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Profiling genome-wide DNA methylation

机译:分析全基因组DNA甲基化

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DNA methylation is an epigenetic modification that plays an important role in regulating gene expression and therefore a broad range of biological processes and diseases. DNA methylation is tissue-specific, dynamic, sequence-context-dependent and trans-generationally heritable, and these complex patterns of methylation highlight the significance of profiling DNA methylation to answer biological questions. In this review, we surveyed major methylation assays, along with comparisons and biological examples, to provide an overview of DNA methylation profiling techniques. The advances in microarray and sequencing technologies make genome-wide profiling possible at a single-nucleotide or even a single-cell resolution. These profiling approaches vary in many aspects, such as DNA input, resolution, genomic region coverage, and bioinformatics analysis, and selecting a feasible method requires knowledge of these methods. We first introduce the biological background of DNA methylation and its pattern in plants, animals and fungi. We present an overview of major experimental approaches to profiling genome-wide DNA methylation and hydroxymethylation and then extend to the single-cell methylome. To evaluate these methods, we outline their strengths and weaknesses and perform comparisons across the different platforms. Due to the increasing need to compute high-throughput epigenomic data, we interrogate the computational pipeline for bisulfite sequencing data and also discuss the concept of identifying differentially methylated regions (DMRs). This review summarizes the experimental and computational concepts for profiling genome-wide DNA methylation, followed by biological examples. Overall, this review provides researchers useful guidance for the selection of a profiling method suited to specific research questions.
机译:DNA甲基化是一种表观遗传修饰,在调节基因表达以及因此广泛的生物学过程和疾病中起着重要的作用。 DNA甲基化是组织特异性的,动态的,依赖序列背景的且可跨代遗传的,这些复杂的甲基化模式突显了对DNA甲基化进行分析以回答生物学问题的重要性。在这篇综述中,我们调查了主要的甲基化检测方法,以及比较和生物学实例,以概述DNA甲基化分析技术。微阵列和测序技术的进步使得以单核苷酸甚至单细胞分辨率进行全基因组分析成为可能。这些概要分析方法在许多方面都有所不同,例如DNA输入,分辨率,基因组区域覆盖率和生物信息学分析,选择可行的方法需要这些方法的知识。我们首先介绍DNA甲基化的生物学背景及其在植物,动物和真菌中的模式。我们提供了概述全基因组DNA甲基化和羟甲基化,然后扩展到单细胞甲基化的主要实验方法的概述。为了评估这些方法,我们概述了它们的优缺点,并在不同平台上进行了比较。由于对计算高通量表观基因组数据的需求不断增加,我们询问了亚硫酸氢盐测序数据的计算流程,并讨论了识别差异甲基化区域(DMR)的概念。这篇综述总结了用于分析全基因组DNA甲基化的实验和计算概念,随后是生物学实例。总的来说,这篇综述为研究人员选择适合特定研究问题的分析方法提供了有用的指导。

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