Detection of allele-specific methylation through a generalized heterogeneous epigenome model.

Detection of allele-specific methylation through a generalized heterogeneous epigenome model.
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DOI:
10.1093/bioinformatics/bts231
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发表时间:
2012-06-15
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
通讯作者:
Ecker JR
Ecker JR
中科院分区:
其他
文献类型:
--
作者:
Peng Q;Ecker JR

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动机:高通量测序使得以单碱基分辨率对整个基因组的 DNA 甲基化进行测序成为可能。然而,样品可能包含许多不同的甲基化模式。例如,不同类型和不同发育阶段的细胞可能具有不同的甲基化模式。等位基因可能存在差异甲基化,这可能部分解释了单细胞类型的大部分表观基因组部分甲基化,并且可能对转录输出产生重大影响。依靠 DNA 序列多态性从异质表观基因组混合物中识别个体模式的方法是不够的,因为甲基胞嘧啶的出现密度比 SNP 高得多。结果:我们开发了一种基于混合模型的方法,用于从异质样本中解析不同的表观基因组。特别是,该模型应用于等位基因特异性甲基化(ASM)的检测。该方法在合成甲基化组上进行测试,并应用于拟南芥单根细胞甲基化组。联系方式:qpeng@cs.ucsd.edu
Motivations: High-throughput sequencing has made it possible to sequence DNA methylation of a whole genome at the single-base resolution. A sample, however, may contain a number of distinct methylation patterns. For instance, cells of different types and in different developmental stages may have different methylation patterns. Alleles may be differentially methylated, which may partially explain that the large portions of epigenomes from single cell types are partially methylated, and may have major effects on transcriptional output. Approaches relying on DNA sequence polymorphism to identify individual patterns from a mixture of heterogeneous epigenomes are insufficient as methylcytosines occur at a much higher density than SNPs. Results: We have developed a mixture model-based approach for resolving distinct epigenomes from a heterogeneous sample. In particular, the model is applied to the detection of allele-specific methylation (ASM). The methods are tested on a synthetic methylome and applied to an Arabidopsis single root cell methylome. Contact: qpeng@cs.ucsd.edu
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