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Biosynthetic potentials of metabolites and their hierarchical organization.

Matthäus F, Salazar C, Ebenhöh O - PLoS Comput. Biol. (2008)

Bottom Line: We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential.A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials.Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Center for Scientific Computing, University of Heidelberg, Heidelberg, Germany.

ABSTRACT
A major challenge in systems biology is to understand how complex and highly connected metabolic networks are organized. The structure of these networks is investigated here by identifying sets of metabolites that have a similar biosynthetic potential. We measure the biosynthetic potential of a particular compound by determining all metabolites than can be produced from it and, following a terminology introduced previously, call this set the scope of the compound. To identify groups of compounds with similar scopes, we apply a hierarchical clustering method. We find that compounds within the same cluster often display similar chemical structures and appear in the same metabolic pathway. For each cluster we define a consensus scope by determining a set of metabolites that is most similar to all scopes within the cluster. This allows for a generalization from scopes of single compounds to scopes of a chemical family. We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential. Our investigations show that this hierarchy is not only determined by the chemical complexity of the metabolites, but also strongly by their biological function. As a general tendency, metabolites which are necessary for essential cellular processes exhibit a larger biosynthetic potential than those involved in secondary metabolism. A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials. Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

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Uncertainty of cluster assignment and fraction of combined biosynthetic potentials assigned to a cluster.Shown are the average uncertainty α of the assignment to clusters (squares), and fraction of the combined biosynthetic potentials which have been assigned to one of the clusters I-XIII (circles) as a function of the seed size σ.
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pcbi-1000049-g003: Uncertainty of cluster assignment and fraction of combined biosynthetic potentials assigned to a cluster.Shown are the average uncertainty α of the assignment to clusters (squares), and fraction of the combined biosynthetic potentials which have been assigned to one of the clusters I-XIII (circles) as a function of the seed size σ.

Mentions: The average value α is plotted against the number of metabolites in the seed in Figure 3 (black squares). It can be seen that the assignment to a cluster is more reliable for larger seed sizes. This is not surprising since larger seeds tend to exhibit a larger biosynthetic potential and, as is the case for the potentials of single metabolites, small scopes cannot reliably be grouped into clusters. Consistent with the choice of parameters in the hierarchical clustering process, in which we merge two clusters if they exhibit a distance of less than 0.2, we only assign the scopes of multiple-compound seeds to a cluster if d0<0.2. As expected from the decreasing uncertainties of cluster assignment, the percentage of assigned clusters increases strongly with increasing seed size (red circles in Figure 3). For a seed size of two, less than 40% of the scopes are assigned to a cluster. For a seed size of 20, almost all scopes are unambiguously assigned to one of the thirteen clusters determined above.


Biosynthetic potentials of metabolites and their hierarchical organization.

Matthäus F, Salazar C, Ebenhöh O - PLoS Comput. Biol. (2008)

Uncertainty of cluster assignment and fraction of combined biosynthetic potentials assigned to a cluster.Shown are the average uncertainty α of the assignment to clusters (squares), and fraction of the combined biosynthetic potentials which have been assigned to one of the clusters I-XIII (circles) as a function of the seed size σ.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2289774&req=5

pcbi-1000049-g003: Uncertainty of cluster assignment and fraction of combined biosynthetic potentials assigned to a cluster.Shown are the average uncertainty α of the assignment to clusters (squares), and fraction of the combined biosynthetic potentials which have been assigned to one of the clusters I-XIII (circles) as a function of the seed size σ.
Mentions: The average value α is plotted against the number of metabolites in the seed in Figure 3 (black squares). It can be seen that the assignment to a cluster is more reliable for larger seed sizes. This is not surprising since larger seeds tend to exhibit a larger biosynthetic potential and, as is the case for the potentials of single metabolites, small scopes cannot reliably be grouped into clusters. Consistent with the choice of parameters in the hierarchical clustering process, in which we merge two clusters if they exhibit a distance of less than 0.2, we only assign the scopes of multiple-compound seeds to a cluster if d0<0.2. As expected from the decreasing uncertainties of cluster assignment, the percentage of assigned clusters increases strongly with increasing seed size (red circles in Figure 3). For a seed size of two, less than 40% of the scopes are assigned to a cluster. For a seed size of 20, almost all scopes are unambiguously assigned to one of the thirteen clusters determined above.

Bottom Line: We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential.A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials.Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Center for Scientific Computing, University of Heidelberg, Heidelberg, Germany.

ABSTRACT
A major challenge in systems biology is to understand how complex and highly connected metabolic networks are organized. The structure of these networks is investigated here by identifying sets of metabolites that have a similar biosynthetic potential. We measure the biosynthetic potential of a particular compound by determining all metabolites than can be produced from it and, following a terminology introduced previously, call this set the scope of the compound. To identify groups of compounds with similar scopes, we apply a hierarchical clustering method. We find that compounds within the same cluster often display similar chemical structures and appear in the same metabolic pathway. For each cluster we define a consensus scope by determining a set of metabolites that is most similar to all scopes within the cluster. This allows for a generalization from scopes of single compounds to scopes of a chemical family. We observe that most of the resulting consensus scopes overlap or are fully contained in others, revealing a hierarchical ordering of metabolites according to their biosynthetic potential. Our investigations show that this hierarchy is not only determined by the chemical complexity of the metabolites, but also strongly by their biological function. As a general tendency, metabolites which are necessary for essential cellular processes exhibit a larger biosynthetic potential than those involved in secondary metabolism. A central result is that chemically very similar substances with different biological functions may differ significantly in their biosynthetic potentials. Our studies provide an important step towards understanding fundamental design principles of metabolic networks determined by the structural and functional complexity of metabolites.

Show MeSH