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计算方法探索染色质状态动力学。

Computational methods to explore chromatin state dynamics.

机构信息

Epigenomics Lab, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

Brief Bioinform. 2022 Nov 19;23(6). doi: 10.1093/bib/bbac439.

Abstract

The human genome is marked by several singular and combinatorial histone modifications that shape the different states of chromatin and its three-dimensional organization. Genome-wide mapping of these marks as well as histone variants and open chromatin regions is commonly carried out via profiling DNA-protein binding or via chromatin accessibility methods. After the generation of epigenomic datasets in a cell type, statistical models can be used to annotate the noncoding regions of DNA and infer the combinatorial histone marks or chromatin states (CS). These methods involve partitioning the genome and labeling individual segments based on their CS patterns. Chromatin labels enable the systematic discovery of genomic function and activity and can label the gene body, promoters or enhancers without using other genomic maps. CSs are dynamic and change under different cell conditions, such as in normal, preneoplastic or tumor cells. This review aims to explore the available computational tools that have been developed to capture CS alterations under two or more cellular conditions.

摘要

人类基因组被几种独特的组合组蛋白修饰所标记,这些修饰塑造了染色质的不同状态及其三维结构。这些标记以及组蛋白变体和开放染色质区域的全基因组图谱绘制通常通过 DNA-蛋白质结合的分析或通过染色质可及性方法来进行。在对某一细胞类型的表观基因组数据集进行生成后,可以使用统计模型来注释 DNA 的非编码区域,并推断组合组蛋白标记或染色质状态(CS)。这些方法涉及对基因组进行分区,并根据其 CS 模式对各个片段进行标记。染色质标签可以实现基因组功能和活性的系统发现,并可以在不使用其他基因组图谱的情况下标记基因体、启动子或增强子。CS 是动态的,会在不同的细胞条件下发生变化,例如在正常、癌前或肿瘤细胞中。本综述旨在探讨已经开发的用于捕获两种或更多种细胞条件下 CS 变化的可用计算工具。

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