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In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan
Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of a medication in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Explorin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018085/ https://www.ncbi.nlm.nih.gov/pubmed/32053711 http://dx.doi.org/10.1371/journal.pone.0228926 |
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author | Jorba, Guillem Aguirre-Plans, Joaquim Junet, Valentin Segú-Vergés, Cristina Ruiz, José Luis Pujol, Albert Fernández-Fuentes, Narcís Mas, José Manuel Oliva, Baldo |
author_facet | Jorba, Guillem Aguirre-Plans, Joaquim Junet, Valentin Segú-Vergés, Cristina Ruiz, José Luis Pujol, Albert Fernández-Fuentes, Narcís Mas, José Manuel Oliva, Baldo |
author_sort | Jorba, Guillem |
collection | PubMed |
description | Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of a medication in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalized medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. Each molecular mechanism generated could be associated to particular individuals, here defined as prototype-patients, hence the generation of models using TPMS technology may be used for detecting adverse effects to specific patients. TPMS operates by (1) modelling the responses in humans with an accurate description of a protein network and (2) applying a Multilayer Perceptron-like and sampling strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a wide range of models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their association with macular degeneration (a potential adverse effect). Among the models generated, we identify a set of mechanisms of action associated to a better response in terms of heart failure treatment, which could also be associated to macular degeneration development. Finally, a set of 30 potential biomarkers are proposed to identify mechanisms (or prototype-patients) more prone of suffering macular degeneration when presenting good heart failure response. All prototype-patients models generated are completely theoretical and therefore they do not necessarily involve clinical effects in real patients. Data and accession to software are available at http://sbi.upf.edu/data/tpms/ |
format | Online Article Text |
id | pubmed-7018085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70180852020-02-26 In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan Jorba, Guillem Aguirre-Plans, Joaquim Junet, Valentin Segú-Vergés, Cristina Ruiz, José Luis Pujol, Albert Fernández-Fuentes, Narcís Mas, José Manuel Oliva, Baldo PLoS One Research Article Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of a medication in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalized medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. Each molecular mechanism generated could be associated to particular individuals, here defined as prototype-patients, hence the generation of models using TPMS technology may be used for detecting adverse effects to specific patients. TPMS operates by (1) modelling the responses in humans with an accurate description of a protein network and (2) applying a Multilayer Perceptron-like and sampling strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a wide range of models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their association with macular degeneration (a potential adverse effect). Among the models generated, we identify a set of mechanisms of action associated to a better response in terms of heart failure treatment, which could also be associated to macular degeneration development. Finally, a set of 30 potential biomarkers are proposed to identify mechanisms (or prototype-patients) more prone of suffering macular degeneration when presenting good heart failure response. All prototype-patients models generated are completely theoretical and therefore they do not necessarily involve clinical effects in real patients. Data and accession to software are available at http://sbi.upf.edu/data/tpms/ Public Library of Science 2020-02-13 /pmc/articles/PMC7018085/ /pubmed/32053711 http://dx.doi.org/10.1371/journal.pone.0228926 Text en © 2020 Jorba 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 Jorba, Guillem Aguirre-Plans, Joaquim Junet, Valentin Segú-Vergés, Cristina Ruiz, José Luis Pujol, Albert Fernández-Fuentes, Narcís Mas, José Manuel Oliva, Baldo In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan |
title | In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan |
title_full | In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan |
title_fullStr | In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan |
title_full_unstemmed | In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan |
title_short | In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan |
title_sort | in-silico simulated prototype-patients using tpms technology to study a potential adverse effect of sacubitril and valsartan |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018085/ https://www.ncbi.nlm.nih.gov/pubmed/32053711 http://dx.doi.org/10.1371/journal.pone.0228926 |
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