Evidence map›Paper›PMID 29547634›Full record

ArticlePloS one2018

Development of a highly sensitive liquid biopsy platform to detect clinically-relevant cancer mutations at low allele fractions in cell-free DNA.

Davina Gale, Andrew R J Lawson, Karen Howarth, Mikidache Madi, Bradley Durham, Sarah Smalley, John Calaway, Shannon Blais, Greg Jones, James Clark and 16 more

Abstract readValidation Study
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing 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

94 citing papers in PubMed.

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34 more citing papers are in PubMed but not listed here.

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

26 authors.

Davina GaleInivata Ltd, Granta Park, Cambridge, United Kingdom.ORCID 0000-0002-4521-8199
Andrew R J LawsonInivata Ltd, Granta Park, Cambridge, United Kingdom.
Karen HowarthInivata Ltd, Granta Park, Cambridge, United Kingdom.
Mikidache MadiInivata Ltd, Granta Park, Cambridge, United Kingdom.
Bradley DurhamInivata Ltd, Granta Park, Cambridge, United Kingdom.
Sarah SmalleyInivata Inc, Research Triangle Park, NC, United States of America.
John CalawayInivata Inc, Research Triangle Park, NC, United States of America.
Shannon BlaisInivata Inc, Research Triangle Park, NC, United States of America.
Greg JonesInivata Inc, Research Triangle Park, NC, United States of America.
James ClarkInivata Ltd, Granta Park, Cambridge, United Kingdom.
Peter DimitrovInivata Ltd, Granta Park, Cambridge, United Kingdom.
Michelle PughInivata Ltd, Granta Park, Cambridge, United Kingdom.
Samuel WoodhouseInivata Ltd, Granta Park, Cambridge, United Kingdom.
Michael EpsteinInivata Ltd, Granta Park, Cambridge, United Kingdom.
Ana Fernandez-GonzalezLGC, Teddington, Middlesex, United Kingdom.
Alexandra S WhaleLGC, Teddington, Middlesex, United Kingdom.
Jim F HuggettLGC, Teddington, Middlesex, United Kingdom.
Carole A FoyLGC, Teddington, Middlesex, United Kingdom.
Gerwyn M JonesLGC, Teddington, Middlesex, United Kingdom.
Hadas Raveh-AmitHorizon Discovery, Waterbeach, Cambridge, United Kingdom.
Karin SchmittHorizon Discovery, Waterbeach, Cambridge, United Kingdom.
Alison DevonshireLGC, Teddington, Middlesex, United Kingdom.
Emma GreenInivata Ltd, Granta Park, Cambridge, United Kingdom.
Tim ForshewInivata Ltd, Granta Park, Cambridge, United Kingdom.
Vincent PlagnolInivata Ltd, Granta Park, Cambridge, United Kingdom.
Nitzan RosenfeldInivata Ltd, Granta Park, Cambridge, United Kingdom.

Funding

Cancer Research UK 20240
6 · The paper itself

Abstract

introductionDetection and monitoring of circulating tumor DNA (ctDNA) is rapidly becoming a diagnostic, prognostic and predictive tool in cancer patient care. A growing number of gene targets have been identified as diagnostic or actionable, requiring the development of reliable technology that provides analysis of multiple genes in parallel. We have developed the InVision™ liquid biopsy platform which utilizes enhanced TAm-Seq™ (eTAm-Seq™) technology, an amplicon-based next generation sequencing method for the identification of clinically-relevant somatic alterations at low frequency in ctDNA across a panel of 35 cancer-related genes. MATERIALS AND

methodsWe present analytical validation of the eTAm-Seq technology across two laboratories to determine the reproducibility of mutation identification. We assess the quantitative performance of eTAm-Seq technology for analysis of single nucleotide variants in clinically-relevant genes as compared to digital PCR (dPCR), using both established DNA standards and novel full-process control material.

resultsThe assay detected mutant alleles down to 0.02% AF, with high per-base specificity of 99.9997%. Across two laboratories, analysis of samples with optimal amount of DNA detected 94% mutations at 0.25%-0.33% allele fraction (AF), with 90% of mutations detected for samples with lower amounts of input DNA.

conclusionsThese studies demonstrate that eTAm-Seq technology is a robust and reproducible technology for the identification and quantification of somatic mutations in circulating tumor DNA, and support its use in clinical applications for precision medicine.

Indexed as

MutationAdultAllelesBiomarkers, TumorCell-Free Nucleic AcidsCirculating Tumor DNADNA Mutational AnalysisDNA, NeoplasmFemaleHigh-Throughput Nucleotide SequencingHumansLiquid BiopsyMaleNeoplasmsNeoplastic Cells, CirculatingPolymerase Chain ReactionBiomarkers, TumorCell-Free Nucleic AcidsCirculating Tumor DNADNA, Neoplasm

Identifiers

PMID29547634
PMCPMC5856404

What OpenQuestion holds

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LicenceCC BY
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.