Identification of hub genes in heart failure by integrated bioinformatics analysis and machine learning

Abstract

ObjectiveTo screen feature genes of heart failure patients through machine learning methods, in order to identify characteristic genes driving heart failure and investigate the progression of heart failureMethodsHeart failure patient samples were downloaded from the public database GEO (Gene Expression Omnibus), including the datasets GSE116250, GSE120895, and GSE59867. GSE116250 and GSE120895 were used as the testing set, while GSE59867 was used as the validation set. LASSO regression analysis and SVM-RFE were utilized to identify feature genes.ResultsAnalysis showed that among the differentially expressed genes between normal and heart failure patients, 9 genes were upregulated and 10 genes were downregulated. ROC curve analysis in the training set showed that TAGLN and SGPP2 had AUC values greater than 0.7. Moreover, SDSL and SMTNL2 had even higher AUC values of greater than 0.9. However, further analysis in the validation set showed that only SDSL had an AUC value greater than 0.7. Western blot experiments, RT-PCR, and ISO-induced experiments confirmed that SDSL was highly expressed in heart failure patients and promoted heart failure progression. In addition, SDSL promoted PARP1 expression and knockdown of SDSL expression led to decreased Cleaved-PARP1 expression and reduced cardiomyocyte apoptosis. Conversely, overexpression of SDSL resulted in increased PARP1 expression and myocardial cell apoptosis. These results suggest that elevated expression of SDSL in cardiomyocytes from heart failure patients may be an important factor promoting the occurrence and development of heart failure.ConclusionsUsing machine learning methods and experimental validation, it has been demonstrated that SDSL is a driving gene in patients with heart failure, providing a new treatment direction for clinical treatment.