A Two-level Approach for Fusing Early Signaling Events and Long Term Cellular Responses

摘要

In biological systems, reactions on different time scales exist and need to be considered for the analysis of physiological reactions such as proliferation. In this contribution we describe a two-level approach to decode biological reactions on a short time-scale, e. g. signaling, into long term cellular responses, e. g. proliferation. First, we derive a valid and parametrized dynamic model for signaling events on the short time-scale using set-based estimation methods allowing to take uncertainties into account. Second, the derived model candidate for early signaling events is fused with a model for long term proliferation using shape-based signaling properties. This approach is realized in the specific case study of Interleukin-6-induced signaling and proliferation. Our modeling approach enables us to consider both, dynamic early signaling events and static long term events. Furthermore, it allows a deeper understanding of how cells process information from early signaling events to long term cellular responses.