Identification of Sjögren's syndrome patient subgroups by clustering of labial salivary gland DNA methylation profiles.
Identification of Sjögren's syndrome patient subgroups by clustering of labial salivary gland DNA methylation profiles.
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DOI：
10.1371/journal.pone.0281891
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
干燥综合征(SS)的异质性表明疾病亚型的存在，这对这种自身免疫性疾病的诊断、管理和治疗构成了重大挑战。以前的工作是根据临床症状区分患者亚组，但尚不清楚症状在多大程度上反映了潜在的病理生物学。本研究的目的是基于全基因组DNA甲基化数据发现有临床意义的SS亚型。我们对收集自SS患者和67例非SS患者的唇涎腺组织的全基因组甲基化数据进行了聚类分析。具体地说，对从变分自动编码器提取的DNA甲基化数据的低维嵌入进行了层次聚类，以揭示未知的异质性。聚集性显示临床上SS的重度和轻度亚组。差异甲基化分析表明，这些SS亚群之间的表观遗传差异表现为MHC的低甲基化和其他基因组区域的高甲基化。SS中LSGs的表观遗传学图谱为疾病异质性的潜在机制提供了新的见解。差异甲基化的CPGS在SS亚群中的甲基化模式不同，支持表观遗传因素在SS异质性中的作用。从表观遗传学特征获得的生物标记物数据可以在定义SS亚组的分类标准的未来迭代中进行探索。
Heterogeneity in Sjögren’s syndrome (SS), increasingly called Sjögren’s disease, suggests the presence of disease subtypes, which poses a major challenge for the diagnosis, management, and treatment of this autoimmune disorder. Previous work distinguished patient subgroups based on clinical symptoms, but it is not clear to what extent symptoms reflect underlying pathobiology. The purpose of this study was to discover clinical meaningful subtypes of SS based on genome-wide DNA methylation data. We performed a cluster analysis of genome-wide DNA methylation data from labial salivary gland (LSG) tissue collected from 64 SS cases and 67 non-cases. Specifically, hierarchical clustering was performed on low dimensional embeddings of DNA methylation data extracted from a variational autoencoder to uncover unknown heterogeneity. Clustering revealed clinically severe and mild subgroups of SS. Differential methylation analysis revealed that hypomethylation at the MHC and hypermethylation at other genome regions characterize the epigenetic differences between these SS subgroups. Epigenetic profiling of LSGs in SS yields new insights into mechanisms underlying disease heterogeneity. The methylation patterns at differentially methylated CpGs are different in SS subgroups and support the role of epigenetic contributions to the heterogeneity in SS. Biomarker data derived from epigenetic profiling could be explored in future iterations of the classification criteria for defining SS subgroups.
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DOI：
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发表时间：
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期刊：
Bioinformatics (Oxford, England)
影响因子：
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发表时间：
1995-01-01
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