SIMBA-GNN: Simulation-augmented Microbiome Abundance Graph Neural Network

Understanding gut microbiome dynamics gut requires deciphering complex, metabolically driven interactions beyond taxonomic profiles. We present<monospace>SIMBA</monospace>, a novel framework that integrates mechanistic metabolic simulations with a graph neural network (GNN) to predict microbial abundances and uncover cross-feeding relationships. By simulating pairwise interactions among gut microbes using metabolic networks, we generate biologically grounded graphs that capture metabolite cross-feeding and functional relationships. Our custom GNN, enhanced with edge-aware attention, is trained through a multi-stage pipeline combining self-supervised learning, simulation-based pretraining, and fine-tuning on real microbial abundance data.<monospace>SIMBA</monospace>achieves state-of-the-art performance (Spearman ρ = 0.85) and enables interpretable insights into keystone taxa and metabolic bottlenecks. This work demonstrates the power of combining metabolic networks with deep learning for precision microbiome analysis.