Integrated Bioinformatics and Machine Learning Algorithms Analyses Highlight Related Pathways and Genes Associated with Alzheimer's Disease

Background: The pathophysiology of Alzheimer's Disease (AD) is still not fully studied. Objective: This study aimed to explore the differently expressed key genes in AD and build a predictive model of diagnosis and treatment. Methods: Gene expression data of the entorhinal cortex of AD, asymptomatic AD, and control samples from the GEO database were analyzed to explore the relevant pathways and key genes in the progression of AD. Differentially expressed genes between AD and the other two groups in the module were selected to identify biological mechanisms in AD through KEGG and PPI network analysis in Metascape. Furthermore, genes with a high connectivity degree by PPI network analysis were selected to build a predictive model using different machine learning algorithms. Besides, model performance was tested with five-fold cross-validation to select the best fitting model. Results: A total of 20 co-expression gene clusters were identified after the network was constructed. Module 1 (in black) and module 2 (in royal blue) were most positively and negatively correlated with AD, respectively. Total 565 genes in module 1 and 215 genes in module 2, respectively, overlapped in two differentially expressed genes lists. They were enriched in the G protein-coupled receptor signaling pathway, immune-related processes, and so on. 11 genes were screened by using lasso logistic regression, and they were considered to play an important role in predicting AD samples. The model built by the support vector machine algorithm with 11 genes showed the best performance. Conclusion: This result shed light on the diagnosis and treatment of AD.