Lainscsek Xenia, Taher Leila
Institute of Biomedical Informatics, Graz University of Technology, Austria.
Brief Bioinform. 2023 Jul 20;24(4). doi: 10.1093/bib/bbad198.
Three-dimensional (3D) genome architecture is characterized by multi-scale patterns and plays an essential role in gene regulation. Chromatin conformation capturing experiments have revealed many properties underlying 3D genome architecture, such as the compartmentalization of chromatin based on transcriptional states. However, they are complex, costly and time consuming, and therefore only a limited number of cell types have been examined using these techniques. Increasing effort is being directed towards deriving computational methods that can predict chromatin conformation and associated structures. Here we present DNA-delay differential analysis (DDA), a purely sequence-based method based on chaos theory to predict genome-wide A and B compartments. We show that DNA-DDA models derived from a 20 Mb sequence are sufficient to predict genome wide compartmentalization at the scale of 100 kb in four different cell types. Although this is a proof-of-concept study, our method shows promise in elucidating the mechanisms responsible for genome folding as well as modeling the impact of genetic variation on 3D genome architecture and the processes regulated thereby.
三维（3D）基因组结构具有多尺度模式的特征，并且在基因调控中起着至关重要的作用。染色质构象捕获实验揭示了许多构成3D基因组结构基础的特性，例如基于转录状态的染色质区室化。然而，这些实验复杂、成本高且耗时，因此使用这些技术研究的细胞类型数量有限。越来越多的努力致力于开发能够预测染色质构象和相关结构的计算方法。在此，我们提出DNA延迟微分分析（DDA），这是一种基于混沌理论的纯序列方法，用于预测全基因组的A和B区室。我们表明，从20 Mb序列推导得出的DNA-DDA模型足以在四种不同细胞类型中以100 kb的尺度预测全基因组的区室化。尽管这是一项概念验证研究，但我们的方法在阐明负责基因组折叠的机制以及模拟遗传变异对3D基因组结构及其调控过程的影响方面显示出前景。
