How to Train Your Neural Network for Molecular Structure Generation from Mass Spectra?

Mass spectrometry serves as a pivotal tool for the analysis of small molecules through an examination of their mass-to-charge ratios. Recent advancements in deep learning have markedly enhanced the analysis of mass spectrometric data, facilitating the prediction of novel small molecule structures without the necessity of extensive databases. Nonetheless, the paucity of annotated datasets impedes the efficacious training of molecular generation models predicated on MS² spectra. To mitigate this limitation, we introduce ctMSNovelist, an avant-garde method that amalgamates pre-training, fine-tuning, and co-training techniques to construct a more precise model for the generation of molecular structures from tandem mass spectrometry data. This novel approach augments both the training regimen and the predictive accuracy of the MSNovelist model, thereby surmounting the obstacle of limited data. The methodology commences with the pretraining of a Variational Autoencoder (VAE) to generate molecular fingerprints derived from SMILES strings. Subsequently, it undergoes fine-tuning to emulate noisy fingerprints originating from mass spectrometry (MS) data. Concurrently, MSNovelist is co-trained utilizing these simulated fingerprints, inclusive of the highly noisy variants produced in the early stages of VAE training. The incorporation of a substantial volume of noisy data serves to enhance model accuracy and avert overfitting. We evaluated ctMSNovelist using the GNPS dataset and attained a SMILES prediction accuracy of 48.8%, representing a 4.1% enhancement over MSNovelist. It is pertinent to note that the sole distinction between ctMSNovelist and MSNovelist in this experiment was the training process. The code and models are publicly available at https://github.com/xfcui/ctMSNovelist.