mNGS in clinical microbiology laboratories: on the road to maturity

Metagenomic next-generation sequencing (mNGS) is increasingly being applied in clinical laboratories for unbiased culture-independent diagnosis. Whether it can be a next routine pathogen identification tool has become a topic of concern. We review the current implementation of this new technology for infectious disease diagnostics and discuss the feasibility of transforming mNGS into a routine diagnostic test. Since 2008, numerous studies from over 20 countries have revealed the practicality of mNGS in the work-up of undiagnosed infectious diseases. mNGS performs well in identifying rare, novel, difficult-to-detect and coinfected pathogens directly from clinical samples and presents great potential in resistance prediction by sequencing the antibiotic resistance genes, providing new diagnostic evidence that can be used to guide treatment options and improve antibiotic stewardship. Many physicians recognized mNGS as a last resort method to address clinical infection problems. Although several hurdles, such as workflow validation, quality control, method standardisation, and data interpretation, remain before mNGS can be implemented routinely in clinical laboratories, they are temporary and can be overcome by rapidly evolving technologies. With more validated workflows, lower cost and turnaround time, and simplified interpretation criteria, mNGS will be widely accepted in clinical practice. Overall, mNGS is transforming the landscape of clinical microbiology laboratories, and to ensure that it is properly utilised in clinical diagnosis, both physicians and microbiologists should have a thorough understanding of the power and limitations of this method.

宏基因组下一代测序（Metagenomic next-generation sequencing，mNGS）正日益应用于临床实验室，用于无偏倚的非培养依赖型诊断。其能否成为下一代常规病原体鉴定工具，已成为备受关注的议题。本文综述了该项新技术在感染性疾病诊断中的当前应用现状，并探讨了将mNGS发展为常规诊断检测手段的可行性。自2008年以来，全球20余个国家的多项研究已证实，mNGS在未确诊感染性疾病的诊疗评估中具备实用价值。mNGS可直接从临床样本中高效鉴定罕见、新型、难以检测以及合并感染的病原体，且通过测序抗生素耐药基因实现耐药性预测的潜力巨大，可为指导治疗方案选择、优化抗菌药物管理提供全新的诊断依据。诸多临床医师已将mNGS作为解决临床感染难题的最后备选手段。尽管在mNGS实现临床实验室常规应用前，仍存在流程验证、质量控制、方法标准化以及数据解读等诸多瓶颈，但这些障碍均为暂时性问题，可借助快速发展的技术手段加以克服。随着流程验证愈发完善、检测成本与周转时间进一步降低，以及解读标准简化，mNGS将在临床实践中获得广泛认可。总体而言，mNGS正在重塑临床微生物实验室的工作格局；为确保其在临床诊断中得到合理应用，临床医师与微生物检验人员均需全面掌握该技术的优势与局限性。