Mathematical methods of information theory appear to provide a useful language to describe how stimuli are encoded in activities of signaling effectors. Exploring the information-theoretic perspective, however, remains conceptually, experimentally and computationally challenging. Specifically, existing computational tools enable efficient analysis of relatively simple systems, usually with one input and output only. Moreover, their robust and readily applicable implementations are missing. Here, we propose a novel algorithm, SLEMI—statistical learning based estimation of mutual information, to analyze signaling systems with high-dimensional outputs and a large number of input values. Our approach is efficient in terms of computational time as well as sample size needed for accurate estimation. Analysis of the NF- κ B single—cell signaling responses to TNF- α reveals that NF- κ B signaling dynamics improves discrimination of high concentrations of TNF- α with a relatively modest impact on discrimination of low concentrations. Provided R-package allows the approach to be used by computational biologists with only elementary knowledge of information theory.

Many components of signaling pathways are functionally pleiotropic, and signaling responses are marked with substantial cell-to-cell heterogeneity. Therefore, biochemical descriptions of signaling require quantitative support to explain how complex stimuli (inputs) are encoded in distinct activities of pathways effectors (outputs). A unique perspective of information theory cannot be fully utilized due to lack of modeling tools that account for the complexity of biochemical signaling, specifically for multiple inputs and outputs. Here, we develop a modeling framework of information theory that allows for efficient analysis of models with multiple inputs and outputs; accounts for temporal dynamics of signaling; enables analysis of how signals flow through shared network components; and is not restricted by limited variability of responses. The framework allows us to explain how identity and quantity of type I and type III interferon variants could be recognized by cells despite activating the same signaling effectors.

BackgroundAs suggested by the origin of the word, sphingolipids are mysterious molecules with various roles in antagonistic cellular processes such as autophagy, apoptosis, proliferation and differentiation. Moreover, sphingolipids have recently been recognized as important messengers in cellular signaling pathways. Notably, sphingolipid metabolism disorders have been observed in various pathological conditions such as cancer and neurodegeneration.ResultsThe existing formal models of sphingolipid metabolism focus mainly on de novo ceramide synthesis or are limited to biochemical transformations of particular subspecies. Here, we propose the first comprehensive computational model of sphingolipid metabolism in human tissue. Contrary to the previous approaches, we use a model that reflects cell compartmentalization thereby highlighting the differences among individual organelles.ConclusionsThe model that we present here was validated using recently proposed methods of model analysis, allowing to detect the most sensitive and experimentally non-identifiable parameters and determine the main sources of model variance. Moreover, we demonstrate the usefulness of our model in the study of molecular processes underlying Alzheimer’s disease, which are associated with sphingolipid metabolism.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0176-9) contains supplementary material, which is available to authorized users.