Evidence map›Paper›PMID 23303777›Full record

ArticleNucleic acids research2013

Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation.

Maura Costello, Trevor J Pugh, Timothy J Fennell, Chip Stewart, Lee Lichtenstein, James C Meldrim, Jennifer L Fostel, Dennis C Friedrich, Danielle Perrin, Danielle Dionne and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 321 papers.

0numbers the graph read from it
0cells of the map it votes in
321citing papers in PubMed
7.8field-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

321 citing papers in PubMed, 561 citations in OpenAlex.

  1. Long-term Survival and Molecular Biomarker Evaluation of a Phase II Cetuximab and Nivolumab Clinical Trial in Recurrent/Metastatic Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  6. Phase II Multicenter Study of Enzalutamide in Metastatic Castration-Resistant Prostate Cancer to Identify Mechanisms Driving Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
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261 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

15 authors at 1 institution in 1 country.

Maura CostelloBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA. costello@broadinstitute.org
Trevor J Pugh
Timothy J Fennell
Chip Stewart
Lee Lichtenstein
James C Meldrim
Jennifer L Fostel
Dennis C Friedrich
Danielle Perrin
Danielle Dionne
Sharon Kim
Stacey B Gabriel
Eric S Lander
Sheila Fisher
Gad Getz
Broad Institute · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
NHGRI NIH HHS HG03067-05NHGRI NIH HHS U54 HG003067
6 · The paper itself

Abstract

As researchers begin probing deep coverage sequencing data for increasingly rare mutations and subclonal events, the fidelity of next generation sequencing (NGS) laboratory methods will become increasingly critical. Although error rates for sequencing and polymerase chain reaction (PCR) are well documented, the effects that DNA extraction and other library preparation steps could have on downstream sequence integrity have not been thoroughly evaluated. Here, we describe the discovery of novel C > A/G > T transversion artifacts found at low allelic fractions in targeted capture data. Characteristics such as sequencer read orientation and presence in both tumor and normal samples strongly indicated a non-biological mechanism. We identified the source as oxidation of DNA during acoustic shearing in samples containing reactive contaminants from the extraction process. We show generation of 8-oxoguanine (8-oxoG) lesions during DNA shearing, present analysis tools to detect oxidation in sequencing data and suggest methods to reduce DNA oxidation through the introduction of antioxidants. Further, informatics methods are presented to confidently filter these artifacts from sequencing data sets. Though only seen in a low percentage of reads in affected samples, such artifacts could have profoundly deleterious effects on the ability to confidently call rare mutations, and eliminating other possible sources of artifacts should become a priority for the research community.

Indexed as

ArtifactsDNA DamageMutationAllelesDNAGenomicsGuanineHigh-Throughput Nucleotide SequencingHumansMelanomaOxidation-ReductionSequence Analysis, DNA8-hydroxyguanineDNAGuanine

Identifiers

PMID23303777
PMCPMC3616734
OpenAlexW2107356675

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.