National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China.
Nucleic Acids Res. 2013 Nov;41(20):9230-42. doi: 10.1093/nar/gkt712. Epub 2013 Aug 14.
Chromatin modifications have been comprehensively illustrated to play important roles in gene regulation and cell diversity in recent years. Given the rapid accumulation of genome-wide chromatin modification maps across multiple cell types, there is an urgent need for computational methods to analyze multiple maps to reveal combinatorial modification patterns and define functional DNA elements, especially those are specific to cell types or tissues. In this current study, we developed a computational method using differential chromatin modification analysis (dCMA) to identify cell-type-specific genomic regions with distinctive chromatin modifications. We then apply this method to a public data set with modification profiles of nine marks for nine cell types to evaluate its effectiveness. We found cell-type-specific elements unique to each cell type investigated. These unique features show significant cell-type-specific biological relevance and tend to be located within functional regulatory elements. These results demonstrate the power of a differential comparative epigenomic strategy in deciphering the human genome and characterizing cell specificity.
近年来，染色质修饰在基因调控和细胞多样性中发挥重要作用已得到充分说明。鉴于在多种细胞类型中全基因组染色质修饰图谱的快速积累，迫切需要计算方法来分析多个图谱，以揭示组合修饰模式并定义功能 DNA 元件，特别是那些特定于细胞类型或组织的元件。在本研究中，我们开发了一种使用差异染色质修饰分析（dCMA）的计算方法来识别具有独特染色质修饰的细胞类型特异性基因组区域。然后，我们将该方法应用于一个具有九个标记的九个细胞类型修饰谱的公共数据集，以评估其有效性。我们发现了每个研究细胞类型特有的细胞类型特异性元件。这些独特的特征表现出显著的细胞类型特异性生物学相关性，并且往往位于功能调节元件内。这些结果证明了差异比较表观基因组策略在破译人类基因组和表征细胞特异性方面的强大功能。
