小柯机器人

德国柏林洪堡大学Ana Pombo等研究人员合作发现，全基因组染色质接触的鉴定产生被Hi-C忽略的见解。该研究于2023年6月19日在线发表于国际一流学术期刊《自然—方法学》。

研究人员开发了multiplex-GAM，这是一种更快和更实惠的基因组结构图谱（GAM）版本，也是一种绘制全基因组染色质接触的无连接技术。研究人员使用小鼠胚胎干细胞对multiplex-GAM和Hi-C进行了详细比较。当检查两种方法检测到的最强接触时，研究人员发现其中只有三分之一是共享的。在GAM中具体发现的最强接触往往涉及“活跃”区域，包括许多转录基因和超级增强子，而在Hi-C中，它们更经常包含“非活跃”区域。这个工作表明，活跃的基因组区域参与了广泛的复杂接触，而这些接触目前在基于连接的方法中被低估，并强调了全基因组接触图谱技术正交进展的必要性。

据介绍，测量三维基因组拓扑结构的技术对于研究基因调控、基因组组装和基因组重排分析越来越重要。Hi-C和其他基于连接的方法已经成为常规，但有特定的偏差。

附：英文原文

Title: Multiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C

Author: Beagrie, Robert A., Thieme, Christoph J., Annunziatella, Carlo, Baugher, Catherine, Zhang, Yingnan, Schueler, Markus, Kukalev, Alexander, Kempfer, Rieke, Chiariello, Andrea M., Bianco, Simona, Li, Yichao, Davis, Trenton, Scialdone, Antonio, Welch, Lonnie R., Nicodemi, Mario, Pombo, Ana

Issue&Volume: 2023-06-19

Abstract: Technology for measuring 3D genome topology is increasingly important for studying gene regulation, for genome assembly and for mapping of genome rearrangements. Hi-C and other ligation-based methods have become routine but have specific biases. Here, we develop multiplex-GAM, a faster and more affordable version of genome architecture mapping (GAM), a ligation-free technique that maps chromatin contacts genome-wide. We perform a detailed comparison of multiplex-GAM and Hi-C using mouse embryonic stem cells. When examining the strongest contacts detected by either method, we find that only one-third of these are shared. The strongest contacts specifically found in GAM often involve ‘active’ regions, including many transcribed genes and super-enhancers, whereas in Hi-C they more often contain ‘inactive’ regions. Our work shows that active genomic regions are involved in extensive complex contacts that are currently underestimated in ligation-based approaches, and highlights the need for orthogonal advances in genome-wide contact mapping technologies.

DOI: 10.1038/s41592-023-01903-1

Source: https://www.nature.com/articles/s41592-023-01903-1

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex