Multi-objective optimisation, sensitivity and robustness analysis in FBA modelling

Jole Costanza, Giovanni Carapezza, Claudio Angione, Pietro Liò, Giuseppe Nicosia

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    1 Citation (Scopus)

    Abstract

    In this work, we propose a computational framework to design in silico robust bacteria able to overproduce multiple metabolites. To this end, we search the optimal genetic manipulations, in terms of knockout, which also guarantee the growth of the organism. We introduce a multi-objective optimisation algorithm, called Genetic Design through Multi-Objective (GDMO), and test it in several organisms to maximise the production of key intermediate metabolites such as succinate and acetate. We obtain a vast set of Pareto optimal solutions; each of them represents an organism strain. For each solution, we evaluate the fragility by calculating three robustness indexes and by exploring reactions and metabolite interactions. Finally, we perform the Sensitivity Analysis of the metabolic model, which finds the inputs with the highest influence on the outputs of the model. We show that our methodology provides effective vision of the achievable synthetic strain landscape and a powerful design pipeline.

    Original languageEnglish
    Title of host publicationComputational Methods in Systems Biology - 10th International Conference, CMSB 2012, Proceedings
    Pages127-147
    Number of pages21
    DOIs
    Publication statusPublished - 30 Oct 2012
    Event10th International Conference on Computational Methods in Systems Biology - London, United Kingdom
    Duration: 3 Oct 20125 Oct 2012

    Publication series

    NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
    Volume7605 LNBI
    ISSN (Print)0302-9743
    ISSN (Electronic)1611-3349

    Conference

    Conference10th International Conference on Computational Methods in Systems Biology
    Abbreviated titleCMSB 2012
    CountryUnited Kingdom
    CityLondon
    Period3/10/125/10/12

    Fingerprint Dive into the research topics of 'Multi-objective optimisation, sensitivity and robustness analysis in FBA modelling'. Together they form a unique fingerprint.

  • Cite this

    Costanza, J., Carapezza, G., Angione, C., Liò, P., & Nicosia, G. (2012). Multi-objective optimisation, sensitivity and robustness analysis in FBA modelling. In Computational Methods in Systems Biology - 10th International Conference, CMSB 2012, Proceedings (pp. 127-147). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 7605 LNBI). https://doi.org/10.1007/978-3-642-33636-2_9