Chromosome conformation capture-based methods, especially Hi-C, enable scientists to detect genome-wide chromatin interactions and study the spatial organization of chromatin, which plays important roles in gene expression regulation, DNA replication and repair etc. Thus, developing computational methods to unravel patterns behind the data becomes critical. Existing computational methods focus on intrachromosomal interactions and ignore interchromosomal interactions partly because there is no prior knowledge for interchromosomal interactions and the frequency of interchromosomal interactions is much lower while the search space is much larger. With the development of single-cell technologies, the advent of single-cell Hi-C makes interrogating the spatial structure of chromatin at single-cell resolution possible. It also brings a new type of frequency information, the number of single cells with chromatin interactions between two disjoint chromosome regions. Considering the lack of computational methods on interchromosomal interactions and the unsurprisingly frequent intrachromosomal interactions along the diagonal of a chromatin contact map, we propose a computational method dedicated to analyzing interchromosomal interactions of single-cell Hi-C with this new frequency information. To the best of our knowledge, our proposed tool is the first to identify regions with statistically frequent interchromosomal interactions at single-cell resolution. We demonstrate that the tool utilizing networks and binomial statistical tests can identify interesting structural regions through visualization, comparison and enrichment analysis and it also supports different configurations to provide users with flexibility. It will be a useful tool for analyzing single-cell Hi-C interchromosomal interactions.

中文翻译：

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基于网络的方法在单细胞分辨率下具有统计上频繁的染色体间相互作用的区域

基于染色体构象捕获的方法，尤其是Hi-C，使科学家能够检测全基因组的染色质相互作用并研究染色质的空间组织，这在基因表达调控，DNA复制和修复等方面起着重要作用。因此，开发了计算方法以揭开数据背后的模式变得至关重要。现有的计算方法集中于染色体内相互作用，而忽略了染色体间相互作用，部分原因是没有关于染色体间相互作用的先验知识，并且染色体间相互作用的频率要低得多，而搜索空间要大得多。随着单细胞技术的发展，单细胞Hi-C的问世使得以单细胞分辨率研究染色质的空间结构成为可能。它还带来了一种新型的频率信息，即两个不相交的染色体区域之间具有染色质相互作用的单个细胞的数量。考虑到缺乏关于染色体间相互作用的计算方法以及沿染色质接触图对角线的染色体内相互作用的频率不足为奇的问题，我们提出了一种利用这种新的频率信息分析单细胞Hi-C染色体间相互作用的计算方法。据我们所知，我们提出的工具是第一个以单细胞分辨率鉴定具有统计学上频繁的染色体间相互作用的区域的工具。我们证明了利用网络和二项式统计检验的工具可以通过可视化识别有趣的结构区域，比较和充实分析，它还支持不同的配置，以为用户提供灵活性。这将是分析单细胞Hi-C染色体间相互作用的有用工具。