CpG methylation signature defines human temporal lobe epilepsy and predicts drug-resistant.

CNS Neuroscience & Therapeutics
Wenbiao XiaoLili Long

Abstract

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 co...Continue Reading

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Citations

Jun 9, 2021·CNS Neuroscience & Therapeutics·Wei ShanQun Wang
Jul 23, 2021·CNS Neuroscience & Therapeutics·Tao-Ran LiRui-Juan Lv
Sep 21, 2021·Epilepsia Open·Daniel Fonseca-BarriendosLuisa Rocha

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Methods Mentioned

BETA
methylation profiling
PCR

Software Mentioned

R
SPSS18
rms
learn
IPA
scikit
minfi R
Mouse Genome Informatics MGI

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