Simultaneous diagnosis of tuberculous pleurisy and malignant pleural effusion using metagenomic next-generation sequencing (mNGS)

Journal of Translational Medicine

Research

Xuejing Chen¹  Xuya Xing¹  Zichen Liu¹  Nanying Che¹  Nana Zhang¹  Kun Li¹  Chen Zhang¹  Fudong Xu¹  Junhua Pan²  Qingfeng Wang³  Yutong Ma⁴  Yaqiong Jia⁴  Qiuxiang Ou⁴ 

[1] Department of Pathology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 9 Beiguan Street, Tongzhou District, 101149, Beijing, China;Department of Science and Technology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 9 Beiguan Street, Tongzhou District, 101149, Beijing, China;Department of Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China;Research & Development, Dinfectome Inc., Nanjing, Jiangsu, China;

关键词: Tuberculous pleurisy;    Pleural effusion;    Malignant neoplasm;    mNGS;    Copy number variant;   

DOI  :  10.1186/s12967-023-04492-x

 received in 2023-05-12, accepted in 2023-08-30,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMetagenomic next-generation sequencing (mNGS) has become a powerful tool for pathogen detection, but the value of human sequencing reads generated from it is underestimated.MethodsA total of 138 patients with pleural effusion (PE) were diagnosed with tuberculous pleurisy (TBP, N = 82), malignant pleural effusion (MPE, N = 35), or non-TB infection (N = 21), whose PE samples all underwent mNGS analysis. Clinical TB tests including culture, Acid-Fast Bacillus (AFB) test, Xpert, and T-SPOT, were performed. To utilize mNGS for MPE identification, 25 non-MPE samples (20 TBP and 5 non-TB infection) were randomly selected to set human chromosome copy number baseline and generalized linear modeling was performed using copy number variant (CNV) features of the rest 113 samples (35 MPE and 78 non-MPE).ResultsThe performance of TB detection was compared among five methods. T-SPOT demonstrated the highest sensitivity (61% vs. culture 32%, AFB 12%, Xpert 35%, and mNGS 49%) but with the highest false-positive rate (10%) as well. In contrast, mNGS was able to detect TB-genome in nearly half (40/82) of the PE samples from TBP subgroup, with 100% specificity. To evaluate the performance of using CNV features of the human genome for MPE prediction, we performed the leave-one-out cross-validation (LOOCV) in the subcohort excluding the 25 non-MPE samples for setting copy number standards, which demonstrated 54.1% sensitivity, 80.8% specificity, 71.7% accuracy, and an AUC of 0.851.ConclusionIn summary, we exploited the value of human and non-human sequencing reads generated from mNGS, which showed promising ability in simultaneously detecting TBP and MPE.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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