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PXD032175

PXD032175 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleQuantitative proteomics and phosphoproteomics of urinary extracellular vesicles define putative diagnostic biosignatures for Parkinson’s disease
DescriptionBackground: 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.
HostingRepositoryPanoramaPublic
AnnounceDate2023-05-16
AnnouncementXMLSubmission_2023-05-16_07:51:50.040.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMarco Hadisurya
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListCarbamidomethyl
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-09 17:41:06ID requested
12023-05-09 10:51:07announced
22023-05-16 07:51:50announced: Added publication link
Publication List
Hadisurya, M., Li, L., Kuwaranancharoen, K. et al. Quantitative proteomics and phosphoproteomics of urinary extracellular vesicles define putative diagnostic biosignatures for Parkinson’s disease. Commun Med 3, 64 (2023). https://doi.org/10.1038/s43856-023-00294-w
Keyword List
submitter keyword: Biomarker discovery, Parkinson's disease, Extracellular vesicles, Exosomes, Proteomics, Phosphoproteomics, LC-MS
Contact List
Anton Iliuk
contact affiliationTymora Analytical Operations
contact emailanton.iliuk@tymora-analytical.com
lab head
Marco Hadisurya
contact affiliationPurdue University
contact emailmhadisur@purdue.edu
dataset submitter
Full Dataset Link List
Panorama Public dataset URI