Evidence map›Paper›PMID 31439014›Full record

ArticleGenome medicine2019

Identifying chemogenetic interactions from CRISPR screens with drugZ.

Medina Colic, Gang Wang, Michal Zimmermann, Keith Mascall, Megan McLaughlin, Lori Bertolet, W Frank Lenoir, Jason Moffat, Stephane Angers, Daniel Durocher and 1 more

Abstract read
In one paragraph

Article in Genome medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.

0numbers the graph read from it
0cells of the map it votes in
154citing papers in PubMed
–field-weighted citation impact
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

154 citing papers in PubMed.

  1. Article
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  4. Epigenetic Repression ofBiomolecules & therapeutics · 2026
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  13. PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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  20. Article

94 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

11 authors.

Medina ColicDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gang WangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michal ZimmermannLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Keith MascallDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Megan McLaughlinDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lori BertoletDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
W Frank LenoirDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jason MoffatDonnelly Centre, University of Toronto, Toronto, ON, Canada.
Stephane AngersDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Daniel DurocherLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Traver HartDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. traver@hart-lab.org.ORCID 0000-0002-1880-3341

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
High-content microscopy platform for multiplex perturbation/multiplex readout studiesR35GM130119 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Traver Hart · 2018 to 2026
$3.9M
CIHR 342551CIHR 361837CIHR 365646CIHR FDN143343NCI NIH HHS P30 CA016672NIGMS NIH HHS R35 GM130119NIGMS NIH HHS R35GM130119
6 · The paper itself

Abstract

backgroundChemogenetic profiling enables the identification of gene mutations that enhance or suppress the activity of chemical compounds. This knowledge provides insights into drug mechanism of action, genetic vulnerabilities, and resistance mechanisms, all of which may help stratify patient populations and improve drug efficacy. CRISPR-based screening enables sensitive detection of drug-gene interactions directly in human cells, but until recently has primarily been used to screen only for resistance mechanisms.

resultsWe present drugZ, an algorithm for identifying both synergistic and suppressor chemogenetic interactions from CRISPR screens. DrugZ identifies synthetic lethal interactions between PARP inhibitors and both known and novel members of the DNA damage repair pathway, confirms KEAP1 loss as a resistance factor for ERK inhibitors in oncogenic KRAS backgrounds, and defines the genetic context for temozolomide activity.

conclusionsDrugZ is an open-source Python software for the analysis of genome-scale drug modifier screens. The software accurately identifies genetic perturbations that enhance or suppress drug activity. Interestingly, analysis of new and previously published data reveals tumor suppressor genes are drug-agnostic resistance genes in drug modifier screens. The software is available at github.com/hart-lab/drugz .

Indexed as

AlgorithmsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsPharmacogenomic VariantsSoftwareDrug DiscoveryGenetic Predisposition to DiseaseHumansMutationPharmacogeneticsChemogenetic interactionsCRISPR screensDrug resistanceSynthetic lethality

Identifiers

PMID31439014
PMCPMC6706933

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.