Current models of the innate immune response have been constructed from decades of studying individual pathogens and cell types in isolation. Though useful, the broad response described by these models means the nuances of pathogen-specific programs are lost to summarisation, and cell-specific aspects of inflammation are under-explored. Whilst the dynamics of cell- and pathogen-specific responses are difficult to compare simultaneously in a dish, we can use computational biology to combine large-scale expression studies into atlases, which allow the major axes of convergence and variation amongst activation states to be identified.
We have compiled an Atlas of Activation from 29 studies describing monocytes, macrophages, and dendritic cells stimulated with over 65 extrinsic and intrinsic stimuli. Our Atlas is an evolving tool that allows users to explore variation within innate responses from multiple perspectives. Sample derivation method, cell type, predicted receptor, and stimulus can be explored at a range of resolutions, from individual receptors and ligands, through to broad categories of treatment such as bacteria, fungi, and viruses. This combined view of experimental factors and cellular diversity aims to characterise relationships between biological and experimental factors, and signalling outcomes, which may help identify new regulators of inflammatory signalling.
In time, our Atlas of Activation will become available for users to explore at www.stemformatics.org, where it will complement our existing transcriptional atlases. Users will be able to project their own expression data onto the Atlas, allowing them to define activation states within their data, and to benchmark the behaviour of their cellular models of immune activation against a broad, highly curated cohort of data reflecting the breadth of pathogenic challenge to the innate immune system.