Empirically establishing drug exposure records directly from untargeted metabolomics data

Haoqi Nina Zhao; Kine Eide Kvitne; Corinna Brungs; Siddharth Mohan; Vincent Charron-Lamoureux; Wout Bittremieux; Runbang Tang; Robin Schmid; Santosh Lamichhane; Yasin El Abiead; Mohammadsobhan S Andalibi; Helena Mannochio-Russo; Madison Ambre; Nicole E Avalon; MacKenzie Bryant; Andrés Mauricio Caraballo-Rodríguez; Martin Casas Maya; Loryn Chin; Ronald J Ellis; Donald Franklin; Sagan Girod; Paulo Wender P Gomes; Lauren Hansen; Robert Heaton; Jennifer E Iudicello; Alan K Jarmusch; Lora Khatib; Scott Letendre; Sarolt Magyari; Daniel McDonald; Ipsita Mohanty; Andrés Cumsille; David J Moore; Prajit Rajkumar; Dylan H Ross; Harshada Sapre; Mohammad Reza Zare Shahneh; Sydney P Thomas; Caitlin Tribelhorn; Helena M Tubb; Corinn Walker; Crystal X Wang; Shipei Xing; Jasmine Zemlin; Simone Zuffa; David S Wishart; Rima Kaddurah-Daouk; Mingxun Wang; Manuela Raffatellu; Karsten Zengler; Tomáš Pluskal; Libin Xu; Rob Knight; Shirley M Tsunoda; Pieter C Dorrestein

doi:10.1101/2024.10.07.617109

Empirically establishing drug exposure records directly from untargeted metabolomics data

bioRxiv [Preprint]. 2024 Oct 10:2024.10.07.617109. doi: 10.1101/2024.10.07.617109.

Authors

Haoqi Nina Zhao^{1

2}, Kine Eide Kvitne^{2

3}, Corinna Brungs⁴, Siddharth Mohan², Vincent Charron-Lamoureux^{1

2}, Wout Bittremieux^{1

2

5}, Runbang Tang², Robin Schmid^{1

2

4}, Santosh Lamichhane^{2

6}, Yasin El Abiead^{1

2}, Mohammadsobhan S Andalibi^{7

8

9}, Helena Mannochio-Russo^{1

2}, Madison Ambre¹⁰, Nicole E Avalon¹¹, MacKenzie Bryant¹⁰, Andrés Mauricio Caraballo-Rodríguez^{1

2}, Martin Casas Maya¹⁰, Loryn Chin¹², Ronald J Ellis^{7

8}, Donald Franklin⁸, Sagan Girod¹³, Paulo Wender P Gomes^{1

2

14}, Lauren Hansen¹⁰, Robert Heaton⁸, Jennifer E Iudicello⁸, Alan K Jarmusch^{1

2

15}, Lora Khatib⁷, Scott Letendre^{9

16}, Sarolt Magyari^{2

17}, Daniel McDonald¹⁰, Ipsita Mohanty^{1

2}, Andrés Cumsille^{2

18}, David J Moore^{8

9}, Prajit Rajkumar², Dylan H Ross^{19

20}, Harshada Sapre², Mohammad Reza Zare Shahneh²¹, Sydney P Thomas^{1

2}, Caitlin Tribelhorn¹⁰, Helena M Tubb¹⁰, Corinn Walker¹⁰, Crystal X Wang^{8

9}, Shipei Xing^{1

2}, Jasmine Zemlin^{1

2

22}, Simone Zuffa^{1

2}, David S Wishart^{12

23}, Rima Kaddurah-Daouk^{24

25

26}, Mingxun Wang²¹, Manuela Raffatellu^{10

22

27}, Karsten Zengler^{11

10

22

28}, Tomáš Pluskal⁴, Libin Xu¹⁹, Rob Knight^{10

22

29

30

31}, Shirley M Tsunoda², Pieter C Dorrestein^{1

2

22}

Affiliations

¹ Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
² Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
³ Department of Pharmacy, University of Oslo, Oslo, Norway.
⁴ Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
⁵ Department of Computer Science, University of Antwerp, Antwerp, Belgium.
⁶ Turku Bioscience Centre, University of Turku and Åbo Akademi University, Tykistönkatu 6A, 20520 Turku, Finland.
⁷ Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
⁸ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
⁹ HIV Neurobehavioral Research Program, University of California San Diego, La Jolla, CA, USA.
¹⁰ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
¹¹ Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA.
¹² Department of Bioengineering, University of California San Diego, La Jolla, California, USA.
¹³ Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
¹⁴ Faculty of Chemistry, Federal University of Pará, Belém, PA, Brazil.
¹⁵ Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
¹⁶ Department of Medicine, University of California San Diego, La Jolla, CA, USA.
¹⁷ Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.
¹⁸ Department of Microbiology and Cell Sciences, University of Florida, Museum Drive, Gainesville, FL, USA.
¹⁹ Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
²⁰ Current address: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
²¹ Department of Computer Science and Engineering, University of California Riverside, Riverside, CA, USA.
²² Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
²³ Department of Computing Science, University of Alberta, Edmonton, AB T6G 2E8, Canada.
²⁴ Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, 27708, USA.
²⁵ Duke Institute of Brain Sciences, Duke University, Durham, NC, USA.
²⁶ Department of Medicine, Duke University, Durham, NC, USA.
²⁷ Chiba University, UC San Diego Center for Mucosal Immunology, Allergy, and Vaccines (CU-UCSD cMAV), La Jolla, CA, USA.
²⁸ Program in Materials Science and Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0418, USA.
²⁹ Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
³⁰ Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
³¹ Halıcıoğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA.

Abstract

Despite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies on exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data independent of clinical records. Our library facilitates stratification of individuals in clinical studies based on the empirically detected medications, exemplified by drug-dependent microbiota-derived N-acyl lipid changes in a human immunodeficiency virus cohort. The GNPS Drug Library holds potential for broader applications in drug discovery and precision medicine.

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Abstract

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