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对大块组织中细胞类型特异性差异甲基化分析的系统评估。

A systematic evaluation of cell-type-specific differential methylation analysis in bulk tissue.

作者信息

Li Shuo, Kuan Pei Fen

机构信息

Department of Applied Mathematics and Statistics, Stony Brook University, Nicolls Road, 11794, New York, USA.

出版信息

Brief Bioinform. 2025 Mar 4;26(2). doi: 10.1093/bib/bbaf170.

Abstract

We conducted a systematic assessment of computational models-CellDMC, TCA, HIRE, TOAST, and CeDAR-for detecting cell-type-specific differential methylation CpGs in bulk methylation data profiled using the Illumina DNA Methylation BeadArrays. This assessment was performed through simulations and case studies involving two epigenome-wide association studies (EWAS) on rheumatoid arthritis and major depressive disorder. Our evaluation provided insights into the strengths and limitations of each model. The results revealed that the models varied in performance across different metrics, sample sizes, and computational efficiency. Additionally, we proposed integrating the results from these models using the minimum p-value ($minpv$) and average p-value ($avepv$) approaches. Our findings demonstrated that these aggregation methods significantly improved performance in identifying cell-type-specific differential methylation CpGs.

摘要

我们对计算模型——CellDMC、TCA、HIRE、TOAST和CeDAR——进行了系统评估,以在使用Illumina DNA甲基化微珠芯片分析的总体甲基化数据中检测细胞类型特异性差异甲基化CpG。该评估通过模拟和案例研究进行,这些案例研究涉及两项关于类风湿性关节炎和重度抑郁症的全表观基因组关联研究(EWAS)。我们的评估揭示了每个模型的优势和局限性。结果表明,这些模型在不同指标、样本量和计算效率方面的表现各不相同。此外,我们建议使用最小p值($minpv$)和平均p值($avepv$)方法整合这些模型的结果。我们的研究结果表明,这些汇总方法在识别细胞类型特异性差异甲基化CpG方面显著提高了性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/151c/12001786/5192dc57f61b/bbaf170f1.jpg

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