Transcriptomics profiling of Parkinson's disease progression subtypes reveals distinctive patterns of gene expression.

Background: Parkinson's Disease (PD) varies widely among individuals, and Artificial Intelligence (AI) has recently helped to identify three disease progression subtypes. While their clinical features are already known, their gene expression profiles remain unexplored. Objectives: The objectives of...

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Publicado en:Journal of Central Nervous System Disease pp. 1 - 18
Autores principales: Fabrizio, Carlo, Termine, Andrea, Caltagirone, Carlo
Formato: algorithm research tables/charts Journal Article
Publicado: Sage Publications Inc. 1/27/2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 1/27/2025
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      pub: Sage Publications Inc.
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        atl: Transcriptomics profiling of Parkinson's disease progression subtypes reveals distinctive patterns of gene expression.
      aug:
        au:
          Fabrizio, Carlo
          Termine, Andrea
          Caltagirone, Carlo
        affil: Data Science Unit, 9362 Santa Lucia Foundation IRCCS, Rome, Italy
      sug:
        subj:
          Gene Expression Profiling
          Parkinson Disease Familial and Genetic
          Disease Progression Familial and Genetic
          Gene Expression Evaluation
          Parkinson Disease Classification
          Disease Progression Risk Factors
          Risk Assessment
          Boosting Machine Learning Algorithms
          Genetic Risk Score
          Prediction Algorithms
          Human
          Retrospective Design
          Record Review
          Prospective Studies
          Machine Learning Algorithms
          RNA
          Sequence Analysis
          Individualized Medicine
          Funding Source
          Parkinson Disease Prognosis
          ROC Curve
          Cell Physiology
          Energy Metabolism
          Genetic Markers
      ab: Background: Parkinson's Disease (PD) varies widely among individuals, and Artificial Intelligence (AI) has recently helped to identify three disease progression subtypes. While their clinical features are already known, their gene expression profiles remain unexplored. Objectives: The objectives of this study were (1) to describe the transcriptomics characteristics of three PD progression subtypes identified by AI, and (2) to evaluate if gene expression data can be used to predict disease subtype at baseline. Design: This is a retrospective longitudinal cohort study utilizing the Parkinson's Progression Markers Initiative (PPMI) database. Methods: Whole blood RNA-Sequencing data underwent differential gene expression analysis, followed by multiple pathway analyses. A Machine Learning (ML) classifier, namely XGBoost, was trained using data from multiple modalities, including gene expression values. Results: Our study identified differentially expressed genes (DEGs) that were uniquely associated with Parkinson's disease (PD) progression subtypes. Importantly, these DEGs had not been previously linked to PD. Gene-pathway analysis revealed both distinct and shared characteristics between the subtypes. Notably, two subtypes displayed opposite expression patterns for pathways involved in immune response alterations. In contrast, the third subtype exhibited a more unique profile characterized by increased expression of genes related to detoxification processes. All three subtypes showed a significant modulation of pathways related to the regulation of gene expression, metabolism, and cell signaling. ML revealed that the progression subtype with the worst prognosis can be predicted at baseline with 0.877 AUROC, yet the contribution of gene expression was marginal for the prediction of the subtypes. Conclusion: This study provides novel information regarding the transcriptomics profiles of PD progression subtypes, which may foster precision medicine with relevant indications for a finer-grained diagnosis and prognosis.
      pubtype: Academic Journal
      doctype:
        algorithm
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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