BowTieBuilder: modeling signal transduction pathways

Sensory proteins react to changing environmental conditions by transducing signals into the cell. These signals are integrated into core proteins that activate downstream target proteins such as transcription factors (TFs). This structure is referred to as a bow tie, and allows cells to respond appropriately to complex environmental conditions. Understanding this cellular processing of information, from sensory proteins (e.g., cell-surface proteins) to target proteins (e.g., TFs) is important, yet for many processes the signaling pathways remain unknown.

Here, we present BowTieBuilder for inferring signal transduction pathways from multiple source and target proteins. Given protein-protein interaction (PPI) data signaling pathways are assembled without knowledge of the intermediate signaling proteins while maximizing the overall probability of the pathway. To assess the inference quality, BowTieBuilder and three alternative heuristics are applied to several pathways, and the resulting pathways are compared to reference pathways taken from KEGG. In addition, BowTieBuilder is used to infer a signaling pathway of the innate immune response in humans and a signaling pathway that potentially regulates an underlying gene regulatory network.

We show that BowTieBuilder, given multiple source and/or target proteins, infers pathways with satisfactory recall and precision rates and detects the core proteins of each pathway.