DepoScope: accurate phage depolymerase annotation and domain delineation using large language models

Bacteriophages (phages) are viruses that infect bacteria. Many of them produce specific enzymes called depolymerases to break down external polysaccharide structures. Accurate annotation and domain identification of these depolymerases are challenging due to their inherent sequence diversity. Hence, we present DepoScope, a machine learning tool that combines a fine-tuned ESM-2 model with a convolutional neural network to precisely identify depolymerase sequences and their enzymatic domains. To accomplish this, we curated a dataset from the INPHARED phage genome database, created a polysaccharide-degrading domain database, and applied sequential filters to construct a high-quality dataset, which are subsequently used to train DepoScope. Our work is the first approach that combines sequence-level predictions with amino-acid-level predictions for an accurate depolymerase detection and functional domain identification. In that way, we believe that DepoScope can enhance our understanding of phage-host interactions at the level of depolymerases. ### Competing Interest Statement The authors have declared no competing interest.