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bioRxiv · 10.64898/2026.06.17.733050

Learning interpretable structural similarity from tandem mass spectra for small molecule analog discovery

Piedrahita Giraldo, J. S.·Da Silva, K. M.·Zare Shahneh, M. R.·Wang, M.·Laukens, K.·De Vijlder, T.·Bittremieux, W.
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Abstract

Analog discovery remains a central bottleneck in mass spectrometry-based untargeted metabolomics, as conventional spectral similarity scores poorly reflect molecular structure. We introduce SIMBA, a transformer-based model that infers two interpretable graph-based distances, maximum common edge subgraph and substructure edit distance, directly from tandem mass spectra. SIMBA consistently retrieves structurally closer analogs than existing methods, enabling structure-aware small molecule identification beyond exact spectral matching.

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Piedrahita Giraldo, J. S., Da Silva, K. M., Zare Shahneh, M. R., Wang, M., Laukens, K., De Vijlder, T., Bittremieux, W.. 2026-06-23. Learning interpretable structural similarity from tandem mass spectra for small molecule analog discovery. https://doi.org/10.64898/2026.06.17.733050

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