Title:Uncovering the Impact of Aggrephagy in the Development of Alzheimer's
Disease: Insights Into Diagnostic and Therapeutic Approaches from
Machine Learning Analysis
Volume: 20
Issue: 9
Author(s): Jiayu Xu, Siqi Gou, Xueyuan Huang, Jieying Zhang, Xuancheng Zhou, Xiangjin Gong, Jingwen Xiong, Hao Chi*Guanhu Yang*
Affiliation:
- School of Clinical Medicine, Affiliated Hospital of
Southwest Medical University, Luzhou, China
- Department of Specialty Medicine, Ohio University, Athens,
OH, USA
Keywords:
Alzheimer's disease, machine learning, diagnostic model, aggrephagy, bioinformatics, drug discovery, high- -throughput sequencing data.
Abstract:
Background: Alzheimer's disease (AD) stands as a widespread neurodegenerative disorder
marked by the gradual onset of memory impairment, predominantly impacting the elderly.
With projections indicating a substantial surge in AD diagnoses, exceeding 13.8 million individuals
by 2050, there arises an urgent imperative to discern novel biomarkers for AD.
Methods: To accomplish these objectives, we explored immune cell infiltration and the expression
patterns of immune cells and immune function-related genes of AD patients. Furthermore, we
utilized the consensus clustering method combined with aggrephagy-related genes (ARGs) for typing
AD patients and categorized AD specimens into distinct clusters (C1, C2). A total of 272 candidate
genes were meticulously identified through a combination of differential analysis and
Weighted Gene Co-Expression Network Analysis (WGCNA). Subsequently, we applied three machine
learning algorithms-namely random forest (RF), support vector machine (SVM), and generalized
linear model (GLM)-to pinpoint a pathogenic signature comprising five genes associated
with AD. To validate the predictive accuracy of these identified genes in discerning AD progression,
we constructed nomograms.
Results: Our analyses uncovered that cluster C2 exhibits a higher immune expression than C1.
Based on the ROC(0.956). We identified five characteristic genes (PFKFB4, PDK3, KIAA0319L,
CEBPD, and PHC2T) associated with AD immune cells and function. The nomograms constructed
on the basis of these five diagnostic genes demonstrated effectiveness. In the validation group,
the ROC values were found to be 0.760 and 0.838, respectively. These results validate the robustness
and reliability of the diagnostic model, affirming its potential for accurate identification of
AD.
Conclusion: Our findings not only contribute to a deeper understanding of the molecular mechanisms
underlying AD but also offer valuable insights for drug development and clinical analysis.
The limitation of our study is the limited sample size, and although AD-related genes were identified
and some of the mechanisms elucidated, further experiments are needed to elucidate the more
in-depth mechanisms of these characterized genes in the disease.
