Journal ArticleDOI
Predicting the Effects of Amino Acid Substitutions on Protein Function
Pauline C. Ng,Steven Henikoff +1 more
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TLDR
An overview of amino acid substitution (AAS) prediction methods, which use sequence and/or structure to predict the effect of an AAS on protein function, and the utility of AAS prediction methods for Mendelian and complex diseases as well as their broader applications for understanding protein function.Abstract:
Nonsynonymous single nucleotide polymorphisms (nsSNPs) are coding variants that introduce amino acid changes in their corresponding proteins. Because nsSNPs can affect protein function, they are believed to have the largest impact on human health compared with SNPs in other regions of the genome. Therefore, it is important to distinguish those nsSNPs that affect protein function from those that are functionally neutral. Here we provide an overview of amino acid substitution (AAS) prediction methods, which use sequence and/or structure to predict the effect of an AAS on protein function. Most methods predict approximately 25–30% of human nsSNPs to negatively affect protein function, and such nsSNPs tend to be rare in the population. We discuss the utility of AAS prediction methods for Mendelian and complex diseases as well as their broader applications for understanding protein function.read more
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Journal ArticleDOI
Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.
TL;DR: This protocol describes the use of the 'Sorting Tolerant From Intolerant' (SIFT) algorithm in predicting whether an AAS affects protein function.
Journal ArticleDOI
Predicting the Functional Effect of Amino Acid Substitutions and Indels
TL;DR: A new algorithm, PROVEAN (Protein Variation Effect Analyzer), is developed, which provides a generalized approach to predict the functional effects of protein sequence variations including single or multiple amino acid substitutions, and in-frame insertions and deletions.
Journal ArticleDOI
PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels
Yongwook Choi,Agnes P. Chan +1 more
TL;DR: A web server to predict the functional effect of single or multiple amino acid substitutions, insertions and deletions using the prediction tool PROVEAN, which provides rapid analysis of protein variants from any organisms, and also supports high-throughput analysis for human and mouse variants at both the genomic and protein levels.
Journal ArticleDOI
Predicting the functional impact of protein mutations: application to cancer genomics
TL;DR: A new functional impact score (FIS) for amino acid residue changes using evolutionary conservation patterns is introduced, estimating that at least 5% of cancer-relevant mutations involve switch of function, rather than simply loss or gain of function.
Journal ArticleDOI
Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models.
Hashem A. Shihab,Julian Gough,David Neil Cooper,Peter D. Stenson,Gary L A Barker,Keith J. Edwards,Ian N. M. Day,Tom R. Gaunt +7 more
TL;DR: The Functional Analysis Through Hidden Markov Models (FATHMM) software and server is described: a species‐independent method with optional species‐specific weightings for the prediction of the functional effects of protein missense variants, demonstrating that FATHMM can be efficiently applied to high‐throughput/large‐scale human and nonhuman genome sequencing projects with the added benefit of phenotypic outcome associations.
References
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TL;DR: The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
Journal ArticleDOI
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TL;DR: The dbSNP database is a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, and is integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data.
Journal ArticleDOI
SIFT: predicting amino acid changes that affect protein function
Pauline C. Ng,Steven Henikoff +1 more
TL;DR: 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.
Journal ArticleDOI
The Future of Genetic Studies of Complex Human Diseases
TL;DR: The identification of the genetic basis of complex human diseases such as schizophrenia and diabetes has proven difficult as mentioned in this paper, and Risch and Merikangas proposed that they can best accomplish this goal by combining the power of the human genome project with association studies.
Journal ArticleDOI
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Amos Marc Bairoch,Rolf Apweiler,Cathy H. Wu,Winona C. Barker,Brigitte Boeckmann,Serenella Ferro,Elisabeth Gasteiger,Hongzhan Huang,Rodrigo Lopez,Michele Magrane,Maria Jesus Martin,Darren A. Natale,Claire O'Donovan,Nicole Redaschi,Lai-Su L. Yeh +14 more
TL;DR: During 2004, tens of thousands of Knowledgebase records got manually annotated or updated; the UniProt keyword list got augmented by additional keywords; the documentation of the keywords and are continuously overhauling and standardizing the annotation of post-translational modifications.
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