Multi-Target Analysis and Design of Mitochondrial Metabolism
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Publication Date
2015-09-16Journal Title
PLoS ONE
ISSN
1932-6203
Publisher
PLoS
Volume
10
Number
e0133825
Language
English
Type
Article
Metadata
Show full item recordCitation
Angione, C., Costanza, J., Carapezza, G., Lio, P., & Nicosia, G. (2015). Multi-Target Analysis and Design of Mitochondrial Metabolism. PLoS ONE, 10 (e0133825)https://doi.org/10.1371/journal.pone.0133825
Abstract
Analyzing and optimizing biological models is often identified as a research priority in biomedical engineering. An important feature of a model should be the ability to find the best condition in which an organism has to be grown in order to reach specific optimal output values chosen by the researcher. In this work, we take into account a mitochondrial model analyzed with flux-balance analysis. The optimal design and assessment of these models is achieved through single- and/or multi-objective optimization techniques driven by epsilon-dominance and identifiability analysis. Our optimization algorithm searches for the values of the flux rates that optimize multiple cellular functions simultaneously. The optimization of the fluxes of the metabolic network includes not only input fluxes, but also internal fluxes. A faster convergence process with robust candidate solutions is permitted by a relaxed Pareto dominance, regulating the granularity of the approximation of the desired Pareto front. We find that the maximum ATP production is linked to a total consumption of NADH, and reaching the maximum amount of NADH leads to an increasing request of NADH from the external environment. Furthermore, the identifiability analysis characterizes the type and the stage of three monogenic diseases. Finally, we propose a new methodology to extend any constraint-based model using protein abundances.
Sponsorship
PL has received funding from (FP7-Health-F5-2012) under grant agreement no. 305280 (MIMOmics). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funder references
EC FP7 CP (305280)
Identifiers
External DOI: https://doi.org/10.1371/journal.pone.0133825
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252593
Rights
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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