Evidence map›Paper›PMID 26659206›Full record

ArticleJournal of clinical microbiology2016

Detection of Rare Drug Resistance Mutations by Digital PCR in a Human Influenza A Virus Model System and Clinical Samples.

Alexandra S Whale, Claire A Bushell, Paul R Grant, Simon Cowen, Ion Gutierrez-Aguirre, Denise M O'Sullivan, Jana Žel, Mojca Milavec, Carole A Foy, Eleni Nastouli and 2 more

Abstract read
In one paragraph

Article in Journal of clinical microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
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

29 citing papers in PubMed.

  1. Article
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  15. Rapid Methods for Antimicrobial Resistance Diagnostics.Antibiotics (Basel, Switzerland) · 2021
    Review
  16. Digital PCR is a sensitive new technique for SARS-CoV-2 detection in clinical applications.Clinica chimica acta; international journal of clinical chemistry · 2020
    Article
  17. Article
  18. Article
  19. Influenza and antiviral resistance: an overview.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020
    Review
  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

12 authors.

Alexandra S WhaleMolecular and Cell Biology Team, LGC, Teddington, United Kingdom alexandra.whale@lgcgroup.com.
Claire A BushellMolecular and Cell Biology Team, LGC, Teddington, United Kingdom.
Paul R GrantVirology Laboratory, Clinical Microbiology and Virology, University College London Hospital NHS Foundation Trust, London, United Kingdom.
Simon CowenStatistics Team, LGC, Teddington, United Kingdom.
Ion Gutierrez-AguirreNational Institute of Biology, Ljubljana, Slovenia.
Denise M O'SullivanMolecular and Cell Biology Team, LGC, Teddington, United Kingdom.
Jana ŽelNational Institute of Biology, Ljubljana, Slovenia.
Mojca MilavecNational Institute of Biology, Ljubljana, Slovenia.
Carole A FoyMolecular and Cell Biology Team, LGC, Teddington, United Kingdom.
Eleni NastouliVirology Laboratory, Clinical Microbiology and Virology, University College London Hospital NHS Foundation Trust, London, United Kingdom.
Jeremy A GarsonDepartment of Infection, Division of Infection and Immunity, University College London, London, United Kingdom.
Jim F HuggettMolecular and Cell Biology Team, LGC, Teddington, United Kingdom Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Digital PCR (dPCR) is being increasingly used for the quantification of sequence variations, including single nucleotide polymorphisms (SNPs), due to its high accuracy and precision in comparison with techniques such as quantitative PCR (qPCR) and melt curve analysis. To develop and evaluate dPCR for SNP detection using DNA, RNA, and clinical samples, an influenza virus model of resistance to oseltamivir (Tamiflu) was used. First, this study was able to recognize and reduce off-target amplification in dPCR quantification, thereby enabling technical sensitivities down to 0.1% SNP abundance at a range of template concentrations, a 50-fold improvement on the qPCR assay used routinely in the clinic. Second, a method was developed for determining the false-positive rate (background) signal. Finally, comparison of dPCR with qPCR results on clinical samples demonstrated the potential impact dPCR could have on clinical research and patient management by earlier (trace) detection of rare drug-resistant sequence variants. Ultimately this could reduce the quantity of ineffective drugs taken and facilitate early switching to alternative medication when available. In the short term such methods could advance our understanding of microbial dynamics and therapeutic responses in a range of infectious diseases such as HIV, viral hepatitis, and tuberculosis. Furthermore, the findings presented here are directly relevant to other diagnostic areas, such as the detection of rare SNPs in malignancy, monitoring of graft rejection, and fetal screening.

Indexed as

Drug Resistance, ViralMutationAntiviral AgentsGenes, ViralHumansInfluenza A virusInfluenza A Virus, H1N1 SubtypeInfluenza, HumanMolecular TypingOseltamivirPolymorphism, Single NucleotideReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSensitivity and SpecificityAntiviral AgentsOseltamivir

Identifiers

PMID26659206
PMCPMC4733194

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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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.