Evidence map›Paper›PMID 38480981›Full record

ArticleNature chemical biology2024

Functional genomic screens with death rate analyses reveal mechanisms of drug action.

Megan E Honeywell, Marie S Isidor, Nicholas W Harper, Rachel E Fontana, Gavin A Birdsall, Peter Cruz-Gordillo, Sydney A Porto, Madison Jerome, Cameron S Fraser, Kristopher A Sarosiek and 3 more

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
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

10 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Comprehensive Analysis of Drug Response using the FLICK Assay.Journal of visualized experiments : JoVE · 2025
    Article
  7. Article
  8. Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024
    Article
  9. The death gaze of MEDUSA.Nature chemical biology · 2024
    Article
  10. Review
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 at 3 institutions in 2 countries.

Megan E HoneywellDepartment of Systems Biology, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-4894-8672
Marie S IsidorProgram in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0003-3396-5389
Nicholas W HarperDepartment of Systems Biology, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-4037-7473
Rachel E FontanaDepartment of Systems Biology, UMass Chan Medical School, Worcester, MA, USA.
Gavin A BirdsallDepartment of Systems Biology, UMass Chan Medical School, Worcester, MA, USA.
Peter Cruz-GordilloDepartment of Systems Biology, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-0264-7348
Sydney A PortoDepartment of Systems Biology, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0009-0009-7329-404X
Madison JeromeProgram in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Cameron S FraserJohn B. Little Center for Radiation Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8180-5913
Kristopher A SarosiekJohn B. Little Center for Radiation Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4618-5085
David A GuertinProgram in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Jessica B SpinelliProgram in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Michael J LeeDepartment of Systems Biology, UMass Chan Medical School, Worcester, MA, USA. michael.lee@umassmed.edu.ORCID http://orcid.org/0000-0003-3378-6196
University of Massachusetts Chan Medical School · USUMass Memorial Health Care · USUniversity of Copenhagen · DK

Funding

Developmental regulation of apoptosis as a modifiable driver of radiotherapy-induced neurocognitive impairment in pediatric patientsR37CA248565 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Kristopher Andrew Sarosiek · 2020 to 2026
$2.6M
Environmental Regulation of Cellular Responses to DNA DamageR01GM127559 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LEE, MICHAEL JUNGHO · 2018 to 2022
$1.8M
Activation of non-apoptotic cell death by the DNA damage responseF31CA268847 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HONEYWELL, MEGAN ELIZABETH · 2022 to 2023
$64k
American Cancer Society (American Cancer Society, Inc.) RSG-17-011-01EPA EP-W-17-011NCI NIH HHS F31 CA268847NCI NIH HHS R37 CA248565NIGMS NIH HHS R01 GM127559Novo Nordisk Foundation Center for Basic Metabolic Research (NovoNordisk Foundation Center for Basic Metabolic Research) NNF18CC0034900
6 · The paper itself

Abstract

A common approach for understanding how drugs induce their therapeutic effects is to identify the genetic determinants of drug sensitivity. Because 'chemo-genetic profiles' are performed in a pooled format, inference of gene function is subject to several confounding influences related to variation in growth rates between clones. In this study, we developed Method for Evaluating Death Using a Simulation-assisted Approach (MEDUSA), which uses time-resolved measurements, along with model-driven constraints, to reveal the combination of growth and death rates that generated the observed drug response. MEDUSA is uniquely effective at identifying death regulatory genes. We apply MEDUSA to characterize DNA damage-induced lethality in the presence and absence of p53. Loss of p53 switches the mechanism of DNA damage-induced death from apoptosis to a non-apoptotic death that requires high respiration. These findings demonstrate the utility of MEDUSA both for determining the genetic dependencies of lethality and for revealing opportunities to potentiate chemo-efficacy in a cancer-specific manner.

Indexed as

DNA DamageGenomicsAntineoplastic AgentsApoptosisCell DeathCell Line, TumorHumansTumor Suppressor Protein p53Antineoplastic AgentsTumor Suppressor Protein p53

Identifiers

PMID38480981
PMCPMC11393183
OpenAlexW4392750950

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.