A novel transformer model of protein domains for viral taxonomy classification.
MOTIVATION: Viruses with carefully curated taxonomic assignments (such as those in the ICTV taxonomy) still represent only a small fraction of viruses identified through sequencing data from virome or microbiome projects. It is therefore critical to develop methods that can assign viruses at multiple taxonomic ranks, so that a virus deemed novel at a given rank may still be placed into a higher-level taxon. Sequence-similarity-based approaches can classify viruses that share substantial genomic similarity with known viruses (e.g. those belonging to the same species or genus); however, their performance drops significantly when applied to more divergent viruses. Recent deep learning models, such as ViTax, which utilize DNA language models, aim to address these limitations, but their performance also degrades when applied to novel viruses lacking genus-level similarity to known references. Proteins are more conserved than genomic sequences, and the multiple proteins encoded by a virus can be leveraged to reveal evolutionary relationships among viruses. RESULTS: We propose a new tool, D2T (Domain-to-Taxonomy), that leverages recent advances in protein language models to improve viral taxonomic assignment. D2T represents a virus as a sequence of protein domain tokens and learns a transformer-based model for taxonomic classification. Experiments on multiple closed-set and open-set datasets show that D2T excels at assigning higher-level taxonomic labels (family and above). Furthermore, by combining D2T with Kraken2, which performs well at the genus level, the hybrid method (K+D2T) achieves accurate viral taxonomic classification across multiple taxonomic ranks. AVAILABILITY AND IMPLEMENTATION: D2T is available as a GitHub repository at https://github.com/mgtools/D2T.