ViTax: adaptive hierarchical viral taxonomy classification with a taxonomy belief tree on a foundation model

Viruses exert a profound influence on both human health and the global ecosystem, yet they remain largely unexplored. Precise taxonomic classification of viral sequences is essential for discovering novel viruses, elucidating their functions, and assessing their implications for public health and environmental monitoring. Traditional taxonomy methods based on genome references are limited by the vast number of unexplored viruses, rapid mutation rates, and high genetic diversity. Additionally, highly imbalanced species distribution and significant variances in inter-species genomic distances across taxonomic units pose challenges to classifier training. Conceptualizing genomic sequences as sentences in a natural language, large language models provide novel approaches for extracting intrinsic viral genome characteristics. In this study, we introduce ViTax, a virus taxonomy classification tool powered by HyenaDNA, a large language foundation model for long-range genomic sequences at single nucleotide resolution. ViTax integrates supervised prototypical contrastive learning to address the highly imbalanced distributions across various taxonomic clades and demonstrates superior performance to current leading methods in virus taxonomy, particularly significant for long sequences. Moreover, ViTax designs a belief mapping tree using the Lowest Common Ancestor algorithm to adaptively assign a sequence to the lowest taxonomy clade with confidence. For the open-set problem, where sequences belong to novel and unexplored genera, ViTax can adaptively assign them to a higher level of known taxonomy with outstanding performance. These capabilities make ViTax a robust tool for advancing the accuracy and reliability of viral taxonomy classification. The code is available at https://github.com/Ying-Lab/ViTax.