Overview of DSPathNet, a novel computational framework to construct a drug-specific signaling pathway network (SPNetwork): metformin as a case.

Step 1: we collected the metformin upstream genes from multiple sources and inferred metformin downstream genes from metformin-induced gene expression data. We also compiled one human SPNetwork. Step 2: we utilized the metformin upstream and downstream genes as seeds to generate a metformin-specific SPNetwork from the human SPNetwork. The process involved longitudinal and lateral movements. Step 3: we utilized disease genes and genome-wide association studies (GWAS) data to evaluate if the metformin-specific SPNetwork was enriched with disease genes for type 2 diabetes (T2D) and cancer, genes associated with metformin action. Furthermore, we derived a crosstalk network of metformin action for T2D and cancer in order to identify key components in the metformin signal transduction via network topological and functional analysis. The nodes in orange correspond to the drug-related upstream genes, the nodes in green to the drug-related downstream genes, and the nodes in red to the nodes common to the upstream and downstream gene networks.