PXD009644

PXD009644 is an original dataset announced via ProteomeXchange.

Title	ProTargetMiner: A proteome library of anticancer molecules for functional discovery
Description	As a further development of our Functional Identification of drug Targets by Expression Proteomics (FITExP) method, a reference dataset was built of the proteomic responses of A549 human adenocarcinoma cells to 56 clinical and experimental anticancer molecules. For each molecule, a concentration was used killing 50% of the cells after 48 h. With 4557 proteins quantified across all treatments and controls, 11 orthogonal dimensions were found in factor analysis of the ProTargetMiner dataset, indicating the action of at least that many distinct cell death modalities. For convenience, the number of dimensions was reduced to three and two, thus producing a “death globe” and “death map”, respectively. As expected, molecules with similar mechanisms of action produced proteome signatures clustering together on the death globe and map. Interrogation of the dataset with partial least square modeling contrasting a given molecule against all other treatments unveiled drug targets and mechanistic proteins, even when the specific protein regulation was as subtle as a 15% change. The mechanisms of action were revealed by mapping the group of target candidates on known protein networks. The dataset allows for unique interrogation approaches, such as defining a set of co-regulated proteins. The core (“untouchable”) proteome consisting of proteins with steady expression levels unaffected by the treatments was also defined; they are found to be involved in proteasome and mRNA surveillance pathway. Finally, a list of proteins most affected by the drugs was compiled; these proteins encompass many known drug targets. The ProTargetMiner represents a resource that may be useful to the community of drug developers or scientists interested in drug action mechanisms and cell death modalities. ProTargetMiner can be easily extended to other drugs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:44:53.466.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amir Ata Saei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-02 03:28:58	ID requested
1	2019-11-01 06:32:28	announced
2	2020-01-13 05:27:34	announced	2020-01-13: Updated publication reference for PubMed record(s): 31844049.
⏵ 3	2024-10-22 04:45:01	announced	2024-10-22: Updated project metadata.

Saei AA, Beusch CM, Chernobrovkin A, Sabatier P, Zhang B, Tokat Ü G, Stergiou E, Gaetani M, V, é, gv, á, ri Á, Zubarev RA, ProTargetMiner as a proteome signature library of anticancer molecules for functional discovery. Nat Commun, 10(1):5715(2019) [pubmed]

10.1038/s41467-019-13582-8;

ProteomeXchange project tag: Reference

submitter keyword: cancer, drug, proteomics, mass spectrometry,A549, resource, expression, chemotherapeutic, database, compound

Roman Zubarev
contact affiliation	Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
contact email	roman.zubarev@ki.se
lab head
Amir Ata Saei
contact affiliation	Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
contact email	amirata.saei.dibavar@ki.se
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/2019/11/PXD009644

PRIDE project URI

• PRIDE
  1. PXD009644
     1. Label: PRIDE project
     2. Name: ProTargetMiner: A proteome library of anticancer molecules for functional discovery