Separability Is Not Alignability: Representations for Spectrum-to-Molecule Retrieval

Karol Musielinski, Fanurs C. E. Teh, Takahiko Koyama, Artur Dubrawski

Identifying a small molecule from its tandem mass spectrum is limited by paired data. Foundation models offer a way around this scarcity: pretrain a spectrum encoder on unlabeled spectra and a molecule encoder on a large corpus of structures, then align the two frozen representations, as in vision-language and as the Platonic Representation Hypothesis suggests. We audit this route on MassSpecGym with spectrum encoders retrained free of test-fold contamination. Alignment needs a metric relating distinct molecules, but the objectives that produce spectrum encoders never see molecular structure: we prove that some predictive objectives fix molecular identity without fixing that metric. Moreover, we find that a candidate-based objective rewards a spectrum-independent prior over the benchmark's decoys, which we isolate. What ultimately addresses data scarcity is not architectural: simulated spectra surpass frozen geometry.