Computation of elementary modes: a unifying framework and the new binary approach
BMC Bioinformatics, (November 2004)Abstract
Background: Metabolic pathway analysis has been recognized as a central approach to the
structural analysis of metabolic networks. The concept of elementary (flux) modes provides a
rigorous formalism to describe and assess pathways and has proven to be valuable for many
applications. However, computing elementary modes is a hard computational task. In recent years
we assisted in a multiplication of algorithms dedicated to it. We require a summarizing point of view
and a continued improvement of the current methods.
Results: We show that computing the set of elementary modes is equivalent to computing the set
of extreme rays of a convex cone. This standard mathematical representation provides a unified
framework that encompasses the most prominent algorithmic methods that compute elementary
modes and allows a clear comparison between them. Taking lessons from this benchmark, we here
introduce a new method, the binary approach, which computes the elementary modes as binary
patterns of participating reactions from which the respective stoichiometric coefficients can be
computed in a post-processing step. We implemented the binary approach in FluxAnalyzer 5.1, a
software that is free for academics. The binary approach decreases the memory demand up to 96%
without loss of speed giving the most efficient method available for computing elementary modes
to date.
Conclusions: The equivalence between elementary modes and extreme ray computations offers
opportunities for employing tools from polyhedral computation for metabolic pathway analysis.
The new binary approach introduced herein was derived from this general theoretical framework
and facilitates the computation of elementary modes in considerably larger networks.
