MS2Query: Reliable and Scalable MS2 Mass Spectral-based Analogue Search

Abstract

Metabolomics-driven discoveries of biological samples remain hampered by the grand challenge of metabolite annotation and identification. Only few metabolites have an annotated spectrum in spectral libraries; hence, searching only for exact library matches generally returns a few hits. An attractive alternative is searching for so-called analogues as a starting point for structural annotations; analogues are library molecules which are not exact matches, but display a high chemical similarity. However, current analogue search implementations are not yet very reliable and relatively slow. Here, we present MS2Query, a machine learning-based tool that integrates mass spectral embedding-based chemical similarity predictors (Spec2Vec and MS2Deepscore) as well as detected precursor masses to rank potential analogues and exact matches. Benchmarking MS2Query on reference mass spectra and experimental case studies demonstrates an improved reliability and scalability. Thereby, MS2Query offers exciting opportunities for further increasing the annotation rate of complex metabolite mixtures and for discovering new biology.