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

Tikam Chand Dakal, Deepak Kala, Gourav Dhiman, Vinod Yadav, Andrey Krokhotin, Nikolay Dokholyan

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Article number6525
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Interleukin-8
Single Nucleotide Polymorphism
Genes
Sequence Homology
Amino Acid Substitution
Computer Simulation
Stomach Neoplasms
Lung Neoplasms
Proteins
Amino Acids

All Science Journal Classification (ASJC) codes

  • General

Cite this

Dakal, Tikam Chand ; Kala, Deepak ; Dhiman, Gourav ; Yadav, Vinod ; Krokhotin, Andrey ; Dokholyan, Nikolay. / Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene. / Dakal, Tikam Chand; Kala, Deepak; Dhiman, Gourav; Yadav, Vinod; Krokhotin, Andrey; Dokholyan, Nikolay.

In: Scientific reports, Vol. 7, No. 1, 6525, 01.12.2017.

Research output: Contribution to journalArticle

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