靶向高通量测序技术及其在感染性疾病中的应用价值
Targeted High-Throughput Sequencing Technology and Its Application Value in Infectious Diseases

全球公共卫生领域的重大威胁之一的感染性疾病，是指主要由病原微生物引发所导致的疾病的统称。传统的病原学检测方法如体外高通量测序技术、质谱法、形态学、免疫相关的抗原抗体检测，以及经典的分离培养与鉴定，仍然是诊断感染性疾病广泛应用的重要手段，但已无法满足临床对快速精准诊断和高效对症治疗的需求。病原靶向高通量测序技术(tNGS)针对特定病原微生物的基因序列设计特异性引物，利用超多重PCR建库体系对目标序列进行靶向正向扩增和富集，之后进行靶向高通量测序。与常规感染性疾病检测技术相比，tNGS的创新之处在于实现了广谱精准的病原检测。当前，国内外的研究主要聚焦于tNGS在呼吸道感染病原体诊断方面的应用。然而，tNGS的潜力并不仅限于此，它同样可以被有效地应用于其他类型的系统性感染，例如中枢神经系统感染等。本文综述了近年来国内外关于tNGS在感染性疾病精准诊断应用的进展，以及其在检测效能、优势和局限性方面的讨论，以确保tNGS在临床疾病诊断中能够得到合理应用。
One of the significant global public health threats is infectious diseases, which are essentially disorders mainly triggered by pathogenic microorganisms. Traditional pathogen detection approaches, such as high-throughput sequencing techniques, mass spectrometry, morphology, antigen-antibody detection, and the classic isolation and identification, remain crucial means for diagnosing infectious diseases. Nevertheless, they fail to fulfill the clinical requirements for rapid, precise diagnosis and efficient targeted treatment. The principle of targeted next-generation sequencing (tNGS) for infectious diseases involves combining multiple polymerase chain reaction (PCR) with second-generation sequencing technology. This technology targets specific gene sequences of pathogenic microorganisms by designing specific primers and utilizes a multi-target PCR library construction system to carry out targeted forward amplification and enrichment of the target sequences. In comparison with conventional infectious disease detection technologies, the novelty of tNGS lies in achieving extensive and precise pathogen detection. Currently, research both domestically and internationally is primarily concentrated on the application of tNGS in the diagnosis of respiratory infection pathogens. However, the potential of tNGS is not restricted to this; it can also be effectively applied to other types of systemic infections, like central nervous system infections. This review summarizes the recent advancements of tNGS in the precise diagnosis of infectious diseases at home and abroad, along with discussions on its detection efficiency, advantages, and limitations, to guarantee the rational application of tNGS in clinical disease diagnosis.