Integrated Analysis of DNA methylation and transcriptome profile to identify key features of age-related macular degeneration

Bioengineered

Zekai Cui¹  Zhijie Wang²  Yinhua Huang²  Kai Liao²  Shibo Tang³  Jiansu Chen⁴  Feixue Chu⁵ 

[1] Aier Eye Institute, Changsha, Chin;Aier School of Ophthalmology, Central South University, Changsha, Chin;Aier Eye Institute, Changsha, Chin;Aier School of Ophthalmology, Central South University, Changsha, Chin;Aier Eye Institute, Changsha, Chin;Cas Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, Chin;Aier School of Ophthalmology, Central South University, Changsha, Chin;Aier Eye Institute, Changsha, Chin;Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, Chin;Institute of Ophthalmology, Medical College, Jinan University, Guangzhou, Chin;Hangzhou Xihu Zhijiang Eye Hospital, Hangzhou, Chin;

关键词: Age-related macular degeneration disease;    DNA methylation;    transcriptome profile;    immune cell infiltration;    data integration;    key genes;   

DOI  :  10.1080/21655979.2021.1976502

来源: Taylor & Francis

【 摘 要 】

Age-related macular degeneration (AMD) is a common vision-threatening disease. The current study sought to integrate DNA methylation with transcriptome profile to explore key features in AMD. Gene expression data were obtained from the Gene Expression Omnibus (GEO, accession ID: GSE135092) and DNA methylation data were obtained from the ArrayExpress repository (E-MTAB-7183). A total of 456 differentially expressed genes (DEGs) and 4827 intragenic differentially methylated CpGs (DMCs) were identified between AMD and controls. DEGs and DMCs were intersected and 19 epigenetically induced (EI) genes and 15 epigenetically suppressed (ES) genes were identified. Immune cell infiltration analysis was performed to estimate the abundance of different types of immune cell in each sample. Enrichment scores of inflammatory response and tumor necrosis factor-alpha (TNFα) signaling via nuclear factor kappa B (NF-κb) were positively correlated with abundance of activated memory CD4 T cells and M1 macrophages. Subsequently, two significant random forest classifiers were constructed based on DNA methylation and transcriptome data. SMAD2 and NGFR were selected as key genes through functional epigenetic modules (FEM) analysis. Expression level of SMAD2, NGFR and their integrating proteins was validated in hydrogen peroxide (H2O2) and TNFα co-treated retinal pigment epithelium (RPE) in vitro. The findings of the current study showed that local inflammation and systemic inflammatory host response play key roles in pathogenesis of AMD. SMAD2 and NGFR provide new insight in understanding the molecular mechanism and are potential therapeutic targets for development of AMD therapy.

【 授权许可】

CC BY