Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations.
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 combina...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5491127?pdf=render |
| _version_ | 1819134087532642304 |
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| author | Edgar Altszyler Alejandra C Ventura Alejandro Colman-Lerner Ariel Chernomoretz |
| author_facet | Edgar Altszyler Alejandra C Ventura Alejandro Colman-Lerner Ariel Chernomoretz |
| author_sort | Edgar Altszyler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T09:57:37Z |
| format | Article |
| id | doaj.art-13a614219520471d9ae5982ff84d403b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T09:57:37Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-13a614219520471d9ae5982ff84d403b2022-12-21T18:30:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e018008310.1371/journal.pone.0180083Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations.Edgar AltszylerAlejandra C VenturaAlejandro Colman-LernerAriel ChernomoretzUltrasensitive 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.http://europepmc.org/articles/PMC5491127?pdf=render |
| spellingShingle | Edgar Altszyler Alejandra C Ventura Alejandro Colman-Lerner Ariel Chernomoretz Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations. PLoS ONE |
| title | Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations. |
| title_full | Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations. |
| title_fullStr | Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations. |
| title_full_unstemmed | Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations. |
| title_short | Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations. |
| title_sort | ultrasensitivity in signaling cascades revisited linking local and global ultrasensitivity estimations |
| url | http://europepmc.org/articles/PMC5491127?pdf=render |
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