CLEF: Cleavage Events Guide Electron Ionization Mass Spectrum Prediction

Mass spectrometry is widely used to identify compounds and analyze molecular structures. Predicting electron ionization (EI) mass spectra from structures can extend reference libraries to compounds without measured spectra. Accurate EI spectrum prediction and reliable retrieval among constitutional isomers are complementary goals. Both depend on modeling how molecular connectivity affects fragment intensities. We introduce CLEF, a structure-guided EI spectrum predictor. It uses atom connectivity, bond types, and candidate cleavage events to score fragment formulas. The events are enumerated from the input structure and matched to formulas by elemental composition. Composition-matched attention updates formula representations with event information. These representations then guide atom pooling and formula scoring, allowing the same formula to receive different weights in constitutional isomers. The model is trained on paired structures and spectra without event annotations. CLEF outperforms six trained baselines in spectrum prediction and isomer retrieval on NIST23 and MoNA, and in MoNA-to-SWGDRUG transfer. With only 25% of NIST23 training data, CLEF achieves spectral accuracy comparable to that of a leading full-data predictor.