In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2021-7-23), p. e1009234-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1009234
DOI:
10.1371/journal.pcbi.1009234.g001
DOI:
10.1371/journal.pcbi.1009234.g002
DOI:
10.1371/journal.pcbi.1009234.g003
DOI:
10.1371/journal.pcbi.1009234.g004
DOI:
10.1371/journal.pcbi.1009234.g005
DOI:
10.1371/journal.pcbi.1009234.t001
DOI:
10.1371/journal.pcbi.1009234.t002
DOI:
10.1371/journal.pcbi.1009234.t003
DOI:
10.1371/journal.pcbi.1009234.s001
DOI:
10.1371/journal.pcbi.1009234.s002
DOI:
10.1371/journal.pcbi.1009234.s003
DOI:
10.1371/journal.pcbi.1009234.s004
DOI:
10.1371/journal.pcbi.1009234.s005
DOI:
10.1371/journal.pcbi.1009234.r001
DOI:
10.1371/journal.pcbi.1009234.r002
DOI:
10.1371/journal.pcbi.1009234.r003
DOI:
10.1371/journal.pcbi.1009234.r004
DOI:
10.1371/journal.pcbi.1009234.r005
DOI:
10.1371/journal.pcbi.1009234.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2193340-6
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