Evidence map›Paper›PMID 29718339›Full record

ArticleNucleic acids research2018

High-resolution mapping of DNA polymerase fidelity using nucleotide imbalances and next-generation sequencing.

Alexandra M de Paz, Thaddeus R Cybulski, Adam H Marblestone, Bradley M Zamft, George M Church, Edward S Boyden, Konrad P Kording, Keith E J Tyo

Open access · goldAbstract readValidation Study
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

17 citing papers in PubMed, 32 citations in OpenAlex.

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  14. Temperature effect on polymerase fidelity.The Journal of biological chemistry · 2021
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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 4 institutions in 1 country.

Alexandra M de PazInterdisciplinary Biological Sciences Program, Northwestern University, Evanston, IL 60208, USA.
Thaddeus R CybulskiInterdepartmental Neuroscience Program, Northwestern University, Chicago, IL 60611, USA.
Adam H MarblestoneBiophysics Program, Harvard University, Boston, MA 02115, USA.
Bradley M ZamftDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
George M ChurchBiophysics Program, Harvard University, Boston, MA 02115, USA.
Edward S BoydenMedia Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Konrad P KordingDepartment of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
Keith E J TyoDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.
Harvard University · USNorthwestern University · USMassachusetts Institute of Technology · USUniversity of Pennsylvania · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008152 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ARDEHALI, HOSSEIN · 1987 to 2021
$24.0M
Recording neural activities onto DNAR01MH103910 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BOYDEN, EDWARD S., CHURCH, GEORGE M · 2013 to 2017
$9.5M
Medical Scientist Training ProgramT32GM144295 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ALAN R HAUSER · 2022 to 2026
$9.1M
NIGMS NIH HHS T32 GM008152NIGMS NIH HHS T32 GM144295NIMH NIH HHS R01 MH103910
6 · The paper itself

Abstract

DNA polymerase fidelity is affected by both intrinsic properties and environmental conditions. Current strategies for measuring DNA polymerase error rate in vitro are constrained by low error subtype sensitivity, poor scalability, and lack of flexibility in types of sequence contexts that can be tested. We have developed the Magnification via Nucleotide Imbalance Fidelity (MagNIFi) assay, a scalable next-generation sequencing assay that uses a biased deoxynucleotide pool to quantitatively shift error rates into a range where errors are frequent and hence measurement is robust, while still allowing for accurate mapping to error rates under typical conditions. This assay is compatible with a wide range of fidelity-modulating conditions, and enables high-throughput analysis of sequence context effects on base substitution and single nucleotide deletion fidelity using a built-in template library. We validate this assay by comparing to previously established fidelity metrics, and use it to investigate neighboring sequence-mediated effects on fidelity for several DNA polymerases. Through these demonstrations, we establish the MagNIFi assay for robust, high-throughput analysis of DNA polymerase fidelity.

Indexed as

DeoxyribonucleotidesDNA-Directed DNA PolymeraseHigh-Throughput Nucleotide SequencingSequence Analysis, DNADeoxyribonucleotidesDNA-Directed DNA Polymerase

Identifiers

PMID29718339
PMCPMC6061839
OpenAlexW2802979607

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.