Genomic surveillance of SARS-CoV-2 variants using pooled WGS

Abstract This study presents the development and validation of a genomic surveillance strategy using Whole Genome Sequencing (WGS) on normalized pooled samples to detect and monitor SARS-CoV-2 variants. A bioinformatics pipeline was designed specifically for analyzing pooled WGS data and was validat...

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Main Authors: Inho Park, Yoonjung Kim, Min Hyuk Choi, Kyung-A Lee
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-99201-7
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author Inho Park
Yoonjung Kim
Min Hyuk Choi
Kyung-A Lee
author_facet Inho Park
Yoonjung Kim
Min Hyuk Choi
Kyung-A Lee
author_sort Inho Park
collection DOAJ
description Abstract This study presents the development and validation of a genomic surveillance strategy using Whole Genome Sequencing (WGS) on normalized pooled samples to detect and monitor SARS-CoV-2 variants. A bioinformatics pipeline was designed specifically for analyzing pooled WGS data and was validated using simulated datasets, pooled samples of reference materials, and pooled clinical samples collected during key periods of the Delta and Omicron variant emergence. The approach was evaluated for its accuracy in estimating variant abundance at both the Phylogenetic Assignment of Named Global Outbreak (PANGO) lineage level and the World Health Organization (WHO) variant level. From the simulation datasets, the method achieved an overall sensitivity of 99.1% and a positive predictive value (PPV) of 99.9% for detecting SARS-CoV-2 variants at the WHO variant level. At the PANGO lineage level, it achieved an overall sensitivity of 82.8% and a PPV of 77.4% when a predicted lineage was considered accurate if it shared more than 90% of markers with any true lineage present in the pooled sample. The accuracy of variant abundance estimation was further validated using pooled samples of reference materials. Analysis of pooled clinical samples showed results consistent with national epidemiological trends, particularly during the emergence of the Delta and Omicron variants in Korea. This pooled WGS-based genomic surveillance strategy offers a scalable and economical solution for monitoring SARS-CoV-2 variants, providing public health authorities with a valuable tool for tracking pandemic dynamics and enabling timely responses.
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spelling doaj-art-600fd21234b14745b9a77bbdaa96d4792025-08-20T02:20:06ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-99201-7Genomic surveillance of SARS-CoV-2 variants using pooled WGSInho Park0Yoonjung Kim1Min Hyuk Choi2Kyung-A Lee3Center for Precision Medicine, Gangnam Severance Hospital, Yonsei University College of MedicineDepartment of Laboratory Medicine, Yonsei University College of MedicineDepartment of Laboratory Medicine, Yonsei University College of MedicineDepartment of Laboratory Medicine, Yonsei University College of MedicineAbstract This study presents the development and validation of a genomic surveillance strategy using Whole Genome Sequencing (WGS) on normalized pooled samples to detect and monitor SARS-CoV-2 variants. A bioinformatics pipeline was designed specifically for analyzing pooled WGS data and was validated using simulated datasets, pooled samples of reference materials, and pooled clinical samples collected during key periods of the Delta and Omicron variant emergence. The approach was evaluated for its accuracy in estimating variant abundance at both the Phylogenetic Assignment of Named Global Outbreak (PANGO) lineage level and the World Health Organization (WHO) variant level. From the simulation datasets, the method achieved an overall sensitivity of 99.1% and a positive predictive value (PPV) of 99.9% for detecting SARS-CoV-2 variants at the WHO variant level. At the PANGO lineage level, it achieved an overall sensitivity of 82.8% and a PPV of 77.4% when a predicted lineage was considered accurate if it shared more than 90% of markers with any true lineage present in the pooled sample. The accuracy of variant abundance estimation was further validated using pooled samples of reference materials. Analysis of pooled clinical samples showed results consistent with national epidemiological trends, particularly during the emergence of the Delta and Omicron variants in Korea. This pooled WGS-based genomic surveillance strategy offers a scalable and economical solution for monitoring SARS-CoV-2 variants, providing public health authorities with a valuable tool for tracking pandemic dynamics and enabling timely responses.https://doi.org/10.1038/s41598-025-99201-7SARS-CoV-2SARS-CoV-2 mutation screeningEpidemiological surveillance
spellingShingle Inho Park
Yoonjung Kim
Min Hyuk Choi
Kyung-A Lee
Genomic surveillance of SARS-CoV-2 variants using pooled WGS
Scientific Reports
SARS-CoV-2
SARS-CoV-2 mutation screening
Epidemiological surveillance
title Genomic surveillance of SARS-CoV-2 variants using pooled WGS
title_full Genomic surveillance of SARS-CoV-2 variants using pooled WGS
title_fullStr Genomic surveillance of SARS-CoV-2 variants using pooled WGS
title_full_unstemmed Genomic surveillance of SARS-CoV-2 variants using pooled WGS
title_short Genomic surveillance of SARS-CoV-2 variants using pooled WGS
title_sort genomic surveillance of sars cov 2 variants using pooled wgs
topic SARS-CoV-2
SARS-CoV-2 mutation screening
Epidemiological surveillance
url https://doi.org/10.1038/s41598-025-99201-7
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