Abstract
Small molecule identification is a crucial task in analytical chemistry and life sciences. One of the most commonly used technologies to elucidate small molecule structures is mass spectrometry. Spectral library search of product ion spectra (MS/MS) is a popular strategy to identify or find structural analogues. This approach relies on the assumption that spectral similarity and structural similarity are correlated. However, popular spectral similarity measures, usually calculated based on identical fragment matches between the MS/MS spectra, do not always accurately reflect the structural similarity. In this study, we propose TransExION, a Transformer based Explainable similarity metric for IONS. TransExION detects related fragments between MS/MS spectra through their mass difference and uses these to estimate spectral similarity. These related fragments can be nearly identical, but can also share a substructure. TransExION also provides a post-hoc explanation of its estimation, which can be used to support scientists in evaluating the spectral library search results and thus in structure elucidation of unknown molecules. Our model has a Transformer based architecture and it is trained on the data derived from GNPS MS/MS libraries. The experimental results show that it improves existing spectral similarity measures in searching and interpreting structural analogues as well as in molecular networking. SCIENTIFIC CONTRIBUTION: We propose a transformer-based spectral similarity metrics that improves the comparison of small molecule tandem mass spectra. We provide a post hoc explanation that can serve as a good starting point for unknown spectra annotation based on database spectra.