CpG_MPs: identification of CpG methylation patterns of genomic regions from high-throughput bisulfite sequencing data.

CpG_MPs: identification of CpG methylation patterns of genomic regions from high-throughput bisulfite sequencing data.
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CpG_MPs:从高通量亚硫酸氢盐测序数据中识别基因组区域的 CpG 甲基化模式

DOI:
10.1093/nar/gks829
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发表时间:
2013-01-07
影响因子:
14.9
通讯作者:
Zhang Y
Zhang Y
中科院分区:
生物学2区
文献类型:
--
作者:
Su J;Yan H;Wei Y;Liu H;Liu H;Wang F;Lv J;Wu Q;Zhang Y

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高通量亚硫酸氢盐测序广泛用于真核生物中以单碱基分辨率测量胞嘧啶甲基化。它允许与基因表达和染色质结构相关的基因组甲基化模式的系统水平分析。然而,缺乏从亚硫酸氢盐测序中大规模鉴定甲基化模式的方法。我们开发了一个全面的工具,CpG_MPs,从亚硫酸氢盐测序数据的基因组区域的甲基化模式的识别和分析。CpG_MP首先将亚硫酸氢盐测序读数标准化为CpG的甲基化水平。然后在不知道预定义区域的情况下,通过热点延伸算法利用相邻CpG的甲基化状态来识别未甲基化区域和甲基化区域。此外,通过将组合算法与香农熵相结合来鉴定成对或多个样品(细胞或组织)中的保守和差异甲基化区域。CpG_MP在细胞分化期间在五个人类亚硫酸氢盐测序数据中鉴定了大量具有不同甲基化模式的基因组区域。观察到不同的序列特征和显著的细胞特异性甲基化模式。这些潜在的功能区域形成了用于细胞分化过程中DNA甲基化的功能分析的候选区域。CpG_MPs是第一个用户友好的工具,用于从亚硫酸氢盐测序数据中识别基因组区域的甲基化模式,允许进一步研究基因组规模甲基化模式的生物学功能。
High-throughput bisulfite sequencing is widely used to measure cytosine methylation at single-base resolution in eukaryotes. It permits systems-level analysis of genomic methylation patterns associated with gene expression and chromatin structure. However, methods for large-scale identification of methylation patterns from bisulfite sequencing are lacking. We developed a comprehensive tool, CpG_MPs, for identification and analysis of the methylation patterns of genomic regions from bisulfite sequencing data. CpG_MPs first normalizes bisulfite sequencing reads into methylation level of CpGs. Then it identifies unmethylated and methylated regions using the methylation status of neighboring CpGs by hotspot extension algorithm without knowledge of pre-defined regions. Furthermore, the conservatively and differentially methylated regions across paired or multiple samples (cells or tissues) are identified by combining a combinatorial algorithm with Shannon entropy. CpG_MPs identified large amounts of genomic regions with different methylation patterns across five human bisulfite sequencing data during cellular differentiation. Different sequence features and significantly cell-specific methylation patterns were observed. These potentially functional regions form candidate regions for functional analysis of DNA methylation during cellular differentiation. CpG_MPs is the first user-friendly tool for identifying methylation patterns of genomic regions from bisulfite sequencing data, permitting further investigation of the biological functions of genome-scale methylation patterns.
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