Centre de Recherches en Cancérologie de Toulouse (CRCT), INSERM U1037, Toulouse 31037, France.
Université Paul Sabatier III, Toulouse 31400, Toulouse, France.
Nucleic Acids Res. 2020 May 7;48(8):4066-4080. doi: 10.1093/nar/gkaa159.
We introduce an R package and a web-based visualization tool for the representation, analysis and integration of epigenomic data in the context of 3D chromatin interaction networks. GARDEN-NET allows for the projection of user-submitted genomic features on pre-loaded chromatin interaction networks, exploiting the functionalities of the ChAseR package to explore the features in combination with chromatin network topology properties. We demonstrate the approach using published epigenomic and chromatin structure datasets in haematopoietic cells, including a collection of gene expression, DNA methylation and histone modifications data in primary healthy myeloid cells from hundreds of individuals. These datasets allow us to test the robustness of chromatin assortativity, which highlights which epigenomic features, alone or in combination, are more strongly associated with 3D genome architecture. We find evidence for genomic regions with specific histone modifications, DNA methylation, and gene expression levels to be forming preferential contacts in 3D nuclear space, to a different extent depending on the cell type and lineage. Finally, we examine replication timing data and find it to be the genomic feature most strongly associated with overall 3D chromatin organization at multiple scales, consistent with previous results from the literature.
我们介绍了一个 R 包和一个基于网络的可视化工具，用于在 3D 染色质相互作用网络的背景下表示、分析和整合表观基因组数据。GARDEN-NET 允许将用户提交的基因组特征投影到预加载的染色质相互作用网络上，利用 ChAseR 包的功能结合染色质网络拓扑性质来探索特征。我们使用发表的造血细胞中的表观基因组和染色质结构数据集来演示该方法，包括数百个个体的原代健康骨髓细胞中的基因表达、DNA 甲基化和组蛋白修饰数据的集合。这些数据集使我们能够测试染色质分类的稳健性，这突出了哪些表观基因组特征（单独或组合）与 3D 基因组结构的关联更强。我们发现证据表明，具有特定组蛋白修饰、DNA 甲基化和基因表达水平的基因组区域在 3D 核空间中形成优先接触，其程度因细胞类型和谱系而异。最后，我们检查复制时间数据，发现它与多个尺度的整体 3D 染色质组织之间的关联最强，这与文献中的先前结果一致。
