ABSTRACT
A recently developed adaptive bi-level optimization algorithm, MOMAKnock, has the objective to maximize the targeted biochemical overproduction as the outer-level problem, and MOMA criterion modeling the survival of mutants as the inner-level objective function. This method gives improved targeted overproductions with more robust knockout strategies. An adaptive solution with piecewise linear approximation to the inner-level objective function has been employed in the original work. In this project, Karush-Kuhn-Tucker (KKT) conditions are used to convert bi-level MOMAKnock to a single level mixed integer programming problem since the inner-level problem is a convex optimization problem. We compare our KKT-based solution strategy with the original adaptive solution strategy by evaluating both strategies on a small E.coli core metabolic network. The experimental results show that our new KKT-based solution is computationally more efficient, and achieves orders of magnitude speedup to obtain the optimal solutions.
- M. R. Antoniewicz, D. F. Kraynie, L. A. Laffend, J. González-Lergier, J. K. Kelleher, and G. Stephanopoulos. Metabolic flux analysis in a nonstationary system: Fed-batch fermentation of a high yielding strain of e. coli producing 1, 3-propanediol. Metabolic Engineering, 9(3):277--292, 2007.Google ScholarCross Ref
- A. P. Burgard, P. Pharkya, and C. D. Maranas. Optknock: a bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnology and Bioengineering, 84(6):647--657, 2003.Google ScholarCross Ref
- J. Edwards and B. Palsson. The escherichia coli mg1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proceedings of the National Academy of Sciences, 97(10):5528--5533, 2000.Google ScholarCross Ref
- J. Kim, J. L. Reed, and C. T. Maravelias. Large-scale bi-level strain design approaches and mixed-integer programming solution techniques. PLoS One, 6(9):e24162, 2011.Google ScholarCross Ref
- S. J. Lee, D.-Y. Lee, T. Y. Kim, B. H. Kim, J. Lee, and S. Y. Lee. Metabolic engineering of escherichia coli for enhanced production of succinic acid, based on genome comparison and in silico gene knockout simulation. Applied and Environmental Microbiology, 71(12):7880--7887, 2005.Google ScholarCross Ref
- J. M. Luengo, B. Garcıa, A. Sandoval, G. Naharro, and E. R. Olivera. Bioplastics from microorganisms. Current Opinion in Microbiology, 6(3):251--260, 2003.Google ScholarCross Ref
- S. Ren, B. Zeng, and X. Qian. Adaptive bi-level programming for optimal gene knockouts for targeted overproduction under phenotypic constraints. BMC Bioinformatics, 14(Suppl 2):S17, 2013.Google ScholarCross Ref
- D. Segre, D. Vitkup, and G. M. Church. Analysis of optimality in natural and perturbed metabolic networks. Proceedings of the National Academy of Sciences, 99(23):15112--15117, 2002.Google ScholarCross Ref
- A. Varma and B. O. Palsson. Metabolic flux balancing: Basic concepts, scientific and practical use. Bio/technology, 12:994--998, 1994.Google Scholar
Index Terms
- A computationally efficient solution strategy for optimal gene knockouts for targeted overproduction
Recommendations
A solution to bi/tri-level programming problems using particle swarm optimization
Multilevel (including bi-level and tri-level) programming aims to solve decentralized decision-making problems that feature interactive decision entities distributed throughout a hierarchical organization. Since the multilevel programming problem is ...
Interactive approach to bi-level integer multi-objective fractional programming problem
This paper proposes an interactive approach for solving bi-level integer multi-objective fractional programming problem. At the first phase of the solution approach, we begin by finding the convex hull of its original set of constraints using the ...
On two new formulations for the fixed charge network design problem with shortest path constraints
Highlights- Two new BILP formulations are proposed for the FCNDP-SPC problem.
- Valid ...
AbstractWe study the fixed charge network design problem with shortest path constraints which is modeled as a bi-level program. We first review three one-level formulations obtained by applying the complementarity slackness theorem, Bellman’s ...
Comments