Bioinformatics Unravels the Epigenetic Mechanisms of Hashimoto’s Thyroiditis: Deciphering Molecular Complexity

ABSTRACT Introduction Recent research in the field of epigenetics has shed light on the impact of epigenetic modifications in the development and progression of Hashimoto’s thyroiditis (HT). However, the epigenetic roles in HT are still not fully elucidated. Objective To exhibit an in silico representation of the epigenetic mechanism in HT development and explicate their function in the pathogenesis of the ailment. Methods Genetic data were retrieved from GEO database (NCBI) for DNA methylation assessment through bioinformatics. We evaluated 6 HT samples from GSE29315 dataset. Normalization of the data was performed to identify differentially expressed genes (DEGs). Standardization of all expression data was accomplished using the R programming language. The R package was employed for the analysis of DEGs. Genes exhibiting an expression fold change greater than 4 and a P-value less than 0.05 were considered to be DEGs. Results The expression data from the 6 HT specimens in GSE29315 (GSM724489, GSM724490, GSM724491, GSM724492, GSM724493, GSM724494) were patterned. In total, 71 DEGs, including 63 positively regulated genes and 7 negatively regulated genes, were identified. An expression density plot was used to display the clustering of DEGs, and average log-expression was constructed to visually display all DEGs in the HT sample. In the in silico simulation of the methylated regions in gene GSE29315, we identify specific CpG sites within the analyzed regions that showed significant methylation changes: Region 1 - Promoter Region: CpG site 1: Hypomethylated (40% methylation), CpG site 2: Hypomethylated (35% methylation), and CpG site 3: Hypomethylated (38% methylation); Region 2 - Enhancer Region: CpG site 4: Hypermethylated (80% methylation). CpG site 5: Hypermethylated (75% methylation), and CpG site 6: Hypermethylated (85% methylation); Region 3 - Transcription Start Site: CpG site 7: Hypomethylated (30% methylation), CpG site 8: Hypomethylated (25% methylation), and CpG site 9: Hypomethylated (28% methylation); Region 4 - Intronic Region: CpG site 10: Hypermethylated (70% methylation), CpG site 11: Hypermethylated (65% methylation), and CpG site 12: Hypermethylated (75% methylation. Conclusion Our analysis of the GSE29315 gene revealed significant hypermethylation in specific regions, which could lead to gene silencing or altered gene expression. Additionally, we identified regions of hypomethylation that may upregulate gene activity.