Identification of a possible proteomic biomarker in Parkinson’s disease: discovery and replication in blood, brain and CSF
<p>Biomarkers to aid diagnosis and delineate progression of Parkinson’s Disease are vital for targeting treatment in the early phases of disease. Here, we aim to discover a multi-protein panel representative of Parkinson’s and make mechanistic inferences from protein expression profiles within...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2022
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| _version_ | 1826310325392113664 |
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| author | Winchester, L Barber, I Lawton, M Ash, J Liu, B Evetts, S Hopkins-Jones, L Lewis, S Bresener, C Malpartida, AB Williams, N Gentlemen, S Wade-Martins, R Ryan, B Nevado-Holgado, A Hu, M Ben-Shlomo, Y Grosset, D Lovestone, S |
| author_facet | Winchester, L Barber, I Lawton, M Ash, J Liu, B Evetts, S Hopkins-Jones, L Lewis, S Bresener, C Malpartida, AB Williams, N Gentlemen, S Wade-Martins, R Ryan, B Nevado-Holgado, A Hu, M Ben-Shlomo, Y Grosset, D Lovestone, S |
| author_sort | Winchester, L |
| collection | OXFORD |
| description | <p>Biomarkers to aid diagnosis and delineate progression of Parkinson’s Disease are vital for targeting treatment in the early phases of disease. Here, we aim to discover a multi-protein panel representative of Parkinson’s and make mechanistic inferences from protein expression profiles within the broader objective of finding novel biomarkers.</p>
<p>We used aptamer-based technology (SomaLogic®) to measure proteins in 1,599 serum samples, 85 CSF samples and 37 brain tissue samples collected from two observational longitudinal cohorts (Oxford Parkinson’s Disease Centre and Tracking Parkinson’s) and the Parkinson’s Disease Brain Bank, respectively. Random forest machine learning was performed to discover new proteins related to disease status and generate multi-protein expression signatures with potential novel biomarkers. Differential regulation analysis and pathway analysis was performed to identify functional and mechanistic disease associations.</p>
<p>The most consistent diagnostic classifier signature was tested across modalities (CSF AUC = 0.74, p-value = 0.0009; brain AUC = 0.75, p-value = 0.006; serum AUC = 0.66, p-value = 0.0002). Focusing on serum samples and using only those with severe disease compared to controls increased the AUC to 0.72 (p-value = 1.0 × 10−04). In the validation dataset we showed that the same classifiers were significantly related to disease status (p-values < 0.001). Differential expression analysis and Weighted Gene Correlation Network Analysis highlighted key proteins and pathways with known relationships to Parkinson’s. Proteins from the complement and coagulation cascades suggest a disease relationship to immune response.</p>
<p>The combined analytical approaches in a relatively large number of samples, across tissue types, with replication and validation, provides mechanistic insights into the disease as well as nominating a protein signature classifier that deserves further biomarker evaluation.</p> |
| first_indexed | 2024-03-07T07:50:17Z |
| format | Journal article |
| id | oxford-uuid:a156c29b-6f8f-4aed-a828-526bf68f25a2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:50:17Z |
| publishDate | 2022 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:a156c29b-6f8f-4aed-a828-526bf68f25a22023-07-05T07:47:14ZIdentification of a possible proteomic biomarker in Parkinson’s disease: discovery and replication in blood, brain and CSFJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a156c29b-6f8f-4aed-a828-526bf68f25a2EnglishSymplectic ElementsOxford University Press2022Winchester, LBarber, ILawton, MAsh, JLiu, BEvetts, SHopkins-Jones, LLewis, SBresener, CMalpartida, ABWilliams, NGentlemen, SWade-Martins, RRyan, BNevado-Holgado, AHu, MBen-Shlomo, YGrosset, DLovestone, S<p>Biomarkers to aid diagnosis and delineate progression of Parkinson’s Disease are vital for targeting treatment in the early phases of disease. Here, we aim to discover a multi-protein panel representative of Parkinson’s and make mechanistic inferences from protein expression profiles within the broader objective of finding novel biomarkers.</p> <p>We used aptamer-based technology (SomaLogic®) to measure proteins in 1,599 serum samples, 85 CSF samples and 37 brain tissue samples collected from two observational longitudinal cohorts (Oxford Parkinson’s Disease Centre and Tracking Parkinson’s) and the Parkinson’s Disease Brain Bank, respectively. Random forest machine learning was performed to discover new proteins related to disease status and generate multi-protein expression signatures with potential novel biomarkers. Differential regulation analysis and pathway analysis was performed to identify functional and mechanistic disease associations.</p> <p>The most consistent diagnostic classifier signature was tested across modalities (CSF AUC = 0.74, p-value = 0.0009; brain AUC = 0.75, p-value = 0.006; serum AUC = 0.66, p-value = 0.0002). Focusing on serum samples and using only those with severe disease compared to controls increased the AUC to 0.72 (p-value = 1.0 × 10−04). In the validation dataset we showed that the same classifiers were significantly related to disease status (p-values < 0.001). Differential expression analysis and Weighted Gene Correlation Network Analysis highlighted key proteins and pathways with known relationships to Parkinson’s. Proteins from the complement and coagulation cascades suggest a disease relationship to immune response.</p> <p>The combined analytical approaches in a relatively large number of samples, across tissue types, with replication and validation, provides mechanistic insights into the disease as well as nominating a protein signature classifier that deserves further biomarker evaluation.</p> |
| spellingShingle | Winchester, L Barber, I Lawton, M Ash, J Liu, B Evetts, S Hopkins-Jones, L Lewis, S Bresener, C Malpartida, AB Williams, N Gentlemen, S Wade-Martins, R Ryan, B Nevado-Holgado, A Hu, M Ben-Shlomo, Y Grosset, D Lovestone, S Identification of a possible proteomic biomarker in Parkinson’s disease: discovery and replication in blood, brain and CSF |
| title | Identification of a possible proteomic biomarker in Parkinson’s disease: discovery and replication in blood, brain and CSF |
| title_full | Identification of a possible proteomic biomarker in Parkinson’s disease: discovery and replication in blood, brain and CSF |
| title_fullStr | Identification of a possible proteomic biomarker in Parkinson’s disease: discovery and replication in blood, brain and CSF |
| title_full_unstemmed | Identification of a possible proteomic biomarker in Parkinson’s disease: discovery and replication in blood, brain and CSF |
| title_short | Identification of a possible proteomic biomarker in Parkinson’s disease: discovery and replication in blood, brain and CSF |
| title_sort | identification of a possible proteomic biomarker in parkinson s disease discovery and replication in blood brain and csf |
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