Fine mapping chromatin contacts in capture Hi-C data
Fine mapping chromatin contacts in capture Hi-C data
复制标题
DOI：
10.1186/s12864-018-5314-5
复制
发表时间：
2019-01-23
期刊：
影响因子：
4.4
通讯作者：
Wallace, Chris
中科院分区：
文献类型：
--
作者：
Eijsbouts, Christiaan Q.;Burren, Oliver S.;Wallace, Chris
背景Hi-C和捕获Hi-C（CHi-C）用于使用高通量测序绘制细胞核中染色质区域之间的物理接触。分析通常考虑独立于其他对的每个可能的碎片对之间的接触的证据。这可能会产生长时间运行的片段，似乎都与相同的诱饵片段的interest.ResultsWe假设，这些长期运行可能会导致从一个较小的子集的直接接触，并提出了一种新的方法，基于贝叶斯稀疏变量选择方法，试图精细映射这些直接接触。我们的模型在概念上是新颖的，利用CHi-C数据中计数的空间模式。虽然我们在拟合模型时仅使用CHi-C计数数据，但我们表明优先级排列的片段显示出预期真实接触的生物学特性：对于对应于基因启动子的诱饵片段，我们鉴定出具有活性染色质的接触片段和对应于先前定义的增强子-靶网络中发现的边缘的接触;相反，对于基因间诱饵片段，我们鉴定了对应于在该细胞类型中表达的基因的启动子的接触片段。我们表明，长期运行的明显共同接触的片段通常可以解释使用一个子集的直接接触，包括
BackgroundHi-C and capture Hi-C (CHi-C) are used to map physical contacts between chromatin regions in cell nuclei using high-throughput sequencing. Analysis typically proceeds considering the evidence for contacts between each possible pair of fragments independent from other pairs. This can produce long runs of fragments which appear to all make contact with the same baited fragment of interest.ResultsWe hypothesised that these long runs could result from a smaller subset of direct contacts and propose a new method, based on a Bayesian sparse variable selection approach, which attempts to fine map these direct contacts. Our model is conceptually novel, exploiting the spatial pattern of counts in CHi-C data. Although we use only the CHi-C count data in fitting the model, we show that the fragments prioritised display biological properties that would be expected of true contacts: for bait fragments corresponding to gene promoters, we identify contact fragments with active chromatin and contacts that correspond to edges found in previously defined enhancer-target networks; conversely, for intergenic bait fragments, we identify contact fragments corresponding to promoters for genes expressed in that cell type. We show that long runs of apparently co-contacting fragments can typically be explained using a subset of direct contacts consisting of