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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Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity.
Audrey E. Hendricks,Audrey E. Hendricks,Elena G. Bochukova,Elena G. Bochukova,Gaëlle Marenne,Julia M. Keogh,Neli Atanassova,Rebecca Bounds,Eleanor Wheeler,Vanisha Mistry,Elana Henning,Antje Körner,Antje Körner,Dawn Muddyman,Shane A. McCarthy,Anke Hinney,Johannes Hebebrand,Robert A. Scott,Claudia Langenberg,Nicholas J. Wareham,Praveen Surendran,Joanna M. M. Howson,Adam S. Butterworth,Adam S. Butterworth,John Danesh,John Danesh,John Danesh,Børge G. Nordestgaard,Børge G. Nordestgaard,Sune F. Nielsen,Sune F. Nielsen,Shoaib Afzal,Shoaib Afzal,Sofia Papadia,Sofie Ashford,Sumedha Garg,Glenn L. Millhauser,Rafael Palomino,Alexandra Kwasniewska,Ioanna Tachmazidou,Stephen O'Rahilly,Eleftheria Zeggini,Inês Barroso,Inês Barroso,I. Sadaf Farooqi +44 more
TL;DR: Analysis of targeted and whole-exome sequencing in 2,548 severely obese children and 1,117 controls found 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously.
Journal ArticleDOI
Gene4Denovo: an integrated database and analytic platform for de novo mutations in humans
Guihu Zhao,Kuokuo Li,Bin Li,Zheng Wang,Zhenghuan Fang,Xiaomeng Wang,Yi Zhang,Tengfei Luo,Qiao Zhou,Lin Wang,Yali Xie,Yijing Wang,Qian Chen,Lu Xia,Yu Tang,Beisha Tang,Kun Xia,Jinchen Li +17 more
TL;DR: Gene4Denovo conveniently allows for the accelerated interpretation of DNM pathogenicity and the clinical implication of DNMs in humans and provides end-users with limited bioinformatics skills to analyse their own genetic data, perform comprehensive annotation, and prioritize candidate genes using custom parameters.
Journal ArticleDOI
Impacts of massively parallel sequencing for genetic diagnosis of neuromuscular disorders
Nasim Vasli,Jocelyn Laporte +1 more
TL;DR: The challenges and benefit of obtaining an accurate genetic diagnosis are reminded, the massively parallel sequencing technology and its novel applications in diagnosis of patients, prenatal diagnosis and carrier detection are introduced, and the limitations and necessary improvements are discussed.
Journal ArticleDOI
Common and rare alleles in apolipoprotein B contribute to plasma levels of low-density lipoprotein cholesterol in the general population.
Marianne Benn,Maria C. A. Stene,Børge G. Nordestgaard,Gorm B. Jensen,Rolf Steffensen,Anne Tybjærg-Hansen,Anne Tybjærg-Hansen +6 more
TL;DR: None of these SNPs predicted risk of ischemic heart disease prospectively in the general population, in a case-control study, or as haplotypes, as predicted from the magnitude of the observed LDL cholesterol effects.
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A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics
Regis A. James,Ian M. Campbell,Edward S. Chen,Philip M. Boone,Mitchell Rao,Matthew N. Bainbridge,James R. Lupski,Yaping Yang,Christine M. Eng,Jennifer E. Posey,Chad A. Shaw,Chad A. Shaw +11 more
TL;DR: This work has developed visually interactive, analytically transparent analysis software that leverages existing disease catalogs, such as the Online Mendelian Inheritance in Man database (OMIM) and the Human Phenotype Ontology (HPO), to integrate patient phenotype and variant data into ranked diagnostic alternatives.
References
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Journal ArticleDOI
Database resources of the National Center for Biotechnology Information
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
TL;DR: In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI’s website.
Journal ArticleDOI
dbSNP: the NCBI database of genetic variation
Stephen T. Sherry,Minghong Ward,Michael Kholodov,Jonathan Baker,Lon Phan,Elizabeth M. Smigielski,Karl Sirotkin +6 more
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
The SWISS-PROT protein sequence data bank and its supplement TrEMBL in 1999.
Amos Marc Bairoch,Rolf Apweiler +1 more
TL;DR: The Human Proteomics Initiative (HPI), a major project to annotate all known human sequences according to the quality standards of SWISS-PROT, is described.
Journal ArticleDOI
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.