Evidence map›Paper›PMID 38291084›Full record

ArticleScientific reports2024

A scalable platform for efficient CRISPR-Cas9 chemical-genetic screens of DNA damage-inducing compounds.

Kevin Lin, Ya-Chu Chang, Maximilian Billmann, Henry N Ward, Khoi Le, Arshia Z Hassan, Urvi Bhojoo, Katherine Chan, Michael Costanzo, Jason Moffat and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Functional Genomics: Principles and Methods.Advances in experimental medicine and biology · 2026
    Review
  5. Review
  6. 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

13 authors.

Kevin LinDepartment of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
Ya-Chu ChangDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
Maximilian BillmannDepartment of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
Henry N WardBioinformatics and Computational Biology Graduate Program, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
Khoi LeDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
Arshia Z HassanDepartment of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
Urvi BhojooDonnelly Centre, University of Toronto, Toronto, ON, Canada.
Katherine ChanProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Michael CostanzoDonnelly Centre, University of Toronto, Toronto, ON, Canada.
Jason MoffatDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Charles BooneDonnelly Centre, University of Toronto, Toronto, ON, Canada.
Anja-Katrin BielinskyDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, MN, USA. azu3jn@virginia.edu.
Chad L MyersDepartment of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA. chadm@umn.edu.

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
Mapping the reference genetic network of a eukaryotic cellR01HG005853 · NHGRI · UNIVERSITY OF TORONTO · PI ANDREWS, BRENDA JEAN, BOONE, CHARLES · 2010 to 2025
$7.6M
Mechanistic insight into genome stability pathwaysR35GM141805 · NIGMS · UNIVERSITY OF VIRGINIA · PI Anja-Katrin Bielinsky · 2021 to 2026
$2.9M
Methods for large-scale analysis of chemical-genetic interactionsR01HG005084 · NHGRI · UNIVERSITY OF MINNESOTA · PI MYERS, CHAD L · 2010 to 2022
$2.9M
Targeted Chemical-Genetic Screen Platform for Identifying Novel AML TherapeuticsF30CA257227 · NCI · UNIVERSITY OF MINNESOTA · PI LIN, KEVIN JENG-YEN · 2021 to 2023
$141k
NCATS NIH HHS UL1 TR002494NCI NIH HHS 5F30CA257227-02NCI NIH HHS F30 CA257227NCI NIH HHS T32 CA009138NHGRI NIH HHS R01 HG005084NHGRI NIH HHS R01 HG005853NIGMS NIH HHS R35 GM141805
6 · The paper itself

Abstract

Current approaches to define chemical-genetic interactions (CGIs) in human cell lines are resource-intensive. We designed a scalable chemical-genetic screening platform by generating a DNA damage response (DDR)-focused custom sgRNA library targeting 1011 genes with 3033 sgRNAs. We performed five proof-of-principle compound screens and found that the compounds' known modes-of-action (MoA) were enriched among the compounds' CGIs. These scalable screens recapitulated expected CGIs at a comparable signal-to-noise ratio (SNR) relative to genome-wide screens. Furthermore, time-resolved CGIs, captured by sequencing screens at various time points, suggested an unexpected, late interstrand-crosslinking (ICL) repair pathway response to camptothecin-induced DNA damage. Our approach can facilitate screening compounds at scale with 20-fold fewer resources than commonly used genome-wide libraries and produce biologically informative CGI profiles.

Indexed as

CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas SystemsDNA DamageGenetic TestingGenomeHumansRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID38291084
PMCPMC10828508

What OpenQuestion holds

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Registered trials

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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.