Knowledge-based computational mutagenesis for predicting the disease potential of human non-synonymous single nucleotide polymorphisms

Journal of Theoretical Biology
Majid Masso, Iosif I Vaisman

Abstract

Certain genetic variations in the human population are associated with heritable diseases, and single nucleotide polymorphisms (SNPs) represent the most common form of such differences in DNA sequence. In particular, substantial interest exists in determining whether a non-synonymous SNP (nsSNP), leading to a single residue replacement in the translated protein product, is neutral or disease-related. The nature of protein structure-function relationships suggests that nsSNP effects, either benign or leading to aberrant protein function possibly associated with disease, are dependent on relative structural changes introduced upon mutation. In this study, we characterize a representative sampling of 1790 documented neutral and disease-related human nsSNPs mapped to 243 diverse human protein structures, by quantifying environmental perturbations in the associated proteins with the use of a computational mutagenesis methodology that relies on a four-body, knowledge-based, statistical contact potential. These structural change data are used as attributes to generate a vector representation for each nsSNP, in combination with additional features reflecting sequence and structure of the corresponding protein. A trained model based on ...Continue Reading

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Citations

Oct 14, 2011·Amino Acids·Loris NanniAlessandra Lumini
May 12, 2012·Computational and Mathematical Methods in Medicine·Zhe ZhangEmil Alexov
Dec 17, 2011·PloS One·Svend B HenriksenSteffen B Petersen
Nov 6, 2013·Journal of Theoretical Biology·Xiao-Hui NiuJing-Bo Xia
Mar 16, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Antonella ChiechiLance A Liotta
Sep 3, 2011·Journal of Theoretical Biology·Feng ChengJae K Lee
Jun 4, 2011·Journal of Theoretical Biology·I RotermanM Banach
Nov 6, 2012·Journal of Theoretical Biology·Zhijun QiuXicheng Wang
Jun 28, 2011·Computational Biology and Chemistry·Daichuan MaMenglong Li
Oct 22, 2011·Journal of Theoretical Biology·Guoqing LiuLu Cai
Oct 18, 2011·Journal of Theoretical Biology·Jin-Long LuDong-Gang Hu
Apr 1, 2014·Antiviral Research·Majid MassoIosif I Vaisman
Nov 9, 2010·Journal of Theoretical Biology·Krishna Kumar KandaswamyGanesan Pugalenthi
Jan 24, 2017·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Shujaat KhanMohammed Bennamoun

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