Distance-based assessment of the localization of functional annotations in 3D genome reconstructions.
Distance-based assessment of the localization of functional annotations in 3D genome reconstructions.
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DOI：
10.1186/1471-2164-15-992
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发表时间：
2014-11-18
期刊：
影响因子：
4.4
通讯作者：
Segal MR
中科院分区：
文献类型：
--
作者：
Capurso D;Segal MR
最近的研究使用Hi-C（染色体构象捕获与下一代测序）的接触数据或三维（3D）基因组重建来评估功能基因组注释在细胞核中的共定位。这些分析基于某个阈值将属于功能注释的数据点对二分为“接近”或“远离”，然后测试“接近”对的富集。我们提出了一种替代方法，避免了数据的二分法，而是直接估计的3D重建内的距离的意义。我们将这种方法应用于恶性疟原虫（疟疾的病原体）和酿酒酵母的3D基因组重建，并将结果与以前的方法进行了比较。我们在恶性疟原虫中发现了着丝粒、端粒、毒力基因和几组发育调控表达的基因的显著3D共定位;在恶性疟原虫中发现了着丝粒和长末端重复序列的显著3D共定位。啤酒。此外，我们测试了实验观察，端粒形成3至7簇恶性疟原虫和S。啤酒。应用亲和传播聚类端粒坐标的3D重建产生了6个端粒集群的生物体。基于距离的评估重复了关键的调查结果，同时避免了数据的二分法（以前产生阈值敏感的结果）。本文的在线版本（doi：10.1186/1471-2164-15-992）包含补充材料，可供授权用户使用。
Recent studies used the contact data or three-dimensional (3D) genome reconstructions from Hi-C (chromosome conformation capture with next-generation sequencing) to assess the co-localization of functional genomic annotations in the nucleus. These analyses dichotomized data point pairs belonging to a functional annotation as “close” or “far” based on some threshold and then tested for enrichment of “close” pairs. We propose an alternative approach that avoids dichotomization of the data and instead directly estimates the significance of distances within the 3D reconstruction. We applied this approach to 3D genome reconstructions for Plasmodium falciparum, the causative agent of malaria, and Saccharomyces cerevisiae and compared the results to previous approaches. We found significant 3D co-localization of centromeres, telomeres, virulence genes, and several sets of genes with developmentally regulated expression in P. falciparum; and significant 3D co-localization of centromeres and long terminal repeats in S. cerevisiae. Additionally, we tested the experimental observation that telomeres form three to seven clusters in P. falciparum and S. cerevisiae. Applying affinity propagation clustering to telomere coordinates in the 3D reconstructions yielded six telomere clusters for both organisms. Distance-based assessment replicated key findings, while avoiding dichotomization of the data (which previously yielded threshold-sensitive results). The online version of this article (doi:10.1186/1471-2164-15-992) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
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DOI：
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