Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Comput Biol Med. 2023 Jul;161:107058. doi: 10.1016/j.compbiomed.2023.107058. Epub 2023 May 21.
Epigenetic modifications are implicated in the onset and progression of obstructive sleep apnea (OSA) and its complications through their bidirectional relationship with long-term chronic intermittent hypoxia (IH). However, the exact role of epigenetic acetylation in OSA is unclear. Here we explored the relevance and impact of acetylation-related genes in OSA by identifying molecular subtypes modified by acetylation in OSA patients. Twenty-nine significantly differentially expressed acetylation-related genes were screened in a training dataset (GSE135917). Six common signature genes were identified using the lasso and support vector machine algorithms, with the powerful SHAP algorithm used to judge the importance of each identified feature. DSCC1, ACTL6A, and SHCBP1 were best calibrated and discriminated OSA patients from normal in both training and validation (GSE38792) datasets. Decision curve analysis showed that patients could benefit from a nomogram model developed using these variables. Finally, a consensus clustering approach characterized OSA patients and analyzed the immune signatures of each subgroup. OSA patients were divided into two acetylation patterns (higher acetylation scores in Group B than in Group A) that differed significantly in terms of immune microenvironment infiltration. This is the first study to reveal the expression patterns and key role played by acetylation in OSA, laying the foundation for OSA epitherapy and refined clinical decision-making.
表观遗传修饰通过与长期慢性间歇性低氧（IH）的双向关系，参与阻塞性睡眠呼吸暂停（OSA）及其并发症的发生和进展。然而，表观遗传乙酰化在 OSA 中的确切作用尚不清楚。本研究通过鉴定 OSA 患者中受乙酰化修饰的分子亚型，探讨了乙酰化相关基因在 OSA 中的相关性和影响。在训练数据集（GSE135917）中筛选了 29 个差异表达显著的乙酰化相关基因。使用lasso 和支持向量机算法鉴定了 6 个共同的特征基因，并使用强大的 SHAP 算法来判断每个鉴定特征的重要性。DSCC1、ACTL6A 和 SHCBP1 在训练和验证（GSE38792）数据集均能很好地校准和区分 OSA 患者与正常人群。决策曲线分析表明，使用这些变量构建的列线图模型可以使患者获益。最后，共识聚类方法对 OSA 患者进行了特征描述，并分析了每个亚组的免疫特征。OSA 患者分为两组乙酰化模式（B 组的乙酰化评分高于 A 组），在免疫微环境浸润方面存在显著差异。这是首次揭示乙酰化在 OSA 中的表达模式和关键作用的研究，为 OSA 的表型治疗和精细化临床决策提供了依据。
