Identification and validation of differentially expressed chromatin regulators for diagnosis of aortic dissection using integrated bioinformatics analysis and machine-learning algorithms.

ABSTRACT

Background: Aortic dissection (AD) is a life-threatening disease. Chromatin regulators (CRs) are indispensable epigenetic regulators. We aimed to identify differentially expressed chromatin regulators (DECRs) for AD diagnosis. Methods: We downloaded the GSE52093 and GSE190635 datasets from the Gene Expression Omnibus database. Following the merging and processing of datasets, bioinformatics analysis was applied to select candidate DECRs for AD diagnosis CRs exertion; DECR identification using the "Limma" package; analyses of enrichment of function and signaling pathways; construction of protein-protein interaction (PPI) networks; application of machine-learning algorithms; evaluation of receiver operating characteristic (ROC) curves. GSE98770 served as the validation dataset to filter DECRs. Moreover, we collected peripheral-blood samples to further validate expression of DECRs by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, a nomogram was built for clinical use. Results: A total of 841 CRs were extracted from the merged dataset. Analyses of functional enrichment of 23 DECRs identified using Limma showed that DECRs were enriched mainly in epigenetic-regulation processes. From the PPI network, 17 DECRs were selected as node DECRs. After machine-learning calculations, eight DECRs were chosen from the intersection of 13 DECRs identified using support vector machine recursive feature elimination (SVM-RFE) and the top-10 DECRs selected using random forest. DECR expression between the control group and AD group were considerably different. Moreover, the area under the ROC curve (AUC) of each DECR was >0.75, and four DECRs (tumor protein 53 (TP53), chromobox protein homolog 7 (CBX7), Janus kinase 2 (JAK2) and cyclin-dependent kinase 5 (CDK5)) were selected as candidate biomarkers after validation using the external dataset and clinical samples. Furthermore, a nomogram with robust diagnostic value was established (AUC = 0.960). Conclusion: TP53, CBX7, JAK2, and CDK5 might serve as diagnostic DECRs for AD diagnosis. These DECRs were enriched predominantly in regulating epigenetic processes.