Evidence map›Paper›PMID 29305388›Full record

ArticleG3 (Bethesda, Md.)2018

Unintended Side Effects of Transformation Are Very Rare in

Ryan Z Friedman, Stacey R Gish, Holly Brown, Lindsey Brier, Nicole Howard, Tamara L Doering, Michael R Brent

Open access · goldAbstract read
In one paragraph

Article in G3 (Bethesda, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

Ryan Z FriedmanCenter for Genome Sciences and Systems Biology, Washington University School of Medicine, Saint Louis, Missouri 63110.ORCID 0000-0001-9013-8676
Stacey R GishDepartment of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri 63110.
Holly BrownCenter for Genome Sciences and Systems Biology, Washington University School of Medicine, Saint Louis, Missouri 63110.
Lindsey BrierCenter for Genome Sciences and Systems Biology, Washington University School of Medicine, Saint Louis, Missouri 63110.
Nicole HowardDepartment of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri 63110.
Tamara L DoeringDepartment of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri 63110.ORCID 0000-0002-5179-7393
Michael R BrentCenter for Genome Sciences and Systems Biology, Washington University School of Medicine, Saint Louis, Missouri 63110 brent@wustl.edu.ORCID 0000-0002-8689-0299
Washington University in St. Louis · US

Funding

PRINCIPLES IN PULMONARY RESEARCHT32HL007317 · NHLBI · WASHINGTON UNIVERSITY · PI Steven Brody, Michael J Holtzman · 1985 to 2026
$16.1M
CAPSULE REGULATION AND VIRULENCE IN CRYPTOCOCCUS NEOFORMANSR01AI087794 · NIAID · WASHINGTON UNIVERSITY · PI BRENT, MICHAEL R, DOERING, TAMARA L · 2011 to 2020
$4.1M
NHLBI NIH HHS T32 HL007317NIAID NIH HHS R01 AI087794
6 · The paper itself

Abstract

Received wisdom in the field of fungal biology holds that the process of editing a genome by transformation and homologous recombination is inherently mutagenic. However, that belief is based on circumstantial evidence. We provide the first direct measurement of the effects of transformation on a fungal genome by sequencing the genomes of 29 transformants and 30 untransformed controls with high coverage. Contrary to the received wisdom, our results show that transformation of DNA segments flanked by long targeting sequences, followed by homologous recombination and selection for a drug marker, is extremely safe. If a transformation deletes a gene, that may create selective pressure for a few compensatory mutations, but even when we deleted a gene, we found fewer than two point mutations per deletion strain, on average. We also tested these strains for changes in gene expression and found only a few genes that were consistently differentially expressed between the wild type and strains modified by genomic insertion of a drug resistance marker. As part of our report, we provide the assembled genome sequence of the commonly used laboratory strain

Indexed as

Transformation, GeneticCryptococcus neoformansDNA Copy Number VariationsGene DeletionGene Expression Regulation, FungalGenome, FungalGenomicsHigh-Throughput Nucleotide SequencingMutagenesis, InsertionalPhenotypeReverse GeneticsSequence Analysis, DNASequence DeletionCryptococcus neoformans strain KN99gene deletiongenome sequenceReverse geneticsyeasts

Identifiers

PMID29305388
PMCPMC5844303
OpenAlexW2782012253

What OpenQuestion holds

Textmetadata
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.