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
More filters
Journal ArticleDOI
A novel adaptive method for the analysis of next-generation sequencing data to detect complex trait associations with rare variants due to gene main effects and interactions.
TL;DR: It is demonstrated that the KBAC has superior power compared to other rare variant analysis methods, such as the combined multivariate and collapsing and weight sum statistic, in the presence of variant misclassification and gene interaction.
Posted ContentDOI
Regional missense constraint improves variant deleteriousness prediction
Kaitlin E. Samocha,Jack A. Kosmicki,Konrad J. Karczewski,Konrad J. Karczewski,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,Emma Pierce-Hoffman,Emma Pierce-Hoffman,Daniel G. MacArthur,Daniel G. MacArthur,Neale Bm,Neale Bm,Mark J. Daly,Mark J. Daly +14 more
TL;DR: This work leveraged the exome sequencing data of 60,706 individuals from the Exome Aggregation Consortium (ExAC) dataset to identify sub-genic regions that are depleted of missense variation and used this depletion as part of a novel missense deleteriousness metric named MPC.
Journal ArticleDOI
RAD21 Mutations Cause a Human Cohesinopathy
Matthew A. Deardorff,Matthew A. Deardorff,Jonathan J. Wilde,Melanie Albrecht,Emma Dickinson,Stephanie Tennstedt,Diana Braunholz,Maren Mönnich,Yuqian Yan,Weizhen Xu,María Concepción Gil-Rodríguez,María Concepción Gil-Rodríguez,Dinah Clark,Hakon Hakonarson,Hakon Hakonarson,Sara Halbach,Laura Daniela Michelis,Abhinav Rampuria,Eva Rossier,Stephanie Spranger,Lionel Van Maldergem,Sally Ann Lynch,Gabriele Gillessen-Kaesbach,Hermann-Josef Lüdecke,Robert G. Ramsay,Robert G. Ramsay,Michael J. McKay,Ian D. Krantz,Ian D. Krantz,Huiling Xu,Huiling Xu,Julia A. Horsfield,Frank J. Kaiser +32 more
TL;DR: It is shown that human mutations in the integral cohesin structural protein RAD21 result in a congenital phenotype consistent with a "cohesinopathy," and that dominant missense mutations result in more severe functional defects and cause worse structural and cognitive clinical findings.
Journal ArticleDOI
Bioinformatics challenges for personalized medicine
TL;DR: This review outlines recent developments in sequencing technologies and genome analysis methods for application in personalized medicine and outlines new methods needed in four areas to realize the potential of personalized medicine.
Journal ArticleDOI
Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior
Ryan N. Doan,Byoung-Il Bae,Beatriz Cubelos,Cindy Chang,Amer A. Hossain,Samira Al-Saad,Nahit Motavalli Mukaddes,Ozgur Oner,Muna Al-Saffar,Muna Al-Saffar,Soher Balkhy,Generoso G. Gascon,Marta Nieto,Christopher A. Walsh,Christopher A. Walsh,Christopher A. Walsh +15 more
TL;DR: Using chromatin interaction sequencing, massively parallel reporter assays, and transgenic mice, genetic evidence is provided that specific HARs are essential for normal development, consistent with suggestions that their evolutionary changes may have altered social and/or cognitive behavior.
References
More filters
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.