Curating the Innate Immunity Interactome

Background: The innate immune response is the first line of defence against invading pathogens and is regulatedby complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on theregulation of innate immunity through the analysis and modelling of these networks. A key initial step in thisprocess is the contextual cataloguing of the components of this system and the molecular interactions thatcomprise these networks. InnateDB (http://www.innatedb.com) is a molecular interaction and pathway databasedeveloped to facilitate systems-level analyses of innate immunity.Results: Here, we describe the InnateDB curation project, which is manually annotating the human and mouseinnate immunity interactome in rich contextual detail, and present our novel curation software system, which hasbeen developed to ensure interactions are curated in a highly accurate and data-standards compliant manner. Todate, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature. Here, wepresent data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced networkand pathway annotation available for systems-level analysis and discuss the challenges that face such curationefforts. Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has thepotential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity.Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and otherbiological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to otherpathways, which as yet, have not been implicated in the innate immune response.Conclusions: In summary, curation of the InnateDB interactome provides a wealth of information to enablesystems-level analysis of innate immunity.