Dali Rola, Blanchette Mathieu
School of Computer Science and McGill Centre for Bioinformatics, McGill University, Montreal, Canada.
Nucleic Acids Res. 2017 Apr 7;45(6):2994-3005. doi: 10.1093/nar/gkx145.
Topologically associating domains (TADs) have been proposed to be the basic unit of chromosome folding and have been shown to play key roles in genome organization and gene regulation. Several different tools are available for TAD prediction, but their properties have never been thoroughly assessed. In this manuscript, we compare the output of seven different TAD prediction tools on two published Hi-C data sets. TAD predictions varied greatly between tools in number, size distribution and other biological properties. Assessed against a manual annotation of TADs, individual TAD boundary predictions were found to be quite reliable, but their assembly into complete TAD structures was much less so. In addition, many tools were sensitive to sequencing depth and resolution of the interaction frequency matrix. This manuscript provides users and designers of TAD prediction tools with information that will help guide the choice of tools and the interpretation of their predictions.
拓扑相关结构域（TADs）被认为是染色体折叠的基本单位，并已证明在基因组组织和基因调控中起关键作用。有几种不同的工具可用于TAD预测，但其特性从未得到过全面评估。在本论文中，我们比较了七种不同TAD预测工具在两个已发表的Hi-C数据集上的输出结果。不同工具之间的TAD预测在数量、大小分布和其他生物学特性方面差异很大。根据TAD的手动注释进行评估，发现单个TAD边界预测相当可靠，但其组装成完整的TAD结构的可靠性则低得多。此外，许多工具对测序深度和相互作用频率矩阵的分辨率敏感。本论文为TAD预测工具的用户和设计者提供了信息，有助于指导工具的选择及其预测结果的解释。
