Inverted duplicate DNA sequences increase translocation rates through sequencing nanopores resulting in reduced base calling accuracy
Inverted duplicate DNA sequences increase translocation rates through sequencing nanopores resulting in reduced base calling accuracy
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DOI：
10.1093/nar/gkaa206
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发表时间：
2020-05-21
影响因子：
14.9
通讯作者：
Gresham, David
中科院分区：
文献类型：
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作者：
Spealman, Pieter;Burrell, Jaden;Gresham, David
反向重复DNA序列是结构变异(SVS)和拷贝数变异(CNV)的共同特征。使用纳米孔测序对包含反向复制DNA序列的CNV进行分析，发现了反复出现的异常行为，其特征是低置信度、错误和错过碱基调用。在酵母和人类样本中都观察到反向复制DNA序列在纳米孔检测到的电流有系统性的升高，移位率增加和取样率降低。反向重复DNA序列的重合显著降低了测序准确率，而易位率增加，这表明二级DNA结构可能会干扰DNA通过纳米孔的运输动力学。
Inverted duplicated DNA sequences are a common feature of structural variants (SVs) and copy number variants (CNVs). Analysis of CNVs containing inverted duplicated DNA sequences using nanopore sequencing identified recurrent aberrant behavior characterized by low confidence, incorrect and missed base calls. Inverted duplicate DNA sequences in both yeast and human samples were observed to have systematic elevation in the electrical current detected at the nanopore, increased translocation rates and decreased sampling rates. The coincidence of inverted duplicated DNA sequences with dramatically reduced sequencing accuracy and an increased translocation rate suggests that secondary DNA structures may interfere with the dynamics of transit of the DNA through the nanopore.