Fig. 1.

Overview of the proposed method for identifying miRNA-gene regulatory comodules. A miRNA-gene comodule is defined as the union of a set of miRNAs (a miRNA module) and a set of genes (a gene module). The inputs are (i) two sets of expression profiles (represented by the matrices X₁ and X₂) for miRNAs and genes, measured on the same set of samples; (ii) a gene–gene interaction network (represented by the matrix A), including protein–protein interactions and DNA–protein interactions; and (iii) a list of predicted miRNA–gene regulatory interactions (represented by the matrix B) based on sequence data. We simultaneously factor the miRNA and gene expression matrices into a common basis W and two coefficient matrices H₁ and H₂. At the same time, additional knowledge is incorporated into this framework with network-regularized constraints. Sparsity constraints are also imposed on this framework so as to obtain easily interpretable solutions. The decomposed matrix components provide information about miRNA-gene regulatory comodules. Then the comodules are identified based on shared components (a column in W) with significant association values in the corresponding rows of H₁ and H₂.