Gene signature-based mapping of immunological systems and diseases.

Background: The immune system is multifaceted, structured by diverse components that interconnect using multilayered dynamic cellular processes. Genomic technologies provide a means for investigating, at the molecular level, the adaptations of the immune system in host defense and its dysregulation in pathological conditions. A critical aspect of intersecting and investigating complex datasets is determining how to best integrate genomic data from diverse platforms and heterogeneous sample populations to capture immunological signatures in health and disease.

Result: We focus on gene signatures, representing highly enriched genes of immune cell subsets from both diseased and healthy tissues. From these, we construct a series of biomaps that illustrate the molecular linkages between cell subsets from different lineages, the connectivity between different immunological diseases, and the enrichment of cell subset signatures in diseased tissues. Finally, we overlay the downstream genes of drug targets with disease gene signatures to display the potential therapeutic applications for these approaches.

Conclusion: An in silico approach has been developed to characterize immune cell subsets and diseases based on the gene signatures that most differentiate them from other biological states. This modular 'biomap' reveals the linkages between different diseases and immune subtypes, and provides evidence for the presence of specific immunocyte subsets in mixed tissues. The over-represented genes in disease signatures of interest can be further investigated for their functions in both host defense and disease.