Metagenomic next-generation sequencing-based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patients

BackgroundMetagenomic next-generation sequencing (mNGS) enables comprehensive profiling of viral communities in clinical samples. However, comparative analyses of the virome across anatomical compartments and disease states remain limited. This study aims to characterize the virome in bronchoalveola...

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Main Authors: Ning Zheng, Hai-Long Yu, Bing-Jie Zhang, Dan Wang, Ya-Liang Ji, Lu-Lu Dai, Wen Li, Sheng-Hui Li, Zhi-Liang Hu, Yi-Shan Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1562965/full
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author Ning Zheng
Hai-Long Yu
Bing-Jie Zhang
Dan Wang
Ya-Liang Ji
Lu-Lu Dai
Wen Li
Sheng-Hui Li
Zhi-Liang Hu
Zhi-Liang Hu
Yi-Shan Zheng
author_facet Ning Zheng
Hai-Long Yu
Bing-Jie Zhang
Dan Wang
Ya-Liang Ji
Lu-Lu Dai
Wen Li
Sheng-Hui Li
Zhi-Liang Hu
Zhi-Liang Hu
Yi-Shan Zheng
author_sort Ning Zheng
collection DOAJ
description BackgroundMetagenomic next-generation sequencing (mNGS) enables comprehensive profiling of viral communities in clinical samples. However, comparative analyses of the virome across anatomical compartments and disease states remain limited. This study aims to characterize the virome in bronchoalveolar lavage fluid (BALF) and peripheral blood samples from patients with various clinical conditions using mNGS.MethodsA total of 338 clinical samples—including 240 BALF and 69 blood samples for DNA sequencing, and 18 BALF and 11 blood samples for RNA sequencing—underwent shotgun metagenomic sequencing. Following removal of host-derived reads, high-quality non-human sequences were aligned to a viral reference database. Virome composition was assessed through alpha and beta diversity metrics. Principal coordinates analysis was used to evaluate disease-related variation, and virus–bacteria associations in BALF were investigated via Spearman correlation.ResultsSequencing yielded an average of 51 million raw reads per sample, resulting in approximately 8 million non-human reads after host filtering. Distinct virome profiles were observed between BALF and blood samples. Bacteriophages dominated all groups, with Siphoviridae and Myoviridae as the most abundant families, although only 13.6% of viral abundance could be assigned to known families. Diversity analyses revealed significant differences between BALF and peripheral blood, and DNA-sequenced BALF samples showed disease-specific viral signatures in pulmonary infections. In contrast, tumor presence had no significant effect on virome composition in either BALF or blood. Network analysis identified complex virus–bacteria correlations in BALF, with genera such as Haemophilus, Megasphaera, and Treponema as key bacterial hosts.ConclusionsThis study reveals pronounced differences in virome composition between the respiratory and circulatory systems and highlights the specific influence of pulmonary disease—but not tumors—on the pulmonary virome. The observed virus–bacteria networks provide novel insights into pulmonary microbial ecology and underscore the importance of integrating host and disease context in virome studies.
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spelling doaj-art-9c0c95a4cf0a40ba927a7f31eacbb6492025-08-20T03:25:49ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-07-011510.3389/fcimb.2025.15629651562965Metagenomic next-generation sequencing-based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patientsNing Zheng0Hai-Long Yu1Bing-Jie Zhang2Dan Wang3Ya-Liang Ji4Lu-Lu Dai5Wen Li6Sheng-Hui Li7Zhi-Liang Hu8Zhi-Liang Hu9Yi-Shan Zheng10Department of Critical Care Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, ChinaPuensum Genetech Institute, Wuhan, ChinaDepartment of Critical Care Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Critical Care Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Critical Care Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Critical Care Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Critical Care Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, ChinaPuensum Genetech Institute, Wuhan, ChinaDepartment of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaDepartment of Critical Care Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, ChinaBackgroundMetagenomic next-generation sequencing (mNGS) enables comprehensive profiling of viral communities in clinical samples. However, comparative analyses of the virome across anatomical compartments and disease states remain limited. This study aims to characterize the virome in bronchoalveolar lavage fluid (BALF) and peripheral blood samples from patients with various clinical conditions using mNGS.MethodsA total of 338 clinical samples—including 240 BALF and 69 blood samples for DNA sequencing, and 18 BALF and 11 blood samples for RNA sequencing—underwent shotgun metagenomic sequencing. Following removal of host-derived reads, high-quality non-human sequences were aligned to a viral reference database. Virome composition was assessed through alpha and beta diversity metrics. Principal coordinates analysis was used to evaluate disease-related variation, and virus–bacteria associations in BALF were investigated via Spearman correlation.ResultsSequencing yielded an average of 51 million raw reads per sample, resulting in approximately 8 million non-human reads after host filtering. Distinct virome profiles were observed between BALF and blood samples. Bacteriophages dominated all groups, with Siphoviridae and Myoviridae as the most abundant families, although only 13.6% of viral abundance could be assigned to known families. Diversity analyses revealed significant differences between BALF and peripheral blood, and DNA-sequenced BALF samples showed disease-specific viral signatures in pulmonary infections. In contrast, tumor presence had no significant effect on virome composition in either BALF or blood. Network analysis identified complex virus–bacteria correlations in BALF, with genera such as Haemophilus, Megasphaera, and Treponema as key bacterial hosts.ConclusionsThis study reveals pronounced differences in virome composition between the respiratory and circulatory systems and highlights the specific influence of pulmonary disease—but not tumors—on the pulmonary virome. The observed virus–bacteria networks provide novel insights into pulmonary microbial ecology and underscore the importance of integrating host and disease context in virome studies.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1562965/fullmetagenomic next-generation sequencingviral compositionbronchoalveolar lavage fluidperipheral bloodvirus-bacteria interactions
spellingShingle Ning Zheng
Hai-Long Yu
Bing-Jie Zhang
Dan Wang
Ya-Liang Ji
Lu-Lu Dai
Wen Li
Sheng-Hui Li
Zhi-Liang Hu
Zhi-Liang Hu
Yi-Shan Zheng
Metagenomic next-generation sequencing-based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patients
Frontiers in Cellular and Infection Microbiology
metagenomic next-generation sequencing
viral composition
bronchoalveolar lavage fluid
peripheral blood
virus-bacteria interactions
title Metagenomic next-generation sequencing-based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patients
title_full Metagenomic next-generation sequencing-based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patients
title_fullStr Metagenomic next-generation sequencing-based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patients
title_full_unstemmed Metagenomic next-generation sequencing-based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patients
title_short Metagenomic next-generation sequencing-based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patients
title_sort metagenomic next generation sequencing based characterization of the viral spectrum in clinical pulmonary and peripheral blood samples of patients
topic metagenomic next-generation sequencing
viral composition
bronchoalveolar lavage fluid
peripheral blood
virus-bacteria interactions
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1562965/full
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