Combinatorial code governing cellular responses to complex stimuli.

Cappuccio, Antonio; Zollinger, Raphaël; Schenk, Mirjam; Walczak, Aleksandra; Servant, Nicolas; Barillot, Emmanuel; Hupé, Philippe; Modlin, Robert L; Soumelis, Vassili (2015). Combinatorial code governing cellular responses to complex stimuli. Nature communications, 6(6847), p. 6847. Nature Publishing Group 10.1038/ncomms7847

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Cells adapt to their environment through the integration of complex signals. Multiple signals can induce synergistic or antagonistic interactions, currently considered as homogenous behaviours. Here, we use a systematic theoretical approach to enumerate the possible interaction profiles for outputs measured in the conditions 0 (control), signals X, Y, X+Y. Combinatorial analysis reveals 82 possible interaction profiles, which we biologically and mathematically grouped into five positive and five negative interaction modes. To experimentally validate their use in living cells, we apply an original computational workflow to transcriptomics data of innate immune cells integrating physiopathological signal combinations. Up to 9 of the 10 defined modes coexisted in context-dependent proportions. Each interaction mode was preferentially used in specific biological pathways, suggesting a functional role in the adaptation to multiple signals. Our work defines an exhaustive map of interaction modes for cells integrating pairs of physiopathological and pharmacological stimuli.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Schenk, Mirjam

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Mirjam Schenk

Date Deposited:

25 Jul 2017 15:16

Last Modified:

11 Mar 2021 06:39

Publisher DOI:

10.1038/ncomms7847

PubMed ID:

25896517

BORIS DOI:

10.7892/boris.102293

URI:

https://boris.unibe.ch/id/eprint/102293

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