Estimating the solution space of Metabolic Networks Mercoledì 11 Marzo 2009 ore 14.30
Andrea Pagnani - Fondazione ISI, Torino
Cellular metabolism is one of the most investigated aspect of cell-wide
biological interactions. While the topological nature of individual
reactions and pathways in the network is quite well understood there is
still a lack of comprehension regarding the global functional behavior of
the system. To get some insight in this direction, in the last few years
powerful theoretical methods such as extreme pathways calculation and
flux-balance analysis have been introduced. In this work we propose a novel
algorithmic strategy that allows for an efficient characterization of the
whole set of stable fluxes compatible with the metabolic constraints. Using
a technique derived from the fields of statistical physics and information
theory we designed a stochastic algorithm to estimate the size of the affine
space containing all possible steady-state flux distributions of metabolic
networks. The algorithm, based on the Bethe approximation, allows the
computation in polynomial time of the volume of a non full-dimensional
convex polytope in high dimensions. We show results for toy models that
compare very well with the results of exact algorithms, as well as for the
E-Coli central metabolism that is intractable using standard techniques. The
algorithm is used to test the effect of gene knock-outs on the size of the
solution space of the E-coli central metabolism. Visita