Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec 1;2(4):214-223.
doi: 10.1089/phage.2021.0007. Epub 2021 Dec 16.

INfrastructure for a PHAge REference Database: Identification of Large-Scale Biases in the Current Collection of Cultured Phage Genomes

Ryan Cook  1 , Nathan Brown  2 , Tamsin Redgwell  3 , Branko Rihtman  4 , Megan Barnes  2 , Martha Clokie  2 , Dov J Stekel  5 , Jon Hobman  5 , Michael A Jones  1 , Andrew Millard  2
Affiliations

INfrastructure for a PHAge REference Database: Identification of Large-Scale Biases in the Current Collection of Cultured Phage Genomes

Ryan Cook et al. Phage (New Rochelle). .

Abstract

Background: With advances in sequencing technology and decreasing costs, the number of phage genomes that have been sequenced has increased markedly in the past decade. Materials and Methods: We developed an automated retrieval and analysis system for phage genomes (https://github.com/RyanCook94/inphared) to produce the INfrastructure for a PHAge REference Database (INPHARED) of phage genomes and associated metadata. Results: As of January 2021, 14,244 complete phage genomes have been sequenced. The INPHARED data set is dominated by phages that infect a small number of bacterial genera, with 75% of phages isolated on only 30 bacterial genera. There is further bias, with significantly more lytic phage genomes (∼70%) than temperate (∼30%) within our database. Collectively, this results in ∼54% of temperate phage genomes originating from just three host genera. With much debate on the carriage of antibiotic resistance genes and their potential safety in phage therapy, we searched for putative antibiotic resistance genes. Frequency of antibiotic resistance gene carriage was found to be higher in temperate phages than in lytic phages and again varied with host. Conclusions: Given the bias of currently sequenced phage genomes, we suggest to fully understand phage diversity, efforts should be made to isolate and sequence a larger number of phages, in particular temperate phages, from a greater diversity of hosts.

Keywords: antibiotic resistance genes; jumbo phages; phage genomes; virulence genes.

PubMed Disclaimer

Conflict of interest statement

No competing financial interests exist.

Figures

FIG. 1.
FIG. 1.
Number of complete phage genomes in GenBank over time. Dates were estimated based on date of submission (for 235 genomes, the date of update was used as no submission date was available). The reference lines showing doubling rates (dashed) begin in 1989, as this is when the number of phage genomes increased beyond the first submission in 1982.
FIG. 2.
FIG. 2.
Overall properties of phages. (A) Proportion of phages isolated on the top 30 most abundant hosts. (B) Distribution of phage genome sizes with colors indicating Baltimore group and labels indicating typical phages for prominent peaks. (C) Proportion of “jumbo phages” on top 30 hosts for which at least one “jumbo phage” has been isolated with the total number of phages isolated against that host shown in brackets after its name.
FIG. 3.
FIG. 3.
Genomic diversity of phages on the top 10 most abundant hosts. (A) Rarefaction curve of phage genera. Genera were defined by vConTACT2 clustering. (B) Rarefaction curve of phage species. Species were defined as 95% identity over 95% of genome length.
FIG. 4.
FIG. 4.
Phylogenetic tree of translated terL gene for 313 “jumbo phages” and their closest relatives. The alignment was produced using MAFFT and tree produced using IQTree using WAG model with 1000 bootstrap repeats. Colored regions indicate viral clades, colored rings indicate viral genus, subfamily, and family (innermost to outermost), and bars indicate genome length with blue and orange bars belonging to nonjumbo and “jumbo” phages, respectively. Bootstrap values indicated by black circles are scaled to the bootstrap value, with a minimum value of 70% displayed.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Suttle CA. Marine viruses—major players in the global ecosystem. Nat Rev Microbiol. 2007;5:801–812. - PubMed
    1. Puxty RJ, Millard AD, Evans DJ, et al. . Viruses inhibit CO2 fixation in the most abundant phototrophs on Earth. Curr Biol. 2016;26:1585–1589. - PubMed
    1. Norman JM, Handley SA, Baldridge MT, et al. . Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell. 2015;160(3):P447–P460. - PMC - PubMed
    1. Monaco CL, Gootenberg DB, Zhao G, et al. . Altered virome and bacterial microbiome in human immunodeficiency virus-associated acquired immunodeficiency syndrome. Cell Host Microbe. 2016;19(3):P311–P322. - PMC - PubMed
    1. Reyes A, Blanton LV., Cao S, et al. . Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc Natl Acad Sci U S A. 2015;112(38):11941–11946. - PMC - PubMed

LinkOut - more resources

-