Yang Yu, Hang Jun
Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
J Biomol Tech. 2013 Jul;24(2):98-103. doi: 10.7171/jbt.13-2402-005.
An unconventional approach for DNA fragmentation was investigated to explore its feasibility as an alternative to the existing DNA fragmentation techniques for next-generation DNA sequencing application. Current methods are based on strong-force liquid shearing or specialized enzymatic treatments. There are shortcomings for these platforms yet to be addressed, including aerosolization of genomic materials, which may result in the cross-contamination and biohazards; the difficulty in multiplexing; and the potential sequence biases. In this proof-of-concept study, we investigated the microwave irradiation as a simple, unbiased, and easy-to-multiplex way to fragment genomic DNA randomly. In addition, heating DNA at high temperature was attempted for the same purpose and for comparison. Adaptive focused acoustic sonication was used as the control. The yield and functionality for the DNA fragments and DNA fragment libraries were analyzed to assess the feasibility and use of the proposed approach. Both microwave irradiation and thermal heating can fragment genomic DNA to the size ranges suitable for next-generation sequencing (NGS) shotgun library preparation. However, both treatments caused severe reduction in PCR amplification efficiency, which led to low production in emulsion PCR (emPCR). The result was improved by amplification prior to emPCR. Further improvements, such as DNA strand repairing, are needed for the method to be applied practically in NGS.
研究了一种非传统的DNA片段化方法,以探索其作为下一代DNA测序应用中现有DNA片段化技术替代方法的可行性。目前的方法基于强力液体剪切或特殊的酶处理。这些平台存在一些尚未解决的缺点,包括基因组材料的雾化,这可能导致交叉污染和生物危害;多重分析的困难;以及潜在的序列偏差。在这项概念验证研究中,我们研究了微波辐射作为一种简单、无偏差且易于多重分析的方法来随机片段化基因组DNA。此外,为了相同目的并进行比较,尝试了高温加热DNA。自适应聚焦声学超声处理用作对照。分析了DNA片段和DNA片段文库的产量和功能,以评估所提出方法的可行性和实用性。微波辐射和热加热都可以将基因组DNA片段化到适合下一代测序(NGS)鸟枪法文库制备的大小范围。然而,两种处理都导致PCR扩增效率严重降低,从而导致乳液PCR(emPCR)产量低。通过在emPCR之前进行扩增,结果得到了改善。该方法要在NGS中实际应用还需要进一步改进,例如DNA链修复。