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Cuproptosis-related genes prediction feature and immune microenvironment in major depressive disorder
Daoyun Lei1,2, Jie Sun1,2, Jiangyan Xia1,2
1Department of Anesthesiology, Zhongda Hospital Southeast University (Jiangbei), Nanjing, 210048 Jiangsu, China.
Background:
Major depressive disorder (MDD) is a severe, unpredictable, ill-cured, relapsing neuropsychiatric disorder. A recently identified type of death called cuproptosis has been linked to a number of illnesses. However, the influence of cuproptosis-related genes in MDD has not been comprehensively assessed in prior study.
Aim:
This investigation intends to shed light on the predictive value of cuproptosis-related genes for MDD and the immunological microenvironment.
Methods:
GSE38206, GSE76826, GSE9653 databases were used to analyze cuproptosis regulators and immune characteristics. To find the genes that were differently expressed, weighted gene co-expression network analysis was employed. We calculated the effectiveness of the random forest model, generalized linear model, and limit gradient lifting to arrive at the best machine prediction model. Nomogram, calibration curve, and decision curve analysis were used to show the anticipated MDD's accuracy.
Results:
This study found that there were activated immune responses and cuproptosis-related genes that were dysregulated in people with MDD compared to healthy controls. Considering the test performance of the learned model and validation on subsequent datasets, the RF model (including OSBPL8, VBP1, MTM1, ELK3, and SLC39A6) was considered to have the best discriminative performance. (AUC = 0.875).
Conclusion:
Our study constructed a prediction model to predict MDD risk and clarified the potential connection between cuproptosis and MDD.
Insights
This study reveals that dysregulated cuproptosis-related genes and activated immune responses are linked to major depressive disorder (MDD). A random forest model accurately predicts MDD risk, highlighting a potential connection between cuproptosis and depression.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Major depressive disorder (MDD) is a severe, relapsing neuropsychiatric condition with complex underlying mechanisms.
- Cuproptosis, a recently identified form of cell death, has been implicated in various diseases, but its role in MDD remains underexplored.
Purpose of the Study:
- To investigate the predictive value of cuproptosis-related genes for major depressive disorder (MDD).
- To explore the association between cuproptosis-related genes and the immunological microenvironment in MDD.
Main Methods:
- Analysis of cuproptosis regulators and immune characteristics using datasets GSE38206, GSE76826, and GSE9653.
- Weighted gene co-expression network analysis to identify differentially expressed genes.
- Development and validation of machine learning models (Random Forest, Generalized Linear Model, Limit Gradient Lifting) for MDD prediction.
Main Results:
- Significant dysregulation of cuproptosis-related genes and activated immune responses were observed in MDD patients compared to healthy controls.
- The Random Forest (RF) model, incorporating genes OSBPL8, VBP1, MTM1, ELK3, and SLC39A6, demonstrated superior discriminative performance with an AUC of 0.875.
- The RF model showed robust predictive accuracy validated on subsequent datasets.
Conclusions:
- A novel prediction model for MDD risk has been developed.
- This study elucidates a potential link between cuproptosis and the pathogenesis of major depressive disorder.
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