V- and V<sub>L</sub>-scores unveil viral signatures and origins of protein families.

Zhou, Kun; Kosmopoulos, James C; Colón, Etan Dieppa; Badciong, Peter John; Anantharaman, Karthik · Nat Commun · 2026

basic_science · Level V

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Abstract

Viruses are key drivers of microbial ecology and evolution, yet their study is hindered due to challenges in culturing. Traditional gene-centric methods, which focus on a few hallmark genes like for capsids, miss much of the viral genome, leaving key viral proteins and functions undiscovered. Here, we introduce two powerful annotation-free metrics, V-score and V<sub>L</sub>-score, designed to quantify the "virus-likeness" of protein families and genomes and create an open-access searchable database, 'V-Score-Search'. By applying V- and V<sub>L</sub>-scores to public protein databases, we link 19 - 59% of protein families with viruses representing a 5 - 8x increase over current estimates. These metrics outperform existing approaches, enabling high efficiency in detection of viral genomes, prophages, and host-derived auxiliary viral genes (AVGs) from fragmented sequences. Remarkably, we identify up to 17 times more AVGs dominated by non-metabolic proteins of unknown function. This innovation unlocks new insights into virus signatures and host interactions, with wide-ranging implications from genomics to biotechnology.