Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations

作者：Altszyler Edgar; Ventura Alejandra C; Colman Lerner Alejandro; Chernomoretz Ariel^*

来源：PLos One, 2017, 12(6): e0180083.

DOI：10.1371/journal.pone.0180083

Ultrasensitive response motifs, capable of converting graded stimuli into binary responses, are well-conserved in signal transduction networks. Although it has been shown that a cascade arrangement of multiple ultrasensitive modules can enhance the system's ultrasensitivity, how a given combination of layers affects a cascade's ultrasensitivity remains an open question for the general case. Here, we introduce a methodology that allows us to determine the presence of sequestration effects and to quantify the relative contribution of each module to the overall cascade's ultrasensitivity. The proposed analysis framework provides a natural link between global and local ultrasensitivity descriptors and it is particularly well suited to characterize and understand mathematical models used to study real biological systems. As a case study, we have considered three mathematical models introduced by O'Shaughnessy et al. to study a tunable synthetic MAPK cascade, and we show how our methodology can help modelers better understand alternative models.

• 出版日期2017-6-29