info:eu-repo/semantics/article
Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations
Fecha
2017-06Registro en:
Altszyler Lemcovich, Edgar Jaim; Ventura, Alejandra; Colman Lerner, Alejandro Ariel; Chernomoretz, Ariel; Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations; Public Library of Science; Plos One; 12; 6; 6-2017; 1-18
1932-6203
CONICET Digital
CONICET
Autor
Altszyler Lemcovich, Edgar Jaim
Ventura, Alejandra
Colman Lerner, Alejandro Ariel
Chernomoretz, Ariel
Resumen
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 wellsuited 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.