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Seeing the forest through the trees: prioritising potentially functional interactions from Hi-C

机译:通过树木看森林:从Hi-C的潜在功能相互作用进行优先级

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Eukaryotic genomes are highly organised within the nucleus of a cell, allowing widely dispersed regulatory elements such as enhancers to interact with gene promoters through physical contacts in three-dimensional space. Recent chromosome conformation capture methodologies such as Hi-C have enabled the analysis of interacting regions of the genome providing a valuable insight into the three-dimensional organisation of the chromatin in the nucleus, including chromosome compartmentalisation and gene expression. Complicating the analysis of Hi-C data, however, is the massive amount of identified interactions, many of which do not directly drive gene function, thus hindering the identification of potentially biologically functional 3D interactions. In this review, we collate and examine the downstream analysis of Hi-C data with particular focus on methods that prioritise potentially functional interactions. We classify three groups of approaches: structural-based discovery methods, e.g. A/B compartments and topologically associated domains, detection of statistically significant chromatin interactions, and the use of epigenomic data integration to narrow down useful interaction information. Careful use of these three approaches is crucial to successfully identifying potentially functional interactions within the genome.
机译:真核基因组高度组织在细胞的细胞核内,允许广泛分散的调节元件,例如增强剂通过三维空间中的物理触点与基因启动子相互作用。最近的染色体构象捕获方法,例如HI-C使得基因组的相互作用区域的分析提供了对细胞核中染色质的三维组织的有价值的洞察,包括染色体分区和基因表达。然而,使HI-C数据的分析复杂化是鉴定的相互作用的大量,其中许多不直接驱动基因函数,从而阻碍了潜在的生物功能3D相互作用的识别。在本次审查中,我们将特别关注优先级功能相互作用的方法,对HI-C数据进行整理和检查高C数据的下游分析。我们分类三组方法:基于结构的发现方法,例如, A / B隔室和拓扑相关结构域,检测统计学上显着的染色质相互作用,以及使用表观谱系数据集成到缩小有用的交互信息。仔细使用这三种方法对于成功识别基因组内的潜在功能性相互作用至关重要。

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