{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:39:16Z","timestamp":1785425956869,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2024YFA1803100"],"award-info":[{"award-number":["2024YFA1803100"]}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LR25H160002"],"award-info":[{"award-number":["LR25H160002"]}]},{"award":["LR25H160002"],"award-info":[{"award-number":["LR25H160002"]}],"id":[{"id":"https:\/\/ror.org\/04aqat463","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82272300"],"award-info":[{"award-number":["82272300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82473319"],"award-info":[{"award-number":["82473319"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["92359303"],"award-info":[{"award-number":["92359303"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82272300"],"award-info":[{"award-number":["82272300"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82473319"],"award-info":[{"award-number":["82473319"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["92359303"],"award-info":[{"award-number":["92359303"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Influenza virus outbreaks remain a persistent public health concern, yet traditional metabolomics methods are inadequate for addressing key analytical challenges of \u201cdark matter\u201d in influenza research. By integrating quantitative MS1 data, MS2-derived fragmentation trees and molecular fingerprints, structure-based comparative metabolomics enhances predictive capability for chemical structures, and enables the discovery of candidate metabolic markers without the need for database spectra. In this study, we established a C57BL\/6J mouse model of H1N1 infection (with PBS as control) and performed structure-based comparative metabolomics on fecal samples using liquid chromatography\u2013mass spectrometry (LC-MS). Quantitative analysis of MS1 data identified 40 differential metabolites, while qualitative analysis of MS2 data enabled their structural annotation. A candidate metabolite marker, LysoPE 15:0, along with other potential metabolic markers, was annotated and validated using Mirror plot, CFM-ID, and sim-Rank-Network. Our findings demonstrate that structure-based comparative metabolomics enables library spectra-free annotation of metabolomic \u201cdark matter\u201d and provides a methodological workflow for discovering candidate metabolite markers in other diseases.<\/jats:p>","DOI":"10.3390\/molecules31132275","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:27:37Z","timestamp":1782746857000},"page":"2275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure-Based Comparative Metabolomics Identifies LysoPE 15:0 as a Candidate Metabolite Marker of Influenza Virus Infection Dynamics"],"prefix":"10.3390","volume":"31","author":[{"given":"Junxiao","family":"Wang","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Synthetic Biotechnology for Microbial Medicine, Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5015-4555","authenticated-orcid":false,"given":"Yuting","family":"Li","sequence":"additional","affiliation":[{"name":"Cancer Institute, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7665-6290","authenticated-orcid":false,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biological Science and Technology, Guangxi Academy of Sciences, Nanning 530007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8055-2072","authenticated-orcid":false,"given":"Wenxia","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Biological Science and Technology, Guangxi Academy of Sciences, Nanning 530007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushen","family":"Du","sequence":"additional","affiliation":[{"name":"Cancer Institute, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Synthetic Biotechnology for Microbial Medicine, Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/infdis\/jiy103","article-title":"A universal influenza vaccine: The strategic plan for the National Institute of Allergy and Infectious Diseases","volume":"218","author":"Erbelding","year":"2018","journal-title":"J. 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