PXD032175-1

PXD032175 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomics and phosphoproteomics of urinary extracellular vesicles define putative diagnostic biosignatures for Parkinson’s disease
Description	Background: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been recognized as genetic risk factors for Parkinson’s disease (PD). However, compared to cancer, fewer genetic mutations contribute to the cause of PD, propelling the search for protein biomarkers for early detection of the disease. Methods: Utilizing 138 urine samples from four groups, healthy individuals (control), healthy individuals with G2019S mutation in the LRRK2 gene (non-manifesting carrier/NMC), PD individuals without G2019S mutation (idiopathic PD/iPD), and PD individuals with G2019S mutation (LRRK2 PD), we applied a proteomics strategy to determine potential diagnostic biomarkers for PD from urinary extracellular vesicles (EVs). Results: After efficient isolation of urinary EVs through chemical affinity followed by mass spectrometric analyses of EV peptides and enriched phosphopeptides, we identify and quantify 4476 unique proteins and 2680 unique phosphoproteins. We detect multiple proteins and phosphoproteins elevated in PD EVs that are known to be involved in important PD pathways, in particular the autophagy pathway, as well as neuronal cell death, neuroinflammation, and formation of amyloid fibrils. We establish a panel of proteins and phosphoproteins as novel candidates for disease biomarkers and substantiate the biomarkers using machine learning, ROC, clinical correlation, and in-depth network analysis. Several putative disease biomarkers are further partially validated in patients with PD using parallel reaction monitoring (PRM) and immunoassay for targeted quantitation. Conclusions: These findings demonstrate a general strategy of utilizing biofluid EV proteome/phosphoproteome as an outstanding and non-invasive source for a wide range of disease exploration.
HostingRepository	PanoramaPublic
AnnounceDate	2023-05-09
AnnouncementXML	Submission_2023-05-09_10:51:07.105.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marco Hadisurya
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-09 17:41:06	ID requested
⏵ 1	2023-05-09 10:51:07	announced
2	2023-05-16 07:51:50	announced	: Added publication link
3	2024-11-02 08:29:10	announced	: Added PubMed Id

Dataset with its publication pending

submitter keyword: Biomarker discovery, Parkinson's disease, Extracellular vesicles, Exosomes, Proteomics, Phosphoproteomics, LC-MS

Anton Iliuk
contact affiliation	Tymora Analytical Operations
contact email	anton.iliuk@tymora-analytical.com
lab head
Marco Hadisurya
contact affiliation	Purdue University
contact email	mhadisur@purdue.edu
dataset submitter

Panorama Public dataset URI