Blood-based gene-expression biomarkers identification for the non-invasive diagnosis of Parkinson's disease using two-layer hybrid feature selection.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. Understanding the molecular mechanism and identifying potential biomarkers of PD promote effective treatments to the patients. Due to less invasiveness and easy accessibility, biomarkers from blood support early detection and diagnosis of PD. This study combined three independent PD microarray gene expression data from blood samples applying the early integration approach. Moderated t-statistics was employed to identify differentially expressed genes (DEGs). Relevant genes were selected using a two-layer embedded wrapper feature selection method with gradient boosting machine (GBM) in the first layer followed by an ensemble of wrappers including Recursive Feature Elimination (RFE), Genetic algorithm (GA) and Bi-directional elimination (Stepwise). All three wrappers were based on logistic regression classifier (LR). The PD-predictability of the generated signature was tested using nine supervised classification models, including eight shallow machine learning and one deep learning. On an independent dataset, GSE72267, Support Vector Machine-Radial (SVMR), and Deep Neural Network (DNN) showed the best performance with AUC 0.821 and 0.82, respectively. Comparison with existing blood-based PD signatures and the biological analysis verified the reliability of the proposed signature.