Life in inherently dynamic and complex. For survival, cells must sense and adapt to their environment through means of interconnected pathways that transduce different signals into gene expression patterns. Certain signals involved in regulating cellular processes can vary over time in a pulsatile fashion.

Ligand-receptor systems, covalent modification cycles, and transcriptional networks are the central components of cell signalling and gene expression systems. While their behavior in reaching a steady state regime under step-like stimulation is well understood, their response under repetitive stimulation, particularly at early time stages is poorly characterized. Yet early-stage responses to external inputs can be as informative as those observed at later stages.

In simple systems, a periodic stimulation produces an initial transient response followed by periodic behavior. Transient responses are particularly relevant when the stimulation has a limited time span, or when the stimulated component’s timescale is slow as compared to the ones of the downstream processes, which may only capture the transient effects.

In this study, we analyze the frequency response of simple motifs at different time stages to dose-conserved pulsatile input signals. We show that in ligand-receptor systems, there is a resonant response in some specific metrics during the transient stages, which is not present in the periodic regime. We suggest this is a general system-level mechanism that cells may use to filter input signals that have consequences for higher order circuits. We evaluate how this behavior in isolated motifs is reflected in similar types of responses in cascades and pathways of which they are a part. Our studies suggest that transient frequency preferences are important dynamic features of cell signalling and gene expression systems, which have been previously overlooked.