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

A parametric integer programming algorithm for bilevel mixed integer programs

We consider discrete bilevel optimization problems where the follower solves an integer program with a fixed number of variables. Using recent results in parametric integer programming, we present polynomial time algorithms for pure and mixed integer bilevel problems. For the mixed integer case where the leader's variables are continuous, our algorithm also detects whether the infimum cost fails to be attained, a difficulty that has been identified but not directly addressed in the literature. In this case it yields a ``better than fully polynomial time'' approximation scheme with running time polynomial in the logarithm of the relative precision. For the pure integer case where the leader's variables are integer, and hence optimal solutions are guaranteed to exist, we present two algorithms which run in polynomial time when the total number of variables is fixed.Comment: 11 page

Inverse Optimization with Noisy Data

Inverse optimization refers to the inference of unknown parameters of an optimization problem based on knowledge of its optimal solutions. This paper considers inverse optimization in the setting where measurements of the optimal solutions of a convex optimization problem are corrupted by noise. We first provide a formulation for inverse optimization and prove it to be NP-hard. In contrast to existing methods, we show that the parameter estimates produced by our formulation are statistically consistent. Our approach involves combining a new duality-based reformulation for bilevel programs with a regularization scheme that smooths discontinuities in the formulation. Using epi-convergence theory, we show the regularization parameter can be adjusted to approximate the original inverse optimization problem to arbitrary accuracy, which we use to prove our consistency results. Next, we propose two solution algorithms based on our duality-based formulation. The first is an enumeration algorithm that is applicable to settings where the dimensionality of the parameter space is modest, and the second is a semiparametric approach that combines nonparametric statistics with a modified version of our formulation. These numerical algorithms are shown to maintain the statistical consistency of the underlying formulation. Lastly, using both synthetic and real data, we demonstrate that our approach performs competitively when compared with existing heuristics

Local strong maximal monotonicity and full stability for parametric variational systems

The paper introduces and characterizes new notions of Lipschitzian and H\"olderian full stability of solutions to general parametric variational systems described via partial subdifferential and normal cone mappings acting in Hilbert spaces. These notions, postulated certain quantitative properties of single-valued localizations of solution maps, are closely related to local strong maximal monotonicity of associated set-valued mappings. Based on advanced tools of variational analysis and generalized differentiation, we derive verifiable characterizations of the local strong maximal monotonicity and full stability notions under consideration via some positive-definiteness conditions involving second-order constructions of variational analysis. The general results obtained are specified for important classes of variational inequalities and variational conditions in both finite and infinite dimensions

Computing semiparametric bounds on the expected payments of insurance instruments via column generation

It has been recently shown that numerical semiparametric bounds on the expected payoff of fi- nancial or actuarial instruments can be computed using semidefinite programming. However, this approach has practical limitations. Here we use column generation, a classical optimization technique, to address these limitations. From column generation, it follows that practical univari- ate semiparametric bounds can be found by solving a series of linear programs. In addition to moment information, the column generation approach allows the inclusion of extra information about the random variable; for instance, unimodality and continuity, as well as the construction of corresponding worst/best-case distributions in a simple way

On the local stability of semidefinite relaxations

We consider a parametric family of quadratically constrained quadratic programs (QCQP) and their associated semidefinite programming (SDP) relaxations. Given a nominal value of the parameter at which the SDP relaxation is exact, we study conditions (and quantitative bounds) under which the relaxation will continue to be exact as the parameter moves in a neighborhood around the nominal value. Our framework captures a wide array of statistical estimation problems including tensor principal component analysis, rotation synchronization, orthogonal Procrustes, camera triangulation and resectioning, essential matrix estimation, system identification, and approximate GCD. Our results can also be used to analyze the stability of SOS relaxations of general polynomial optimization problems.Comment: 23 pages, 3 figure

Mathematical programs with complementarity constraints: convergence properties of a smoothing method

In this paper, optimization problems $P$ with complementarity constraints are considered. Characterizations for local minimizers $\bar{x}$ of $P$ of Orders 1 and 2 are presented. We analyze a parametric smoothing approach for solving these programs in which $P$ is replaced by a perturbed problem $P_{\tau}$ depending on a (small) parameter $\tau$. We are interested in the convergence behavior of the feasible set $\cal{F}_{\tau}$ and the convergence of the solutions $\bar{x}_{\tau}$ of $P_{\tau}$ for $\tau\to 0.$ In particular, it is shown that, under generic assumptions, the solutions $\bar{x}_{\tau}$ are unique and converge to a solution $\bar{x}$ of $P$ with a rate $\cal{O}(\sqrt{\tau})$. Moreover, the convergence for the Hausdorff distance $d(\cal{F}_{\tau}$, $\cal{F})$ between the feasible sets of $P_{\tau}$ and $P$ is of order $\cal{O}(\sqrt{\tau})$