Global relative input-output sensitivities of the feed-forward loops in genetic networks

The feed-forward loops (FFLs) are fundamental network motifs with three components from gene regulatory networks to signaling transduction networks. Over the last decade, the structures and functions of FFLs, as well as the intrinsic relationships between different FFLs have received increasing attention from various disciplines. Based on the proposed global relative parameter sensitivities (GRPS) algorithm, this paper aims at investigating the global relative input-output sensitivities (GRIOS) of FFLs in genetic networks. The results indicate that the most frequently appeared C1 and I1 configurations are quite insensitive under various levels of inputs and also rather robust to system parameters. It follows that the functions of above circuits are robust for different inputs. It is also the reason why C1 and I1 are ubiquitous in various real-world genetic networks, especially in sensory related transcriptional networks. Moreover, the proposed GRIOS approach sheds some light on the potential practical applications, such as the synthetic genetic circuits and biological experimental design.