基于生物信息学的Hi-C研究现状与发展趋势

染色体的空间交互作用被视为影响基因表达调控的重要因素,高通量染色体构象捕获(high-throughput chromosome conformation capture,Hi-C)技术已成为3D基因组学中探索染色体空间交互作用的主要实验手段之一。随着Hi-C样本数据的持续累积以及分析处理流程复杂度的不断提升,基于生物信息学的Hi-C数据分析对探究基因表达的时空调控机制而言,是机遇也是挑战。本文从生物信息学角度,综合阐述了Hi-C的国内外研究现状及发展动态,包括数据标准化、多级结构分析、数据可视化以及三维建模,重点剖析了多级结构中的A/B区室(A/B compartments)、拓扑相关域(topological associated domains,TADs)和染色质环(chromain looping),在此基础上分析了该方向未来可能的研究热点及发展趋势,以期为将基因表达调控的探索从传统线性空间进一步拓展到三维结构空间提供支持。

Current status and future perspectives in bioinformatical analysis of Hi-C data

The spatial interaction of chromosomes is regarded as an important issue affecting the regulation of gene expression,and the high-throughput chromosome conformation capture(Hi-C)technology has become the primary tool to explore the temporal and spatial interactions of chromosomes in three-dimensional genomics.With the continuous accumulation of Hi-C samples and the increasing complexity of pipelines,the bioinformatic analysis of Hi-C data has been considered an opportunity and a challenge for understanding the spatial regulation mechanism of gene expression.In this paper,the current status and development outline of bioinformatic methods for Hi-C data are introduced,including data normalization,multi-level structure analysis,data visualization and 3D modeling,especially of multi-level structure at A/B compartments,topological associated domains(TADs)and chromain looping levels.Based on this,we provide the outlook of future hotspots and trends in this area.Hopefully our insight will be beneficial for the exploration of gene expression 88 Hereditas(Beijing)2020第42卷regulation from the traditional linear model to the 3D mode.