CGmapTools improves the precision of heterozygous SNV calls and supports allele-specific methylation detection and visualization in bisulfite-sequencing data
CGmapTools improves the precision of heterozygous SNV calls and supports allele-specific methylation detection and visualization in bisulfite-sequencing data
复制标题
CGmapTools 提高了杂合 SNV 调用的精度，并支持亚硫酸氢盐测序数据中的等位基因特异性甲基化检测和可视化
DOI：
10.1093/bioinformatics/btx595
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发表时间：
2018-02-01
期刊：
影响因子：
5.8
通讯作者：
Ni, Zhongfu
中科院分区：
文献类型：
--
作者：
Guo, Weilong;Zhu, Ping;Ni, Zhongfu
动机：DNA甲基化对植物和动物的基因沉默和印记都很重要。在亚硫酸氢盐测序的最新进展允许检测单核苷酸变异（SNVs）实现高灵敏度，但准确地识别杂合子SNVs从部分C到T转换sequences.Results的仍然具有挑战性：我们设计了两种方法，贝叶斯WC和BinomWC，大大提高了杂合子SNV调用的精度从类似的80%到99%，同时保留可比的召回。通过这些SNV调用，我们提供了等位基因特异性DNA甲基化（ASM）分析和可视化读取上的甲基化状态的功能。将ASM分析应用于先前的数据集，我们发现平均1.5%的研究区域显示等位基因甲基化，这些区域显着富集转座子元件，并且可能被相同的细胞类型共享。动态片段策略用于低覆盖率数据中的DMR分析，并且能够使用公共癌症数据集找到与肿瘤发生相关的关键基因相关的差异甲基化区域（DMR）。最后，我们将40个应用程序集成到软件包CGmapTools中来分析DNA甲基化组。该软件包使用CGmap作为格式接口，并设计了二进制格式以减少文件大小并支持快速数据检索，并可用于上下文，基因，bin，区域和样本分析和可视化。
Motivation: DNA methylation is important for gene silencing and imprinting in both plants and animals. Recent advances in bisulfite sequencing allow detection of single nucleotide variations (SNVs) achieving high sensitivity, but accurately identifying heterozygous SNVs from partially C-to-T converted sequences remains challenging.Results: We designed two methods, BayesWC and BinomWC, that substantially improved the precision of heterozygous SNV calls from similar to 80% to 99% while retaining comparable recalls. With these SNV calls, we provided functions for allele-specific DNA methylation (ASM) analysis and visualizing the methylation status on reads. Applying ASM analysis to a previous dataset, we found that an average of 1.5% of investigated regions showed allelic methylation, which were significantly enriched in transposon elements and likely to be shared by the same cell-type. A dynamic fragment strategy was utilized for DMR analysis in low-coverage data and was able to find differentially methylated regions (DMRs) related to key genes involved in tumorigenesis using a public cancer dataset. Finally, we integrated 40 applications into the software package CGmapTools to analyze DNA methylomes. This package uses CGmap as the format interface, and designs binary formats to reduce the file size and support fast data retrieval, and can be applied for context-wise, genewise, bin-wise, region-wise and sample-wise analyses and visualizations.