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Measuring information transmission from single-cell heterogenous dynamical responses

From Q-bio

At the level of single cells, surface receptors convert extracellular cues into activation of transcription factors that control cellular decisions. A considerable unresolved issue is how information about ligand binding is encoded into nuclear activity of the transcription factors. A growing number of studies supports the hypothesis that this is achieved by temporal regulation of their activities. The current challenge is to recognise the features of temporal activity profile that represent information about a given stimulus.

A natural strategy to decipher this temporal coding is to scan cellular responses across a range of considered stimuli and identify most sensitive features of temporal profiles. Methods however to quantify sensitivity and information capacity at the single cell level, where stochastic effects play a major role, are virtually missing. We have developed a statistical framework to measure information of cellular outcomes from time-resolved, single cell, heterogeneous responses.

We use the method to analyse nuclear translocation of the NF-kB transcription factor upon TNF stimulation in mouse embryonic fibroblasts. We identified how the information capacity of the system changes with inclusion of time series data and indicate the essential features of the nuclear NF-kB temporal profile. Our method provides essential methodological advancement needed to gain understanding how temporal activity profiles encode information about a given stimulus.