Connect the dots A systems level approach for analyzing the miRNA-mediated cell death network

In recent years, substantial research interests have arisen to decipher miRNA function in cell death modules such as apoptosis and autophagy. Despite enormous success, it is increasingly evident that systems biology approaches that analyze the intra-and inter-modular connectivity are essential to uncover the generic organizing principles of the miRNA-mediated cell death network. We therefore constructed the miRDeathDB database to archive experimentally confirmed programmed cell death (PCD)-associated miRNAs together with their target proteins. Based on global analysis of the miRNA-mediated cell death network, we find there are two classes of miRNAs important to the cell death output. One class tends to have more regulatory links to proteins within death modules, whereas the other one lies on the boundary between modules, and tends to connect with more protein pairs across the modules. These findings indicate that miRNAs provide a novel communication mechanism between PCD-related proteins involved in both intra-and inter-cell death modules. Furthermore, miRDeathDB can also facilitate researcher access to a variety of resources centered on PCD-associated miRNAs.