What Lies Beneath? Taking the Plunge into the Murky Waters of Phage Biology

The sequence revolution revealed that bacteria-infecting viruses, known as phages, are Earth’s most abundant biological entities. Phages have far-reaching impacts on the form and function of microbial communities and play a fundamental role in ecological processes. However, even well into the sequencing revolution, we have only just begun to explore the murky waters around the phage biology iceberg. Many viral reads cannot be assigned to a culturable isolate, and reference databases are biased toward more easily collectible samples, which likely distorts our conclusions. This minireview points out alternatives to mapping reads to reference databases and highlights innovative bioinformatic and experimental approaches that can help us overcome some of the challenges in phage research and better decipher the impact of phages on microbial communities. Moving beyond the identification of novel phages, we highlight phage metabolomics as an important influencer of bacterial host cell physiology and hope to inspire the reader to consider the effects of phages on host metabolism and ecosystems at large. We encourage researchers to report unassigned/unknown sequencing reads and contigs and to continue developing alternative methods to investigate phages within sequence data.