Evidence map›Paper›PMID 29743009›Full record

ArticleBMC genomics2018

Muver, a computational framework for accurately calling accumulated mutations.

Adam B Burkholder, Scott A Lujan, Christopher A Lavender, Sara A Grimm, Thomas A Kunkel, David C Fargo

Abstract read
In one paragraph

Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

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  11. How asymmetric DNA replication achieves symmetrical fidelity.Nature structural & molecular biology · 2021
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  13. Review
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  18. GC content elevates mutation and recombination rates in the yeastProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
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.

Adam B BurkholderIntegrative Bioinformatics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, Durham, NC, 27709, USA.
Scott A LujanLaboratory of Genomic Integrity and Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, Durham, NC, 27709, USA.
Christopher A LavenderIntegrative Bioinformatics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, Durham, NC, 27709, USA.
Sara A GrimmIntegrative Bioinformatics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, Durham, NC, 27709, USA.
Thomas A KunkelLaboratory of Genomic Integrity and Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, Durham, NC, 27709, USA.
David C FargoIntegrative Bioinformatics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, Durham, NC, 27709, USA. fargod@niehs.nih.gov.

Funding

Studies Of DNA Mismatch RepairZIAES065089 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KUNKEL, THOMAS A · 2009 to 2025
$17.8M
Structure-Function Studies Of DNA Replication FidelityZ01ES065070 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KUNKEL, THOMAS A · 1991 to 2008
$4.3M
Computational systems enhancing the understanding of genomic and epigenomic features that define and differentiate chromatin environments at promoters and enhancersZIAES103312 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI FARGO, DAVID · 2016 to 2020
$3.7M
Intramural NIH HHS Z01 ES065070NIEHS NIH HHS Z01 ES065070NIEHS NIH HHS Z01 ES103312
6 · The paper itself

Abstract

backgroundIdentification of mutations from next-generation sequencing data typically requires a balance between sensitivity and accuracy. This is particularly true of DNA insertions and deletions (indels), that can impart significant phenotypic consequences on cells but are harder to call than substitution mutations from whole genome mutation accumulation experiments. To overcome these difficulties, we present muver, a computational framework that integrates established bioinformatics tools with novel analytical methods to generate mutation calls with the extremely low false positive rates and high sensitivity required for accurate mutation rate determination and comparison.

resultsMuver uses statistical comparison of ancestral and descendant allelic frequencies to identify variant loci and assigns genotypes with models that include per-sample assessments of sequencing errors by mutation type and repeat context. Muver identifies maximally parsimonious mutation pathways that connect these genotypes, differentiating potential allelic conversion events and delineating ambiguities in mutation location, type, and size. Benchmarking with a human gold standard father-son pair demonstrates muver's sensitivity and low false positive rates. In DNA mismatch repair (MMR) deficient Saccharomyces cerevisiae, muver detects multi-base deletions in homopolymers longer than the replicative polymerase footprint at rates greater than predicted for sequential single-base deletions, implying a novel multi-repeat-unit slippage mechanism.

conclusionsBenchmarking results demonstrate the high accuracy and sensitivity achieved with muver, particularly for indels, relative to available tools. Applied to an MMR-deficient Saccharomyces cerevisiae system, muver mutation calls facilitate mechanistic insights into DNA replication fidelity.

Indexed as

Genome, FungalMutation AccumulationSoftwareComputational BiologyFathersHigh-Throughput Nucleotide SequencingHumansMaleMutation RateReference StandardsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Analysis, DNASaccharomyces cerevisiae ProteinsDNA-seqIndelMutationMutation accumulationMutation rate

Identifiers

PMID29743009
PMCPMC5944071

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LicenceCC BY
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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.