Evidence map›Paper›PMID 27060140›Full record

ArticleNucleic acids research2016

Simple, multiplexed, PCR-based barcoding of DNA enables sensitive mutation detection in liquid biopsies using sequencing.

Anders Ståhlberg, Paul M Krzyzanowski, Jennifer B Jackson, Matthew Egyud, Lincoln Stein, Tony E Godfrey

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
7.6field-weighted citation impact, top 2% 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

66 citing papers in PubMed, 145 citations in OpenAlex.

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  15. Scalable Combinatorial Assembly of Synthetic DNA for Tracking Applications.International journal of molecular sciences · 2023
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  19. Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
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6 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

6 authors at 3 institutions in 3 countries.

Anders StåhlbergDepartment of Surgery, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA Department of Pathology, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 1F, 405 30 Gothenberg, Sweden anders.stahlberg@gu.se.
Paul M KrzyzanowskiOntario Institute for Cancer Research, MaRS Centre, 661 University Avenue, Suite 510, Toronto, Ontario M5G 0A3, Canada.
Jennifer B JacksonDepartment of Surgery, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA.
Matthew EgyudDepartment of Surgery, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA.
Lincoln SteinOntario Institute for Cancer Research, MaRS Centre, 661 University Avenue, Suite 510, Toronto, Ontario M5G 0A3, Canada.
Tony E GodfreyDepartment of Surgery, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA godfreyt@bu.edu.
Boston University · USOntario Institute for Cancer Research · CAUniversity of Gothenburg · SE

Funding

Innovative approach to cancer detection and treatment monitoringR21CA172999 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GODFREY, TONY E · 2013 to 2014
$397k
NCI NIH HHS R21 CA172999
6 · The paper itself

Abstract

Detection of cell-free DNA in liquid biopsies offers great potential for use in non-invasive prenatal testing and as a cancer biomarker. Fetal and tumor DNA fractions however can be extremely low in these samples and ultra-sensitive methods are required for their detection. Here, we report an extremely simple and fast method for introduction of barcodes into DNA libraries made from 5 ng of DNA. Barcoded adapter primers are designed with an oligonucleotide hairpin structure to protect the molecular barcodes during the first rounds of polymerase chain reaction (PCR) and prevent them from participating in mis-priming events. Our approach enables high-level multiplexing and next-generation sequencing library construction with flexible library content. We show that uniform libraries of 1-, 5-, 13- and 31-plex can be generated. Utilizing the barcodes to generate consensus reads for each original DNA molecule reduces background sequencing noise and allows detection of variant alleles below 0.1% frequency in clonal cell line DNA and in cell-free plasma DNA. Thus, our approach bridges the gap between the highly sensitive but specific capabilities of digital PCR, which only allows a limited number of variants to be analyzed, with the broad target capability of next-generation sequencing which traditionally lacks the sensitivity to detect rare variants.

Indexed as

DNA Barcoding, TaxonomicDNA Mutational AnalysisMultiplex Polymerase Chain ReactionMutationBiopsyCell LineDNA PrimersGene LibraryHigh-Throughput Nucleotide SequencingHumansReproducibility of ResultsSensitivity and SpecificitySequence Analysis, DNADNA Primers

Identifiers

PMID27060140
PMCPMC4914102
OpenAlexW2323555810

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.