Unraveling the viral dark matter through viral metagenomics

Abstract

Viruses are part of the microbiome and have essential roles in immunology, evolution, biogeochemical cycles, health, and disease progression. Viruses influence a wide variety of systems and processes, and the continued discovery of novel viruses is anticipated to reveal new mechanisms influencing the biology of diverse environments. While the identity and roles of viruses continue to be discovered and understood through viral metagenomics, most of the sequences in virome datasets cannot be attributed to known viruses or may be only distantly related to species already described in public sequence databases, at best. Such viruses are known as the viral dark matter. Ongoing discoveries from the viral dark matter have provided insights into novel viruses from a variety of environments, as well as their potential in immunological processes, virus evolution, health, disease, therapeutics, and surveillance. Increased understanding of the viral dark matter will continue with a combination of cultivation, microscopy, sequencing, and bioinformatic efforts, which are discussed in the present review.

Viral Metagenomics as a Tool to Track Sources of Fecal Contamination: A One Health Approach

“…Viral metagenomics refers to the sequencing and analysis of DNA and/or RNA originating from viruses, also known as the virome. The first study documenting the use of viral metagenomics was published in 2002, where the technique was applied to characterize marine viromes [ 32 ], and numerous discoveries have been made using viral metagenomics over the last 20 years [ 33 ]. In addition, viral metagenomics has enabled the development of various applications that range from diagnostics to microbial source tracking, monitoring, and surveillance [ 33 ].…”

“…The first study documenting the use of viral metagenomics was published in 2002, where the technique was applied to characterize marine viromes [ 32 ], and numerous discoveries have been made using viral metagenomics over the last 20 years [ 33 ]. In addition, viral metagenomics has enabled the development of various applications that range from diagnostics to microbial source tracking, monitoring, and surveillance [ 33 ]. Generally, viral metagenomic sequencing is similar to microbiome sequencing, which usually targets bacteria and may include, but is not limited to, sample collection, sample processing, sequencing, and bioinformatics ( Figure 1 ).…”

“…Indeed, up to 99% of the sequences expected to be of viral origin cannot be taxonomically classified in certain sample types due to the high degree of sequence divergence [ 112 ]. This viral fraction lacking similarity to known viruses, and for which additional bioinformatic and cultivation efforts are needed, is known as the viral dark matter [ 33 , 113 ], and studies seeking to provide greater insight into the viral dark matter are published on a routine basis. Such studies have resulted in the discovery of crAssphage [ 36 ], and other viruses and viral groups, including corona-like viruses [ 114 ], redondoviruses [ 115 ], and candidate viral families “Quimbyviridae”, “Flandersviridae”, and “Gratiaviridae” [ 116 ].…”

Discovery of novel RNA viruses through analysis of fungi-associated next-generation sequencing data

“…In recent decades, the significant advancements in omics have transformed the field of virology and enabled researchers to detect potential viruses in a variety of environmental samples, helping us to expand the known diversity of viruses and explore the “dark matter” of viruses that may exist in vast quantities [ 4 ]. In most cases, the hosts of these newly discovered viruses exhibit only asymptomatic infections [ 5 , 6 ], and they even play an important role in maintaining the balance, stability, and sustainable development of the biosphere [ 7 ]. But some viruses may be involved in the emergence and development of animal or plant diseases.…”

Characterization and genome analysis of Vibrio phage vB_VhaP_PG11, representing a new viral genus

“…These sequences are called viral dark matter (Krishnamurthy and Wang, 2017). The discovery of viruses from dark matter usually depends on the prediction of hypothetical viruses using comparisons with the reference virus gene and genome sequences (Santiago-Rodriguez and Hollister, 2022). The reference virus genomes are often derived from sequencing results of isolated viruses.…”