Advanced fault diagnosis methods in molecular networks.

Analysis of the failure of cell signaling networks is an important topic in systems biology and has applications in target discovery and drug development. In this paper, some advanced methods for fault diagnosis in signaling networks are developed and then applied to a caspase network and an SHP2 ne...

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Autores principales: Iman Habibi, Effat S Emamian, Ali Abdi
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/cd0cb0fa723f4717b61e515c45a3f0b9
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spelling oai:doaj.org-article:cd0cb0fa723f4717b61e515c45a3f0b92021-11-25T05:57:39ZAdvanced fault diagnosis methods in molecular networks.1932-620310.1371/journal.pone.0108830https://doaj.org/article/cd0cb0fa723f4717b61e515c45a3f0b92014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108830https://doaj.org/toc/1932-6203Analysis of the failure of cell signaling networks is an important topic in systems biology and has applications in target discovery and drug development. In this paper, some advanced methods for fault diagnosis in signaling networks are developed and then applied to a caspase network and an SHP2 network. The goal is to understand how, and to what extent, the dysfunction of molecules in a network contributes to the failure of the entire network. Network dysfunction (failure) is defined as failure to produce the expected outputs in response to the input signals. Vulnerability level of a molecule is defined as the probability of the network failure, when the molecule is dysfunctional. In this study, a method to calculate the vulnerability level of single molecules for different combinations of input signals is developed. Furthermore, a more complex yet biologically meaningful method for calculating the multi-fault vulnerability levels is suggested, in which two or more molecules are simultaneously dysfunctional. Finally, a method is developed for fault diagnosis of networks based on a ternary logic model, which considers three activity levels for a molecule instead of the previously published binary logic model, and provides equations for the vulnerabilities of molecules in a ternary framework. Multi-fault analysis shows that the pairs of molecules with high vulnerability typically include a highly vulnerable molecule identified by the single fault analysis. The ternary fault analysis for the caspase network shows that predictions obtained using the more complex ternary model are about the same as the predictions of the simpler binary approach. This study suggests that by increasing the number of activity levels the complexity of the model grows; however, the predictive power of the ternary model does not appear to be increased proportionally.Iman HabibiEffat S EmamianAli AbdiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e108830 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Iman Habibi
Effat S Emamian
Ali Abdi
Advanced fault diagnosis methods in molecular networks.
description Analysis of the failure of cell signaling networks is an important topic in systems biology and has applications in target discovery and drug development. In this paper, some advanced methods for fault diagnosis in signaling networks are developed and then applied to a caspase network and an SHP2 network. The goal is to understand how, and to what extent, the dysfunction of molecules in a network contributes to the failure of the entire network. Network dysfunction (failure) is defined as failure to produce the expected outputs in response to the input signals. Vulnerability level of a molecule is defined as the probability of the network failure, when the molecule is dysfunctional. In this study, a method to calculate the vulnerability level of single molecules for different combinations of input signals is developed. Furthermore, a more complex yet biologically meaningful method for calculating the multi-fault vulnerability levels is suggested, in which two or more molecules are simultaneously dysfunctional. Finally, a method is developed for fault diagnosis of networks based on a ternary logic model, which considers three activity levels for a molecule instead of the previously published binary logic model, and provides equations for the vulnerabilities of molecules in a ternary framework. Multi-fault analysis shows that the pairs of molecules with high vulnerability typically include a highly vulnerable molecule identified by the single fault analysis. The ternary fault analysis for the caspase network shows that predictions obtained using the more complex ternary model are about the same as the predictions of the simpler binary approach. This study suggests that by increasing the number of activity levels the complexity of the model grows; however, the predictive power of the ternary model does not appear to be increased proportionally.
format article
author Iman Habibi
Effat S Emamian
Ali Abdi
author_facet Iman Habibi
Effat S Emamian
Ali Abdi
author_sort Iman Habibi
title Advanced fault diagnosis methods in molecular networks.
title_short Advanced fault diagnosis methods in molecular networks.
title_full Advanced fault diagnosis methods in molecular networks.
title_fullStr Advanced fault diagnosis methods in molecular networks.
title_full_unstemmed Advanced fault diagnosis methods in molecular networks.
title_sort advanced fault diagnosis methods in molecular networks.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/cd0cb0fa723f4717b61e515c45a3f0b9
work_keys_str_mv AT imanhabibi advancedfaultdiagnosismethodsinmolecularnetworks
AT effatsemamian advancedfaultdiagnosismethodsinmolecularnetworks
AT aliabdi advancedfaultdiagnosismethodsinmolecularnetworks
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