Temporal pattern recognition through analog molecular computation

TL;DR

This paper introduces design principles for molecular circuits capable of recognizing specific temporal patterns in signaling molecules, enabling cells to decode information encoded in timing rather than just concentration.

Contribution

It presents novel design strategies for circuits that respond selectively to temporal features of molecular signals, advancing molecular computation for pattern recognition.

Findings

Circuits can distinguish pulse period, duty cycle, and pulse count independently.

Design principles are validated through chemical reaction network simulations.

DNA strand displacement reactions implement the proposed circuits.

Abstract

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 abstract 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.