小柯机器人

科学家开发出用于解决多重DNA FISH中染色质结构的空间基因组对准器
2023-01-06 14:04

美国加州大学圣迭戈分校任兵研究小组开发出用于解决多重DNA FISH中染色质结构的空间基因组对准器。相关论文于2023年1月2日在线发表在《自然—生物技术》杂志上。

研究人员报告了一个空间基因组对准器,通过将信号与DNA聚合物模型对准,从噪声中解析出真正的染色质信号。通过利用分离成像位点的基因组距离,这个对准器估计了在三维空间中分离聚合物上位点的空间距离。然后,这个对准器评估了观察到的属于这些位点的信号连接的物理概率,从而追踪染色质结构。
 
研究人员证明,这种空间基因组对准器可以有效地从DNA 多重荧光原位杂交(FISH)数据中建立跨尺度的染色体结构模型,并用于预测间期细胞中的染色体倍体。用这种方法重新处理以前的全基因组染色体追踪数据揭示在非同步小鼠胚胎干细胞的S/G2期细胞中,姐妹染色单体的空间聚集,并提供了额外数量染色体的证据,其在成年小鼠皮层的有丝分裂后神经元中保持紧密配对。
 
据悉,多重FISH是一种广泛使用的分析三维基因组组织的方法,但从嘈杂的荧光信号中得出染色体构象具有挑战性,而且追踪染色质并不直接。
 
附:英文原文

Title: A spatial genome aligner for resolving chromatin architectures from multiplexed DNA FISH

Author: Jia, Bojing Blair, Jussila, Adam, Kern, Colin, Zhu, Quan, Ren, Bing

Issue&Volume: 2023-01-02

Abstract: Multiplexed fluorescence in situ hybridization (FISH) is a widely used approach for analyzing three-dimensional genome organization, but it is challenging to derive chromosomal conformations from noisy fluorescence signals, and tracing chromatin is not straightforward. Here we report a spatial genome aligner that parses true chromatin signal from noise by aligning signals to a DNA polymer model. Using genomic distances separating imaged loci, our aligner estimates spatial distances expected to separate loci on a polymer in three-dimensional space. Our aligner then evaluates the physical probability observed signals belonging to these loci are connected, thereby tracing chromatin structures. We demonstrate that this spatial genome aligner can efficiently model chromosome architectures from DNA FISH data across multiple scales and be used to predict chromosome ploidies de novo in interphase cells. Reprocessing of previous whole-genome chromosome tracing data with this method indicates the spatial aggregation of sister chromatids in S/G2 phase cells in asynchronous mouse embryonic stem cells and provides evidence for extranumerary chromosomes that remain tightly paired in postmitotic neurons of the adult mouse cortex.

DOI: 10.1038/s41587-022-01568-9

Source: https://www.nature.com/articles/s41587-022-01568-9

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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