Novel insights into systemic sclerosis using a sensitive computational method to analyze whole-genome bisulfite sequencing data.
Clin Epigenetics
; 15(1): 96, 2023 06 03.
Article
em En
| MEDLINE
| ID: mdl-37270501
ABSTRACT
BACKGROUND:
Abnormal DNA methylation is thought to contribute to the onset and progression of systemic sclerosis. Currently, the most comprehensive assay for profiling DNA methylation is whole-genome bisulfite sequencing (WGBS), but its precision depends on read depth and it may be subject to sequencing errors. SOMNiBUS, a method for regional analysis, attempts to overcome some of these limitations. Using SOMNiBUS, we re-analyzed WGBS data previously analyzed using bumphunter, an approach that initially fits single CpG associations, to contrast DNA methylation estimates by both methods.METHODS:
Purified CD4+ T lymphocytes of 9 SSc and 4 control females were sequenced using WGBS. We separated the resulting sequencing data into regions with dense CpG data, and differentially methylated regions (DMRs) were inferred with the SOMNiBUS region-level test, adjusted for age. Pathway enrichment analysis was performed with ingenuity pathway analysis (IPA). We compared the results obtained by SOMNiBUS and bumphunter.RESULTS:
Of 8268 CpG regions of ≥ 60 CpGs eligible for analysis with SOMNiBUS, we identified 131 DMRs and 125 differentially methylated genes (DMGs; p-values less than Bonferroni-corrected threshold of 6.05-06 controlling family-wise error rate at 0.05; 1.6% of the regions). In comparison, bumphunter identified 821,929 CpG regions, 599 DMRs (of which none had ≥ 60 CpGs) and 340 DMGs (q-value of 0.05; 0.04% of all regions). The top ranked gene identified by SOMNiBUS was FLT4, a lymphangiogenic orchestrator, and the top ranked gene on chromosome X was CHST7, known to catalyze the sulfation of glycosaminoglycans in the extracellular matrix. The top networks identified by IPA included connective tissue disorders.CONCLUSIONS:
SOMNiBUS is a complementary method of analyzing WGBS data that enhances biological insights into SSc and provides novel avenues of investigation into its pathogenesis.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Escleroderma Sistêmico
/
Metilação de DNA
Tipo de estudo:
Diagnostic_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article