Metabolomics/methods; Gene Library; Cluster Analysis; Tandem Mass Spectrometry/methods; Access to Information; Metabolomics; Tandem Mass Spectrometry; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all)
Abstract :
[en] 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 MS/MS spectra originating from published untargeted metabolomics experiments. Entries in this library, or "suspects," were derived from unannotated spectra that could be linked in a molecular network to an annotated spectrum. Annotations were propagated to unknowns 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 for download or for data analysis through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Bittremieux, Wout ; Department of Computer Science, University of Antwerp, 2020, Antwerpen, Belgium. wout.bittremieux@uantwerpen.be
Avalon, Nicole E ; Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, 92093, USA
Thomas, Sydney P; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
Kakhkhorov, Sarvar A ; Laboratory of Physical and Chemical Methods of Research, Center for Advanced Technologies, Tashkent, 100174, Uzbekistan ; Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg C, Denmark
Aksenov, Alexander A; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA ; Department of Chemistry, University of Connecticut, Storrs, CT, 06269, USA ; Arome Science inc., Farmington, CT, 06032, USA
Gomes, Paulo Wender P ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
Aceves, Christine M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA
Caraballo-Rodríguez, Andrés Mauricio; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
Gauglitz, Julia M; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
Gerwick, William H ; Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, 92093, USA ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA
Huan, Tao ; Department of Chemistry, University of British Columbia, Vancouver, BC, V6T 1Z1, Canada
Jarmusch, Alan K ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA ; Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, 27709, USA
Kaddurah-Daouk, Rima F; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, 27701, USA ; Department of Medicine, Duke University, Durham, NC, 27710, USA ; Duke Institute of Brain Sciences, Duke University, Durham, NC, 27710, USA
Kang, Kyo Bin ; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, 04310, Korea
Kim, Hyun Woo ; College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, Goyang, 10326, Korea
KONDIC, Todor ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Environmental Cheminformatics > Team Emma SCHYMANSKI
Mannochio-Russo, Helena ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA ; Department of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University, Araraquara, 14800-901, Brazil
Meehan, Michael J; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
Melnik, Alexey V; Department of Chemistry, University of Connecticut, Storrs, CT, 06269, USA ; Arome Science inc., Farmington, CT, 06032, USA
Nothias, Louis-Felix; Université Côte d'Azur, CNRS, ICN, Nice, France ; Interdisciplinary Institute for Artificial Intelligence (3iA) Côte d'Azur, Nice, France
O'Donovan, Claire; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
Panitchpakdi, Morgan; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
Petras, Daniel ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA ; Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, 72076, Tuebingen, Germany ; Department of Biochemistry, University of California Riverside, Riverside, CA, 92507, USA
Schmid, Robin ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
van der Hooft, Justin J J ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA ; Bioinformatics Group, Wageningen University & Research, 6708 PB, Wageningen, The Netherlands
Weldon, Kelly C; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
Yang, Heejung ; Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University, Chuncheon, 24341, Korea
Xing, Shipei; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA ; Department of Chemistry, University of British Columbia, Vancouver, BC, V6T 1Z1, Canada
Zemlin, Jasmine; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA
Wang, Mingxun; Department of Computer Science and Engineering, University of California Riverside, Riverside, CA, 92507, USA
Dorrestein, Pieter C ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA. pdorrestein@health.ucsd.edu ; Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, 92093, USA. pdorrestein@health.ucsd.edu
This research was supported in part by BBSRC-NSF award 2152526. This research was supported in part by National Institutes of Health awards R01 GM107550, U19 AG063744, U01AG061359, R03 CA211211, P41 GM103484, T32 HD123456. This research was supported in part by the National Institute of Aging’s Accelerating Medicines Partnership for AD (AMP-AD) and was supported by NIH grants 1R01AG069901-01A1, U01AG061357, as well as by the Alzheimer Gut Microbiome Project grant 1U19AG063744. This research was supported in part by federal award DE-SC0021340 subaward 1070261-436503. This research was supported in part by the Gordon and Betty Moore Foundation through grant GBMF7622. This research was supported in part by the Intramural Research Program of National Institute of Environmental Health Sciences of the National Institutes of Health (ZIC ES103363). WB acknowledges support by the University of Antwerp Research Fund. This research was supported in part by the National Center for Complementary and Integrative Health of the NIH under award number F32AT011475 to N.E.A. E.L.S. and T.K. acknowledge funding support from the Luxembourg National Research Fund (FNR) for project A18/BM/12341006. M.W. was partially supported by the US Department of Energy Joint Genome Institute operated under Contract No. DE-AC02-05CH11231. D.P. was supported by the Deutsche Forschungsgemeinschaft (DFG) through the CMFI Cluster of Excellence (EXC 2124). S.A.K. was supported by the Fund for Financing Science and Supporting Innovation under the Ministry of Innovative Development of the Republic of Uzbekistan. K.B.K. was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (NRF-2020R1C1C1004046). H.W.K. was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT) (2018R1A5A2023127). H.M.-R. acknowledges the Brazilian National Council for Scientific and Technological Development (CNPq, #142014/2018-4) and the Brazilian Fulbright Commission for the scholarships provided. L.-F.N. has been supported by the French government, through the UCA Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-15-IDEX-01. J.J.J.vd.H. was supported by an ASDI eScience grant from the Netherlands eScience Center (ASDI.2017.030). C.O.D. was supported by EMBL core funds. The Alzheimer’s disease metabolomics data was funded wholly or in part by the Alzheimer’s Gut Microbiome Project (AGMP) NIH grant U19AG063744 awarded to R.F.K.-D. at Duke University in partnership with a large number of academic institutions. More information about the project and the institutions involved can be found at https://alzheimergut.org/meet-the-team/ . J.E.D.I.
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