Purdue University Tao Lab - Hadisurya_Parkinson's_Disease

Quantitative proteomics and phosphoproteomics of urinary extracellular vesicles define putative diagnostic biosignatures for Parkinson’s disease
Data License: CC BY 4.0 | ProteomeXchange: PXD032175 | doi: https://doi.org/10.6069/b1ah-0x76
  • Organism: Homo sapiens
  • Instrument: Q Exactive HF-X
  • SpikeIn: No
  • Keywords: Biomarker discovery, Parkinson's disease, Extracellular vesicles, Exosomes, Proteomics, Phosphoproteomics, LC-MS
  • Lab head: Anton Iliuk Submitter: Marco Hadisurya
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.
Created on 11/2/22, 11:24 PM
Clustergrammer Heatmap
070422_MJFF_Proteins_and_Peptides_PRM_Manually_Curated_for_Supplementary_Data_2022-11-02_12-38-03.sky.zip2022-11-02 23:23:1917535331036