On predicting transport proteins and their substrates for the reconstruction of metabolic networks

The reconstruction of a metabolic network is a key step in systems biology and synthetic biology. A genome-scale network reconstruction builds a map to represent the gene-protein-reaction (GPR) association between the genes, the proteins which are the gene products, to the reaction that is carried out by the protein. For metabolism, the reaction is a metabolic reaction, and the protein is an enzyme catalysing the reaction. The transport of substrates across membranes is modeled by transport reactions. For higher organisms, the cellular compartments are important, so models include the extracellular space, the cytosol, the mitochondrion, and sometimes the peroxisome. The prediction of transport proteins for the GPR association, in particular, the specific substrate, or substrates, the protein transports across the membrane, and which membrane, is not as developed as the prediction of the GPR association for enzymes. In this paper, we illustrate the deficiencies in the state-of-the-art, and present our initial work to improve the prediction of GPR associations for transmembrane transporters.