Curation of mass spectrometry reference data for improved identification and dereplication of cyanobacterial specialized metabolites

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Abstract

High-resolution tandem mass spectrometry (HRMS/MS) is a powerful tool for screening organic compounds in complex samples. A critical step in identifying candidate structures is the comparison of sample HRMS/MS spectra with those in reference spectral libraries. The effectiveness of this spectral matching hinges on two key factors: (i) how well the library’s content aligns with the suspect compound list, and (ii) the quality and diversity of the reference spectra for each compound. Yet, the scarcity of natural product reference materials on the market often necessitates non-targeted analysis. In this study, we systematically acquired and curated HRMS/MS reference spectra for specialized metabolites from cyanobacteria, which are vastly underrepresented in current libraries. Previously, MassBank EU included spectra for only 14 such compounds. We have significantly expanded the publicly available data, contributing 2911 unique spectra representing 150 distinct cyanobacterial metabolites. A proof-of-concept analysis demonstrates up to 5-fold increased annotation success and revealed shortcomings in current libraries, underscoring the need for continued data enrichment. In particular, future efforts should prioritize the inclusion of HRMS/MS spectra for diverse adduct ions to improve identification confidence and broaden analytical coverage.
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Abstract High-resolution tandem mass spectrometry (HRMS/MS) is a powerful tool for screening organic compounds in complex samples. A critical step in identifying candidate structures is the comparison of sample HRMS/MS spectra with those in reference spectral libraries. The effectiveness of this spectral matching hinges on two key factors: (i) how well the library’s content aligns with the suspect compound list, and (ii) the quality and diversity of the reference spectra for each compound. Yet, the scarcity of natural product reference materials on the market often necessitates non-targeted analysis. In this study, we systematically acquired and curated HRMS/MS reference spectra for specialized metabolites from cyanobacteria, which are vastly underrepresented in current libraries. Previously, MassBank EU included spectra for only 14 such compounds. We have significantly expanded the publicly available data, contributing 2911 unique spectra representing 150 distinct cyanobacterial metabolites. A proof-of-concept analysis demonstrates up to 5-fold increased annotation success and revealed shortcomings in current libraries, underscoring the need for continued data enrichment. In particular, future efforts should prioritize the inclusion of HRMS/MS spectra for diverse adduct ions to improve identification confidence and broaden analytical coverage. Competing Interest Statement The authors have declared no competing interest.

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last seen: 2026-05-20T01:45:00.602351+00:00