AntCaller: an accurate variant caller incorporating ancient DNA damage
AntCaller: an accurate variant caller incorporating ancient DNA damage
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AntCaller：结合古代 DNA 损伤的准确变异识别器
DOI：
10.1007/s00438-017-1358-5
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发表时间：
2017-12-01
影响因子：
3.1
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
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作者：
Zhou, Boyan;Wen, Shaoqing;Zhang, Hong
从沉积物、骨骼和牙齿等古代样本中获得的古代DNA是一种重要的遗传资源，可用于重建人类、动物和植物的进化史。高通量测序技术的应用，使古代DNA的研究能够在全基因组尺度上进行。然而，死后DNA损伤主要是由胞嘧啶脱氨为尿嘧啶（或胞嘧啶甲基化为胸腺嘧啶）引起的，这可能会混淆变异召唤和下游分析。在本文中，我们开发了一个Python程序来实现一个新的变体调用器“AntCaller”，它从测序数据中提取核苷酸替换信息，并根据贝叶斯规则计算每种基因型的概率。通过模拟研究和实际数据分析表明，我们的方法降低了核苷酸错配引起的错误发现率，在调用精度方面优于两种主流变体调用器（即GATK和SAMtools）。在DNA严重受损的实际应用中，AntCaller仍然优于GATK和SAMtools结合质量评分召回。
Ancient DNA obtained from ancient samples, such as sediments, bones, and teeth, is an important genetic resource that can be used to reconstruct an evolutional history of humans, animals, and plants. The application of high-throughput sequencing enables the research of ancient DNA to be conducted in a whole genome scale. However, post-mortem DNA damage mainly caused by deamination of cytosine to uracil (or methylated cytosine to thymine) may confound the variant calling and downstream analysis. In this article, we develop a Python program to implement a new variant caller, “AntCaller”, which extracts the information on nucleotide substitutions from sequencing data and calculates the probability of each genotype based on a Bayesian rule. Through both simulation studies and real data analyses, it was shown that our method reduced the false discovery rate caused by nucleotide misincorporations and outperformed two mainstream variant callers (i.e., GATK and SAMtools) in terms of calling accuracy. In a real application with serious DNA damage, AntCaller still outperformed GATK and SAMtools combined with quality score recalling.