Serra François, Baù Davide, Goodstadt Mike, Castillo David, Filion Guillaume J, Marti-Renom Marc A
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Spain.
PLoS Comput Biol. 2017 Jul 19;13(7):e1005665. doi: 10.1371/journal.pcbi.1005665. eCollection 2017 Jul.
The sequence of a genome is insufficient to understand all genomic processes carried out in the cell nucleus. To achieve this, the knowledge of its three-dimensional architecture is necessary. Advances in genomic technologies and the development of new analytical methods, such as Chromosome Conformation Capture (3C) and its derivatives, provide unprecedented insights in the spatial organization of genomes. Here we present TADbit, a computational framework to analyze and model the chromatin fiber in three dimensions. Our package takes as input the sequencing reads of 3C-based experiments and performs the following main tasks: (i) pre-process the reads, (ii) map the reads to a reference genome, (iii) filter and normalize the interaction data, (iv) analyze the resulting interaction matrices, (v) build 3D models of selected genomic domains, and (vi) analyze the resulting models to characterize their structural properties. To illustrate the use of TADbit, we automatically modeled 50 genomic domains from the fly genome revealing differential structural features of the previously defined chromatin colors, establishing a link between the conformation of the genome and the local chromatin composition. TADbit provides three-dimensional models built from 3C-based experiments, which are ready for visualization and for characterizing their relation to gene expression and epigenetic states. TADbit is an open-source Python library available for download from https://github.com/3DGenomes/tadbit.
基因组序列不足以理解细胞核中进行的所有基因组过程。要做到这一点，了解其三维结构是必要的。基因组技术的进步以及新分析方法的发展，如染色体构象捕获（3C）及其衍生技术，为基因组的空间组织提供了前所未有的见解。在这里，我们介绍TADbit，一个用于三维分析和建模染色质纤维的计算框架。我们的软件包以基于3C实验的测序读数作为输入，并执行以下主要任务：（i）预处理读数，（ii）将读数映射到参考基因组，（iii）过滤和标准化相互作用数据，（iv）分析所得的相互作用矩阵，（v）构建选定基因组区域的三维模型，以及（vi）分析所得模型以表征其结构特性。为了说明TADbit的使用，我们自动对果蝇基因组中的50个基因组区域进行了建模，揭示了先前定义的染色质颜色的差异结构特征，建立了基因组构象与局部染色质组成之间的联系。TADbit提供了基于3C实验构建的三维模型，这些模型可用于可视化，并用于表征它们与基因表达和表观遗传状态的关系。TADbit是一个开源的Python库，可从https://github.com/3DGenomes/tadbit下载。
