Evidence map›Paper›PMID 24336569›Full record

ArticleScience (New York, N.Y.)2014

Genetic screens in human cells using the CRISPR-Cas9 system.

Tim Wang, Jenny J Wei, David M Sabatini, Eric S Lander

Open access · greenAbstract readEvaluation Study
In one paragraph

Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,657 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,657citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

1,657 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Pooled it
  2. CRISPR/Cas Systems: Biological Basis and Genome Editing Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Innate immune recognition ofInfection and immunity · 2026
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026
    Review
  17. Article
  18. Article
  19. Article
  20. A pooled image-based CRISPR screen identifies EAF1 as abioRxiv : the preprint server for biology · 2026
    Article

1,597 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

4 authors at 4 institutions in 1 country.

Tim WangDepartment of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Jenny J Wei
David M Sabatini
Eric S Lander
Broad Institute · USHarvard University · USHoward Hughes Medical Institute · USWhitehead Institute for Biomedical Research · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Regulation of the mTOR Pathway By NutrientsR01CA103866 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2004 to 2021
$7.0M
NCI NIH HHS CA103866NCI NIH HHS R01 CA103866NHGRI NIH HHS 2U54HG003067-10NHGRI NIH HHS U54 HG003067
6 · The paper itself

Abstract

The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system for genome editing has greatly expanded the toolbox for mammalian genetics, enabling the rapid generation of isogenic cell lines and mice with modified alleles. Here, we describe a pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single-guide RNA (sgRNA) library. sgRNA expression cassettes were stably integrated into the genome, which enabled a complex mutant pool to be tracked by massively parallel sequencing. We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines. A screen for resistance to the nucleotide analog 6-thioguanine identified all expected members of the DNA mismatch repair pathway, whereas another for the DNA topoisomerase II (TOP2A) poison etoposide identified TOP2A, as expected, and also cyclin-dependent kinase 6, CDK6. A negative selection screen for essential genes identified numerous gene sets corresponding to fundamental processes. Last, we show that sgRNA efficiency is associated with specific sequence motifs, enabling the prediction of more effective sgRNAs. Collectively, these results establish Cas9/sgRNA screens as a powerful tool for systematic genetic analysis in mammalian cells.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsGene Knockout TechniquesGenetic TestingAntigens, NeoplasmAntimetabolites, AntineoplasticAntineoplastic Agents, PhytogenicDNA-Binding ProteinsDNA Mismatch RepairDNA Topoisomerases, Type IIDrug Resistance, NeoplasmEtoposideGene LibraryGenome-Wide Association StudyHumansPoly-ADP-Ribose Binding ProteinsRNAAntigens, NeoplasmAntimetabolites, AntineoplasticAntineoplastic Agents, PhytogenicDNA-Binding ProteinsDNA Topoisomerases, Type IIEtoposidePoly-ADP-Ribose Binding ProteinsRNAThioguanineTOP2A protein, humanTop2a protein, mouse

Identifiers

PMID24336569
PMCPMC3972032
OpenAlexW1594078235

What OpenQuestion holds

Textmetadata
LicenceTDM
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.