Exploiting memory effects to detect the boundaries of biochemical subnetworks

Abstract: Partial measurements of biochemical reaction networks are ubiquitous and limit our ability to reconstruct the topology of the reaction network and the strength of the interactions amongst both the observed and the unobserved molecular species. Here, we show how we can utilize noisy time series of such partially observed networks to determine which species of the observed part form its boundary, i.e. have significant interactions with the unobserved part. This opens a route to reliable network reconstruction. The method exploits the memory terms arising from projecting the dynamics of the entire network onto the observed subnetwork. We apply it to the dynamics of the Epidermal Growth Factor Receptor (EGFR) network and show that it works even for substantial noise levels.