Reverse engineering the inflammatory “clock”: from computational modeling to rational resetting

Properly-regulated inflammation is central to homeostasis, and becomes dysregulated after traumatic injury, hemorrhage, and sepsis. Inflammation is a dynamic, complex system whose function, like that of an analog clock, cannot be discerned simply from a laundry list of its parts (data). Dynamic approaches to data-driven computational modeling can be thought of as the “gears” and “hands” of the “clock,” and have led to insights regarding principal drivers, dynamic networks, feedbacks, and regulatory switches. In parallel, mechanistic computational models have given an abstracted sense of how the inflammatory “clock” works, leading to in silico models of critically ill individuals and populations. Integrating data-driven and mechanistic modeling may point the way to a rational “resetting” of inflammation via model-driven precision medicine.