Integrative analysis identifies gene signatures mediating the effect of DNA methylation on asthma severity and lung function.
Integrative analysis identifies gene signatures mediating the effect of DNA methylation on asthma severity and lung function.
复制标题
DOI：
10.1186/s13148-023-01611-9
复制
发表时间：
2024-01-20
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
DNA甲基化（DNAm）改变在调节哮喘基因表达中起关键作用。为了研究表观遗传学和转录组学变化在哮喘中的作用，我们使用了来自支气管上皮细胞（BEC）的公开可用的DNAm（哮喘患者，n = 96和对照组，n = 46）和基因表达（哮喘患者，n = 79和对照组，n = 39）数据。我们进行了差异甲基化/表达和加权共甲基化/共表达网络分析，以确定与哮喘严重程度和肺功能相关的共甲基化和共表达模块。对于同时具有DNAm和基因表达数据的受试者（哮喘患者，n = 79，对照组，n = 39），使用机器学习技术对CpG和差异表达基因（DEG）进行优先排序，以预测哮喘风险，并使用中介分析来揭示介导DNAm对BEC中哮喘严重程度和肺功能影响的DEG。最后，我们在气道上皮细胞（AECs）数据集中验证了CpG及其相关DEG和哮喘风险预测模型。基于18个CpG和28个DEG的哮喘风险预测模型在发现BEC数据集（受试者工作特征曲线下面积（AUC）= 0.99）和验证AEC数据集（AUC = 0.82）中均显示出较高的准确性。三个共甲基化和六个共表达模块中的基因在包括WNT/β-连环蛋白信号传导和notch信号传导的多个途径中富集。此外，我们在BEC中鉴定了35个与DEG相关的CpG，其中包括cg 01975495（SERPINE 1），cg 10528482（SLC 9A 3），cg 25477769（HNF 1A）和cg 26639146（CD 9），cg 17945560（TINAGL 1）和cg 10290200（FLNC）在内的17个CpG在AEC中复制。这些DEG介导DNAm与哮喘严重程度和肺功能之间的关联。总的来说，我们的研究探讨了DNA甲基化和基因表达变化在哮喘中的作用，并深入了解了DNA甲基化对哮喘、哮喘严重程度和肺功能影响的潜在机制。在线版本包含补充材料，可通过10.1186/s13148-023-01611-9获得。
DNA methylation (DNAm) changes play a key role in regulating gene expression in asthma. To investigate the role of epigenetics and transcriptomics change in asthma, we used publicly available DNAm (asthmatics, n = 96 and controls, n = 46) and gene expression (asthmatics, n = 79 and controls, n = 39) data derived from bronchial epithelial cells (BECs). We performed differential methylation/expression and weighted co-methylation/co-expression network analyses to identify co-methylated and co-expressed modules associated with asthma severity and lung function. For subjects with both DNAm and gene expression data (asthmatics, n = 79 and controls, n = 39), machine-learning technique was used to prioritize CpGs and differentially expressed genes (DEGs) for asthma risk prediction, and mediation analysis was used to uncover DEGs that mediate the effect of DNAm on asthma severity and lung function in BECs. Finally, we validated CpGs and their associated DEGs and the asthma risk prediction model in airway epithelial cells (AECs) dataset. The asthma risk prediction model based on 18 CpGs and 28 DEGs showed high accuracy in both the discovery BEC dataset with area under the receiver operating characteristic curve (AUC) = 0.99 and the validation AEC dataset (AUC = 0.82). Genes in the three co-methylated and six co-expressed modules were enriched in multiple pathways including WNT/beta-catenin signaling and notch signaling. Moreover, we identified 35 CpGs correlated with DEGs in BECs, of which 17 CpGs including cg01975495 (SERPINE1), cg10528482 (SLC9A3), cg25477769 (HNF1A) and cg26639146 (CD9), cg17945560 (TINAGL1) and cg10290200 (FLNC) were replicated in AECs. These DEGs mediate the association between DNAm and asthma severity and lung function. Overall, our study investigated the role of DNAm and gene expression change in asthma and provided an insight into the mechanisms underlying the effects of DNA methylation on asthma, asthma severity and lung function. The online version contains supplementary material available at 10.1186/s13148-023-01611-9.
登录
查看更多内容
影响因子：
5.7
作者：
Clifford RL;Yang CX;Fishbane N;Patel J;MacIsaac JL;McEwen LM;May ST;Castellanos-Uribe M;Nair P;Obeidat M;Kobor MS;Knox AJ;Hackett TL
通讯作者：
Hackett TL
影响因子：
5.7
作者：
通讯作者：
--
DOI：
10.1093/ijnp/pyab043
发表时间：
2021-11-12
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Liu A;Dai Y;Mendez EF;Hu R;Fries GR;Najera KE;Jiang S;Meyer TD;Stertz L;Jia P;Walss-Bass C;Zhao Z
通讯作者：
Zhao Z
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
5.8
作者：
Kursa, Miron B.;Rudnicki, Witold R.
通讯作者：
Rudnicki, Witold R.