Using Shared Features Improves Metabolite Effect Estimation

Abstract

External biological knowledge provides valuable information about relationships among metabolites, yet this information is usually not incorporated directly into statistical estimation procedures. Most existing approaches estimate metabolite effects independently, ignoring known biochemical structure such as shared subclasses and pathway membership. We propose a Bayesian hierarchical framework that improves metabolite effect estimates by incorporating external biological information describing relationships among metabolites. The proposed method improves metabolite-specific estimates by allowing related metabolites to borrow information from one another while preserving metabolite-level inference. We evaluate the methodology using simulation studies across a range of sample sizes and heterogeneity regimes together with three metabolomics applications involving distinct biological annotation structures. Across both simulated and real datasets, incorporating external biological information consistently improves metabolite effect estimation. Gains are most pronounced when sample sizes are small and metabolite classes are informative, i.e. more homogenous within classes.