Paulsen Jonas, Sekelja Monika, Oldenburg Anja R, Barateau Alice, Briand Nolwenn, Delbarre Erwan, Shah Akshay, Sørensen Anita L, Vigouroux Corinne, Buendia Brigitte, Collas Philippe
Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Institut BFA, Université Paris 7-CNRS, Paris, France.
Genome Biol. 2017 Jan 30;18(1):21. doi: 10.1186/s13059-016-1146-2.
Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. Chrom3D reveals unexpected spatial features of LAD regulation in cells from patients with a laminopathy-causing lamin mutation. Chrom3D is freely available on github.
当前的三维(3D)基因组建模平台受到限制,因为它们无法考虑基因座在细胞核中的径向位置。我们展示了Chrom3D,这是一个用户友好的全基因组3D计算建模框架,可模拟拓扑相关结构域(TAD)相对于彼此以及相对于核周的位置。Chrom3D整合了染色体构象捕获(Hi-C)和层粘连蛋白相关结构域(LAD)数据集,以生成能够概括在单细胞中检测到的TAD径向分布的结构集合。Chrom3D揭示了患有导致核纤层病的核纤层蛋白突变的患者细胞中LAD调控的意外空间特征。Chrom3D可在github上免费获取。