학술논문
Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics
Document Type
article
Author
Wout Bittremieux; Nicole E. Avalon; Sydney P. Thomas; Sarvar A. Kakhkhorov; Alexander A. Aksenov; Paulo Wender P. Gomes; Christine M. Aceves; Andrés Mauricio Caraballo-Rodríguez; Julia M. Gauglitz; William H. Gerwick; Tao Huan; Alan K. Jarmusch; Rima F. Kaddurah-Daouk; Kyo Bin Kang; Hyun Woo Kim; Todor Kondić; Helena Mannochio-Russo; Michael J. Meehan; Alexey V. Melnik; Louis-Felix Nothias; Claire O’Donovan; Morgan Panitchpakdi; Daniel Petras; Robin Schmid; Emma L. Schymanski; Justin J. J. van der Hooft; Kelly C. Weldon; Heejung Yang; Shipei Xing; Jasmine Zemlin; Mingxun Wang; Pieter C. Dorrestein
Source
Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)
Subject
Language
English
ISSN
2041-1723
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 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.