Genomic-Informed Heterogeneous Graph Learning for Spatiotemporal Avian Influenza Outbreak Forecasting

Accurate forecasting of Avian Influenza Virus (AIV) outbreaks within wild bird populations necessitates models that account for complex, multi-scale transmission patterns driven by diverse factors. While conventional spatiotemporal epidemic models are robust for human-centric diseases, they rely on spatial homophily and diffusive transmission between geographic regions. This simplification is incomplete for AIV as it neglects valuable genomic information critical for capturing dynamics like high-frequency reassortment and lineage turnover at the case level (e.g., genetic descent across regions), which are essential for understanding AIV spread. To address these limitations, we systematically formulate the AIV forecasting problem and propose BLUE (bi-layer genomic-aware heterogeneous graph fusion pipeline). This pipeline integrates genetic, spatial, and ecological data to achieve highly accurate outbreak forecasting. It 1) defines a multi-layered graph structure incorporating information from diverse sources and multiple layers (case and location), 2) applies cross-relation smoothing to smooth information flow across edge types, 3) performs graph fusion that preserves critical structural patterns backed by theoretical spectral guarantees, and 4) forecasts future outbreaks using an autoregressive graph sequence model to capture transmission dynamics. To support research, we release the Avian-US dataset, which provides comprehensive genetic, spatial, and ecological data on US avian influenza outbreaks. BLUE demonstrates superior performance over existing baselines, highlighting the efficacy of integrating multi-layer information for infectious disease forecasting. The code is available at: https://github.com/cruiseresearchgroup/BLUE.