Related Experiment Video
Updated: Jul 24, 2025
Author Spotlight: Advancing Alzheimer's Research – Exploring Early Detection and Multi-Omics Approaches
Published on: December 15, 2023
Identification and prediction of m7G-related Alzheimer's disease subtypes: insights from immune infiltration and
Chao Ma1,2, Jian Li3, Yuhua Chi1
1Department of General Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China.
Introduction:
Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder that primarily affects older individuals. N7-methylguanosine (m7G) is a common RNA chemical modification that impacts the development of numerous diseases. Thus, our work investigated m7G-related AD subtypes and established a predictive model.
Methods:
The datasets for AD patients, including GSE33000 and GSE44770, were obtained from the Gene Expression Omnibus (GEO) database, which were derived from the prefrontal cortex of the brain. We performed differential analysis of m7G regulators and examined the immune signatures differences between AD and matched-normal samples. Consensus clustering was employed to identify AD subtypes based on m7G-related differentially expressed genes (DEGs), and immune signatures were explored among different clusters. Furthermore, we developed four machine learning models based on the expression profiles of m7G-related DEGs and identified five important genes from the optimal model. We evaluated the predictive power of the 5-gene-based model using an external AD dataset (GSE44770).
Results:
A total of 15 genes related to m7G were found to be dysregulated in patients with AD compared to non-AD patients. This finding suggests that there are differences in immune characteristics between these two groups. Based on the differentially expressed m7G regulators, we categorized AD patients into two clusters and calculated the ESTIMATE score for each cluster. Cluster 2 exhibited a higher ImmuneScore than Cluster 1. We performed the receiver operating characteristic (ROC) analysis to compare the performance of four models, and we found that the Random Forest (RF) model had the highest AUC value of 1.000. Furthermore, we tested the predictive efficacy of a 5-gene-based RF model on an external AD dataset and obtained an AUC value of 0.968. The nomogram, calibration curve, and decision curve analysis (DCA) confirmed the accuracy of our model in predicting AD subtypes.
Conclusion:
The present study systematically examines the biological significance of m7G methylation modification in AD and investigates its association with immune infiltration characteristics. Furthermore, the study develops potential predictive models to assess the risk of m7G subtypes and the pathological outcomes of patients with AD, which can facilitate risk classification and clinical management of AD patients.
Insights
This study identifies N7-methylguanosine (m7G) related subtypes in Alzheimer's disease (AD) and develops a predictive model. A 5-gene Random Forest model accurately predicts AD subtypes, aiding in risk classification and clinical management.
Area of Science:
- Neuroscience
- Genomics
- Immunology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder with complex underlying mechanisms.
- N7-methylguanosine (m7G) is an RNA modification implicated in various diseases, including neurodegeneration.
Purpose of the Study:
- To investigate m7G-related subtypes in Alzheimer's disease.
- To establish a predictive model for AD risk stratification based on m7G-related gene expression.
Main Methods:
- Utilized GEO datasets (GSE33000, GSE44770) from AD patients' prefrontal cortex.
- Performed differential expression analysis of m7G regulators and immune signatures.
- Employed consensus clustering to identify AD subtypes and developed machine learning models, including Random Forest.
Main Results:
- Identified 15 dysregulated m7G-related genes in AD patients.
- Categorized AD patients into two clusters with distinct immune characteristics.
- Developed a 5-gene Random Forest model with high predictive accuracy (AUC=0.968) on an external dataset.
Conclusions:
- m7G modification plays a significant role in AD pathogenesis and is associated with immune infiltration.
- The developed predictive model facilitates risk classification and clinical management of AD patients.
- This research highlights the potential of m7G-related biomarkers for AD diagnosis and treatment.
