  Mathematical methods of information theory constitute essential tools 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 to
analyze signaling data within the framework of information theory. Our approach
enables robust as well as statistically and computationally efficient analysis
of signaling systems with high-dimensional outputs and a large number of input
values. Analysis of the NF-kB single - cell signaling responses to TNF-a
uniquely reveals that the NF-kB signaling dynamics improves discrimination of
high concentrations of TNF-a with a modest impact on discrimination of low
concentrations. Our readily applicable R-package, SLEMI - statistical learning
based estimation of mutual information, allows the approach to be used by
computational biologists with only elementary knowledge of information theory.
