PXD032175
PXD032175 is an original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2024-11-02 |
AnnouncementXML | Submission_2024-11-02_08:29:09.367.xml |
DigitalObjectIdentifier | |
ReviewLevel | 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 |
Dataset History
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 |
Publication List
Hadisurya M, Li L, Kuwaranancharoen K, Wu X, Lee ZC, Alcalay RN, Padmanabhan S, Tao WA, Iliuk A, Quantitative proteomics and phosphoproteomics of urinary extracellular vesicles define putative diagnostic biosignatures for Parkinson's disease. Commun Med (Lond), 3(1):64(2023) [pubmed] |
Keyword List
submitter keyword: Biomarker discovery, Parkinson's disease, Extracellular vesicles, Exosomes, Proteomics, Phosphoproteomics, LC-MS |
Contact List
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 |
Full Dataset Link List
Panorama Public dataset URI |