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. 2018 Jan 15;244:218-229.
doi: 10.1016/j.virusres.2017.10.014. Epub 2017 Oct 18.

A Decade of RNA Virus Metagenomics Is (Not) Enough

Free PMC article

A Decade of RNA Virus Metagenomics Is (Not) Enough

Alexander L Greninger. Virus Res. .
Free PMC article


It is hard to overemphasize the role that metagenomics has had on our recent understanding of RNA virus diversity. Metagenomics in the 21st century has brought with it an explosion in the number of RNA virus species, genera, and families far exceeding that following the discovery of the microscope in the 18th century for eukaryotic life or culture media in the 19th century for bacteriology or the 20th century for virology. When the definition of success in organism discovery is measured by sequence diversity and evolutionary distance, RNA viruses win. This review explores the history of RNA virus metagenomics, reasons for the successes so far in RNA virus metagenomics, and methodological concerns. In addition, the review briefly covers clinical metagenomics and environmental metagenomics and highlights some of the critical accomplishments that have defined the fast pace of RNA virus discoveries in recent years. Slightly more than a decade in, the field is exhausted from its discoveries but knows that there is yet even more out there to be found.

Keywords: Conjoined circles; Metagenomics; RNA virus; Viral discovery.


Fig. 1
Fig. 1
Growth everywhere. Publications by year for “RNA virus metagenomics” (A) and “virome” (B) over the past decade using the “Results by Year” graph from Pubmed. Number of viral species (C), genera (D), and families (E) assigned by the ICTV over the past four decades (ICTV, 2017a, ICTV, 2017b). Changepoint analysis with the “at most one change” statistical test was significant at year 1996 for genera and family data and 2015 for species data (“changepoint, ” n.d.).
Fig. 2
Fig. 2
The conjoined circles of metagenomic success. The increased output of modern-day sequencers has led to increased metagenomic sequencing of samples, both environmental and clinical. This in turn has led to an explosion in the NCBI Genbank and WGS databases. New discoveries beget the discovery of more divergent new viruses and organisms as they are now alignable to new references in the database. Rather than searching through gapped alignments, the increased coverage of the Genbank reference database allows for more exact k-mer searching, which allows for faster, more sensitive alignments of reads. This in turn makes metagenomic sequencing more useful, especially in the clinic, which in turn begets more sequencing.

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