| Title: | Leveraging machine learning to predict Parkinson's disease using pre-symptomatic proteomics data |
| Journal: | Brain |
| Published: | 14 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40804706/ |
| DOI: | https://doi.org/10.1093/brain/awaf303 |
Publication 19739
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Abstract
In Parkinson's disease, non-motor symptoms precede the characteristic motor manifestations by up to 20 years. However, predicting the disease risk remains challenging. We applied machine learning to 2937 plasma proteins assayed in UK Biobank participants with Parkinson's disease to predict disease outcome up to 14 years before diagnosis. Of the 446 proteins found to be dysregulated in incident cases compared with controls, a subset of 23 predicted disease with an area under the curve (AUC) value of 0.78 in incident and 0.795 in prevalent cases. The utility of the identified proteomic signatures was validated in an independent cohort, based on 16 proteins shared across datasets, leading to a validation AUC of up to 0.76. Parkinson's disease-related pathways, including neuron death and amyloid-β clearance, were enriched up to 9 years before diagnosis. Furthermore, a co-expression network analysis revealed protein modules associated with disease risk and time-to-diagnosis. Our findings underscore the potential of applying machine learning to large-scale proteomics data from pre-symptomatic patients for early disease prediction.</p>
10 Keywords
- Aged
- Biomarkers
- Cohort Studies
- Female
- Humans
- Machine Learning
- Male
- Middle Aged
- Parkinson Disease
- Proteomics
5 Authors
- Shirley Nieves-Rodriguez
- Liping Hou
- Christopher D Whelan
- Shuwei Li
- Abolfazl Doostparast Torshizi
2 Applications
| Application ID | Title |
|---|---|
| 52293 | Large-scale whole genome sequencing of the UK Biobank cohort to generate and evaluate therapeutic hypotheses regarding targets, biomarkers and pathways implicated in disease |
| 65851 | Large-scale proteomic profiling to facilitate genetics-guided drug discovery and precision medicine: The UK Biobank - Pharma Proteomics Project (UKB-PPP) |
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