Global overview and major challenges of host prediction methods for uncultivated phages

Bacterial communities play critical roles across all of Earth's biomes, affecting human health and global ecosystem functioning. They do so under strong constraints exerted by viruses, that is, bacteriophages or 'phages'. Phages can reshape bacterial communities' structure, influence long-term evolution of bacterial populations, and alter host cell metabolism during infection. Metagenomics approaches, that is, shotgun sequencing of environmental DNA or RNA, recently enabled large-scale exploration of phage genomic diversity, yielding several millions of phage genomes now to be further analyzed and characterized. One major challenge however is the lack of direct host information for these phages. Several methods and tools have been proposed to bioinformatically predict the potential host(s) of uncultivated phages based only on genome sequence information. Here we review these different approaches and highlight their distinct strengths and limitations. We also outline complementary experimental assays which are being proposed to validate and refine these bioinformatic predictions.

Automated summary

Bacterial communities play critical roles in Earth's biomes, influenced by viruses like bacteriophages. Metagenomics approaches have enabled exploration of phage genomic diversity, but a major challenge is the lack of direct host information. Various methods and experimental assays are being used to validate and refine predictions for uncultivated phages.