Origins and challenges of viral dark matter

Krishnamurthy, Siddharth R.; Wang, David

doi:10.1016/j.virusres.2017.02.002

Cited by 192 publications

(174 citation statements)

References 71 publications

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“…14,41 Thus, while the specific immune mechanisms responsible for regulating Anelloviridae in vivo are unknown, it has been proposed that monitoring levels in blood might serve as a "functional" measure of immune activity to manage organ transplant immunosuppression. Individual recipients where there was significant detection of these perioperative lineages in either BAL (A) or serum (B) are indicated by the asterisk (P < .05; Wilcoxon Rank Sum Test) 25,54 Illuminating this viral dark matter may reveal uncharacterized viruses that may play a role in lung health and disease. In addition, a novel observation here is that Anelloviridae within the lung allograft are also relatively de- A value of 1 is highly uneven coverage suggesting lack of detection while 0 is even coverage across the genome suggesting highly confident detection.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional transfer of Anelloviridae lineages between graft and host during lung transplantation

Abbas

Young

Clarke

et al. 2019

American Journal of Transplantation

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Solid organ transplantation disrupts virus-host relationships, potentially resulting in viral transfer from donor to recipient, reactivation of latent viruses, and new viral infections. Viral transfer, colonization, and reactivation are typically monitored using assays for specific viruses, leaving the behavior of full viral populations (the "virome") understudied. Here we sought to investigate the temporal behavior of viruses from donor lungs and transplant recipients comprehensively. We interrogated the bronchoalveolar lavage and blood viromes during the peritransplant period and 6-16 months posttransplant in 13 donor-recipient pairs using shotgun metagenomic sequencing. Anelloviridae, ubiquitous human commensal viruses, were the most abundant human viruses identified. Herpesviruses, parvoviruses, polyomaviruses, and bacteriophages were also detected. Anelloviridae populations were complex, with some donor organs and hosts harboring multiple contemporaneous lineages. We identified transfer of Anelloviridae lineages from donor organ to recipient serum in 4 of 7 cases that could be queried, and immigration of lineages from recipient serum into the allograft in 6 of 10 such cases. Thus, metagenomic analyses revealed that viral populations move between graft and host in both directions, showing that organ transplantation involves implantation of both the allograft and commensal viral communities.

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Section: Discussionmentioning

confidence: 99%

Bidirectional transfer of Anelloviridae lineages between graft and host during lung transplantation

Abbas

Young

Clarke

et al. 2019

American Journal of Transplantation

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“…One challenge is that, among a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 those that are alignable to reference viruses, sequences can be misclassified due to the remoteness of the similarity and/or low stringency. An even more significant problem is that in most virome studies, more than 50% of the sequences in virus-enriched preparations have no detectable sequence similarity to any known reference sequences; these unalignable sequences are referred to as viral "dark matter" [8] and may include novel, highly divergent viruses that are unrecognizable. Thus, most current virome studies are presenting only a partial view of the virome because the dark matter sequences are typically ignored.…”

Section: Inability To Identify All Viruses Due To the Absence Of A Unmentioning

confidence: 99%

5 challenges in understanding the role of the virome in health and disease

Wang

2020

PLoS Pathog

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“…No doubt the 'virtuous cycle' of metagenomic sequencing will only increase in breadth and depth in the coming years with a concomitant growth of new bioinformatic algorithms leading to discovery of even more new organisms and further decrease in so-called unalignable viral "dark matter" (Fig. 2) Krishnamurthy and Wang, 2017). Turning the crank on RNA virus discovery metagenomics is now the provenance of undergraduate theses Shean et al, 2017;Zaaijer et al, 2016).…”

Section: Remaining Frontiersmentioning

confidence: 99%

A decade of RNA virus metagenomics is (not) enough

2018

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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.

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Origins and challenges of viral dark matter

Cited by 192 publications

References 71 publications

Bidirectional transfer of Anelloviridae lineages between graft and host during lung transplantation

Bidirectional transfer of Anelloviridae lineages between graft and host during lung transplantation

5 challenges in understanding the role of the virome in health and disease

A decade of RNA virus metagenomics is (not) enough

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