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Lim E, Xu H, Wu P, et al. Network analysis of drug effect on triglyceride-associated DNA methylation. BMC Proc. 2018;12:27doi: 10.1186/s12919-018-0130-0.
Lim, E., Xu, H., Wu, P., Posner, D., Wu, J., Peloso, G. M., Pitsillides, A. N., DeStefano, A. L., Adrienne Cupples, L., & Liu, C. T. (2018). Network analysis of drug effect on triglyceride-associated DNA methylation. BMC proceedings, 1227. https://doi.org/10.1186/s12919-018-0130-0
Lim, Elise, et al. "Network analysis of drug effect on triglyceride-associated DNA methylation." BMC proceedings vol. 12 (2018): 27. doi: https://doi.org/10.1186/s12919-018-0130-0
Lim E, Xu H, Wu P, Posner D, Wu J, Peloso GM, Pitsillides AN, DeStefano AL, Adrienne Cupples L, Liu CT. Network analysis of drug effect on triglyceride-associated DNA methylation. BMC Proc. 2018 Sep 17;12:27. doi: 10.1186/s12919-018-0130-0. eCollection 2018. PMID: 30275881; PMCID: PMC6157190.
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BMC Proc. 2018 Sep 17;12:27. doi: 10.1186/s12919-018-0130-0. eCollection 2018.

Network analysis of drug effect on triglyceride-associated DNA methylation.

BMC proceedings

Elise Lim, Hanfei Xu, Peitao Wu, Daniel Posner, Jiayi Wu, Gina M Peloso, Achilleas N Pitsillides, Anita L DeStefano, L Adrienne Cupples, Ching-Ti Liu

Affiliations

  1. 1Department of Biostatistics, Boston University, 801 Massachusetts Avenue 3rd Floor, Boston, MA 02118 USA.
  2. 2Department of Genetics and Genomics, Boston University, 72 East Concord Street, Boston, MA 02118 USA.

PMID: 30275881 PMCID: PMC6157190 DOI: 10.1186/s12919-018-0130-0

Abstract

BACKGROUND: DNA methylation, an epigenetic modification, can be affected by environmental factors and thus regulate gene expression levels that can lead to alterations of certain phenotypes. Network analysis has been used successfully to discover gene sets that are expressed differently across multiple disease states and suggest possible pathways of disease progression. We applied this framework to compare DNA methylation levels before and after lipid-lowering medication and to identify modules that differ topologically between the two time points, revealing the association between lipid medication and these triglyceride-related methylation sites.

METHODS: We performed quality control using beta-mixture quantile normalization on 463,995 cytosine-phosphate-guanine (CpG) sites and deleted problematic sites, resulting in 423,004 probes. We identified 14,850 probes that were nominally associated with triglycerides prior to treatment and performed weighted gene correlation network analysis (WGCNA) to construct pre- and posttreatment methylation networks of these probes. We then applied both WGCNA module preservation and generalized Hamming distance (GHD) to identify modules with topological differences between the pre- and posttreatment. For modules with structural changes between 2 time points, we performed pathway-enrichment analysis to gain further insight into the biological function of the genes from these modules.

RESULTS: Six triglyceride-associated modules were identified using pretreatment methylation probes. The same 3 modules were not preserved in posttreatment data using both the module-preservation and the GHD methods. Top-enriched pathways for the 3 differentially methylated modules are sphingolipid signaling pathway, proteoglycans in cancer, and metabolic pathways (

CONCLUSIONS: The same 3 modules, which were differentially methylated between pre- and posttreatment, were identified using both WGCNA module-preservation and GHD methods. Pathway analysis revealed that triglyceride-associated modules contain groups of genes that are involved in lipid signaling and metabolism. These 3 modules may provide insight into the effect of fenofibrate on changes in triglyceride levels and these methylation sites.

Conflict of interest statement

Not applicable.Not applicable.The authors declare they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

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