Integration of transcriptomic data identifies key hallmark genes in hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy (HCM) represents one of the most common inherited heart diseases. To identify key molecules involved in the development of HCM, gene expression patterns of the heart tissue samples in HCM patients from multiple microarray and RNA-seq platforms were investigated. Methods The significant genes were obtained through the intersection of two gene sets, corresponding to the identified differentially expressed genes (DEGs) within the microarray data and within the RNA-Seq data. Those genes were further ranked using minimum-Redundancy Maximum-Relevance feature selection algorithm. Moreover, the genes were assessed by three different machine learning methods for classification, including support vector machines, random forest and k-Nearest Neighbor. Results Outstanding results were achieved by taking exclusively the top eight genes of the ranking into consideration. Since the eight genes were identified as candidate HCM hallmark genes, the interactions between them and known HCM disease genes were explored through the protein-protein interaction (PPI) network. Most candidate HCM hallmark genes were found to have direct or indirect interactions with known HCM diseases genes in the PPI network, particularly the hub genes JAK2 and GADD45A. Conclusions This study highlights the transcriptomic data integration, in combination with machine learning methods, in providing insight into the key hallmark genes in the genetic etiology of HCM.

Automated summary

This study identified key genes involved in the development of HCM by analyzing gene expression patterns in heart tissue samples from HCM patients, and further evaluated these genes using machine learning methods. The top eight ranked genes were identified as candidate HCM hallmark genes, and their interactions with known HCM disease genes were explored through a protein-protein interaction network. Most candidate HCM hallmark genes were found to have direct or indirect interactions with known HCM disease genes, particularly the hub genes JAK2 and GADD45A.