A mostly traditional approach improves alignment of bisulfite-converted DNA.

A mostly traditional approach improves alignment of bisulfite-converted DNA.
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DOI:
10.1093/nar/gks275
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发表时间:
2012-07
影响因子:
14.9
通讯作者:
Asai K
Asai K
中科院分区:
生物学2区
文献类型:
--
作者:
Frith MC;Mori R;Asai K

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基因组DNA中的胞苷有时会被甲基化。这会影响许多生物过程和疾病。测量甲基化的标准方法是使用亚硫酸氢盐,它将未甲基化的胞嘧啶转化为胸腺嘧啶,然后对DNA进行测序,并将其与参考基因组序列进行比较。我们描述了一种用于将DNA读数与正确的基因组位置进行比对的关键步骤的方法。我们的方法建立在经典的比对技术,包括似然比分数和间隔种子。在一个现实的基准,我们的方法有一个更好的组合的灵敏度,特异性和速度比其他九个高通量亚硫酸氢盐校准。该研究使DNA甲基化的分析更加准确和合理。它还说明了如何适应通用的比对方法与扭曲的基础模式的特殊情况下:这应该是其他特殊情况下,如古代DNA和AT丰富的基因组信息。
Cytosines in genomic DNA are sometimes methylated. This affects many biological processes and diseases. The standard way of measuring methylation is to use bisulfite, which converts unmethylated cytosines to thymines, then sequence the DNA and compare it to a reference genome sequence. We describe a method for the critical step of aligning the DNA reads to the correct genomic locations. Our method builds on classic alignment techniques, including likelihood-ratio scores and spaced seeds. In a realistic benchmark, our method has a better combination of sensitivity, specificity and speed than nine other high-throughput bisulfite aligners. This study enables more accurate and rational analysis of DNA methylation. It also illustrates how to adapt general-purpose alignment methods to a special case with distorted base patterns: this should be informative for other special cases such as ancient DNA and AT-rich genomes.
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