Does multi-way, long-range chromatin contact data advance 3D genome reconstruction?

Does multi-way, long-range chromatin contact data advance 3D genome reconstruction?
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DOI:
10.1186/s12859-023-05170-x
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发表时间:
2023-02-24
期刊:
影响因子:
3
通讯作者:
--
中科院分区:
生物学4区
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用于从提供严格成对相互作用的构象捕获分析推断染色质的三维(3D)构型的方法,特别是Hi-C,使用伴随的接触矩阵作为输入。最近的分析,特别是通过标记扩展的交互的拆分池识别(SPRITE),捕获了多路交互,而不仅仅是成对的接触。除了异常高阶染色质相互作用的例子外,这些分析产生的接触比Hi-C跨越了明显更大的基因组距离。这些属性预计将对3D基因组重建产生影响,这是一项尚未利用多路接触数据进行的任务。然而,使用基于距离的重建技术执行这样的3D重建需要将多路接触帧化为(成对的)距离。比较这样做的方法,并评估远程和多途径接触的结果影响,是本研究的目标。我们通过多维缩放获得了在不同加权方案下的3D重建,用于将Sprite多路接触映射到成对距离。在Procrstes配准后比较结果构型,并评估相关Procrstes均方根误差与关键特征(如多路和/或远程接触的程度)之间的关系。我们发现,这些特征对3D重建的影响令人惊讶地有限,我们将这一发现归因于它们的影响被成对接触的优势所削弱。使用Sprite多向接触数据的基于距离的3D基因组重建不会受到用于将多向交互转换为成对距离的加权方案的明显影响。
Methods for inferring the three-dimensional (3D) configuration of chromatin from conformation capture assays that provide strictly pairwise interactions, notably Hi-C, utilize the attendant contact matrix as input. More recent assays, in particular split-pool recognition of interactions by tag extension (SPRITE), capture multi-way interactions instead of solely pairwise contacts. These assays yield contacts that straddle appreciably greater genomic distances than Hi-C, in addition to instances of exceptionally high-order chromatin interaction. Such attributes are anticipated to be consequential with respect to 3D genome reconstruction, a task yet to be undertaken with multi-way contact data. However, performing such 3D reconstruction using distance-based reconstruction techniques requires framing multi-way contacts as (pairwise) distances. Comparing approaches for so doing, and assessing the resultant impact of long-range and multi-way contacts, are the objectives of this study. We obtained 3D reconstructions via multi-dimensional scaling under a variety of weighting schemes for mapping SPRITE multi-way contacts to pairwise distances. Resultant configurations were compared following Procrustes alignment and relationships were assessed between associated Procrustes root mean square errors and key features such as the extent of multi-way and/or long-range contacts. We found that these features had surprisingly limited influence on 3D reconstruction, a finding we attribute to their influence being diminished by the preponderance of pairwise contacts. Distance-based 3D genome reconstruction using SPRITE multi-way contact data is not appreciably affected by the weighting scheme used to convert multi-way interactions to pairwise distances.
染色体接触图的标准化。
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