Shotgun Metagenomic Sequencing Analysis as a Diagnostic Strategy for Patients with Lower Respiratory Tract Infections

Conventional diagnostic methods (CDMs) for lower respiratory infections (LRIs) have limitations in detecting causative pathogens. This study evaluates the utility of shotgun metagenomic sequencing (SMS) as a complementary diagnostic tool using bronchoalveolar lavage (BAL) fluid. Sixteen BAL fluid sa...

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Main Authors: Ha-eun Cho, Min Jin Kim, Jongmun Choi, Yong-Hak Sohn, Jae Joon Lee, Kyung Sun Park, Sun Young Cho, Ki-Ho Park, Young Jin Kim
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/6/1338
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author Ha-eun Cho
Min Jin Kim
Jongmun Choi
Yong-Hak Sohn
Jae Joon Lee
Kyung Sun Park
Sun Young Cho
Ki-Ho Park
Young Jin Kim
author_facet Ha-eun Cho
Min Jin Kim
Jongmun Choi
Yong-Hak Sohn
Jae Joon Lee
Kyung Sun Park
Sun Young Cho
Ki-Ho Park
Young Jin Kim
author_sort Ha-eun Cho
collection DOAJ
description Conventional diagnostic methods (CDMs) for lower respiratory infections (LRIs) have limitations in detecting causative pathogens. This study evaluates the utility of shotgun metagenomic sequencing (SMS) as a complementary diagnostic tool using bronchoalveolar lavage (BAL) fluid. Sixteen BAL fluid samples from pneumonia patients with positive CDM results—including bacterial/fungal cultures; PCR for <i>Mycobacterium tuberculosis</i> or cytomegalovirus; and the BioFire<sup>®</sup> FilmArray<sup>®</sup> Pneumonia Panel (BioFire Diagnostics LLC, Salt Lake City, UT, USA)—underwent 10 Gb SMS on the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Reads were aligned to the NCBI RefSeq database; with fungal identification further supported by internal transcribed spacer (ITS) analysis. Antibiotic resistance genes (ARGs) were annotated using the Comprehensive Antibiotic Resistance Database. Microbial reads accounted for 0.00002–0.04971% per sample. SMS detected corresponding bacteria in 63% of cases, increasing to 69% when subdominant taxa were included. Fungal reads were low; however, <i>Candida</i> species were identified in four samples via ITS. No viral reads were detected. ARGs meeting perfect match criteria were found in two cases. This is the first real-world study comparing SMS with CDMs, including semiquantitative PCR, in BAL fluid for LRI. SMS shows promise as a supplementary diagnostic method, with further research needed to optimize its performance and cost-effectiveness.
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spelling doaj-art-a147e24dd4114e3c8bc9163cf99b7fd62025-08-20T03:29:35ZengMDPI AGMicroorganisms2076-26072025-06-01136133810.3390/microorganisms13061338Shotgun Metagenomic Sequencing Analysis as a Diagnostic Strategy for Patients with Lower Respiratory Tract InfectionsHa-eun Cho0Min Jin Kim1Jongmun Choi2Yong-Hak Sohn3Jae Joon Lee4Kyung Sun Park5Sun Young Cho6Ki-Ho Park7Young Jin Kim8Department of Laboratory Medicine, Graduate School, Kyung Hee University, Kyung Hee University Hospital, Seoul 02447, Republic of KoreaDepartment of Laboratory Medicine, Seegene Medical Foundation, Seoul 04805, Republic of KoreaDepartment of Laboratory Medicine, Seegene Medical Foundation, Seoul 04805, Republic of KoreaDepartment of Laboratory Medicine, Seegene Medical Foundation, Seoul 04805, Republic of KoreaDepartment of Laboratory Medicine, Seegene Medical Foundation, Seoul 04805, Republic of KoreaDepartment of Laboratory Medicine, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of KoreaDepartment of Laboratory Medicine, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of KoreaDepartment of Infectious Diseases, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of KoreaDepartment of Laboratory Medicine, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of KoreaConventional diagnostic methods (CDMs) for lower respiratory infections (LRIs) have limitations in detecting causative pathogens. This study evaluates the utility of shotgun metagenomic sequencing (SMS) as a complementary diagnostic tool using bronchoalveolar lavage (BAL) fluid. Sixteen BAL fluid samples from pneumonia patients with positive CDM results—including bacterial/fungal cultures; PCR for <i>Mycobacterium tuberculosis</i> or cytomegalovirus; and the BioFire<sup>®</sup> FilmArray<sup>®</sup> Pneumonia Panel (BioFire Diagnostics LLC, Salt Lake City, UT, USA)—underwent 10 Gb SMS on the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Reads were aligned to the NCBI RefSeq database; with fungal identification further supported by internal transcribed spacer (ITS) analysis. Antibiotic resistance genes (ARGs) were annotated using the Comprehensive Antibiotic Resistance Database. Microbial reads accounted for 0.00002–0.04971% per sample. SMS detected corresponding bacteria in 63% of cases, increasing to 69% when subdominant taxa were included. Fungal reads were low; however, <i>Candida</i> species were identified in four samples via ITS. No viral reads were detected. ARGs meeting perfect match criteria were found in two cases. This is the first real-world study comparing SMS with CDMs, including semiquantitative PCR, in BAL fluid for LRI. SMS shows promise as a supplementary diagnostic method, with further research needed to optimize its performance and cost-effectiveness.https://www.mdpi.com/2076-2607/13/6/1338shotgun metagenomic sequencingbronchoalveolar fluid (BAL)lower respiratory infection
spellingShingle Ha-eun Cho
Min Jin Kim
Jongmun Choi
Yong-Hak Sohn
Jae Joon Lee
Kyung Sun Park
Sun Young Cho
Ki-Ho Park
Young Jin Kim
Shotgun Metagenomic Sequencing Analysis as a Diagnostic Strategy for Patients with Lower Respiratory Tract Infections
Microorganisms
shotgun metagenomic sequencing
bronchoalveolar fluid (BAL)
lower respiratory infection
title Shotgun Metagenomic Sequencing Analysis as a Diagnostic Strategy for Patients with Lower Respiratory Tract Infections
title_full Shotgun Metagenomic Sequencing Analysis as a Diagnostic Strategy for Patients with Lower Respiratory Tract Infections
title_fullStr Shotgun Metagenomic Sequencing Analysis as a Diagnostic Strategy for Patients with Lower Respiratory Tract Infections
title_full_unstemmed Shotgun Metagenomic Sequencing Analysis as a Diagnostic Strategy for Patients with Lower Respiratory Tract Infections
title_short Shotgun Metagenomic Sequencing Analysis as a Diagnostic Strategy for Patients with Lower Respiratory Tract Infections
title_sort shotgun metagenomic sequencing analysis as a diagnostic strategy for patients with lower respiratory tract infections
topic shotgun metagenomic sequencing
bronchoalveolar fluid (BAL)
lower respiratory infection
url https://www.mdpi.com/2076-2607/13/6/1338
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