Decipher macrophage-fibroblast-cardiomyocyte signaling interactions associated with heart failure using deep graph neural network models and single-cell RNA-seq data

Abstract

Heart failure is a major cause of mortality. In these recent studies, novel evidence, using single-cell transcriptomic data, was reported to indicate that macrophages and fibroblasts play important roles in heart failure. The involvement of macrophages in inflammation and the relationship between inflammation and fibrosis has been established. However, the underlying molecular targets and signaling pathways mediating signaling interactions among macrophages, fibroblasts, and cardiomyocytes remain unclear. In this study, analyzing the scRNA-seq datasets using deep learning models, we ranked the cell-type specific molecular targets; and uncovered the dysfunctional intra- and inter-cellular signaling pathways that are potentially associated with heart failure. The signaling targets and pathways could be helpful in identifying effective medications for heart disease inflammation management to prevent heart failure.