Innate Immune Signaling Pathways in Reactome (94.13)

Abstract Toll-like receptors (TLR) play a key role in the innate immune system, providing vertebrates with a critical first line of defense against invading microbial pathogens. With the increasing body of molecular data relating to TLR function, organizing this information is useful to biologists and immunologists. We have used Reactome (www.reactome.org), a manually curated pathway database, to organize TLR data so that it can be viewed like an electronic textbook. TLR signaling cascades were authored by experts, maintained by the Reactome editorial staff and cross-referenced to publicly available bioinformatics resources. The Reactome data model generalizes the concept of a biochemical reaction to encompass any transformation of an input set of physical entities into an output set, and thus allows us to integrate TLR cascades with other innate immune processes, adaptive immunity, metabolic pathways, and other signaling processes. Since TLR-signaling molecules and pathways and the signaling pathways they initiate are highly conserved, Reactome provides pathway inference for 22 species based upon improved orthology prediction methods. A new entity-level pathway viewer and pathway analysis tools facilitate searching and visualizing pathway data and the analysis of user-supplied high-throughput data sets. All data content and software can be freely used and redistributed under open source terms.