An Ensemble Spectral Prediction (ESP) model for metabolite annotation.

motivationA key challenge in metabolomics is annotating measured spectra from a biological sample with chemical identities. Currently, only a small fraction of measurements can be assigned identities. Two complementary computational approaches have emerged to address the annotation problem: mapping candidate molecules to spectra, and mapping query spectra to molecular candidates. In essence, the candidate molecule with the spectrum that best explains the query spectrum is recommended as the target molecule. Despite candidate ranking being fundamental in both approaches, limited prior works incorporated rank learning tasks in determining the target molecule.

resultsWe propose a novel machine learning model, Ensemble Spectral Prediction (ESP), for metabolite annotation. ESP takes advantage of prior neural network-based annotation models that utilize multilayer perceptron (MLP) networks and Graph Neural Networks (GNNs). Based on the ranking results of the MLP- and GNN-based models, ESP learns a weighting for the outputs of MLP and GNN spectral predictors to generate a spectral prediction for a query molecule. Importantly, training data is stratified by molecular formula to provide candidate sets during model training. Further, baseline MLP and GNN models are enhanced by considering peak dependencies through label mixing and multi-tasking on spectral topic distributions. When trained on the NIST 2020 dataset and evaluated on the relevant candidate sets from PubChem, ESP improves average rank by 23.7% and 37.2% over the MLP and GNN baselines, respectively, demonstrating performance gain over state-of-the-art neural network approaches. However, MLP approaches remain strong contenders when considering top five ranks. Importantly, we show that annotation performance is dependent on the training dataset, the number of molecules in the candidate set and candidate similarity to the target molecule. AVAILABILITY AND IMPLEMENTATION: The ESP code, a trained model, and a Jupyter notebook that guide users on using the ESP tool is available at https://github.com/HassounLab/ESP.