Evidence map›Paper›PMID 23985916›Full record

ArticleJournal of clinical microbiology2013

Detection of cytomegalovirus drug resistance mutations by next-generation sequencing.

Malaya K Sahoo, Martina I Lefterova, Fumiko Yamamoto, Jesse J Waggoner, Sunwen Chou, Susan P Holmes, Matthew W Anderson, Benjamin A Pinsky

Open access · bronzeAbstract readEvaluation Study
In one paragraph

Article in Journal of clinical microbiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

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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

8 authors at 2 institutions in 1 country.

Malaya K SahooDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Martina I Lefterova
Fumiko Yamamoto
Jesse J Waggoner
Sunwen Chou
Susan P Holmes
Matthew W Anderson
Benjamin A Pinsky
Stanford University · USPortland VA Medical Center · US

Funding

EMERGING INFECTIOUS DISEASEST32AI007502 · NIAID · STANFORD UNIVERSITY · PI Prasanna Jagannathan, DAVID A. RELMAN · 1995 to 2026
$6.8M
Heterogeneous in situ data: Kernals, Distances and TreesR01GM086884 · NIGMS · STANFORD UNIVERSITY · PI HOLMES, SUSAN P · 2008 to 2011
$895k
Alternative antiviral drug targets for human cytomegalovirus infectionI01BX000925 · VA · PORTLAND VA MEDICAL CENTER · PI CHOU, SUNWEN · 2011 to 2014
–
BLRD VA I01 BX000925NIAID NIH HHS T32 AI007502NIGMS NIH HHS R01 GM086884
6 · The paper itself

Abstract

Antiviral therapy for cytomegalovirus (CMV) plays an important role in the clinical management of solid organ and hematopoietic stem cell transplant recipients. However, CMV antiviral therapy can be complicated by drug resistance associated with mutations in the phosphotransferase UL97 and the DNA polymerase UL54. We have developed an amplicon-based high-throughput sequencing strategy for detecting CMV drug resistance mutations in clinical plasma specimens using a microfluidics PCR platform for multiplexed library preparation and a benchtop next-generation sequencing instrument. Plasmid clones of the UL97 and UL54 genes were used to demonstrate the low overall empirical error rate of the assay (0.189%) and to develop a statistical algorithm for identifying authentic low-abundance variants. The ability of the assay to detect resistance mutations was tested with mixes of wild-type and mutant plasmids, as well as clinical CMV isolates and plasma samples that were known to contain mutations that confer resistance. Finally, 48 clinical plasma specimens with a range of viral loads (394 to 2,191,011 copies/ml plasma) were sequenced using multiplexing of up to 24 specimens per run. This led to the identification of seven resistance mutations, three of which were present in <20% of the sequenced population. Thus, this assay offers more sensitive detection of minor variants and a higher multiplexing capacity than current methods for the genotypic detection of CMV drug resistance mutations.

Indexed as

Drug Resistance, ViralMutation, MissenseAdolescentAdultAgedAntiviral AgentsCytomegalovirusCytomegalovirus InfectionsDNA-Directed DNA PolymeraseDNA, ViralFemaleHigh-Throughput Nucleotide SequencingHumansMaleMicrobial Sensitivity TestsMiddle AgedAntiviral AgentsDNA-Directed DNA PolymeraseDNA, Viralganciclovir kinasePhosphotransferases (Alcohol Group Acceptor)UL54 protein, Human herpesvirus 5Viral Proteins

Identifiers

PMID23985916
PMCPMC3889754
OpenAlexW2120413632

What OpenQuestion holds

Textmetadata
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.