EpiMix 是一种利用 DNA 甲基化进行表观基因组亚型分型的综合工具。
EpiMix is an integrative tool for epigenomic subtyping using DNA methylation.
发表日期：2023 Jul 24
作者：
Yuanning Zheng, John Jun, Kevin Brennan, Olivier Gevaert
来源：
Epigenetics & Chromatin
摘要：
DNA甲基化（DNAme）是影响基因表达的重要的表观遗传因素，其变异导致癌症、免疫和心血管疾病的发生。最近的技术进步使得我们能够对大规模人类群体中的DNAme进行全基因组的分析。针对这些异质性群体级的数据，需要一种能够更敏感地检测差异性甲基化谱的分析方法。我们开发了一种端到端的分析框架，命名为“EpiMix”，用于DNAme和基因表达的群体级分析。与现有方法相比，EpiMix在检测只存在于少数患者亚集中的异常DNAme方面具有更高的敏感性。我们将EpiMix的基于模型的分析扩展到蛋白编码基因的顺式调控元件、远端增强子以及编码microRNA和长非编码RNA（lncRNA）的基因。利用来自两个独立研究的细胞类型特异性数据，我们发现了儿童食物过敏的表观遗传机制以及非小细胞肺癌中与生存相关的、甲基化驱动的非编码RNA。© 2023 The Author(s).
DNA methylation (DNAme) is a major epigenetic factor influencing gene expression with alterations leading to cancer and immunological and cardiovascular diseases. Recent technological advances have enabled genome-wide profiling of DNAme in large human cohorts. There is a need for analytical methods that can more sensitively detect differential methylation profiles present in subsets of individuals from these heterogeneous, population-level datasets. We developed an end-to-end analytical framework named "EpiMix" for population-level analysis of DNAme and gene expression. Compared with existing methods, EpiMix showed higher sensitivity in detecting abnormal DNAme that was present in only small patient subsets. We extended the model-based analyses of EpiMix to cis-regulatory elements within protein-coding genes, distal enhancers, and genes encoding microRNAs and long non-coding RNAs (lncRNAs). Using cell-type-specific data from two separate studies, we discover epigenetic mechanisms underlying childhood food allergy and survival-associated, methylation-driven ncRNAs in non-small cell lung cancer.© 2023 The Author(s).