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ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Clinical Microbiology
Volume 14 - 2024 |
doi: 10.3389/fcimb.2024.1398190
This article is part of the Research Topic Targeted metagenomics in pathogen detection View all 10 articles
The value of metagenomic next-generation sequencing with different nucleic acid extracting methods of cell-free DNA or whole-cell DNA in the diagnosis of non-neutropenic pulmonary aspergillosis
Provisionally accepted- 1 Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
- 2 Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
- 3 The Second Affiliated Hospital of Suzhou University, Suzhou, China
- 4 Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Liaoning Province, China
- 5 Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
- 6 Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
- 7 Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
- 8 Department of Respiratory and Critical Medicine, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Liaoning Province, China
- 9 Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing medical university, Nanjing, China
- 10 Department of Research and Development, Hugobiotech Co. Ltd., Beijing, China
- 11 Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Liaoning Province, China
Purpose:Metagenomic next-generation sequencing(mNGS) is a novel molecular diagnostic technique. For nucleic acid extraction methods, both whole-cell DNA (wcDNA) and cell-free DNA (cfDNA) are widely applied with the sample of bronchoalveolar lavage fluid (BALF). We aim to evaluate the clinical value of mNGS with cfDNA and mNGS with wcDNA for the detection of BALF pathogens in non-neutropenic pulmonary aspergillosis.Methods: mNGS with BALF-cfDNA, BALF-wcDNA and conventional microbiological tests (CMTs) were performed in suspected non-neutropenic pulmonary aspergillosis. The diagnostic value of different assays for pulmonary aspergillosis was compared.Results: BALF-mNGS (cfDNA, wcDNA) outperformed CMTs in terms of microorganisms detection. Receiver operating characteristic (ROC) analysis indicated BALF-mNGS (cfDNA, wcDNA) was superior to culture and BALF-GM. Combination diagnosis of either positive for BALF-mNGS (cfDNA, wcDNA) or CMTs is more sensitive than CMTs alone in the diagnosis of pulmonary aspergillosis (BALF-cfDNA+CMTs/BALF-wcDNA+CMTs vs. CMTs : ROC analysis : 0.813 vs.0.66, P=0.0142/0.796 vs.0.66, P=0.0244; Sensitivity : 89.47% vs. 47.37%, P=0.008/84.21% vs. 47.37%, P=0.016). BALF-cfDNA showed a significantly greater reads per million (RPM) than BALF-wcDNA. The area under the ROC curve (AUC) for RPM of Aspergillus detected by BALF-cfDNA, used to predict "True positive" pulmonary aspergillosis patients, was 0.779, with a cut-off value greater than 4.5.Conclusion:We propose that the incorporation of BALF-mNGS (cfDNA, wcDNA) with CMTs improves diagnostic precision in the identification of non-neutropenic pulmonary aspergillosis when compared to CMTs alone. BALF-cfDNA outperforms BALF-wcDNA in clinical value.
Keywords: Metagenomic next-generation sequencing (mNGS), cell-free DNA, whole-cell DNA, non-neutropenic pulmonary aspergillosis, Pulmonary Aspergillosis
Received: 09 Mar 2024; Accepted: 09 Jul 2024.
Copyright: © 2024 Cai, Sun, Zhong, Cai, Cao, Wang, Sun, Tao, Ma, Huang, Yan, Zhong, Wang, Lu, Guan, Song, Wang, Li and Su. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xin Su, Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Liaoning Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Yuchen Cai
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