Metabolic Circuit Design Automation by Multi-objective BioCAD

  • Andrea Patané
  • Piero ConcaEmail author
  • Giovanni Carapezza
  • Andrea Santoro
  • Jole Costanza
  • Giuseppe Nicosia
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 10122)


We present a thorough in silico analysis and optimization of the genome-scale metabolic model of the mycolic acid pathway in M. tuberculosis. We apply and further extend meGDMO to account for finer sensitivity analysis and post-processing analysis, thanks to the combination of statistical evaluation of strains robustness, and clustering analysis to map the phenotype-genotype relationship among Pareto optimal strains. In the first analysis scenario, we find 12 Pareto-optimal single gene set knockout, which completely shut down the pathway, hence critically reducing the pathogenicity of M. tuberculosis; as well as 34 genotypically different strains in which the production of mycolic acid is severely reduced.


Metabolic pathways Mycolic acid maximization M. tuberculosis Global sensitivity analysis Robustness analysis Clustering analysis Optimization 


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Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  • Andrea Patané
    • 1
  • Piero Conca
    • 1
    • 2
    Email author
  • Giovanni Carapezza
    • 1
  • Andrea Santoro
    • 1
    • 2
    • 3
  • Jole Costanza
    • 3
  • Giuseppe Nicosia
    • 1
  1. 1.Department of Mathematics and Computer ScienceUniversity of CataniaCataniaItaly
  2. 2.Consiglio Nazionale delle Ricerche (CNR)CataniaItaly
  3. 3.Istituto Italiano di Tecnologia (IIT)MilanItaly

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