Mapping short DNA sequencing reads and calling variants using mapping quality scores
Mapping short DNA sequencing reads and calling variants using mapping quality scores
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DOI：
10.1101/gr.078212.108
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发表时间：
2008-11-01
期刊：
影响因子：
7
通讯作者：
Durbin, Richard
中科院分区：
文献类型：
--
作者：
Li, Heng;Ruan, Jue;Durbin, Richard
新的测序技术预示着DNA序列使用的新纪元。然而，其中一些技术产生的读数非常短，通常只有几十个碱基对，为了有效地使用这些读数，需要新的算法和软件。特别是，在有效地将短读数与参考基因组进行比对以及处理这种比对中的歧义或缺乏准确性方面存在一个主要问题。在这里，我们引入映射质量的概念，这是一种衡量读取器实际来自映射算法所对齐的位置的置信度的度量。我们描述了软件MAQ，它可以通过将鸟枪短读数映射到参考基因组来构建组件，使用质量分数来推导例如来自人类样本的二倍体基因组的共识序列的基因型调用。MAQ充分利用配对信息，并估计每次读取对齐的错误概率。还使用结合了作图质量、来自原始序列质量分数的错误概率、两个单倍型的采样以及站点相关错误的经验模型的贝叶斯统计模型来推导最终的基因呼叫的错误概率。在模拟数据和真实数据的基础上，对读取作图和基因调用进行了评估。MAQ是准确的、高效的、通用的和用户友好的。它可以在http://maq.上免费获得SourceForge。NET。
New sequencing technologies promise a new era in the use of DNA sequence. However, some of these technologies produce very short reads, typically of a few tens of base pairs, and to use these reads effectively requires new algorithms and software. In particular, there is a major issue in efficiently aligning short reads to a reference genome and handling ambiguity or lack of accuracy in this alignment. Here we introduce the concept of mapping quality, a measure of the confidence that a read actually comes from the position it is aligned to by the mapping algorithm. We describe the software MAQ that can build assemblies by mapping shotgun short reads to a reference genome, using quality scores to derive genotype calls of the consensus sequence of a diploid genome, e. g., from a human sample. MAQ makes full use of mate-pair information and estimates the error probability of each read alignment. Error probabilities are also derived for the final genotype calls, using a Bayesian statistical model that incorporates the mapping qualities, error probabilities from the raw sequence quality scores, sampling of the two haplotypes, and an empirical model for correlated errors at a site. Both read mapping and genotype calling are evaluated on simulated data and real data. MAQ is accurate, efficient, versatile, and user-friendly. It is freely available at http://maq. sourceforge. net.