Evidence map›Paper›PMID 27283361›Full record

ArticleNature communications2016

Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens.

Richard T Timms, Sam A Menzies, Iva A Tchasovnikarova, Lea C Christensen, James C Williamson, Robin Antrobus, Gordon Dougan, Lars Ellgaard, Paul J Lehner

Open access · goldAbstract readComparative Study
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.9field-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

48 citing papers in PubMed, 72 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. High expression ofTranslational cancer research · 2021
    Article
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

9 authors at 2 institutions in 2 countries.

Richard T TimmsDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.ORCID 0000-0001-7275-597X
Sam A MenziesDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
Iva A TchasovnikarovaDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.ORCID 0000-0002-0477-0956
Lea C ChristensenDepartment of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark.
James C WilliamsonDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
Robin AntrobusDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
Gordon DouganWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
Lars EllgaardDepartment of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark.ORCID 0000-0002-7018-0137
Paul J LehnerDepartment of Medicine, Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
University of Copenhagen · DKWellcome Sanger Institute · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing 'gold standard' method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum-associated degradation (ERAD) of MHC class I molecules. The two approaches show high concordance (>70%), successfully identifying the majority of the known components of the canonical glycoprotein ERAD pathway. Both screens also identify a role for the uncharacterized gene TXNDC11, which we show encodes an EDEM2/3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox.

Indexed as

Genetic TestingHaploidyalpha-GlucosidasesAnimalsCRISPR-Cas SystemsEndoplasmic Reticulum-Associated DegradationFluorescent DyesGenes, ReporterGlycoproteinsHEK293 CellsHeLa CellsHistocompatibility Antigens Class IHumansMammalsOxidation-ReductionProtein Bindingalpha-GlucosidasesFluorescent DyesGlycoproteinsHistocompatibility Antigens Class IThioredoxins

Identifiers

PMID27283361
PMCPMC4906395
OpenAlexW2336927518

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.