Evidence map›Paper›PMID 31586052›Full record

ArticleNature communications2019

De novo identification of essential protein domains from CRISPR-Cas9 tiling-sgRNA knockout screens.

Wei He, Liang Zhang, Oscar D Villarreal, Rongjie Fu, Ella Bedford, Jingzhuang Dou, Anish Y Patel, Mark T Bedford, Xiaobing Shi, Taiping Chen and 2 more

Erratum issuedOpen access · goldAbstract read
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. An erratum has been issued. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

43 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Article
  3. AI platform for CRISPR functional mapping and function-based drug design.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Wei HeDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.
Liang ZhangDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.
Oscar D VillarrealDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.
Rongjie FuDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.
Ella BedfordDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.
Jingzhuang DouDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.
Anish Y PatelDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.ORCID http://orcid.org/0000-0002-9218-4104
Mark T BedfordDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.ORCID http://orcid.org/0000-0002-8899-1050
Xiaobing ShiCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, 49503, USA.ORCID http://orcid.org/0000-0001-5242-8189
Taiping ChenDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.ORCID http://orcid.org/0000-0002-2524-6440
Blaine BartholomewDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA.ORCID http://orcid.org/0000-0003-4014-9750
Han XuDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, 78957, USA. hxu4@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USVan Andel Institute · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

High-throughput CRISPR-Cas9 knockout screens using a tiling-sgRNA design permit in situ evaluation of protein domain function. Here, to facilitate de novo identification of essential protein domains from such screens, we propose ProTiler, a computational method for the robust mapping of CRISPR knockout hyper-sensitive (CKHS) regions, which refer to the protein regions associated with a strong sgRNA dropout effect in the screens. Applied to a published CRISPR tiling screen dataset, ProTiler identifies 175 CKHS regions in 83 proteins. Of these CKHS regions, more than 80% overlap with annotated Pfam domains, including all of the 15 known drug targets in the dataset. ProTiler also reveals unannotated essential domains, including the N-terminus of the SWI/SNF subunit SMARCB1, which is validated experimentally. Surprisingly, the CKHS regions are negatively correlated with phosphorylation and acetylation sites, suggesting that protein domains and post-translational modification sites have distinct sensitivities to CRISPR-Cas9 mediated amino acids loss.

Indexed as

AlgorithmsCell Line, TumorComputational BiologyCRISPR-Cas SystemsDatasets as TopicGene Knockout TechniquesHigh-Throughput Screening AssaysHumansModels, GeneticProtein DomainsProtein Processing, Post-TranslationalRNA, Guide, CRISPR-Cas SystemsSMARCB1 ProteinSoftwareRNA, Guide, CRISPR-Cas SystemsSMARCB1 ProteinSMARCB1 protein, human

Identifiers

PMID31586052
PMCPMC6778102
OpenAlexW2978187183

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.