Despite extensive efforts, extracting medication exposure information from clinical records remains challenging. To complement this approach, here we show the Global Natural Product Social Molecular Networking (GNPS) Drug Library, a tandem mass spectrometry (MS/MS) based resource designed for drug screening with untargeted metabolomics. This resource integrates MS/MS references of drugs and their metabolites/analogs with standardized vocabularies on their exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data, supporting flexible summarization at multiple ontology levels to align with different research goals. We demonstrate its application by stratifying participants in a human immunodeficiency virus (HIV) cohort based on detected drug exposures. We uncover drug-associated alterations in microbiota-derived N-acyl lipids that are not captured when stratifying by self-reported medication use. Overall, GNPS Drug Library provides a scalable resource for empirical drug screening in clinical, nutritional, environmental, and other research disciplines, facilitating insights into the ecological and health consequences of drug exposures. While not intended for immediate clinical decision-making, it supports data-driven exploration of drug exposures where traditional records are limited or unreliable.

Biological Sciences Division Pacific Northwest National Laboratory Richland WA USA

Catalan Institute for Water Research Girona Spain

Center for Microbiome Innovation University of California San Diego La Jolla CA USA

Chiba University UC San Diego Center for Mucosal Immunology Allergy and Vaccines La Jolla CA USA

Collaborative Mass Spectrometry Innovation Center University of California San Diego La Jolla CA USA

Department of Bioengineering University of California San Diego La Jolla California USA

Department of Biological Sciences University of Alberta Edmonton AB Canada

Department of Computer Science and Engineering University of California Riverside Riverside CA USA

Department of Computer Science and Engineering University of California San Diego La Jolla CA USA

Department of Computer Science University of Antwerp Antwerp Belgium

Department of Computing Science University of Alberta Edmonton AB Canada

Department of Environmental Chemistry Institute of Environmental Assessment and Water Research Barcelona Spain

Department of Medicinal Chemistry University of Washington Seattle WA USA

Department of Medicine Duke University Durham NC USA

Department of Medicine University of California San Diego La Jolla CA USA

Department of Neurosciences University of California San Diego La Jolla CA USA

Department of Obstetrics Gynecology and Reproductive Sciences University of California San Diego La Jolla CA USA

Department of Pediatrics University of California San Diego La Jolla CA USA

Department of Pharmaceutical Sciences University of Vienna Vienna Austria

Department of Pharmacy University of Oslo Oslo Norway

Department of Plant Pathology University of Wisconsin Madison Madison WI USA

Department of Psychiatry and Behavioral Sciences Duke University Durham NC USA

Department of Psychiatry University of California San Diego La Jolla CA USA

Duke Institute of Brain Sciences Duke University Durham NC USA

Faculty of Chemistry Federal University of Pará Belém PA Brazil

Halıcıoğlu Data Science Institute University of California San Diego La Jolla CA USA

HIV Neurobehavioral Research Program University of California San Diego La Jolla CA USA

Immunity Inflammation and Disease Laboratory Division of Intramural Research National Institute of Environmental Health Sciences National Institutes of Health Research Triangle Park Bethesda NC USA

Institute of Biomedicine and Turku Bioscience Centre University of Turku and Åbo Akademi University Tykistönkatu 6A 20520 Turku Finland

Institute of Microbiology Eidgenössische Technische Hochschule Zürich Zürich Switzerland

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Prague Czechia

Program in Materials Science and Engineering University of California San Diego La Jolla CA USA

Scripps Institution of Oceanography University of California San Diego La Jolla CA USA

Shu Chien Gene Lay Department of Bioengineering University of California San Diego La Jolla CA USA

Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San Diego La Jolla CA USA

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bioRxiv. 2024 Oct 26:2024.10.07.617109. doi: 10.1101/2024.10.07.617109. PubMed

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A Perspective on Unintentional Fragments and Their Impact on the Dark Metabolome, Untargeted Profiling, Molecular Networking, Public Data, and Repository Scale Analysis