Evidence map›Paper›PMID 28474669›Full record

ArticleNature communications2017

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens.

David W Morgens, Michael Wainberg, Evan A Boyle, Oana Ursu, Carlos L Araya, C Kimberly Tsui, Michael S Haney, Gaelen T Hess, Kyuho Han, Edwin E Jeng and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 248 papers.

0numbers the graph read from it
0cells of the map it votes in
248citing papers in PubMed
15.0field-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

248 citing papers in PubMed, 396 citations in OpenAlex.

  1. Trial
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  11. Review
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  13. Review
  14. simCRISPR: Modeling Experimental Complexity in Pooled CRISPR Screens.bioRxiv : the preprint server for biology · 2026
    Article
  15. Article
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  17. Article
  18. Article
  19. Article
  20. Concordant transcriptional and morphological remodeling revealed bybioRxiv : the preprint server for biology · 2026
    Article

188 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

15 authors at 2 institutions in 1 country.

David W MorgensDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Michael WainbergDepartment of Computer Science, Stanford University, Stanford, California 94305, USA.
Evan A BoyleDepartment of Genetics, Stanford University, Stanford, California 94305, USA.ORCID 0000-0003-4494-9771
Oana UrsuDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Carlos L ArayaDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
C Kimberly TsuiDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Michael S HaneyDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Gaelen T HessDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Kyuho HanDepartment of Genetics, Stanford University, Stanford, California 94305, USA.ORCID 0000-0003-4259-8736
Edwin E JengDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Amy LiDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Michael P SnyderDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
William J GreenleafDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Anshul KundajeDepartment of Genetics, Stanford University, Stanford, California 94305, USA.ORCID 0000-0003-3084-2287
Michael C BassikDepartment of Genetics, Stanford University, Stanford, California 94305, USA.
Stanford University · USStanford Health Care · US

Funding

INSTITUTIONAL TRAINING GRANT IN GENOME SCIENCET32HG000044 · NHGRI · STANFORD UNIVERSITY · PI MICHAEL P. SNYDER · 1995 to 2026
$32.2M
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2M
GENETICS TRAINING PROGRAM FOR PHD CANDIDATEST32GM007790 · NIGMS · STANFORD UNIVERSITY · PI BRUNET, ANNE, KINGSLEY, DAVID M · 1985 to 2020
$12.8M
High-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4M
Accelerating drug development and repurposing using systematic genetic interactioDP2HD084069 · NICHD · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C · 2014 to 2014
$2.4M
NHGRI NIH HHS P50 HG007735NHGRI NIH HHS T32 HG000044NHGRI NIH HHS UM1 HG009436NICHD NIH HHS DP2 HD084069NIGMS NIH HHS T32 GM007790
6 · The paper itself

Abstract

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens.

Indexed as

Genomic LibraryCell LineClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDNA DamageGene TargetingHigh-Throughput Screening AssaysHumansPolysaccharidesRicinRNA, Guide, CRISPR-Cas SystemsRNA InterferencePolysaccharidesRicinRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID28474669
PMCPMC5424143
OpenAlexW2611446801

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.