PXD027733

PXD027733 is an original dataset announced via ProteomeXchange.

Title	Phenotypic quantitative high throughput screening with Caenorhabditis elegans
Description	Quantitative high throughput screening (qHTS) pharmacologically evaluates libraries of drugs and investigational agents for potential therapeutic uses, toxicological risk assessment, and increasingly for academic chemical tool discovery. Phenotypic HTS assays aim to interrogate molecular pathways and networks, often relying on cell culture systems, historically with less emphasis on multicellular organisms. C. elegans has served as a powerful eukaryotic model organism for human biology and disease by virtue of genetic conservation and experimental tractability, as well as a surrogate for infectious parasitic nematodes. Here we describe a paradigm to enable C. elegans in qHTS using 384-well microtiter plate laser scanning cytometry for rapid signal acquisition with concurrent quantification of the fluorescent protein-encoded phenotype. E. coli ghost capsules are used as a non-replicating nutrient source to allow compound titration exposures over the full 7-day life cycle to mitigate complications from bacterial overgrowth. We demonstrate the method using 643 anti-infective biased agents tested in 7-pt titration to assess feasibility of nematode-based in vivo qHTS. A pharmacological profile from the primary screen confirmed the efficacy of known anti-parasitic molecules, such as ivermectin and levamisole as well as illuminating anthelmintic properties of general chemical classes, including -secretase, bromodomain and proteasome inhibitors. We anticipate a broader application of laser scanning cytometry-based qHTS will enable the analysis of C. elegans orthologous transgenic phenotypes of human pathologies to facilitate drug discovery for a range of therapeutic indications.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:46:00.431.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD027733
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dingyin Tao
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-05 08:59:14	ID requested
1	2023-05-30 10:55:42	announced
2	2023-11-14 08:48:27	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:46:01	announced	2024-10-22: Updated project metadata.

10.1242/dmm.049863;

10.6019/PXD027733;

Dranchak PK, Oliphant E, Queme B, Lamy L, Wang Y, Huang R, Xia M, Tao D, Inglese J, In vivo quantitative high-throughput screening for drug discovery and comparative toxicology. Dis Model Mech, 16(3):(2023) [pubmed]

submitter keyword: model organisms, laser cytometry,drug discovery, infectious disease, genetic disorders, high-throughput screening

Dingyin Tao
contact affiliation	National Center for Advancing Translational Sciences, National Institutes of Health
contact email	dingyin.tao@nih.gov
lab head
Dingyin Tao
contact affiliation	National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS)
contact email	dingyin.tao@nih.gov
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/05/PXD027733

PRIDE project URI

• PRIDE
  1. PXD027733
     1. Label: PRIDE project
     2. Name: Phenotypic quantitative high throughput screening with Caenorhabditis elegans