CNRS, UPS, MCD, Centre de Biologie Intégrative (CBI), University of Toulouse, 31062, Toulouse, France.
BMC Bioinformatics. 2022 Mar 2;23(1):82. doi: 10.1186/s12859-022-04614-0.
BACKGROUND/AIM: In higher eukaryotes, the three-dimensional (3D) organization of the genome is intimately related to numerous key biological functions including gene expression, DNA repair and DNA replication regulations. Alteration of 3D organization, in particular topologically associating domains (TADs), is detrimental to the organism and can give rise to a broad range of diseases such as cancers.
Here, we propose a versatile regression framework which not only identifies TADs in a fast and accurate manner, but also detects differential TAD borders across conditions for which few methods exist, and predicts 3D genome reorganization after chromosomal rearrangement. Moreover, the framework is biologically meaningful, has an intuitive interpretation and is easy to visualize.
The novel regression ranks among top TAD callers. Moreover, it identifies new features of the genome we called TAD facilitators, and that are enriched with specific transcription factors. It also unveils the importance of cell-type specific transcription factors in establishing novel TAD borders during neuronal differentiation. Lastly, it compares favorably with the state-of-the-art method for predicting rearranged 3D genome.
背景/目的：在高等真核生物中，基因组的三维（3D）组织与包括基因表达、DNA 修复和 DNA 复制调控在内的众多关键生物学功能密切相关。3D 组织的改变，特别是拓扑关联结构域（TAD）的改变，对生物体是有害的，并可能导致广泛的疾病，如癌症。
在这里，我们提出了一个通用的回归框架，该框架不仅能够快速准确地识别 TAD，还能够检测到条件差异的 TAD 边界，而这些条件的方法很少，并且能够预测染色体重排后的 3D 基因组重排。此外，该框架具有生物学意义，具有直观的解释，并且易于可视化。
新的回归方法在 TAD 调用者中名列前茅。此外，它还确定了我们称之为 TAD 促进因子的基因组的新特征，这些特征富含特定的转录因子。它还揭示了在神经元分化过程中，细胞类型特异性转录因子在建立新的 TAD 边界中的重要性。最后，它与预测重排 3D 基因组的最新方法相比具有优势。
