Evidence map›Paper›PMID 36376301›Full record

ArticleNature communications2022

Multiplexed and reproducible high content screening of live and fixed cells using Dye Drop.

Caitlin E Mills, Kartik Subramanian, Marc Hafner, Mario Niepel, Luca Gerosa, Mirra Chung, Chiara Victor, Benjamin Gaudio, Clarence Yapp, Ajit J Nirmal and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
7.4field-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

22 citing papers in PubMed, 30 citations in OpenAlex.

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  18. Dissecting sources of variability in patient response to targeted therapy: anti-HER2 therapies as a case study.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2023
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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

12 authors at 1 institution in 2 countries.

Caitlin E Mills *Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0002-2608-4084
Kartik Subramanian *Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Marc Hafner *Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0003-1337-7598
Mario NiepelLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0003-1415-6295
Luca GerosaLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Mirra ChungLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Chiara VictorLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Benjamin GaudioLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Clarence YappLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Ajit J NirmalLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Nicholas ClarkLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.
Peter K SorgerLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA. peter_sorger@hms.harvard.edu.ORCID 0000-0002-3364-1838
Harvard University · US

Funding

Illuminating Function of the Understudied Druggable KinomeU24DK116204 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHNSON, GARY L. · 2017 to 2022
$13.6M
Pharmaco Response Signatures and Disease MechanismU54HL127365 · NHLBI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2014 to 2019
$13.1M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SHARPE, ARLENE H. · 2018 to 2022
$10.8M
NCI NIH HHS U54 CA225088NHLBI NIH HHS U54 HL127365NIDDK NIH HHS U24 DK116204
6 · The paper itself

Abstract

High-throughput measurement of cells perturbed using libraries of small molecules, gene knockouts, or different microenvironmental factors is a key step in functional genomics and pre-clinical drug discovery. However, it remains difficult to perform accurate single-cell assays in 384-well plates, limiting many studies to well-average measurements (e.g., CellTiter-Glo®). Here we describe a public domain Dye Drop method that uses sequential density displacement and microscopy to perform multi-step assays on living cells. We use Dye Drop cell viability and DNA replication assays followed by immunofluorescence imaging to collect single-cell dose-response data for 67 investigational and clinical-grade small molecules in 58 breast cancer cell lines. By separating the cytostatic and cytotoxic effects of drugs computationally, we uncover unexpected relationships between the two. Dye Drop is rapid, reproducible, customizable, and compatible with manual or automated laboratory equipment. Dye Drop improves the tradeoff between data content and cost, enabling the collection of information-rich perturbagen-response datasets.

Indexed as

Antineoplastic AgentsDrug DiscoveryCell SurvivalHigh-Throughput Screening AssaysMicroscopyStaining and LabelingAntineoplastic Agents

Identifiers

PMID36376301
PMCPMC9663587
OpenAlexW4308995521

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.