Machine learning and bioinformatics to identify 8 autophagy-related biomarkers and construct gene regulatory networks in dilated cardiomyopathy

Abstract

Abstract Dilated cardiomyopathy (DCM) is a condition of impaired ventricular remodeling and systolic diastole that is often complicated by arrhythmias and heart failure with a poor prognosis. This study attempted to identify autophagy-related genes (ARGs) with diagnostic biomarkers of DCM using machine learning and bioinformatics approaches. Differential analysis of whole gene microarray data of DCM from the Gene Expression Omnibus (GEO) database was performed using the NetworkAnalyst 3.0 platform. Differentially expressed genes (DEGs) matching (|log2FoldChange ≥ 0.8, p value < 0.05|) were obtained in the GSE4172 dataset by merging ARGs from the autophagy gene libraries, HADb and HAMdb, to obtain autophagy-related differentially expressed genes (AR-DEGs) in DCM. The correlation analysis of AR-DEGs and their visualization were performed using R language. Gene Ontology (GO) enrichment analysis and combined multi-database pathway analysis were served by the Enrichr online enrichment analysis platform. We used machine learning to screen the diagnostic biomarkers of DCM. The transcription factors gene regulatory network was constructed by the JASPAR database of the NetworkAnalyst 3.0 platform. We also used the drug Signatures database (DSigDB) drug database of the Enrichr platform to screen the gene target drugs for DCM. Finally, we used the DisGeNET database to analyze the comorbidities associated with DCM. In the present study, we identified 23 AR-DEGs of DCM. Eight (PLEKHF1, HSPG2, HSF1, TRIM65, DICER1, VDAC1, BAD, TFEB) molecular markers of DCM were obtained by two machine learning algorithms. Transcription factors gene regulatory network was established. Finally, 10 gene-targeted drugs and complications for DCM were identified.