Temporal Pattern Recognition through Analog Molecular Computation.

Living cells communicate information about physiological conditions by producing signaling molecules in a specific timed manner. Different conditions can result in the same total amount of a signaling molecule, differing only in the pattern of the molecular concentration over time. Such temporally coded information can be completely invisible to even state-of-the-art molecular sensors with high chemical specificity that respond only to the total amount of the signaling molecule. Here, we demonstrate design principles for circuits with temporal specificity, that is, molecular circuits that respond to specific temporal patterns in a molecular concentration. We consider pulsatile patterns in a molecular concentration characterized by three fundamental temporal features: time period, duty fraction, and number of pulses. We develop circuits that respond to each one of these features while being insensitive to the others. We demonstrate our design principles using general chemical reaction networks and with explicit simulations of DNA strand displacement reactions. In this way, our work develops building blocks for temporal pattern recognition through molecular computation.