VBayesMM: Variational Bayesian neural network to prioritize important relationships of high-dimensional microbiome multiomics data

The analysis of high-dimensional microbiome multiomics datasets is crucial for understanding the complex interactions between microbial communities and host physiological states across health and disease conditions. Despite their importance, current methods such as the microbe–metabolite vectors (MMvec) approach, often fail to efficiently identify keystone species. This arises from the vast dimensionality of metagenomics data which complicates the inference of significant relationships, particularly the estimation of co-occurrence probabilities between microbes and metabolites. Here we propose the variational Bayesian microbiome multiomics (VBayesMM) approach, which enhances MMvec by incorporating a spike-and-slab prior within a Bayesian neural network. This allows VBayesMM to rapidly and precisely identify crucial microbial species, improving the accuracy of estimated co-occurrence probabilities between microbes and metabolites, while also robustly managing the uncertainty inherent in high-dimensional data. Moreover, we have implemented variational inference to address computational bottlenecks, enabling scalable analysis across extensive multiomics datasets. Our comparative evaluation of large-scale human and mouse multiomics datasets demonstrates that VBayesMM not only outperforms existing methods in accuracy but also provides a scalable solution for analyzing massive datasets. VBayesMM enhances the interpretability of the Bayesian neural network by identifying a core set of influential microbial species, thus facilitating a deeper understanding of their probabilistic relationships with the host.