Standardized Whole-Blood Transcriptional Profiling Enables the Deconvolution of Complex Induced Immune Responses

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Systems approaches for the study of immune signaling pathways have been traditionally based on purified cells or cultured lines. However, in vivo responses involve the coordinated action of multiple cell types, which interact to establish an inflammatory microenvironment. We employed standardized whole-blood stimulation systems to test the hypothesis that responses to Toll-like receptor ligands or whole microbes can be defined by the transcriptional signatures of key cytokines. We found 44 genes, identified using Support Vector Machine learning, that captured the diversity of complex innate immune responses with improved segregation between distinct stimuli. Furthermore, we used donor variability to identify shared inter-cellular pathways and trace cytokine loops involved in gene expression. This provides strategies for dimension reduction of large datasets and deconvolution of innate immune responses applicable for characterizing immunomodulatory molecules. Moreover, we provide an interactive R-Shiny application with healthy donor reference values for induced inflammatory genes.

Detaljer

Författare
  • Milieu Intérieur Consortium
Enheter & grupper
Externa organisationer
  • Pasteur Institute
  • Genentech, Inc
  • University of the Republic
  • Curie Institute, Paris
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)2777-2791
Antal sidor15
TidskriftCell Reports
Volym16
Utgivningsnummer10
StatusPublished - 2016 sep 1
PublikationskategoriForskning
Peer review utfördJa