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High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes

Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression...

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Detalles Bibliográficos
Autores principales: Hidalgo, Marta R., Cubuk, Cankut, Amadoz, Alicia, Salavert, Francisco, Carbonell-Caballero, José, Dopazo, Joaquin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354899/
https://www.ncbi.nlm.nih.gov/pubmed/28042959
http://dx.doi.org/10.18632/oncotarget.14107
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author Hidalgo, Marta R.
Cubuk, Cankut
Amadoz, Alicia
Salavert, Francisco
Carbonell-Caballero, José
Dopazo, Joaquin
author_facet Hidalgo, Marta R.
Cubuk, Cankut
Amadoz, Alicia
Salavert, Francisco
Carbonell-Caballero, José
Dopazo, Joaquin
author_sort Hidalgo, Marta R.
collection PubMed
description Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measurements of changes in the activity of signaling circuits, which ultimately constitute high-throughput estimations of cell functionalities caused by gene activity within the pathway. Moreover, such estimations can be obtained either at cohort-level, in case/control comparisons, or personalized for individual patients. The accuracy of the method is demonstrated in an extensive analysis involving 5640 patients from 12 different cancer types. Circuit activity measurements not only have a high diagnostic value but also can be related to relevant disease outcomes such as survival, and can be used to assess therapeutic interventions.
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spelling pubmed-53548992017-04-24 High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes Hidalgo, Marta R. Cubuk, Cankut Amadoz, Alicia Salavert, Francisco Carbonell-Caballero, José Dopazo, Joaquin Oncotarget Research Paper Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measurements of changes in the activity of signaling circuits, which ultimately constitute high-throughput estimations of cell functionalities caused by gene activity within the pathway. Moreover, such estimations can be obtained either at cohort-level, in case/control comparisons, or personalized for individual patients. The accuracy of the method is demonstrated in an extensive analysis involving 5640 patients from 12 different cancer types. Circuit activity measurements not only have a high diagnostic value but also can be related to relevant disease outcomes such as survival, and can be used to assess therapeutic interventions. Impact Journals LLC 2016-12-22 /pmc/articles/PMC5354899/ /pubmed/28042959 http://dx.doi.org/10.18632/oncotarget.14107 Text en Copyright: © 2017 Hidalgo et al. http://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Paper
Hidalgo, Marta R.
Cubuk, Cankut
Amadoz, Alicia
Salavert, Francisco
Carbonell-Caballero, José
Dopazo, Joaquin
High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes
title High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes
title_full High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes
title_fullStr High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes
title_full_unstemmed High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes
title_short High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes
title_sort high throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354899/
https://www.ncbi.nlm.nih.gov/pubmed/28042959
http://dx.doi.org/10.18632/oncotarget.14107
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