Integration of transcriptomic data identifies key hallmark genes in hypertrophic cardiomyopathy

Jing Xu,Xiangdong Liu,Qiming Dai

doi:10.1186/s12872-021-02147-7

Abstract

BackgroundHypertrophic 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.MethodsThe 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.ResultsOutstanding 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.ConclusionsThis 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.

Highlights

Hypertrophic cardiomyopathy (HCM) represents one of the most common inherited heart diseases
Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac muscle disorder characterized by left ventricle hypertrophy in the absence of abnormal loading conditions [1]
Four datasets contain gender information, and one of them with MYH7/MYBPC3 genotype information. Both microarray and RNA sequencing (RNA-Seq) data analysis were conducted and the gene expression values were obtained for each technology separately

Summary

Introduction

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. Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac muscle disorder characterized by left ventricle hypertrophy in the absence of abnormal loading conditions [1]. HCM occurs in at least 1 in 500 of the general population, making it one of the most common inherited heart diseases [2]. RNA-Seq can simultaneously detect whole gene expression levels [4]. Existing evidence showed a high consistency between microarray and RNA-Seq [5, 6].

Methods

Results

Discussion

Conclusion