Finding MEMo: minimum sets of elementary flux modes.

Metabolic network reconstructions are widely used in computational systems biology for in silico studies of cellular metabolism. A common approach to analyse these models are elementary flux modes (EFMs), which correspond to minimal functional units in the network. Already for medium-sized networks, it is often impossible to compute the set of all EFMs, due to their huge number. From a practical point of view, this might also not be necessary because a subset of EFMs may already be sufficient to answer relevant biological questions. In this article, we study MEMos or minimum sets of EFMs that can generate all possible steady-state behaviours of a metabolic network. The number of EFMs in a MEMo may be by several orders of magnitude smaller than the total number of EFMs. Using MEMos, we can compute generating sets of EFMs in metabolic networks where the whole set of EFMs is too large to be enumerated.

Elementary Vectors and Conformal Sums in Polyhedral Geometry and their Relevance for Metabolic Pathway Analysis.

A fundamental result in metabolic pathway analysis states that every flux mode can be decomposed into a sum of elementary modes. However, only a decomposition without cancelations is biochemically meaningful, since a reversible reaction cannot have different directions in the contributing elementary modes. This essential requirement has been largely overlooked by the metabolic pathway community. Indeed, every flux mode can be decomposed into elementary modes without cancelations. The result is an immediate consequence of a theorem by Rockafellar which states that every element of a linear subspace is a conformal sum (a sum without cancelations) of elementary vectors (support-minimal vectors). In this work, we extend the theorem, first to "subspace cones" and then to general polyhedral cones and polyhedra. Thereby, we refine Minkowski's and Carathéodory's theorems, two fundamental results in polyhedral geometry. We note that, in general, elementary vectors need not be support-minimal; in fact, they are conformally non-decomposable and form a unique minimal set of conformal generators. Our treatment is mathematically rigorous, but suitable for systems biologists, since we give self-contained proofs for our results and use concepts motivated by metabolic pathway analysis. In particular, we study cones defined by linear subspaces and nonnegativity conditions - like the flux cone - and use them to analyze general polyhedral cones and polyhedra. Finally, we review applications of elementary vectors and conformal sums in metabolic pathway analysis.