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下一代测序技术在生物防御中的应用:生物威胁检测、法医学和临床。

Next-Generation Sequencing for Biodefense: Biothreat Detection, Forensics, and the Clinic.

机构信息

Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD.

出版信息

Clin Chem. 2019 Mar;65(3):383-392. doi: 10.1373/clinchem.2016.266536. Epub 2018 Oct 23.

DOI:10.1373/clinchem.2016.266536
PMID:30352865
Abstract

BACKGROUND

Next-generation sequencing (NGS) is revolutionizing a variety of molecular biology fields including bioforensics, biosurveillance, and infectious disease diagnostics. For pathogen detection, the ability to sequence all nucleic acids in a sample allows near limitless multiplexability, free from a priori knowledge regarding an etiologic agent as is typically required for targeted molecular assays such as real-time PCR. Furthermore, sequencing capabilities can generate in depth genomic information, allowing detailed molecular epidemiological studies and bioforensics analysis, which is critical for source agent identification in a biothreat outbreak. However, lack of analytical specificity, inherent to NGS, presents challenges for regulated applications such as clinical diagnostics and molecular attribution.

CONTENT

Here, we discuss NGS applications in the context of preparedness and biothreat readiness. Specifically, we investigate current and future applications of NGS technologies to affect the fields of biosurveillance, bioforensics, and clinical diagnostics with specific focus on biodefense.

SUMMARY

Overall, there are many advantages to the implementation of NGS for preparedness and readiness against biowarfare agents, from forensics to diagnostics. However, appropriate caveats must be associated with any technology. This includes NGS. While NGS is not the panacea replacing all molecular techniques, it will greatly enhance the ability to detect, characterize, and diagnose biowarfare agents, thus providing an excellent addition to the biodefense toolbox of biosurveillance, bioforensics, and biothreat diagnosis.

摘要

背景

下一代测序(NGS)正在彻底改变包括法医、生物监测和传染病诊断在内的各种分子生物学领域。对于病原体检测,能够对样本中的所有核酸进行测序,可以实现近乎无限的多重检测能力,而无需像实时 PCR 等靶向分子检测那样,事先对病原体有一定的了解。此外,测序能力可以生成深度基因组信息,允许进行详细的分子流行病学研究和法医分析,这对于在生物威胁爆发中确定源头病原体至关重要。然而,NGS 固有的分析特异性缺乏,给临床诊断和分子归因等监管应用带来了挑战。

内容

本文结合备灾和生物威胁应对能力,讨论了 NGS 的应用。具体而言,我们研究了 NGS 技术在生物监测、法医和临床诊断领域的当前和未来应用,特别关注生物防御。

总结

总体而言,NGS 在应对生物战剂的准备和应对方面具有许多优势,从法医到诊断。然而,任何技术都必须有适当的注意事项。这包括 NGS。虽然 NGS 并不是替代所有分子技术的灵丹妙药,但它将极大地增强检测、表征和诊断生物战剂的能力,从而为生物监测、法医和生物威胁诊断的生物防御工具箱提供极好的补充。

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Clin Chem. 2019 Mar;65(3):383-392. doi: 10.1373/clinchem.2016.266536. Epub 2018 Oct 23.
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