title: Gene signature-based mapping of immunological systems and diseases.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bio-Innovation, Sanofi Global Biotherapeutics, 38 Sidney Street, Cambridge, MA, 02139, USA. hong.liu@sanofi.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Bio-Innovation, Sanofi Global Biotherapeutics, 38 Sidney Street, Cambridge, MA, 02139, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Liu
authors.affiliation: Bioinformatics Program, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Toups
authors.affiliation: Bio-Innovation, Sanofi Global Biotherapeutics, 38 Sidney Street, Cambridge, MA, 02139, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Soos
authors.affiliation: Bio-Innovation, Sanofi Global Biotherapeutics, 38 Sidney Street, Cambridge, MA, 02139, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Arendt
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D018390:Gene Targeting; D023281:Genomics / Q000379:methods; D006801:Humans; D007107:Immune System; D007154:Immune System Diseases / Q000235:genetics*; D051379:Mice; D059467:Transcriptome
keywords: Enrichment analysis; Gene set; Gene signature; Immune cell; Immune disease; Network-based analysis