Algorithms for network analysis in systems-ADME/Tox using the MetaCore and MetaDrug platforms

The authors have previously applied two integrated platforms, MetaCore™ and MetaDrug™, for the assembly and analysis of human biological networks as a useful method for the integration and functional interpretation of high-throughput experimental data. The present study demonstrates in detail the specific algorithms that are used in both software platforms. Using a standard set of genes as input, namely CYP3A4 (an enzyme), PXR (a nuclear hormone receptor), MDR1 (a transporter) and hERG (an ion channel) related to the absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) of xenobiotics, we have now generated networks with each algorithm. The relative advantages and disadvantages of these algorithms are explained using these examples as well as appropriate instances of utility to illustrate further the particular circumstances for their use. In addition, the benefits of the different network algorithms are identified when compared with algorithms available in other products, where this inf...