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Denis Thieffry

Computational systems biology

This team is part of the Computional Biology Center.

Main lines of research


Our team combines three interdisciplinary approaches to model the behaviour of molecular regulatory networks.
The first approach leans on the development of the software suite RSAT (http://www.rsat.eu) devoted to the analysis of functional genomic data (ChIP-seq, transcriptome) in order to delineate cis-regulatory regions (promoters, enhancers) and their role in the control of gene expression.

The second approach leans on the development of methodologies for the joint analysis of complementary large-scale functional genomic data (RNA-seq, miRNA-seq, ChIP-seq at buulk and single-cell resolution) in order to decipher the molecular mechanisms driving a given biological state

The second approach leans on the development of the software GINsim (http://www.ginsim.org) devoted to the dynamical modelling and the analysis or large signalling/regulatory networks.
These methodological developments are motivated by and applied to the study of regulatory networks controlling cell specification, differentiation and reprogramming in animals, in particular of cells of the immune system, in close collaboration with several experimental teams.
Tools and models are systematically made available to the scientific community.

Selected recent publications
  • Abbas A, Vu Manh TP, Valente M, Collinet N, Attaf N, Dong C, Naciri K, Chelbi R, Brelurut G, Cervera-Marzal I, Rauwel B, Davignon J-L, Bessou G, Thomas-Chollier M, Thieffry D, Villani A-C, Milpied P, Dalod M*, Elena Tomasello* (2020). Single-cell analysis of mouse plasmacytoid dendritic cells unravels their activation trajectory and their molecular regulation in vivo during a viral infection. Nature Immunology 21 : 983-97.
  • Grandclaudon M, Perrot-Dockès M, Trichot C, Karpf L, Abouzid O, Chauvin C, Sirven P, Abou-Jaoudé W, Berger F, Hupé P, Thieffry D, Sansonnet L, Chiquet J, Levy-Leduc C, Soumelis V (2019). A quantitative multivariate model of human dendritic cell-T helper cell communication. Cell 179 : 432-447.
  • Rodríguez-Jorge O, Kempis-Calanis LA, Abou-Jaoudé W, Gutiérrez-Reyna DY, Hernandez C, Ramirez-Pliego O, Thomas-Chollier M, Spicuglia S, Santana MA*, Thieffry D* (2019). Synergy between T cell receptor and Toll-like receptor 5 signaling for CD4+ T cell activation. Science Signaling 12 : eaar3641.
  • Nga Thi Thuy Nguyen NT, Contreras-Moreira B, Castro-Mondragon JA, Santana-Garcia W, Ossio R, Robles-Espinoza CD, Bahin M, Collombet S, Vincens P, Thieffry D, van Helden J*, Medina-Rivera A*, Thomas-Chollier M* (2018) . RSAT 2018 : Regulatory Sequence Analysis Tools 20th Anniversary. Nucleic Acids Research 46 : W209-14.
  • Collombet S, van Oevelen C, Sardina Ortega JL, Abou-Jaoudé W, Di Stefano B, Thomas-Chollier M, Graf T, Thieffry D (2017). Logical modeling of lymphoid and myeloid cell specification and transdifferentiation. PNAS 114 : 5792–9.



  • Logical model for the lymphoid and myeloid cell specification and (...)
    Logical model for the lymphoid and myeloid cell specification and transdifferentiation (built with GINsim software)
    Development of methodologies for the joint analysis of complementary (...)
    Development of methodologies for the joint analysis of complementary large-scale functional genomic data (RNA-seq, miRNA-seq, ChIP-seq at bulk and single-cell resolutions)
    Molecular map for the main MAPK pathways (built with CellDesigner (...)
    Molecular map for the main MAPK pathways (built with CellDesigner Software)
    ChIP-exo signal covering ChIP-seq peaks allows to infer genomic binding (...)
    ChIP-exo signal covering ChIP-seq peaks allows to infer genomic binding modes of cooperating transcription factors