Background
Influenza A virus (IAV) poses a significant threat to animal health globally, with its ability to overcome species barriers and cause pandemics. Rapid and accurate IAV subtypes and host source prediction is crucial for effective surveillance and pandemic preparedness. Deep learning has emerged as a powerful tool for analyzing viral genomic sequences, offering new ways to uncover hidden patterns associated with viral characteristics and host adaptation.

Findings
We introduce WaveSeekerNet, a novel deep learning model for accurate and rapid prediction of IAV subtypes and host source. The model leverages attention-based mechanisms and efficient token mixing schemes, including the Fourier Transform and the Wavelet Transform, to capture intricate patterns within viral RNA and protein sequences. Extensive experiments on diverse datasets demonstrate WaveSeekerNet’s superior performance to existing models that use the traditional self-attention mechanism. Notably, WaveSeekerNet rivals VADR (Viral Annotation DefineR) in subtype prediction using the high-quality RNA sequences, achieving the maximum score of 1.0 on metrics, including the Balanced Accuracy, F1-score (Macro Average), and Matthews Correlation Coefficient. Our approach to subtype and host source prediction also exceeds the pretrained ESM-2 (Evolutionary Scale Modeling) models with respect to generalization performance and computational cost. Furthermore, WaveSeekerNet exhibits remarkable accuracy in distinguishing between human, avian, and other mammalian hosts. The ability of WaveSeekerNet to flag potential cross-species transmission events underscores its significant value for real-time surveillance and proactive pandemic preparedness efforts.

Conclusions
WaveSeekerNet’s superior performance, efficiency, and ability to flag potential cross-species transmission events highlight its potential for real-time surveillance and pandemic preparedness. This model represents a significant advancement in applying deep learning for IAV classification and holds promise for future epidemiological, veterinary studies, and public health interventions.