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Formal reasoning about systems biology using theorem proving
System biology provides the basis to understand the behavioral properties of complex biological organisms at different levels of abstraction. Traditionally, analysing systems biology based models of various diseases have been carried out by paper-and-pencil based proofs and simulations. However, the...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495343/ https://www.ncbi.nlm.nih.gov/pubmed/28671950 http://dx.doi.org/10.1371/journal.pone.0180179 |
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author | Rashid, Adnan Hasan, Osman Siddique, Umair Tahar, Sofiène |
author_facet | Rashid, Adnan Hasan, Osman Siddique, Umair Tahar, Sofiène |
author_sort | Rashid, Adnan |
collection | PubMed |
description | System biology provides the basis to understand the behavioral properties of complex biological organisms at different levels of abstraction. Traditionally, analysing systems biology based models of various diseases have been carried out by paper-and-pencil based proofs and simulations. However, these methods cannot provide an accurate analysis, which is a serious drawback for the safety-critical domain of human medicine. In order to overcome these limitations, we propose a framework to formally analyze biological networks and pathways. In particular, we formalize the notion of reaction kinetics in higher-order logic and formally verify some of the commonly used reaction based models of biological networks using the HOL Light theorem prover. Furthermore, we have ported our earlier formalization of Zsyntax, i.e., a deductive language for reasoning about biological networks and pathways, from HOL4 to the HOL Light theorem prover to make it compatible with the above-mentioned formalization of reaction kinetics. To illustrate the usefulness of the proposed framework, we present the formal analysis of three case studies, i.e., the pathway leading to TP53 Phosphorylation, the pathway leading to the death of cancer stem cells and the tumor growth based on cancer stem cells, which is used for the prognosis and future drug designs to treat cancer patients. |
format | Online Article Text |
id | pubmed-5495343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54953432017-07-18 Formal reasoning about systems biology using theorem proving Rashid, Adnan Hasan, Osman Siddique, Umair Tahar, Sofiène PLoS One Research Article System biology provides the basis to understand the behavioral properties of complex biological organisms at different levels of abstraction. Traditionally, analysing systems biology based models of various diseases have been carried out by paper-and-pencil based proofs and simulations. However, these methods cannot provide an accurate analysis, which is a serious drawback for the safety-critical domain of human medicine. In order to overcome these limitations, we propose a framework to formally analyze biological networks and pathways. In particular, we formalize the notion of reaction kinetics in higher-order logic and formally verify some of the commonly used reaction based models of biological networks using the HOL Light theorem prover. Furthermore, we have ported our earlier formalization of Zsyntax, i.e., a deductive language for reasoning about biological networks and pathways, from HOL4 to the HOL Light theorem prover to make it compatible with the above-mentioned formalization of reaction kinetics. To illustrate the usefulness of the proposed framework, we present the formal analysis of three case studies, i.e., the pathway leading to TP53 Phosphorylation, the pathway leading to the death of cancer stem cells and the tumor growth based on cancer stem cells, which is used for the prognosis and future drug designs to treat cancer patients. Public Library of Science 2017-07-03 /pmc/articles/PMC5495343/ /pubmed/28671950 http://dx.doi.org/10.1371/journal.pone.0180179 Text en © 2017 Rashid et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Rashid, Adnan Hasan, Osman Siddique, Umair Tahar, Sofiène Formal reasoning about systems biology using theorem proving |
title | Formal reasoning about systems biology using theorem proving |
title_full | Formal reasoning about systems biology using theorem proving |
title_fullStr | Formal reasoning about systems biology using theorem proving |
title_full_unstemmed | Formal reasoning about systems biology using theorem proving |
title_short | Formal reasoning about systems biology using theorem proving |
title_sort | formal reasoning about systems biology using theorem proving |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495343/ https://www.ncbi.nlm.nih.gov/pubmed/28671950 http://dx.doi.org/10.1371/journal.pone.0180179 |
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