Detection of Pulmonary Infectious Pathogens From Lung Biopsy Tissues by Metagenomic Next-Generation Sequencing.
Detection of Pulmonary Infectious Pathogens From Lung Biopsy Tissues by Metagenomic Next-Generation Sequencing.
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DOI：
10.3389/fcimb.2018.00205
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发表时间：
2018
影响因子：
5.7
通讯作者：
Wang H
中科院分区：
文献类型：
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作者：
Li H;Gao H;Meng H;Wang Q;Li S;Chen H;Li Y;Wang H
宏基因组下一代测序（mNGS）是一种基于序列鉴定病原微生物的综合方法。然而，关于mNGS在肺部感染中应用于肺活检组织的报道仍然很少。在这项研究中，我们应用mNGS检测20例肺部疾病患者的肺活检组织中是否存在病原微生物，提示可能存在感染。我们应用了一种新的数据管理方法，用于基于mNGS数据识别病原体物种。我们确定了识别感染性病原体所需的独特读段和相对丰度的阈值。15例患者肺部感染的潜在病原体通过mNGS鉴定。与培养法比较，mNGS法对细菌的敏感性和特异性分别为100.0%（95%CI：31.0-100.0%）和76.5%（95%CI：49.8-92.2%），对真菌的敏感性和特异性分别为57.1%（95%CI：20.2-88.2%）和61.5%（95%CI：32.2-84.9%）。mNGS与培养法相比，阳性预测值（PPV）（细菌42.9%，真菌44.4%）远低于阴性预测值（NPV）（细菌100%，真菌72.7%）。与组织病理学方法比较，mNGS法对真菌和结核分枝杆菌的特异性最高（100.0和94.1%），PPV法特异性最高（100.0和75.0%）。该研究表明，肺活检组织的mNGS可用于检测患者肺部病原体的存在（或不存在），在速度和灵敏度方面具有潜在优势。然而，需要准确的数据管理和mNGS的解释，并应结合临床表现和传统的实验室诊断方法的观察。
Metagenomic next-generation sequencing (mNGS) is a comprehensive approach for sequence-based identification of pathogenic microbes. However, reports on the use of mNGS in pulmonary infection applied to lung biopsy tissues remain scarce. In this study, we applied mNGS to detect the presence of pathogenic microbes in lung biopsy tissues from 20 patients with pulmonary disorders indicating possible infection. We applied a new data management for identifying pathogen species based on mNGS data. We determined the thresholds for the unique reads and relative abundance required to identify the infectious pathogens. Potential pathogens of pulmonary infections in 15 patients were identified by mNGS. The comparison between mNGS and culture method resulted that the sensitivity and specificity were 100.0% (95% CI: 31.0–100.0%) and 76.5% (95% CI: 49.8–92.2%) for bacteria, 57.1% (95% CI: 20.2–88.2%) and 61.5% (95% CI: 32.2–84.9%) for fungi. The positive predictive value (PPV) (42.9% for bacteria, 44.4% for fungi) was much lower than negative predictive value (NPV) (100% for bacteria, 72.7% for fungi) in mNGS vs. culture method. The mNGS showed the highest specificity (100.0 and 94.1%) and PPV (100.0 and 75.0%) in the evaluation of fungi and MTBC respectively, when compared with histopathology method. The study indicated that mNGS of lung biopsy tissues can be used to detect the presence (or absence) of pulmonary pathogens in patients, with potential benefits in speed and sensitivity. However, accurate data management and interpretation of mNGS are required, and should be combined with observations of clinical manifestations and conventional laboratory-based diagnostic methods.