A maximum likelihood algorithm for reconstructing 3D structures of human chromosomes from chromosomal contact data.

A maximum likelihood algorithm for reconstructing 3D structures of human chromosomes from chromosomal contact data.
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DOI:
10.1186/s12864-018-4546-8
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发表时间:
2018-02-23
期刊:
影响因子:
4.4
通讯作者:
Cheng J
Cheng J
中科院分区:
生物学2区
文献类型:
--
作者:
Oluwadare O;Zhang Y;Cheng J

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染色体构象捕获技术,特别是Hi-C技术的发展,使得基因组空间构象的分析和研究成为生物信息学和计算生物学的重要课题。在高通量下一代测序技术的帮助下,Hi-C 技术可以生成全基因组、大规模染色体内和染色体间相互作用数据,能够详细描述基因组内的空间相互作用。这些数据可用于重建染色体的 3D 结构,从而可用于研究 DNA 复制、基因调控、基因组相互作用、基因组折叠和基因组功能。在这里,我们引入了一种称为 3DMax 的最大似然算法,用于根据 Hi-C 数据构建染色体的 3D 结构。 3DMax 采用最大似然方法来推断染色体的 3D 结构,同时自动重新估计用于将相互作用频率 (IF) 转换为距离的转换因子 (α)。我们的结果表明,3DMax 从模拟的 Hi-C 数据集生成的模型比大多数现有方法更好地匹配真实模型。 3DMax 对于结构变化和噪声更加稳健。与真实的 Hi-C 数据集相比,3DMax 构建的染色体模型比大多数方法更适合数据,并且比所有其他方法更快。 3DMax 重建的模型与荧光原位杂交 (FISH) 实验以及有关人类染色体组织(例如染色体区室化)的现有知识一致。 3DMax 是重建 3D 染色体模型的有效方法。结果以及为模拟和真实 Hi-C 数据集生成的模型可在此处获取:http://sysbio.rnet.missouri.edu/bdm_download/3DMax/。源代码可在此处获取:https://github.com/BDM-Lab/3DMax。您可以在此处找到演示如何使用 3DMax 的短视频:https://youtu.be/ehQUFWoHwfo。
The development of chromosomal conformation capture techniques, particularly, the Hi-C technique, has made the analysis and study of the spatial conformation of a genome an important topic in bioinformatics and computational biology. Aided by high-throughput next generation sequencing techniques, the Hi-C technique can generate genome-wide, large-scale intra- and inter-chromosomal interaction data capable of describing in details the spatial interactions within a genome. These data can be used to reconstruct 3D structures of chromosomes that can be used to study DNA replication, gene regulation, genome interaction, genome folding, and genome function. Here, we introduce a maximum likelihood algorithm called 3DMax to construct the 3D structure of a chromosome from Hi-C data. 3DMax employs a maximum likelihood approach to infer the 3D structures of a chromosome, while automatically re-estimating the conversion factor (α) for converting Interaction Frequency (IF) to distance. Our results show that the models generated by 3DMax from a simulated Hi-C dataset match the true models better than most of the existing methods. 3DMax is more robust to structural variability and noise. Compared on a real Hi-C dataset, 3DMax constructs chromosomal models that fit the data better than most methods, and it is faster than all other methods. The models reconstructed by 3DMax were consistent with fluorescent in situ hybridization (FISH) experiments and existing knowledge about the organization of human chromosomes, such as chromosome compartmentalization. 3DMax is an effective approach to reconstructing 3D chromosomal models. The results, and the models generated for the simulated and real Hi-C datasets are available here: http://sysbio.rnet.missouri.edu/bdm_download/3DMax/. The source code is available here: https://github.com/BDM-Lab/3DMax. A short video demonstrating how to use 3DMax can be found here: https://youtu.be/ehQUFWoHwfo.
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