Phage quest: a beginner's guide to explore viral diversity in the prokaryotic world.

Abstract

The increasing interest in finding new viruses within (meta)genomic datasets has fueled the development of computational tools for virus detection and characterization from environmental samples. One key driver is phage therapy, the treatment of drug-resistant bacteria with tailored bacteriophage cocktails. Yet, keeping up with the growing number of automated virus detection and analysis tools has become increasingly difficult. Both phage biologists with limited bioinformatics expertise and bioinformaticians with little background in virus biology will benefit from this guide. It focuses on navigating routine tasks and tools related to (pro)phage detection, gene annotation, taxonomic classification, and other downstream analyses. We give a brief historical overview of how detection methods evolved, starting with early sequence-composition assessments to today's powerful machine-learning and deep learning techniques, including emerging language models capable of mining large, fragmented, and compositionally diverse metagenomic datasets. We also discuss tools specifically aimed at detecting filamentous phages (Inoviridae), a challenge for most phage predictors. Rather than providing an exhaustive list, we emphasize actively maintained and state-of-the-art tools that are accessible via web or command-line interfaces. This guide provides basic concepts and useful details about automated phage analysis for researchers in different biological and medical disciplines, helping them choose and apply appropriate tools for their quest to explore the genetic diversity and biology of the smallest and most abundant replicators on Earth.