Evidence map›Paper›PMID 31165867›Full record

ArticleNucleic acids research2019

Massively parallel profiling and predictive modeling of the outcomes of CRISPR/Cas9-mediated double-strand break repair.

Wei Chen, Aaron McKenna, Jacob Schreiber, Maximilian Haeussler, Yi Yin, Vikram Agarwal, William Stafford Noble, Jay Shendure

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 2 pooled it
10.1field-weighted citation impact, top 1% 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

135 citing papers in PubMed, 2 syntheses or guidelines pooled it, 234 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. In vivo systematic detection of the outcomes of CRISPR-Cas9-mediated DNA repair in skeletal muscle stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  18. Regenerative base editing enables deep lineage recording.bioRxiv : the preprint server for biology · 2026
    Article
  19. Article
  20. Review

75 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

8 authors at 3 institutions in 1 country.

Wei ChenMolecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, USA.
Aaron McKennaDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Jacob SchreiberPaul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA.
Maximilian HaeusslerSanta Cruz Genomics Institute, University of California, Santa Cruz, CA 95064, USA.
Yi YinDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Vikram AgarwalDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
William Stafford NobleDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
University of Washington · USBrotman Baty Institute · USUniversity of California, Santa Cruz · US

Funding

The UCSC Genome BrowserU41HG002371 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI KENT, WILLIAM JAMES · 2012 to 2021
$36.6M
Massively parallel reporter assays and genome editing of ENCODE predicted regulatory elementsUM1HG009408 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, SHENDURE, JAY ASHOK · 2017 to 2021
$7.6M
Encoding genomic architecture in the encyclopedia: linking DNA elements, chromatin state, and gene expression in 3DU01HG009395 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI LESLIE, CHRISTINA S · 2017 to 2021
$3.7M
Predictive Modeling of Alternative Splicing and Polyadenylation from Millions of Random SequencesR01HG009136 · NHGRI · UNIVERSITY OF WASHINGTON · PI SEELIG, GEORG, SHENDURE, JAY ASHOK · 2017 to 2020
$2.3M
Multidimensional cell recording with single-cell genomicsR00HG010152 · NHGRI · DARTMOUTH COLLEGE · PI MCKENNA, AARON H · 2019 to 2021
$729k
Multidimensional cell recording with single-cell genomicsK99HG010152 · NHGRI · UNIVERSITY OF WASHINGTON · PI MCKENNA, AARON H · 2018 to 2018
$97k
NHGRI NIH HHS K99 HG010152NHGRI NIH HHS R00 HG010152NHGRI NIH HHS R01 HG009136NHGRI NIH HHS U01 HG009395NHGRI NIH HHS U41 HG002371NHGRI NIH HHS UM1 HG009408
6 · The paper itself

Abstract

Non-homologous end-joining (NHEJ) plays an important role in double-strand break (DSB) repair of DNA. Recent studies have shown that the error patterns of NHEJ are strongly biased by sequence context, but these studies were based on relatively few templates. To investigate this more thoroughly, we systematically profiled ∼1.16 million independent mutational events resulting from CRISPR/Cas9-mediated cleavage and NHEJ-mediated DSB repair of 6872 synthetic target sequences, introduced into a human cell line via lentiviral infection. We find that: (i) insertions are dominated by 1 bp events templated by sequence immediately upstream of the cleavage site, (ii) deletions are predominantly associated with microhomology and (iii) targets exhibit variable but reproducible diversity with respect to the number and relative frequency of the mutational outcomes to which they give rise. From these data, we trained a model that uses local sequence context to predict the distribution of mutational outcomes. Exploiting the bias of NHEJ outcomes towards microhomology mediated events, we demonstrate the programming of deletion patterns by introducing microhomology to specific locations in the vicinity of the DSB site. We anticipate that our results will inform investigations of DSB repair mechanisms as well as the design of CRISPR/Cas9 experiments for diverse applications including genome-wide screens, gene therapy, lineage tracing and molecular recording.

Indexed as

CRISPR-Cas SystemsDNA Breaks, Double-StrandedDNA End-Joining RepairMutationBase SequenceDNA CleavageGene EditingGenome, HumanHumansModels, GeneticSequence Deletion

Identifiers

PMID31165867
PMCPMC6735782
OpenAlexW2970098032

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.