Fishing for phages in metagenomes: what do we catch, what do we miss?

Metagenomics and metatranscriptomics have become the principal approaches for discovery of novel bacteriophages and preliminary characterization of their ecology and biology. Metagenomic sequencing dramatically expanded the known diversity of tailed and non-tailed phages with double-stranded DNA genomes and those with single stranded DNA genomes, whereas metatranscriptomics led to the discovery of thousands of new single-stranded RNA phages. Apart from expanding phage diversity, metagenomics studies discover major novel groups of phages with unique features of genome organization, expression strategy and virus-host interaction, such as the putative order 'crAssvirales', which includes the most abundant human-associated viruses. The continued success of metagenomics hinges on the combination of the most powerful computational methods for phage genome assembly and analysis including harnessing CRISPR spacers for the discovery of novel phages and host assignment. Together, these approaches could make a comprehensive characterization of the earth phageome a realistic goal.