Signaling hypergraphs

•We review common computational representations of signaling pathways.•These approaches cannot adequately model multi-way molecular reactions that are common in pathways.•We highlight hypergraphs as an under-utilized abstraction for representing such interactions.•We summarize challenges and opportunities presented by signaling hypergraphs.

Signaling pathways function as the information-passing mechanisms of cells. A number of databases with extensive manual curation represent the current knowledge base for signaling pathways. These databases motivate the development of computational approaches for prediction and analysis. Such methods require an accurate and computable representation of signaling pathways. Pathways are often described as sets of proteins or as pairwise interactions between proteins. However, many signaling mechanisms cannot be described using these representations. In this opinion, we highlight a representation of signaling pathways that is underutilized: the hypergraph. We demonstrate the usefulness of hypergraphs in this context and discuss challenges and opportunities for the scientific community.