Background Metagenomic next-generation sequencing (mNGS) for pathogen detection is becoming increasingly available as a method to identify pathogens in cases of suspected infection. mNGS analyzes the nucleic acid content of patient samples with high-throughput sequencing technologies to detect and characterize microorganism DNA and/or RNA. This unbiased approach to organism detection enables diagnosis of a broad spectrum of infection types and can identify more potential pathogens than any single conventional test. This can lead to improved ability to diagnose patients, although there remains concern regarding contamination and detection of nonclinically significant organisms. Content We describe the laboratory approach to mNGS testing and highlight multiple considerations that affect diagnostic performance. We also summarize recent literature investigating the diagnostic performance of mNGS assays for a variety of infection types and recommend further studies to evaluate the improvement in clinical outcomes and cost-effectiveness of mNGS testing. Summary The majority of studies demonstrate that mNGS has sensitivity similar to specific PCR assays and will identify more potential pathogens than conventional methods. While many of these additional organism detections correlate with the expected pathogen spectrum based on patient presentations, there are relatively few formal studies demonstrating whether these are true-positive infections and benefits to clinical outcomes. Reduced specificity due to contamination and clinically nonsignificant organism detections remains a major concern, emphasizing the importance of careful interpretation of the organism pathogenicity and potential association with the clinical syndrome. Further research is needed to determine the possible improvement in clinical outcomes and cost-effectiveness of mNGS testing.

中文翻译：

---

宏基因组学和下一代测序在传染病诊断中的作用

背景 用于病原体检测的宏基因组下一代测序 (mNGS) 作为一种在疑似感染病例中识别病原体的方法正变得越来越可用。mNGS 使用高通量测序技术分析患者样本的核酸含量，以检测和表征微生物 DNA 和/或 RNA。这种不偏不倚的生物体检测方法能够诊断广泛的感染类型，并且可以识别出比任何单一常规检测更多的潜在病原体。这可以提高诊断患者的能力，尽管仍然存在对非临床显着微生物的污染和检测的担忧。内容 我们描述了 mNGS 测试的实验室方法，并强调了影响诊断性能的多个考虑因素。我们还总结了最近研究 mNGS 检测对各种感染类型的诊断性能的文献，并建议进一步研究以评估 mNGS 检测的临床结果和成本效益的改善。总结 大多数研究表明，mNGS 具有与特定 PCR 检测相似的灵敏度，并且将比传统方法识别更多的潜在病原体。虽然许多这些额外的微生物检测与基于患者表现的预期病原体谱相关，但很少有正式研究证明这些是否是真阳性感染和对临床结果的益处。由于污染和临床上无意义的微生物检测导致的特异性降低仍然是一个主要问题，强调仔细解释有机体致病性和与临床综合征的潜在关联的重要性。需要进一步的研究来确定 mNGS 测试在临床结果和成本效益方面的可能改进。