Using a large-scale knowledge database on reactions and regulations to propose key upstream regulators of various sets of molecules participating in cell metabolism

Table 1 Modeling encyclopedic information as a set of regulated reactions used to build a causality graph

^aObtained from the TRANSPATH database that includes a description of biochemical reactions, protein-protein interactions, and transcription factors involved in signal transduction of mammalian cells.
^bReactions and effects (i.e., causal dependencies) were unified in the concept of regulated reactions, which corresponded to a set of substrates, products and regulators (activators, inhibitors or modulators). These regulators included transcription factors (assuming the regulated gene as the product of a reaction using a non-limiting unknown substrate) and enzymes (catalyzing biochemical reactions between substrates and products). A Boolean attribute was added to distinguish between reversible and irreversible reactions.
^cThe regulated reactions were converted in a causality graph to model the variations in the amounts of molecules, fluxes and reaction speeds (nodes), and to predict their consequences (edges). Because nodes were shared between various regulated reactions, the conversion of the regulated reaction network in the causality graph led to a large increase in the number of nodes and edges.

ISSN: 1752-0509