An improved multi-parametric programming algorithm for flux balance analysis of metabolic networks

Flux balance analysis has proven an effective tool for analyzing metabolic networks. In flux balance analysis, reaction rates and optimal pathways are ascertained by solving a linear program, in which the growth rate is maximized subject to mass-balance constraints. A variety of cell functions in response to environmental stimuli can be quantified using flux balance analysis by parameterizing the linear program with respect to extracellular conditions. However, for most large, genome-scale metabolic networks of practical interest, the resulting parametric problem has multiple and highly degenerate optimal solutions, which are computationally challenging to handle. An improved multi-parametric programming algorithm based on active-set methods is introduced in this paper to overcome these computational difficulties. Degeneracy and multiplicity are handled, respectively, by introducing generalized inverses and auxiliary objective functions into the formulation of the optimality conditions. These improvements are especially effective for metabolic networks because their stoichiometry matrices are generally sparse; thus, fast and efficient algorithms from sparse linear algebra can be leveraged to compute generalized inverses and null-space bases. We illustrate the application of our algorithm to flux balance analysis of metabolic networks by studying a reduced metabolic model of Corynebacterium glutamicum and a genome-scale model of Escherichia coli. We then demonstrate how the critical regions resulting from these studies can be associated with optimal metabolic modes and discuss the physical relevance of optimal pathways arising from various auxiliary objective functions. Achieving more than five-fold improvement in computational speed over existing multi-parametric programming tools, the proposed algorithm proves promising in handling genome-scale metabolic models.Comment: Accepted in J. Optim. Theory Appl. First draft was submitted on August 4th, 201

An Exponential Lower Bound on the Complexity of Regularization Paths

For a variety of regularized optimization problems in machine learning, algorithms computing the entire solution path have been developed recently. Most of these methods are quadratic programs that are parameterized by a single parameter, as for example the Support Vector Machine (SVM). Solution path algorithms do not only compute the solution for one particular value of the regularization parameter but the entire path of solutions, making the selection of an optimal parameter much easier. It has been assumed that these piecewise linear solution paths have only linear complexity, i.e. linearly many bends. We prove that for the support vector machine this complexity can be exponential in the number of training points in the worst case. More strongly, we construct a single instance of n input points in d dimensions for an SVM such that at least \Theta(2^{n/2}) = \Theta(2^d) many distinct subsets of support vectors occur as the regularization parameter changes.Comment: Journal version, 28 Pages, 5 Figure

Adjoint-based predictor-corrector sequential convex programming for parametric nonlinear optimization

This paper proposes an algorithmic framework for solving parametric optimization problems which we call adjoint-based predictor-corrector sequential convex programming. After presenting the algorithm, we prove a contraction estimate that guarantees the tracking performance of the algorithm. Two variants of this algorithm are investigated. The first one can be used to solve nonlinear programming problems while the second variant is aimed to treat online parametric nonlinear programming problems. The local convergence of these variants is proved. An application to a large-scale benchmark problem that originates from nonlinear model predictive control of a hydro power plant is implemented to examine the performance of the algorithms.Comment: This manuscript consists of 25 pages and 7 figure