Preprint

Open Access Repository-Scale Propagated Nearest Neighbor Suspect Spectral Library for Untargeted Metabolomics

Wout BittremieuxCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USANicole E. AvalonScripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USASydney P. ThomasCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USASarvar A. KakhkhorovLaboratory of Biotechnology, Center for Advanced Technologies, Tashkent 100174, UzbekistanAlexander A. AksenovCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAPaulo Wender Portal GomesCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAChristine M. AcevesDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USAAndrés Mauricio Caraballo‐RodríguezSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla CA 9093, USAJulia M. GauglitzCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAWilliam H. GerwickScripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USATao HuanAlan K. JarmuschCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USARima Kaddurah‐DaoukDepartment of Medicine, Duke University, Durham, NC 27710, USAKyo Bin KangCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Sookmyung Women’s University, Seoul 04310, KoreaHyun Woo KimCollege of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, Goyang 10326, KoreaTodor KondićLuxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367 Belvaux, LuxembourgHelena Mannochio-RussoCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAMichael J. MeehanCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAAlexey V. MelnikDepartment of Chemistry, University of Connecticut, Storrs, CT 06269, USALouis‐Félix NothiasInstitute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, 1211 Geneva, SwitzerlandClaire O’DonovanEuropean Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, United KingdomMorgan PanitchpakdiCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USADaniel PetrasCMFI Cluster of Excellence, Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, 72076 Tuebingen, GermanyRobin SchmidCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAEmma SchymanskiLuxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367 Belvaux, LuxembourgJustin J. J. van der HooftBioinformatics Group, Wageningen University, 6708PB Wageningen, the NetherlandsKelly C. WeldonCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAHeejung YangLaboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University, Chuncheon 24341, KoreaShipei XingJasmine ZemlinCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAMingxun WangCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USAPieter C. DorresteinCollaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA 92093, USA

bioRxiv (Cold Spring Harbor Laboratory)repository2022en

ABI

Abstract

Abstract Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of public MS/MS spectra. Annotations were propagated based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer’s brain phenotype. The nearest neighbor suspect spectral library is openly available through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.

Topics

Metabolomics and Mass Spectrometry Studies Analytical Chemistry and Chromatography Advanced Chemical Sensor Technologies

Identifiers

DOI: 10.1101/2022.05.15.490691

Citations and references

Cited by 066 references

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