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计算方法和下一代测序方法分析表观遗传学数据:方法和应用分析。

Computational methods and next-generation sequencing approaches to analyze epigenetics data: Profiling of methods and applications.

机构信息

Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA.

Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA; Comprehensive Center for Healthy Aging, University of Alabama Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294, USA; Comprehensive Cancer Center, University of Alabama Birmingham, 1802 6th Avenue South, Birmingham, AL 35294, USA; Nutrition Obesity Research Center, University of Alabama Birmingham, 1675 University Boulevard, Birmingham, AL 35294, USA; Comprehensive Diabetes Center, University of Alabama Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA.

出版信息

Methods. 2021 Mar;187:92-103. doi: 10.1016/j.ymeth.2020.09.008. Epub 2020 Sep 14.

Abstract

Epigenetics is mainly comprised of features that regulate genomic interactions thereby playing a crucial role in a vast array of biological processes. Epigenetic mechanisms such as DNA methylation and histone modifications influence gene expression by modulating the packaging of DNA in the nucleus. A plethora of studies have emphasized the importance of analyzing epigenetics data through genome-wide studies and high-throughput approaches, thereby providing key insights towards epigenetics-based diseases such as cancer. Recent advancements have been made towards translating epigenetics research into a high throughput approach such as genome-scale profiling. Amongst all, bioinformatics plays a pivotal role in achieving epigenetics-related computational studies. Despite significant advancements towards epigenomic profiling, it is challenging to understand how various epigenetic modifications such as chromatin modifications and DNA methylation regulate gene expression. Next-generation sequencing (NGS) provides accurate and parallel sequencing thereby allowing researchers to comprehend epigenomic profiling. In this review, we summarize different computational methods such as machine learning and other bioinformatics tools, publicly available databases and resources to identify key modifications associated with epigenetic machinery. Additionally, the review also focuses on understanding recent methodologies related to epigenome profiling using NGS methods ranging from library preparation, different sequencing platforms and analytical techniques to evaluate various epigenetic modifications such as DNA methylation and histone modifications. We also provide detailed information on bioinformatics tools and computational strategies responsible for analyzing large scale data in epigenetics.

摘要

表观遗传学主要由调节基因组相互作用的特征组成,因此在广泛的生物学过程中起着至关重要的作用。表观遗传机制,如 DNA 甲基化和组蛋白修饰,通过调节 DNA 在核内的包装来影响基因表达。大量研究强调了通过全基因组研究和高通量方法分析表观遗传学数据的重要性,从而为癌症等基于表观遗传学的疾病提供了关键的见解。最近的进展已经朝着将表观遗传学研究转化为高通量方法,如基因组规模分析,取得了进展。在所有这些方法中,生物信息学在实现与表观遗传学相关的计算研究方面起着关键作用。尽管在表观基因组分析方面取得了重大进展,但理解各种表观遗传修饰(如染色质修饰和 DNA 甲基化)如何调节基因表达仍然具有挑战性。下一代测序(NGS)提供了准确和并行的测序,从而使研究人员能够理解表观基因组分析。在这篇综述中,我们总结了不同的计算方法,如机器学习和其他生物信息学工具、公开可用的数据库和资源,以识别与表观遗传机制相关的关键修饰。此外,本综述还侧重于了解使用 NGS 方法进行的与表观基因组分析相关的最新方法学,范围从文库制备、不同的测序平台和分析技术到评估各种表观遗传修饰,如 DNA 甲基化和组蛋白修饰。我们还提供了关于负责分析表观遗传学中大规模数据的生物信息学工具和计算策略的详细信息。

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