Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection

Background: Human papillomaviruses have been shown to dysregulate the gene expression and DNA methylation profiles of their host cells over the course of infection. However, there is a lack of information on the impact of low-risk HPV infection and wart formation on host cell's expression and m...

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Main Authors: Mansour A. Alghamdi, Laith N. AL-Eitan, Amneh H. Tarkhan
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S240584402303308X
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author Mansour A. Alghamdi
Laith N. AL-Eitan
Amneh H. Tarkhan
author_facet Mansour A. Alghamdi
Laith N. AL-Eitan
Amneh H. Tarkhan
author_sort Mansour A. Alghamdi
collection DOAJ
description Background: Human papillomaviruses have been shown to dysregulate the gene expression and DNA methylation profiles of their host cells over the course of infection. However, there is a lack of information on the impact of low-risk HPV infection and wart formation on host cell's expression and methylation patterns. Therefore, the objective of this study is to analyse the genome and methylome of common warts using an integrative approach. Methods: In the present study, gene expression (GSE136347) and methylation (GSE213888) datasets of common warts were obtained from the GEO database. Identification of the differentially expressed and differentially methylated genes was carried out using the RnBeads R package and the edgeR Bioconductor package. Next, functional annotation of the identified genes was obtained using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Network construction and analyses of the gene-gene, protein-protein, and signaling interactions of the differentially expressed and differentially methylated genes was performed using the GeneMANIA web interface, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the Signaling Network Open Resource 2.0 (SIGNOR 2.0), respectively. Lastly, significant hub genes were identified using the Cytoscape application CytoHubba. Results: A total of 276 genes were identified as differentially expressed and differentially methylated in common warts, with 52% being upregulated and hypermethylated. Functional enrichment analysis identified extracellular components as the most enriched annotations, while network analyses identified ELN, ITGB1, TIMP1, MMP2, LGALS3, COL1A1 and ANPEP as significant hub genes. Conclusions: To the best knowledge of the authors, this is the first integrative study to be carried out on non-genital warts induced by low-risk HPV types. Future studies are required to re-validate the findings in larger populations using alternative approaches.
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spelling doaj.art-facc15342690438a954adafa448cf7672023-05-31T04:46:38ZengElsevierHeliyon2405-84402023-05-0195e16101Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infectionMansour A. Alghamdi0Laith N. AL-Eitan1Amneh H. Tarkhan2Department of Anatomy, College of Medicine, King Khalid University, Abha, 61421, Saudi Arabia; Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha, 61421, Saudi Arabia; Corresponding author. Department of Anatomy, College of Medicine, King Khalid University, Abha, 61421, Saudi Arabia.Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan; Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, 22110, Jordan; Corresponding author. Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan.Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, 22110, JordanBackground: Human papillomaviruses have been shown to dysregulate the gene expression and DNA methylation profiles of their host cells over the course of infection. However, there is a lack of information on the impact of low-risk HPV infection and wart formation on host cell's expression and methylation patterns. Therefore, the objective of this study is to analyse the genome and methylome of common warts using an integrative approach. Methods: In the present study, gene expression (GSE136347) and methylation (GSE213888) datasets of common warts were obtained from the GEO database. Identification of the differentially expressed and differentially methylated genes was carried out using the RnBeads R package and the edgeR Bioconductor package. Next, functional annotation of the identified genes was obtained using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Network construction and analyses of the gene-gene, protein-protein, and signaling interactions of the differentially expressed and differentially methylated genes was performed using the GeneMANIA web interface, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the Signaling Network Open Resource 2.0 (SIGNOR 2.0), respectively. Lastly, significant hub genes were identified using the Cytoscape application CytoHubba. Results: A total of 276 genes were identified as differentially expressed and differentially methylated in common warts, with 52% being upregulated and hypermethylated. Functional enrichment analysis identified extracellular components as the most enriched annotations, while network analyses identified ELN, ITGB1, TIMP1, MMP2, LGALS3, COL1A1 and ANPEP as significant hub genes. Conclusions: To the best knowledge of the authors, this is the first integrative study to be carried out on non-genital warts induced by low-risk HPV types. Future studies are required to re-validate the findings in larger populations using alternative approaches.http://www.sciencedirect.com/science/article/pii/S240584402303308XHPVHuman papillomavirusWartsGene expressionDNA methylation
spellingShingle Mansour A. Alghamdi
Laith N. AL-Eitan
Amneh H. Tarkhan
Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection
Heliyon
HPV
Human papillomavirus
Warts
Gene expression
DNA methylation
title Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection
title_full Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection
title_fullStr Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection
title_full_unstemmed Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection
title_short Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection
title_sort integrative analysis of gene expression and dna methylation to identify biomarkers of non genital warts induced by low risk human papillomaviruses infection
topic HPV
Human papillomavirus
Warts
Gene expression
DNA methylation
url http://www.sciencedirect.com/science/article/pii/S240584402303308X
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