DEPhT: a novel approach for efficient prophage discovery and precise extraction

Abstract

Advances in genome sequencing have produced hundreds of thousands of bacterial genome sequences, many of which have integrated prophages derived from temperate bacteriophages. These prophages play key roles by influencing bacterial metabolism, pathogenicity, antibiotic resistance, and defense against viral attack. However, they vary considerably even among related bacterial strains, and they are challenging to identify computationally and to extract precisely for comparative genomic analyses. Here, we describe DEPhT, a multimodal tool for prophage discovery and extraction. It has three run modes that facilitate rapid screening of large numbers of bacterial genomes, precise extraction of prophage sequences, and prophage annotation. DEPhT uses genomic architectural features that discriminate between phage and bacterial sequences for efficient prophage discovery, and targeted homology searches for precise prophage extraction. DEPhT is designed for prophage discovery in Mycobacterium genomes but can be adapted broadly to other bacteria. We deploy DEPhT to demonstrate that prophages are prevalent in Mycobacterium strains but are absent not only from the few well-characterized Mycobacterium tuberculosis strains, but also are absent from all ∼30 000 sequenced M. tuberculosis strains.

Systematic analysis of prophage elements in actinobacterial genomes reveals a remarkable phylogenetic diversity

“…In contrast, Virsorter2 25 completely missed this sequence and has recently been found to be less effective 29 than other prophage prediction tools, including VIBRANT 26 , PhiSpy 30 , and Phigaro 31 . Moreover, we also validated if our findings are comparable with the previously published studies on the discovered prophages present in M. abscessus genomes 16,32,33 . The resulting analysis showed high accordance in terms of the number of identified prophage sequences by our analysis using VIBRANT as compared to the DEPhT tool recently described by Gauthier et al 33 (Supplementary Table S2).…”

Mycobacteriophages: From Petri dish to patient

“…The frequency of lysogeny varies enormously depending on various parameters (e.g., growth state, multiplicity of infection), and can be as low as a few percent, or greater than 50% of infections. The prevalence of temperate phages varies depending on the host, and this is reflected in the richness of resident prophages in sequenced bacterial genomes [ 13 ]. It should be noted that some types of temperate phages do not lyse the host cell when replicating, including filamentous phages (inoviruses) such as Pseudomonas phage Pf [ 14 ].…”

Unusual prophages in Mycobacterium abscessus genomes and strain variations in phage susceptibilities

“…To identify integrated prophages in the genomes of these M . abscessus strains, each was analyzed using PHASTER [ 35 ], DEPhT [ 36 ], BLAST [ 37 ], and other bioinformatic tools. Complete prophages were identified and could be bioinformatically extracted from eleven strains as well as the type strains of M .…”

“…Bacterial genome sequences were analyzed for prophage content using PHASTER [ 35 ] and DEPhT [ 36 ], and the attB sites confirmed as described by Dedrick et al . [ 30 ].…”