PITUFO is a java software to find minimal sets of precursors of target compounds in a metabolic network. The original method and a biological application were described in the WABI 2008 (Workshop on Algorithms in BioInformatics). Enumerating Precursor Sets of Target Metabolites in a Metabolic Network Abstract: We present the first exact method based on the topology of a metabolic
network to find minimal sets of metabolites (called
precursors) sufficient to produce a set of target metabolites.
In contrast with previous proposals, our model takes into account
self-regenerating metabolites involved in cycles, which may be
used to generate target metabolites from potential precursors.
We analyse the complexity of the problem and we propose an
algorithm to enumerate all minimal precursor sets for a set of
target metabolites. The algorithm can be applied to identify a
minimal medium necessary for a cell to ensure some metabolic
functions. It can be used also to check inconsistencies caused
by misannotations in a metabolic network. We present two illustrations
of these applications.
---- An application of the method in the context of studying the metabolic interactions inside a complex symbiotic system involving an insect host and two bacterial endosymbionts was publish in 2008, in PLOS Computational Biology. Graph-Based Analysis of the Metabolic Exchanges between Two Co-Resident Intracellular Symbionts, Baumannia cicadellinicola and Sulcia muelleri, with Their Insect Host, Homalodisca coagulata Abstract: Endosymbiotic bacteria from different species can live inside cells of
the same eukaryotic organism. Metabolic exchanges occur between host and
bacteria but also between different endocytobionts. Since a complete
genome annotation is available for both, we built the metabolic network
of two endosymbiotic bacteria, Sulcia muelleri and Baumannia cicadellinicola, that live inside specific cells of the sharpshooter Homalodisca coagulata
and studied the metabolic exchanges involving transfers of carbon atoms
between the three. We automatically determined the set of metabolites
potentially exogenously acquired (seeds) for both metabolic networks. We
show that the number of seeds needed by both bacteria in the carbon
metabolism is extremely reduced. Moreover, only three seeds are common
to both metabolic networks, indicating that the complementarity of the
two metabolisms is not only manifested in the metabolic capabilities of
each bacterium, but also by their different use of the same environment.
Furthermore, our results show that the carbon metabolism of S. muelleri may be completely independent of the metabolic network of B. cicadellinicola. On the contrary, the carbon metabolism of the latter appears dependent on the metabolism of S. muelleri,
at least for two essential amino acids, threonine and lysine. Next, in
order to define which subsets of seeds (precursor sets) are sufficient
to produce the metabolites involved in a symbiotic function, we used a
graph-based method, PITUFO, that we recently developed. Our results
highly refine our knowledge about the complementarity between the
metabolisms of the two bacteria and their host. We thus indicate seeds
that appear obligatory in the synthesis of metabolites are involved in
the symbiotic function. Our results suggest both B. cicadellinicola and S. muelleri
may be completely independent of the metabolites provided by the
co-resident endocytobiont to produce the carbon backbone of the
metabolites provided to the symbiotic system (., thr and lys are only exploited by B. cicadellinicola to produce its proteins). |