PXD027463

PXD027463 is an original dataset announced via ProteomeXchange.

Title	Proteomic landscapes of inherited platelet disorders with different etiologies
Description	Background: Inherited Platelet Disorders (IPDs) are a heterogeneous group of rare diseases that are caused by defects in early megakaryopoiesis, pro-platelet formation and/or mature platelet function. Although genomic sequencing is increasingly used to identify genetic variants underlying IPD, this technique does not disclose resulting molecular changes that impact platelet function. Proteins are the functional units that shape platelet function, however insights into how variants that cause IPDs impact platelet proteomes is limited. Objectives: To profile the platelet proteomics signatures of inherited platelet disorders. Methods: We performed unbiased label free quantitative mass spectrometry (MS)-based proteome profiling on platelets of 34 IPD patients with variants in 13 ISTH TIER1 genes that affect different stages of platelet development. Results: In line with the phenotypical heterogeneity between IPDs, proteomes were diverse between IPDs. We observed extensive proteomic alterations in patients with a GFI1B variant and for genetic variants in genes encoding proteins that impact cytoskeletal processes (MYH9, TUBB1 and WAS). Utilizing the diversity between IPDs, we clustered protein dynamics, revealing disrupted protein-protein-complexes. This analysis furthermore grouped proteins with similar cellular- function and location, classifying mitochondrial protein constituents and identifying both known and putative novel alpha granule associated proteins. Conclusions: With this study we demonstrate a MS-based proteomics perspective to IPDs. By integrating the effects of IPDs that impact different aspects of platelet function, we dissected the biological contexts of protein alterations to gain further insights into the biology of platelet (dys)function.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:27:10.082.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Arie Hoogendijk
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-21 05:41:15	ID requested
1	2023-01-31 16:36:48	announced
⏵ 2	2023-11-14 08:27:10	announced	2023-11-14: Updated project metadata.

Kreft IC, Huisman EJ, Cnossen MH, van Alphen FPJ, van der Zwaan C, van Leeuwen K, van Spaendonk R, Porcelijn L, Veen CSB, van den Biggelaar M, de Haas M, Meijer AB, Hoogendijk AJ, Proteomic landscapes of inherited platelet disorders with different etiologies. J Thromb Haemost, 21(2):359-372.e3(2023) [pubmed]

submitter keyword: Human, platelets, Orbitrap Fusion

M. van den Biggelaar
contact affiliation	Department of Molecular Hematology, Sanquin Research
contact email	m.vandenbiggelaar@sanquin.nl
lab head
Arie Hoogendijk
contact affiliation	Department of Molecular Hematology, Sanquin Research, Amsterdam
contact email	a.hoogendijk@sanquin.nl
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/2023/01/PXD027463

PRIDE project URI

• PRIDE
  1. PXD027463
     1. Label: PRIDE project
     2. Name: Proteomic landscapes of inherited platelet disorders with different etiologies