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
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Whole-genome reconstruction and mutational signatures in gastric cancer
Niranjan Nagarajan,Denis Bertrand,Axel M. Hillmer,Zhi Jiang Zang,Fei Yao,Fei Yao,Pierre-Étienne Jacques,Audrey S.M. Teo,Ioana Cutcutache,Zhenshui Zhang,Wah Heng Lee,Yee Yen Sia,Song Gao,Pramila N. Ariyaratne,Andrea Ho,Xing Yi Woo,Lavanya Veeravali,Choon Kiat Ong,Niantao Deng,Kartiki V. Desai,Chiea Chuen Khor,Chiea Chuen Khor,Martin L. Hibberd,Martin L. Hibberd,Atif Shahab,Jaideepraj Rao,Mengchu Wu,Ming Teh,Feng Zhu,Sze Yung Chin,Brendan Pang,Jimmy Bok Yan So,Guillaume Bourque,Richie Soong,Wing-Kin Sung,Bin Tean Teh,Steven G. Rozen,Xiaoan Ruan,Khay Guan Yeoh,Patrick Tan,Patrick Tan,Yijun Ruan,Yijun Ruan +42 more
TL;DR: This first whole-genome analysis of two gastric adenocarcinomas revealed the architecture of a wild-type KRAS amplification, a common driver event in gastric cancer, and discovered three distinct mutational signatures - against a genome-wide backdrop of oxidative and microsatellite instability-related mutations, the first exome-specific mutational signature is identified.
Journal ArticleDOI
Frequent epigenetics inactivation of KEAP1 gene in non-small cell lung cancer
Lucia Anna Muscarella,Paola Parrella,Vito D'Alessandro,Annamaria la Torre,Raffaela Barbano,Andrea Fontana,Antonio Tancredi,Vito Guarnieri,Teresa Balsamo,Michelina Coco,Massimiliano Copetti,Fabio Pellegrini,Patrizia De Bonis,Michele Bisceglia,Gerardo Scaramuzzi,Evaristo Maiello,Vanna Maria Valori,Giuseppe Merla,Gianluigi Vendemiale,Vito Michele Fazio +19 more
TL;DR: The results suggest that deregulation of the NRF2/KEAP1 system could play a pivotal role in the cancerogenesis of NSCLC and identifying patients with KEAP1 genetic and epigenetic abnormalities may contribute to disease progression prediction and response to therapy in lung cancer patients.
Journal ArticleDOI
Sudden cardiac death with autopsy findings of uncertain significance: potential for erroneous interpretation
Michael Papadakis,Hariharan Raju,Elijah R. Behr,Sofia V. de Noronha,Nicholas Spath,Alexandros Kouloubinis,Mary N. Sheppard,Sanjay Sharma +7 more
TL;DR: In this article, the authors explored the hypothesis that sudden cardiac deaths represent sudden arrhythmic death syndrome (SADS) and found that a similar proportion of primary arrhythmogenic syndromes to a contemporary series of SADS.
Journal ArticleDOI
Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation.
John S. K. Kauwe,Matthew H. Bailey,Perry G. Ridge,Rachel Perry,Mark E. Wadsworth,Kaitlyn L. Hoyt,Lyndsay A. Staley,Celeste M. Karch,Oscar Harari,Carlos Cruchaga,Benjamin J. Ainscough,Kelly R. Bales,Eve H. Pickering,Sarah Bertelsen,Anne M. Fagan,Holtzman David M,John C. Morris,Alison Goate +17 more
TL;DR: The genetic associations reported here are novel and suggest mechanisms for genetic control of CSF and plasma levels of these disease-related proteins/pathways may be valuable therapeutic targets for AD.
Journal ArticleDOI
Joint mouse–human phenome-wide association to test gene function and disease risk
Xusheng Wang,Ashutosh K. Pandey,Megan K. Mulligan,Evan G. Williams,Khyobeni Mozhui,Z. Li,Virginija Jovaisaite,L. Darryl Quarles,Zhousheng Xiao,Jinsong Huang,John A. Capra,Zugen Chen,William L. Taylor,Lisa Bastarache,Xinnan Niu,Katherine S. Pollard,Katherine S. Pollard,Daniel C. Ciobanu,Alexander O. Reznik,Artem Tishkov,Igor B. Zhulin,Junmin Peng,Stanley F. Nelson,Joshua C. Denny,Johan Auwerx,Lu Lu,Robert W. Williams +26 more
TL;DR: A large murine population segregating for ∼5 million sequence variants is tested using a novel reverse genetic strategy and several novel associations are discovered, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans.
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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Journal ArticleDOI
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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.