4Cin: A computational pipeline for 3D genome modeling and virtual Hi-C analyses from 4C data.
4Cin: A computational pipeline for 3D genome modeling and virtual Hi-C analyses from 4C data.
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DOI：
10.1371/journal.pcbi.1006030
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发表时间：
2018-03
影响因子：
4.3
通讯作者：
Devos DP
中科院分区：
文献类型：
--
作者：
Irastorza-Azcarate I;Acemel RD;Tena JJ;Maeso I;Gómez-Skarmeta JL;Devos DP
基于3C的方法的使用揭示了染色质的3D组织对于基因组生物学的关键方面的重要性。然而，3C技术的不同变体的不同警告限制了它们的范围和可以从这些方法中受益的科学领域的范围。为了解决这些限制，我们提出了4Cin，一种基于4C-seq或任何类型的4C-seq-like数据（例如来自NG Capture-C的数据）生成3D模型并导出基因组位点的虚拟Hi-C（vHi-C）热图的方法。3D基因组组织是通过综合考虑来自少至四个4C-seq实验的空间距离来确定的。从4C-seq数据获得的3D模型及其相关的vHi-C图谱允许推断给定基因组区域内的所有染色体接触，从而促进拓扑关联结构域（Topological Associating Domains，简称SNP）边界的识别。因此，4Cin提供了一个更便宜，方便和通用的替代其他可用的技术，同时提供了一个全面的3D拓扑分析。通过研究与疾病表型相关的基因组结构变体的突变修饰，并以定量的方式进行3D染色质结构的跨物种进化比较，我们证明了我们的方法的广泛潜力和新的应用范围。染色质构象捕获（3C）方法已经揭示了染色质的3D组织的重要性，这是理解基因组生物学许多方面的关键。但这些方法都有各自的局限性。在这里，我们介绍了4Cin，一种从少量4C-seq实验中生成染色质3D模型的软件，这是一种基于3C的方法，可以提供一个片段与基因组之间的接触频率（一个与所有）。这些3D模型用于推断给定基因组区域内的所有染色体接触（许多对许多）。接触图有助于识别拓扑关联域边界。我们的软件提供了一个更便宜，方便和通用的替代其他可用的技术，同时提供了一个全面的三维拓扑分析。我们将我们的软件应用于两个不同的基因座，以研究与疾病表型相关的基因组结构变异的修饰，并以定量的方式比较两个不同物种的染色质组织。
The use of 3C-based methods has revealed the importance of the 3D organization of the chromatin for key aspects of genome biology. However, the different caveats of the variants of 3C techniques have limited their scope and the range of scientific fields that could benefit from these approaches. To address these limitations, we present 4Cin, a method to generate 3D models and derive virtual Hi-C (vHi-C) heat maps of genomic loci based on 4C-seq or any kind of 4C-seq-like data, such as those derived from NG Capture-C. 3D genome organization is determined by integrative consideration of the spatial distances derived from as few as four 4C-seq experiments. The 3D models obtained from 4C-seq data, together with their associated vHi-C maps, allow the inference of all chromosomal contacts within a given genomic region, facilitating the identification of Topological Associating Domains (TAD) boundaries. Thus, 4Cin offers a much cheaper, accessible and versatile alternative to other available techniques while providing a comprehensive 3D topological profiling. By studying TAD modifications in genomic structural variants associated to disease phenotypes and performing cross-species evolutionary comparisons of 3D chromatin structures in a quantitative manner, we demonstrate the broad potential and novel range of applications of our method. Chromatin conformation capture (3C) methods have revealed the importance of the 3D organization of the chromatin, which is key to understand many aspects of genome biology. But each of these methods have their own limitations. Here we present 4Cin, a software that generates 3D models of the chromatin from a small number of 4C-seq experiments, a 3C-based method that provides the frequency of contacts between one fragments and the genome (one vs all). These 3D models are used to infer all chromosomal contacts within a given genomic region (many vs many). The contact maps facilitate the identification of Topological Associating Domains boundaries. Our software offers a much cheaper, accessible and versatile alternative to other available techniques while providing a comprehensive 3D topological profiling. We applied our software to two different loci to study modifications in genomic structural variants associated to disease phenotypes and to compare the chromatin organization in two different species in a quantitative manner.
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通讯作者：
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