Evidence map›Paper›PMID 31100083›Full record

ArticlePloS one2019

Identification and quantification of defective virus genomes in high throughput sequencing data using DVG-profiler, a novel post-sequence alignment processing algorithm.

Trent J Bosma, Konstantinos Karagiannis, Luis Santana-Quintero, Natalia Ilyushina, Tatiana Zagorodnyaya, Svetlana Petrovskaya, Majid Laassri, Raymond P Donnelly, Steven Rubin, Vahan Simonyan and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 33 citations in OpenAlex.

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  12. The ageing virus hypothesis: Epigenetic ageing beyond the Tree of Life.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  13. Article
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  19. High-resolution mapping reveals the mechanism and contribution of genome insertions and deletions to RNA virus evolution.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Trent J BosmaDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Konstantinos KaragiannisDepartment of Biochemistry and Molecular Medicine, George Washington University Medical Center, Washington, DC, United States of America.
Luis Santana-QuinteroOffice of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.ORCID 0000-0002-4290-1021
Natalia IlyushinaDivision of Biotechnology Review and Research II, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.ORCID 0000-0001-8178-0472
Tatiana ZagorodnyayaDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Svetlana PetrovskayaDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Majid LaassriDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Raymond P DonnellyDivision of Biotechnology Review and Research II, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Steven RubinDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Vahan SimonyanOffice of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Christian J SauderDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.ORCID 0000-0001-5490-402X
Center for Biologics Evaluation and Research · USCenter for Drug Evaluation and Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Most viruses are known to spontaneously generate defective viral genomes (DVG) due to errors during replication. These DVGs are subgenomic and contain deletions that render them unable to complete a full replication cycle in the absence of a co-infecting, non-defective helper virus. DVGs, especially of the copyback type, frequently observed with paramyxoviruses, have been recognized to be important triggers of the antiviral innate immune response. DVGs have therefore gained interest for their potential to alter the attenuation and immunogenicity of vaccines. To investigate this potential, accurate identification and quantification of DVGs is essential. Conventional methods, such as RT-PCR, are labor intensive and will only detect primer sequence-specific species. High throughput sequencing (HTS) is much better suited for this undertaking. Here, we present an HTS-based algorithm called DVG-profiler to identify and quantify all DVG sequences in an HTS data set generated from a virus preparation. DVG-profiler identifies DVG breakpoints relative to a reference genome and reports the directionality of each segment from within the same read. The specificity and sensitivity of the algorithm was assessed using both in silico data sets as well as HTS data obtained from parainfluenza virus 5, Sendai virus and mumps virus preparations. HTS data from the latter were also compared with conventional RT-PCR data and with data obtained using an alternative algorithm. The data presented here demonstrate the high specificity, sensitivity, and robustness of DVG-profiler. This algorithm was implemented within an open source cloud-based computing environment for analyzing HTS data. DVG-profiler might prove valuable not only in basic virus research but also in monitoring live attenuated vaccines for DVG content and to assure vaccine lot to lot consistency.

Indexed as

AlgorithmsGenome, ViralAnimalsChromosome MappingDatasets as TopicDefective VirusesDNA PrimersHigh-Throughput Nucleotide SequencingHumansMolecular TypingMumps virusParainfluenza Virus 5Real-Time Polymerase Chain ReactionSendai virusSensitivity and SpecificityDNA Primers

Identifiers

PMID31100083
PMCPMC6524942
OpenAlexW2945572186

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.