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

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.

Duffy, DarraghPasteur Institute (author)
Rouilly, VincentPasteur Institute (author)
Posseme, CélinePasteur Institute (author)
Djebali, RaoufPasteur Institute (author)
Illanes, GabrielPasteur Institute,University of the Republic (author)
Libri, ValentinaPasteur Institute (author)
Albaud, BenoitCurie Institute, Paris (author)
Gentien, DavidCurie Institute, Paris (author)
Piasecka, BarbaraPasteur Institute (author)
Hasan, MilenaPasteur Institute (author)
Fontes, MagnusLund University,Lunds universitet,Matematikcentrum,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Mathematical Sciences,Departments at LTH,Faculty of Engineering, LTH,Pasteur Institute(Swepub:lu)math-mfo (author)
Quintana-Murci, LluisPasteur Institute (author)
Albert, Matthew L.Pasteur Institute (author)
Pasteur InstituteGenentech, Inc (creator_code:org_t)
Milieu Intérieur Consortium

By the author/editor: Urrutia, Alejand ...; Duffy, Darragh; Rouilly, Vincent; Posseme, Céline; Djebali, Raouf; Illanes, Gabriel; show more...; Libri, Valentina; Albaud, Benoit; Gentien, David; Piasecka, Barbar ...; Hasan, Milena; Fontes, Magnus; Quintana-Murci, ...; Albert, Matthew ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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