ReDirection: a numerically robust R-package to characterize every reaction of a user-defined biochemical network with the probable dissociation constant

Abstract

AbstractBiochemical networks integrate enzyme-mediated substrate conversions with non-enzymatic complex formation and disassembly to accomplish complex biochemical and physiological function. The multitude of theoretical studies utilizing empirical/clinical data notwithstanding, the parameters used in these analyses whilst being theoretically sound are likely to be of limited biomedical relevance. There is need for a computational tool which can ascribe functionality to and generate potentially testable hypotheses for a biochemical network. “ReDirection” characterizes every reaction of a user-defined biochemical network with the probable dissociation constant and does so by combinatorially summing all non-redundant and non-trivial vectors of a null space generated subspace from the stoichiometry number matrix of the modelled biochemical network. This is followed by defining and populating a reaction-specific sequence vector with numerical values drawn from each row of this subspace, computing several descriptors and partitioning selected terms into distinct subsets in accordance with the expected outcomes (forward, reverse, equivalent) for a reaction. “ReDirection” computes the sums of all the terms that comprise each outcome-specific subset, maps these to strictly positive real numbers and bins the same to a reaction-specific outcome vector. The p1-norm of this vector is the probable dissociation constant for a reaction and is used to assign and annotate the reaction. “ReDirection” iterates these steps recursively until every reaction of the modelled biochemical network has been assigned an unambiguous outcome. “ReDirection” works on first principles, does not discriminate between enzymatic and non-enzymatic reactions, offers a mathematically rigorous and biochemically relevant environment to explore user-defined biochemical networks under naive and perturbed conditions and can be used to address empirically intractable biochemical problems. The utility and relevance of “ReDirection” is highlighted with an investigation of a constrained biochemical network of human Galactose metabolism. “ReDirection” is freely available and accessible from the comprehensive R archive network (CRAN) with the URL (https://cran.r-project.org/package=ReDirection).