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ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Clinical Microbiology
Volume 14 - 2024 |
doi: 10.3389/fcimb.2024.1498512
This article is part of the Research Topic Advances in the Diagnosis and Management of Infectious Diseases View all 5 articles
Title：Diagnosis Value of Targeted and Metagenomic Sequencing in Respiratory Tract Infection
Provisionally accepted
Yukun Kuang
1*
Weiping Tan
1*
Chaohui Hu
2*
Zehan Dai
2
Lihong Bai
1*
Jiyu Wang
1*
Huai Liao
1*
Haihong Chen
1
Rongling He
1*
Pengyuan Zhu
2*
Jun Liu
2*
Canmao Xie
1*
Zunfu Ke
3,4*
Kejing Tang
1,5*- 1 Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- 2 KingCreate Biotechnology Company Limited, Guangzhou, China
- 3 Department of Pathology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
- 4 Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
- 5 Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Background Targeted next-generation sequencing (tNGS) has become a trending tool in the field of infection diagnosis, but also concern is raising about its performance compared with metagenomic next-generation sequencing (mNGS). This study aims to explore the clinical feasibility of a tNGS panel for respiratory tract infection diagnosis and compare it with mNGS in the same cohort of inpatients.Methods 180 bronchoalveolar lavage fluid samples were collected and sent to two centers for mNGS and tNGS blinded tests, respectively. The concordance between pathogen reports of both methods and the clinical significance among samples with/without known aetiology was further evaluated.Overall, both methods displayed high agreement on pathogen reports, as the average percent agreement reached 95.29%. But tNGS presented a slightly higher detection rate per species than mNGS (PWilcoxon=1.212e-05; standard mean difference = 0.2887091), as detection rates for 32 out of 48 species were higher than those of mNGS. Due to limitations of panel coverage, tNGS identified 28 fewer species than mNGS, among which only 3 were considered clinically relevant. In reference to composite reference standard, accuracy, sensitivity, and specificity combining both tNGS and mNGS reached 95.61%, 96.71%, and 95.68%, respectively, while positive prediction value (PPV) was low at 48.13%, which was caused by low agreement regarding opportunistic pathogens. tNGS and mNGS improved the aetiology identification in 30.6% (55/180) and 33.9% (61/180) cases, respectively.Collectively, tNGS presented a similar overall performance in pathogen identification compared to mNGS, but and outperformed in some pathogens. This study also demonstrated that deployment of tNGS significantly improves aetiology identification in routine practice and provides hints for clinical decisions. The low agreement between clinical diagnosis and NGS report towards opportunistic pathogens implies that adjudication is essential for report interpretation. Finally, We proposed tNGS as a diagnosis option in clinical practice due to its cost-efficiency.
Keywords: broad-spectrum pathogen identification, Targeted next-generation sequencing (TNGS), Metagenomic next-generation sequencing (mNGS), Diagnosis value, respiratory tract infection
Received: 19 Sep 2024; Accepted: 13 Nov 2024.
Copyright: © 2024 Kuang, Tan, Hu, Dai, Bai, Wang, Liao, Chen, He, Zhu, Liu, Xie, Ke and Tang. 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:
Yukun Kuang, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Weiping Tan, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Chaohui Hu, KingCreate Biotechnology Company Limited, Guangzhou, China
Lihong Bai, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Jiyu Wang, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Huai Liao, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Rongling He, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Pengyuan Zhu, KingCreate Biotechnology Company Limited, Guangzhou, China
Jun Liu, KingCreate Biotechnology Company Limited, Guangzhou, China
Canmao Xie, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Zunfu Ke, Department of Pathology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
Kejing Tang, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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