AUTHOR=Chen Peipei , Long Bo , Xu Yi , Wu Wei , Zhang Shuyang TITLE=Identification of Crucial Genes and Pathways in Human Arrhythmogenic Right Ventricular Cardiomyopathy by Coexpression Analysis JOURNAL=Frontiers in Physiology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01778 DOI=10.3389/fphys.2018.01778 ISSN=1664-042X ABSTRACT=

As one common disease causing young people to die suddenly due to cardiac arrest, arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of heart muscle whose progression covers one complicated gene interaction network that influence the diagnosis and prognosis of it. In our research, differentially expressed genes (DEGs) were screened, and we established a weighted gene coexpression network analysis (WGCNA) and gene set net correlations analysis (GSNCA) for identifying crucial genes as well as pathways related to ARVC pathogenic mechanism (n = 12). In the research, the results demonstrated that there were 619 DEGs in total between non-failing donor myocardial samples and ARVC tissues (FDR < 0.05). WGCNA analysis identified the two gene modules (brown and turquoise) as being most significantly associated with ARVC state. Then the ARVC-related four key biological pathways (cytokine–cytokine receptor interaction, chemokine signaling pathway, neuroactive ligand receptor interaction, and JAK-STAT signaling pathway) and four hub genes (CXCL2, TNFRSF11B, LIFR, and C5AR1) in ARVC samples were further identified by GSNCA method. Finally, we used t-test and receiver operating characteristic (ROC) curves for validating hub genes, results showed significant differences in t-test and their AUC areas all greater than 0.8. Together, these results revealed that the new four hub genes as well as key pathways that might be involved into ARVC diagnosis. Even though further experimental validation is required for the implication by association, our findings demonstrate that the computational methods based on systems biology might complement the traditional gene-wide approaches, as such, might offer a new insight in therapeutic intervention within rare diseases of people like ARVC.