A bioinformatics workflow to detect genes with DNA methylation alterations: A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin

Nhan Nguyen; Matthias Lienhard; Ralf Herwig; Jos Kleinjans; Danyel Jennen

doi:10.1145/3510427.3510437

A bioinformatics workflow to detect genes with DNA methylation alterations: A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin

Nhan Nguyen^*, Matthias Lienhard, Ralf Herwig, Jos Kleinjans, Danyel Jennen

^*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceeding › Conference article in proceeding › Academic

Abstract

Epigenetic modification such as DNA methylation can be influenced by different exposure conditions. Alterations in DNA methylation status can then lead to changes in gene and protein expressions. Therefore, studying DNA methylation is needed to provide a comprehensive view of cellular mechanisms. One of the cost-effective technologies to detect DNA methylation is methylated DNA immunoprecipitation-sequencing (MeDIP-seq). While some tools have been developed to analyze the MeDIP-seq data, they mainly focus on methylated genome regions. Thus, there is still a demand for an analysis process that can detect genes with significant differential methylation. In this study, we developed a workflow built on the QSEA package, a recent launched MeDIP-seq analysis tool in R, to analyze DNA methylation at gene levels. This workflow offers an approach to identify candidate genes with strong methylation alterations. We applied this workflow to analyze MeDIP-seq data from cardiac tissues exposed to epirubicin (EPI), which is an antitumor agent with cardiotoxic adverse effects. Several genes that had strong methylation alteration such as HDAC4, EHMT1, SNHG14, SDHA, IGF1R, ADAP1, and NCOR2, were determined and can be candidates for further EPI-induced cardiotoxicity investigation.

Original language	English
Title of host publication	Proceedings of 2022 12th International Conference on Bioscience, Biochemistry and Bioinformatics, ICBBB 2022
Publisher	Association for Computing Machinery
Pages	63-69
Number of pages	7
ISBN (Electronic)	9781450387385
DOIs	https://doi.org/10.1145/3510427.3510437
Publication status	Published - 7 Jan 2022
Event	12th International Conference on Bioscience, Biochemistry and Bioinformatics - Onine, Tokai University, Tokyo, Japan Duration: 7 Jan 2022 → 10 Jan 2022 Conference number: 12 http://www.icbbb.org/icbbb2022.html

Publication series

Series	ACM International Conference Proceeding Series

Conference

Conference	12th International Conference on Bioscience, Biochemistry and Bioinformatics
Abbreviated title	ICBBB 2022
Country/Territory	Japan
City	Tokyo
Period	7/01/22 → 10/01/22
Internet address	http://www.icbbb.org/icbbb2022.html

Keywords

DNA methylation
epirubicin
MeDIP-seq
toxicogenomics

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10.1145/3510427.3510437Licence: CC BY

Cite this

Nguyen, N., Lienhard, M., Herwig, R., Kleinjans, J., & Jennen, D. (2022). A bioinformatics workflow to detect genes with DNA methylation alterations: A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin. In Proceedings of 2022 12th International Conference on Bioscience, Biochemistry and Bioinformatics, ICBBB 2022 (pp. 63-69). Association for Computing Machinery. https://doi.org/10.1145/3510427.3510437

Nguyen, Nhan ; Lienhard, Matthias ; Herwig, Ralf et al. / A bioinformatics workflow to detect genes with DNA methylation alterations : A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin. Proceedings of 2022 12th International Conference on Bioscience, Biochemistry and Bioinformatics, ICBBB 2022. Association for Computing Machinery, 2022. pp. 63-69 (ACM International Conference Proceeding Series).

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title = "A bioinformatics workflow to detect genes with DNA methylation alterations: A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin",

abstract = "Epigenetic modification such as DNA methylation can be influenced by different exposure conditions. Alterations in DNA methylation status can then lead to changes in gene and protein expressions. Therefore, studying DNA methylation is needed to provide a comprehensive view of cellular mechanisms. One of the cost-effective technologies to detect DNA methylation is methylated DNA immunoprecipitation-sequencing (MeDIP-seq). While some tools have been developed to analyze the MeDIP-seq data, they mainly focus on methylated genome regions. Thus, there is still a demand for an analysis process that can detect genes with significant differential methylation. In this study, we developed a workflow built on the QSEA package, a recent launched MeDIP-seq analysis tool in R, to analyze DNA methylation at gene levels. This workflow offers an approach to identify candidate genes with strong methylation alterations. We applied this workflow to analyze MeDIP-seq data from cardiac tissues exposed to epirubicin (EPI), which is an antitumor agent with cardiotoxic adverse effects. Several genes that had strong methylation alteration such as HDAC4, EHMT1, SNHG14, SDHA, IGF1R, ADAP1, and NCOR2, were determined and can be candidates for further EPI-induced cardiotoxicity investigation.",

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author = "Nhan Nguyen and Matthias Lienhard and Ralf Herwig and Jos Kleinjans and Danyel Jennen",

note = "Funding Information: We would like to thank Olivia Clayton from InSphero and Roche{\textquoteright}s staffs, who delivered the samples. This work was supported by the 7th Framework Programme of the European Union (FP7/2007-2013), grant no. 602156 for the HeCaToS project. Publisher Copyright: {\textcopyright} 2022 Owner/Author.; 12th International Conference on Bioscience, Biochemistry and Bioinformatics, ICBBB 2022 ; Conference date: 07-01-2022 Through 10-01-2022",

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language = "English",

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Nguyen, N, Lienhard, M, Herwig, R, Kleinjans, J & Jennen, D 2022, A bioinformatics workflow to detect genes with DNA methylation alterations: A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin. in Proceedings of 2022 12th International Conference on Bioscience, Biochemistry and Bioinformatics, ICBBB 2022. Association for Computing Machinery, ACM International Conference Proceeding Series, pp. 63-69, 12th International Conference on Bioscience, Biochemistry and Bioinformatics, Tokyo, Japan, 7/01/22. https://doi.org/10.1145/3510427.3510437

A bioinformatics workflow to detect genes with DNA methylation alterations: A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin. / Nguyen, Nhan; Lienhard, Matthias; Herwig, Ralf et al.
Proceedings of 2022 12th International Conference on Bioscience, Biochemistry and Bioinformatics, ICBBB 2022. Association for Computing Machinery, 2022. p. 63-69 (ACM International Conference Proceeding Series).

Research output: Chapter in Book/Report/Conference proceeding › Conference article in proceeding › Academic

TY - GEN

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T2 - 12th International Conference on Bioscience, Biochemistry and Bioinformatics

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AU - Kleinjans, Jos

AU - Jennen, Danyel

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N2 - Epigenetic modification such as DNA methylation can be influenced by different exposure conditions. Alterations in DNA methylation status can then lead to changes in gene and protein expressions. Therefore, studying DNA methylation is needed to provide a comprehensive view of cellular mechanisms. One of the cost-effective technologies to detect DNA methylation is methylated DNA immunoprecipitation-sequencing (MeDIP-seq). While some tools have been developed to analyze the MeDIP-seq data, they mainly focus on methylated genome regions. Thus, there is still a demand for an analysis process that can detect genes with significant differential methylation. In this study, we developed a workflow built on the QSEA package, a recent launched MeDIP-seq analysis tool in R, to analyze DNA methylation at gene levels. This workflow offers an approach to identify candidate genes with strong methylation alterations. We applied this workflow to analyze MeDIP-seq data from cardiac tissues exposed to epirubicin (EPI), which is an antitumor agent with cardiotoxic adverse effects. Several genes that had strong methylation alteration such as HDAC4, EHMT1, SNHG14, SDHA, IGF1R, ADAP1, and NCOR2, were determined and can be candidates for further EPI-induced cardiotoxicity investigation.

AB - Epigenetic modification such as DNA methylation can be influenced by different exposure conditions. Alterations in DNA methylation status can then lead to changes in gene and protein expressions. Therefore, studying DNA methylation is needed to provide a comprehensive view of cellular mechanisms. One of the cost-effective technologies to detect DNA methylation is methylated DNA immunoprecipitation-sequencing (MeDIP-seq). While some tools have been developed to analyze the MeDIP-seq data, they mainly focus on methylated genome regions. Thus, there is still a demand for an analysis process that can detect genes with significant differential methylation. In this study, we developed a workflow built on the QSEA package, a recent launched MeDIP-seq analysis tool in R, to analyze DNA methylation at gene levels. This workflow offers an approach to identify candidate genes with strong methylation alterations. We applied this workflow to analyze MeDIP-seq data from cardiac tissues exposed to epirubicin (EPI), which is an antitumor agent with cardiotoxic adverse effects. Several genes that had strong methylation alteration such as HDAC4, EHMT1, SNHG14, SDHA, IGF1R, ADAP1, and NCOR2, were determined and can be candidates for further EPI-induced cardiotoxicity investigation.

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KW - toxicogenomics

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M3 - Conference article in proceeding

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EP - 69

BT - Proceedings of 2022 12th International Conference on Bioscience, Biochemistry and Bioinformatics, ICBBB 2022

PB - Association for Computing Machinery

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ER -

Nguyen N, Lienhard M, Herwig R, Kleinjans J, Jennen D. A bioinformatics workflow to detect genes with DNA methylation alterations: A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin. In Proceedings of 2022 12th International Conference on Bioscience, Biochemistry and Bioinformatics, ICBBB 2022. Association for Computing Machinery. 2022. p. 63-69. (ACM International Conference Proceeding Series). doi: 10.1145/3510427.3510437

A bioinformatics workflow to detect genes with DNA methylation alterations: A case study of analyzing MeDIP-seq data in cardiac microtissue exposed to epirubicin

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