TY - JOUR

T1 - Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics

AU - Bittremieux, Wout

AU - Avalon, Nicole E.

AU - Thomas, Sydney P.

AU - Kakhkhorov, Sarvar A.

AU - Aksenov, Alexander A.

AU - Gomes, Paulo Wender P.

AU - Aceves, Christine M.

AU - Caraballo-Rodríguez, Andrés Mauricio

AU - Gauglitz, Julia M.

AU - Gerwick, William H.

AU - Huan, Tao

AU - Jarmusch, Alan K.

AU - Kaddurah-Daouk, Rima F.

AU - Kang, Kyo Bin

AU - Kim, Hyun Woo

AU - Kondić, Todor

AU - Mannochio-Russo, Helena

AU - Meehan, Michael J.

AU - Melnik, Alexey V.

AU - Nothias, Louis Felix

AU - O’Donovan, Claire

AU - Panitchpakdi, Morgan

AU - Petras, Daniel

AU - Schmid, Robin

AU - Schymanski, Emma L.

AU - van der Hooft, Justin J.J.

AU - Weldon, Kelly C.

AU - Yang, Heejung

AU - Xing, Shipei

AU - Zemlin, Jasmine

AU - Wang, Mingxun

AU - Dorrestein, Pieter C.

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-023-44035-y

DO - 10.1038/s41467-023-44035-y

M3 - Journal article

C2 - 38123557

AN - SCOPUS:85180195952

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 8488

ER -