Evidence map›Paper›PMID 33305328›Full record

ArticleNucleic acids research2021

Deploying MMEJ using MENdel in precision gene editing applications for gene therapy and functional genomics.

Gabriel Martínez-Gálvez, Parnal Joshi, Iddo Friedberg, Armando Manduca, Stephen C Ekker

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

13 citing papers in PubMed, 19 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

5 authors at 3 institutions in 1 country.

Gabriel Martínez-GálvezDept. of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Parnal JoshiProgram in Bioinformatics and Computational Biology, Iowa State University, Ames, IA, USA.
Iddo FriedbergProgram in Bioinformatics and Computational Biology, Iowa State University, Ames, IA, USA.
Armando ManducaDept. of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Stephen C EkkerDept. of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Iowa State University · USMayo Clinic in Florida · USMayo Clinic · US

Funding

Systematic Vertebrate Functional GenomicsR01GM063904 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI EKKER, STEPHEN CARL · 2001 to 2025
$10.7M
In vivo model of microglia inflammasome signaling in neuroinflammationR24OD020166 · OD · IOWA STATE UNIVERSITY · PI CLARK, KARL J, EKKER, STEPHEN CARL · 2016 to 2023
$7.1M
NIGMS NIH HHS R01 GM063904NIH HHS R24 OD020166Wellcome Trust
6 · The paper itself

Abstract

Gene-editing experiments commonly elicit the error-prone non-homologous end joining for DNA double-strand break (DSB) repair. Microhomology-mediated end joining (MMEJ) can generate more predictable outcomes for functional genomic and somatic therapeutic applications. We compared three DSB repair prediction algorithms - MENTHU, inDelphi, and Lindel - in identifying MMEJ-repaired, homogeneous genotypes (PreMAs) in an independent dataset of 5,885 distinct Cas9-mediated mouse embryonic stem cell DSB repair events. MENTHU correctly identified 46% of all PreMAs available, a ∼2- and ∼60-fold sensitivity increase compared to inDelphi and Lindel, respectively. In contrast, only Lindel correctly predicted predominant single-base insertions. We report the new algorithm MENdel, a combination of MENTHU and Lindel, that achieves the most predictive coverage of homogeneous out-of-frame mutations in this large dataset. We then estimated the frequency of Cas9-targetable homogeneous frameshift-inducing DSBs in vertebrate coding regions for gene discovery using MENdel. 47 out of 54 genes (87%) contained at least one early frameshift-inducing DSB and 49 out of 54 (91%) did so when also considering Cas12a-mediated deletions. We suggest that the use of MENdel helps researchers use MMEJ at scale for reverse genetics screenings and with sufficient intra-gene density rates to be viable for nearly all loss-of-function based gene editing therapeutic applications.

Indexed as

AlgorithmsDNA Breaks, Double-StrandedDNA End-Joining RepairFrameshift MutationINDEL MutationLoss of Function MutationAnimalsBacterial ProteinsCaspase 9Datasets as TopicEmbryonic Stem CellsGene EditingGenetic TherapyGenomicsHumansMiceBacterial ProteinsCaspase 9

Identifiers

PMID33305328
PMCPMC7797032
OpenAlexW3111788708

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.