Exploring Epigenetic Methylation Patterns in Parkinson's Disease through WGCNA Analysis

سال انتشار: 1402
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 26

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شناسه ملی سند علمی:

IBIS12_134

تاریخ نمایه سازی: 12 آبان 1403

چکیده مقاله:

Parkinson's disease (PD) involves progressive loss of dopaminergic neurons in the substantianigra, causing motor and non-motor symptoms. Epigenetic mechanisms play a crucial role in PDpathogenesis, reflecting the interplay of genetics and the environment. This study aimed to identifydifferential methylated positions (DMP) and regions (DMRs) of PD patients compared to healthysamples, shedding light on the epigenetic factors underlying Parkinson's disease.We conducted a comprehensive analysis of DNA methylation patterns in PD using data obtained fromIllumina EPIC arrays. Data were downloaded from PPMI [۱]. In total, ۲۱۴ sporadic PD and ۸۷ healthycontrol samples were analyzed. The identification DMPs was performed using the limma package.Next, WGCNA [۲] was employed to construct co-methylation networks and detect modules of highlycorrelated DMPs and DMRs associated with PD phenotypes. Preprocessing steps, including qualitycontrol, normalization, and batch correction, were performed using the ChAMP package in R [۳]. DMPsand DMRs between PD and healthy control samples were identified based on stringent statisticalcriteria. Hub genes derived from WGCNA analysis were subjected to enrichment analysis, to improveour understanding of the molecular pathways underlying PD pathogenesis.Our analysis identified ۱۴۸۶۶ DMPs and ۱۰۱ DMRs (adjusted P-values of ۰.۰۱ and ۰.۰۵, respectively).Utilizing WGCNA, we delineated ۲۰ clusters and identified ۱۳ hub genes associated with DMPs.Notably, BMP۴ and MTHFD۲ emerged as significant candidates, potentially influencing Parkinson'sdisease pathophysiology. However, none of the DMR modules achieved significance. These findingsshed light on PD-associated methylation alterations and underscore pathways, including mitochondrialdysfunction, neuroinflammation, and synaptic transmission implicated in PD pathogenesis.Our analysis revealed distinct methylation patterns associated with PD, characterized by widespreadalterations in DNA methylation levels at specific genomic loci. WGCNA identified modules of comethylatedloci showing differential methylation patterns between PD and healthy control samples.

کلیدواژه ها:

Parkinson’s disease ، DNA methylation Analysis ، Weighted Gene Co-expression Network Analysis

نویسندگان

Fateme Vafaee Sharbaf

Laboratory of Complex Biological Systems and Bioinformatics (CBB), Department of Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

Zahra Salehi

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical . Sciences, Tehran, Iran- Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran

Abdollah Safari

School of Mathematics, Statistics and Computer Science, College of Science, University of Tehran, Tehran,Iran

Kaveh Kavousi

Laboratory of Complex Biological Systems and Bioinformatics (CBB), Department of Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran