Machine Learning-Based Bioactivity Classification of Natural Products Using LC-MS/MS Metabolomics

-generated fragmentation spectra, we have trained a ML model capable of predicting a compound's drug class. This approach enables the rapid identification of bioactive scaffolds from LC-MS/MS data, even without reference experimental spectra. The model was trained on a diverse set of molecular fingerprints generated by SIRIUS 5 to effectively classify compounds based on their core pharmacophores. Our model robustly classified 21 diverse bioactive drug classes, achieving accuracies greater than 93% on experimental spectra. This study underscores the potential of ML combined with MFPs to dereplicate bioactive natural products based on pharmacophore, streamlining the discovery process and expediting improved methods of isolating novel antibacterial and antifungal agents.