Screening for marker mitochondrial genes in pathogenesis of intervertebral disc degeneration based on integrated weighted gene co-expression network analysis and advanced machine learning
Screening for marker mitochondrial genes in pathogenesis of intervertebral disc degeneration based on integrated weighted gene co-expression network analysis and advanced machine learning
Objective To screen marker mitochondrial genes in intervertebral disc degeneration(IDD)using weighted gene co-expression network analysis(WGCNA)and advanced machine learning.Methods Intervertebral disc degeneration microarray data were downloaded from the Gene Expression Omnibus(GEO)database,and WGCNA was employed to intersect the IDD related gene modules and mitochondrial genes in the GSE70362 dataset.Advanced machine learning approaches(support vector machine-recursive feature elimination[SVM-RFE],least absolute shrinkage and selection operator[LASSO]regression and random forest[RF]algorithm)were used to screen the marker mitochondrial genes in IDD further.The effectiveness of the marker mitochondrial genes was validated using receiver operating characteristic(ROC)curve.External validation was conducted using the GSE15227 dataset.Additionally,the Cibersort algorithm was utilized to evaluate the correlation between marker mitochondrial genes and immune cell infiltration.Results Four marker mitochondrial genes(BNIP3,ISCU,MCUB and SPTLC2)were identified by integrated WGCNA and machine learning algorithms.The ROC curve showed an area under the curve(AUC)for BNIP3,ISCU,MCUB and SPTLC2 as 0.562,0.780,0.766 and 0.702,respectively.External dataset validation revealed that only the expression of BNIP3 exhibited statistically significant difference(P<0.05).Immunocyte differential analysis showed that compared to the normal control group,the number of monocytes in IDD patients was fewer,and the difference was statistically significant(P<0.05).BNIP3 was positively correlated with regulatory T cells(Tregs,r=0.43)and negatively correlated with follicular helper T cells(r=-0.40).Conclusions Mitochondrial gene BNIP3 ISCU,MCUB and SPTLC2 can serve as novel biomarkers,and BNIP3 may participate in the occurrence of IDD by regulating immune cells.The above genes can serve as potential targets for the treatment of IDD based on mitochondrial homeostasis strategies.
维普
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