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

Local Hidden Variable Theories for Quantum States

While all bipartite pure entangled states violate some Bell inequality, the relationship between entanglement and non-locality for mixed quantum states is not well understood. We introduce a simple and efficient algorithmic approach for the problem of constructing local hidden variable theories for quantum states. The method is based on constructing a so-called symmetric quasi-extension of the quantum state that gives rise to a local hidden variable model with a certain number of settings for the observers Alice and Bob.Comment: 8 pages Revtex; v2 contains substantial changes, a strengthened main theorem and more reference

Getting Feasible Variable Estimates From Infeasible Ones: MRF Local Polytope Study

This paper proposes a method for construction of approximate feasible primal solutions from dual ones for large-scale optimization problems possessing certain separability properties. Whereas infeasible primal estimates can typically be produced from (sub-)gradients of the dual function, it is often not easy to project them to the primal feasible set, since the projection itself has a complexity comparable to the complexity of the initial problem. We propose an alternative efficient method to obtain feasibility and show that its properties influencing the convergence to the optimum are similar to the properties of the Euclidean projection. We apply our method to the local polytope relaxation of inference problems for Markov Random Fields and demonstrate its superiority over existing methods.Comment: 20 page, 4 figure

A Sparse Multi-Scale Algorithm for Dense Optimal Transport

Discrete optimal transport solvers do not scale well on dense large problems since they do not explicitly exploit the geometric structure of the cost function. In analogy to continuous optimal transport we provide a framework to verify global optimality of a discrete transport plan locally. This allows construction of an algorithm to solve large dense problems by considering a sequence of sparse problems instead. The algorithm lends itself to being combined with a hierarchical multi-scale scheme. Any existing discrete solver can be used as internal black-box.Several cost functions, including the noisy squared Euclidean distance, are explicitly detailed. We observe a significant reduction of run-time and memory requirements.Comment: Published "online first" in Journal of Mathematical Imaging and Vision, see DO

Efficient Algorithms for Asymptotic Bounds on Termination Time in VASS

Vector Addition Systems with States (VASS) provide a well-known and fundamental model for the analysis of concurrent processes, parameterized systems, and are also used as abstract models of programs in resource bound analysis. In this paper we study the problem of obtaining asymptotic bounds on the termination time of a given VASS. In particular, we focus on the practically important case of obtaining polynomial bounds on termination time. Our main contributions are as follows: First, we present a polynomial-time algorithm for deciding whether a given VASS has a linear asymptotic complexity. We also show that if the complexity of a VASS is not linear, it is at least quadratic. Second, we classify VASS according to quantitative properties of their cycles. We show that certain singularities in these properties are the key reason for non-polynomial asymptotic complexity of VASS. In absence of singularities, we show that the asymptotic complexity is always polynomial and of the form $\Theta(n^k)$, for some integer $k\leq d$, where $d$ is the dimension of the VASS. We present a polynomial-time algorithm computing the optimal $k$. For general VASS, the same algorithm, which is based on a complete technique for the construction of ranking functions in VASS, produces a valid lower bound, i.e., a $k$ such that the termination complexity is $\Omega(n^k)$. Our results are based on new insights into the geometry of VASS dynamics, which hold the potential for further applicability to VASS analysis.Comment: arXiv admin note: text overlap with arXiv:1708.0925