SIFT: predicting amino acid changes that affect protein function
Pauline C. Ng,Steven Henikoff +1 more
TLDR
SIFT is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study and can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms.Abstract:
Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to affect protein function. SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study. We have shown that SIFT can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms. SIFT is available at http://blocks.fhcrc.org/sift/SIFT.html.read more
Citations
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Rapid intraspecific evolution of miRNA and siRNA genes in the mosquito Aedes aegypti.
Scott A. Bernhardt,Mark P. Simmons,Ken E. Olson,Barry J. Beaty,Carol D. Blair,William C. Black +5 more
TL;DR: Knock-out, silencing and mutagenesis of genes in the exogenous siRNA (exo-siRNA) regulatory network demonstrate the importance of this RNAi pathway in antiviral immunity in Drosophila and mosquitoes and both exo-SIRNA and miRNA pathway genes appear to be undergoing rapid, positive, diversifying selection.
Journal ArticleDOI
Identification and Validation of Genetic Variants that Influence Transcription Factor and Cell Signaling Protein Levels
Ronald J. Hause,Amy L. Stark,Nirav N. Antao,Lidija K. Gorsic,Sophie H. Chung,Christopher D. Brown,Shan S. Wong,Daniel F. Gill,Jamie Myers,Lida Anita To,Kevin P. White,M. Eileen Dolan,Richard B. Jones +12 more
TL;DR: The results suggest that protein-based mechanisms might functionally buffer genetic alterations that influence mRNA expression levels and that pQTLs might contribute phenotypic diversity to a human population independently of influences on mRNA expression.
Journal ArticleDOI
Identification of pathogenic missense mutations using protein stability predictors.
TL;DR: It is observed that the utility of computational stability predictors is highly heterogeneous across different proteins, and that they are all inferior to the best performing variant effect predictors for identifying pathogenic mutations.
Journal ArticleDOI
Genome bioinformatic analysis of nonsynonymous SNPs
David F. Burke,Catherine L. Worth,Eva-Maria Priego,Tammy M. K. Cheng,Luc J. Smink,John A. Todd,Tom L. Blundell +6 more
TL;DR: It is shown that, in general, the prediction tools are able distinguish disease causing mutations from those mutations which are thought to have a neutral affect, and rare mutations are consistently predicted to be deleterious as often as commonly occurring nsSNPs.
Journal ArticleDOI
Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants.
Sumaiya Iqbal,Eduardo Pérez-Palma,Jakob Berg Jespersen,Patrick May,David Hoksza,David Hoksza,Henrike O. Heyne,Henrike O. Heyne,Henrike O. Heyne,Shehab S. Ahmed,Zaara T. Rifat,M. Sohel Rahman,Kasper Lage,Kasper Lage,Aarno Palotie,Aarno Palotie,Jeffrey R. Cottrell,Florence F. Wagner,Mark J. Daly,Arthur J. Campbell,Dennis Lal +20 more
TL;DR: A wide-scale characterization of missense variants from 1,330 disease-associated genes using >14,000 protein structures is performed, identifying 3D features associated with pathogenic and benign variants that unveiled the mutations’ effect at the molecular level.
References
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David L. Wheeler,Deanna M. Church,Ron Edgar,Scott Federhen,Wolfgang Helmberg,Thomas L. Madden,Joan Pontius,Gregory D. Schuler,Lynn M. Schriml,Edwin Sequeira,Tugba O. Suzek,Tatiana Tatusova,Lukas Wagner +12 more
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Predicting Deleterious Amino Acid Substitutions
Pauline C. Ng,Steven Henikoff +1 more
TL;DR: A tool that uses sequence homology to predict whether a substitution affects protein function is constructed, which may be used to identify plausible disease candidates among the SNPs that cause missense substitutions.
Journal ArticleDOI
Human non‐synonymous SNPs: server and survey
TL;DR: A World Wide Web server is presented to predict the effect of an nsSNP on protein structure and function and the dependence of selective pressure on the structural and functional properties of proteins is studied.