Development of network-based pathway definitions: the need to analyze real metabolic networks

摘要

A recent article addresses the important issue of network-based metabolic pathway analysis. Various methods have been used to define systemic pathways for metabolic networks based on network connectivity including heuristic analysis and computer-aided artificial intelligence synthesis. A rigorous mathematical analysis to define network-based pathways has been developed based on the topological structure of biochemical networks. One of the first of such approaches was stoichio-metric network analysis (SNA), which defined 'extreme currents' through chemical systems. Elementary mode analysis, and the similar extreme pathway analysis, use convex mathematics to find network-based pathways though the network. These pathways correspond to a set of convex basis vectors that generate the solution space containing all allowable steady state flux distributions, and have been reviewed. The Opinion article seeks to contrast two closely related approaches to network-based pathway definitions, elementary flux modes (ELMO) and extreme pathways (EXPA). The resulting comparison, albeit potentially informative from a mathematical and algorithmic standpoint, unfortunately falls short in recognizing the biochemical, physiological and practical aspects of using such systemic pathway definitions for analyzing the properties of real metabolic systems.