association studies for human complex trait genetics. Genetics. 2011;187:367–383. - PMC - PubMed
    1. Roach J.C., Glusman G., Smit A.F.A., Huff C.D., Hubley R., Shannon P.T. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science. 2010;328:636–639. - PMC - PubMed
    1. Ng P.C. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31:3812–3814. - PMC - PubMed
    1. Bromberg Y., Rost B. SNAP: predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res. 2007;35:3823–3835. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources