Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.

Metabolic adaptations to complex perturbations, like the response to pharmacological treatments in multifactorial diseases such as cancer, can be described through measurements of part of the fluxes and concentrations at the systemic level and individual transporter and enzyme activities at the mole...

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Autores principales:	Pedro de Atauri, Míriam Tarrado-Castellarnau, Josep Tarragó-Celada, Carles Foguet, Effrosyni Karakitsou, Josep Joan Centelles, Marta Cascante
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8f4e2159d42e41bf8158d242fb172797
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spelling	oai:doaj.org-article:8f4e2159d42e41bf8158d242fb1727972021-12-02T19:57:23ZIntegrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.1553-734X1553-735810.1371/journal.pcbi.1009234https://doaj.org/article/8f4e2159d42e41bf8158d242fb1727972021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009234https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Metabolic adaptations to complex perturbations, like the response to pharmacological treatments in multifactorial diseases such as cancer, can be described through measurements of part of the fluxes and concentrations at the systemic level and individual transporter and enzyme activities at the molecular level. In the framework of Metabolic Control Analysis (MCA), ensembles of linear constraints can be built integrating these measurements at both systemic and molecular levels, which are expressed as relative differences or changes produced in the metabolic adaptation. Here, combining MCA with Linear Programming, an efficient computational strategy is developed to infer additional non-measured changes at the molecular level that are required to satisfy these constraints. An application of this strategy is illustrated by using a set of fluxes, concentrations, and differentially expressed genes that characterize the response to cyclin-dependent kinases 4 and 6 inhibition in colon cancer cells. Decreases and increases in transporter and enzyme individual activities required to reprogram the measured changes in fluxes and concentrations are compared with down-regulated and up-regulated metabolic genes to unveil those that are key molecular drivers of the metabolic response.Pedro de AtauriMíriam Tarrado-CastellarnauJosep Tarragó-CeladaCarles FoguetEffrosyni KarakitsouJosep Joan CentellesMarta CascantePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 7, p e1009234 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Pedro de Atauri Míriam Tarrado-Castellarnau Josep Tarragó-Celada Carles Foguet Effrosyni Karakitsou Josep Joan Centelles Marta Cascante Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.
description	Metabolic adaptations to complex perturbations, like the response to pharmacological treatments in multifactorial diseases such as cancer, can be described through measurements of part of the fluxes and concentrations at the systemic level and individual transporter and enzyme activities at the molecular level. In the framework of Metabolic Control Analysis (MCA), ensembles of linear constraints can be built integrating these measurements at both systemic and molecular levels, which are expressed as relative differences or changes produced in the metabolic adaptation. Here, combining MCA with Linear Programming, an efficient computational strategy is developed to infer additional non-measured changes at the molecular level that are required to satisfy these constraints. An application of this strategy is illustrated by using a set of fluxes, concentrations, and differentially expressed genes that characterize the response to cyclin-dependent kinases 4 and 6 inhibition in colon cancer cells. Decreases and increases in transporter and enzyme individual activities required to reprogram the measured changes in fluxes and concentrations are compared with down-regulated and up-regulated metabolic genes to unveil those that are key molecular drivers of the metabolic response.
format	article
author	Pedro de Atauri Míriam Tarrado-Castellarnau Josep Tarragó-Celada Carles Foguet Effrosyni Karakitsou Josep Joan Centelles Marta Cascante
author_facet	Pedro de Atauri Míriam Tarrado-Castellarnau Josep Tarragó-Celada Carles Foguet Effrosyni Karakitsou Josep Joan Centelles Marta Cascante
author_sort	Pedro de Atauri
title	Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.
title_short	Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.
title_full	Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.
title_fullStr	Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.
title_full_unstemmed	Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.
title_sort	integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/8f4e2159d42e41bf8158d242fb172797
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Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations.

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