Abstract
Biological discovery has been driven by advances in throughput and resolution of analysis technologies. They have also created an indelible bias for snapshot-based knowledge. Even though recent methods such as multi-omics single-cell assays have empowered immunological investigations, they still provide snapshots of cellular behaviors and thus, have inherent limitations in reconstructing unsynchronized dynamic events across individual cells. Here, we present a rationale for how NF-κB may convey specificity of contextual information through subtle quantitative features of its signaling dynamics. The next frontier of predictive understanding should involve functional characterization of NF-κB signaling dynamics and their immunological implications. This may help solve the apparent paradox that a ubiquitously activated transcription factor can shape accurate responses to different immune challenges.