Evidence map›Paper›PMID 30032200›Full record

ArticleNucleic acids research2018

Decoding non-random mutational signatures at Cas9 targeted sites.

Amir Taheri-Ghahfarokhi, Benjamin J M Taylor, Roberto Nitsch, Anders Lundin, Anna-Lina Cavallo, Katja Madeyski-Bengtson, Fredrik Karlsson, Maryam Clausen, Ryan Hicks, Lorenz M Mayr and 2 more

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 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

68 citing papers in PubMed, 119 citations in OpenAlex.

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  8. Disruption of Microhomology-mediated End-joining in Ewing Sarcoma.bioRxiv : the preprint server for biology · 2025
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8 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

12 authors at 2 institutions in 2 countries.

Amir Taheri-GhahfarokhiTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Benjamin J M TaylorDiscovery Biology, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Cambridge, UK.
Roberto NitschTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Anders LundinTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Anna-Lina CavalloTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Katja Madeyski-BengtsonTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Fredrik KarlssonQuantitative Biology, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Maryam ClausenTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Ryan HicksTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Lorenz M MayrTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Mohammad Bohlooly-YTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Marcello MarescaTranslational Genomics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
AstraZeneca (Sweden) · SEAstraZeneca (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mutation patterns at Cas9 targeted sites contain unique information regarding the nuclease activity and repair mechanisms in mammalian cells. However, analytical framework for extracting such information are lacking. Here, we present a novel computational platform called Rational InDel Meta-Analysis (RIMA) that enables an in-depth comprehensive analysis of Cas9-induced genetic alterations, especially InDels mutations. RIMA can be used to quantitate the contribution of classical microhomology-mediated end joining (c-MMEJ) pathway in the formation of mutations at Cas9 target sites. We used RIMA to compare mutational signatures at 15 independent Cas9 target sites in human A549 wildtype and A549-POLQ knockout cells to elucidate the role of DNA polymerase θ in c-MMEJ. Moreover, the single nucleotide insertions at the Cas9 target sites represent duplications of preceding nucleotides, suggesting that the flexibility of the Cas9 nuclease domains results in both blunt- and staggered-end cuts. Thymine at the fourth nucleotide before protospacer adjacent motif (PAM) results in a two-fold higher occurrence of single nucleotide InDels compared to guanine at the same position. This study provides a novel approach for the characterization of the Cas9 nucleases with improved accuracy in predicting genome editing outcomes and a potential strategy for homology-independent targeted genomic integration.

Indexed as

DNA End-Joining RepairINDEL MutationSoftwareA549 CellsAlgorithmsBase SequenceCell LineCRISPR-Associated Protein 9Datasets as TopicDNA-Directed DNA PolymeraseDNA Polymerase thetaFrancisellaHumansNucleotide MotifsPolymorphism, Single NucleotideRecombinant ProteinsCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9DNA-Directed DNA PolymeraseDNA Polymerase thetaRecombinant Proteins

Identifiers

PMID30032200
PMCPMC6144780
OpenAlexW2883625359

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.