CpG methylation signature defines human temporal lobe epilepsy and predicts drug-resistant.
CpG methylation signature defines human temporal lobe epilepsy and predicts drug-resistant.
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CpG 甲基化特征定义人类颞叶癫痫并预测耐药性
DOI：
10.1111/cns.13394
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发表时间：
2020-10
影响因子：
5.5
通讯作者：
Long L
中科院分区：
文献类型：
--
作者：
Xiao W;Liu C;Zhong K;Ning S;Hou R;Deng N;Xu Y;Luo Z;Fu Y;Zeng Y;Xiao B;Long H;Long L
颞叶癫痫（TLE）是成人中最常见的局灶性癫痫综合征，并且经常产生耐药性。研究调查了外周 DNA 甲基化特征作为诊断或预后分子生物标志物的价值。我们的目的是探索用于 TLE 诊断和耐药性预测的甲基化生物标志物。我们首先对 TLE 患者进行全基因组 DNA 甲基化分析，然后在训练队列中选择候选 CpG，并通过使用机器学习算法在另一个独立队列中进行验证。此外，还生成了包含 DNA 甲基化和临床病理数据的列线图，以预测整个患者队列中的药物反应。最后，使用 Ingenuity Pathway Analysis 对 CpG 相关基因进行生物信息学分析。经过筛选和验证，确定了 8 个 CpG 作为诊断生物标志物，曲线下面积 (AUC) 为 0.81，6 个 CpG 作为耐药预测生物标志物，AUC 为 0.79。耐药预测列线图包括甲基化风险评分、病程、癫痫发作频率和海马硬化，AUC高达0.96。生物信息学分析表明药物反应相关的CpGs对应基因与DNA甲基化密切相关。这项研究证明了使用外周 DNA 甲基化特征作为癫痫诊断和耐药预测的分子生物标志物的能力。
Temporal lobe epilepsy (TLE) is the most common focal epilepsy syndrome in adults and frequently develops drug resistance. Studies have investigated the value of peripheral DNA methylation signature as molecular biomarker for diagnosis or prognosis. We aimed to explore methylation biomarkers for TLE diagnosis and pharmacoresistance prediction. We initially conducted genome‐wide DNA methylation profiling in TLE patients, and then selected candidate CpGs in training cohort and validated in another independent cohort by employing machine learning algorithms. Furthermore, nomogram comprising DNA methylation and clinicopathological data was generated to predict the drug response in the entire patient cohort. Lastly, bioinformatics analysis for CpG‐associated genes was performed using Ingenuity Pathway Analysis. After screening and validation, eight CpGs were identified for diagnostic biomarker with an area under the curve (AUC) of 0.81 and six CpGs for drug‐resistant prediction biomarker with an AUC of 0.79. The nomogram for drug‐resistant prediction comprised methylation risk score, disease course, seizure frequency, and hippocampal sclerosis, with AUC as high as 0.96. Bioinformatics analysis indicated drug response–related CpGs corresponding genes closely related to DNA methylation. This study demonstrates the ability to use peripheral DNA methylation signature as molecular biomarker for epilepsy diagnosis and drug‐resistant prediction.
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影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
2.2
作者：
Belhedi, N.;Perroud, N.;Salzmann, A.
通讯作者：
Salzmann, A.
影响因子：
24.5
作者：
Church TR;Wandell M;Lofton-Day C;Mongin SJ;Burger M;Payne SR;Castaños-Vélez E;Blumenstein BA;Rösch T;Osborn N;Snover D;Day RW;Ransohoff DF;PRESEPT Clinical Study Steering Committee, Investigators and Study Team
通讯作者：
PRESEPT Clinical Study Steering Committee, Investigators and Study Team
影响因子：
2.6
作者：
Huang, Lisu;Li, Shi;Li, Ling
通讯作者：
Li, Ling
影响因子：
78.8
作者：
Koch, Alexander;Joosten, Sophie C.;van Engeland, Manon
通讯作者：
van Engeland, Manon