Combinatorial Code Governing Cellular Responses to Complex Stimuli

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Apr 22

PMID 25896517

Citations 17

Authors

Antonio Cappuccio

Raphael Zollinger

Mirjam Schenk

Aleksandra Walczak

Nicolas Servant

Emmanuel Barillot

Philippe Hupe

Robert L Modlin

Vassili Soumelis

Affiliations

Soon will be listed here.

Abstract

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.

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