Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene

Abstract Here we report an in-silico approach for identification, characterization and validation of deleterious non-synonymous SNPs (nsSNPs) in the interleukin-8 gene using three steps. In first step, sequence homology-based genetic analysis of a set of 50 coding SNPs associated with 41 rsIDs using...

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Autores principales:	Tikam Chand Dakal, Deepak Kala, Gourav Dhiman, Vinod Yadav, Andrey Krokhotin, Nikolay V. Dokholyan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9a6375912c24d70811c11d176d6384b
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spelling	oai:doaj.org-article:d9a6375912c24d70811c11d176d6384b2021-12-02T15:05:48ZPredicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene10.1038/s41598-017-06575-42045-2322https://doaj.org/article/d9a6375912c24d70811c11d176d6384b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06575-4https://doaj.org/toc/2045-2322Abstract Here we report an in-silico approach for identification, characterization and validation of deleterious non-synonymous SNPs (nsSNPs) in the interleukin-8 gene using three steps. In first step, sequence homology-based genetic analysis of a set of 50 coding SNPs associated with 41 rsIDs using SIFT (Sorting Intolerant from Tolerant) and PROVEAN (Protein Variation Effect Analyzer) identified 23 nsSNPs to be putatively damaging/deleterious in at least one of the two tools used. Subsequently, structure-homology based PolyPhen-2 (Polymorphism Phenotyping) analysis predicted 9 of 23 nsSNPs (K4T, E31A, E31K, S41Y, I55N, P59L, P59S, L70P and V88D) to be damaging. According to the conditional hypothesis for the study, only nsSNPs that score damaging/deleterious prediction in both sequence and structural homology-based approach will be considered as ‘high-confidence’ nsSNPs. In step 2, based on conservation of amino acid residues, stability analysis, structural superimposition, RSMD and docking analysis, the possible structural-functional relationship was ascertained for high-confidence nsSNPs. Finally, in a separate analysis (step 3), the IL-8 deregulation has also appeared to be an important prognostic marker for detection of patients with gastric and lung cancer. This study, for the first time, provided in-depth insights on the effects of amino acid substitutions on IL-8 protein structure, function and disease association.Tikam Chand DakalDeepak KalaGourav DhimanVinod YadavAndrey KrokhotinNikolay V. DokholyanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-18 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tikam Chand Dakal Deepak Kala Gourav Dhiman Vinod Yadav Andrey Krokhotin Nikolay V. Dokholyan Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene
description	Abstract Here we report an in-silico approach for identification, characterization and validation of deleterious non-synonymous SNPs (nsSNPs) in the interleukin-8 gene using three steps. In first step, sequence homology-based genetic analysis of a set of 50 coding SNPs associated with 41 rsIDs using SIFT (Sorting Intolerant from Tolerant) and PROVEAN (Protein Variation Effect Analyzer) identified 23 nsSNPs to be putatively damaging/deleterious in at least one of the two tools used. Subsequently, structure-homology based PolyPhen-2 (Polymorphism Phenotyping) analysis predicted 9 of 23 nsSNPs (K4T, E31A, E31K, S41Y, I55N, P59L, P59S, L70P and V88D) to be damaging. According to the conditional hypothesis for the study, only nsSNPs that score damaging/deleterious prediction in both sequence and structural homology-based approach will be considered as ‘high-confidence’ nsSNPs. In step 2, based on conservation of amino acid residues, stability analysis, structural superimposition, RSMD and docking analysis, the possible structural-functional relationship was ascertained for high-confidence nsSNPs. Finally, in a separate analysis (step 3), the IL-8 deregulation has also appeared to be an important prognostic marker for detection of patients with gastric and lung cancer. This study, for the first time, provided in-depth insights on the effects of amino acid substitutions on IL-8 protein structure, function and disease association.
format	article
author	Tikam Chand Dakal Deepak Kala Gourav Dhiman Vinod Yadav Andrey Krokhotin Nikolay V. Dokholyan
author_facet	Tikam Chand Dakal Deepak Kala Gourav Dhiman Vinod Yadav Andrey Krokhotin Nikolay V. Dokholyan
author_sort	Tikam Chand Dakal
title	Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene
title_short	Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene
title_full	Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene
title_fullStr	Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene
title_full_unstemmed	Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene
title_sort	predicting the functional consequences of non-synonymous single nucleotide polymorphisms in il8 gene
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d9a6375912c24d70811c11d176d6384b
work_keys_str_mv	AT tikamchanddakal predictingthefunctionalconsequencesofnonsynonymoussinglenucleotidepolymorphismsinil8gene AT deepakkala predictingthefunctionalconsequencesofnonsynonymoussinglenucleotidepolymorphismsinil8gene AT gouravdhiman predictingthefunctionalconsequencesofnonsynonymoussinglenucleotidepolymorphismsinil8gene AT vinodyadav predictingthefunctionalconsequencesofnonsynonymoussinglenucleotidepolymorphismsinil8gene AT andreykrokhotin predictingthefunctionalconsequencesofnonsynonymoussinglenucleotidepolymorphismsinil8gene AT nikolayvdokholyan predictingthefunctionalconsequencesofnonsynonymoussinglenucleotidepolymorphismsinil8gene
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Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene

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