BACKGROUND Preeclampsia (PE) is a heterogeneous, hypertensive disorder of pregnancy, with no robust biomarkers or effective treatments. PE increases the risk of poor outcomes for both the mother and the baby. Methylation-mediated transcriptional dysregulation motifs (methTDMs) could contribute the PE development. However, precise functional roles of methTDMs in PE have not been globally described. METHODS Here, we develop a comprehensive and computational pipeline to identify PE-specific methTDMs following TF, gene, methylation expression profile, and experimentally verified TF-gene interactions. RESULTS The regulation patterns of methTDMs are multiple and complex in PE and contain relax inhibition, intensify inhibition, relax activation, intensify activation, reverse activation, and reverse inhibition. A core module is extracted from global methTDM network to further depict the mechanism of methTDMs in PE. The common and specific features of any two kinds of regulation pattern are also analyzed in PE. Some key methylation sites, TFs, and genes such as IL2RG are identified in PE. Functional analysis shows that methTDMs are associated with immune-, insulin-, and NK cell-related functions. Drug-related network identifies some key drug repurposing candidates such as NADH. CONCLUSION Collectively, the study highlighted the effect of methylation on the transcription process in PE. MethTDMs could contribute to identify specific biomarkers and drug repurposing candidates for PE.

中文翻译：

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甲基化介导的转录失调的鉴定和特征决定了子痫前期中甲基化的作用。

背景技术子痫前期（PE）是一种异质性妊娠高血压疾病，没有可靠的生物标志物或有效的治疗方法。PE会增加母亲和婴儿结局不良的风险。甲基化介导的转录失调基序（methTDM）可能有助于PE的发展。但是，尚未全面描述methTDM在PE中的确切功能作用。方法在这里，我们开发了一条综合的计算流程，可根据TF，基因，甲基化表达谱以及经过实验验证的TF基因相互作用来鉴定PE特异的methTDM。结果methTDM的调控模式在PE中是复杂的，并且包含放松抑制，增强抑制，放松激活，增强激活，反向激活和反向抑制。从全球methTDM网络中提取了一个核心模块，以进一步描述PE中methTDM的机制。在PE中还分析了任何两种调节模式的共同特征和特定特征。在PE中鉴定出一些关键的甲基化位点，TF和诸如IL2RG的基因。功能分析表明，methTDM与免疫，胰岛素和NK细胞相关功能有关。毒品相关网络确定了一些关键的药物替代用途，例如NADH。结论集体研究强调了甲基化对PE转录过程的影响。MethTDM可以帮助确定PE的特定生物标志物和药物替代用途。在PE中鉴定出一些关键的甲基化位点，TF和诸如IL2RG的基因。功能分析表明，methTDM与免疫，胰岛素和NK细胞相关功能有关。毒品相关网络确定了一些关键的药物替代用途，例如NADH。结论集体研究强调了甲基化对PE转录过程的影响。MethTDM可以帮助确定PE的特定生物标志物和药物替代用途。在PE中鉴定出一些关键的甲基化位点，TF和诸如IL2RG的基因。功能分析表明，methTDM与免疫，胰岛素和NK细胞相关功能有关。毒品相关网络确定了一些关键的药物替代用途，例如NADH。结论集体研究强调了甲基化对PE转录过程的影响。MethTDM可以帮助确定PE的特定生物标志物和药物替代用途。