Revisiting Connectivity Map from a gene co-expression network analysis

The Connectivity Map (CMap) is a tool that has been extensively utilized to study drug repositioning and side-effect prediction. However, most of these analyses rely on signature genes, ignoring the pathways by which those genes are regulated, as well as the functional overlap of redundant genes. The present study utilized a systems biology approach referred to as Weighted Gene Co-expression Network Analysis (WGCNA) to dissect the transcriptional profiles of CMap and reveal these hidden factors. Seven common modules associated with protein binding, extracellular matrix organization and translation were identified. Furthermore, drugs were clustered based on module expression to infer their mechanism of action (MoA) based on common activity profiles. As an extension of this, an example of disease-based module projection to identify novel drugs was provided. The analysis developed in the present study may provide a novel framework for drug repositioning or discovering MoAs.