Current challenges to virus discovery by meta-transcriptomics

Cobbin, Joanna C. A.; Charon, Justine; Harvey, Erin; Holmes, Edward C.; Mahar, Jackie E.

doi:10.1016/j.coviro.2021.09.007

Cited by 59 publications

(50 citation statements)

References 54 publications

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“…The new viral sequences identified using RdRp-scan can be used as queries for a second round of BLASTp/HMM-profile searches which in turn may illuminate new parts of the RNA virus phylogeny. Finally, the addition of de novo prediction-based structures, such as those made using AlphaFold2 49 and potentially available in AlphaFold protein structure database (https://alphafold.ebi.ac.uk/), could also be integrated to the structural-based comparison steps and are expected to enlarge the scale of structural comparison across the RNA virus phylogeny 16 .…”

Section: Resultsmentioning

confidence: 99%

“…Protein structures are up to ten times more conserved than nucleotide sequences 15 . Integrating protein structural-comparison steps into metagenomic pipelines is therefore expected to greatly extend our limit of detection 16,17 , potentially enabling the identification of sequences in the range of 10 to 30% identity (the protein “twilight zone” 13 ) and for which corresponding viruses might be referred to as the “viral dusk matter”. The viral RNA-dependent RNA polymerase (RdRp or replicase) is the most conserved protein in RNA viruses 18–20 .…”

Section: Introductionmentioning

confidence: 99%

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RdRp-scan: A Bioinformatic Resource to Identify and Annotate Divergent RNA Viruses in Metagenomic Sequence Data

Charon

Buchmann

Sadiq

et al. 2022

Preprint

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Despite a rapid expansion in the number of known RNA viruses following the advent of metagenomic sequencing, the identification and annotation of highly divergent RNA viruses remains challenging, particularly from poorly characterized hosts and environmental samples. Protein structures are more conserved than primary sequence data, such that structure-based comparisons provide an opportunity to reveal the viral “dusk matter”: viral sequences with low, but detectable, levels of sequence identity to known viruses with available protein structures. Here, we present a new open computational and resource – RdRp-scan – that contains a standardized bioinformatic toolkit to identify and annotate divergent RNA viruses in metagenomic sequence data based on the detection of RNA dependent RNA polymerase (RdRp) sequences. By combining RdRp-specific Hidden Markov models (HMM) and structural comparisons we show that RdRp-scan can efficiently detect RdRp sequences with identity levels as low as 10% to those from known viruses and not identifiable using standard sequence-to-sequence comparisons. In addition, to facilitate the annotation and placement of newly detected and divergent virus-like sequences into the known diversity of RNA viruses, RdRp-scan provides new custom and curated databases of viral RdRp sequences and core motif, as well as pre-built RdRp alignments. In parallel, our analysis of the sequence diversity detected by RdRp-scan revealed that while most of the taxonomically unassigned RdRps fell into pre-established clusters, some sequences cluster into potential new orders of RNA viruses related to the Wolframvirales and Tolivirales. Finally, a survey of the conserved A, B and C RdRp motifs within the RdRp-scan sequence database revealed additional variations of both sequence and position, which might provide new insights into the structure, function and evolution of viral RdRps.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RdRp-scan: A Bioinformatic Resource to Identify and Annotate Divergent RNA Viruses in Metagenomic Sequence Data

Charon

Buchmann

Sadiq

et al. 2022

Preprint

Self Cite

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“…Of note, since we rely on the sequence only, host assignation in our study is based on the host identified for the best BLAST match, which can be quite distantly related to our sequences. We grouped putative hosts into large families like humans, swine, or bats ( Figure 3 ), but this information should be considered as indicative, and not definitive, as some sequences may have been detected in samples that are not their replicating host, and hosts may be misidentified in databases ( Cobbin et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Human and Animal RNA Virus Diversity Detected by Metagenomics in Cameroonian Clams

et al. 2021

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Many recent pandemics have been recognized as zoonotic viral diseases. While their origins remain frequently unknown, environmental contamination may play an important role in emergence. Thus, being able to describe the viral diversity in environmental samples contributes to understand the key issues in zoonotic transmission. This work describes the use of a metagenomic approach to assess the diversity of eukaryotic RNA viruses in river clams and identify sequences from human or potentially zoonotic viruses. Clam samples collected over 2years were first screened for the presence of norovirus to verify human contamination. Selected samples were analyzed using metagenomics, including a capture of sequences from viral families infecting vertebrates (VirCapSeq-VERT) before Illumina NovaSeq sequencing. The bioinformatics analysis included pooling of data from triplicates, quality filtering, elimination of bacterial and host sequences, and a deduplication step before de novo assembly. After taxonomic assignment, the viral fraction represented 0.8–15% of reads with most sequences (68–87%) remaining un-assigned. Yet, several mammalian RNA viruses were identified. Contigs identified as belonging to the Astroviridae were the most abundant, with some nearly complete genomes of bastrovirus identified. Picobirnaviridae sequences were related to strains infecting bats, and few others to strains infecting humans or other hosts. Hepeviridae sequences were mostly related to strains detected in sponge samples but also strains from swine samples. For Caliciviridae and Picornaviridae, most of identified sequences were related to strains infecting bats, with few sequences close to human norovirus, picornavirus, and genogroup V hepatitis A virus. Despite a need to improve the sensitivity of our method, this study describes a large diversity of RNA virus sequences from clam samples. To describe all viral contaminants in this type of food, and being able to identify the host infected by viral sequences detected, may help to understand some zoonotic transmission events and alert health authorities of possible emergence.

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“…Evidence was presented on the utility of meta-transcriptomics to study different environments, demonstrating a huge phylogenetic diversity of viruses, and the identification of sediments and animal feces as rich sources of viruses. The importance of the study of ancient virus history was also stated, to get clues on the co-divergence and cross-species transmission ( Cobbin et al, 2021 ; Zhang et al, 2019 ).…”

Section: Plenary Keynote Sessionsmentioning

confidence: 99%

World Society for Virology first international conference: Tackling global virus epidemics

et al. 2022

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This communication summarizes the presentations given at the 1st international conference of the World Society for Virology (WSV) held virtually during 16–18 June 2021, under the theme of tackling global viral epidemics. The purpose of this biennial meeting is to foster international collaborations and address important viral epidemics in different hosts. The first day included two sessions exclusively on SARS-CoV-2 and COVID-19. The other two days included one plenary and three parallel sessions each. Last not least, 16 sessions covered on-demand submitted talks. In total, 270 scientists from 49 countries attended the meeting, including 40 invited keynote speakers.

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Current challenges to virus discovery by meta-transcriptomics

Cited by 59 publications

References 54 publications

RdRp-scan: A Bioinformatic Resource to Identify and Annotate Divergent RNA Viruses in Metagenomic Sequence Data

RdRp-scan: A Bioinformatic Resource to Identify and Annotate Divergent RNA Viruses in Metagenomic Sequence Data

Human and Animal RNA Virus Diversity Detected by Metagenomics in Cameroonian Clams

World Society for Virology first international conference: Tackling global virus epidemics

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