Interpretable Machine Learning on Metabolomics Data Reveals Biomarkers for Parkinson’s Disease

[Image: see text] The use of machine learning (ML) with metabolomics provides opportunities for the early diagnosis of disease. However, the accuracy of ML and extent of information obtained from metabolomics can be limited owing to challenges associated with interpreting disease prediction models and analyzing many chemical features with abundances that are correlated and “noisy”. Here, we report an interpretable neural network (NN) framework to accurately predict disease and identify significant biomarkers using whole metabolomics data sets without a priori feature selection. The performance of the NN approach for predicting Parkinson’s disease (PD) from blood plasma metabolomics data is significantly higher than other ML methods with a mean area under the curve of >0.995. PD-specific markers that predate clinical PD diagnosis and contribute significantly to early disease prediction were identified including an exogenous polyfluoroalkyl substance. It is anticipated that this accurate and interpretable NN-based approach can improve diagnostic performance for many diseases using metabolomics and other untargeted ‘omics methods.