Evidence map›Paper›PMID 31492858›Full record

ArticleNature communications2019

Mitigation of off-target toxicity in CRISPR-Cas9 screens for essential non-coding elements.

Josh Tycko, Michael Wainberg, Georgi K Marinov, Oana Ursu, Gaelen T Hess, Braeden K Ego, Aradhana, Amy Li, Alisa Truong, Alexandro E Trevino and 11 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
6.3field-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

96 citing papers in PubMed, 164 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Increased Intermembrane Space [CaCirculation research · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Article

36 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

21 authors at 5 institutions in 1 country.

Josh TyckoDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-4108-0575
Michael WainbergDepartment of Computer Science, Stanford University, Stanford, CA, 94305, USA.
Georgi K MarinovDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Oana UrsuDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Gaelen T HessDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Braeden K EgoDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
AradhanaDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Amy LiDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Alisa TruongDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Alexandro E TrevinoCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, 94305, USA.
Kaitlyn SpeesDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
David YaoDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Irene M KaplowDepartment of Computer Science, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-8924-8269
Peyton G GreensideDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
David W MorgensDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Douglas H PhanstielDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.
Michael P SnyderDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0003-0784-7987
Lacramioara BintuDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
William J GreenleafDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA. wjg@stanford.edu.ORCID http://orcid.org/0000-0003-1409-3095
Anshul KundajeDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA. akundaje@stanford.edu.
Michael C BassikDepartment of Genetics, Stanford University, Stanford, CA, 94305, USA. bassik@stanford.edu.ORCID http://orcid.org/0000-0001-5185-8427
Stanford University · USChan Zuckerberg Initiative (United States) · USStanford Health Care · USStanford Medicine · USUniversity of North Carolina at Chapel Hill · 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
Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
High-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4M
Mechanisms of Dynamic Chromatin Looping During Differentiation - Common Fund Data SupplementR35GM128645 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Douglas H. Phanstiel · 2018 to 2026
$3.4M
The development and application of tools to characterize the 4D nucleomeR00HG008662 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PHANSTIEL, DOUGLAS H. · 2017 to 2019
$747k
NHGRI NIH HHS P50 HG007735NHGRI NIH HHS R00 HG008662NHGRI NIH HHS RM1 HG007735NHGRI NIH HHS T32 HG000044NHGRI NIH HHS UM1 HG009436NIGMS NIH HHS R35 GM128645
6 · The paper itself

Abstract

Pooled CRISPR-Cas9 screens are a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we investigate Cas9, dCas9, and CRISPRi/a off-target activity in screens for essential regulatory elements. The sgRNAs with the largest effects in genome-scale screens for essential CTCF loop anchors in K562 cells were not single guide RNAs (sgRNAs) that disrupted gene expression near the on-target CTCF anchor. Rather, these sgRNAs had high off-target activity that, while only weakly correlated with absolute off-target site number, could be predicted by the recently developed GuideScan specificity score. Screens conducted in parallel with CRISPRi/a, which do not induce double-stranded DNA breaks, revealed that a distinct set of off-targets also cause strong confounding fitness effects with these epigenome-editing tools. Promisingly, filtering of CRISPRi libraries using GuideScan specificity scores removed these confounded sgRNAs and enabled identification of essential regulatory elements.

Indexed as

CRISPR-Cas SystemsGene Expression Regulation, NeoplasticComputational BiologyEpigenesis, GeneticEpigenomicsGene EditingGenome, HumanHEK293 CellsHumansK562 CellsRegulatory Elements, TranscriptionalRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID31492858
PMCPMC6731277
OpenAlexW2971775201

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.