title: Generic flux coupling analysis.
abstract: Flux coupling analysis (FCA) has become a useful tool for aiding metabolic reconstructions and guiding genetic manipulations. Originally, it was introduced for constraint-based models of metabolic networks that are based on the steady-state assumption. Recently, we have shown that the steady-state assumption can be replaced by a weaker lattice-theoretic property related to the supports of metabolic fluxes. In this paper, we further extend our approach and develop an efficient algorithm for generic flux coupling analysis that works with any kind of qualitative pathway model. We illustrate our method by thermodynamic flux coupling analysis (tFCA), which allows studying steady-state metabolic models with loop-law thermodynamic constraints. These models do not satisfy the lattice-theoretic properties required in our previous work. For a selection of genome-scale metabolic network reconstructions, we discuss both theoretically and practically, how thermodynamic constraints strengthen the coupling results that can be obtained with classical FCA. A prototype implementation of tFCA is available at http://hoverboard.io/L4FC.
authors.affiliation: Freie Universität Berlin, Arnimallee 6, Room 101, 14195 Berlin, Germany; Berlin Mathematical School, Berlin, Germany; International Max Planck Research School for Computational Biology and Scientific Computing, Max Planck Institute for Molecular Genetics, Ihnestr 63-73, 14195 Berlin, Germany. Electronic address: arne.c.reimers@gmail.com.
authors.forename: Arne C
authors.initials: AC
authors.lastname: Reimers
authors.affiliation: Freie Universität Berlin, Arnimallee 6, Room 101, 14195 Berlin, Germany; Forschungszentrum Matheon, Technische Universität Berlin, Straße des 17. Juni 136, 10623 Berlin, Germany. Electronic address: goldsteiny.de@gmail.com.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Goldstein
authors.affiliation: Freie Universität Berlin, Arnimallee 6, Room 101, 14195 Berlin, Germany; Forschungszentrum Matheon, Technische Universität Berlin, Straße des 17. Juni 136, 10623 Berlin, Germany. Electronic address: alexander.bockmayr@fu-berlin.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bockmayr
mesh_terms: D000465:Algorithms; D023281:Genomics; D055641:Mathematical Concepts; D064688:Metabolic Flux Analysis; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D011382:Programming, Linear; D013816:Thermodynamics
keywords: Flux coupling analysis; Metabolic network; Qualitative model; Thermodynamic constraint