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Abstract:

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. © 2017 Altszyler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Registro:

Documento: Artículo
Título:Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations
Autor:Altszyler, E.; Ventura, A.C.; Colman-Lerner, A.; Chernomoretz, A.
Filiación:Laboratorio de Inteligencia Artificial Aplicada, Universidad de Buenos Aires, Departamento de Computacion -CONICET, Ciudad Universitaria, Pabellon I, Buenos Aires, C1428EHA, Argentina
IFIBYNE-UBACONICET, Departamento de Fisiologia, Biologia Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellon II, Buenos Aires, C1428EHA, Argentina
Departamento de Fisica FCEN UBA -IFIBA CONICET, Ciudad Universitaria, Pabellon I, Buenos Aires, C1428EHA, Argentina
Fundacion Instituto Leloir, Av Patricias Argentinas 435, Buenos Aires, C1405BWE, Argentina
Palabras clave:mitogen activated protein kinase; analytic method; analytical parameters; Article; biological model; case study; conceptual framework; cytology; mathematical model; quantitative analysis; sensitivity analysis; signal transduction; MAPK signaling; statistical model; MAP Kinase Signaling System; Models, Biological; Models, Statistical; Signal Transduction
Año:2017
Volumen:12
Número:6
DOI: http://dx.doi.org/10.1371/journal.pone.0180083
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:mitogen activated protein kinase, 142243-02-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n6_p_Altszyler

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Citas:

---------- APA ----------
Altszyler, E., Ventura, A.C., Colman-Lerner, A. & Chernomoretz, A. (2017) . Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations. PLoS ONE, 12(6).
http://dx.doi.org/10.1371/journal.pone.0180083
---------- CHICAGO ----------
Altszyler, E., Ventura, A.C., Colman-Lerner, A., Chernomoretz, A. "Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations" . PLoS ONE 12, no. 6 (2017).
http://dx.doi.org/10.1371/journal.pone.0180083
---------- MLA ----------
Altszyler, E., Ventura, A.C., Colman-Lerner, A., Chernomoretz, A. "Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations" . PLoS ONE, vol. 12, no. 6, 2017.
http://dx.doi.org/10.1371/journal.pone.0180083
---------- VANCOUVER ----------
Altszyler, E., Ventura, A.C., Colman-Lerner, A., Chernomoretz, A. Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations. PLoS ONE. 2017;12(6).
http://dx.doi.org/10.1371/journal.pone.0180083