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多维尺度分析方法可以利用 Hi-C 数据特性重建基因组 DNA 环。

Multidimensional scaling methods can reconstruct genomic DNA loops using Hi-C data properties.

机构信息

Department of Physics, Chuo University, Tokyo, Japan.

出版信息

PLoS One. 2023 Aug 17;18(8):e0289651. doi: 10.1371/journal.pone.0289651. eCollection 2023.

Abstract

This paper proposes multidimensional scaling (MDS) applied to high-throughput chromosome conformation capture (Hi-C) data on genomic interactions to visualize DNA loops. Currently, the mechanisms underlying the regulation of gene expression are poorly understood, and where and when DNA loops are formed remains undetermined. Previous studies have focused on reproducing the entire three-dimensional structure of chromatin; however, identifying DNA loops using these data is time-consuming and difficult. MDS is an unsupervised method for reconstructing the original coordinates from a distance matrix. Here, MDS was applied to high-throughput chromosome conformation capture (Hi-C) data on genomic interactions to visualize DNA loops. Hi-C data were converted to distances by taking the inverse to reproduce loops via MDS, and the missing values were set to zero. Using the converted data, MDS was applied to the log-transformed genomic coordinate distances and this process successfully reproduced the DNA loops in the given structure. Consequently, the reconstructed DNA loops revealed significantly more DNA-transcription factor interactions involved in DNA loop formation than those obtained from previously applied methods. Furthermore, the reconstructed DNA loops were significantly consistent with chromatin immunoprecipitation followed by sequencing (ChIP-seq) peak positions. In conclusion, the proposed method is an improvement over previous methods for identifying DNA loops.

摘要

本文提出了多维尺度分析(MDS)应用于基因组相互作用的高通量染色体构象捕获(Hi-C)数据,以可视化 DNA 环。目前,基因表达调控的机制还了解甚少,DNA 环形成的位置和时间仍不确定。先前的研究集中于复制染色质的整个三维结构;然而,使用这些数据识别 DNA 环既费时又困难。MDS 是一种从距离矩阵重建原始坐标的无监督方法。在这里,MDS 被应用于高通量染色体构象捕获(Hi-C)数据的基因组相互作用,以可视化 DNA 环。通过取倒数将 Hi-C 数据转换为距离,通过 MDS 再现环,并将缺失值设置为零。使用转换后的数据,将 MDS 应用于对数转换的基因组坐标距离,并且该过程成功地再现了给定结构中的 DNA 环。因此,重建的 DNA 环显示出比以前应用的方法更多的 DNA-转录因子相互作用参与 DNA 环形成。此外,重建的 DNA 环与染色质免疫沉淀测序(ChIP-seq)峰位置显著一致。总之,该方法优于以前用于识别 DNA 环的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b2/10434948/50664439b240/pone.0289651.g001.jpg

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