PXD017167

PXD017167 is an original dataset announced via ProteomeXchange.

Title	Integrated phosphoproteomic profiling and causal analysis reveal signaling relations in GPVI/ITAM-mediated platelet activation programs
Description	Platelets engage cues of pending endothelial dysfunction through coordinated adhesion, secretion and aggregation responses. These rapid changes in platelet phenotype are orchestrated by intracellular mechanisms that remain systematically undefined. This study develops a TMT-SPS-MS3 phosphoproteomics workflow to detail ~3,800 significant protein phosphorylation events associated with the progression of ITAM-mediated activation programs initiated by the platelet collagen receptor GPVI. With literature-guided causal inference tools, >200 site-specific signaling relations are mapped from phosphoproteomics data among key GPVI effectors (i.e., Syk, PLC gamma 2, PKC delta) and less characterized targets, including several Ras/MAPK axis proteins (i.e., KSR1). Networks highly regulated in GPVI/ITAM signaling out of context of curated knowledge are also highlighted, including Rab GTPase systems. In addition to serving as a model for generating and testing hypotheses from omics datasets, this study puts forth a means to identify hemostatic effectors and biomarkers relevant to thrombosis, vascular inflammation and other platelet-associated disease states.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:15:25.577.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-17 03:49:17	ID requested
1	2020-11-20 06:21:07	announced
⏵ 2	2024-10-22 05:15:26	announced	2024-10-22: Updated project metadata.

10.1182/blood.2020005496;

Babur Ö, Melrose AR, Cunliffe JM, Klimek J, Pang J, Sepp AI, Zilberman-Rudenko J, Tassi Yunga S, Zheng T, Parra-Izquierdo I, Minnier J, McCarty OJT, Demir E, Reddy AP, Wilmarth PA, David LL, Aslan JE, Phosphoproteomic quantitation and causal analysis reveal pathways in GPVI/ITAM-mediated platelet activation programs. Blood, 136(20):2346-2358(2020) [pubmed]

submitter keyword: Human, platelets, causal pathways, cardiovascular disease, isobaric labeling, activation, phosphopeptide enrichment, quantitative proteomics, signaling

Dr. Joseph E. Aslan
contact affiliation	Knight Cardiovascular Institute Oregon Health & Science University 3303 SW Bond Ave Portland, Oregon 97239, USA
contact email	aslanj@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
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/2020/11/PXD017167

PRIDE project URI

• PRIDE
  1. PXD017167
     1. Label: PRIDE project
     2. Name: Integrated phosphoproteomic profiling and causal analysis reveal signaling relations in GPVI/ITAM-mediated platelet activation programs