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Metabolic Pathways Analysis 2009 |
Description: Biology is relying more and
more on mathematics. Systems biology
analyzes the properties of molecular networks as they have been determined on
the basis of experiments. Stoichiometric
Network Analysis (SNA) starts from the biochemical fact that essentially all
molecular reactions inside cells are converted by dedicated proteins (enzymes).
Then, by virtue of the high homology of metabolic enzymes between species, a
genome-scale stoichiometric model can be reconstructed for a particular species
given its genome. With this knowledge, for instance steady-state flux
distributions, the viability of organisms upon mutations, alternative flux
distributions for mutants and many more aspects can be predicted with SNA. It also allows for more sophisticated
mathematical analysis that touches on the limits of present-day
mathematics. Some mathematical problems
in current SNA are: 1. Enumeration
of extreme fluxes immediately touches upon a famous open problem in
computational geometry. Computational
experiments have shown that even moderate size metabolic networks give rise to
enormous numbers of extreme fluxes. How
to condense this information? 2. The
space of all steady-state fluxes can be represented in different ways. It is
necessary to deepen our understanding of the relationship between (condensed
representations of) extreme fluxes and extreme solutions to Flux Balance
Analysis (FBA) programs. 3. It
is desirable to develop a unifying framework to tie together the major
geometric components of SNA: extreme fluxes/vectors, cones, (FBA) polyhedra and
the aforementioned problem of enumerating polyhedral vertices. 4. Optimization
in SNA often relies on linear programming. Many problems immediately yield
challenging algorithmic questions, not in the least because, although being
NP-hard, the typical features of the stoichiometric matrix may be exploited in
the design of practically fast enough algorithms. Thus, many of the current
biological problems we would like to tackle with SNA require new useful concepts
and analysis methods each firmly based on rigorous mathematics. This needs to be done preferably in close
collaboration with biologists to guarantee the usefulness of the developed
methods. A first workshop in this
direction was organized in Aims: In general, bring together
the leaders of the field to discuss its status, standardization of tools and
future directions. A main aim is to establish an official mixed consortium of
researchers from Mathematics/Computer Science and researchers from Biology to
work together on understanding biologic networks in all its different aspects.
It would be a fantastic achievement if the workshop reports will become the
basis for a proposal to the EU for enhancing the structure of such a consortium
within the 7^{th} Framework Program. [Back] |